When Stanley Prusiner coined the term “prion” in 1982, which he defined as a small
infectious pathogen containing protein but lacking nucleic acid, the scientific world
watched amazed a revolution in the fields of biology and medicine. Prusiner deservedly
won the 1997 Nobel Prize for his achievement succeeding Carleton Gajdusek who had
won the same prize in 1976 for his discoveries in this field[1].
Prion diseases are neurodegenerative conditions that have long incubation periods
and progress inexorably once clinical symptoms appear. Five human prion diseases are
currently recognized: Kuru – currently extinct, Creutzfeldt-Jakob disease (CJD), variant
Creutzfeldt-Jakob disease (vCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and
fatal familial insomnia (FFI)[2].
GSS is an extremely rare disease with an incidence of 1 to 10 cases per 100 million
persons/year. It is inherited in an autosomal dominant pattern with virtual complete
penetrance. To date, less than30 separate kindreds have been identified throughout
the world[3].
The clinical hallmark of GSS is a progressive cerebellar ataxiaalong with dementia
of different levelsin patients entering midlife, although the onset of symptoms in
older patients has been reported. The course of the illness typically advances for
approximately five years until death. Dysesthesia, hyporeflexia, and proximal weakness
in the legs are also early signs. Contrary to what is found in CJD, myoclonus istypically
absent in GSS. The presence and degree of dementia is also highly variable among affected
families and within individuals from the same family. Part of the variability of expression
of this illness has been attributed at least in part to differences in the underlying
PRNP mutation or the associated polymorphisms in codon 129[3].
The diagnosis of GSS is very difficult to be made based solely on clinical grounds.
The cerebrospinal fluid (CSF) and the electroencephalogram (EEG) are unspecific. Magnetic
resonance imaging (MRI) is neither specific nor sensitive but may show areas of decreased
T2 signal in the striatum and midbrain in some patients. The best way to diagnose
GSS in vivo is through the demonstration of PRNP gene mutations since the vast majority of cases
are familial, and all patients with definite GSS have been found to have these mutations.
The neuropathological analysis of brain tissue reveals the presence of kuru-like plaques
in highest density in the cerebellum but also elsewhere in the brain. These plaques
are often multicentric with radiating spicules and are accompanied by microglial changes;
they stain for PrPSc and are PAS positive[2],[3].
In the present issue of Arquivos de Neuropsiquiatria, Smid et al presents the most
comprehensive clinical, genetic and neuropathological study on GSS ever made in Brazilian
families. This important report emphasizes the need to maintain a high level of suspicion
for the diagnosis of GSS in cases of slow-onset cerebellar ataxia, associated or not
with dementia, particularly in those cases who run in families. At the same time,
this study emphasizes the need to support a network of nationally coordinated researchers
with different areas of expertise that can serve as reference to other physicians
to contribute, each one in their own capacity, to the diagnosis of cases of rare neurological
diseases[4].
