Upper limb motor evoked potentials as outcome measure in progressive multiple sclerosis.

OBJECTIVE: To assess the usefulness of upper limb (UE) motor evoked potential (MEPs) as a marker of motor impairment in a cohort of people with progressive multiple sclerosis (PwPMS). METHODS: we evaluated UE and lower extremities (LE) MEPs, 6-minutes walk-test (6MWT), 10-meter walk-test (10MWT), EDSS, 9-hole peg-test (9HPT), and measures of strength (MRC) and tone (MAS) to the UE and LE in 50 PwPMS (EDSS 4.0-6.5; P ≥ 3, C ≤ 2). RESULTS: Bilateral absence of LE-MEPs, found in 74% of cases, was associated with worse 10MWT and 6MWT. UE-MEPs were rarely absent (8%) but often delayed (74%). Abnormal UE-MEPs were associated with worse performance at 9HPT (25.8 vs 33.2 s). UE-MEPs latency correlated with 10MWT (rho = 0.597), 6MWT (rho = -0.425) and EDSS (rho = 0.296). CONCLUSION: UE-MEPs may represent a clinically relevant outcome measure to quantify corticospinal tract integrity in PwPMS, at least when LE-MEPs cannot provide a measurable response. SIGNIFICANCE: The strive for novel remyelination strategies in MS points to the need for quantitative conduction measurements in addition to clinical outcomes. The frequent absence of MEPs to the lower limbs in PwPMS may greatly limits their usefulness in monitoring progression or response to therapies. With this respect, the upper extremities may represent a better target.

Neuromyelitis optica spectrum disorder and multiple sclerosis in a Sardinian family.

The coexistence of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in the same family is a rare event. We report a familial case originating from Sardinia of two siblings: one with NMOSD and one with MS. Human leukocyte antigen (HLA) typing showed that the two affected siblings were HLA-identical, sharing risk-increasing alleles, while a younger unaffected sister was haploidentical to her siblings but she also carried protective alleles. Our findings confirm the role of HLA in raising the risk to develop CNS inflammatory diseases and provide further knowledge on the relationship between NMOSD and MS.

Predictors of effectiveness of multidisciplinary rehabilitation treatment on motor dysfunction in multiple sclerosis.

OBJECTIVES: To identify clinical predictors of effectiveness of a motor rehabilitation treatment in a cohort of multiple sclerosis (MS) patients. MATERIALS AND METHODS: We analysed 212 consecutive patients who underwent a short-term (3-7 weeks) intensive (two hours per day, five days per week), individualised, goal-oriented inpatient rehabilitation program. Activity limitation and impairment were measured on admission and discharge of the rehabilitation trial using the motor sub-items of the Functional Independence Measure (mFIM) and the Expanded Disability Status Scale (EDSS) score. Multivariate logistic regression models have been tested to evaluate the role of clinical baseline features on rehabilitation effectiveness. RESULTS: According to pre-defined outcome measures, 75.1% of MS patients improved in either activity limitation (≥5 points delta mFIM) or impairment (≥1.0 delta EDSS score if baseline EDSS was ≤5.5, or ≥0.5 if baseline EDSS was >5.5), and 35.4% of MS patients improved in both outcomes. A relapsing-remitting course of disease, a more severe baseline impairment and activity limitation level, a shorter disease duration and a less severe balance dysfunction were predictive of the effectiveness of rehabilitation. DISCUSSION: These data confirm that an intensive inpatient rehabilitation program is able to produce a short-term relevant improvement on clinical and functional outcome measures and suggest some clinical features which can be considered as potential predictors of the outcome of rehabilitative intervention.

Effect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trial.

AIM: This study assessed the efficacy of long-term l-arginine (l-arg) therapy in preventing or delaying type 2 diabetes mellitus. METHODS: A mono-centre, randomized, double-blind, parallel-group, placebo-controlled, phase III trial (l-arg trial) was conducted on 144 individuals affected by impaired glucose tolerance (IGT) and metabolic syndrome (MS). l-Arg/placebo was administered (6.4 g/day) on a background structured lifestyle intervention for 18 months plus a 12-month extended follow-up period after study drug termination. Fasting glucose levels and glucose tolerance after oral glucose tolerance test were evaluated throughout the study. RESULTS: After 18 months, l-arg as compared with placebo did not reduce the cumulative incidence of diabetes [21.4 and 20.8%, respectively, hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.58-1.86] while the cumulative probability to become normal glucose tolerant (NGT) increased (42.4 and 22.1%, respectively, HR, 2.60; 95% CI, 1.51-4.46, p < 0.001). The higher cumulative probability to become of NGT was maintained during the extended period in subjects previously treated with l-arg (HR, 3.21; 95% CI, 1.87-5.51; p < 0.001). At the end of the extended period, the cumulative incidence of diabetes in subjects previously treated with l-arg was reduced as compared with placebo (27.2 and 47.1%, respectively, HR, 0.42; 95% CI, 0.24-0.75, p < 0.05). During both periods, l-arg significantly improved insulin sensitivity and ß-cell function. CONCLUSION: Among persons with IGT and MS, the supplementation of l-arg for 18 months does not significantly reduce the incidence of diabetes but does significantly increase regression to NGT.

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.

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.

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.

Anton's syndrome following callosal disconnection.

Anosognosia for cortical blindness, also called Anton's syndrome, is a rare neurological disorder usually following bilateral lesions to occipital cortices. Neuropsychological, morphological and functional neuroimaging (SPECT and fMRI) findings are reported in a patient who incurred Anton's syndrome after an ischaemic lesion confined to the left occipital lobe involving the corpus callosum. The present case study suggests that Anton's syndrome may also follow from lesions disconnecting the occipital cortices.

Magnetic resonance diffusion-weighted images in Creutzfeldt-Jakob disease: case report.

We describe the diffusion-weighted MRI findings and follow-up in a case of autopsy-proven Creutzfeldt-Jakob disease that revealed abnormal hyperintensity in the cortex and basal ganglia.

Peripheral neuropathy in scleroderma.

Nervous system involvement is rare in progressive systemic sclerosis (PSS). We present a clinical pathological and immunological study of two patients with peripheral sensory motor neuropathy and PSS. In both, the sural nerve biopsies showed axonal degeneration with increased endoneurial connective tissue. There were also clusters of myelinated fibres indicating axonal regeneration. Only mild microangiopathic changes were evident in the endo, peri and epineurial vessels. By Western immunoblots, patients' sera contained a band of reactivity to a protein from peripheral nerve identified as collagen type I. Primary involvement of the peripheral nerves during PSS is very unusual. Abnormal production of collagen tissue and presence of microvascular disease are considered to be two possible causes of neuropathy. We think that our results suggest the important role of the connective tissue proliferation in the pathogenesis of PSS neuropathy.

Lambert-Eaton myasthenic syndrome and polyneuropathy in a patient with epidermoid carcinoma of the lung.

We describe a patient affected by the Lambert-Eaton myasthenic syndrome, sensory motor axonal neuropathy and epidermoid carcinoma of the lung. Serum autoantibodies to voltage-operated calcium channels were detected. After lobectomy, voltage-operated calcium channel-related structures were demonstrated in the patient's tumor. By immunocytochemistry, the patient's IgG reacted with neural structures and particularly with intermediate filaments. We think that these autoantibodies may be implicated in the pathogenesis of the neurological symptomatology.

Early detection of skin and muscular involvement in Lafora disease.

Two 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.

Muscle fibre type and habitual snoring.

Although anatomical abnormalities of the upper airway have been recorded in some patients with obstructive sleep apnoea (OSA), a muscle tone dysregulation also seems to have an important role in this disorder. Since habitual snoring is the initial stage of OSA, the structural characteristics of upper airway muscles (medium pharyngeal constrictor muscle [MPCM]) from 13 men (9 non-snorers and 4 habitual snorers) were studied. MPCM fibre structure in non-snorers was broadly similar to that in normal limb muscles, with the exception that fibre diameters were smaller for all fibre types. Compared with limb muscles, MPCM had a smaller proportion of type IIb fibres and a higher proportion of types I and IIa fibres. MPCM in habitual snorers had an abnormal distribution of fibre types (low percentage of type I and type IIb fibres and high percentage of type IIa fibres) compared with non-snorers (p less than 0.001) and the type IIa fibres were hypertrophic. No myopathic or neurogenic changes were seen. Two possible hypotheses explain the abnormal distribution of fibre types in snorers. First, a constitutionally determined reduction of slow alpha-motor neurons induces an adaptive transformation of type IIb to type IIa fibres and a hypertrophy of type IIa fibres; or, second, motor neurons change their patterns of discharge and, hence, of activation, and modify fibre-type distribution of MPCM as an adaptation to the anatomical characteristic of upper airway and habitual snoring.

Polyneuropathy associated with IgA monoclonal gammopathy: a hypothesis of its pathogenesis.

We describe three patients with chronic progressive polyneuropathy associated with IgA monoclonal gammopathy. Two patients had a prominent sensory neuropathy and one had a prominent motor neuropathy. Sural nerve biopsies showed axonal degeneration in all cases. In immunocytochemical studies patients' IgG immunostained axons. By Western immunoblot a band of IgG reactivity with an axonal protein of 66 kDa was found. No band of IgA and IgM were found. We suggest the possibility that the IgA monoclonal protein may act as a stimulating factor of preexisting B cell clones eliciting an immune reaction against nerve antigens.

Morphological and functional evaluation of peripheral nerve regeneration in the rat using an expanded polytetrafluoroethylene (PTFE) microprosthesis.

The aim of our study was to evaluate in the rat the ability of a polytetrafluoroethylene microprosthesis (PTFE), to guide the peripheral nerve regeneration between the two extremities of a transected sciatic nerve. In 15 adult male Wistar rats, weighing 200 g, a segment of the right sciatic nerve was resected, leaving a gap of about 1 cm, bridged with microprosthesis, using our original microsurgical technique. Neurophysiological evaluations were performed at 6 and 9 months post-operatively to study the distal motor latency either in the right sciatic nerve or in the unoperated control side. In all the rats myoelectrical responses with an increased latency of the operated side were produced from the interosseous muscle of the foot. The animals were sacrificed 9 months post surgery. Histological sections at the level of the graft were done in all the rats, and in 10 animals biopsies of the tibialis anterior muscle (TA) of each side were performed. An active process of axonal regeneration was documented inside the graft, with no infiltration of nerve fibers through the wall of the prosthesis. A connective fibrous reaction was present around the external wall of the graft. Muscle biopsies showed definite signs of muscle reinnervation, with residual features of variable degree of denervation. These findings stress and confirm the ability of the PTFE graft to allow effective regeneration in a peripheral nerve gap in the rat.

Prognostic value of the nervous system involvement in HIV patients.

About 30-40% of AIDS patients present CNS and/or PNS involvement, due to direct action of HIV virus or opportunistic infections. Nervous system involvement in the HIV correlated syndromes is not a rare occurrence; nevertheless no studies about prognosis of AIDS related syndromes have been published yet. We tested 38 HIV positive patients for the assessment of neurological complications by means of clinical and instrumental evaluations: multimodal evoked potentials, EMG/ENG studies, nerve and muscle biopsy. At the baseline evaluation, 26/38 patients had neurological complications: 14 of CNS, 9 of PNS, 3 of both CNS and PNS. At follow-up, 16/37 patients had developed AIDS and 10/16 patients with AIDS died. Of these 16 patients, 14 had clinical and neurophysiological alterations at the baseline evaluation. Our results suggest that the presence of clinical and/or neurophysiological nervous system involvement in patients with HIV-related syndromes constitutes a negative prognostic factor for developing AIDS.

Prevalence of dementia in adult patients with trisomy 21.

Neuropathological lesions characteristic of Alzheimer's disease (AD) are found in all the brains of patients with trisomy 21 who die after age 40 years. However, clinical signs of AD are much less frequent in these patients. Previous studies indicate prevalence figures ranging from 15% to 51% of adult patients. We report here on the prevalence rate of dementia in a population of adult patients with trisomy 21 with mild retardation living at home. For all these patients accurate and reliable anamnestic data could be obtained from parents and caregivers. All underwent neurological examination, cognitive testing, and, if necessary, further bioimaging and neurophysiological studies. Dementia was diagnosed according to clinical NINCDS/ADRDA criteria slightly modified. Dementia was found in 9 of 50 (18%) patients age 20-52 years, but its prevalence increased from 0 in the age group 20-29, to 33% in the age group 30-39, and to 55% in the age group 40-52. All the demented patients had signs of brain atrophy on CT scans and slow EEGs. Dementia is an important problem for patients with trisomy 21 older than age 30 years.