Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.

Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles provided the highest rates of REM sleep phasic EMG activity in subjects with RBD.

BackgroundCorpus callosum (CC) is a common target for multiple sclerosis (MS) pathology. We investigated the influence of CC damage on physical disability and cognitive dysfunction using a multimodal approach.MethodsTwenty-one relapsing-remitting MS patients and 13 healthy controls underwent structural MRI and diffusion tensor of the CC (fractional anisotropy; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity). Interhemisferic transfer of motor inhibition was assessed by recording the ipsilateral silent period (iSP) to transcranial magnetic stimulation. We evaluated cognitive function using the Brief Repeatable Battery and physical disability using the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC) z-score.ResultsThe iSP latency correlated with physical disability scores (r ranged from 0.596 to 0.657, P values from 0.004 to 0.001), and with results of visual memory (r = −0.645, P = 0.002), processing speed (r = −0.51, P = 0.018) and executive cognitive domain tests (r = −0.452, P = 0.039). The area of the rostrum correlated with the EDSS (r = −0.442, P = 0.045). MD and RD correlated with cognitive performance, mainly with results of visual and verbal memory tests (r ranged from −0.446 to −0.546, P values from 0.048 to 0.011). The iSP latency correlated with CC area (r = −0.345, P = 0.049), volume (r = −0.401, P = 0.002), MD (r = 0.404, P = 0.002) and RD (r = 0.415, P = 0.016).ConclusionsWe found evidence for structural and microstructural CC abnormalities associated with impairment of motor callosal inhibitory conduction in MS. CC damage may contribute to cognitive dysfunction and in less extent to physical disability likely through a disconnection mechanism.

This study analyzed the relationship between the density of intraepidermal nerve fibers (IENF) and the characteristics of either nociceptive laser-evoked potentials (LEPs) or contact heat-evoked potentials (CHEPs) in patients with painful sensory polyneuropathy with the aim to determine which parameters of LEPs and CHEPs more reliably reflect IENF loss. A total of 96 patients and 35 healthy volunteers took part in the study. Based on clinical examination, nerve conduction tests, and quantitative sensory testing, we identified 52 patients with small-fiber neuropathy (SFN), 40 with mixed (small-fiber and large-fiber) neuropathy (MFN), and 4 who were excluded from the analysis because of no evidence of involvement of small fibers. The latency of the N2 was delayed for both LEPs and CHEPs in patients with MFN and for CHEPs only in patients with SFN. The amplitude of the vertex N2/P2 potential was similarly reduced in both types of neuropathy, but LEPs were more frequently absent than CHEPs in MFN patients (68% vs 40%). In general, latency and amplitude of LEPs and CHEPs were well correlated with IENF density. SFN patients were characterized by abnormal EPs and slightly decreased but morphologically abnormal IENF. MFN patients were characterized by frequently absent LEPs and CHEPs and a rather severe IENF loss. The correlation between nociceptive evoked potentials (laser-evoked potentials and contact heat-evoked potentials) and skin biopsy aids in the diagnosis of painful neuropathies.

Excessive tonic and phasic EMG activity during REM sleep increases over time in subjects with idiopathic RBD. This finding suggests that, in subjects with idiopathic RBD, there is an underlying progressive pathologic process damaging the brainstem structures that modulate REM sleep.

BackgroundFabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP).MethodsIn this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function.ResultsAll Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients.ConclusionSmall fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.

Cold allodynia is a common sign of neuropathic pain patients but its underlying mechanisms are still largely unknown, partly because the populations of neurons responding to cold stimuli and their transduction mechanisms have not been fully determined. We report a patient with a small-fiber neuropathy of unknown origin, whose main complaint is cold allodynia. Microneurographic recordings showed ongoing spontaneous activity and abnormal responses to cold and menthol in identified subtypes of C-nociceptors. These findings provide the first direct evidence in human of abnormal peripheral nociceptor behavior potentially responsible for cold allodynia. The responsiveness of C-nociceptors to menthol suggests an abnormal expression or function of TRPM8 channels in this patient with a small-fiber polyneuropathy.

We provided a reliable method to quantify the innervation density of dermal nerves that might improve the diagnostic yield of skin biopsy.