Nystagmus encephalopathy

Initially, there is a confused state, Korsakoff s psychosis, that is characterized by confabulation and loss of recent memory, although memory for past events may be unimpaired. Later, clear neurological signs develop - Wernicke s encephalopathy. This is characterized by nystagmus and extraocular palsy. Postmortem examination shows hemorrhagic lesions in the thalamus, pontine tegmentum, and mammillary body, with severe damage to astrocytes, neuronal dendrites, and myelin sheaths. 

Therefore, coma, seizures, and apnea may be seen at lower serum levels than in adults. Other manifestations of neurologic toxicity are nystagmus, ataxia, choreoathetoid movements, encephalopathy, absent corneal reflexes, decreased deep tendon reflexes, urinary retention, and dystonias. A cyclic clinical course can be seen, with a waxing and waning of symptoms. This may be due to the presence of a pharmacobezor in the gut or more commonly due to a decrease in gastrointestinal motility produced by the prominent anticholinergic effects of carbamazepine. 

Fetal phenytoin syndrome cerebellar syndrome (ataxia, nystagmus) chronic encephalopathy (cognitive dysfunction) extrapyramidal syndrome (chorea, dyskinesia) peripheral neuropathy Acute encephalopathy (sedation, coma) chronic encephalopathy (cognitive dysfunction)... 

The thiamin (vitamin BO molecule contains a quaternary ammonium functionality and is thus badly absorbed. In healthy patients the necessary amounts of thiamin are absorbed thanks to an active transport mechanism coupled with ATP consumption. However, these mechanisms are rapidly saturable and easily inhibited, especially by chronic alcoholic consumption. As a consequence of the insufficient absorption of thiamin, alcoholism often entails Wernicke s encephalopathy (neurological disorders such as nystagmus, ocular motor nerve paralysis, memory losses, disorientation). The design of lipophilic prodrugs, able to reach the CNS by passive diffusion was then undertaken compounds like (a) and (b) result from lipophilic disulphide derivation of the open ring thiolate anion corresponding to thiamine (Fig. 33.39). 

Kesler, A., Stolovitch, C., Hoffmann, C., Avni, 1., and Morad, Y. (2005). Acute ophthalmoplegia and nystagmus in infants fed a thiamine-deficient formula an epidemic of Wernicke encephalopathy. J. Neuroophthalmol. 25 169-172. 

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" ]. 

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