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Objective To evaluate the safety and assess the different symptom improvements found after a combined low frequency primary motor cortex and high frequency prefrontal cortex stimulation using the deep TMS (dTMS) H-coil, as an add-on treatment for Parkinson´s disease (PD). Methods: 45 PD patients underwent 14 dTMS sessions; each consisting of 1Hz stimulation of the primary motor cortex for 15 min, followed by 10Hz stimulation of the prefrontal cortex for 15 min. Clinical assessments were performed, at the START, MIDDLE, and END of therapy as well as at FOLLOW-UP after 30 days, using MDS-UPDRS, TINETTI, UP&GO, SCOPA, HDRS21, BDI and self-applied daily motor assessment scales. Results: Treatment was well tolerated, without serious adverse effects. Treatment induced significant PD symptom improvements at END and at FOLLOW-UP, in all subscales of the UPDRS, gait speed, depressive symptoms, balance, autonomic symptoms and a 73% increase in daily ON time. Conclusions: In the cohort of PD patients treated, dTMS was well tolerated with only minor adverse effects. The dTMS induced significant improvements in motor, postural, and motivational symptoms of PD patients and may potentiate concurrent levodopa treatment. Significance: The present study demonstrates that dTMS may have a much wider spectrum of beneficial effects than previously reported for TMS, including enhancement of levodopa effects, suggesting that future clinical trials with dTMS should include a broader range of symptom measurements.

Background: Movement disorders in Huntington´s disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial.Methods: In a conrolled double-blind phase 6 patients (4 chorea-dominant, 2 Westphal-variant) with predominant movement disorder were randomly assigned to either the sequence of 6 week internal-/6 week external-pallidal stimulation, or vice versa, followed by further 3 months chronic pallidal stimulation at the target with best effect-side-effect ratio. Primary endpoints were changes in the Unified Huntington´s Disease Rating Scale motor-score, chorea subscore and total motor-score 4 (blinded video ratings), comparing internal- versus external-pallidal stimulation, and 6 month versus baseline. Secondary endpoints assessed scores on dystonia, hypokinesia, cognition, mood, functionality/disability and quality-of-life. Results: Intention-to-treat analysis of all patients (n=3 in each treatment sequence): Both targets were equal in terms of efficacy. Chorea subscores decreased significantly over 6 months (-5.3 (60.2%), p=0.037). Effects on dystonia were not significant over the group due to it consisting of three responders (>50% improvement) and three non-responders. Westphal patients did not improve. Cognition was stable. Mood and some functionality/disability and quality-of-life scores improved significantly. 8 adverse events and 2 additional serious adverse events - mostly internal-pallidal stimulation-related - resolved without sequalae. No procedure-related complications occurred.Conclusion: Pallidal deep brain stimulation was demonstrated to be a safe treatment option for the reduction of chorea in Huntington´s disease. Their effects on chorea and dystonia and on quality-of-life, should be examined in larger controlled trials.

There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Vitamin D is actively under investigation as a potential intervention for epilepsy. Vitamin D is fat soluble steroid which shows promise in animal models of epilepsy. Basic research has shed light on the possible mechanisms by which Vitamin D may reduce seizures, and animal data support the efficacy of Vitamin D in rat and mouse models of epilepsy. Very little clinical data exists to support the treatment of human epilepsy with Vitamin D, but positive findings from preliminary clinical trials warrant larger Phase I and II clinical trials in order to more rigorously determine the potential therapeutic value of Vitamin D as a treatment for human epilepsy.

IntroductionAging and age-associated disorders such as Parkinson’s disease (PD) are often associated with turning difficulties, which can lead to falls and fractures. Valid assessment of turning and turning deficits specifically in non-standardized environments may foster specific treatment and prevention of consequences.MethodsRelative orientation, obtained from 3D-accelerometer and 3D-gyroscope data of a sensor worn at the lower back, was used to develop an algorithm for turning detection and qualitative analysis in PD patients and controls in non-standardized environments. The algorithm was validated with a total of 2,304 turns ≥90° extracted from an independent dataset of 20 PD patients during medication ON- and OFF-conditions and 13 older adults. Video observation by two independent clinical observers served as gold standard.ResultsIn PD patients under medication OFF, the algorithm detected turns with a sensitivity of 0.92, a specificity of 0.89, and an accuracy of 0.92. During medication ON, values were 0.92, 0.78, and 0.83. In older adults, the algorithm reached validation values of 0.94, 0.89, and 0.92. Turning magnitude (difference, 0.06°; SEM, 0.14°) and duration (difference, 0.004 s; SEM, 0.005 s) yielded high correlation values with gold standard. Overall accuracy for direction of turning was 0.995. Intra class correlation of the clinical observers was 0.92.ConclusionThis wearable sensor- and relative orientation-based algorithm yields very high agreement with clinical observation for the detection and evaluation of ≥90° turns under non-standardized conditions in PD patients and older adults. It can be suggested for the assessment of turning in daily life.

Sudden infant death syndrome (SIDS) is an unexplained death in infants that usually occurs during sleep. The cause of SIDS remains unknown and multifactorial. In this regard, the diving reflex (DR), a peripheral subtype of trigeminocardiac reflex (TCR) is also hypothesized as one of the possible mechanisms for this condition. The TCR is a well-established neurogenic reflex which manifests as bradycardia, hypotension, apnea, and gastric hyper motility. The TCR shares many similarities with the DR which is a significant physiological adaptation to withstand hypoxia during apnea in many animal species including humans in clinical manifestation and mechanism of action. The DR is characterized by breath-holding (apnea), bradycardia and vasoconstriction leading to rising in blood pressure. Several studies have described congenital anomalies of autonomic nervous system in the pathogenesis of SIDS such as hypoplasia, delayed neuronal maturation or decreased neuronal density of arcuate nucleus, hypoplasia and neuronal immaturity of the hypoglossal nucleus. The abnormalities of autonomic nervous system in SIDS may explain the role of TCR in this syndrome involving sympathetic and parasympathetic nervous system. We reviewed the available literature to identify the role of TCR in the etiopathogenesis of SIDS and the pathways and cellular mechanism involved in it. This synthesis will help to update our knowledge and improve our understanding about this mysterious, yet common condition and will open the door for further research in this field.

Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of Parkinson's disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD sub-phenotypes, such as age at onset, disease severity or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants may also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of L-dopa induced dyskinesia (LID), is an additional relevant sub-phenotype. LID may share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.

Postanoxic encephalopathy is the key determinant of death or disability after successful cardiopulmonary resuscitation. Animal studies have provided proof-of-principle evidence of efficacy of divergent classes of neuroprotective treatments to promote brain recovery. However, apart from targeted temperature management (TTM), neuroprotective treatments are not included in current care of patients with postanoxic encephalopathy after cardiac arrest. We aimed to review the clinical evidence of efficacy of neuroprotective strategies to improve recovery of comatose patients after cardiac arrest and to propose future directions. We performed a systematic search of the literature to identify prospective, comparative clinical trials on interventions to improve neurological outcome of comatose patients after cardiac arrest. We included 53 studies on 21 interventions. None showed unequivocal benefit. TTM at 33 or 36°C and adrenaline (epinephrine) are studied most, followed by xenon, erythropoietin, and calcium antagonists. Lack of efficacy is associated with heterogeneity of patient groups and limited specificity of outcome measures. Ongoing and future trials will benefit from systematic collection of measures of baseline encephalopathy and sufficiently powered predefined subgroup analyses. Outcome measurement should include comprehensive neuropsychological follow-up, to show treatment effects that are not detectable by gross measures of functional recovery. To enhance translation from animal models to patients, studies under experimental conditions should adhere to strict methodological and publication guidelines.