Polypharmacy in Treatment of Behavioral Issues in Dementia-Use of Atypical Antipsychotics.

Behavioral and psychological symptoms of dementia (BPSD) may occur in most patients with dementia. Symptoms such as agitation, aggression, and psychosis often lead to higher rates of hospitalization, morbidity, and mortality. Despite the prevalence of BPSD, safe and effective treatment options are limited. This often leads to off-label prescribing and trends toward polypharmacy. Notwithstanding modest efficacy in BPSD, antipsychotics seem to be one of the most commonly prescribed medications in its treatment. Polypharmacy with antipsychotics is particularly troublesome due to the increased risk of potentially lethal adverse effects. As such, their use should be judiciously monitored with the goal of gradual dose reduction.

Clinical Features and Outcomes of Anti-N-Methyl-d-Aspartate Receptor Encephalitis in Infants and Toddlers.

OBJECTIVE: We describe the clinical features and outcomes of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis in infants and toddlers. METHODS: This was a single-center retrospective study. Infants and toddlers who met the diagnostic criteria for anti-NMDAR encephalitis were recruited for the study. Data on clinical features, treatment, and long-term outcomes were collected retrospectively. RESULTS: A total of 41 patients (age range: six to 34 months; median age: 23 months; female: 19) were enrolled in this study. Nineteen (46%) patients exhibited classical anti-NMDAR encephalitis, whereas 22 (54%) patients exhibited anti-NMDAR encephalitis after viral encephalitis. There was a high presentation of movement disorders (100%), developmental regression (90%), abnormal behaviors (90%). All patients were administered first-line therapy, with only 17% of them being administered second-line immunotherapy. Two patients succumbed to the disease, whereas none of them relapsed. At the long-term follow-up (more than one year), 20 of 35 (57%) exhibited satisfactory outcomes (modified Rankin Scale ≤2). Compared with patients with classical anti-NMDAR encephalitis (n = 18), patients after viral encephalitis (n = 17) were more likely to have worse clinical outcomes. They exhibited a higher modified Rankin Scale/Pediatric Cerebral Performance Category score and more frequent seizures. A predictor of poor outcome was presentation after viral encephalitis (odds ratio 35.7, 95% confidence interval 4.64 to 275.03, P = 0.001). CONCLUSION: Anti-NMDAR encephalitis in infants and toddlers clinically presents with movement disorders, developmental regression, and abnormal behaviors. Interestingly, this group had a higher proportion of patients after viral encephalitis, which is regarded as the only risk factor for poor outcomes.

Open schools! Weighing the effects of viruses and lockdowns on children.

This review weighs the risk of infection with SARS-CoV-2 against the side effects of school closures on physical and mental health, education, and well-being of those affected by the school closures. Whereas short term effects - decreased learning and food security, and increased anxiety, violence against children, child labor and teen pregnancies - are frequently discussed, the long-term effects of school closures will be much more detrimental across the lifespan of the "Generation Corona": Existing pandemics of inactivity and myopia, already affecting billions of people, are worsening due to less physical exercise and less time spent outdoors, poor diet, weight gain, and increased screen time during lockdowns, causing future increases of stroke, heart attack, cancer, and blindness. Socio-emotional complications of isolation, learned helplessness, economic and existential insecurity will include increased depression and suicide, decreased empathy and increased loneliness. Together with decreased educational attainment and economic productivity, the amount of ensuing increased future global morbidity and mortality justifies immediate action of school reopening.

Quality of Life in Advanced Dementia with Late Onset, Young Onset, and Very Young Onset.

BACKGROUND: Advanced stages of dementia are characterized by severe cognitive and physical impairment. It has not yet been investigated whether persons with young onset dementia (YOD) and late onset dementia (LOD) differ in advanced disease stages. OBJECTIVES: To compare quality of life (QoL) between persons with advanced YOD and LOD; to explore the determinants of QoL; to investigate whether YOD and LOD differ with regard to symptoms and care. METHODS: The study was performed in the context of EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of YOD and LOD in Germany). Persons with advanced dementia (PWAD) were assessed and caregivers were interviewed. QoL was measured with the proxy rating Quality of Life in Late Stage Dementia (QUALID) scale. RESULTS: 93 persons with YOD and 98 with LOD were included. No significant differences in QoL were detected. Determinants of QoL were similar in YOD and LOD. Behavioral and psychological symptoms of dementia (BPSD), suffering and other distressing symptoms were associated with a lower QoL. In YOD but not in LOD antipsychotic treatment was associated with low QoL. The group of persons who were younger than 65 years at the time of the study visit experienced significantly more distressing symptoms than older PWAD. CONCLUSION: Overall, persons with advanced YOD do not appear to be disadvantaged compared to old and oldest PWAD. Special attention, however, must be paid to the group of the very young persons who seem to be particularly vulnerable.

Assessment of children in the autistic spectrum disorder that carry the Thr92Ala-DIO2 polymorphism.

INTRODUCTION: A polymorphism in the type 2 deiodinase (Thr92Ala-DIO2) gene has been associated with behavioral and cognitive dysfunction as well as neurodegeneration and oxidative stress in the central nervous system. OBJECTIVE: To test whether the minor allele (Ala92) frequency (MAF) is increased in children in the autism spectrum disorder (ASD), and whether carriers of the minor allele exhibit more severe symptoms and/or worse adaptive behavior. STUDY DESIGN: ASD children were evaluated at baseline and yearly throughout the study by psychologists using the following tools: autism behavior checklist, Vineland Adaptative Behaviour Scales II, non-verbal intelligence test SON-R 21/2-7, SON-R 6-40, Weschler scale for intelligence, and autism treatment evaluation checklist. SETTINGS: Academic outpatient mental health facility in Sao Paulo, Brazil. PARTICIPANTS: ASD boys and girls younger than 18 years of age. 132 consecutive ASD children, mostly boys (~ 80%); ~ 50% was classified as verbal. Exclusion criteria were coexistence of sensory and/or physical impairment, or any associated genetic syndromes. RESULTS: Median follow-up was for an uninterrupted period of 937 days (139-1375 days), which did not vary significantly among the genotypes. The MAF was 47% in ASD patients vs. 51% in a local reference population with similar ethnic background; the clinical severity and progression were not affected by the minor allele. Carriers of the minor allele exhibited higher adaptive behavior in the domains "daily living skills" and "communication", which correlated positively with the dose of the minor allele. CONCLUSION: The MAF is not different in ASD children, but carriers of the Thr92Ala-DIO2 polymorphism exhibited higher adaptive behavior.

Increased prevalence of impulse control disorder symptoms in endocrine diseases treated with dopamine agonists: a cross-sectional study.

INTRODUCTION: Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions. MATERIALS AND METHODS: A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP). RESULTS: Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82). DISCUSSION: Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.

PTSD Susceptibility and Challenges: Pathophysiological Consequences of Behavioral Symptoms.

INTRODUCTION: Posttraumatic stress disorder (PTSD) can develop during the aftermath of traumatic events. Although many are impacted by several stressors, nearly 3.6% suffer from PTSD in the United States with higher incidence reported in military service personnel. Any injury to the blood-brain barrier can ignite an array of biological signaling molecules in the immune-privileged brain parenchyma, which can disrupt the synaptic neural network, resulting in altered behavior. MATERIALS AND METHODS: In this preliminary study, we compared 20 PTSD veterans with age-matched healthy veterans to identify plasma levels of brain-specific protein markers using enzyme-linked immunosorbent assay/immunofluorometric sandwich assay for neurotrophic factors and neuropoietic cytokines, and catalytic activity of matrix metalloproteinase (MMP) by zymography. RESULTS: We observed an increased level of glial fibrillary acidic protein, tumor necrosis factor-alpha, interleukin 6, and MMP2 and MMP9 but decreased level of brain-derived neurotrophic factor, nerve growth factor-beta, and negligible difference in astroglial marker S100 calcium-binding protein B compared to controls. CONCLUSION: Identification of neural biomarkers is essential to understand the subclinical symptoms for the diagnosis PTSD, which may not be visible by magnetic resonance imaging (MRI/fMRI) and may take years to clinically manifest.

Cognitive outcome of pediatric epilepsy surgery across ages and different types of surgeries: A monocentric 1-year follow-up study in 306 patients of school age.

OBJECTIVE: The neuropsychological outcome of pediatric epilepsy surgery has been reported before, but only few studies compared different major types of surgery in differentially located epilepsies. METHODS: Neuropsychological performance of 306 children and adolescents (ages 6-17 years) were assessed before and one year after epilepsy surgery. Individual impairments, changes into and out of impairment, as well as intraindividually meaningful positive or negative changes were examined. Regression analyses addressed the effects of site, side, pathology, type of surgery, seizure outcome, and drug change on the cognitive and behavioral domains. RESULTS: Preoperatively 85% of the patients had cognitive impairments in at least one domain, 71% had behavioral problems. Postoperatively the number of impaired patients dropped considerably: 21-50% of the patients changed from impaired to unimpaired, individually significant gains were registered in 16-42%. Seizure freedom was achieved in 81% of all patients. The number of antiepileptic drugs decreased significantly. Seizure freedom, a younger age at evaluation, a later age at onset, a lower antiepileptic drug load, and less baseline damage predict better cognitive and behavioral outcomes. Gender, pathology, localization, and lateralization had little or no impact. CONCLUSION: Differentially located and lateralized epilepsies hardly differed in cognition and behavior indicating nonspecific developmental rather than domain specific impairments. Childhood epilepsy surgery is very successful and the functional improvements one year after surgery confirm the general relevance of baseline damage, mental reserve capacities, functional plasticity, the preservation of functional tissues and the functional release due to seizure freedom and drug load reduction.

Characterisation and outcome of neuropsychiatric symptoms in patients with anti-NMDAR encephalitis.

BACKGROUND: Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms. OBJECTIVE: To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE. METHODS: This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale. RESULTS: 24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259). CONCLUSIONS: Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.

Alemtuzumab significantly improves posterior fossa syndrome presented as a relapse of multiple sclerosis.

BACKGROUND: Posterior fossa syndrome (PFS) is a rare manifestation of ponto-mesencephalic lesions frequently reported in post-surgical pediatric tumors, rarely described as a consequence of vascular, infective or inflammatory lesions. OBJECTIVE: The aim of this article is to report the clinical and neuroradiological characteristics of a patient with an acute PFS presentation as a relapse in relapsing-remitting MS, significantly responsive to Alemtuzumab treatment. CASE REPORT: 24-year-old patient affected by multiple sclerosis developed motor-cognitive and behavioral syndrome related to an extensive ponto-mesencephalic lesion under Fingolimod treatment. CONCLUSION: Our case highlights the significant and rapid effect of Alemtuzumab therapy on both cognitive and motor symptoms occurring during a MS relapse with atypical neuroradiological localization.

Association of brain amyloidosis with the incidence and frequency of neuropsychiatric symptoms in ADNI: a multisite observational cohort study.

OBJECTIVE: To investigate the relationship between amyloid burden and frequency of existing and incidence of new neuropsychiatric symptoms (NPS) in elderly with and without cognitive decline. METHODS: 275 cognitively normal controls (NC), 100 subjective memory complaint (SMC), 559 mild cognitive impairment (MCI) and 143 Alzheimer's disease dementia subjects from the Alzheimer's Disease Neuroimaging Initiative received (18F)-florbetapir positron emission tomography (PET) scans. Yearly neuropsychiatric inventory (Neuropsychiatric Inventory (NPI)/NPI-Questionnaire) data were collected from the study partners at each visit. Mean standard uptake volume ratios (SUVR) normalised to whole cerebellum were obtained. Positive amyloid PET scan was defined as mean SUVR ≥1.17. Fisher's exact test was used to compare frequency and incidence between amyloid positive and amyloid negative subjects. Survival analyses were used to estimate of neuropsychiatric symptoms (NPS) between amyloid positive and amyloid negative subjects. Survival analyses were used to estimate hazard ratios for developing the most common NPS by amyloid status. RESULTS: No differences in NPS frequency were seen between amyloid positive and amyloid negative NC, SMC, MCI or dementia groups. MCI subjects with amyloid pathology however tended to have greater frequency x severity (FxS) of anxiety, hallucinations, delusions, apathy, disinhibition, irritability, aberrant motor behavior, and appetite, but not agitation, depression, night-time disturbances, or elation. MCI subjects with amyloid pathology were at greater risk for developing apathy, anxiety and agitation over time. Baseline presence of agitation and apathy and new onset agitation, irritability and apathy predicted faster conversion to dementia among MCI subjects. CONCLUSIONS: Amyloid pathology is associated with greater rate of development of new NPS in MCI. Anxiety and delusions are significant predictors of amyloid pathology. Agitation, irritability and apathy are significant predictors for conversion from MCI to dementia.

Association of behavioral risk factors with self-reported and symptom or measured chronic diseases among adult population (18-69 years) in India: evidence from SAGE study.

BACKGROUND: The objective is to analyze the behavioral risk factors among the adult population and to identify the determinants of and their association with self-reported and symptom or measured chronic diseases in India. METHODS: The study utilized data from the Study on Global Aging and Adult Health (SAGE), Wave 1 (2007). Logistic regression was applied to examine the association of self-reported and symptom or measured chronic diseases with behavioral risk factors and socioeconomic-demographic covariates. RESULTS: The results show that the prevalence of the symptom or measured chronic diseases was higher (41.9%) than that of the self-reported chronic diseases (24.1%). The moderate and vigorous physical activity was less likely to be associated with self-reported depression, arthritis, and stroke, but more likely to be associated with the symptom or measured based arthritis and asthma compared to physical inactivity. Adequate intake of fruits and vegetables was significantly less likely to be associated with angina, COPD, and asthma; however, it was more than three times more likely to be associated (OR: 3.45; 95% CI: 1.99-5.97) with self-reported depression. Infrequent moderate alcohol drinking was statistically two times more associated (OR: 1.83; 95% CI: 1.04-3.21) with the symptom or measured based COPD than non-drinking. Likewise, any type of tobacco use was found to be about four times more associated (OR: 3.59; 95% CI: 1.07-12.13) with self-reported stroke. Both self-reported and symptom or measured hypertension, arthritis, and diabetes were associated with overweight, while hypertension was associated with obesity. Females and increased age came out as significant predictors of both self-reported and symptom or measured chronic diseases. CONCLUSION: The prevalence of chronic diseases and their association with BRFs and socioeconomic and demographic covariates differ markedly when assessed against self-reported criteria versus symptom or measured criteria. Adequate intake of fruits and vegetables is a crucial behavior that controls and delays the onset of chronic diseases. The study suggests that the National Program should remain focused on behavioral risk factors for maximum returns on health outcomes and that proper awareness and knowledge must be spread about healthy lifestyle behaviors throughout the country.

Meningioma and psychiatric symptoms: An individual patient data analysis.

Meningioma is a slow-growing benign tumor arising from meninges and is usually asymptomatic. Though neuropsychiatric symptoms are common in patients with brain tumors, they often can be the only manifestation in cases of meningioma. Meningiomas might present with mood symptoms, psychosis, memory disturbances, personality changes, anxiety, or anorexia nervosa. The diagnosis of meningioma could be delayed where only psychiatric symptoms are seen. A comprehensive review of the literature and individual patient data analysis was conducted, which included all case reports, and case series on meningioma and psychiatric symptoms till September 2018 with the search terms "meningioma" and "psychiatric symptoms/ depression/ bipolar disorder/mania/ psychosis/ obsessive-compulsive disorder". Search engines used included PubMed, MEDLINE, PsycINFO, Cochrane database and Google Scholar. Studies reported varied psychiatric symptoms in cases with meningioma of differing tumor site, size and lateralization. Factors which led to a neuroimaging work-up included the occurrence of sudden new or atypical psychiatric symptoms, a lack of response to typical line of treatment and the presence of neurological signs or symptoms such as headache, seizures, diplopia, urinary incontinence etc. This review emphasizes on the need of neurological examination and neuroimaging in the patients presenting to psychiatry especially with atypical symptoms.

Maternal inflammation during pregnancy and offspring psychiatric symptoms in childhood: Timing and sex matter.

OBJECTIVE: Maternal infection during pregnancy has been associated with increased risk of offspring psychopathology, including depression. As most infections do not cross the placenta, maternal immune responses to infection have been considered as potentially contributing to this relationship. This study examined whether gestational timing of maternal inflammation during pregnancy is associated with offspring internalizing and/or externalizing symptoms during childhood and, further, whether fetal sex moderated this relationship. METHOD: Participants were 737 pregnant women and their offspring who were continuously followed through late childhood. Archived first and second trimester sera were analyzed for markers of inflammation [interleukin 8 (IL-8), IL-6, IL-1 receptor antagonist (IL-1ra), and soluble tumor necrosis factor receptor-II (sTNF-RII)]. When offspring were aged 9-11, mothers completed a questionnaire assessing psychological symptoms. RESULTS: Multivariate regression analyses indicated that elevated IL-8 in the first trimester was associated with significantly higher levels of externalizing symptoms in offspring. Higher IL-1ra in the second trimester was associated with higher offspring internalizing symptoms. Further, second trimester IL-1ra was associated with increased internalizing symptoms in females only. CONCLUSION: These findings demonstrate that elevated maternal inflammation during pregnancy is associated with the emergence of separate psychological phenotypes and that timing of exposure and fetal sex matter for offspring outcomes. Given that internalizing and externalizing symptoms in childhood increase risk for a variety of mental disorders later in development, these findings potentially have major implications for early intervention and prevention work.

α-synuclein expression from a single copy transgene increases sensitivity to stress and accelerates neuronal loss in genetic models of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by the formation of α-synuclein-containing protein aggregates called Lewy bodies within the brain. A crucial role for α-synuclein in the pathogenesis of PD is also suggested by the fact that point mutations, increased copy number, or polymorphisms in the α-synuclein gene SNCA all cause or contribute to the development of PD. In addition to SNCA, an increasing number of other genes have been implicated in PD. While mutations in at least some of these genes have been shown to cause the formation of Lewy bodies, the role of α-synuclein in these genetic forms of PD remains poorly defined. Since C. elegans do not have a homolog of α-synuclein, this organism provides the opportunity to identify synergism between α-synuclein and other genes implicated in PD. To do this, we generated a novel C. elegans model in which wild-type α-synuclein is ubiquitously expressed from a single copy transgene, and examined the resulting effect on phenotypic deficits in PD deletion mutants affecting PARK2/pdr-1, PINK1/pink-1, DJ-1/djr-1.1 and ATP13A2/catp-6. While the PD deletion mutants exhibit only mild phenotypic deficits in absence of α-synuclein, expression of wild-type α-synuclein caused increased sensitivity to multiple stresses, induced deficits in dopamine-dependent behavior, and accelerated loss of dopamine neurons. Overall, these results suggest that the recessive loss of function mutations act together with α-synuclein to cause PD, and that α-synuclein lowering strategies may be effective in genetic forms of PD.

Refining the psychiatric syndrome of anti-N-methyl-d-aspartate receptor encephalitis.

OBJECTIVE: To review the psychiatric symptoms of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, in an attempt to differentiate the presentation from a primary psychiatric disorder. METHOD: A systematic literature review of PubMed and EMBASE of all published cases of anti-NMDA receptor encephalitis was performed from inception to January 2018. RESULTS: There were 706 cases of anti-NMDA receptor encephalitis identified. Cases were typically young (mean age 22.6 years, SD 14.8), female (F : M ratio 3.5 : 1) and presented with significant behavioural disturbance. Reported behaviour was most commonly severe agitation and aggression, abnormal speech, and catatonia. Psychosis occurred in 45.8% of cases. Investigation results were inconsistent (MRI abnormal in 35.6%, EEG abnormal in 83.0%) and non-specific. Psychiatric treatment often required multiple psychotropics, and there may be increased risk of significant side-effects such as neuroleptic malignant syndrome. Prognosis was usually good; however, cognitive and behavioral symptoms remained prominent during recovery, and psychiatrist involvement was required in this period. CONCLUSION: The presentation of anti-NMDA receptor encephalitis is variable. However, there are often psychiatric features which are atypical to a primary psychiatric illness, such as severe agitation, speech abnormalities, and catatonia, which may help early identification.

PTSD and gender: could gender differences in war trauma types, symptom clusters and risk factors predict gender differences in PTSD prevalence?

The female-male ratio in the prevalence of post-traumatic stress disorder (PTSD) is approximately 2:1. Gender differences in experienced trauma types, PTSD symptom clusters, and PTSD risk factors are unclear. We aimed to address this gap using a cross-sectional design. A sample of 991 civilians (522 women, 469 men) from South Lebanon was randomly selected in 2007, after the 2006 war. Trauma types were grouped into disaster and accident, loss, chronic disease, non-malignant disease, and violence. PTSD symptom clusters involved re-experiencing, avoidance, negative cognitions and mood, and arousal. These were assessed using parts I and IV of the Arabic version of the Harvard Trauma Questionnaire (HTQ). Risk factors were assessed using data from a social support and life events questionnaire in multiple regression models. Females were twice as likely as males to score above PTSD threshold (24.3 vs. 10.4%, p ˂ 0.001). Total scores on all trauma types were similar across genders. Females scored higher on all symptom clusters (p < 0.001). Social support, social life events, witnessed traumas, and domestic violence significantly were associated with PTSD in both genders. Social support, social life events, witnessed traumas and domestic violence were significantly associated with PTSD in both genders. Conversely, gender difference in experienced traumas was not statistically significant. These findings accentuate the need to re-consider the role of gender in the assessment and treatment of PTSD.

Is It Feasible to Identify Natural Clusters of TSC-Associated Neuropsychiatric Disorders (TAND)?

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder with multisystem involvement. The lifetime prevalence of TSC-Associated Neuropsychiatric Disorders (TAND) is in the region of 90% in an apparently unique, individual pattern. This "uniqueness" poses significant challenges for diagnosis, psycho-education, and intervention planning. To date, no studies have explored whether there may be natural clusters of TAND. The purpose of this feasibility study was (1) to investigate the practicability of identifying natural TAND clusters, and (2) to identify appropriate multivariate data analysis techniques for larger-scale studies. METHODS: TAND Checklist data were collected from 56 individuals with a clinical diagnosis of TSC (n = 20 from South Africa; n = 36 from Australia). Using R, the open-source statistical platform, mean squared contingency coefficients were calculated to produce a correlation matrix, and various cluster analyses and exploratory factor analysis were examined. RESULTS: Ward's method rendered six TAND clusters with good face validity and significant convergence with a six-factor exploratory factor analysis solution. The "bottom-up" data-driven strategies identified a "scholastic" cluster of TAND manifestations, an "autism spectrum disorder-like" cluster, a "dysregulated behavior" cluster, a "neuropsychological" cluster, a "hyperactive/impulsive" cluster, and a "mixed/mood" cluster. CONCLUSIONS: These feasibility results suggest that a combination of cluster analysis and exploratory factor analysis methods may be able to identify clinically meaningful natural TAND clusters. Findings require replication and expansion in larger dataset, and could include quantification of cluster or factor scores at an individual level.

Brain infusion of α-synuclein oligomers induces motor and non-motor Parkinson's disease-like symptoms in mice.

Parkinson's disease (PD) is characterized by motor dysfunction, which is preceded by a number of non-motor symptoms including olfactory deficits. Aggregation of α-synuclein (α-syn) gives rise to Lewy bodies in dopaminergic neurons and is thought to play a central role in PD pathology. However, whether amyloid fibrils or soluble oligomers of α-syn are the main neurotoxic species in PD remains controversial. Here, we performed a single intracerebroventricular (i.c.v.) infusion of α-syn oligomers (α-SYOs) in mice and evaluated motor and non-motor symptoms. Familiar bedding and vanillin essence discrimination tasks showed that α-SYOs impaired olfactory performance of mice, and decreased TH and dopamine levels in the olfactory bulb early after infusion. The olfactory deficit persisted until 45days post-infusion (dpi). α- SYO-infused mice behaved normally in the object recognition and forced swim tests, but showed increased anxiety-like behavior in the open field and elevated plus maze tests 20 dpi. Finally, administration of α-SYOs induced late motor impairment in the pole test and rotarod paradigms, along with reduced TH and dopamine content in the caudate putamen, 45 dpi. Reduced number of TH-positive cells was also seen in the substantia nigra of α-SYO-injected mice compared to control. In conclusion, i.c.v. infusion of α-SYOs recapitulated some of PD-associated non-motor symptoms, such as increased anxiety and olfactory dysfunction, but failed to recapitulate memory impairment and depressive-like behavior typical of the disease. Moreover, α-SYOs i.c.v. administration induced motor deficits and loss of TH and dopamine levels, key features of PD. Results point to α-syn oligomers as the proximal neurotoxins responsible for early non-motor and motor deficits in PD and suggest that the i.c.v. infusion model characterized here may comprise a useful tool for identification of PD novel therapeutic targets and drug screening.

Cognition and behavorial morbidity associated with sleep disordered breathing in children / Alteraciones cognitivas y conductuales en los trastornos respiratorios del sueño (TRS) en niños

Sleeep disorder breathing (SDB) in chilhood includes a broad spectrum of disease ranging from primary snoring to more severe forms of obstructive sleep apnea syndrome. They may be associated with alterations different than those seen in adults, e.g., children present a low percentage of daytime sleepiness. Nevertheless, they present great difficulties in their learning, and failure in memory and attention and reports of behavior of aggressiveness. We analyze in the present review the cognitive and behavioral deficits asscoaited with the RDS and the main tests that are made for its study

Los trastornos respíratorios del sueño (TRS) en la infancia incluyen un amplio espectro que comprende desde el ronquido primario hasta las formas más graves de síndrome de apnea obstructiva del sueño (SAOS). Los niños presentan sintomatología asociada distinta a los adultos, como un bajo porcentaje de sonmolencia diurna. No obstante refieren dificultades en su aprendizaje, fallas en memoria, atención y cambios en su hiperactividad y agresividad. Se analizan los déficit cognitivos y conductuales asociados a los TRSy las principales pruebas neuropsicológicas o test que se realizan para su estudio