ABSTRACT
BACKGROUND: Task-specific dystonia (TSFD) is a disabling movement disorder. Effective treatment options are currently limited. Zolpidem was reported to improve primary focal and generalized dystonia in a proportion of patients. The mechanisms underlying its therapeutic effects have not yet been investigated. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover trial of single-dose zolpidem in 24 patients with TSFD. Patients were clinically assessed using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Writers' Cramp Rating Scale (WCRS), and Visual Analogue Scale (VAS), before and after receiving placebo and zolpidem. Transcranial magnetic stimulation was conducted on placebo and zolpidem to compare corticospinal excitability - active and resting motor thresholds (AMT and RMT), resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short-interval intracortical inhibition curve (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Eight patients underwent brain FDG-PET imaging on zolpidem and placebo. RESULTS: Zolpidem treatment improved TSFD. Zolpidem compared to placebo flattened rest and active input/output curves, reduced ICF and was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum. Correlations were found between changes in dystonia severity on WCRS and changes in active input/output curve and in brain metabolism, respectively. Patients with lower RMT, and higher rest and active input/output curves exhibited better response to zolpidem compared to placebo. CONCLUSIONS: Zolpidem improved TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor networks.
Subject(s)
Cross-Over Studies , Dystonic Disorders , Fluorodeoxyglucose F18 , Positron-Emission Tomography , Transcranial Magnetic Stimulation , Zolpidem , Humans , Zolpidem/pharmacology , Male , Female , Adult , Double-Blind Method , Middle Aged , Dystonic Disorders/drug therapy , Dystonic Disorders/diagnostic imaging , Dystonic Disorders/physiopathology , GABA-A Receptor Agonists/pharmacology , Young Adult , Outcome Assessment, Health CareABSTRACT
BACKGROUND: Transcutaneous electrostimulation of the auricular branch of the vagal nerve (taVNS) has the propensity to reach diffuse neuromodulatory networks, which are dysfunctional in Parkinson's disease (PD). Previous studies support the use of taVNS as an add-on treatment for gait in PD. OBJECTIVES: We assessed the effect of taVNS at 25 Hz (taVNS25), taVNS at 100 Hz (taVNS100), and sham earlobe stimulation (sVNS) on levodopa responsive (arm swing velocity, arm range of motion, stride length, gait speed) and non-responsive gait characteristics (arm range of motion asymmetry, anticipatory postural adjustment [APA] duration, APA first step duration, APA first step range of motion), and turns (first turn duration, double 360° turn duration, steps per turn) in advanced PD. METHODS: In our double blind sham controlled within-subject randomized trial, we included 30 PD patients (modified Hoehn and Yahr stage, 2.5-4) to assess the effect of taVNS25, taVNS100, and sVNS on gait characteristics measured with inertial motion sensors during the instrumented stand and walk test and a double 360° turn. Separate generalized mixed models were built for each gait characteristic. RESULTS: During taVNS100 compared to sVNS arm swing velocity (P = 0.030) and stride length increased (P = 0.027), and APA duration decreased (P = 0.050). During taVNS25 compared to sVNS stride length (P = 0.024) and gait speed (P = 0.021) increased and double 360° turn duration decreased (P = 0.039). CONCLUSIONS: We have found that taVNS has a frequency specific propensity to improve stride length, arm swing velocity, and gait speed and double 360° turn duration in PD patients. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Subject(s)
Parkinson Disease , Humans , Parkinson Disease/physiopathology , Parkinson Disease/therapy , Male , Female , Aged , Middle Aged , Double-Blind Method , Gait/physiology , Transcutaneous Electric Nerve Stimulation/methods , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Levodopa/therapeutic use , Levodopa/pharmacology , Range of Motion, Articular/physiologyABSTRACT
fMRI studies show activation of cerebellum during transcutaneous auricular vagal nerve stimulation (taVNS); however, there is no evidence whether taVNS induced activation of the cerebellum translates to the cerebellar closed loops involved in motor functions. We assessed the propensity of taVNS at 25 Hz (taVNS25) and 100 Hz (taVNS100) to modulate cerebello-thalamo-cortical pathways using transcranial magnetic stimulation. In our double blind within-subjects study thirty-two participants completed one visit during which cerebellar brain inhibition (CBI) was assessed at baseline (no stimulation) and in a randomized order during taVNS100, taVNS25, and sham taVNS (xVNS). Generalized linear mixed models with gamma distribution were built to assess the effect of taVNS on CBI. The estimated marginal means of linear trends during each taVNS condition were computed and compared in a pairwise fashion with Benjamini-Hochberg correction for multiple comparisons. CBI significantly increased during taVNS100 compared to taVNS25 and xVNS (p = 0.0003 and p = 0.0465, respectively). The taVNS current intensity and CBI conditioning stimulus intensity had no significant effect on CBI. taVNS has a frequency dependent propensity to modulate the cerebello-thalamo-cortical pathway. The cerebellum participates in closed-loop circuits involved in motor, cognitive, and affective operations and may serve as an entry for modulating effects of taVNS.
ABSTRACT
Neurophysiological evidence that transcutaneous auricular vagal nerve stimulation (taVNS) affects neuronal signalling at the cortical level is sparse. We used transcranial magnetic stimulation to assess the effect of taVNS on the excitability of intracortical GABAergic and cholinergic circuits. In this within-subject, double-blind study on 30 healthy participants, we used TMS paradigms to assess the effect of a single session of taVNS at 100 Hz and sham earlobe VNS (sVNS) on short-interval intracortical inhibition (SICI) curve and short-latency afferent inhibition (SAI). Control experiment was performed on additional 15 participants using the same experimental settings, but delivering no stimulation (xVNS). Bayesian statistics were used to assess the differences, producing % values that reflect the certainty that the values of interest were decreased during or after stimulation compared with baseline. taVNS increased SICI (96.3%), whereas sVNS decreased SICI (1.2%). SAI was not affected by taVNS, although it was decreased during sVNS (1.34% and 9.1%, for interstimulus intervals 20 and 24 ms, respectively). The changes in TMS parameters detected during sVNS were present in the same direction in the control experiment with no stimulation. Our study provides evidence that taVNS increases the activity of cortical GABAAergic system, leaving cortical cholinergic circuits unaffected. Changes in intracortical cortical excitability during sVNS, which were also observed in the control experiment with no stimulation were likely the effect of expectation related to participation in an interventional study.
Subject(s)
Transcranial Magnetic Stimulation , Vagus Nerve Stimulation , Humans , Bayes Theorem , Cholinergic Agents , Evoked Potentials, Motor/physiology , Neural Inhibition/physiology , Double-Blind MethodABSTRACT
BACKGROUND: Functional Neurological Disorders (FND) are common in clinical practice. It is recognized that FND may present at onset or during the course of other neurological diseases (functional comorbidity). CASES: We report a clinical series of three patients who initially presented positive signs of a functional movement disorder (FMD) and were later diagnosed with a Creutzfeldt-Jakob disease (CJD). All patients presented with unilateral functional tremor, two patients also had functional limb weakness. All patients progressed to an asymmetric corticobasal syndrome, fulfilling clinical criteria of CJD. They had a rapid progression and died within 2-3 months. CONCLUSIONS: FND may be the initial clinical presentation of neurodegenerative diseases reflecting a dysfunction across brain circuits that are involved in the pathophysiology of FND. A positive diagnosis of FND is essential as it is an adequate examination and a close follow-up of these patients in neurology clinics.
Subject(s)
Creutzfeldt-Jakob Syndrome , Humans , Creutzfeldt-Jakob Syndrome/diagnosis , Creutzfeldt-Jakob Syndrome/diagnostic imaging , Brain/diagnostic imaging , Diagnosis, DifferentialSubject(s)
Occupational Diseases , Parkinson Disease , Beekeeping , Friends , Humans , Surveys and QuestionnairesABSTRACT
BACKGROUND: With the progression of Parkinson's disease (PD), pulsatile treatment with oral levodopa causes maladaptive changes within basal ganglia-thalamo-cortical circuits, which are clinically expressed as motor fluctuations and dyskinesias. At the level of the motor cortex, these changes may be detected using transcranial magnetic stimulation (TMS), as abnormal corticospinal and intracortical excitability and absent response to plasticity protocols. OBJECTIVE: We investigated the effect of continuous dopaminergic stimulation on cortical maladaptive changes related to oral levodopa treatment. METHODS: Twenty patients with advanced PD were tested using TMS within 1 week before and again 6 months after the introduction of levodopa-carbidopa intestinal gel. We measured resting and active motor thresholds, input/output curve, short interval intracortical inhibition curve, cortical silent period, and response to intermittent theta burst stimulation. Patients were clinically assessed with Part III and Part IV of the Movement Disorders Society Unified Parkinson's Disease Rating Scale. RESULTS: Six months after the introduction of levodopa-carbidopa intestinal gel, motor fluctuations scores (P = 0.001) and dyskinesias scores (P < 0.001) were reduced. Resting and active motor threshold (P = 0.012 and P = 0.015) and x-intercept of input/output curve (P = 0.005) were also decreased, while short-interval intracortical inhibition and response to intermittent theta bust stimulation were improved (P = 0.026 and P = 0.031, respectively). Changes in these parameters correlated with clinical improvement. CONCLUSIONS: In patients with advanced PD, switching from intermittent to continuous levodopa delivery increased corticospinal excitability and improved deficient intracortical inhibition and abnormal motor cortex plasticity, along with amelioration of motor fluctuations and dyskinesias. Continuous dopaminergic stimulation ameliorates maladaptive changes inflicted by chronic pulsatile dopaminergic stimulation. © 2022 International Parkinson and Movement Disorder Society.
Subject(s)
Dyskinesias , Motor Cortex , Parkinson Disease , Carbidopa/pharmacology , Carbidopa/therapeutic use , Dopamine , Humans , Levodopa/pharmacology , Levodopa/therapeutic use , Motor Cortex/physiology , Parkinson Disease/drug therapyABSTRACT
BACKGROUND: In the sharp contrast with the existing literature, we frequently observe minipolymyoclonus, tremor and pseudodystonic thumb posturing in patients with motor neuron disease. We conducted a clinical and electrophysiological study to describe phenomenology, prevalence and pathophysiology of involuntary movements in motor neuron disease. METHODS: We included 77 consecutive patients. Involuntary movements were assessed at rest and on action. Patients were videotaped. Arm muscle tone, power and deep tendon reflexes were evaluated. Accelerometry with electromyography was recorded in a subset of patients. RESULTS: Involuntary movements were observed in 68.9% of patients and could be separated into rest minipolymyoclonus, thumb tremor, pseudodystonic thumb posture, action minipolymyoclonus, and action tremor. One-third of patients reported negative impact of involuntary movements on hand use. Logistic regression showed that rest minipolymyoclonus and thumb tremor were more likely to occur in patients with more prominent distal muscle weakness and less spasticity. Similarly, action involuntary movements were more likely to appear in weaker patients. Patients with brisk tendon reflexes were more likely to display action tremor than action minipolymyoclonus. Action tremor was characterized by accelerometer and corresponding electromyography peak frequency, which decreased with mass loading, suggesting a mechanical-reflex tremor. CONCLUSIONS: Involuntary movements are common, but poorly recognized feature of motor neuron disease that may add to functional impairment. Results of our study suggest that involuntary movements are likely of peripheral origin, with a non-fused contraction of enlarged motor units being a common driving mechanism. Minipolymyoclonus appears if no synchronization of motor units occurs. When synchronization occurs via stretch reflex, mechanical-reflex tremor is generated.
Subject(s)
Dyskinesias , Motor Neuron Disease , Electromyography , Hand , Humans , Motor Neuron Disease/complications , Phenotype , TremorABSTRACT
BACKGROUND: Generation of functional tremor relies on the structures involved in the control of voluntary movements. The clinical diagnosis is based on the presence of "positive signs", which are expression of cognitive and motor distractibility and reflect functional tremor dependence on explicit motor control. In patients who manifest less distractibility, habitual (implicit) control may be of greater significance. Habitual behaviours are inflexible and difficult to eradicate. OBJECTIVES: To investigate if motor and cognitive distractibility predicts response to treatment with repetitive transcranial magnetic stimulation. METHODS: 21 patients with functional tremor underwent 5-day repeated sessions of continuous theta burst stimulation over primary motor cortex. A battery of tests to provoke positive signs was performed during accelerometry recordings and the total functional tremor accelerometry score was calculated for each patient. Response to treatment was measured as change in tremor amplitude, expressed as total power of the spectra between 1 and 30 Hz. RESULTS: On the group level, cTBS significantly changed postural tremor amplitude (Z = -1.9; p = 0.05), with the median decrease of 40%, IQR (-90-(+24)). There was a positive correlation between the functional tremor accelerometry score and reduction of postural tremor amplitude with treatment (rs = -0.75, p < 10-3). Responders had higher functional tremor accelerometry scores compared to non-responders (p = 0.001). The total functional tremor accelerometry score was a significant predictor of treatment response (OR = 2.8, p = 0.03; 95% CI 1.1; 7.2). CONCLUSIONS: Patients who are more distractible are better candidates for treatment with transcranial magnetic stimulation. The likely explanation is the between-subjects differences on the reliance of functional tremor generation on explicit vs. implicit motor network.
Subject(s)
Essential Tremor , Motor Cortex , Evoked Potentials, Motor/physiology , Humans , Transcranial Magnetic Stimulation , Tremor/therapyABSTRACT
BACKGROUND: Smell loss is a common symptom of COVID-19 infection. Majority of the studies that evaluated olfactory impairment in COVID-19 used questionnaires (subjective smell evaluations) and did not compare the results with objective or semiobjective measures of smell. We performed smell testing in hospitalised and self-isolated patients with COVID-19 and control participants. METHODS: Fifty-five COVID-19 and 44 control participants underwent smell testing, using Burghart Snifï¬n' Sticks 'Screening 12 Test'. Participants also rated their smelling capability on the numerical scale. Differences between groups and correlation between smell loss and time from acute onset of symptoms were tested, as well as correlation between results of smell test and subjective assessment of smell. RESULTS: Hospitalised patients with COVID-19 correctly determined 6.5/12 odorants compared with 10/12 in the self-isolated and 11/12 in the control group (p<0.001). Hyposmia or anosmia were present in 87.5% of hospitalised and 29.0% of self-isolated patients (p<0.001). The correlation between subjective self-assessment and results of smell testing was non-significant in both groups of patients with COVID-19, while there was a moderate positive correlation (p=0.001, Spearman's correlation coefficient=0.499) in control participants. CONCLUSION: Contrary to some previous reports suggesting that the presence of olfactory loss may predict milder course of disease, our study found that a vast majority of hospitalised patients with COVID-19 had prominent olfactory impairment. The absence of correlation between self-rated and objective smell evaluation in patients with COVID-19 indicates that subjective smell assessment is unreliable.
Subject(s)
COVID-19 , Olfaction Disorders , Humans , COVID-19/complications , COVID-19/diagnosis , Smell , Anosmia , SARS-CoV-2 , Olfaction Disorders/diagnosis , Olfaction Disorders/etiologyABSTRACT
BACKGROUND: Based on the promising results from preclinical studies, bee venom has been investigated as a neuroprotective agent in Parkinson's disease. OBJECTIVE: To assess if longstanding exposure to bee venom is associated with decreased risk for Parkinson's disease among beekeepers. METHODS: Questionnaire gathering information about diagnosis of Parkinson's disease and exposure to bee stings was posted to 6500 members of Slovenian beekeepers' organisation. RESULTS: We received 1298 responses (response rate 20.1%). Twenty beekeepers, all older than 60 years, were diagnosed with Parkinson's disease. The prevalence of Parkinson's disease in beekeepers aged ≥60 years was 3.9%, which is above the reported 0.6-1.3% prevalence of PD in this age group in European population. There was no difference in parameters reflecting bee venom exposure between beekeepers with and without Parkinson's disease. CONCLUSIONS: Continuous exposure to bee venom does not affect neurodegeneration to the extent where it could prevent the expression of Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society.
Subject(s)
Bee Venoms , Insect Bites and Stings , Occupational Diseases , Parkinson Disease , Animals , Bees , Epidemiologic Studies , Occupational Diseases/epidemiology , Parkinson Disease/epidemiologyABSTRACT
A 66-year-old right-handed female medical doctor suffered two consecutive cardioembolic strokes, initially affecting the right frontal lobe and the right insula, followed by a lesion in the left temporal lobe. The patient presented with distinctive phenomenology of general auditory agnosia with anosognosia for the deficit. She did not understand verbal requests and her answers to oral questions were fluent but unrelated to the topic. However, she was able to correctly answer written questions, name objects, and fluently describe their purpose, which is characteristic for verbal auditory agnosia. She was also unable to recognise environmental sounds or to recognise and repeat any melody. These inabilities represent environmental sound agnosia and amusia, respectively. Surprisingly, she was not aware of the problem, not asking any questions regarding her symptoms, and avoiding discussing her inability to understand spoken language, which is indicative of anosognosia. The deficits in our patient followed a distinct pattern of recovery. The verbal auditory agnosia was the first to resolve, followed by environmental sound agnosia. Amusia persisted the longest. The patient was clinically assessed from the first day of symptom onset and the evolution of symptoms was video documented. We give a detailed account of the patient's behaviour and provide results of audiological and neuropsychological evaluations. We discuss the anatomy of auditory agnosia and anosognosia relevant to the case. This case study may serve to better understand auditory agnosia in clinical settings. It is important to distinguish auditory agnosia from Wernicke's aphasia, because use of written language may enable normal communication.
Subject(s)
Agnosia , Aphasia , Aged , Aphasia, Wernicke , Female , Humans , Neuropsychological Tests , Temporal Lobe/diagnostic imagingABSTRACT
BACKGROUND: Progressive supranuclear palsy (PSP) features parkinsonism characterized by early postural instability, falls and prominent eye movement abnormalities that consist of saccadic slowing, followed by gaze limitation. Nystagmus is not considered typical for PSP, being more commonly associated with multiple system atrophy. OBJECTIVES: To describe the prevalence and phenomenology of nystagmus in patients with PSP. METHODS: 42 patients with probable PSP underwent detailed clinical eye movement examination. Patients with nystagmus performed video-nystagmography. T-test, Chi-Square test and Wilcoxon signed-rank test were used to test differences in demographic data, disease duration and PSP subtype between patients with and without nystagmus, and for analysis of video-nystagmographic data. RESULTS: Among 42 patients with PSP, we identified 15 patients (35,7%) with gaze-evoked nystagmus, predominantly horizontal. Clinically, 10/15 patients had symmetrical or asymmetrical gaze - evoked nystagmus (Type 1), while 5/15 patients had dissociated gaze-evoked nystagmus related to internuclear ophthalmoplegia (Type 2). Nystagmus and eye movement abnormalities were further characterized by video-nystagmography. There was no significant difference in age, disease duration or PSP subtypes between patients with and without nystagmus. CONCLUSION: Central nystagmus is present in more than a third of patients with progressive supranuclear palsy. It may present as symmetrical or asymmetrical gaze-evoked nystagmus or as dissociated gaze-evoked nystagmus related to internuclear ophthalmoplegia and probably arises from neurodegeneration of the neural integrator. Nystagmus in PSP has been a hitherto under-described feature and its presence should not deter clinicians from a diagnosis of PSP.
Subject(s)
Nystagmus, Pathologic/etiology , Nystagmus, Pathologic/physiopathology , Supranuclear Palsy, Progressive/complications , Supranuclear Palsy, Progressive/physiopathology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Nystagmus, Pathologic/epidemiology , Prevalence , Slovenia/epidemiology , Supranuclear Palsy, Progressive/epidemiologyABSTRACT
Patients with movement disorders experience fluctuations unrelated to disease progression or treatment. Extrinsic factors that contribute to the variable expression of movement disorders are environment related. They influence the expression of movement disorders through sensory-motor interactions and include somatosensory, visual, and auditory stimuli. Examples of somatosensory effects are stimulus sensitivity of myoclonus on touch and sensory amelioration in dystonia but also some less-appreciated effects on parkinsonian tremor and gait. Changes in visual input may affect practically all types of movement disorders, either by loss of its compensatory role or by disease-related alterations in the pathways subserving visuomotor integration. The interaction between auditory input and motor function is reflected in simple protective reflexes and in complex behaviors such as singing or dancing. Various expressions range from the effect of music on parkinsonian bradykinesia to tics. Changes in body position affect muscle tone and may result in marked fluctuations of rigidity or may affect dystonic manifestations. Factors intrinsic to the patient are related to their voluntary activity and cognitive, motivational, and emotional states. Depending on the situation or disease, they may improve or worsen movement disorders. We discuss various factors that can influence the phenotypic variability of movement disorders, highlighting the potential mechanisms underlying these manifestations. We also describe how motor fluctuations can be provoked during the clinical assessment to help reach the diagnosis and appreciated to understand complaints that seem discrepant with objective findings. We summarize advice and interventions based on the variability of movement disorders that may improve patients' functioning in everyday life. © 2020 International Parkinson and Movement Disorder Society.
Subject(s)
Dystonic Disorders , Movement Disorders , Cognition , Dystonic Disorders/therapy , Emotions , Humans , Movement Disorders/etiology , TremorABSTRACT
More than 30 patients with multiple sclerosis (MS) and Parkinson's disease (PD) have been reported so far. Theories on the co-occurrence of MS and PD range from coincidental to causal. There has been only one report of MS in young onset PD in a patient heterozygous for Parkin mutation. We report a patient with MS who developed signs typical for PD and was found to be heterozygous mutation carrier in the gene for glucocerebrosidase (GBA1), a well-known risk factor for PD.
ABSTRACT
Background: We have commonly observed involuntary jerks and tremor in patients with motor neuron disease (MND), even though these features are not considered typical for the disease.Objectives: We conducted prospective clinical and electrophysiological study to explore the prevalence, phenomenology and pathophysiology of involuntary movements in MND.Methods: Seventy-four consecutive patients were clinically examined and video-recorded. Based on regularity and distribution, movements observed at rest position were classified as minipolymyoclonus (MPMC) or rest thumb tremor (RTT) and movements present during action as action MPMC or action tremor. In 11 patients with tremor, accelerometry was recorded at (a) rest position, (b) with arms outstretched (postural condition) and (c) at postural condition with 500 g mass attached to the hand.Results: Involuntary movements were present in 54 patients (73%). Rest MPMC was present in 26 patients (35%), RTT in 22 patients (31%), action MPMC in 22 patients (30%) and action tremor in 20 patients (27%), with some overlap. Sixteen patients (22%) reported negative impact of involuntary movements on their ability to use hands. Regression model showed that lower distal muscle power and less prominent upper motor neuron involvement significantly increased the odds of MND patient having involuntary movements. Sex, age and disease duration did not significantly predict the occurrence of involuntary movements. At rest, tremor frequency ranged from 5.2 to 8.2 Hz, at postural position from 4.9 Hz to 7.6 Hz and during postural position with mass attached from 3.6 Hz to 7.6 Hz. On the group level, tremor peak frequency statistically significantly decreased from 6.1 Hz to 5 Hz without versus with loading.Discussion and conclusions: Involuntary movements are very common yet largely overlooked feature of MND that may also have negative impact on patient's functional abilities. Lower distal muscle power increases and the presence of upper motor neuron signs decreases the probability of involuntary movements. Together with finding of decrease in tremor frequency with mass loading, these results suggest that generation of involuntary movements is of peripheral origin.
ABSTRACT
BACKGROUND: Demographic and clinical studies imply that female sex may be protective for PD, but pathophysiological evidence to support these observations is missing. In early PD, functional changes may be detected in primary motor cortex using transcranial magnetic stimulation. OBJECTIVE: We hypothesised that if pathophysiology differs between sexes in PD, this will be reflected in differences of motor cortex measurements. METHODS: Forty-one newly diagnosed PD patients (22 males, 19 females) were clinically assessed using MDS-UPDRS part III, and various measures of cortical excitability and sensorimotor cortex plasticity were measured over both hemispheres, corresponding to the less and more affected side, using transcranial magnetic stimulation. Twenty-three healthy (10 men, 13 women) participants were studied for comparison. RESULTS: Among patients, no significant differences between sexes were found in age, age of diagnosis, symptom duration, and total or lateralized motor score. However, male patients had disturbed interhemispheric balance of motor thresholds, caused by decreased resting and active motor thresholds in the more affected hemisphere. Short interval intracortical inhibition was more effective in female compared to male patients in both hemispheres. Female patients had a preserved physiological focal response to sensorimotor plasticity protocol, whereas male patients showed an abnormal spread of the protocol effect. CONCLUSION: The study provides one of the first neurophysiological evidences of sex differences in early PD. Female patients have a more favorable profile of transcranial magnetic stimulation measures, possibly reflecting a more successful cortical compensation or delayed maladaptive changes in the sensorimotor cortex. © 2019 International Parkinson and Movement Disorder Society.