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Paroxysmal movement disorders include two groups of intermittent neurologic disorders: paroxysmal dyskinesia, in which episodes of involuntary hyperkinetic movements (mainly chorea and/or dystonia) occur with preserved consciousness, and episodic ataxias, which are characterized by discrete attacks of cerebellar dysfunction, sometimes associated with progressive ataxia. Since episodic ataxias are individually discussed in Chapter 8 of this volume, we herein provide a deep overview of phenotypic, genetic, pathophysiologic, diagnostic, and treatment aspects of paroxysmal dyskinesia, following the trigger-based nomenclature which distinguishes paroxysmal kinesigenic dyskinesia, paroxysmal nonkinesigenic dyskinesia, and paroxysmal exercise-induced dyskinesia. Emerging paroxysmal dyskinesia not fulfilling the criteria for the above-mentioned subtypes will also be discussed. Phenotypic and genotypic overlap among paroxysmal movement disorders, epilepsy, and migraine have progressively emerged, thus shedding light on a shared pathophysiologic framework. Advances in our understanding of the pathomechanisms underlying paroxysmal movement disorders, which involve dysfunctions of ion channels, proteins associated with the vesical synaptic cycle machinery, and proteins involved in neuronal energy metabolism, point toward a discrete number of converging pathophysiologic pathways and may lay foundations for developing target-specific therapies., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Paroxismal non-kinesigenic dyskinesia (PNKD) is a rare movement disorder manifesting as choreatic/dystonic movements, usually lasting from minutes to up to 4 h, with perserved consciousness during attacks. Primary PNKD are idiopathic or genetic disorders while secondary PNKD are associated with various neurologic and medical conditions. We present a case with PNKD and right sided hemidystonia in association with celiac disease, responsive to gluten-free diet, not previously reported in available literature. In conclusion, diagnostic tests for celiac disease should be a part of etiological investigations in patients with otherwise unexplained movement disorders including PKND. Gluten free diet could produce a favorable clinical response in those patients., (Copyright © 2019. Published by Elsevier B.V.)

Background: Sydenham's chorea is the most common acquired movement disorder of adolescence. This clinical manifestation of acute rheumatic fever has a clear and documented relationship with Group A streptococcal infections. The symptoms are involuntary choreiform movements that can affect the face and all extremities. The pathophysiology remains unclear., Case Report: A 12-year-old female was brought to the emergency department with a 2-week history of involuntary muscle spasms of her right arm and leg. Her parents reported intermittent slurred speech and difficulty grasping utensils. Physical examination revealed an awake, alert, age-appropriate female with normal cranial nerves. Patient was found to have choreoathetoid movements on the right extremities with dystonia of right leg with ambulation. Neurology consultation, computed tomography of the head, and magnetic resonance imaging of the brain did not show any acute pathology. Echocardiogram did show mild tricuspid regurgitation, suggestive of rheumatic fever. Anti-streptolysin O titer was markedly elevated, along with DNAse-B antibodies. The patient had marked improvement of movement disorder at just over 1 week later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Sydenham's chorea is a rare but important movement disorder often related to Group A streptococcus and rheumatic fever. The incidence of rheumatic fever has been decreasing in North America but continues to be much more prevalent in developing countries as well as immigrant populations. This diagnosis is rare and can occasionally be misdiagnosed as a "fidgety" child or as a psychiatric manifestation. Sydenham's chorea is important to diagnose because acute treatment and prophylactic antibiotics can help improve symptoms and minimize cardiac damage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Neuroacanthocytosis (NA) syndromes are a group of rare diseases characterized by neurological disorders and misshaped spiky red blood cells (acanthocytes) including Chorea-Acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington disease-like 2 (HDL 2), pantothenate kinase-associated neurodegeneration (PKAN), abeta- and hypobetalipoproteinemia and aceruloplasminemia. This clinically and genetically heterogeneous group of diseases shares main clinical features presenting most often as a hyperkinetic movement disorder. Even though these are long noted disease conditions, we still know only little on the underlying disease mechanisms. The current review focuses upon ChAc as the core entity of NA syndromes caused by mutations in the VPS13A gene. The support of patient organizations and the ERA-NET initiative yielded to different multidisciplinary efforts with significant progress on our understanding of ChAc. Disturbances in two pathways are currently considered to be significantly involved in the pathophysiology of ChAc, namely elevated Lyn kinase phosphorylation and decreased signaling via Phosphoinositide 3-kinase (PI3K). These recent developments may reveal potential drugable targets for causative therapies of ChAc., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Benign hereditary chorea (BHC) is a rare autosomal dominant disease that is characterized by non-progressive chorea with early-childhood-onset, congenital hypothyroidism, and neonatal respiratory distress. Although tetrabenazine and levodopa are partly effective for chorea and drop attacks in some patients, there is no standard treatment option. We herein describe a childhood case of BHC that presented with l-thyroxine-responsive drop attacks. A genetic analysis revealed an interstitial deletion that included two enhancer regions of NKX2-1, providing genetic confirmation of BHC. This is the first report to inform the connection between thyroid function and drop attacks in BHC. Moreover, our findings identify l-thyroxine as a therapeutic option for the management of drop attacks in BHC., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

The complementation group F of Xeroderma pigmentosum (XP-F) is rare in the Caucasian population, and usually devoid of neurological symptoms. We report two cases, both Caucasian, who exhibited progressive cerebellar ataxia, chorea, a mild subcortical frontal cognitive impairment, and in one case severe polyneuropathy. Brain MRI demonstrated cerebellar (2/2) and cortical (1/2) atrophy. Both patients had only mild sunburn sensitivity and no skin cancer. Mini-exome sequencing approach revealed in ERCC4, two heterozygous mutations, one of which was never described (c.580-584+1delCCAAGG, exon 3), in the first case, and an already reported homozygous mutation, in the second case. These cases emphasize that XP-F is a rare cause of recessive cerebellar ataxia and can in some cases clinically mimic Huntington's disease due to chorea and executive impairment. The association of ataxia, chorea, and sun hypersensitivity are major guidance for the diagnosis, which should not be missed, in order to prevent skin neoplastic complications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Two siblings born to non-consanguineous parents showed nystagmus and sudden opistotonic posturing from the early infancy, and subsequent developmental delay and marked choreiform movements with hypotonia in the childhood. The brother had a mild postnatal microcephaly. Brain MRI of the sister showed mild delay of myelination, dilated anterior horn and mild cerebellar atrophy. Whole exome sequencing (WES) revealed compound heterozygous mutations in MED17 gene in both siblings: c.1013-5A>G and c.1484T>G mutations transmitted from their father and mother, respectively. The c.1013-5A>G mutation caused insertion of 4 bases of intron 6 in the transcript, resulting in frameshift (p. Ser338Asnfs*15), and mutant transcript underwent nonsense-mediated mRNA decay in lymphoblastoid cells derived from two siblings. The c.1484T>G mutation substituted a leucine residue, which is highly conserved among the vertebrates, and was predicted to be damaging by in silico analysis programs. Both mutations were not registered in dbSNP data and in our 575 control exomes. These results suggest that the siblings' mutations are likely to be pathogenic. This is the second case report concerning MED17 mutations. Compared with the first reported cases of Caucasian Jewish origin, the clinical symptoms and courses are much milder and slower, respectively, in our cases. Genotype difference (a homozygous mutation versus compound heterozygous mutations) might explain these clinical differences between two cases, though early-onset nystagmus and later choreiform movements were unique in our cases. Clinical spectrum and phenotype-genotype correlations in this rare mutation should be further elucidated., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

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.)

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.)

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.)

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.)

Huntington's disease (HD) is caused by a triplet repeat expansion in the IT15 gene on chromosome 4 encoding huntingtin. Gene mutations are found in about 99% of cases, with symptoms and signs suggestive of HD. This implies the existence of other causes of this syndrome, and, in recent years, several other distinct genetic disorders have been identified that can present with a clinical picture indistinguishable from HD, termed HD-like (HDL) syndromes. So far, four genes associated with HDL syndromes have been identified, including the prion protein gene (HDL1), the junctophilin 3 gene (HDL2) and, the gene encoding the TATA box-binding protein (HDL4). In addition, a single family with a recessively inherited HD phenocopy, the exact genetic basis of which is currently unknown (HDL3), has been described. These disorders, however, account for only a small proportion of HDL cases, and the list of HDL genes and conditions is set to grow. In this article, we review the currently identified HD phenocopy disorders and discuss clinical clues to facilitate further investigations. We will concentrate on the four so-called HDL syndromes mentioned above. Other genetic choreatic syndromes such as dentatorubral-pallidoluysian atrophy, neuroferritinopathy, pantothenate kinase-associated neurodegeneration, and chorea-acanthocytosis are also briefly discussed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent attacks of dyskinesia, in which movement of one body part produces involuntary movements of other body parts. Surround inhibition (SI), a mechanism for suppression of unwanted movements, could be deficient in these patients. To test this idea, we performed a transcranial magnetic stimulation (TMS) study in drug-naive patients with PKD., Methods: TMS was set to be triggered by self-initiated flexion of the index finger at different intervals. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest. Normalized MEP amplitudes of the patients' self-triggered TMS sessions at different intervals were compared to those of the controls., Results: During index finger flexion, MEP amplitudes from the little finger muscle were unchanged in both the patients and normal subjects, however, post-movement MEP enhancement observed in the normal subjects was absent in patients with PKD. These results suggest that the functional operation of SI is itself preserved, but that post-movement excitation of surrounding muscles is deficient in PKD., Conclusions: This finding may represent that the operation of SI is extended to the post-movement period, perhaps as a compensatory mechanism for preventing unwanted movement in surrounding muscles., Significance: While many types of impaired inhibition have been described previously in PKD, this is the first possible example of increased inhibition., (Copyright 2010 International Federation of Clinical Neurophysiology. All rights reserved.)

Objective: Examine the level of intra- and inter-limb coherency in non-dyskinetic and dyskinetic patients with Parkinson's disease (PD)., Patients & Methods: Using a magnetic tracking system, whole-body 3D movements were assessed in 10 dyskinetic patients with clear monophasic peak-dose levodopa-induced dyskinesia (LID), in 10 non-dyskinetic patients and in 10 control subjects, standing with their arms out. Patients were tested during their best ON period. Coherency in the kinematics of pairs of body segments was assessed by spectral analysis. For each pair examined, we calculated the highest coherency between 0.5 and 3.0Hz and the frequency at which this maximum coherency occurred., Results: Analysis of variance showed that for 34 out of the 44 (77.3%) comparisons we studied, there were significant differences between the means of coherencies of the groups. Typically, the control group had the highest coherency and the patients with LID had the lowest. Patients with LID also tended to have their maximum coherency at higher frequencies than the control and non-dyskinetic patient groups (30 out of 44 comparisons were significant). These trends appeared in all types of inter-segment comparisons, including bilaterally symmetric segments, biomechanically linked segments (in which coherencies were higher overall in all groups, but still different between groups) and in other comparisons, but the trends were not so clear for comparisons involving the feet., Conclusion: LID is indeed incoherent in the frequency domain, suggesting that body segments may be driven by different neural outputs. The challenges of dealing with these incoherent involuntary movements when planning and executing voluntary movements must certainly play a role in motor difficulties observed in patients with LID. The fact that both dyskinetic and non-dyskinetic patients showed less coherency than controls suggests that levodopa may alter postural control by decreasing stiffness and increasing limb independence., (Copyright 2010 Elsevier B.V. All rights reserved.)

Three cases of hemichorea-hemiballismus (HC-HB) associated with nonketotic hyperglycemia were reported. Of them two patients presented as HC-HB and the remaining one as generalized chorea-ballismus (CB). Brain MRI showed characteristic T1-weighted high-intensity lesions in the contralateral or bilateral striatum without edema or mass effect. They all had a prior history of respiratory or urinary infection. Cerebrospinal fluid test in two patients showed an elevation of protein concentration with normal cell and an increased IgG content and elevated IgG index or 24 h IgG intrathecal synthesis rate. These results suggested that inflammation within the central nervous system may participate in the pathogenesis of chorea and ballismus induced by NKH.

We report herein the case of a 9-year-old girl with life-threatening hyperkinetic involuntary movement of unknown etiology. Medical treatment was ineffective for her stereotypy and choreoathetotic/ballistic movements, but bilateral stimulation of the globus pallidus immediately alleviated these symptoms. Pallidal deep-brain stimulation may be considered the therapy of choice for children with intractable hyperkinetic movement disorders.

Tic disorders are commonly considered to be childhood syndromes. Newly presenting tic disorders during adulthood are uncommon and mostly described in relation to an acquired brain lesion or as incidental tics, particularly in context with other neurological or psychiatric diseases. Tic disorder involving the ears is extremely uncommon with only few studies in English literature. In the present case, we describe an adult patient with new-onset idiopathic tics disorder involving both ears, causing social embarrassment. In addition, our patient had recent onset of the tics without any childhood or family history of tic disorders. The single most important component of management is an accurate diagnosis. At the same time, tics should be differentiated from other movement disorders such as chorea, stereotypy, and dystonias.

Benign hereditary chorea (BHC) is an autosomal dominant disorder of early onset characterised by non progressive choreic movements with normal cognitive function occasionally associated with hypothyroidism and respiratory problems. Numerous pieces of evidence link BHC with TITF-1/NKX2.1 gene mutations. We studied a patient with a familial benign hereditary chorea and normal thyroid and respiratory function. Sequence analysis of TITF-1 revealed the presence of a heterozygous C>T substitution at nucleotide 532, predicted to change an arginine (CGA) with a stop codon (TGA) at position 178 (R178X). A functional analysis shows that the mutated TTF-1 is not binding DNA, nor activating the canonical thyroid target gene promoter or interfering with the ability of wild type TTF-1 to activate transcription. In addition, the mutated protein is predominantly cytoplasmic, rather than nuclear as in the case of the wild type TTF-1. Thus, we have identified a new mutation in the TTF-1 coding gene in a patient with benign hereditary chorea. The results show that the mutation leads to a haploinsufficiency of TITF-1 and opens the question of genotype/phenotype correlation.

Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) research is based on the hypothesis that infections trigger changes in behavior and movement in children., Methods: We enrolled 693 children (ages 3 to 12 years) into a systematic, longitudinal study. Data were collected monthly for 8 months (October-May) to determine point prevalence of Group A Streptococcal (GAS) infections, tics, behavior, and choreiform movements. Simultaneous throat cultures were obtained, and relational analyses were made between GAS and movement/observation ratings., Results: Combined behavior/GAS associations (concurrent with or 3 subsequent months to GAS) revealed a strong relationship, relative risk (RR) of 1.71 (p < .0001). Detailed analysis revealed that balance/swaying and non-tic grimacing were responsible for a significant proportion of this association (RR = 2.92, p < .0001). A strong seasonal pattern was found, with fall being more significant for GAS infections and observation ratings (p < .0001) compared with winter/spring. Children with repeated streptococcus (n = 64) showed higher rates of behavior and distal choreiform observations (p = .005)., Conclusions: Motor/behavior changes were noted to occur in relationship to positive GAS culture with support that repeated GAS increases risk.

Objective: To investigate the underlying mechanism responsible for paroxysmal kinesigenic dyskinesia (PKD)., Methods: We performed a transcranial magnetic stimulation (TMS) study in 12 drug-naïve patients with PKD and 10 healthy volunteers. TMS parameters included resting motor threshold, recruitment curve of motor evoked potential amplitudes, short intracortical inhibition and facilitation, long intracortical inhibition (LICI), and silent period. We also measured compound muscle action potential., Results: LICI, representing GABA-mediated inhibition, was significantly reduced in the patients (P = 0.033), while results for all other TMS parameters tested were comparable between the two groups., Conclusions and Significance: These results suggest that a specific type of corticospinal inhibitory mechanism is impaired in patients with PKD.

Background: Among patients with tic disorders, a distinctive clinical profile of obsessive-compulsive symptomatology has been described. The present investigation was designed to document the phenomenology of obsessive-compulsive symptoms (OCS) among patients with Sydenham chorea (SC), the neurologic variant of rheumatic fever. We hypothesized that OCS occurring in association with SC would be similar to those among patients with tic disorders., Methods: The authors studied the presence of OCS in 73 patients with SC by using the Yale-Brown Obsessive-Compulsive Scale at the Pediatric Clinics of the University of Sao Paulo Medical Center in Sao Paulo, Brazil (n = 45) and at the National Institute of Mental Health in Bethesda, Maryland (n = 28)., Results: The most frequent symptoms observed among subjects with comorbid SC and OCS were aggressive, contamination, and somatic obsessions and checking, cleaning, and repeating compulsions. A principal component factor analysis yielded a five-factor solution (accounting for 64.5% of the total variance), with contamination and symmetry obsessions and cleaning compulsions loading highly., Conclusions: The symptoms observed among the SC patients were different from those reported by patients with tic disorders but were similar to those previously noted among samples of pediatric patients with primary obsessive-compulsive disorder.

Background: The natural history of valvular regurgitation detected by echocardiography in Sydenham's chorea has been lacking., Methods: Clinical assessment and transthoracic color Doppler echocardiography were independently performed for each patient with an initial attack of Sydenham's chorea and also for each normal control (Khon Kaen University, Thailand; 1991-2001) at the time of their presentations. Serial clinical examinations and echocardiography were done for each patient at 1- and at 5-year follow-up., Results: Of 44 patients, 17 (39%) had carditis (valvulitis) evident by auscultation at the time of the initial attack. Three (11%) of the 27 patients with no clinical evidence of carditis had echocardiographic evidence of acute mitral regurgitation (subclinical valvulitis). All 17 patients with carditis had echocardiographic evidence of acute mitral regurgitation. None of the 88 control children had evidence of pathologically significant valvular regurgitation. Of the 15 patients with carditis regularly followed, the persistence of a mitral regurgitation murmur and of pathologically significant valvular regurgitation by echocardiography were 33% (5/15) and 60% (9/15), respectively, at 1-year follow-up, but the persistence of both was 25% (1/4) at 5-year follow-up., Conclusions: Color Doppler echocardiography is a useful tool in the early diagnosis of rheumatic carditis (valvulitis) and at 1-year follow-up of rheumatic valvular heart disease in the patients with initial Sydenham's chorea but the incremental benefit beyond 5 years after the initial attack might be minimal.

Objective: Choreic movements of patients with Huntington's disease (HD) may result from an abnormal control of sensory inputs. In order to further examine the pathophysiology of facial choreic movements (FCM), we carried out a neurophysiological study, including prepulse inhibition of the blink reflex (BR), in HD patients with and without FCM., Methods: The study was conducted in 20 genetically proven HD patients with Unified Huntington Disease Rating Scale (UHDRS) scores of FCM ranging between 0 and 3, and in 12 age-matched healthy volunteers who served as control subjects. We counted the number of spontaneous blinks, recorded the electromyographic activity underlying FCM, and analyzed latency, amplitude, and duration of the BR responses to electrical and auditory stimuli. Prepulse inhibition was studied by comparing the responses to test trials with those to control trials. In control trials BRs were obtained to either a single supraorbital nerve electrical stimulus (EBR) or to a 90dB auditory stimulus (ABR). In test trials, the same stimuli were preceded by the prepulse, which was either a weak acoustic tone or a weak electrical stimulus to the third finger, delivered 30-150 ms before., Results: Spontaneous blinking rate was abnormally low in 3 patients, and abnormally high in 9 patients. Mean duration of the BR was longer in patients than in control subjects. In prepulse trials, the percentage inhibition of the BR was abnormally reduced in 15 patients to at least one sensory modality, and significantly correlated with the score of FCM., Conclusions: Our results suggest that the severity of FCM in patients with HD might be an expression of a disturbance in motor control partly related to an abnormal processing of sensory inputs. Such abnormality involves circuits used in prepulse inhibition of the BR.

Mutations in ion channels, or channelopathies, often lead to neurological disorders in which normal behavior is interrupted by attacks of debilitating symptoms such as pain, weakness or abnormal motor control. Attacks are often precipitated by similar stimuli, including stress, caffeine, ethanol, exercise or fatigue. The tottering mouse inherits a mutation in P/Q-type calcium channels and reliably exhibits attacks of abnormal movements, or dyskinesia. To determine if this mouse mutant is an appropriate model to study episodic neurological disorders, tottering mice were exposed to different environmental conditions or drugs known to precipitate attacks in humans. Stress, caffeine and ethanol all reliably induced attacks in tottering mice. Since calcium influx has previously been implicated in stress-induced tottering mouse attacks, the L-type calcium channel antagonist, nimodipine, and the NMDA receptor antagonist, MK 801, were tested for their ability to prevent attacks caused by caffeine or ethanol administration. Nimodipine blocked both caffeine- and ethanol-induced attacks, while MK 801 was effective against stress- and caffeine-induced attacks. These results support a common role for excess neuronal excitability and increased calcium influx in attacks triggered by diverse agents. Together, these results suggest that the tottering mouse is a novel model to investigate triggers of episodic neurological disorders.

Background: Sydenham's chorea is still the most frequently seen form of acquired chorea in childhood in developing world despite the use of antibiotics. It is a debilitating illness lasting for weeks or months and requires drug therapy., Objective: To evaluate and compare the efficacies of sodium valproate and carbamazepine in the treatment of the choreiform movements in Sydenham's chorea., Design: A prospective trial carried out with 24 children with Sydenham's chorea., Patients: Twenty-four patients were divided into two groups having similar demographic and clinical properties. One group (n = 17) was given carbamazepine (15 mg/kg per day) and the other (n = 7) was given sodium valproate (20-25 mg/kg per day). As soon as the symptoms were taken under control, doses of the drugs were tapered slowly. The duration of the drug use was recorded. The time of response to therapy was compared between the groups and the patients were monitored for the adverse effects., Results: There was no significant difference between the groups with respect to the time of clinical improvement and time of complete remission, duration of the therapy and the recurrence rates. Clinical improvement began by 8.0 +/- 4.0 days in sodium valproate and 7.4 +/- 8.2 days in carbamazepine group (P = 0.88). In the whole group no adverse effect was seen due to the drugs., Conclusion: Carbamazepine and valproic acid are equally effective and safe drugs in the treatment of choreiform movements in Sydenham chorea.

Background: Clinical data across the globe especially in genetic diseases like Huntington's disease (HD) is most helpful when collected using standardized formats. This helps in proper comparison of clinical and genetic data., Methods: Herein, we report clinical data on 26 genetically confirmed HD patients from 19 Indian families predominantly from South India. Clinical data and evaluation was performed using standardized formats used by the Huntington Disease Study Group., Results: Adult onset HD was commonest while Juvenile HD (onset <20 years) was observed in approximately 15% of patients. Chorea was the commonest presenting symptom (n=23, 88.5%) while remaining presented with psychiatric symptoms (n=3, 11.5%). Impairment of saccades was observed in approximately 75% of patients. Mean (SD) CAG repeats in the abnormal allele was 48.4 (8.7). Total motor score but not the total behavioral score worsens with duration of symptoms. The functional checklist score correlates with total motor score rather than with duration of symptoms., Conclusions: We detail clinical characteristics in genetically confirmed HD patients from a predominantly South Indian cohort. We observed a slightly higher occurrence of Juvenile HD. Functional disabilities in our patients correlate with worsening of motor rather than behavioral symptoms.

We describe the unusual case of a 51-year-old woman with spinocerebellar ataxia type 1 (SCA1) who showed choreiform movements in addition to cerebellar ataxia. To date, extrapyramidal signs including involuntary movements have been rarely reported in SCA1. Surface electromyogram in our patient revealed grouped discharges whose duration was longer than that of chorea observed in HD, indicating that the involuntary movements represented choreoathetosis rather than pure chorea. These choreiform movements have not been seen in non-hereditary spinocerebellar ataxia. Therefore, if "sporadic" cases of cerebellar ataxia show such movements, the possibility of genetic origin of the ataxia is high and a surveillance of various forms of hereditary spinocerebellar ataxia including SCA1 is required.

We have studied the function of inhibitory interneurons within the motor cortex in several movement disorders using a paired-pulse magnetic stimulation technique. Their function was disturbed in patients with dystonia or focal lesions of the basal ganglia. On the other hand, the inhibition was normal in patients with chorea or essential tremor. The inhibitory circuit in the motor cortex must be functionally involved in some movement disorders probably because of changes of the inputs from basal ganglia to motor cortices, but not involved in the others. This difference in the functional involvement of inhibitory interneurons of the motor cortex may reflect different pathogenesis of these movement disorders.

A male adolescent presented with aggression, depressed mood, and severe movement disorder that developed at age 5 after exposure to neuroleptics. Evaluation revealed acanthocytes in his blood, which led to a differential diagnosis of tardive dyskinesia versus choreoacanthocytosis. However, this is unusually young age of onset for these conditions. Differential diagnosis, medication management of the movement disorder, and pathophysiological mechanisms in tardive dyskinesia and choreoacanthocytosis are discussed.

A 51-year-old man developed weakness and muscle atrophy in the legs at the age of 41, later followed by choreiform involuntary movements. Neurological and laboratory examinations revealed severe muscle weakness and atrophy, and areflexia in all the extremities, acanthocytosis and an elevated serum creatine kinase level. Together with these findings, the weak expression of Kell blood group antigens and the absence of the Kx antigen led to a definite diagnosis of McLeod syndrome for his condition. Brain magnetic resonance imaging revealed marked atrophy of the head of the caudate nuclei. Although immunocytochemical analysis of dystrophin in muscle specimens from our patient revealed normal staining, we found prominent fiber size variability, central nuclei, and connective tissue proliferation as well as necrotic and regenerating fibers, which are as a whole compatible with the myopathology of muscular dystrophy. Moreover, muscle computerized tomography of the lower extremities revealed the 'selectivity pattern' characteristically reported in muscular dystrophies including Duchenne type muscular dystrophy. The muscular symptoms and pathology in McLeod syndrome have been reported to be mild, but the present case clearly shows that the muscular features in this condition may be much more severe than previously thought.

We compared the regularity of involuntary muscle contractions in patients with Huntington's disease, vascular chorea, hemiballism and parkinsonian tremor to clarify the nature of phasic involuntary movements caused by lesions in the basal ganglia. Rectified and smoothed electromyograms (EMGs) in involuntary contractions of the predominantly affected muscles were analyzed. After detecting the muscle whose EMG waves showed the most regular rhythm, the frequency, coefficients of variation of interval, amplitude and rise time of the successive EMG waves were compared. The regularity of the intervals of the EMG waves in vascular chorea was significantly greater than that in Huntington's chorea, and some patients with vascular chorea showed a regular rhythm the degree of which approximated that of parkinsonian tremor. The regularity of the intervals of the EMG waves in hemiballism was greater than that in Huntington's chorea, but lower than that in vascular chorea. The regularities of interval, amplitude and rise time all showed the same ordering across the patient groups. The high regularity of muscle contraction intervals in vascular chorea and hemiballism may arise from neural circuits that are abnormally activated as well as those producing tremor.

We describe the combination of acute bilateral ballism and anterior opercular syndrome in a 75-year-old female hypertensive patient with bilateral multiple small infarcts involving the basal ganglia, the subcortical white matter and the area of the subthalamic nucleus, detected by CT scan and MRI. These clinical manifestations were accompanied by apathy, somnolence and cognitive changes usually observed in cortical involvement. Pathogenetic mechanisms for this unusual clinical picture are discussed on the basis of CT, MRI, and SPECT findings.

Incapacitating respiratory distress was the presenting manifestation of a choreiform movement disorder. Because the patient also had asthma, respiratory distress was at first mistakenly attributed to this condition. Despite vigorous asthma management, there was no improvement. However, once the neurologic condition was recognized, use of specific therapy (haloperidol and reserpine) resulted in rapid and sustained remission of respiratory symptoms.

A patient is presented with paroxysmal choreoathetosis precipitated by movement, sound and photic stimulation associated with an arterio-venous malformation (AVM) who responded to carbamazepine treatment. Hemodynamic circulatory disorder of the sensory-motor cortices having AVM may alter striatal function and produce paroxysmal choreoathetosis. This finding supports the concept that paroxysmal choreoathetosis results from an abnormality at the connections between basal ganglia and cerebral cortices.

Extrapyramidal symptoms are extremely rare in multiple sclerosis. We examined a patient with a ten year history of multiple sclerosis, who developed choreoathetoid movements of both upper extremities. To our knowledge this is the second case report of this association.

Visual, brain-stem auditory and somatosensory evoked potentials were obtained in two patients with choreoacanthocytosis. Only minor SSEP amplitude reduction was found in one patient. Therefore evoked potentials were not helpful in identifying patients with symptoms of this disorder of up to 8 years duration.

During the last decade nine adult patients were seen with an unilateral choreoathetosis or choreoballism of acute onset. In seven a hemodynamically significant lesion in a carotid artery has been detected; in four the artery was completely occluded. In one there was a subclavian steal syndrome, and in another the etiology remained unclear. Three patients had their dyskinesia at the same side as the carotid artery lesion, and four at the controlateral side.