Drug-induced cerebellar ataxia: a systematic review.

BACKGROUND AND OBJECTIVES: Cerebellar ataxia can be induced by a large number of drugs. We here conducted a systemic review of the drugs that can lead to cerebellar ataxia as an adverse drug reaction (ADR). METHODS: We performed a systematic literature search in Pubmed (1966 to January 2014) and EMBASE (1988 to January 2014) to identify all of the drugs that can have ataxia as an ADR and to assess the frequency of drug-induced ataxia for individual drugs. Furthermore, we collected reports of drug-induced ataxia over the past 20 years in the Netherlands by querying a national register of ADRs. RESULTS: Drug-induced ataxia was reported in association with 93 individual drugs (57 from the literature, 36 from the Dutch registry). The most common groups were antiepileptic drugs, benzodiazepines, and antineoplastics. For some, the number needed to harm was below 10. Ataxia was commonly reversible, but persistent symptoms were described with lithium and certain antineoplastics. CONCLUSIONS: It is important to be aware of the possibility that ataxia might be drug-induced, and for some drugs the relative frequency of this particular ADR is high. In most patients, symptoms occur within days or weeks after the introduction of a new drug or an increase in dose. In general, ataxia tends to disappear after discontinuation of the drug, but chronic ataxia has been described for some drugs.

Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature.

Five patients with adult-onset metachromatic leukodystrophy (MLD) underwent allo-SCT. Conditioning was reduced in intensity and grafts were obtained from voluntary unrelated donors. All but one graft were depleted of T-lymphocytes. Patient age at transplantation varied from 18 to 29 (median, 27) years. Two patients rejected their graft and MLD progressed. The recipient of the unmanipulated graft converted to complete donor chimerism with normalization of arylsulphatase A (ARSA) levels. Despite ARSA normalization, he deteriorated. Another patient was a mixed chimera. Following escalated doses of donor lymphocyte infusions he converted to complete donor chimerism. His levels of ARSA correlated positively with the percentage of donor cells and MLD was not progressive. The fifth patient died after 35 days from complications associated with GVHD. We conclude that results of allo-SCT in symptomatic MLD patients are poor. However, allo-SCT may stop progression of MLD in selected patients.

Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations.

BACKGROUND: In the clinically and genetically heterogeneous group of the hereditary spastic paraplegias (HSPs), mutations in the SPAST gene are most frequently found and cause a pure autosomal dominant form. OBJECTIVE: To provide the clinical and genetic characteristics of Dutch patients with HSP due to a SPAST mutation (SPG4). METHODS: SPAST mutation carriers were identified through a comprehensive national database search. Available medical records were reviewed. RESULTS: 151 mutation carriers carried 60 different changes in the SPAST gene, of which one was a known polymorphism, and 27 were novel. Missense mutations were most frequently found (39%). Clinical information was available from 72 mutation carriers. Age at onset ranged from 1 to 63 years with a bimodal peak distribution in the first decade and above age 30. The predominantly pure spastic paraplegia was accompanied by deep sensory disturbances and sphincter problems in almost 50%. An additional hand tremor was found in 10%. Patients with missense mutations and exon deletions did not reveal a distinctive phenotype. CONCLUSIONS: Dutch SPAST mutation carriers show a broad mutation spectrum, with 27 novel mutations in the present series. A bimodal peak distribution in age at onset was found and an accompanying tremor as peculiar feature of SPG4. The pathogenicity of S44L, the first exon 4 mutation, and a possible autosomal recessive mode of inheritance are discussed.

[From psychiatric symptoms to paraneoplastic syndrome]. / Van psychiatrisch symptoom tot paraneoplastisch syndroom.

Two patients, a 38-year-old man and a 32-year-old woman, were admitted to a psychiatric ward. The first patient suffered from a mood disorder, personality changes and complained of several, hitherto unexplained physical symptoms. Finally the patient was diagnosed with paraneoplastic cerebellar degeneration associated with Hodgkin's disease. The second patient presented with psychosis and panic disorders, but the condition was later found to be caused by paraneoplastic limbic encephalitis due to ovarian teratomas. These cases illustrate that patients with paraneoplastic neurological syndromes may present with psychiatric symptoms which can hamper an early diagnosis.