Neurotoxicity encephalopathy

Aiuminum-containing antacids - Constipation (may lead to intestinal obstruction) aluminum-intoxication osteomalacia and hypophosphatemia accumulation of aluminum in serum, bone, and the CNS (aluminum accumulation may be neurotoxic) encephalopathy. 

One of the most sensitive systems affected by lead exposure is the nervous system. Encephalopathy is characterized by symptoms such as coma, seizures, ataxia, apathy, bizarre behavior, and incoordination (CDC 1985). Children are more sensitive to neurological changes. In children, encephalopathy has been associated with PbB levels as low as 70 pg/dL (CDC 1985). The most sensitive peripheral index of neurotoxicity of lead is reported to be slowed conduction in small motor libers of the ulnar nerve in workers with 30-40 pg/dL lead in blood (Landrigan 1989). Other potential biomarkers of lead suggested for neurotoxicity in workers are neurological and behavioral tests, as well as cognitive and visual sensory function tests (Williamson and Teo 1986). However, these tests are not specific to elevated lead exposure... 

Neurotoxicity. There is a very large database on the neurotoxic effects of lead. The most severe neurobehavioral effect of lead toxicity in adults is lead encephalopathy (Kehoe 1961a Kumar et al. 1987 Smith et al. 1978). Early symptoms, which may develop within weeks of initial exposure, include dullness, irritability, poor attention span, headache, muscular tremor, loss of memory, and hallucinations. These symptoms worsen, sometimes abruptly, to delirium, convulsions, paralysis, coma, and death. 

Chronic exposure to Pb has been shown to cause anaemia, neurotoxic effects, such as reduced cognitive performance and reduced peripheral nerve conduction velocity, and nephrotoxicity. Children are more sensitive to exposure to Pb than adults, especially during the first 2 years of life [41], For children, exposure to lead can cause growth retardation, affect the neuropsychological development and cause encephalopathy [39]. Adverse reproductive effects due to lead exposure have been observed for both men and women. Exposure of pregnant women to low concentrations of lead is associated with miscarriages and low birth weights [40],... 

Chlordecone causes a number of neurotoxic responses in humans and animals exposed to sufficiently high levels. Tremor that is accentuated by intentional acts, sustained postural movement, anxiety, or fatigue has been observed in workers exposed to high levels of chlordecone. Tremorograms have been used to objectively assess the tremor associated with chlordecone exposure in humans (Taylor et al. 1978). An infrared reflection technique and oculography have been used to assess the oculomotor disturbances caused by chlordecone (Taylor et al. 1978). Standard tests for memory and intelligence can be used to determine the presence of encephalopathy, but in the absence of baseline preexposure levels for individuals, subtle changes may be difficult to detect. 

The risk of severe neurotoxic reactions is sharply increased in patients with impaired renal function or prerenal azotemia. These include disturbances of vestibular and cochlear function, optic nerve dysfunction, peripheral neuritis, arachnoiditis, and encephalopathy. The incidence of clinically detectable, irreversible vestibular damage is particularly high in patients treated with streptomycin. 

Biochemical changes such as increased aminolaevulinate excretion and inhibition of amino-laevulinate dehydrase may be detected in urine and blood, respectively, at blood lead levels of 0.4 to 0.6 mg mL-1. Anemia is a late feature, however. Neurotoxicity may be detectable at blood lead levels of 0.8 to 1.0 mg mL-1. At blood lead levels greater than 1.2 mg mL-1, encephalopathy occurs. Peripheral nerve palsies are rare, and the foot and wrist drop, which were once characteristic of occupational lead poisoning, only occur after excessive exposure and are now rarely seen. Similarly, seizures and impaired consciousness may result from involvement of the CNS. Bone changes are usually seen in children and are detected as bands at the growing ends of the bones and a change in bone shape. 

Lactitol 40 is a disaccharide that has been used in the management of hepatic encephalopathy, a major neuropsychiatric complication of both acute and chronic liver failure. It has mild laxative properties and is used to reduce the production and absorption of gut-derived neurotoxic substances symptomatic of hepatic encephalopathy. Although long considered a first-line pharmacological treatment, there is a lack of sufficient evidence to support lactitol s efficacy and continued use when weighed against other suitable therapeutic alternatives such as oral antibiotics <2006MI94>. 

It remains remarkable that, after the discovery of chronic Al encephalopathy and numerous reports of patients suffering from this syndrome, fourteen years passed before the first publication on acute Al neurotoxicity appeared [62], Acute Al encephalopathy is a devastating, often fatal disease that is the result of iatrogenic exposure to Al. Unfortunately, in spite of efforts to avoid Al exposure as much as possible, recently new sources of serious exposure have been added to the growing list of sources of Al exposure. In contrast to a fascinating history and abundant literature, many uncertainties about Al toxicity still exist. Clinical data in humans on acute Al neurotoxicity are very limited and we will, therefore, compare our experience in one of the two documented outbreaks in dialysis centers, with that of the literature. 

Slow, relatively low exposure accumulation of Al over a period of years can lead to a number of clinical manifestations, some of which seem to be bypassed in acute Al encephalopathy due to extremely high exposure to Al. Al encephalopathy is a clinical syndrome and, as can be seen in Table 5, there are similarities and differences in the neurological symptoms of acute and chronic Al encephalopathy. In chronic Al encephalopathy microcytic anemia [41, 93, 95—98] and EEG changes [99-104] can precede clinical symptoms [105]. It is unknown if these symptoms can also precede the clinical symptoms of acute encephalopathy. In contrast to acute Al encephalopathy, where speech disturbances are absent, speech disorders are an important presenting clinical sign of neurotoxicity in chronic Al encephalopathy. The neurological basis of the speech apraxia is obscure but it appears to have elements of dysarthria and dysphasia [33, 73], The initial... 

Some authors claim to have had patients with Al neurotoxicity symptoms when the highest s-Al concentration was 17 to 22 pg/L [156, 157]. It seems very unlikely that these patients indeed suffered from Al encephalopathy because... 

Pediatric patients are particularly at risk for Al neurotoxicity. The development of the brain occurs in the first year of life. High permeability of the immature blood-brain barrier to Al, the increased uptake of Al via a relatively poorly developed gastrointestinal tract, immature formation and function of the kidneys and high Al to body ratios probably all contribute to the Al toxicity [144, 145, 162-165], Children not on dialysis were intoxicated by Al-containing phosphate binders and developed encephalopathy [78, 162, 164, 166, 167],... 

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]. 

Cellular and molecular mechanisms of neurotoxicity are also influenced by the fact that neurons are postmitotic and do not divide. Thus, the capacity for replacement of damaged cells does not exist in the nervous system, whereas most other organ systems have a well-established capacity for regeneration. Many neurotoxins can cause encephalopathy and an important concept in neurotoxicology is the delayed manifestation of symptoms sometimes up to years after the exposure started. Several agents show a lag time between exposure and neurotoxicity. Examples are the organophosphate chemical warfare agents [245], bismuth intoxications [246] and methylmercury... 

Because the CNS is sensitive to ammonia, its metabolism in the brain and the neurotoxicity associated with hyperammonia and hepatic encephalopathy (the proximate source of damage in the latter is also ammonia) is reviewed here. Hepatic encephalopathy (HE) or congenital and acquired hyperammonemia result in excessive ammonia accumulation within the CNS. The condition is due... 

Neurologic Neurotoxicity, intracranial hypertension, headache, tremor, encephalopathy, seizure... 

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