Early clinical signs and imaging findings in Gerstmann-Straussler-Scheinker syndrome (Pro102Leu)

Objective: To determine the clinical and radiologic features of Gerstmann-Straussler-Scheinker syndrome caused by Pro102Leu mutation in PRNP ( GSS102). Methods: The authors report 11 patients ( nine families) with clinically and radiologically diagnosed GSS102. Results: All patients showed mild gait disturbance, dysesthesia and hyporeflexia of the lower legs, and truncal ataxia, and 9 of 11 patients showed proximal leg muscle weakness during the early stage of the disease. Dementia was not a main symptom during the early stage. Brain MRI and EEG abnormalities were not prominent initially. SPECT ( N-isopropyl-p-[ I-123] iodoamphetamine) analyzed by the three-dimensional stereotactic surface projection ( SSP) method detected abnormalities in five patients early during the course of the illness. SPECT findings showed diffusely decreased cerebral blood flow, demonstrated by a mosaic pattern, with the lowest perfusion noted in the occipital lobes. In contrast, blood flow to the cerebellum was preserved. These studies suggested sites of pathology in GSS102, with the main lesions probably located in the cerebrum and the spinal cord ( posterior horn and spinocerebellar tract) instead of the cerebellum. Conclusions: Key features for early diagnosis of Gerstmann-Straussler-Scheinker syndrome caused by Pro102Leu mutation in PRNP ( GSS102) are truncal ataxia, dysesthesia and hyporeflexia of the lower legs, and mild dysarthria. Normal cerebellar MRI and abnormal cerebral SPECT findings are characters of early GSS102.