Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroferritinopathy is a recently recognised genetic disease resulting in a dominantly inherited movement disorder. The condition was mapped by linkage analysis to chromosome 19q13.3 and found to be due to a single adenine insertion in the ferritin light chain (FTL) gene at position 460-461 which is predicted to alter the C terminus of the FTL polypeptide. Clinical features of neuroferritinopathy are highly variable, with chorea, dystonia, and Parkinsonian features predominating in different affected individuals. The most consistent feature is a dystonic dysarthria. Symptoms and abnormal physical signs appear to be restricted to the nervous system and onset is typically in the fourth to sixth decades. Low serum ferritin also characterises this condition. Brain MR imaging of affected patients demonstrates iron deposition in the basal ganglia, progressing over years to cystic degeneration, and brain histochemistry shows abnormal aggregates of ferritin and iron. Now that the molecular basis of the condition is known, therapeutic interventions to reduce or reverse brain iron deposition are being evaluated. This rare disease provides evidence of a central role for iron metabolism in neurodegenerative disorders.
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PMID:Neuroferritinopathy: a window on the role of iron in neurodegeneration. 1254 46

Monozygotic (MZ), 46-year-old, male twins, carrying the same Huntington disease (HD) mutation, presented with a different clinical course. In one of the twins, the disease process started at the age of 32 years with chorea, dysarthria, and a depressed mood. Over 14 years, the disease progressed to total functional dependence. The second twin presented at age 35 with gait disturbances. His behavior became aggressive with an obsessive pattern, whereas the motor features included hypokinesia, rigidity, gait unsteadiness, and dysarthria. This is the first report of genetic identity associated with different age of disease onset as well as a different motor and behavioral phenotype. Postzygotic events are a likely explanation for the observed differences of phenotype in these genetically identical twins.
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PMID:Different phenotypic expression in monozygotic twins with Huntington disease. 1467 93

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months ('staged surgery'). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day ('simultaneous surgery'). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the 'off' and 'on' drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5%) and 'on' (35.5%) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the 'off' and 'on' medication states preoperatively and at 2 years postoperatively also revealed a significant improvement. All of the cardinal features of Parkinson's disease as well as activities of daily living (ADL) scores significantly improved (P < 0.01). Levodopa-induced dyskinesias were reduced by 50% (P < 0.01), and the mean daily levodopa dose was reduced by 47% at the time of the last evaluation compared with baseline (P < 0.0001). Dyskinesias occurred intraoperatively or in the immediate postoperative hours in 13 patients, but were generally mild and short lasting. Three patients developed severe generalized chorea that gradually resolved within the next 3-6 months. Three patients experienced severe and persistent postoperative dysarthria. In two, this coincided with the patients exhibiting large bilateral lesions also suffering from severe dyskinesias. No patient exhibited permanent cognitive impairment. The motor benefit has persisted for a follow-up of 3-6 years. This study indicates that bilateral subthalamotomy may induce a significant and long-lasting improvement of advanced Parkinson's disease, but the clinical outcome was variable. This variability may depend in large part on the precise location and volume of the lesions. Further refinement of the surgical procedure is mandatory.
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PMID:Bilateral subthalamotomy in Parkinson's disease: initial and long-term response. 1568 66

Spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of disorders. Current molecular classification corresponds to the order of gene description (SCA1-SCA 25). The prevalence of SCAs is estimated to be 1-4/100,000. Patients exhibit usually a slowly progressive cerebellar syndrome with various combinations of oculomotor disorders, dysarthria, dysmetria/kinetic tremor, and/or ataxic gait. They can present also with pigmentary retinopathy, extrapyramidal movement disorders (parkinsonism, dyskinesias, dystonia, chorea), pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioral symptoms), peripheral neuropathy. SCAs are also genetically heterogeneous and the clinical diagnosis of subtypes of SCAs is complicated by the salient overlap of the phenotypes between genetic subtypes. The following clinical features have some specific values for predicting a gene defect: slowing of saccades in SCA2, ophthalmoplegia in SCA1, SCA2 and SCA3, pigmentary retinopathy in SCA7, spasticity in SCA3, dyskinesias associated with a mutation in the fibroblast growth factor 14 (FGF 14) gene, cognitive impairment/behavioral symptoms in SCA17 and DRPLA, seizures in SCA10, SCA17 and DRPLA, peripheral neuropathy in SCA1, SCA2, SCA3, SCA4, SCA8, SCA18 and SCA25. Neurophysiological findings are compatible with a dying-back axonopathy and/or a neuronopathy. Three patterns of atrophy can be identified on brain MRI: a pure cerebellar atrophy, a pattern of olivopontocerebellar atrophy, and a pattern of global brain atrophy. A remarkable observation is the presence of dentate nuclei calcifications in SCA20, resulting in a low signal on brain MRI sequences. Several identified mutations correspond to expansions of repeated trinucleotides (CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA, CTG repeats in SCA8). A pentanucleotide repeat expansion (ATTCT) is associated with SCA10. Missense mutations have also been found recently. Anticipation is a main feature of SCAs, due to instability of expanded alleles. Anticipation may be particularly prominent in SCA7. It is estimated that extensive genetic testing leads to the identification of the causative gene in about 60-75 % of cases. Our knowledge of the molecular mechanisms of SCAs is rapidly growing, and the development of relevant animal models of SCAs is bringing hope for effective therapies in human.
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PMID:The wide spectrum of spinocerebellar ataxias (SCAs). 1589 52

We report on a 50-year-old woman who presented with an 8-year history of involuntary movements, unsteadiness, and cognitive decline. Examination revealed multidomain cognitive deficits, jerky ocular pursuit movements, hypometric saccades, gaze impersistence, dysarthria, upper limb dystonia, and widespread chorea. TATA-binding protein gene test revealed trinucleotide expansion allele sizes of 47 and 39 repeats, confirming the diagnosis of spinocerebellar ataxia type 17 (SCA-17). Magnetic resonance imaging (MRI) showed marked cerebellar atrophy and putaminal rim hyperintensity. This is the first case of SCA-17 reported to show MRI signal change in the basal ganglia, and extends the phenotypic manifestation of SCA-17.
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PMID:Spinocerebellar ataxia type 17: extension of phenotype with putaminal rim hyperintensity on magnetic resonance imaging. 1603 35

Most movement disorders, reflecting degenerative disorders, develop in a slowly progressive fashion. Some movement disorders, however, manifest with an acute onset. We wish to give an overview of the management and therapy of those acute-onset movement disorders.Drug-induced movement disorders are mainly caused by dopamine-receptor blockers (DRB) as used as antipsychotics (neuroleptics) and antiemetics. Acute dystonic reactions usually occur within the first four days of treatment. Typically, cranial pharyngeal and cervical muscles are affected. Anticholinergics produce a prompt relief. Akathisia is characterized by an often exceedingly bothersome feeling of restlessness and the inability to remain still. It is a common side effect of DRB and occurs within few days after their initiation. It subsides when DRB are ceased. Neuroleptic Malignant Syndrome is a rare, but life-threatening adverse reaction to DRB which may occur at any time during DRB application. It is characterised by hyperthermia, rigidity, reduced consciousness and autonomic failure. Therapeutically immediate DRB withdrawal is crucial. Additional dantrolene or bromocriptine application together with symptomatic treatment may be necessary. Paroxysmal dyskinesias are childhood onset disorders characterised by dystonic postures, chorea, athetosis and ballism occurring at irregular intervals. In Paroxysmal Kinesigenic Dyskinesia they are triggered by rapid movements, startle reactions or hyperventilation. They last up to 5 minutes, occur up to 100 times per day and are highly sensitive to anticonvulsants. In Paroxysmal Non-Kinesiogenic Dyskinesia they cannot be triggered, occur less frequently and last longer. Other paroxysmal dyskinesias include hypnogenic paroxysmal dyskinesias, paroxysmal exertional dyskinesia, infantile paroxysmal dystonias, Sandifer's syndrome and symptomatic paroxysmal dyskinesias. In Hereditary Episodic Ataxia Type 1 attacks of ataxia last for up to two minutes, may be accompanied by dysarthria and dystonia and usually respond to phenytoin. In Type 2 they can last for several hours, may be accompanied by vertigo, headache and malaise and usually respond to acetazolamide. Symptomatic episodic ataxias can occur in a number of metabolic disorders, but also in multiple sclerosis and Behcet's disease.
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PMID:Diagnosis and management of acute movement disorders. 1620 29

Benign hereditary chorea (BHC) is an autosomaldominant disorder of early onset characterized by a slowly progressing or nonprogressing chorea, without cognitive decline or other progressive neurologic dysfunction, but also by the existence of heterogeneity of the clinical presentation within and among families. The genetic cause of BHC is the presence of either point mutations or deletions in the thyroid transcription factor 1 gene (TITF1). We studied a Portuguese BHC family composed of two probands: a mother and her only son. The patients were identified in a neurology out-patient clinic showing mainly involuntary choreiform movements since childhood, myoclonic jerks, falls, and dysarthria. We performed magnetic resonance imaging (MRI), electroencephalogram (EEG), nerve conduction studies, thyroid ultrasound scan, biochemical thyroid tests, and electrocardiogram (ECG). We excluded Huntington disease by appropriate genetic testing and sequenced the entire TITF1 gene for both patients. The patients showed MRI alterations: (1) in the mother, abnormal hyperintense pallida and cortical cerebral/cerebellar atrophy; and (2) in the son, small hyperintense foci in the cerebellum and subtle enlargement of the fourth ventricle. Sequence analysis of the TITF1 gene in these patients revealed the presence of a heterozygous C > T substitution at nucleotide 745, leading to the replacement of a glutamine at position 249 for a premature stop codon. A previously undescribed nonsense mutation in the TITF1 gene was identified as being the genetic cause of BHC in this family.
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PMID:Nonsense mutation in TITF1 in a Portuguese family with benign hereditary chorea. 1622 Mar 45

A 50-year-old man presented with worsening, virtually lifelong, chorea and progressive behavioural disturbance, involving disinhibition and hoarding, over 10 years. Clinical assessment revealed chorea, dysarthria, areflexia, an inappropriately jovial, impulsive manner and neuropsychological evidence of frontosubcortical dysfunction. Investigation results included an elevated creatine kinase, caudate atrophy and hypoperfusion, acanthocytes in the peripheral blood and the McLeod phenotype. DNA studies demonstrated a single-base deletion at position 172 in exon 1 of the XK gene, giving rise to a premature stop codon at position 129 in exon 2.
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PMID:McLeod syndrome: life-long neuropsychiatric disorder due to a novel mutation of the XK gene. 1631 60

We describe the neurological manifestations of 119 patients with WD (93 index cases and 26 affected family members) seen between 1963 and 2004. The mean age at symptoms onset was 19.6 years (range, 7-37 years). Medical records were reviewed for the patient's first neurological examination. The most frequent neurological manifestations observed were dysarthria (91%), gait disturbance (75%), risus sardonicus (72%), dystonia (69%), rigidity (66%), tremor (60%), and dysphagia (50%). Less frequent manifestations were chorea (16%) and athetosis (14%). Rare neurological presentations were seizures (4.2%), and pyramidal signs (3%).
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PMID:Neurological manifestations in Wilson's disease: Report of 119 cases. 1707 70

A 53-year-old man who had worked for 17 years manufacturing car batteries, with overt exposure to lead, developed a clinical picture initially characterized by signs of parkinsonism, followed by atypical signs such as loss of memory, reduction of eye movement, dysarthria, chorea-like dyskinesia and sexual impotence. The diagnosis of atypical parkinsonism was eventually changed to progressive supranuclear palsy-like parkinsonism. The patient was treated with various anti-Parkinson's disease drugs, including levodopa, with modest improvement. The symptoms deteriorated progressively, leading to permanent occupational disability with noticeable limitation of daily activities. Toxicological studies revealed abnormally high blood levels of lead. Discontinuation of lead exposure was followed first by clinical stabilization and then steady improvement. This case confirms recent reports that link exposure to lead and its compounds with degenerative diseases of the central nervous system, such as Parkinson's disease.
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PMID:Progressive supranuclear palsy-like parkinsonism resulting from occupational exposure to lead sulphate batteries. 1740 69


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