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Objective: To determine whether an accelerated protocol of 48 Hz cerebellar repetitive transcranial magnetic stimulation results in improved motor function in individuals with Parkinson's disease. Methods: In this double‐blind randomized sham‐controlled study, 35 individuals with Parkinson's disease and stable medical treatment were randomized to either sham or verum transcranial magnetic stimulation. The stimulation was applied bilaterally and medial over the cerebellum and comprised a novel accelerated protocol encompassing two sessions per day on 5 consecutive days. Patients were assessed at baseline, on day 5 after the last stimulation and 1 month post intervention. Measurements included dynamic posturography, UPDRS III, 8‐Meter walk test, and Timed Up and Go test. Results: The accelerated protocol was safe and feasible in an outpatient setting. Patients in the verum group showed significant improvement (p < 0.001) of motor symptoms as measured in the UPDRS III. Improvement was mainly carried by the domains rigor, bradykinesia, and gait and persisted after 1 month (p = 0.009), whereas tremor remained unchanged. Interpretation: The effect of a high‐dose transcranial magnetic stimulation in patients with Parkinson's disease is encouraging and comparable to other studies using much longer stimulation protocols. This short‐term intervention of 5 days facilitates the future application in an outpatient setting. Reduction in hospitalization rates directly benefits patients with motor impairment. [ABSTRACT FROM AUTHOR]

Background: In absence of drug therapy options, standard treatment for spinocerebellar ataxia consists of symptomatic physiotherapy and speech therapy. New therapeutic options are urgently needed. Transcranial magnetic stimulation is a promising therapeutic option, but applicability is limited by lengthy duration of stimulation protocols. Methods: In this randomized sham controlled clinical trial, patients were assigned to verum (n = 15) or sham (n = 18) cerebellar transcranial magnetic stimulation. To yield best possible treatment effects, both intervention groups received intensified physiotherapy for the duration of the study. Results: Ataxia severity was reduced by 1.6 points on the Scale for assessment and Rating of Ataxia among patients in the verum group (p < 0.001). Clinical improvement was significantly larger in the verum group, compared to the sham group (p < 0.01). The treatment effect was mainly carried by improved appendicular coordination. Patients in the verum group also significantly improved in the 8 Meter Walk Test (p < 0.05) and PATA rate (p < 0.01). Conclusions: Cerebellar rTMS ameliorates ataxia severity in patient with spinocerebellar ataxia. Condensing treatment duration to only 5 days without reduction of treatment effects facilitates applicability and therefore broadens availability to larger patient populations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cerebellar ataxia, neuropathy and bilateral vestibular areflexia (CANVAS) is a rare neurodegenerative disease affecting the cerebellum, the peripheral nervous system and the vestibular system. Due to the lack of approved drugs, therapy comprises physiotherapy and speech therapy. Transcranial magnetic stimulation is a promising non-invasive therapeutic option to complement classical symptomatic therapies. OBJECTIVE: To test feasibility of the combination of transcranial magnetic stimulation using an accelerated protocol and standard symptomatic therapy in patients with CANVAS. METHODS: Eight patients with genetically confirmed CANVAS were assigned to either verum or sham cerebellar transcranial magnetic stimulation using an accelerated protocol. Treatment duration was limited to 5 days. Additionally, patients in both groups received symptomatic therapy (speech and physiotherapy) for the duration of the study. RESULTS: All patients completed the stimulation protocol. Adverse events were rare. Ataxia severity improved in the verum group only. CONCLUSION: The combination of transcranial magnetic stimulation and classic symptomatic therapy is feasible in a neuro-rehabilitation setting and potentially ameliorates ataxia severity. [ABSTRACT FROM AUTHOR]

Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in the blood of Alzheimer's disease (AD) patients. Epigenetic DNA modifications of the TNF-α promoter may account for the observed upregulation. Methods: We analyzed blood samples of 50 AD patients and 55 controls plus 4 AD and 4 control cortex samples using bisulfite sequencing PCR. Results: A significant hypomethylation of the TNF-α promoter was found in AD patients' brains but not in their blood. Cortical TNF-α promoter DNA was higher methylated than blood-derived DNA, both in AD patients and controls. Conclusion: In AD patients, epigenetic mechanisms of TNF-α gene regulation, like aberrant DNA methylation, are not relevant in blood. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD), and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. We found that methylation of human SNCA intron 1 decreased gene expression, while inhibition of DNA methylation activated SNCA expression. Methylation of SNCA intron 1 was reduced in DNA from sporadic PD patients' substantia nigra, putamen, and cortex, pointing toward a yet unappreciated epigenetic regulation of SNCA expression in PD. [ABSTRACT FROM AUTHOR]

Background: Retinal artery occlusion leads to dramatic and irreversible vision loss. There is currently no evidence-based standard therapy. According to the German guidelines on retinal artery occlusions, intravenous fibrinolysis therapy can be performed up to a time window of 4 h 30 min., Methods: Two patients were treated accordingly., Results: In patient 1, systemic lysis therapy was used in branch retinal artery occlusion (BRAO) of the inferior temporal retinal artery with macular involvement 4 h 15 min after symptom onset. Immediately after the therapy, the patient reported significant improvement in symptoms. Three months after therapy, retinal function was good, but with subtle atrophy of the inner neurosensory retina. Patient 2, 2 h 30 min after onset of symptoms of the inferior temporal BRAO, the patient experienced further deterioration, with clinical signs of a central retinal artery occlusion (CRAO). Visual acuity deteriorated to light perception. Emergency intravenous lysis therapy, administered 3 h later, gave an improvement in visual acuity with preservation of the inferior visual field. In both patients, a marked improvement in visual acuity was observed immediately after the lysis therapy: Patient 1: right eye, best corrected visual acuity (BCVA) initial 0.5, BCVA 3 days after lysis therapy 1.0, no defects in Goldmann visual field. Patient 2: left eye, BCVA initial 0.4, then sudden deterioration to light perception, BCVA 1 month after lysis therapy 0.6, persisting visual field defects in the superior hemisphere with preservation of the inferior visual field., Conclusions: Two patients with acute retinal artery occlusion were treated successfully with systemic intravenous fibrinolysis., Competing Interests: F. Raber: keine. K. Reinkling: keine. S. Schmitz-Valckenberg: Unterstützung von Forschungsprojekten und klinischen Studien durch Alcon/Novartis, Allergan, Bayer, Bioeq/Formycon, Centervue, Genentech/Roche, Heidelberg Engineering, Katairo, Optos, ZeissMeditec; Beratung, Honorare, Reisekosten: Alcon/Novartis, Allergan, Bayer, Galimedix, Genentech/Roche, Zeiss Meditec. K. Althaus: Vortragstätigkeit Boehringer Ingelheim. O. Kaut: keine. M. Witry: keine. G. E. Lang: Vortragstätigkeit Carl Zeiss Meditec., (Georg Thieme Verlag KG Stuttgart · New York.)