Neurodegenerative changes in patients with clinical history of bipolar disorders

Neurodegeneration in bipolar disorder (BPD) is poorly understood. Therefore, the current study was designed to assess the immunohistochemical changes in neurodegenerative markers in patients with BPD. Eleven consecutive autopsy cases diagnosed with BPD were analyzed. Sections were obtained from archival paraffin blocks of representative areas and stained using conventional methods, as well as immunostained with several antibodies to screen for neurodegenerative diseases. Age‐ and non‐argyrophilic grains (AGs) degeneration matched controls were selected for each case. Clinical information was retrospectively collected from medical charts. All patients were men, and the average age of death was 70 years. Neuropathological diagnoses included dementia with grains (2), argyrophilic grain disease (2), corticobasal degeneration (CBD, 1), Lewy body disease (1), hypoxic encephalopathy (1) and cerebral infarction (1). All cases showed AGs to various degrees. Three patients died in their 50s; one demonstrated dementia with Lewy bodies, while the other two showed abundant AGs in the thalamus and amygdala. Of the three patients who died in their 60s, one showed AGs preferentially in the thalamus and amygdala, while the others demonstrated limbic predominance. The patients who died in/after their 70s demonstrated AGs similar to controls, except for the patient with CBD. Our data provides potentiality that neurodegenerative diseases may be an underlying pathology in certain cases of BPD.     

The occipitofrontalis muscle is composed of two physiologically and anatomically different muscles separately affecting the positions of the eyebrow and hairline.

After the surgical correction of aponeurotic blepharoptosis or blepharoplasty, the positions of the eyebrow and hairline change as if the frontal belly is independent from the occipital belly of the occipitofrontalis muscle. Therefore, the occipitofrontalis muscle was studied physiologically with electromyographic evaluation in healthy subjects and anatomically with cadaver dissections. Along with contraction of the levator muscle to maintain an adequate visual field, at a less upward gaze position, contraction of only the frontal belly was induced, and at a more upward gaze position, contraction of both the frontal and the occipital bellies was always induced to lift the eyebrow with the upper eyelid skin. The superficial fascia overlying the occipital belly becomes the temporoparietal fascia and ends at the superior end of the frontal belly, thus creating a superficial musculoaponeurotic system that lifts the eyebrow and pulls the scalp forwards. Beneath the superficial musculoaponeurotic system, the occipital belly of the occipitofrontalis muscle becomes the galea aponeurotica and inserts into the underside of the frontal belly, thus creating a deep musculoaponeurotic system that pulls the superficial musculoaponeurotic system with the scalp backwards. Thus, the occipitofrontalis muscle appears to be composed of two physiologically and anatomically different muscles.     

Successful treatment of autoimmune hemolytic anemia associated with multicentric Castleman disease by anti-interleukin-6 receptor antibody (tocilizumab) therapy

We describe herein the successful treatment of severe autoimmune hemolytic anemia (AIHA) in a patient with multicentric Castleman disease (MCD) by humanized anti-interleukin-6 (IL-6) receptor antibody (tocilizumab) therapy. Inflammatory anemia is commonly reported; however, AIHA is a very rare complication of MCD. In 1996, a 45-year-old Japanese woman was referred to our hospital because of generalized lymphadenopathy, anemia and skin eruptions. Lymph node biopsy demonstrated MCD. She was treated with prednisolone (1 mg/kg/day), which improved the anemia and skin eruptions. In 2009, she suddenly developed Coombs-positive hemolytic anemia. The blood count was as follows: hemoglobin 4.7 g/dl, platelets 490 × 10(9)/l and white blood cell count 9.8 × 10(9)/l. Both direct and indirect Coombs' tests were strongly positive. She was treated with 8 mg/kg tocilizumab every 2 weeks. One month later, her hemoglobin levels rose dramatically to 10.9 g/dl and her haptoglobin level, hypergammaglobulinemia and clinical symptoms had also markedly improved. To the best of our knowledge, this is the first report of the efficacy of tocilizumab in AIHA associated with MCD. The well-established role of IL-6 in the pathogenesis of MCD may have been responsible for the improvement in the AIHA associated with MCD. Anti-IL-6 receptor antibody treatment could be an attractive therapeutic approach for AIHA associated with MCD.     

Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats

We investigated if agouti-related peptide (AgRP), an endogenous antagonist of melanocortin receptors (MC3-R and MC4-R), effects energy expenditure in rats. Fragments of the carboxyl-terminal, AgRP (83-132), and the amino-terminals, AgRP (25-51) and AgRP (54-82), were administered intracerebroventricularly (ICV). Food intake, body weight and fat weight changes were measured 5 and/or 24 h after a single ICV injection of the fragments. Oxygen consumption and colonic temperature were measured as indices of energy expenditure, during 3 and 24 h after the ICV injections, respectively. An oral glucose tolerance test was performed 24 h after ICV AgRP (83-132) injection. Binding experiments were performed in HEK-293 cells that over-expressed human MC4-R. AgRP (83-132), but not AgRP (25-51) nor AgRP (54-82), induced a potent and long-lasting increase in the cumulative food intake. Both the carboxyl-terminal and amino-terminal AgRP fragments significantly decreased oxygen consumption and colonic temperature. Despite the absence of hyperphagia and cross-reactivities with MC4-R, AgRP (25-51) and AgRP (54-82) significantly increased body weight and epididymal/mesenteric fat weight. AgRP (83-132) did not affect glucose and insulin responses to the oral glucose tolerance test. AgRP causes a potent and long-lasting decrease in energy expenditure; an effect that is exhibited by carboxyl-terminal fragments and amino-terminal fragments that lack antagonist activity at the MC receptors. This suggests that the amino-terminal region of AgRP plays a regulatory role in energy metabolism.     

Alpha2-macroglobulin gene polymorphisms show racial diversity and are not associated with Alzheimer's disease

Two genetic markers of the plasma protein alpha2-macroglobulin, a 5 bp deletion/insertion at the 5' splice site of exon 18 (A2MI) and the GTC/ATC (VaIIO00IIe) in exon 24 (A2M2), may have roles in the development of Alzheimer's disease (AD). Genotyping and linkage analysis of these markers in 426 Japanese sporadic AD patients, 85 autopsy-confirmed Caucasian AD cases, and, as controls, 382 Japanese and 65 Caucasians who were cognitively normal and 140 Japanese Parkinson's disease patients showed racial diversity in the frequencies and relationship of the two markers. Comparison of genotype and allele frequencies, stratification of the samples by the presence of the apolipoprotein E epsilon4 allele, and logistic regression analysis revealed no association of these markers with AD in either racial group.     

Intracerebroventricularly administered urocortin inhibits gastric emptying in mice

Urocortin, a recently identified member of the corticotropin-releasing factor (CRF) family, is implicated in the central control of appetite and energy metabolism. We previously reported that peripherally administered urocortin inhibits gastric emptying in conscious mice. In this study, we investigated the effect of intracerebroventricularly administered urocortin on gastric emptying, food intake and body weight in mice. Urocortin decreased food intake and body weight gain more potently than CRF. It significantly decreased gastric emptying of a solid meal; an effect that was inhibited by simultaneous administration of alpha-helical CRF9-41, a CRF antagonist. These results suggest that the potent anorectic properties of urocortin may be partly due to the anti-gastroprokinetic activity of the peptide.     

Cranial MR imaging of sequelae of prefrontal lobotomy

BACKGROUND AND PURPOSE: Although prefrontal lobotomy is an obsolete treatment for schizophrenia, we still encounter patients who have undergone this procedure. The purpose of this study was to describe the MR imaging findings of sequelae of prefrontal lobotomy. METHODS: We retrospectively reviewed cranial MR images of eight patients with schizophrenia who underwent prefrontal lobotomy approximately 50 years previously. RESULTS: In all patients, a bilateral cavitary lesion with a thick wall was found in the frontal white matter. The genu of the corpus callosum was mildly to markedly atrophic. The size and location of the cavity and the degree of callosal atrophy were correlated. CONCLUSION: MR imaging is useful for the diagnosis of sequelae of prefrontal lobotomy, including cavitary lesions with dense walls of gliosis and secondary degeneration of the genu of the corpus callosum.     

Etiology and pathogenesis of aponeurotic blepharoptosis

How and why aponeurotic blepharoptosis develops was investigated in terms of the relationship between the levator aponeurosis and Mueller's muscle functioning as the muscle spindle of the levator muscle. A total of 200 consecutive patients with moderate to severe acquired blepharoptosis completed questionnaires regarding their history of physical irritations to the eyelids, and intraoperative conditions of the levator aponeurosis and Mueller's muscle were evaluated. Several kinds of physical irritations to the eyelids were reported, such as habitual rubbing of the eyelids, contact lens usage, cataract surgery, and continuous rubbing of the eyelids while crying all night. The two main findings for aponeurosis were that it was disinserted from the tarsus, resulting in a large amount of play between the aponeurosis and the tarsus, and that the aponeurosis and Mueller's muscle were attenuated and elongated. The authors believe that rubbing may have caused disinsertion as well as attenuation and elongation of the aponeurosis, which result in transmission failures between the levator muscle and the tarsus as well as between the levator muscle and the mechanoreceptor of Mueller's muscle, leading to clinical blepharoptosis.     

Comparison between patient characteristics and cranial MR findings in chronic thinner intoxication

Chronic thinner intoxication is one of the most serious social problems among teenagers and young adults in Japan. The purpose of this study was to evaluate clinical characteristics of patients with thinner intoxication who had positive MR findings. During the past 4 years, cranial MR imaging of 85 patients (51 males and 34 females) with chronic thinner intoxication was done at a national psychiatric hospital. The MR imaging was performed on a 1.0-T scanner with use of standard pulse sequences including fluid-attenuated inversion recovery (FLAIR). The established characteristic MR findings of chronic thinner intoxication were observed in 8 of the 85 patients: 4 males and 4 females. The female patients tended toward emaciation and were approximately 5 years younger than the male patients. Six of the 8 patients had severe neurological symptoms such as cerebellar ataxia and decreased visual acuity. In contrast, only 3 of 77 (4%) patients with normal MR findings had mild neurological abnormalities such as tremor. If patients with chronic thinner intoxication have significant neurological symptoms, MR imaging should be performed for evaluation of brain abnormalities. Emaciated female patients may be particularly vulnerable to neurological damage caused by thinner intoxication.