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

Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results.
 ...
PMID:[Hepatolenticular degeneration]. 226 49

We report a 53-year-old right handed woman with a 5-year history of slowly progressive clumsiness of her right hand. Neurologic symptoms was otherwise unremarkable except for mild dysarthria. Brain CT and MRI revealed a focal atrophic change in the left precentral gyrus. She was thought to have the primary progressive limb-kinetic apraxia. Electrophysiological studies were performed to explore physiologic mechanism of her apraxia. Surface EMG revealed co-contraction of antagonistic muscles in her right upper extremity with rhythmic myoclonic discharges. C-reflex was positive after median nerve stimulation only on the affected side. SEPs elicited by the median nerve stimulation were not enlarged and the SEP recovery curves showed no abnormal facilitation or inhibition. In addition, the premyoclonus spike was demonstrated by Jerk-locked averaging. Transcranial magnetic stimulation using double pulse paradigm revealed a decrease in the level of cortico-cortical inhibition on the motor cortex in the affected side. Median nerve stimulation given prior to the transcortical magnetic stimulation on the size of the magnetic evoked potential (MEP) revealed abnormal facilitations on the affected side, especially at conditioning-test interval of 60-80 ms. Therefore, our results indicate increase in the excitability of motor cortical neurons in primary progressive limb-kinetic apraxia, likely due to a decreased excitability of cortico-cortical inhibitory mechanism as a result of focal degeneration of cortical neurons.
 ...
PMID:[Primary progressive limb-kinetic apraxia: a case report with an electrophysiological study]. 1039 51

Wilson disease is an autosomal recessive disease that produces a copper accumulation in many organs, initially in the liver, progressing to liver cirrhosis, and in the brain, with different neurologic symptoms. Diagnosis is based on clinical, biochemical, and genetic tests. Different treatments based on chelating agents may help reduce the disease's spontaneous morbidity and mortality. We describe three patients who presented Wilson disease before 18 years of age, with initial neurologic symptoms between 1998 and 2010. After comparison with literature reports, their clinical symptoms, progression, and care allowed us to propose a treatment algorithm. Neurologic symptoms are present in 35% of the patients with Wilson disease such as dystonia, extrapyramidal syndrome, dysarthria, dysphagia, and psychiatric symptoms. The time to diagnosis remains too long and may account for the increased severity of the illness encountered and problems treating these patients. The first treatment choice must be triethylenetetramine, which causes fewer side effects of initial worsening of symptoms compared to D-penicillamine. Zinc therapy is the first treatment for asymptomatic patients or those on maintenance treatment. Finally, liver transplantation is a potential treatment even if the patient presents severe neurological disability because it may improve clinical symptoms. However, further research is warranted on this matter.
 ...
PMID:[Diagnosis and care of Wilson disease with neurological revelation]. 2226 Dec 59

Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal lipid storage disease associated with impaired intracellular cholesterol trafficking. A wide spectrum of clinical phenotype has been described, with a possible onset at all ages of life from the neonatal period to adulthood, more often in childhood. Typically, hepatosplenomegaly, dystaxia, dysphagia, dysarthria and dementia are presented in NPC patients. Neurologic symptoms vary according to the onset age, but prolonged neonatal cholestasis, splenomegaly, cataplexy and vertical supranuclear gaze palsy are more specific signs to the diagnosis of the disease. Impaired cholesterol trafficking and unesterified cholesterol accumulation in the late endosomes and lysosomals, as a results of mutations in NPC1 or NPC2 genes, are initial for the disease, and defective cellular autophagy, defective lysosomal calcium homeostasis and oxidative stress may all play roles in the physiological processes. The definite diagnosis requires demonstration of unesterified cholesterol accumulated in fibroblasts cultured from skin biopsies or of pathogenic mutation of NPC1/NPC2 genes. Miglustat, the only available treatment approved to date, can alleviate neurological symptoms and slow disease progression when administered earlier.
...
PMID:[Research advances in diagnosis and therapy of Niemann-Pick disease type C]. 2601 11

Vogt-Koyanagi-Harada disease is a rare multisystemic granulomatous autoimmune disorder affecting pigmented tissues such as the choroid, meninges, inner ear, and the skin. Neurologic symptoms are usually mild. Clinical manifestations include generalized muscle weakness, headache, meningismus, vertigo, decreased visual acuity, hearing loss and mental changes ranging from mild confusion to psychosis, hemiparesis, dysarthria, and aphasia. Seizures are very rare. We describe a case of 18F-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) and software-fused PET-magnetic resonance imaging (MRI) in Vogt-Koyanagi-Harada disease with seizure.
 ...
PMID:F-18 FDG PET Findings for Vogt-Koyanagi-Harada Disease. 2855 46

Neurologic symptoms in Wilson disease (WD) appear at an older age compared to hepatic symptoms and manifest in patients with misdiagnosed liver disease, in patients when the hepatic stage is clinically silent, in the case of non-compliance with anti-copper treatment, or with treatment failure. Neurologic symptoms in WD are caused by nervous tissue damage that is primarily a consequence of extrahepatic copper toxicity. Copper levels in brain tissues as well as cerebrospinal fluid (CSF) are diffusely increased by a factor of 10 and its toxicity involves various mechanisms such as mitochondrial toxicity, oxidative stress, cell membrane damage, crosslinking of DNA, and inhibition of enzymes. Excess copper is initially taken-up and buffered by astrocytes and oligodendrocytes but ultimately causes dysfunction of blood-brain-barrier and demyelination. Most severe neuropathologic abnormalities, including tissue rarefaction, reactive astrogliosis, myelin palor, and presence of iron-laden macrophages, are typically present in the putamen while other basal ganglia, thalami, and brainstem are usually less affected. The most common neurologic symptoms of WD are movement disorders including tremor, dystonia, parkinsonism, ataxia and chorea which are associated with dysphagia, dysarthria and drooling. Patients usually manifest with various combinations of these symptoms while purely monosymptomatic presentation is rare. Neurologic symptoms are largely reversible with anti-copper treatment, but a significant number of patients are left with residual impairment. The approach for symptomatic treatment in WD is based on guidelines for management of common movement disorders. The vast majority of WD patients with neurologic symptoms have abnormalities on brain magnetic resonance imaging (MRI). Pathologic MRI changes include T2 hyperintensities in the basal ganglia, thalami and white matter, T2 hypointensities in the basal ganglia, and atrophy. Most importantly, brain damage and neurologic symptoms can be prevented with an early initiation of anti-copper treatment. Introducing population WD screening, e.g., by exome sequencing genetic methods, would allow early treatment and decrease the neurologic burden of WD.
 ...
PMID:Neurologic impairment in Wilson disease. 3117 1