Efficacy of levetiracetam on upper limb movement in multiple sclerosis patients with cerebellar signs: a multicenter double-blind, placebo-controlled, crossover study.

BACKGROUND AND PURPOSE: The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients. METHODS: In this multicenter double-blind placebo-controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2-week wash-out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine-hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self-defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration. RESULTS: Forty-eight subjects (45.2 ± 10.4 years) were randomly allocated into two groups (n = 24 each). 9HPT significantly improved in the LEV phase in both groups (P < 0.001). The LEV treatment phase led to a significant improvement (P < 0.01) of all clinical outcomes in group 1 and in dexterity in group 2. No significant changes were reported during both placebo phases in the two groups. Considering the kinematic analysis, only normalized jerk significantly improved after treatment with LEV (T0-T1) in group 1. CONCLUSIONS: Levetiracetam treatment seems to be effective in improving upper limb dexterity in MS patients with cerebellar signs.

Dysphagia in neurological diseases: a literature review.

Dysphagia is defined as an impairment of this complex and integrated sensorimotor system. It is estimated that 400,000 to 800,000 individuals worldwide develop neurogenic dysphagia per year. Neurogenic dysphagia is typically occurring in patients with neurological disease of different etiologies. A correct and early diagnosis and an appropriate management of dysphagia could be useful for improving patient's quality of life and may help to prevent or delay death. In the present review, we discuss thoroughly the anatomy and physiology of swallowing and also the pathophysiological mechanisms involved in impaired swallowing, as well as the diagnosis, management, and potential treatments of neurogenic dysphagia. Assessment of neurogenic dysphagia includes medical history, physical exam, and instrumental examinations (fiberoptic endoscopic evaluation of swallowing, videofluoroscopic swallowing study, electromyography). Pharmacological treatment of these problems includes oral anticholinergic drugs. Surgical myotomy of the cricopharyngeal muscle showed an important improvement of oropharyngeal dysphagia associated to upper esophageal sphincter hyperactivity. Chemical myotomy of the upper esophageal sphincter by local injections of botulinum toxin type A into the cricopharyngeal muscle has been proposed as an alternative less invasive and less unsafe than surgical myotomy.

Cerebral venous thrombosis at high altitude: A systematic review.

BACKGROUND AND OBJECTIVE: High altitude may be a factor associated with cerebral venous thrombosis (CVT). As our knowledge of CVT at high altitude is limited, it was decided to pool such information from the available case studies to determine whether high altitude can predispose to CVT. METHODS: A systematic review of the literature was performed for cases reporting CVT at high altitude. Searches of the PubMed database (up to July 2016) were performed for publications, using 'cerebral venous thrombosis' and 'high altitude' as keywords. Cross-referencing was also done to complete the search. RESULTS: Ultimately, 13 articles were included in our systematic review. The population consisted of 17 patients, predominately male (14/17), with a mean age of 32 (range: 19-47) years. Altitude range was 3000-8200m. Nine patients stayed at high altitude for>2 weeks; the duration of high altitude stay was unknown for the remainder. A hypercoagulable state was found in nine patients: secondary polycythemia in five; protein C deficiency in one; protein S deficiency in one; and factor V Leiden mutations in two. No comorbidities were found in any of these patients. CONCLUSION: Long-term stays at high altitude in association with a hypercoagulable state - in particular, congenital or acquired thrombophilia - appears to predispose to CVT. The association of CVT with a single exposure to high altitude seems low, but the risk cannot as yet be specifically estimated.

Proposal of model for personalized early adapted cancer screening in people living with HIV: experience of "Gaetano Martino" Hospital University of Messina.

Human immunodeficiency virus (HIV) infection has historically been related to the development of specific cancers, some of which are so closely linked to the infection, such as Kaposi's Sarcoma (KS), that they have earned the name Acquired Immuno-Deficiency Syndrome (AIDS)-defining cancers (ADCs). While the development of antiretroviral therapy (ART) has decreased the incidence of AIDS-defining cancers, the resulting aging of people living with HIV (PLWH) highlighted an increased occurrence of other forms of cancer. At the "Gaetano Martino" hospital in Messina, we developed a multidisciplinary approach by creating a bridge between the Oncology Unit and the Infectious Diseases Unit to carry out screening and a more rapid diagnostic and therapeutic journey for cancers in PLWH. The goal is to improve the diagnosis of various types of cancer by involving other professionals, such as gastroenterologists and gynecologists, to ensure faster access to treatment and, therefore, a greater chance of survival. In addition, our multidisciplinary approach has also included vaccine screening, offered by the "Gaetano Martino" hospital and useful for preventing the development of specific forms of cancer in the entire population and particularly in PLWH.

Single-fiber electromyography in hyperCKemia: the value of fiber density.

Although persistently raised serum creatine kinase (sCK), or hyperCKemia, is considered the biological hallmark of neuromuscular diseases, pauci- or asymptomatic- or isolated-hyperCKemia can often be found. Single-fiber electromyography (SFEMG) is an electrophysiological technique of great value in the assessment of neuromuscular, neuropathic and myopathic disorders. We hypothesize that SFEMG fiber density (FD) evaluation is able to detect subclinical electrophysiological abnormalities indicating a myopathic process in subjects with hyperCKemia. Nineteen subjects with hyperCKemia without evident clinical signs of muscle involvement and 15 healthy controls were studied. Electrophysiological investigations including nerve conduction studies (NCS), quantitative EMG (QEMG), SFEMG with focus on FD measurements, and muscle biopsy were performed. NCS, QEMG, SFEMG were normal in all controls. In subjects with hyperCKemia, NCS were normal; QEMG was abnormal in 5, while both SFEMG and muscle biopsy disclosed abnormalities in 12 subjects. The mean FD value was 2.6 ± 0.5 in the control and 4 ± 1.4 (p = 0.003) in the hyperCKemia group. SFEMG revealed subclinical changes in the majority of subjects with hyperCKemia. To the best of our knowledge, this is the first study demonstrating that SFEMG FD evaluation is able to detect the presence of muscle diseases, which are in a subclinical phase and would remain unidentified otherwise. SFEMG may be used to distinguish hyperCKemia associated to asymptomatic muscle disorders from idiopathic hyperCKemia. We believe that SFEMG FD evaluation should be added to the routine examinations in the screening of idiopathic hyperCKemia.

Botulinum toxin improves dysphagia associated with multiple sclerosis.

OBJECTIVE: To evaluate the efficacy of botulinum neurotoxin type A (BoNT/A) for severe oro-pharyngeal dysphagia associated with multiple sclerosis (MS). PATIENTS AND METHODS: BoNT/A was injected percutaneously into the hyperactive cricopharyngeal muscle of 14 dysphagic MS patients under electromyographic control. Patients were evaluated by videofluoroscopic and electromyographic examinations and by the Penetration/Aspiration Scale (PAS), at week 1, 4, 12, 16, 18, and 24 after BoNT/A injection. RESULTS: All patients showed a significant improvement in all the swallowing outcome measures. CONCLUSION: No specific treatment for oro-pharyngeal dysphagia related to MS has been described to date. Our preliminary findings suggest a potential benefit from BoNT/A treatment in MS patients with dysphagia associated with upper esophageal sphincter hyperactivity.

Validation of the DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis.

Swallowing problems can complicate the course of multiple sclerosis (MS). However, no validated questionnaire for the assessment of dysphagia in MS is currently available. We previously developed a 10-item DYsphagia in Multiple Sclerosis questionnaire (DYMUS). In the present study, this questionnaire was submitted to a validation process. Thirteen Italian MS centres took part in this research in which DYMUS was administered to 1734 consecutive MS patients during routine checkups outside relapse. The questionnaire showed very good internal consistency (Cronbach's alpha = 0.914). It was then subdivided into two subscales, both of which also showed very good internal consistency: Cronbach's alpha was 0.885 for the 'dysphagia for solids' subscale and 0.864 for the 'dysphagia for liquids' subscale. The DYMUS questionnaire was found to be an easy and reliable tool for detecting dysphagia and also for the preliminary selection of patients requiring more specific instrumental analyses, and those suitable for aspiration prevention programmes.

The DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis.

Swallowing problems can be relevant, even if underestimated, in Multiple Sclerosis (MS) patients. However, no specific questionnaire for the assessment of dysphagia in MS is available. We built a questionnaire (DYsphagia in MUltiple Sclerosis, DYMUS) that was administered to 226 consecutive MS patients (168 F, 58 M, mean age 40.5 years, mean disease duration 10.1 years, mean EDSS 3.1) during control visits in four Italian MS Centres. DYMUS was abnormal in 80 cases (35%). The patients who claimed to have swallowing problems had a significantly higher mean DYMUS score that the other patients (p<0.0001). Mean DYMUS scores were significantly higher in the progressive forms (p=0.003). DYMUS values were significantly correlated to EDSS (p=0.0007). DYMUS showed a very good internal consistency (Cronbach's alpha 0.877). Factor analysis allowed us to sub-divide DYMUS in two sub-scales, 'dysphagia for solid' and 'dysphagia for liquid', both of them had a very good internal consistency (Cronbach's alpha 0.852 and 0.870 respectively). DYMUS demonstrated to be an easy and consistent tool to detect dysphagia and its main characteristics in MS. It can be used for preliminary selection of patients to submit to more specific instrumental analyses, and to direct toward programs for prevention of aspiration.

Botulinum toxin therapy: functional silencing of salivary disorders.

Botulinum toxin (BTX) is a neurotoxic protein produced by Clostridium botulinum, an anaerobic bacterium. BTX therapy is a safe and effective treatment when used for functional silencing of the salivary glands in disorders such as sialoceles and salivary fistulae that may have a post-traumatic or post-operative origin. BTX injections can be considered in sialoceles and salivary fistulae after the failure of or together with conservative treatments (e.g. antibiotics, pressure dressings, or serial aspirations). BTX treatment has a promising role in chronic sialadenitis. BTX therapy is highly successful in the treatment of gustatory sweating (Frey's syndrome), and could be considered the gold standard treatment for this neurological disorder.

Identification and treatment of metabolic abnormalities in patients with vertigo.

Hyperinsulinism, impaired glucose tolerance, and hypertriglyceridemia may be risk factors for atherosclerotic heart disease and have also been described in patients with vertigo, whose symptoms and findings responded to appropriate dietary therapy. We studied 100 patients in an otolaryngology practice to determine the role of these abnormalities in identifying patients suitable for dietary therapy and to assess the efficacy of dietary therapy in the treatment of vertigo in such selected patients. The determination of hyperinsulinism and hypertriglyceridemia were of value as supplements to the traditional glucose tolerance test in detecting reversible metabolic vertigo. Reactive hypoglycemia was found in only four patients and thus appears overdiagnosed as a cause of vertigo. Insulin resistance appears to be the basic abnormality in this syndrome, which, in our series, occurred predominantly in overweight patients.

Improvement of diabetic autonomic gustatory sweating by botulinum toxin type A.

Fourteen diabetic subjects with gustatory sweating were treated by intracutaneous injections of botulinum toxin type A into the affected facial skin areas. In all subjects, sweating (measured by Minor starch iodine test) ceased within 4 days, with the maximal follow-up time lasting 24 weeks. This therapeutic approach, which could be used to reduce the severity of diabetic gustatory sweating, appears to be long lasting, adverse effect free, and minimally invasive.

Involvement of the noradrenergic system in modulating the blink reflex in humans.

Several researches have shown that the spinal reflex transmission in animals, as well as humans, was inhibited by alpha(2)-agonists, due to a disfacilitation of tonic noradrenergic control on motoneuronal output. To understand better the mechanisms regulating certain aspects of motor activity, here we reinvestigated the possible role of noradrenergic systems in modulating reflex activity of the brainstem in humans. To this aim, blink reflex responses (R1 and R2) evoked by electrical stimulation of the supraorbital nerve were electromyographically recorded in healthy volunteers. Both R1 and R2 areas were measured at 10-min intervals before and after i.v. injection of alpha(2)-agonist clonidine (0.5 microg/kg). The substance induced consistent depression of R1, which reached its maximum 40 min after drug administration (-43% of the control values). Ipsilateral R2 area resulted little affected by clonidine (-15% at 50 min), whereas no effects were observed in contralateral R2. Blood pressure values were never altered by drug injections. These results, taken together with previous observations, support the hypothesis that alpha(2)-agonist substances may cause a transient inactivation of noradrenergic neurons, thus releasing neurons involved in the circuitry of the blink reflex from a facilitatory drive. Since clonidine differentially modulated blink reflex responses, it is likely to assume that such a disfacilitation concerns mostly pontine units mediating the R1. However, the complexity of clonidine's effects at multiple pre- and postsynaptic sites does not allow us to exclude that other systems are involved in the alpha(2)-mediated control of facial motoneurons.

Supratentorial atrophy in spinocerebellar ataxia type 2: MRI study of 20 patients.

There have been only few studies of brain magnetic resonance imaging (MRI) in spinocerebellar ataxia (SCA) type 2. We investigated 20 SCA2 patients, from 11 Sicilian families, and 20 age-matched control subjects using MRI. Our data confirm that olivopontocerebellar atrophy (OPCA) is the typical pattern in SCA2. We found no significant correlation between infratentorial atrophy, disease duration, or the number of CAG repeats in our SCA2 patients, but there was supratentorial atrophy in 12 patients, with a significant correlation between supratentorial atrophy and disease duration. OPCA appears to represent the "core" of the SCA2: however, central nervous system involvement is not limited to pontocerebellar structures. We therefore consider central nervous system degeneration in SCA2 as a widespread atrophy. MRI is helpful in diagnosing SCA, but it is not diagnostic in the absence of clinical and molecular studies. We suggest that serial MRI may play a role in evaluating "in vivo" the progressive steps of neurodegeneration in SCA2, for a better comprehension of the pathophysiology of this disorder.

Spinocerebellar ataxia type 2 in southern Italy: a clinical and molecular study of 30 families.

Autosomal dominant cerebellar ataxia type I is the most common form of dominant ataxia. A genetic heterogeneity has been identified with five different loci (SCA1, 2, 3, 4, and 6). A pathological expansion of a CAG sequence has been identified in SCA1, 2, 3, and 6. We performed molecular analysis in 51 families with autosomal dominant cerebellar ataxia type I, mainly originating from southern Italy and Sicily. Thirty families carry an expanded CAG sequence within SCA2 gene. The mean number of repeats was 39.9 +/- 3.3 in 85 expanded alleles, with a range of 34-52. The number of triplets was inversely correlated with age at onset and explained 76% of the variance. The best fit was obtained with an exponential relationship between variables. Expanded alleles were unstable when transmitted from parents to offspring. Expansions were more common than contractions, accounting for 59% of the total meioses and for 80% of the father-child transmissions. The mean intergenerational variation was 1.9 repeats (range -3 to +15) with higher values for male transmissions. Bulbar and autonomic signs were related to disease duration, pyramidal signs to CAG size, cerebellar features and peripheral neuropathy to both. Among the remaining 21 families, three carried the SCA1 and one the SCA6 mutation. This study suggests that SCA2 is the prevalent mutation in southern Italy.

Central motor conduction to lower limb after transcranial magnetic stimulation in spinocerebellar ataxia type 2 (SCA2).

OBJECTIVES: To evaluate central motor conduction to lower limbs in spinocerebellar ataxia type 2 (SCA2). METHODS: Transcranial magnetic stimulation was performed to study the corticospinal tracts of 18 patients with SCA2. RESULTS: Central motor conduction time (CMCT) to lower limbs and thresholds were abnormal in 8 patients (44%); CMCT and thresholds were significantly correlated with disease duration and disability. CONCLUSIONS: Corticospinal tract involvement is more frequent than previously reported in SCA2. Prolonged CMCT and increased threshold should not be used to differentiate between various type of autosomal dominant cerebellar ataxia. Similar to that reported in Friedreich's ataxia, we suggest that examining central motor conduction to the lower limbs may assist in evaluating the progressive steps of neurodegeneration in SCA2.

Diabetes insipidus in neurobrucellosis.

Brucellosis is an infection due to Brucella species and is characterized by acute febrile illness, chilly sensations, sweats, weakness, generalized malaise, body aches and headache. The involvement of the nervous system is rare. A few cases have been reported with symptoms and sign of optic neuritis, meningoencephalitis, meningomyelitis and cranial nerve palsy. We report a case with culture proven neurobrucellosis who presented with diabetes insipidus along with systemic signs. Neuroimaging revealed multiple lesions in brain parenchyma, including the suprasellar region. Both diabetes and suprasellar lesions improved markedly with specific antibiotic therapy.

The maintenance of an allergy diagnosis and treatment center.

This article summarizes the role of allergy personnel in maintaining an in vitro allergy diagnosis and treatment center. The equipment necessary for the efficient maintenance of such a center is outlined.

[Symptomatic management in multiple sclerosis]. / Aspetti sintomatici della sclerosi multipla.

Multiple sclerosis is an autoimmune disease, characyerized by demylinization of white matter of Central Nervous System (CNS). Its etiology is still unknown. In the world, about 2.000.000 of people are affected by MS, with higher prevalence in North-America and North-Europe. Two are the essential features of the therapeutical management in MS: 1) immunomodulating therapy, which consists of "disease modifing drugs"; 2) symptomatic treatment. Only some patients can benefit of immunomodulating therapy, whereas symptomatic treatment can be helpfull to everbody. In the following pages the authors will review the medical options used in the diagnostic, prognostic and therapeutic management of MS.

[Neurogenic dysphagia: physiology, physiopathology and rehabilitative treatment]. / La disfagia in neurologia: fisiologia, fisiopatologia e trattamento riabilitativo.

Swallowing is both a voluntary than a reflex function. It consist in transporting feeding from mouth to the stomach. Swallowing function occurs with very frequency during the day and needs complex neuromuscular coordination. Several neurologic diseases determine swallowing disorders. Dysphagia, is the difficulty in swallowing. In slight disorders, swallowing function is sufficiently compensated, symptoms are few or absent. Sometimes the patient is able to compensate and obtains a safe deglutition. Rehabilitation of swallowing disorders is based on the assessment of all symptoms and troubles causing dysphagia and on the improvement of the specific disabilities. Rehabilitation is aimed to make patient able for a safe oral feeding. We can use classic specific physiotherapy, compensatory movements of head and neck, electrostimulation, and the chemical myotomia by botulinum toxin injection.

The eminent anatomists who discovered the upper oesophageal sphincter.

OBJECTIVE: To discover the anatomist who first identified the upper oesophageal sphincter. METHOD: The authors searched dozens of antique anatomy textbooks kept in the old section of the 'Vincenzo Pinali' Medical Library of Padua University, looking for descriptions of the upper oesophageal sphincter. RESULTS: The oesophageal sphincter was drawn correctly only in 1601, by Julius Casserius, in the book De vocis auditusque organis historia anatomica… (which translates as 'An Anatomical History on the Organs of Voice and Hearing …'), and was properly described by Antonio Maria Valsalva in 1704 in the book De aure humana tractatus… ('Treatise on the Human Ear …'). CONCLUSION: Anatomists Casserius and Valsalva can be considered the discoverers of the 'oesophageal sphincter'.