Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid progress has been made in the identification of mitochondrial DNA mutations which are typically associated with diseases of the nervous system and muscle. The well established mitochondrial disorders are maternally inherited and males and females are equally affected. An exception is Leber's hereditary optic atrophy (LHON) which is observed much more frequently in males than in females. There are three common point mutations in LHON which can be homoplasmic or heteroplasmic. In mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) most mutations are single base changes and lie within the tRNA-Leu gene. Point mutations in myoclonic epilepsy with ragged red fibres (MERRF) usually occur within the tRNA-Lys gene but mutations of the tRNA-Leu gene are also observed. MELAS and MERRF mutations are heteroplasmic and there is considerable clinical overlap between these diseases. Point mutations within the ATPase6 gene result in either neuropathy, ataxia and retinitis pigmentosa (NARP) or in Leigh's syndrome. The latter occurs if the mutation is present in the majority of mitochondria (extreme heteroplasmy). Finally, mitochondrial DNA deletions are the cause underlying Kearns-Sayre syndrome (KSS). Apart from the well-established mitochondrial diseases, there is increasing evidence that mitochondrial mutations may also play a role in the neurodegenerative disorders Parkinson, Alzheimer and Huntington disease. The complex I defect found in Parkinson disease is especially interesting in this respect. However, no causative mitochondrial mutation has as yet been established in any of these three common disorders.
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PMID:Recent developments in the molecular genetics of mitochondrial disorders. 951 82

A 66-year-old woman was admitted to the hospital with a neurological syndrome characterized by ataxia and diplopia. Magnetic resonance of the brain documented an ischemic medullary lesion. Examination of the heart revealed a grade 2/6 systolic murmur at the left sternal border and apex that radiated towards the axilla. The echocardiography study showed a mild mitral regurgitation, and an abnormally enlarged posterior papillary muscle was found in the left ventricle. Two weeks after admission, the patient died suddenly due to a stroke. At autopsy, a recent vast swollen ischemic cerebral infraction was found. Furthermore, two old infarcts were observed in the spleen. A cardiac examination showed a white-gray ulcered mass in the left ventricle and histological analysis revealed a rhabdomyosarcoma.
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PMID:Cardiac rhabdomyosarcoma: a clinicopathologic and electron microscopy study. 961 53

Acute infarction confined to the territory of the white matter medullary arteries is a poorly characterised acute stroke subtype. 22 patients with infarction confined to this vascular territory on CT and/or MRI were identified from a series of 1,800 consecutive admissions to our stroke unit (1.2%) between August 1993 and March 1997. 19 patients had small infarcts (< 1.5 cm maximum diameter) and 3 large infarcts (> 1.5 cm). Small infarcts were associated with a history of smoking (69%), hypertension (58%), and hyperlipidaemia (37%), and less frequently with atrial fibrillation (21%). Significant (>50%) ipsilateral carotid stenosis (16%) was a less frequent finding in this group. Patients most commonly presented with weakness and/or sensory disturbance affecting mainly the upper limbs, but dysarthria, dysphasia, and ataxia were also seen. Large infarcts were infrequent in our series, but did not differ significantly from small infarcts with respect to clinical presentation or risk factor profiles (p > 0.05 for all comparisons). The majority of symptomatic patients with white matter medullary infarcts are associated with small (< 1.5 cm diameter) lesions and a risk factor profile consistent with small vessel disease. More data are required to elucidate the mechanism of larger (> 1.5 cm) infarcts. Because of the potential overlap between white matter medullary infarcts and internal watershed infarcts, suggested criteria for each are presented.
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PMID:White matter medullary infarcts: acute subcortical infarction in the centrum ovale. 971 27

Since the first identification in 1988 of pathogenic mitochondrial DNA (mtDNA) mutations, the mitochondrial diseases have emerged as a major clinical entity. The most striking feature of these disorders is their marked heterogeneity, which extends to their clinical, biochemical, and genetic characteristics. The major mitochondrial encephalomyopathies include MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes), MERRF (myoclonic epilepsy with ragged red fibers), KSS/CPEO (Kearns-Sayre syndrome/chronic progressive external ophthalmoplegia), and NARP/MILS (neuropathy, ataxia, and retinitis pigmentosum/maternally inherited Leigh syndrome) and they typically present highly variable multisystem defects that usually involve abnormalities of skeletal muscle and/or the CNS. The primary emphasis here is to review recent investigations of these mitochondrial diseases from the standpoint of how the complexities of mitochondrial genetics and biogenesis might determine their varied features. In addition, the mitochondrial encephalomyopathies are compared and contrasted to Leber hereditary optic neuropathy, a mitochondrial disease in which the pathogenic mtDNA mutations produce a more uniform and focal neuropathology. All of these disorders involve, at some level, a mitochondrial respiratory chain dysfunction. Because mitochondrial genetics differs so strikingly from the Mendelian inheritance of chromosomes, recent research on the origin and subsequent segregation and transmission of mtDNA mutations is reviewed.
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PMID:Human mitochondrial diseases: answering questions and questioning answers. 977 Feb 97

A 55-year-old woman, who had two episodes of difficulty in putting a key into a keyhole probably due to optic ataxia at age 52 and 54 years old, developed speaking errors and was admitted to our hospital. She was 152.5 cm in height and 52.5 kg in weight. Neurological examination revealed right homonymous hemianopsia and sensory aphasia. A CSF examination revealed lymphocytic pleocytosis of 88/microliter. Serum lactate and pyruvate were remarkably increased after an aerobic exercise test. A few ragged-red fibers were present in the biopsied brachial biceps muscle. Brain MRI by FLAIR method showed scattered high signal lesions in the left temporal lobe, bilateral parieto-occipital lobes, left insular cortex and left thalamus. The left superficial temporal lesion was enhanced by gadolinium-DTPA. The proton MRS demonstrated the lactic acid peak as well as the decrease of NAA/choline ratio (0.38) in the left parieto-occipital region. Thus, she was diagnosed as a case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and successfully treated with ubidecarenone (150 mg/day). Six months later, she again developed seizure, right hemiparesis and deterioration of aphasia and presented again CSF lymphocytic pleocytoses of 15/microliter. Brain MRI demonstrated new lesions in the left temporoparietal lobes, left insular cortex and left corona radiata. Therefore, CSF pleocytosis appeared to be associated with stroke-like episodes in this case. Although the mechanism of CSF pleocytosis remains to be elucidated, it may involve the breakdown of blood-brain barrier caused by mitochondrial dysfunction. Otherwise, an inflammatory process similar to that in cases of Leber disease, who developed multiple sclerosis-like additional lesions in the central nervous system, may also take place in MELAS.
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PMID:[A case of MELAS showing CSF pleocytosis associated with stroke-like episodes]. 986 8

We prospectively studied motor symptoms in 32 patients with CT- or MRI-proven acute pure parietal stroke. A transient, mild, 'pseudoparesis' of the hand (90%), was noted, improved by visual attention and prompting, associated with non-awareness of muscle power (53%), transient soft pyramidal signs (50%), unilateral akinesia (100%) and motor hemineglect (37%) in non-dominant lesions. Lower motoneurone-type atrophy was not observed in this acute phase. We called 'poikilotonia' the striking unpredictable variations in muscle tone, ranging from extreme hypertonia to hypotonia, found in all patients. When maintaining postures, patients showed large oscillations (100%), laterodeviation or levitation of the arm (60%), especially in the case of large or posterior lesions, or, occasionally (3%), motor persistence or even hemicatalepsy (3%). Limb kinetic and manipulatory apraxia, with inadequate organization and anticipation of motor sequences and synergies, motor arrests, perplexity, unrecognizable gestures and loss of bimanual coordination, was a constant finding (100%). Other apraxias (62%) and difficulty in copying intransitive gestures of the hand (84%) were associated with posterior lesions involving the supramarginal gyrus. When reaching towards objects, all patients showed abnormal anticipatory hand shaping, but visuomotor ataxia (3%) was only seen with bilateral posterior stroke. Sensory (70%) or pseudocerebellar (4%) ataxia, was seen in both anterior and posterior lesions. Avoidance behaviors (34%) were not uncommon, but had no localizing value. Of the dyskinesias, hand dystonia (84%) was frequent, but athetosis (16%), asterixis (15%), postural tremor (15%), myoclonus (9%) and stereotypia (9%), were uncommon. The abnormal eye movements were unilateral hypo-akinesia of exploratory saccades (43%), abnormal ipsilateral pursuit and contralateral optokinetic nystagmus in the case of posterior lesions, and oculomotor apraxia with bilateral posterior lesions. In conclusion, parietal motor syndrome can be recognized during bedside examination, and probably reflects the loss of multiple sensory feedback to motor programs, especially those directed to the extrapersonal space.
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PMID:Parietal motor syndrome: a clinical description in 32 patients in the acute phase of pure parietal strokes studied prospectively. 987 53

This report concerns an autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with unusual neuropathological findings. The patient was a Japanese woman who was 21 years old at the time of death. Her mother is a patient with genetically confirmed MELAS. Her clinical manifestations included convulsions and lactic acidosis in the latter half of the first decade of life, followed by deafness, dementia, muscle weakness in the lower extremities, slight ataxia in the upper and lower extremities, and diabetes mellitus. Muscle biopsy revealed ragged-red fibers, and genetic study showed a point mutation at nucleotide pair 3243 in mitochondrial DNA. She died of lactic acidosis. In the clinical course, she did not develop stroke-like episodes. The neuropathological examination revealed not only minute to small necrotic foci in the cerebral cortex, amygdala, hippocampus, and cerebellum, but also prominent white matter gliosis in the central nervous system and cerebellar cortical degeneration of granular cell type. Our neuropathological findings, including prominent white matter gliosis of the central nervous system and cerebellar cortical degeneration of granular cell type, may indicate morphologically widespread cellular dysfunction, not restricted to either neuronal or vascular derangement, in the brain pathology of MELAS.
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PMID:MELAS with prominent white matter gliosis and atrophy of the cerebellar granular layer: a clinical, genetic, and pathological study. 1033 91

Cerebral infarction is a well-documented complication of systemic lupus erythematosus (SLE), that usually occurs several years after the diagnosis of SLE. To our knowledge, however, strokes associated with vertebrobasilar artery involvement were not reported to present as an initial manifestation of SLE. We report two patients, who presented with vertebrobasilar territory infarction as an initial manifestation of SLE. Patient 1 was a 16-year-old girl, who developed dysarthria and ataxia. MRI showed multiple infarcts in the pons, cerebellum and thalamus. Four-vessel cerebral angiography showed multifocal stenoses in the vertebral and basilar arteries with beaded appearance. Patient 2 was a 26-year-old woman, who developed headache associated with dysarthria, dizziness and ataxia. MRI showed multiple infarcts in the cerebellum, medulla, pons, midbrain and thalamus. Cerebral angiography revealed occlusion of both vertebral arteries at the first cervical vertebral level with non-visualization of the basilar artery. Both patients were diagnosed as having SLE supported by laboratory results. Although rare, posterior circulation stroke can present as an initial manifestation of SLE, which may be attributed to vasculitis or dissection in the vertebral/basilar artery.
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PMID:Vertebrobasilar artery territory infarction as an initial manifestation of systemic lupus erythematosus. 1035 Feb 8

MELAS syndrome is typically characterized by normal early development and childhood-onset recurrent neurologic deficits (stroke-like episodes), seizures, short stature, lactic acidosis, and ragged red fibers on muscle biopsy specimens. It is usually, but not invariably, associated with the A3243G point mutation in the mitochondrial DNA tRNALeu(UUR) gene. We report 3 unrelated children with the A3243G mutation who presented with severe psychomotor delay in early infancy. One patient's clinical picture was more consistent with Leigh syndrome, with apneic episodes, ataxia, and bilateral striatal lesions on brain magnetic resonance imaging (MRI). The second patient had generalized seizures refractory to treatment and bilateral occipital lesions on brain MRI. The third child had atypical retinal pigmentary changes, seizures, areflexia, and cerebral atrophy on brain MRI. All patients had several atypical features in addition to early onset: absence of an acute or focal neurologic deficit, variable serum and cerebrospinal fluid lactate levels, lack of ragged red fibers in muscle biopsy specimens. The proportion of mutant mtDNA in available tissues was relatively low (range, 5% to 51% in muscle; 4% to 39% in blood). These observations further extend the phenotypic expression of the A3243G "MELAS" mutation. Our findings confirm previous observations that there is poor correlation between abundance of mutant mtDNA in peripheral tissues and neurologic phenotype. This suggests that other factors contribute to the phenotypic expression of this mutation.
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PMID:Infantile encephalopathy associated with the MELAS A3243G mutation. 1035 36

Unilateral cerebellar infarcts in the territory of the superior cerebellar artery (SCA) have been studied in recent years to delineate the clinical presentation and stroke mechanism, but most studies excluded bilateral infarctions. We have studied patients with bilateral SCA infarctions to provide data on clinical findings, stroke distribution and outcome. We collected data of 8 patients with bilateral SCA infarctions recognized by computed tomography and/or magnetic resonance imaging. The most common clinical presentation of patients with bilateral SCA infarctions were nausea, vomiting or vertigo (6 patients), often associated with ataxia and dysarthria (5 patients). Further symptoms were variable and depended on additional infarcts in other vascular territories. Infarcts were often partial or scattered with equal distribution between the medial and lateral branches of the SCA. Complete infarction within the SCA area occurred in less than half of the cases. Clinical outcome was either benign (full recovery in 3 patients) or fatal (5 patients). Predictors for a good clinical recovery were young age, few vascular risk factors, only partial involvement of the SCA territory without involvement of other vascular territories, and absent limb weakness on clinical presentation.
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PMID:Presentation and prognosis of bilateral infarcts in the territory of the superior cerebellar artery. 1054 90


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