STN-DBS is an effective long-term treatment in PD, improving a broad spectrum of symptoms, including tremor, rigidity, and bradykinesia (Fig. 1a) together with dopaminergic treatment. Among axial symptoms, gait disorders are common in PD. This study examines the long-term effects of different combinations of these two treatments in a cohort of advanced PD patients by means of the iTUG. Observational study on consecutive PD patients previously treated with bilateral STN-DBS. Disease severity was assessed using the UPDRS part III. Accelerometric data were acquired using an inertial sensor (G-WALK, BTS Bioengineering). Three iTUG trials were recorded in each of four stimulation and drug conditions: on-stimulation/off-medication, off-stimulation/off-medication, on-stimulation/on- medication and while preforming a cognitive task (counting backward, DUAL TASK) with both stimulation and medication on. Data were segmented into six phases (e.g., rising from chair, walking) as in [1]. A set of indices was computed including durations, RMS amplitudes, peak accelerations, peak angular velocities, indices of symmetry (improved Harmonic Ratio) and smoothness (Spectral Arc) [1]. A one-way non-parametric ANOVA was carried out, with the condition as a factor, followed by paired comparisons when appropriated. Statistical significance was set at 5% for all analyses. Twenty-five patients were re-evaluated 3 to 7 years after STN-DBS surgery, with a mean five-year postoperative follow-up. Clinical characteristics were age 64(5) y, 8/17 F/M, PD duration 16(5) y, distance from STN-DBS intervention 5(1) y, median (IQR) UPDRS-III 12(12), WHS 5(1), FAC 5(2). Most patients were able to perform the test in all conditions. Both STN-DBS alone and the combination of STN-DBS and medications led to an improvement of clinical motor scores and most iTUG parameters (p<0.001). In particular: 1) the elevation/sitting gestures and the turn phases differently improved in the different conditions; 2) on average, the effect of the DUAL TASK condition led to indices similar to those in the off-off condition 3) data from the DUAL TASK condition suggest the existence of two subgroups of patients, whose performance is either affected or not affected by the cognitive task (Fig. 1). The protocol resulted feasible. Our results indicate that both STN-DBS and levodopa can improve walking ability even in the long-term after surgery. Results during DUAL TASK suggest the use of attentional strategies in the rehabilitation of selected patients, as indicated in the EU physiotherapy guidelines for PD [2]. A rehabilitative intervention should be strongly recommended in those patients whose performance in DUAL TASK becomes so impaired as in the STIM-OFF/MED-OFF, as measured by the iTUG. In conclusion, the iTUG test could be used in PD patients with STN-DBS to support the selection of tailored rehabilitative interventions and to identify patients whose performance is highly affected during cognitive tasks.

•VoA – DBS is effective on both dystonia and tremor.•VoA – DBS benefits are not impaired by tolerance or side effects.•The variable VoA-DBS outcome previously reported were not proven by VTA simulation.•Application of new consensus on tremor classification may improve patient selection.

Takotsubo cardiomyopathy (TTS) is a reversible dysfunction of the left ventricle without coronary disease, probably related to excessive catecholamine release induced by stressful factors in predisposed people. ECG may present with ST segment elevation or T wave inversion.1 Several neurological conditions predispose to TTS, included epilepsy.2 We describe a patient who developed TTS after recurrent seizures. A 78 years old man with parossistic atrial fibrillation and epilepsy symptomatic of previous ischemic stroke was hospitalized for relapsing of repeated partial seizures. In Emergency Room, cerebral CT, blood exams and ECG excluded urgent abnormalities. Three hours after hospitalization the patient appeared sweaty with hypotension (90/50 mmHg). No other symptoms. ECG showed T wave inversion. Echocardiography demonstrated a hypokinesia apex with EF 35% and modest rise of troponin. Coronary angiography showed apical ballooning and vessels unharmed. The patient slowly recovered ventricular dysfunction. This case seems worthy of mention to underline that shared cardiovascular risk factors can account for the relationship between epilepsy and heart disease, in addition to genetics and etiological factors. Therefore, we think that ECG recordings after seizures could be indicated. Timely recognition of this syndrome is important to provide adequate supportive care and prevent complications.

Dystonia is considered a “network” disease with an abnormal cortical plasticity induced by by paired-associated-stimulation. In this study, we applied the PAS-TMS paradigm in healthy subjects, with the aim to collect reliable data from both hemispheres in order to put the basis to future application in focal dystonia. We studied 7 healthy subjects (4 females; mean age 32.33 ± 6.79 years). We applied electrical stimulatrion of median nerve electrical and MEPs from both abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles (2), following Stefan et al. technique, with ISI set to 25 ms. MEPs before and after PAS protocol, evaluating first the dominant and then controlateral motor cortical area. Every subject performed the study in the same experimental session. Comparison between MEPs before and after PAS on homologous hemisphere disclosed a trend toward an increased of amplitude, but without reaching statistical significance for both ABP and FDI muscles, according to Quartarone et al. At the same time, no significant difference was detected by evaluating paired inter-hemisphere analysis. These bilateral findings in normal subjects could be a possible beginning for future application on focal movement disorders.

Peripheral neuropathy (PN) is a significant concern and potential cause of withdrawal in patients with Parkinson's disease (PD) treated with Levodopa/Carbidopa Intestinal Gel (LCIG) infusion. Vitamin B deficiency and/or hyperhomocysteinemia levodopa‐related are considered possible causative factors. In this study, we evaluated PN incidence in LCIG‐PD patients treated since the beginning of infusion with vitamins B supplementation.

Leucine-rich glioma inactivated 1(LGI1) antibodies are frequently associated with a common form of limbic encephalitis (LE) presenting with cognitive impairment, tonic-clonic and distinctive facio-brachial dystonic seizures (FBDS), not related with a specific EEG pattern. We describe clinical-EEG features of three patients with LGl1-LE with different response to immunotherapy. Three pts, admitted to our Neurology department for LE with positive test for LGI1 antibodies, performed video-EEG monitoring and immunotherapy. Video and still images showed frequently (3–40 episodes/day) paroxysmal brief events characterized by facial grimacing and sometimes dystonic arm posturing, with alternating side, suggestive for FBDS. We observed electrodecremental events (EDEs) or a contralateral slow-wave before “dystonic seizures” but not a clear ictal-EEG pattern. In all of the patients interictal EEG was normal. Furthermore, Video-EEG monitoring revealed multiple daily electrographic temporal seizures. Immunotherapy were associated with control of FBDS in two of three presented patients, with different latency. Video-EEG monitoring of our LGI1-LE patients showed frequent FBDS and bilateral temporal seizures. The lack of a clear ictal-EEG pattern for FBDS and the positive response to immunotherapy, support the hypothesis that dystonic episodes does not have a cortical origin, but are rather related to a possible basal ganglionic dysfunction.

To describe a novel ATP7A-related phenotype associating distal motor neuropathy and autonomic dysfunction. Next-generation sequencing analysis of a lower-motor neuron diseases gene panel was performed in two sibs presenting with distal motor neuropathy plus an autonomic dysfunction, which main manifestation was retrograde ejaculation and chronic diarrhea. Probands were subjected to dysmorphological, neurological, biochemical and electrophysiological evaluation including nerve conduction studies, sympathetic skin responses (SSR), cutaneous flowmetry (CF), Quantitative Sensory Testing (QST) and local skin axonal reflexes (AR). We also performed a skin biopsy. A novel pathogenic missense mutation (p.A991D) was identified in the X-linked ATP7A gene, segregating in both brother and inherited from the healthy mother. Biochemical studies showed reduced serum copper and ceruloplasmin. Clinical and neurophysiological evaluation documented large and small fibers neuropathy with severe autonomic involvement. Mutations in the ATP7A gene have been classically associated to the severe infantile neurodegenerative Menkes disease (MD) and the Occipital Horn Syndrome (OHS). In 2010, ATP7A missense mutations were identified in two families with a pure axonal distal motor neuropathy (dHMN-SMAX3). The novel phenotype we describe bridges dHMN to MD-OHS and highlights that the full spectrum of ATP7A-related diseases represents a clinical continuum with no clear-cut genotype-phenotype correlations.

Objectives: Dystonias are movement disorders characterized by sustained muscle contractions and abnormal postures. Twenty-five DYT genetic loci have been described, so far. Clinically, the disorder can occur in isolation or in combination with other neurological signs.

Here we report on a 64-year-old Caucasian man admitted to the Neurology department due to a history of severe hypoacusia, nausea, stipsis, cerebellar ataxia and progressing consciousness impairment, which raised up the clinical suspicion of acute cerebellitis and suggested the introduction of oral corticosteroids. At day 7, a mild improvement of cerebellar symptoms was followed by the onset of orthostatic hypotension, four limb sensory impairment and areflexia. The spinal tap displayed a mild protein increase (78 mg/dl) and high-titer of anti-Hu (ANNA-1) antibodies in CSF. The same antibodies were also found after blood testing. Nerve conduction velocities (NCV) of the four limbs showed a picture of severe peripheral neuropathy with predominant sensory and axonal features, absence of sympathetic skin response. No sensory evoked potentials were detectable either at upper and lower limbs, while cranial district reflexes and NCV were not affected. Autonomic tests confirmed severe orthostatic hypotension with mild parasympathetic involvement. A PET study highlighted a hypercaptation in the right paratracheal region, which a bronchoscopy with transbronchial biopsy identified as a possible lung cancer. Therefore, the patient was diagnosed with dysimmune rhombencephalitis and polyneuropathy in a likely paraneoplastic syndrome.