Objective measurement of oral function in adults with spinal muscular atrophy.

BACKGROUND: Impairment of bulbar function in adult individuals with spinal muscular atrophy (SMA) usually is not assessed by established motor scores. Measurements of oral function including quantitative muscle and endurance tests are able to detect subtle changes. The aim of this study was to systematically evaluate the measurement of maximum bite force and endurance, maximum tongue pressure and endurance, as well as maximum mouth opening in adult individuals with SMA types 2 and 3. METHODS: Data from oral function tests in 43 individuals were analyzed. Differences in oral function between individuals with different SMA types and numbers of SMN2 copies were tested. Spearman´s rho correlations among oral function measures themselves as well as with established clinical outcome scales were analyzed. RESULTS: The absolute maximum measures of oral function (maximum bite force, maximum tongue pressure, maximum mouth opening) were able to discriminate between individuals with different SMA types, individuals with a different number of SMN2 copies and with different walking abilities. The pairwise correlations of the absolute maximum measures of oral function were fair to moderate in size; the same was true for their correlations with the established motor scores. All correlations assessing endurance measures of oral function were weaker and statistically insignificant. CONCLUSIONS: Among the oral function tests maximum tongue pressure and maximum mouth opening are particulary promising as clinical and sensitive outcome measures for clinical trials. Oral function tests may supplement existing motor scores, in particular concerning specific questions about bulbar function or in severely affected non-ambulatory individuals where mild (treatment-related) changes would otherwise remain undetected. Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/search/de/trial/DRKS00015842.

[Congenital myasthenic syndromes in adulthood : Challenging, rare but treatable]. / Kongenitale myasthene Syndrome im Erwachsenenalter : Diagnostisch herausfordernd, selten, aber behandelbar.

The congenital myasthenic syndromes (CMS) represent a heterogeneous group of diseases with a broad spectrum of phenotypes. The common characteristic is an inherited genetic defect of the neuromuscular junction. Although in some patients the specific gene defect remains to be detected, the increasing identification of causative genes in recent years has already provided unique insights into the functionality of structural proteins at the neuromuscular junction. Neonatal and early childhood onset is observed in most CMS subtypes; however, late onset in adolescence or adulthood also occurs and establishing the diagnosis at these stages imposes particular challenges. To enable appropriate therapeutic interventions for an at least in principle treatable condition, determining the genetic cause is warranted. In this overview, the critical clinical and diagnostic features of the different CMS subtypes are presented and illustrated using typical cases. Furthermore, specific diagnostic clues are outlined. Finally, the overlap between CMS and muscular dystrophies is discussed. Illustrating characteristic patient examples, the essential clinical and additional diagnostic findings of various CMS subtypes and special diagnostic indications are presented.

Sensorimotor training and whole-body vibration training have the potential to reduce motor and sensory symptoms of chemotherapy-induced peripheral neuropathy-a randomized controlled pilot trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and clinically relevant side effect of chemotherapy. The symptoms diminish patients' quality of life and represent a decisive limiting factor for medical therapy. To date, effective treatment options are lacking. Specific exercise interventions have proven promising to target relevant symptoms. We conducted a prospective, four-armed, randomized, controlled trial, to evaluate the effects of sensorimotor training (SMT) and whole-body vibration training (WBV) on patients with CIPN. Participants (N = 40) were randomized to either one of two intervention groups (SMT N = 10 or WBV N = 10) or oncological control group (N = 10) and matched by gender and age with a healthy control (N = 10). The intervention groups exercised twice a week for 6 weeks. Primary endpoint was the reduction of CIPN-related symptoms (improve peripheral deep sensitivity, Achilles tendon reflex (ASR) and patellar tendon reflex (PSR), light-touch perception, sense of position, and lower leg strength). Secondary endpoints were nerve conduction velocity and amplitude, balance control, quality of life, and CIPN-related pain. Patients exercising improved sensory and associated motor symptoms. Significant intergroup differences were found for the tendon reflexes (ASR P = .017 and PSR P = .020), peripheral deep sensitivity (P = .010), and pain (P = .043). Furthermore, tendencies were found regarding the subjective improvement of symptoms (P = .075) and two subscales of the EORTC-QLQ-C30 questionnaire: pain (P = .054) and dyspnea (P = .054). The results for the SMT group were superior regarding the tendon reflexes, and a tendency regarding the subjective report of symptoms, while WBV was superior regarding pain. SMT and WBV behold a large potential to reduce CIPN-related symptoms and can be considered feasible and safe for patients with CIPN (compliance 97.5%, no adverse events).Registration: DRKS00013027.

["Therapy-resistant polymyositis" - is the diagnosis correct?] / "Therapierefraktäre Polymyositis" ­ stimmt die Diagnose?

We report the case of a 32-year-old woman with severely elevated serum creatine kinase (CK; 80,000 U/l) and progressive proximal pareses. As muscular biopsy showed inflammatory infiltrates, polymyositis was suspected and immunosuppressive treatment was initiated. However, clinical improvement could not be achieved. Gene sequencing of the DYSF-gene showed a previously unreported homozygous mutation. In summary, elevated serum CK and inflammatory infiltrates in the muscle biopsy are not specific for polymyositis, but may also occur in degenerative diseases (muscular dystrophy), such as dysferlinopathy.

[Chronic Inflammatory Demyelinating Polyneuropathy]. / Chronische inflammatorische demyelinisierende Polyneuropathie.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic progressive or relapsing autoimmune neuropathy with heterogeneous clinical presentation. Symptoms typically include symmetrical, proximal and/or distal paresis and sensory loss. Atypical CIDP variants are increasingly recognized, including subtypes with rapid onset as well as variants with pure sensory, focal or marked asymmetrical deficits. Diagnosis is established by compatible symptoms, characteristic electrophysiological features and cerebrospinal fluid analysis. In unequivocal cases, inflammatory infiltrates in sural nerve biopsy support the diagnosis. Recent studies suggest that diagnostic imaging techniques such as MRI and nerve ultrasound may become useful tools for establishing the diagnosis. First-line therapies include immunoglobulines, steroids, and plasmapheresis. Immunosuppressant agents and monoclonal antibodies are used in therapy-refractory cases or as cortison-saving agents.

Spinal cord injury without radiographic abnormality (SCIWORA) in adults: MRI type predicts early neurologic outcome.

OBJECTIVES: The present study aimed to analyse the clinical and neuroimaging features of a consecutive series of adult patients with spinal cord injury without radiographic abnormality (SCIWORA) receiving early magnetic resonance imaging (MRI), and to apply the recently proposed MRI classification system. METHODS: Grade of neurologic impairment at admission and discharge was reported according to the American Spinal Injury Association Impairment Scale (AIS). A detailed analysis and categorisation of the extra- and intramedullary MRI findings was performed, and the relationship between imaging type and neurological outcome was described. RESULTS: Twenty-six adult patients (17 male and 9 female) with SCIWORA were identified (mean age of 52 years). The distribution of the initial AIS grade was 8% A (n=2), 19% B (n=5), 31% C (n=8) and 42% D (n=11) at admission and 15% (n=4) C, 58% (n=15) D and 27% (n=7) E at discharge, respectively. Type I SCIWORA was found in 23% (n=6) and type II in 77% (n=20) (IIa: 0%, IIb: 25%, IIc: 75%). The mean improvement of AIS grade in patients with type I lesions was 1.5 (median 1, range 1-3) and 0.9 (median 1, range 0-3) in type II. CONCLUSION: The findings underline the prognostic role of early MRI for adult patients with SCIWORA and support the use of the recently introduced MRI classification system. LEVEL OF EVIDENCE: Prognostic study, level III.

[Chemotherapy-induced Peripheral Neuropathy]. / Chemotherapie-induzierte Polyneuropathie.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and relevant side effect of antineoplastic agents such as cisplatin, paclitaxel, vincristine and bortezomib. Over the last years, significant progress has been achieved in elucidating the underlying pathomechanisms of CIPN using both in vivo and in vitro models. These studies suggest that mitochondrial toxicity, disturbed axonal transport, toxic effects on Schwann cells and activation of the immune system contribute to the pathogenesis of CIPN. This review provides an overview of the current pathogenetic concepts of CIPN. In addition, experimental approaches that aim at preventing or ameliorating neurotoxic effects of antineoplastic agents are discussed.

[25-year old patient with angina pectoris during religious fasting]. / 25-jähriger Patient mit pektanginösen Beschwerden während des muslimischen Fastenmonats.

UNLABELLED: HISTORY AND PRESENTATION AT ADMISSION: A 25-year-old male patient presented with acute left sided chest pain. The patient reported no physical exercise but daytime fasting (with neither food nor liquid intake) which he had started several days before. INVESTIGATIONS: ECG, echocardiography and chest X-ray were normal, but blood examination revealed elevated levels for creatine kinase (CK) and lactate dehydrogenase (LDH). Ischemic lactate ammonia test revealed no increase of lactate during exercise. Muscle biopsy confirmed suspected diagnosis of glycogen storage disease type V (McArdle's disease). TREATMENT AND COURSE: As causal treatments are unavailable for McArdle's disease, careful counselling regarding adequate exercise and regular, carbohydrate rich nutrition are mandatory to ameliorate symptoms. CONCLUSION: McArdle's disease represents a rare differential diagnosis of cardiac chest pain and somatoform myalgic complaints. When taking the patient's history, questions regarding the "Second wind"-phenomenon are helpful for initiating the adequate investigations early on.

[Differential diagnostics of diseases of the brachial plexus]. / Differenzialdiagnose von Erkrankungen des Plexus brachialis.

Progressive, atrophic, asymmetrically distributed flaccid paresis of arm and hand muscles represents a frequent symptom of neuromuscular diseases that can be attributed to injury of the arm nerves, the plexus or the cervical roots. A timely and exact diagnosis is mandatory; however, the broad spectrum of differential diagnoses often represents a diagnostic challenge. A large variety of neuromuscular disorders need to be considered, encompassing autoimmune mediated inflammatory neuropathic conditions, such as multifocal motor neuropathy, as well as chronic degenerative and nerve compression disorders. This review provides an overview of the most frequent disorders of the upper plexus and cervical roots and summarizes the characteristic clinical features as well as electrodiagnostic and laboratory test results. In addition the diagnostic value of magnetic resonance imaging and sonography is discussed.

[Thrombolysis for acute stroke--a nationwide analysis of regional medical care]. / Thrombolyse des akuten Schlaganfalls--Eine deutschlandweite Analyse der regionalen Versorgung.

BACKGROUND: This study aims at investigating ischaemic stroke therapy in Germany by using secondary data. The focus lies on the performance of thrombolysis. METHODS: Statutory quality report data for 2010 were obtained. All hospitals (n = 1302) treating patients suffering from an ischaemic stroke either on a neurological, internal, geriatric or intensive care unit were analysed. The treatment situation, defined as the experience in performing thrombolysis, was displayed cartographically. Potential variables that may influence the thrombolysis rate were analysed. RESULTS: 78 % of the 198,500 ischaemic stroke cases were treated on a ward specialised in the stroke treatment (i. e., a stroke unit). The mean thrombolysis rate in neurological departments was 9.1 %. Thrombolysis rates between departments ranged from 0 to 38 %. Significant factors influencing the thrombolysis rate were the total number of ischaemic strokes treated as well as the existence of a stroke unit. DISCUSSION: In Germany, to date regional differences in the treatment of ischaemic stroke exist. Experience in the treatment of ischaemic stroke patients and the availability of a stroke unit both increase the thrombolysis rate. Data suggest that in Germany there is still room for improvement of appropriate ischaemic stroke treatment.

A case of relapsing-remitting neuroborreliosis? Challenges in the differential diagnosis of recurrent myelitis.

We report the case of a 31-year-old woman with 4 episodes of myelitis with pleocytosis, a positive Borrelia burgdorferi serology with positive antibody indices, and full recovery each time after antibiotic and steroid treatment, suggesting neuroborreliosis. We nevertheless believe that recurrent neuroborreliosis is improbable based on the levels of the chemokine CXCL13 in cerebrospinal fluid and favor the diagnosis of post-infectious autoimmune-mediated transverse myelitis possibly triggered by an initial neuroborreliosis as the cause of the relapses observed in our patient. We demonstrate the diagnostic steps and procedures which were important in the differential diagnosis of this unusual and challenging case.

[Guillain-Barré syndrome after exposure to influenza]. / Guillain-Barré-Syndrom nach Exposition mit Influenza.

Guillain-Barré Syndrome (GBS) is an acquired, monophasic inflammatory polyradiculoneuritis of autoimmune origin, which occurs after infection and occasionally also after vaccination. Seasonal and pandemic influenza vaccines have in particular been implicated as triggers for GBS. However, a number of recent studies indicate that infection with influenza virus may also cause GBS. This review summarizes the epidemiological and experimental data of the association of GBS with exposure to influenza antigens by immunization (including vaccines against A/H1N1/2009) and infection. Vaccination against influenza is associated with a very low risk for the occurrence of GBS. In contrast infection with influenza may play a more important role as a triggering factor for GBS than previously assumed.

Central nervous system involvement in patients with monoclonal gammopathy and polyneuropathy.

BACKGROUND AND PURPOSE: To evaluate clinical presentation of patients with the clinical triad of monoclonal gammopathy, polyneuropathy and signs of CNS involvement. METHODS: Nineteen patients with monoclonal protein (M-protein, 9 IgM, 10 IgG) were studied. Clinical examination, MRI, cerebrospinal fluid analysis and immune reactivity against myelin-associated glycoprotein and gangliosides in serum were obtained. By immunohistochemistry, different binding patterns of M-proteins to human CNS tissue were investigated. RESULTS: Nine out of 19 patients (four IgM, five IgG) showed one or more clinical signs of CNS involvement. Clinical features associated with signs of CNS pathology were disease duration and greater concentration of IgM paraprotein. The IgM M-protein of two patients strongly stained the cortex/cerebellar neurons in human brain sections. CONCLUSION: Our results complement previous reports that some patients with monoclonal gammopathy and polyneuropathy can develop solitary or disseminated signs of CNS involvement. It indicates that pathological effects of M-proteins are not necessarily restricted to the peripheral nervous system. The specificity and affinity of circulating M-protein to antigens in the CNS might be critical for the development of different clinical phenotypes.

Leopold Ordenstein: on paralysis agitans and multiple sclerosis.

In 1868 the German Leopold Ordenstein (1835-1902) published in Paris a doctoral thesis in French language under the patronage of Jean-Martin Charcot (1825-1893). For the first time, multiple sclerosis and Parkinson's disease were clearly recognized as different clinical entities, based on clinical and pathological data. Ordenstein's work represents today a fundamental and often credited, yet still widely unknown, contribution to the history of these two diseases. The present paper delivers a synopsis of this key document. In addition, the life and work of Leopold Ordenstein will be reviewed.

[Plasma exchange as a therapeutic option in neurological disorders]. / Plasmaaustausch als Therapieoption bei neurologischen Erkrankungen.

Plasma exchange is a therapeutic procedure commonly used in various neurological disorders. Here we review its current role as a treatment option in diseases of the central and peripheral nervous system.

[Multiple sclerosis: potential therapeutic options and update of ongoing studies]. / Multiple Sklerose: potenzielle Therapieansätze und Update laufender Studien.

The therapeutic options for the treatment of multiple sclerosis (MS) have experienced enormous progress over recent years. Despite these encouraging developments, available therapies are only partially effective, and the ultimate goal of curing MS is still far from being attained. The improved understanding of the cellular and molecular mechanisms of MS (immune) pathogenesis together with recent shifts in paradigms led to a variety of new therapeutic targets and approaches. In addition to modulation of the inflammatory process, therapeutic approaches focussing on active neuroprotection, remyelinization, and regeneration have become increasingly important. Based on current concepts of the MS pathogenesis, this article summarizes new therapeutic approaches. Substances and strategies currently tested in clinical trials are reviewed.

[Jean-Martin Charcot in German neurology]. / Jean-Martin Charcot im Spiegel der deutschen Nervenheilkunde.

Jean-Martin Charcot (1825-1893), well known as the founder of modern neurology, was the most celebrated neurologist in the nineteenth century. His international success stemmed not only from mastery descriptions of various neurological disorders but also from his many contacts with scientists all over the world. The aim of this article is to review Charcot's ambivalent relationship to German neuropsychiatry of the time and to examine the German reception of his personality and work. Wilhelm Erb, Ludwig Hirt, Ernst von Leyden, Max Nonne, Adolph Strümpell, and other German physicians cultivated -to varying degrees - professional contacts with Charcot and, based on the fascination of his personality and significance of his work, were long and intensively influenced by the Salpêtrière school. The extent of their admiration became apparent in 1882 by the award of an honorary doctorate to Charcot by the University of Würzburg. Along with increasingly severe criticism of Charcot's research on hysteria and hypnosis, most German neuropsychiatrists became estranged, without neglecting his importance to the development of neurology in Germany.