Christopher Fricke

Failure to confirm benefit of acetyl- dl -leucine in degenerative cerebellar ataxia: a case series

Recently, Strupp and co-workers [1] demonstrated that acetyl-DL-leucine (Tanganil ; Pierre Fabre Médicament, Boulogne, France) may lead to substantial symptomatic improvement in various forms of degenerative cerebellar ataxia (DCA) differing widely in symptom duration, severity and etiology. Medication was given for about 7 days, and 12 of their 13 patients benefited, while no side effects were reported [1]. However, endpoints were assessed unblinded, rendering objective evaluation of treatment response difficult. Here, we report our observations in a series of patients suffering from DCA who were treated with acetyl-DL-leucine. Pharmacological treatment was combined with physioand occupational therapy as both are important non-pharmaceutical components of the treatment of DCA [2, 3]. The study was conducted as a series of individual treatment efforts and confirms to the 1964 Declaration of Helsinki and its later amendments. After they had given informed consent for the off-label use of acetyl-DL-leucine, 10 patients with DCA (Table 1) were treated in-hospital with 5 g acetyl-DL-leucine once daily for a total duration of 7 days. Furthermore, each patient received altogether five sessions of physiotherapy at 45 min and five sessions of occupational therapy at 30 min, individually matched to the patient’s symptoms and including dedicated gait and balance training. Video-recorded measurements at baseline (off-drug) and on day 7 of active treatment (on-drug) were based on the Scale for the Assessment and Rating of Ataxia (SARA) [5, 6]. SARA scores were assessed from the video recordings by three investigators who were blinded with regard to the time point of video recording. Additionally, patients were asked about their subjective improvement on medication, and possible side effects during treatment were evaluated. Statistical analyses were performed with SPSS version 20.0 (IBM Corporation; New York, NY, USA). A p value \0.05 was considered as statistically significant. There was excellent interrater agreement for assessment of SARA scores from video recordings with an intraclass correlation (absolute mode) between investigators of C0.97 (p\ 0.001). Mean and median SARA scores were similar between baseline and at day 7 of treatment with acetyl-DLleucine (Wilcoxon signed-rank test; p = 0.17, respectively, p = 0.38; Table 2). During in-hospital treatment, no side effects were observed. Although 7 of 10 patients reported subjective amelioration of cerebellar symptoms, we failed to detect any significant improvement as measured by SARA in assessments blinded to treatment status to reduce rater bias [7]. As physiotherapy was shown to be beneficial for individuals with DCA [2, 3], it is unlikely to have obscured any positive effect of acetyl-DL-leucine. Notably, (pre-)clinical trials studied acetyl-DL-leucine only in vestibular diseases [8, 9], so its potential mode of action in DCA remains speculative. One limitation of our case series is that, in contrast to Strupp and co-workers [1], patients in our case series received the liquid formulation of acetyl-DL-leucine orally, because Tanganil tablets were no longer available in Germany. Since both, the solid and liquid formulation contain neither stabilizers nor any active pharmaceutical & Joseph Classen joseph.classen@medizin.uni-leipzig.de

Assessment of brainstem function with auricular branch of vagus nerve stimulation in Parkinson’s disease

Background The efferent dorsal motor nucleus of the vagal nuclei complex may degenerate early in the course of Parkinson’s disease (PD), while efferent nucleus ambiguous, the principal source of parasympathetic vagal neurons innervating the heart, and afferent somatosensory nuclei remain intact. Objective To obtain neurophysiological evidence related to this pattern, we tested processing of afferent sensory information transmitted via the auricular branch of the vagus nerve (ABVN) which is known to be connected to autonomic regulation of cardiac rhythm. Methods In this cross-sectional observational study, we recorded (i) somatosensory evoked potentials (ABVN-SEP) and (ii) cutaneo-cardioautonomic response elicited by stimulation of the ABVN (modulation of heart-rate variability (HRV index; low frequency power, ln(LF), high frequency power, ln(HF); ln(LF/HF) ratio)) in 50 PD patients and 50 age and sex matched healthy controls. Additionally, auditory evoked potentials and trigeminal nerve SEP were assessed. Results Neither ABVN-SEP nor any of the other functional brainstem parameters differed between patients and controls. Although HRV index was decreased in PD patients, modulation of ln(LF/HF) by ABVN-stimulation, likely indicating cardiac parasympathetic activation, did not differ between both groups. Conclusions Findings do not point to prominent dysfunction of processing afferent information from ABVN and its connected parasympathetic cardiac pathway in PD. They are consistent with the known pattern of degeneration of the vagal nuclei complex of the brainstem.

Sonographic abnormality of the substantia nigra in melanoma patients

Evidence derived from large epidemiological studies suggests an association between Parkinsons disease (PD) and malignant melanoma. Transcranial sonography of the midbrain reveals an extended echogenic substantia nigra (SN) area in a high proportion of patients with PD. This characteristic, in the context of PD, may signal degeneration of dopaminergic nigrostriatal projection neurons. Demonstration of an increased prevalence of abnormal echogenic SN in melanoma patients could add weight to the hypothesis of an underlying common pathogenic pathway of both diseases.

Light pigmentation phenotype is correlated with increased substantia nigra echogenicity

This study was undertaken to address the question of whether pigmentation may be mechanistically linked with Parkinsons disease.

Differential spatial representation of precision and power grasps in the human motor system

Power and precision grasps are two interrelated, kinematically distinct types of finger movements. We examined whether these types of motor actions may be spatially differently represented in the human central nervous system. In healthy participants representations of finger movements were mapped by delivering single pulse TMS to multiple scalp regions covering the left primary motor cortex (M1). Finger joint motions were recorded from the right hand using a data glove. Principal component analysis was used to extract local subspaces representing the TMS-evoked movement data from each scalp region. Voluntary power and precision grasps were reconstructed with these subspaces. The spatial properties of these reconstructions were analyzed for each grasp type using a general linear model. We found overlapping, yet distinct spatial representations for precision and power grasps with precision grasps represented slightly posterior compared to a more uniform distribution for power grasps. Differential spatial encoding of both grasp types may point towards a representation of power grasps within a phylogenetically older M1 area at the crown of the precentral gyrus and of precision grasps in a newer area in the depth of the central sulcus. Results also support the idea of separate synergistic movement representations in the human motor system.

Structural abnormality of substantia nigra induced by methamphetamine abuse

Background: Methamphetamine abuse has been linked to an increased risk of Parkinsons disease.

PB 17 Short-term shaping of cortico-muscular synergies

This article has been removed: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been removed at the request of the Publisher, as the authors did not give permission for the abstract to be published.This article has been removed: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been removed at the request of the Publisher, as the authors did not give permission for the abstract to be published.