A Comprehensive Study of Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease

The clinical benefits of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) remain controversial. We performed a comprehensive study to examine whether rTMS is a safe and effective treatment for PD. Twelve PD patients received rTMS once a week. The crossover study design consisted of 4-week sham rTMS followed by 4-week real rTMS. The Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn and Yahr Stage, Schwab and England ADL Scale, Actigraph, Mini-Mental State Examination, Hamilton Depression Scale, Wechsler Adult Intelligence Scale-revised, and cerebral blood flow (CBF) and cerebrospinal fluid (CSF) examinations were used to evaluate the rTMS effects. Under both drug-on and drug-off conditions, the real rTMS improved the UPDRS scores significantly, while the sham rTMS did not. There were no significant changes in the results of the neuropsychological tests, CBF and CSF. rTMS seems to be a safe and effective therapeutic option for PD patients, especially in a wearing-off state

Posterior reversible encephalopathy syndrome with extensive cytotoxic edema after blood transfusion: a case report and literature review

Abstract Background Posterior reversible encephalopathy syndrome (PRES) is described as a clinical-radiological disease entity with good prognosis. In brain MRI, PRES generally presents with vasogenic edema. Although PRES is induced by various causes, a small number of PRES cases have occurred after red cell blood transfusion. It is unclear whether there are characteristic features in PRES after blood transfusion. Case presentation Here, we report a case of 75-year-old Japanese woman who had acute exacerbation of subacute anemia by bleeding from gastric ulcer. After receiving a red cell blood transfusion, she showed disturbance of consciousness with extensive cytotoxic and small vasogenic edema in the occipitoparietal area on brain MRI. She was diagnosed as PRES and suffered irreversible impairments of visual acuity and fields in both eyes. We summarized and discussed clinical features of cases with PRES after blood transfusion. Conclusions A total of 21 cases including the present one have been reported as PRES after blood transfusion. Of the cases, 20 of 21 were female, and 15 of 17 developed PRES in the course of chronic anemia lasting over 1 month. Anemia was severe in 15 of 20 cases, with hemoglobin levels < 3.5 g/dl. In 14 of 17 cases, hemoglobin levels increased to 5 g/dl by red cell blood transfusion until the onset of PRES. On brain MRI, 2 of 21 cases showed cytotoxic edema and 3 of 21 cases showed irreversible neurological disturbance. In this patient, the occurrence of PRES in subacute anemia and the presence of extensive cytotoxic brain edema with irreversible neurological deficits were characteristic points. When treating severe anemia, even with a subacute progression, we should consider a possibility that PRES occurs after blood transfusion with extensive cytotoxic brain edema and irreversible neurological changes

Serum matrix metalloproteinase 3 levels are associated with an effect of iguratimod as add-on therapy to biological DMARDs in patients with rheumatoid arthritis.

OBJECTIVE:The aim of this study was to clarify whether serum matrix metalloproteinase 3 (MMP-3) levels are associated with an effect of iguratimod as add-on therapy to biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA). METHODS:Forty three patients with RA were treated with iguratimod as add-on therapy to bDMARDs. They were classified into remission and non-remission groups at 24 weeks of iguratimod therapy. Remission was defined as a state with a disease activity score (DAS) <2.6 in 28 joints (termed DAS remission) and total power Doppler ultrasound (US) score <3 (termed US remission). The serum MMP-3 levels at baseline and at 12 weeks were compared between these two groups. RESULTS:There were no significant differences in the serum MMP-3 levels at baseline between the DAS and US remission groups and the non-remission group. The serum MMP-3 levels at 12 weeks in the US remission group were significantly lower than those in the non-remission group. The ratios of the serum MMP-3 levels at baseline to those at 12 weeks in both the DAS and US remission groups were significantly lower than those in the non-remission group. An MMP-3 ratio <0.86 was determined as the cut-off value to predict US remission at 24 weeks. CONCLUSION:Our findings suggest that the ratios of the serum MMP-3 levels at baseline to those at 12 weeks could be used to predict remission in RA patients who are administered iguratimod as an add-on to bDMARDs

Zonisamide attenuates α-synuclein neurotoxicity by an aggregation-independent mechanism in a rat model of familial Parkinson's disease.

The anti-epileptic agent zonisamide (ZNS) has been shown to exert protective effects in neurotoxin-based mouse models of Parkinson disease. However, it is unknown whether ZNS can attenuate toxicity of familial Parkinson's disease-causing gene products. In this study, we investigated the effects of ZNS on neurodegeneration induced by expression of A53T α-synuclein in the rat substantia nigra using a recombinant adeno-associated virus vector. Expression of A53T α-synuclein yielded severe loss of nigral dopamine neurons and striatal dopamine nerve terminals from 2 weeks to 4 weeks after viral injection. Oral administration of ZNS (40 mg/kg/day) significantly delayed the pace of degeneration at 4 weeks after viral injection as compared with the vehicle group. This effect lasted until 8 weeks after viral injection, the final point of observation. ZNS treatment had no impact on the survival of nigrostriatal dopamine neurons in rats expressing green fluorescent protein. Quantification of striatal Ser129-phosphorylated α-synuclein-positive aggregates showed that these aggregates rapidly formed from 2 weeks to 4 weeks after viral injection. This increase was closely correlated with loss of nigrostriatal dopamine neurons. However, ZNS treatment failed to alter the number of all striatal Ser129-phosphorylated α-synuclein-positive aggregates, including small dot-like and large round structures. The number of these aggregates was almost constant at 4 weeks and 8 weeks after viral injection, although ZNS persistently prevented loss of nigrostriatal dopamine neurons during this period. Also, ZNS treatment did not affect the number of striatal aggregates larger than 10 µm in diameter. These data show that ZNS attenuates α-synuclein-induced toxicity in a manner that is independent of the formation and maturation of α-synuclein aggregates in an in vivo model of familial Parkinson's disease, suggesting that ZNS may protect nigrostriatal dopamine neurons by modulating cellular damage or a cell death pathway commonly caused by neurotoxins and α-synuclein

Additional file 1: Figure S1. of Mechanisms underlying extensive Ser129-phosphorylation in α-synuclein aggregates

Effects of Ca2+ on Ser129-phosphorylation of α-syn in rat primary cortical neurons. Cell lysates (10 μg/lane) were loaded on SDS-PAGE and analyzed by western botting with EP1536Y, Syn-1, or anti-β-actin (AC-15) antibody. a Effect of A23187 concentrations on Ser129-phosphorylation. Primary cortical neurons were treated with A23187 at the indicated concentrations for 8 h. b, c Effect of extracellular Ca2+ chelator EGTA (b) or intracellular Ca2+ chelator BAPTA-AM (B-AM) (c) on A23187-induced Ser129-phosphorylation. Cells were incubated in media containing 0.25 μM A23187 with the indicated concentrations of EGTA or BAPTA-AM for 8 h. d Effect of CaM inhibitor W-7 on A23187-induced Ser129-phosphorylation. Cells were incubated in media containing 0.25 μM A23187 with the indicated concentrations of W-7 for 8 h. Representative blots are shown. Relative band intensities of Ser129-phosphorylated α-syn and total α-syn were normalized to those of β-actin. Graphs show relative ratios to vehicle control cells. Data represent means ± SD and P values were estimated by one-way ANOVA with Bonferroni correction or Welch-ANOVA with Games-Howell post hoc test for unequal-variances (*, P < 0.05; **, P < 0.01). (TIFF 2872 kb