Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis.

BACKGROUND: In depressed patients, alterations in the hypothalamo-pituitary-adrenocortical (HPA) system are the most consistent neurobiological finding. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines. METHODS: We examined alterations in plasma levels of tumor necrosis factor-alpha (TNF-alpha), levels of its soluble receptors p55 (sTNF-R p55) and p75 (sTNF-R p75) as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 70 depressed inpatients without inflammation. RESULTS: On admission, TNF-alpha levels were inversely associated with the ACTH response to the combined dex/CRH test. Changes in TNF-alpha, sTNF-R p55, and sTNF-R p75 plasma levels from admission to discharge were positively correlated with the dex/CRH test outcome at discharge. Subgroup analysis revealed that this association was restricted to those patients achieving remission. In this subgroup, TNF-alpha levels at discharge were also positively correlated with dex/CRH test response at discharge. CONCLUSIONS: Our results suggest that elevated HPA axis activity in acute depression suppresses TNF-alpha system activity, while after remission, when HPA axis activity has normalized, the TNF-alpha system seems to gain influence on the HPA system.     

Lifetime prevalence and projected lifetime risk of DSM-IV disorders in Te Rau Hinengaro: the New Zealand Mental Health Survey

OBJECTIVE: To estimate the lifetime prevalence and projected lifetime risk at age 75 years of DSM-IV disorders in New Zealand. METHOD: A nationwide face-to-face household survey carried out in 2003-2004. A fully structured diagnostic interview, the World Health Organization Composite International Diagnostic Interview (CIDI 3.0), was used. There were 12,992 completed interviews from participants aged 16 years and over. The overall response rate was 73.3%. In this paper, the outcomes reported are lifetime prevalence and projected lifetime risk at age 75 years. RESULTS: The lifetime prevalence of any disorder was 39.5%. The lifetime prevalences for disorder groups were: anxiety disorders, 24.9%; mood disorders, 20.2%; substance use disorders, 12.3%; and eating disorders, 1.7%. The prevalences for all disorders were higher in the younger age groups. Females had higher prevalences of anxiety, mood and eating disorders compared with males; males had higher prevalences of substance use disorders. The estimated projected lifetime risk of any disorder at age 75 years was 46.6% with the median age of onset being 18 years. Adjustment for age, sex, education and household income did not remove all differences between Māori and the composite other ethnic group in the risk of disorder (hazard ratio = 1.1-1.4). After adjustment, hazard ratios for Pacific people ranged from 0.8 to 2.5. CONCLUSIONS: These results confirm those of other studies: mental disorders are relatively common and tend to have early onset. Females are more likely to experience anxiety, mood and eating disorders than males, who experience more substance use disorders. Adjustment for socioeconomic factors and demography does not explain all ethnic differences, although remaining differences are small relative to cohort and even sex differences.     

The outcome of children with intractable seizures: a 3- to 6-year follow-up of 67 children who remained on the ketogenic diet less than one year

PURPOSE: To determine the long-term outcome of children with difficult-to-control seizures who remained on the ketogenic diet for <1 year. METHODS: Between 1994 and 1996, 150 children with epilepsy, refractory to at least two medications, initiated the ketogenic diet according to the Hopkins protocol. Three to six years after diet initiation, all the families were contacted by telephone or questionnaire to assess their child's current seizure status, medications, and therapies. RESULTS: Sixty-seven children discontinued the diet within 1 year of initiation. Follow-up data were available for 54 of these children. Ten subsequently had surgery, and three underwent VNS implantation. These operated-on children were significantly more likely to be >50% controlled at follow-up than were those managed with medications alone (p < 0.05). A statistically significant difference in long-term outcome was noted between those who responded while on the diet, even if they discontinued it before 1 year, and those who did not (p < 0.05), but no statistical correlation was found between length of time that they had remained on the diet and long-term prognosis. CONCLUSIONS: Almost half of the children who discontinued the diet during the first year had a decrease in seizures when assessed 3-6 years later. Twenty-two percent of these had become seizure free without surgery. We were unable to ascertain whether this may have been due to new medications. Those who saw some improvement while on the diet were more likely to have a favorable long-term outcome. Resective surgery, in children who were candidates, or vagal nerve stimulation (VNS) implantation, was more likely to result in significant seizure improvement than was management with medications alone. Whether or not the diet was effective, most families did not regret trying it and would recommend it to others.     

Restless legs syndrome and motor activity during sleep in spinocerebellar ataxia type 6

BACKGROUND AND PURPOSE: We investigated the frequency of restless legs syndrome (RLS) and sleep disturbance in spinocerebellar ataxia type 6 (SCA6). PATIENTS AND METHODS: Five patients out of three multigenerational SCA6 families underwent a standardized investigation protocol including clinical interview for RLS, neurophysiological evaluation as well as the clinical assessment of ataxia. Polysomnography (PSG) was performed during two consecutive nights. RESULTS: Two out of five patients fulfilled the clinical criteria for RLS. A periodic leg movements in sleep (PLMS) index>15/h was present in four of the five patients; a PLMS index>5/h was present in all patients. Significant disturbance of rapid eye movement (REM) sleep was not found. None of the patients had REM sleep behaviour disorder. Only one patient had mild REM sleep without atonia. CONCLUSIONS: Our pilot study suggests only minor sleep abnormalities in SCA6.     

Interleukin-12 is reduced in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia

Interleukin-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines, such as Interferon-gamma and Tumor Necrosis Factor-alpha. There is little information about the involvement of IL-12 in the pathophysiology of Alzheimer's disease (AD) and other tauopathies. OBJECTIVES: The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with AD and frontotemporal dementia (FTD). PATIENTS AND METHODS: We measured by immunoassay cerebrospinal fluid (CSF) IL-12 levels in 19 patients with AD and 7 patients with FTD in comparison with CSF IL-12 levels in 30 patients with non-inflammatory neurological diseases served as neurological control patients (NCTRL). IL-12 levels were correlated with age, age of disease onset, disease duration, MMSE score, and rate of dementia progression. Abeta42 and Total tau (tau(T)) levels in CSF were also measured. RESULTS: Patients with AD had significantly lower CSF IL-12 levels compared with NCTRL patients (p<0.001). Patients with FTD had also lower CSF IL-12 levels compared with NCTRL patients (p<0.05). Age, sex, disease duration and MMSE score did not affect IL-12 levels in any of the groups. In AD a significant positive correlation was noted between IL-12 levels and tau(T) levels (Rs=0.46, p=0.048). CONCLUSIONS: Our findings may suggest a reduced inflammatory reaction during the course of AD and FTD. A neurotrophic role of IL-12 and other proinflammatory cytokines cannot be excluded.     

Acute traumatic spinal cord injury, 1993-2000A population-based assessment of methylprednisolone administration and hospitalization

BACKGROUND: Administration of methylprednisolone sodium succinate (MPSS) after acute traumatic spinal cord injury (TSCI) is controversial. This study compared differences in acute care charge, hospital stay, and related variables as a function of MPSS receipt. METHODS: Determinants of MPSS administration were examined after acute TSCI for South Carolina patients during the period 1993 to 2000 in a multivariate logistic regression model. RESULTS: Administration of MPSS was documented for 48.7% of 1,227 randomly selected patients with TSCI. Patients admitted via trauma centers and emergency departments were more likely to receive MPSS (trama center level 1 odds ratio [OR], 4.06; 95% CI confidence interval [CI], 2.11-7.83; emergency department OR, 1.64; 95% CI, 1.20-2.23). Hospital charge and length of stay were significantly higher for MPSS recipients. CONCLUSIONS: The study findings indicate MPSS use is associated with higher acute care charges and longer hospital stays. These findings suggest the need for outcome studies to assess the long-term benefits of MPSS administration.     

Prevalence of extraesophageal reflux in patients with symptoms of gastroesophageal reflux.

OBJECTIVES: To compare the prevalence of extraesophageal reflux (EER) in patients with heartburn, posterior laryngitis (PL), and in healthy controls.Study design and setting A retrospective and prospective study including a total of 101 subjects who underwent 24-hour dual-probe pH monitoring. RESULTS: 52% of the subjects with heartburn had EER. No significant differences were found between the PL and heartburn groups for any pharyngeal reflux parameters. However, supine pharyngeal reflux was significantly more prevalent in heartburn patients with GERD than in PL patients and healthy controls (P < 0.05). Significant positive correlation (P < 0.01) was found between the percentage of time pH <4 in the pharynx and in the distal esophagus. CONCLUSION: EER occurs in the majority of heartburn patients who are lacking laryngeal symptoms. Abnormal distal esophageal acid exposure makes the occurrence of EER more likely. SIGNIFICANCE: EER appears to be a continuum without clear-cut differences between the groups.     

Intravenous iron supplementation in children on hemodialysis

BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in children with ESRD on HD and the effect on iron status measured. METHODS: Fourteen patients were divided into three groups according to their actual iron status. Group A--iron deficient (ferritin (F)<100 microg/L, or F 100-400 microg/L and transferrin saturation (TSAT)<20%). These patients were treated with i.v. iron-sucrose 3 mg/kg/dialysis. Group B--iron-replete (F 100-400 microg/L and TSAT> or =20%, or TSAT>50%). These patients received 0.3 mg/kg/dialysis iron-sucrose. Group C--possible iron-overloaded (F>400 microg/L). These patients were not treated with iron. RESULTS: Group A--3 mg/kg/dialysis of iron-sucrose resulted in a major increase in F, indicating possible iron overload. Therefore, the iron-deficient patients received 1 mg/kg/dialysis iron-sucrose during 22 periods of 2-14 (mean 5) weeks: the median F increased from 186 to 343 microg/L (p<0.001). Group B--0.3 mg/kg/dialysis iron-sucrose resulted in adequate iron levels during 22 periods of 2-60 (mean 9) weeks. CONCLUSION: In children, 3 mg/kg/dialysis iron-sucrose complex results in a possible iron overload. Dosage of 1 mg/kg/dialysis and 0.3 mg/kg/dialysis seem adequate for correction and maintenance therapy respectively.