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Pain represents a common symptom of several diseases and is often associated with a reduction in rehabilitation outcomes and recovery. The effectiveness of pain alleviation by botulinum toxin has been recently demonstrated. We searched in PubMed the papers about this topic published in the last ten years, and we selected clinical trials, guidelines, meta-analyses, reviews, and systematic reviews. We used different approaches: multiperspective presentation, lexical evaluation, and systematic review. The systematic review was only performed for the randomized controlled trials. We predominantly found reviews and trials about the rehabilitation of stroke/brain injury and epicondylitis. The most common outcome measures were pain, function, and spasticity. Among the common words, pain was the most frequent and the terms were grouped into different families, especially concerning the outcomes. Rehabilitation showed a relatively low frequency. Finally, the systematic review showed moderate-low levels of bias which confirms the effectiveness of botulinum toxin for pain treatment. The current literature about botulinum toxin is wide and globally diffuse but with some limitations in study strategies and clearness in the formal presentation. The evidence justifies the use of botulinum toxin in treating pain in different diseases.

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.

Peripheral nervous system diseases are a complex and heterogenous group of diseases affecting the different nerves with various severity and impact on quality of life. The current literature does not provide a structured guide for the rehabilitation of these conditions. We performed a lexical literature evaluation based on graph theory to clarify this topic. We performed a search on PubMed and calculated the frequencies of the words indicating rehabilitation approaches, nerves, and diseases. We found the usefulness of exercises and different physical agents, like laser and ultrasound therapy and neuromuscular stimulation vibration therapy. Orthoses are useful for entrapment, trauma, and hereditary diseases. Correct knowledge and assessment of the neuropathies are fundamental for the therapeutic decision and to guide rehabilitation. Despite the usefulness shown by the different approaches to modulating pain, improving muscle strength and endurance, and ameliorating balance and the sensory system, further studies are needed to define the best-personalized protocols.

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle shortening (i.e., muscle contracture). Although the mechanism of action of BoNT-A on p-ROM is far from understood, pain relief may be hypothesized to play a role. To test this hypothesis, a retrospective investigation of p-ROM and pain was conducted in post-stroke patients treated with BoNT-A for upper limb hypertonia. Among 70 stroke patients enrolled in the study, muscle tone (Modified Ashworth Scale), pathological postures, p-ROM, and pain during p-ROM assessment (Numeric Rating Scale, NRS) were investigated in elbow flexors (48 patients) and in finger flexors (64 patients), just before and 3-6 weeks after BoNT-A treatment. Before BoNT-A treatment, pathological postures of elbow flexion were found in all patients but one. A decreased elbow p-ROM was found in 18 patients (38%). Patients with decreased p-ROM had higher pain-NRS scores (5.08 ± 1.96, with a pain score ≥8 in 11% of cases) than patients with normal p-ROM (0.57 ± 1.36) ( p < 0.001). Similarly, pathological postures of finger flexion were found in all patients but two. A decreased finger p-ROM was found in 14 patients (22%). Pain was more intense in the 14 patients with decreased p-ROM (8.43 ± 1.74, with a pain score ≥ 8 in 86% of cases) than in the 50 patients with normal p-ROM (0.98 ± 1.89) ( p < 0.001). After BoNT-A treatment, muscle tone, pathological postures, and pain decreased in both elbow and finger flexors. In contrast, p-ROM increased only in finger flexors. The study discusses that pain plays a pivotal role in the increase in p-ROM observed after BoNT-A treatment.

Objective: To develop and validate a quick observational clinical tool, the Functional ASsessment Test for Upper Limb (FAST-UL), for the evaluation of upper limb impairment in goal-directed functional-oriented motor tasks after stroke., Design: Observational, cross-sectional, psychometric study., Setting: Inpatient and outpatient rehabilitation clinic., Participants: A total of 188 post-stroke survivors (mean age 65.2±17.7 years, 61% men, 48% with ischemic stroke and 66% in the sub-acute phase; N=188)., Interventions: Not applicable., Main Outcome Measures: Principal component analysis and Rasch analysis through a Partial Credit Model were used to assess the structure and psychometric properties of the 5 items of the FAST-UL (Hand to Mouth [HtM], Reach to Target, Prono-Supination, Grasp and Release, and Pinch and Release [PaR])., Results: The Cronbach's α equal to 0.96 was indicative of an acceptable internal consistency; the reliability, as measured through the Person Separation Reliability equal to 0.87, was good. The FAST-UL tool was unidimensional. All the FAST-UL items were found to fit well the Rasch measurement model. The easiest to perform FAST-UL item was the HtM movement while the most difficult was the PaR movement., Conclusions: The FAST-UL is a quick, easy-to-administer observational assessment tool of upper limb motor impairment in post-stroke survivors with good item-level psychometric properties., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD., Objective: To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients., Methods: A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus., Results: Eighty-five papers were used to inform the Panel's statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions., Conclusions: The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD., (© 2021. The Author(s).)

This observational study aimed at investigating pain in stroke patients with upper limb spastic dystonia. Forty-one consecutive patients were enrolled. A 0-10 numeric rating scale was used to evaluate pain at rest and during muscle tone assessment. Patients were asked to indicate the most painful joint at passive mobilization (shoulder, elbow, wrist-fingers). The DN4 questionnaire was administered to disclose neuropathic pain. All patients were assessed just before and 1 month after incobotulinumtoxin-A treatment. Pain was present in 22 patients, worsened or triggered by passive muscle stretching. DN4 scored < 4 in 20 patients. The most painful joints were wrist-fingers in 12 patients, elbow in 5 patients and shoulder in the remaining 5 patients. Both elbow and wrist-fingers pain correlated with muscle tone. BoNT-A treatment reduced pain in all the joints, including the shoulder. We discussed that nociceptive pain is present in a vast proportion of patients with upper limb spastic dystonia. BoNT-A treatment reduced both spastic dystonia and pain in all the joints but the shoulder, where the effect on pain could be mediated by the reduction of pathological postures involving the other joints.

Background: Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD., Objective: To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management., Methods: A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus., Results: The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed., Conclusions: The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Nothing to declare.

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.

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., (© 2020 European Academy of Neurology.)

Background: Dysphagia in the elderly, known as presbydysphagia, has become a relevant public health problem in several countries. Swallowing disorders may be a consequence of different neurological disorders (secondary presbydysphagia) or the expression of the aging process itself (primary presbydysphagia). We aimed to test the therapeutic potential of two different non-invasive brain stimulation (NIBS) techniques in subjects with primary or secondary presbydysphagia., Methods: A blinded randomized controlled trial with crossover design was carried out in 42 patients, randomly assigned to anodal transcranial direct current stimulation (tDCS) or intermittent theta-burst stimulation (TBS) group. Both tDCS and TBS were applied for 5 consecutive days over the right swallowing motor cortex. The swallowing function was assessed before and 1 and 3 months after the stimulation using the Dysphagia Outcome and Severity Scale (DOSS), scored based on clinical assessment and fiberoptic endoscopic evaluation of swallowing. An electrophysiological method was also applied to evaluate changes in the reproducibility of the swallowing behavior., Key Results: Both real tDCS and TBS had beneficial effects on the swallowing function in patients with primary and secondary presbydysphagia. Anodal tDCS resulted in an improvement of 0.5 points in DOSS at 1-month follow-up (P = .014), whereas intermittent TBS induced an increase of 0.7 and 0.6 points at 1- and 3-month follow-up evaluations, respectively (P = .0001 and P = .005, respectively). Reproducibility of both the oral and pharyngeal phases of swallowing significantly increased at 1-month follow-up., Conclusions and Inferences: Our results suggest that non-invasive cortical stimulation may be useful for dysphagia recovery in elderly patients., (© 2020 John Wiley & Sons Ltd.)

Objectives: This study aims to evaluate the effect of botulin toxin A in patients with multiple sclerosis (MS) affected by spasmodic dysphonia (SD) and to show the safety and effectiveness of this treatment in long-term observation., Materials and Methods: This is a pilot study on three relapsing-remitting MS patients with SD and their response to botulin toxin A., Results: None of the patients reported dysphagia or other adverse events. Significant improvement was observed in terms of both voice quality and laryngostroboscopy results. The treatment effect was durable for 6-8 months., Conclusions: Botulin toxin A is a safe treatment that can be successfully used to treat SD in patients with MS. Larger studies are necessary to confirm our results., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: we investigated the effect of anodal transcranial direct current stimulation (tDCS) applied over the pharyngeal motor area in dysphagia associated with multiple sclerosis (MS)., Methods: Eighteen MS patients with dysphagia associated with brainstem involvement were randomized to receive either "real" or "sham" tDCS., Primary Outcome: The Penetration/Aspiration Scale (PAS)., Secondary Outcomes: changes in electromyographic (EMG) parameters and pharyngeal cortical motor evoked potentials (MEPs). Patients were evaluated at baseline (T 0 ), at the end of 5-session cycle of tDCS stimulations (T 1 ), after two (T 2 ), and four (T 3 ) weeks., Results: the PAS values were significantly lower in the active group than in "sham" group at T 1 , and at T 3 . Over the post-stimulation periods, PAS significantly improved only in the "real" group. As regards the secondary outcomes, we observed a statistically significant difference between the 2 groups only in the MEPs amplitude at T 1 . The comparison between baseline and each of the post-stimulation times showed significant differences only of the "real" group across all the secondary parameters., Conclusions: Our findings support a beneficial effect of anodal tDCS applied to the pharyngeal motor cortex in MS-associated dysphagia., Significance: Considering its safety and efficacy, tDCS may represent an important resource in MS-associated dysphagia., (Copyright © 2019. Published by Elsevier B.V.)

Objective: Muscle cramps occur in >50% of diabetic patients and reduce the quality of life. No effective treatment is available. We evaluated the clinical effectiveness of botulinum toxin A (BTX-A) injections for treating cramps in diabetic patients with neuropathy., Methods: This single-center, double-blind, placebo-controlled perspective study investigated the efficacy and safety of BTX-A intramuscular injection for treating calf or foot cramps refractory to common pharmacological drugs. Fifty diabetic patients with peripheral neuropathy and cramps were randomly assigned to 2 matched groups. BTX-A (100 or 30 units) or saline was injected on each side into the gastrocnemius or the small flexor foot muscles. Changes in pain intensity (primary outcome) and cramp frequency were evaluated over the course of 20 weeks after BTX-A administration. Cramp interference in daily life and the electrophysiological cramp threshold frequency were also measured. The treatment was repeated 5 months after first injection in 19 responders., Results: All outcome measures improved significantly after BTX-A compared with placebo. The changes with respect to baseline were already significant after 1 week and persisted up to week 14. Only 5 of 25 (20%) patients were nonresponders (<50% decrease of the primary outcome). The responses to a second BTX-A injection provided results similar to the first administration. Mild pain at the injection site (4/25 cases) was the only adverse event, and it disappeared within 2 to 3 days., Interpretation: Local BTX-A infiltration is an efficacious and safe procedure for obtaining a sustained amelioration of muscle cramps associated with diabetic neuropathy. Ann Neurol 2018;84:682-690., (© 2018 American Neurological Association.)

Background : Sialorrhoea and drooling are disabling manifestations of different neurological disorders. The aim of this study was to evaluate the effects of botulinum neurotoxin type A (BoNT/A) injection on hypersalivation in 90 patients with neurological diseases of different aetiologies, and to define the minimum number of injected salivary glands to reduce sialorrhoea. Determining the minimum number of glands that need to be engaged in order to have a significant reduction in drooling may be very useful for establishing the minimum total dosage of BoNT/A that may be considered effective in the treatment of hypersalivation. Methods : Twenty-five mouse units (MU) of BoNT/A ( onabotulinumtoxin A, Botox; Allergan, Irvine, CA, USA; 100 MU/2 mL, 0.9% saline; or incobotulinumtoxin A , Xeomin; Merz Pharma, Germany; 100 MU/2 mL, 0.9% saline) were percutaneously injected into the parotid (p) glands and/or submandibular (s) glands under ultrasound control. On this basis, patients were divided into three groups. In group A (30 patients), BoNT/A injections were performed into four glands; in group B (30 patients), into three glands, and in group C (30 patients), into two glands. Patients treated in three glands (group B) were divided into two subgroups based on the treated glands (2 p + 1 s = 15 patients; 2 s + 1 p = 15 patients). Similarly, patients being injected in two glands (group C) were subdivided into three groups (2 p = 10 patients; 1 p + 1 s = 10 patients; 2 s = 10 patients). In patients who were injected in three and two salivary glands, saline solution was injected into the remaining one and two glands, respectively. Assessments were performed at baseline and at 2 weeks after the injections. Results : BoNT/A significantly reduced sialorrhoea in 82 out of 90 patients. The effect was more evident in patients who had four glands injected than when three or two glands were injected. The injections into three glands were more effective than injections into two glands. Conclusions : Our results have shown that BoNT/A injections induced a significant reduction in sialorrhoea in most patients (91%). In addition, we demonstrated that sialorrhoea associated with different neurological diseases was better controlled when the number of treated glands was higher., Competing Interests: The authors declare no conflict of interest. We had no founding sponsor.

Neurogenic dysphagia (ND) can occur in patients with nervous system diseases of varying etiologies. Moreover, recovery from ND is not guaranteed. The therapeutic approaches for oropharyngeal ND have drastically changed over the last decade, mainly due to a better knowledge of the neurophysiology of swallowing along with the progress of neuroimaging and neurophysiological studies. For this reason, it is a priority to develop a treatment that is repeatable, safe, and can be carried out at the bedside as well as for outpatients. Pharyngeal electrical stimulation (PES) is a novel rehabilitation treatment for ND. PES is carried out via location-specific intraluminal catheters that are introduced transnasally and enable clinicians to stimulate the pharynx directly. This technique has demonstrated increasingly promising evidence in improving swallowing performance in patients with ND associated with stroke and multiple sclerosis, probably by increasing the corticobulbar excitability and inducing cortical reorganization of swallowing motor cortex. In this article, we update the reader as to both the physiologic background and past and current studies of PES in an effort to highlight the clinical progress of this important technique., Competing Interests: Disclosure S Hamdy is a director, chief scientific officer, and shareholder in the company Phagenesis Ltd, which is involved in the medical device sector for dysphagia and markets Phagenyx™. The authors report no other conflicts of interest in this work.

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Osteoporosis is the most common bone disease affecting millions of people worldwide, particularly in elderly or in post-menopausal women. The pathogenesis is useful to understand the possible mechanism of action of anti-osteoporotic drugs. Early diagnosis, possible with several laboratory and instrumental tests, allows a major accuracy in the choice of anti-osteoporosis drugs. Treatment of osteoporosis is strictly related to severity of pathology and consists on prevention of fragility fractures with a correct lifestyle and adequate nutritional supplements, and use of pharmacological therapy, started in patients with osteopenia and history of fragility fracture of the hip or spine. The purpose of this review is to focus on main current pharmacological products to treat osteoporotic patients.

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., (© Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.)

Background and Aims: Neurogenic dysphagia linked to failed relaxation of the upper esophageal sphincter (UES) can be treated by injecting botulinum toxin (BTX) into the cricopharyngeal (CP) muscle. We compared the effects of this treatment in different neurological disorders with dysphagia, to evaluate its efficacy over time including the response to a second injection. Materials and Methods: Sixty-seven patients with neurogenic dysphagia associated with incomplete or absent opening of the UES (24 with brainstem or hemispheric stroke, 21 with parkinsonian syndromes, 12 with multiple sclerosis, and 10 with spastic-dystonic syndromes secondary to post-traumatic encephalopathy) were treated with the injection of IncobotulinumtoxinA (dose 15-20 U) into the CP muscle under electromyographic guidance. The patients were assessed at baseline and after the first and second treatment through clinical evaluation and fiberoptic endoscopy of swallowing, while their dysphagia was quantified using the Dysphagia Outcome and Severity Scale (DOSS). An electrokinesiographic/electromyographic study of swallowing was performed at baseline. Results : Most patients responded to the first BTX treatment: 35 patients (52.2%) were classified as high responders (DOSS score increase >2 levels), while other 19 patients (28.4%) were low responders (DOSS score increase of ≤2 levels). The effect of the first treatment usually lasted longer than 4 months (67%), and in some cases up to a year. The treatment efficacy remained high also after the second injection: 31 patients (46.3%) qualified as high responders and other 22 patients (32.8%) showed a low response. Only in the parkinsonian syndromes group we observed a reduction in the percentage of high responders as compared with the first treatment. Side effects were mostly mild and reported in non-responders following the first injection. A severe side effect, consisting of ingestion pneumonia, was observed following the second BTX injection in two patients who had both been non-responders to the first. Non-responders were characterized electromyographically by higher values of the oropharyngeal interval. Conclusion: These findings confirm the effectiveness of IncobotulinumtoxinA injection in the treatment of neurogenic dysphagia due to hyperactivity and relaxation failure of the UES. Caution should be used as regards, the re-injection in non-responders to the first treatment.

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked epileptic seizures. The majority of people given a diagnosis of epilepsy have a good prognosis, but 20-30 % will develop drug-resistant epilepsy. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. It consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (Neuro-Cybernetic Prosthesis). In 1997, the Food and Drug Administration approved VNS as adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. This article reviews the literature from 1988 to nowadays. We discuss thoroughly the anatomy and physiology of vagus nerve and the potential mechanisms of actions and clinical applications involved in VNS therapy, as well as the management, safety, tolerability and effectiveness of VNS therapy. VNS for partial seizures appears to be an effective and well tolerated treatment in adult and pediatric patients. People noted improvements in feelings of well-being, alertness, memory and thinking skills, as well as mood. The adverse effect profile is substantially different from the adverse effect profile associated with antiepileptic drugs, making VNS a potential alternative for patients with difficulty tolerating antiepileptic drug adverse effects. Despite the passing years and the advent of promising neuromodulation technologies, VNS remains an efficacy treatment for people with medically refractory epilepsy. Past and ongoing investigations in other indications have provided signals of the therapeutic potential in a wide variety of conditions.

CP is the most common cause of chronic disability in childhood occurring in 2-2.5/1000 births. It is a severe disorder and a significant number of patients present cognitive delay and difficulty in walking. The use of botulinum toxin (BTX) has become a popular treatment for CP especially for spastic and dystonic muscles while avoiding deformity and pain. Moreover, the combination of physiotherapy, casting, orthotics and injection of BTX may delay or decrease the need for surgical intervention while reserving single-event, multi-level surgery for fixed musculotendinous contractures and bony deformities in older children. This report highlights the utility of BTX in the treatment of cerebral palsy in children. We include techniques for administration, side effects, and possible resistance as well as specific use in the upper and lower limbs muscles.

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'.

Objective: We performed an electrophysiological study of swallowing (EPSS) in multiple sclerosis (MS) to describe oropharyngeal swallowing abnormalities and to analyze their correlations with dysphagia and with overall neurological impairment., Methods: Neurological examinations were quantified using the Kurtzke Functional Systems and the Expanded Disability Status Scale (EDSS). Dysphagia was evaluated using the Dysphagia in Multiple Sclerosis (DYMUS) questionnaire, while fiberoptic endoscopic evaluation of swallowing (FEES) was used to establish the degree of aspiration and penetration, graded using the penetration-aspiration scale (PAS). The EPSS measured the duration of suprahyoid/submental muscle EMG activity (SHEMG-D), the duration of the laryngeal-pharyngeal mechanogram (LPM-D), and the duration of the pause in cricopharyngeal muscle EMG activity (CPEMG-PD); it also measured the interval between onset of the suprahyoid/submental muscle EMG activity (SHEMG) and onset of the laryngeal-pharyngeal mechanogram (I-SHEMG-LPM)., Results: 92% of patients showed at least one electrophysiological abnormality. I-SHEMG-LPM correlated positively with the DYMUS questionnaire. I-SHEMG-LPM, SHEMG-D, and DYMUS correlated positively with the PAS. Moderate to severe bladder sphincter dysfunction was associated with a significant reduction, or absence, of CPEMG-PD., Conclusion: EPSS improves our understanding of the pathophysiology of dysphagia in MS., Significance: This investigation could be useful in MS patients with swallowing abnormalities., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Deficit of tactile sensation in patients with MS is frequent and can be associated with interference with daily life activities. Transcranial direct current stimulation (tDCS) showed to increase tactile discrimination in healthy subjects., Objective: In the present study, we investigated whether tDCS may be effective in ameliorating tactile sensory deficit in MS patients., Methods: Patients received sham or real anodal tDCS of the somatosensory cortex for 5 consecutive days in a randomized, double blind, sham-controlled study. Discrimination thresholds of spatial tactile sensation were measured using the grating orientation task (GOT). As secondary outcomes we also measured subjective perception of tactile sensory deficit through a visual analog scale (VAS), quality of life and overall disability to evaluate the impact of the treatment on patients daily life. Evaluations were performed at baseline and during a 4-week follow-up period., Results: Following anodal but not sham tDCS over the somatosensory cortex, there was a significant improvement of discriminatory thresholds at the GOT and increased VAS for sensation scores. Quality of life, and disability changes were not observed., Conclusion: Our results indicate that a five day course of anodal tDCS is able to ameliorate tactile sensory loss with long-lasting beneficial effects and could thus represent a therapeutic tool for the treatment of tactile sensory deficit in MS patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: Obstructive sleep apnea syndrome (OSAS) is a chronic condition, characterized by recurrent episodes of upper airway collapse during sleep, which affects up to 5% of adults in the Western population. The muscle tone of the human body ordinarily relaxes during sleep, thus causing airway obstruction and leading to sleep apnea. We report a case of a 68-years old male in which dystonic closure of the larynx during sleep caused OSAS. The sleep endoscopy was crucial in establishing the diagnosis of laryngeal dystonia. A botulinum toxin injection in the vocal cord improved the OSAS. These findings define a novel sleep-related breathing disorder., (Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objective: Treatment options for dysphagia associated with multiple sclerosis (MS) are currently limited. In this study we investigated whether intraluminal electrical pharyngeal stimulation facilitates swallowing recovery in dysphagic MS patients., Patients and Methods: Twenty dysphagic MS patients were randomized to receive 5 Hz "real" pharyngeal stimulation (10 patients) for 10 min or "sham" pharyngeal stimulation for 10 min (10 patients). Patients were evaluated by videofluoroscopic, and electromyographic examinations, and by the Penetration/Aspiration Scale (PAS) performed before (T0) and immediately after the last session of 5 consecutive days of electrical pharyngeal stimulation (T1), and then after two (T2), and four (T3) weeks of 5 consecutive days of pharyngeal electrical stimulation., Results: Patients who received "real" stimulation showed a significant improvement in all the swallowing outcome measures as compared with those receiving "sham" stimulation., Conclusions: No specific treatment for oro-pharyngeal dysphagia related to MS has been described to date. Our preliminary findings suggest a potential benefit of intraluminal electrical pharyngeal stimulation for the treatment of dysphagia caused by MS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: This study looked at the effect of botulinum toxin type A (BoTox-A) in patients with amyotrophic lateral sclerosis (ALS) with dysphagia due to isolated upper motor neuron (UMN) involvement or combined UMN/lower motor neuron (LMN) impairment associated with oral phase or oropharyngeal muscles involvement. Establishing whether different pathophysiologic mechanisms underlie different responses to BoTox-A treatment may have important implications for patient management., Patients and Methods: We screened 35 patients with sporadic ALS with dysphagia and included in the study 20 out of 35 with upper esophageal sphincter (UES) hyperactivity. We divided these 20 patients into 2 groups, based on the presence or absence of LMN impairment. Irrespective of the groups, we treated all 20 patients with BoTox-A injected into the UES. The study outcome was dysphagia severity scored using the Penetration/Aspiration Scale (PAS), measured before and 2, 4, and 20 weeks after injection., Results: Significant mean PAS reduction was noted at weeks 2 and 4. The botulinum-dependent PAS reduction was entirely associated with the variability shown by the group of patients with no sign of LMN impairment (group 2) and was not observed in group 1., Conclusions: The significant improvement observed in patients with isolated UES dysfunction suggests that a different pathophysiology of ALS dysphagia predisposes patients to a different response to treatment with BoTox-A. This treatment may represent an alternative treatment to percutaneous endoscopic gastrostomy (PEG) or prolong PEG-free time., Classification of Evidence: This study provides Class III evidence that botulinum is more effective at 2 and 4 weeks in improving dysphagia in patients with ALS with UES hyperactivity without LMN involvement (vs those with LMN involvement).

The superior laryngeal nerve (SLN) has been attributed much less clinical significance than the recurrent laryngeal nerve. It has sometimes been described as the 'neglected' nerve in thyroid surgery, although injury to this nerve can cause significant disability. The external branch of the SLN is the only motor supply to the cricothyroid muscle, which increases the tension of the ipsilateral vocal fold during highfrequency phonation, particularly in women and voice professionals. Damage to this nerve can manifest as ipsilateral cricothyroid muscle paralysis, and clinical symptoms may include a hoarse, breathy voice, frequent throat clearing, vocal fatigue or diminished vocal frequency range, especially when rising pitch. SLN paralysis can be a significant issue for those whose careers depend largely on a full range of voice. The famous opera soprano, Amelita Galli-Curci, suffered SLN injury during thyroid surgery with distressing consequences.

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.

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., (© 2010 The Author(s). European Journal of Neurology © 2010 EFNS.)

It is known that 15-20% of oropharyngeal carcinomas develop distant metastases that involve most commonly lung, liver and bone. Clival metastasis from oropharyngeal squamous cell carcinoma has not been previously reported in the English literature. We describe the rare occurrence of clival metastasis from tonsillar carcinoma presenting with abducent paralysis and discuss diagnostic and therapeutic rational approaches. Despite neoadjuvant chemotherapy (cisplatinum/etoposide/epirubicin followed by taxotere), extended left tonsillectomy and ipsilateral radical neck dissection and external radiotherapy (60 Gy) for tonsillar carcinoma, the patient developed clival metastasis and died of disease. The overall prognosis of patients with clival metastases is extremely poor, with an overall median survival of about 2.5 years. Cranial nerve palsy occurrence is associated with a poorer prognosis with an average survival of only 5 months.

Objective: No specific treatment for oropharyngeal dysphagia related to diabetic neuropathy has been described to date. Chemical myotomy of the cricopharyngeus (CP) muscle by botulinum neurotoxin type A (BoNT/A) has been effective in reducing or abolishing dysphagia associated with upper esophageal sphincter (UES) hyperactivity of different etiologies. In the present study, we evaluated the efficacy of BoNT/A injections into the CP muscle in diabetic patients with severe oropharyngeal dysphagia associated with diabetic autonomic and/or somatic peripheral neuropathy., Research Design and Methods: Twelve type 2 diabetic patients with severe dysphagia for both solid and liquid foods associated with autonomic and/or peripheral somatic neuropathy were investigated. Swallowing function was evaluated by clinical examination, videofluoroscopy, and simultaneous needle electromyography (EMG) of the CP and pharyngeal inferior constrictor (IC) muscles. Clinical evaluation using a four-level dysphagia severity score was performed every other day for the 1st week and thereafter every other week until week 24. Videofluoroscopy and EMG follow-up were carried out at week 1, 4, 12, 16, 18, and 24 after BoNT/A injection. BoNT/A was injected percutaneously into the CP muscle under EMG control., Results: BoNT/A induced the complete recovery of dysphagia in 10 patients and had a significant (P = 0.0001, ANOVA) improvement in 2 patients within 4 +/- 1.1 days (range 3-7). Clinical improvement was confirmed by videofluoroscopy and EMG., Conclusions: Our findings suggest a potential benefit from BoNT/A treatment in dysphagia associated with diabetic neuropathy. Randomized controlled trials are needed to confirm this observation.

Purpose: Parotid fistula is a well-known complication of parotidectomy or penetrating injury of the parotid gland. The management of parotid fistula has been controversial, and numerous conservative and surgical treatment methods have been described., Methods: We report 3 cases of parotid fistula after partial parotidectomy, which were treated by botulinum toxin injection under electromyographic control into the residual substance of parotid gland., Results: Complete healing of the fistula was achieved with a single botulinum toxin treatment in all patients. No side effects were observed after the treatment. The patients are disease-free after 21, 18, and 14 months, respectively., Conclusions: In the considered cases, the localized injection of botulinum toxin into the parotid gland resulted to an effective and long-lasting treatment of postparotidectomy fistula.

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.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder mapped on chromosome 12. Different results have been reported in spinocerebellar ataxias following transcranial magnetic stimulation (TMS). TMS-induced cortical silent period (CSP) was prolonged in different cerebellar disorders. Here we evaluate the duration of the TMS-induced CSP following a single magnetic stimulus in a large homogeneous group of SCA2 patients compared with idiopathic cerebellar ataxia (IDCA) patients with similar disease duration and severity, and in 20 healthy controls. The CSP duration in both arm and leg muscles was significantly (p<0.005) longer in patients than in controls. A significant positive correlation between disease duration and CSP prolongation in both SCA2 and IDCA was found. No correlation between age, onset and CSP duration emerged in either group. This study shows a prolongation of the TMS-induced silent period in both SCA2 and IDCA indicating that the cortical inhibitory mechanism is dependent on the disease duration and severity. Thus, the cerebellum seems to exert a pliable physiological influence on the cortico-spinal system through control of inhibitory cortical interneurons.