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Objective: To investigate the cause of the motor asymmetry in Wilson's disease (WD) patients using functional MRI., Methods: Fifty patients with WD and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. All study subjects underwent diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI), and resting-state functional MRI (rs-fMRI) of the brain. Six regions of interest (ROI) were chosen. Fiber volumes between ROIs on DTI, corrected phase (CP) values on SWI, amplitude of low-frequency fluctuation (ALFF), and regional homogeneity (REHO) values on rs-fMRI were determined. Asymmetry index (right or left value/left or right value) was evaluated., Results: Asymmetry of rigidity, tremor, choreic movement, and gait abnormality (asymmetry index = 1.33, 1.39, 1.36, 1.40), fiber tracts between the GP and substantia nigra (SN), GP and PU, SN and thalamus (TH), SN and cerebellum, head of the caudate nucleus (CA) and SN, PU and CA, CA and TH, TH and cerebellum (asymmetry index = 1.233, 1.260, 1.269, 1.437, 1.503, 1.138, 1.145, 1.279), CP values in the TH, SN (asymmetry index = 1.327, 1.166), ALFF values, and REHO values of the TH (asymmetry index = 1.192, 1.233) were found. Positive correlation between asymmetry index of rigidity and fiber volumes between the GP and SN, SN and TH ( r  = .221, .133, p  = .043, .036), and tremor and fiber volumes between the CA and TH ( r  = .045, p  = .040) was found., Conclusions: The neurological symptoms of patients with WD were asymmetry. The asymmetry of fiber projections may be the main cause of motor asymmetry in patients with WD.

Objective: To determine whether neuroanatomically heterogeneous strokes causing hemichorea-hemiballismus localize to a common functional network., Methods: We identified 29 cases of lesion-induced hemichorea-hemiballismus from the literature and mapped each lesion volume onto a reference brain. Using a recently validated technique termed lesion network mapping, we tested whether these lesions belonged to the same functional network. To accomplish this, the network of brain regions functionally connected to each lesion was identified using a connectome dataset from healthy participants. Network maps were overlapped to identify any region functionally connected to our set of lesions. Specificity was evaluated using a case-control design; control cohorts included a group of similar lesions randomized to different brain locations and a second group of lesions causing a separate movement disorder, asterixis. Reproducibility was evaluated using an independent cohort of 10 additional hemichorea-hemiballismus cases., Results: Lesions showed heterogeneity in anatomical location, consistent with prior reports. However, at least 90% of these lesions showed network overlap in the posterolateral putamen. This result was specific to lesions causing hemichorea-hemiballismus and reproducible in an independent cohort. The putaminal overlap site was itself connected to a broader motor network that predicted the distribution of lesions causing hemichorea-hemiballismus., Conclusions: Strokes causing hemichorea-hemiballismus, while anatomically heterogeneous, localize to a common functional network. Specifically, lesions occur in regions functionally connected to the posterolateral putamen, a region previously implicated in hyperkinetic movement disorders. Lesion network mapping may be useful in identifying the neuroanatomical substrates of heterogeneous lesion-based disorders., (© 2016 American Academy of Neurology.)

Choreoathetoid involuntary movements are rarely reported in patients with frontotemporal lobar degeneration (FTLD), suggesting their exclusion as a supportive feature in clinical diagnostic criteria for FTLD. Here, we identified three cases of the behavioral variant of frontotemporal dementia (bvFTD) that display chorea with fused in sarcoma (FUS)-positive inclusions (FTLD-FUS) and the basophilic inclusion body disease (BIBD) subtype. We determined the behavioral and cognitive features in this group that were distinct from other FTLD-FUS cases. We also reviewed the clinical records of 72 FTLD cases, and clarified additional clinical features that are predictive of the BIBD pathology. Symptom onset in the three patients with chorea was at 44.0 years of age (±12.0 years), and occurred in the absence of a family history of dementia. The cases were consistent with a clinical form of FTD known as bvFTD, as well as reduced neurological muscle tone in addition to chorea. The three patients showed no or mild parkinsonism, which by contrast, increased substantially in the other FTLD cases until a later stage of disease. The three patients exhibited severe caudate atrophy, which has previously been reported as a histological feature distinguishing FTLD-FUS from FTLD-tau or FTLD-TAR DNA-binding protein 43. Thus, our findings suggest that the clinical feature of choreoathetosis in bvFTD might be associated with FTLD-FUS, and in particular, with the BIBD subtype.

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.

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_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.

Benign hereditary chorea (BHC, MIM 118700) is a rare autosomal dominant disorder manifesting with chorea in conjunction with hypothyroidism and respiratory problems, a triad also named "brain-lung-thyroid syndrome". BHC is characterized by childhood onset with minimal or no progression into adult life and normal cognitive function. The genetic basis of BHC has been partially resolved, when mutations in the TTF1 gene on chromosome 14q13 encoding the thyroid transcription factor-1 have been identified in a number of BHC patients, suggesting that aberration of TTF1 transcriptional function or haploinsufficiency is associated with this disorder. TTF1 (also known as TITF1, TEBP or NKX2-1), belonging to the NKX2 homeodomain transcription factor family, has been implicated in several important molecular pathways essential for brain, thyroid and lung morphogenesis. Clinical evaluation of TTF1 gene mutations carrier patients exposed the involvement of each of the triad's components characterized by heterogeneity between index cases and even within families. This review highlights the current updates on expanded clinical aspects of BHC, imaging and treatment experience, its genetic markers, proposed molecular mechanisms, animal models and link to cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The major objective of this project was to characterize the systemic disposition of the pyrethroid, deltamethrin (DLT), in immature rats, with emphasis on the age dependence of target organ (brain) dosimetry. Postnatal day (PND) 10, 21, and 40 male Sprague-Dawley rats received 0.4, 2, or 10 mg DLT/kg by gavage in glycerol formal. Serial plasma, brain, fat, liver, and skeletal muscle samples were collected for up to 510 h and analyzed for DLT and/or 3-phenoxybenzoic acid (PBA) content by high-performance liquid chromatography. Toxicokinetic data from previous experiments of the same design with young adult (PND 90) rats (Kim, K.-B., Anand, S. S., Kim, H. J., White, C. A., and Bruckner, J. V. [2008]. Toxicokinetics and tissue distribution of deltamethrin in adult Sprague-Dawley rats. Toxicol. Sci. 101, 197-205) were used to compare to immature rat data. Plasma and tissue DLT levels were inversely related to age. Preweanlings and weanlings showed markedly elevated brain concentrations and pronounced salivation, tremors, choreoathetosis, and eventual fatalities. Plasma DLT levels did not reliably reflect brain levels over time. Plasma:brain ratios were time and dose dependent, but apparently not age dependent. Brain levels were better correlated with the magnitude of salivation and tremors than plasma levels. Hepatic intrinsic clearance of DLT progressively increased during maturation, as did the hepatic extraction ratio. Thus, limited capacity to metabolically inactivate DLT appeared primarily responsible for the inordinately high target organ doses and acute neurotoxicity in pups and weanling rats. Hepatic blood flow was not rate limiting in any age group. Limited DLT hydrolysis was manifest in vivo in the pups by relatively low plasma PBA levels. Elevated exposure of the immature brain to a pyrethroid may prove to be of consequence for long-term, as well as short-term neurotoxicity.

A 31-year-old woman with moyamoya disease presented with choreiform movements persisting for 4.5 years. Magnetic resonance imaging showed a fine vascular plexus in the base of the brain but no parenchymal brain damage. Cerebral angiography revealed intracranial vascular abnormalities compatible with moyamoya disease. Single photon emission computed tomography with N-isopropyl-p-(123)I-iodoamphetamine showed definite reduction of the regional cerebral blood flow (rCBF) in the bilateral striata and frontotemporoparietal cortex. rCBF study with acetazolamide administration indicated marked decrease of rCBF reserve in those regions. She underwent indirect bypass surgery (encephalo-duro-arterio-myo-synangiosis) under a diagnosis of moyamoya disease. The choreic involuntary movements disappeared shortly after surgery. Postoperative angiography showed neovascularization in the extracranial to intracranial direction, associated with dramatic increase in rCBF in the involved regions.

Benign hereditary chorea is an autosomal dominant disease with an early onset of symptoms. In some families, symptoms tend to decrease in adulthood, suggesting that the disorder results from a developmental disturbance in the brain. Individuals with benign hereditary chorea, a nonprogressive disease, have normal or slightly below normal intelligence. The locus for benign hereditary chorea is on chromosome 14. Benign hereditary chorea is a result of mutations in the thyroid transcription factor 1 gene. Previous neuroimaging and pathological investigations of the brain showed no notable abnormalities in patients with this condition. In this study, 5 patients from 1 family with typical clinical features of benign hereditary chorea are presented. Clinical severity varied considerably in the family. Brain magnetic resonance imaging results were normal. Brain single photon emission computed tomography in 3 children, performed 1 hour after intravenous injection of 0.35 mCi/kg of body weight of technetium 99m ethyl cysteinate dimer, showed markedly decreased uptake in the right striatum and the right thalamus in 1 child. The oldest child had mildly reduced uptake in the right putamen and the left thalamus. Brain single photon emission computed tomographic findings in the youngest child were normal. Contrary to other reports of radionuclide brain imaging, notable brain single photon emission computed tomography changes were detected in 2 of 5 patients. Brain single photon emission computed tomography findings did not seem to correlate with the clinical status of the children.

The X-linked McLeod neuroacanthocytosis syndrome is a multisystem disorder with central nervous system manifestations resembling Huntington's disease. We examined 5 McLeod patients and 5 asymptomatic heterozygous females with fast multiple spin-echo spectroscopic imaging. Three patients with pronounced psychiatric or cognitive manifestations had pathological N-acetyl aspartate/(creatine + choline) ratios in frontal, temporal, and insular areas, with an individual pattern. Two patients with a severe choreatic movement disorder had unilateral thalamic alterations. One patient with moderate movement disorder and personality disorder had bilateral occipital alterations. One female heterozygote had unilateral insular metabolic alterations, possibly indicating subclinical cerebral involvement. Although the prominent psychiatric and cognitive manifestations in McLeod patients suggest significant and widespread cortical abnormalities, previous neuroradiological and histopathological data had not revealed definite extrastriatal pathology. Our findings demonstrating metabolic abnormalities in different brain regions of McLeod patients might either reflect neuronal dysfunction due to impaired basal ganglia-thalamo-cortical circuits or subtle structural alterations in the particular cerebral areas., (Copyright 2006 S. Karger AG, Basel.)

Background A 75-year-old woman with rheumatoid arthritis presented with a 4-year history of chorea to a hospital movement disorder clinic. The involuntary movements were initially mild, affecting only the right side of the body, but gradually worsened and became bilateral. There was no relevant family history. Medications included hormone replacement therapy (HRT), diclofenac sodium, vitamin D, folic acid, methotrexate and zopiclone. On examination, bilateral choreiform movements were seen, affecting the face and limbs, with the right side more severely affected than the left. Investigations Neuropsychological testing, laboratory blood and DNA testing, echocardiogram, MRI of the brain, and brain perfusion single-photon emission computed tomography (SPECT) scanning.Diagnosis HRT-related chorea, possibly caused by a predisposition secondary to rheumatoid arthritis and small-vessel ischemic disease, or subclinical childhood rheumatic fever. Management Discontinuation of HRT.

We report four cases of adult recurrence of Sydenham's chorea (SC). The first episodes all followed childhood tonsillopharyngitis. Many years later, subsequent episodes appeared after the triggering circumstances: throat or cutaneous infection, pregnancy, childbirth, contraceptive treatment or stress. Other inflammatory diseases were ruled out and streptococcal serology was weakly positive. Magnetic Resonance Imaging (MRI) revealed focal areas of T2 hypersignal in the caudate nucleus, the pallidum, the putamen and the white matter. One year later, repeat MRI variously gave evidence of the persistence, disappearance or even new appearance of abnormalities. Specific features of SC recurrence in the adult may include: a personal history of chorea after a throat infection during childhood; a second episode of isolated chorea with or without slight neuropsychological disorders; streptococcal serology weakly positive; focal hypersignals involving the basal ganglia; the triggering circumstances. Since SC is considered to be an autoimmune disease, the progressive MRI abnormalities suggest that certain circumstances may trigger the reactivation of persistent immune disorders.

We report on a patient with senile chorea, treated with deep brain stimulation of the left globus pallidus internus and subsequently the left ventralis oralis posterior nucleus of the thalamus. Deep brain field potential recordings and functional imaging using single photon emission tomography enabled us to suggest pathophysiological mechanisms for the symptoms., (Copyright 2004 Movement Disorder Society)

Group A streptococcal infections cause a wide range of neuropsychiatric disorders, such as Sydenham's chorea, tics, obsessive-compulsive disorders, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography, single-photon emission computed tomography) imaging studies in patients with Sydenham's chorea have suggested reversible striatal abnormalities. The objective of this study was to investigate the cerebral perfusion patterns of the subcortical structures by using hexamethylpropylenamine oxime single-photon emission computed tomography (HMPAO-SPECT) in seven cases of Sydenham's chorea and two cases of streptococcal tic disorder. HMPAO-SPECT studies revealed a hyperperfusion pattern in two and a hypoperfusion pattern in five of the chorea patients and in two patients with tic disorder. The results are discussed in relation to the duration and severity of the symptoms and the response to therapy. Functional imaging findings can be variable in Sydenham's chorea, and hyperperfusion of the striatum and thalamus could be an indicator of the response to therapy and the severity of symptoms. However, the number of cases so far investigated by either SPECT or positron emission tomography is still too limited to draw any firm conclusions.

Fibroblast growth factor 14 (FGF14) belongs to a distinct subclass of FGFs that is expressed in the developing and adult CNS. We disrupted the Fgf14 gene and introduced an Fgf14(N-beta-Gal) allele that abolished Fgf14 expression and generated a fusion protein (FGF14N-beta-gal) containing the first exon of FGF14 and beta-galactosidase. Fgf14-deficient mice were viable, fertile, and anatomically normal, but developed ataxia and a paroxysmal hyperkinetic movement disorder. Neuropharmacological studies showed that Fgf14-deficient mice have reduced responses to dopamine agonists. The paroxysmal hyperkinetic movement disorder phenocopies a form of dystonia, a disease often associated with dysfunction of the putamen. Strikingly, the FGF14N-beta-gal chimeric protein was efficiently transported into neuronal processes in the basal ganglia and cerebellum. Together, these studies identify a novel function for FGF14 in neuronal signaling and implicate FGF14 in axonal trafficking and synaptosomal function.

Five female patients developed chorea concurrent with, or shortly after a hyperglycemic episode (admission glucose values 500-1,000 mg/dL). In four of these five patients, there was no prior history of diabetes mellitus. The chorea continued despite correction of blood glucose and persisted to the time of last follow-up, 6 months to 5 years later. The chorea developed subacutely over 2 days to 1 month and was generalized in one, unilateral in three, and involved right > left lower extremity in the other; the severity initially reached ballistic proportions in two. Associated clinical features were nil in four of these patients, but cognitive impairment and personality change occurred in one. The histories and laboratory studies identified no predisposing factors other than the hyperglycemia. The chorea was sufficiently troublesome to require administration of neuroleptic medication in all five cases. Four of the five cases had high signal intensity within basal ganglia on T1-weighted magnetic resonance (MR) imaging, as has previously been described; however, this was not seen in one case (who had the most severe clinical condition). Most previously described cases have involved a reversible clinical syndrome, in contrast to our patients. The pathogenic mechanisms remain uncertain., (Copyright 2001 Movement Disorder Society.)

Regional cerebral glucose metabolism (rCMRGlu-18FDG) was measured in 6 cases with rigid type Parkinson's disease (PD) (2 cases with dopa-induced dyskinesia = DID), 6 cases with chorea (Ch), 5 cases with essential tremor (EssT) and 2 cases with normal subjects (N). The effects of L-Dopa on rCMRGlu was studied in 3 cases with PD. With the aid of depth microrecording study, stereotactic pallidotomy was performed in all cases with PD. Thalamotomy was performed in 3 cases with Ch. In the EssT and N group, the metabolic pattern was high in the frontal cortex (FCx) but low in the lenticular nucleus (LN). In contrast, all cases with a rigid type PD showed lower rCMRGlu in FCx (premotor, prefrontal area). However, 4 out of 6 cases were higher in LN than the control group. Administration of L-Dopa shifted rCMRGlu toward the normal pattern in this group. Five out of 6 cases with Ch represented higher rCMRGlu in FCx (3 focal, 2 diffuse) but lower in LN. Moreover, when DID occurred, it showed almost the same pattern as in Ch. Electrophysiological studies showed high background neuronal activity (BNA) in the medial segment of the globus pallidus (GP) but low BNA in the lateral segment of the GP in the rigid type of PD. In cases with Ch, irregular burst discharges were often encountered in ventro-oral thalamus. From these results, the on-going changes of basal ganglia-thalamocortical motor circuit in cases with a rigid type PD, DID and Ch are discussed. The underlying mechanisms of Parkinsonian rigidity was considered to contrast with those of DID and Ch within the same motor circuit.

Senile chorea, a late-onset, slowly progressive disorder without mental changes, is a poorly characterized entity. It is often thought to represent late-onset Huntington's disease in which the chorea precedes the mental changes and the family history is absent due to parental death before symptoms. The following case differs pathologically from Huntington's disease and from previous reports of senile chorea.

Our stereotactic experiences in agreement with the literature showed, that different target points could influence the same motor disturbance. To choose the best target point or target point combinations we generally implant the electrodes into VL, Vim, CM, P, dentate nucleus and motor cortex. To ensure the correct sequence of therapeutic lesions we developed an investigation system, taking into consideration the resting and the working state of the motor system. We elicited events centrally (stimulation of the different target points) and peripherally (reflexes) and recorded the evoked potentials at the non-stimulated sites along with the motor and motor modulation effects in the appropriate muscles. The elicited events depend on the site of stimulation and registration and on the state of muscle activity. The centrally and peripherally elicited events influence each other. With our technique the elicited events and their functional dependency is most explicit within the motor system. The results help to explain some basic motor functions and help to answer some of our therapeutic questions.

1. Experimental models of ballism, chorea and Parkinson's disease have been developed in the primate, and the underlying neural mechanisms which mediate these disorders of movement have been investigated using the 2-deoxyglucose uptake technique. 2. In ballism, the subthalamic nucleus is either lesioned or underactive. Because of the excitatory nature of subthalamic efferent fibres, this leads to abnormal underactivity of neurons in the medical segment of the globus pallidus which project to the ventral anterior and ventral lateral nuclei of the thalamus, and to the pedunculopontine nucleus of the caudal midbrain. 3. In chorea, there is underactivity of GABAergic striatal (putaminal) neurons which project to the lateral segment of the globus pallidus. This leads to overacting of lateral pallidal neurons and, thus, physiological inhibition of the subthalamic nucleus. Common neural mechanisms, therefore, underlie the appearance of dyskinesia in ballism and chorea. 4. In parkinsonism, there is overactivity of putaminal neurons projecting to the lateral pallidal segment. This results in excessive inhibition of lateral pallidal neurons and, as a consequence, disinhibition of the subthalamic nucleus. Overactivity of the subthalamic nucleus provides excessive drive upon medial pallidal neurons projecting to thalamic and pedunculopontine nuclei.

The pathophysiology of chorea in systemic lupus erythematosus (SLE) is uncertain. Pathologic examination has not identified a specific location for the causative lesion(s) and immunologic mechanisms have been suggested in its etiology. In other choreic disorders, such as Huntington's disease and benign hereditary chorea, glucose hypometabolism in the striatum has been demonstrated by positron computed tomography (PCT) using [18F]deoxyglucose. With this technique we have studied four patients with chorea secondary to SLE. In these patients the regional distribution of cerebral glucose metabolism was normal. In particular, striatal glucose metabolism was within the normal range, even though the ratio of striatal to cortical glucose metabolism was increased. Our results show that striatal hypometabolism, as seen in other disorders manifesting chorea, is not the PCT correlate of the dyskinesia.

Electroencephalographic studies were done in rheumatic fever patients in order to determine the distribution of normal and abnormal EEG patterns in different clinical forms. The duration of EEG abnormalities related to rheumatic activity was compared with the duration of increased sedimentation rate and tachycardia. Rheumatic fever cases were divided into four groups: (1) acute active rheumatic carditis, (2) acute polyarthritis without carditis, (3) nonactive old rheumatic valvular heart disease, and (4) Sydenham's chorea. EEG findings were within normal limits in acute polyarthritis and in nonactive rheumatic valvular heart disease, but there were abnormal EEG findings in 29 per cent of chorea and in 94 per cent of active carditis cases. In active carditis all EEG changes returned to normal approximately within 8 weeks, whereas the sedimentation rate and tachycardia returned to normal within a shorter period.