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Background: The demonstration of positive signs during neurological examination is a cornerstone of the diagnosis of functional movement disorders, however, the available data supporting the diagnostic value of some of these signs is limited. Objectives: To determine the diagnostic value (sensitivity and specificity) of the "whack‐a‐mole" (WAM) and "swivel chair" (SC) tests in patients with functional movement disorders (FMD). Methods: We enrolled patients with functional and organic movements in the WAM test if they exhibited tremor, dystonia, myoclonus, chorea, or tics. For the SC test, patients with a gait disorder as their primary impairment were recruited. Two blinded movement disorder specialists rated the presence of these signs in edited videos. Results: Inclusion criteria were met by 42 patients with FMD and 65 patients with organic movement disorders. Both tests demonstrated high specificity (means, 78% and 96%), but their sensitivity was low (means, 52% and 37%). Interobserver agreement for the WAM sign was 0.77 in the FMD group, against 0.28 in patients with organic movement disorders, whereas Movement Disorders Clinical Practice for Review Only for the SC sign was 0.69 in both groups. Conclusions: The present study indicates that physicians must be cautious in the application and interpretation of these clinical signs in the diagnosis of functional movement disorders, and they should be carefully considered and used as necessary. [ABSTRACT FROM AUTHOR]

Background: A better understanding of pain in adult‐onset idiopathic dystonia (AOID) is needed to implement effective therapeutic strategies. Objective: To develop a new rating instrument for pain in AOID and validate it in cervical dystonia (CD). Methods: Development and validation of the Pain in Dystonia Scale (PIDS) comprised three phases. In phase 1, international experts and participants with AOID generated and evaluated the preliminary items for content validity. In phase 2, the PIDS was drafted and revised by the experts, followed by cognitive interviews to ensure self‐administration suitability. In phase 3, the PIDS psychometric properties were assessed in 85 participants with CD and retested in 40 participants. Results: The final version of PIDS evaluates pain severity (by body‐part), functional impact, and external modulating factors. Test–retest reliability showed a high‐correlation coefficient for the total score (0.9, P < 0.001), and intraclass correlation coefficients were 0.7 or higher for all items in all body‐parts subscores. The overall PIDS severity score showed high internal consistency (Cronbach's α, 0.9). Convergent validity analysis revealed a strong correlation between the PIDS severity score and the Toronto Western Spasmodic Torticollis Rating Scale pain subscale (0.8, P < 0.001) and the Brief Pain Inventory‐short form items related to pain at time of the assessment (0.7, P < 0.001) and impact of pain on daily functioning (0.7, P < 0.001). Conclusion: The PIDS is the first specific questionnaire developed to evaluate pain in all patients with AOID, here, demonstrating high‐level psychometric properties in people with CD. Future work will validate PIDS in other forms of AOID. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background and purpose: Acute health events, including infections, can trigger the onset of functional neurological disorder (FND). It was hypothesized that a proportion of people with long COVID might be experiencing functional symptoms. Methods: A systematic review of studies containing original data on long COVID was performed. The frequency and characteristics of neurological symptoms were reviewed, looking for positive evidence suggesting an underlying functional disorder and the hypothesized causes of long COVID. Results: In all, 102 studies were included in our narrative synthesis. The most consistently reported neurological symptoms were cognitive difficulties, headaches, pain, dizziness, fatigue, sleep‐related symptoms and ageusia/anosmia. Overall, no evidence was found that any authors had systematically looked for positive features of FND. An exception was three studies describing temporal inconsistency. In general, the neurological symptoms were insufficiently characterized to support or refute a diagnosis of FND. Moreover, only 13 studies specifically focused on long COVID after mild infection, where the impact of confounders from the general effects of severe illness would be mitigated. Only one study hypothesized that some people with long COVID might have a functional disorder, and another eight studies a chronic‐fatigue‐syndrome‐like response. Discussion: Neurological symptoms are prevalent in long COVID, but poorly characterized. The similarities between some manifestations of long COVID and functional disorders triggered by acute illnesses are striking. Unfortunately, the current literature is plagued by confounders, including the mixing of patients with initial mild infection with those with severe acute medical complications. The hypothesis that long COVID might in part correspond to a functional disorder remains untested. [ABSTRACT FROM AUTHOR]

Background: Subthalamic nucleus (STN) stimulation is an effective treatment for Parkinson's disease and induced local field potential (LFP) changes that have been linked with clinical improvement. STN stimulation has also been used in dystonia although the internal globus pallidus is the standard target where theta power has been suggested as a physiomarker for adaptive stimulation. Objective: We aimed to explore if enhanced theta power was also present in STN and if stimulation‐induced spectral changes that were previously reported for Parkinson's disease would occur in dystonia. Methods: We recorded LFPs from 7 patients (12 hemispheres) with isolated craniocervical dystonia whose electrodes were placed such that inferior, middle, and superior contacts covered STN, zona incerta, and thalamus. Results: We did not observe prominent theta power in STN at rest. STN stimulation induced similar spectral changes in dystonia as in Parkinson's disease, such as broadband power suppression, evoked resonant neural activity (ERNA), finely‐tuned gamma oscillations, and an increase in aperiodic exponents in STN‐LFPs. Both power suppression and ERNA localize to STN. Based on this, single‐pulse STN stimulation elicits evoked neural activities with largest amplitudes in STN, which are relayed to the zona incerta and thalamus with changing characteristics as the distance from STN increases. Conclusions: Our results show that STN stimulation–induced spectral changes are a nondisease‐specific response to high‐frequency stimulation, which can serve as placement markers for STN. This broadens the scope of STN stimulation and makes it an option for other disorders with excessive oscillatory peaks in STN. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Impaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia yet the results from individual studies are conflicting and underpowered. Objective: To systematically examine the influence of dystonia, dystonia subtype, and clinical features over eyeblink conditioning within a statistical model which controlled for the covariates age and sex. Methods: Original neurophysiological data from all published studies (until 2019) were shared and compared to an age‐ and sex‐matched control group. Two raters blinded to participant identity rescored all recordings (6732 trials). After higher inter‐rater agreement was confirmed, mean conditioning per block across raters was entered into a mixed repetitive measures model. Results: Isolated dystonia (P = 0.517) and the subtypes of isolated dystonia (cervical dystonia, DYT‐TOR1A, DYT‐THAP1, and focal hand dystonia) had similar levels of eyeblink conditioning relative to controls. The presence of tremor did not significantly influence levels of eyeblink conditioning. A large range of eyeblink conditioning behavior was seen in both health and dystonia and sample size estimates are provided for future studies. Conclusions: The similarity of eyeblink conditioning behavior in dystonia and controls is against a global cerebellar learning deficit in isolated dystonia. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains an open research question. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration.Objectives: The aim of this study was to deeply characterize phenogenotypically PLA2G6-related parkinsonism in the largest cohort ever reported.Methods: We report 14 new cases of PLA2G6-related parkinsonism and perform a systematic literature review.Results: PLA2G6-related parkinsonism shows a fairly distinct phenotype based on 86 cases from 68 pedigrees. Young onset (median age, 23.0 years) with parkinsonism/dystonia, gait/balance, and/or psychiatric/cognitive symptoms were common presenting features. Dystonia occurred in 69.4%, pyramidal signs in 77.2%, myoclonus in 65.2%, and cerebellar signs in 44.6% of cases. Early bladder overactivity was present in 71.9% of cases. Cognitive impairment affected 76.1% of cases and psychiatric features 87.1%, the latter being an isolated presenting feature in 20.1%. Parkinsonism was levodopa responsive but complicated by early, often severe dyskinesias. Five patients benefited from deep brain stimulation. Brain magnetic resonance imaging findings included cerebral (49.3%) and/or cerebellar (43.2%) atrophy, but mineralization was evident in only 28.1%. Presynaptic dopaminergic terminal imaging was abnormal in all where performed. Fifty-four PLA2G6 mutations have hitherto been associated with parkinsonism, including four new variants reported in this article. These are mainly nontruncating, which may explain the phenotypic heterogeneity of childhood- and late-onset PLA2G6-associated neurodegeneration. In five deceased patients, median disease duration was 13.0 years. Brain pathology in three cases showed mixed Lewy and tau pathology.Conclusions: Biallelic PLA2G6 mutations cause early-onset parkinsonism associated with dystonia, pyramidal and cerebellar signs, myoclonus, and cognitive impairment. Early psychiatric manifestations and bladder overactivity are common. Cerebro/cerebellar atrophy are frequent magnetic resonance imaging features, whereas brain iron deposition is not. Early, severe dyskinesias are a tell-tale sign. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Impulsivity is common in people with Parkinson's disease (PD), with many developing impulsive compulsive behavior disorders (ICB). Its pathophysiological basis remains unclear. Objectives: We aimed to investigate local field potential (LFP) markers of trait impulsivity in PD and their relationship to ICB. Methods: We recorded subthalamic nucleus (STN) LFPs in 23 PD patients undergoing deep brain stimulation implantation. Presence and severity of ICB were assessed by clinical interview and the Questionnaire for Impulsive‐Compulsive Disorders in PD‐Rating Scale (QUIP‐RS), whereas trait impulsivity was estimated with the Barratt Impulsivity Scale (BIS‐11). Recordings were obtained during the off dopaminergic states and the power spectrum of the subthalamic activity was analyzed using Fourier transform‐based techniques. Assessment of each electrode contact localization was done to determine the topography of the oscillatory activity recorded. Results: Patients with (n = 6) and without (n = 17) ICB had similar LFP spectra. A multiple regression model including QUIP‐RS, BIS‐11, and Unified PD Rating Scale‐III scores as regressors showed a significant positive correlation between 8–13 Hz power and BIS‐11 score. The correlation was mainly driven by the motor factor of the BIS‐11, and was irrespective of the presence or absence of active ICB. Electrode contact pairs with the highest α power, which also correlated most strongly with BIS‐11, tended to be more ventral than contact pairs with the highest beta power, which localize to the dorsolateral motor STN. Conclusions: Our data suggest a link between α power and trait impulsivity in PD, irrespective of the presence and severity of ICB. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background and purpose: On the basis of occasional strong placebo responses, increased susceptibility to placebo has been proposed as a characteristic of functional neurological disorder (FND). The aim of this study was to clarify whether people with FND have a stronger placebo analgesic response than healthy controls. Methods: A study using a classic placebo paradigm, with additional conditioning and open‐label components, was performed in 30 patients with FND, and in 30 healthy controls. Ratings of mildly to moderately painful electrotactile stimuli were compared before and after the application of a placebo "anaesthetic" cream versus a control cream, after an additional conditioning exposure, and after full disclosure (open‐label component). Results: Pain intensity ratings at the placebo compared to the control site were similarly reduced in both groups. The conditioning exposure had no additional effect. After placebo disclosure a residual analgesic effect remained. Conclusion: Patients with FND did not have stronger placebo responses than healthy controls. The notion of generally increased suggestibility or increased suggestibility to placebo in FND seems mistaken. Instead, occasional dramatic placebo responses may occur because functional symptoms are inherently more changeable than those due to organic disease. [ABSTRACT FROM AUTHOR]

Background: Evidence supports that neurodevelopmental diseases, such as Tourette syndrome (TS), may involve dysfunctional neural‐immune crosstalk. This could lead to altered brain maturation and differences in immune and stress responses. Dendritic cells (DCs) play a major role in immunity as professional antigen‐presenting cells; changes in their frequency have been observed in several autoimmune conditions. Methods: In 18 TS patients (15 on stable pharmacological treatment, three unmedicated) and 18 age‐matched healthy volunteers (HVs), we explored circulating blood‐derived DCs and their relationship with clinical variables and brain metabolites, measured via proton magnetic resonance spectroscopy (1H‐MRS). DC subsets, including plasmacytoid and myeloid type 1 and 2 dendritic cells (MDC1, MDC2), were studied with flow cytometry. 1H‐MRS was used to measure total choline, glutamate plus glutamine, total creatine (tCr), and total N‐acetylaspartate and N‐acetylaspartyl‐glutamate levels in frontal white matter (FWM) and the putamen. Results: We did not observe differences in absolute concentrations of DC subsets or brain inflammatory metabolites between patients and HVs. However, TS patients manifesting anxiety showed a significant increase in MDC1s compared to TS patients without anxiety (p = 0.01). We also found a strong negative correlation between MDC1 frequency and tCr in the FWM of patients with TS (p = 0.0015), but not of HVs. Conclusion: Elevated frequencies of the MDC1 subset in TS patients manifesting anxiety may reflect a proinflammatory status, potentially facilitating altered neuro‐immune crosstalk. Furthermore, the strong inverse correlation between brain tCr levels and MDC1 subset frequency in TS patients suggests a potential association between proinflammatory status and metabolic changes in sensitive brain regions. [ABSTRACT FROM AUTHOR]

Although it is possible that benefits might be seen with more realistic, longer, or more intense training, we believe that these data sound a note of caution about the use of distorted feedback and hence VR in FMD treatment. 2 Bullock K, Won AS, Bailenson J, Friedman R. Virtual reality-delivered Mirror visual feedback and exposure therapy for FND: a midpoint report of a randomized controlled feasibility study. Keywords: functional tremor; functional neurological disorder; beliefs; visual feedback; virtual reality EN functional tremor functional neurological disorder beliefs visual feedback virtual reality 275 277 3 02/07/22 20220201 NES 220201 There has been considerable interest in virtual reality (VR) and augmented reality as useful tools in neurorehabilitation.1 This interest has extended recently to functional movement disorders (FMD).2 VR has potential relevance to FMD rehabilitation for several reasons, including its effectiveness in modification of beliefs and attention diversion. [Extracted from the article]

Functional movement disorder (FMD) is a common manifestation of functional neurological disorder. FMD can occur alongside other neurological conditions, but especially in patients with established Parkinson's disease (PD). An interesting observation emerging across cohort studies and case series is that FMD can precede the diagnosis of PD, suggesting that FMD may itself be a prodromal symptom of neurodegeneration. Such a notion would have significant clinical implications for the assessment and management of people with FMD, particularly with respect to decisions around the use of auxiliary investigations, counselling, and follow‐up. In this Viewpoint we review the evidence concerning the temporal relationship between FMD and PD. We discuss the potential explanations and mechanisms for FMD as a prodromal symptom of PD, and highlight clinical considerations and important outstanding questions in the field. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Patients with functional movement disorders also typically have functional somatic symptoms, including pain, fatigue, and sensory disturbance. A potentially unifying mechanism for such symptoms is a failure in processing of sensory inputs. Prepulse inhibition is a neurophysiological method that allows for the study of preconscious somatosensory processing.Objective: The objective of this study was to assess prepulse inhibition in patients with functional movement disorders and healthy control subjects.Methods: We analyzed the effect of a weak electrical stimulus to the index finger (prepulse) on the magnitude of the R2 response of the blink reflex induced by electrical stimuli delivered to the supraorbital nerve in 22 patients with clinically established functional movement disorders and 22 matched controls. Pain, depression, anxiety, and obsessive-compulsive symptoms were assessed using self-rated questionnaires. In addition, in patients we assessed motor symptom severity.Results: Prepulses suppressed the R2 response of the blink reflex in both groups, by 36.4% (standard deviation: 25.6) in patients and by 67.3% (standard deviation: 16.4) in controls. This difference was significant (P < 0.001). There was no significant correlation between motor and nonmotor symptom measures and prepulse inhibition size.Conclusions: Impaired prepulse inhibition of the blink reflex suggests an abnormal preconscious processing of somatosensory inputs, which can be interpreted within predictive coding accounts of both functional movement disorders and functional somatic syndromes. Our results, along with previous findings of a reduced prepulse inhibition in fibromyalgia syndrome, support a possible unified pathophysiology across functional neurological and somatic syndromes with noteworthy implications for diagnostic classification and development of novel biomarkers and treatments. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus-dystonia syndrome as a result of mutations in the ɛ-sarcoglycan gene (DYT11). Specifically, a cerebellar-dependent saccadic adaptation task is dramatically impaired in this patient group.Objectives: The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions.Methods: Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged-matched controls.Results: Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions.Conclusions: DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Keywords: functional overlay, functional movement disorders, movement disorders, attention, movement specific reinvestment scale EN functional overlay, functional movement disorders, movement disorders, attention, movement specific reinvestment scale 159 161 3 01/06/21 20210101 NES 210101 Attention is crucial in functional movement disorders (FMD), demonstrated by worsening of functional movement disorders when attention is directed towards the affected limb and improvement by distraction. As detailed in Table 1, we found that functional and other movement disorders patients scored equally highly on the MSRS, with both groups scoring significantly higher than healthy controls in the total and the two sub-scores. These observations might help explain why an estimated 10%-15% of movement disorders patients have an additional functional movement disorder and why 12% of patients with a neurological disease also display "symptoms unexplained by the disease".6,7 The increased attention to the body in patients with movement disorders triggered by the presence of physical symptoms might make them more susceptible to developing a functional neurological disorder in addition. [Extracted from the article]

Background: In a small group of patients, we have previously shown that a combination of electrophysiological tests was able to distinguish functional (psychogenic) tremor and organic tremor with excellent sensitivity and specificity.Objectives: This study aims to validate an electrophysiological test battery as a tool to diagnose patients with functional tremor with a "laboratory-supported" level of certainty.Methods: For this prospective data collection study, we recruited 38 new patients with functional tremor (mean age 37.9 ± 24.5 years; mean disease duration 5.9 ± 9.0 years) and 73 new patients with organic tremor (mean age 55.4 ± 25.4 years; mean disease duration 15.8 ± 17.7 years). Tremor was recorded at rest, posture (with and without loading), action, while performing tapping tasks (1, 3, and 5 Hz), and while performing ballistic movements with the less-affected hand. Electrophysiological tests were performed by raters blinded to the clinical diagnosis. We calculated a sum score for all performed tests (maximum of 10 points) and used a previously suggested cut-off score of 3 points for a diagnosis of laboratory-supported functional tremor.Results: We demonstrated good interrater reliability and test-retest reliability. Patients with functional tremor had a higher average score on the test battery when compared with patients with organic tremor (3.6 ± 1.4 points vs 1.0 ± 0.8 points; P < .001), and the predefined cut-off score for laboratory-supported functional tremor yielded a test sensitivity of 89.5% and a specificity of 95.9%.Conclusion: We now propose this test battery as the basis of laboratory-supported criteria for the diagnosis of functional tremor, and we encourage its use in clinical and research practice. [ABSTRACT FROM AUTHOR]

Background The natural fluctuation of motor symptoms of Parkinson's disease ( PD) makes judgement of any change challenging and the use of clinical scales such as the International Parkinson and Movement Disorder Society ( MDS)- UPDRS imperative. Recently developed commodity mobile communication devices, such as smartphones, could possibly be used to assess motor symptoms in PD patients in a convenient way with low cost. We provide the first report on the development and testing of stand-alone software for mobile devices that could be used to assess both tremor and bradykinesia of PD patients. Methods We assessed motor symptoms with a custom-made smartphone application in 14 patients and compared the results with their MDS- UPDRS scores. Results We found significant correlation between five subscores of MDS- UPDRS (rest tremor, postural tremor, pronation-supination, leg agility, and finger tapping) and eight parameters of the data collected with the smartphone. Conclusions These results provide evidence as a proof of principle that smartphones could be a useful tool to objectively assess motor symptoms in PD in clinical and experimental settings. [ABSTRACT FROM AUTHOR]

Background: A contribution of aberrant interoceptive awareness to the perception of premonitory urges in Gilles de la Tourette syndrome (GTS) has been hypothesized.Methods: We assessed interoceptive awareness in 19 adults with GTS and 25 age-matched healthy controls using the heartbeat counting task. We also used multiple regression to explore whether the severity of premonitory urges was predicted by interoceptive awareness or severity of tics and obsessive-compulsive symptoms.Results: We observed lower interoceptive awareness in GTS compared with controls. Interoceptive awareness was the strongest predictor of premonitory urges in GTS, with greater interoceptive awareness being associated with more urges. Greater tic severity was also associated with higher rates of premonitory urges.Conclusion: The observed relationship between severity of premonitory urges and interoceptive awareness suggests that interoception might be involved in self-reported premonitory urges in GTS. High levels of interoceptive awareness might reflect a self-attentive capacity to perceive urges. [ABSTRACT FROM AUTHOR]

Background A number of neurophysiological abnormalities have been described in patients with Parkinson's disease, but very few longitudinal studies of how these change with disease progression have been reported. We describe measures of motor cortex inhibition and plasticity at 6 and 12 mo in 12 patients that we previously reported at initial diagnosis. Given the well-known interindividual variation in these measures, we were particularly concerned with the within-subject changes over time. Methods Patients were assessed clinically, and transcranial magnetic stimulation (TMS) was used to measure motor cortical excitability, inhibition (short interval intracortical inhibition, cortical silent period), and plasticity (response to excitatory paired associative stimulation protocol) in both hemispheres. All measurements were performed 6 mo and 12 mo after the baseline experiments. Results Asymmetry in clinical motor symptoms was reflected in asymmetry of plasticity and inhibition. In the group as a whole, little change was seen in any of the parameters over 12 mo. However, analysis of within-individual data showed clear correlations between changes in clinical asymmetry and asymmetry of response to paired associative stimulation protocol and cortical silent period. Conclusions Longitudinal changes in cortical silent period and response to paired associative stimulation protocol in Parkinson's disease reflect dynamic effects on motor cortex that are related to progression of motor signs. They are useful objective markers of early disease progression that could be used to detect effects of disease-modifying therapies. The decline in heightened plasticity that was present at disease onset may reflect failure of compensatory mechanisms that maintained function in the preclinical state. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background Obsessional slowness (OS) denotes a rare condition of disablingly slow motor performance. It was originally described in patients with obsessive-compulsive disorder as a 'primary' condition; however, subsequent reports have included heterogeneous clinical populations. We wished to reassess patients with this diagnosis at our own institution and also revisit the literature to provide an overview of this condition. Methods Clinical documentation and videos of 3 patients diagnosed with OS in the National Hospital for Neurology and Neurosurgery (London, UK) were reviewed. One of the patients was clinically reappraised. A systematic review of published articles with sufficient clinical patient information was also conducted. Results Our 3 cases were male with symptom onset in adolescence or early adulthood. Motor slowness with poverty of movement and a history of obsessive-compulsive symptoms were characteristic. Poor speech production, bizarre postures, mannerisms, echophenomena, and oculogyric tics were also noted. Dopaminergic imaging was normal in 2 cases. One case had autistic features. Systematic literature review identified 77 further cases. Male preponderance with symptom onset mainly during the second decade and presence of obsessive-compulsive symptoms were noted. Additional motor and neuropsychiatric features were often present. Conclusion The existence of OS as a 'primary' condition is doubtful. This diagnosis has been given to characterize different clinical presentations ranging from obsessive-compulsive disorder with motor slowness resulting from covert obsessive-compulsive symptoms to catatonia. Clinicians should be aware of this syndrome to separate it from juvenile parkinsonism and other causes of motor slowness given that diagnostic approaches and treatment strategies differ. [ABSTRACT FROM AUTHOR]

We studied two unrelated families with several members suffering from geniospasm. Here, we aim to clarify the pathophysiology underlying the hereditary geniospasm through testing of brainstem excitability by the recovery cycles of the blink reflex ( BR) and the masseteric inhibitory reflex ( MIR). The R2 component of the BR and the SP2 component of the MIR and their recovery cycle were analyzed in 3 patients and 8 healthy, age-matched subjects as the control group. Patients with geniospasm exhibited a different excitability of the BR, compared to the control, group, as shown by the larger R2 component area of BR in controls than patients. Notably, the mean recovery index was 0.61 ± 0.19 in geniospasm patients and 0.40 ± 0.15 in controls ( P ≤ 0.05). Interestingly, the recovery cycle of the MIR showed a loss of inhibition in both patients studied, as indicated by the behavior of the SP2 component. Our cases showed a partial impairment of the activity of brainstem inhibitory interneurons, indicated by the abnormal recovery cycle of MIR. These results would implicate a mechanism akin to brainstem myoclonus for the generation of geniospasm. [ABSTRACT FROM AUTHOR]

Surround inhibition is a physiological mechanism that is hypothesised to improve contrast between signals in the central nervous system. In the human motor system, motor surround inhibition (m SI) can be assessed using transcranial magnetic stimulation ( TMS). We evaluated whether it is possible to modulate m SI, using a paradigm able to induce plastic effects in primary motor cortex ( M1). Fifteen healthy volunteers participated in the experiments. To assess m SI, we delivered single pulses at rest and at the onset of a right thumb abduction. TMS pulses over abductor digiti minimi ( ADM; surround muscle) hotspot were delivered when EMG activity in right abductor pollicis brevis ( APB; active muscle) > 100 μV was detected. Paired associative stimulation ( PAS) was delivered using peripheral median nerve electric stimulation and TMS over APB M1 area at an interstimulus interval of 21.5 ms for the real PAS ( PAS21.5) and 100 ms for the sham PAS ( PAS100). To verify the effect of PAS21.5 on m SI we collected 20 MEPs from ADM at rest and during APB movements before ( T0) and 5 ( T1), 15 ( T2) and 30 ( T3) minutes after PAS21.5. mSI from APB to ADM was present at baseline. PAS21.5 increased the amount of m SI compared with baseline whereas there was no effect after PAS100. Our results suggest that m SI is an adaptable phenomenon depending on prior experience. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Primary dystonia is characterized neurophysiologically by reduced inhibitory mechanisms and abnormal regulation of plasticity responses. The potential of anodal cerebellar transcranial direct current stimulation as a therapeutic tool in writing dystonia was examined, after the observation that cerebellar stimulation reduces responses to an associative plasticity protocol in healthy subjects. Methods Ten patients with writing dystonia completed a two-part study (sham and anodal) in which cerebellar stimulation was given simultaneously with paired associative stimulation. Electrophysiological and clinical parameters were measured before and after stimulation. Results Clinical symptoms were unchanged by cerebellar stimulation. Patients exhibited much variability in the size and direction of their plasticity responses. Excessive or topographically abnormal plasticity responses were not observed. In the subgroup of patients with facilitatory responses to paired associative stimulation in the sham condition, anodal cerebellar stimulation retained its ability to reduce the magnitude of plasticity response. Conclusions Our limited understanding of intersubject variability of plasticity responses in writing dystonia currently undermines cerebellar stimulation as a novel treatment in this subset of dystonia. Cerebellar stimulation may be beneficial in other neurological disorders with consistently exaggerated plasticity. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Surround inhibition ( SI) is a neural process that has been extensively investigated in the sensory system and has been recently probed in the motor system. Muscle-specific modulation of corticospinal excitability at the onset of an isolated finger movement has been assumed to reflect the presence of SI in the motor system. This study attempted to characterise this phenomenon in a large cohort of normal volunteers and investigate its relationship with muscle activity in the hand. Corticospinal excitability of the pathways projecting to three hand muscles [first dorsal interosseus ( FDI), abductor pollicis brevis (APB) and abductor digiti minimi ( ADM)] and electromyographic ( EMG) activity of the same muscles were assessed in 31 healthy volunteers during an isolated index finger movement. In the agonist FDI muscle both corticospinal excitability and EMG activity were found to be increased at the onset of the movement ( P < 0.001 and P < 0.001, respectively). On the contrary, in the surround ADM, there was dissociation between the corticospinal excitability (decreased: P < 0.001) and EMG activity (increased: P < 0.001). Cross-correlation analysis of the EMG activity showed that neuronal signals driving the agonist and surround muscles are not synchronised when SI is present. The results suggest a distinctive origin of the neuronal signals driving the agonist and surround muscles. In addition, they indicate that cortical output might be simultaneously modulated by voluntary and non-voluntary activity, generated in cortical and subcortical structures, respectively. [ABSTRACT FROM AUTHOR]

ABSTRACT Much attention has focused on the hypothesis that there is enhanced plasticity of sensorimotor circuits in patients with dystonia. A common experimental method to assess plasticity in dystonia research is paired associative stimulation (PAS). Excessive, nonfocal effects of PAS were observed in early studies of dystonia; however, these large effects have not been uniformly replicated. In this viewpoint, data from 15 patients with writing dystonia are presented. We suggest that, as in healthy individuals, the effects of PAS are highly variable. A review of previous studies examining PAS in writing dystonia highlights the range of results that have been observed. We conclude that current experimental evidence cannot be fully explained by the notion that PAS responses in writing dystonia are consistently excessive or nonspecific. The variability of PAS responses is such that enhanced plasticity should not be considered a dystonic fingerprint, because the direction of response can vary, and there is overlap between patient and healthy data. We also discuss evidence questioning the assumption that PAS responses are a clear correlate to levels of synaptic plasticity; we need to define more specifically what PAS responses signify in the dystonic brain. Our conclusions are limited to PAS in writing dystonia; however, much variation exists with other plasticity protocols. Large multicenter studies of both focal and generalized forms of dystonia, probing variability of individual neurophysiological profiles, are encouraged. This will reveal the true role of plasticity in the pathophysiology of dystonia and may expose subject-specific therapeutic interventions that are currently concealed. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT Successive attempts at rebranding may be behind at least some of the proliferation of terms we have at our disposal when describing patients with what are now most often referred to as 'psychogenic,' 'conversion,' or 'somatoform' symptoms. The most popular term in the movement disorder literature, 'psychogenic,' provides the aetiology of the disorder within the name, indicating that the symptoms are 'born of the mind.' Here we argue that it is logical to stop using a term that defines the disorder with regard to a poorly defined aetiology that is not supported by current evidence, and, instead, to use a broad term-functional-not as a 'polite eponym' but as a term that is freer from such assumptions and does not reinforce dualistic thinking. The main argument for change is not political or even practical, but scientific. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writer's dystonia (WD) occurs in relatives of 20% of MD patients. We conducted a 2-stage genome-wide association study in whites. Genotypes at 557,620 single-nucleotide polymorphisms (SNPs) passed stringent quality control for 127 patients and 984 controls. Ten SNPs revealed P < 10−5 and entered the replication phase including 116 MD patients and 125 healthy musicians. A genome-wide significant SNP ( P < 5 × 10−8) was also genotyped in 208 German or Dutch WD patients, 1,969 Caucasian, Spanish, and Japanese patients with other forms of focal or segmental dystonia as well as in 2,233 ethnically matched controls. Genome-wide significance with MD was observed for an intronic variant in the arylsulfatase G ( ARSG) gene (rs11655081; P = 3.95 × 10−9; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66-7.05). rs11655081 was also associated with WD ( P = 2.78 × 10−2) but not with any other focal or segmental dystonia. The allele frequency of rs11655081 varies substantially between different populations. The population stratification in our sample was modest (λ = 1.07), but the effect size may be overestimated. Using a small but homogenous patient sample, we provide data for a possible association of ARSG with MD. The variant may also contribute to the risk of WD, a form of dystonia that is often found in relatives of MD patients. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT The putative involvement of the cerebellum in the pathogenesis of cortical myoclonic syndromes has been long hypothesized, as neuropathological changes in patients with cortical myoclonus have most commonly been found in the cerebellum rather than in the suspected culprit, the primary somatosensory cortex. A model of increased cortical excitability due to loss of cerebellar inhibitory control via cerebello-thalamo-cortical connections has been proposed, but evidence remains equivocal. Here, we explore this hypothesis by examining syndromes that present with cortical myoclonus and ataxia. We first describe common clinical characteristics and underlying neuropathology. We critically view information on cerebellar physiology with regard to motorcortical output and compare findings between hypothesized and reported neurophysiological changes in conditions with cortical myoclonus and ataxia. We synthesize knowledge and focus on neurochemical changes in these conditions. Finally, we propose that the combination of alterations in inhibitory neurotransmission and the presence of cerebellar pathology are important elements in the pathogenesis of cortical myoclonus. © 2014 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Key points Sensory mismatch negativity is impaired in patients with cerebellar lesions, suggesting that the cerebellum may play an important role in this form of sensory processing., Anodal transcranial direct current stimulation over the right cerebellar hemisphere increased the amplitude of sensory mismatch negativity to stimuli delivered to the right hand while cathodal transcranial direct current stimulation reduced it., The cerebellum appears to be an important node in the network mediating sensory mismatch negativity, and tDCS is a useful method with which to manipulate sensory mismatch negativity for experimental studies., Abstract Appropriate orientation towards potentially salient novel environmental stimuli requires a system capable of detecting change in the sensorium. Mismatch negativity (MMN), an evoked potential calculated by subtracting the response to a standard repeated stimulus and a rare 'oddball' stimulus, is proposed as such a change detection mechanism. It is most widely studied in the auditory domain, but here we chose to explore the mechanism of somatosensory MMN, and specifically its dependence on the cerebellum. We recorded event-related potentials (ERPs) evoked in response to auditory and sensory stimuli from 10 healthy subjects before and after anodal, cathodal and sham transcranial direct current stimulation (tDCS) of the right cerebellar hemisphere. There was a significant increase in peak amplitude of somatosensory MMN after anodal tDCS ( F(1,9) = 8.98, P < 0.02, mean difference anodal pre-post: −1.02 μV) and a significant reduction in peak amplitude of somatosensory MMN after cathodal tDCS ( F(1,9) = 7.15, P < 0.03, mean difference cathodal pre-post: 0.65 μV). The amplitude of auditory MMN was unchanged by tDCS. These results reveal the capability of tDCS to cause bidirectional modulation of somatosensory MMN and the dependence of somatosensory MMN on the cerebellum. [ABSTRACT FROM AUTHOR]

ABSTRACT The pathogenesis and the genetic basis of adult-onset primary torsion dystonia remain poorly understood. Because of markedly reduced penetrance in this disorder, a number of endophenotypes have been proposed; many of these may be epiphenomena secondary to disease manifestation. Mediational endophenotypes represent gene expression; the study of trait (endophenotypic) rather than state (phenotypic) characteristics avoids the misattribution of secondary adaptive cerebral changes to pathogenesis. We argue that abnormal temporal discrimination is a mediational endophenotype; its use facilitates examination of the effects of age, gender, and environment on disease penetrance in adult-onset dystonia. Using abnormal temporal discrimination in unaffected first-degree relatives as a marker for gene mutation carriage may inform exome sequencing techniques in families with few affected individuals. We further hypothesize that abnormal temporal discrimination reflects dysfunction in an evolutionarily conserved subcortical-basal ganglia circuit for the detection of salient novel environmental change. The mechanisms of dysfunction in this pathway should be a focus for future research in the pathogenesis of adult-onset primary torsion dystonia. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT Propriospinal myoclonus is a rare movement disorder that is hypothesized to arise from a spinal generator that transmits activity up and down the spinal cord via long propriospinal pathways. Polymyography is mandatory for the diagnosis, but the typical electrophysiological pattern described for propriospinal myoclonus has been also found in patients with psychogenic axial jerks, supported by the presence of a Bereitschaftspotential (BP; from German, 'readiness potential,' also called the premotor potential). We evaluated polymyographic findings in 65 patients referred to us with a clinical diagnosis of propriospinal myoclonus and also looked for the presence of the BP, as detected by jerk-locked back-averaging. At clinical reassessment by a movement disorder specialist, nearly one-half of the patients had clinical clues suggestive of a psychogenic cause of the jerks. Electrophysiological studies were carried out on all 65 patients. Polymyography findings revealed an incongruent electromyographic pattern for propriospinal myoclonus in 84.6% of patients and the presence of the BP in 86.1% of the entire cohort. When taking into account either the presence of BP and/or incongruence of polymyographic features, all patients, including the approximately 50% clinically diagnosed as organic propriospinal myoclonus by a movement disorder expert, had strong neurophysiological evidence for a psychogenic origin of their jerks. The clinical distinction of propriospinal myoclonus from psychogenic axial jerks is unreliable. This is the largest cohort of patients with axial jerks reported so far and we suggest that most of the patients with a clinical picture that clinically resembles propriospinal myoclonus are likely to be psychogenic. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT Background We investigated whether clinical improvement observed after deep brain stimulation (DBS) of the globus pallidus internus (GPi) in cervical dystonia (CD) is paralleled by the normalisation of temporal discrimination thresholds (TDTs), a marker of abnormal sensory processing in CD. Methods TDT was tested in 11 patients with CD after they received DBS and was compared with TDT scores from 24 patients with CD and a group of 61 controls. Results A clear clinical response to GPi-DBS was demonstrated (total Toronto Western Spasmodic Torticollis Rating Scale scores fell from 50 to 18; P < 0.001). In contrast, TDT remained abnormal in the CD-DBS group ( P < 0.001) and was not significantly different from the abnormal TDT range observed in CD. Conclusions Underlying sensory abnormalities in temporal discrimination observed in dystonia do not seem to be corrected by successful GPi-DBS. This adds further data to the ongoing debate regarding which pathophysiological abnormalities observed in dystonia are likely to be causal in the genesis of the disease rather than epiphenomena observed secondary to abnormal motor activity. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT It has been reported that patients who have Parkinson's disease have a high prevalence of somatisation (functional neurological symptoms) compared with patients who have other neurodegenerative conditions. Numerous explanations have been advanced for this phenomenon. Here, with illustrative cases, we discuss this topic, including its clinical importance, and suggest a link between the pathophysiology of Parkinson's disease and the proposed propensity to develop functional symptoms. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT The abnormal movements seen in motor conversion disorder are affected by distraction and entrainment, similar to voluntary movement. Unlike voluntary movement, however, patients lack a sense of control for the abnormal movements, a failure of 'self-agency.' The action-effect binding paradigm has been used to quantify the sense of self-agency, because subjective contraction of time between an action and its effect only occurs if the patient feels that they are the agent responsible for the action. We used this paradigm, coupled with emotional stimuli, to investigate the sense of agency with voluntary movements in patients with motor conversion disorder. Twenty patients with motor conversion disorder and 20 age-matched and sex-matched healthy volunteers used a rotating clock to judge the time of their own voluntary key presses (action) and a subsequent auditory tone (effect) after they completed conditioning blocks in which high, medium, and low tones were coupled to images of happy, fearful, and neutral faces. The results replicated those produced previously: it was reported that an effect after a voluntary action occurred earlier, and the preceding action occurred later, compared with trials that used only key presses or tones. Patients had reduced overall binding scores relative to healthy volunteers, suggesting a reduced sense of agency. There was no effect of the emotional stimuli (faces) or other interaction effects. Healthy volunteers with subclinical depressive symptoms had higher overall binding scores. We demonstrate that patients with motor conversion disorder have decreased action-effect binding for normal voluntary movements compared with healthy volunteers, consistent with the greater experience of lack of control. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT The syndrome of deafness-dystonia is rare and refers to the association of hearing impairment and dystonia when these are dominant features of a disease. Known genetic causes include Mohr-Tranebjaerg syndrome, Woodhouse-Sakati syndrome, and mitochondrial disorders, but the cause frequently remains unidentified. The aim of the current study was to better characterize etiological and clinical aspects of deafness-dystonia syndrome. We evaluated 20 patients with deafness-dystonia syndrome who were seen during the period between 1994 and 2011. The cause was identified in only 7 patients and included methylmalonic aciduria, meningoencephalitis, perinatal hypoxic-ischemic injury, large genomic deletion on chromosome 7q21, translocase of inner mitochondrial membrane 8 homolog A ( TIMM8A) mutation (Mohr-Tranebjaerg syndrome), and chromosome 2 open reading frame 37 ( C2orf37) mutation (Woodhouse-Sakati syndrome). The age of onset and clinical characteristics in these patients varied, depending on the etiology. In 13 patients, the cause remained unexplained despite extensive work-up. In the group of patients who had unknown etiology, a family history for deafness and/or dystonia was present the majority of patients, suggesting a strong genetic component. Sensory-neural deafness always preceded dystonia. Two clinical patterns of deafness-dystonia syndrome were observed: patients who had an onset in childhood had generalized dystonia (10 of 13 patients) with frequent bulbar involvement, whereas patients who had a dystonia onset in adulthood had segmental dystonia (3 of 13 patients) with the invariable presence of laryngeal dystonia. Deafness-dystonia syndrome is etiologically and clinically heterogeneous, and most patients have an unknown cause. The different age at onset and variable family history suggest a heterogeneous genetic background, possibly including currently unidentified genetic conditions. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT Mutations or exon deletions of the epsilon-sarcoglycan (SGCE) gene cause myoclonus-dystonia (M-D), but a subset of M-D patients are mutation-negative and the sensitivity and specificity of current genetic testing criteria are unknown. We screened 46 newly enrolled M-D patients for SGCE mutations and deletions; moreover, 24 subjects previously testing negative for SGCE mutations underwent gene dosage analysis. In our combined cohorts, we calculated sensitivity, specificity, positive and negative predictive values, and area under the curve of 2 published sets of M-D diagnostic criteria. A stepwise logistic regression was used to assess which patients' characteristics best discriminated mutation carriers and to calculate a new mutation predictive score ('new score'), which we validated in previously published cohorts. Nine of 46 (19.5%) patients of the new cohort carried SCGE mutations, including 5 novel point mutations and 1 whole-gene deletion; in the old cohort, 1 patient with a complex phenotype carried a 5.9-Mb deletion encompassing SGCE. Current diagnostic criteria had a poor ability to discriminate SGCE-positive from SGCE-negative patients in our cohort; conversely, age of onset, especially if associated with psychiatric features (as included in the new score), showed the best discriminatory power to individuate SGCE mutation carriers, both in our cohort and in the validation cohort. Our results suggest that young age at onset of motor symptoms, especially in association with psychiatric disturbance, are strongly predictive for SGCE positivity. We suggest performing gene dosage analysis by multiple ligation-dependent probe amplification (MLPA) to individuate large SGCE deletions that can be responsible for complex phenotypes. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT Classical galactosemia is an autosomal recessive inborn error of metabolism leading to toxic accumulation of galactose and derived metabolites. It presents with acute systemic complications in the newborn. Galactose restriction resolves these symptoms, but long-term complications, such as premature ovarian failure and neurological problems including motor dysfunction, may occur despite adequate treatment. The objective of the current study was to determine the frequency and phenotype of motor problems in adult patients with classical galactosemia. In this cross-sectional study, adult patients with a biochemically confirmed diagnosis of galactosemia attending our clinic were assessed with an interview and neurological examination and their notes retrospectively reviewed. Patients were classified according to the presence/absence of motor dysfunction on examination. Patients with motor dysfunction were further categorized according to the presence/absence of reported motor symptoms. Forty-seven patients were included. Thirty-one patients showed evidence of motor dysfunction including: tremor (23 patients), dystonia (23 patients), cerebellar signs (6 patients), and pyramidal signs (4 patients). Tremor and dystonia were often combined (16 patients). Thirteen patients reported motor symptoms, with 8 describing progressive worsening. Symptomatic treatment was effective in 4 of 5 patients. Nonmotor neurological features (cognitive, psychiatric, and speech disorders) and premature ovarian failure were more frequent in patients with motor dysfunction. Motor dysfunction is a common complication of classical galactosemia, with tremor and dystonia the most frequent findings. Up to one third of patients report motor symptoms and may benefit from appropriate treatment. Progressive worsening is not uncommon and may suggest ongoing brain damage in a subset of patients. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Functional neurological symptoms are one of the most common conditions observed in neurological practice, but understanding of their underlying neurobiology is poor. Historic psychological models, based on the concept of conversion of emotional trauma into physical symptoms, have not been implemented neurobiologically, and are not generally supported by epidemiological studies. In contrast, there are robust clinical procedures that positively distinguish between organic and functional motor signs that rely primarily on distracting attention away from movement or accessing it covertly. We aimed to investigate the neurobiological principles underpinning these techniques and implications for understanding functional symptoms. We assessed 11 patients with functional motor symptoms and 11 healthy controls in three experimental set-ups, where voluntary movements were made either with full explicit control or could additionally be influenced automatically by factors of which participants were much less aware (one-back reaching, visuomotor transformation, and precued reaction time with variable predictive value of the precue). Patients specifically failed in those tasks where preplanning of movement could occur and under conditions of increasing certainty regarding the movement to be performed. However, they implicitly learned to adapt to a visuomotor transformation as well as healthy controls. We propose that when the movement to be performed can be preplanned or is highly predicted, patients with functional motor symptoms shift to an explicit attentive mode of processing that impairs kinematics of movement control, but movement becomes normal when such processes cannot be employed (e.g., during unexpected movement or implicit motor adaptation). © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

ABSTRACT Background Functional movement disorders (FMDs) are thought to be rare in the elderly. Clinical characteristics of the elderly people who develop FMDs are rarely reported. The objective of this study was to highlight the clinical characteristics of FMD in the elderly and compared these with a cohort of patients with a younger age of onset. Methods The authors performed a retrospective review of the clinical records of patients with FMD who were seen at their center in the last 5 years and had consented to be included in research studies. Patients fulfilling currently accepted diagnostic criteria for FMD as documented, clinically established, or probable were included. Results Of 151 patients with FMD who were identified and had sufficient information, 21.0% (n=33) had an onset after age 60 years (elderly group). The mean age of onset of FMD was 63.5 years (standard deviation, 5.2 years) in the elderly group and 35.5 years (standard deviation, 12.6 years) in the younger group. Tremor was the most common movement disorder in both groups (elderly group, 33.3%; younger group: 38.9%). Fixed dystonia was not observed in any patient who had an FMD onset after age 60 years. Gait abnormalities were significantly more common in the elderly group (69.7%) than in younger patients (23.5%; P<0.001). Associated psychogenic nonepileptic seizures tended to be more common in elderly patients (18.2%) compared with younger patients (13%; P=0.06). Conclusions Contrary to common perceptions, FMDs are not uncommon in the elderly, and 1 in 5 patients in the current cohort, onset of FMD occurred after age 60 years. Gait abnormalities and psychogenic nonepileptic seizures may be more common in older patients. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Cerebrotendinous xanthomatosis is an autosomal recessive inborn error of cholesterol metabolism. It presents with systemic and neurological symptoms, rarely including parkinsonism. Presented here are a clinical description of a new family with cerebrotendinous xanthomatosis and parkinsonism and a review of 13 additional cases reported in the literature. The index case developed corticobasal syndrome, previously not reported in cerebrotendinous xanthomatosis. His brother had parkinsonism with cerebellar features and cognitive impairment. In a literature review, median age of onset of parkinsonism was found to be 40 years. Nearly all patients had other neurological symptoms: cognitive (93%), pyramidal (93%), or cerebellar (53%). All patients had walking difficulties, with falls in 27%. Systemic features were common: cataracts (93%) or tendon xanthomata (87%). Frequent MRI abnormalities included cerebellar atrophy (100%), cerebral atrophy (80%), and dentate nuclei signal changes (80%). Functional dopaminergic imaging often demonstrated presynaptic denervation. Improvement with levodopa was frequent (91%) but mild. Progressive neurological decline occurred in 92% of patients despite treatment with chenodeoxycholic acid. Cerebrotendinous xanthomatosis should be considered in the differential diagnosis of atypical parkinsonism, including corticobasal syndrome, particularly with early age of onset and in the context of a complex neurological phenotype. Tendon xanthomata, early-onset cataracts, and radiological findings of cerebellar atrophy with lesions of the dentate nuclei are useful clinical clues. Symptomatic treatment with levodopa may help, but progressive neurological decline is frequent despite treatment with chenodeoxycholic acid. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

The majority of patients with anti- N-methyl-D-aspartate-receptor encephalitis (NMDAE) present a characteristic movement disorder, which consists of complex bilateral stereotyped movements of the arms, with perioral and eye movements, and less frequently involvement of the legs. We have observed striking similarities in the characteristics of the abnormal movements observed in NMDAE and those described in Status Dissociatus, which is characterized by a complete breakdown of state-determining boundaries (wakefulness, REM and NREM sleep) and can result from pathophysiologically diverse disorders (e.g. fatal familial insomnia, delirium tremens, Morvan's syndrome). Here, we suggest that the state of paradoxical responsiveness in which NMDAE patients present these stereotyped movements may be that of Status Dissociatus and discuss the clinical similarities and pathophysiological explanations that support such a suggestion. This hypothesis explains why patients that seem to be unconscious have a movement disorder that is not epileptic and may have management implications, since many patients with NMDAE-related movement disorder are treated with anticonvulsants that may not be indicated. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

It has been 50 years since the first patients with tardive dyskinesia (TD) were described, but the pathophysiology is only partially understood and effective treatments have remained elusive. Newer atypical antipsychotics with less nonspecific activity at dopamine receptors have not heralded the end of tardive dyskinesia and merely highlight the incomplete understanding of the disorder. We present an overview of the existing pathophysiology of the disorder and incorporate recent developments in genetics and the study of human synaptic plasticity in other hyperkinetic movement disorders. We propose a hypothesis that dopamine-receptor sensitization and altered function of the N-methyl-D-aspartate receptor produces maladaptive synaptic plasticity, which allows the encoding of abnormal motor programs, and propose studies that would falsify or support this hypothesis. In conclusion, a maladaptive synaptic plasticity' hypothesis goes some way toward filling in the gaps of existing theories of TD with the pathophysiology of other hyperkinetic movement disorders. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Palatal tremor is characterized by rhythmic movements of the soft palate and can be essential or symptomatic. Some patients can have palatal movements as a special skill or due to palatal tics. Psychogenic palatal tremor is recognized but rarely reported in the literature. Methods: We retrospectively evaluated all patients with palatal tremor seen in our center over a period of 10 years. Results: Of 17 patients with palatal tremor, we identified 10 patients with isolated palatal tremor. In 70% of those the diagnosis of psychogenic palatal tremor could be made. Of the remainder, 2 had palatal tics and 1 essential palatal tremor. Conclusions: We suggest that psychogenic palatal tremor may be underrecognized and propose that targeted clinical examination of positive signs for psychogenic movement disorders in these patients is essential. The correct identification of such patients has important clinical and scientific implications. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Approximately 10% of patients clinically diagnosed with early Parkinson's disease (PD) subsequently have normal dopaminergic functional imaging. Transcranial sonography (TCS) has been shown to detect midbrain hyperechogenicity in approximately 90% of Parkinson's disease (PD) patients and 10% of the healthy population. The aim of this study was to investigate the prevalence of midbrain hyperechogenicity in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDD), in comparison to PD patients. Methods: TCS was performed in 14 patients with SWEDD and 19 PD patients. Results: There was a significantly increased area of echogenicity in the PD group (0.24 ± 0.06 cm2), compared to the group of patients with SWEDD (0.13 ± 0.06 cm2; P < 0.001). One (9.1%) of these patients, compared to 14 (82.5%) of the PD patients, was found to have hyperechogenicity ( P < 0.001). Conclusions: We conclude that TCS is useful to distinguish PD patients from patients with suspected parkinsonism and SWEDD. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Copyright of Journal of Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The reliability and applicability of published diagnostic criteria for psychogenic movement disorders (PMDs) have never been examined. Methods: Eight movement disorder and six general neurologists rated 14 patients diagnosed with PMD and 14 patients diagnosed with organic movement disorders. Raters provided a dichotomous judgment (i.e., psychogenic or organic) upon review of video-based movement phenomenology and a category of diagnostic certainty based on the Fahn-Williams and Shill-Gerber criteria after accessing standardized clinical information. We measured interobserver agreement on the diagnosis and clinical certainty judgment of PMD. Results: In both groups of raters, agreements were 'fair' on the video-based dichotomous judgment, but improved to 'substantial' after access to standardized clinical information. 'Slight' to 'poor' agreement was reached for the 'probable' and 'possible' categories of diagnostic certainty corresponding to both diagnostic criteria. Conclusions: Diagnosis according to clinical available criteria for PMD yields poor diagnostic agreement. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Copyright of Journal of Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The foundations of the clinical classification of movement disorders rest on the precise definition of the words used to describe the disorders. Here we argue that the current use of the term stereotypy falls well short of the precision needed for either clinical or academic use, and fails both to provide a clinically useful diagnostic category and to define a set of conditions that are linked pathophysiologically. The difficulty in defining this concept is not a new one as our review of the history of the term demonstrates. We synthesise this historical background, explore why clinicians have felt it necessary to use the category of stereotypy for certain movements rather than the related category of tics, discuss the multiple uses of the term in current research and clinical practice and on this basis suggest a new definition and classification. © 2011 Movement Disorder Society [ABSTRACT FROM AUTHOR]

A confident clinical diagnosis of psychogenic tremor is often possible, but, in some cases, a "laboratory-supported" level of certainty would aid in early positive diagnosis. Various electrophysiological tests have been suggested to identify patients with psychogenic tremor, but their diagnostic reliability has never been assessed "head to head" nor compared to forms of organic tremor other than essential tremor or PD. We compared baseline tremor characteristics (e.g., frequency and amplitude) as well as electrophysiological tests previously reported to distinguish psychogenic and organic tremor in a cohort of 13 patients with psychogenic tremor and 25 patients with organic tremor, the latter including PD, essential-, dystonic-, and neuropathic tremors. We assessed between-group differences and calculated sensitivity and specificity for each test. A number of tests, including entrainment or frequency changes with tapping, pause of tremor during contralateral ballistic movements, increase in tremor amplitude with loading, presence of coherence, and tonic coactivation at tremor onset, revealed significant differences on a group level, but there was no single test with adequate sensitivity and specificity for separating the groups (33%-77% and 84%-100%, respectively). However, a combination of electrophysiological tests was able to distinguish psychogenic and organic tremor with excellent sensitivity and specificity. A laboratory-supported level of diagnostic certainty in psychogenic tremor is likely to require a battery of electrophysiological tests to provide sufficient specificity and sensitivity. Our data suggest such a battery that, if supported in a prospective study, may form the basis of laboratory-supported criteria for the diagnosis of psychogenic tremor. [ABSTRACT FROM AUTHOR]