Neurofibromatous neuropathy: An ultrastructural study

Plexiform neurofibroma is pathognomonic of neurofibromatosis 1 (NF1). An NF1-associated peripheral neuropathy has been described in a small minority of NF1 patients but its histopathological features are poorly characterized. We report the case of a 46-year-old woman presenting with bilateral supraclavicular painful masses without other stigmata of NF1. MRI showed bilateral plexiform lesions extending from cervical roots to the elbows. Nerve conduction studies documented a sensory motor polyneuropathy. Morphometric analysis of sural nerve biopsy showed a preferential loss of large-caliber myelinated fibers with a g ratio of 0.515, and the presence of regeneration clusters. By electron microscopy, marked and diffuse endoneurial fibrosis with an altered relationship between Schwann cells (SC) and collagen fibrils was observed. Moreover both myelinating and non-myelinating SC were characterized by the presence of various cell degradation products. These changes suggest that, in neurofibromatous neuropathy, a widespread axonal atrophy and degeneration take place independently on the presence of tumoral infiltration, possibly due to an impairment in SC-axon cross talk. In this case, the coexistence of plexiform neurofibromas with a peripheral neuropathy strongly suggests a diagnosis of NF1 even without fulfillment of clinical criteria. We propose that in the presence of plexiform neurofibromas, electrophysiological studies should be performed also in asymptomatic patients, in order to detect the existence of a subclinical neuropathy

Upper motor neuron involvement in X-linked recessive bulbospinal muscular atrophy

Objective: Clinicopathological findings of X-linked recessive bulbospinal muscular atrophy (SBMA) are indicative of lower motor neuron and primary sensory neuron involvement. The aim of our study was to investigate the presence of subclinical upper motor neuron (UMN) dysfunction in this disease. Methods: Two siblings with clinical presentation, routine electrophysiological tests, histopathological features of muscle and nerve biopsies and genetic testing consistent with diagnosis of SBMA underwent transcranial magnetic stimulation (TMS). The analysed parameters were motor evoked potential (MEP) threshold, silent period (SP) and central motor conduction time. Intracortical inhibition with paired pulses from 1 to 6 ms interstimulus intervals (ISIs) was evaluated in the older brother. Results: MEP parameters were significantly altered in limb and cranial muscles and MEP suppression after paired stimulation significantly reduced in the older brother. MEP abnormalities were present in one lower limb, but SP abolished in all limbs, in the younger brother. Conclusions: Subclinical involvement of UMNs may be present in patients affected by SBMA. This finding suggests that the array of neuronal systems whose function may be affected by the pathogenic process of SBMA is larger than it was considered so far. Significance: TMS is a sensitive diagnostic tool for the identification of UMN dysfunction and should be included in the diagnostic evaluation of patients with SBMA

Validation of the nerve axon reflex for the assessment of small nerve fibre dysfunction

Objective: To validate nerve-axon reflex-related vasodilatation as an objective method to evaluate C-nociceptive fibre function by comparing it with the standard diagnostic criteria. Methods: Neuropathy was evaluated in 41 patients with diabetes (26 men and 15 women) without peripheral vascular disease by assessing the Neuropathy Symptom Score, the Neuropathy Disability Score (NDS), the vibration perception threshold (VPT), the heat detection threshold (HDT), nerve conduction parameters and standard cardiovascular tests. The neurovascular response to 1% acetylcholine (Ach) iontophoresis was measured at the forearm and at both feet by laser flowmetry. An age-matched and sex-matched control group of 10 healthy people was also included. Results: Significant correlations were observed between the neurovascular response at the foot and HDT (rs=-0.658; p<0.0001), NDS (rs=-0.665; p<0.0001), VPT (rs=-0.548; p = 0.0005), tibial nerve conduction velocity (rs = 0.631; p = 0.0002), sural nerve amplitude (r s = 0.581; p = 0.0002) and autonomic function tests. According to the NDS, in patients with diabetes who had mild, moderate or severe neuropathy, a significantly lower neurovascular response was seen at the foot than in patients without neuropathy and controls. A neurovascular response <50% was found to be highly sensitive (90%), with a good specificity (74%), in identifying patients with diabetic neuropathy. Conclusion: Small-fibre dysfunction can be diagnosed reliably with neurovascular response assessment. This response is already reduced in the early stages of peripheral neuropathy, supporting the hypothesis that small-fibre impairment is an early event in the natural history of diabetic neuropathy

Percutaneous tibial nerve stimulation produces effects on brain activity: study on the modifications of the long latency somatosensory evoked potentials

Long-latency somatosensory evoked potentials (LL-SEP) provide information on the function of somatosensory cortical structures. Percutaneous tibial nerve stimulation (PTNS) is indicated in the treatment of lower urinary tract dysfunction. Aim of this study was to evaluate LL-SEP in patients with overactive bladder syndrome (OAB) treated by means of PTNS

Neurofibromatous neuropathy: An ultrastructural study

Neurofibromatosis 1 (NF1) is a common genetic disorder characterized by the presence of neurofibromas arising from the proliferation of Schwann cells (SC) and perineurial cells. At variance with NF2, the incidence of an associated polyneuropathy is very low in NF1, and its histopathological features are poorly characterized. We report the sporadic case of a 46-year-old woman presenting with bilateral subclavicular painful masses. MRI showed bilateral plexiform lesions extending from cervical roots to the elbows; a malignant nature of lesions was ruled out by PET-TC. A biopsy of the larger lesion had histological features of plexiform neurofibroma. Although the patient had no peripheral nerve symptoms, nerve conduction studies documented a sensory-motor polyneuropathy, which was confirmed by sural nerve biopsy. Electron microscopy showed dramatic loss of large and small myelinated, as well as unmyelinated axons together with numerous regeneration clusters. An increased number of fibroblast cell processes and a large amount of collagen fibrils characterized the endoneurium. A combined involvement of myelinating and non-myelinating SC was evidenced by the high frequency of alterations such as: irregularities and degradation figures of myelin, lipofuscin deposition, pseudo-onion bulb structures and collagen pockets substituting unmyelineted axons. These changes suggest that in neurofibromatous neuropathy, a widespread axonal degeneration takes place independently of the presence of tumoral infiltration, possibly due to an impairment in SC-axon cross-talk