Accumulation of misfolded α-synuclein is the pathological hallmark of Parkinson’s disease (PD). Nevertheless, little is known about the mechanism contributing to α-synuclein aggregation and its further toxicity to dopaminergic neurons. Since oxidative stress can increase the expression and aggregation levels of α-synuclein, NADPH oxidases (NOXs), which are responsible for ROS generation, could be major players in α-synucleinopathy. Previously, we demonstrated that Nox1 is expressed in dopaminergic neurons of the PD animal models as well as postmortem brain tissue of PD patients, being responsible for oxidative stress and subsequent neuronal degeneration. Here, using paraquat (PQ)-based in vitro and in vivo PD models, we show that Nox1 has a crucial role in modulating the behavior of α-synuclein expression and aggregation in dopaminergic neurons. We observed in differentiated human dopaminergic cells that Nox1 and α-synuclein expression are increased under PQ exposure. Nox1 knockdown significantly reduced both α-synuclein expression and aggregation, supporting the role of Nox1 in this process. Furthermore, in rats exposed to PQ, the selective knockdown of Nox1 in the substantia nigra, using adeno-associated virus encoding Nox1-specific shRNA, largely attenuated the PQ-mediated increase of α-synuclein and ubiquitin expression levels as well as α-synuclein aggregates (proteinase-K resistant) and A11 oligomers. Significant reductions in oxidative stress level and dopaminergic neuronal loss were also observed. Our data reveal a new mechanism by which α-synuclein becomes a neuropathologic protein through Nox1-mediated oxidative stress. This finding may be used to generate new therapeutic interventions that slower the rate of α-synuclein aggregation and the progression of PD pathogenesis.

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ObjectiveTo investigate balance control according to the severity of knee osteoarthritis (OA) using clinical tests and Tetra-ataxiometric posturography (Tetrax®).MethodA total 80 patients with primary knee OA classified according to American College of Rheumatology criteria, and 40 age-matched controls were enrolled in this study. Of those with OA, 39 patients had mild OA (Kellgren-Lawrence [KL] grade 1, 2) and the other 41 had moderate to severe OA (KL grade 3, 4). The postural control capabilities of the subjects were assessed using the timed up and go test (TUG), Berg balance scale (BBS), and Tetrax®, which utilizes two paired force plates to measure vertical pressure fluctuations over both heels and forefeet. The subjects were checked for their stability index (ST), Fourier index, weight distribution index (WDI), and synchronization index (SI) in eight positions using Tetrax®.ResultsPatients with moderate to severe OA exhibited significantly higher stability indices in all positions than patients with mild OA. The Fourier index was also higher in patients with moderate to severe OA than in patients with mild OA. However, the weight distribution index and synchronization of both heels and forefeet were not significantly different in the three groups.ConclusionThese findings suggest that patients with moderate to severe OA have more deficits in balance control than those with mild disease. Therefore, evaluation of balance control and education aimed at preventing falls would be useful to patients with knee OA.

The purpose of this study was to investigate the mechanisms of aspiration with respect to the viscosity of ingested material in patients with dysphagia. Seventy patients with dysphagia underwent videofluoroscopic swallow studies (VFSS) between May 1, 2009 and September 30, 2009. Based on the findings of the VFSS, patients were divided into three groups: a thick-fluid aspiration group, a thin-fluid aspiration group, and a no-aspiration group. Kinematic analyses were performed during thick-fluid swallowing. Among our 70 patients, 23 had thick-fluid aspiration, 20 had thin-fluid aspiration, and 27 had no aspiration. A shortened duration of upper esophageal sphincter (UES) opening, a shorter interval between UES opening and peak pharyngeal constriction, and a diminished extent of laryngeal elevation were all significant risk factors for thick-fluid aspiration. A prolonged latency of the swallowing reflex, pharyngeal transit time, and the interval between bolus arrival at the vallecula and laryngeal elevation were all significant risk factors for thin-fluid aspiration. Our kinematic analysis of dysphagia employing the VFSS indicated that the mechanisms relevant to aspiration differed with respect to food viscosity.

ObjectiveTo evaluate the relationships between tongue pressure and different aspects of the oral-phase swallowing function.MethodsWe included 96 stroke patients with dysphagia, ranging in age from 40 to 88 years (mean, 63.7 years). Measurements of tongue pressure were obtained with the Iowa Oral Performance Instrument, a device with established normative data. Three trials of maximum performance were performed for lip closure pressure (LP), anterior hard palate-to-tongue pressure (AP), and posterior hard palate-to-tongue pressure (PP); buccal-to-tongue pressures on both sides were also recorded (buccal-to-tongue pressure, on the weak side [BW]; buccal-to-tongue pressure, on the healthy side [BH]). The average pressure in each result was compared between the groups. Clinical evaluation of the swallowing function was performed with a videofluoroscopic swallowing study.ResultsThe average maximum AP and PP values in the intact LC group were significantly higher than those in the inadequate lip closure group (AP, p=0.003; PP, p<0.001). AP and PP showed significant relationships with bolus formation (BF), mastication, premature bolus loss (PBL), tongue to palate contact (TP), and oral transit time (OTT). Furthermore, LP, BW, and BH values were significantly higher in the groups with intact mastication, without PBL and intact TP.ConclusionThese findings indicate that the tongue pressure appears to be closely related to the oral-phase swallowing function in post-stroke patients, especially BF, mastication, PBL, TP and OTT.

ObjectiveTo evaluate the association between baseline characteristics, three physical performance tests and fall history in a sample of the elderly from Korean population.MethodsA total of 307 participants (mean age, 76.70±4.85 years) were categorized into one of two groups, i.e., fallers and non-fallers. Fifty-two participants who had reported falling unexpectedly at least once in the previous 12 months were assigned to the fallers group. Physical performance tests included Short Physical Performance Battery (SPPB), Berg Balance Scale (BBS), Timed Up and Go test. The differences between the two study groups were compared and we analyzed the correlations between fall histories and physical performance tests.ResultsSPPB demonstrated a significant association with fall history. Although the BBS total scores did not show statistical significance, two dynamic balance test items of BBS (B12 and B13) showed a significant association among fallers.ConclusionThis study suggests that SPPB and two dynamic balance test items of the BBS can be used in screening for risk of falls in an ambulatory elderly population.

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Monomelic amyotrophy (MMA), also known as Hirayama disease, is a sporadic juvenile muscular atrophy in the distal upper extremities. This disorder rarely involves proximal upper extremities and presents minimal sensory symptoms with no upper motor neuron (UMN) signs. It is caused by anterior displacement of the posterior dural sac and compression of the cervical cord during neck flexion. An 18-year-old boy visited our clinic with a 5-year history of left upper extremity pain and slowly progressive weakness affecting the left shoulder. Atrophy was present in the left supraspinatus and infraspinatus. On neurological examination, positive UMN signs were evident in both upper and lower extremities. Electrodiagnostic study showed root lesion involving the fifth to seventh cervical segment of the cord with chronic and ongoing denervation in the fifth and sixth cervical segment innervated muscles. Cervical magnetic resonance imaging (MRI) showed asymmetric cord atrophy apparent in the left side and intramedullary high signal intensity along the fourth to sixth cervical vertebral levels. With neck flexion, cervical MRI revealed anterior displacement of posterior dural sac, which results in the cord compression of those segments. The mechanisms of myelopathy in our patient seem to be same as that of MMA. We report a MMA patient involving proximal limb with UMN signs in biomechanical concerns and discuss clinical importance of cervical MRI with neck flexion. The case highlights that clinical variation might cause misdiagnosis.