Ultrasound-based motion analysis demonstrates bilateral arm hypokinesia during gait in heterozygous PINK1 mutation carriers.

Carriers of a single heterozygous PINK1 (PTEN-induced putative kinase 1) gene mutation provide an ideal opportunity to study the development of parkinsonian motor signs from the very beginning. Measuring tools that reliably represent mild motor symptoms could also facilitate the assessment of future neuroprotective therapies and early diagnosis of Parkinson's disease (PD). We investigated nine family members carrying a heterozygous PINK1 mutation in comparison with 25 age-matched healthy controls. Arm kinematics were quantified during treadmill walking at four different speeds using ultrasound-based motion analysis. Heterozygous PINK1 mutation carriers showed a bilateral reduction of arm swing amplitudes (P = 0.003) and arm anteversion (P = 0.001), which was more pronounced on the predominantly affected body side but also was present, albeit to a lesser degree, contralaterally (amplitude P = 0.01, anteversion P = 0.002, repeated measures analysis of covariance [rmANCOVA]). Single post-hoc comparisons revealed similar results for all speeds on both body sides (P < 0.05) except for 2.0 km/h on the less affected side. A single heterozygous mutation in the PINK1 gene is associated with a bilateral dopaminergic dysfunction in this family. Ultrasound-based three-dimensional motion analysis of arm swing during gait is a suitable tool to quantify even subtle hypokinesia in mildly affected PINK1 mutation carriers, which tends to be easily overlooked on the less affected body side during clinical examination. Therefore, this technique is a promising application in early stage PD and in at-risk populations for the disease.

The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.

Mutations in the PINK1 gene cause autosomal recessive familial Parkinson's disease (PD). The gene encodes a mitochondrial protein kinase that plays an important role in maintaining mitochondrial function and integrity. However, the pathophysiological link between mutation-related bioenergetic deficits and the degenerative process in dopaminergic neurons remains to be elucidated. We performed phosphorous ((31)P) and proton ((1)H) 3-T magnetic resonance spectroscopic imaging (MRSI) in 11 members of a German family with hereditary PD due to PINK1 mutations (PARK6) compared to 23 age-matched controls. All family members had prior 18-Fluorodopa (FDOPA) positron emission tomography (PET). The striatal FDOPA uptake was correlated with quantified metabolic brain mapping in MRSI. At group level, the heterozygous PINK1 mutation carriers did not show any MRSI abnormalities relative to controls. In contrast, homozygous individuals with manifest PD had putaminal GPC, PCr, HEP and ß-ATP levels well above the 2SD range of controls. Across all subjects, the FDOPA K(i) values correlated positively with MI (r = 0.879, p<0.001) and inversely with ß-ATP (r = -0.784, p = 0.008) and GPC concentrations (r = -0.651, p = 0.030) in the putamen. Our combined imaging data suggest that the dopaminergic deficit in this family with PD due to PINK1 mutations relates to osmolyte dysregulation, while the delivery of high energy phosphates was preserved. Our results corroborate the hypothesis that PINK1 mutations result in reduced neuronal survival, most likely due to impaired cellular stress resistance.

Belly dancer's syndrome following central pontine and extrapontine myelinolysis.

We report on a woman with delayed-onset of belly dancer's syndrome 5 months after central pontine and extrapontine myelinolysis (CPM/EPM) and severe hyponatriemia. This case demonstrates that basal ganglia lesions in EPM can be the underlying pathoanatomic substrate for the rarely observed belly dancer's syndrome. The sequential appearance of extrapyramidal symptoms might reflect an ongoing but ineffective or deficient remyelination process. The presence of CPM/EPM should be considered in patients with involuntary dyskinesias of the abdominal wall.