Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD--sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immunoreactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spongiosis. This includes status spongiosus ("spongiform state"), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of "burnt-out" CJD), "spongy" changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.

The aim of the present study was to determine whether routine integration of positron emission tomography (PET) with 18F-labeled fluorodeoxyglucose (FDG) in the planning of stereotactic brain biopsy increases the technique's diagnostic yield. Forty-three patients underwent combined FDG-PET- and computerized tomography (CT)-guided stereotactic biopsy of intracranial lesions according to a previously described technique. In 36 patients, an area of abnormal FDG uptake was used to guide at least one stereotactic biopsy trajectory. A total of 90 stereotactic trajectories were performed; among them, 55 were based on FDG-PET-defined targets and 35 were based on CT-defined targets. Histological diagnosis was obtained in all patients, but six of the 90 trajectories were nondiagnostic; all six were based on targets defined by CT only. Differences between the diagnostic yield of trajectories based on FDG-PET-defined targets and those based on CT-defined targets were statistically significant in patients with contrast-enhanced lesions, but not in patients with nonenhancing lesions. These results support the view the FDG-PET may contribute to the successful management of brain tumor patients requiring stereotactic biopsy. Because no significant increase in discomfort or morbidity related to the technique was found, it is suggested that the development of similar techniques integrating PET data in the planning of stereotactic biopsy should be considered by centers performing stereotactic surgery and having access to PET technology.

Cerebrospinal fluid aminoacid analysis in a girl with severe psychomotor retardation, hypotonia, hyperreflexia and growth acceleration showed highly increased levels of free gamma-aminobutyric acid (4.8 mumol/l; range in twenty controls 0.04-0.12, median 0.08), homocarnosine, a dipeptide of gamma-aminobutyric acid and histidine (23.4 mumol/l; control range 4.0-8.7, median 7.6) and of beta-alanine, an alternative substrate for gamma-aminobutyric acid-transaminase (0.48 mumol/l; control range 0.02-0.06, median 0.05). Liver gamma-aminobutyric acid-transaminase activity was deficient (0.07 mumol/mg protein h; range in ten controls 0.31-0.69, median 0.38). Fasting plasma growth hormone levels were increased (7.9-38.4 ng/ml; nl less than 5). Brain evoked responses were suggestive of leukodystrophy. A brother of this patient, showing a similar clinical picture, had died at one year. Postmortem examination of his brain showed leukodystrophy of the type seen in amino acidopathies such as phenylketonuria. This appears to be the first report of gamma-aminobutyric acid-transaminase deficiency.

No abstract

Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion disease) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. Autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories with experience in handling tissue from transmissible spongiform encephalopathies. In particular, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potential infectious material must be adequately decontaminated by specific means.