Ultrasound guidance increases the success rate of peripheral i.v. cannulation, especially in patients with known or predicted difficult i.v. access.

Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation.

Objective:The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus.Methods: After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis. Results:The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects.Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p ϭ 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p ϭ 0.08). The VDADL score decreased from 6.00 to 1.50 (p ϭ 0.02). 4AP was well-tolerated.Conclusions: This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life. Level of evidence:This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias. Neurology Episodic ataxia type 2 (EA2) is a rare autosomal dominant hereditary disorder caused by heterozygous mutations of the gene CACNA1A on chromosome 19p13.1 The carbonic anhydrase inhibitor acetazolamide has been the drug of first choice for the preventive treatment of episodic ataxia (EA) and especially EA2 (doses of 250 -1,000 mg/day), 2,3 because of the serendipitous discovery of its dramatic impact. 4 Its efficacy, however, has never been proven in a randomized controlled trial. 5,6 Acetazolamide effectively prevents or attenuates the attacks in approximately 50%-75% of all patients with EA2. 7 Clinical experience, however, shows that many patients stop this treatment in the long run because they develop adverse effects or are no longer responsive. 5,6 Furthermore, the adverse effects of acetazolamide (such as nephrocalcinosis, hyperhidrosis, paresthesia, muscle stiffening with easy fatigability, and gastrointestinal disturbances) limit its usage. 6 In view of the need to identify an alternative treatment option to acetazolamide and on the basis of pilot studies in subjects with downbeat nystagmus 8 and EA 9 as well as findings from animal studies, 10,11 we conducted a prospective randomized, doubleblind, placebo-controlled crossover study of 4AP in familial EA with nystagmus (the majority

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be an effective treatment for Parkinson's disease (PD). The intraoperative positioning of DBS electrodes and postoperative adjustment of the stimulation parameters, however, require continuous, precise evaluation. Moreover, ambulatory measurements of the symptoms would also help to evaluate changes in the progression of PD in these patients. To this aim, we objectified rigidity measurements via surface EMG recordings of the Mm. biceps (bic) and triceps brachii (tric) in patients treated with chronic stimulation of the STN. We show that cessation and initiation of DBS have effects on the EMG profile during standardized extension and flexion movements in the elbow joint. These data correlate significantly with clinical ratings. Thus, EMG recordings of the Mm. bic and tric during this standardized extension-flexion movement can be used to objectively measure rigidity and to monitor its course over time. In view of its low technical requirements, this technique lends itself to use during DBS implantation surgery and in the clinical environment.

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Previous studies have shown that cerebellar transcranial direct current stimulation (tDCS) leads to faster adaptation of arm reaching movements to visuomotor rotation and force field perturbations in healthy subjects. The first aim of the present study was to confirm a stimulation-dependent effect on motor adaptation. Second, we investigated whether tDCS effects differ depending on onset, that is, before or at the beginning of the adaptation phase. A total of 120 healthy and right-handed subjects (60 women, mean age 23.2 ± SD 2.7 yr, range 18–31 yr) were tested. Subjects moved a cursor with a manipulandum to one of eight targets presented on a vertically orientated screen. Three baseline blocks were followed by one adaptation block and three washout blocks. Sixty subjects did a force field adaptation task (FF), and 60 subjects did a visuomotor adaptation task (VM). Equal numbers of subjects received anodal, cathodal, or sham cerebellar tDCS beginning either in the third baseline block or at the start of the adaptation block. In FF and VM, tDCS and the onset of tDCS did not show a significant effect on motor adaptation (all P values >0.05). We were unable to support previous findings of modulatory cerebellar tDCS effects in reaching adaptation tasks in healthy subjects. Prior to possible application in patients with cerebellar disease, future experiments are needed to determine which tDCS and task parameters lead to robust tDCS effects. NEW & NOTEWORTHY Transcranial direct current stimulation (tDCS) is a promising tool to improve motor learning. We investigated whether cerebellar tDCS improves motor learning in force field and visuomotor tasks in healthy subjects and what influence the onset of stimulation has. We did not find stimulation effects of tDCS or an effect of onset of stimulation. A reevaluation of cerebellar tDCS in healthy subjects and at the end of the clinical potential in cerebellar patients is demanded.

Objective To investigate the safety and efficacy of N-acetyl-l-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann–Pick disease type C (NPC) patients. Methods In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6–12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments. Results 33 subjects aged 7–64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. Conclusions NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. Clinicaltrials.gov identifier NCT03759639.