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Background and Purpose: The neurophysiological characteristics of motor cortex have been well characterized in patients with Huntington's disease. We present the first data on cortical excitability in patients with Sydenham's chorea., Methods: Motor cortex excitability was examined using transcranial magnetic stimulation in 16 patients in the early clinical stages of Sydenham's chorea and in 17 age- and sex-matched control subjects. Investigations included resting and active motor threshold, motor evoked potential, input-output curves, contralateral silent period, and transcallosal inhibition., Results: Resting and active motor threshold were significantly higher and motor evoked potentials were significantly smaller in patients in comparison with controls. The input-output curves were shallower in both hemispheres of patients with chorea compared with controls. No significant differences were seen in silent period or transcallosal inhibition duration., Conclusion: Sydenham's chorea is characterized by reduced excitability of corticospinal output similar to that observed in Huntington's disease., (© 2014 International Parkinson and Movement Disorder Society.)

We describe a patient with hypertension, diabetes mellitus, recurrent strokes, congestive heart failure, chronic atrial fibrillation and renal failure,who was hospitalized twice for chorea. A thorough work-up excluded all common causes for chorea in the elderly. The patient's HbA1c was > 17% and the brain computerized tomography revealed dense lesions in the basal ganglia compatible with Chorea Hyperglycemia Basal Ganglia syndrome. This syndrome includes a combination of chorea, hyperglycemia and dense lesions in the basal ganglia. The hemichorea in this syndrome is provoked by non-ketotic hyperglycemia and improves with insulin treatment. The radiographic picture also improves after there is control of glucose levels and clinical improvement.

Background: Paroxysmal dyskinesia is a rare neurological disorder characterized by paroxysmal movement disorders. Paroxysmal movement disorders include kinesigenic choreoathetosis, nonkinesigenic choreoathetosis or dyskinesia (PNKD), exercise-induced choreoathetosis, and hypnogenic paroxysmal dystonia. There have been some sporadic reports of PNKD occurrences in Chinese Mainland, but none has been reported on familial PNKD. Proband and methods A 32 years old male admitted to the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China in 2009 with recurrent limb involuntary movements spanning over 30 years was diagnosed with PNKD. Family history was collected to identify if it was a case of familial or sporadic PNKD. Mutation and linkage analysis were performed to identify the pathogenic gene and the localization of the same., Results: There were five generations of 26 patients, out of which 3 of these patients died. Follow-up was conducted on 17 out of the 23 patients alive and 9 normal family members. The pedigree showed autosomal dominant inheritance, whom could be divided into light, moderate, and severe group according to clinical signs, spontaneous attack and response to drugs. All patients harbored c.20C>T (p.A7V) mutation in exon 1 of the PNKD/MR-1 gene. Preliminary linkage analyses using phenocopy rates of 0.0001 and 0.1 suggested that linkage signal localizes between D2S126 and D2S377. The functional consequence of the mutation in the disease pathogenesis is pending investigation. Conclusions We report the first case of familial paroxysmal non-kinesigenic dyskinesia (PNKD) in Chinese Mainland, which coincidentally is also the largest case of familial PNKD ever reported. This article is part of a Special Issue entitled Brain and Memory., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Chorea is a common movement disorder which can be caused by a large variety of diseases including neurodegenerative diseases, metabolic diseases, and autoimmune diseases, or can be secondary to structural changes. The basal ganglia seem to be mainly involved in the pathophysiology indicating the vulnerability of this region. The diagnosis can be challenging, especially if chorea occurs during the treatment of neuropsychiatric conditions, and in these cases, it is difficult to distinguish between medication side effects (i.e., tardive dyskinesia) and the development of a neurodegenerative disease. Most therapeutic approaches are predominantly symptomatic, with a focus on multidisciplinary care for many patients. Nevertheless, some underlying diseases can be successfully treated and must not be missed. In this review, we summarize recent new developments in the differential diagnosis of chorea syndromes and suggest a pathway for a successful diagnosis of chorea in infancy, childhood, and adulthood for daily practice.

Chaining or cascading of different actions and responses is necessary to accomplish a goal. Yet, little is known about the functional neuroanatomical-electrophysiological mechanisms mediating these processes. Computational models suggest that medium spiny neurons (MSNs) play an important role in action cascading, but this assumption has hardly been tested relating neuroanatomical and electrophysiological parameters in a human model of circumscribed MSN dysfunction. As a possible human model of circumscribed MSN dysfunction, we investigate benign hereditary chorea in a case-control study applying bootstrap statistics. To investigate these mechanisms, we used a stop-change paradigm, where we apply mathematical constraints to describe the degree of how task goals are activated with more or less overlap during action cascading. We record event-related potentials and analyze neural synchronization processes. The results show that MSN dysfunctions lead to deficits in action cascading processes only when two response options seek simultaneous access to response selection resources. Attentional selection processes are not affected, but processes reflecting the transition between stimulus evaluation and responding are affected. The results underline computational models of MSN functioning and show that dysfunction in these networks leads to a more parallel and hence inefficient response selection.

Introduction: Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare movement disorder characterized by sudden attacks of involuntary movements. Familial PNKD is an autosomal dominant trait, caused by mutations in the myofibrillogenesis regulator 1 (MR-1) gene on chromosome 2q35. Three different mutations have been described; all of them reside in the N-terminal region common to isoforms L and S, that has been suggested to code for a mitochondrial targeting sequence, necessary for the correct sub-cellular localization of the protein into mitochondria., Methods: We report on four patients of the same family, affected by PNKD. Skin fibroblasts were used to analysed oxygen consumption and to measure mitochondrial matrix calcium response after agonist stimulation. Mitotracker-based visualization was also used to assess fragmentation of the mitochondrial network., Results: the paroxysmal movements were dystonic in two patients and dystonic/choreiform in the other ones; in three cases the symptoms started in one limb and then generalized, while in one case remained focal. Three had a very early onset, within the first two years of life. The frequency of episodes showed a great variability, ranging from 2 times a day to 3 times a year, while the duration of the attacks ranged from 2 min to 1,5 h, always with sudden onset and end and complete recover in between. All affected subjects harbored a heterozygous C to T substitution in MR-1, causing an Ala9Val amino acid change in the N-terminal region. A significant reduction of oxygen consumption and altered calcium homeostasis were found in mutant fibroblasts compared to controls, while no difference was detected in mitochondrial network., Conclusions: The data on reduced oxygen consumption and altered calcium homeostasis obtained on mutant fibroblasts are the first evidences, in physiological conditions, of a mitochondrial dysfunction in PNKD., (Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Variations in clinical presentation can lead to delays in the diagnosis and initiation of treatment of anti-N-methyl-D-aspartate receptor encephalitis. Most patients have an EEG study performed early in the course of their illness. Although not specific, there may be clues in the electroclinical features that should alert clinicians and electroencephalographers to the possibility of this diagnosis. This case is a reminder that anti- anti-N-methyl-D-aspartate receptor encephalitis may present initially with a movement disorder as the sole symptom, without features of an encephalopathy. In addition, it adds to the growing body of evidence that recognition of certain electroclinical clues may shorten the time to diagnosis. [Published with video sequence].

Costeff syndrome (CS) is a rare autosomal-recessive neurological disorder, which is known almost exclusively in patients of Iraqi Jewish descent, manifesting in childhood with optic atrophy, ataxia, chorea and spastic paraparesis. Our aim was to study the clinical spectrum of CS and natural history using a cross-sectional study design. Consecutive patients with CS were recruited to the study. Patients were diagnosed based on clinical features, along with elevated urinary levels of methylglutaconic and methylglutaric acid, and by identification of the disease-causing mutation in the OPA3 gene in most. All patients were examined by a neurologist and signs and symptoms were rated. 28 patients with CS (16 males, 21 families, age at last observation 28.6 ± 16.1 years, range 0.5-68 years) were included. First signs of neurological deficit appeared in infancy or early childhood, with delayed motor milestones, choreiform movements, ataxia and visual disturbances. Ataxia and chorea were the dominant motor features in childhood, but varied in severity among patients and did not seem to worsen with age. Pyramidal dysfunction appeared later and progressed with age (r = 0.71, p < 0.001) leading to spastic paraparesis and marked gait impairment. The course of neurological deterioration was slow and the majority of patients could still walk beyond the fifth decade. While visual acuity seemed to deteriorate, it did not correlate with age. CS is a rare neurogenetic disorder that causes serious disability and worsens with age. Spasticity significantly increases over the years and is the most crucial determinant of neurological dysfunction.

Paroxysmal dyskinesias are rare, heterogeneous group of disorders characterised by recurrent attacks of involuntary movements. The four classic categories of paroxysmal dyskinesias are kinesigenic, nonkinesigenic, exercise-induced and hypnogenic. There are some patients that do not fit in these four groups of paroxysmal dyskinesia and are termed as "mixed type". We describe a 13-year-old girl who had features of both paroxysmal kinesigenic dyskinesia and paroxysmal nonkinesigenic dyskinesia that was misdiagnosed as refractory epilepsy. She improved substantially with a combination of carbamazepine and clonazepame. It is important to recognize the clinical presentation of paroxysmal dyskinesias and distinguish these movement disorders from other disorders, such as psychogenic disorders and epilepsia, for deciding the treatment and prognosis of the patients. This case highlights the importance of the recognition of a rare paroxysmal movement disorders.

Background: The step-by-step determination of the spatio-temporal parameters of gait is clinically relevant since it provides an estimation of the variability of specific gait patterns associated with frequent geriatric syndromes. In recent years, several methods, based on the use of magneto-inertial units (MIMUs), have been developed for the step-by-step estimation of the gait temporal parameters. However, most of them were applied to the gait of healthy subjects and/or of a single pathologic population. Moreover, spatial parameters in pathologic populations have been rarely estimated step-by-step using MIMUs. The validity of clinically suitable MIMU-based methods for the estimation of spatio-temporal parameters is therefore still an open issue. The aim of this study was to propose and validate a method for the determination of both temporal and spatial parameters that could be applied to normal and heavily compromised gait patterns., Methods: Two MIMUs were attached above each subject's ankles. An instrumented gait mat was used as gold standard. Gait data were acquired from ten hemiparetic subjects, ten choreic subjects, ten subjects with Parkinson's disease and ten healthy older adults walking at two different gait speeds. The method detects gait events (GEs) taking advantage of the cyclic nature of gait and exploiting some lower limb invariant kinematic characteristics. A combination of a MIMU axes realignment along the direction of progression and of an optimally filtered direct and reverse integration is used to determine the stride length., Results: Over the 4,514 gait cycles analyzed, neither missed nor extra GEs were generated. The errors in identifying both initial and final contact at comfortable speed ranged between 0 and 11 ms for the different groups analyzed. The stride length was estimated for all subjects with less than 3% error., Conclusions: The proposed method is apparently extremely robust since gait speed did not substantially affect its performance and both missed and extra GEs were avoided. The spatio-temporal parameters estimates showed smaller errors than those reported in previous studies and a similar level of precision and accuracy for both healthy and pathologic gait patterns. The combination of robustness, precision and accuracy suggests that the proposed method is suitable for routine clinical use.

Periodic lateralized epileptiform discharges (PLEDs) on electroencephlography (EEG) usually indicate an acute, diffuse, and severe cerebral insult. Although hyperglycemic hemichorea-hemiballisum (HCHB) and striatal hyperintensity on T1-weighted magnetic resonance (MR) images is an accepted clinical entity, PLEDs have not previously been reported. Herein, we report a 74-year-old man with hyperglycemic HCHB, hyperintense putamen on T1-MR images and PLEDs on EEG. Aggressive sugar control with neuroleptic treatment only slightly improved the severity of HCHB. We also tried titrated oral and intravenous haloperidol, clonazepam, and propranolol sequentially and in combination; however, the effects were poor. Unlike the generally reversibility of hyperglycemic HCHB, the condition was still present 6 months later. Hyperglycemia can cause HCHB and produce subcortical type-PLEDs, which may explain the findings in our patient. In conclusion, PLEDs can be found in patients with hyperglycemic HCHB and striatal hyperintensity on T1-weighted MR images, and the appearance of PLEDs may indicate an irreversible outcome. EEG should be considered in such circumstances., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

Background: Chorea as a nonprogressive abnormality is often associated with Sydenham chorea in the pediatric population. Benign hereditary chorea is a condition where chorea presents before age 5 years and runs a very slowly progressive course., Patients: We present a family that was thought to have a variant of Huntington disease but on genetic testing was confirmed to have benign hereditary chorea. We describe a 7-year-old girl in this family who presented with involuntary movements and hyperactivity., Results: Our family was determined to have benign hereditary chorea after extensive genetic testing and follow-up., Conclusions: When chorea presents as a familial entity, the differential diagnosis is limited and is often misdiagnosed as Huntington disease. In this family benign hereditary chorea was found to be the cause., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: P300 event-related potentials (ERPs), objective measures related to cognitive processing, have not been studied in Sydenham's chorea (SC) patients., Purpose: To assess cognitive impairment with P300 ERPs., Method: Seventeen patients with SC and 20 unaffected healthy children were included. Stanford-Binet test was used for psychometric assessment, and odd-ball paradigm was used for auditory ERPs., Results: There was no significant difference in P300 latencies between the SC-pretreatment group, SC-posttreatment group and control group (p>0.05). Mean interpeak latencies in SC-pretreatment group and SC-posttreatment group showed significant prolongation compared with the control group (p<0.05). Mean interpeak latencies in SC-posttreatment group were significantly decreased compared with SC-pretreatment group (p<0.05). Compared to controls, patients did not show significant difference in Stanford-Binet intelligence examination., Conclusion: This report suggests that interpeak latencies and amplitudes of P300 ERPs could be useful for detecting and monitoring cognitive impairment in SC patients.

Movement disorders are common following cerebrovascular accidents and they can be hyperkinetic, including hemichorea and hemiballismus, or hypokinetic, as seen in parkinsonian disorders. Monochorea has also been reported due to stroke, albeit rarely. We report a 47-year-old gentleman who presented with a history of sudden onset choreiform movement of his left lower limb. On clinical examination his motor power was normal and there were no abnormal movements in any other limb. MRI of his brain was suggestive of an infarct in the right globus pallidus interna extending up to the posterior limb of the internal capsule. He was treated with clonazepam and trihexyphenidyl. His movements improved significantly within 3 months. Monochorea in a lower limb due to an infarct in the globus pallidus interna is unusual and highlights the complexity of the pathophysiology of chorea., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Processing errors is a major requirement for behavioral adaptation. While it has been assumed that the basal ganglia play an important role in initiating these processes, the role of the striatal microstructure for these processes remains to be uncovered. Previous studies in basal ganglia diseases could not elucidate the relevance of the striatal medium spiny neuron (MSN) microstructure unambiguously because structural alterations occur together with alterations in various neurotransmitter systems. We present and examine a possible model that allows the examination of MSN dysfunction unbiased by other modulations, i.e. a case of 'benign hereditary chorea' (BHC) in comparison to healthy controls. We apply event-related potentials (ERPs) to uncover the underlying neurophysiological mechanisms underlying post-error behavioral adaptation. The BHC patient revealed a smaller error-related negativity (ERN) together with almost absent behavioral adaptation after an error and generally more error-prone behavior. Performance monitoring processes unrelated to errors, as well as response inhibition processes, were not affected in the BHC patient. The results suggest that the striatal MSN microstructural integrity is more important for error-related behavioral adaptation than for other response monitoring processes unrelated to errors., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Unlabelled: OBJECT.: To date, experience of globus pallidus internus (GPi) deep brain stimulation (DBS) in the treatment of Huntington's disease (HD) has been limited to a small number of case reports. The aim of this study was to analyze long-term motor outcome of a cohort of HD patients treated with GPi DBS., Methods: Seven patients with pharmacologically resistant chorea and functional impairment were included in a prospective open-label study from 2008 to 2011. The main outcome measure was the motor section of the Unified Huntington's Disease Rating Scale. The primary end point was reduction of chorea., Results: Patients underwent MRI-guided bilateral GPi implantation. The median duration of follow-up was 3 years. A significant reduction of chorea was observed in all patients, with sustained therapeutic effect; the mean improvement on the chorea subscore was 58.34% at the 12-month follow-up visit (p = 0.018) and 59.8% at the 3-year visit (p = 0.040). Bradykinesia and dystonia showed a nonsignificant trend toward progressive worsening related to disease evolution and partly to DBS. The frequency of stimulation was 130 Hz for all patients. DBS-induced bradykinesia was managed by pulse-width reduction or bipolar settings. Levodopa mildly improved bradykinesia in 4 patients. Regular off-stimulation tests confirmed a persistent therapeutic effect of DBS on chorea., Conclusions: GPi DBS may provide sustained chorea improvement in selected HD patients with pharmacologically resistant chorea, with transient benefit in physical aspects of quality of life before progression of behavioral and cognitive disorders. DBS therapy did not improve dystonia or bradykinesia. Further studies including quality of life measures are needed to evaluate the impact of DBS in the long-term outcome of HD.

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disorder which causes an hypercoagulation state characterized by thrombotic events, repetitive miscarriages and the presence of antiphospholipid antibodies. APS may be an isolated disease (primary APS) or associated to systemic lupus erythematous or another autoimmune conditions (secondary APS). Neuropsychiatric manifestations accompanying APS include migraine, epilepsy, chorea, dementia or psychosis. Detailed descriptions of clinical cases are lacking, and correlations between clinical and analytical findings are far from being well known. We review literature concerning neuropsychiatric manifestations in general and psychosis in particular, in patients suffering from AFS., Case Report: A 23 years-old female who presented a primary AFS with a clinical debut consisting of neuropsychiatric manifestations characterized by psychosis (with two delusion episodes) and abnormal movements such as choreiform and hemiballistic movements, initially understood as conversive symptoms., Conclusions: We discuss the pathogenesis of the psychotic and motor manifestations. The etiology is nowadays not completely understood, but cerebral small vessel thrombosis might explain part of the manifestations. We also review the role of antipsychotic and antithrombotic medication for these patients. Currently, our patient remains asymptomatic without any antipsychotic agent, only being treated with antiagregant and antipalludic therapy.

Background: Recently, PRRT2 gene mutations have been identified as a causative factor of paroxysmal kinesigenic dyskinesia (PKD). However, evidence is still lacking with respect to the genotype to phenotype correlation in PKD patients., Methods: We recruited a cohort of PKD patients with or without PRRT2 mutations for the study, and followed them for 6 months to observe the response to carbamazepine treatment., Results: Thirty-four participants were included in this study; 16 patients were positive for a hot-spot p.R217Pfs 8 heterozygous PRRT2 gene mutation, while the other 18 patients were negative for PRRT2 gene mutations. PRRT2 mutations were found to be associated with a younger age of onset, bilateral presence and a higher frequency of attacks. Furthermore, the follow-up study revealed that p.R217Pfs 8-positive patients showed dramatic improvement with complete abolition of dyskinetic episodes with carbamazepine treatment, while only 7 of the 18 patients without PRRT2 mutations showed a response to the antiepileptic drug., Conclusions: Our study indicated that positivity for PRRT2 mutation is a predictor of younger age of onset and more frequent of attacks in PKD patients. Interestingly, the presence of PRRT2 mutations also predicted a good response to carbamazepine therapy, especially at low dose. Therefore, genetic testing shows potential clinical significance for guiding the choice of medication for individual PKD cases., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Chorea rarely complicates ischemic or hemorrhagic cerebral vascular lesions. Clinical symptoms usually involve one side of the body while the injury is situated on the contralateral cerebral hemisphere. Spontaneous remission is the norm, but sometimes symptomatic treatment is required. A 58-year-old male patient who suffers from untreated high blood pressure, type II obesity, smokes 6 packs of cigarettes per year and has a moderate intake of alcohol is presented. The patient’'s recent history began three days before he appeared at the Emergency Department. His symptoms were ceaseless, involuntary movements in his left arm and foot during day and night with no restriction of voluntary movements. Physical examination and laboratory tests revealed no other findings. Magnetic resonance imaging of the brain showed hyperintensity in the right posterolateral thalamic region consistent with ischemic cerebrovascular disease. Symptomatic therapy was indicated and his underlying conditions were addressed. The importance of this case lies on the low prevalence as well as the scarcity of publications regarding vascular causes of hemichorea, including diagnosis, therapy and prognosis.

GLUT1 deficiency syndrome (GLUT1DS) is a treatable neurometabolic disorder in which glucose transport into the brain is disturbed. Besides the classic phenotype of intellectual disability, epilepsy, and movement disorders, other phenotypes are increasingly recognized. These include, for example, idiopathic generalized epilepsy and paroxysmal exercise-induced dyskinesia. Since the disorder has only been recognized for two decades and is mostly diagnosed in children, little is known about the disease course. Our purpose was to investigate the disease course of GLUT1DS patients with the classic, complex phenotype from infancy into adulthood. We performed a systematic literature review as well as a cohort study, including GLUT1DS patients aged 18 years and older. The literature search yielded a total of 91 adult GLUT1DS patients, of which 33 patients (one-third) had a complex phenotype. The cohort study included seven GLUT1DS patients with a complex phenotype who were prospectively followed up in our clinic from childhood into adulthood. Our results show that epilepsy is a prominent feature during childhood in classic GLUT1DS patients. During adolescence, however, epilepsy diminishes or even disappears, but new paroxysmal movement disorders, especially paroxysmal exercise-induced dyskinesia, either appear or worsen if already present in childhood. Intellectual disability was not systematically assessed, but cognitive functions appeared to be stabile throughout life. Like children, adolescents may benefit from a ketogenic diet or variants thereof.

Background: Nonketotic hyperglycemia is a rare cause of hemichorea. Patients with hemichorea associated with nonketotic hyperglycemia (HCNH) always have a favorable prognosis when given prompt treatment., Methods: We reviewed the medical records of 12 patients with HCNH in our hospital between January 2005 and January 2013. The clinical data, laboratory findings, and imaging features of the patients were collected., Results: All 12 patients were admitted to the hospital with a complaint of involuntary movements. Ten patients had a history of diabetes, while the other 2 patients had not been diagnosed. The mean level of blood glucose on admission was 330.7 ± 107.8 mg/dl, and the ketones were negative. A cranial computed tomography scan showed hyperdensity in the striatum, which quickly resolved. Magnetic resonance imaging showed hyperintensity on T1-weighted images without change over several months. Nearly all of the patients experienced relief from the hemichorea symptoms after correcting hyperglycemia with a combination of dopamine receptor inhibitors and the sedative lorazepam, if necessary., Conclusion: HCNH is a benign disorder, the pathogenesis of which remains unclear. Radiologic changes can provide guidance for early treatment and generally give an estimation of the degree of injury., (© 2014 S. Karger AG, Basel.)

Objective: To evaluate the clinical associations between rheumatic fever and antiphospholipid syndrome and the impact of coexistence of these two diseases in an individual., Methods: Systematic review in electronics databases, regarding the period from 1983 to 2012. The keywords: "Rheumatic Fever," "Antiphospholipid Syndrome," and "Antiphospholipid Antibody Syndrome" are used., Results: were identified 11 cases described in the literature about the association of rheumatic fever and antiphospholipid syndrome. Clinical presentation of rheumatic fever was characterized by the predominance of carditis (11/11) and chorea (7/11). Regarding the manifestations of APS, the stroke was observed in 7/11 (63.6%), with one of them having probable embolic origin., Conclusion: The present study brings the information that the association between APS and RF is quite rare, however, is of great clinical importance. Doctors who deal with the RF should include in their differential diagnosis the APS, especially in the presence of stroke in patients with RF and whose echocardiogram does not show intracavitary thrombi.

The proline-rich transmembrane protein 2 (PRRT2) gene has been recently identified as a causative gene of paroxysmal kinesigenic dyskinesia (PKD), with an insertion mutation c.649&#95;650insC (p.P217fsX7) reported as the most common mutation. However, the pathogenic mechanism of the mutation of PRRT2 remains largely unknown. Resting-state functional magnetic resonance imaging is a promising approach to assess cerebral function and reveals underlying functional changes. Resting-state functional magnetic resonance imaging was performed in 4 Chinese PKD patients with p.P217fsX7 mutation, 6 Chinese PKD patients without the mutation, and 10 healthy control subjects. Voxel-based analysis was used to characterize alterations in the amplitude of low-frequency fluctuation (ALFF). When compared with the healthy control subjects, both groups of PKD patients showed alterations in spontaneous brain activities within cortical-basal ganglia circuitry. Besides, the group of patients with p.P217fsX7 mutation also exhibited increased ALFF in the right postcenral gyrus and right rolandic operculum area, while the alteration of ALFF in group of patients without the mutation additionally involved the middle orbitofrontal cortex. Direct comparative analysis between these two patient groups revealed significantly increased ALFF in the right postcentral gyrus in the group with p.P217fsX7 mutation. Increased spontaneous brain activity in the cortical-basal ganglia circuitry, especially in the motor preparation areas, is a common pathophysiology in PKD. Differences in the spatial patterns of increased ALFF between patients with and those without the mutation might reflect the distinct pathological mechanism resulting from PRRT2 mutation.

Background: The objective of this study was to clarify the excitability profiles of the somatosensory cortices in patients with paroxysmal kinesigenic dyskinesia., Methods: Whole-head magnetoencephalography was used to record the somatosensory evoked fields elicited by paired-pulse electric stimulation of the median nerve in 15 patients with paroxysmal kinesigenic dyskinesia and in a control group of 18 age-matched, healthy volunteers. Twelve of the patients were studied in both the drug-off and drug-on state., Results: The paired-pulse inhibition ratios of the primary somatosensory cortical P35m responses and the secondary somatosensory cortical responses were significantly greater in drug-off patients with paroxysmal kinesigenic dyskinesia compared with either the drug-on patients or the control group. No significant difference in paired-pulse inhibition ratio was observed between the drug-on patients with paroxysmal kinesigenic dyskinesia and the control group., Conclusions: In patients with paroxysmal kinesigenic dyskinesia, intracortical inhibition of the primary and secondary somatosensory cortical areas is impaired, and the associated hyperexcitable phenomenon is modulatable by antiepileptic drugs., (© 2013 Movement Disorder Society.)

Paroxysmal dyskinesia (PD) is a group of rare neurological conditions which was divided into paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD) and paroxysmal exercise-induced dyskinesia (PED) according to their clinical features. PRRT2 gene was initially identified as the major gene responsible for PKD followed by presence of various PRRT2 mutations discovered in families with benign familial infantile convulsions (BFIC) and infantile convulsions and choreoathetosis (ICCA). We describe a family with characteristic PD showing overlaps in clinical pictures among the three PD subgroups, and a nonsense PRRT2 mutation c.649C>T (p.Arg217X) was also detected. This broadens the phenotypic spectrum in PRRT2-related disorders. In addition, an unusual exercise trigger observed in the proband, likely representing an underestimated occurrence, together with the current clinical PD classification is also elucidated., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: To characterize movement-related neural oscillatory activity and to clarify its neurophysiologic role in paroxysmal kinesigenic dyskinesia (PKD)., Methods: We recorded neuromagnetic event-related desynchronization (ERD) and event-related synchronization (ERS) activities in response to a self-paced finger-lifting task in 16 patients with PKD and 17 healthy controls., Results: The amplitude of α-ERD was comparable between the healthy controls and patients with PKD, whereas either the contralateral or ipsilateral β-ERS was decreased. The peak latency of contralateral β-ERS was delayed in patients with PKD. Patients with less frequent dyskinetic attacks demonstrated a larger ipsilateral β-ERS. Moreover, some patients with PKD revealed a lesser degree of contralateral preponderance of β-ERS generation., Conclusions: The present data imply a decreased postmovement inhibition of motor cortex in patients with PKD, and the inhibitory function in the contralateral hemisphere is more affected than that in the ipsilateral hemisphere.

Background: Paroxysmal kinesigenic dyskinesia is a neurological condition characterised by brief attacks of involuntary movements triggered by sudden voluntary movements., Methods: We describe the clinical, polygraphic, and genetic features of an Italian family with paroxysmal kinesigenic dyskinesia., Results: Paroxysmal kinesigenic dyskinesia manifested as brief choreoathetosic-dystonic attacks precipitated by sudden movements, varying in severity and frequency, amongst the four affected family members. The disorder follows an autosomal dominant transmission and affects female members. Mutation of SLC2A1, MR1, CACNA1A, and ATP1A2 genes was excluded by direct sequencing. Mutation analysis of the PRRT2 gene revealed a single nucleotide duplication, c.649dupC, resulting in the frameshift mutation p.Arg217Profs*8 in all affected members., Conclusion: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal movement disorder and is often misdiagnosed clinically as epilepsy. We describe a family with paroxysmal kinesigenic dyskinesia associated with PRRT2 gene mutation, mild intrafamilial clinical heterogeneity, and benign course. [Published with video sequences].

Paroxysmal dyskinesia (PxD) is a group of movement disorders characterized by recurrent episodes of involuntary movements. Familial paroxysmal kinesigenic dyskinesia (PKD) is caused by PRRT2 mutations, but a distinct etiology has been suggested for sporadic PKD. Here we describe a cohort of patients collected from our movement disorders outpatient clinic in the period 1996-2011. Fifteen patients with sporadic PxD and 23 subjects from three pedigrees with familial PKD were screened for mutations in candidate genes. PRRT2 mutations co-segregated with PKD in two families and occurred in two sporadic cases of PKD. No mutations were detected in patients with non-kinesigenic or exertion-induced dyskinesia, and none in other candidate genes including PNKD1 (MR-1) and SLC2A1 (GLUT1). Thus, PRRT2 mutations also cause sporadic PKD as might be expected given the variable expressivity and reduced penetrance observed in familial PKD. Further genetic heterogeneity is suggested by the absence of candidate gene mutations in both sporadic and familial PKD suggesting a contribution of other genes or non-coding regions.

Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder in autosomal dominant inheritance. The clinical features and genetic findings of PNKD, rarely described in the Asians, were mostly delineated from European families. The present study characterized the clinical and genetic findings of a Taiwanese PNKD family. The clinical features of our five patients in successive three generations included onset age less than 10 years, attack duration between 3 min and 4h, and a variety of aura symptoms. The attacks were provoked not by sudden action but by emotional stress, caffeine, fatigue, heavy exercise and sleep deprivation. Sleep could abolish or diminish the attack and the attacks responded well to clonazepam. Sequencing the whole coding region of PNKD/MR-1 gene identified a heterozygous c.20 C>T (p.Ala7Val) mutation which was clearly segregated in the five affected patients. Comparing our patients with previously reported 18 families with PNKD/MR-1 mutations, the majority of the patients exhibited quite similar manifestations in attack patterns and precipitating factors. The recurrent conservative mutations in different ethnicities indicate importance in the pathogenesis of PNKD., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and is characterized by involuntary, intermittent movements induced by sudden movements. Here, we describe 24 patients with PKD, whose clinical data were analyzed. The attacks of involuntary movements were all short lasting, and could involve extremities, trunk, neck, or face without alteration of consciousness. The motor function was normal between attacks, and in some cases, attacks could be evoked during examination. Most patients had normal electroencephalogram (EEG) and neuroimaging results, but 2 cases had abnormal EEGs, and another 2 cases had bilateral calcification of basal ganglion on brain computed tomography (CT) scans. Previous history of misdiagnosis was a predominant feature, while treatments based on misdiagnosis sometimes did lead to improvement. Here, we discuss the clinical characteristics, especially the abnormalities of investigations and misdiagnosis, and recent insights into the pathophysiology of PKD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Tetrabenazine (TBZ) is a monoamine storage inhibitor that was first introduced in the 1970s for the management of hyperkinetic movement disorders. Despite acceptance and usage worldwide, TBZ was only recently approved in the United States for the treatment of Huntington chorea. This review focuses on the use of TBZ in various hyperkinetic movement disorders, which are considered "rare" or "orphan" diseases, to help practitioners better understand its clinical role and use., Objective: This review describes the clinical efficacy and tolerability of TBZ in the management of dystonia, Huntington chorea, tardive dyskinesia (TDk), and tic disorders., Methods: A Cochrane Library, EMBASE, MedlinePlus, PubMed, and clinical trials database search (up to May 2012) was conducted to identify articles and studies using the subject terms tetrabenazine, Huntington disease, dystonia, tardive dyskinesia, Tourette, tics, and hyperkinetic movement. Only English-language articles were reviewed., Results: TBZ variably undergoes extensive first-pass metabolism to active metabolites, some of which are metabolized by the cytochrome P450 2D6 isozyme. Pharmacology studies demonstrate that TBZ reversibly inhibits the activity of vesicular monoamine transporter 2, resulting in depletion of central dopamine. For management of dystonias, 1 of 3 small prospective blinded studies and 4 of 5 retrospective studies reported clinical benefit with TBZ use in pediatrics and adults. For Huntington chorea, 2 randomized, double-blind, placebo-controlled studies along with open-label studies demonstrate the effectiveness of TBZ in adults. For TDk, 9 of 11 studies (prospective controlled and retrospective) reported positive benefit. For Gilles de la Tourette syndrome, 9 of 11 studies (prospective controlled and retrospective) reported positive benefit on motor and phonic tics in pediatric and adult patients. Overall, adverse effects are dose and age related and include depression, fatigue, parkinsonism, and somnolence., Conclusions: TBZ is an effective oral therapy for chorea of Huntington disease and may be considered as an alternative agent for the management of dystonia, TDk, and tic disorders (these latter 3 conditions are off-label uses in the United States). The drug possesses an acceptable tolerability profile and has been used in pediatric and adult populations., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

We describe the long-term follow-up of a patient affected by chorea mollis, a rare variant of Sydenham's chorea of which there are very few reports in the literature. Our patient, a previously healthy 8-year-old boy developed progressive clumsiness, gait disturbance, generalised hypotonia and muscle weakness, choreic movements of the limbs and behavioural disturbances. Following the diagnosis of chorea mollis, the patient received prophylaxis (monthly injections of benzathine benzyl penicillin). Within a few weeks, his clinical conditions worsened and he became bedridden and incapable of standing and walking without assistance. The choreic movements were successfully treated with sodium valproate. Independent walking was achieved 14 months after the onset of the disease. At a 4-year follow-up, the patient showed a full neurological and psychiatric recovery. The clinical course observed in our patient shows that chorea mollis may not only have a dramatic course, but also have a good long-term prognosis.

Many types of spinocerebellar ataxias (SCAs) manifest as progressive disorders with cerebellar involvement. SCA type 27 (SCA27) is a rare type of SCA caused by mutations in the fibroblast growth factor 14 gene (FGF14). FGF14 disruption caused by a de novo reciprocal chromosomal translocation between chromosomes 13 and 21 was identified in a patient with the phenotype of paroxysmal non-kinesigenic dyskinesia (PNKD). This indicated genetic heterogeneity of PNKD, since 60% of the patients with PNKD exhibit mutations in another gene responsible for PNKD, the myofibrillogenesis regulator 1 gene (MR-1). We hypothesized that the remaining 40% of patients with PNKD may have FGF14 mutations; therefore, the nucleotide sequences of MR-1 and FGF14 were analyzed in another six patients with PNKD, but no nucleotide alterations were observed in these genes for these patients. Further studies should be conducted on the phenotypic heterogeneity of FGF14 mutations and/or haploinsufficiency in SCA27 and PNKD., (Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Paroxysmal nonkinesigenic dyskinesia (PNKD) is an autosomal dominant episodic movement disorder. Patients have episodes that last 1 to 4 hours and are precipitated by alcohol, coffee, and stress. Previous research has shown that mutations in an uncharacterized gene on chromosome 2q33-q35 (which is termed PNKD) are responsible for PNKD. Here, we report the generation of antibodies specific for the PNKD protein and show that it is widely expressed in the mouse brain, exclusively in neurons. One PNKD isoform is a membrane-associated protein. Transgenic mice carrying mutations in the mouse Pnkd locus equivalent to those found in patients with PNKD recapitulated the human PNKD phenotype. Staining for c-fos demonstrated that administration of alcohol or caffeine induced neuronal activity in the basal ganglia in these mice. They also showed nigrostriatal neurotransmission deficits that were manifested by reduced extracellular dopamine levels in the striatum and a proportional increase of dopamine release in response to caffeine and ethanol treatment. These findings support the hypothesis that the PNKD protein functions to modulate striatal neuro-transmitter release in response to stress and other precipitating factors.

Episodic head tremor anecdotally occurs in the Doberman pinscher dog breed, but it is not described in sufficient detail in the literature. We evaluated 87 Doberman pinschers affected with episodic head tremor and appropriate controls. The data analyzed were collected through detailed questionnaires, elaborate telephone interviews, and video recordings. Affected dogs underwent clinical, neurological, and laboratory examination, and a detailed diagnostic workup was conducted in 5 affected dogs. Pedigrees of affected dogs were collected and reviewed. The affected dogs expressed individual phenotypes of either horizontal or vertical head movements, but rarely did a dog exhibit head movements in both directions. There was considerable variation in duration (10 seconds to 3 hours; median: 3 minutes), frequency of occurrence (1-20 episodes/day; median: 2/day) of head tremor and length of the period without head tremor (1-1,800 days; median: 60 days). Subtle dystonic posturing of the head and neck during head tremor was evident on video recordings of 5 dogs. Certain exceptional conditions such as illness, surgery, some medications, heat, pseudopregnancy, or pregnancy triggered episodes. Two main important forms of episodic head tremor were identified: a familial early-onset form (age < 1 year) that affected littermates and a sporadic form. Affected dogs were traced back to 1 common sire, also including sporadic cases. Episodic head tremor is an inherited, paroxysmal movement disorder that affects the Doberman pinscher breed. Identification of the causative genes in the future will allow us to obtain a more detailed description of the syndrome., (Copyright © 2011 Movement Disorder Society.)

Objective: The aim of this work was to describe chorea during systemic lupus erythematosus or antiphospholipid antibodies and its long-term outcome., Methods: We retrospectively analyzed clinical features, laboratory findings, imaging characteristics, and outcome in a series of 32 patients., Results: Most patients were women (28 of 32), and mean age at onset of chorea was 20.6 (9-62) years. Chorea was inaugural for 28 patients. Improvement was observed with various treatments. During follow-up (12.2 ± 11.3 years), severe manifestations of systemic lupus erythematosus were rare. Antiphospholipid antibodies were repeatedly positive for 90% of the patients. Twelve patients developed arterial thrombosis. Prophylactic treatment with antithrombotic therapy might reduce the risk of further thrombosis (8% versus 57%; P = 0.01). Cardiac valvulopathy occurred in 22 patients during follow-up. Chorea relapsed in 8 cases., Conclusions: Chorea had a good outcome in itself. This long-term follow-up shows, for the first time, that these patients have substantial risk for further arterial thrombosis., (Copyright © 2011 Movement Disorder Society.)

Chorea and other movement disorders are rarely described as paraneoplastic. The aim of this study was to describe 13 patients with paraneoplastic chorea and dystonia collected by the members of the paraneoplastic neurological syndrome (PNS) EuroNetwork and to review 29 cases from the literature. We analyzed neurological symptoms, severity of the neurological syndrome, delay in neurological diagnosis, associated cancer, oncological and neurological treatments received, and outcome. Eleven (1.2%) out of 913 patients with PNS were identified in the EuroNetwork register. Two more patients not included in the register were added. The overall population consisted of 13 patients with a median age of 75 years (range 49-82 years). In most patients, the movement disorder was classical choreoathetosis with symmetric involvement of the trunk, neck, and limbs. A minority of patients presented unilateral chorea, dystonia, and orobuccal dyskinesia. Associated symptoms, as polyneuropathy, encephalitis, psychiatric disturbances, or visual defects, were often present. The movement disorder usually had a subacute course. The most frequently associated cancer was small cell lung cancer (SCLC). Lymphoma, bowel, or kidney cancers were also reported. CV2/CRMP5 was the most frequently associated antibody, followed by Hu. Hyperintense lesions of the basal ganglia on T2-weighted images were seldom observed. Response to cancer therapy was observed in a minority of patients, but survival was short (17 months). As in other neurological diseases, movement disorders should also be suspected as paraneoplastic when they develop subacutely in older patients (usually over 50) and often in the presence of other ancillary neurological symptoms.