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Background/aims Individuals who are severely disabled from stroke (survivors of severely disabling stroke) experience poorer outcomes compared to those who are less disabled from stroke. However, there is a paucity of evidence describing current therapy practice in the management of severely disabling stroke. The aim of the study was to describe intervention and outcome measure use by physiotherapists and occupational therapists in the rehabilitation of physical function of survivors of severely disabling stroke. Methods A mixed-methods survey was conducted, involving an online questionnaire and follow-up interviews. Survey participants were UK-based physiotherapists and occupational therapists with experience treating stroke. Questionnaire data were analysed with descriptive and inferential statistics. Interview data were analysed using content analysis. Results A total of 452 therapists (59% physiotherapists) responded to the questionnaire. Out of the respondents, 18 self-selected therapists participated in follow-up interviews to explain questionnaire data. Whole body positioning, training of upper limb handling and positioning, and sitting balance practice were the most frequently used interventions. Inpatient-based therapists performed more active rehabilitation interventions, whereas community-based therapists performed more training and education. The Barthel Index, Modified Rankin Scale and National Institutes for Health Stroke Scale were the most frequently used outcome measures. Outcome measure use was generally low and was more likely to be completed when it was part of a national audit. Reasons for low outcome measure use were perceived lack of time and insensitivity to detect clinical change. Conclusions A variety of interventions and outcome measures are used in the rehabilitation of survivors of severely disabling stroke. There is a need to evaluate the effectiveness of frequently used interventions and identify outcome measures that are sensitive to the needs of survivors of severely disabling stroke.

Tendon adhesion formation describes the development of fibrotic tissue between the tendon and its surrounding tissues, which commonly occurs as a reaction to injury or surgery. Its impact on function and quality of life varies from negligible to severely disabling, depending on the affected area and extent of adhesion formed. Thus far, treatment options remain limited with prophylactic anti-inflammatory medications and revision surgeries constituting the only tools within the doctors' armamentarium - neither of which provides reliable outcomes. In this review, the authors aim to collate the current understanding of the pathophysiological mechanisms underlying tendon adhesion formation, highlighting the significant role ascribed to the inflammatory cascade in accelerating adhesion formation. The bulk of this article will then be dedicated to critically appraising different therapeutic structures like nanoparticles, hydrogels and fibrous membranes fabricated by various cutting-edge technologies for adhesion formation prophylaxis. Emphasis will be placed on the role of the fibrous membranes, their ability to act as drug delivery vehicles as well as the combination with other therapeutic structures (e.g., hydrogel or nanoparticles) or fabrication technologies (e.g., weaving or braiding). Finally, the authors will provide an opinion as to the future direction of the prevention of tendon adhesion formation in view of scaffold structure and function designs.

Introduction: Cluster headache [CH] is a severely disabling trigeminal autonomic cephalalgia [TAC]. Approximately 1 in 1,000 adults are affected by CH. Calcitonin gene-related peptide [CGRP] is an ...

Background Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare but severely disabling variant within the spectrum of trigeminal autonomic cephalalgia lacking evidence-based treatment. Case We report a case of chronic SUNCT in a 67-year-old man refractory to various guideline-conforming treatment attempts responding excellently to galcanezumab. Conclusions This case report indicates that monoclonal antibodies against calcitonin gene-related peptide, specifically galcanezumab, might be a treatment option for SUNCT warranting further investigation.

Objectives/hypothesis Respiratory laryngeal dystonia (RLD) is poorly understood and rarely reported in the literature. Patients have atypical laryngeal movement resulting in airway obstruction. This motion is neurogenic in nature, is constant while awake, nonepisodic, and non-trigger dependent. Given its rarity, it is often misdiagnosed for inducible laryngeal obstruction; however, it is refractory to medical and behavioral management. Although this condition has been addressed in the literature, this report is the largest case series characterizing presenting symptomology, multimodal treatment outcomes, and longitudinal course of these patients, and proposes a set of diagnostic criteria to aid in clinical identification of RLD patients. Our objectives were to characterize RLD clinically and offer diagnostic guidelines to clinicians. Study design A prospective case series with a retrospective analysis at a tertiary referral center. Methods A review of clinical records and videostroboscopic analysis of 16 patients treated for respiratory laryngeal dystonia from October 2005 to October 2018 was performed. Results Sixteen patients with respiratory laryngeal dystonia were included. The common features of this group were persistent, nonepisodic dyspnea and stridor with laryngoscopic evidence of paradoxical vocal fold motion. Our patients had no structural neurologic abnormalities. These patients typically failed respiratory retraining therapy and medical management of laryngeal irritants. In our series, 100% of patients underwent respiratory retraining therapy, 68.8% received laryngeal botulinum toxin injection, and 31.3% required tracheostomy. Conclusions RLD is a rare and challenging condition. The disorder can be severely disabling, and treatment options appear limited. A multidisciplinary approach may be helpful. Some patients responded to laryngeal botulinum injection and medical management, whereas others required tracheostomy for symptom control. Laryngoscope, 2020.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare and severely disabling autosomal dominant disease that is yet to be clearly understood. The purpose of this review is to present recent literature on pathophysiology, clinical features, diagnosis and treatment of FOP.FOP is characterized by congenital great toe deformity and progressive heterotopic ossifications in connective tissue. Heterotopic ossifications occur after painful flare-ups that can arise spontaneously or can be triggered by minor trauma. Each flare-up ultimately causes restriction of related-joint, and along with the others eventually leads to immobility. Death is usually caused by pulmonary complications because of chest wall involvement. The causative gene of FOP is activin A receptor type 1 (ACVR1), a bone morphogenetic protein-signalling component, which normally acts to inhibit osteoblastogenesis. The treatment of FOP is still preventive and supportive.Although there are still gaps in the underlying mechanism of FOP, effective treatment options, such as potential pharmacologic targets and cell-based therapies are promising for the future. Some of these were tested without a clinical trial setting, and are currently in the process of evidence-based research.

Because of the demographic shift and the increased proportion of patients surviving acute critical illnesses, the number of people living with severely disabling chronic diseases and, consequently, the demand for rehabilitation are expected to increase sharply over time. As underscored by the World Health Organization, there is substantial evidence that the provision of inpatient rehabilitation in specialized rehabilitation units to people with complex needs is effective in fostering functional recovery, improving health-related quality of life, increasing independence, reducing institutionalization rate, and improving prognosis. Recent studies in the real world setting reinforce the evidence that patients with ischemic heart disease or stroke benefit from rehabilitation in terms of improved prognosis. In addition, there is evidence of the effectiveness of rehabilitation for the prevention of functional deterioration in patients with complex and/or severe chronic diseases. Given this evidence of effectiveness, rehabilitation should be regarded as an essential part of the continuum of care. Nonetheless, rehabilitation still is underdeveloped and underused. Efforts should be devoted to foster healthcare professional awareness of the benefits of rehabilitation and to increase referral and participation.

Myelopathy is a broad term used to describe a heterogeneous group of disorders that affects the spinal cord; the focus of this article will be a subgroup of these disorders with an autoimmune and inflammatory-based pathology. Symptoms typically develop over hours or days and then worsen over a matter of days to weeks, but sometimes can have a more insidious or subacute presentation, which can make the diagnosis more puzzling. Despite relatively low incidence rates, almost a third of affected patients are left with severely disabling symptoms. Prompt recognition of the underlying etiology is essential so that a specific targeted therapy can be implemented for optimal outcomes. The authors discuss a systematic approach to immune-mediated myelopathies, with a focus on the unique characteristics of each that may aid in diagnosis.

Purpose of review Neurotoxicity from antineoplastic treatment remains a challenge in oncology. Cancer treatment-induced central nervous system (CNS) injury can be therapy-limiting, severely disabling, and even fatal. While emerging cancer immunotherapies have revolutionized oncology during the past decade, their immunomodulatory properties can cause immune-related adverse effects (IRAE) across organ systems, including the nervous system. Central neurologic IRAEs from chimeric antigen receptor T cells (CAR-T) and immune checkpoint inhibitors (ICPI) are challenging complications of such therapies.We aim to provide clinicians with a comprehensive review of the relevant forms of CAR-T and ICPI-associated CNS toxicity, focusing on clinical features of such complications, diagnostic workup, predictive biomarkers, and management considerations in affected patients. Recent findings Unique forms of CAR-T and ICPI-related CNS toxicity have been characterized in the recent literature. CAR-T-related neurotoxicity is common and clinically well delineated. ICPI-related CNS toxicity is relatively rare but includes a heterogenous spectrum of severe and diagnostically challenging conditions. While putative risk factors, neurotoxicity biomarkers, imaging correlates and treatment strategies have been put forward, development of tailored diagnostic and management consensus guidelines awaits further clinical investigation. Summary As CAR-T and ICPI become more widely adopted, early recognition, documentation, and management of immunotherapy-related CNS toxicity are of paramount importance in the clinical setting.

Background Traditionally, palliative care has focused on patients suffering from life-threatening somatic diseases such as cancer or progressive neurological disorders. In contrast, despite the often chronic, severely disabling, and potentially life-threatening nature of psychiatric disorders, there are neither palliative care units nor clinical guidelines on palliative measures for patients in psychiatry. Main text This paper contributes to the growing literature on a palliative approach in psychiatry and is based on the assumption that a change of perspective from a curative to a palliative approach could help promote patient-centeredness and increase quality of life for severely ill patients in psychiatry as well as in somatic medicine. To exemplify this, we offer three different clinical scenarios: severe and enduring anorexia nervosa, treatment-refractory schizophrenia, and chronic suicidality and persistent self-injury in borderline personality disorder. Conclusion We emphasize that many typical interventions for treatment-refractory psychiatric disorders may indeed be of a palliative nature. Furthermore, introducing traditional features of palliative care, e.g. so-called goals of care conversations, could aid even further in ensuring that caregivers, patients, and families agree on which treatment goals are to be prioritized in order to optimize quality of life in spite of severe, persistent mental disorder.

Oromandibular dystonia (OMD) is a severely disabling disorder with limited available therapies. Current oral medications for OMD are ineffective and may pose further risks of aspiration particularly in combination states of jaw and tongue dystonia. We advocate the use of Botulinum neurotoxin (BoNT) injection with proper muscle site selection and dosing as the most effective treatment in OMD clinically. Targeting muscle for injection should involve not only an astute clinical examination and understanding the patient’s history, but perhaps also guided by instrumentation. Based on our previous and present case series, we present specific localization techniques for BoNT in OMD patients subsequent to methodical patient selection, proper BoNT reconstitution and conversion. We believe adequate knowledge and appropriate technique will give our patients greatest benefit and will minimize risk of adverse events following treatment.

Neuromyelitis optica (NMO), considered to be mediated by autoantibodies, often cause severely disabling disorders of the central nervous system, and predominantly cause optic nerve damage and longitudinally extensive transverse myelitis. Remarkable progress has been made in deciphering NMO pathogenesis during the past decade. In 2015, the International Panel for NMO Diagnosis proposed the unifying term "NMO spectrum disorders" (NMOSD) and the updated NMOSD criteria reflects a wide range of disease and maintains reasonable specificity. Moreover, cumulative findings have indicated that NMOSD are frequently associated with multiple autoimmune diseases, thereby presenting complex clinical symptoms that make this disease more difficult to recognize. Notably, most neurologists do not heed these symptoms or comorbid conditions in patients with NMOSD. Whereas previous reviews have focused on pathogenesis, treatment, and prognosis in NMOSD, we summarize the present knowledge with particular emphasis on atypical manifestations and autoimmune comorbidities in patients with NMOSD. Furthermore, we emphasized the identification of these atypical characteristics to enable a broader and better understanding of NMOSD, and improve early accurate diagnosis and therapeutic decision making.

Parkinson's disease (PD) is an incurable, progressive neurological condition, with symptoms impacting movement, walking, and posture that eventually become severely disabling. Advanced PD (aPD) has a significant impact on quality-of-life (QoL) for patients and their caregivers/families. Levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of advanced levodopa-responsive PD with severe motor fluctuations and hyper-/dyskinesia when available combinations of therapy have not given satisfactory results.To determine the cost-effectiveness of LCIG vs standard of care (SoC) for the treatment of aPD patients.A Markov model was used to evaluate LCIG vs SoC in a hypothetical cohort of 100 aPD patients with severe motor fluctuations from an Irish healthcare perspective. Model health states were defined by HoehnYahr (HY) scale-combined with amount of time in OFF-time-and death. SoC comprised of standard oral therapy ± subcutaneous apomorphine infusion and standard follow-up visits. Clinical efficacy, utilities, and transition probabilities were derived from published studies. Resource use was estimated from individual patient-level data from Adelphi 2012 UK dataset, using Irish costs, where possible. Time horizon was 20 years. Costs and outcomes were discounted at 4%. Both one-way and probabilistic sensitivity analyses were conducted.The incremental cost-effectiveness ratio for LCIG vs SOC was €26,944/quality adjusted life year (QALY) (total costs and QALYs for LCIG vs SoC: €537,687 vs €514,037 and 4.37 vs 3.49, respectively). LCIG is cost-effective at a payer threshold of €45,000. The model was most sensitive to health state costs.LCIG is a cost-effective treatment option compared with SoC in patients with aPD.

Background Open reduction and internal fixation of distal humerus fractures is standard of care with good to excellent outcome for most patients. However, nonunions of the distal humerus still occur. These are severely disabling problems for the patient and a challenge for the treating physician. Fortunately, a combination of standard nonunion techniques with new plate designs and fixation methods allow even the most challenging distal humeral nonunion to be treated successfully. Questions/Purposes The purpose of this manuscript is to describe our current technique in treating distal humeral nonunion as it has evolved over the last four decades. We have now follow-up on 62 treated patients. Methods A few key steps are essential to obtain bone healing while regaining or preserving elbow motion. These include careful planning, extensile exposure, release of the ulnar nerve, capsular release and mobilization of the distal fragment, debridement, and finally stable fixation after alignment with application of bone graft. Results The vast majority of distal humeral nonunions can be treated successfully with open reduction and internal fixation. Conclusion Important components of the treatment plan are careful preoperative planning, extensile approach, debridement, and solid fixation with—locking—plates and liberal use of bone graft. Electronic supplementary material The online version of this article (doi:10.1007/s11420-017-9551-y) contains supplementary material, which is available to authorized users.

Background Migraine is a common and severely disabling neurological disorder affecting millions of patients in Europe. Despite the availability of evidence-based national and international guidelines, the management of migraine patients often remains poor, which is often attributed to a low availability of headache specialists. The aim of this study was to investigate the adherence to national guidelines and to assess the possible potential of optimized therapy regimens in migraine patients. Methods We collected data of migraine patients presenting to our out-patient clinic via standardized questionnaires regarding headache, diagnostics and experience with previous treatments. We also assessed the efficacy of treatment started by our center. Results 1,935 migraine patients were included between 2010 and 2018. In the 12 months before consulting our headache clinic 89.5% of the patients had consulted a general practitioner and 74.9% had consulted a neurologist because of their migraine. Nevertheless, 50% of the patients underwent unnecessary diagnostics and 34.2% had not been treated according to evidence-based treatment guidelines. Out of 1,031 patients who had not been prescribed a preventative treatment 627 (60.8%) had in average 3 or more migraine attacks per month and thus qualified for a preventative treatment. These patients missed in the 3 months prior to consultation on average 5 work or school days. Initiating a preventative treatment was effective in 71.2% of the patients, that provided follow-up data. Conclusions Our data suggest, that many migraine patients to this day do not receive state-of-the-art therapy. Adherence to national and international European guidelines could improve the outcome in migraine patients. Future research should try to answer why guidelines are not followed.

Background: Complex regional pain syndrome type-1 (CRPS-1) is a severely disabling painful disease challenging to treat. This multicenter, randomized, double-blind placebo-controlled trial examined the efficacy of intramuscular (i.m.) neridronate in CRPS-1 patients. Methods: A total of 78 patients diagnosed with CRPS-1 (aged 59.5 ± 10.3, 66.7% female) were randomly assigned to 25 mg (i.m.) neridronate ( N = 41) given once daily for 16 consecutive days or placebo control ( N = 37). Efficacy was assessed after 30 days using a visual analogue scale (VAS) pain score and the number of patients achieving ⩾50% reduction in VAS score. Change in clinical signs and symptoms, quality of life (QoL) using Short Form Health Survey (SF-36) and the McGill Pain Questionnaire were also assessed. Results: After 30 days, VAS score decreased significantly to a greater extent in neridronate-treated patients versus placebo (31.9 ± 23.3 mm versus 52.3 ± 27.8 mm, p = 0.0003). Furthermore, the proportion of patients achieving a VAS reduction of ⩾50% was greater in the neridronate group (65.9% versus 29.7%, p = 0.0017). Clinical signs and symptoms were improved significantly in the neridronate group versus placebo for edema (72.5% versus 79.9%, p = 0.03), pain during motion (70% versus 83.3%, p = 0.0009), allodynia (20% versus 63.3%, p = 0.0004), and hyperalgesia (20% versus 56.7%, p = 0.0023). Whereas no difference was observed for QoL measures using the SF-36 questionnaire, three of the four pain variables using the McGill Pain Questionnaire improved significantly in the neridronate group. No serious drug-related adverse events were reported during the study. Conclusion: In patients with acute CRPS-1, i.m. injections of 25 mg neridronate were associated with clinically relevant benefit compared with placebo controls. Trial registration: EU Clinical Trials Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001156-28

Adequate ligament balancing has a tremendous impact on successful total knee arthroplasty. In case of instability, severely disabling symptoms require revision surgery. Here we present a case of early total knee arthroplasty failure due to secondary valgus laxity, which was successfully treated with medial collateral ligament (MCL) reconstruction. For anatomical MCL reconstruction, a flattened semitendinosus autograft was used to reconstruct the superficial medial collateral and the posterior oblique ligament.

Idiopathic clubfoot has a tremendous worldwide prevalence. If left untreated, the deformity has severely disabling effects on mobility and quality of life. Given its prevalence and significance, numerous studies are published on this condition every year. In this article, we attempt to highlight important themes and findings of studies published on idiopathic clubfoot over the past 3 years.

Purpose To provide a review of the diagnostic criteria, pathophysiology, and potential treatments of the complications of migraine as identified by the International Classification of Headache Disorders 3β, with the exception of status migrainosus. Method Migraine with aura may be associated with the onset of rare, but significantly disabling neurological symptoms. This review provides an overview of the associated complications that may arise from migraine with aura. Conclusion The complications of migraine that arise from migraine aura are infrequently encountered in clinical practice; however, they can be severely disabling for patients. As these conditions are encountered, thorough diagnostic evaluation is necessary. In some cases, it may be difficult to find a consistently reliable therapeutic option for these patients; however, as more cases enter the literature, a greater understanding of these conditions and how to treat them may arise.

Cancers of the head and neck region are a severely disabling group of diseases with no method for early detection. Analysis of exhaled breath volatile organic compounds shows promise as biomarkers for early detection and disease monitoring. This article reviews breath analysis in the setting of head and neck cancer, with a practical focus on breath sampling techniques, detection technologies and valid data analysis methods. Title and abstract keyword searches were conducted on PubMed and Embase databases to identify English language studies without a time-period limitation. The main inclusion criteria were human studies comparing head and neck cancer patients to healthy controls using exhaled breath analysis. Multiple breath collection techniques, three major detection technologies and multiple data analysis methods were identified. However, the variability in techniques and lack of methodological standardization does not allow for adequate study replication or data pooling. Twenty-two volatile organic compounds identified in five studies have been reported to discriminate head and neck cancer patients from healthy controls. Breath analysis for detection of head and neck cancer shows promise as a non-invasive detection tool. However, methodological standardization is paramount for future research study design to provide the potential for translating these techniques into routine clinical use.

Hemarthroses and muscle bleeds are well-known and well-documented complications in pediatric and young adult hemophilia patients. In contrast, deep bleeds in atypical locations can be a diagnostic challenge, since clinicians and radiologists are often unfamiliar with their clinical and radiological features. Some atypical bleeds, however, can be life-threatening or severely disabling, highlighting the need for prompt, accurate diagnosis. Rare bleeds include central nervous system bleeds (including intracranial and spinal hematomas), urogenital bleeds, intra-abdominal bleeds (mesenteric and gastrointestinal wall hematomas) and pseudo tumors in unusual locations like the sinonasal cavities. Because clinical assessment can be difficult, clinicians and radiologists should be aware of the possibility of these rare complications in their hemophilia patients, so that they can avoid unnecessary invasive diagnostic and surgical procedures and institute prompt, appropriate treatment. The purpose of this review is to illustrate the imaging features of bleeds that occur in rare locations in young (i.e., children and young adults) patients with hemophilia to make the reader more familiar with these conditions.

Many clinical trials using gene therapy have shown significant therapeutic benefits and exceptional safety records. Increasing evidence is verifying the long sought-after promise that gene therapy will genetically 'cure' some severely disabling diseases. In particular, the first gene therapy bioproduct for RPE65-associated Leber's congenital amaurosis, which was approved by the US Food and Drug Administration in 2017, has provided tremendous encouragement to the field of gene therapy. Recent developments in genome editing technologies have significantly advanced our capability to precisely engineer genomes in eukaryotic cells. Programmable nucleases, particularly the CRISPR/Cas system, have been widely adopted in studies applying genome engineering therapy to ocular diseases with the hope of managing these diseases. In this review article, we summarize the current approaches that have been developed in the area of gene therapy for ocular disease. We also discuss the challenges and opportunities facing gene therapy for ocular diseases, as well as its prospects.

Acquired brain injury (ABI) is known to be severely disabling. On average, 40% of employees return to work (RTW) within two years after injury. There is, however, limited research on what might contribute to successful RTW.To examine factors that might impact the time-to first RTW for patients with ABI, participating in a RTW-program.The study was designed as a cohort study of patients on sick leave due to mild or moderate ABI (n = 137). The mean age of the patients was 51 years, and 58% were men. The most common diagnoses were stroke (75%) and traumatic brain injury (12%). Data were collected through questionnaires, and combined with register data on sickness absence. Survival analyses were used to analyse the effect of different variables on time to first RTW (full or partial), at one- and two-year follow-up.Generally, women (HR = 0.447; CI: 0.239-0.283) had higher RTW-rates than men, and patients with non-comorbid impairments returned to work earlier than patients with multiple impairments. Although not statistically significant, receiving individual consultations and participating in group-sessions were generally associated with a delayed RTW at both follow-up-times. The only service-related factor significantly associated with delayed RTW was meetings with the social insurance office (HR = 0.522; CI: 0.282-0.965), and only at one-year follow-up.Women and patients with non-comorbid impairments returned to work earlier than men and patients with multiple impairments. There seems to be an association between intense and long-lasting participation in the RTW program and prolonged time-to first-RTW, even after controlling for level of cognitive impairments and comorbidity. Implications for Rehabilitation Acquired brain injury (ABI) is known to be severely disabling, and persons with ABI often experience difficulties in regard to returning to work. This study provides information on prognostic factors that might contribute to return to work (RTW) for patients with acquired brain injury, both at the individual level, but also in regard to service and timing characteristics. Knowledge about such factors provide rehabilitation professionals with information about effective service components that might help patients with ABI to RTW, and thus makes it possible to adapt and adjust the services to the patient's situation. Furthermore, having more knowledge on factors that contribute to RTW gives clinics the opportunity to select patients that might benefit the most from these services, thereby making them more effective.

International audience; AbstractBackgroundFibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling, and life-shortening genetic disorder that causes the formation of heterotopic bone within soft connective tissue. Previous studies found that the FOP prevalence was about one in every two million lives. The aim of this study is to estimate the FOP prevalence in France by probabilistic record-linkage of 2 national databases: 1) the PMSI (Programme de médicalisation des systèmes d’information), an administrative database that records all hospitalization activities in France and 2) CEMARA, a registry database developed by the French Centres of Reference for Rare Diseases.ResultsUsing a capture-recapture methodology to adjust the crude number of patients identified in both data sources, 89 FOP patients were identified, which results in a prevalence of 1.36 per million inhabitants (CI95% = [1.10; 1.68]). FOP patients’ mean age was 25 years, only 14.9% were above 40 years, and 53% of them were males. The first symptoms – beside toe malformations- occurred after birth for 97.3% of them. Mean age at identified symptoms was 7 years and above 18 years for only 6.9% of patients. Mean age at diagnosis was 10 years, and above 18 years for 14.9% of the patients. FOP patients were distributed across France.ConclusionsDespite the challenge of ascertaining patients with rare diseases, we report a much higher prevalence of FOP in France than in previous studies elsewhere. We suggest that efforts to identify patients and confirm the diagnosis of FOP should be reinforced and extended at both national and European level.

Chronic migraine (CM) is a severely disabling neurological condition characterized by episodes of pulsating unilateral or bilateral headache. The United States Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox®) for the prophylactic treatment of CM in 2010. It has been shown that onabotulinumtoxinA is effective in the reduction of headache frequency and severity in patients with CM. Treatment is well tolerated by the patients. This review reports on the history of botulinum neurotoxin (BoNT) in CM and presents the current clinical evidence for the use of onabotulinumtoxinA in the treatment of CM.

Gait impairment in Parkinson's Disease (PD) is often severely disabling, yet frequently remains refractory to treatment. The locus coeruleus (LC) has diffuse noradrenergic projections that are thought to play a role in gait function. Enhancement of norepinephrine transmission may improve gait in some PD patients. We hypothesized that the severity of PD pathology, and more specifically, Lewy bodies and neuronal loss in the LC, would correlate with the severity of gait dysfunction in PD.Autopsy data from 51 patients, collected through the Morris K. Udall Parkinson's Disease Research Center, were correlated with clinical gait-related measures, including individual Unified Parkinson's Disease Rating Scale (UPDRS) Part II and III questions, total UPDRS Part III scores, and timed up-and-go speed (TUG).Neither the presence nor degree of Lewy body pathology in the LC on autopsy was associated with a higher UPDRS part III gait score. LC tau deposition and frontal Lewy body deposition were not correlated with any of the assessed gait measures. The degree of Lewy body pathology, independent of Braak stage, was positively associated with the severity of motor symptoms overall (UPDRS Part III total score).Neither the degree of Lewy body nor tau pathology in the LC is associated with severity of gait disorders in PD. This finding may have implications for targeted noradrenergic therapies in patients with refractory gait disorders.

Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

Obsessional slowness is regarded as an uncommon but severely disabling variant of obsessive-compulsive disorder. This paper examines the psychopathology, classification, pathophysiology and treatment of obsessional slowness. It argues that primary obsessional slowness does not require classification as a separate syndrome because it can be found to be secondary to recognised phenomena of obsessive-compulsive disorder or anankastic personality disorder. The treatment described in the literature is not thought to be successful in the long term, and controlled trials are required to evaluate new strategies and antidepressant medication.