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Vacuolar protein sorting 35 (VPS35) was recently reported to be a pathogenic gene for late- onset autosomal dominant Parkinson's disease (PD), using exome sequencing. To date, VPS35 mutations have been detected only in whites with PD. The aim of the present study was to determine the incidence and clinical features of Asian PD patients with VPS35 muta- tions. We screened 7 reported nonsynonymous mis- sense variants of VPS35, including p.D620N, known as potentially disease-associated variants of PD, in 300 Japanese index patients with autosomal dominant PD and 433 patients with sporadic PD (SPD) by direct sequencing or high-resolution melting (HRM) analysis. In addition, we screened 579 controls for the p.D620N mutation by HRM analysis. The p.D620N mutation was detected in 3 patients with autosomal dominant PD (1.0%), in 1 patient with SPD (0.23%), and in no con- trols. None of the other reported variants of VPS35 were detected. Haplotype analysis suggested at least 3 independent founders for Japanese patients with p.D620N mutation. Patients with the VPS35 mutation showed typical tremor-predominant PD. We report Asian PD patients with the VPS35 mutation. Although VPS35 mutations are uncommon in PD, the frequency of such mutation is relatively higher in Japanese than reported in other populations. In VPS35, p.D620N sub- stitution may be a mutational hot spot across different ethnic populations. Based on the clinical features, VPS35 should be analyzed in patients with PD, espe- cially autosomal dominant PD or tremor-predominant PD. V C 2012 Movement Disorder Society

Purpose Side population (SP) cells were isolated and the possibility whether lens epithelial cells contain stem cells was investigated. Methods Mouse lens epithelial cells were stained by Hoechst 33342 and then sorted by fluorescence-activated cell sorting (FACS). The expression of stem cell markers in sorted SP cells and the main population of epithelial cells were analyzed by quantitative real-time PCR. Localization of SP cells in the mouse lens was studied by fluorescence microscopy. Results The sorted cells contained SP cells, which were no longer separable by FACS following treatment with verapamil. The number of SP cells decreased with aging, but the adult mouse lens still contained SP cells. Phase contrast microscopy revealed that SP cells were smaller in size than non-SP cells. SP cells were localized near the equator region in lens epithelial cell layers. SP cells expressed higher levels of the stem cell markers ATP-binding cassette transporter G2 (ABCG2), p75 neurotrophin receptor (p75NTR), nestin (nes), B-cell lymphoma 2 (Bcl2), and cell surface antigen Sca-1 mRNA than the main population cells. These results suggest that SP cells contain a high proportion of stem cells. Conclusions The SP cells in the lens contain stem cells, and these stem cells are localized around the germinative zone.

Several studies have reported that olfactory dysfunction is an early neuropathological manifestation of Parkinson's disease (PD). Reduced cardiac meta-iodobenzylguanidine ((123)I-MIBG) uptake may be one of the earliest signs of PD. We studied the relation of olfactory dysfunction to cardiovascular dysautonomia in patients with PD. The study group comprised 66 patients with PD (70.5 years) and 26 controls (70.3 years) for olfactory assessment, 21 controls (72.1 years) for cardiac (123)I-MIBG scintigraphy and heart rate variability (HRV), assessed using the coefficient of variation for RR intervals (HRV), and 23 controls (69.2 years) for orthostatic blood pressure response. Olfactory function was assessed by the odor stick identification test Japan (OSIT-J), and cardiovascular autonomic function was evaluated by (123)I-MIBG scintigraphy of the heart, the fall in orthostatic blood pressure, and HRV. Patients with PD had a significantly lower OSIT-J score than did the controls (4.1 +/- 3.0 vs. 9.9 +/- 1.7, p = 0.001). The OSIT-J score was unrelated to variables other than gender, including age, disease duration, motor score on the unified Parkinson's disease rating scale, score on the mini-mental state examination, motor phenotype, visual hallucinations, and dopaminergic medication on multiple regression and logistic regression analyses. The OSIT-J score was related to the heart/mediastinum ratio of cardiac (123)I-MIBG uptake, the fall in orthostatic blood pressure, and HRV, after adjustment for other clinical variables. Olfactory dysfunction in PD was, thus, significantly related to both cardiac sympathetic and parasympathetic dysfunction, as well as vascular sympathetic dysfunction. As non-motor symptoms of PD, olfactory dysfunction and autonomic network failure appear to be closely related in PD.

We examined the relation of maximum phonation time (MPT) and vital capacity (VC) and reviewed the usefulness of MPT as a respiratory function screening.18 healthy adult subjects (8 men and 10 women), and 32 myopathic patients (24 men and 8 women).MPT and VC were measured in sitting position. Six patients were tested with and without air stacking by glossopharyngeal respiration.In healthy subjects, MPT was 29.9 +/- 11.8 seconds in men and 21.7 +/- 7.8 seconds in women. Second trials showed good reproducibility. The healthy group had no correlation between MPT and VC. The patient group showed a significant positive correlation between MPT and VC (r2= 0.25, p=0.003). All patients with MPT less than 15 seconds showed VC less than 1.5 l and %VC less than 50%. Air-stacking by glossopharyngeal respiration significantly increased the MPT.MPT is a useful screening test for respiratory muscle weakness. The patients are easily aware of the effect of air-stacking by glossopharyngeal respiration.

We report a 46-year-old woman with chronic inflammatory demyelinating polyneuropathy (CIDP) in whom swelling of the first branch of the trigeminal nerves in the bilateral orbits were observed as subcutaneous masses in the upper eyelids. The disease developed when the patient was 33 years old, and weakness of the four limbs, double vision, unilateral hypoglossal neuroparalysis, and unilateral facial paralysis frequently occurred during the course of the illness. On nerve conduction studies, conduction block was detected in the motor nerves. Steroid therapy and immunoglobulin treatment improved the symptoms. At 43 years old, subcutaneous phymas were noted in the bilateral upper eyelids, and fat-suppressed MRI detected the phymas localized along the upper region of the superior straight muscle in the bilateral orbits, and the muscles were slightly compressed downward. The masses branched in the orbits, and were diagnosed as nerve swelling of the supraorbital nerve, the first branch of the trigeminal nerve. Fat-suppressed MRI also identified nerve swelling of the extracranial maxillary and mandibular nerves. However, the patient had no subjective sensory disturbance in the trigeminal nerve region. Blink reflex did not induce R1 and R2 exhibited low amplitude and delayed latency. MRI confirmed asymmetric nerve swelling in the regions of the bilateral median nerves with motor nerve conduction block. Lumbar MRI detected nerve swelling in the peripheral nerves distant from the lumbar ganglion. MRI detected no nerve swelling in the arachnoid space such as the cervical cord, thoracic cord, or cauda equina. Aggravation of CIDP was treated with steroids and immunoglobulin. Diplopia occasionally appeared, but was not consistent with aggravation of CIDP. The bilateral supraorbital nerves remained unchanged for three years on MRI.