Works In Progress AbstractsThese works in progress abstracts were presented at theAmerican Neurological Association’s 127th Annual Meetingin New York, October 13–16, 2002.

PLATFORMS

1. A Role for Neuregulin-1 in Muscle SpindleDifferentiationNeil A. Shneider, Simon Hippenmeyer, Carmen Birchmeier,Thomas Jessell, Silvia Arber, and Steve Burden;Basel, Switzerland, Berlin, Germany, and New York, NY

Muscle spindles are specialized, stretch-sensitive mechanorecep-tors in skeletal muscle that are innervated by both motor andsensory axons. Differentiation of muscle spindles depends on in-nervation by group IA proprioceptive afferents, which presum-ably supply an inductive signal to the nascent muscle spindle.Using a genetic approach in the mouse, we have identifiedneuregulin-1 (Nrg-1), a ligand for ErbB receptor complexes, as acrucial factor in the initiation of muscle spindle differentiation.In the absence of neuronal Nrg-1 expression, the peripheral end-ings of IA afferent axons contact primary myotubes normally butsubsequently fail to elaborate typical, spiral endings around nas-cent muscle spindles. These IA afferent neurons, deleted ofNrg-1, also fail to induce expression of a set of genetic markers ofearly spindle differentiation in primary myotubes. In contrast, thedevelopment and morphology of central projections of group IA

afferents does not appear to be affected. Together, these findingsdemonstrate that Nrg-1 supplied by proprioceptive sensory neu-rons is essential for the initiation of muscle spindle differentiation.In addition, we provide genetic evidence that Nrg1 isoforms con-taining an immunoglobulin (Ig)–like domain are sufficient to in-duce early muscle spindle differentiation in vivo, consistent withan isoform-specific function for Ig-Nrg1 in the afferent-dependentinduction of muscle spindles.

2. A New Recessive Syndrome of Cerebellar Ataxiawith Saccadic Intrusions and Sensorimotor Neuropathy(CASI) Maps to Chr1p36Barbara E. Swartz, Sheng Li, R. John Leigh,Eugene Dulaney, Irina N. Bespalova, and Margit Burmeister;Cleveland, OH, Ann Arbor, MI, and Burlington, VT

We have reported a family of Slovenian descent, with at least 5of 14 siblings (1 woman) affected by progressive ataxia, macro-saccadic oscillations that intrude on fixation, and sensorimotorneuropathy. Neither parent and none of more than 50 offspringare affected, indicating probable autosomal recessive inheritance.Median age of onset is 36 years with slow progression. SCA1-3,6-8, Friedreich’s ataxia, and EPM1 were excluded by commer-cial tests whereas linkage to known recessive ataxias (19p13.3;21q) was excluded. A genome scan with 374 tetrameric micro-satellite markers was performed by Marshfield/WI Center forMedical Genetics for the mother and five affected and four un-affected individuals. Markers on 1p36 could not be excludedand underwent additional testing (ABI’s 5cM genome scanpanel, U of Mi sequencing core). Several markers were com-pletely informative, showing linkage with a maximal LOD score(at 0cM) of 3.03. The region is flanked by markers D1S468 andD1S507, which span approximately 30cM or approximately 13megabases. Within this interval, more than 20 additional mark-ers were tested for homozygosity. The five affected are homozy-gous in an area of 1 to 3Mbp near the KIF1B gene, which codes

for kinesin. Mutations in KIF1B cause dominant Charcot–Marie–Tooth (CMT) disease type 2A and may be a candidategene for this disorder. Mutation testing is in progress. CMT2Ais a dominant sensory neuropathy with some overlapping symp-toms, but CASI shows specific findings: limb and gait ataxia,horizontal macrosaccadic oscillations with increased saccadicspeed, pyramidal tract signs, and myoclonus. CASI is recessive,whereas CMT2A is dominant. It is possible that mutations inthe same gene lead to both CMT2A and CASI, but that hy-pothesis remains to be proved. Because the biology of saccadiceye movements is well documented, the mechanisms wherebythe kinesin protein affects neuronal function is especially acces-sible to study.

POSTERS

1. A Gene Mutated in Juvenile Myoclonic EpilepsyEncodes a Protein with EF-handT. Suzuki, A. V. Delgado-Escueta, M. E. Alonso, R. Morita,M. T. Medina, S. Ganesh, D. Bai, T. Sugimoto,J. N. Bailey, A. Ochoa, J. A. Prado, A. Rasmussen,J. R. Peek, S. Cordova, F. Rubio-Donnadieu, X. Inoue,M. Osawa, S. Kaneko, H. Oguni, and K. Yamakawa;Saitama, Tokyo, Shizuoka, and Aomori, Japan,Los Angeles, CA, Mexico City, Mexico,Tegucigalpa, Honduras, and Delhi, India

Among idiopathic generalized epilepsies, juvenile myoclonic epi-lepsy (JME) is the most common, accounting for 12 to 30% of allepilepsies. We previously mapped convulsive and electroencepha-logram traits of JME to a 7cM region (EJM1) of chromosome6p12-11. More recently, recombinations of 21 new families fromMexico narrowed EJM1 further between D6S1960 and 255gt/1180e22 where we found “myoclonin/EFHC1.” Mutational anal-ysis in the 21 JME families showed mutations segregating in 21epilepsy or electroencephalogram polyspike wave affected mem-bers of six unrelated families. Those include three heterozygous(Phe229Leu in Families 3 and 4; Asp210Asn in Family 5;Asp253Tyr in Family 6) and one doubly heterozygous missensemutation (Pro77Thr and Arg221His in Families 1 and 2). Thesemutations were not observed in 232 unrelated healthy controls(102 Mexicans, 96 Japanese, and 34 whites). The only knownfunctional domain is the EF-hand motif, suggesting a role in sens-ing, binding, and modulating neuronal calcium. Mutations inmyoclonin/EFHC1 could be influenced by sleep deprivation andalcohol and affect calcium binding and intracellular calcium con-centrations and shift voltage to the depolarizing potentials of ep-ilepsy. Production of transgenic EFHC1 mouse models is neces-sary to prove that EFHC1 is indeed a gene for JME.

2. Bilateral Frontoparietal Polymicrogyria: AnAutosomal Recessive Syndrome of CorticalMalformation with Distinct Clinical andRadiological FeaturesBernard Chang, Xianhua Piao, and Christopher A. Walsh;Boston, MA

Polymicrogyria is a common malformation of cortical develop-ment characterized by an excessive number of small gyri and ab-normal cortical lamination. Multiple familial syndromes ofregion-specific bilateral symmetric polymicrogyria have been re-ported. We previously have described two families with bilateralfrontoparietal polymicrogyria (BFPP), an autosomal recessive syn-drome that we mapped to a locus on chromosome 16q12-21.Here, we extend our observations to include 18 patients from 10chromosome 16–linked kindreds, allowing us to define the clin-

AMERICAN NEUROLOGICAL ASSOCIATION 127TH ANNUAL MEETINGOCTOBER 13–16, 2002—NEW YORK, NY

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ical and radiological features of BFPP in detail. The syndrome ischaracterized by cognitive and motor delay of at least moderateseverity, seizures, dysconjugate gaze, and bilateral pyramidal andcerebellar signs. Magnetic resonance imaging demonstrates sym-metric polymicrogyria affecting the frontoparietal regions most se-verely, as well as ventriculomegaly, bilateral white matter signalchange, and hypoplasia of the brainstem and cerebellar vermis.We have refined our genetic mapping and describe two apparentfounder mutations, one of which is present in two families withBFPP and associated microcephaly. Because 11 of our patientsinitially were classified as having other malformations, the syn-drome of BFPP appears to be more common than previously rec-ognized and may be frequently misdiagnosed.

3. Sodium Channel MyastheniaAkira Tsujino, Chantal Maertens, Kinji Ohno,Xin-Ming Shen, C. Michael Harper, Stephen Cannon,and Andrew G. Engel; Rochester, MN, Boston, MA,and Dallas, TX

A 20-year-old woman had abrupt attacks of respiratory and bul-bar paralysis since birth lasting 3 to 30 minutes recurring one tothree times per month, ptosis, limited ocular ductions, andmarked fatigable weakness and was mentally retarded. Nervestimulation at 2Hz elicited no decremental response. Ten- or50Hz stimulation for 1 minute reduced the evoked muscle ac-tion potential by approximately 85%, and 2Hz stimulation nowelicited a significant decrement. Intercostal muscle studies at30°C showed no abnormality of the resting membrane potential,evoked quantal release, synaptic potentials and currents, orAChR channel kinetics, but the muscle fibers were electricallyinexcitable. Pursuing this clue, we sequenced SCN4A encodingthe skeletal muscle sodium channel (NaV1.4) and detected twomutations involving conserved residues, not present in 400 nor-mal alleles: S246L in the S4/S5 cytoplasmic linker in domain Iand V1442E in the S3/S4 extracellular linker in domain IV.Asymptomatic mother and sister carry S246L; the father’s DNAwas unavailable. The genetically engineered V1442E-Na channelexpressed in HEK cells shows marked enhancement of fast in-activation close to the resting potential and enhanced use-dependent inactivation on high-frequency stimulation; S246L islikely a benign mutation. The V1442E sodium channel muta-tion defines a novel disease mechanism and a novel phenotypewith myasthenic features.

4. Apolipoprotein E Genotype Is a Risk Factor forDiabetic NeuropathyR. S. Bedlack, D. Kelling, D. Edelman, J. W. Gibbs III,W. Strittmatter, and J. Morgenlander; Concord, NC,and Durham, NC

We tested the hypothesis that apolipoprotein E (APOE) genotypepredicts diabetic neuropathy using a cross-sectional study of dia-betic patients in a primary care clinic. APOE genotype was ob-tained from cheek cells and characterized as high-risk (E4/E4 orE3/E4) or normal. Neuropathy was measured by the NeuropathyImpairment Score in the Lower Limbs (NISLL). A stepwise re-gression model was created using APOE genotype, age, diabetesduration, glycemic control, and triglycerides to predict NISLL.Covariates related to outcome with p value less than 0.05 wereadded. Approximately 19% of 187 patients had high-risk geno-type, and 74% had 1 point or higher on NISLL. Our best modelincluded age, duration of diabetes, and APOE status and pre-dicted NISLL with p value of 0.0083. Each component of thismodel predicted NISLL at p value less than 0.05 after adjustmentfor the other two components. Age was predictive at p value of

0.0001, with 2 points of NISLL for every 10 years of age. Dura-tion of diabetes was predictive at p value of 0.0044, with 2 pointsof NISLL for every 10 years of diabetes. APOE status was predic-tive at p value of 0.03, with high-risk patients having 3.12 morepoints than normal risk patients. High-risk APOE genotype pre-dicts diabetic neuropathy. Markers such as this may help directresource-intensive interventions that prevent neuropathy or itscomplications.

5. Autoantibody Reactivity to Myelin/OligodendrocyteGlycoprotein Correlates with Progressive Forms ofMultiple SclerosisClaude P. Genain, Antje Fuhrmann, Til Menge,Hans-Christian von Budingen, Stacey Bae, Amy Swerdlin,Alan Evangelista, Carolyn Woo, Daniel Pelletier,Emmanuelle Waubant, Douglas Goodin, Mariko Kita,Scott Zamvil, Bruce Cree, Donald Goodkin,and Stephen Hauser; San Francisco, CA, and Seattle, WA

The significance of humoral immunity against myelin/oligoden-drocyte glycoprotein (MOG) is unclear, because anti–MOG an-tibodies are found in both multiple sclerosis (MS) and controlsubjects. We used specific ELISA systems to measure serum an-tibody reactivity against MOG (recombinant extracellular do-main) and native myelin basic protein (MBP) in 18 controls, 27patients with relapsing remitting (RR) MS, 17 patients with sec-ondary progressive (SP) MS, and 32 patients with primary pro-gressive (PP) MS, diagnosed according to Poser criteria, Age-matched controls were included. Consistent with previousstudies of Western blotting, antibodies to MOG were found in38% of controls and 33% of RRMS patients. However, theseautoantibodies were detected at considerably higher frequenciesin patients with SPMS (76%) and PPMS (89%). All SPMS andPPMS patients had EDSS values above 3.0 at the time of sam-pling. Compared with MOG, the incidence of antibodiesagainst MBP was lower across all MS groups (23%, 25%, and19%, respectively). Detailed analyses of epitope recognition ofMOG are in progress. The heightened occurrence of anti–MOGautoantibodies in SPMS and PPMS may reflect specific mecha-nisms of disease in these chronic forms. We also propose thatanti–MOG antibody titers might serve as paraclinical markers ofprogression and brain atrophy in MS.

6. The Frequency of Frontotemporal Lobar Dementiain an Amyotrophic Lateral Sclerosis Population: IsNeuropsychological Testing or NeuroimagingMore Sensitive?Catherine Lomen-Hoerth, Jennifer Murphy, Roland Henry,Marni Hillinger, Cynthia Chin, Joel Kramer,and Dallas Forshew; San Francisco, CA

We evaluated 23 consecutive amyotrophic lateral sclerosis (ALS;probable or definite by World Federation of Neurology criteria)patients without known dementia presenting to the ALS Centerat UCSF who consented to neuroimaging and neuropsycholog-ical testing. A battery of neuropsychological tests was adminis-tered to each patient. Patients also had anatomical and perfusionmagnetic resonance imaging (MRI) scans with whole-brain cov-erage and a subset had MR spectroscopy studies focusing on the

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frontal and temporal lobes. Quantitative measurement of brainatrophy was made with normalized values for head size and age.

Of the 23 patients, 13 had neuroimaging abnormalities.Seven patients had both frontal and temporal atrophy, four hadfrontal atrophy, and one had temporal atrophy. One additionalpatient had no atrophy on MRI but had abnormal perfusion ofhis frontal lobes. Nine patients had abnormalities on neuropsy-chological testing typical of FTLD (frontotemporal dementia,primary progressive aphasia, or semantic dementia), and all thesepatients had abnormal imaging.

Among 23 consecutive patients with ALS, we found cognitiveabnormalities in 40% and radiological abnormalities in 57%.Longitudinal follow-up is in progress to determine if any of thenormal subjects or subjects with radiological abnormalities de-velop cognitive abnormalities over time. Thus, FTLD is themost common dementia found in ALS and is an underrecog-nized feature.

7. Pretranslational Events Involving the MyHC GenesMay Contribute to the Selective Myosin Depletion inAcute Quadriplegic MyopathyTahseen Mozaffar, Fadia Haddad, Lily Qin, Ming Zeng,and Kenneth M. Baldwin; Irvine, CA

Acute quadriplegic myopathy (AQM) is characterized by flaccidquadriparesis, electrical inexcitability of muscle membranes, andmuscle atrophy with selective myosin heavy chain (MyHC) de-pletion, especially in fast-twitch muscles. Use of glucocorticoidsin the setting of pharmacological neuromuscular blockade(“functional denervation”) may precipitate this disease in hu-mans. We studied mRNA expression of MyHC and actin genesand various MyHC isoforms in plantaris muscle in a rat modelof AQM at 1 week, after unilateral denervation followed byhigh-dose parenteral dexamethasone treatment (den-dex). Con-trols included untreated animals and animals treated with dener-vation alone or dexamethasone alone. A highly significant reduc-tion in muscle weight, protein content, myofibrillar content,and DNA content was seen in plantaris in den-dex animals. Asevere selective MyHC protein content reduction with only amild reduction in total Actin protein content was seen, leadingto highly significant elevated actin to MyHC ratio. Slot-blotanalysis of MyHC and actin total mRNA showed elevated actinto MyHC mRNA ratio (p � 0.01) suggesting a disproportion-ate reduction in MyHC message in den-dex animals. MyHCisoform mRNA analysis showed only mild reduction in MyHCIIX signal in the den-dex animals. Pretranslational events involv-ing the MyHC genes may contribute to the selective MyHCdepletion seen in AQM.

8. Acute Segmental Motor Syndrome: An UnusualNeuromuscular Presentation of West NileVirus InfectionR. A. Lewis, J. A. Loeb, M. E. Shy, A. K. Shah,W. J. Kupsky, A. C. Tselis, and J. Li; Detroit, MI

Our objective was to describe an unusual neuromuscular syn-drome caused by West Nile virus (WNV). West Nile virus(WNV) is a RNA virus and belongs to the flavivirus family tax-onomically. Reports of WNV from Israel and New York Cityhave mentioned flaccid paralysis, axonal neuropathy, and diffuselimb weakness in 10% of the patients, but there has not been adetailed characterization of the neuromuscular aspects of the disease.WNV infection has been endemic in south Michigan during sum-mer 2002. In September 2002, we encountered a group of casespresenting with a peculiar acute segmental motor syndrome(ASMS), which has not been previously described in the medicalliterature to our knowledge. Five patients, three men and twowomen, were studied. Ages ranged from 24 to 68 years. They all

were examined by one of us. Workup included magnetic resonanceimaging (MRI) of brain/spine, lumbar puncture, electrophysiology,serology, and nerve and muscle biopsy. Two of these patients hadpositive IgM antibodies to WNV by ELISA test, but the results ofthe ELISA test on other patients were pending at the time we wrotethis abstract. Only the two cases with positive test are describedbelow.

Patient 1 is a 36-year-old woman who had been healthy untilapproximately 1 week before the presentation, when she devel-oped “flu-like” symptoms. On the day of presentation, she wokeup with low back pain and paralysis of the left leg. At no time didshe have confusion, neck stiffness, or central nervous systemsymptoms or signs. Neurological examination showed a flaccidleft leg (0/5 MRC), slightly reduced sensation to pinprick in thatleg, and reduced deep tendon reflexes in that limb. Her brain andspine MRI results were negative. CSF showed a lymphocytosis(65 cells with 88% lymphocytes). Electromyelogram (EMG) test-ing showed no motor conduction slowing. Although sensorynerve action potentials (SNAPs) were normal, the amplitudeswere less than those of the contralateral side. Needle EMG de-tected diffuse denervation in the left leg and correspondingparaspinal muscles. Sural nerve biopsy showed a few fibers under-going axonal degeneration, but most fibers were well preserved.Muscle biopsy showed scattered necrotizing muscle fibers. Patient2 (a 45-year-old man) presented with confusion and bifacialweakness and the sudden onset of left leg weakness. His examshowed two-fifths strength in the left leg and four-fifths strengthin the right leg. His mental status cleared in 3 days, but his motordeficits persisted. NCS showed normal sensory studies, and EMGshowed denervation in the left leg and to a lesser extent in theright leg. Muscle biopsy showed striking changes of scattered ne-crotic muscle fibers. The three cases awaiting confirmation all hadsevere segmental motor defecits with minimal sensory findings,which evolved in an acute or subacute fashion. These cases rep-resent a new syndrome of WNV infection. Some patients mayhave minimal or no central nervous system symptoms and presentwith a neuromuscular disorder. Our patients were not old or im-munologically compromised, and it will be important for neurol-ogists to recognize this presentation and consider the possibility ofWNV infection. The direct cause for the paralysis is not yet clear.It may be from unilateral motor polyradiculopathies or motorneuron lesions. Sensory nerves and muscles were involved butmay not be major contributors to the weakness.

Summer Medical StudentResearch ProjectsThe ANA awarded two medical student travel awards. Authors aremedical students who served as a summer intern or worked on aresearch project in neurology and were the first author of the ab-stract. These abstracts were presented at the 127th annual meetingin New York.

1. Memory Retention and Spatial Learning after FocalCerebral Ischemia in the TNF-� Transgenic RatShea A. Godwin, Mary L. Holtz, Thomas C. Foster,Susan D. Craddock, Mark S. Kindy, David S. Grass,and L. Creed Pettigrew; Lexington, KY, Charlestown, SC,and Cranbury, NJ

Our objective was to determine whether overexpression of themurine TNF-� gene affects spatial learning in a rat model offocal cerebral ischemia. We constructed a transgenic rat over-

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expressing the murine TNF-� gene with its own promoter.Wild-type (WT; n � 3) and transgenic (n � 6) rats with highlevels of TNF-� in brain underwent focal ischemia for 1 hour.After 7 days, all animals were tested for learning by spatialdiscrimination in a Morris water maze. Both groups learned aspatial discrimination task before ischemia, taking significantlyless time to find an escape platform over serial trials (escapelatencies: WT 34.1 � 15.1 to 8.7 � 9.2 sec; p � 0.005;transgenic 44.3 � 10.9 to 25.8 � 22 sec; p � 0.05; Fisher’stest). Postischemic WT rats showed no differential search strat-egy (spending �25% of allotted time in a target quadrant).Transgenic rats performed similarly but preferred a quadrant ad-jacent to the target (38 � 11%; p � 0.05; t test). PostischemicWT (27 � 5%) and transgenic (21 � 7%) rats had no signif-icant difference in infarct volume. TNF-� overexpressed inbrain could alter synaptic activity in hippocampal and corticalcircuits needed for learning behavior. These results show the po-tential of our transgenic animal as a unique prototype to evalu-ate the effect of TNF-� on cognition in vivo.

2. Sensory and Motor Cortical Interactions inComplex Voluntary Movements: Validation andExtension of the Postulates of A. R. LuriaAshish A. Bhimani, Ana Solodkin, Petr Hlustik,and Steven L. Small;

The anatomical organization of the human motor system hasdeep significance for motor function and remediation in neu-rology. Noted Russian neuropsychologist Aleksandr R. Luriadesigned several tasks to investigate disturbances of complexvoluntary movement, thought to involve the premotor corticesand their interaction with the parietal lobe (PL). We usedfunctional brain imaging to reevaluate Luria’s postulates andto elaborate the neural circuitry underlying task performance.Six healthy adults (aged 21 � 2 years, four right-handed) per-formed the hand imitation, fist-edge-palm, and piano-keytasks during blood oxygen level dependent functional mag-netic resonance imaging at 3T. As expected, premotor and pa-rietal cortices were active in all three tasks. Although the pri-mary sensory area, PL, and ventral portion of the lateralpremotor cortex were preferentially activated in the imitationtask, the supplementary motor area proved to be sensitive indistinguishing the imitation task from the fist-edge-palm andpiano-key tasks, both of which incorporate elements of se-quential movement and self-pacing. Right PL was more activethan left in both imitation and fist-edge-palm, and the piano-key task showed a high degree of bilateral activation in theprimary motor cortex. Our results uphold the postulates ofA. R. Luria while providing further characterization of thesensory-motor circuits involved in these complex behaviors.

Derek-Denny-BrownNeurological Scholar AwardsSelected by the membership advisory committee, these awards weregiven to newly elected members of the Association who have achievedsignificant stature in neurological research. These abstracts were pre-sented at the 127th annual meeting in New York.

1. Advances in Hereditary Spastic ParaplegiaJohn K. Fink, Ann Arbor, MI

The hereditary spastic paraplegias (HSPs) are clinically andgenetically diverse disorders that share the primary feature ofprogressive, often severe, lower extremity spastic weakness.These disorders are classified according to the mode of in-heritance and whether progressive spasticity occurs in isola-tion (“uncomplicated HSP”) or with other neurologic abnor-malities (“complicated HSP”). The major neuropathologicfeature of uncomplicated HSP is axonal degeneration involv-ing both motor (corticospinal tracts) and sensory (dorsal col-umn) fibers. Axonal degeneration is maximal in the terminalportions of these fibers which are among the longest de-scending and ascending tracts. Neuronal cell bodies of de-generating fibers are largely preserved. There have been greatstrides in our understanding of the HSP’s. We have learnedthat HSP shows extreme genetic heterogeneity. 18 genetictypes of HSP (10 autosomal dominant, five autosomal reces-sive, and 3 X-linked) have been identified. Discovery of sixHSP genes (spastin, atlastin, paraplegin, L1 cell adhesionmolecule, proteolipid protein, and chaperonin 60) paves theway for elucidating the molecular cascades that underlieHSP. Until recently, HSP was a clinical diagnosis based onfamily history, neurologic signs, and careful exclusion of al-ternate diagnostic possibilities. Genetic testing for SPG4(spastin) gene mutation is currently available and testing forSPG3A (atlastin) mutations is expected soon. Together,SPG4 and SPG3A gene testing can be used to confirm thediagnosis and for prenatal diagnosis in more than 50% ofindividuals with dominantly inherited HSP. Finally, creationof laboratory animal models of HSP is in progress. Theseanimals will provide valuable resources to explore HSP’s mo-lecular pathophysiology as well as opportunities to developtreatments for HSP and related disorders.

2. The Basal Ganglia and Involuntary Movements:Impaired Inhibition of Competing Motor PatternsJonathan W. Mink, Rochester, NY

The basal ganglia are a system of interconnected nuclei in theforebrain and midbrain that play an important role in the con-trol of movement. The motor circuits of the basal ganglia areorganized anatomically and physiologically to facilitate desiredvoluntary motor patterns and to inhibit unwanted competingmotor patterns. Studies in non-human primates have shown thatblocking the normal basal ganglia inhibitory output causes in aninability to inhibit competing motor patterns with resulting ex-cess motor output that interferes with voluntary movement.This excess motor output is in the form of muscular cocontrac-tion that produces postures resembling those seen in human dys-tonia. Current popular models of basal ganglia functional anat-omy propose that chorea is also caused by reduced basal gangliaoutput, but the specific mechanisms producing chorea are notwell understood. Our quantitative kinematic and EMG investi-gations of chorea in human subjects show that chorea is notsimply a series of random muscle bursts. Instead, chorea appearsto be spatially non-random with a high degree of correlationamong related muscle groups. Thus, chorea can be characterizedas disinhibition of unwanted motor patterns. These and otherfindings provide the basis for better understanding the patho-physiology of chorea.

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