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Case Reports Indian Pediatrics 2001; 38: 417-419 |
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Levamisole Induced Ataxia |
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Levamisole is an immunomodulating drug, used in pediatric practice as an antihelminthic drug(1). Its toxicity is usually mild and gastrointestinal upset, blood dyscrasias, flu like syndrome are the commoner side effects while ataxia, blurred vision, confusion, parasthesias and tremors are rare. Encephalitis like syndrome as a result of Levamisole toxicity has not been reported till date in the pediatric age group. We report here a case of neuro-logical syndrome with dominant involvement of cerebellum with high doses of Levamisole.
A 3½-year-old female child, product of a nonconsanguineous marriage, first in the sibling order was admitted to this hospital with presenting complaints of sudden onset of abnormal behavior (hyperkinesis, parasthesias, fidgetiness, instability of gait and frequent falls). History revealed that child had sought medical consultation for anorexia and was prescribed Liv 52 and Levamisole. She was, inadvertently given Levamisole in high doses of 100 mg BD for three days, following which she developed the above mentioned clinical features. There was no history of any previous neurological illness or antecedent throat infec-tion. Examination revealed a well nourished child weighing 13 kg with essentially normal general and systemic examination. Neuro-logically she was garrulous, restless and agitated. Cranial nerves, sensory and motor examination were within normal limits. She was ataxic, had a broad based gait and dysdiadokokinesis. Her blood count and CSF analysis were normal. MRI brain did not show any demylinating changes in the white matter. The child was observed in the hospital and recovered fully within 48 h without any intervention.
On performing an extensive Medline search we did not find any published report in pediatric age group of Levamisole toxicity leading to dominantly cerebellar neurological manifestation. Review, however revealed that till 1996, a total of 16 cases, of 5-FU (5-fluro- uracil) and Levamisole toxicity had been reported in adults. MRI findings were similar in all these sixteen cases, showing evidence of multiple enhancing lesions with predilection for periventricular area(2,3). In addition, Kimmel and colleagues reported one patient from Mayo Clinic with a similar clinical and MRI picture that was being treated with Levamisole alone for malignant melanoma(4). Reported 5-FU-Lev related 16 cases showed certain consistent features; namely, all these patients were elderly (above 50 years) females and they were receiving combination of 5-FU-Lev as an adjustants for colonic malignancies for the duration of 6-10 weeks. The encephalitic picture comprised of ataxia, anxiety, insomnia, headache, dizziness and seizures. MRI findings were multifocal white matter lesions with widespread hyperintensity of periventricular and hemispheric white matter with almost symmetrical disposition. Similar lesions were present in cerebellar hemispheres. These findings were compatible with multifocal demylination of possible inflammatory origin. Both 5-FU and Levamisole have been incriminated in causation of such neurological syndromes. There are, however, no reports of 5-FU alone causing such a syndrome(2). Furthermore, patients of colonic cancer who were on 5-FU-Lev, and had developed this neurological syndrome on discontinuation of the drugs recovered and did not develop any further neurotoxicity on re-introduction of 5-FU, thus confirming role of Levamisole alone in causation of neurotoxicity(4). The mechanism by which Levamisole induces multifocal leucoencephalopathy remains uncertain. It has been suggested that Levamisole due to its immunological potential induces a hypersensitive inflammatory reac-tion with cerebral perivascular cuffing by mononuclear cells. Bozlik and Gilbert(5) have suggested that since Levamisole inhibits alkaline phosphatase activity in brain capillaries, this could result in functional abnormality of blood brain barrier provoking an immune response in a subset of susceptible patients and leading to the development of an inflammatory leucoencephalopathy. Differential diagnosis of such an encephalitic syndrome in Pediatric age group would include multicentric gliomas, CNS lymphomas, toxoplasmosis, progressive multifocal leucoencephalopathy and diffuse necrotizing leucoencephalopathy associated with chemotherapy and immunosupression. In conclusion, we feel that clinically manifest neurotoxicity, presenting with ataxia, can occur without any changes on MRI in children on administration of high doses of Levamisole for short duration. Contributors: AKD conceived the idea, co–ordinated the study and drafted the paper; he will act as the guarantor for the paper, RKG helped in drafting the paper, and collection of the references, RKS assisted in proof reading. Funding: None.
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