Clinical features of drug-induced Parkinsonism

Drug-induced Parkinsonism is often reversible after withdrawal of the causative drug. Its clinical course, however, is not well understood, as the majority of cases are caused by drugs prescribed by departments outside of neurology. We reviewed 21 cases of drug-induced parkinsonism for several factors, including age, sex, causative drug and reason for prescription, department by which it was prescribed, and outcome. The age at onset ranged from 40 to 87 years, with an average Hoehn and Yahr Scale score of 4, indicating severe disability. Sulpiride was the most commonly observed causative drug (71.4%). All causative drugs were prescribed in non-neurological departments and over one half were prescribed in non-psychiatric departments; most were prescribed to treat depression or abdominal discomfort. Ten patients (48%) were previously diagnosed with a neuromuscular disease, including cerebrovascular diseases and Parkinson’s disease. Recovery was observed in 15 cases (71%) after withdrawal of the causative drug, but lingering symptoms were observed in the remaining cases. It is suggested that physicians should be more cautious of Parkinsonian side effects when prescribing such drugs

Clinical features of drug-induced Parkinsonism

Drug-induced Parkinsonism is often reversible after withdrawal of the causative drug. Its clinical course, however, is not well understood, as the majority of cases are caused by drugs prescribed by departments outside of neurology. We reviewed 21 cases of drug-induced parkinsonism for several factors, including age, sex, causative drug and reason for prescription, department by which it was prescribed, and outcome. The age at onset ranged from 40 to 87 years, with an average Hoehn and Yahr Scale score of 4, indicating severe disability. Sulpiride was the most commonly observed causative drug (71.4%). All causative drugs were prescribed in non-neurological departments and over one half were prescribed in non-psychiatric departments; most were prescribed to treat depression or abdominal discomfort. Ten patients (48%) were previously diagnosed with a neuromuscular disease, including cerebrovascular diseases and Parkinson’s disease. Recovery was observed in 15 cases (71%) after withdrawal of the causative drug, but lingering symptoms were observed in the remaining cases. It is suggested that physicians should be more cautious of Parkinsonian side effects when prescribing such drugs

The CHC22 Clathrin-GLUT4 Transport Pathway Contributes to Skeletal Muscle Regeneration

Mobilization of the GLUT4 glucose transporter from intracellular storage vesicles provides a mechanism for insulin-responsive glucose import into skeletal muscle. In humans, clathrin isoform CHC22 participates in formation of the GLUT4 storage compartment in skeletal muscle and fat. CHC22 function is limited to retrograde endosomal sorting and is restricted in its tissue expression and species distribution compared to the conserved CHC17 isoform that mediates endocytosis and several other membrane traffic pathways. Previously, we noted that CHC22 was expressed at elevated levels in regenerating rat muscle. Here we investigate whether the GLUT4 pathway in which CHC22 participates could play a role in muscle regeneration in humans and we test this possibility using CHC22-transgenic mice, which do not normally express CHC22. We observed that GLUT4 expression is elevated in parallel with that of CHC22 in regenerating skeletal muscle fibers from patients with inflammatory and other myopathies. Regenerating human myofibers displayed concurrent increases in expression of VAMP2, another regulator of GLUT4 transport. Regenerating fibers from wild-type mouse skeletal muscle injected with cardiotoxin also showed increased levels of GLUT4 and VAMP2. We previously demonstrated that transgenic mice expressing CHC22 in their muscle over-sequester GLUT4 and VAMP2 and have defective GLUT4 trafficking leading to diabetic symptoms. In this study, we find that muscle regeneration rates in CHC22 mice were delayed compared to wild-type mice, and myoblasts isolated from these mice did not proliferate in response to glucose. Additionally, CHC22-expressing mouse muscle displayed a fiber type switch from oxidative to glycolytic, similar to that observed in type 2 diabetic patients. These observations implicate the pathway for GLUT4 transport in regeneration of both human and mouse skeletal muscle, and demonstrate a role for this pathway in maintenance of muscle fiber type. Extrapolating these findings, CHC22 and GLUT4 can be considered markers of muscle regeneration in humans

Beta-synemin expression in cardiotoxin-injected rat skeletal muscle

Background: β-synemin was originally identified in humans as an α-dystrobrevin-binding protein through a yeast two-hybrid screen using an amino acid sequence derived from exons 1 through 16 of α-dystrobrevin, a region common to both α-dystrobrevin-1 and -2. α-Dystrobrevin-1 and -2 are both expressed in muscle and co-localization experiments have determined which isoform preferentially functions with β-synemin in vivo. The aim of our study is to show whether each α-dystrobrevin isoform has the same affinity for β-synemin or whether one of the isoforms preferentially functions with β-synemin in muscle. Methods: The two α-dystrobrevin isoforms (-1 and -2) and β-synemin were localized in regenerating rat tibialis anterior muscle using immunoprecipitation, immunohistochemical and immunoblot analyses. Immunoprecipitation and co-localization studies for α-dystrobrevin and β-synemin were performed in regenerating muscle following cardiotoxin injection. Protein expression was then compared to that of developing rat muscle using immunoblot analysis.Results: With an anti-α-dystrobrevin antibody, β-synemin co-immunoprecipitated with α-dystrobrevin whereas with an anti-β-synemin antibody, α-dystrobrevin-1 (rather than the -2 isoform) preferentially co-immunoprecipitated with β-synemin. Immunohistochemical experiments show that β-synemin and α-dystrobrevin co-localize in rat skeletal muscle. In regenerating muscle, β-synemin is first expressed at the sarcolemma and in the cytoplasm at day 5 following cardiotoxin injection. Similarly, β-synemin and α-dystrobrevin-1 are detected by immunoblot analysis as weak bands by day 7. In contrast, immunoblot analysis shows that α-dystrobrevin-2 is expressed as early as 1 day post-injection in regenerating muscle. These results are similar to that of developing muscle. For example, in embryonic rats, immunoblot analysis shows that β-synemin and α-dystrobevin-1 are weakly expressed in developing lower limb muscle at 5 days post-birth, while α-dystrobrevin-2 is detectable before birth in 20-day post-fertilization embryos. Conclusion: Our results clearly show that β-synemin expression correlates with that of α-dystrobrevin-1, suggesting that β-synemin preferentially functions with α-dystrobrevin-1 in vivo and that these proteins are likely to function coordinately to play a vital role in developing and regenerating muscle

Development of a Teaching Material for the Human Skeleton using a Visual Information Compensation Function

Abstract: We investigated the use of a talking pen (Touch Memo ® ) combined with a specially labeled model of the human skeleton as a self-learning material on anatomy for visually impaired students. The talking pen replays previously input information when a dot-code label (re-recordable label) is touched. This study aimed to obtain students' evaluations of sites at which the dot-code labels can be attached at the indicative positions on the skeleton model to ensure ease of use, thereby determining the most user-friendly ways to use the labels for visually impaired students. Twenty-two visually impaired students specializing in acupuncture and moxibustion participated in the study. Four sites of attachment of the dot-code label to the skeleton module were examined: (a) directly to the bone, (b) head of a wooden screw in the skeleton model, (c) inside a hole of a 3.5-mm diameter, and (d) inside a hole with a 5-mm diameter. The participants evaluated the talking pen using a 5-point scale on the basis of recognition of the dot-code label and the responsiveness of the talking pen to the dot-code label. The results showed that students experienced more difficulty in recognizing the dot-code label by touch and in getting the talking pen to respond when the label was attached to a 3.5-mm hole than when it was attached by other means. In addition, regardless of t he degree of visual impairment, the most user-friendly sites were when the label was attached to the model directly and when it was attached to a 5-mm hole. However, attaching the label directly to the skeleton model often peeled off; therefore, we conclude that the use of the model with a 5-mm hole should be used and improved further

Development of a Teaching Material for the Human Skeleton using a Visual Information Compensation Function

We investigated the use of a talking pen (Touch Memo®) combined with a specially labeled model of the human skeleton as a self-learning material on anatomy for visually impaired students. The talking pen replays previously input information when a dot-code label (re-recordable label) is touched. This study aimed to obtain students’ evaluations of sites at which the dot-code labels can be attached at the indicative positions on the skeleton model to ensure ease of use, thereby determining the most user-friendly ways to use the labels for visually impaired students. Twenty-two visually impaired students specializing in acupuncture and moxibustion participated in the study. Four sites of attachment of the dot-code label to the skeleton module were examined: (a) directly to the bone, (b) head of a wooden screw in the skeleton model, (c) inside a hole of a 3.5-mm diameter, and (d) inside a hole with a 5-mm diameter. The participants evaluated the talking pen using a 5-point scale on the basis of recognition of the dot-code label and the responsiveness of the talking pen to the dot-code label. The results showed that students experienced more difficulty in recognizing the dot-code label by touch and in getting the talking pen to respond when the label was attached to a 3.5-mm hole than when it was attached by other means. In addition, regardless of the degree of visual impairment, the most user-friendly sites were when the label was attached to the model directly and when it was attached to a 5-mm hole. However, attaching the label directly to the skeleton model often peeled off; therefore, we conclude that the use of the model with a 5-mm hole should be used and improved further

Miller Fisher syndrome with sinus arrest

Dysautonomia in Guillain-Barre syndrome (GBS) rarely causes serious cardiovascular complications, such as sinus arrest. Miller Fisher syndrome (MFS) is recognized as a variant of GBS. There have been few reports regarding the association between MFS and dysautonomia. We describe a case of a 68-year-old man with ophthalmoplegia, bulbar palsy, truncal ataxia, and areflexia. He was diagnosed with MFS because he exhibited the classical clinical triad and had elevated serum anti- GQ1b immunoglobulin G levels. A magnetic resonance imaging scan of his head was normal. His 24-hour Holter recording showed sinus arrest. He was treated with intravenous immunoglobulin, whereupon his symptoms gradually improved. This included the sinus arrest, which was considered a symptom of dysautonomia in MFS. Therefore, clinicians should be mindful of dysautonomia not only in GBS patients, but also in cases of MFS