Nucleolar characteristics of reducing bodies in reducing body myopathy

Reducing body myopathy is a rare muscle disease defined by abnormal inclusions in affected muscle fibers that can be stained with menadione-nitroblue tetrazolium. The origin of these inclusions has not been determined. Here we show that reducing bodies bear characteristics of nucleoli. Ultrastructurally, muscle biopsy specimens of a patient with adult-onset reducing body myopathy showed granular structures of reducing bodies with features similar to the granules of nucleoli, which consisted of pre-ribosomes. In addition, reducing bodies were positive for histochemistry of argyrophilic nucleolar organizer regions (a method for detecting the areas where ribosomal RNA is actively transcribed in the nucleolus), and for antibodies against nucleoli and nuclear ribonucleoprotein. The current findings suggest that reducing bodies contain pre-ribosomes and their associated proteins of the nucleolus and that formation of reducing bodies may result from defects of processing and assembly of ribosomes.     

Intracytoplasmic chromophobe inclusion bodies in an anaplastic meningioma

Intracytoplasmic inclusion bodies are rarely found in meningiomas. A 74-year-old woman had an anaplastic meningioma with intracytoplasmic chromophobe inclusion bodies (CIB) histologically. These CIB were various shapes, e.g. round, teardrop-like, fusiform, horseshoe-like, crescentic and perinuclear. The size of CIB ranged from 7 to 14 μm and the nuclei of the tumor cells with CIB were often eccentric. Most CIB were immunopositive only for vimentin, staining more intensely than surrounding cytoplasm in a comparative study using adjacent sections stained with hematoxylin-eosin and vimentin. CIB showed loosely textured filamentous structures which were in parallel and entangled arrangements ultrastructurally. The diameter of the filaments was 13–14 nm and they were thicker than normal intermediate filaments. Moreover, these filaments appeared to be studded with granular and fuzzy substances. These findings suggest that CIB are mainly composed of abnormally synthesized and arranged vimentin filaments. Received: 1 July 1996 / Revised: 20 September 1996 / Accepted: 27 September 1996     

Clinical and muscle magnetic resonance imaging study of an Italian family with autosomal dominant inclusion body myopathy not linked to known genetic loci

Abstract The objective was to report a clinical, pathological and muscle magnetic resonance (MR) study of an Italian family with an autosomal dominant inclusion body myopathy (AD-IBM). Eight subjects (age range 20–56 years; 5 females and 3 males) belonging to four generations were studied. Onset of disturbances (distal weakness at lower limbs) ranged from 20 to 28 years. CK levels were increased to five times. Only in an early stage oedema of involved muscles has been demonstrated by muscle MR. Quadriceps femoris was characteristically spared; in the last phases a mild involvement of the vasti became evident with persistent sparing of the rectus femori. Rimmed vacuoles and hyperphosphorylated tau filaments were evident at muscle biopsy. Linkage analysis excluded the association of the disease to chromosome loci 14q11, 17p13.1, 2p13, 19p13. The study suggests that quadriceps sparing is a characteristic feature also of AD-IBM. This finding could represent a muscle-image hallmark helpful in diagnosis of autosomal dominant muscular disorders.     

Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy

Frontotemporal dementia with inclusion body myopathy and Paget’s disease of bone (IBMPFD) is a rare, autosomal dominant disorder caused by mutations in the gene valosin-containing protein (VCP). The CNS pathology is characterized by a novel pattern of ubiquitin pathology distinct from sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions without VCP mutations. Yet, the ubiquitin-positive inclusions in IBMPFD also stain for TAR DNA binding protein, a feature that links this rare disease with the pathology associated with the majority of sporadic FTD as well as disease resulting from different genetic alterations. VCP, a member of the AAA-ATPase gene family, associates with a plethora of protein adaptors to perform a variety of cellular processes including Golgi assembly/disassembly and regulation of the ubiquitin–proteasome system. However, the mechanism whereby mutations in VCP lead to CNS, muscle, and bone disease is largely unknown. In this report, we review current literature on IBMPFD, focusing on the pathology of the disease and the biology of VCP with respect to IBMPFD.     

Small heat-shock protein is expressed in meningiomas and in granulofilamentous inclusion bodies

Summary The cellular expression of estrogen receptor-related small heat-shock protein (HSP27) in meningiomas was investigated immunologically. A cytoplasmic distribution of HSP27 was demonstrated in surgical specimens of 22 of 26 cases with meningiomas and cultured meningioma cells derived from two individuals. By Western blotting, HSP27 was detected in every tissue homogenate of 17 cases studied. Thus, HSP27 appears to be constitutively expressed in most meningiomas. In anaplastic portions of one papillary meningioma, there were numerous granulofilamentous inclusion bodies [Goldman JE et al. (1980) Cancer 46:156–161]. The inclusion bodies were immunopositive for HSP27 despite the negativity of the tumor cytoplasms. Thus, HSP27 seems to participate in the formation of certain inclusion bodies in meningioma cells, like B-crystallin which participates in the formation of Rosenthal fibers in astrocytes.Supported by a Grant-in-Aid for General Scientific Research (No. 04670213) from the Ministry of Education, Science and Culture of Japan (T.I.)     

Sporadic distal myopathy

Summary The sporadic distal myopathies are uncommon primary muscle diseases, the pathogenesis of which is still unclear. The inclusion body myositides are inflammatory myopathies, the distal form of which presents some features resembling those of sporadic distal myopathy. A case is reported of a patient showing features of both the first and the second forms.     

Familial inclusion body myopathy with desmin storage

We report two adult familial cases of inclusion body myopathy (IBM) with desmin storage in skeletal muscle. Clinically, both patients presented late-onset, progressive, symmetrical, both proximal and distal muscle weakness. Muscle biopsy findings were identical in both cases and consisted of marked variability in fiber size, increased number of central nuclei and vacuolation involving 10% of fibers. Single or multiple vacuoles were located subsarcolemmally or in the center, and were rimmed by basophilic material. At the ultrastructural level, tubulofilamentous nuclear and cytoplasmic inclusions of 16–21 nm in diameter were frequently observed. In addition, large subsarcolemmal and central deposits composed of electron-dense granular material were present in many fibers. Immunocytochemistry revealed staining for desmin, vimentin and ubiquitin within both inclusions and vacuolated fibers. Possible structural and functional associations between these two types of muscle changes remain unclear. They may either represent two coexistent disease processes or merely reflect an abnormal form of muscle fiber degradation, with unidentifiable specificity. Received: 30 January 1998 / Revised: 15 June 1998 / Accepted: 20 October 1998     

Atypical neuronal inclusion bodies in meningioangiomatosis

A case of meningioangiomatosis not associated with neurofibromatosis 2 in a 24-year-old man is reported. Abundant neurofibrillary tangles and threads, shown by immunohistochemistry and ultrastructural analysis to be similar to those seen in Alzheimer’s disease, were found in the residual neuropil. Another lesion consisting of argyrophilic globular inclusion bodies with radial fibrils was found at the periphery. Single and double immunostaining with a panel of antibodies showed similarities between these inclusions and Pick bodies. Received: 18 August 1997 / Revised, accepted: 10 December 1997     

Hypokalaemic myopathy in alcoholism

We describe the clinical and pathological features of a patient with an acute painless proximal myopathy due to hypokalaemia associated with alcoholism. There was an excellent response to treatment with potassium supplements. The importance of recognition of low potassium states in alcohol-dependent patients with muscular weakness is emphasized.     

Muscle fiber degeneration in distal myopathy with rimmed vacuole formation

In 11 patients with distal myopathy with rimmed vacuole formation (DMRV), a well-known autosomal recessively inherited disorder, the rimmed vacuole formation appears to be the main pathological change accounting for the progressive muscle fiber degeneration. To gain a better understanding of the pathophysiology of the vacuole formation, we applied Congo red and immunohistochemical stains to muscle biopsies from these patients and the results were compared with those of patients with inclusion body myositis (IBM). The vacuoles in DMRV contained Congophilic amyloid material and deposits immunoreactive for -amyloid protein, both the NH₂ and COOH termini of -amyloid protein precursor, ubiquitin, and tau protein. These results were similar to those seen in our present cases of IBM as well as in previously reported cases. Therefore, there may be no pathogenetic differences in the formation of rimmed vacuoles in DMRV and IBM. Nevertheless, the degenerative process involved in rimmed vacuole formation in various diseases may share a common pathogenetic mechanism with that in amyloid-plaque formation in Alzheimer's disease brain as has been proposed previously.     

Coexistence of X-linked recessive Emery-Dreifuss muscular dystrophy with inclusion body myositis-like morphology

We reported three cases (two familial and one sporadic) of X-linked Emery-Dreifuss muscular dystrophy (EDMD), genetically documented. Two patients demonstrated a typical inclusion body myositis (IBM)-like morphology. The third patient had only minor changes. Patients had elbow and ankle contractures, progressive wasting of humeroperoneal muscles and cardiac failure (pacemaker implantation in all). There was a mutation within the Xq28 gene and complete absence of emerin in the nuclear membrane. Mononuclear cell infiltrations, rimmed vacuoles, amyloid deposits, as well as cytoplasmic and nuclear tubulofilamentous muscle inclusions were most unusual findings. Coexistence of IBM-like morphology and X-linked recessive EDMD might indicate that pathological features of IBM are nonspecific and may be present in other neuromuscular disorders.     

Inflammatory and non-inflammatory inclusion body myositis

Summary In ten patients with inclusion body myositis (IBM) five muscular biopsies showed profuse inflammatory exudates and three showed a few scattered inflammatory cells with partial invasion in some muscle fibers. No inflammatory cells were seen in two cases. In all patients, histopathological, histomorphometric and immunocytochemical studies were performed. Immunocytochemistry for the class I and class II major histocompatibility complex gene product (MHC) was performed in all cases and in ten control muscles including: normal muscles [3], dermatomyositis [3], polymyositis [3], scleroderma [1]. In the five cases of IBM with inflammatory exudates, subsets of lymphocytes were analyzed with a panel of monoclonal antibodies against B cells, T4 cells, T8 cells, K and natural killer cells and macrophages. Some muscle fibers expressed class I MHC antigens in the inflammatory cases of IBM. These fibers were near the inflammatory exudates and occasionally showed a partial invasion. No expression of class I MHC was found in normal muscles and in non-inflammatory cases of IBM. The antigen which triggers the mononuclear cells in the inflammatory forms of IBM is probably not the filamentous inclusions in rimmed vacuoles. In other inflammatory myopathies, expression of class I MHC was present on all fibers in polymyositis, only in the perifascicular area in dermatomyositis and in scleroderma. It could be suggested that the term inclusion body muscle disease be applied to cases with rimmed vacuoles and IBM-like filaments without inflammatory cells.     

Congenital myopathy with type II muscle fiber hypoplasia

An unusual congenital neuromuscular disease characterized by atypically small type II muscle fibers is reported. The patients were a 9-year-old boy and a 3-year-old boy, both of whom showed motor retardation with proximal muscle wasting and hypotonia. Muscle biopsy revealed hypoplastic type II fibers and normal type I fibers. The observed hypoplasia seems to be a primary alteration.     

Glucocorticoid-sensitive hereditary inclusion body myositis

We report a hereditary muscle disorder with features of inclusion body myositis (IBM) in two adult sisters with slowly progressive asymmetrical muscle weakness. The findings of light microscopic and ultrastructural investigations of muscle biopsy specimens were consistent with a diagnosis of IBM. Both patients improved and stabilized on immunosuppressive treatment with corticosteroids and azathioprine. This differentiates our patients from other sporadic and familial cases of IBM. Clinical and histological features are described and compared with those of other previously reported families with IBM.     

Mitochondrial changes in acute myopathy after treatment of respiratory failure with mechanical ventilation (acute relaxant-steroid myopathy)

A case of acute myopathy was observed in the course of treatment of respiratory failure with mechanical ventilation combined with prolonged neuromuscular blockade and administration of corticosteroids. A muscle biopsy revealed degeneration of muscle fibres. Electron microscopy showed loss of thick filaments as well as nemaline rods, vacuoles and cytoplasmic bodies. The mitochondria were increased in number, many harbouring paracrystalline inclusions, which were hitherto unknown in this condition.