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)

Fabry's disease (FD) is a rare, sex-linked disorder resulting from alpha-galactosidase deficiency. Cerebrovascular complications have been reported in the literature but have not been systematically analyzed. We report 2 patients and review 51 previously reported cases (descriptive meta-analysis) to clarify the clinical, radiologic, and pathologic features. The average age at onset of cerebrovascular symptoms was 33.8 years for hemizygous individuals (n = 43) and 40.3 years of heterozygotes (n = 10). The most frequent symptoms and signs were as follows (in descending order of frequency): hemiparesis, vertigo/dizziness, diplopia, dysarthria, nystagmus, nausea/vomiting, head pain, hemiataxia, and ataxia of gait, in the hemizygote group; and memory loss, dizziness, ataxia, hemiparesis, loss of consciousness and hemisensory symptoms, in the heterozygote group. The vertebrobasilar circulation was symptomatic in 67% of the hemizygotes and 60% of the heterozygotes. Intracerebral hemorrhage was found in 4 patients (3 hemizygotes and 1 heterozygote). Elongated, ectatic, tortuous vertebral and basilar arteries were the most common angiographic and pathologic features. For the hemizygotes, the recurrence rate for cerebrovascular disease was 76% and the death rate was 55%; 86% of the heterozygotes had recurrent cerebrovascular event(s) and 40% died. The cerebrovascular manifestations of FD, in both hemizygotes and heterozygotes, are predominantly due to dilative arteriopathy of the vertebrobasilar circulation, frequently recur, and portend a poor prognosis.
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PMID:Cerebrovascular complications of Fabry's disease. 868 96

CADASIL disease (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) was described in 1991 by Tourmier-Lasserve. Two years later the same authors described its association with chromosome 19; nonetheless, the mutations in gene Notch3 were not described until 1996. Clinical findings depend on the age at onset. The early form of the illness is found in young patients, generally less than 30 years old, and the main clinical manifestation is a migraine headache with subcortical lesions in the white matter, while in the later form ischemic events and behavioral symptoms are predominant. Anatomo-pathological findings in CADASIL include the presence of osmophilic granular deposits in vessel walls, skin, muscles and cerebral arteries. We present a patient with CADASIL and cavernous angioma. We studied a 40-year-old woman who underwent surgery for a left temporal-parietal cavernous angioma, with aphasia as the only symptom, two years before admission. Her family history showed that her father had suffered from vascular dementia. She was admitted to our hospital with right-side hemiparesis and dysarthria. A CT scan showed the presence of ischemic vascular lesions and former surgery sequelae. The duplex scan of the neck vessels and a transesophageal echocardiogram ruled out an embolic source. Laboratory tests including VDRL, HIV, prothrombotic profile and rheumatologic screening tests were normal. An MRI in T2W and FLAIR showed the presence of multiple subcortical cerebral lesions and hyperintensity in the white matter (leukoencephalopaty). We found a left acute putaminal-capsular infarct in the diffusion-MRI. The MRA was normal. Analysis of the cerebrospinal fluid was unremarkable. A molecular DNA test was performed, and a nucleotide substitution in position 583 in exon 4 of gene Notch3 was detected. This mutation was found only in CADASIL patients. The association with cavernous angioma has not been previously reported, and we believe that it was unrelated to CADASIL, either clinically or genetically. To our knowledge, this is the first case of CADASIL diagnosed by molecular DNA test in our country.
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PMID:[Cadasil: a case with molecular diagnosis]. 1196 50

Fabry's disease is an X linked inborn error of metabolism due to deficient activity of the lysosomal enzyme alpha galactosidase A. Previously unrecognised Fabry's disease presenting in a 52 year old man being investigated for progressive dysarthria and ataxia is discussed. Brain magnetic resonance imaging suggested the presence of small vessel disease but skin biopsy (done to exclude cerebral autosomal dominant arteriopathy with subcortical infarcts and leucencephalopathy) showed typical changes of Fabry's disease. This diagnosis was confirmed by subsequent enzyme assays. The authors contend that Fabry's disease should be excluded, at least on clinical grounds, in patients with otherwise unexplained cerebrovascular disease.
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PMID:Neurological presentation of Fabry's disease in a 52 year old man. 1218 77

A 38-year-old man was admitted to our hospital with headache, dysarthria and paraparesis. Brain CT and diffusion MRI disclosed cerebral infarction at bilateral anterior cerebral artery (ACA) territories. His symptoms and signs deteriorated in several days despite intensive antithrombotic therapy, resulting in right hemiparesis, akinetic mutism, memory disturbance, change of personality, urinary incontinence, forced grasping, and starting delay of speech and motion. Cerebral angiography demonstrated occlusion with contrast pooling at the right ACA A2 portion. Stenosis and dilatation were found at left ACA A2 portion. An intimal flap was also demonstrated on serial angiography. This case was diagnosed as cerebral infarction caused by dissection of bilateral ACA. Although no definite primary arteriopathy was demonstrated, bilateral dissection could be occurred simultaneously.
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PMID:[A case of juvenile cerebral infarction caused by bilateral anterior cerebral artery dissection]. 1266 Nov 8

A cerebral arteriopathy with subcortical infarcts and leukoencephalopathy is described with a pedigree suggestive for an autosomal dominant condition. In contrast to the vasculopathy designated with the acronym CADASIL, no deposits of granular osmiophilic material were detected in the vasculature and no point mutations in the NOTCH 3 gene were found. The disease occurred in a family living near Hamburg, Germany, and affected 11 women and 11 men over the last six generations. Onset of the disease was between the age of 12 and 50. Clinical symptoms included gait disturbances, dysarthria, sensomotoric deficits and a progressive dementia. Migraine-like complaints and epileptic seizures were observed in one case each. Cranial computer tomography and magnetic resonance imaging scans showed large confluent areas with decreased density in the white matter and small necroses in the brain stem, the basal ganglia and the white matter. A correlation with factors predisposing for vascular diseases could not be demonstrated. In five cases an autopsy was performed which disclosed an angiopathy affecting predominantly the penetrating arteries with consecutive lacunar infarcts, diffuse demyelination and rarefication of the subcortical white matter and degeneration of the pyramidal tracts. Histologically, the vessels showed concentric and excentric intimal proliferation, an elastosis and hyalinosis, splitting of the lamina elastica interna and a degeneration of the tunica muscularis. Electron microscopy revealed fragmentation and thickening of the basal lamina but electron-dense granules characteristic for CADASIL were not detected.
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PMID:Subcortical angiopathic encephalopathy in a German kindred suggests an autosomal dominant disorder distinct from CADASIL. 1522 37

The term lacuna, or cerebral infarct, refers to a well-defined, subcortical ischemic lesion at the level of a single perforating artery, determined by primary disease of the latter. The radiological image is that of a small, deep infarct. Arteries undergoing these alterations are deep or perforating arteries with a diameter ranging between 100 and 400 microm, numbering 6-12, that generally originate at right angles directly from the main arteries. The concept of lacunar syndrome was introduced in clinical practice to describe those clinical pictures that generally, although not always, have a cerebral infarct of lacunar type as the underlying mechanism. Classic clinical syndromes induced by lacunar infarcts are, in decreasing order of frequency, pure motor stroke, pure sensory stroke, sensorimotor stroke, ataxic hemiparesis, and dysarthria with motor disability of one hand, as well as a number of rare or incomplete syndromes. Small lacunar infarct that will then degenerate into a lacuna is caused by a reduction of blood flow to a perforating artery. In turn, this is the result of various arterial disorders, the most frequent of which include microatheroma, lipohyalinosis, fibrinoid necrosis, and Charcot-Bouchard aneurysm. Other forms of arteriopathy that can affect small vessels include amyloid angiopathy, and cerebral autosomic dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Hemodynamic disorders also can be a cause of the disease. Diagnosis is made with 1,5 Tesla MRI and prognosis is generally good.
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PMID:Lacunar infarct. 1683 26

We report the rare presentation of lacunar stroke syndrome secondary to single perforator mouth occlusion from radiation-induced middle cerebral artery (MCA) stem arteriopathy. A 30-year-old female had acute-onset right-sided ataxic hemiparesis and dysarthria. As a child, she had a medulloblastoma of the posterior fossa and had surgery followed by cranial radiotherapy. She had no significant vascular risk factors. Acute CT showed extensive bilateral basal ganglia and left thalamic calcification; DWI showed a left internal capsule lacunar infarct; and MRA and CTA showed a 50% stenosis of the proximal left MCA.
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PMID:Lacunar stroke attributable to radiation-induced intracranial arteriopathy. 1766 19

We report herein a 61-year-old man with diffuse leukoencephalopathy, subcortical infarcts and cervical and lumbar spondylosis. Medical history included baldness and lumbar spondylosis at young-adult onset. His parents were consanguineous (cousin). He had been experiencing severe lumbago since 20-years-old, with hair loss starting around the same time. He noticed dysarthria and gait disturbance at 59-years-old. He was admitted to our hospital at 61-years-old with aggravation of gait disturbance. On admission, no abnormalities were evident on physical examination except for diffuse baldness. Neurological findings included mild dementia, bilateral hyperreflexia, paraparesis, right Babinski's sign, and pseudobulbar palsy. Blood pressure was normal. T2-weighted imaging of the brain revealed diffuse high-intensity in the periventricular white matter and subcortical infarcts in the brainstem and bilateral basal ganglia. Marked lumbar deformations were observed on spinal MRI. Clinical features in this case met the criteria for cerebral autosomal recessive arteriopathy with subcortical infarctions and leukoencephalopathy (CARASIL), apart from late onset of cerebral infarction.
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PMID:[Late-onset leukoencephalopathy without hypertension in a case of young-adult-onset alopecia and spondylosis: a variant of CARASIL?]. 1861 51

We report the case of a 66-year-old female who presented with dysarthria and dysphonia. Brain MRI abnormalities showed confluent white matter lesions and subcortical lacunar infarcts, suggesting cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), confirmed by the presence of a heterozygous mutation in the Notch3 gene. Clinical signs and course were consistent with amyotrophic lateral sclerosis (ALS) as was the electromyographic pattern. The possible pathogenic role for a mutation in the Notch3 gene is discussed considering recent data on hypoxia in the pathophysiology of ALS.
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PMID:CADASIL and ALS: a link? 1948 2

A 60-year-old man visited our hospital because of left hemiparesis in September 2006. Magnetic resonance imaging (MRI) revealed a high-intensity lesions in the right corona radiata on diffusion-weighted images and a high-intensity lesions in the basal ganglia and deep white matter on T2-weighted images. He recovered with no sequelae. Antithrombotic agents such as aspirin were given to prevent stroke, but stroke recurred three times over the course of 3 years. In February 2009, neurological examination revealed right hemiparalysis and dysarthria. Dysphagia and cognitive decline had been progressing gradually. We suspected cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) on the basis of the clinical and family history. An Arg75Pro mutation in the Notch3 gene was found, but did not involve a cysteine residue. Antithrombotic agents were ineffective. We tried lomerizine hydrochloride, which was reported to prevent stroke in a patient with CADASIL. In Japan, lomerizine hydrochloride is used to prevent migraine and to selectively inhibit cerebral artery contraction. During treatment with lomerizine hydrochloride (5 mg/day) for more than 3 years, there was no recurrence of cerebral infarction and no further deterioration of cognitive function or MRI findings. There is no evidence supporting the efficacy of antithrombotic agents in CADASIL patients. Moreover, antithrombotic agents have been reported to increase the frequency of clinically silent microbleeds on MRI in CADASIL. Lomerizine hydrochloride might therefore be one option for the treatment of CADASIL.
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PMID:[A case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in which lomerizine hydrochloride was suggested to prevent recurrent stroke]. 2442 44


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