Nervous system toxicity encephalopathy

Nervous system Fluorouracil can cause acute nervous system toxicity. Acute cerebellar syndrome affects up to 5% of patients and is usually self-limiting after withdrawal. It can occur within weeks to months of starting fluorouracil and presents with ataxia, nystagmus, and dysarthria [77, 78 ]. An encephalopathy can occur rarely and is often associated with markedly raised ammonia concentrations in the absence of underlying liver disease. Ischemic stroke has also been reported and the risk appears to be increased when fluorouracil is combined with cisplatin [60, 79 ]. Other rare adverse reactions include oculomotor disturbances, focal dystonia, parkinsonian syndrome, peripheral neuropathy, and seizures [80 ]. Dihydropyrimidine dehydrogenase deficiency also increases the risk of nervous system toxicity [81" ]. 

Most untreated aminoacidopathies damage the brain. The pathophysiological factors that explain the encephalopathy remain unknown. Injury probably results from the accumulation of an amino acid or amino acid metabolite that is toxic to the nervous system, especially to the... 

Ibrahim et al. 1963). Aiken and Braitman (1989) determined that cyanide has a direct effect on neurons not mediated by its inhibition of metabolism. Consistent with the view that cyanide toxicity is due to the inability of tissue to utilize oxygen is a report that in cyanide-intoxicated rats, arterial p02 levels rose, while carbon dioxide levels fell (Brierley et al. 1976). The authors suggested that the low levels of carbon dioxide may have led to vasoconstriction and reduction in brain blood flow therefore, brain damage may have been due to both histotoxic and anoxic effects. Partial remyelination after cessation of exposure has been reported, but it is apparent that this process, unlike that in the peripheral nervous system, is slow and incomplete (Hirano et al. 1968). The topographic selectivity of cyanide-induced encephalopathy may be related to the depth of acute intoxication and distribution of blood flow, which may result in selected regions of vascular insufficiency (Levine 1969). 

Soluble inorganic arsenic is acutely toxic, and ingestion of large doses leads to gastrointestinal symptoms, disturbances of cardiovascular and nervous system functions, and eventually death. In survivors, bone marrow depression, haemolysis, hepatomegaly, melanosis, polyneuropathy, and encephalopathy may be observed. 

Cases of toxic encephalopathy and macro-qAic anemia have been reported from industrial exposures that may have been as low as 60 ppm. Symptoms were headache, drowsiness, lethargy, and weakness. Manifestations of central nervous system instability included ataxia, dysarthria, tremor, and somnolence. These effects were usually reversible. In acute exposures, the central nervous system effects were the more pronounced, whereas prolonged exposure to lower concentrations primarily produced evidence of depression of erythrocyte formation. When exposure was reduced to 20 ppm, no further cases occurred. 

The most notable toxicological effects of carbon disulfide are on the nervous system, including damage to the peripheral nervous system.18 Individuals exposed to carbon disulfide have lost consciousness. Decreased nerve conduction velocities have been observed in workers exposed to 10 to 20 ppm of carbon disulfide in the workplace over periods of 10 to 20 years. Brain abnormalities suggesting toxic encephalopathy have been observed in exposed workers. Some studies have suggested the possibility of mental performance and personality disorders in workers exposed to carbon disulfide, including heightened levels of anxiety, introversion, and depression. 

Most of the Al absorbed from the respiratory tract accumulates in the lungs. Pulmonary lesions have been described in employees of Al processing or manufacturing industries and encephalopathy after Al inhalation has been reported. Al is widely distributed and has many industrial uses, and toxicity from occupational exposure is assumed to be extremely rare [2, 177]. Nevertheless, a recent study investigating adverse effects on the central nervous system of Al welders found an Al-exposure-related increase in blood and urine Al concentrations, deficits in neuropsychological test performance and mild diffuse EEG abnormalities. Therefore, the potential for Al-induced neurotoxicity in those occupationally exposed to Al fumes may be greater than previously suspected [177]. 

SAFETY PROFILE Poison by ingestion. Moderately toxic by intraperitoneal route. Questionable carcinogen. Human systemic effects by ingestion and inhalation loss of appetite, anemia, malaise, insomnia, headache, irritability, muscle and joint pains, tremors, flaccid paralysis without anesthesia, hallucinations and distorted perceptions, muscle weakness, gastritis, and liver changes. The major organ systems affected are the nervous system, blood system, and kidneys. Lead encephalopathy is accompanied by severe cerebral edema, increase in cerebral spinal fluid pressure, proliferation and swelling of endothelial cells in capillaries and... 

GI pain and bleeding pulmonary edema anemia, destruction of red blood cells liver necrosis, kidney failure encephalopathy and other central and peripheral nervous system disorders. Chronic toxicity can lead to systemic hypotension skin disorders such as eczema, hyperkeratosis, melanosis, ulceration, skin cancers blood problems such as anemia, acute leukemia kidney failure delirium, encephalopathy, seizures, neuropathy. 

Chronic sahcylate intoxication is commonly associated with chronic daily headaches, lethargy, confusion, or coma. Since headache is a feature, it can easily be misdiagnosed if the physician is not aware that aspirin has been over-used. Depression of mental status is usually present at the time of diagnosis, when the serum salicylate concentration is at a peak. The explanation of depression, manifested by irritability, lethargy, and unresponsiveness, occurring 1-3 days after the start of therapy for aspirin intoxication, lies in a persistently high concentration of salicylate in the central nervous system, while the serum salicylate concentration falls to non-toxic values. The delayed unresponsiveness associated with sahcylate intoxication appears to be closely associated with the development of cerebral edema of uncertain cause. The encephalopathy that ensues appears to be directly related to increased intracranial pressure, a known effect of prostaglandin synthesis inhibitors it responds to mannitol (98). 

The main adverse effects of phenmetrazine reflect central nervous system stimulation and resemble those of other stimulants. There have been reports of encephalopathy as a result of phenmetrazine toxicity. There were also two cases of damage to the central nervous system after longterm treatment with phenmetrazine in one, there were disseminated lesions, and in the other, hemiparesis and sensory motor aphasia (3). 

Organic lead is also toxic to central nervous system (encephalopathy). 

The precise pathogenesis of the central nervous system (CNS) signs and symptoms that accompany liver failure (hepatic encephalopathy) in patients such as Percy Veere is not completely understood. These changes are, however, attributable in part to toxic materials that are derived from the metabolism of nitrogenous substrates by bacteria in the gut that circulate to the liver in the portal vein. These materials "bypass" their normal metabolism by the liver cells, however, because the acute inflammatory process of viral hepatitis severely limits the ability of liver cells to degrade these compounds to harmless metabolites. As a result, these toxins are "shunted" into the hepatic veins unaltered and eventually reach the brain through the systemic circulation ("portal-systemic encephalopathy"). 

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