Neuropathy associated with “benign” anti-myelin-associated glycoprotein IgM gammopathy: Clinical,immunological, neurophysiological pathological findings and response to treatment in 33 cases

We studied 33 patients presenting with a peripheral neuropathy associated with non-malignant anti-myelin-associated glycoprotein (MAG) IgM monoclonal gammopathy (MG) in an attempt to delineate their clinical, immunological, electrophysiological and pathological characteristics; we also reviewed our experience concerning long-term follow-up and therapy. Peripheral neuropathy associated with non-malignant anti-MAG IgM MG was observed mostly in males (sex ratio 7.2), and mean age at onset was 67 years (range 46–81). A predominantly sensory pattern was noted in more than 80% of cases, although some patients were affected by a predominantly motor peripheral neuropathy. Although disease progression was slow in most cases, 45% of patients suffered severe disability, and in 2 cases, the patient's death appeared to stem directly from the neuropathy. The electrophysiological findings were indicative of a demyelinating process in 90% of cases, and electron microscopic examination of nerve biopsy specimens demonstrated widening of the myelin lamellae in more than 95% of cases. Most of our patients showed a disappointing response to steroids and chemotherapy or plasma exchanges. Intravenous immune globulin, evaluated in 17 patients, had a transient, mostly subjective effect in 35% and led to a clear-cut improvement in 24% of cases. We did not observe any correlation between the severity of the clinical picture and the anti-sulphoglucuronyl paragloboside antibody titre; in individual cases, clinical improvement occurred without lowering of IgM levels. Although the severity and the rate of progression may greatly vary from patient to patient, the combination of clinical, electrophysiological and pathological features delineates a characteristic pattern in peripheral neuropathy associated with non-malignant anti-MAG IgM MG.     

Autosomal dominant centronuclear myopathy]

In a family 6 members in 3 generations were affected by centronuclear myopathy (CNM) of autosomal dominant inheritance. The apparent onset was in the early forties and the disease progressed slowly. Limb weakness was predominant. Strabismus was present in 5 cases and calves hypertrophy in 3. Serum creatinine kinase was always within the normal range. In one case myotonic bursts were found at electromyography. In 2 cases brain stem auditory evoked potential studies demonstrated abnormal prolongation of interpeak latencies I-III and favoured subclinical nervous system involvement. Muscular biopsies showed typical features of centronuclear myopathy with 50 to 80% central nuclei. In two cases immunocytochemical labelling of dystrophin showed staining in the sarcoplasm in favour of an arrest in the morphogenesis of developing myofiber. Others families with autosomal dominant CNM in the literature and also some sporadic adult cases had similar clinical features.     

Slow degeneration of zebrafish Rohon-Beard neurons during programmed cell death.

Rohon-Beard cells are large, mechanosensory neurons located in the dorsal spinal cord of anamniote vertebrates. In most species studied to date, these cells die during development. We followed labeled Rohon-Beard cells in living zebrafish embryos and found that they degenerate slowly, over many days. During degeneration, the soma shrinks and finally disappears, and the processes become beady in appearance and finally break apart, but they do not retract. Zebrafish Rohon-Beard cells apparently fragment their DNA, as revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) labeling, before undergoing degenerative morphologic changes. We also followed the development of labeled dorsal root ganglion neurons, as they are developing at the same stages that Rohon-Beard cells are degenerating. We found that, although axons of both cell types extend into similar regions, Rohon-Beard cells degenerate normally in mutants lacking dorsal root ganglia, providing evidence that interactions between the two cell types are not responsible for Rohon-Beard cell degeneration. Developmental Dynamics 229:30-41,2004.     

Severe axonal polyneuropathy with onset in the postpartum period

We report two patients who presented severe polyneuropathy in the postpartum period. Electrophysiological studies evidenced an axonal process which was associated with proximal demyelination in the second patient. In both cases, a peripheral nerve biopsy showed severe axonal Wallerian-like degeneration and no feature of demyelination. The first patient had a dramatic loss of myelinated fibres, and severe disability persisted for several months. These two patients are different from cases of acute or chronic inflammatory demyelinating polyradiculoneuropathy previously reported in relation with pregnancy.     

Sampling Patients Within and Across Health Care Providers: Multi-Stage Non-Nested Samples in Health Services Research

In order to better inform study design decisions when sampling patients within and across health care providers we develop a simulation-based approach for designing complex multi-stage samples. The approach explores the tradeoff between competing design goals such as precision of estimates, coverage of the target population and cost.We elicit a number of sensible candidate designs, evaluate these designs with respect to multiple sampling goals, investigate their tradeoffs, and identify the design that is the best compromise among all goals. This approach recognizes that, in the practice of sampling, precision of the estimates is not the only important goal, and that there are tradeoffs with coverage and cost that should be explicitly considered. One can easily add other goals. We construct a sample frame with all phase III clinical cancer treatment trials that are conducted by cooperative oncology groups of the National Cancer Institute from October 1, 1998 through December 31, 1999. Simulation results for our study suggest sampling a different number of trials and institutions than initially considered.Simulations of different study designs can uncover efficiency gains both in terms of improved precision of the estimates and in terms of improved coverage of the target population. Simulations enable us to explore the tradeoffs between competing sampling goals and to quantify these efficiency gains. This is true even for complex designs where the stages are not strictly nested in one another.     

A comparison of schizophrenic patients in different community support treatment approaches

Recent advances in the care of the chronically mentally ill in the community have resulted in a community support system approach to maintaining chronically mentally ill persons outside the hospital. Yet, very little is known of what a community support system actually is for the chronic mental patient. This paper looks at three different sorts of community support programs and compares a sample of patients within them with respect to network variables, role performance, and demographic variables. Implications regarding the use of network oriented approaches are discussed and directions for further research are explored.     

Anger Dimensions and Mental Health Following a Disaster: Distribution and Implications After a Major Bushfire

Anger is an important dimension of affect and a prominent feature of posttraumatic mental health, but it is commonly overlooked in postdisaster settings. We aimed to examine the distribution and implications of significant anger problems in the aftermath of a natural disaster, via analyses of Beyond Bushfires survey data from 736 residents of rural communities 5 years after the 2009 Black Saturday bushfires in Victoria, Australia. Assessments included the five‐item Dimensions of Anger Reaction (DAR‐5) scale along with measures of PTSD, depression, and significant mental illness, and indicators of life satisfaction, suicidality, hostile aggressive behavior, and violence exposure. The results indicated that approximately 10% of respondents from areas highly affected by the bushfires scored above the provisional cutoff criteria for significant anger problems on the DAR‐5, which was a more than 3‐fold increase, OR = 3.26, relative to respondents from areas of low‐to‐moderate bushfire impact. The rates were higher among women, younger participants, and those who were unemployed, and co‐occurred commonly, although not exclusively, with other postdisaster mental health problems. Anger problems were also associated with lower life satisfaction, β = ?.31, an 8‐fold increase in suicidal ideation, OR = 8.68, and a nearly 13‐fold increase in hostile aggressive behavior, OR = 12.98. There were associations with anger problems and violence exposure, which were reduced when controlling for covariates, including probable PTSD. The findings provide evidence indicating that anger is a significant issue for postdisaster mental health and should be considered routinely alongside other posttraumatic mental health issues.     

How expensive are unlimited substance abuse benefits under managed care?

Substance abuse (SA) care has been excluded from recent federal and state legislation mandating equal benefits for mental health and medical care (parity), largely because of cost concerns. This article studies how many patients are affected by SA coverage limits and the likely implications of limits on insurance payments, using 1996–97 claims from 25 managed care plans with unlimited SA benefits. Changing even stringent limits on annual SA benefits has a small absolute effect on overall insurance costs under managed care, even though a large percentage of SA patients are affected. Removing an annual limit of $10,000 per year on SA care is estimated to increase insurance payments by about 6 cents per member per year, removing a limit of $1,000 increases payments by about $3.40. As long as care is comprehensively managed, parity for SA in employer-sponsored health plans is not very costly.