Impact of muscle biopsy on the clinical decision-making process in patients with suspected idiopathic inflammatory myopathy.

BACKGROUND: The significance of muscle biopsy as a diagnostic tool in idiopathic inflammatory myopathies (IIM) remains elusive. We aimed to determine the diagnostic weight that has been given to muscle biopsy in patients with suspected IIM, particularly in terms of clinical diagnosis and therapeutic decisions. MATERIAL AND METHODS: In this retrospective multicentric study, we analyzed muscle biopsy results of adult patients with suspected IIM referred to a tertiary center between January 1, 2007, and October 31, 2021. Information regarding referral department, suspected diagnosis, biopsy site, demographic, clinical, laboratory data, and imaging results were extracted. Statistical analyses included the level of agreement between suspected and histological diagnosis and calculation of diagnostic performance (positive and negative predictive values, positive and negative likelihood ratios, sensitivity, and specificity of muscle biopsy in relation to clinical diagnosis and/or treatment initiation). Performance was tested in different strata based on clinical pre-test probability. RESULTS: Among 758 muscle biopsies, IIM was histologically compatible in 357/758 (47.1%) cases. Proportion of IIM was higher if there was a solid clinical pre-test probability (64.3% vs. 42.4% vs. 48% for high, medium and low pre-test probability). Sensitivity and specificity of muscle biopsy were highest (82%) when the diagnosis by the clinician was used as outcome scenario. Negative predictive value was only moderate (between 63% and 80%) and lowest if autoantibodies were positive (35%). CONCLUSION: In patients with clinically suspected IIM, approximately 50% of biopsies revealed features indicative of IIM. Diagnostic performance of muscle biopsy was moderate to high depending on clinical pre-test probability.

Bulbospinal muscular atrophy (Kennedy disease) responsive to immunoglobulins?

A 61 year old man with facial diplegia, quadruparesis, tongue atrophy/fasciculations, bulbar speech, muscle weakness/wasting, hypotonia, tremor, dysdiadochokinesia, absent tendon reflexes, fasciculations, and gynecomastia, received immunoglobulins for suspected immune-neuropathy with limited benefit. After reconsideration, Kennedy disease was diagnosed upon 44 CAG repeats in AR. In conclusion, immunoglobulins exhibit limited benefit on immune-neuropathy in patients with coexisting KD.

Treatment for paraneoplastic neuropathies.

BACKGROUND: It is not unusual to observe peripheral nervous system involvement in people with tumours outside the nervous system. Any part of the peripheral nervous system can be involved, from sensory and motor neurons to nerve roots and plexuses, from distal trunks to neuromuscular junctions. Pathogenesis also varies from direct infiltration by cancer cells, to treatment toxicity, to metabolic derangement, cachexia, infections and paraneoplastic syndromes.Paraneoplastic neurological syndromes are symptoms or signs resulting from damage to organs or tissues that are remote from the site of the malignancy or its metastases. The pathogenesis is thought to be immune-mediated as a result of a cross-reaction against antigens shared by the tumour and nervous system cells.Paraneoplastic neuropathies are the most frequently reported paraneoplastic syndromes. They are, however, heterogeneous and require several therapeutic approaches. This review was undertaken to systematically assess any data available from randomised controlled trials (RCTs) on the treatment of paraneoplastic syndromes of the peripheral nervous system and not the whole range of paraneoplastic neurological syndromes. OBJECTIVES: To assess the benefits and harms of treatments for paraneoplastic neuropathies. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2012), CENTRAL (2012, Issue 1), MEDLINE (January 1966 to February 2012), EMBASE (January 1980 to February 2012) and LILACS (January 1982 to February 2012) for RCTs, quasi-RCTs, historically controlled studies and trials with concurrent controls.We adapted this strategy to search MEDLINE from 1966 and EMBASE from 1980 for comparative cohort studies, case-control studies and case series. SELECTION CRITERIA: We planned to include all RCTs and quasi-RCTs (in which allocation is not random but is intended to be unbiased, for example alternate allocation) of any treatment for paraneoplastic neuropathies. Since we expected there to be few or no included studies, we also planned to assess and summarise observational studies, prospective and retrospective comparative cohort studies, case-control studies and case series that met minimum criteria in the discussion. DATA COLLECTION AND ANALYSIS: Three review authors selected the trials for inclusion. When there was any disagreement we reached an agreement by discussion. Two review authors extracted data independently onto a specially designed data extraction form. We would have collected adverse event data from included studies. MAIN RESULTS: Despite many reports on paraneoplastic neuropathy, we identified no RCT or quasi-RCTs for inclusion in this review. We found only six studies, involving 54 participants, from among the non-randomised evidence that were judged by predefined criteria to be of suitable quality for inclusion in the discussion. These studies were not readily comparable. The treatments focused on tumour treatment and immunomodulation, mainly intravenous immunoglobulin. AUTHORS' CONCLUSIONS: At present there are no RCTs or quasi-RCTs of treatment for paraneoplastic neuropathies on which to base practice. There is only evidence from case series, case reports or expert opinion (class IV evidence) for the effect of immunomodulation (intravenous immunoglobulin, plasma exchange, steroid treatment or chemotherapy) on paraneoplastic neuropathy.  

Myeloid sarcoma in the central nervous system: case report and review of the literature.

Myeloid sarcomas are rare manifestations of mainly myeloblastic leukemia. Their occurrence in the central nervous system is exceptional and current literature is limited to case studies. A case is added herewith and a review was performed to investigate clinical characteristics and treatment options of central nervous system myeloid sarcoma. A 61-year-old female with acute myeloblastic leukemia (FAB M5) and progressive left sided hemiparesis showed a right parieto-occipital epidural lesion mimicking meningioma. Partial resection was performed to reveal a myeloid sarcoma. Reviewing the literature we identified 44 cases with sufficient description of the diagnosis, treatment and follow up to one year. In these patients different treatment regimens were applied. However, when systemic chemotherapy or irradiation was included in the treatment regimen, patients showed the best 1-year survival proportion.

The end-of-life hospital setting in patients with glioblastoma.

Despite aggressive treatment, outcome of patients with glioblastoma is poor. Several distinct clinical problems arise in the terminal stage of this disease. The purpose of this study was to evaluate the end-of-life phase in a hospital setting in patients with glioblastoma. Twenty-nine consecutive patients with glioblastoma, who died in our department, were included in this analysis regarding symptoms, medication, diagnostics, and interventional procedures. The patients were comparable with respect to age, gender, and overall survival with data from the literature. Relevant clinical symptoms, medications, diagnostics, well as interventional procedures increased continuously toward end of life. Pain, epileptic seizures, and symptoms of brain edema were the most frequent clinical symptoms. According to this, most patients were on antiepileptic drugs (AED), steroids, and analgesics. In the last phase, symptoms from brain edema, fever, decrease of vigilance, dysphagia, and pneumonia were the prominent clinical features. Our study demonstrates that the end of life in patients with glioblastoma has several periods with different clinical aspects with respect to symptoms and treatment.

Visualizing central effects of S-adenosyl-L-methionine (SAMe), a natural molecule with antidepressant properties, by pharmaco-EEG mapping.

In a double-blind, placebo-controlled, cross-over study, the central effects of the natural molecule S-adenosyl-L-methionine (SAMe), or ademetionine (ADE), used in low doses as a nutraceutical and in higher doses as a pharmaceutical, were investigated by means of EEG mapping and psychometry. Ten young, normal healthy volunteers of both sexes, with a mean age of 25.2+3.9 yr received, in random order, infusions of 800 mg ADE in 250 ml of isotonic solution, and placebo consisting of 250 ml of isotonic solution administered over 30 min for 7 d, with a wash-out period of 3 wk in between. EEG recordings and psychometric tests were carried out 0, 1, 3 and 6 h after drug administration on days 1 and 7. While there were no significant changes in psychometric findings, multivariate analyses of the EEG results based on MANOVA/Hotelling T 2 tests demonstrated significant encephalotropic effects of ADE compared to placebo. ADE-induced changes were characterized by a decrease in total power, an increase in absolute delta power and a decrease in absolute alpha and beta power, further by an increase in relative delta and beta power and a decrease in relative alpha power, a slowing of the delta/theta centroid, an acceleration of the alpha centroid as well as a slowing of the centroid of the total power spectrum. These changes are typical of classical antidepressants of the thymoleptic type such as imipramine and amitriptyline. Time-efficacy calculations demonstrated a significant central effect of ADE in the first hour after the first infusion, declining slowly until the third hour and thereafter steeply until the sixth hour; a further significant effect was after 1 wk of daily infusions and in the third hour after one superimposed infusion on day 7 of subacute treatment. Our pharmaco-EEG findings suggest both inhibitory and excitatory drug effects at the neurophysiological level, underlying the antidepressant properties well-documented in clinical trials.