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.     

An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding

Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [¹⁸F]-setoperone for 5-HT2 binding potential (BP) and [¹¹C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [¹⁸F]-setoperone and with [¹¹C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as ≥50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP.     

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.     

Non-invasive magnetic resonance imaging assessment of myocardial changes and the effects of angiotensin-converting enzyme inhibition in diabetic rats

A non-invasive cine magnetic resonance imaging (MRI) technique was developed to allow, for the first time, detection and characterization of chronic changes in myocardial tissue volume and the effects upon these of treatment by the angiotensin-converting enzyme (ACE) inhibitor captopril in streptozotocin (STZ)-diabetic male Wistar rats. Animals that had been made diabetic at the ages of 7, 10 and 13 weeks and a captopril-treated group of animals made diabetic at the age of 7 weeks were scanned. The findings were compared with the results from age-matched controls. All animal groups (n = 4 animals in each) were consistently scanned at 16 weeks. Left and right ventricular myocardial volumes were reconstructed from complete data sets of left and right ventricular transverse sections which covered systole and most of diastole using twelve equally incremented time points through the cardiac cycle. The calculated volumes remained consistent through all twelve time points of the cardiac cycle in all five experimental groups and agreed with the corresponding post-mortem determinations. These gave consistent myocardial densities whose values could additionally be corroborated by previous reports, confirming the validity of the quantitative MRI results and analysis. The myocardial volumes were conserved in animals whose diabetes was induced at 13 weeks but were significantly increased relative to body weight in animals made diabetic at 7 and 10 weeks. Captopril treatment, which was started immediately after induction of diabetes, prevented the development of this relative hypertrophy in both the left and right ventricles. We have thus introduced and validated quantitative MRI methods in a demonstration, for the first time, of chronic myocardial changes in both the right and left ventricles of STZ-diabetic rats and their prevention by the ACE inhibitor captopril.     

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.     

Histological comparison of implanted cadaveric and porcine dermal matrix grafts.

OBJECTIVES: Histological comparison of human-based (AlloDerm) and porcine-based (ENDURAGen) dermal matrices regarding tissue incorporation and neovascularization as potential soft tissue augmentation materials. STUDY DESIGN: In vivo, rat model. METHODS: Subcutaneous implantation of 1-mm thick, 1 cm x 1 cm pieces of AlloDerm, ENDURAGen, and meshed ENDURAGen was performed in 24 Sprague Dawley rats. Implant materials were harvested at 4 (n = 12) and 8 weeks (n = 12). Histological quantification of soft tissue ingrowth and microvascular density was performed following hematoxylin-eosin staining and CD34 immunohistochemistry, respectively. RESULTS: AlloDerm showed significantly greater soft tissue ingrowth and microvascular density compared with both ENDURAGen and meshed ENDURAGen at 4 and 8 weeks (P < 0.001). CONCLUSIONS: Although these results may differ in human host tissues, AlloDerm seems to be a more suitable dermal matrix implant than ENDURAGen for cases in which tissue incorporation and neovascularization are sought for the optimal outcome based on this animal model.     

Treatment Integrity and Therapeutic Change: Commentary on Perepletchikova and Kazdin

Perepletchikova and Kazdin's (this issue) analysis of the treatment integrity literature should guide future research and practice on this vital issue facing clinical research and practice. This commentary considers the construct of treatment integrity and those factors that moderate the relationship between treatment integrity and treatment outcome. Specifically, this paper examines the three components of treatment integrity specified by Perepletchikova and Kazdin (treatment adherence, therapist competence, treatment differentiation), the relationship between treatment integrity and treatment outcome, and measurement and validation issues involving treatment integrity.