We aimed at seeking more precise diagnostic information on the sensory nervous system involvement described in patients with amyotrophic lateral sclerosis (ALS). We investigated large myelinated ...nerve fibers with nerve conduction study and small-nerve fibers with Quantitative Sensory Testing (QST) (assessing thermal-pain perceptive thresholds) and skin biopsy (assessing intraepidermal nerve fiber density) in 24 consecutive patients with ALS, 11 with bulbar-onset and 13 with spinal-onset. In 23 of the 24 patients, regardless of ALS onset, nerve conduction study invariably showed large myelinated fiber sparing. In patients with bulbar-onset ALS, QST found normal thermal-pain perceptive thresholds and skin biopsy disclosed normal intraepidermal nerve fiber density. Conversely, in patients with spinal-onset, thermal-pain thresholds were abnormal and distal intraepidermal nerve fiber density was reduced. Sensory nervous system involvement in ALS differs according to disease onset. Patients with spinal-onset but not those with bulbar-onset ALS have concomitant distal small-fiber neuropathy. Neurologists should therefore seek this ALS-related non-motor feature to improve its diagnosis and treatment.
Introduction Cannabinoids proved to be effective in several experimental neuropathic pain models, and there is increasing evidence for their use in human neuropathic pain conditions. Objectives In ...this study we aimed at testing whether dronabinol inhibits nociceptive transmission in humans. To do so we verified whether dronabinol modulates the nociceptive-mediated laser evoked potentials (LEPS). Methods We conducted a double blind randomized controlled trial in fourteen healthy volunteers. All subjects underwent two separate sessions: one with 5 mg of dronabinol and the other with 1.5 mg of bromazepam as control drug. The two sessions were randomly alternated among subjects. In each session LEPs were recorded from 32 scalp electrodes after hand stimulation. Each session consisted of two recording blocks: before oral administration of dronabinol or bromazepam and 60 min after dronabinol or bromazepam. Results Both the dronabinol and the bromazepam left the LEP latency unchanged. While the dronabinol reduced the N1-, N2-, P2-LEP components ( P < 0.01), bromazepam did not produce any significant changes. Discussion Our findings show that dronabinol inhibits nociceptive transmission, thus suggesting that it might play an important role in the treatment of neuropathic pain.
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.
The activity of motor cortical inhibitory circuits was studied with paired transcranial magnetic stimuli in 16 patients with Parkinson's disease 'off' therapy, five patients 'off' and 'on' therapy, ...and 11 normal subjects. Paired stimuli were delivered at short (3-20 ms) as well as long (100-250 ms) intervals during slight voluntary contraction. The intensity of the conditioning stimulus was subthreshold (80%) at short, and suprathreshold (150%) at long intervals. In addition, the silent period following a single magnetic shock given at 150% of threshold was measured. With short interstimulus intervals, no significant difference between patients and normal subjects could be detected. With long interstimulus intervals, the test response was significantly more inhibited in patients than in normal subjects. Although the cortical silent period was found to be slightly shorter, the recovery of motor evoked potentials was incomplete in patients with Parkinson's disease. This alteration could be partially reverted in dopaminergic therapy. In conclusion, the responsiveness of motor cortices to suprathreshold magnetic stimuli delivered after the end of the silent period is impaired in patients with Parkinson's disease, possibly due to prolonged activity in intracortical inhibitory circuits. The positive effect of L-dopa suggests that dopaminergic modulation of cortical activity, most probably at basal ganglia level, is involved in the pathogenesis of this phenomenon.
Our aim was to investigate whether rapid changes in visual input or prolonged visual deafferentation modify primary motor cortex (M1) excitability in healthy subjects. rTMS, consisting of 10 stimuli ...delivered at 5 Hz, at 120% of resting motor threshold was delivered over M1 in 13 healthy volunteers. They were instructed to relax under eyes-opened (EO) and eyes-closed (EC) resting conditions. Two experimental sessions were performed. In the first session, subjects were tested in both EO and EC conditions in order to see whether short visual deprivation affected the M1 excitability, through the possible changes in the motor evoked potential (MEP) amplitude during the rTMS. In the second session, rTMS was delivered both under EO with room lights on and after 30 min of blindfolding in order to evaluate the effects of prolonged visual deprivation on the M1 excitability. A short-term visual deprivation left the MEP facilitation unchanged during 5 Hz-rTMS trains, whilst 30 min of blindfolding significantly decreased the MEP facilitation. The short-term visual deprivation condition did not significantly influence the M1 excitability, whereas prolonged visual deafferentation decreased rTMS-induced MEP facilitation. Prolonged visual deafferentation can significantly modulate motor cortical synaptic plasticity.
EMG, blink reflex and nerve conduction studies in Bell’s palsy can help to determine the site of nerve injury and the lesion characterization: neurapraxia, axonotmesis and neurotmesis. Aim of this ...study was to determine electrophysiology role in predicting clinical outcome. We recruited 92 patients in a longitudinal prospective study. Three neurophysiological evaluations were performed 10–14 days, 17–21 days and 3 months after palsy onset. Clinical evaluation used the House-Brackmann scale, in a 6 months follow-up period. Reinnervation ( p < 0.05; R = 0.49) and maximum contraction trace measured from orbicularis oculi ( p < 0.05; R = 0.48) and oris ( p < 0.05; R = 0.49) at baseline correlated with HB clinical scale. The presence of denervation at baseline significantly related with HB scale at second evaluation (orbicularis oculi: p < 0.05; R = 0.30; orbicularis oris: p < 0.05; R = 0.29). Combination of blink reflex and ENG demonstrated 2%-increased risk of not reaching the main outcome (HB scale ⩽2) for each additional point of degeneration index in patients who had absence of blink reflex. Regarding synkinesis, at first neurophysiological evaluation only the presence of orbicularis oculi denervation (HR = 3.31, p = 0.041) was associated with a poor prognosis. Baseline ENG/EMG and 17–21 days after palsy onset ENG and blink reflex are related to clinical outcomes in Bell’s palsy.
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.
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.
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.
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.
3,4-DAP may modulate brain motor activity in patients with MS, probably by enhancing excitatory synaptic transmission.
The cortical silent period evoked by magnetic transcranial stimulation and the peripheral silent period were studied in healthy subjects after intravenous injection of diazepam, baclofen or ...thiopental. None of the drugs tested changed the peripheral silent period. But, unexpectedly, diazepam significantly shortened the cortical silent period, the inhibitory effect lasting about 30 min. In experiments using paired transcranial stimuli, the conditioning shock inhibited the test response to a similar extent with and without diazepam. Although baclofen did not change the cortical silent period, it reduced the size of the H reflex in the forearm muscles. Thiopental also left the duration of the cortical silent period unchanged. These findings show that the cortical silent period can be modified pharmacologically. Diazepam possibly shortens the silent period by modulating GABA A receptors at a subcortical site.
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