Mycophenolate mofetil in dermatomyositis: is it safe?

The authors report 10 patients with idiopathic dermatomyositis treated with mycophenolate mofetil in combination with corticosteroids. Successful steroid taper without disease relapse was achieved in six patients; however, in three patients, treatment was associated with opportunistic infections, leading to death in one patient. The disproportionately high rate of opportunistic infections in this group is considered.

Etanercept treatment in corticosteroid-dependent myasthenia gravis.

The authors report a prospective pilot trial of etanercept in corticosteroid-dependent autoimmune myasthenia gravis. Eleven patients were enrolled, with eight completing the 6-month trial. Two patients were withdrawn owing to disease worsening, and one patient was withdrawn because of an erythematous skin rash. Six of the eight patients who completed the trial improved, based on quantitative measures of muscle strength and lowering of corticosteroid requirement.

[Can the treatment with L-carnitine improve the inflammation in chronic hemodialysis patients?]. / Può il trattamento con L-carnitina migliorare lo stato infiammatorio dei pazienti in trattamento emodialitico cronico?

PURPOSE: Inflammation in patients on chronic hemodialysis (HD) is related to malnutrition and atherosclerosis; anemia is also often present in these patients. It has been demonstrated that l-carnitina treatment, in addition to reducing the need for erythropoietin (EPO), improves nutritional parameters and cardiac performance. METHODS: To evaluate the effect of l-carnitine on the inflammatory pathology in patients on chronic HD, we studied 11 patients with no sure signs of malnutrition, flogistic and infective pathologies and with C-reactive protein (CRP) <2 mg/dL. We evaluated at baseline, after 6 and 12 months CRP, serum albumin, hemoglobin (Hb),nPCR and EPO weekly requirement. RESULTS: We observed a reduction in CRP (from 0.88 +/- 0.65 to 0.42 +/- 0.17 mg/dL after 6 months and to 0.50 + 0.36 mg/dL after 12 months), an increase in serum albumin (from 10.9 +/- 1.23 to 2.08 +/- 1.88 and to 11.8 +/- 1.15 g/dL) and an increase in nPCR (from 0.96 +/- 0.09 to 1.15 +/- 0.2 and to 1.16 +/- 0.18 g/kg/die); EPO weekly requirement decreased (from 7363 +/- 2941 to 5909 +/- 3207 units after 6 months and to 5363 +/- 3139 units after 12 months). CONCLUSION: These results seem to underline a positive effect of l-carnitine on the inflammatory pathology of patients on chronic hemodialytic treatment.

Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety, and tolerability.

The authors report a retrospective analysis of the use of mycophenolate mofetil (MyM) in 85 patients with autoimmune myasthenia gravis. The Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) was used to characterize the treatment response in each patient. Sixty-two patients (73%) achieved a PIS status indicating improvement. Quantitative strength testing performed on the majority of patients before and after treatment also improved. Side effects to MyM were observed in 27% of patients but required discontinuation in only 6%.

Monomelic amyotrophy with late progression.

Monomelic amyotrophy is a sporadic juvenile-onset disease that presents with gradual onset of weakness and atrophy in the hand muscles unilaterally. Generally, this disease is considered a 'benign' and non-progressive motor neuron disease, which stabilizes within five years of onset. We discuss a case that illustrates that monomelic amyotrophy may rarely exhibit late clinical progression to the lower extremities after a prolonged period of disease stability.

HMG-CoA Reductase Inhibitor Myopathy: Clinical, Electrophysiological, and Pathologic Data in Five Patients.

OBJECTIVES: To define the clinical, electrophysiological, and pathologic features of the myopathy associated with the use of HMG CoA reductase inhibitors. METHODS: Five patients with myopathy associated with HMG CoA reductase inhibitors were evaluated. Complete histories, physical examinations, manual muscle testing, serum creatine kinase, urine myoglobin measurements, electrodiagnostic studies, and muscle biopsy were performed. RESULTS: Consistent features in our patients included a subacute onset of myalgias and weakness, electromyography demonstrating electrical myotonia, elevated creatine kinase levels, and in some patients myoglobinuria despite a relative lack of muscle necrosis on muscle biopsy and preserved myofibrillatory architecture by electron microscopy. All patients experienced resolution of symptoms within 3 weeks of drug discontinuation. CONCLUSIONS: We postulate that the constellation of clinical, electrophysiological, and pathologic findings among our patients with HMG CoA reductase inhibitor myopathy may be explained by the early toxic effects of HMG CoA reductase inhibitors on muscle membrane organelles and sarcolemmal function. Patients on concurrent therapy with cyclosporine, gemfibrozil, and antifungal agents of the azole groups are at an increased risk of developing this toxic myopathy.

Treatment of myasthenia gravis with mycophenolate mofetil: a case report.

We report a patient with myasthenia gravis (MG) who had marked clinical benefit in response to treatment with mycophenolate mofetil as documented by serial quantitative measures of strength and muscle fatigue. Our patient had experienced either adverse side effects or a suboptimal response to the usual immunosuppressive agents used in MG. Mycophenolate mofetil was used in combination with cyclosporine and prednisone and allowed for significant reductions in dosage of these immunosuppressants. We conclude that mycophenolate mofetil deserves further study as a therapeutic agent in MG. In particular, its role as a steroid-sparing agent and as a drug to be used in combination immunotherapy in more severe or refractory cases of MG should be investigated.

Electrodiagnostic significance of supramaximally stimulated A-waves.

A-waves are generally considered a nonspecific finding of unclear electrodiagnostic and clinical significance. We systematically identified A-waves during routine F-wave studies and defined them as supramaximally elicited reproducible intermediate to late responses that are clearly separate from the M-responses. In patients with A-waves, we noted electrophysiologic diagnoses, the nerve in which the A-wave was identified, the presence of A-waves in multiple nerves, and A-wave morphology. In 54 of 1,258 studies performed, A-waves were present in one or more nerves. Electrophysiologic diagnoses in patients with A-waves included diffuse axonal neuropathy (11.5%), demyelinating neuropathy (66.7%), motor neuron disease (6.5%), radiculopathy (3.6%), mononeuropathy (3.9%), and normal (tibial nerve only) 0.7%. A-waves were abnormal when found in any nerve except the tibial nerve. They were particularly prevalent and present in multiple nerves in acquired and hereditary demyelinating neuropathies, and they more often had a complex morphology. We postulate that demyelination is the crucial underlying pathophysiologic correlate of the supramaximally stimulated A-wave.

Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

Treatment with interferon-alpha (IFN-alpha) has been associated with the occurrence of a number of autoimmune disorders. We report a case of chronic inflammatory demyelinating polyneuropathy (CIDP) occurring in a patient with a chronic viral hepatitis C infection who received a novel, long-acting form of IFN-alpha. After withdrawal of the interferon treatment, this patient responded to a single extended course of plasma exchange that resulted in a complete clinical remission of symptoms without relapse.

Prominent inflammatory changes on muscle biopsy in patients with Miyoshi myopathy.

Miyoshi myopathy is a rare autosomal recessive distal myopathy characterized by early and prominent involvement of the posterior compartment of the legs. We describe two patients with the clinical diagnosis of Miyoshi myopathy who demonstrated marked inflammatory changes on muscle biopsy of clinically less affected muscles. This report illustrates the importance of recognizing the marked variability in histopathology of Miyoshi myopathy which may include an inflammatory infiltrate on muscle biopsy which mimics the histopathologic picture of an inflammatory myopathy.

Distinguishing clinical and electrodiagnostic features of X-linked bulbospinal neuronopathy.

X-linked bulbospinal neuronopathy (XLBSN) or Kennedys disease is a rare inherited neuromuscular disease characterized by adult-onset muscle weakness, usually in a limb-girdle distribution. It is frequently misdiagnosed despite a distinctive clinical presentation, usually due to the absence of a clear family history, and perhaps also due to failure of recognition. Accurate diagnosis is crucial for genetic counseling purposes and because alternative diagnoses usually carry a poorer prognosis. We evaluated 4 patients with XLBSN and one symptomatic female heterozygote patient. Based on our clinical observations in these patients and a systematic review of previously reported cases, the following clinical and electrophysiologic features when present in the setting of adult-onset muscle weakness, are strongly suggestive of the disorder: 1) facial weakness, 2) facial twitching or fasciculations, 3) tongue weakness and atrophy, 4) postural hand tremor, 5) hypo- or areflexia, and 6) absent or low-amplitude sensory nerve action potentials despite clinically normal sensation. We also hypothesize regarding the possibility of partial expression of the abnormal XLBSN gene in a symptomatic heterozygote female patient.

Complex repetitive discharges: cause or effect of neurogenic muscle hypertrophy?

We report a patient with adult-onset spinal muscular atrophy (SMA) of the scapulohumeral type with neurogenic muscle hypertrophy (NMH) in markedly weakened biceps muscles in association with continuous complex repetitive discharges (CRDs). This is an apparently unique case due to the bilaterality of the NMH associated with CRDs as well as the well-circumscribed symmetric upper extremity distribution of the hypertrophy. The possible mechanisms of NMH in association with spontaneous motor activity are discussed.

Conduction block and continuous motor unit activity in chronic acquired demyelinating polyneuropathy.

The term continuous motor unit activity (CMUA) may be used to refer to the involuntary, sustained activity of motor units caused by hyperactivity of peripheral motor nerves. CMUA has been reported in association with acquired neuropathies such as chronic inflammatory demyelinating polyneuropathy. The precise mechanism responsible for the excess muscle activity is not defined, but the activity is believed to originate in the peripheral nerves, perhaps at sites of focal demyelination. We describe a case of an acquired, demyelinating neuropathy associated with distal motor conduction block in which CMUA was observed in muscles innervated by blocked axons. Despite the prolonged disease duration of nearly 40 years, marked clinical and electrophysiological improvement as well as resolution of the CMUA were observed following immunosuppressive therapy. A relationship between the chronic motor conduction block and the excess muscle activity is postulated.

Circulating levels of IGF-I in patients with chronic uremia on conservative dietary treatment.

The assessment of nutritional status is a very important step in the clinical management of chronic uremic patients, because of the influences of chronic renal failure and of dietary manipulations on the energy and protein metabolism. In this study some serum biochemical markers of protein nutrition, including IGF-I and pre-albumin, have been measured in chronic renal failure patients treated with two different low-protein diets, according to the residual renal function for several months. Our results showed no significant changes of IGF-I, pre-albumin or albumin serum levels in the patients treated with a very low-protein diet (0.3 g/Kg b.w. per day) supplemented with essential amino acids and ketoacids, in comparison with the patients on a conventional low-protein (0.6 g/Kg b.w. per day) diet.

Safety and efficacy anticoagulation in extracorporeal hemodialysis by simultaneous administration of low-dose prostacyclin and low molecular weight heparin.

BACKGROUND: The aim of this work is to describe an approach allowing extracorporeal hemodialysis (HD) with administration of low molecular weight heparin (LMWH) and to compare the dialyzer efficiency of this approach versus infractionated heparin (UFH) used alone. METHODS: Low molecular weight heparin (Nadroparin, molecular weight 4500 d) administered in a single injection (dose 3075 IU AXa) plus prostacyclin (Epoprostenol sodium salt, molecular weight 375 d) by continuous infusion (3 ng/kg/min) have been used as anticoagulants during hemodialysis in 8 patients. In comparison, standard continuous heparinization by unfractionated heparin was used. Hemodialysis efficiency (dialyzer clearance for urea, creatinine, uric acid and phosphate), coagulation (activated partial thromboplastin time, antithrombin III, fibrinogen platelet count, prothrombin time) and hemodynamic parameters (blood arterial pressure and heart rate) were also evaluated during dialysis. RESULTS AND CONCLUSIONS: Simultaneous infusion of low molecular weight heparin plus prostacyclin allowed safe and effective anticoagulation without affecting hemodialysis efficiency.

Peripheral neuropathy and connective tissue disease. Watch for this twosome when hunting for a diagnosis.

Coexistent peripheral neuropathy and connective tissue disease is fairly common, possibly because immune-mediated factors are often present in both disorders. Awareness of the association between the two conditions can be important during diagnostic evaluation, because neuropathy is sometimes the presenting feature of previously unrecognized connective tissue disease. In this article, the authors examine clinical findings in vasculitic, nonvasculitic, and treatment-related neuropathy, concentrating on the essentials of diagnosis and treatment.

Coagulation activation in extracorporeal hemodialysis.

The authors evaluated the behavior of protein C activity, factor X and factor VII coagulant activity and serum lipoprotein(a) before and after dialytic treatment in patients on maintenance hemodialysis. They observed depressed protein C activity that significantly (p < 0.005) increased and became normal immediately after hemodialysis while factor X and factor VII increased (p < 0.01; p < 0.05) despite heparinization together with amount of serum lipoprotein(a). In vitro incubation (30' at 37 degrees C) of uremic and healthy blood showed a decrease in serum lipoprotein(a) concentration. After heparin addition (final concentration 0.5 U/ml) lipoprotein(a) increased in the uremic blood only. The clinical and physiopathological implications of these results are discussed.

[Coagulation in hemodialysis]. / Coagulazione in emodialisi.

The authors have evaluated the behaviour of protein C activity, factor X and factor VII coagulant activity, and serum lipoprotein(a) before and after haemodialytic treatment in the plasma of patients on maintenance haemodialysis. The plasma level of protein C activity, depressed before haemodialysis, significantly increased during the course of haemodialysis; factor X and factor VII increased as well despite heparinization; serum lipoprotein(a) was abnormally elevated before haemodialysis and did not change after haemodialysis. In vitro incubation (30' at 37 degrees C) of uremic and healthy blood samples resulted in a decrease of serum lipoprotein(a) concentration. After heparin addition (final concentration 0.5 U/ml) lipoprotein(a) became higher in uremic blood only.