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.

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.

Neurophysiology of the pelvic floor in clinical practice: a systematic literature review.

Neurophysiological testing of the pelvic floor is recognized as an essential tool to identify pathophysiological mechanisms of pelvic floor disorders, support clinical diagnosis, and aid in therapeutic decisions. Nevertheless, the diagnostic value of these tests in specific neurological diseases of the pelvic floor is not completely clarified. Seeking to fill this gap, the members of the Neurophysiology of the Pelvic Floor Study Group of the Italian Clinical Neurophysiology Society performed a systematic review of the literature to gather available evidence for and against the utility of neurophysiological tests. Our findings confirm the utility of some tests in specific clinical conditions [e.g. concentric needle electromyography, evaluation of sacral reflexes and of pudendal somatosensory evoked potentials (pSEPs) in cauda equina and conus medullaris lesions, and evaluation of pSEPs and perineal sympathetic skin response in spinal cord lesions], and support their use in clinical practice. Other tests, particularly those not currently supported by high-level evidence, when employed in individual patients, should be evaluated in the overall clinical context, or otherwise used for research purposes.

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.

Intracortical excitability in patients with relapsing-remitting and secondary progressive multiple sclerosis.

We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing-remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

Acute and chronic effects of ethanol on cortical excitability.

OBJECTIVE: We designed this study to find out whether 5Hz repetitive transcranial magnetic stimulation (rTMS) would disclose changes in cortical plasticity after acute intake of ethanol and in patients with chronic alcohol consumption. METHODS: Ten stimuli-5Hz-rTMS trains were applied over the primary motor cortex in 10 healthy subjects before and after acute ethanol intake and in 13 patients with chronic ethanol abuse, but negative blood ethanol levels when studied. The motor evoked potential (MEP) amplitude and the cortical silent period (CSP) duration during the course of rTMS trains were measured. Short-interval intracortical inhibition (3ms) and intracortical facilitation (10ms) were studied by paired-pulse TMS in 4 healthy subjects and 4 patients. RESULTS: In healthy subjects before and after acute ethanol intake, 5Hz-rTMS produced a significant increase in the MEP size and CSP duration during rTMS. The first CSP in the train was significantly longer after than before ethanol intake. In patients 5Hz-rTMS failed to produce the normal MEP facilitation but left the CSP increase unchanged. CONCLUSIONS: Acute and chronic ethanol intake alters cortical excitability and short-term plasticity of the primary motor cortex as tested by the MEP size facilitation and CSP lengthening after 5Hz-rTMS. SIGNIFICANCE: This finding suggests that rTMS is a valid tool for investigating the effects of ethanol on cortical plasticity in humans.

Excitatory and inhibitory after-effects after repetitive magnetic transcranial stimulation (rTMS) in normal subjects.

We investigated the post-train effects of repetitive transcranial magnetic stimulation (rTMS) on motor evoked potential (MEP) size and cortical silent period (SP) duration. rTMS was delivered over the primary motor cortex in trains of 5, 10, 20, 40 and 60 stimuli in normal subjects at rest and in trains of 5, 10 and 20 stimuli during voluntary muscle contraction. The intensity of stimulation was 120% of resting motor threshold. Test MEPs were delivered at different interstimulus intervals after rTMS ended. At rest, 5 Hz trains produced an increase in the MEP size that persisted after the end of the trains. Trains of 5 stimuli produced after-effects that persisted for 0.5 s, whereas trains of 40 and 60 stimuli produced a facilitation that lasted for several seconds. 5 Hz-rTMS delivered during muscle contraction increased the SP duration during stimulation but the increase persisted for only 1 s after the train ended. The present experiments show that the after-effects of rTMS on MEP amplitude and SP duration have different time-courses. rTMS probably elicits its after-effects on excitatory and inhibitory cortical elements through different physiological mechanisms.

Case report of adult-onset Allgrove syndrome.

Allgrove syndrome is a rare autosomal recessive disorder characterised by childhood onset, alacrima, oesophageal achalasia, adrenocortical insufficiency, neurological and occasionally autonomic involvement. Although the disease has been associated with mutations in the ALADIN gene on chromosome 12q13, it is genetically heterogeneous. The case we report is interesting because of its onset in adulthood, long duration of disease and prominent neurological dysfunctions. After the onset of neurological abnormalities the diagnosis went unrecognised for years until the patient presented for evaluation of dysphagia. The presence of achalasia with dysphagia, adrenal insufficiency, reduced tear production, optic atrophy and peripheral motor-sensory neuropathy with axonal loss led us to clinically diagnose Allgrove syndrome even though a genetic study showed no mutations in the ALADIN gene exons. The case we report shares many clinical features with Allgrove syndrome and, even with the limitations of a single case, underlines the variability in this syndrome and the need for appropriate investigations along with a multidisciplinary approach.

Topiramate and cortical excitability in humans: a study with repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency and suprathreshold intensity progressively increases the size of muscle evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. The aim of this study was to evaluate the effects of topiramate (TPM) at different doses on cortical excitability variables tested with rTMS. We tested the facilitation of the MEP size and CSP duration evoked by focal rTMS in eight patients before and after treatment with TPM at different doses for chronic neuropathic pain. In each patient, rTMS (5 Hz frequency-120% resting motor threshold) was applied at baseline and during the TPM induction phase (drug intake schedule: week I 25 mg/day, week II 50 mg/day, week III 75 mg/day, week IV 100 mg/day) and total TPM plasma concentrations were measured. The effects on the MEP size of 5 Hz-rTMS delivered over repeated sessions were tested in eight control subjects. TPM had no effect on the resting motor threshold. Antiepileptic treatment at increasing doses abolished the normal rTMS-induced MEP facilitation. ANOVA showed that this was a dose-related effect. Accordingly, in patients receiving TPM at higher doses (75 and 100 mg) rTMS failed to elicit the MEP facilitation. TPM left the progressive lengthening of the CSP during the rTMS train unchanged. In control subjects, rTMS applied over repeated sessions elicited a constant increase in MEP size. Our results suggest that TPM modulates the excitatory intracortical interneurons probably by altering rTMS-induced synaptic potentiation. These drug-induced effects are related to TPM doses and plasma concentrations. In conclusion, rTMS may be useful for quantifying the effectiveness of antiepileptic drugs and for assessing individual responses to different drugs but acting through similar mechanisms, thus combining functional neurophysiological information and laboratory data.

Effects of repetitive transcranial magnetic stimulation in a patient with fixation-off sensitivity.

Aim of the present study was to evaluate the acute and long-term effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on focal epileptiform interictal EEG activity in a patient with fixation-off sensitivity and partial epilepsy. Real and sham rTMS were delivered over the vertex. Two trains of 500 stimuli per day were delivered at 0.33 Hz frequency and threshold intensity for five consecutive days. The number of posterior EEG spikes and spike-and-wave complexes/min before and after the application of rTMS were compared in a blinded manner. In our patient, real-rTMS induced a long-lasting decrease in the number of posterior EEG spikes and spike-and-wave complexes/min. Despite the limitations of a single case report, our study confirms that low-frequency rTMS significantly reduces interictal focal epileptic activity over time.

Altered response to rTMS in patients with Alzheimer's disease.

OBJECTIVE: In this study, we tested the excitability of cortical motor areas in patients with Alzheimer's disease. Because repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability, possibly by inducing a short-term increase in synaptic efficacy, we used rTMS to investigate motor cortex excitability in patients with Alzheimer's disease. METHODS: We tested the changes in the size and threshold of motor evoked potential (MEP) and cortical silent period (CSP) duration evoked by focal rTMS delivered in 10 trains of 10 stimuli at 5Hz frequency and 120% rMth intensity in a group of patients with Alzheimer's disease, and age-matched controls. In a further session, rTMS was also delivered at 1Hz frequency (trains of 10 stimuli, 120% rMth). RESULTS: Whereas in control subjects, 5Hz-rTMS elicited normal MEPs that progressively increased in size during the train, in patients, it elicited MEPs that decreased in size. The increase in the duration of the CSP was similar in patients and healthy controls. One hertz rTMS left the MEP amplitude unchanged in patients and healthy controls. CONCLUSIONS: The lack of MEP facilitation reflects an altered response to 5Hz-rTMS in patients with Alzheimer's disease. SIGNIFICANCE: Our rTMS findings strongly suggest an altered cortical plasticity in excitatory circuits within motor cortex in patients with Alzheimer's disease.

Venlafaxine and bladder function.

BACKGROUND: Occasional case reports describe urinary incontinence in patients taking the selective serotonin and norepinephrine reuptake inhibitor antidepressant venlafaxine. OBJECTIVE: In this study the authors investigated the possible effect of venlafaxine on urinary function in a series of 9 patients with urinary retention resulting from spinal cord lesions. They primarily sought to understand whether the reported venlafaxine-induced urinary incontinence was a specific drug-induced effect and, if so, whether venlafaxine might be an effective treatment of urinary retention. METHODS: During a 1-week baseline period, patients measured postvoiding residual volume through a catheter and recorded the number of micturitions within 24 hours. At the end of the baseline period, venlafaxine 75 mg extended-release on a once-daily evening administration schedule was added to their therapy for 1 week. RESULTS: None of the patients reported severe/uncontrollable side effects while taking venlafaxine. Extended-release venlafaxine (75 mg/day) significantly reduced the postvoiding residual volume and increased the micturition rate; the volume diminished on the first day of treatment and remained stable over the ensuing days. CONCLUSION: These findings suggest that venlafaxine could be useful to improve voiding in patients with spinal cord disease.

Synaptic potentiation induced by rTMS: effect of lidocaine infusion.

Repetitive transcranial magnetic stimulation (rTMS) delivered at various intensities and frequencies excites cortical motor areas. Trains of stimuli (at 5-Hz frequency, and suprathreshold intensity) progressively increase the size of motor evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. Because antiepileptic drugs, acting mainly on sodium channels, depress MEP facilitation during rTMS, we suggested that rTMS trains facilitate the MEP size by inducing synaptic potentiation primarily involving voltage-gated sodium channels. The aim of this study was to evaluate the effect of lidocaine-a drug that acts selectively on sodium channels-on the rTMS-induced changes in cortical excitability. We tested the changes in motor threshold, MEP size, CSP duration evoked by focal rTMS and the M-wave amplitude in healthy subjects before and after lidocaine infusion. Lidocaine abolished the normal rTMS-induced facilitation of MEPs but left the other rTMS variables and the M-wave unchanged. Our results suggest that the MEP facilitation related to rTMS-induced synaptic potentiation results from an increase in cortical excitatory interneuron excitability that involves voltage-gated sodium channels.

Abscesos y flemones del cuello: nuestra experiencia / Neck abscesses: our experience

Antecedentes: Los abscesos y flemones de cuello son una patología grave signada por una elevada morbimortalidad. Objetivo: Efectuar un análisis de nuestros casos y sacar conclusiones para disminuir la morbimortalidad merced a tratamiento adecuado de estos pacientes. Diseño: Análisis retrospectivo. Población: 89 pacientes tratados con procesos infecciosos de distinto origen que desarrollaron abscesos y flemones en el cuello. Método: Revisión de datos de historias clínicas. Resultados: De 89 casos, fueron operados con drenaje y desbridamiento de los tejidos del cuello 84 (94,38 por ciento). 12 pacientes tuvieron mediastinitis descendente. La mortalidad de la serie por sepsis grave fue del 6,74 por ciento. Conclusiones: Las infecciones del cuello son una entidad grave. Su complicación más temida es la mediastinitis descendente. Deben ser intervenidos quirúrgicamente en forma urgente, drenando el absceso cervical y cuando es necesario, el mediastino

Abscesos y flemones del cuello: nuestra experiencia / Neck abscesses: our experience

Antecedentes: Los abscesos y flemones de cuello son una patología grave signada por una elevada morbimortalidad. Objetivo: Efectuar un análisis de nuestros casos y sacar conclusiones para disminuir la morbimortalidad merced a tratamiento adecuado de estos pacientes. Diseño: Análisis retrospectivo. Población: 89 pacientes tratados con procesos infecciosos de distinto origen que desarrollaron abscesos y flemones en el cuello. Método: Revisión de datos de historias clínicas. Resultados: De 89 casos, fueron operados con drenaje y desbridamiento de los tejidos del cuello 84 (94,38 por ciento). 12 pacientes tuvieron mediastinitis descendente. La mortalidad de la serie por sepsis grave fue del 6,74 por ciento. Conclusiones: Las infecciones del cuello son una entidad grave. Su complicación más temida es la mediastinitis descendente. Deben ser intervenidos quirúrgicamente en forma urgente, drenando el absceso cervical y cuando es necesario, el mediastino (AU)

Enhanced brain motor activity in patients with MS after a single dose of 3,4-diaminopyridine.

BACKGROUND: 3,4-diaminopyridine (3,4-DAP), a potassium (K+) channel blocker, improves fatigue and motor function in multiple sclerosis (MS). Although it was thought to do so by restoring conduction to demyelinated axons, recent experimental data show that aminopyridines administered at clinical doses potentiate synaptic transmission. OBJECTIVE: To investigate motor cerebral activity with fMRI and transcranial magnetic stimulation (TMS) after a single oral dose of 3,4-DAP in patients with MS. METHODS: Twelve right-handed women (mean +/- SD age 40.9 +/- 9.3 years) underwent fMRI on two separate occasions (under 3,4-DAP and under placebo) during a simple motor task with the right hand. FMRI data were analyzed with SPM99. After fMRI, patients underwent single-pulse TMS to test motor threshold, amplitude, and latency of motor evoked potentials, central conduction time, and the cortical silent period; paired-pulse TMS to investigate intracortical inhibition (ICI) and intracortical facilitation (ICF); and quantitative electromyography during maximal voluntary contraction. RESULTS: FMRI motor-evoked brain activation was greater under 3,4-DAP than under placebo in the ipsilateral sensorimotor cortex and supplementary motor area (p < 0.05). 3,4-DAP decreased ICI and increased ICF; central motor conduction time and muscular fatigability did not change. CONCLUSION: 3,4-DAP may modulate brain motor activity in patients with MS, probably by enhancing excitatory synaptic transmission.

Ovarian hormones and cortical excitability. An rTMS study in humans.

OBJECTIVE: Ovarian steroids influence neural excitability. Using repetitive transcranial magnetic stimulation (rTMS) we investigated changes in cortical excitability during the menstrual cycle. METHODS: Eight women underwent rTMS on Days 1 and 14 of the menstrual cycle. As a control group, 8 age-matched men were also tested twice, with a 14-day interval between the two experimental sessions. Repetitive magnetic pulses were delivered in trains of 10 stimuli (5 Hz frequency and 120% of the motor threshold calculated at rest) to the left motor area of the first dorsal interosseous muscle. RESULTS: In women, the motor evoked potential (MEP) size did not increase on Day 1, but it increased progressively during the train on Day 14. The duration of the silent period progressively lengthened during the train on both days. In men the MEP increased in size, and the silent period lengthened to a similar extent on both days. CONCLUSIONS: In women, hormone changes related to the menstrual cycle alter cortical excitability. SIGNIFICANCE: Low estrogen levels probably reduce cortical excitability because their diminished action on sodium channels reduces recruitment of excitatory interneurons during rTMS thus abolishing the MEP facilitation.

Antiepileptic drugs and cortical excitability: a study with repetitive transcranial stimulation.

Repetitive transcranial magnetic stimulation (rTMS) delivered at various intensities and frequencies excites cortical motor areas. Trains of stimuli (at 5 Hz frequency, and suprathreshold intensity) progressively increase the size of muscle evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. The aim of this study was to evaluate the effect of the antiepileptic drugs carbamazepine, gabapentin, and topiramate on cortical excitability variables tested with rTMS. We tested the changes in motor threshold, MEP size and CSP duration evoked by focal rTMS in 23 patients with neuropathic pain before and after a 1-week course of treatment with carbamazepine, gabapentin, topiramate and placebo. None of the three antiepileptic drugs changed the resting or active magnetic and electrical motor threshold. Antiepileptic treatment, but not placebo, abolished the normal rTMS-induced facilitation of MEPs, but left the progressive lengthening of the CSP during the rTMS train unchanged. Our results suggest that carbamazepine, gabapentin and topiramate modulate intracortical excitability by acting selectively on excitatory interneurons.