Mauro Comola

Sensorimotor Functional Connectivity Changes in Amyotrophic Lateral Sclerosis

We investigated whether the functional connections to the primary sensorimotor cortex (SMC) at rest are abnormal in 26 patients with amyotrophic lateral sclerosis (ALS) and whether such changes are related to the corticospinal tract (CST) damage, measured using diffusion tensor magnetic resonance imaging (DT MRI). ALS patients versus controls showed a significantly increased functional connectivity between the left SMC and the right cingulate cortex, parahippocampal gyrus, and cerebellum-crus II. No right SMC connectivity changes were found. The pattern of increased functional connectivity to the left SMC was more widespread when considering only patients with no CST DT MRI abnormalities than the whole group of patients. In this patient group, functional connectivity was also increased between the right SMC and the right parahippocampal gyrus. On the contrary, in ALS patients with CST damage (as assessed using DT MRI) versus controls, functional connectivity was increased between the left SMC and the right cingulate cortex only, while it was decreased between the right SMC and the right cerebellum-lobule VI. In ALS patients, disease severity correlated with reduced SMC functional connectivity. Functional brain changes do occur in ALS with mild disability. These changes might have a role in compensating for (limited) structural damage and might exhaust with increasing burden of disease pathology.

Corneal confocal microscopy reveals trigeminal small sensory fiber neuropathy in amyotrophic lateral sclerosis.

Although subclinical involvement of sensory neurons in amyotrophic lateral sclerosis (ALS) has been previously demonstrated, corneal small fiber sensory neuropathy has not been reported to-date. We examined a group of sporadic ALS patients with corneal confocal microscopy, a recently developed imaging technique allowing in vivo observation of corneal small sensory fibers. Corneal confocal microscopy (CCM) examination revealed a reduction of corneal small fiber sensory nerve number and branching in ALS patients. Quantitative analysis demonstrated an increase in tortuosity and reduction in length and fractal dimension of ALS patients’ corneal nerve fibers compared to age-matched controls. Moreover, bulbar function disability scores were significantly related to measures of corneal nerve fibers anatomical damage. Our study demonstrates for the first time a corneal small fiber sensory neuropathy in ALS patients. This finding further suggests a link between sporadic ALS and facial-onset sensory and motor neuronopathy (FOSMN) syndrome, a rare condition characterized by early sensory symptoms (with trigeminal nerve distribution), followed by wasting and weakness of bulbar and upper limb muscles. In addition, the finding supports a model of neurodegeneration in ALS as a focally advancing process.

Mapping early changes of cortical motor output after subcortical stroke: A transcranial magnetic stimulation study

After acute stroke several changes in cortical excitability occur involving affected (AH) and unaffected hemisphere (UH) but whether they contribute to motor recovery is still controversial. We performed transcranial magnetic stimulation mapping of several upper limb muscles over the two hemispheres in thirteen patients at 4-12 days from subcortical stroke and after 1 month. The occurrence of mirror movements (MMs) on the healthy side during contraction of paretic muscles was measured. At baseline, cortical excitability parameters over the AH decreased in comparison with controls, while excitability over the UH increased correlating with severity of motor deficits of the affected arm at baseline as well as with poor recovery. At follow-up, map parameters of the UH became closer to those of controls independently from recovery, while for the AH the number of responsive sites increased significantly. Ipsilateral motor evoked responses (iMEPs) in the affected arm were never elicited. We observed an early impairment in dexterity of the ipsilesional hand that recovered over-time but persistently differed in comparison with controls. MMs occurrence increased at baseline correlating with reduced cortical excitability of the AH as well as with increased map density over the UH. The acute increased excitability of the UH after stroke has a negative prognostic value on recovery and negatively affects motor performance of the ipsilesional hand. Moreover, the absence of iMEPs and the normalization of motor cortical excitability at follow-up indicate that the UH primary motor area does not contribute to recovery.

Recommendations for the management of urinary disorders in multiple sclerosis: a consensus of the Italian Multiple Sclerosis Study Group.

Urinary disorders are uncommon in the initial phases of multiple sclerosis, but increase in frequency as the disease progresses, with a negative impact on quality of life. The goal of this study was to propose a protocol for the diagnosis and treatment of urinary disorders in multiple sclerosis, based on data from the scientific literature and the experience of Italian clinical centres. In particular, the following clinical aspects were considered: what to do with patients with asymptomatic multiple sclerosis; what to do with symptomatic patients; how and when to perform a second-level diagnostic evaluation; and how to treat urinary disorders. A diagnostic–therapeutic algorithm is proposed, that can be applied in Italian clinical centres.

Deep Repetitive Transcranial Magnetic Stimulation With H-coil on Lower Limb Motor Function in Chronic Stroke: A Pilot Study

OBJECTIVES To assess the efficacy of high-frequency (20 Hz) brain stimulation on lower limb motor function in subjects with chronic (> 6 mo) subcortical stroke. DESIGN Double-blind, placebo-controlled crossover study. SETTING University hospital. PARTICIPANTS Right-handed subjects (N=10) affected by a first-ever subcortical stroke in the territory of the middle cerebral artery were included in this study. INTERVENTIONS Repetitive transcranial magnetic stimulation (rTMS) was delivered with the H-coil, specifically designed to target deeper and larger brains regions. Each subject received both real and sham rTMS in a random sequence. The 2 rTMS cycles (real or sham) were composed of 11 sessions each, administered over 3 weeks and separated by a 4-week washout period. MAIN OUTCOME MEASURES Lower limb functions were assessed by the lower limb Fugl-Meyer scale, the 10-m walk test, and the 6-minute walk test before and 1 day after the end of each treatment period, as well as at a 4-week follow-up. RESULTS Real rTMS treatment was associated with a significant improvement in lower limb motor function. This effect persisted over time (follow-up) and was significantly greater than that observed with sham stimulation. A significant increase in walking speed was also found after real rTMS, but this effect did not reach statistical significance in comparison with the sham stimulation. CONCLUSIONS These data demonstrated that 3 weeks of high-frequency deep rTMS could induce long-term improvements in lower limb functions in the chronic poststroke period, lasting at least 1 month after the end of the treatment.

Early detection of skin and muscular involvement in lafora disease

SummaryTwo siblings with Lafora disease (LD) are described: one with epilepsy, myoclonus, EEG abnormalities, severe dementia and many Lafora bodies (LBs) in muscle and skin tissue; the other with myoclonus epilepsy, EEG abnormalities and LBs in muscle and in skin tissue, without dementia. The findings suggest that the diagnosis of LD by skin and muscular biopsy is possible in the early stage of the disease, when there are myoclonic epilepsy and EEG abnormalities, before the onset of dementia.

Cortical activation to voluntary movement in amyotrophic lateral sclerosis is related to corticospinal damage: Electrophysiological evidence

OBJECTIVES The time course of mu and beta sensorimotor rhythms, with event-related desynchronisation (ERD) to preparation and execution of voluntary movement followed by synchronisation (ERS) after movement, is considered to indicate cortical activation and idling, respectively. We investigated ERD and ERS in amyotrophic lateral sclerosis (ALS) patients and the relationship with anatomical and neurophysiological measures of corticospinal tract damage. METHODS Pre-movement mu and beta ERD, and post-movement beta ERS were analysed in 16 ALS patients and 15 healthy controls performing self-paced brisk right thumb extensions. Apparent diffusion coefficient (ADC) of corticospinal tract was measured with magnetic resonance imaging (MRI). Motor-evoked potentials (MEPs) to the right abductor pollicis brevis were obtained using transcranial magnetic stimulation (TMS). RESULTS Movement-related electromyographic activity was similar in the two groups. Post-movement ERS was significantly reduced in ALS group and negatively correlated with the amount of corticospinal damage as from MRI and TMS measures. ERD did not significantly differ between groups. CONCLUSIONS Alterations of cortical activity in ALS patients were limited to the post-movement phase, as indicated by reduced ERS, and could be linked to reduced cortical inhibition rather than to generalised hyperexcitability. SIGNIFICANCE The correlation between ERS and corticospinal damage severity might be interpreted as a functional compensation or dysfunction of inhibitory systems paralleling corticospinal damage.

Peripheral neuropathy associated with mycosis fungoides.

A 56 year old man with acute sensory-motor polyneuropathy associated with mycosis fungoides is described. EMG studies showed diffuse signs of muscle denervation. A skin biopsy specimen showed a lymphocyte infiltration in the dermis, composed of mycosis cells characterised by deep invaginations of the nuclear membrane, and small Pautriers microabscesses in the epidermis. Sural nerve biopsy revealed endoneurial fibrosis, a decreased number of myelinated fibres and acute axonal degeneration.

Churg Strauss syndrome presenting as acute neuropathy resembling Guillain Barré syndrome: case report.

JO N 3035 by rapidly progressive weakness of the lower limbs. She had a two year history of asthma and rhinitis with positive atopic tests for Parietaria and Dermatophagoides pteronyssinus (two of the most important pollen and house dust allergen sources); the year before she underwent surgical treatment for nasal polyposis. General examination was unremarkable, neurological examination revealed bilateral weakness of ankle dorsiflexion [right: Medical Research Council grade (MRC) 4, left: MRC 3], knee jerks were diminished and ankle jerks were absent. Joint position sense was markedly reduced in the feet and ankles (left > right). Lumbosacral MRI was normal. Nerve conduction studies (NCS) were normal in the upper limbs, while the lower limbs showed normal sensory action potentials (SAPs) and reduced amplitude of the left peroneal compound motor action potential (CMAP); F waves could not be elicited from left peroneal and tibial nerves. Cortical and spinal motor evoked potentials (MEPs) recorded from the left foot muscles were absent, while central and peripheral conduction times to the right foot muscles were normal Table 1). A working diagnosis of GBS was made. Intravenous immunoglobulin (IVIG) therapy was started. The next day motor examination revealed paralysis of the left leg distal muscles and marked weakness (MRC: 3) of the right leg distal muscles. Hematochemical investigations revealed: Hemoglobin: 11.1 g/dL, eosinophils 28 %, C-reactive protein: 31.4, absent antineutrophil cytoplasmic antibodies (ANCA). Chest-X-ray and CSF analysis were normal. Retrospective evaluation of nasal polyps histology revealed an eosinophilic infiltrate. A diagnosis of CSS was made, high-dose steroid therapy was started, with subsequent partial improvement of the neurologiNilo Riva Federica Cerri Calogera Butera Stefano Amadio Angelo Quattrini Raffaella Fazio Mauro Comola Giancarlo Comi

Different Frontal Involvement in ALS and PLS Revealed by Stroop Event-Related Potentials and Reaction Times

Background: A growing body of evidence suggests a link between cognitive and pathological changes in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobar degeneration (FTLD). Cognitive deficits have been investigated much less extensively in primary lateral sclerosis (PLS) than in ALS. Objective: To investigate bioelectrical activity to Stroop test, assessing frontal function, in ALS, PLS, and control groups. Methods: Thirty-two non-demented ALS patients, 10 non-demented PLS patients, and 27 healthy subjects were included. Twenty-nine electroencephalography channels with binaural reference were recorded during covert Stroop task performance, involving mental discrimination of the stimuli and not vocal or motor response. Group effects on event-related potentials (ERPs) latency were analyzed using statistical multivariate analysis. Topographic analysis was performed using low-resolution brain electromagnetic tomography (LORETA). Results: Amyotrophic lateral sclerosis patients committed more errors in the execution of the task but they were not slower, whereas PLS patients did not show reduced accuracy, despite a slowing of reaction times (RTs). The main ERP components were delayed in ALS, but not in PLS, compared with controls. Moreover, RTs speed but not ERP latency correlated with clinical scores. ALS had decreased frontotemporal activity in the P2, P3, and N4 time windows compared to controls. Conclusion: These findings suggest a different pattern of psychophysiological involvement in ALS compared with PLS. The former is increasingly recognized to be a multisystems disorder, with a spectrum of executive and behavioral impairments reflecting frontotemporal dysfunction. The latter seems to mainly involve the motor system, with largely spared cognitive functions. Moreover, our results suggest that the covert version of the Stroop task used in the present study, may be useful to assess cognitive state in the very advanced stage of the disease, when other cognitive tasks are not applicable.