Roberto Eleopra

Motor neuron disease in the province of Ferrara, Italy, in 1964–1982

We carried out an intensive incidence, prevalence, and mortality survey of motor neuron disease (MND) in the province of Ferrara, northern Italy. Based on 72 patients, the mean incidence per year for the period 1964 through 1982 was 0.98 cases per 100,000. On December 31, 1981, the prevalence rate was 3.95 per 100,000. In the 19-year period the average mortality rate was 0.83 per 100,000 per year. The disease was more common in men, in individuals aged 50 to 70 years, and in residents in rural areas engaged in agricultural work. A retrospective case-control study, confirming a significantly higher frequency of MND in farmers and persons living in rural areas, revealed that the disease was more common in the lower social classes to which most unskilled and heavy laborers belong. In addition, a significantly increased risk for MND was found in patients with previous histories of trauma, but confounding variables may account for this association.

Botulinum neurotoxin serotype C: a novel effective botulinum toxin therapy in human

Botulinum neurotoxin (BoNT) serotype A is commonly used in the treatment of focal dystonia. Nevertheless, some patients are or become resistant to this serotype. Consequently, other different serotypes have to be used. A comparison of the neuromuscular blockade induced by BoNT type A and C in the extensor digitorum brevis muscles of voluntary subjects was studied, by evaluating the amplitude variation over the time (until 90 days) of the compound muscular action potential elicited by supramaximal electrical stimulation of the peroneal nerve at the ankle. A very similar effect and temporal profile, was observed for each serotype. On this basis, two patients with idiopathic facial hemispasm and one with blepharospasm were treated with BoNT serotype C with very beneficial long lasting effects.

Management of Parotid Sialocele With Botulinum Toxin

INTRODUCTION Parotid sialoceles are relatively common as a complication of trauma with penetrating injury to the parotid gland or as a complication after parotidectomy. The management of parotid sialoceles has been unsatisfactory and numerous methods of treatment have been described. A case is presented of a patient who developed a sialocele after a penetrating injury to the parotid area. Initially conservative measures (percutaneous aspiration and pressure dressing) were unsuccessfully applied to manage the sialocele. More aggressive approaches were avoided by injecting botulinum toxin into the parotid gland. The present paper describes this simple and effective sialocele management technique.

Botulinum toxin treatment in the facial muscles of humans: Evidence of an action in untreated near muscles by peripheral local diffusion

In a population of subjects with blepharospasm and facial hemispasm treated for the first time with botulinum toxin type A (BT) in the orbicularis oculi muscle, we performed an electrophysiologic study (compound muscle action potential and motor evoked potential) to assess whether BT effect could be detected in near untreated muscles (orbicularis oris and masseter).There was a significant BT action in nearly untreated muscles with different peripheral innervation that can be explained by local diffusion of the drug. NEUROLOGY 1996;46: 1158-1160

Neurophysiological study of corticomotor pathways in restless legs syndrome.

OBJECTIVE To test the variations in cerebral motor excitability in patients with primary restless legs syndrome (RLS) by using electrophysiological techniques. In RLS patients periodic legs movements (PLMs) in sleep and wake have been described and it is hypothesised that PLMs result from a sleep-related disinhibition of descending central motor inhibitory pathways. Moreover, in primary RLS, these modifications are still debated. METHODS In 15 patients with primary RLS, transcranial magnetic stimulation (TMS) was carried out using several paradigms, particularly paired pulse TMS with short interstimulus intervals (ISI) in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. RESULTS Short ISI paired TMS showed a significant decrease in inhibition and increase in facilitation in ADM muscles. This result was even more evident in TA muscles of patients as compared to the controls and these modifications were more evident in the limbs which were more affected by PLM. Moreover, intracortical (corticocortical) inhibition (ICI) and intracortical facilitation (ICF) unchanged their biphasic time course. CONCLUSIONS In our study the changes in short paired-pulse ICI and ICF revealed the presence of an altered excitability of central motor pathways, with good correlation with asymmetric distribution of symptoms.

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology.

Surgery of insular nonenhancing gliomas: volumetric analysis of tumoral resection, clinical outcome, and survival in a consecutive series of 66 cases.

BACKGROUND Despite intraoperative technical improvements, the insula remains a challenging area for surgery because of its critical relationships with vascular and neurophysiological functional structures. OBJECTIVE To retrospectively investigate the morbidity profile in insular nonenhancing gliomas, with special emphasis on volumetric analysis of tumoral resection. METHODS From 2000 to 2010, 66 patients underwent surgery. All surgical procedures were conducted under cortical-subcortical stimulation and neurophysiological monitoring. Volumetric scan analysis was applied on T2-weighted magnetic resonance images (MRIs) to establish preoperative and postoperative tumoral volume. RESULTS The median preoperative tumor volume was 108 cm. The median extent of resection was 80%. The median follow-up was 4.3 years. An immediate postoperative worsening was detected in 33.4% of cases; a definitive worsening resulted in 6% of cases. Patients with extent of resection of > 90% had an estimated 5-year overall survival rate of 92%, whereas those with extent of resection between 70% and 90% had a 5-year overall survival rate of 82% (P < .001). The difference between preoperative tumoral volumes on T2-weighted MRI and on postcontrast T1-weighted MRI ([T2 - T1] MRI volume) was computed to evaluate the role of the diffusive tumoral growing pattern on overall survival. Patients with preoperative volumetric difference < 30 cm demonstrated a 5-year overall survival rate of 92%, whereas those with a difference of > 30 cm had a 5-year overall survival rate of 57% (P = .02). CONCLUSION With intraoperative cortico-subcortical mapping and neurophysiological monitoring, a major resection is possible with an acceptable risk and a significant result in the follow-up.

Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.

The ϵ‐sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus–dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus–dystonia. To evaluate the relevance of SGCE in myoclonus–dystonia, we sequenced the entire coding region of the ϵ‐sarcoglycan gene in 16 patients with either sporadic or familial myoclonus–dystonia. No mutations were found. This study suggests that ϵ‐sarcoglycan does not play an important role in sporadic myoclonus–dystonia and supports genetic heterogeneity in familial cases.

The role of gustatory flushing in Frey's syndrome and its treatment with botulinum toxin type A

Abstract. After parotid surgery, gustatory sweating and flushing occur more frequently, the former reportedly in 15–100 % of cases, while no reliable data are available for the latter. Although botulinum toxin (BoNT) is effective in controlling sweating, little is known about its effect on flushing. In 17 patients suffering from Freys syndrome after parotid surgery, we studied the gustatory flushing phenomenon as compared to gustatory sweating, analyzing their frequency, area, type of stimulus and response to BoNT administration. Cutaneous blood flow (CBF) was monitored by laser Doppler flowmetry (LDF) on affected and unaffected areas of the cheek in basal conditions and after meals, before and then 1 month after starting the BoNT injections. The Minor test was used to identify the sweating area. Flushing was observed in 7 of 17 patients after masticatory activity, spicy meals or citrus fruits. No clinical data correlated with any presence of flushing. Flushing regressed completely after BoNT administration and CBF reached similar values in the affected and unaffected sites. No adverse effects were observed. BoNT administration proved an effective and safe treatment for gustatory sweating and flushing in patients with Freys syndrome.

Paroxysmal itch caused by gain-of-function Nav1.7 mutation

Summary A novel clinical syndrome is described, characterized by paroxysmal itch and ensuing burning pain triggered by warmth and spicy food associated with a gain‐of‐function Nav1.7 variant. ABSTRACT Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Nav1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co‐segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.