Prognostic value of cutaneous reinnervation with GAP-43 in oxaliplatin-induced neuropathy.

Background and purpose: Oxaliplatin-induced neuropathy (OIN) implies axonal damage of both small and large sensory nerve fibers. We aimed at comparing the neurophysiological changes occurred after treatment and the capability to recovery based on histological marker of re-innervation GAP-43. Methods: 48 patients with cancer were assessed before and after chemotherapy (at 3 months and 12 months if available). We recorded ulnar and sural sensory nerve action potentials (SNAP), determined quantitative sensory thresholds for warm and cold (WDT, CDT), pain thresholds and collected a distal biopsy of skin to assess the intra-epidermal nerve fiber density (IENFD) with PGP9.5 and GAP-43 markers (in a subgroup of 19 patients). Results: Increased WDT and CDT as well as diminished IENFD at distal leg were already found in 30% of oncologic patients before treatment. After oxaliplatin, there was a significant increase in thermal thresholds in 52% of patients, and a decrease of SNAP amplitude in the sural nerve in 67% patients. IENFD was reduced in 47% and remained unchanged in 37% after oxiplatin. The density of GAP-43 + fibers and GAP-43/PGP 9.5 ratio was similar before and after treatment showing that cutaneous re-innervation is preserved despite no clinical recovery was observed after one year. Conclusion: Non-selective axonal loss affects sensory fibers in OIN. However, the presence of intra-epidermal regenerative sprouts detected by GAP-43 may reduce the impact of neurotoxicity in the small fibers with long-term sequelae mostly on myelinated nerve endings. Pre-oxaliplatin GAP-43 failed to identify patients with higher risk of damage or worse recovery after treatment

Small fibre function in patients with meralgia paresthetica

Abstract Introduction: Patients with meralgia paresthetica (MP) usually experience not only paraesthesias and decreased tactile sensation, but also painful dysesthesias in the distribution of the lateral femoral cutaneous nerve (LFCN). We aimed at assessing whether there is any functional impairment of small fibres of the LFCN in patients with MP. Methods: We carried out a clinical, psychophysical and neurophysiological study in 14 patients with MP and 14 healthy control subjects. We assessed pain in the last 2 months, thermal thresholds and small fibres conduction by using a visual analogue scale (VAS-pain), quantitative sensory testing (QST) and contact heat-evoked potentials (CHEPs), respectively. Data were grouped for control subjects, non-affected side and affected side of patients with MP. Results: Patients marked a VAS-pain of 4.3 ± 1.5. In the affected side, thresholds for warm and heat pain sensations were elevated and the amplitude of CHEPs was reduced in comparison to the non-affected side and controls (Bonferroni's test; p < 0.001 for all comparisons). The amplitude of CHEPs correlated inversely with duration of the symptoms (r = À0.57, p = 0.002), as well as with heat pain thresholds (r = À0.18, p = 0.01). No significant correlations were found between CHEPs and VAS-pain (p > 0.05 for all correlations). Conclusion: Besides the involvement of large myelinated fibres, partial loss of function in small fibres may also account for the painful symptoms of patients with MP, especially in those with longer disease duration.

Influence of corpus callosum damage on cognition and physical disability in multiple sclerosis: a multimodal study.

Background Corpus 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. Methods Twenty-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. Results The 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). Conclusions We 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

Evidence of neurophysiological improvement of early manifestations of small-fiber dysfunction after liver transplantation in a patient with familial amyloid neuropathy

Introduction: Small fiber polyneuropathy (SFP) is a common heralding clinical manifestation of damage to the nervous system in patients with familial amyloidosis. The diagnosis of SFP is a significant factor in the decision to treat a previously asymptomatic gene carrier, as treatment would prevent irreversible nerve damage. This requires detection of the earliest but unequivocal signs of peripheral nerve involvement. Case report: We present the case of a young female who was diagnosed of SFP, supported by data from quantitative sensory testing. She had preserved sensory nerve action potentials in the distalmost nerves of her feet and recordable nociceptive evoked potentials. She was successfully transplanted the liver from a previously healthy donor, and recovered fully of her symptoms and signs. Improvement was documented with repeated psychophysical and electrodiagnostic testing in the course of 4 years after transplantation. Significance: This case illustrates the utility of psychophysical testing to support the diagnosis of SFP. Keywords: Small fiber polyneuropathy, Familial amyloidosis, Quantitative sensory testing, Nociceptive evoked potentials, Psychophysical testing, Liver transplantatio

Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study

Background Fabry 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). Methods In 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. Results All 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. Conclusion Small 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

Clinical utility of contact heat evoked potentials (CHEPs) in a case of mentalis nerve lesion

Objective: Nociceptive evoked potentials are still infrequently used in electrodiagnostic studies of single patients. We report a case in which the results of contact heat evoked potentials (CHEPs) provided unique information for the diagnosis. Methods: After biopsy for a local cementoma, a 21-year-old woman presented with neuropathic pain in the distribution of her left mentalis nerve. A CT scan showed a well circumscribed lesion near the mentalis nerve groove. We examined brainstem reflexes and evoked potentials conveyed through the mentalis nerve. Results: Blink reflex responses recorded from the orbicularis oculi, jaw jerk and masseteric silent period recorded from the masseter muscles and long latency evoked potentials recorded from Cz to electrical stimulation of the mentalis nerve were all within normal values, with no differences between sides. However, CHEPs, recorded from Cz to thermoalgesic stimulation of the left mentalis area were decreased to approximately 1/3 their size in comparison to stimulation to the unaffected side. Conclusion: While the patient reported symptoms and had neuroimaging signs of mentalis neuropathy, the sole electrophysiological abnormality identified was that of CHEPs, which specifically test small, unmyelinated fibers. Significance: Nociceptive evoked potentials can provide unique information on damage of small nerve fibers in specific cases. Keywords: Contact heat evoked potentials, Facial pain, Brainstem reflexes, Small fiber neuropath