Alison M. Emslie-Smith

Major histocompatibility complex class I antigen expression, immunolocalization of interferon subtypes, and T cell-mediated cytotoxicity in myopathies☆

Major histocompatibility complex class I (MHC-I) expression on target cells is a prerequisite for antigen-specific T cell-mediated cytotoxicity (TCMC). Enhanced MHC-I expression has been attributed to interferons (IFNs) released from inflammatory cells. In previous studies, we found evidence of TCMC (invasion of non-necrotic muscle fibers by cytotoxic T cells) in polymyositis (PM) and in inclusion body myositis (IBM). We occasionally found evidence of TCMC in Duchenne dystrophy (DD) but not in dermatomyositis (DM). This study examines the relationships between TCMC, MHC-I expression, and IFN immunoreactivity in these diseases and normal controls. In controls, reactivity for MHC-I was confined to blood vessels. In all diseases, regenerating fibers expressed MHC-I. In IBM, PM and DD, all nonnecrotic muscle fibers invaded by CD8+ cells and some adjacent fibers expressed MHC-I. In DM, myriad muscle fibers expressed MHC-I but none were invaded by CD8+ cells. In all diseases, only a few mononuclear cells and no muscle fiber surfaces were immunoreactive for IFNs. We conclude that MHC-I expression on muscle fibers is necessary but not sufficient for TCMC in myopathy; that the biological significance of increased MHC-I expression in DM remains undefined; and that currently available and appropriately controlled immunocytochemical methods show no relationship between increased MHC-I expression on muscle fibers and local IFN synthesis by mononuclear cells.

Myofibrillar myopathy with abnormal foci of desmin positivity. I. Light and electron microscopy analysis of 10 cases

A number of myopathies whose common denominator is abnormal foci of desmin positivity have been described under the rubrics of spheroid body myopathy, cytoplasmic body myopathy, Mallory body myopathy, myopathy with granulofilamentous inclusions, desmin storage myopathy, and intermediate filament myopathy. In this study we reevaluate the light microscopic and ultrastructural features of the myopathy with abnormal foci of desmin positivity. In 10 cases of the disease, ultrastructural analysis reveals 2 major types of lesions: (a) foci of myofibrillar destruction and (b) hyaline structures that appear as spheroidal bodies on electron microscopy. The foci of myofibrillar destruction consist of fiber areas containing disrupted myofilaments, Z-disk-derived bodies, dappled dense structures of Z-disk origin, and streaming Z-disks that are sometimes adjacent to lakes of dense material. The spheroid bodies are composed of compacted and degraded myofibrillar elements. Membrane-bound vacuoles harboring degenerating membranous organelles are a less frequent and probably secondary abnormality. None of the lesions in muscle comprise 8 to 10 nm intermediate filaments. The findings imply that spheroid body myopathy, cytoplasmic body myopathy, Mallory body myopathy, and myopathy with granulofilamentous inclusions are consequences of a single or closely related pathologic processes. Because the common denominator appears to be focal dissolution of the myofibrils followed by accumulation of the products of the degradative process, we propose the term myofibrillar myopathy to cover the observed spectrum of pathologic changes.

Myasthenia, thymoma, presynaptic antibodies, and a continuum of neuromuscular hyperexcitability

To the Editor: We read with interest the case report by R. Staudinger and K. Henry1 describing the clinical improvement in a patient with AIDS-associated myelopathy after the use of highly active antiretroviral combination therapy. This is the first reported case of improvement of myelopathy with antiretroviral agents, and it may have important implications in the understanding of the pathogenesis and treatment of this rare but disabling complication of HIV infection. However, a number of considerations must be made before accepting the conclusions that the improvement resulted from antiretroviral treatment. First, we think that the authors should have quantified the evaluation of spinal cord function in order to strengthen their conclusions. Objective measurement of spinal cord function, such as central conduction time (CCT) of the somatosensory evoked potentials (SEPs), can be used to monitor the clinical progression of the disease.2 Neurophysiologic tests would have supported the clinical diagnosis at baseline and repeat SEPs could have helped determine whether the observed clinical improvement was accompanied by improved conduction of electrical impulses through the spinal cord. We have recently encountered a similar patient with AIDS-associated myelopathy whose symptoms improved greatly after the introduction of highly active antiretroviral combination therapy. However, despite a subjective improvement of strength a few weeks after starting therapy, he had slight worsening of CCT when SEPs were repeated. It is therefore possible that the clinical improvement observed after starting antiretroviral medications was related to the overall improvement of the patient’s general health that accompanied the dramatic increase in CD4 cell count and suppression of plasma viral load. The authors also argue that the dramatic reduction of the viral load may explain the clinical improvement, yet they do not report CSF viral load before and after starting combination antiretroviral therapy. Although the relationship between plasma and CSF viral load is not completely understood, there is a known relationship between AIDS-dementia and elevated CSF viral burden, and in individual patients there may be no association between plasma and CSF viral loads.3 Finally, although the antiretroviral regimens most effective in treating HIV-related CNS disorders have not yet been established, the regimen used in this patient included only one drug (stavudine) with favorable CSF penetration.4-6 We believe that objective measures of spinal cord function and measurement of CSF viral load should have been used to support the hypothesis that the clinical improvement was related to viral load suppression rather than the consequence of general health improvement.

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease

Objectives To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. Methods 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers’ ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. Results Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. Conclusions The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM.

Colchicine-induced myoneuropathy mimicking polyradiculoneuropathy.

We report a patient with colchicine-induced myoneuropathy. Myoneuropathy is an under-recognized complication of colchicine. The weakness seen in our patient improved fairly rapidly after discontinuation of colchicine.

A 49-year-old man with contractures, weakness, and cardiac arrhythmia

The patient first noticed elbow contractures in childhood, and had always had small biceps muscles. He was never able to run as fast as his peers, and described a sensation of muscle tightening if he tried to run or move quickly, but was unaware of other weakness or functional limitation. At age 44 years, during preoperative assessment for an inguinal hernia repair, he was found to be in asymptomatic atrial flutter and was placed on warfarin. He underwent successful cardioversion, but was again in atrial flutter 2 months later. He was referred to Mayo Clinic, where atrial fibrillation with right bundle branch block and left anterior fascicular block was diagnosed. Transesophageal echocardiogram at that time was normal apart from a patent foramen ovale with bidirectional shunting. He was cardioverted successfully to normal sinus rhythm with first-degree atrioventricular block, right bundle branch block, and left anterior fascicular block. Five years later, routine serologic evaluation revealed mildly elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which remained elevated for 1 year, suspected to be related to his liver, so he returned to Mayo Clinic for gastroenterologic evaluation. During this evaluation, serum creatine kinase (CK) was found to be elevated at 1,146 U/L (normal 52–336 U/L), which prompted neurologic referral. The patient was an active hog farmer. He routinely rode a stationary exercise bike for 35 minutes each night at a rate of 30–32 miles per hour without difficulty. He had recently noticed problems carrying heavy bales or feed sacks, and had difficulty lifting up to 50 pounds past the level of his chest. He developed tightness in his leg muscles if he carried 30–40 pounds up stairs. He denied muscle pain, new muscle atrophy, or episodes of dark urine. He had no difficulty squatting or rising from chairs, speaking, chewing, or swallowing …