Inclusion body myositis (IBM) is a progressive muscle disease affecting patients over the age of 40, with distinctive clinical and histopathological features. The typical clinical phenotype is ...characterized by prominent involvement of deep finger flexors and quadriceps muscles. Less common presentations include isolated dysphagia, asymptomatic hyper-CKemia, and axial or limb weakness beyond the typical pattern. IBM is associated with marked morbidity as majority of patients eventually become wheelchair dependent with limited use of their hands and marked dysphagia. Furthermore, IBM mildly affects longevity with aspiration pneumonia and respiratory complications being the most common cause of death. On muscle biopsy, IBM is characterized by a peculiar combination of endomysial inflammation, rimmed vacuoles, and protein aggregation. These histopathological features are reflective of the complexity of underlying disease mechanisms. No pharmacological treatment is yet available for IBM. Monitoring for swallowing and respiratory complications, exercise, and addressing mobility issues are the mainstay of management. Further research is needed to better understand disease pathogenesis and identify novel therapeutic targets.
Inclusion body myositis is the most common acquired myopathy after the age of 50. It is characterized by progressive asymmetric weakness predominantly affecting the quadriceps and/or finger flexors. ...Loss of ambulation and dysphagia are major complications of the disease. Inclusion body myositis can be associated with cytosolic 5′-nucleotidase 1A antibodies. Muscle biopsy usually shows inflammatory cells surrounding and invading non-necrotic muscle fibers, rimmed vacuoles, congophilic inclusions, and protein aggregates. Disease pathogenesis remains poorly understood and consists of an interplay between inflammatory and degenerative pathways. Antigen-driven, clonally restricted, cytotoxic T cells represent a main feature of the inflammatory component, whereas abnormal protein homeostasis with protein misfolding, aggregation, and dysfunctional protein disposal is the hallmark of the degenerative component. Inclusion body myositis remains refractory to treatment. Better understanding of the disease pathogenesis led to the identification of novel therapeutic targets, addressing both the inflammatory and degenerative pathways.
Skeletal muscle‐related symptoms are common in both acute coronavirus disease (Covid)‐19 and post‐acute sequelae of Covid‐19 (PASC). In this narrative review, we discuss cellular and molecular ...pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post‐viral fatigue syndrome. Patients with severe Covid‐19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid‐19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post‐intensive care unit (ICU) syndrome and ICU‐acquired weakness and likely explain a substantial part of Covid‐19‐acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS‐CoV‐2‐specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid‐19 and PASC.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by progressive weakness and sensory loss, often affecting patientsʼ ability to walk and perform activities of daily ...living independently. With the lack of a diagnostic biomarker, the diagnosis relies on clinical suspicion, clinical findings, and the demonstration of demyelinating changes on electrodiagnostic (EDx) testing and nerve pathology. As a result, patients can often be misdiagnosed with CIDP and unnecessarily treated with immunotherapy. Interpreting the EDx testing and cerebrospinal fluid findings in light of the clinical phenotype, recognizing atypical forms of CIDP, and screening for CIDP mimickers are the mainstays of the approach to patients suspected of having CIDP, and are detailed in this review. We also review the currently available treatment options, including intravenous immunoglobulin (IVIg), corticosteroids (CCS), and plasma exchange (PE), and discuss how to approach treatment‐refractory cases. Finally, we emphasize the need to adopt objective outcome measures to monitor treatment response.
Chloroquine (CQ) and hydroxychloroquine (HCQ) have been associated with muscle toxicity, mostly described as a proximal myopathy with evidence of lysosomal dysfunction on muscle biopsy. In this ...retrospective study, we aimed to define the clinical phenotype, laboratory features, and treatment outcomes of CQ/HCQ myopathy, as well as the safety profile of these drugs. We identified 13 patients seen between 2000 and 2019, with a median age at presentation of 66 years (range 53-89); 11 were females. At onset of symptoms, patients were on CQ or HCQ for a minimum of 6 months and up to 21 years. Diagnosis was often delayed by a median of 6 months (range 3-48). At presentation, 13 patients reported limb weakness, with five requiring assistance in walking. Ten reported dysphagia, often severe, resulting in marked weight loss or aspiration pneumonia. Nine reported respiratory symptoms, which were multifactorial in four, and four reported severe neck weakness. Myopathy clinical phenotype showed predominant involvement of one or more of the following: proximal limb muscle weakness (12 patients), dysphagia (9), axial weakness (4), and respiratory failure (5). Eleven patients had a cardiac evaluation showing prolonged QT interval in 10 and CQ/HCQ cardiomyopathy (CMP) in four. Ten out of 12 patients markedly improved after discontinuing the medication, but most were left with some residual weakness. Eleven patients had a muscle biopsy showing a myopathy with rimmed vacuoles and marked acid phosphatase reactivity. Nine had elevated creatine kinase level up to 1,199 U/L. Twelve patients had an electromyography (EMG), which showed myopathic motor unit potentials with fibrillation potentials in 11 and myotonic discharges in 3. Higher cumulative dose and longer exposure duration were associated with more severe disability and more common cardiac and swallow involvement, indicating a cumulative dose effect. Herein, we demonstrate that long-term exposure to CQ and HCQ may result in a myopathy with a wide spectrum of clinical presentation and predilection for swallowing, respiratory, and cardiac muscles, often with marked associated morbidity. Once accurately diagnosed and the drug is discontinued, patients usually improve but often fail to return to baseline.
To define the peripheral neuropathy phenotypes associated with Castleman disease.
We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January ...2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups.
There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group.
There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study.
Introduction/Aims
We aimed to describe the clinical phenotype, histopathological findings and overall survival (OS) of the immune‐mediated neuromuscular complications of graft‐versus‐host disease ...(GVHD).
Methods
We conducted a retrospective chart review of adult patients presenting with immune‐mediated neuromuscular complications of GVHD to Mayo Clinic, between April 2013 and July 2018.We collected clinical and laboratory characteristics, histopathological findings, response to treatment and survival data.
Results
We identified 20 patients with a mean age at presentation of 55 y. Mean time from transplant to neurological presentation was 14 mo. Myositis was the most common complication seen in 17 patients, manifesting with predominantly axial and/or proximal weakness. Eleven patients had a muscle biopsy showing diffuse perimysial, predominantly macrophagic infiltration in 10, 3 of them with perimysial perivascular lymphocytic collections, and endomysial and perimysial lymphocytic infiltration in 1. Only two patients had a neuropathic complication: one each with acute inflammatory demyelinating polyradiculoneuropathy and neuralgic amyotrophy. A single patient had a myasthenic syndrome presenting with fluctuating foot drop. Nineteen patients were treated and all responded to immunosuppressive agents; however, 11 had further GVHD flares requiring escalation of therapy. After a median follow‐up of 83 mo, seven (35%) patients died: five from progressive GVHD and two from infections. The 5‐y OS from time of transplant was 68%.
Discussion
Myositis is the most common immune‐mediated neuromuscular complication of GVHD while peripheral neuropathy and myasthenic syndromes appear less common. The macrophage‐predominant infiltration on muscle biopsy deserves further study to better clarify the role of macrophages in GVHD pathogenesis.
Myofibrillar myopathies (MFM) are a clinically and genetically heterogenous group of inherited myopathies characterized by aggregation of Z-disc proteins. Mutations in desmin account for ~7% of MFM. ...We report here a Hmong family with an autosomal dominant MFM caused by a novel variant in the desmin gene. The proband presented with lower limb followed by upper limb weakness starting in the 5th decade. On examination, there was distal more than proximal muscle weakness. One sibling was similarly affected, while another had an asymptomatic elevation of creatine kinase. Genetic testing revealed a novel p.Ser13Tyr variant, which was predicted by
algorithms to alter protein function. Muscle biopsy revealed a MFM. Muscle MRI demonstrated selective involvement of the tensor fasciae latae, semitendinosus, sartorius, gracilis, gastrocnemius, soleus, and peroneus longus muscles. In this family, the histological and MRI findings assisted in the interpretation of genetic testing results.
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