Levetiracetam,lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer’s disease

The objective of the study described here was to evaluate the efficacy, tolerability, and cognitive effects of levetiracetam (LEV) in patients with seizures and Alzheimer’s disease (AD). This was a prospective, randomized, three-arm parallel-group, case–control study of 95 patients taking LEV (n = 38), phenobarbital (PB) (n = 28), and lamotrigine (LTG) (n = 29). A 4-week dose adjustment was followed by a 12-month evaluation period. The three groups were compared to a control group (n = 68) to evaluate cognitive effects of the antiepileptic drugs. We examined drug effects cross-sectionally at baseline, 6 months, and 12 months. There were no significant differences in efficacy among the three AEDs. LEV caused fewer adverse events than the other AEDs. PB produced persistent negative cognitive side effects. LEV was associated with improved cognitive performance, specifically attention level and oral fluency items. LTG had a better effect on mood. LEV had a benign neuropsychological side effect profile, making it a cognitively safe drug to use for controlling established seizures in elderly patients with Alzheimer’s disease.     

Exercise,microglia, and beyond–workout to communicate with microglia

正Microglia are brain-resident immune cells that use their ramified processes to survey the brain parenchyma. They maintain brain homeostasis by mediating immune responses through cytokine release, phagocytosing pathogens and protein aggregation(Salter et al., 2017).     

Does alexithymia differentiate between patients with nonepileptic seizures, patients with epilepsy, and nonpatient controls?

Considering the evidence of an association between alexithymia and somatization, this study aimed to discover whether alexithymia could distinguish patients with psychogenic nonepileptic seizures (NES) from those with epilepsy (ES) and nonpatient controls (C). Toronto Alexithymia Scale (TAS-20) scores were obtained from 21 matched participants from each of these groups, together with measures of anxiety and depression. Overall TAS-20 scores did not differentiate the three groups after controlling for anxiety and depression, but scores on certain subscales of the TAS-20 differed significantly between the patient groups and the controls. Although alexithymia could not discriminate individuals with NES from those with organic manifestations, whether the etiology of alexithymia may differ according to patient group was discussed. Given that 90.5% of NES patients were identified as alexithymic, treatment approaches used for individuals with alexithymia may be usefully applied to those with NES.     

Adolescents with Diabetes and Their Parents’ Perceptions of Mental Health Screening,Assessment, and Feedback

This study examined adolescents with diabetes and their parents’ reactions to mental health screenings, assessments, and feedback. Most parents and adolescents did not report negative affect, but 15- and 16-year olds and referred adolescents showed greater levels of concern with assessment outcomes. Among those referred to mental health services, parents anticipated barriers in costs, insurance, and lack of qualified providers. Adolescents reported scheduling conflicts, time, and confidentiality concerns. Respondents perceived feedback as an important component of the clinical process and findings indicated a need for clinicians to incorporate psychosocial screenings and feedback in healthcare visits for adolescents with diabetes.     

Hepatic,lipid and genetic factors associated with obesity: crosstalk with alcohol dependence?

Objectives: Alcohol dependence represents a leading cause of mortality and morbidity. Understanding the variables that contribute to this diagnosis and its severity is critical. An overlap between factors that may predispose people to become obese and those that may increase the risk of alcohol dependence may exist. However, data in the literature are not conclusive. Therefore, this study aimed to identify the association between alcohol dependence and obesity-related factors, including biochemical and genetic factors.

Methods: In a case–control study with 829 participants, factors involved with metabolism and obesity were assessed, including biochemical lipid and liver markers, and the fat mass and obesity-associated (FTO) single nucleotide polymorphism (SNP) rs8050136.

Results: Increased triglycerides, having one or two minor A alleles for rs8050136 and being a smoker were associated with increased risk of alcohol dependence, while increased low-density lipoprotein cholesterol was associated with decreased risk. In addition, having abnormal gamma-glutamyl transferase and being female were factors associated with an increased severity of alcohol dependence.

Conclusions: Our preliminary findings suggest a link between alcohol dependence and obesity-related biochemical and genetic factors. Future studies are needed to better understand if these factors may play a predictive role and/or may act as biomarkers for treatment response.     

Decreased sleep quality in Parkinson’s patients is associated with higher anxiety and depression prevalence and severity,and correlates with pain intensity and quality

Objective: Pain, poor sleep quality, restless legs syndrome (RLS), and other symptoms are frequently reported by patients with Parkinson’s disease (PD). However, the impact that pain severity and interference has on non-motor symptoms (NMS) has not been extensively studied. The objective of the present study is to explore the relationship between sleep quality in PD to pain and other NMS that affect quality of life.Methods: The study included 100 PD patients and 100 age and gender-matched controls assessed for pain severity and pain interference using the Brief Pain Inventory and sleep quality using the Pittsburgh Sleep Quality Index. Participants were also evaluated for their subjective levels of anxiety and depression using the Hospital Anxiety and Depression Scale.Results: PD patients with poor sleep quality had greater pain severity and pain interference than controls and PD patients with good or borderline sleep quality. PD patients with poor sleep quality also had the greatest case-ness and severity for depression and anxiety. However, RLS was not significantly correlated with depression, anxiety or pain.Discussion: Poor sleep quality in PD patients is related to greater pain severity, pain interference, and more radiating and paresthestic pain that is independent of RLS. There is a higher prevalence of depression and anxiety in PD patients compared to controls, especially in PD patients with poor sleep quality. Our findings suggest a relationship between poor sleep quality in PD with pain, anxiety and depression. Prospective studies are warranted to investigate the causal relationship.     

Are obstetrical,perinatal, and infantile difficulties associated with pediatric bipolar disorder?

Martelon MK, Wilens TE, Anderson JP, Morrison NR, Wozniak J. Are obstetrical, perinatal, and infantile difficulties associated with pediatric bipolar disorder? Bipolar Disord 2012: 14: 507–514. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Despite increasing acknowledgement of bipolar disorder (BD) in childhood, there is a paucity of literature that has investigated obstetrical, perinatal, and infantile difficulties and their potential link with BD. To this end, we examined difficulties during delivery, immediate post‐birth, and infancy and the association with BD in childhood. Methods: From two similarly designed, ongoing, longitudinal, case‐control family studies of pediatric BD (N = 327 families), we analyzed 338 children and adolescents [mean (± standard deviation) age: 12.00 ± 3.37 years]. We stratified them into three groups: healthy controls (N = 98), BD probands (N = 120), and their non‐affected siblings (N = 120). All families were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and substance use. Mothers were directly questioned regarding the pregnancy, delivery, and infancy difficulties that occurred with each child using a module from the Diagnostic Interview for Children and Adolescents‐Parent Version (DICA‐P). Results: Mothers of BD subjects were more likely to report difficulties during infancy than mothers of controls [odds ratio (95% confidence interval) = 6.6 (3.0, 14.6)]. Specifically, children with BD were more likely to have been reported as a stiffened infant [7.2 (1.1, 47.1)] and more likely to have experienced ‘other’ infantile difficulties [including acting colicky; 4.9 (1.3, 18.8)] compared to controls. We found no significant differences between groups in regards to obstetrical or perinatal difficulties (all p values > 0.05). Conclusions: While our results add to previous literature on obstetrical and perinatal difficulties and BD, they also highlight characteristics in infancy that may be prognostic indicators for pediatric BD.     

Acute zoster plasma contains elevated amyloid,correlating with Aβ42 and amylin levels,and is amyloidogenic

Journal of NeuroVirology - Herpes zoster is associated with an increased dementia and neovascular macular degeneration risk and a decline in glycemic control in diabetes mellitus. Because amyloid...     

Treatment of Cognitive, Psychiatric, and Affective Disorders Associated with Parkinson’s Disease

Neuropsychiatric symptoms are common in Parkinson’s disease (PD) and add significantly to the burden of disease. These symptoms are most commonly part of the disease spectrum owing to pathological changes within relevant brain regions. Neuropsychiatric problems include disorders of cognition, ranging from mild cognitive impairment to dementia, psychotic symptoms, including, most commonly, well-formed visual hallucinations and paranoid delusions, and mood disorders, such as depression and anxiety. The other common cause of neuropsychiatric problem is secondary to use of dopaminergic drugs. Some PD patients may develop behavioral disorders, including impulse control disorders (ICDs) and addictive symptoms. Psychosis can be due to a mixture of underlying pathology, with triggering or worsening of symptoms with changes to PD medications. Currently, management of these disorders primarily uses therapies developed for general psychiatry and cognitive neurology, rather than specifically for PD. However, significant adverse effects, such as worsening of the motor symptoms of PD, can limit use of some drug therapies. Identification of drug-induced symptoms, such as ICDs, enables withdrawal of the offending drug as the principal management strategy. Research is ongoing in an effort to develop more specific therapies for PD-related neuropsychiatric symptoms.     

Speed and trajectory of changes of insomnia symptoms during acute treatment with cognitive–behavioral therapy,singly and combined with medication

ObjectivesTo examine the speed and trajectory of changes in sleep/wake parameters during short-term treatment of insomnia with cognitive–behavioral therapy (CBT) alone versus CBT combined with medication; and to explore the relationship between early treatment response and post-treatment recovery status.MethodsParticipants were 160 adults with insomnia (mean age, 50.3 years; 97 women, 63 men) who underwent a six-week course of CBT, singly or combined with 10 mg zolpidem nightly. The main dependent variables were sleep onset latency, wake after sleep onset, total sleep time, sleep efficiency, and sleep quality, derived from sleep diaries completed daily by patients throughout the course of treatment.ResultsParticipants treated with CBT plus medication exhibited faster sleep improvements as evidenced by the first week of treatment compared to those receiving CBT alone. Optimal sleep improvement was reached on average after only one week for the combined treatment compared to two to three weeks for CBT alone. Early treatment response did not reliably predict post-treatment recovery status.ConclusionsAdding medication to CBT produces faster sleep improvement than CBT alone. However, the magnitude of early treatment response is not predictive of final response after the six-week therapy. Additional research is needed to examine mechanisms involved in this early treatment augmentation effect and its impact on long-term outcome.     

Handedness,eyedness, and hand–eye crossed dominance in patients with different addictions

ObjectiveSome neurologic and psychiatric disorders such as schizophrenia, depression, autism and migraine are referred to as cerebral lateralization abnormalities. In this study the possible relationships among handedness, eye dominance, and crossed hand–eye dominance in patients with different addictions mentioned above are investigated.MethodsThirty three patients with cigarette, 35 patients with alcohol, 133 patients with heroin, 117 patients with hashish, 13 patients with drug addictions and 102 age matched controls were included in the study. Six of 13 patients with drug addictions were addicted to diazepam, 5 to pethidine and 2 to clonazepam. The patient group included 307 men and 24 women who ranged in age from 15 to 70 years. Handedness was ascertained by using the Edinburgh Handedness Inventory. Eye dominance was measured only by the near-far alignment test. Diagnoses were made on the basis of information provided from clinical interviews and Structured Clinical Interview for DSM-IV.ResultsPatients with heroin and hashish had a significantly increased frequency of left-handedness in comparison with the other patients and controls (chi square = 29.36, p < 0.001). Patients with cigarette, alcohol, heroin and hashish addictions had a significantly increased frequency of left-eyedness in comparison with controls (chi square = 25.24, p < 0.01). Also, patients with cigarette, alcohol, heroin and hashish addictions had a significantly increased frequency of the crossed hand–eye dominance in comparison with controls (chi square = 19.11, p < 0.01).ConclusionsDifferent addictions such as cigarette, alcohol, heroin and hashish may be associated with abnormal handedness distribution and accepted as cerebral lateralization abnormalities.     

Galantamine-based hybrid molecules with acetylcholinesterase, butyrylcholinesterase and γ-secretase inhibition activities

We previously designed novel peptides-containing galantamine analogues. These compounds we analyzed for their putative inhibitory effect towards acetylcholinesterase, butyrylcholinesterase and γ-secretase, three activities of which could be central to various neurodegenerative pathologies including Alzheimer's disease. These pharmacological agents were virtually equipotent on acetylcholinesterase activity but display drastically higher inhibitory activities towards butyrylcholinesterase with several compounds displaying an about 100-fold higher activity than that harboured by galantamine. Strikingly, two of the galantamine amides that displayed low activity towards acetylcholinesterase exhibited the highest inhibitory potency towards butyrylcholinesterase (106 to 133 times more active than galantamine). Interestingly, five compounds show a rather good γ-secretase inhibitory potency while they retain their ability to inhibit AChE and/or BuChE activity. Thus, we have been able to design novel compounds with significant inhibitory activity against several of the enzymes responsible for key dysfunctions taking place in several neurodegenerative diseases. These mixed inhibitors could therefore be envisioned as potential pharmacological tools aimed at circumventing the degenerative processes taking place in these major pathologies.     

Missionaries with the hopeless? Inebriety,mental deficiency and the Burdens

The late nineteenth‐ and early twentieth‐century campaign for the treatment of ‘inebriates’ used many of the themes used by campaigners for the care of the ‘feeble‐minded’. The inebriate reformatories admitted mainly women, and their low rate of success was blamed on the inmates being ‘mental defectives’, rather than a result of the methods used. When the reformatories closed, these were reused as institutions under the Mental Deficiency Act of 1913. Having been missionaries, the Reverend H. N. Burden and his wives managed inebriate reformatories and then switched to running colonies for ‘mental defectives’. The present article examines some of the links between the two movements.     

μ-suppression during action observation and execution correlates with BOLD in dorsal premotor, inferior parietal, and SI cortices

The discovery of mirror neurons in the monkey, that fire during both the execution and the observation of the same action, sparked great interest in studying the human equivalent. For over a decade, both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have been used to quantify activity in the human mirror neuron system (MNS)-yet, little is still known about how fMRI and EEG measures of the MNS relate to each other. To test the frequent assumption that regions of the MNS as evidenced by fMRI are the origin of the suppression of the EEG μ-rhythm during both action execution and observation, we recorded EEG and BOLD-fMRI signals simultaneously while participants observed and executed actions. We found that the suppression of the μ-rhythm in EEG covaried with BOLD activity in typical MNS regions, inferior parietal lobe (IPL), dorsal premotor (dPM) and primary somatosensory cortex (BA2), during both action observation and execution. In contrast, in BA44, only nonoverlapping voxels correlated with μ-suppression during observation and execution. These findings provide direct support for the notion that μ-suppression is a valid indicator of MNS activity in BA2, IPL, and dPM, but argues against the idea that mirror neurons in BA44 are the prime source of μ-suppression. These results shed light on the neural basis of μ-suppression and provide a basis for integrating more closely the flourishing but often separate literatures on the MNS using fMRI and EEG.     

How do changes in body functions and structures,activity, and participation relate in children with cerebral palsy?

Rehabilitation increasingly addresses the International Classification of Functioning, Disability and Health's (ICF) concepts of activity and participation, but little is known about associations between changes in body functions and structures, activity, and participation. We conducted a before-and-after study of 35 ambulatory children with spastic diplegia or hemiplegic cerebral palsy, mean age 5 years 6 months (SD 2 y 2 mo). Children were in Gross Motor Function Classification System (GMFCS) Levels I (n=11), II (n=12), or III (n=12). We assessed body functions and structures, activity, and participation at baseline and at 2 months and 6 months post-botulinum toxin type A (BoNT-A) injection. Repeated-measures analysis of variance evaluated change, and linear regression assessed relationships. Baseline score relationships were moderate to strong but, despite similar directions of change at 2 months, change score relationships between measures of body functions and structures (spasticity and timed walk), activity (Gross Motor Function Measure and Pediatric Evaluation of Disability Inventory), and participation (Pediatric Outcomes Data Collection Instrument) at 2 months and 6 months were poor to fair (r<0.40). Predictor combinations accounted for <69% of variation in activity and participation change scores. Predictors often pertained to baseline score, GMFCS level, or age. Relationships between changes at different ICF levels are complex, and activity and participation gains post-BoNT-A are likely to be influenced by the child and environment factors.     

Are sexual media exposure,parental restrictions on media use and co-viewing TV and DVDs with parents and friends associated with teenagers' early sexual behaviour?

Sexual content in teenagers' media diets is known to predict early sexual behaviour. Research on sexual content has not allowed for the social context of media use, which may affect selection and processing of content. This study investigated whether sexual media content and/or contextual factors (co-viewing, parental media restrictions) were associated with early sexual behaviour using 2251 14–15 year-olds from Scotland, UK. A third (n = 733) reported sexual intercourse. In multivariable analysis the likelihood of intercourse was lower with parental restriction of sexual media and same-sex peer co-viewing; but higher with mixed-sex peer co-viewing. Parental co-viewing, other parental restrictions on media and sexual film content exposure were not associated with intercourse. Findings suggest the context of media use may influence early sexual behaviour. Specific parental restrictions on sexual media may offer more protection against early sex than other restrictions or parental co-viewing. Further research is required to establish causal mechanisms.