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Häufig werden uns als Rheumatologen Patienten mit einer Muskelschwäche und Erhöhung der Kreatinkinase (CK) vorgestellt. Nicht immer kann eine Myositis als Ursache der Beschwerden festgestellt werden. Wir präsentieren 2 Kasuistiken aus unserer Klinik, deren Diagnose erst mithilfe der Muskelbiopsie gestellt werden konnte: Im ersten Fall handelt es sich um einen Patienten mit einer Muskelschwäche, einem pathologischen Gewichtsverlust und einer deutlichen CK-Erhöhung. Mithilfe der Muskelbiopsie konnte die Diagnose einer immunvermittelten nekrotisierenden Myopathie bedingt durch HMG-CoA-Reduktase-Autoantikörper nach Statineinnahme gestellt werden. Die zweite Patientin präsentierte sich mit krampfartigen und brennenden Muskelschmerzen sowie einer Schwäche der Extremitäten ohne relevante CK-Erhöhung. Auch hier erfolgte die histologische Untersuchung eines betroffenen Muskels, in der sich ein Myoadenylat-Deaminase-Mangel zeigte. Dieser konnte in einer genetischen Untersuchung bestätigt werden.

Wir berichten über eine 32-jährige Patientin mit einer progredienten proximal betonten Tetraparese und deutlich erhöhten CK-Werten (bis 80.000 U/l). Bei Nachweis von entzündlichen Veränderungen in der Muskelbiopsie wurde unter Annahme einer Polymyositis eine immunsuppressive Therapie erfolglos durchgeführt. In der humangenetischen Diagnostik konnte eine bisher nicht bekannte homozygote Mutation im Dysferlin-Gen nachgewiesen werden. Auch degenerative Erkrankungen (Muskeldystrophien), wie z. B. eine Dysferlinopathie, können mit ausgeprägten entzündlichen Veränderungen einhergehen. We report the case of a 32-year-old woman with severely elevated serum creatine kinase (CK; 80,000 U/l) and progressive proximal pareses. As muscular biopsy showed inflammatory infiltrates, polymyositis was suspected and immunosuppressive treatment was initiated. However, clinical improvement could not be achieved. Gene sequencing of the DYSF-gene showed a previously unreported homozygous mutation. In summary, elevated serum CK and inflammatory infiltrates in the muscle biopsy are not specific for polymyositis, but may also occur in degenerative diseases (muscular dystrophy), such as dysferlinopathy.

Glutamate-mediated neurodysfunction plays a crucial role in the pathogenesis of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) encephalitis. The regulation of glutamatergic neurotransmission in inflammation is a complex interaction between activation of immune mediators and adaptive changes in the functional elements of the glutamatergic synapse. Our studies in simian immunodeficiency virus (SIV)-infected macaques disclosed disruption of excitatory amino acid transporters (EAATs), the cardinal glutamate clearing system, during SIV infection and a dramatic loss of EAATs associated with development of rapid acquired immunodeficiency syndrome (AIDS) which was paralleled by activated microglia. N-methyl-D-aspartate (NMDA) receptor activation is involved in the pathogenetic cascades of neurodegenerative disorders including HIV dementia. The NMDA receptor antagonist memantine is being discussed as a potential adjunctive therapeutic drug for HIV dementia. Interestingly, in the SIV animal model, treatment with memantine during early asymptomatic stage prevented the onset of dopamine deficits in the brains of SIV-infected macaques and specifically up-regulated the brain-derived neurotrophic factor (BDNF). Our data support the glutamate hypothesis for the development of HIV dementia and suggest that the impairment of glutamate clearing plays an important role in the pathogenesis of HIV dementia and SIV encephalitis. Moreover, memantine might be a suitable drug for the treatment of HIV dementia due to its neuroprotective effect.

Zusammenfassung: Wir schildern den 9-jährigen Krankheitsverlauf einer türkischstämmigen Patientin mit chronisch-parenchymatösem Neuro-Behçet, bei der im Verlauf Myalgien und erhöhte Muskelenzyme auftraten. Bei elektromyographisch und bioptisch festgestellter Myopathie erfolgte differenzialdiagnostisch die Abgrenzung zu Medikamentennebenwirkungen. Nach Erhöhung einer kombinierten Immunsuppression war keine Erkrankungsaktivität sowohl der Myopathie als auch des Behçet-Syndroms mehr nachweisbar.

Bei der adulten Form des Morbus Pompe (Glykogenose Typ II), einer generalisierten, lysosomalen Speicherkrankheit aufgrund eines Mangels der sauren α-1,4-Glukosidase (alternativ: saure Maltase), findet sich meist eine progrediente, proximal und an den Beinen betonte Muskelschwäche. Beeinträchtigungen der Atemmuskulatur im Verlauf sind häufig. In vorliegendem Fall war die respiratorische Insuffizienz das einzige Symptom und führte zu dem klinischen Bild eines Patienten, der sich zu Fuß, sein eigenes Beatmungsgerät tragend in unserer Ambulanz vorstellte. Nur eine Muskelbiopsie der Interkostalmuskulatur ermöglichte letztendlich die Diagnosestellung.

Abstract: A 47-year-old Greek man presented with a 4-week history of speech difficulties. CT and MRI revealed a low-density multilobulated cystic frontal mass with peripheral ring contrast enhancement adjacent to the sylvian fissure. Examination was normal. Blood tests revealed leucocytosis (16,000 cells/μl) and an elevated erythrocyte sedimentation rate (30/52). A malignant brain tumour was suspected and surgically removed. Histological examination disclosed intracerebral neurocysticercosis.

Electron microscopic, fluorescence microscopic, and immunohistochemical studies earlier performed on archivalcerebral tissue from Max Bielchowsky's original three patients revealed curvilinear bodies rich in subunit C of mitochondrial ATP synthase (SCMAS). Recent progress in the elucidation of CLN2, i.e. identification of the defective lysosomal enzyme tripeptidyl-peptidase I (TPP-I) and mutations in the CLN2 gene have further corroborated earlier data. Immunohistochemically the absence of the TPP-I protein could be confirmed in the archival tissues using pathological controls. Unlike biochemistry, immunohistochemistry enables examination of these archival tissues elucidating the causative defect. Complementary molecular studies identified mutations in the CLN2 gene in the archival tissues and thereby convincingly demonstrated that these three children truly had classic late infantile neuronal ceroid lipofuscinosis (LINCL), now called CLN2. This archival study documents the possibilities to revalidate disease-specific original nosologic reports. Chloroquine is toxic to lysosomal enzymes and results in lysosomal storage. The material is autofluorescent andgives the ultrastructural pattern of curvilinear profiles, thus resembling classic late infantile NCL, representing a good experimental model. In humans chloroquine therapy may cause a myopathy (and retinopathy) and, as recently suggested, an encephalopathy marked by lysosomal accretion in several cell types including neurons. Immunohistochemically, SCMAS also accumulates, further strengthening morphologic similarity between LINCL and human chloroquine intoxication.

Summary A 30-year-old woman presented with lifethreatening ventricular tachycardia without overt heart disease. Ultrastructural investigation of endomyocardial biopsy disclosed abnormally structured and often enlarged mitochondria. Morphometry revealed the ratio of volume density of mitochondria to myofibrils to be markedly increased to 0.667 as compared with five controls (mean: 0.46; range: 0.445–0.479). Investigation of mitochondrial respiratory chain enzymes revealed a 90% reduction in activity of cytochromec oxidase. Our data suggest that mitochondrial cardiomyopathy may induce malignant ventricular arrhythmias.

In a patient with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), a pontine infarction occurred about 6 months after the ophthalmological manifestation. We report the first case with histopathologically proven vasculitis shown by muscle biopsy and the first positron emission tomographic documentation in APMPPE. The ophthalmological and cerebral symptoms responded well to steroid treatment. Long-term immunosuppression (e.g. azathioprine 1–2 mg/kg) seems to decrease the risk of recurrent systemic vasculitis.

Duchenne muscular dystrophy (DMD) and the allelic milder form of Becker muscular dystrophy (BMD) are caused by mutations of the dystrophin gene on the short arm of the X chromosome. One third of affected indviduals are expected to result from de novo mutations. Genetic counselling of families with sporadic cases is complicated by the potential meiotic origin of the mutation in the mother resulting in germline mosaicism. Here we present direct evidence for combined somatic and germline mosaicism for a deletion of the dystrophin gene, thereby proving the mitotic origin of this deletion and pinpointing a further potential pitfall for genetic counselling. The mother of a BMD son and a BMD carrier daughter, both carrying a deletion of dystrophin cDNA 7 (0.5 kb Hind III fragment) and cNDA 8, was herself clinically healthy and had normal creatine kinase levels. A muscle specimen of the mother showed mild overall pathology as well as focal dystrophin deficiency. In contrast chromosomal in situ suppression (CISS) hybridization of metaphase chromosomes using a cosmid clone of the corresponding cDNA deleted in her son revealed no evidence of somatic mosaicism in their lymphocytes. These results emphasize the value of an approach correlating genetic and immunological data for the definition of a carrier state in BMD or DMD. The possibility of somatic mosaicism should be considered when genetic counselling of a family with a sporadic case of BMD or DMD is performed.

Human sural nerve biopsies of eight cases with acute, subacute and chronic polyradiculoneuritis were studied by means of immunohistochemistry to characterize the inflammatory infiltrates. In addition, the structural changes of the endoneurial blood vessels were examined by electron microscopy, since both factors are likely to contribute to disturbances of the blood-nerve barrier. By use of six monoclonal antibodies, it was shown that the inflammatory infiltrates in cases with more acute polyradiculoneuritis are predominantly recruited by Leu 3a- and Leu 4-positive T lymphocytes. In more chronic polyradiculoneuritis beside of few Leu 3a-positive and Leu 4-positive T lymphocytes also B cells occurred. Leu M3-positive macrophages were detected in all cases with floride myelin degeneration. Since immunoreactivity for antigens of the HLA-D-locus (Leu-HAL-DR and Leu 10) were present on the infiltrating mononuclear cells, it can be postulated that they represent active and immunocompetent cells. Ultrastructurally, the amount of pinocytotic vesicles in the endothelial cells of the endoneurial blood vessels was increased. Moreover, a prominent folding of the luminal and abluminal surface of vascular endothelial cells and diminution of the intercellular tight junctions were observed. These findings appear suitable to explain the increased leakage of serum proteins across the blood-nerve barrier in polyradiculoneuritis sharing general features of cell-mediated immunity.

The pathological findings, including immunohistochemical and electron microscopical findings, in three infants who died unexpectedly of cardiac tumor or cardiomyopathy are reported. The first was a 13-month-old boy with tuberous sclerosis and multiple rhabdomyomas of the heart, who presented with a postpartal cardiac murmur and moderate cardiomegaly. The further history was unknown. The rhabdomyoma nodules were composed of spider cells containing small amounts of desmin and myosin as well as isolated myofibrils. Microscopically small glioma nodules contained high amounts of GFAP. The second case, a boy 4 months of age, died of a large benign fibrous histiocytoma of the heart after an uneventful history. Tumor cells contained alpha- I-anti-chymotrypsin and lysozyme. The third case, a girl 2 months of age, died unexpectedly of histiocytoid cardiomyopathy. The affected cells contained fat droplets, glycogen granules, many leptomer myofibrils and small amounts of myosin and desmin.

Three unrelated, sporadic patients with muscle coenzyme Q10 (CoQ10) deficiency presented at 32, 29, and 6 years of age with proximal muscle weakness and elevated serum creatine kinase (CK) and lactate levels, but without myoglobinuria, ataxia, or seizures. Muscle biopsy showed lipid storage myopathy, combined deficiency of respiratory chain complexes I and III, and CoQ10 levels below 50% of normal. Oral high-dose CoQ10 supplementation improved muscle strength dramatically and normalized serum CK.