The natural history of Canavan disease: 23 new cases and comparison with patients from literature.

BACKGROUND: Canavan disease (CD, MIM # 271900) is a rare and devastating leukodystrophy of early childhood. To identify clinical features that could serve as endpoints for treatment trials, the clinical course of CD was studied retrospectively and prospectively in 23 CD patients. Results were compared with data of CD patients reported in three prior large series. Kaplan Meier survival analysis including log rank test was performed for pooled data of 82 CD patients (study cohort and literature patients). RESULTS: Onset of symptoms was between 0 and 6 months. Psychomotor development of patients was limited to abilities that are usually gained within the first year of life. Macrocephaly became apparent between 4 and 18 months of age. Seizure frequency was highest towards the end of the first decade. Ethnic background was more diverse than in studies previously reported. A CD severity score with assessment of 11 symptoms and abilities was developed. CONCLUSIONS: Early hallmarks of CD are severe psychomotor disability and macrocephaly that develop within the first 18 months of life. While rare in the first year of life, seizures increase in frequency over time in most patients. CD occurs more frequently outside Ashkenazi Jewish communities than previously reported. Concordance of phenotypes between siblings but not patients with identical ASPA mutations suggest the influence of yet unknown modifiers. A CD severity score may allow for assessment of CD disease severity both retrospectively and prospectively.

Leucoencefalopatía tóxica fatal: tres casos asociados al consumo de pasta base de cocaína / Fatal toxic leukoencephalopathy associated with consumption of pasta base of cocaine: Report of three cases

The prevalence of drug-associated toxic encephalopathy is unknown, but it is an uncommon condition. Toxic leukoencephalopathy was described associated with heroin consumption, it has been less commonly described with the use of cocaine and there are no reports of its association with consumption pasta base of cocaine (PBC). We report two females aged 31 years and a male aged 19 years, consumers of PBC who developed a fatal toxic leukoencephalopathy. They initiated their disease with severe and persistent headache, sequential focal neurologic deficits and a progressive impairment of consciousness that culminated with their death. Laboratory parameters such as blood count, cerebrospinal fluid analyses or infectious biological indices were normal. MRI showed multifocal lesions in brain white matter of both hemispheres confirming the leukoencephalopathy. There was no response to the use of methylprednisolone.