Treating patients with schizophrenia deficit with erythropoietin?

This systematic review summarizes and critically appraises the literature on the effect of erythropoietin (EPO) in schizophrenia patients and the pathophysiological mechanisms that may explain the potential of its use in this disease. EPO is mainly known for its regulatory activity in the synthesis of erythrocytes and is frequently used in treatment of chronic anemia. This cytokine, however, has many other properties, some of which may improve the symptoms of psychiatric illness. The review follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Three databases (Medline, Web of Science, and Cochrane) were searched combining the search terms 'erythropoietin AND (psychotic disorders OR schizophrenia)'. Seventy-eight studies were included in qualitative synthesis, a meta-analytic approach being prohibited. The findings suggest that several EPO cerebral potential properties may be relevant for schizophrenia treatment, such as neurotransmission regulation, neuroprotection, modulation of inflammation, effects on blood-brain barrier permeability, effects on oxidative stress and neurogenesis. Several potentially detrimental side-effects of EPO therapy, such as increased risk of thrombosis, cancer, increased metabolic rate and mean arterial blood pressure leading to cerebral ischemia could severely limit or halt the use of EPO. Overall, because the available data are inconclusive, further efforts in this field are warranted.     

Mitochondrial encephalomyopathy with pilovacuolar inclusion or phenocopy with mitochondrial artefact?

Summary The case of a 33-year-old man with clinical features of mitochondrial encephalomyopathy is presented. He suffered from recurrent cerebral infarctions, cerebellar ataxia, deafness, retinopathy, weakness, and cardiac and renal disorders. Biochemical and light microscope investigations of skeletal muscle did not show any mitochondrial abnormality. Electron microscopy revealed the presence of a hitherto unreported peculiar pilovacuolar inclusion in numerous mitochondria, composed of an electron dense pile or rod within a vacuole, while globular or crystalline inclusions were absent.     

Antipsychotic treatment withα-methyltyrosine in combination with thioridazine: Prolactin response and interaction with dopaminergic precursor pools

Summary The antipsychotic effect of-methyltyrosine (-MT) in combination with thioridazine was investigated by means of rating scales for social behaviour and mental symptoms The clinical effect was also evaluated in relation to the serum concentrations of-MT and thioridazine and to the increase in prolactin secretion in response to the interaction with hypothalamic dopaminergic mechanisms. The interactions between the serum levels of-MT and those of the transmitter precursors phenylalanine and tyrosine were analysed. The results confirmed the ability of-MT (2g/day) to potentiate the antipsychotic effect of thioridazine, whereby the dose of neuroleptic drug required to control psychotic symptoms may be markedly reduced. None of the four patients who completed the trial showed side effects that could be ascribed to-MT. The antipsychotic effect of thioridazine, alone or in combination with-MT, correlated well with the prolactin response in the individual patient. No important interference with serum phenylalanine or tyrosine levels was noted during treatment with-MT.     

Narcolepsy with cataplexy associated with H1N1 vaccination

IntroductionIt has been suggested that the H1N1 vaccine may be a trigger for the onset of narcolepsy-cataplexy, a rare disease whose autoimmune origin is suspected.ObservationsWe report two patients (a 9-year-old boy and an 18-year-old man) with severe narcolepsy-cataplexy, in whom the illness appeared within 3–4 weeks after H1N1 vaccination. In both cases, symptoms developed unusually abruptly and they presented with severe daytime sleepiness and multiple daily cataplexy attacks. Other similar cases have been recently reported associated with H1N1 vaccine.ConclusionAlthough no formal link can be established, the unusual characteristics of the reported cases and the striking temporal relationship suggests that narcolepsy may be the result of an autoimmune reaction triggered by H1N1 vaccination in susceptible individuals.     

Is treatment with growth hormone effective in children with cerebral palsy?

Children with cerebral palsy (CP) often have poor linear growth during childhood, resulting in a diminished final adult height. Here we report a female with CP and short stature but without growth hormone (GH) deficiency who exhibited increased growth during treatment with GH. We also report two other children with CP who were treated with GH: one female with a history of leukemia, and a male with Klinefelter syndrome. These two children were both found to be GH-deficient by insulin provocative GH testing and responded to treatment with increased growth rate. Growth improved to a greater extent in the two children with apparent GH deficiency. In summary, it is felt that GH therapy might be beneficial for children with CP and warrants further investigation.     

Association of apolipoprotein E ε4 allele with cognitive impairment in patients with epilepsy and interaction with phenytoin monotherapy

Cognitive impairment implicates many factors beyond phenytoin monotherapy in patients with epilepsy. Apolipoprotein E ε4 allele has been reported to play a role in severe memory impairment that ultimately progresses to Alzheimer's disease (AD); however, knowledge about its role in cognitive impairment in patients with epilepsy is lacking. Our study proposes the possible involvement of the APOE ε4 allele in cognitive impairment in patients with epilepsy which is further worsened by phenytoin monotherapy. Assessment of the APOE ε4 allele in a population with epilepsy will help to identify the patients vulnerable to cognitive impairment and, therefore, the corrective therapy that needs to be addressed.     

Do children with obesity implicitly identify with sedentariness and fat food?

We investigated whether youngsters with obesity (n=39) differed from a control group (n=39) in their self-reported attitudes towards and in their implicit identification with physical activity and food. Self-reported attitudes were assessed using a rating scale; implicit identification was assessed using a self-concept Implicit Association Task (IAT). Results revealed a marked group difference on the implicit identification with food: Only youngsters without obesity identified themselves more with non-fat food than with fat food.     

Living with a brother or sister with epilepsy: Siblings’ experiences

Background and purposeThere is conflicting evidence about the impact of disability upon siblings, and very little research on the siblings of children with epilepsy. There is some evidence that siblings who have less accurate information exhibit more distress. The aim of this study was to assess siblings’ response to having a brother or sister with epilepsy and to begin to develop information for them.MethodsParents of children attending paediatric neurology outpatient departments were invited to participate in a pilot study. Parents who consented to take part were asked if they had previously received information for siblings. Parents and siblings participated in a semi-structured interview and siblings were also invited to submit a personal account of living with a brother or sister who had epilepsy.ResultsTwenty-five families with a child with epilepsy aged 2.5–15 years initially agreed to take part. None of the families stated that they had ever seen or received any information specifically for siblings. Fourteen siblings from the 25 families, aged 8–25 years, provided a personal account of what it was like living with a brother or sister with epilepsy. Siblings’ accounts included both negative and positive feelings, and specifically feelings of care and love for their sibling.ConclusionThis initial study suggests that siblings of children with epilepsy have many positive but also early negative feelings. The results are limited by the size of the study, the fact that most siblings were older sisters, and the mean time since diagnosis was 6 years. Finally, it is hoped that the personal accounts collected in this study will be published for the benefit of other siblings of children with epilepsy.     

Should children with Bell's palsy be treated with corticosteroids? A systematic review

The objective of this study was to evaluate the effect of corticosteroids in the treatment of pediatric Bell's palsy. A systematic review of trials that included pediatric (< 16 years old) cases with Bell's palsy and involved the use of steroids was conducted. Eight trials were identified, five of which were randomized, and prednisone was used in six trials, whereas corticotropin was used in the other two. The methods of randomization and allocation concealment of the treatments used were rarely reported. Only one trial was done exclusively in children; none of the other seven trials analyzed the pediatric cases separately. Four trials reported some benefit from steroids. The pediatric trial did not provide evidence for benefit from corticosteroids. There was substantial heterogeneity in the population and interventions used; hence a meta-analysis was not done. Based on this systematic review, we do not recommend the routine use of steroids in children with Bell's palsy.     

IgG from patients with Guillain-Barré syndrome interact with nicotinic acetylcholine receptor channels

In Guillain-Barré syndrome (GBS), immunoglobulin G (IgG) antibodies block neuromuscular transmission pre- and postsynaptically and thus are of potential pathogenic relevance. We investigated whether IgG from GBS patients has a direct interaction with nicotinic acetylcholine receptor (nAChR) channels. Purified IgG fractions from six GBS patients that blocked neuromuscular transmission in a previous study were analyzed by the patch-clamp technique in combination with an ultrafast system for solution exchange. Sera from three patients with other inflammatory neurological disorders were used as controls. Mouse myotubes expressing native embryonic-type nAChR channels and human embryonic kidney (HEK) 293 cells transiently transfected with recombinant adult-type nAChR channels were used. Repeated 20-ms pulses of acetylcholine (ACh) were applied to outside-out patches in the presence of GBS-IgG. IgG of the patients had a significant reversible blocking action on embryonic- and adult-type nAChR channels with some variability in the magnitude of the block. Activation and desensitization kinetics were not affected when GBS-IgG was applied. None of the control sera blocked the AChR channels. The observed postsynaptic block effect fulfills the criteria of a channel-blocking IgG antibody similar to those seen in autoimmune myasthenia and may contribute to muscle weakness during the acute phase of GBS.     

Predictors of treatment outcome in adults with ADHD treated with OROS® methylphenidate

Background

We conducted a post-hoc analysis of the Long-Acting MethylpheniDate in Adult attention-deficit hyperactivity disorder (LAMDA) study to investigate predictors of response in adults with ADHD randomly assigned to Osmotic Release Oral System (OROS)^®-methylphenidate hydrochloride (MPH) 18, 36 or 72 mg or placebo.

Methods

LAMDA comprised a 5-week, double-blind (DB) period, followed by a 7-week, open-label (OL) period. A post-hoc analysis of covariance and a logistic regression analysis were undertaken to detect whether specific baseline parameters or overall treatment compliance during the double-blind phase contributed to response. The initial model included all covariates as independent variables; a backward stepwise selection method was used, with stay criteria of p < 0.10. Six outcomes were considered: change from baseline CAARS:O-SV (physician-rated) and CAARS:S-S (self-report) scores at DB and OL end points, and response rate (≥ 30% decrease in CAARS:O-SV score from baseline) and normalization of CAARS:O-SV score at DB end point.

Results

Taking into account a significant effect of OROS^®-MPH treatment versus placebo in the original analysis (p ≤ 0.015), across the outcomes considered in this post-hoc analysis, higher baseline CAARS scores were most strongly predictive of superior outcomes. Male gender and lower academic achievement were also predictive for improved results with certain outcomes.

Conclusions

Several baseline factors may help to predict better treatment outcomes in adults receiving OROS^®-MPH; however, further research is required to confirm these findings and examine their neurobiological underpinnings.     

Parent–child interaction of mothers with depression and their children with ADHD

Attention deficit/hyperactivity disorder (ADHD) is a developmental disorder that may have a chronic and pervasive impact on the child's function and cause long-term stress to parents. A higher rate of depression is associated with mothers of children with ADHD. This observational study aimed to investigate the effect of maternal depression and the child's ADHD on the quality of the parent–child interaction in children with ADHD and their mothers with depression. The study participants comprised 39 mother–son dyads including children with ADHD and mothers with depression, children with ADHD and mothers without depression, and children without ADHD and mothers without depression. The Specific Affect Coding System, 20-code version was used to code interactional affect, including positive engagement, negative engagement, negative disengagement, and neural affect. There were no statistically significant group-by-context interaction effects or group effects on all affective variables between the group of children with ADHD and mothers without depression and the group of children without ADHD and mothers without depression. Stimulant medication may account for these nonsignificant findings. No significant difference of positive affect between neutral and conflict-solving contexts was observed in depressed mothers whose children were diagnosed as ADHD. Children with ADHD whose mothers were depressed were less positive in their parent–child interaction compared with children in the other groups. Maternal depression may play an important role in the affective presentation of dyads of children with ADHD and mothers with depression. Implications for clinical practice and future research are provided.     

Is EEG useful in assessing patients with acute encephalitis treated with acyclovir?

EEG has been used widely in diagnosing encephalitis, as it demonstrates rather typical abnormalities, especially in herpes simplex virus encephalitis (HSVE). We analysed 204 EEG recordings from 98 consecutive acyclovir-treated patients with acute encephalitis between 1984 and 1994. Periodic complexes (PC) in the acute phase predicted poor outcome (Kendall tau 0.40, P<0.001). However, unlike in many other diseases, e.g. stroke and intracerebral haemorrhage, the diffuse slowing of the background activity at acute phase did not predict outcome (Kendall tau −0.6, P=0.35). At follow-up, the emergence of diffuse slow background activity was significantly associated with a less favourable outcome (Kendall tau 0.33, P=0.0016). Among clinical variables, only epileptic seizures early during the course of the disease correlated significantly with outcome. EEG does have value as a prognostic indicator in acute encephalitides, but it seems that diffuse slowing of background activity or irritative features acutely are not as important as previously thought, based on the experiences of the pre-acyclovir era.     

Is depression associated with microvascular disease in patients with type 2 diabetes?

We hypothesize that late-life depression is a manifestation of microvascular disease in patients with type 2 diabetes. We conducted a clinic-based cross-sectional study, comparing retinal vascular caliber, a marker of microvascular disease, in participants with type 2 diabetes with major depression (n=34), without depression (n=27) and healthy non-diabetic controls (n=38). Retinal vascular caliber was measured from digital retinal photographs using a validated computer-assisted method. After adjusting for age and gender, there was a trend of increasing retinal arteriolar caliber from healthy controls (132.6 microm), to diabetic patients without depression (139.2 microm), and diabetic patients with major depression (145.3 microm, P=0.008). The trend in retinal arteriolar caliber remains significant after adjusting for duration of diabetes, but not after further adjusting for vascular risk factors. Our findings suggest that there is variation in the retinal vascular caliber between type 2 diabetic patients with and without major depression and non-diabetic controls. This variation was largely related to poorer diabetes control and a higher frequency of vascular risk factors in diabetic patients, particularly those with depression. Studies with larger sample size may provide further insights into this association.