differences in motor unit loss and axonal regeneration rate between sporadic and familiar amyotrophic lateral sclerosis an undervalued field of research

Amyotrophic Lateral Sclerosis (ALS) is a clinically and genetically heterogeneous, late-onset, neurodegenerative disorder of the motor system [1]. Five to ten percent of cases are familial and about 20% of these cases have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. Since its discovery, mutations in Cu/Zn superoxide dismutase (SOD-1) have stimulated a huge amount of interest [2], but the pathogenic mechanisms underlying disease's induction in familiar cases are still elusive. The most accepted hypothesis is that familiar ALS, SOD-1 positive could be caused by a neuronal damage, due to a gradual accumulation of a toxic product SOD-1 this cumulative damage leads to a disruption of the cytoskeleton and organelle trafficking within motor neuron dendrites. Aggregates do not exclusively occur in neurons, but also in glial cells, raising the question of whether mutant SOD-1 expression in neurons is sufficient per se to induce pyramidal degeneration and sustain disease evolution over time [3]. The familial form is clinically indistinguishable from the sporadic one and to date only few studies have tried to highlight electromyographic differences between sporadic and familiar ALS forms

Cerebellar Transcranial Direct Current Stimulation (ctDCS) Effect in Perception and Modulation of Pain

Transcranial direct stimulation (tDCS) in the treatment of intractable or marginally tractable pain is experiencing an increasing diffusion in many fields worldwide. Recently, new modality of tDCS application has been proposed and applied, as cerebellar transcranial direct current stimulation (ctDCS). Indeed, the cerebellum has been proved to play a role in pain processing and to be involved in a wide number of integrative functions. In this chapter, we encompass the history of the technique, analysis of principles, a general description, including the methodological procedures of ctDCS; then, main clinical applications and their main effects in perceptive threshold of pain and other sensation, pain intensity, and laser evoked potentials (LEPs) changes

Unilateral Application of Cathodal tDCS Reduces Transcallosal Inhibition and Improves Visual Acuity in Amblyopic Patients

Objective: Amblyopia is a neurodevelopmental disorder characterized by visual acuity and contrast sensitivity loss, refractory to pharmacological and optical treatments in adulthood. In animals, the corpus callosum (CC) contributes to suppression of visual responses of the amblyopic eye. To investigate the role of interhemispheric pathways in amblyopic patients, we studied the response of the visual cortex to transcranial Direct Current Stimulation (tDCS) applied over the primary visual area (V1) contralateral to the "lazy eye." Methods: Visual acuity (logMAR) was assessed before (T0), immediately after (T1) and 60' following the application of cathodal tDCS (2.0 mA, 20') in 12 amblyopic patients. At each time point, Visual Evoked Potentials (VEPs) triggered by grating stimuli of different contrasts (K90%, K20%) were recorded in both hemispheres and compared to those obtained in healthy volunteers. Results: Cathodal tDCS improved visual acuity respect to baseline (p < 0.0001), whereas sham polarization had no significant effect. At T1, tDCS induced an inhibitory effect on VEPs amplitudes at all contrasts in the targeted side and a facilitation of responses in the hemisphere ipsilateral to the amblyopic eye; compared with controls, the facilitation persisted at T2 for high contrasts (K90%; Holm-Sidak post hoc method, p < 0.001), while the stimulated hemisphere recovered more quickly from inhibition (Holm-Sidak post hoc method, p < 0.001). Conclusions: tDCS is a promising treatment for amblyopia in adults. The rapid recovery of excitability and the concurrent transcallosal disinhibition following perturbation of cortical activity may support a critical role of interhemispheric balance in the pathophysiology of amblyopia

Transcutaneous Spinal Direct Current Stimulation (tsDCS) Modulates Human Corticospinal System Excitability

This study aimed to assess the effects of thoracic anodal and cathodal transcutaneous spinal direct current stimulation (tsDCS) on upper- and lower-limb corticospinal excitability. Yet, despite studies assessing thoracic tsDCS influences the spinal ascending tract and reflexes, none assessed the effects of this technique over upper- and lower-limb corticomotorneuronal connections. In 14 healthy subjects we recorded motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and hand abductor digiti minimi (ADM) muscles before (baseline, B), and at a different time-points (0 and 30 minutes) after anodal or cathodal tsDCS (2.5 mA, 20 minutes, T9-T11 level). In 8 of the 14 subjects we also tested the soleus H-reflex, the F-waves from AH and ADM before and after tsDCS. Both anodal and cathodal tsDCS left the upper-limb MEPs and F-wave unchanged. Conversely, while leaving lower-limb H-reflex unchanged, they oppositely affected lower-limb MEPs: whereas anodal tsDCS increased resting motor threshold (mean\ub1SEM 107.33 \ub1 3.3%, increase immediately after tsDCS, and 108.37 \ub1 3.2% increase 30 min after tsDCS compared to baseline), and had no effects on MEP area and latency, cathodal tsDCS increased MEP area (139.71 \ub1 12.9% increase immediately after tsDCS and 132.74 \ub122.0% increase 30 min after tsDCS compared to baseline) without affecting resting motor threshold and MEP latency. Our results show that tsDCS induces polarity specific changes in corticospinal excitability that last for more than 30 min after tsDCS offset and selectively affect responses in lower-limb muscles innervated by lumbar and sacral motorneurons

Epilepsy and phenylketonuria: a case description and EEG-fMRI findings.

Phenylketonuria (PKU) is characterized by phenylalanine accumulation due to phenylalanine hydroxylase deficiency. Up to 50% of PKU patients experience seizures. We evaluated an adult PKU patient who suffered from absences and primarily generalized tonicclonic seizures, associated with generalized spikeand-wave discharges (GSWs) on EEG. An analysis of blood oxygenation level-dependent (BOLD) signal changes during interictal epileptiform discharges showed early activation of the left perirolandic cortex followed by a BOLD signal decrease within cortical regions belonging to the default mode network and left frontoparietal cortex. Moreover, deactivation of the head of the right caudate nucleus and the left thalamus was observed. The fMRI pattern observed in our patient during GSWs is similar but not identical to that observed in idiopathic generalized epilepsy, suggesting different neurophysiological mechanisms. This is the first description of BOLD-fMRI patterns in a PKU patient with epilepsy. Similar studies in more patients might help to uncover the pathophysiology of seizures in this disease

Iatrogenic Rhabdomyolisis and Guillain-Barre’ Syndrome: a Dangerous Association.

Guillan-Barré Syndrome (GBS) is an acute, symmetrical polyneuropathy with a clinical manifestation of flaccid paralysis with areflexia and variable sensory disturbance. GBS has an incidence of 1-2 cases/100.000 inhabitants for year. The pathological spectrum of GBS includes Acute Inflammatory Demyelinating Polyneuropathy (AIDP), Acute Motor Axonal Neuropathy (AMAN) and Acute Motor Sensory Axonal Neuropathy (AMSAN). We report a case of an 81-year-old man with GBS (subtype AMSAN), secondary to a previous Micoplasma Pneumoniae infection, who presented with an elevation of Creatin Kinase (CK) serum levels, and worsened by a co-administration of statins and clarithromycin. By our knowledge there are few cases in the literature in which the association of these drugs contributed to worsening GBS

Defective chromatic and achromatic visual pathways in developmental dyslexia: Cues for an integrated intervention programme.

Abstract PURPOSE: As well as obtaining confirmation of the magnocellular system involvement in Developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system. METHODS: Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects. RESULTS: Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD. CONCLUSION: These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams

Differential Motor Neuron Impairment and Axonal Regeneration in Sporadic and Familiar Amyotrophic Lateral Sclerosis with SOD-1 Mutations: Lessons from Neurophysiology

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O−2) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS patients (34 males; 26 females) were enrolled in the study and examined basally (T0) and every 4 months (T1, T2, and T3). Fifteen of these patients are SOD-1 symptomatic mutation carriers (nine males, six females). We used Macro-EMG and Motor Unit Number Estimation (MUNE) in order to evaluate the neuronal loss and the re-innervation process at the onset of disease and during follow-up period. Results and Discussion: SOD-1 mutation carriers have a higher number of motor units at the moment of diagnosis when compared with the sporadic form, despite a more dramatic drop in later stages. Moreover, in familiar SOD-1 ALS there is not a specific time interval in which the axonal regeneration can balance the neuronal damage. Taken together, these results strengthen the idea of a different pathogenetic mechanism at the base of sALS and fALS