Polyneuropathy with osteosclerotic myeloma--POEMS syndrome. A case report.

A rare form of plasma cell dyscrasia characterized by associated polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes has been termed the POEMS syndrome. The pathophysiology is unknown; plasma cell dyscrasia is essential; secondary manifestations are unexplained. We report a 67-year-old man with a 7-month history of progressive weakness and numbness of the legs. Clinical examination revealed sensorimotor polyneuropathy, predominantly affecting the lower extremities, hepatomegaly, and skin haemangiomas. Additional investigations disclosed IgG-lambda monoclonal serum protein, endocrine abnormalities, elevated cerebrospinal fluid protein level and an osteoblastic lesion of the lumbar vertebra. Biopsy of the osteosclerotic vertebra showed a marked lymphoplasmocytic infiltrate. MRI of the liver disclosed two haemangiomas; this association has not been reported previously.

Unusual association of multiple sclerosis and tomaculous neuropathy.

We describe two cases in which multiple sclerosis (MS) occurred in association with tomaculous neuropathy, presenting as chronic, distal sensorimotor polyneuropathy. In Case 1, monoclonal gammopathy of undetermined significance with monoclonal IgG lambda reactive against GM1 ganglioside, was also detected. The diagnosis of tomaculous neuropathy was established after sural nerve biopsy. Teased fibers examination revealed focal 'sausage-like' thickenings of the myelin sheaths in intact fibers and in fibers with segmental demyelination. Electron microscopy showed them to be due, mostly, to multiple windings of redundant myelin and concentric apposition of numerous lamellae, in contact with an intact myelin sheath. These are the first reported cases of tomaculous neuropathy in patients with MS. Whether the combination of the two conditions is purely coincidental or suggests the possible causal relation between MS and tomaculous neuropathy, is not certain.

Academic attainment and special educational needs in extremely preterm children at 11 years of age: the EPICure study.

AIM: To assess academic attainment and special educational needs (SEN) in extremely preterm children in middle childhood. METHODS: Of 307 extremely preterm (< or =25 weeks) survivors born in the UK and Ireland in 1995, 219 (71%) were re-assessed at 11 years of age and compared to 153 classmates born at term, using standardised tests of cognitive ability and academic attainment and teacher reports of school performance and SEN. Multiple imputation was used to correct for selective dropout. RESULTS: Extremely preterm children had significantly lower scores than classmates for cognitive ability (-20 points; 95% CI -23 to -17), reading (-18 points; -22 to -15) and mathematics (-27 points; -31 to -23). Twenty nine (13%) extremely preterm children attended special school. In mainstream schools, 105 (57%) extremely preterm children had SEN (OR 10; 6 to 18) and 103 (55%) required SEN resource provision (OR 10; 6 to 18). Teachers rated 50% of extremely preterm children as having below average attainment compared with 5% of classmates (OR 18; 8 to 41). Extremely preterm children who entered compulsory education an academic year early due to preterm birth had similar academic attainment but required more SEN support (OR 2; 1.0 to 3.6). CONCLUSIONS: Extremely preterm survivors remain at high risk for learning impairments and poor academic attainment in middle childhood. A significant proportion require full-time specialist education and over half of those attending mainstream schools require additional health or educational resources to access the national curriculum. The prevalence and impact of SEN are likely to increase as these children approach the transition to secondary school.

Cyclosporine in the treatment of myasthenia gravis.

Cyclosporine A (CsA) treatment was evaluated in 52 patients with severe generalized myasthenia gravis (MG) whose illness was not controlled by anticholinesterase drugs, thymectomy, corticosteroids, and azathioprine. The efficacy of CsA treatment was expressed by mean disability score quotient (MDSQ), which was obtained by comparing mean disability score (MDS) at the beginning of the treatment with the MDS at the end of the follow-up period. For the entire group of patients MDSQ was 53.3%, indicating moderate improvement. Analyzing individual cases, eight patients (15%) did not improve, 17 (33%) showed moderate improvement, 20 (38%) showed remarkable improvement, and seven patients (14%) achieved complete remission. The most common side effects were rise of serum creatinine (seven), hypertension (two), gingival hyperplasia (two), hypertrichosis (six), myalgia (10), and 'flu-like' symptoms (10 patients). The results of this study suggest that CsA is efficacious and safe treatment in severe and resistant forms of MG.

The features of myasthenia gravis with autoantibodies to MuSK.

OBJECTIVES: To determine if myasthenia gravis (MG) with antibodies to MuSK is a distinct subgroup of seronegative MG. METHODS: We assayed antibodies to muscle specific tyrosine kinase (MuSK) in 55 MG patients who had no antibodies to acetylcholine receptors and looked for the specific phenotype, comparing clinical features of anti-MuSK positive and anti-MuSK negative MG patients. RESULTS: MG with anti-MuSK antibodies was characterised by a striking prevalence of female patients (15 women, two men). Age at onset ranged from 22 to 52 years, with 70.6% of patients presenting at < 40 years of age. The majority of patients (82.4%) had prevalent involvement of facial and bulbar muscles. One third of them did not respond well to anticholinesterase drugs. Steroid immunosuppression was effective in eight patients (44.4%). Nine patients underwent thymectomy; six of these had no thymus pathology, while three had a hyperplastic thymus. At the end of the observation period, six (35.3%) patients were in remission, five (29.4%) improved, four (23.6%) did not change, and two (11.7%) had died. CONCLUSIONS: MG patients with antibodies to MuSK have characteristic clinical features that are different from features of the remaining seronegative MG patients. This emphasises the predictive value of anti-MuSK antibody analysis in seronegative MG patients.

[Clinical heterogeneity in patients with ocular myopathies]. / Heterogenost klinickog ispoljavanja kod bolesnika s okularnom miopatijom.

We present the results of clinical, electrophysiological, and biopsy studies in patients with ocular myopathy. Nine patients (four women and five men) were included in these investigations. According to the biopsy findings the patients were divided into patients with oculocraniosomaltic syndrome (OCSS) and patients with oculopharyngeal muscular dystrophy (OPMD). The presented clinical features, especially in the OCSS groups was more variable. Associated neurological and multisystem disturbances were characteristic of OCSS. Biopsy findings were of essential significance in distinguish these two conditions, especially in cases of the late onset.

[McArdle's disease]. / Mak Ardlova (McArdle) bolest.

Glycogenosis type V (McArdle disease) is a serious metabolic disorder with an exercise intolerance, myalgia, early fatigue and stiffness of exercising muscles, relieved++ by rest. The authors present a case report of patient with McArdle's disease, and diagnostic procedures which can be used in different diagnostic of metabolic myopathies, especially between myoadenylate deaminase deficiency and different types of gly(geno)lytic myopathies. The importance of "ischemic forearm test" and muscle biopsy is emphasized.

[Mitochondrial encephalomyoneuropathy. Case report]. / Mitohondrijska encefalomioneuropatija (prikaz bolesnika).

Mitochondrial myopathies and encephalomyopathies constitute a group of degenerative disorders characterized by a striking degree of clinical, biochemical and genetic heterogenity. We present a case of a 42-year old woman with clinical, electrophysiological and laboratory features of a mitochondrial encephalomyoneuropathy. A muscle biopsy specimen showed ragged-red fibres. Signs of demyelination and remyelination of a few fibers were observed in a sural nerve biopsy specimen. MR imaging revealed symmetrical multifocal white matter lesions predominantly in the parieto-occipital region. We stress the benefitial therapeutic effect of CoQ since it resulted in marked alleviation of some signs of the disease.

[Guillain-Barre syndrome and antibodies to ganglioside GM1. Case report]. / Giljen-Bareov sindrom i antitela protive gangliozida GM1. Prikaz bolesnice.

A sudden onset of the syndrome Guillain-Barré in 48-year-old woman presenting as an acute motor neuropathy was associated with antibodies against ganglioside GM1 detected by ELISA. The neurological examination revealed flaccid quadriplegia without affection of the sensory system, and the additional investigation showed mild increase of the CSF protein content, demyelination of the peripheral motor nerves and significantly increased titer of the serum and CSF anti-GM1 antibodies. Several copruculture for Campylobacter jejuni gave negative results. There was a significant correlation between the severity of the clinical picture and the titer of the serum anti-GM1 antibodies. The patient completely and spontaneously recovered after five weeks. According to the clinical and laboratory parameters the patient could be classified as an axonal, and according to electromyographic findings and the course of the disease as the classical form of the syndrome Guillain-Barré.

[Cerebrospinal fluid findings in patients with acute and chronic inflammatory demyelinating polyradiculoneuropathies]. / Nalaz u likvoru kod bolesnika s akutnom i hronicnom inflamcionom demijelinizacionom poliradikuloneuropatijom.

We studied the cerebrospinal fluid (CSF) in patients with acute (AIDP) and chronic inflammatory demyelinating poliradiculoneuropathy (CIDP). In order to assess its possible contribution in establishing the diagnostic approach, we analyzed the cell content, concentrations of total proteins, albumin and IgG, CSF/serum albumin quotient and the qualitative study of IgG. Sixteen patients with AIDP and 16 patients with CIDP, fulfilling the accepted diagnostic criteria, were included in this study. CSF features were not used as exclusion criteria. The cell count and concentration of total proteins were determined by standard procedures. CSF albumin was performed and IgG were done by single radial immunodiffusion, and the qualitative analysis of IgG by agarose isoelectric focusing of unconcentrated CSF. The incidence of elevated levels of total CSF proteins was identical in patients with AIDP and CIDP, reaching 94%. The mean level of CSF protein was similar in patients with AIDP and CIDP, 1100 and 1150 mg/l, respectively. The cell count was elevated in 3 (19%) patients with AIDP and normal in patients with CIDP. There were no significant differences in the mean level of any of CSF parameters between patients with AIDP and CIDP. Local synthesis of CSF oligoclonal IgG was found in 2 patients with CIDP and was not detected in patients with AIDP. No association between CSF and clinical parameters was recorded. The results of this study confirm that an elevated CSF protein and low CSF cell count are features highly supportive of the diagnosis of both AIDP and CIDP. The most intriguing finding is the detection of locally produced CSF oligoclonal IgG which may suggest the associated inflammation within the central nervous system in a number of patients with CIDP, and furthermore a pathogenic link between CIDP and multiple sclerosis.

[Diagnostic problems in patients with myasthenia gravis]. / Dijagnosticki problemi kod bolesnika s miastenijom gravis.

Myasthenia gravis (MG) is an antigen-specific autoimmune disease in which antibodies directed against nicotinic acetylcholine receptors of the postsynaptic muscle membrane (nAChR) impair neuromuscular transmission. MG is clinically characterized by abnormal muscle fatigue and weakness. The initial symptoms and signs are often unrecognized. Therefore, we analyzed the diagnostic errors and duration of diagnostic delay in patients affected with MG (n = 444) in a ten-year period (January 1, 1983-December 31, 1992) in Yugoslavia. The initial diagnosis was correct in 44.4% of patients and erroneous in 38.4%; 17.2% of patients were admitted without an initial diagnosis. The average duration of diagnostic delay was 11 months. We present the differential diagnostic difficulties in MG and discuss the principles of diagnostic strategy which may reduce the risk of diagnostic errors in MG.

Epidemiological and clinical characteristics of myasthenia gravis in Belgrade, Yugoslavia (1983-1992).

This is the first epidemiological study of myasthenia gravis (MG) in the area of Belgrade. During the survey period (1983 1992), 124 incidental cases of MG were observed, producing an average annual incidence rate of 7.1 per million population (women, 8.3; men, 5.8). Age and sex specific incidence rates for females demonstrated a bimodal pattern, with the first peak in the age group between 20 and 40, and the second peak in the age group 70-80. The age-specific rates for males showed unimodal pattern, reaching a maximum in the age group between 60 and 80. There was a tendency of more frequent disease appearance in the urban as opposed to the suburban districts. On the prevalence day, December 31, 1992, the point prevalence rate was 121.5 per million (women, 142.5; men, 98.8). Only for incidental cases, the point prevalence rate was 77.1 (women, 83.2; men, 70.4). The average annual mortality rate was 0.47 per million (females, 0.52; males, 0.42), while cumulative lethality was 5.6 (women, 5.6; men, 5.7). Most frequently initial symptoms were ocular, occurring in 58% patients. Through the period of investigation ocular symptoms were generalized in 68%, most frequently in the first 2 years (62.5%). Thymoma was confirmed in 11.3% of patients. In this group there was equal presence of both sexes, older median age at onset, and more severe clinical course of MG. Associated autoimmune disease was found in 17 out of 124 incidental cases (13.7%). The most common were thyroid diseases (7.3%). Family history of MG was recorded in 2 cases belonging to 1 family (1.6%).

Motor neuron disease and monoclonal gammopathy.

In a study to determine the prevalence of monoclonal gammopathy (MG) among patients with motor neuron disease (MND), 6 out of 56 (10.7%) were found to have a monoclonal paraprotein. Of these 6 patients, 4 had an IgG and 2 had an IgA paraprotein. The clinical syndromes consisted of amyotrophic lateral sclerosis in 2 patients, lower motor neuron syndrome with preserved reflexes in at least one limb in 3 patients, and motor neuropathy with multifocal conduction block in 1 patient. The presence of gammopathy appears to correlate with the absence of marked upper motor neuron involvement and with elevated CSF protein concentration. An underlying malignant disorder was ruled out in all 6 patients, and they were considered to have MG of undetermined significance (MGUS). In a control group of 121 age-matched patients with other neuroimmunological disorders, 5 patients (4.13%) had MG. Four of these had gammopathy associated with malignant myeloma, and 1 had MGUS. These results support previous reports of increased prevalence of MGUS in patients with MND and suggest that an autoimmune mechanism may play a role in the disease.