Clinico-genetic comparisons of paroxysmal kinesigenic dyskinesia patients with and without PRRT2 mutations.

BACKGROUND AND PURPOSE: Mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesias (PKD); however, not many detailed clinico-genetic correlations have been performed. METHODS: To investigate PRRT2 mutations in a mixed Asian PKD population and perform clinico-genetic correlations, we recruited patients between 2002 and 2011 and administered a standardized questionnaire. RESULTS: Amongst 29 unrelated patients with PKD recruited, five PRRT2 mutations were present in 15 patients. Three mutations (c.649dupC, c.649delC, c.649C>T) were previous reported, while three were novel mutations (c.604delT; c.609_611delACC/p.Ser202Hisfs; c.697_698delAG/p.Ser233Trp fsX5). Clinico-genetic correlations revealed that a history of seizures was more common in patients with PRRT2 mutations, although this did not reach statistical significance (P= 0.08). A younger age of onset, non-Chinese, and the presence of premonitory sensations were significantly associated with PRRT2 mutations in the univariate analysis. Multivariate logistic regression analysis demonstrated that age of onset [odds ratio (OR) = 0.59, P = 0.025] and premonitory sensation (OR = 10.67, P = 0.028) were independently associated with positive PRRT2 mutation. CONCLUSIONS: PRRT2 mutations are common in patients with PKD, and a double PRRT2 mutation is reported for the first time. PRRT2 mutations are significantly associated with a younger age of onset and the presence of premonitory sensation in our population.

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

OBJECTIVE: To determine the clinical and radiologic features of Gerstmann-Sträussler-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-[(123)I]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-Sträussler-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.

Mechanomyographic determination of post-activation potentiation in myopathies.

OBJECTIVE: There is a need to provide an index of muscle contractility in evaluating myopathies especially in the clinical setting. This study was conducted to investigate if the mechanomyogram post-activation potentiation (MMG-PAP) can be used as an index of muscle contractile force potentiation (force-PAP), if it differs between normal and myopathic muscles, and if it can reflect abnormalities in muscle fiber anatomy. METHODS: The correlation between MMG-PAP and force-PAP was evaluated in 12 normal subjects after maximum voluntary contraction (MVC) of the biceps brachii muscle. The same method was then applied to study MMG-PAP in 16 patients with myopathies, 16 disease and 25 normal controls. Mean fiber diameters and the proportions of type 1 and 2 fibers in biopsied biceps brachii muscle were determined and compared with MMG-PAP values. RESULTS: There was a significant positive correlation between force-PAP (197 +/- 148%) and MMG-PAP (135 +/- 68%) immediately after MVC (P < 0.05). The mean MMG-PAP in myopathies (66 +/- 53%) was significantly lower than those of the disease (128 +/- 34%; P < 0.005) and normal controls (120 +/- 56%; P < 0.005). Patients with non-dystrophic myopathies, including those with myositis, had significantly lower MMG-PAP values (38 +/- 20%; P < 0.005) than those with muscular dystrophy (148 +/- 23%). MMG-PAP did not clearly correlate with either type 2 fiber atrophy or type 2 fiber disproportion based on muscle biopsy analysis of myopathic patients. CONCLUSIONS: This study shows that MMG-PAP can be used as an index of muscle contractility and that it is significantly lower in non-dystrophic myopathies compared to normal subjects. MMG-PAP does not seem to reflect abnormal muscle fiber anatomy. SIGNIFICANCE: MMG-PAP may become a valuable non-invasive tool in augmenting routine clinical electrophysiologic studies especially in evaluating muscle contractility in myopathies.

PARK6-linked autosomal recessive early-onset parkinsonism in Asian populations.

The authors performed linkage analysis in 39 families with autosomal recessive early-onset PD (AR-EOPD) negative for parkin and DJ-1 mutations. Eight families including three Japanese, two Taiwanese, one Turkish, one Israeli, and one Philippine showed evidence of linkage with PARK6 with multipoint log of the odds (lod) score of 9.88 at D1S2732. The results indicate worldwide distribution of PARK6-linked parkinsonism.