PRION DISEASE AND ANESTHESIA

The transmissible spongiform encephalopathies (TSE) represent a group of neurodegenerative diseases with lethal outcome. They include Creutz feldt-Jakob disease (CJD) and kuru, among others in humans, scrapie in sheep and spongiform encephalopathy in cattle (bovine spongiform ence phalopathy: BSE). Some are autosomal dominant disorders like CJD, Gers tmann-Straussler-Scheinker disease (GSS), with point mutation of the p rion protein gene. Most of these diseases are idiopathic rather than s poradic. latrogenic CJD could be obtained by central inoculation (neur osurgical instruments or dura mater grafts) or by peripheral inoculati on (pituitary hormone therapy). A new variant clinicopathological type of CJD (nvCJD) has been reported. The nvCJD has strain characteristic s distinct from other types of CJD, close to those of BSE transmitted (studies with intracerebral inoculation), consistent with BSE being th e source of this new disease. All of these spongiform encephalopathies (SE) are characterized by spongiform degeneration of the brain, react ive gliosis in the cortical and subcortical gray matter, neuronal loss and presence of the abnormal isoform of the cellular prion protein (P rPc). In prion disease, PrPc undergoes conformational changes involvin g a shift from alpha-helix to beta-sheet structure. These neurologic l esions are characterized by major variations from case to case. Neurop athological studies in sporadic CDJ have emphasized phenotypic variati ons. Clinical presentation with a wide spectrum of manifestations is a rapidly progressive dementia, associated with myoclonus or akinetic m utism and cortical blindness. The clinical course is atypical and when the characteristic triphasic abnormal EEG of CJD is absent, there is an urgent need for a premortem diagnostic test. Histopathological exam ination of a brain biopsy carries a risk of major morbidity and may mi ss the site of disease. The 14-3-3 immunoassay of cerebrospinal fluid strongly supports a diagnosis of CJD. Western blot analysis of human t onsil biopsy may allow an early or preclinical diagnosis. It has been suggested that CJD might be transmitted by blood products derived from patients with CJD during the prodromal stage, although CJD linked aet iologically to blood transfusion has not been demonstrated. In animal studies, intracerebral inoculation of infected cells has been associat ed with development of disease, but never after peripheral inoculation into the blood stream. For the most part of conformational changes of PrPc, the remarkable resistance of the infectious agent (PrP alone or combined) to ordinary sterilising procedures is a major problem. Beca use of this resistance, current recommendations are to recognize patie nts at risks and to use disposable medical devices. This is particular ly true in anaesthesia during endotracheal intubation, spinal anaesthe sia, and to a lesser extent with peripheral nerve blocks. All instrume nts used for patients with CJD must be destroyed. The economic consequ ences of these measures have highlighted the essential importance of a n early diagnosis.