Background. Recent evidence from both monkey and human studies suggests that the reticulospinal tract may contribute to recovery of arm and hand function after stroke. In this study, we evaluated a marker of reticulospinal output in stroke survivors with varying degrees of motor recovery. Methods. We recruited 95 consecutive stroke patients presenting 6 months to 12 years after their index stroke, and 19 heathy control subjects. Subjects were asked to respond to a light flash with a rapid wrist flexion; at random, the flash was paired with either a quiet or loud (startling) sound. The mean difference in electromyogram response time after flash with quiet sound compared with flash with loud sound measured the StartReact effect. Upper limb function was assessed by the Action Research Arm Test (ARAT), spasticity was graded using the Modified Ashworth Scale (MAS) and active wrist angular movement using an electrogoniometer. Results. StartReact was significantly larger in stroke patients than healthy participants (78.4 vs 45.0 ms, P < .005). StartReact showed a significant negative correlation with the ARAT score and degree of active wrist movement. The StartReact effect was significantly larger in patients with higher spasticity scores. Conclusion. We speculate that in some patients with severe damage to their corticospinal tract, recovery led to strengthening of reticulospinal connections and an enhanced StartReact effect, but this did not occur for patients with milder impairment who could use surviving corticospinal connections to mediate recovery.

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Background: Spinocerebellar ataxia type 12 (SCA12) is a rare form of an autosomal-dominant ataxic disorder associated with an expansion of CAG repeat length. Here, we present a large case series of patients with SCA12 and describe a wide range of typical and rare symptoms. Methods: Twenty-one consecutive patients with genetically proven SCA12 underwent detailed neurological examination. We assessed clinical characteristics using validated rating scales for evaluating motor features in SCA. Nonmotor symptoms and quality of life were assessed using appropriate, validated scales. Correlations of CAG repeat length with both severity score and age of onset were explored. Results: The mean age of onset was 51 years, and most patients were descendants of a single, endogamous Indian community (Agarwal). Tremor was the most common initial presenting symptom (90%). Hand dystonia was present in 14 of 21 patients, and most patients in the cohort presented with gait disturbance. Neuropsychiatric manifestations were common coexisting features. The CAG repeat length was significantly correlated (r = À0.760; P = 0.0001) with early age of onset, but not with disease severity. Tremor affected the quality of life in 18 of 21 patients, because they had difficulty in handling liquids. Conclusions: Tremor was the most common, nonataxic symptom at initial presentation in patients with SCA12. Proximal upper limb tremor, typically with high amplitude and low frequency, can raise a strong diagnostic suspicion. Associated hand dystonia was a common coexisting motor feature. Various nonmotor features were also observed in several cases which require therapeutic attention.

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled crossover trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson’s disease (PD) patients. In a subgroup of patients, we measured selected neurotrophin levels and markers of inflammation and oxidative stress in serum, before and after the experimental intervention. Thirty-three PD patients with associated freezing of gait were randomised to either nVNS or sham. After baseline assessments, patients were instructed to deliver 6 two-minute stimulations (total 12 min/day) of the nVNS/sham device (electroCore, Inc. USA) for one month at home. Patients were then re-assessed. After a washout period of one month, the same patients were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters were observed with nVNS, including walking speed, stance time and step length, compared to sham. Similarly, overall motor function (MDS-UPDRS III) also improved significantly following nVNS stimulation. Serum Tumor Necrosis Factor (TNF)-α and glutathione levels decreased and brain-derived neurotrophic factor (BDNF) levels increased significantly (p < 0.05) after treatment with nVNS. Here we present the first double-blind sham-controlled trial evidence of the efficacy and safety of nVNS in the treatment of gait and motor function in patients with PD.

Background. In monkey, reticulospinal connections to hand and forearm muscles are spontaneously strengthened following corticospinal lesions, likely contributing to recovery of function. In healthy humans, pairing auditory clicks with electrical stimulation of a muscle induces plastic changes in motor pathways (probably including the reticulospinal tract), with features reminiscent of spike-timing dependent plasticity. In this study, we tested whether pairing clicks with muscle stimulation could improve hand function in chronic stroke survivors. Methods. Clicks were delivered via a miniature earpiece; transcutaneous electrical stimuli at motor threshold targeted forearm extensor muscles. A wearable electronic device (WD) allowed patients to receive stimulation at home while performing normal daily activities. A total of 95 patients >6 months poststroke were randomized to 3 groups: WD with shock paired 12 ms before click; WD with clicks and shocks delivered independently; standard care. Those allocated to the device used it for at least 4 h/d, every day for 4 weeks. Upper-limb function was assessed at baseline and weeks 2, 4, and 8 using the Action Research Arm Test (ARAT), which has 4 subdomains (Grasp, Grip, Pinch, and Gross). Results. Severity across the 3 groups was comparable at baseline. Only the paired stimulation group showed significant improvement in total ARAT (median baseline: 7.5; week 8: 11.5; P = .019) and the Grasp subscore (median baseline: 1; week 8: 4; P = .004). Conclusion. A wearable device delivering paired clicks and shocks over 4 weeks can produce a small but significant improvement in upper-limb function in stroke survivors.