[Inclusion body myositis--a rarely recognized disorder]. / Zárványtestes myositis--egy ritikán felismert betegség.

Inclusion body myositis is the most common disabling inflammatory myopathy in the elderly. It is more frequent in men and after the age of 50 years. Inflammatory and degenerative features coexist. There is a T-cell mediated autoimmunity driven by in situ clonally expanded cytotoxic CD8-positive T-cells invading non-necrotic muscle fibres expressing MHC-I antigen. The hallmarks of degeneration are the deposition of protein aggregates and the formation of vesicles. The course of the disease is slow and the diagnosis is usually set after several years. The muscle weakness and wasting is assymetric, affecting predominantly distal muscles of the upper extremity and proximal muscles of the legs. The signs and clinical course can be characteristic, but the diagnosis is established by muscle biopsy. There is currently no evidence based effective treatment for sIBM. Prednisone, azathioprine, methotrexate, cyclosporine and IFN-beta failed. Oxandrolon did not improve symptoms. Treatment with intravenous immunglobuline (IVIG) induced in some patients a transient improvement of swallowing and of muscle strenght, but the overall study results were negative. A T-cell depleting monoclonal antibody (alemtuzumab), in a small uncontrolled study slowed down disease progression for a six-month period. Repeated muscle biopsies showed the reduction of T-cells in the muscle and the suppression of some degeneration associated molecules. An effective therapeutic mean should act on both aspects of the pathomechanism, on the inflammatory and the degenerative processes as well.

Classification and diagnostic investigation in inflammatory myopathies: a study of 99 patients.

OBJECTIVE: Insights into the pathogenesis of inflammatory myopathies have led to new diagnostic methods. The aims of our study were (1) to evaluate the consequences of using the classification of Amato/European Neuromuscular Centre Workshop (ENMC) compared to that of Bohan and Peter; and (2) to evaluate any diagnostic benefit in using an extended pathological investigation. METHODS: From a consecutive retrospective database, we evaluated 99 patients for classification. Patients with inclusion body myositis (IBM) were classified according to Griggs, et al. In addition to routine stainings and immunohistochemistry, a multilevel serial sectioning procedure was performed on paraffin-embedded material, to identify scarce pathological findings. RESULTS: Classification according to Bohan and Peter could be performed for 83 of the 99 patients, whereas only 60 patients met the Amato/ENMC criteria, the latter resulting in the following diagnostic groups: IBM (n = 18), nonspecific myositis (n = 14), polymyositis (n = 12), dermatomyositis (n = 10), dermatomyositis sine dermatitis (n = 5), and immune-mediated necrotizing myopathy (n = 1). Most of the Amato/ENMC diagnostic groups harbored patients from several of the Bohan and Peter groups, which included a substantial group lacking proximal muscle weakness. The serial sectioning procedure was essential for classification of 9 patients (15%), and led to a more specific diagnosis for 13 patients (22%) according to Amato/ENMC. CONCLUSION: The classification of Amato/ENMC was more restrictive, forming groups based on clinical criteria and specified myopathological findings, which clearly differed from the groups of the Bohan and Peter classification. An extended pathological investigation increased the diagnostic yield of a muscle biopsy and highlights the quantity and specificity of certain pathological findings.

External ophthalmoplegia associated with Hashimoto's thyroiditis and recovered on corticosteroid treatment.

Five-year follow-up of a young male patient is presented. Total external ophthalmoplegia developed 1 week after an upper respiratory tract infection. After 3 years of the course, hyperthyreosis and clinical signs of thyroid-associated ophthalmopathy occurred. Hashimoto's thyroiditis and ultrastructural signs of mitochondrial damage of striated muscle were found by histological investigations. The paresis of the external ocular muscles recovered after long-term corticosteroid treatment. On the basis of clinical symptoms and histological results, the authors supposed that an immunological reaction had caused mitochondrial damage in the striated muscles, which also resulted in thyroiditis. This case history points that autoimmune mechanism more frequently might participate in the pathogenesis of chronic external ophthalmoplegia, and the symptoms might precede organ-specific or perhaps systemic autoimmune disorders.

Sensory ataxic neuropathy with dysarthria/dysphagia and ophthalmoplegia (SANDO). Two case reports.

Case histories of two unrelated patients suffering from sensory ataxic neuropathy, dysarthria/dysphagia and external ophthalmoplegia (SANDO) are reported. Both patients showed compound heterozygosity for POLG1 gene mutations, and presented with symptom of the clinical characteristics of SANDO. A patient with a p.A467T and p.W748S, well-known mutations showed a progressive course with early onset and multisystem involvement, including symptoms characteristics for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). The second patient showed a less well-known p.T251I and p.G848S mutations with late onset and dysphagia/dysarthria dominated, moderate symptoms. This later is the second published case history, when these POLG1 gene mutations are the possible background of late onset SANDO, dominantly presenting with bulbar symptoms.

Asymmetric calf hypertrophy of neurogenic origin.

A 47-year-old male presented with painful swelling of the right calf. His medical history was negative, except for a herniation of disc LIV-V 5 years before. Physical examination revealed unilateral calf hypertrophy with moderate weakness of plantarflexion, mild paresis of dorsiflexion. Electromyography showed a peripheral neurogenic lesion in the right anterior tibial muscle, but normal findings were obtained from the unaffected quadriceps muscle. Histological examination of the right gastrocnemic muscle showed neurogenic changes with typical targetoid fibers, but no pathological changes were present in the quadriceps muscle. Chronic asymmetric spinal muscular atrophy is an infrequent neuromuscular disease and because of asymmetric appearance, it might be difficult to distinguish from other, acquired neurogenic muscle diseases such as radiculopathy caused by intervertebral disc herniation. Our case confirms that muscular hypertrophy can follow partial denervation in humans.

25 years' experience in the treatment of gestational trophoblastic neoplasia in Hungary.

OBJECTIVE: To review our clinical experience in the treatment of gestational trophoblastic neoplasia (GTN) over the past 25 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2001, we treated 355 patients with GTN. The patients were between 14 and 53 years of age, with an average of 28.3. Primary chemotherapy was selected based on the patient's stage of gestational trophoblastic tumor (GTT) and prognostic score. RESULTS: We found metastases in 49.3% (175 of 355) of our patients. Of 173 patients, 162 (93.2%) achieved remission as a result of methotrexate therapy. In 11 patients (6.8%) complete remission was achieved by combination chemotherapy, in some cases assisted by operation. Of 68 patients, 63 (92.6%) achieved remission as a result of actinomycin D therapy, and 5 (7.4%) achieved complete remission by combination chemotherapy. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% successful therapy in cases of nonmetastatic and low-risk metastatic disease. CONCLUSION: According to our experience, methotrexate/folinic acid or actinomycin D should be the primary treatment in patients with nonmetastatic or low-risk metastatic GTN. Patients with resistance to single-agent chemotherapy regularly achieve remission with combination chemotherapy.

Distal myopathy with rimmed vacuoles and cerebellar atrophy.

Distal myopathies constitute a clinically and pathologically heterogeneous group of genetically determined neuromuscular disorders, where the distal muscles of the upper or lower limbs are affected. The disease of a 41-year-old male patient started with gait disturbances, when he was 25. The progression was slow, but after 16 years he became seriously disabled. Neurological examination showed moderate to severe weakness in distal muscles of all extremities, marked cerebellar sign and steppage gait. Muscle biopsy resulted in myopathic changes with rimmed vacuoles. Brain MRI scan showed cerebellar atrophy. This case demonstrates a rare association of distal myopathy and cerebellar atrophy.

[Amyotrophic lateral sclerosis in Baranya county, Hungary]. / Amyotrophiás lateralsclerosis Baranya megyében az elmúlt 54 év tükrében.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease resulting in loss of upper and lower motoneurons. Here we analyzed the clinical and epidemiological data of 202 ALS patients admitted to our department between 1950 and 2004. Risk and protective factors influencing onset and progression of the disease were examined. We also analyzed the relationship between first clinical symptoms/signs and prognosis of the disease. Our data suggest the importance of toxic factors in the initiation of the disease and the effect of clinical phenotype on the progression of ALS.

[Diagnosis and therapy of myotonic dystrophy in our practice of neuromuscular care]. / Neuromuscularis gondozásunkban észlelt dystrophia myotonicában szenvedó betegek ismertetése.

INTRODUCTION: Myotonic dystrophy is the most frequent, autosomal dominantly inherited muscular dystrophy. The typical neurological picture (facial myopathy, myotonia, muscle atrophy) may be associated with cardial, endocrine and ocular symptoms. METHODS: The diagnosis is based on electromyography, muscle biopsy and genetical tests. Muscle histology is characterized by high frequency of central nuclei. Genetical tests detect CTG repeat expansion of the involved gene. AIMS: Authors summarize 9 cases found in the Neurology Clinic of Pecs University in the last three years. RESULTS: The prevalence is lower than expected, therefore some cases might be unrecognized. After recognizing the typical clinical picture, electrophysiological, muscle biopsy, brain MRI, psychologic and molecular genetic studies were performed. Six patients belonged to 3 families and 3 sporadic cases were found. In all except one patient mild neurocognitive deficit was detected. Three patients had cataract and cardiac involvement. CONCLUSIONS: The authors emphasize that in cases of cardial, endocrine and central nervous system involvement myotonic dystrophy must be considered and detailed examinations are necessary for early detection of the specific organ manifestations.

[Early onset dementias: three cases]. / Fiatalkori dementiák--Három beteg kórtörténetének ismertetése.

INTRODUCTION: Dementia is a decline of intellectual abilities. The etiology of dementia syndrome is diverse. The authors describe three patients with early-onset dementia. CASE REPORTS: The first patient was a 44 years old male with mild gait, body ataxia, memory loss, slowness and apathy Investigations proved AIDS dementia syndrome. In the second case of a 37 years old female patient, herpes simplex encephalitis was suspected due to sudden onset of speech arrest and to brain MRI and CSF findings. Her symptoms improved during antiviral treatment but later progressive dementia developed. CSF serological tests proved the presence of neurolues-dementia paralytica. The third patient was a 38-years-old female. Neurological examination was performed because of progressive memory loss, changed behaviour and impaired attention. Neuropsychological test showed severe dementia. Metachromatic leukodystrophy was proven by decreased arylsulfatase activity. CONCLUSIONS: It is not easy to recognize the early symptoms of dementia. In these cases, besides detailed history, neurological examination and neuropsychological tests, brain MRI and cerebral spinal fluid serological tests were indispensable for a correct diagnosis, especially in the young patients.

Effect of nickel (ni(2+)) on primary human ovarian granulosa cells in vitro.

Human ovarian granulosa cells obtained from women undergoing in vitro fertilization were exposed to 15.6, 31.25, 62.5, 125, 250, 500, 1000 muM Ni(2+) for 48 h. To determine the site of action of Ni(2+), the granulosa cells were stimulated to produce progesterone (P) by using maximally stimulating amounts of human chorionic gonadotropin (0.1 IU/ml hCG) or dibutyryl cyclic adenosine monophosphate (1 mM db-cAMP). The luteinizing hormone (LH) analog hCG was chosen because resultant P production requires an intact membrane receptor and db-cAMP was used to test for post LH receptor defects caused by Ni(2+). Progesterone content of the culture medium was determined by radioimmunoassay (RIA), and viability of the cells was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction test. Concentration-dependent depression in both hGC and db-cAMP stimulated P production was seen at 15.625 muM or higher concentration of Ni(2+), which is not cytotoxic on human ovarian granulosa cells. The viability of cells was unaffected up to 31.25 muM and decreased significantly at 62.5 muM. Our results show a dose-related depression in stimulated P production of granulosa cells at a dose that does not induce significant cytotoxic action. These data indicate that the effect of Ni(2+) on P production is not due to cytotoxicity, and the cellular site(s) of inhibitory action appears to be subsequent to the membrane receptor and production of cAMP.

Recent advances in molecular biology of gestational trophoblastic diseases. A review.

Gestational trophoblastic diseases are interrelated conditions characterized by abnormal growth of chorionic tissues with various propensities for local invasion and metastasis. Complete mole is a unique conception in that all nuclear DNA is paternally derived and all cytoplasmic DNA is maternally derived. In contrast, partial mole generally has a triploid karyotype, where the extra haploid set of chromosomes is paternally derived: Gestational trophoblastic diseases are characterized by altered expression of several growth regulatory factors and oncogenes. While differences in expression of oncoproteins may be important to the development of gestational trophoblastic disease, the precise molecular changes that are critical to pathogenesis remain unknown.