Blood-CSF barrier integrity in amyotrophic lateral sclerosis.

The integrity of the blood-CSF barrier plays a major role in inflammation, but also in shielding the central nervous system from external and systemic - potentially toxic - factors. Here we report results of measurements of the albumin quotient - which is thought to mirror the integrity of the blood/CSF barrier - in 1059 amyotrophic lateral sclerosis patients. The results were compared with groups of patients suffering from Alzheimer´s disease, facial palsy and tension headache. The albumin quotient, an accepted measure of the blood/CSF barrier integrity, was not significantly different from control populations. In addition, we found that the albumin quotient correlated with survival of the patients; this effect was mainly driven by male patients and influenced by age, BMI and diabetes mellitus. We conclude that the blood/CSF barrier is intact in this large cohort of ALS patients and that the albumin quotient correlates with survival. Whether this is important for the pathogenesis of the disease, requires mechanistic studies.

[Expert recommendations for magnetic resonance imaging of muscle disorders]. / Expertenempfehlung zur Magnetresonanztomographie bei Muskelerkrankungen.

BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.

Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS.

OBJECTIVE: Elevated levels of neurofilament light (NfL) and heavy (NfH) chain in amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) and serum reflect neuro-axonal degeneration and are used as diagnostic biomarkers. However, studies comparing the differential diagnostic potential for ALS of all four parameters are missing. Here, we measured serum NfL/NfH and CSF NfL/NfH in a large cohort of ALS and other neurological disorders and analysed the differential diagnostic potential. METHODS: In total CSF and serum of 294 patients were analysed. The diagnostic groups comprised: ALS (n=75), frontotemporal lobar degeneration (FTLD) (n=33), Alzheimer's disease (n=20), Parkinson's disease (dementia) (n=18), Creutzfeldt-Jakob disease (n=11), non-neurodegenerative controls (n=77) (Con) and 60 patients who were seen under the direct differential diagnosis of a patient with ALS (Con.DD). RESULTS: CSF and serum NfL and NfH showed significantly increased levels in ALS (p<0.0001) compared with Con and Con.DD. The difference between ALS and FTLD was markedly stronger for NfH than for NfL. CSF and serum NfL demonstrated a stronger correlation (r=0.84 (95% CI 0.80 to 0.87), p<0.001) than CSF and serum NfH (r=0.68 (95% CI 0.61 to 0.75), p<0.0001). Comparing ALS and Con.DD, receiver operating characteristic analysis revealed the best area under the curve (AUC) value for CSF NfL (AUC=0.94, 95% CI 0.91 to 0.98), followed by CSF NfH (0.93, 95% CI 0.88 to 0.98), serum NfL (0.93, 95% CI 0.89 to 0.97) and serum NfH (0.88, 95% CI 0.82 to 0.94). CONCLUSION: Our results demonstrate that CSF NfL and NfH as well as serum NfL are equally suited for the differential diagnosis of ALS, whereas serum NfH appears to be slightly less potent.

Familial Cerebellar Ataxia and Amyotrophic Lateral Sclerosis/Frontotemporal Dementia with DAB1 and C9ORF72 Repeat Expansions: An 18-Year Study.

BACKGROUND: Coding and noncoding repeat expansions are an important cause of neurodegenerative diseases. OBJECTIVE: This study determined the clinical and genetic features of a large German family that has been followed for almost 2 decades with an autosomal dominantly inherited spinocerebellar ataxia (SCA) and independent co-occurrence of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). METHODS: We carried out clinical examinations and telephone interviews, reviewed medical records, and performed magnetic resonance imaging and positron emission tomography scans of all available family members. Comprehensive genetic investigations included linkage analysis, short-read genome sequencing, long-read sequencing, repeat-primed polymerase chain reaction, and Southern blotting. RESULTS: The family comprises 118 members across seven generations, 30 of whom were definitely and five possibly affected. In this family, two different pathogenic mutations were found, a heterozygous repeat expansion in C9ORF72 in four patients with ALS/FTD and a heterozygous repeat expansion in DAB1 in at least nine patients with SCA, leading to a diagnosis of DAB1-related ataxia (ATX-DAB1; SCA37). One patient was affected by ALS and SCA and carried both repeat expansions. The repeat in DAB1 had the same configuration but was larger than those previously described ([ATTTT]≈75 [ATTTC]≈40-100 [ATTTT]≈415 ). Clinical features in patients with SCA included spinocerebellar symptoms, sometimes accompanied by additional ophthalmoplegia, vertical nystagmus, tremor, sensory deficits, and dystonia. After several decades, some of these patients suffered from cognitive decline and one from additional nonprogressive lower motor neuron affection. CONCLUSION: We demonstrate genetic and clinical findings during an 18-year period in a unique family carrying two different pathogenic repeat expansions, providing novel insights into their genotypic and phenotypic spectrums. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Pattern of paresis in ALS is consistent with the physiology of the corticomotoneuronal projections to different muscle groups.

OBJECTIVE: A recent neuroanatomical staging scheme of amyotrophic lateral sclerosis (ALS) indicates that a cortical lesion may spread, as a network disorder, both at the cortical level and via corticofugal tracts, including corticospinal projections providing direct monosynaptic input to α-motoneurons. These projections are involved preferentially and early in ALS. If these findings are clinically relevant, the pattern of paresis in ALS should primarily involve those muscle groups that receive the strongest direct corticomotoneuronal (CM) innervation. METHODS: In a large cohort (N=436), we analysed retrospectively the pattern of muscle paresis in patients with ALS using the UK Medical Research Council (MRC) scoring system; we subsequently carried out two independent prospective studies in two smaller groups (N=92 and N=54). RESULTS: The results indicated that a characteristic pattern of paresis exists. When pairs of muscle groups were compared within patients, the group known to receive the more pronounced CM connections was significantly weaker. Within patients, there was greater relative weakness (lower MRC score) in thumb abductors versus elbow extensors, for hand extensors versus hand flexors and for elbow flexors versus elbow extensors. In the lower limb, knee flexors were relatively weaker than extensors, and plantar extensors were weaker than plantar flexors. CONCLUSIONS: These findings were mostly significant (p<0.01) for all six pairs of muscles tested and provide indirect support for the concept that ALS may specifically affect muscle groups with strong CM connections. This specific pattern could help to refine clinical and electrophysiological ALS diagnostic criteria and complement prospective clinicopathological correlation studies.

Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis.

OBJECTIVE: To determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS). METHODS: This single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer's disease, 19 with Parkinson's disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology. RESULTS: Serum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time. CONCLUSIONS: Serum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.

Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression.

OBJECTIVES: Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). METHODS: Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con). CHIT1 and neurofilament levels were determined in cerebrospinal fluid (CSF) and blood and analysed with regard to diagnostic sensitivity and specificity and prognostic performance. Additionally, postmortem tissue was analysed for CHIT1 expression. RESULTS: In ALS, CHIT1 CSF levels were higher compared with Con (p<0.0001), DCo (p<0.05) and neurodegenerative diseases (AD p<0.05, PD p<0.01, FTLD p<0.0001) except CJD. CHIT1 concentrations were correlated with ALS disease progression and severity but not with the survival time, as did neurofilaments. Serum CHIT1 levels were not different in ALS compared with any other study group. In the spinal cord of patients with ALS, but not Con, AD or CJD cases, CHIT1 was expressed in the corticospinal tract and CHIT1 staining colocalised with markers of microglia (IBA1) and macrophages (CD68). CONCLUSIONS: CHIT1 concentrations in the CSF of patients with ALS may reflect the extent of microglia/macrophage activation in the white matter of the spinal cord. CHIT1 could be a potentially useful marker for differential diagnosis and prediction of disease progression in ALS and, therefore, seems suitable as a supplemental marker for patient stratification in therapeutic trials.

Amyotrophic lateral sclerosis and denervation alter sphingolipids and up-regulate glucosylceramide synthase.

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. Growing evidence suggests a link between changes in lipid metabolism and ALS. Here, we used UPLC/TOF-MS to survey the lipidome in SOD1(G86R) mice, a model of ALS. Significant changes in lipid expression were evident in spinal cord and skeletal muscle before overt neuropathology. In silico analysis also revealed appreciable changes in sphingolipids including ceramides and glucosylceramides (GlcCer). HPLC analysis showed increased amounts of GlcCer and downstream glycosphingolipids (GSLs) in SOD1(G86R) muscle compared with wild-type littermates. Glucosylceramide synthase (GCS), the enzyme responsible for GlcCer biosynthesis, was up-regulated in muscle of SOD1(G86R) mice and ALS patients, and in muscle of wild-type mice after surgically induced denervation. Conversely, inhibition of GCS in wild-type mice, following transient peripheral nerve injury, reversed the overexpression of genes in muscle involved in oxidative metabolism and delayed motor recovery. GCS inhibition in SOD1(G86R) mice also affected the expression of metabolic genes and induced a loss of muscle strength and morphological deterioration of the motor endplates. These findings suggest that GSLs may play a critical role in ALS muscle pathology and could lead to the identification of new therapeutic targets.

Hypothalamic atrophy is related to body mass index and age at onset in amyotrophic lateral sclerosis.

OBJECTIVE: Our objective was to study the hypothalamic volume in a cohort of patients with amyotrophic lateral sclerosis (ALS) including symptomatic and presymptomatic ALS mutation carriers. METHODS: High-resolution three-dimensional T1-weighted MRI datasets from 251 patients with sporadic ALS, 19 symptomatic and 32 presymptomatic ALS mutation carriers and 112 healthy controls (HC) were retrospectivally registered for manual delineation of the hypothalamus. The volume of the hypothalamus, in total or subdivided, was normalised to the intracranial volume and adjusted to age. Correlation analyses were performed with clinical and metabolic outcomes. Pathologically defined ALS stages were determined in vivo by diffusion tensor imaging (DTI). RESULTS: We observed a severe atrophy of the hypothalamus both in patients with sporadic ALS (-21.8%, p<0.0001) and symptomatic ALS mutation carriers (-13.4%, p<0.001). The atrophy in patients with sporadic ALS was observed in both the anterior (-27.6% p<0.0001) and the posterior parts of the hypothalamus (-17.7%, p<0.0001). Notably, this atrophy was also observed in presymptomatic ALS mutation carriers (-15.5%, p<0.001) and was unrelated to whole brain volume atrophy or disease stage as assessed using DTI or functional status. Hypothalamic volume was correlated with body mass index (BMI) in patients with sporadic ALS (p=0.0434, ρ=+0.1579), and this correlation was much stronger in patients with familial ALS (fALS) (p=0.0060, ρ=+0.6053). Anterior hypothalamic volume was correlated with age at onset, but not with survival after MRI. CONCLUSIONS: Hypothalamus is atrophied in ALS, even in premorbid stages, and correlates with BMI, especially in fALS. Decreased anterior hypothalamic volume is associated with earlier onset of disease.

The concept and diagnostic criteria of primary lateral sclerosis.

OBJECTIVES: Primary lateral sclerosis (PLS) is commonly considered as a motor neuron disease (MND) variant which almost exclusively affects upper motor neurons (UMN). There is still no consensus whether PLS should be regarded as an independent disease entity separate from amyotrophic lateral sclerosis (ALS) or as a comparatively slowly progressive variant of ALS. Given these different views, clinical diagnosis of PLS is a challenge. In this multicenter study, we analyzed clinical features of patients diagnosed with PLS in four specialized MND centers. MATERIAL AND METHODS: We retrospectively analyzed clinical, laboratory, imaging, and electrophysiological data of 76 patients with PLS diagnosed in four specialized ALS centers. We analyzed the concept of the disease based on our findings and an extensive review of the literature. RESULTS: We found that 79% of patients showed asymmetrical symptoms, 60% showed clinical or electrophysiological signs of lower motor neuron (LMN) involvement after a mean of 8.4 ± 5.0 years, and extrapyramidal and/or non-motoric symptoms were frequently observed. Interestingly, none of the patients diagnosed with PLS fulfilled the diagnostic criteria proposed by Pringle et al. in 1992. CONCLUSIONS: Our data show that PLS as a disease entity is still not well enough defined and that there are different concepts about its clinical presentation. We believe that further prospective longitudinal studies are needed in order to refine diagnostic criteria to reflect current clinical practice. Furthermore, neuropathological and neuroimaging approaches might help to arrange PLS in the MND spectrum and its classification.

Life course body mass index and risk and prognosis of amyotrophic lateral sclerosis: results from the ALS registry Swabia.

Weight loss appears as a strong predictor of survival of patients with amyotrophic lateral sclerosis, yet no data are currently available to describe the life course history of pre-diagnostic body mass index (BMI) in these patients. 393 ALS cases (mean age: 65.8 years, 57.3% men) and 791 controls matched by age and sex from a population-based case-control study of the ALS Registry Swabia were analyzed. Differences of BMI change in cases and controls over time were modeled using a multilevel additive model. In addition, survival in ALS cases by BMI change was modeled using an accelerated failure time model adjusted for prognostic factors. In ALS cases, BMI was consistently higher than in controls in the 20-70 years before the interview. Conditional logistic regression revealed an odds ratio of 1.05 (95% confidence interval (CI) 1.00-1.11, p = 0.041) per 1 kg/m2 higher BMI 35-45 years before interview. However, a sharp decrease was evident in the BMI of ALS cases about 10 years before disease onset. Moreover, weight loss was strongly associated with shorter survival in ALS patients. Illustrating this, patients with stable weight showed a median survival time of 22.1 (95%-CI 19.2-25.0) months, as compared to 13.4 (95%-CI 10.5-16.3) months for patients with weight loss of 2.5 kg/m2 over the last 3 months before the interview. Thus, alterations in body weight are present in ALS patients already decades before clinical manifestation of ALS, while weight loss precedes motor symptoms of several years and is associated with poor prognosis.

Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients.

OBJECTIVES: Biomarkers for the diagnosis of motoneuron diseases (MND) are urgently needed to improve the diagnostic pathway, patient stratification and monitoring. The aim of this study was to validate candidate markers for MND in cerebrospinal fluid (CSF) and specify cut-offs based on large patient cohorts by especially considering patients who were seen under the initial differential diagnosis (MND mimics). METHODS: In a prospective study, we investigated CSF of 455 patients for neurofilament light chain (NfL), phosphorylated heavy chain (pNfH), tau protein (Tau) and phospho-tau protein (pTau). Analysed cohorts included patients with apparently sporadic and familial amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) (MND, n=253), MND mimics (n=85) and neurological control groups. Cut-off values were specified, and diagnostic performance and correlation with progression were analysed. RESULTS: Nfs were significantly higher in the MND group compared to the control groups, whereas Tau and pTau did not differ. At a cut-off level of 2200 pg/mL for NfL, a 77% diagnostic sensitivity (CI 71% to 82%), 85% specificity (CI 79% to 90%) and 87% positive predictive value (PPV) (CI 81% to 91%) were achieved. For pNfH, we calculated 83% sensitivity (CI 78% to 88%), 77% specificity (CI 71% to 83%) and 82% PPV (CI 77% to 86%) at 560 pg/mL. There were no significant differences between sporadic and genetic ALS or PLS. Nf levels were elevated at early disease stage, and correlated moderately with MND progression and duration. CONCLUSIONS: Neurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients. Their value as prognostic markers should be investigated further.

Histological characterization and biochemical analysis of paraspinal muscles in neuromuscularly healthy subjects.

INTRODUCTION: There are no generally accepted histopathological reference values in paraspinal skeletal muscle biopsies. METHODS: We examined multifidii muscle biopsies from 20 neuromuscularly healthy subjects using routine histological stains and biochemical analyses of respiratory chain enzymes. RESULTS: Staining showed incomplete myopathic features, such as increased variability in fiber size, type 1 hypertrophy, rounded fiber shape, endomysial fibrosis, and replacement by adipose tissue. Acid phosphatase reaction was positive in up to 35% of the selected muscle fibers. Mitochondrial changes were obvious but revealed no selective age dependence. Reduced complex I, cytochrome c oxidase (COX), and citrate synthase (CS) could be observed. CONCLUSIONS: Because the increased variability in morphological details can easily be misinterpreted as myopathic changes, analysis of paraspinal muscles should take into consideration that incomplete myopathic features and reduced oxidative enzyme activities for complex I, COX, and CS are normal variations at this location.

Novel ETFDH mutation and imaging findings in an adult with glutaric aciduria type II.

INTRODUCTION: Glutaric aciduria type II (GAII) is a rare autosomal recessive disorder with variable clinical course. The disorder is caused by a defect in the mitochondrial electron transfer flavoprotein or the electron transfer flavoprotein dehydrogenase (ETFDH). METHODS: We performed clinical characterization, brain and whole body MRI, muscle histopathology, and genetic analysis of the ETFDH gene in a young woman. RESULTS: She presented with rhabdomyolysis and severe quadriparesis. We identified a novel homozygous missense mutation in ETFDH (c.1544G>T, p.Ser515Ile). Body fat MRI revealed a large amount of subcutaneous fat but no increase in visceral fat despite steatosis of liver and muscle. Diffusion tensor imaging (DTI) of cerebral MRI revealed reduced directionality of the white matter tracts. Histopathological findings showed lipid storage myopathy. CONCLUSIONS: In this study, we highlight diagnostic clues and body fat MRI in this rare metabolic disorder.

Clinical spreading of muscle weakness in amyotrophic lateral sclerosis (ALS): a study in 910 patients.

BACKGROUND: Neuroanatomical staging of sporadic amyotrophic lateral sclerosis (ALS) indicates that neurodegeneration may spread corticofugally. METHODS: We conducted an observational study to define the initial sites of disease onset and the clinical progression ('spreading patterns') of motor deficits in a cohort of 910 ALS patients in Germany. RESULTS: Mean age of ALS onset was 59.0 ± 12.6 years for males and 61.2 ± 10.5 years for females, the mean ALSFRS-R was 35.1 ± 9.2, and 7.7% of the cohort reported a family history. Onset of motor symptoms was bulbar/upper limb in 26.8%/35.9%, the right arm initially being slightly more often affected than the left (18.5% vs.16.3%). Testing on concordance of handedness and onset in the dominant arm did not reach significance. Lower limb onset was observed in 37.3%. Unilateral limb onset patients reported horizontal spreading about three times more often than vertical spreading. 71/244 bulbar onset patients reported spreading pattern to the legs, and 17/339 lumbar onset patients reported spreading secondarily to the bulbar region. DISCUSSION: Our results indicate that, although the phenotype of so-called 'spinal' or 'intraspinal' spreading predominated, we also observed an additional clinical spreading pattern: 29.1% of patients with bulbar onset experienced spreading clinically to the legs (vice versa in 5.0% of lumbar onset patients). For obvious neuroanatomical reasons, this pattern hardly can be explained solely by a 'spinal' or an 'intraspinal' pattern of spreading. Instead, these findings complement insights from previous clinical and clinicopathological studies supporting a cortical initiation of ALS.

Coping as a resource to allow for psychosocial adjustment in fatal disease: results from patients with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal disorder, which imposes a severe emotional burden on patients. Appropriate coping mechanisms may alleviate this burden and facilitate wellbeing, with social support known to be a successful coping strategy. This observational study aimed to determine the interplay of general coping traits of hope for success and fear of failure, coping behavior of social activity, and patients' wellbeing. Methods: In this cross-sectional study, patients with ALS from a clinical-epidemiological registry in Southwestern Germany were interviewed regarding coping traits (achievement-motivated behavior: hope for success and fear of failure), coping behavior of social activity, and psychosocial adjustment, determined using measures of depressiveness, anxiety [both measured by Hospital Anxiety and Depression Scale (HADS)], and quality of life [Anamnestic Comparative Self-Assessment (ACSA)]. Demographics, clinical [ALS Functional Rating Scale revised version (ALSFRS-R)], and survival data were recorded. Results: A total of 868 patients [60.70% male patients, mean age: 64.70 (±10.83) years, mean ALSFRS-R: 37.36 ± 7.07] were interviewed. Anxiety in patients was found to be associated with a high fear of failure. In contrast, a generally positive attitude in patients exemplified in high hopes for success was associated with better wellbeing. Finally, coping behavior of social activity explained up to 65% of the variance of depressiveness among the patients with ALS. Conclusion: In this study, we present evidence that the wellbeing of patients with ALS is not an immediate fatalistic consequence of physical degradation but rather determined by coping traits and behavior, which may be trained to substantially increase the wellbeing of patients with ALS.

[Expert recommendations for magnetic resonance imaging of muscle disorders]. / Expertenempfehlung zur Magnetresonanztomographie bei Muskelerkrankungen.

BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.