Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurologic paraneoplastic syndromes (NPSs) result from damage to the nervous system due to the remote effects of cancer not related to metastasis, infection, or metabolic derangements. NPSs are rare, affecting 1 in 10,000 patients with cancer. Pathogenesis is likely related to the immune mechanisms: normal neural tissue is mistakenly attacked due to the similarity in the onconeural antigens expressed by the tumor cells. Among the various "classic" and other NPSs, this review focuses on paraneoplastic movement disorders, including ataxia due to cerebellar degeneration, stiff-person syndrome, opsoclonus-myoclonus syndrome, chorea, parkinsonism, and tremor. The recently described syndrome of paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis is also included, given that these patients have complex movements such as stereotypies and dyskinesias in addition to psychiatric symptoms, altered sensorium, and other neurologic signs. Although variable, treatment and prognosis of NPSs rely heavily on treatment of the underlying malignancy and immunotherapy.
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PMID:Paraneoplastic movement disorders. 1951 80

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 microg/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 microg/l, P = 0.0004; itself higher than the normal level (3.4 microg/l, range from 0.5 to 17.2 microg/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level > or =7 microg/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels > or =7 microg/l is 46%. Therefore, selection of patients with an AFP level above 7 microg/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy.
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PMID:Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. 1969 32

Chorea is an involuntary movement that appears along with many diseases, it is commonly described as a frequent, brief, sudden, and twitch-like movement that is manifested in various parts of the body in a chaotic pattern. Huntington disease (HD) is a representative neurodegenerative disorder that presents with chorea. Although HD is caused by a CAG-repeat expansion in the IT-15 gene which encodes huntingtin, a small group of patients showing the symptoms and signs of HD do not have the causative CAG-repeat expansion, thereby showing that autosomal-dominant chorea is genetically heterogeneous. Recent studies have demonstrated that such disorders include dentatorubral pallidoluysian atrophy (DRPLA), spinocerebellar ataxia type 17 (SCA17), Huntington disease like 1 (HDL1), Huntington disease like 2 (HDL2), and benign hereditary chorea (BHC). We recently identified 2 Japanese families with adult-onset benign chorea that was inherited in an autosomal-dominant pattern that was linked to chromosome 8q22.2-q23.3, and we named this disease "benign hereditary chorea type 2 (BHC2)". Chorea can also be caused by a wide range of other hereditary diseases and sporadic disease such as metabolic, infectious, inflammatory, vascular, and drug-induced syndromes. In this article, we have reviewed the clinical features of the disorders associated with chorea.
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PMID:[Differential diagnosis of chorea]. 1969 86

Inborn errors of metabolism (IEM) are a group of genetic disorders characterized by dysfunction of an enzyme or other protein involved in cellular metabolism.(1) Most IEMs involve the nervous system (neuro-metabolic diseases or NMD). NMD often present with a complex clinical picture: psychomotor retardation and/or regression, pyramidal signs, ataxia, hypotonia and epilepsy and movement disorders.(1) Movement disorders are more frequently part of this complex picture than a predominant symptom, however in some instances the clinical picture may be summarized in an invalidating movement disorder.(2) On a phenomenology basis, one can distinguish eight main types of movement disorders: dystonia and athetosis, chorea, tremor with or without parkinsonism, ballismus, myoclonus, tics and stereotypies. Most of these abnormal involuntary movements generate from a dysfunction or a lesion in the basal ganglia, excepting myoclonus, the origin of which can vary (cortical, brainstem, basal ganglia, spinal and even peripheral nervous system).(3) Classically the most frequently observed movement disorders in NMD are: dystonia, myoclonus, chorea, tremor and parkinsonism (Fig. 1). The primary goal of this article is, departing from the literature and a large personal series, to describe the types of movement disorders most frequently observed in NMD and to discuss their clinical value in the setting of specific types of NMD.
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PMID:Movement disorders in neuro-metabolic diseases. 2001 70

To assess the spectrum of movement disorders, we reviewed video recordings and charts of 57 patients with Glut-1 deficiency. Eighty-nine percent of patients with Glut-1 deficiency syndrome had a disturbance of gait. The most frequent gait abnormalities were ataxic-spastic and ataxic. Action limb dystonia was observed in 86% of cases and mild chorea in 75%. Cerebellar action tremor was seen in 70% of patients, myoclonus in 16%, and dyspraxia in 21%. Nonepileptic paroxysmal events occurred in 28% of patients, and included episodes of ataxia, weakness, Parkinsonism and nonkinesogenic dyskinesias. The 40 patients (70%) who were on the ketogenic diet had less severe gait disturbances but more dystonia, chorea, tremor, myoclonus, dyspraxia, and paroxysmal events compared with the 17 patients on a conventional diet. Poor dietary compliance and low ketonuria appear to trigger the paroxysmal events in some patients. Gait disturbances and movement disorders are frequent in patients with Glut-1 deficiency and are signs of chronic and intermittent pyramidal, cerebellar and extrapyramidal circuit dysfunction. These clinical symptoms reflect chronic nutrient deficiency during brain development and may be mitigated by chronic ketosis.
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PMID:The spectrum of movement disorders in Glut-1 deficiency. 2006 28

In this article we reviewed the results obtained with the technique of paired-pulse transcranial magnetic stimulation (TMS) in normal subjects and in patients with movement disorders (Parkinson's disease, dystonia, chorea, Tourette's syndrome, myoclonus, essential tremor, and ataxia). Results on short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and long-interval intracortical inhibition (LICI) are reported and discussed for each type of movement disorder.
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PMID:Consensus paper on short-interval intracortical inhibition and other transcranial magnetic stimulation intracortical paradigms in movement disorders. 2063 84

We screened a cohort of 181 patients with features of primary progressive ataxia and chorea for spinocerebellar ataxias 17 (SCA17) mutation after excluding other known SCAs, Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and non-genetic causes. This study included patients with known family history of SCA, those with sporadic onset and cases of uncertain family history. Two unrelated patients with Huntington's disease-like phenotype and cerebellar signs are described with homozygous expansions of 47 and 48 CAG/CAA repeats. A family member with early signs of ataxia was found to carry 37 and 48 repeats. There were fewer CAA interruptions in the repeat sequences of patients than in the controls. The normal repeat range in controls was 21-42, with 91% of the alleles located between 33 and 39 repeats. This is the first report of rare homozygous SCA17 mutation in Indian patients presenting with HD-like phenotype.
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PMID:Spinocerebellar ataxia type 17 in Indian patients: two rare cases of homozygous expansions. 2110 34

Juvenile Huntington disease (JHD) is a rare clinical entity characterized by disease onset before the age of 21. JHD accounts for <10% of Huntington disease patients. Transmission of JHD is paternal in 80-90% of cases. Patients with JHD usually carry more than 60 CAG repeats within the HTT gene. We report here on a 23-month-old boy presenting with global developmental delay first noted at 18 months of age. Clinical examination showed truncal hypotonia, postural and intentional tremor, limb rigidity, and ataxia. Cerebral magnetic resonance imagery (MRI) showed reduced cerebellar volume. Six months later, his 47-year-old father was seen for a 4-year history of progressive dementia with severe behavioral disturbance and chorea. Cerebral MRI showed discrete global and caudate atrophy. DNA analysis revealed a very large and heterogeneous expansion (210-250 CAG) in the child and a 43 CAG expansion of the HTT gene in the father. This unusual case demonstrates that very early onset JHD due to large CAG expansions should be considered in cases of global developmental delay associated with reduced cerebellar volume, including cases without known HD family history.
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PMID:Juvenile Huntington disease in an 18-month-old boy revealed by global developmental delay and reduced cerebellar volume. 2141 77

Ataxia with oculomotor apraxia type1 (AOA1, MIM 208920) is a rare autosomal recessive disease caused by mutations in the APTX gene. We screened a cohort of 204 patients with cerebellar ataxia and 52 patients with early-onset isolated chorea. APTX gene mutations were found in 13 ataxic patients (6%). Eleven patients were homozygous for the known p.W279X, p.W279R, and p.P206L mutations. Three novel APTX mutations were identified: c.477delC (p.I159fsX171), c.C541T (p.Q181X), and c.C916T (p.R306X). Expression of mutated proteins in lymphocytes from these patients was greatly decreased. No mutations were identified in subjects with isolated chorea. Two heterozygous APTX sequence variants (p.L248M and p.D185E) were found in six families with ataxic phenotype. Analyses of coenzyme Q10 in muscle, fibroblasts, and plasma demonstrated normal levels of coenzyme in five of six mutated subjects. The clinical phenotype was homogeneous, irrespectively of the type and location of the APTX mutation, and it was mainly characterized by early-onset cerebellar signs, sensory neuropathy, cognitive decline, and oculomotor deficits. Three cases had slightly raised alpha-fetoprotein. Our survey describes one of the largest series of AOA1 patients and contributes in defining clinical, molecular, and biochemical characteristics of this rare hereditary neurological condition.
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PMID:Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients. 2146 57

The spinocerebellar ataxias (SCA) are a large group of inherited disorders affecting the cerebellum and its afferent and efferent pathways. Their hallmark symptom is slowly progressive, symmetrical, midline, and appendicular ataxia. Some may also have associated hyperkinetic movements (chorea, dystonia, myoclonus, postural/action tremor, restless legs, rubral tremor, tics), which may aid in differential diagnosis and provide treatable targets to improve performance and quality of life in these progressive, incurable conditions. The typical dominant ataxias with associated hyperkinetic movements are SCA1-3, 6-8, 12, 14, 15, 17, 19-21, and 27. The common recessive ataxias with associated hyperkinetic movements are ataxia telangiectasia and Friedreich's ataxia. Fragile X tremor-ataxia syndrome (FXTAS) and multiple-system atrophy (a sporadic ataxia which is felt to have a genetic substrate) also have hyperkinetic features. A careful work-up should be done in all apparently sporadic cases, to rule out acquired causes of ataxia, some of which can cause hyperkinetic movements in addition to ataxia. Some testing should be done even in individuals with a confirmed genetic cause, as the presence of a secondary factor (nutritional deficiency, thyroid dysfunction) can contribute to the phenotype.
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PMID:Spinocerebellar degenerations. 2149 73


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