Ophthalmoplegia due to Miller Fisher syndrome in a patient with myasthenia gravis

Here, we describe a 79-year-old man, admitted to our unit for worsening diplopia and fatigue, started a few weeks after an episode of bronchitis and flu vaccination. Past medical history includes myasthenia gravis (MG), well-controlled by Pyridostigmine, Azathioprine, and Prednisone. During the first days, the patient developed progressive ocular movement abnormalities up to complete external ophthalmoplegia, severe limb and gait ataxia, and mild dysarthria. Deep tendon reflexes were absent in lower limbs. Since not all the symptoms were explainable with the previous diagnosis of myasthenia gravis, other etiologies were investigated. Brain MRI and cerebrospinal fluid analysis were normal. Electromyography showed a pattern of predominantly sensory multiple radiculoneuritis. Suspecting Miller Fisher syndrome (MFS), the patient was treated with plasmapheresis with subsequent clinical improvement. Antibodies against GQ1b turned out to be positive. MFS is an immune-mediated neuropathy presenting with ophthalmoplegia, ataxia, and areflexia. Even if only a few cases of MFS overlapping with MG have been described so far, the coexistence of two different autoimmune disorders can occur. It is always important to evaluate possible differential diagnosis even in case of known compatible diseases, especially when some clinical features seem atypical

Transcranial direct current stimulation (tDCS) and language

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia

Transcutaneous spinal direct current stimulation

In the past 10\u2009years renewed interest has centered on non-invasive transcutaneous weak direct currents applied over the scalp to modulate cortical excitability ("brain polarization" or transcranial direct current stimulation, tDCS). Extensive literature shows that tDCS induces marked changes in cortical excitability that outlast stimulation. Aiming at developing a new, non-invasive, approach to spinal cord neuromodulation we assessed the after-effects of thoracic transcutaneous spinal DC stimulation (tsDCS) on somatosensory potentials (SEPs) evoked in healthy subjects by posterior tibial nerve (PTN) stimulation. Our findings showed that thoracic anodal tsDCS depresses the cervico-medullary PTN-SEP component (P30) without eliciting adverse effects. tsDCS also modulates post-activation H-reflex dynamics. Later works further confirmed that transcutaneous electric fields modulate spinal cord function. Subsequent studies in our laboratory showed that tsDCS modulates the flexion reflex in the human lower limb. Besides influencing the laser evoked potentials (LEPs), tsDCS increases pain tolerance in healthy subjects. Hence, though the underlying mechanisms remain speculative, tsDCS modulates activity in lemniscal, spinothalamic, and segmental motor systems. Here we review currently available experimental evidence that non-invasive spinal cord stimulation (SCS) influences spinal function in humans and argue that, by focally modulating spinal excitability, tsDCS could provide a novel therapeutic tool complementary to drugs and invasive SCS in managing various pathologic conditions, including pain

Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis

BACKGROUND: The debilitating fatigue that patients with multiple sclerosis (MS) commonly experience during day-to-day living activities responds poorly to current therapeutic options. Direct currents (DC) delivered through the scalp (transcranial DC stimulation or tDCS) at weak intensities induce changes in motor cortical excitability that persist for almost an hour after current offset and depend on current polarity. tDCS successfully modulates cortical excitability in various clinical disorders but no information is available for MS related fatigue. OBJECTIVE: In this study we aimed to assess fatigue symptom after five consecutive sessions of anodal tDCS applied over the motor cortex in patients with MS. METHODS: We enrolled 25 patients with MS all of whom experienced fatigue. We delivered anodal and sham tDCS in random order in two separate experimental sessions at least 1 month apart. The stimulating current was delivered for 15 minutes once a day for 5 consecutive days. In each session the Fatigue Impact Scale (FIS) and the Back Depression Inventory (BDI) were administered before the treatment (baseline), immediately after treatment on day five (T1), one week (T2) and three weeks (T3) after the last tDCS session. RESULTS: All patients tolerated tDCS well without adverse events. The fatigue score significantly decreased after anodal tDCS in 65% of the patients (responders). After patients received tDCS for 5 days their FIS scores improved by about 30% and the tDCS-induced benefits persisted at T2 and T3. CONCLUSION: Our preliminary findings suggest that anodal tDCS applied over the motor cortex, could improve fatigue in most patients with MS. \ua9 2014-IOS Press and the authors. All rights reserved

Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort

Background: GBA variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in GBA carriers are scarce. Objective: To elucidate the impact of GBA variants on long-term DBS outcome in a large Italian cohort. Methods: We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) GBA prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS. Results: We included 365 patients with PD, of whom 73 (20%) carried GBA variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms. At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up. Conclusions: Evaluation of long-term impact of GBA variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up

Estimulação cerebral na promoção da saúde e melhoria do desempenho físico

O avanço tecnológico das últimas décadas tem proporcionado o uso eficaz de técnicas não-invasivas na neuromodulação cerebral. Atualmente, as principais técnicas de neuromodulação são a estimulação magnética transcraniana (EMT) e a estimulação transcraniana por corrente contínua (ETCC). Por meio de revisão da literatura, o presente estudo aborda: a) história da estimulação cerebral; b) mecanismos de ação estudados através da neurofisiologia motora, farmacologia, neuroimagem e animais experimentais; c) perspectivas de aplicações da estimulação cerebral para promoção da saúde e melhoria do desempenho físico, incluindo o controle autonômico cardíaco e hipotensão pós-exercício, o controle de apetite e a modulação da fadiga e desempenho físico; e d) aspectos de segurança referentes ao uso da ETCC. Dessa forma, a ETCC parece ser uma técnica efetiva e segura para modular a função cerebral e podemos vislumbrar algumas perspectivas de aplicação no âmbito da ingestão alimentar, saúde cardiovascular e desempenho físico.The technological advances of the last decades have provided the effective use of noninvasive techniques in neuromodulation with concomitant health benefits. Currently, the main neuromodulation techniques are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Through literature review, this study addresses the a) history of brain stimulation and the b) mechanisms of action studied by motor neurophysiology, pharmacology, neuroimaging, and experimental animals. Moreover, it is presented the c) perspectives for applications of brain stimulation for promoting health and improving physical performance, including cardiac autonomic control and post-exercise hypotension, control and modulation of appetite, fatigue and physical performance. Finally, we describe d) the security aspects related to the use of tDCS. Thus, tDCS seems to be an effective and safe technique to modulate brain function and suggests some application associated to food intake, cardiovascular health and physical performance

Neurostimulation, doping, and the spirit of sport

There is increasing interest in using neuro-stimulation devices to achieve an ergogenic effect in elite athletes. Although the World Anti-Doping Authority (WADA) does not currently prohibit neuro-stimulation techniques, a number of researchers have called on WADA to consider its position on this issue. Focusing on trans-cranial direct current stimulation (tDCS) as a case study of an imminent so-called ‘neuro-doping’ intervention, we argue that the emerging evidence suggests that tDCS may meet WADA’s own criteria (pertaining to safety, performance-enhancing effect, and incompatibility with the ‘spirit of sport’) for a method’s inclusion on its list of prohibited substances and methods. We begin by surveying WADA’s general approach to doping, and highlight important limitations to the current evidence base regarding the performance-enhancing effect of pharmacological doping substances. We then review the current evidence base for the safety and efficacy of tDCS, and argue that despite significant shortcomings, it may be sufficient for WADA to consider prohibiting tDCS, in light of the comparable flaws in the evidence base for pharmacological doping substances. In the second half of the paper, we argue that the question of whether WADA ought to ban tDCS turns significantly on the question of whether it is compatible with the ‘spirit of sport’ criterion. We critique some of the previously published positions on this, and advocate our own sport-specific and application-specific approach. Despite these arguments, we finally conclude by suggesting that tDCS ought to be monitored rather than prohibited due to compelling non-ideal considerations

Alzheimer\u2019s disease: from molecular pathogenesis to innovative therapies

Alzheimer\u2019s disease is the most common neurodegenerative disorder and most prevalent cause of dementia in the elderly. Current standard treatment of Alzheimer\u2019s disease is based on the use of acetylcholinesterase inhibitors, which have shown symptomatic benefits on cognitive, functional and behavioral symptoms of the disease. A growing body of evidence suggests that the accumulation of amyloid \u3b2-peptides may play a pivotal role in the pathogenesis of Alzheimer\u2019s disease (amyloid hypothesis). The incremental progress in elucidating the molecular basis of Alzheimer\u2019s disease is pointing the way towards more targeted and pathogenically specific treatment approaches. This review analyzes the available data on the new directions of Alzheimer\u2019s disease therapy, with particular focus on secretase inhibitors, amyloid \u3b2-peptide vaccination,anti-inflammatory agents, metal chelators and cholesterol-lowering drugs