Minor Cognitive Deficits Research Articles

Distinct functional subnetworks of cognitive domains in older adults with minor cognitive deficits.

Although past research has established a relationship between functional connectivity and cognitive function, less is known about which cognitive domains are associated with which specific functional networks. This study investigated associations between functional connectivity and global cognitive function and performance in the domains of memory, executive function and psychomotor speed in 166 older adults aged 75-91 years (mean = 80.3 ± 3.8) with minor cognitive deficits (Mini-Mental State Examination scores between 21 and 27). Functional connectivity was assessed within 10 standard large-scale resting-state networks and on a finer spatial resolution between 300 nodes in a functional connectivity matrix. No domain-specific associations with mean functional connectivity within large-scale resting-state networks were found. Node-level analysis revealed that associations between functional connectivity and cognitive performance differed across cognitive functions in strength, location and direction. Specific subnetworks of functional connections were found for each cognitive domain in which higher connectivity between some nodes but lower connectivity between other nodes were related to better cognitive performance. Our findings add to a growing body of literature showing differential sensitivity of functional connections to specific cognitive functions and may be a valuable resource for hypothesis generation of future studies aiming to investigate specific cognitive dysfunction with resting-state functional connectivity in people with beginning cognitive deficits.

Mastering Health Following Minor Stroke—A Qualitative Explorative Study

BackgroundPatients with minor stroke or transient ischemic attack are encouraged to adopt a healthy lifestyle to prevent recurrent stroke. After discharge health behaviour is performed in an individual everyday context and must be properly understood within this context, including which aspects act as facilitators or barriers for healthy behaviour. ObjectivesTo explore the experience of daily life in patients discharged home after minor stroke or transient ischemic attack, focusing on perceived health and reflection on health behaviour, and how this is associated with their overall experience of returning to their everyday context in relation to potential sequelae of stroke. MethodsSemi-structured qualitative interviews were conducted 3 - 13 months after discharge with sixteen patients discharged home after minor stroke or transient ischemic attack. Inductive thematic analysis was performed to analyse the interviews. ResultsParticipants associated their health and behaviour within a lens of worrying for future life prospect and triggered by perceived intrusive changes in their life condition. Even though some found it possible to resume participation in everyday life within weeks, they became increasingly aware that minor cognitive deficits, difficulties with planning, multi-tasking, memory, and fatigue influenced their health believes and behavioural patterns. The need for social and professional support had to be balanced against a wish for independence. ConclusionPatients with minor stroke or transient ischemic attacks experience changes as both being concrete in the form of persisting symptoms and abstract in the form of worries and uncertainty about the future. Perceived health was associated with a new sense of vulnerability due to realisations about the risk of recurrent stroke. Worries were anchored within the individual to handle, but for some they serve as a motivator to regulate their behaviour in order to master health.

Silent Cerebral Infarction on Brain MRI Is Associated with Cognitive Impairment in Ittp Survivors in Hematological Remission

▪BACKGROUND: Individuals with immune mediated thrombotic thrombocytopenic purpura (iTTP) frequently exhibit cognitive impairment and are at higher risk of stroke than matched controls. However, the etiology of cognitive impairment in these individuals has not been established. We conducted this prospective study to examine the patterns of cognitive impairment and to test the hypothesis that cognitive impairment in iTTP survivors is associated with silent cerebral infarction (SCI, ischemic lesions on brain MRI without corresponding overt neurodeficits), which are also a risk factor for future stroke.METHODS: We prospectively enrolled adult (age ≥ 18 years) patients with iTTP and age- and sex-matched controls without prior iTTP or stroke. iTTP was diagnosed based on ADAMTS13 activity <10% during an acute episode. All study assessments were performed after achieving hematological remission (platelet count >150x10 9/L for at least 30 days after stopping plasma exchange and/or caplacizumab). Participants undergo annual study visits including the following study measures: 1) NIH stroke scale to rule out acute stroke, 2) NIH ToolBox Cognition battery, a comprehensive iPad based neurobehavioral tool that has been validated across multiple populations and for which normative control data are available. The NIH ToolBox Cognition Battery tests multiple cognitive domains (Figure 1) including executive function (dimensional change card sort test, flanker inhibitory control and attention test), processing speed (pattern comparison test), episodic memory (picture sequence memory test), working memory (list sort working memory test), language (oral reading recognition, picture vocabulary test). We used T scores adjusted for age, sex, race and educational attainment where the normative mean T score is 50 with standard deviation (SD) of 10. Mild and major cognitive impairment are defined as a T scores that are 1-2 SD below mean and > 2SD below mean for any domain, respectively; 2) Brain MRI: SCI is defined as a infarct-like lesion (punctate T2 and FLAIR hyperintensity) without corresponding neurodeficits. The Chi-squared test and Mann Whitney test were used to compare categorical and continuous variables across groups, respectively.RESULTS: Between September 2020 and June 2021, we enrolled 34 participants including 28 iTTP patients and 6 controls. Demographics and clinical characteristics of patients and controls are summarized in Table 1. NIH Stroke Scale score was 0 in all controls and all but one iTTP patient (score = 1). Among iTTP patients, 28.6% (8/28) had prior stroke (including during acute episodes).(i) iTTP survivors demonstrate cognitive deficits affecting executive function and processing speed: Among iTTP patients, 46.4% had cognitive impairment in at least one domain including 25% (7/28) with major cognitive impairment and 21.4% (6/28) with mild cognitive impairment (> 1 SD below mean T score). Among controls, 0% had major cognitive impairment and 16.6% (1/6) had mild cognitive impairment. Figure 1 shows detailed cognitive testing results for iTTP patients and controls. iTTP patients most commonly had deficits (T score < 40) in executive function (flanker inhibition test, dimensional change card sort test) and processing speed (pattern comparison test) (Table 1).(ii) Silent cerebral infarction is associated with major cognitive impairment: MRI was completed in 24 iTTP patients and all controls. SCI was present in 50% (12/24) of iTTP patients (representative image, figure 2A) and 16.6% (1/6) controls. Another 29.1% (7/24) had evidence of prior stroke. Rate of SCI was 35.7% in patients without cognitive deficits, 50% in those with minor cognitive deficits and 83.3% in those with major cognitive deficits. SCI was present in 83.3% (5/6) with major cognitive impairment versus 38.9% (7/18) without major cognitive impairment (P = 0.05) (Figure 2B).CONCLUSIONS: Cognitive deficits in iTTP survivors primarily affect executive function and processing speed and are associated with SCI suggesting ischemic etiology. Whether SCI occur during acute episodes or during remission (with remission ADAMTS13 as a risk factor) is being studied prospectively with serial MRI and cognitive assessment. iTTP patients may benefit from neurocognitive testing and referral to neuropsychological therapy, where appropriate, and aggressive measures to address risk factors for cerebrovascular disease. [Display omitted] DisclosuresNaik: Rigel: Research Funding. Lanzkron: GBT: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company; Novartis: Research Funding; Novo Nordisk: Consultancy; Imara: Research Funding; CSL Behring: Research Funding; Shire: Research Funding; Bluebird Bio: Consultancy. Chaturvedi: Sanofi Genzyme: Other: Advisory board member; Argenx: Other: Advisory board member; UCB: Other: Advisory board participation; Dova: Other: Advisory board member; Alexion: Other: Advisory board member.

Differential roles of ARID1B in excitatory and inhibitory neural progenitors in the developing cortex

Genetic evidence indicates that haploinsufficiency of ARID1B causes intellectual disability (ID) and autism spectrum disorder (ASD), but the neural function of ARID1B is largely unknown. Using both conditional and global Arid1b knockout mouse strains, we examined the role of ARID1B in neural progenitors. We detected an overall decrease in the proliferation of cortical and ventral neural progenitors following homozygous deletion of Arid1b, as well as altered cell cycle regulation and increased cell death. Each of these phenotypes was more pronounced in ventral neural progenitors. Furthermore, we observed decreased nuclear localization of β-catenin in Arid1b-deficient neurons. Conditional homozygous deletion of Arid1b in ventral neural progenitors led to pronounced ID- and ASD-like behaviors in mice, whereas the deletion in cortical neural progenitors resulted in minor cognitive deficits. This study suggests an essential role for ARID1B in forebrain neurogenesis and clarifies its more pronounced role in inhibitory neural progenitors. Our findings also provide insights into the pathogenesis of ID and ASD.

Human immunodeficiency virus Type‐1 single‐stranded RNA activates the NLRP3 inflammasome and impairs autophagic clearance of damaged mitochondria in human microglia

Despite the availability of antiretroviral therapy (ART) that fully suppresses human immunodeficiency virus type-1 (HIV), markers of inflammation and minor neurocognitive impairment are frequently identified in HIV-infected persons. Increasing data support that low-level replication defective viral RNA is made by infected cells despite the absence of infectious virus. Specific GU-rich single-stranded RNA from the HIV long terminal repeat region (ssRNA40) signaling through toll-like receptor (TLR)-7 and -8 has been shown to induce the secretion of interleukin-1β (IL-1β) in primary monocytes. Here, we examined the activation of microglial cells by HIV ssRNA40 and the potential subsequent neurotoxicity. Our findings show that exposure of human primary microglia to ssRNA40 activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Following exposure to ssRNA40, pro-inflammatory cytokines IL-1β, IL-18, and neurotoxic cytokines TNF-α, IL-1α, and C1q expression and extracellular secretion are increased. The released cytokines are functional since culture supernatants from ssRNA40 exposed microglia-induced toxicity of human primary neurons. Moreover, inflammasome activation of microglia increased ROS generation with a loss of mitochondrial membrane potential and mitochondrial integrity. Treatment with ssRNA40 resulted in a blockade of autophagy/mitophagy mediated negative regulation of NLRP3 inflammasome activity with the release of inflammatory cytokines, caspase-1 activation, and pyroptotic microglial cell death. Thus, HIV ssRNA mediated activation of microglial cells can contribute to neurotoxicity and neurodegeneration via secretion of inflammatory and neurotoxic cytokines. These findings provide a potential mechanism that explains the frequent minor cognitive deficits and chronic inflammation that persist in HIV-infected persons despite treatment with suppressive ART.

Late-Life Depressive Symptoms Are Associated With Functional Impairment Cross-sectionally and Over Time: Results of the AgeMooDe Study.

This study examines the relationship between late-life depressive symptoms, cognitive and functional impairment in a cohort of very old community-based participants. A sample of 1,226 primary care patients was assessed at baseline (Mage = 80.6 years). Statistical analyses were conducted using baseline and 12-month follow-up data. At baseline, depressed participants showed minor cognitive deficits compared with nondepressed participants, whereas functional deficits were pronounced. Depressive symptoms and global cognition were not associated longitudinally. In contrast, follow-up functional impairment was predicted by baseline level and increase of depressive symptoms between baseline and follow-up. Reversely, follow-up depressive symptoms were predicted by functional decline between baseline and follow-up, whereas baseline functional status was not predictive. Depressive symptoms and global cognitive function were not associated longitudinally, but level and increase of depressive symptoms over time predicted functional impairment after 1 year. Interventions to reduce depressive symptoms, or to encourage coping strategies might be promising to reduce functional impairment. Elevated follow-up depressive symptoms were only predicted by functional decline, supposedly emphasizing that incident functional impairment might be associated with an acute increase of depressive symptoms. Psychological adjustment processes were not examined, but might be targeted in future.

Connexin43 Containing Gap Junction Channels Facilitate HIV Bystander Toxicity: Implications in NeuroHIV.

Human immunodeficiency virus-1 (HIV-1) infection compromises the central nervous system (CNS) in a significant number of infected individuals, resulting in neurological dysfunction that ranges from minor cognitive deficits to frank dementia. While macrophages/microglia are the predominant CNS cells infected by HIV, our laboratory and others have shown that HIV-infected astrocytes, although present in relatively low numbers with minimal to undetectable viral replication, play key role in NeuroAIDS pathogenesis. Our laboratory has identified that HIV “hijacks” connexin (Cx) containing channels, such as gap junctions (GJs) and hemichannels (HCs), to spread toxicity and apoptosis to uninfected cells even in the absence of active viral replication. In this study, using a murine model with an astrocyte-directed deletion of Cx43 gene (hGFAP-cre Cx43fl/fl) and control Cx43fl/fl mice, we examined whether few HIV-infected human astrocytoma cells (U87-CD4-CCR5), microinjected into the mouse cortex, can spread toxicity and apoptosis through GJ-mediated mechanisms, into the mouse cells, which are resistant to HIV infection. In the control Cx43fl/fl mice, microinjection of HIV-infected U87-CD4-CCR5 cells led to apoptosis in 84.28 ± 6.38% of mouse brain cells around the site of microinjection, whereas hGFAP-cre Cx43fl/fl mice exhibited minimal apoptosis (2.78 ± 1.55%). However, simultaneous injection of GJ blocker, 18α-glycyrrhetinic acid, and Cx43 blocking peptide along with microinjection of HIV-infected cells prevented apoptosis in Cx43fl/fl mice, demonstrating the Cx43 is essential for HIV-induced bystander toxicity. In conclusion, our findings demonstrate that Cx43 expression, and formation of GJs is essential for bystander apoptosis during HIV infection. These findings reveal novel potential therapeutic targets to reduce astrocyte-mediated bystander toxicity in HIV-infected individuals because despite low to undetectable viral replication in the CNS, Cx channels hijacked by HIV amplify viral neuropathogenesis.

Falls Are Associated With Lower Self-Reported Functional Status in Patients After Stroke

ObjectiveTo evaluate the association between falls and functional status after stroke. DesignSecondary analysis of data from the randomized controlled FIT-Stroke trial. Outcomes were measured at the time of discharge from inpatient rehabilitation (t0) and after 12 weeks (t1). Between t0 and t1, all patients attended an outpatient rehabilitation program that included the FIT-Stroke intervention. SettingNine centers for rehabilitation medicine. ParticipantsOutpatients after stroke (N=250) with mild cognitive impairments (Mini-Mental State Examination [MMSE] score ≥24), discharged home after inpatient rehabilitation and able to walk 10m independently. InterventionsNot applicable. Main Outcome MeasuresThe primary outcome was the change in Stroke Impact Scale (SIS)-16 score. The independent variable was ≥1 falls after stroke. The outcome was corrected for type of outpatient rehabilitation (group allocation), severity of hemiplegia (Motricity Index [MI]), and cognition (MMSE) at baseline using multiple regression analysis. ResultsComplete data were available for 199 patients, with a mean age of 58±10 years, MMSE score of 28.1±2, and MI score of 130±43. Fifty-five patients (28%) reported falls during the 12 weeks after discharge from inpatient rehabilitation. Falls were significantly associated with less improvement in functional status as assessed with the SIS-16 (P=.009). ConclusionsAlmost 30% of this stroke population with minor cognitive deficits and moderate to high mobility scores reported falls during the 12 weeks of outpatient rehabilitation. Falls were negatively associated with self-reported functional status measured by the change in SIS-16 score. Therefore, it is important to identify patients with high risk of falls and implement strategies to reduce falls.

The changing phenotype of iodine deficiency disorders: a review of thirty-five years of research in north-eastern Sicily.

Iodine deficiency disorders (IDD) still represent a major public health problem, with almost 30% of the world population being exposed to the consequences of nutritional iodine deficiency (ID). In Italy, despite a sustained policy of iodine prophylaxis, more than 10% of people is still affected with goiter, and a presumably higher rate of subjects may suffer from minor cognitive deficits due to inadequate iodine supply during antenatal life. This review of systematic observational studies carried out over thirty-five years (1980-2015) in a sentinel ID area in North-eastern Sicily highlights the changing phenotypes of IDD in this region. Over the years profound improvements in nutritional iodine status in North-eastern Sicily has occurred, due to both silent and active iodine prophylaxis. Endemic cretinism, resulting from severe iodine deficiency, has been progressively replaced by less serious deficits of intellectual and cognitive abilities, which nevertheless deserve proper attention.

The Ethical Inclusion of Children With Psychotic Disorders in Research: Recommendations for an Educative, Multimodal Assent Process

This article addresses the issue of properly assenting children with psychotic disorders to participate in clinical research. Due to the protective concerns with such a vulnerable population, additional precautions are necessary to ensure that youth with psychotic disorders assent to research with an appropriate level of understanding regarding study procedures. Current literature suggests that positive/negative symptoms and minor cognitive deficits do not interfere with the ability to comprehend study-related information for adults with psychosis if the study information is presented through an educative process. Similarly, youth benefit from repeated presentation of procedures and periodic assessment of their comprehension. An integrated educative process is proposed that emphasizes the importance of an interactive consent through repetition and participant/investigator feedback.

Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians

Small for gestational age (SGA) is defined by weight (in utero estimated fetal weight or birth weight) below the 10th percentile (professional consensus). Severe SGA is SGA below the third percentile (professional consensus). Fetal growth restriction (FGR) or intra-uterine growth restriction (IUGR) usually correspond with SGA associated with evidence indicating abnormal growth (with or without abnormal uterine and/or umbilical Doppler): arrest of growth or a shift in its rate measured longitudinally (at least two measurements, 3 weeks apart) (professional consensus). More rarely, they may correspond with inadequate growth, with weight near the 10th percentile without being SGA (LE2).Birthweight curves are not appropriate for the identification of SGA at early gestational ages because of the disorders associated with preterm delivery. In utero curves represent physiological growth more reliably (LE2). In diagnostic (or reference) ultrasound, the use of growth curves adjusted for maternal height and weight, parity and fetal sex is recommended (professional consensus). In screening, the use of adjusted curves must be assessed in pilot regions to determine the schedule for their subsequent introduction at national level. This choice is based on evidence of feasibility and the absence of any proven benefits for individualized curves for perinatal health in the general population (professional consensus).Children born with FGR or SGA have a higher risk of minor cognitive deficits, school problems and metabolic syndrome in adulthood. The role of preterm delivery in these complications is linked.The measurement of fundal height remains relevant to screening after 22 weeks of gestation (Grade C). The biometric ultrasound indicators recommended are: head circumference (HC), abdominal circumference (AC) and femur length (FL) (professional consensus). They allow calculation of estimated fetal weight (EFW), which, with AC, is the most relevant indicator for screening. Hadlock's EFW formula with three indicators (HC, AC and FL) should ideally be used (Grade B). The ultrasound report must specify the percentile of the EFW (Grade C). Verification of the date of conception is essential. It is based on the crown–rump length between 11 and 14 weeks of gestation (Grade A). The HC, AC and FL measurements must be related to the appropriate reference curves (professional consensus); those modelled from College Francais d’Echographie Fetale data are recommended because they are multicentere French curves (professional consensus).Whether or not a work-up should be performed and its content depend on the context (gestational age, severity of biometric abnormalities, other ultrasound data, parents’ wishes, etc.) (professional consensus). Such a work-up only makes sense if it might modify pregnancy management and, in particular, if it has the potential to reduce perinatal and long-term morbidity and mortality (professional consensus).The use of umbilical artery Doppler velocimetry is associated with better newborn health status in populations at risk, especially in those with FGR (Grade A). This Doppler examination must be the first-line tool for surveillance of fetuses with SGA and FGR (professional consensus). A course of corticosteroids is recommended for women with an FGR fetus, and for whom delivery before 34 weeks of gestation is envisaged (Grade C). Magnesium sulphate should be prescribed for preterm deliveries before 32–33 weeks of gestation (Grade A). The same management should apply for preterm FGR deliveries (Grade C). In cases of FGR, fetal growth must be monitored at intervals of no less than 2 weeks, and ideally 3 weeks (professional consensus).Referral to a Level IIb or III maternity ward must be proposed in cases of EFW <1500g, potential birth before 32–34 weeks of gestation (absent or reversed umbilical end-diastolic flow, abnormal venous Doppler) or a fetal disease associated with any of these (professional consensus). Systematic caesarean deliveries for FGR are not recommended (Grade C). In cases of vaginal delivery, fetal heart rate must be monitored continuously during labour, and any delay before intervention must be faster than in low-risk situations (professional consensus). Regional anaesthesia is preferred in trials of vaginal delivery, as in planned caesareans.Morbidity and mortality are higher in SGA newborns than in normal-weight newborns of the same gestational age (LE3). The risk of neonatal mortality is two to four times higher in SGA newborns than in non-SGA preterm and full-term infants (LE2). Initial management of an SGA newborn includes combatting hypothermia by maintaining the heat chain (survival blanket), ventilation with a pressure-controlled insufflator, if necessary, and close monitoring of capillary blood glucose (professional consensus).Testing for antiphospholipids (anticardiolipin, circulating anticoagulant, anti-beta2-GP1) is recommended in women with previous severe FGR (below third percentile) that led to birth before 34 weeks of gestation (professional consensus). It is recommended that aspirin should be prescribed to women with a history of pre-eclampsia before 34 weeks of gestation, and/or FGR below the fifth percentile with a probable vascular origin (professional consensus). Aspirin must be taken in the evening or at least 8h after awakening (Grade B), before 16 weeks of gestation, at a dose of 100–160mg/day (Grade A).

Differential relationship between neurological and cognitive dysfunction in first episode psychosis patients and in healthy individuals

The minor neurological and cognitive deficits consistently reported in psychoses may reflect the same underlying brain dysfunction. Still, even in healthy individuals minor neurological abnormalities are associated with worse cognitive function. Therefore, establishing which neurological and cognitive deficits are specific to psychosis is essential to inform the pathophysiology of this disorder. We evaluated a large epidemiological sample of patients with first episode psychosis (n=242) and a population-based sample of healthy individuals (n=155), as part of the AESOP study. We examined neurological soft signs using the Neurological Evaluation Scale (Buchanan and Heinrichs, 1989), and generalized and specific cognitive deficits (memory; verbal abilities; attention, concentration and mental speed; executive functions and working memory; language; visual constructual/perceptual abilities). In patients, more neurological signs across all subscales were associated with worse general cognitive function, while in controls this was only present for sensory integration and sequencing signs. Furthermore, in patients, but not in healthy individuals, more sensory integrative signs were associated with deficits in specific cognitive domains, such as memory, verbal abilities, language, visual/perceptual, executive function (p ranging <0.001–0.002); sequencing signs with language, executive function, and attention (p<0.001–0.004); and motor signs with poorer verbal abilities (p=0.001). These findings indicate the presence of specific associations between neurological and cognitive deficits in psychosis that are distinct from those of healthy individuals.

Hanging-induced burst suppression pattern in EEG

Lethal suspension (hanging) is one of the most common methods of attempting suicide. Spinal fractures, cognitive and motor deficits as well as epileptic seizures can be detected after unsuccessful hanging attempts. Introduced here is the case of a 25-year-old man exemplifying the clinical observations stated hereafter, who was conveyed to our emergency room after having survived attempted suicide by hanging, with his post-anoxic burst-suppression electroencephalography (BS-EEG) pattern and clinical diagnoses in the post-comatose stage. The patient's state of consciousness was gradually improved over a period of time. His neuropsychiatric assessment proved that memory deficit, a slight lack of attention and minor executive dysfunction was observed a month after the patient was discharged. Although the BS-EEG pattern indicates severe brain dysfunction, it is a poor prognostic factor; rarely, patients survive with minor cognitive deficits and can perform their normal daily activities.

Effects of DSP4 and methylphenidate on spatial memory performance in rats

In this experiment, we have investigated the spatial memory performance of rats following a central noradrenaline depletion induced by three different doses of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) and following administration of three different doses of methylphenidate (MPH). The rats were required to find food pellets hidden on a holeboard. The sole administration of DSP4 induced only minor cognitive deficits. However, the treatment with MPH increased the reference memory error, the impulsivity and the motor activity of the DSP4-treated rats. Since the noradrenergic terminals in a DSP4-treated rat are significantly reduced, the administration of MPH has little effect on the noradrenergic system and increases dopaminergic rather than noradrenergic activity, resulting in an imbalance with relatively high dopaminergic and low noradrenergic activities. It is suggested that a reduction of noradrenaline and an increase of dopamine induce ADHD-related deficits and that the depletion of noradrenaline is not sufficient for an appropriate rat model of ADHD.

Minor Cognitive Deficits and Mood States in HIV-1 Infected Men

The aim of this study is to evaluate cognitive deficits and the psychoemotional state of patients affected by HIV-1. The sample, composed of 30 male HIV-1 positive patients aged on average 35.59, was assessed using a psychodiagnostic protocol based on the Wechsler Adult Intelligence Scale—Revised (WAIS-R) and the Profile of Mood State (POMS) applied at the three phases of observation: baseline (T1), 6 months later (T2), and 18 months later (T3). The outcomes were compared using a non-parametric statistical technique in a multivariate context (NPC test). The results highlight significative differences in responses during the three different phases of observation (T1, T2, T3) showing, in particular, reduced cognitive performance at T3 with increased anxiety, depression, aggressiveness, asthenia, and cerebral confusion. It is thus suggested that in the study sample the condition of disease accelerates the decline of specific brain mechanisms, resulting in psychiatric disorders with reduced quality of social and working life.

Pre- and post-conditioning treatment with an ultra-low dose of Δ 9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage

Preconditioning, a phenomenon where a minor noxious stimulus protects from a subsequent more severe insult, and post-conditioning, where the protective intervention is applied following the insult, offer new insight into the neuronal mechanism(s) of neuroprotection and may provide new strategies for the prevention and treatment of brain damage. We have previously reported that a single administration of an extremely low dose of Δ 9-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) to mice induced minor long-lasting cognitive deficits. In the present study we examined the possibility that such a low dose of THC will protect the mice from more severe cognitive deficits induced by the epileptogenic drug pentylenetetrazole (PTZ). THC (0.002 mg/kg, a dose that is 3–4 orders of magnitude lower than the doses that induce the conventional effects of THC) was administered 1–7 days before, or 1–3 days after the injection of PTZ (60 mg/kg). The consequences of this treatment were studied 3–7 weeks later by various behavioral tests that evaluated different aspects of memory and learning. We found that a single administration of THC either before or after PTZ abolished the PTZ-induced long-lasting cognitive deficits. Biochemical studies indicated a concomitant reduction in phosphorylated-ERK (extracellular signal-regulated kinase) in the cerebella of mice 7 weeks following the injection of THC. Our results suggest that a pre- or post-conditioning treatment with extremely low doses of THC, several days before or after brain injury, may provide safe and effective long-term neuroprotection.

Modulations of behavioral consequences of minor cortical ischemic lesion by application of free radicals scavengers

Functional and morphological consequences of ischemic lesions are partially related to the production of reactive oxygen species (ROS). The aim of the study was to create a unilateral photothrombic lesion with minimal morphological changes and minor sensorimotor and cognitive deficits and also to test whether the application of ROS scavengers after the end of induction of ischemia had improved the functional outcome. Adult Wistar male rats were randomly divided into five groups: naive control, sham operated animals, animals with induced ischemia, and two groups of animals with induced ischemia and subsequent ROS scavenger application -melatonin or tempol. The group subjected to ischemia showed a significant decline in performance in sensorimotor tests and the Morris water maze (MWM) test, compared to control animals. Tempol (50 mg/kg, i.p.) did not improve sensorimotor function and did not change spatial learning. Melatonin (100 mg/kg, i.p.), on the contrary, resulted in a significant improvement in animals' performances. All the ischemia subjected animals had increased speed of swimming in the MWM test, compared to the control group. Our findings showed that subsequent application of ROS scavengers improve ischemia outcomes, with melatonin being more potent. Conversely, neither melatonin, nor tempol decreased swimming speed cased by ischemia.

Post-partum pituitary apoplexy with bilateral third nerve palsy and bilateral carotid occlusion

This study describes a patient with post-partum collapse secondary to pituitary apoplexy with bilateral carotid artery occlusion. A 29-year-old female, post delivery of a healthy child, presented with a Glasgow Coma Scale score of 3, fixed dilated pupils, complete ophthalmoplegia, and bilateral compression of the internal carotid arteries. These symptoms were due to a giant pituitary macroadenoma. She underwent a craniotomy and subsequently survived with minor cognitive deficits and functional vision. Bilateral carotid occlusion caused by pituitary apoplexy is rare, yet survival with only minor deficits is possible.

鳥獣人物戯画絵巻より得た図版の特性ならびに神経心理検査への応用の可能性に関する研究

Certain minor cognitive deficits cannot be detected by conventional neuropsychological tests. Moreover, conventional tests can only partially examine higher cognitive functioning, therefore complicated test batteries must be used to identify minor cognitive deficits. The Choju-Giga Test (CGT), developed by Minoshita et al. (2004), was designed to fill the gap in testing. Three pictures cards, 1, 2, and 3, are used for the CGT. A test of the effectiveness of the CGT was conducted in this study. Card 1 and card 2 were regarded by all participants as pictures which portray informal situations such as family, relatives, or friends. However, the theme of ‘organized relationship’ was assigned to card 3 by a quarter of all participants. The number of words used in explaining card 3 was significantly more than for card 1, and there was also a significant difference in the position of characters in the pictures assigned by participants only to card 3.Paul et al. (2004) hypothesized that TAT pictures for neuropsychological test must include complex social situations. This study suggests however that card 3 is more effective than the other 2 cards in detecting subtle cognitive deficits.

Neurointensive care management of raised intracranial pressure caused by severe valproic acid intoxication

We describe the neurointensive care (NIC) management of a patient with severe cerebral swelling and raised intracranial pressure (ICP) after severe sodium valproic acid (VPA) intoxication. A previously healthy 25-year old male with mild tonic-clonic epilepsy was found unconscious with serum VPA levels >10,000 micromol/l. The patient deteriorated to Glasgow Motor Scale score (GMS) 2 and a CT scan showed signs of raised ICP. Early ICP was elevated, >50 mm Hg, and continuous EEG monitoring showed isoelectric readings. The patient was treated with an ICP-guided protocol including mild hyperventilation, normovolemia, head elevation and intermittent doses of mannitol. Due to refractory elevations of ICP, high-dose pentobarbital infusion was initiated, and ICP gradually normalised. There were several systemic complications including coagulopathy, hypocalcemia and pancreatitis. The patient remained in a depressed level of consciousness for 2 months but gradually recovered, showing a good recovery with minor subjective cognitive deficits by 6 months. We conclude that NIC may be an important treatment option in cases of severe intoxication causing cerebral swelling.