Karlheinz Reiners

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Most patients with multiple sclerosis (MS) experience walking impairment during the course of their disease. From an MS patient's perspective, walking ability is the most important bodily function.1 Currently, sustained-release oral fampridine (fampridine-SR) is the only drug approved for the symptomatic treatment of walking disability due to MS. Fampridine is a potassium channel blocker that improves the impaired axonal conduction associated with CNS demyelination.2 However, only a subpopulation of MS patients with walking disability respond to fampridine.3 Herein, we prospectively evaluated whether pre-therapy motor-evoked potentials (MEP), reflecting pyramidal demyelination by an increased central motor conduction time (CMCT), are suited as a predictive therapeutic response marker.

Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.

Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B).

Introduction: Persistently elevated serum creatine kinase (CK) is frequently associated with predisposition to malignant hyperthermia (MH). We investigated whether a minimally invasive metabolic test is suitable to diagnose MH susceptibility among patients with hyperCKemia. Methods: Thirty‐nine participants were included: 10 were MH susceptible (MHS); 21 MH were non‐susceptible (MHN); and 8 had MHN with persistent hyperCKemia >500 U/L. Microdialysis probes were inserted into the vastus lateralis muscle, and halothane or caffeine was injected via an attached microtubing catheter. Lactate concentrations in dialysis samples were measured spectrophotometrically. Results: Baseline lactate did not differ between the groups. After local application of halothane or caffeine, a significant lactate increase was detected only in the MHS group. Conclusions: Test results were not influenced by hyperCKemia. To avoid risks and complications of a surgical muscle biopsy this microdialysis test might be a useful screening tool for MH susceptibility among patients with persistent CK elevation. Muscle Nerve 47: 677–681, 2013

Die Diagnostik peripherer Nervenschädigungen beruht bislang vor allem auf neurophysiologischen Untersuchungsverfahren. Technische Fortschritte im Bereich der Magnetresonanztomografie (MRT) ermöglichen zunehmend, die Magnetresonanz (MR)-Neurografie auch in der Abklärung von Erkrankungen des peripheren Nervensystems einzusetzen. Anhand experimenteller Untersuchungen wird dargestellt, wie die MR-Neurografie axonale und entmarkende Läsionen peripherer Nerven sichtbar machen kann. Im klinischen Einsatz kann die MR-Neurografie in Kombination mit neurophysiologischen Verfahren die Diagnosefindung bei fokalen Nervenläsionen im Rahmen von Engpass-Syndromen, traumatischen oder anderen Läsionen verbessern. Sie leistet insbesondere einen wertvollen Beitrag zur exakten Lokalisationsdiagnostik in Körperregionen, die der Elektrodiagnostik schwer zugänglich sind. Aber auch bei Polyneuropathien können durch die MR-Neurografie neue pathophysiologische Erkenntnisse gewonnen werden, wie anhand der diabetischen Neuropathie erläutert wird. The diagnostic work-up of peripheral neuropathies largely depends on neurophysiological investigations. Recently, progress in magnetic resonance imaging (MRI) has lead to new perspectives in the diagnostics of disorders of the peripheral nervous system (PNS). Experimental data show how MR neurography visualises axonal and demyelinating lesions of the PNS. In clinical use, difficult cases of focal nerve compres­sion, traumatic or inflammatory lesions can be solved by the combination of MR neurography and neurophysiology. In particular, the localisation of nerve lesions can be improved by MR techniques. Furthermore, MR neurography enables new insights in the pathophysiology of neuropathies which will be shown for diabetic polyneuropathy.

Trotz unklarer Evidenz scheint die minimal-invasive Hüftendoprothetik derzeit mit noch geringfügig höheren Komplikationsraten behaftet zu sein als die gebräuchlichen Standardverfahren. Eine der seltensten, jedoch schwerwiegendsten Komplikationen stellt die Nervenläsion dar. Durch eine präoperative Analyse der Risikofaktoren, eine genaue Kenntnis der Anatomie und der minimal-invasiven Techniken lässt sich das Risiko für Nervenschäden auf ein Minimum reduzieren. Bei eingetretenem Nervenschaden sind die ersten diagnostischen Schritte die Lokalisation der Läsion und eine Quantifizierung des Schädigungsmusters. Hierzu sollte umgehend eine klinische Erhebung des neurologischen Defizits erfolgen. Abgesehen von wenigen Fällen einer isolierten transienten Leitungsverzögerung oder kompletten Durchtrennung liegt meist ein kombiniertes Schädigungsmuster vor. So können gleichzeitig eine Störung der Leitungsfunktion (Neurapraxie) und eine strukturelle Nervenschädigung (Axonotmesis oder Neurotmesis) vorliegen. Da Denervierungszeichen im Elektromyogramm erst nach etwa einer Woche nachweisbar sind, ist es in den ersten Tagen nach der Läsion nicht möglich, die Prognose mit elektrophysiologischen Methoden verlässlich abzuschätzen. Die vorliegende Übersichtsarbeit soll als Leitfaden zur Prävention, Diagnostik und Therapie von Nervenläsionen bei minimal-invasiver Hüftendoprothetik dienen. Although there is no clear evidence, minimally invasive hip arthroplasty seems to be associated with slightly higher complication rates compared to standard procedures. Major nerve palsy is one of the least common but most distressing complications. The key for minimizing the incidence of nerve lesions is to analyze preoperative risk factors, accurate knowledge of the anatomy and minimally invasive techniques. Once clinical signs of nerve injury are evident, the first diagnostic steps are localization of the lesion and quantification of the damage pattern. Therefore, clinical assessment of the neurological deficits should be performed as soon as possible. Apart from rare cases of isolated transient conduction blockade or complete transection, the damage pattern is mostly combined. Thus, there can be evidence for dysfunction of nerve conduction (neuropraxia) and structural nerve damage (axonotmesis or neurotmesis) simultaneously. Because the earliest signs of denervation are detectable via electromyography after 1 week, it is not possible to make any reliable prognosis within the first days after nerve injury using electrophysiological methods. This review article should serve as a guideline for prevention, diagnostics and therapy of neural lesions in minimally invasive hip arthroplasty.