Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder?

OBJECTIVE: Several findings suggest that some patients with depressive or bipolar disorder may be at increased risk of developing dementia. The present study aimed to investigate whether the risk of developing dementia increases with the number of affective episodes in patients with depressive disorder and in patients with bipolar disorder. METHODS: This was a case register study including all hospital admissions with primary affective disorder in Denmark during 1970-99. The effect of the number of prior episodes leading to admission on the rate of readmission with a diagnosis of dementia following the first discharge after 1985 was estimated. A total of 18,726 patients with depressive disorder and 4248 patients with bipolar disorder were included in the study. RESULTS: The rate of a diagnosis of dementia on readmission was significantly related to the number of prior affective episodes leading to admission. On average, the rate of dementia tended to increase 13% with every episode leading to admission for patients with depressive disorder and 6% with every episode leading to admission for patients with bipolar disorder, when adjusted for differences in age and sex. CONCLUSION: On average, the risk of dementia seems to increase with the number of episodes in depressive and bipolar affective disorders.     

Chlamydia pneumoniae seropositivity in adults with acute ischemic stroke: A case�Ccontrol study

Background:

Causative role of Chlamydia pneumoniae infection in patients with acute ischemic stroke (AIS) remains unresolved till date.

Aim:

To investigate the role of C. pneumoniae antibodies in AIS.

Materials and Methods:

Patients with AIS and sex- and environment-matched controls were enrolled. Antibodies to C. pneumoniae (IgA, IgG and IgM) were measured using enzyme-linked immunosorbent assay (ELISA).

Results:

A total of 51 patients and 48 controls were enrolled. The IgA seropositivity was significantly associated with AIS (unadjusted odds ratio 3.1; 95% CI 1.38, 6.96; P = 0.005), whereas IgG (unadjusted OR 0.44; 95% CI 0.18, 1.09; P = 0.07) and IgM (unadjusted OR 1.1; 95% CI 0.36, 3.3; P = 0.88) were not. There was no difference in IgA or IgG positivity in different stroke subtypes. On multivariate analysis after adjusting for sex, hypertension, diabetes mellitus, smoking and alcohol, the IgA seropositivity yielded an adjusted OR for stroke (4.72; 95% CI 1.61, 13.83; P = 0.005), while IgG seropositivity did not (OR 0.25; 95% CI 0.08, 0.83; P = 0.23).

Conclusions:

An increased risk of AIS was demonstrated in patients seropositive for C. pneumoniae for IgA antibodies.     

Phasic cholinergic signaling in the hippocampus: Functional homology with the neocortex?

Acetylcholine (ACh) acts as a neurotransmitter in both the hippocampus and neocortex to facilitate learning, memory, and cognitive function. Here we show that transient muscarinic ACh receptor (mAChR) activation inhibits action potential generation in CA1, but not in CA3, pyramidal neurons via activation of an SK-type calcium-activated potassium conductance. Hyperpolarizing responses generated by focal ACh application near the somata of CA1 pyramidal neurons were blocked by atropine or the M1-like mAChR antagonist pirenzepine, but not by the M2-like mAChR antagonist methoctramine. Inhibitory cholinergic responses required intracellular calcium signaling, as evidenced by their sensitivity to depletion of internal calcium stores or internal calcium chelation. Cholinergic inhibition did not require GABAergic synaptic transmission, but was blocked by apamin, an SK channel antagonist. In contrast to inhibitory effects in CA1 neurons, ACh was primarily depolarizing, and enhanced action potential firing in CA3 pyramidal neurons. These results, when combined with recent data in neocortical neurons, suggest a functional homology in phasic cholinergic signaling in the hippocampus and neocortex whereby ACh preferentially inhibits those neurons in the lower cortical layers (CA1 and layer 5 neurons) that provide the majority of extracortical efferent projections.     

Determination of the brain�Cblood partition coefficient for water in mice using MRI

Cerebral blood flow (CBF) quantification is a valuable tool in stroke research. Mice are of special interest because of the potential of genetic engineering. Magnetic resonance imaging (MRI) provides repetitive, noninvasive CBF quantification. Many MRI techniques require the knowledge of the brain–blood partition coefficient (BBPC) for water. Adopting an MRI protocol described by Roberts et al (1996) in humans, we determined the BBPC for water in 129S6/SvEv mice from proton density measurements of brain and blood, calibrated with deuterium oxide/water phantoms. The average BBPC for water was 0.89±0.03 mL/g, with little regional variation within the mouse brain.     

Coexpression of angiopoietin-1 with VEGF increases the structural integrity of the blood�Cbrain barrier and reduces atrophy volume

Vascular endothelial growth factor (VEGF)-induced neovasculature is immature and leaky. We tested if coexpression of angiopoietin-1 (ANG1) with VEGF improves blood–brain barrier (BBB) integrity and VEGF neuroprotective and neurorestorative effects using a permanent distal middle cerebral artery occlusion (pMCAO) model. Adult CD-1 mice were injected with 2 × 10⁹ virus genomes of adeno-associated viral vectors expressing VEGF (AAV-VEGF) or ANG1 (AAV-ANG1) individually or together in a 1:1 ratio into the ischemic penumbra 1 hour after pMCAO. AAV-LacZ was used as vector control. Samples were collected 3 weeks later. Compared with AAV-LacZ, coinjection of AAV-VEGF and AAV-ANG1 reduced atrophy volume (46%, P=0.004); injection of AAV-VEGF or AAV-ANG1 individually reduced atrophy volume slightly (36%, P=0.08 and 33%, P=0.09, respectively). Overexpression of VEGF reduced tight junction protein expression and increased Evans blue extravasation. Compared with VEGF expression alone, coexpression of ANG1 with VEGF resulted in upregulation of tight junction protein expression and reduction of Evans blue leakage (AAV-ANG1/AAV-VEGF: 1.4±0.3 versus AAV-VEGF: 2.8±0.7, P=0.001). Coinjection of AAV-VEGF and AAV-ANG1 induced a similar degree of angiogenesis as injection of AAV-VEGF alone (P=0.85). Thus, coexpression of ANG1 with VEGF improved BBB integrity and resulted in better neuroprotection compared with VEGF expression alone.     

How to approach the patient with muscular symptoms in the general neurological practice?

Muscle symptoms and signs are a frequent reason for general neurological consultations. Weakness is the most reliable clinical indicator of myopathy. Fatigue and exercise intolerance and myalgias frequently occur in non-myopathic conditions. Cramps and myoglobinuria are more often due to systemic factors than being a sign of a metabolic or other myopathy. Contractures and myotonia are rare findings but when present are strong leads towards specific myopathic diagnoses. Serum creatine kinase (CK) is the single most useful screening laboratory study. Creatine kinase increase does not only occur in myopathies, and some myopathies cause no CK increase. Rapid recruitment of short duration, low amplitude motor unit potentials is the most typical hallmark of needle electromyography in myopathies. Critical appreciation of the clinical, laboratory and electromyography findings will help general neurologists select the few patients that need referral for muscle biopsy and genetic studies.     

Mechanisms of antinociceptive effects of ouabain in combination with neostigmine in the rat***★

BACKGROUND： It has been previously shown that intrathecal administration of either ouabain or neosdgmine can produce antinociceptive effects. Moreover, ouabain and neostigmine are differently associated with acetylcholine.
OBJECTIVE： It has been hypothesized that intrathecal administration of ouabain, in combination with neostigmine, can produce antinociceptive synergistic effects. Atropine, as a competitive antagonist, was pre-injected to verify the mechanisms of action.
DESIGN, TIME AND SETTING： This study was a randomized, controlled, animal experiment, performed at the State Key Laboratory of Oncology in Southern China between May 2006 and February 2007.
MATERIALS： A total of 102 healthy, adult, Sprague Dawley rats were included. Ouabain and neostigmine （Sigma, USA）, as well as atropine （Tanabe Seiyaku, Japan）, were also used.
METHODS： Varied doses of ouabain, neostigmine, and a combination of the two were intrathecally injected into rats. Six rats were allotted for each dose group. Intrathecal pretreatment with atropine was tested 10 minutes prior to intrathecal administration of neostigmine or the combination of ouabain and neostigmine.
MAIN OUTCOME MEASURES： Tail-flick tests were performed to measure tail-flick latency （seconds） prior to and after administration. The response in the tail-flick test was expressed as the percentage of maximum possible effect （% MPE）, where % MPE = [tail-flick latency after administration （seconds） -mean baseline value for tail-flick latency]/[ 10 seconds - the mean baseline value for tail-flick latency （seconds）] x 100%.
RESULTS： Rat spinal intrathecal administration of either ouabain or neostigmine alone produced antinociceptive effects in a dose-dependent manner. Intrathecally administration of neostigmine （0.05, 0.1, 0.3 μg ） in combination with ouabain （1 μ g ） produced enhanced antinociceptive effects, with a % MPE of 29%, 78%, and 95%, respectively （P 〈 0.05）. Intrathecally administration of 0.3μg neost     

Electroconvulsive therapy in Parkinsonian patients with the “on-off” syndrome

Summary Marked, abrupt and disabling oscillations in motor performance—the on-off phenomenon-frequently occur in the course of long-term levo-dopa therapy for Parkinson's disease. Although these fluctuations are usually refractory to available medications it has recently been suggested that electroconvulsive therapy (ECT) may be beneficial.Five Parkinsonian patients with incapacitating and unpredictable on-off changes who were free of significant depression were given conventional bilateral ECT while usual drug regimens were maintained. While ECT was well tolerated, after a total of six treatments no significant improvement in Parkinsonian disabilities or on-off changes were seen.     

Which collateral effects influence in the adherence with antipsychotic medication?

The collateral effects of antipsychotic medication, specially the mental aspects of extrapyramidal symptoms, sexual disorders and weight gain, constitute an important cause of lack of adherence to treatment. The common characteristic to all these effects is that they produce a high subjective distress. This is more related to the capacity to generate suffering to the patient than to the objective severity of a collateral effect. In this paper these collateral effects are revised. The conclusion is that, in spite of the fact that new antipsychotics show an improvement with regard to their collateral effects profile, these drugs include a new profile of distressing effects that must be evaluated and corrected, as a way to optimize the patient's adherence to antipsychotic treatment.     

Trafficking among youth in conflict with the law in São Paulo,Brazil

Background

Engagement in drug trafficking may place a child or youth at risk for exposure to severe violence, drug abuse, and death. However, little is know about the nature of youth involvement in drug trafficking. The purpose of this study is to describe drug trafficking behaviour of delinquent youth and identify adverse experiences as potential predictors of trafficking.

Methods

Cross-sectional sample of youth (12–17 years of age) incarcerated in detention facilities for delinquent or criminal acts in São Paulo City, Brazil. Structured face-to-face interviews completed with 325 youth (289 boys, 36 girls).

Results

Approximately half of the boys and girls in this sample have had at least some role in drug trafficking prior to incarceration. Though youth who had engaged in drug trafficking activities did not differ on basic socio-demographic variables, they were more likely to have been exposed to a number of adverse experiences. Beyond heavy substance use, no longer attending school, gang involvement, witnessing violence, and easier access to guns, drugs and alcohol remained significantly related to trafficking involvement in the final regression model. Girls experienced a very similar pattern of adverse exposures as boys.

Conclusion

Special efforts may be required for rehabilitation of youth who engage in drug trafficking. Potential targets may include keeping or re-engaging delinquent youth in school for longer periods of time and reducing youth exposure to violence in poor urban communities.

     

Changes in the blood–brain barrier status closely correlate with the rate of disease progression in patients with multiple system atrophy: A longitudinal study

BackgroundThe pathomechanisms responsible for disease progression in multiple system atrophy are unknown. The blood–brain barrier status may act as a modifier of disease progression in neurodegenerative diseases.MethodsWe evaluated the 12-month longitudinal change of the blood–brain barrier in 16 multiple system atrophy patients and analyzed its correlation with changes in clinical severity.ResultsThe baseline blood–brain barrier index did not correlate significantly with change in disease severity. However, changes in the blood–brain barrier indices over 12 months had significant positive correlations with changes in total unified multiple system atrophy rating scale (r = 0.56, p = 0.024) and part II scores (r = 0.56, p = 0.025). These correlation coefficients were higher after adjusting for baseline neurological deficits.ConclusionsThese data suggest that changes in the blood–brain barrier status are closely coupled with the rate of disease progression in multiple system atrophy, potentially acting as a contributor to disease progression.     

Neuronal firing patterns in the subthalamic nucleus in patients with akinetic-rigid-type Parkinson’s disease

Recent studies suggest that Parkinson’s disease (PD) is associated with pathological synchronous oscillatory activity in the basal ganglia. Beta frequency band (β-FB) oscillations likely contribute to bradykinesia and rigidity in PD; however, details of the relationship between these two phenomena remain unclear. To explore β-FB oscillatory activity in relation to motor signs of bradykinesia and rigidity, we studied 17 patients with akinetic-rigid type PD who had electrodes implanted into the subthalamic nucleus (STN) for deep brain stimulation therapy. Microelectrode recordings were obtained in the STN during surgery and neuronal activity was analyzed offline. The spectral characteristics were calculated. Of 155 neurons from 30 STN, 56 (36.1%) had β-FB oscillatory activity. Neurons with oscillatory activity were localized in the dorsal two-thirds of the STN. These data indicate that β-FB oscillatory activity may be of particular importance in the generation of motor deficits in PD.     

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

ObjectivesThis study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD.MethodsThis cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes‐closed and eyes‐open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD.ResultsThe PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose).ConclusionAlterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.