Italian consensus on treatment of spasticity in multiple sclerosis.

BACKGROUND: Spasticity is a frequent multifactorial manifestation of multiple sclerosis (MS), affecting mostly the chronic courses of the disease. Its impact on patient functioning and quality of life is profound. Treatment of spasticity includes oral and intrathecal anti-spastic drugs, muscle injections with relaxant agents, physical therapy, electrical and magnetic stimulation and peripheral nerve stimulation, alone or in various combinations. METHODS: This Italian consensus on the treatment of spasticity in MS was produced by a large group of Italian MS experts in collaboration with neurophysiologists, experts in the production of guidelines and patients' representatives operating under the umbrella of the Italian Neurological Society, the Associazione Italiana Sclerosi Multipla and the European Charcot Foundation. This guideline was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 11 questions were formulated following the PICO framework (patients, intervention, comparator, outcome). Controlled studies only were included in the analysis. RESULTS: Despite some consistent limitations due to the poor methodological quality of most studies, there was a consensus on a strong recommendation for the use of intrathecal baclofen, oromucosal spray of nabiximols and intramuscular injection of botulinum toxin. The level of recommendation was weak for oral baclofen, tizanidine, gabapentin, benzodiazepines and transcranial magnetic stimulation. CONCLUSIONS: There is a clear need for new larger multicentre well-designed clinical trials with a duration that allows the persistence of the effects and the long-term safety of the interventions to be evaluated.

Involvement of cortico-subcortical circuits in normoacousic chronic tinnitus: A source localization EEG study.

OBJECTIVE: To better characterize brain circuits dysfunctions in normoacousic tinnitus sufferers. METHODS: 17 normoacousic chronic, unilateral high-pitched tinnitus sufferers (6 females, 43.6 ± 9.8 y.o, disease duration 22 ± 35 months) underwent a 29-channel resting-state electroencephalography (EEG - 5 min opened-eyes, 5 min closed-eyes) and auditory oddball paradigm for event-related potentials analyses (ERPs - N1, P2 and P300). Cortical 3D distribution of current source density was computed with sLORETA. Results were compared with 17 controls (9 females, 45.7 ± 15.1 y.o). RESULTS: Eyes opened, tinnitus sufferers had lower alpha and beta sources in the left inferior parietal lobule. Eyes closed, tinnitus sufferers had decreased alpha sources in the left inferior temporal and post-central gyri, and low gamma sources in the left middle temporal gyrus. EEG data did not correlate with tinnitus sufferers' clinical features. Subjects with tinnitus had shorter N1 and P2 latencies. P300 did not differ between groups. sLORETA solutions showed decreased sources of these ERPs in the left inferior temporal gyrus in the tinnitus group. CONCLUSIONS: We showed cortico-thalamo-cortical involvements in normoacousic tinnitus with hyperexcitability of the left auditory cortex and inferior temporal gyrus. SIGNIFICANCE: This might reflect processes of maladaptive cortical plasticity and memory consolidation. Further validation is needed to establish the value of this tool in customizing therapeutic approach.

Treatment of Wernicke's encephalopathy with high dose of thiamine in a patient with pyloric sub-stenosis: description of a case.

Wernicke's encephalopathy (WE) is an acute or subacute syndrome that results from a deficiency in vitamin B1 (thiamine). The syndrome is characterised by a classical triad of symptoms: nystagmus and ophthalmoplegia,mental-status changes, and unsteadiness of stance and gait. When patients with WE are inappropriately treated with low doses of thiamine, mortality rates average out at 20% and Korsakoff's Psychosis develops in about 85% of survivors(Sechi and Serra in Lancet Neurol 6(5):442­455,2007). We report the case of a patient with a pyloric substenosis that developed a WE, and was treated with high doses of thiamine showing after few days of treatment a great improvement of neurological and neuroradiological assessment, even though cognitive impairment was still severe at discharge and at 6 months follow-up.

Event-related desynchronization in reaction time paradigms: a comparison with event-related potentials and corticospinal excitability.

OBJECTIVES: To study cortical activity in different motor tasks, we compared event-related desynchronization (ERD) and event-related potentials (ERPs) in different reaction time (RT) paradigms with the time course of corticospinal excitability. METHODS: Nine right-handed, normal subjects performed right or left thumb extensions in simple, choice and go/no go auditory RT paradigms. Eight subjects had participated in a previous study evaluating changes in corticospinal excitability during the same paradigms. Twenty-nine EEG channels with electrooculogram and bilateral EMG monitoring were collected. ERPs and ERD of 10 and 18-22 Hz bands were obtained with respect to tone administration and EMG onset. RESULTS: Trials with movement showed lateralized ERP components, corresponding to the motor potential (MP), both in the averages on the tone and on EMG. The MP corresponded well in time and location to the rise in corticospinal excitability on the moving side observed in the previous study. Sensorimotor ERD, followed by event-related synchronization (ERS), was present for trials with movements and for the no go. ERD was present contralaterally during movement preparation and in no go trials, while it was bilateral during motor execution. No go ERD was followed more rapidly by ERS than in trials with movement. This finding suggests that in no go trials, there is a brief active process in the sensorimotor areas. ERD and ERS do not correspond, respectively, in time and location to increases and decreases in corticospinal excitability. In fact, ERD is bilateral during movement execution, when corticospinal inhibition of the side at rest is observed. Contralateral no go ERS occurs later than corticospinal inhibition, which is bilateral. CONCLUSIONS: These findings may suggest that ERD is compatible with both corticospinal activation and inhibition, ERS indicating the removal of either, resulting in cortical idling.

Human corticospinal excitability evaluated with transcranial magnetic stimulation during different reaction time paradigms.

The aim of this study was to evaluate corticospinal excitability of both hemispheres during the reaction time (RT) using transcranial magnetic stimulation (TMS). Nine right-handed subjects performed right and left thumb extensions in simple (SRT), choice (CRT) and go/no-go auditory RT paradigms. TMS, inducing motor-evoked potentials (MEPs) simultaneously in the extensor pollicis brevis muscles bilaterally, was applied at different latencies from the tone. For all paradigms, MEP amplitudes on the side of movement increased progressively in the 80-120 ms before EMG onset, while the resting side showed inhibition. The inhibition was significantly more pronounced for right than for left thumb movements. For the left SRT, significant facilitation occurred on the right after EMG onset. Initial bilateral facilitation occurred in SRT trials with slow RT. After no-go tones, bilateral inhibition occurred at a time corresponding to the mean RT to go tones. The timing of the corticospinal rise in excitability on the side of movement was independent of task difficulty and RT. This suggests that corticospinal activation is, to some extent, in series and not in parallel with stimulus processing and response selection. Corticospinal inhibition on the side not to be moved implies that suppression of movement is an active process. This inhibition is more efficient for right- than for left-side movements in right-handed subjects, possibly because of left hemispheric dominance for movement.

Measuring evoked responses in multiple sclerosis.

Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions.