A case of motor neuron involvement in Gaucher disease.

Gaucher disease (GD) is a genetic disorder characterized by an accumulation of glucosylceramide in cells in the monocyte-macrophage system. We describe a case of a 33-year-old man with a previous diagnosis of type 3 GD who displayed a progressive weakening of the limbs followed by upper motor neuron involvement. A diagnosis of definite Amyotrophic Lateral Sclerosis was made. This is the first reported case of concurrent Gaucher disease and the ALS phenotype in the same patient.

Comparison of high-frequency and ultrahigh-frequency probes in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: High-frequency ultrasound (HFUS 18-20 MHz) performed on patients with chronic inflammatory demyelinating polyneuropathy (CIDP) shows a focal enlargement, particularly in the proximal segments of upper-arm motor nerves. Ultrahigh frequency ultrasound (UHFUS 30-70 MHz), having a higher spatial resolution, enables a better characterization of nerve structures. The aim of this study was to compare the two ultrasound probes in the evaluation of motor nerve characteristics in CIDP patients. METHODS: Eleven patients with definite or probable CIDP underwent an ultrasound evaluation of median and ulnar nerves, bilaterally. Nerve and fascicle cross-sectional area (CSA), vascularization, and echogenicity were assessed. RESULTS: Nerve and fascicle CSA were increased in the proximal segments, especially in the median nerve, in 9/11 patients and in 10/11 patients at the HFUS and UHFUS evaluations, respectively. A statistically significant difference between CSA values obtained with the two probes was found only for fascicle values. UHFUS allowed for a more precise estimation of fascicle size and number than the HFUS. We were able to identify nerve vascularization in 4/11 patients at UHFUS only. CONCLUSION: UHFUS gives more detailed information on the changes in the internal nerve structure in CIDP patients. In particular, it permits to better characterize fascicle size and morphology, and to have a precise estimation of their number. Its frequency range also allows to evaluate nerve vascularization. SIGNIFICANCE: Ultrasound evaluation could become an adjunctive diagnostic tool for CIDP. Further studies are needed to validate the examined parameters as biomarkers for the evaluation and follow-up of CIDP patients.

Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes an impairment in both the upper and lower motor neurons. The recent description of numerous non-motor signs points to an involvement of the neocortex networks that is more complex than was previously believed. Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation, can enhance motor output in the contralateral hand through an NMDA-mediated sensorimotor mechanism. OBJECTIVE: To describe the effects of PAS on ALS patients before and after Riluzole intake compared with healthy subjects. METHODS: PAS was used to detect differences between 24 newly-diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from the abductor pollicis brevis was considered before PAS, immediately after (T0) and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. Statistical significance was calculated using RM-ANOVA. RESULTS: In healthy controls, PAS significantly increased MEP amplitude at T10, T20 and T30 (p < 0.05). In ALS patients, a significant increase in MEP amplitude was also observed after 60 min (p < 0.05), thus demonstrating NMDA-mediated enhanced facilitatory plasticity. After two weeks of riluzole intake, no MEP amplitude increase was evident after PAS at any time point. In three monomelic-onset ALS patients, a long lasting sensorimotor facilitation was evident only in the hemisphere corresponding to the affected side and appeared in the opposite hemisphere when the patients manifested contralateral symptoms. CONCLUSIONS: PAS may be considered a useful tool when investigating NMDA-mediated neocortical networks in ALS patients and the modulation of such networks after anti-glutamatergic drug intake.

Vitamin D in amyotrophic lateral sclerosis.

Vitamin D supplementation has been proposed as a potential treatment to delay amyotrophic lateral sclerosis (ALS) progression. The aims of this study were to compare retrospectively vitamin D blood levels in ALS patients with those in healthy subjects; to correlate vitamin D blood levels with clinical functions in patients; and to evaluate whether administration of vitamin D could modify the clinical progression of the disease. Vitamin D blood levels were evaluated in 57ALS patients and in 57 healthy subjects. In the ALS patients the following clinical variables were evaluated every 3 months: Medical Research Council scale (MRC) score; revised ALS functional rating scale (ALSFRS-R) score; forced vital capacity (FVC). Twentyfour patients were treated with high doses of cholecalciferol. No significant differences were found between the vitamin D blood levels in the ALS patients (18.8 ± 12.2) and the healthy subjects (20.7 ± 10.1). The vitamin D levels in the ALS patientsdid not correlate with recorded clinical parameters. No clinical differences in terms of ALSFRS-R, MRC or FVC were found between the treated and the untreated patients over time. In ALS, as in other chronic neurological diseases, levels of vitamin D in blood appeared reduced, but no difference was found between the levels in ALS patients and in healthy subjects. Oral vitamin D supplementation in ALS patients was not associated with better prognosis in comparison with untreated ALS patients. Further prospective controlled studies are needed to clarify the effect of vitamin D on the progression of ALS disease.

H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy.

BACKGROUND: Painful neuropathy is associated with plasticity changes in the nervous system. Standard repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique used to study changes in cortical excitability and to inhibit pain perception. Deep rTMS is a newer development that allows direct activation of deeper neuronal populations, by a unique coil design termed the H-coil. This study was designed to assess whether deep rTMS applied over the motor cortical lower-limb representation relieves pain in patients with diabetic neuropathy. METHODS: Patients were randomly assigned to receive daily real or sham H-coil rTMS for 5 consecutive days. After a 5-week washout period, they crossed over to the alternative treatment for additional 5 days (according to a crossover study design). Outcome measures were changes in the visual analogue scale (VAS) for pain and in area and threshold of RIII nociceptive flexion reflex (RIII reflex). RESULTS: Of the 25 patients randomized, 23 completed the study. After real rTMS, the VAS scores decreased significantly (p=0.01), and so did RIII reflex area (p<0.01), while no significant effects in these variables were induced by the sham rTMS treatment. The rTMS-induced changes in the outcome measures disappeared about 3 weeks after stimulation. All patients tolerated stimulation well. CONCLUSIONS: Deep H-coil rTMS provides pain relief in patients with diabetic neuropathy. This innovative technique can induce a therapeutic effect on brain areas that otherwise remain difficult to target. rTMS may produce its analgesic effects, inducing motor cortex plasticity and activating descending inhibitory pain control systems.

Dysphagia in amyotrophic lateral sclerosis: prevalence and clinical findings.

OBJECTIVES: To characterize swallowing deficits in amyotrophic lateral sclerosis (ALS); investigate the delay in dysphagia onset; estimate correlations between dysphagia severity and patients' functional status; identify the symptom(s) most likely to predict dysphagia. MATERIALS AND METHODS: A group of 49 consecutive patients with ALS, 14 with bulbar onset and 35 with spinal onset, underwent swallowing evaluation including bedside and fiberoptic endoscopic examination to detect dysphagia. RESULTS: Patients with dysphagia were more likely than those without to have bulbar onset ALS (P = 0.02); more severely impaired chewing (P = 0.01); and tongue muscle deficits (P = 0.001). The only variable measured at first examination significantly associated with dysphagia was a more than mild tongue muscle deficit. The only variable useful in predicting dysphagia was a chewing deficit. In 10 of the 49 patients studied, swallowing evaluation disclosed an impaired cough reflex. CONCLUSIONS: Dysphagia in patients with ALS correlates significantly with bulbar onset and with oral swallowing impairment. Fiberoptic swallowing evaluation is a useful tool for detecting swallowing deficits and laryngeal sensitivity in patients with ALS. An impaired cough reflex is an unexpected finding in many patients with ALS.

Chronic treatment with rivastigmine in patients with Alzheimer's disease: a study on primary motor cortex excitability tested by 5 Hz-repetitive transcranial magnetic stimulation.

OBJECTIVE: To investigate changes in cortical excitability and short-term synaptic plasticity we delivered 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in 11 patients with mild-to-moderate Alzheimer's disease (AD) before and after chronic therapy with rivastigmine. METHODS: Resting motor threshold (RMT), motor evoked potential (MEP), cortical silent period (CSP) after single stimulus and MEP facilitation during rTMS trains were tested three times during treatment. All patients underwent neuropsychological tests before and after receiving rivastigmine. rTMS data in patients were compared with those from age-matched healthy controls. RESULTS: At baseline, RMT was significantly lower in patients than in controls whereas CSP duration and single MEP amplitude were similar in both groups. In patients, rTMS failed to induce the normal MEP facilitation during the trains. Chronic rivastigmine intake significantly increased MEP amplitude after a single stimulus, whereas it left the other neurophysiological variables studied unchanged. No significant correlation was found between patients' neuropsychological test scores and TMS measures. CONCLUSIONS: Chronic treatment with rivastigmine has no influence on altered cortical excitability and short-term synaptic plasticity as tested by 5 Hz-rTMS. SIGNIFICANCE: The limited clinical benefits related to cholinesterase inhibitor therapy in patients with AD depend on factors other than improved plasticity within the cortical glutamatergic circuits.

Transcutaneous spinal direct current stimulation inhibits nociceptive spinal pathway conduction and increases pain tolerance in humans.

Despite concerted efforts from pharmacologic research into neuropathic pain, many patients fail to achieve sufficient pain relief with medication alone. For this reason, increasing interest centres on neurostimulation techniques. We assessed whether transcutaneous spinal direct current stimulation (tsDCS) modulates conduction in ascending nociceptive spinal pathways. We measured changes induced by anodal and cathodal tsDCS over the thoracic spinal cord on face- and foot-laser evoked potentials (LEPs) and foot-cold pressor test responses in 20 healthy subjects. Whereas anodal tsDCS reduced the amplitude of the N1 and N2 components of foot-LEPs (P<0.05) neither anodal nor cathodal tsDCS changed LEPs evoked by face stimulation. Pain tolerance to the cold pressor test was significantly higher after anodal than after cathodal tsDCS (P<0.05). Conversely, no difference was found in the pain threshold or pain ratings to the cold pressor test between the two polarity conditions. Our data suggest that anodal tsDCS over the thoracic spinal cord might impair conduction in the ascending nociceptive spinal pathways, thus modulating LEPs and increasing pain tolerance in healthy subjects.