Medicine › Neurology

Neurological disorders and treatments

Works Count: 75100

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This cluster of papers focuses on the use of deep brain stimulation (DBS) for neurological disorders such as Parkinson's disease, treatment-resistant depression, epilepsy, and dystonia. The research explores the effects of DBS on the subthalamic nucleus, basal ganglia circuitry, and the treatment outcomes for various neurological conditions.

Keywords

Deep Brain Stimulation; Parkinson's Disease; Subthalamic Nucleus; Basal Ganglia; Treatment-Resistant Depression; Neuromodulation; Epilepsy; Dystonia; Circuitry; Neurological Disorders

The Cerebral Cortex of Man: A Clinical Study of Localization of Function

1968-10-07

Wilder Penfield , Theodore P. Rasmussen

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The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism

1994-08-01

Hagai Bergman , Thomas Wichmann , Benny Karmon +1 more

1. The neuronal mechanisms underlying the major motor signs of Parkinson's disease were studied in the basal ganglia of parkinsonian monkeys. Three African green monkeys were systemically treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine … 1. The neuronal mechanisms underlying the major motor signs of Parkinson's disease were studied in the basal ganglia of parkinsonian monkeys. Three African green monkeys were systemically treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) until parkinsonian signs, including akinesia, rigidity, and a prominent 4- to 8-Hz tremor, appeared. The activity of neurons in the subthalamic nucleus (STN) and in the internal segment of the globus pallidus (GPi) was recorded before (STN, n = 220 cells; GPi, n = 175 cells) and after MPTP treatment (STN, n = 326 cells; GPi, n = 154 cells). 2. In STN the spontaneous firing rate was significantly increased from 19 +/- 10 (SD) spikes/s before to 26 +/- 15 spikes/s after MPTP treatment. Division of STN neurons recorded after MPTP treatment into cells with rhythmic bursts of discharge occurring at 4–8 Hz (as defined by autocorrelation analysis) and neurons without 4- to 8-Hz periodic activity revealed an even more prominent increase in the firing rate of the 4- to 8-Hz oscillatory neurons. 3. In GPi overall changes in the average firing rate of cells were inconsistent between different animals and behavioral states. However, the average firing rate of the subpopulation of neurons with 4- to 8-Hz periodic oscillatory activity after treatment with MPTP was significantly increased over that of all neurons before MPTP treatment (from 53 to 76 spikes/s, averaged across monkeys). 4. In the normal state the percentage of neurons with burst discharges (as defined by autocorrelation analysis) was 69% and 78% in STN and GPi, respectively. After MPTP treatment the percentage of cells that discharged in bursts was increased to 79% and 89%, respectively. At the same time the average burst duration decreased (from 121 +/- 98 to 81 +/- 99 ms in STN and from 213 +/- 120 to 146 +/- 134 ms in GPi) with no significant change in the average number of spikes per burst. 5. Periodic oscillatory neuronal activity at low frequency, highly correlated with tremor, was detected in a large number of cells in STN and GPi after MPTP treatment (average oscillation frequency 6.0 and 5.1 Hz, respectively). The autocorrelograms of spike trains of these neurons confirm that the periodic oscillatory activity was very stable. The percentage of cells with 4- to 8-Hz periodic activity significantly increased from 2% to 16% in STN and from 0.6% to 25% in GPi with the MPTP treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

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Consensus Statement of the Movement Disorder Society on Tremor

2008-10-20

Günther Deuschl , Peter G. Bain , Mitchell F. Brin

This is a proposal of the Movement Disorder Society for a clinical classification of tremors. The classification is based on the distinction between rest, postural, simple kinetic, and intention tremor … This is a proposal of the Movement Disorder Society for a clinical classification of tremors. The classification is based on the distinction between rest, postural, simple kinetic, and intention tremor (tremor during target-directed movements). Additional data from a medical history and the results of a neurologic examination can be combined into one of the following clinical syndromes defined in this statement: enhanced physiologic tremor, classical essential tremor (ET), primary orthostatic tremor, task- and position-specific tremors, dystonic tremor, tremor in Parkinson's disease (PD), cerebellar tremor, Holmes' tremor, palatal tremor, drug-induced and toxic tremor, tremor in peripheral neuropathies, or psychogenic tremor. Conditions such as asterixis, epilepsia partialis continua, clonus, and rhythmic myoclonus can be misinterpreted as tremor. The features distinguishing these conditions from tremor are described. Controversial issues are outlined in a comment section for each item and thus reflect the open questions that at present cannot be answered on a scientific basis. We hope that this statement provides a basis for better communication among clinicians working in the field and stimulates tremor research.

Primate models of movement disorders of basal ganglia origin

1990-07-01

Mahlon R. DeLong

An Essay on the Shaking Palsy

2002-05-01

James Parkinson

Apathy and the Functional Anatomy of the Prefrontal Cortex–Basal Ganglia Circuits

2005-10-05

Richard Lévy , Bruno Dubois

The clinical signs grouped under the concept of apathy are a common feature of prefrontal and basal ganglia lesions or dysfunctions and can therefore help to improve our understanding of … The clinical signs grouped under the concept of apathy are a common feature of prefrontal and basal ganglia lesions or dysfunctions and can therefore help to improve our understanding of the functional anatomy of the prefrontal-basal ganglia system. Apathy is here defined as a quantitative reduction of voluntary, goal-directed behaviors. The underlying mechanisms responsible for apathy can be divided into three subtypes of disrupted processing: 'emotional-affective', 'cognitive' and 'auto-activation'. Apathy due to the disruption of 'emotional-affective' processing refers to the inability to establish the necessary linkage between emotional-affective signals and the ongoing or forthcoming behavior. It may be related to lesions of the orbital-medial prefrontal cortex or to the related subregions (limbic territory) within the basal ganglia (e.g. ventral striatum, ventral pallidum). Apathy due to the disruption of 'cognitive' processing refers to difficulties in elaborating the plan of actions necessary for the ongoing or forthcoming behavior. It may be related to lesions of the dorsolateral prefrontal cortex and the related subregions (associative territory) within the basal ganglia (e.g. dorsal caudate nucleus). The disruption of 'auto-activation' processing refers to the inability to self-activate thoughts or self-initiate actions contrasting with a relatively spared ability to generate externally driven behavior. It is responsible for the most severe form of apathy and in most cases the lesions affect bilaterally the associative and limbic territories of the internal portion of the globus pallidus. It characterizes the syndrome of 'auto-activation deficit' (also known as 'psychic akinesia' or 'athymormia'). This syndrome implies that direct lesions of the basal ganglia output result in a loss of amplification of the relevant signal, consequently leading to a diminished extraction of this signal within the frontal cortex. Likewise, apathy occurring in Parkinson's disease could be interpreted as secondary to the loss of spatial and temporal focalization of the signals transferred to the frontal cortex. In both situations (direct basal ganglia lesions and nigro-striatal dopaminergic loss), the capacity of the frontal cortex to select, initiate, maintain and shift programs of actions is impaired.

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New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: The striatopallidal, amygdaloid, and corticopetal components of substantia innominata

1988-10-01

George F. Alheid , Lennart Heimer

THE BASAL GANGLIA: FOCUSED SELECTION AND INHIBITION OF COMPETING MOTOR PROGRAMS

1996-11-01

Jonathan W. Mink

Basal ganglia and cerebellar loops: motor and cognitive circuits

2000-03-01

Frank A. Middleton , Peter L. Strick

Functional architecture of basal ganglia circuits: neural substrates of parallel processing

1990-07-01

Garrett E. Alexander , Michael D. Crutcher

Diagnosis and management of diabetic autonomic neuropathy.

1982-10-02

D J Ewing , B F Clarke

Background: β-Carboline alkaloids (e.g., harmane) are highly tremorogenic chemicals. Animal protein (meat) is the major dietary source of these alkaloids. The authors previously demonstrated that blood harmane concentrations were … Background: β-Carboline alkaloids (e.g., harmane) are highly tremorogenic chemicals. Animal protein (meat) is the major dietary source of these alkaloids. The authors previously demonstrated that blood harmane concentrations were elevated in patients with essential tremor (ET) vs controls. Whether this difference is due to greater animal protein consumption by patients or their failure to metabolize harmane is unknown. Objective: The aim of this study was to determine whether patients with ET and controls differ with regard to 1) daily animal protein consumption and 2) the correlation between animal protein consumption and blood harmane concentration. Methods: Data on current diet were collected with a semiquantitative food frequency questionnaire and daily calories and consumption of animal protein and other food types was calculated. Blood harmane concentrations were log-transformed (logHA). Results: The mean logHA was higher in 106 patients than 161 controls (0.61 ± 0.67 vs 0.43 ± 0.72 g−10/mL, p = 0.035). Patients and controls consumed similar amounts of animal protein (50.2 ± 19.6 vs 49.4 ± 19.1 g/day, p = 0.74) and other food types (animal fat, carbohydrates, vegetable fat) and had similar caloric intakes. In controls, logHA was correlated with daily consumption of animal protein (r = 0.24, p = 0.003); in patients, there was no such correlation (r = −0.003, p = 0.98). Conclusions: The similarity between patients and controls in daily animal protein consumption and the absence of the normal correlation between daily animal protein consumption and logHA in patients suggests that another factor (e.g., a metabolic defect) may be increasing blood harmane concentration in patients.

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Cortical and Subcortical Contributions to Stop Signal Response Inhibition: Role of the Subthalamic Nucleus

2006-03-01

Adam R. Aron , Russell A. Poldrack

Suppressing an already initiated manual response depends critically on the right inferior frontal cortex (IFC), yet it is unclear how this inhibitory function is implemented in the motor system. It … Suppressing an already initiated manual response depends critically on the right inferior frontal cortex (IFC), yet it is unclear how this inhibitory function is implemented in the motor system. It has been suggested that the subthalamic nucleus (STN), which is a part of the basal ganglia, may play a role because it is well placed to suppress the “direct” fronto-striatal pathway that is activated by response initiation. In two experiments, we investigated this hypothesis with functional magnetic resonance imaging and a Stop-signal task. Subjects responded to Go signals and attempted to inhibit the initiated response to occasional Stop signals. In experiment 1, Going significantly activated frontal, striatal, pallidal, and motor cortical regions, consistent with the direct pathway, whereas Stopping significantly activated right IFC and STN. In addition, Stopping-related activation was significantly greater for fast inhibitors than slow ones in both IFC and STN, and activity in these regions was correlated across subjects. In experiment 2, high-resolution functional and structural imaging confirmed the location of Stopping activation within the vicinity of the STN. We propose that the role of the STN is to suppress thalamocortical output, thereby blocking Go response execution. These results provide convergent data for a role for the STN in Stop-signal response inhibition. They also suggest that the speed of Go and Stop processes could relate to the relative activation of different neural pathways. Future research is required to establish whether Stop-signal inhibition could be implemented via a direct functional neuroanatomic projection between IFC and STN (a “hyperdirect” pathway).

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Functional significance of the cortico–subthalamo–pallidal ‘hyperdirect’ pathway

2002-06-01

Atsushi Nambu , Hironobu Tokuno , Masahiko Takada

The Basal Ganglia and Adaptive Motor Control

1994-09-23

Ann M. Graybiel , Toshihiko Aosaki , Alice W. Flaherty +1 more

The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel … The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

Concurrent activation of striatal direct and indirect pathways during action initiation

2013-01-22

Guohong Cui , Sang Beom Jun , Xin Jin +4 more

The functional anatomy of basal ganglia disorders

1989-01-01

Roger L. Albin , Anne B. Young , John B. Penney

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Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus

1991-02-01

Alim Louis Benabid , Pierre Pollak , D. Hoffmann +5 more

Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system

1970-12-01

Urban Ungerstedt , Gordon W. Arbuthnott

Reversal of Experimental Parkinsonism by Lesions of the Subthalamic Nucleus

1990-09-21

Hagai Bergman , Thomas Wichmann , Mahlon R. DeLong

Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian … Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.

Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation

1995-01-01

Patricia Limousin , Pierre Pollak , Abdelhamid Benazzouz +5 more

Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidium in basal ganglia circuitry

1995-01-01

André Parent , Lili‐Naz Hazrati

Combined (Thalamotomy and Stimulation) Stereotactic Surgery of the VIM Thalamic Nucleus for Bilateral Parkinson Disease

1987-01-01

A.L. Benabid , Pierre Pollak , Antoine Louveau +2 more

Stereotactic thalamotomy of the thalamic nucleus ventralis intermedius (VIM) is routinely used for movement disorders. During this procedure, it has been observed that high-frequency (100 Hz) stimulation of VIM was … Stereotactic thalamotomy of the thalamic nucleus ventralis intermedius (VIM) is routinely used for movement disorders. During this procedure, it has been observed that high-frequency (100 Hz) stimulation of VIM was able to stop the extrapyramidal tremor. In patients with bilateral tremor of extrapyramidal origin, who were resistant to drug therapy, the therapeutic protocol associated (1) a radiofrequency VIM thalamotomy for the most disabled side, and (2) a continuous VIM stimulation for the other side using stereotactically implanted electrodes, connected to subcutaneous stimulators. VIM thalamotomy relieved the tremor in all operated cases. Side effects were mild and regressive. VIM stimulation strongly decreased the tremor but failed to suppress it as completely as thalamotomy did. This was due in part to the fact that programmable stimulator frequency rate is limited to 130 Hz, while it appeared that the optimal stimulation frequency was 200 Hz. This therapeutic protocol appears to be of interest for patients with bilateral extrapyramidal movement disorders.

Optical Deconstruction of Parkinsonian Neural Circuitry

2009-03-20

Viviana Gradinaru , Murtaza Mogri , Kimberly R. Thompson +2 more

Deep brain stimulation (DBS) is a therapeutic option for intractable neurological and psychiatric disorders, including Parkinson's disease and major depression. Because of the heterogeneity of brain tissues where electrodes are … Deep brain stimulation (DBS) is a therapeutic option for intractable neurological and psychiatric disorders, including Parkinson's disease and major depression. Because of the heterogeneity of brain tissues where electrodes are placed, it has been challenging to elucidate the relevant target cell types or underlying mechanisms of DBS. We used optogenetics and solid-state optics to systematically drive or inhibit an array of distinct circuit elements in freely moving parkinsonian rodents and found that therapeutic effects within the subthalamic nucleus can be accounted for by direct selective stimulation of afferent axons projecting to this region. In addition to providing insight into DBS mechanisms, these results demonstrate an optical approach for dissection of disease circuitry and define the technological toolbox needed for systematic deconstruction of disease circuits by selectively controlling individual components.

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Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop

1995-01-01

André Parent , Lili‐Naz Hazrati

Five-Year Follow-up of Bilateral Stimulation of the Subthalamic Nucleus in Advanced Parkinson's Disease

2003-11-12

Paul Krack , Alina Batir , Nadège Van Blercom +7 more

Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown.We conducted … Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown.We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson's Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up.As compared with base line, the patients' scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which off-medication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide.Patients with advanced Parkinson's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson's disease.

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Localization of the motor hand area to a knob on the precentral gyrus. A new landmark

1997-01-01

Tarek Yousry

Using functional magnetic resonance imaging (fMRI) we have evaluated the anatomical location of the motor hand area. The segment of the precentral gyrus that most often contained motor hand function … Using functional magnetic resonance imaging (fMRI) we have evaluated the anatomical location of the motor hand area. The segment of the precentral gyrus that most often contained motor hand function was a knob-like structure, that is shaped like an omega or epsilon in the axial plane and like a hook in the sagittal plane. On the cortical surface of cadaver specimens this precentral knob corresponded precisely to the characteristic 'middle knee' of the central sulcus that has been described by various anatomists in the last century. We were then able to show that this knob is a reliable landmark for identifying the precentral gyrus directly. We therefore conclude that neural elements involved in motor hand function are located in a characteristic 'precentral knob' which is a reliable landmark for identifying the precentral gyrus under normal and pathological conditions. It faces and forms the 'middle knee' of the central sulcus, is located just at the cross point between the precentral sulcus and the central sulcus, and is therefore also visible on the cortical surface.

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Neurostimulation for Parkinson's Disease with Early Motor Complications

2013-02-13

W.M. Michael Schuepbach , Jörn Rau , Karina Knudsen +7 more

Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at … Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease.In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia.For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group.Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

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Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy

2010-03-20

Robert S. Fisher , Vicenta Salanova , Thomas C. Witt +7 more

We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy.Participants were adults with medically refractory partial seizures, including secondarily generalized … We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy.Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation.One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events.Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

Motor control and aging: Links to age-related brain structural, functional, and biochemical effects

2009-10-21

Rachael D. Seidler , Jessica A. Bernard , Taritonye B. Burutolu +5 more

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A double‐blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease

2003-08-28

C. Warren Olanow , Christopher G. Goetz , Jeffrey H. Kordower +7 more

Abstract Thirty‐four patients with advanced Parkinson's disease participated in a prospective 24‐month double‐blind, placebo‐controlled trial of fetal nigral transplantation. Patients were randomized to receive bilateral transplantation with one or four … Abstract Thirty‐four patients with advanced Parkinson's disease participated in a prospective 24‐month double‐blind, placebo‐controlled trial of fetal nigral transplantation. Patients were randomized to receive bilateral transplantation with one or four donors per side or a placebo procedure. The primary end point was change between baseline and final visits in motor component of the Unified Parkinson's Disease Rating Scale in the practically defined off state. There was no significant overall treatment effect ( p = 0.244). Patients in the placebo and one‐donor groups deteriorated by 9.4 ± 4.25 and 3.5 ± 4.23 points, respectively, whereas those in the four‐donor group improved by 0.72 ± 4.05 points. Pairwise comparisons were not significant, although the four‐donor versus placebo groups yielded a p value of 0.096. Stratification based on disease severity showed a treatment effect in milder patients ( p = 0.006). Striatal fluorodopa uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination. Fifty‐six percent of transplanted patients developed dyskinesia that persisted after overnight withdrawal of dopaminergic medication (“off”‐medication dyskinesia). Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on these results.Ann Neurol 2003;54:403–414

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Adaptive deep brain stimulation in advanced Parkinson disease

2013-07-12

Simon Little , A Pogosyan , Spencer Neal +7 more

Objective Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof‐of‐principle of this approach … Objective Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof‐of‐principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. Methods We tested BCI‐controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Results Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% ( p = 0.03) and 27% ( p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements ( p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation. Interpretation BCI‐controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Ann Neurol 2013;74:449–457

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Reciprocal Limbic-Cortical Function and Negative Mood: Converging PET Findings in Depression and Normal Sadness

1999-05-01

Helen S. Mayberg , Mario Liotti , Stephen K. Brannan +7 more

Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. … Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state.Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [15O]water and [18F]fluorodeoxyglucose, respectively.With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen--limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions.Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression.

A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease

2006-08-30

Günther Deuschl , Carmen Schade‐Brittinger , Paul Krack +7 more

Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management.In this randomized-pairs trial, we enrolled 156 patients with … Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management.In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III).Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08).In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

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Striatonigrostriatal Pathways in Primates Form an Ascending Spiral from the Shell to the Dorsolateral Striatum

2000-03-15

Suzanne N. Haber , Julie L. Fudge , Nikolaus R. McFarland

Clinical manifestations in diseases affecting the dopamine system include deficits in emotional, cognitive, and motor function. Although the parallel organization of specific corticostriatal pathways is well documented, mechanisms by which … Clinical manifestations in diseases affecting the dopamine system include deficits in emotional, cognitive, and motor function. Although the parallel organization of specific corticostriatal pathways is well documented, mechanisms by which dopamine might integrate information across different cortical/basal ganglia circuits are less well understood. We analyzed a collection of retrograde and anterograde tracing studies to understand how the striatonigrostriatal (SNS) subcircuit directs information flow between ventromedial (limbic), central (associative), and dorsolateral (motor) striatal regions. When viewed as a whole, the ventromedial striatum projects to a wide range of the dopamine cells and receives a relatively small dopamine input. In contrast, the dorsolateral striatum (DLS) receives input from a broad expanse of dopamine cells and has a confined input to the substantia nigra (SN). The central striatum (CS) receives input from and projects to a relatively wide range of the SN. The SNS projection from each striatal region contains three substantia nigra components: a dorsal group of nigrostriatal projecting cells, a central region containing both nigrostriatal projecting cells and its reciprocal striatonigral terminal fields, and a ventral region that receives a specific striatonigral projection but does not contain its reciprocal nigrostriatal projection. Examination of results from multiple tracing experiments simultaneously demonstrates an interface between different striatal regions via the midbrain dopamine cells that forms an ascending spiral between regions. The shell influences the core, the core influences the central striatum, and the central striatum influences the dorsolateral striatum. This anatomical arrangement creates a hierarchy of information flow and provides an anatomical basis for the limbic/cognitive/motor interface via the ventral midbrain.

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Pathological synchronization in Parkinson's disease: networks, models and treatments

2007-05-26

Constance Hammond , Hagai Bergman , Peter Brown

Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease

2008-12-09

Alim Louis Benabid , Stéphan Chabardès , John Mitrofanis +1 more

Responsive cortical stimulation for the treatment of medically intractable partial epilepsy

2011-09-15

Martha J. Morrell

This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy.A total … This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy.A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation.Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function.Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures.This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

Adipsia and Aphagia after 6‐Hydroxydopamine Induced Degeneration of the Nigro‐striatal Dopamine System

1971-12-01

Urban Ungerstedt

Abstract The functional role of the nigro‐striatal dopamine (DA) system has been investigated on the basis of a recent detailed mapping of its path and a new method of lesioning … Abstract The functional role of the nigro‐striatal dopamine (DA) system has been investigated on the basis of a recent detailed mapping of its path and a new method of lesioning the catecholamine systems selectively by intracerebral injection of 6‐hydroxydopamine (6‐OH‐DA). The investigation was especially focused on the symptoms of adipsia, aphagia, hypokinesia and catalepsia after lateral hypothalamic lesions as such lesions may interrupt the ascending DA axons. Electrocoagulations or 6‐OH‐DA lesions were performed bilaterally at several sites along the DA pathway and the behavioural effects were evaluated in relation to the histochemically detected lesion of the DA pathway. It was concluded that bilateral complete degeneration of the nigro‐striatal DA pathway produces severe, long lasting adipsia and aphagia, hypoactivity, difficulties to initiate activity and loss of exploratory behaviour and curiosity. Experiments with DA receptor stimulating and blocking drugs supported the lesion results. Catalepsia and somnolence were attributed to the interruption of other pathways. The results suggest an important role for the nigro‐striatal DA system and the striatum in the control of behaviour. A number of symptoms earlier related to the hypothalamus may in fact be due to disturbance of the nigro‐striatal DA system.

Freezing of gait: moving forward on a mysterious clinical phenomenon

2011-07-25

John G. Nutt , Bastiaan R. Bloem , Nir Giladi +3 more

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Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease<subtitle>A Randomized Controlled Trial</subtitle>

2009-01-06

Frances M. Weaver

Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.To compare 6-month outcomes for … Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy.Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006.Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists.The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events.Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events.clinicaltrials.gov Identifier: NCT00056563.

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The neostriatal mosaic: multiple levels of compartmental organization

1992-04-01

Charles R. Gerfen

Pallidal versus Subthalamic Deep-Brain Stimulation for Parkinson's Disease

2010-06-02

Kenneth A. Follett , Frances M. Weaver , Matthew Stern +7 more

Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared … Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation).At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events.Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months.Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)

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Electrical Stimulation of the Subthalamic Nucleus in Advanced Parkinson's Disease

1998-10-15

Patricia Limousin , Paul Krack , Pierre Pollak +4 more

In many patients with idiopathic Parkinson's disease, treatment with levodopa is complicated by fluctuations between an "off" period (also referred to as "off medication"), when the medication is not working … In many patients with idiopathic Parkinson's disease, treatment with levodopa is complicated by fluctuations between an "off" period (also referred to as "off medication"), when the medication is not working and the motor symptoms of parkinsonism are present, and an "on" period, when the medication is causing improved mobility (also referred to as "on medication"), often accompanied by debilitating dyskinesias. In animal models of Parkinson's disease, there is overactivity in the subthalamic nucleus, and electrical stimulation of the subthalamic nucleus improves parkinsonism. We therefore sought to determine the efficacy and safety of electrical stimulation of the subthalamic nucleus in patients with Parkinson's disease.

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Transplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease

2001-03-08

Curt R. Freed , Paul Greene , Robert E. Breeze +7 more

Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than … Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known.

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Selective Cortical Undercutting As a Means of Modifying and Studying Frontal Lobe Function in Man

1949-01-01

Matthew Volpini , Peter Giacobbe , G. Rees Cosgrove +3 more

There is an urgent need to develop safe and effective treatments for patients with treatment-resistant depression (TRD). Several neurosurgical procedures have been developed to treat the dysfunctional brain circuits implicated … There is an urgent need to develop safe and effective treatments for patients with treatment-resistant depression (TRD). Several neurosurgical procedures have been developed to treat the dysfunctional brain circuits implicated in major depression.This review describes the most common ablative procedures used to treat major depressive disorder: anterior cingulotomy, subcaudate tractotomy, limbic leucotomy, and anterior capsulotomy. The efficacy and safety of each are discussed and compared with other current and emerging modalities, including deep brain stimulation (DBS) and MR-guided focused ultrasound (MRgFUS).The PubMed and MEDLINE electronic databases were used in this study, through July 2016. Keywords, including "treatment resistant depression," and "ablative neurosurgery," etc. were used to generate reference hits.Approximately a third to half of patients who underwent ablative procedures achieved a treatment response and/or remission. The efficacy and safety profiles corresponding to both ablative procedures and DBS were very similar.The longitudinal experience with ablative procedures shows that there remains an important role for accurate, discrete lesions in disrupting affective circuitry in the treatment of TRD. New modalities, such as MRgFUS, have the potential to further improve the accuracy of ablative procedures, while enhancing safety by obviating the need for open brain surgery.

Electroencephalography and clinical neurophysiology

1994-11-01

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Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society

2017-11-30

Kailash P. Bhatia , Peter G. Bain , Nin Bajaj +7 more

Consensus criteria for classifying tremor disorders were published by the International Parkinson and Movement Disorder Society in 1998. Subsequent advances with regard to essential tremor, tremor associated with dystonia, and … Consensus criteria for classifying tremor disorders were published by the International Parkinson and Movement Disorder Society in 1998. Subsequent advances with regard to essential tremor, tremor associated with dystonia, and other monosymptomatic and indeterminate tremors make a significant revision necessary.Convene an international panel of experienced investigators to review the definition and classification of tremor.Computerized MEDLINE searches in January 2013 and 2015 were conducted using a combination of text words and MeSH terms: "tremor", "tremor disorders", "essential tremor", "dystonic tremor", and "classification" limited to human studies. Agreement was obtained using consensus development methodology during four in-person meetings, two teleconferences, and numerous manuscript reviews.Tremor is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: Axis 1-clinical characteristics, including historical features (age at onset, family history, and temporal evolution), tremor characteristics (body distribution, activation condition), associated signs (systemic, neurological), and laboratory tests (electrophysiology, imaging); and Axis 2-etiology (acquired, genetic, or idiopathic). Tremor syndromes, consisting of either isolated tremor or tremor combined with other clinical features, are defined within Axis 1. This classification scheme retains the currently accepted tremor syndromes, including essential tremor, and provides a framework for defining new syndromes.This approach should be particularly useful in elucidating isolated tremor syndromes and syndromes consisting of tremor and other signs of uncertain significance. Consistently defined Axis 1 syndromes are needed to facilitate the elucidation of specific etiologies in Axis 2. © 2017 International Parkinson and Movement Disorder Society.

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Deep Brain Stimulation for Treatment-Resistant Depression

2005-03-01

Helen S. Mayberg , Andrés M. Lozano , Valerie Voon +5 more

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Deep-Brain Stimulation of the Subthalamic Nucleus or the Pars Interna of the Globus Pallidus in Parkinson's Disease

2001-09-27

José Á. Obeso , C. Warren Olanow , María Rodríguez‐Oroz +3 more

Increased neuronal activity in the subthalamic nucleus and the pars interna of the globus pallidus is thought to account for motor dysfunction in patients with Parkinson's disease. Although creating lesions … Increased neuronal activity in the subthalamic nucleus and the pars interna of the globus pallidus is thought to account for motor dysfunction in patients with Parkinson's disease. Although creating lesions in these structures improves motor function in monkeys with induced parkinsonism and patients with Parkinson's disease, such lesions are associated with neurologic deficits, particularly when they are created bilaterally. Deep-brain stimulation simulates the effects of a lesion without destroying brain tissue.We performed a prospective, double-blind, crossover study in patients with advanced Parkinson's disease, in whom electrodes were implanted in the subthalamic nucleus or pars interna of the globus pallidus and who then underwent bilateral high-frequency deep-brain stimulation. We compared scores on the motor portion of the Unified Parkinson's Disease Rating Scale when the stimulation was randomly assigned to be turned on or off. We performed unblinded evaluations of motor function preoperatively and one, three, and six months postoperatively.Electrodes were implanted bilaterally in 96 patients in the subthalamic-nucleus group and 38 patients in the globus-pallidus group. Three months after the procedures were performed, double-blind, crossover evaluations demonstrated that stimulation of the subthalamic nucleus was associated with a median improvement in the motor score (as compared with no stimulation) of 49 percent, and stimulation of the pars interna of the globus pallidus with a median improvement of 37 percent (P<0.001 for both comparisons). Between the preoperative and six-month visits, the percentage of time during the day that patients had good mobility without involuntary movements increased from 27 percent to 74 percent (P<0.001) with subthalamic stimulation and from 28 percent to 64 percent (P<0.001) with pallidal stimulation. Adverse events included intracranial hemorrhage in seven patients and infection necessitating removal of the leads in two.Bilateral stimulation of the subthalamic nucleus or pars interna of the globus pallidus is associated with significant improvement in motor function in patients with Parkinson's disease whose condition cannot be further improved with medical therapy.

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Chapter 6 Basal ganglia-thalamocortical circuits: Parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions

1991-01-01

Garrett E. Alexander , Michael D. Crutcher , Mahlon R. DeLong

Basal ganglia contribute to a wide variety of behavioral functions, including skeletomotor, oculomotor, cognitive, and limbic processes. This chapter focuses on the basal ganglia-thalamocortical circuits. Basal ganglia-thalamocortical circuits are organized … Basal ganglia contribute to a wide variety of behavioral functions, including skeletomotor, oculomotor, cognitive, and limbic processes. This chapter focuses on the basal ganglia-thalamocortical circuits. Basal ganglia-thalamocortical circuits are organized in a parallel manner and remain largely segregated from one another, both structurally and functionally. The central theme of the segregated circuits hypothesis is that structural convergence and functional integration occurs within each of the identified circuits. In primates, the basal ganglia motor pathways are focused principally on the putamen and its connections. This part of the neostriatum receives topographic projections from primary motor cortex (MC). The focus of the terminals originating in the putamen appears to lie somewhat dorsal to that of the terminals arising from the body of the caudate. The basal ganglia-thalamocortical circuits might be seen as having a unified role in modulating the operations of the entire frontal lobe, and thereby influencing—by common mechanisms, such as diverse frontal lobe processes—the maintenance and switching of behavioral sets and the planning and execution of limb and eye movements.

A Case of Vertical Diplopia after Thalamic Deep Brain Stimulation for Essential Tremor

2025-06-25

Rena Far , Suresh Subramaniam , Camila C. Aquino +1 more | Movement Disorders Clinical Practice

Delta—fast ripple coupling suppression: designing a brain-mimetic stimulation paradigm for seizure abolishment

2025-06-24

Uilki Tufa , Joshua Dian , Anya Zahra +4 more | Frontiers in Neuroscience

Deep brain stimulation can be an effective alternative treatment for patients that are intractable to antiseizure medication and do not meet surgical inclusion criteria. Clinical trials have demonstrated the safety … Deep brain stimulation can be an effective alternative treatment for patients that are intractable to antiseizure medication and do not meet surgical inclusion criteria. Clinical trials have demonstrated the safety of thalamic stimulation using a high frequency stimulus but with limited efficacy. Our group has previously shown, in silico, the success of stimulation with a brain-mimetic therapeutic poly-rhythmic signal, outperforming mono-rhythmic waveforms. In this study we extend our findings to an in vivo model and investigate a thalamic continuous stimulation paradigm using a brain-mimetic signal, where the amplitude of a high frequency rhythm is modulated by the phase of a low frequency rhythm forming a phase-amplitude coupled (PAC) waveform, to suppress seizure-like events (SLEs) in a hippocampal-kindled mouse model. We aim to show that application of our proposed “Dithered Effective Phase-Amplitude Coupled Electrical Rhythmic Stimulation (DEPACERS)” is more effective in seizure control than mono-rhythmic stimulation. Bipolar electrodes were implanted in the CA3 of the hippocampus and in the contralateral medial dorsal nucleus of the thalamus, allowing for stimulation and iEEG recordings. Video analysis was used for assessment of animal motor behavior. Mice were kindled daily through unilateral CA3 stimulations reaching evoked convulsive SLEs, then spontaneous recurrent seizures. To test suppression in fully kindled mice, thalamic stimulation using a PAC waveform was applied continuously for 15 min, followed by hippocampal stimulation to evoke an SLE. We found a 1 Hz–100 Hz phase-amplitude PAC waveform to be effective in suppressing SLEs (confirmed by iEEG and video analysis) and increasing kindling threshold. Low frequency and interictal spike suppression following interictal stimulus administration was found as a marker to assess the effective stimulus parameters. DEPACERS outperformed mono-rhythmic stimuli in evoked SLEs. These findings are important in the development of novel brain stimulation strategies for epileptic patients.

Diagnosis of Multiple System Atrophy-Parkinsonian Type [MSA-P] from Atypical Parkinsonism with Dual Tracer (FDG + DOPA) PET/MRI Brain

2025-06-24

Ramesh Krishnan , Pushpendra Nath Renjen , Amarnath Jena +1 more | Apollo Medicine

Objective: This case report demonstrates the potential of dual tracer imaging (fluorodeoxyglucose + dihydroxyphenylalanine (FDG + DOPA)) positron emission tomography/magnetic resonance imaging (PET/MRI) brain in diagnosing and distinguishing the patients … Objective: This case report demonstrates the potential of dual tracer imaging (fluorodeoxyglucose + dihydroxyphenylalanine (FDG + DOPA)) positron emission tomography/magnetic resonance imaging (PET/MRI) brain in diagnosing and distinguishing the patients with multiple system atrophy-Parkinsonian type (MSA-P) from atypical Parkinsonism. Methods: A 65-year-old male presented with postural instability, urinary symptom in form of urgency, hesitancy, precipitancy followed by incontinence, slowness of all activity of daily living (ADL) with stiffness of all limbs, slurred speech and difficulty in swallowing for four years. It was clinically suspected as atypical Parkinson’s disease. The DOPA PET/MRI revealed asymmetric reduced patchy uptake in bilateral striatum qualitatively and quantitatively more prominently in bilateral putamen (right> left—maximum standardised uptake value (SUVmax): putamen left 2.18; right 1.91; caudate nucleus left 2.71; right 2.62). Bilateral putamen is atrophic with heterogeneous signal changes. Midbrain Pons ratio measures 0.6 (reported threshold of 0.52). Results: All of these features when put together help us to point it towards the MSA-P which was further confirmed by 18F-FDG study which showed regional FDG hypometabolism in bilateral putamen with relative sparing bilateral caudate, palladium and thalamus. Conclusion: Dual tracer PET/MRI will be the key to reliable uses in the diagnosis of clinically suspected neurodegenerative disorder and accurate prediction of therapeutic intervention.

Resting-state Alpha Reactivity Is Reduced in Parkinson’s Disease and Associated With Gait Variability

2025-06-24

Ellen Lirani‐Silva , Layla Cupertino Salloum e Silva , Diego Orcioli‐Silva +4 more | Neurorehabilitation and neural repair

BackgroundThe extent to which the cholinergic system contributes to gait impairments in Parkinson's disease (PD) remains unclear. Electroencephalography (EEG) alpha reactivity, which refers to change in alpha power over occipital … BackgroundThe extent to which the cholinergic system contributes to gait impairments in Parkinson's disease (PD) remains unclear. Electroencephalography (EEG) alpha reactivity, which refers to change in alpha power over occipital electrodes upon opening the eyes, has been suggested as a marker of cholinergic function. We compared alpha reactivity between people with PD and healthy individuals and explored its potential association with gait measures.MethodsEyes-closed and eyes-open resting-state EEG data were recorded from 20 people with idiopathic PD and 19 healthy individuals with a 64-channel EEG system. Alpha reactivity was calculated as the relative change in alpha power (8-13 Hz) over occipital electrodes from eyes-closed to eyes-open. Gait spatiotemporal measures were obtained with an electronic walkway.ResultsAlpha reactivity was reduced in people with PD compared to healthy individuals (U = 105, P = .017); the rank-biserial correlation of .447 indicated a moderate effect size. When controlling for global cognition (Mini Mental State Examination), the group difference in alpha reactivity was no longer significant. Alpha reactivity associated with measures of gait variability only (ρ = -.437 to -.532).ConclusionsResting-state alpha reactivity is reduced in PD, suggesting impaired cholinergic function. Reduced alpha reactivity was associated with greater gait variability, indicating a role of the cholinergic system in the mechanisms underlying gait variability. Therefore, the cholinergic system may represent a target for treatments aiming to reduce gait variability and alpha reactivity should be further explored as an endpoint for clinical trials.

Sequential Brain Shift Patterns During Staged Bilateral Deep Brain Stimulation Surgery for Parkinson's Disease

2025-06-24

Junhyung Kim , Sungyang Jo , Sun Ju Chung +2 more | Operative Neurosurgery

Brain shift is a major contributor to targeting errors in stereotactic procedures. This study investigates sequential brain shift patterns during deep brain stimulation (DBS) surgery and discusses the clinical implications … Brain shift is a major contributor to targeting errors in stereotactic procedures. This study investigates sequential brain shift patterns during deep brain stimulation (DBS) surgery and discusses the clinical implications of using a staged bilateral targeting strategy in Parkinson's disease. Quantitative image analysis was conducted for 210 DBS procedures in 105 patients with Parkinson's disease undergoing staged bilateral operations. Brain shift was quantified by coordinate displacements of subcortical structures, including the globus pallidus internus (GPi) and subthalamic nucleus (STN), across 4 MRI sessions during the 2 staged DBS procedures. Brain shift was evaluated in 3 configurations: pre-first vs post-first DBS MRIs (ⅰ), pre-first vs post-second DBS MRIs (ⅱ), and pre-second vs post-second DBS MRIs (ⅲ). Brain shift was predominant in posterior, inferior, and medial directions, with greater magnitude in the GPi than in the STN. After the first DBS procedure (ⅰ), clinically relevant brain shift (displacement >3 mm) was observed in 6.8% of the GPi, while none was noted in the STN. After the second DBS procedure (ⅱ), brain shift was observed in up to 20.3% of the GPi and 4.1% of the STN on the second targeted side. However, when evaluated relative to the rescanned MRI (ⅲ), brain shifts within the second DBS procedure were reduced to 4.1% for the GPi and none for the STN, supporting the importance of precise target adjustment via a staged bilateral strategy. The extent of pneumocephalus showed the strongest correlation with the posterior displacement of the GPi, and low intraoperative mean arterial pressure appeared to be significantly associated with an increased risk of brain shift in this cohort. These findings suggest that brain shift should be an important consideration in bilateral DBS surgery, and staged operations may provide particular advantages when targeting the GPi.

A Systematic Approach to Evaluating and Addressing Disparities in Deep Brain Stimulation

2025-06-24

Anthony E. Bishay , Natasha Hughes , Sarah K. Bick | Movement Disorders Clinical Practice

Lesioning the Subthalamic Nucleus Using Magnetic Resonance Imaging‐Guided Focused Ultrasound in Parkinson's Disease: Subthalamotomy Effectively Describes the Procedure

2025-06-23

Steffen Paschen , Elena Natera‐Villalba , Rafael Rodríguez‐Rojas +7 more | Movement Disorders

Lesion of the Subthalamic Nucleus Should Not be Labeled “Subthalamotomy”; A Plea for Anatomical Accuracy and Compliance with Historical Legacy

2025-06-23

Marwan Hariz , Jean Régis , Ludvic Zrinzo +3 more | Movement Disorders

Personalizing Responsive Neurostimulation for Epilepsy

2025-06-23

Vikram R. Rao | Journal of Clinical Neurophysiology

Over the past 20 years, responsive neurostimulation (RNS), a closed-loop device for treating certain forms of drug-resistant focal epilepsy, has become ensconced in the epileptologist's therapeutic armamentarium. Through neuromodulatory effects, … Over the past 20 years, responsive neurostimulation (RNS), a closed-loop device for treating certain forms of drug-resistant focal epilepsy, has become ensconced in the epileptologist's therapeutic armamentarium. Through neuromodulatory effects, RNS therapy gradually reduces seizures over years, providing diagnostically valuable intracranial recordings along the way. However, the neuromodulatory potential of RNS therapy has not been fully harnessed. Seizure reduction is often slow, outcomes vary across individuals and defy prognostication, seizure freedom is uncommon, and many patients do not derive significant benefit. These limitations may stem from the "black box" nature of RNS therapy. The antiseizure mechanism(s) of RNS remain poorly understood, and, in the absence of first principles to inform selection of the candidates most likely to benefit, the ideal brain regions to target, and the most effective stimulation parameters, contemporary use of RNS therapy is largely empiric. Fortunately, recent advances in neuroimaging, neurophysiology, artificial intelligence, and engineering have made the goal of rational, personalized neurostimulation a near-term reality. Here, we review recent progress toward this goal, focusing on novel approaches to patient selection, brain network topology, state-dependent effects, and stimulation parameter optimization. By considering the who, where, when, and how of RNS, we highlight emerging paradigm shifts that will help usher in a new age of RNS therapy that is more personalized and more effective.

Tremor Asymmetry and the Development of Bilateral Phase‐Specific Deep Brain Stimulation for Postural Tremor

2025-06-23

Shenghong He , Alceste Deli , Timothy O. West +7 more | Movement Disorders

Abstract Background Tremor phase‐locked deep brain stimulation (DBS) has been shown to modulate symptom severity in postural tremor, including essential and dystonic tremor, with less energy than existing systems. Previous … Abstract Background Tremor phase‐locked deep brain stimulation (DBS) has been shown to modulate symptom severity in postural tremor, including essential and dystonic tremor, with less energy than existing systems. Previous studies focused on unilateral stimulation; it remains unknown how tremor asymmetry interacts with stimulation in the context of bilateral phase‐locked DBS. Methods Archival limb acceleration from nine essential tremor patients was analyzed for asymmetries in tremor amplitude, frequency, and instability, and their relationship with continuous high‐frequency DBS (cDBS). Bilateral phase‐locked DBS was tested in one essential tremor and one dystonic tremor patient. Results Postural tremor is asymmetric, with larger tremor power linked to smaller amplitude and frequency stability in one hand. These asymmetries were significantly reduced during cDBS, with greater effects on larger amplitude tremors. Bilateral phasic DBS effects were also asymmetric. Conclusions This study enhances understanding of tremor asymmetry and its relationship with DBS, offering insights for patient‐specific tremor treatments. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Identification and Challenges of Dopamine Dysregulation Syndrome: A Case Report

2025-06-22

Asna Sulaiman , Idris Leppla | Cureus

A novel heterozygous variant of FUS gene associated with juvenile ALS and premature tremor onset: a case report

2025-06-22

Verónica Rodríguez-García , José Antonio Venta-Sobero , María del Carmen Chima-Galán | Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

Juvenile amyotrophic lateral sclerosis (JALS) is neurodegenerative disease of the upper and lower motor neurons of rare incidence. Although fused in sarcoma (FUS) mutations in JALS patients have been associated … Juvenile amyotrophic lateral sclerosis (JALS) is neurodegenerative disease of the upper and lower motor neurons of rare incidence. Although fused in sarcoma (FUS) mutations in JALS patients have been associated with movement disorders, here we described the case of a young girl with very early onset of tremor, years before commencement of weakness; once symptoms of JALS were stablished, a typical rapid disease progression from spinal to bulbar symptoms were noticed. Genetic testing revealed a novel mutation in FUS gene causative of a protein dysfunction. This case emphasizes the fact that some mutations within the FUS in JALS patients may produce a symptom onset with tremor.

Pediatric Genetic Dystonias: Current Diagnostic Approaches and Treatment Options

2025-06-20

Graziana Ceraolo , Giulia Spoto , Carla Consoli +3 more | Life

Genetic dystonias are a heterogeneous group of movement disorders characterized by involuntary, sustained muscle contractions that cause repetitive movements and abnormal postures. Often beginning in childhood, they can significantly affect … Genetic dystonias are a heterogeneous group of movement disorders characterized by involuntary, sustained muscle contractions that cause repetitive movements and abnormal postures. Often beginning in childhood, they can significantly affect quality of life. Although individually rare, genetic causes are collectively relevant in pediatric dystonias, with over 250 associated genes. Among these, TOR1A, SGCE, and KMT2B are the most frequently reported in pediatric forms. Diagnosis is challenging due to the wide clinical and genetic variability. Recent advances in genetic testing, including whole-exome and whole-genome sequencing, have improved the early identification of causative variants. Functional data on selected mutations are helping to refine genotype–phenotype correlations. Management typically requires a multidisciplinary approach. Symptomatic treatments include anticholinergics, benzodiazepines, and botulinum toxin, while deep brain stimulation can be effective in refractory cases, especially in patients with TOR1A variants. Disease-modifying therapies are also emerging, such as gene therapy for AADC deficiency, highlighting the potential of precision medicine. This review provides an updated overview of pediatric genetic dystonias, with a focus on differential diagnosis and treatment strategies. Early and accurate diagnosis, together with personalized care, is key to improving outcomes in affected children.

14th Panhellenic Conference on Alzheimer’s Disease and the 6th Mediterranean Conference on Neurodegenerative Diseases, 13 February–16 February, Thessaloniki, Greece

2025-06-20

Magda Tsolaki | NeuroSci

At the 14th Panhellenic Conference on Alzheimer’s Disease and 6th Mediterranean Conference on neurodegenerative diseases, we experienced an exciting journey, following the patient through the stages of their neurodegenerative disease: … At the 14th Panhellenic Conference on Alzheimer’s Disease and 6th Mediterranean Conference on neurodegenerative diseases, we experienced an exciting journey, following the patient through the stages of their neurodegenerative disease: onset, diagnosis, progression, and eventual outcome. Fighting alongside him are researchers, doctors, psychologists, biologists, chemists, pharmacists, nurses, trainers, physiotherapists, speech therapists, occupational therapists, electrical engineers, architects, and other scientists, even actors and musicians, who aim to prevent and cure the disease, limit its progression, and improve the quality of life of those affected by it. Among them, their caregivers stand out as the most dedicated companions. In a collection of abstracts that reflects the work of all of the above, we capture the results of our biennial scientific meeting, which, thanks to them, is constantly evolving in a promising way.

Quantum-classical deep learning hybrid architecture with graphene-printed low-cost capacitive sensor for essential tremor detection

2025-06-20

Javier Villalba-Díez , Ana González‐Marcos | Scientific Reports

Abstract This study presents a novel hardware and software architecture combining capacitive sensors, quantum-inspired algorithms, and deep learning applied to the detection of Essential Tremor. At the core of this … Abstract This study presents a novel hardware and software architecture combining capacitive sensors, quantum-inspired algorithms, and deep learning applied to the detection of Essential Tremor. At the core of this architecture are graphene-printed capacitive sensors, which provide a cost-effective and efficient solution for tremor data acquisition. These sensors, known for their flexibility and precision, are specifically calibrated to monitor tremor movements across various fingers. A distinctive feature of this study is the incorporation of quantum-inspired computational filters—namely, Quantvolution and QuantClass —into the deep learning framework. This integration offers improved processing capabilities, facilitating a more nuanced analysis of tremor patterns. Initial findings indicate greater stability in loss variability; however, further research is necessary to confirm these effects across broader datasets and clinical environments. The approach highlights a promising application of quantum-inspired methods within healthcare diagnostics.

Responsive Neurostimulation of Thalamic and Nonthalamic Targets in Pediatric and Young Adult Patients With Intractable Epilepsy

2025-06-20

Thomas Larrew , Hansel M. Greiner , Ravindra Arya +7 more | Neurosurgery

BACKGROUND AND OBJECTIVES: Epilepsy is a significant cause of morbidity and has negative effects on cognitive and psychosocial development in pediatric and young adult patients. For pediatric patients who have … BACKGROUND AND OBJECTIVES: Epilepsy is a significant cause of morbidity and has negative effects on cognitive and psychosocial development in pediatric and young adult patients. For pediatric patients who have epileptogenic foci that are poorly localized, deep, bilateral, or in eloquent regions and are not candidates for resection, responsive neurostimulation (RNS) may be an option. The study objective was to demonstrate safety and seizure outcomes from RNS in pediatric and young adults with intractable epilepsy with a specific focus on differences between thalamic and nonthalamic RNS lead implantation. METHODS: The authors describe a single institution's experience with RNS in patients with drug-resistant epilepsy who were not candidates for seizure focus resection. An Institutional Review Board–approved retrospective review was conducted of all pediatric and young adult patients who underwent RNS implantation at Cincinnati Children's Hospital Medical Center between 2019 and 2023. RESULTS: In total, 24 patients met the inclusion criteria for the study. Seven had thalamic targets whereas 17 had nonthalamic targets. The mean patient age at the time of surgery was 13.8 years (range 5-30), with a mean follow-up of 13 months. Thirteen patients (54%) had prior surgery for seizure control. The median global seizure percentage reduction was 68% in the nonthalamic group and 80% in the thalamic group, a nonsignificant difference, resulting in a reduction of 74% for all study patients ( P = .816). Two adverse events (8.3%) included a wound infection and a lead repositioning. CONCLUSION: RNS implantation in pediatric and young adult patients with epilepsy seems to be a safe and efficacious modality for lowering seizure burden in cases where resection of epileptogenic foci is not a viable option. Thalamic and nonthalamic RNS targeting both lead to impactful seizure reduction. This study adds to the growing body of evidence suggesting that RNS is appropriate in pediatric and young adult patients.

Deep Brain Stimulation for <scp>VPS16</scp>‐Related Dystonia: A Multicenter Study

2025-06-20

Tatiana Svoreňová , Luigi Romito , Ahmet Kaymak +7 more | Annals of Neurology

Objective The objective was to evaluate the effects of deep brain stimulation (DBS) in an international cohort of patients with VPS16 ‐related dystonia. Methods This observational study collected preoperative and … Objective The objective was to evaluate the effects of deep brain stimulation (DBS) in an international cohort of patients with VPS16 ‐related dystonia. Methods This observational study collected preoperative and postoperative demographic, clinical, stimulation, genetic, neuroimaging, and neurophysiological data of medically refractory DYT‐ VPS16 patients with implanted DBS in 10 international centers. Motor symptoms and disability outcomes were assessed using the Burke‐Fahn‐Marsden Dystonia Rating Scale Motor (BFMDRS‐M) and Disability (BFMDRS‐D) scales. A cut‐off threshold for considering response to DBS was set at 25% of BFMDRS‐M improvement at the last follow‐up (FU) compared to baseline. Results The cohort consisted of 26 participants (17 men, 65.4%). Age at dystonia onset and surgery was 17.8 ± 10.9 and 35.3 ± 14.8 years, respectively. At the last FU, 102.5 ± 57.3 months (range, 2–216), the mean BFMDRS‐M improvement was 41.6 ± 37.3% (26/26 patients) and 34.8 ± 42.6% for the BFMDRS‐D (23/26 patients). Most patients (19/26, 73%) were considered responders. Higher motor improvement was associated with stimulation of the ventroposterior portion of the internal globus pallidus. A significant inverse relationship was observed between improvement in BFMDRS‐M at last FU, and the presence of spasticity ( p = 0.027) and fixed skeletal deformities ( p = 0.001) before surgery. Non‐responders had a younger age at disease onset and at implantation, shorter disease duration at DBS surgery, and higher baseline BFMDRS scores. Interpretation DBS was an effective treatment for three‐quarters of patients with pathogenic VPS16 variants in our cohort. Mean motor improvement was most pronounced at the 1‐year FU, but persisted at the last FU despite disease progression. ANN NEUROL 2025

Genetic Profile and Symptom Pattern Explain Variability of Deep Brain Stimulation Effect in Dystonia

2025-06-20

Mahboubeh Ahmadipour , Luigi Romito , Antonio Emanuele Elia +4 more | Annals of Clinical and Translational Neurology

ABSTRACT Objective Bilateral globus pallidus pars interna deep brain stimulation (GPi‐DBS) is a recognized and effective treatment option for drug‐resistant dystonia patients. However, the clinical GPi‐DBS outcomes vary significantly. Herein, … ABSTRACT Objective Bilateral globus pallidus pars interna deep brain stimulation (GPi‐DBS) is a recognized and effective treatment option for drug‐resistant dystonia patients. However, the clinical GPi‐DBS outcomes vary significantly. Herein, we explored the pre‐implant factors affecting GPi‐DBS effectiveness. Methods Genetic profiles, symptom distribution, age at onset, disease duration, and severity of a cohort of 31 GPi‐DBS dystonia patients were collected. Dystonia motor severity was evaluated before and after GPi‐DBS using the Burke–Fahn–Marsden Dystonia‐Rating‐Scale (BFMDRS‐M). We assessed the interplay of the aforementioned factors in determining the BFMDRS‐M improvement through a multilinear regression analysis. Results BFMDRS‐M score showed a significant improvement (47.8%) since the first year, remaining stable at 5 years (54.3%). Lower limb (0.20), upper limb (0.16) and trunk (0.24) symptoms showed a significantly larger improvement compared to cranial symptoms (0.07, p < 0.05). Consequently, patients with more pronounced lower limb motor symptoms displayed a greater GPi‐DBS effect ( p < 0.01). However, pre‐treatment localization of motor symptoms accounted only for 31% of the Inter‐Patient Variability (IPV) in post‐GPi‐DBS improvement. Amelioration varied also across genetic profiles, with the largest improvement reported for DYT‐TOR1A patients ( n = 9, 64.2% in the first year), predicting 36% of IPV. Interestingly, combining motor and genetic profiles predicted 73% of the IPV. Including the clinical profile of the patient (age at onset, disease severity and duration) increased prediction accuracy to 81%. Interpretation Our results suggest that motor and genetic profiles contribute independently to the efficacy of the GPi‐DBS treatment. These results may support a personalized prediction of DBS outcomes in dystonia patients.

Deep Brain Stimulation for Status Dyskineticus in <scp>ADCY5</scp>‐Related Dyskinesia in a 60‐Year‐Old Woman

2025-06-20

Ana Moreno‐Estébanez , Marta Ruíz-López , Beatriz Tijero +7 more | Movement Disorders Clinical Practice

Modeling characteristics of neuronal firing in the thalamocortical network of connections in control and parkinsonian primates

2025-06-20

Cynthia Ferrell , Jiang Qian , Margaret Olivia Leu +2 more | Journal of Computational Neuroscience

According to current anatomical models, motor cortical areas, the basal ganglia, and the ventral motor thalamus form partially closed (re-entrant) loop structures. The normal patterning of neuronal activity within this … According to current anatomical models, motor cortical areas, the basal ganglia, and the ventral motor thalamus form partially closed (re-entrant) loop structures. The normal patterning of neuronal activity within this network regulates aspects of movement planning and execution, while abnormal firing patterns can contribute to movement impairments, such as those seen in Parkinson's disease. Most previous research on such firing pattern abnormalities has focused on parkinsonism-associated changes in the basal ganglia, demonstrating, among other abnormalities, prominent changes in firing rates, as well as the emergence of synchronized beta-band oscillatory burst patterns. In contrast, abnormalities of neuronal activity in the thalamus and cortex are less explored. However, recent studies have shown both changes in thalamocortical connectivity and anatomical changes in corticothalamic terminals in Parkinson's disease. To explore these changes, we created a computational framework to model the effects of changes in thalamocortical connections as they may occur when an individual transitions from the healthy to the parkinsonian state. A 5-dimensional average neuronal firing rate model was fitted to replicate neuronal firing rate information recorded in healthy and parkinsonian primates. The study focused on the effects of (1) changes in synaptic weights of the reciprocal projections between cortical neurons and thalamic principal neurons, and (2) changes in synaptic weights of the cortical projection to thalamic interneurons. We found that it is possible to force the system to change from a healthy to a parkinsonian state, including the emergent oscillatory activity, by only adjusting these two sets of synaptic weights. Thus, this study demonstrates that small changes in the afferent and efferent connections of thalamic neurons could contribute to the emergence of network-wide firing patterns that are characteristic for the parkinsonian state.

Deep brain stimulation for the treatment of Alzheimer’s disease: A safer and more effective strategy

2025-06-19

Fan Zhang , Yao Meng , Wei Zhang | Neural Regeneration Research

Abstract Alzheimer’s disease is the most common type of cognitive disorder, and there is an urgent need to develop more effective, targeted and safer therapies for patients with this condition. … Abstract Alzheimer’s disease is the most common type of cognitive disorder, and there is an urgent need to develop more effective, targeted and safer therapies for patients with this condition. Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation. As an emerging therapeutic approach, deep brain stimulation shows significant promise as a potential new therapy for Alzheimer’s disease. Here, we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer’s disease based on existing clinical and basic research. In clinical studies, the most commonly targeted sites include the fornix, the nucleus basalis of Meynert, and the ventral capsule/ventral striatum. Basic research has found that the most frequently targeted areas include the fornix, nucleus basalis of Meynert, hippocampus, entorhinal cortex, and rostral intralaminar thalamic nucleus. All of these individual targets exhibit therapeutic potential for patients with Alzheimer’s disease and associated mechanisms of action have been investigated. Deep brain stimulation may exert therapeutic effects on Alzheimer’s disease through various mechanisms, including reducing the deposition of amyloid-β, activation of the cholinergic system, increasing the levels of neurotrophic factors, enhancing synaptic activity and plasticity, promoting neurogenesis, and improving glucose metabolism. Currently, clinical trials investigating deep brain stimulation for Alzheimer’s disease remain insufficient. In the future, it is essential to focus on translating preclinical mechanisms into clinical trials. Furthermore, consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer’s disease, including cognitive function, neuropsychiatric symptoms, quality of life and changes in Alzheimer’s disease biomarkers. Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows, such as the prodromal and even the preclinical stages of Alzheimer’s disease. Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer’s disease.

A Case Report of Essential Tremor Aggravated After Lumbar Surgery, Improved by Combined Korean Medical Treatment

2025-06-19

Moon-young Ki , Seon-uk Jeon , Eun-je Seol +4 more | The Journal of Internal Korean Medicine

Essential tremor (ET) is a common movement disorder that typically presents as a kinetic or postural tremor. Although anxiety, stress, and fatigue are known aggravating factors, postoperative exacerbation of tremors … Essential tremor (ET) is a common movement disorder that typically presents as a kinetic or postural tremor. Although anxiety, stress, and fatigue are known aggravating factors, postoperative exacerbation of tremors has rarely been reported. We present the case of an 80-year-old woman with ET whose bilateral arm and jaw tremors worsened after lumbar surgery. She received Korean medical treatment, including Boikyangwi-tang, deer antler, acupuncture, and electroacupuncture. After 40 days, the modified Fahn-Tolosa-Marin Tremor Rating Scale regional tremor score improved from 17 to 9, the task performance score from 48 to 32, and the Modified Barthel Index related to upper limb function score from 8 to 16. Subjective tremor severity was notably reduced, especially in the jaw. This case suggests that Korean medicine, including the herbal prescription Boikyangwi-tang, deer antler, and acupuncture, may be beneficial for managing essential tremors aggravated after surgery.

Psychopathological Disorders at the Onset of Juvenile Parkinsonism in Childhood

2025-06-19

A. V. Goryunova , Yu. S. Shevchenko , L Yu Danilova +4 more | Neuroscience and Behavioral Physiology

The future of Parkinson’s care: a need to expand access

2025-06-19

Sana Aslam , Anjail Sharrief , Samantha K. Holden +4 more | Frontiers in Neurology

Parkinson’s disease (PD) affects over one million Americans, with prevalence expected to double by 2040, creating rising challenges for healthcare systems. While neurologist-led care, particularly by movement disorder specialists (MDS), … Parkinson’s disease (PD) affects over one million Americans, with prevalence expected to double by 2040, creating rising challenges for healthcare systems. While neurologist-led care, particularly by movement disorder specialists (MDS), is associated with improved patient outcomes, only a small fraction of PD patients access this level of expertise. Many, various, barriers lead to delays or missed opportunities for advanced treatments such as deep brain stimulation and infusion therapies. This Perspective article issues a call to action for improving referral pathways and care coordination in PD, addressing both clinical and systems-level gaps. We propose several pragmatic strategies, including the development of standardized referral criteria supported by clinical decision tools, expanded use of telemedicine and eConsult platforms, and enhanced provider and patient education to promote timely and appropriate access to specialty care. As early diagnostic technologies become more available, the need for structured referral pathways will become even more critical.

Neurochemical Mechanisms of Tremor in Parkinson’s Disease

2025-06-19

I.A. Putyatin , Nataliya Titova | Neuroscience and Behavioral Physiology

Structural connectivity of the basal ganglia from patient-individual tractography is key for understanding the effects of deep brain stimulation in Parkinson’s Disease

2025-06-18

Ricardo Loução , Martin Köcher , Gregor A. Brandt +7 more | Stereotactic and Functional Neurosurgery

Background: In Parkinson's disease (PD) patients, modulation of the fibre tracts of the cortico-basal ganglia-thalamo-cortical loop is the presumed mechanism of action of deep brain stimulation (DBS) of the subthalamic … Background: In Parkinson's disease (PD) patients, modulation of the fibre tracts of the cortico-basal ganglia-thalamo-cortical loop is the presumed mechanism of action of deep brain stimulation (DBS) of the subthalamic nucleus (STN). Therefore, we explored patient-individual cortical structural connectivity of the volume of tissue activated (VTA), as well as DBS-induced modulation of fibre tracts connecting the STN with cortical and subcortical nodes, and their correlation with therapeutic effects. Patients and Methods: A retrospective cohort of n = 69 PD patients treated with bilateral DBS of the STN was analysed. Clinical response was assessed from the DBS-induced change in the UPDRS-III motor scores (total and symptom-specific sub-scores) under regular medication after a median follow-up of 9.0 (range 2.6 – 20.2) months. Tractography based on patient-individual diffusion-weighted MRI was employed in two ways. Whole brain tractography was used to identify the cortical connections of fibres passing the VTAs, and reconstruction of specific white matter pathways of the motor loop connecting the STN with the basal ganglia and cortex were used to identify the proportion of fibres within these pathways which was modulated by STN-DBS. This proportion of pathway modulation was used in a correlative analysis with clinical outcomes. Results: Fibres traversing the VTAs were primarily connected to the supplementary motor area (SMA) and to a lesser degree to the premotor cortex. Within the pathways connecting the STN with the cortical and subcortical nodes, on average 30-40% (range 10-80%) of the fibres were modulated by STN-DBS. This proportion correlated significantly with the percentage change in UPDRS motor score for fibres connecting the STN with the SMA (ρ=0.28), pre-SMA (ρ=0.26), ventral and dorsal pre-motor cortices (ρ=0.26 and ρ=0.29, respectively), and the globus pallidus externus (GPe, ρ=0.26) and internus (GPi, ρ=0.29). Also, good clinical responses for both tremor and rigidity were associated with a significantly (p < 0.05) higher proportion of modulated fibres for the same cortico- and sub-cortico-STN connections. Conclusions: Patient-individual tractography reveals that, in PD, most of the cortical fibres traversing the VTA are connected to the SMA. In addition, clinical efficacy is related to the proportion of DBS-affected fibres connecting the STN with nodes of both the hyperdirect (cortex-STN) and the indirect pathways (STN-basal ganglia). As such, patient-specific tractography, in particular in the basal ganglia, could be used in a clinical context as a tool to guide therapy.

Dominant twin peaks: a novel conjecture for the pathophysiologic basis of tremor frequency and fluctuation time in Parkinson’s disease

2025-06-18

Furrukh S. Khan , Dmitry S. Novikov , Brian Dalm +3 more | Frontiers in Neuroscience

Background With the commercial availability of deep brain stimulation neurostimulators and sensing leads capable of recording deep brain Local Field Potentials, researchers now commonly study the spectral characteristics of Local … Background With the commercial availability of deep brain stimulation neurostimulators and sensing leads capable of recording deep brain Local Field Potentials, researchers now commonly study the spectral characteristics of Local Field Potentials recorded from the subthalamic nucleus of patients with Parkinson’s disease. Correlating subthalamic synchronized oscillatory activity with motor impairment in Parkinson’s disease patients has recently gained attention in the literature. Objective Based on the deep brain recordings of a Parkinson’s disease patient our objective is to (i) Use actual measurements of the patient’s tremor to support a hypothesis that connects the features of the Local Field Potential’s beta-band spectrum (13–31 Hz), with the lower frequency (4–8 Hz) features of the patient’s tremor, such as tremor frequency and tremor fluctuation time and (ii) Justify the hypothesis through theoretical reasoning based on communication theory in Electrical Engineering. Methods Tremor characteristics (i.e., tremor frequency and tremor fluctuation time) derived from limb coordinate time-series were obtained from a video of the patient by using Google’s MediaPipe Artificial Intelligence Framework. Spectra of the deep brain recordings and measured tremor time-series were analyzed using the Fast Fourier Transform. Burst trains in the deep brain signals and tremor bursts in the measured tremor signal were investigated by using Continuous Wave Transform scalograms. Results Support for the hypothesis is provided by a close agreement between the measured results of the tremor (from a patient’s video) and the predictions of the hypothesis based on the Local Filed Potential deep brain spectrum. We show that the defining features in the scalogram obtained from the deep brain signal are directly related to the features in the scalogram of the measured tremor. We provide a theoretical justification of the hypothesis by relating features of the deep brain beta-bursts, seen in the Local Field Potential scalogram, to a pair of beta-band dominant peaks found in the spectrum of the deep brain signal by leveraging the phenomena of “beating” (amplitude modulation) from communications theory. Conclusion We conclude that tremor properties of a Parkinson’s disease patient, like tremor frequency and tremor fluctuation duration, can be obtained from the patient’s subthalamic nucleus beta-band spectrum.

Frustrative nonreward, sucrose consumption, and the basal ganglia: Role of chemogenetic activation of projections from the nucleus accumbens to the globus pallidus internus, globus pallidus externus, and ventral pallidum

2025-06-18

Christopher Hagen , Jacqueline Suárez , Mauricio R. Papini | Neurobiology of Learning and Memory

Subthalamic nucleus or globus pallidus internus deep brain stimulation for the treatment of parkinson’s disease: An artificial intelligence approach

2025-06-18

David Shin , Timothy Tang , Johnny L. Carson +7 more | Journal of Clinical Neuroscience

Correction: Four dimensions of individualization in brain stimulation for psychiatric disorders: context, target, dose, and timing

2025-06-18

Ghazaleh Soleimani , Michael A. Nitsche , Colleen A. Hanlon +3 more | Neuropsychopharmacology

Modeling and optimizing deep brain stimulation to enhance gait in Parkinson’s disease: personalized treatment with neurophysiological insights

2025-06-18

Hamid Fekri Azgomi , Kenneth H. Louie , Jessica E. Bath +7 more | npj Parkinson s Disease

Abstract The effects of deep brain stimulation (DBS) on gait in Parkinson’s disease (PD) are variable due to challenges in gait assessment and limited understanding of stimulation parameters’ impacts on … Abstract The effects of deep brain stimulation (DBS) on gait in Parkinson’s disease (PD) are variable due to challenges in gait assessment and limited understanding of stimulation parameters’ impacts on neural activity. We developed a data-driven approach to identify optimal DBS parameters to improve gait and uncover neurophysiological signatures of gait enhancement. Field potentials from the globus pallidus (GP) and motor cortex were recorded in three patients with PD (PwP) using implanted bidirectional neural stimulators during overground walking. We developed a Walking Performance Index (WPI) to assess gait metrics. DBS parameters were systematically varied to study their impacts on gait and neural dynamics. We were able to predict and identify personalized DBS settings that improved the WPI using a Gaussian Process Regressor. Improved walking correlated with reduced pallidal beta power during key gait phases. These findings, along with identified person-specific neural spectral biomarkers, underscore the importance of personalized, data-driven interventions for gait enhancement in PwP. ClinicalTrials.gov registration: NCT-03582891.

Neuropsychological and neurobehavioral outcomes of responsive neurostimulation in epilepsy: A systematic review and meta‐analysis

2025-06-18

Marco Málaga , Yosefa A. Modiano , Zulfi Haneef | Epilepsia

Abstract Objective The Responsive Neurostimulation System (RNS) is a US Food and Drug Administration‐approved closed‐loop brain neurostimulation device for patients with drug‐resistant epilepsy. Given the cognitive/neurobehavioral impact of epilepsy and … Abstract Objective The Responsive Neurostimulation System (RNS) is a US Food and Drug Administration‐approved closed‐loop brain neurostimulation device for patients with drug‐resistant epilepsy. Given the cognitive/neurobehavioral impact of epilepsy and the putative neuroplasticity with neuromodulation, we aimed to understand the effect of RNS on cognition. Methods We systematically searched four databases, PubMed/Medline, EMBASE, Web of Science, and Cochrane, from inception until April 2025. Primary outcomes were neuropsychological tests in global intellectual functioning and across five cognitive domains: language, memory, executive functioning, visuospatial functioning, and attention/processing speed. We also included measures evaluating depression and anxiety symptoms and quality of life in epilepsy. A random‐effects meta‐analysis was performed when at least two measures were available across studies, calculating the standardized mean difference (SMD) and 95% confidence interval (CI) between baseline and postoperative testing at or over 12 months. Results Of 2227 articles identified, we included 10 studies in our qualitative systematic review and five nonduplicated studies (373 patients) in our meta‐analysis. Intellectual functioning, cognitive functioning, depression, anxiety, and quality of life either improved or remained stable across the included studies. Meta‐analysis revealed nonsignificant changes in intellectual functioning (SMD = −.03, 95% CI = −.49 to .42) and two of the five cognitive domains: language (Boston Naming Test: SMD = .12, 95% CI = −.10 to .33; Verbal Comprehension Index: SMD = −.16, 95% CI = −.58 to .26) and visuospatial functioning (Perceptual Reasoning Index: SMD = .07, 95% CI = −.36 to .49). The remaining domains could not be evaluated given the limited number of studies. For mood, meta‐analysis revealed a nonsignificant decrease in depression score (Beck Depression Inventory‐II: SMD = −.14, 95% CI = −.33 to .06). GRADE (Grading of Recommendations Assessment, Development, and Evaluation) certainty of evidence was moderate for intellectual and visuospatial functioning and high for language and depression measures. Significance Our systematic review and meta‐analysis suggest that RNS does not impact neuropsychological and neurobehavioral outcomes at a group level, at least for the measures examined. We review putative mechanisms by which RNS may impact cognition and offer suggestions for future research in this domain.

Empirical classification of fatigue-induced physiological tremor in robot-assisted manipulation tasks using BiLSTM-GRU network

2025-06-17

Poongavanam Palani , Siddhant Panigrahi , Gunarajulu Renganathan +2 more | Frontiers in Rehabilitation Sciences

Introduction Physiological tremor arises due to stress, anxiety, fatigue, alcohol or caffeine. Under conventional circumstances, the physiological tremor would not be detrimental. Still, the mere presence of such a tremor … Introduction Physiological tremor arises due to stress, anxiety, fatigue, alcohol or caffeine. Under conventional circumstances, the physiological tremor would not be detrimental. Still, the mere presence of such a tremor during any microsurgical procedure can be catastrophic. In these instances, it is necessary to predict the progression of the tremor. This article proposes a novel sensing methodology and adds a distinctive feature to aid in classification. The classification of the progressive stages of fatigue-induced physiological tremor (FIPT) is based on the hybrid bidirectional long short-term memory neural network with a Gated Recurrent Unit (BiLSTM-GRU) presented in this work. Methodology Twenty healthy participants volunteered in the study, where a teleoperation stage was set up using the Geomagic Haptic device—Touch. On the master end, the participants were seated comfortably and asked to trace the patterns embedded over an image of an organ that was displayed on the screen. The EMG and MMG ACC signals from the Mindrove Armband and cross-sectional area changes, MMGCSAC, calculated from area measurement using the vision sensor, were recorded. The pattern-tracing task (PTT) was carried out over five repetitions, with fatigue-inducing exercise occurring between task epochs, thus accumulating fatigue throughout the data collection process. The extracted features from human movement aid the classification of the stages of tremor using BiLSTM-GRU, showing the significance of a cross-sectional area informed model. Results The stages of progression of tremor are classified into five levels in this study, and classified using BiLSTM GRU with four different input feature sets. The performance evaluation metrics, such as the accuracy, precision, recall and F1 score, have been reported to ascertain the efficiency of the proposed feature group. The proposed feature set and classification strategy are capable of estimating stages of FIPT with 99% classification accuracy. This can be used to design state-of-the-art movement training platforms for both experienced and novice surgeons that allow informed decision making to attend to their tremor condition, either by taking a break or including a limb support to minimize its effects. At the same time, the identification methodology can be extended to pathological tremor rehabilitation and any other movement disorder diagnostics.

Efficacy and safety of multiple-target deep brain stimulation in non-parkinsonian movement disorders: a systematic review

2025-06-17

Evangelos Kalogirou , Spyridon Voulgaris , George Α. Alexiou | Neurosurgical Review

Parameterization of intraoperative human microelectrode recordings: Linking action potential morphology to brain anatomy

2025-06-17

Matthew Baker , Bryan T. Klassen , Michael A. Jensen +5 more | PLoS Computational Biology

Deep brain stimulation (DBS) is a targeted manipulation of brain circuitry to treat neurological and neuropsychiatric conditions. Optimal DBS lead placement is essential for treatment efficacy. Current targeting practice is … Deep brain stimulation (DBS) is a targeted manipulation of brain circuitry to treat neurological and neuropsychiatric conditions. Optimal DBS lead placement is essential for treatment efficacy. Current targeting practice is based on preoperative and intraoperative brain imaging, intraoperative electrophysiology, and stimulation mapping. Electrophysiological mapping using extracellular microelectrode recordings aids in identifying functional subdomains, anatomical boundaries, and disease-correlated physiology. The shape of single-unit action potentials may differ due to different biophysical properties between cell-types and brain regions. Here, we describe a technique to parameterize the structure and duration of sorted spike units using a novel algorithmic approach based on canonical response parameterization, and illustrate how it may be used on DBS microelectrode recordings. Isolated spike shapes are parameterized then compared using a spike similarity metric and grouped by hierarchical clustering. When spike morphology is associated with anatomy, we find regional clustering in the human globus pallidus. This method is widely applicable for spike removal and single-unit characterization and could be integrated into intraoperative array-based technologies to enhance targeting and clinical outcomes in DBS lead placement.

Alpha-synuclein overexpression without vocalization deficits in a mouse model of parkinsonism.

2025-06-17

Brandon Rodgers , Allison J. Schaser | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Voice deficits are common in Parkinson’s disease (PD) and significantly impact quality of life by increasing stress, social isolation, and caregiver burden. However, despite this impact, there are currently … Abstract Voice deficits are common in Parkinson’s disease (PD) and significantly impact quality of life by increasing stress, social isolation, and caregiver burden. However, despite this impact, there are currently no treatments that target the underlying pathophysiology of PD in the vocalization system. The goal of this study was to examine the effect of one possible underlying mechanism responsible for the complex voice deficits that exist in PD; overexpression of the protein alpha-synuclein. Results show that overexpression of alpha-synuclein, prior to the development of alpha-synuclein aggregate pathology, does not result in significant vocalization deficits. A small but statistically significant increase in the total number of complex vocalizations was found in mice overexpressing alpha-synuclein compared to wildtype mice, but there were no differences in complexity ratio or any of the other specific vocalization parameters tested. Results provide a critical foundational understanding of the impact of overexpression versus aggregation of alpha-synuclein on voice deficits in PD. Future work will focus on manipulation of alpha-synuclein aggregate pathology, and not overexpression alone, to reduce or eliminate the burden of PD specific voice disorders. Summary Statement This study shows that overexpression of alpha-synuclein alone does not result in significant vocalization deficits, indicating that alpha-synuclein aggregate pathology within the vocalization system is required to induce vocalization deficits.

A Systematic Clinical Framework for Postimplantation Monitoring in Thalamic Neuromodulation: Insights From Twiddler's Syndrome.

2025-06-17

Shalin Shah , Ganne Chaitanya , Jeston Chin +2 more | PubMed

This case described a 25-year-old pregnant woman with refractory multifocal epilepsy, diagnosed in 2020 and treated with bilateral thalamic deep brain stimulation (DBS) targeting the centromedian and pulvinar nuclei. Prior … This case described a 25-year-old pregnant woman with refractory multifocal epilepsy, diagnosed in 2020 and treated with bilateral thalamic deep brain stimulation (DBS) targeting the centromedian and pulvinar nuclei. Prior to DBS, she experienced daily focal seizures, often progressing to generalized tonic-clonic seizures despite optimal medication. Presurgical evaluations revealed multifocal epilepsy with right hemispheric involvement and diffuse band heterotopia. Given the extensive neurophysiological and radiographic findings, DBS was chosen over resective surgery. Following implantation in December 2023, initial stimulation settings resulted in some seizure control but also development of new symptoms, including shock-like sensations down her neck. After 43 seizure-free days, she experienced a prolonged seizure in April 2024, prompting further investigation. Imaging revealed migration of the right pulvinar electrode, which was identified as the likely cause. This resultant displacement, called the "Twiddler's Syndrome," is a phenomenon where device manipulation causes malfunction or dislodgment. This resulted from the patient's habit of massaging her neck. After adjusting DBS settings and turning off right pulvinar stimulation, her symptoms resolved, and she remained seizure-free for two months. This case emphasizes the need for careful postimplantation monitoring, imaging, and awareness of hardware-related issues like Twiddler's Syndrome, highlighting the importance of well-planned surgical strategies to optimize outcomes in neuromodulation therapies.

Jerky tremor with dystonia in PHARC syndrome: An uncommon neurological presentation

2025-06-16

Sahil Mehta , Saurabh Mishra , Jagdeep Singh +2 more | Parkinsonism & Related Disorders

MRI-guided Focused Ultrasound VIM Thalamotomy with Indwelling GPi DBS Electrodes: A Case Report

2025-06-16

Alexander P. Glaser , David D. Liu , P. Jason White +4 more | Stereotactic and Functional Neurosurgery

Introduction: Deep brain stimulation (DBS) is the gold-standard surgical treatment for Essential Tremor (ET) and Tremor-dominant Parkinson’s Disease (TdPD). However, despite appropriate electrode placement and programming, patients may develop tremor … Introduction: Deep brain stimulation (DBS) is the gold-standard surgical treatment for Essential Tremor (ET) and Tremor-dominant Parkinson’s Disease (TdPD). However, despite appropriate electrode placement and programming, patients may develop tremor recurrence due to disease progression. MRI-guided focused ultrasound (MRgFUS) thalamotomy is an alternative treatment to DBS and has been shown to yield durable tremor control in both ET and TdPD patients. However, MRgFUS thalamotomy in a patient with indwelling DBS electrodes has not been previously reported. Case Presentation: We present the case of a 77-year-old male with progressive TdPD who underwent bilateral globus pallidus internus (GPi) DBS with subsequent right unilateral VIM thalamotomy 23 months after DBS due to progressive tremor recurrence. At 6 month follow up, his tremor has completely resolved. Discussion: This is the first report of MRgFUS thalamotomy for recurrent tremor with indwelling DBS electrodes. We found that MRgFUS thalamotomy as salvage therapy with implanted GPi DBS electrodes is both safe and effective. It represents a novel potential treatment paradigm for TdPD patients with persistent tremor despite otherwise effective GPi DBS.

Leveraging wavelet scattering transform on accelerometry data for classification of Parkinson’s tremor

2025-06-16

Brenda G. Muñoz-Mata , Guadalupe Dorantes-Méndez , Ildefonso Rodríguez‐Leyva +1 more | The European Physical Journal Special Topics

Twenty-five-year experience with apomorphine pump in Parkinson's disease: A real-life long-term retrospective tolerance study

2025-06-16

Sina R. Potel , Maria Chondrogiorgi , Andrea Gozzi +7 more | Journal of Parkinson s Disease

Background Continuous subcutaneous apomorphine infusion (CSAI) is a standard of care treatment in advanced Parkinson's disease (PD) to treat motor fluctuations. However, literature about its long-term data is scarce. Objective … Background Continuous subcutaneous apomorphine infusion (CSAI) is a standard of care treatment in advanced Parkinson's disease (PD) to treat motor fluctuations. However, literature about its long-term data is scarce. Objective The aim of this study was to report about CSAI tolerance and discontinuation predictors in a large monocentric cohort. Methods Consecutive PD patients who had CSAI were included. CSAI duration, discontinuation rates at 3, 12, 24, 36, 48, and 60 months, demographic data, MDS-UPDRS motor score, adverse events (AEs), discontinuation reasons and predictive factors were analyzed with logistic regression. Results A total of 208 patients were included from 1999 to 2023 (51% male; age: 67.4 ± 8.3 years; PD duration: 11.2 ± 5.0 years). In the overall group, CSAI duration was 25.0 ± 32.9 months (median: 13.0, range: 0.1–260.0). Ninety-five patients (45.7%) discontinued CSAI after 12.7 ± 15.3 months (median: 8.0). Main discontinuation causes were switching to deep brain stimulation (44.2%) and low efficacy (15.8%). Sixty% of discontinuations occurred within the first year. CSAI duration was the only significant difference between ongoing CSAI (116) and discontinued patients (35.4 ± 39.7 vs. 11.1 ± 18.4 months; p < 0.001), after excluding 42 CSAI-to-DBS. About 79.8% patients had AEs, mainly hallucinations (41.3%) and nodules (24.0%). The best discontinuation predictors were CSAI duration and baseline off medication MDS-UPDRS motor score. Conclusions These results may help clinicians better select patients, anticipate and manage AEs, and predict CSAI discontinuation.

Cancer-Related Movement Disorders: A Scoping Review and Diagnostic Approach

2025-06-16

Laura Schroeder , Ethan Snow , Casandra Chen +4 more | Neuro-Oncology Practice

Abstract Cancer-related movement disorders (CRMDs) comprise a diverse group of neurological complications of cancer. They result from varied etiologies and can be associated with compromised quality of life and poor … Abstract Cancer-related movement disorders (CRMDs) comprise a diverse group of neurological complications of cancer. They result from varied etiologies and can be associated with compromised quality of life and poor prognosis. CRMDs can be divided into two broad categories: movement disorders (MDs) resulting from cancer-related processes, such as direct tumor infiltration and paraneoplastic disease, and those that are a consequence of cancer-directed treatments, including classic therapies, such as chemotherapy and radiation therapy, novel treatments (e.g., immunotherapies and CAR T-Cell therapies), and various supportive treatments. A clear understanding of the breadth of CRMDs is vital, as effective management relies upon accurately identifying their underlying etiology. In this scoping review, we provide a comprehensive categorization of CRMDs based on their underlying etiology and phenomenology. Additionally, we propose a structured framework to guide the diagnostic evaluation and management of CRMDs, with the goal of facilitating timely diagnosis and, ultimately, improved patient outcomes.

Dystonia: The Ability to Forget

2025-06-16

Mark Hallett | Parkinsonism & Related Disorders

Deep brain stimulation-induced local evoked potentials outperform spectral features in spatial and clinical STN mapping

2025-06-16

Enrico Opri , Faiçal Isbaine , Seyyed Bahram Borgheai +6 more | medRxiv (Cold Spring Harbor Laboratory)

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapy for Parkinson′s Disease (PD). Yet, optimizing lead placement and stimulation programming remains challenging. Current techniques rely … Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapy for Parkinson′s Disease (PD). Yet, optimizing lead placement and stimulation programming remains challenging. Current techniques rely on imaging and intraoperative microelectrode recordings (MER), while programming rely on trial-and-error clinical testing, which can be time-consuming. DBS-induced local evoked potentials (DLEP), also known as evoked resonant neural activity (ERNA), have emerged as a potential alternative electrophysiological marker for mapping. However, direct comparisons with traditional spectral features, such as beta-band, high-frequency oscillations (HFOs), and aperiodic component have been lacking. Approach: We evaluated DLEP across 39 STN DBS leads across 31 subjects with PD undergoing DBS surgery, using both a single-pulse and high-frequency burst stimulation paradigms. We developed a novel artifact-removal method to enable monopolar DLEP recovery, including estimating the DLEP amplitudes at stimulated contacts, further enhancing spatial sampling of DLEP. We evaluated spectral features and DLEP in respect to imaging-based and MER-based localization, and its predictive power for post-operative programming. Main Results: DLEP showed great spatial consistency, maximizing within STN with 100% accuracy for single-pulse and 84.62% for burst stimulation, surpassing spectral measures including beta (89.74%) and HFO (82.05%). DLEP better correlated with clinical outcomes (single-pulses ρ=-0.33, high-frequency bursts ρ=-0.26), than spectral measures (beta ρ=-0.25, HFO ρ=0.05). Furthermore, single-pulses at low-frequencies are sufficient for DLEP-based mapping. Significance: We show how DLEP provide higher STN-spatial specificity and correlation with postoperative programming compared to spectral features. To support clinical translation of DLEP, we developed two methods aimed to recover artifact-free DLEP and estimating DLEP amplitudes at stimulating contacts. DLEP appear distinct from beta and HFO activity, yet strongly tied to aperiodic spectral components, suggesting that DLEP amplitude reflects underlying STN excitability. This study highlights that DLEP are a robust and clinically valuable marker for DBS targeting and programming.