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)

Acanthocytosis occurs because of ultrastructural abnormalities of the erythrocyte membranous skeleton resulting in reduced membrane fluidity. At least three hereditary neurological conditions are associated with it, although as yet the pathogenesis of the neurological features is unknown. In abetalipoproteinaemia, an autosomal recessive condition, vitamin E deficiency results in a progressive spinocerebellar syndrome associated with peripheral neuropathy and retinitis pigmentosa. Neuroacanthocytosis is also probably an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysarthria, areflexia, seizures and dementia. McLeod syndrome is an X-linked recessive disorder usually presenting in males as a benign myopathy with areflexia, in association with a particular abnormality of expression of Kell blood group antigens. However, occasionally the neurological features are more severe and indistinguishable from those of neuroacanthocytosis. Recent advances in molecular genetics may assist better understanding of the disease mechanisms and the search for more effective treatments.
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PMID:Acanthocytosis and neurological disorders. 1128 40

The term acanthocytosis is derived from the Greek for "thorn" and is used to describe a peculiar spiky appearance of erythrocytes. Acanthocytosis is found to be associated with at least three hereditary neurological disorders that are generally referred to as neuroacanthocytosis. Abetalipoproteinaemia is an autosomal recessive condition, characterised by absence of serum apolipoprotein B containing lipoproteins leading to fat intolerance and fat-soluble vitamin deficiency. This results in a progressive spinocerebellar ataxia with peripheral neuropathy and retinitis pigmentosa. Chorea-acanthocytosis is also an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysphagia, dysarthria, areflexia, seizures and dementia. Some of its features, including choreic movements, peripheral neuropathy with areflexia, elevated serum creatine kinase levels and myopathy are shared by another form of neuroacanthocytosis, McLeod syndrome. Patients affected by this X-linked disorder also show abnormal expression of Kell blood group antigens and a permanent haemolytic state. In addition to these cases, acanthocytosis is occasionally associated with other neurological disorders, such as Hallervorden-Spatz disease. For each of the neuroacanthocytosis syndromes we review the main clinical features and their molecular bases. The recent molecular genetics findings are the first step towards the understanding of the pathogenetic mechanisms and eventually the search for effective treatments.
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PMID:Clinical features and molecular bases of neuroacanthocytosis. 1218 48

The case of a 63-year-old woman who presented with status epilepticus, coma and hypoventilation is reported. A primary neurological cause was considered. Hypothermia led to further investigations and a diagnosis of severe hypothyroidism. The neurological complications of hyperthyriodism include alteration in mental status with slowness, decreased concentration and lethargy, headache, cranial nerve palsies, dysarthria, hoarseness, myopathy, neuropathy, reflex changes, ataxia, and psychotic episodes. Our patient suffered from a rare consequence of severe hypothyroidism presenting with status epilepticus and she died despite treatment. To our knowledge this is the second patient to be reported with myxoedema coma with this kind of presentation. Despite therapeutic options, there is a high mortality rate.
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PMID:Status epilepticus caused by a myxoedema coma. 1712 58

Recognizing an ALS-mimic can be challenging. Here, we describe a patient with a slowly progressive dysarthria and dysphagia, with fasciculations of the tongue and general hyperreflexia, fulfilling the diagnostic criteria of 'clinical probable ALS'. Because of a non-conclusive EMG, a muscle biopsy was performed that surprisingly showed widespread nemaline rods. The clinical features and the histological findings were compatible with a sporadic late onset nemaline myopathy. Three years after initial presentation the patient died and post-mortem examination not only showed nemaline bodies in every muscle examined, but also revealed an unsuspected final diagnosis: sarcoid brainstem encephalitis. Nemaline rods can be found in various disorders, and neurosarcoidosis should be added to this list.
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PMID:A case of neuromuscular mimicry. 1691 50

Neurological paraneoplastic syndromes (NPS) are rare disorders in association with malignancy and the presence of various antineuronal antibodies. The persistence of antineuronal antibodies for years after the eradication of the tumor without clinical manifestations of a NPS has not been reported. In a 64-year-old woman with a history of gynecologic malignancy, treated by surgery and chemotherapy with docetaxel and carboplatin, ptosis, hypertelorism, dysarthria, short stature, upper and lower limb weakness, exaggerated tendon reflexes and recurrent creatine-kinase elevation were found. Nerve conduction studies disclosed polyneuropathy and muscle biopsy nonspecific myopathic features. Though anti-Yo antibodies were repeatedly positive, the clinical findings and polyneuropathy were rather attributed to a suspected metabolic myopathy or chemotherapy than a NPS. Anti-Yo antibodies remained positive at 5 further determinations. During the 5 years of follow up there was improvement of polyneuropathy and no relapse of the malignancy, as assessed clinically, by tumor markers, computed tomography scans and 18-fluorodeoxyglucose positron emission tomography. Anti-Yo antibodies may occur without the typical clinical manifestations of a NPS and may persist for years without the development of a NPS or relapse of the tumor.
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PMID:Asymptomatic persistence of anti-Yo antibodies for 5 years without relapse of malignancy. 1764 47

Mutations in POLG gene are responsible for a wide spectrum of clinical disorders with altered mitochondrial DNA (mtDNA) integrity, including mtDNA multiple deletions and depletion. Sensory ataxic neuropathy with ophthalmoparesis (SANDO) caused by mutations in POLG gene, fulfilling the clinical triad of sensory ataxic neuropathy, dysarthria and/or dysphagia and ophthalmoparesis, has described in a few reports. Here we described five cases of adult onset autosomal recessive sensory ataxic neuropathy with ophthalmoplegia. All patients had ataxia, neuropathy, myopathy, and progressive external ophthalmoplegia (PEO). The muscle pathology revealed ragged-red and cytochrome c oxidase (COX) negative fibers in three patients. However, deficiencies in the activities of mitochondrial respiratory chain enzyme complexes were not detected in any of the patients' muscle samples. Multiple deletions of mtDNA were detected in blood and muscle specimens but mtDNA depletion was not found. Due to these diagnostic difficulties, POLG-related syndromes are definitively diagnosed based on the presence of deleterious mutations in the POLG gene.
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PMID:Sensory ataxic neuropathy with ophthalmoparesis caused by POLG mutations. 1858 14

Progressive external ophthalmoplegia (PEO) can be caused by a disorder characterized by multiple mitochondrial DNA (mtDNA) deletions due to mutations in the TWINKLE gene, encoding a mtDNA helicase. We describe a 71-year-old woman who had developed PEO at age 55 years. She had cataracts, diabetes, paresthesias, cognitive defects, memory problems, hearing loss, and sensory ataxia. She had muscle weakness with ragged red fibers on biopsy. MRI showed static white matter changes. A c.908G>A substitution (p.R303Q) in the TWINKLE gene was identified. Multiple mtDNA deletions were detected in muscle but not blood by a PCR-based method, but not by Southern blot analysis. MtDNA copy number was maintained in blood and muscle. A systematic literature search was used to identify the genotypic and phenotypic spectrum of dominant TWINKLE-related disease. Patients were adults with PEO and symptoms including myopathy, neuropathy, dysarthria or dysphagia, sensory ataxia, and parkinsonism. Diabetes, cataract, memory loss, hearing loss, and cardiac problems were infrequent. All reported mutations clustered between amino acids 303 and 508 with no mutations at the N-terminal half of the gene. The TWINKLE gene should be analyzed in adults with PEO even in the absence of mtDNA deletions in muscle on Southern blot analysis, and of a family history for PEO. The pathogenic mutations identified 5' beyond the linker region suggest a functional role for this part of the protein despite the absence of a primase function in humans. In our patient, the pathogenesis involved multiple mtDNA deletions without reduction in mtDNA copy number.
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PMID:Finding twinkle in the eyes of a 71-year-old lady: a case report and review of the genotypic and phenotypic spectrum of TWINKLE-related dominant disease. 1935 76

Infection of the central nervous system with Nocardia sp. usually manifests as supratentorial abscesses. Supratentorial and cerebellar abscesses from infection with Nocardia sp. following immunosuppression with long-term corticosteroids for idiopathic thrombocytopenia (ITP) have not been reported. An 83 years-old, human immunodeficiency virus (HIV)-negative, polymorbid male with ITP for which he required corticosteroids since age 53 years developed tiredness, dyspnoea, hemoptysis, abdominal pain, and progressive gait disturbance. Imaging studies of the lung revealed an enhancing tumour in the right upper lobe with central and peripheral necrosis, multiple irregularly contoured hyperdensities over both lungs, and right-sided pleural effusions. Sputum culture grew Nocardia sp. Neurological diagnostic work-up revealed dysarthria, dysphagia, ptosis, hypoacusis, tremor, dysdiadochokinesia, proximal weakness of the lower limbs, diffuse wasting, and stocking-type sensory disturbances. The neurological deficits were attributed to an abscess in the upper cerebellar vermis, myopathy from corticosteroids, and polyneuropathy. Meropenem for 37 days and trimethoprime-sulfamethoxazole for 3 months resulted in a reduction of the pulmonary, but not the cerebral lesions. Therefore, sultamicillin was begun, but without success. Long-term therapy with corticosteroids for ITP may induce not only steroid myopathy but also immune-incompetence with the development of pulmonary and cerebral nocardiosis. Cerebral nocardiosis may not sufficiently respond to long-term antibiotic therapy why switching to alternative antibiotics or surgery may be necessary.
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PMID:Cerebellar nocardiosis and myopathy from long-term corticosteroids for idiopathic thrombocytopenia. 2004 27

Mitochondria is an intracellular double membrane-bound structure and it can provide energy for intracellular metabolism. The metabolism includes Krebs cycle, beta-oxidation and lipid synthesis. The density of mitochondria is different in various tissues dependent upon the demands of oxidative phosphorylation. Mitochondrial diseases can occur by defects either in mitochondrial DNA or nuclear DNA. Human mitochondrial DNA (mtDNA) encoding for 22 tRNAs, 2 rRNAs and 13 mRNAs that are translated in the mitochondria. Mitochondrial genetic diseases are most resulted from defects in the mtDNA which may be point mutations, deletions, or mitochondrial DNA depletion. These patterns of inheritance in mitochondrial diseases include sporadic, maternally inherited, or of Mendelian inheritance. Mitochondrial DNA depletion is caused by defects in the nuclear genes that are responsible for maintenance of integrity of mtDNA or deoxyribonucelotide pools and mtDNA biogenesis. The mtDNA depletion syndrome (MDS) includes the following categories: progressive external ophthalmoplegia (PEO), predominant myopathy, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), sensory-ataxic neuropathy, dysarthria, and ophthalmoplegia (SANDO) and hepato-encephalopathy. The most common tissues or organs involved in MDS and related disorders include the brain, liver and muscles. These involved genes are divided into two groups including 1) DNA polymerase gamma (POLG, POLG2) and Twinkle genes whose products function directly at the mtDNA replication fork, and 2) adenine nucleotide translocator 1, thymidine phosphorylase, thymidine kinase 2, deoxyguanosine kinase, ADP-forming succinyl-CoA synthetase ligase, MPV17 whose products supply the mitochondria with deoxyribonucleotide triphosphate pools needed for mtDNA replication, and possible mutation in the RRM2B gene. The development has provided new information about the importance of the biosynthetic pathway of the nucleotides for mtDNA replication. Further investigation on the understatanding between the nuclear and mitochondrial genomes is expected.
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PMID:[Mitochondrial disease and mitochondrial DNA depletion syndromes]. 2032 99

This was a single-centre, prospective study to assess the frequency of neurological complications and their impact on prolonged hospitalization in 137 liver transplant patients presenting between September 1997 and June 2010. Neurological complications were seen in 22 (16%) patients during their postoperative stay in the intensive care unit. Complications included new-onset, recurrent headache (five patients), generalized seizures (four patients), dysarthria (two patients), delirium with agitation (three patients), persistent flapping tremor (two patients), alteration in level of consciousness (three patients), central pontine myelinolysis (one patient), myopathy (one patient) and visual hallucinations (one patient). Seizures were associated with immunosuppressive drug toxicity (tacrolimus). Myopathy presenting as quadriplegia was diagnosed by muscle biopsy. The patient with central pontine myelinolysis lived in a persistent vegetative state for 2 years and died of pneumonia. In conclusion, neurological complications are frequently encountered after liver transplantation, and are an important cause of severe morbidity and prolonged intensive care unit and hospital stay.
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PMID:Neurological complications after liver transplantation. 2198 51


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