Hoffmann’s syndrome in the differential work-up of myopathic complaints: a case report

Abstract Background Hoffmann’s syndrome is a rare form of hypothyroid myopathy in adults, which is mainly characterized by muscular weakness and muscular pseudohypertrophy. Case presentation We report about a 61-year-old Western European man with myalgia, myxedema and pseudohypertrophy of the calf muscles. Laboratory tests revealed significantly elevated thyroid stimulating hormone (TSH) and creatine kinase (CK). Muscle MRI showed muscular hypertrophy of the lower limbs, but no signs of myositis or myopathy (no gadolinium enhancement, no edema, no fatty degeneration). In addition, electromyography (EMG) detected spontaneous activity. After the beginning of thyroxin-therapy it took six months until the muscle weakness improved and the myalgia regressed. Conclusions Here, we focus on diagnostic routines and typical findings to differentiate Hoffmann’s syndrome from other myopathies. Clinical hallmarks of Hoffmann’s syndrome are pseudohypertrophy and weakness of the calf muscles in combination with elevated CK and elevated TSH. EMG is well suited to detect the involvement of the muscles and muscle MRI helps to differentiate it from other myopathies. Hoffmann’s syndrome is a rare myopathy due to hypothyroidism and plays a role in the differential diagnosis of myopathic complaints even if hypothyroidism has not been detected before

Electrodiagnostic Testing and Nerve Ultrasound of the Carpal Tunnel in Patients with Type 2 Diabetes

In diabetic patients, controversies still exist about the validity of electrodiagnostic and nerve ultrasound diagnosis for carpal tunnel syndrome (CTS). We analyzed 69 patients with type 2 diabetes. Nerve conduction studies and peripheral nerve ultrasound of the median nerve over the carpal tunnel were performed. CTS symptoms were assessed using the Boston Carpal Tunnel Questionnaire. Polyneuropathy was assessed using the Neuropathy Symptom Score and the Neuropathy Disability Score. Although 19 patients reported predominantly mild CTS symptoms, 37 patients met the electrophysiological diagnosis criteria for CTS, and six patients were classified as severe or extremely severe. The sonographic cross-sectional area (CSA) of the median nerve at the wrist was larger than 12 mm2 in 45 patients (65.2%), and the wrist-to-forearm-ratio was larger than 1.4 in 61 patients (88.4%). Receiver operating characteristic analysis showed that neither the distal motor latency, the median nerve CSA, nor the wrist-to-forearm-ratio could distinguish between patients with and without CTS symptoms. Diagnosis of CTS in diabetic patients should primarily be based upon typical clinical symptoms and signs. Results of electrodiagnostic testing and nerve ultrasound have to be interpreted with caution and additional factors have to be considered especially polyneuropathy, but also body mass index and hyperglycemia

The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies

Abstract A relevant number of cancer patients who receive potentially neurotoxic cytostatic agents develop a chemotherapy-induced peripheral neuropathy over time. Moreover, the increasing use of immunotherapies and targeted agents leads to a raising awareness of treatment-associated peripheral neurotoxicity, e.g., axonal and demyelinating neuropathies such as Guillain–Barré-like syndromes. To date, the differentiation of these phenomena from concurrent neurological co-morbidities or (para-)neoplastic nerve affection as well as their longitudinal monitoring remain challenging. Neuromuscular ultrasound (NMUS) is an established diagnostic tool for peripheral neuropathies. Performed by specialized neurologists, it completes clinical and neurophysiological diagnostics especially in differentiation of axonal and demyelinating neuropathies. No generally approved biomarkers of treatment-induced peripheral neurotoxicity have been established so far. NMUS might significantly extend the repertoire of diagnostic and neuromonitoring methods in this growing patient group in short term. In this article, we present enlargements of the dorsal roots both in cytostatic and in immunotherapy-induced neurotoxicity for the first time. We discuss related literature regarding new integrative applications of NMUS for cancer patients by reference to two representative case studies. Moreover, we demonstrate the integration of NMUS in a diagnostic algorithm for suspected peripheral neurotoxicity independently of a certain cancer treatment regimen emphasizing the emerging potential of NMUS for clinical routine in this interdisciplinary field and prospective clinical trials

Additional file 1 of The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies

Additional file 1. Table S1: Detailed NMUS measurements of the presented patients

Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease

OBJECTIVE: To determine the diagnostic performance and prognostic value of phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) in CSF as possible biomarkers for amyotrophic lateral sclerosis (ALS) at the diagnostic phase. METHODS: We measured CSF pNfH and NfL concentrations in 220 patients with ALS, 316 neurologic disease controls (DC), and 50 genuine disease mimics (DM) to determine and assess the accuracy of the diagnostic cutoff value for pNfH and NfL and to correlate with other clinical parameters. RESULTS: pNfH was most specific for motor neuron disease (specificity 88.2% [confidence interval (CI) 83.0%-92.3%]). pNfH had the best performance to differentially diagnose patients with ALS from DM with a sensitivity of 90.7% (CI 84.9%-94.8%), a specificity of 88.0% (CI 75.7%-95.5%) and a likelihood ratio of 7.6 (CI 3.6-16.0) at a cutoff of 768 pg/mL. CSF pNfH and NfL levels were significantly lower in slow disease progressors, however, with a poor prognostic performance with respect to the disease progression rate. CSF pNfH and NfL levels increased significantly as function of the number of regions with both upper and lower motor involvement. CONCLUSIONS: In particular, CSF pNfH concentrations show an added value as diagnostic biomarkers for ALS, whereas the prognostic value of pNfH and NfL warrants further investigation. Both pNfH and NfL correlated with the extent of motor neuron degeneration. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that elevated concentrations of CSF pNfH and NfL can accurately identify patients with ALS.status: publishe

Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial

Background Rasagiline, a monoamine oxidase B inhibitor with neuroprotective potential in Parkinson's disease, has shown a disease-modifying effect in the SOD1-Gly93Ala low-expressing mouse model of amyotrophic lateral sclerosis, both alone and in combination with riluzole. We sought to test whether or not rasagiline 1 mg/day can prolong survival in patients with amyotrophic lateral sclerosis also receiving riluzole. Methods Patients with possible, probable, or definite amyotrophic lateral sclerosis were enrolled to our randomised, placebo-controlled, parallel-group, double-blind, phase 2 trial from 15 German network for motor neuron diseases (MND-NET) centres (university hospitals or clinics). Eligible patients were aged at least 18 years, had onset of progressive weakness within the 36 months before the study, had disease duration of more than 6 months and less than 3 years, and had a best-sitting slow vital capacity of at least 50%. After a 4-week screening period, eligible patients were randomly assigned (1:1) to receive either rasagiline (1 mg/day) or placebo in addition to riluzole (100 mg/day), after stratification for site of onset (bulbar or spinal) and study centre. Patients and all personnel assessing outcome parameters were masked to treatment allocation. Patients were followed up 2, 6, 12, and 18 months after randomisation. The primary endpoint was survival time, defined as the time to death or time to study cutoff date (ie, the last patient's last visit plus 14 days). Analyses of primary outcome and safety measures were done in all patients who received at least one dose of trial treatment (intention-to-treat population). The trial is registered with ClinicalTrials.gov, number NCT01879241. Findings Between July 2, 2013, and Nov 11, 2014, 273 patients were screened for eligibility, and 252 patients were randomly assigned to receive rasagiline (n=127) or placebo (n=125). 126 patients taking rasagiline and 125 taking placebo were included in the intention-to-treat analysis. For the primary outcome, the survival probability at the end of the study was 0.43 (95% CI 0.25-0.59) in the rasagiline group (n=126) and 0.53 (0.43-0.62) in the placebo group (n=125). The estimated effect size (hazard ratio) was 0.91 (one-sided 97.5% CI -infinity to 1.34; p=0.31). Rasagiline was well tolerated, and most adverse events were due to amyotrophic lateral sclerosis disease progression rather than treatment; the most frequent of these were dysphagia (32 [25%] taking rasagiline vs 24 [19%] taking placebo) and respiratory failure (25 [20%] vs 31 [25%]). Frequency of adverse events were comparable between both groups. Interpretation Rasagiline was safe in patients with amyotrophic lateral sclerosis. There was no difference between groups in the primary outcome of survival, although post-hoc analysis suggested that rasagiline might modify disease progression in patients with an initial slope of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised greater than 0.5 points per month at baseline. This should be confirmed in another clinical trial. Copyright (C) 2018 Elsevier Ltd. All rights reserved