Neuropsychiatric disturbances in acute subarachnoid haemorrhage

Background: Acute and unexpected neuropsychiatric disturbances can herald subarachnoid haemorrhage (SAH). We investigated the risk factors for neuropsychiatric disturbances in acute SAH and analysed the relation between neuropsychiatric disturbances and location and amount of haematic densities and hydrocephalus. Methods: We assessed a sample of 108 consecutive patients with an acute (≤4 days) SAH (61 aneurysmal, 47 non‐aneurysmal SAH), before aneurysmal treatment, using DSM‐IV‐TR criteria and the Montgomery Åsberg Depression Rating Scale and Mania Rating Scale, the Denial of Illness Scale, the Catastrophic Reaction Scale and the Apathy Evaluation Scale, excluding patients with severe consciousness or language disturbance. Performance on each scale was related to (i) the total amount of haematic densities in 10 basal cisterns/fissures and in the four ventricles, using the Hijdra et al. rating scale, (ii) the haematic densities in the prepontine cistern and the convexity of the brain and (iii) hydrocephalus. Results: Depression (45%), apathy (42%), denial (21%) and catastrophic reaction (17%) were frequent in acute SAH patients. Mania was present in two patients. Denial was associated with higher haematic densities in the left and right basal sylvian fissure and in the 4th ventricle (P < 0.01) and with hydrocephalus (P = 0.05). Catastrophic reaction and depression were associated with previous mood disorder (P < 0.007). Apathy was associated with blood in the left or right lateral ventricles (P < 0.03). Conclusions: In the first 4 days of SAH, depression, apathy, catastrophic reaction and denial were rather frequent. SAH haematic densities were associated with denial and apathy, but not with depression, mania or catastrophic reaction.     

Neuropsychiatric background of severe drawing disturbances

Drawing ability is a primary human skill, which first appeared in the paleolithic art. In spite of this fact, neuropsychology of drawing has been a neglected subject of brain research. In the Crisis Intervention Department at the Budapest Social Center (Hungary), five patients with local brain lesions were identified, who had severe drawing disturbances. This was defined when the form representation in the House-Tree-Person drawing test was was not maintained and was associated with altered figure-perception. Patients were underwent detailed neurological, mental and neuropsychological assessment. Computer tomography of the head was performed at different hospitals in Budapest. House-Tree-Person drawing test was used, which was complemented with copy and visual memory tasks (with Rey-picture), as well as with spontaneous drawing, if it was necessary. Severe drawing disturbances were found in patients with severe right frontal, right temporo-parietal, diffuse right fronto-parieto-temporal, left occipito-temporal lesions and with bilateral basal ganglia lesions with enlarged ventriculi. Impairment of copying figures was sometimes seen without associated impairment of drawing on verbal instructions. Visual memory, visual images in long-term memory, visual analysis, the ability of adequat placement of parts into the whole representation, visuomotor transfer and perhaps the motor drawing programs could be altered separately. Severe drawing disturbance might occur with perfectly maintained writing capabilities. The data indicated that drawing ability requires the intact activity of nearly the whole brain, but it also includes several subfunctions, which could be altered relatively separately.     

Neuropsychiatric disturbances in Parkinson's disease clusters in five groups with different prevalence of dementia

OBJECTIVE: To investigate the inter-relationship of neuropsychiatric disturbances in Parkinson's disease (PD) by cluster analysis and describe the properties of the clusters. METHOD: A total of 139 patients were assessed using the neuropsychiatric inventory (NPI). A cluster-analysis was used to investigate the inter-relationship of NPI items. The clusters were profiled regarding dementia (PDD) and major depression. RESULTS: A total of 39 patients showed no neuropsychiatric symptoms. The remaining 100 patients (43% PDD) were divided in to five clusters. The largest group (42, 31% PDD) showed symptoms of mild depression, followed by a group (29, 79.3% PDD) with hallucinations and mild other symptoms. The third group (14, 7.1% PDD) had sleep disturbances exclusively. The fourth group (8, 25% PDD) showed apathy, anxiety and depression. The smallest group (7, 57.1% PDD) had high scores on several NPI items. CONCLUSION: Our PD sample can be divided in to clusters based on the NPI, with different prevalence of dementia and depression.     

Neuropsychiatric symptoms in Parkinson's disease

Neuropsychiatric symptoms are common in Parkinson's disease, even at the earliest stages, and have important consequences for quality of life and daily functioning, are associated with increased carer burden and increased risk for nursing home admission. In addition to cognitive impairment, a wide range of neuropsychiatric symptoms have been reported. In this article, the epidemiology, clinical course, diagnosis, and management of some of the most common neuropsychiatric symptoms in PD are discussed: depression, anxiety, apathy, fatigue, and psychotic symptoms. Although much is known regarding the prevalence and course of these symptoms, the empirical evidence for how to manage these symptoms is limited at best. There is thus an urgent need for systematic studies for the pharmacological and non‐pharmacological management of these symptoms. © 2009 Movement Disorder Society     

Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors

To determine whether neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) are influenced by antibodies against the human N-methyl-D-aspartate (NMDA) receptor types NR2a or NR2b. A decapeptide was synthesized containing a sequence motif present in the extracellular ligand-binding domain of NMDA receptors NR2a and NR2b, bound by the monoclonal murine anti-DNA antibody R4A. In an ELISA with the murine monoclonal R4v as positive control, plasma samples of 57 patients with SLE were examined for the anti-peptide (anti-NR2) antibody after the patients had been subjected to comprehensive psychological and cognitive testing. Poor performance on the Visual Paired Associates test (immediate), the Grooved Pegboard test, as well as high scores on the Beck Depression Inventory, and scales D-2 (depression), Pd-4 (psychopathic deviate), Sc-8 (schizophrenia), and Ma-9 (hypomania) of the MMPI-2 were significantly associated with elevated levels of anti-NR2 antibodies. The findings in several domains indicate an association between anti-NR2 antibodies and depressed mood in addition to decreased short-time memory and learning. Antibodies to NMDA receptors thus may represent one of several mechanisms for cerebral dysfunction in patients with SLE.     

Neuropsychiatric co-morbidities in non-demented Parkinson's disease

Objective:

To evaluate neuropsychiatric co-morbidities (depression, psychosis and anxiety) in non-demented patients with Parkinson''s disease (PD).

Background:

Non-motor symptoms like neuropsychiatric co-morbidities are common in Parkinson''s disease and may predate motor symptoms. Currently there is scarcity of data regarding neuropsychiatry manifestations in Indian patients with PD.

Methods:

In this cross-sectional study consecutive 126 non-demented patients with PD (MMSE ≥25) were enrolled. They were assessed using Unified Parkinson''s disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Schwab and England (S&E) scale of activity of daily life. Mini-international neuropsychiatric interview (MINI) was used for diagnosis of depression, psychosis and anxiety. Beck''s depression inventory (BDI), Brief psychiatric rating scale (BSRS) and Hamilton rating scale for anxiety (HAM-A) scales were used for assessment of severity of depression, psychosis and anxiety respectively.

Results:

Mean age and duration of disease was 57.9 ± 10.9 years and 7.3 ± 3.6 years respectively. At least one of the neuropsychiatric co-morbidity was present in 64% patients. Depression, suicidal risk, psychosis and anxiety were present in 43.7%, 31%, 23.8% and 35.7% respectively. Visual hallucinations (20.6%) were most frequent, followed by tactile (13.5%), auditory (7.2%) and olfactory hallucinations (1.6%). Patients with depression had higher motor disability (UPDRS-motor score 33.1 ± 14.0 vs 27.3 ± 13.3; and UPDRS-total 50.7 ± 21.8 vs 41.0 ± 20.3, all p values <0.05). Patients with psychosis were older (63.6 ± 8.0 years vs 56.1 ± 11.1 years, p < 0.05) and had longer duration of illness (8.6 ± 3.4 years vs 6.9 ± 3.5, p < 0.05).

Conclusions:

About two third patients with Parkinson''s disease have associated neuropsychiatric co-morbidities. Depression was more frequent in patients with higher disability and psychosis with longer duration of disease and older age. These co-morbidities need to be addressed during management of patients with PD.     

Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease

BACKGROUND: A polymorphism locating at position 73 of cystatin C (CST3) exon 1 was suggested to be associated with Alzheimer disease (AD), but with contradictory results. The relationship between the CST3 genotype and the cystatin C plasma level in AD remains unknown. OBJECTIVE: We aim to determine the association between CST3 polymorphism and the plasma levels of cystatin C in AD and nondemented control individuals. METHOD: The polymorphisms of the CST3 genotype were determined using PCR followed by restriction fragment length polymorphism analysis, and the plasma cystatin C concentrations were quantified by sandwich ELISA in 175 AD and 461 control subjects. RESULTS: Although the CST3A allele frequencies were similar between the two groups, the CST3A/A homozygote was significantly associated with late-onset AD. As expected, the established AD genetic risk factor APOE epsilon4 allele was overrepresented in the AD cohort. The plasma cystatin C levels were lower in the AD patients than in the control group. Furthermore, plasma cystatin C levels were associated positively with age and negatively with CST3A allele in the control group. CONCLUSION: The homozygous CST3A/A genotype confers a risk for AD in Taiwan Chinese. Such an association may be due to the reduced level of cystatin C in the peripheral circulation.     

Neuropsychiatric aspects of Huntington's disease

OBJECTIVE: Neuropsychiatric symptoms are common in Huntington's disease and have been considered its presenting manifestation. Research characterising these symptoms in Huntington's disease is variable, however, encumbered by limitations within and across studies. Gaining a better understanding of neuropsychiatric symptoms is essential, as these symptoms have implications for disease management, prognosis, and quality of life for patients and caregivers. METHOD: Fifty two patients with Huntington's disease were administered standardised measures of cognition, psychiatric symptoms, and motor abnormalities. Patient caregivers were administered the neuropsychiatric inventory. RESULTS: Ninety eight per cent of the patients exhibited neuropsychiatric symptoms, the most prevalent being dysphoria, agitation, irritability, apathy, and anxiety. Symptoms ranged from mild to severe and were unrelated to dementia and chorea. CONCLUSIONS: Neuropsychiatric symptoms are prevalent in Huntington's disease and are relatively independent of cognitive and motor aspects of the disease. Hypothesised links between neuropsychiatric symptoms of Huntington's disease and frontal-striatal circuitry were explored. Findings indicate that dimensional measures of neuropsychiatric symptoms are essential to capture the full range of pathology in Huntington's disease and are vital to include in a comprehensive assessment of the disease.     

Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease

OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.     

Neuropsychiatric symptoms in Alzheimer’s disease

Neuropsychiatric symptoms (NPS) are core features of Alzheimer’s disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these symptoms are currently known to manifest commonly in very early disease and in prodromal phases, such as mild cognitive impairment. Despite decades of research, reliable treatments for dementia-associated NPS have not been found, and those that are in widespread use present notable risks for people using these medications. An Alzheimer’s Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer’s disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics.     

Dystrophic microglia in late-onset Alzheimer's disease

Here, we summarize current understanding of functional involvement of microglial cells in the most common neurodegenerative disease to affect humans, which is sporadic or late-onset Alzheimer's disease (LOAD). Our review narrowly focuses on insights obtained from post-mortem neuropathological examinations of human brains paying particular attention to microglia as these cells have long been implicated as pivotal players in the cellular processes that lead to AD-type neurodegeneration. Although complete understanding of the roles played by microglia in AD neurodegeneration remains elusive, our studies thus far have illuminated microglial involvement in LOAD, showing that microglial dystrophy, the morphological manifestation of senescence, can be integrated with other hallmark pathological features of AD, such as intraneuronal neurofibrillary degeneration (NFD) and extracellular deposits of amyloid-beta (Aβ) protein. We have demonstrated an in situ correlation between microglial dystrophy and presence of NFD suggesting that neurodegeneration is secondary to aging-related microglial deterioration, a concept founded on the notion that proper neuronal function is dependent on presence of healthy microglia. Diseased or weakened glia are detrimental for neuronal well-being because their ability to provide neuronal support may be impaired. Our most recent work also links microglial dystrophy with Aβ deposits by showing that there is a chronic, yet futile microglial reaction to insoluble amyloid deposits. This inability of microglia to remove aggregated amyloid (a foreign body) causes microglial exhaustion and thereby exacerbates already ongoing aging-dependent microglial deterioration. An eventual total loss of functional microglia in advanced LOAD promotes widespread NFD, dementia, and brain failure.     

Neuropsychiatric aspects of treated Wilson's disease

The objective of the current cross-sectional study was to use standardized psychiatric interviews (the Structured Clinical Interview for DSM-IV Axis I Disorders and the Neuropsychiatric Inventory; NPI) in order to better characterize psychiatric symptoms in 50 consecutive, treated and clinically stable patients with Wilson's disease (WD). Nine patients (18%) had one, 7 patients (14%) had two, and 20 (40%) had ≥ 3 neuropsychiatric symptoms present. The most often endosed symptoms were anxiety (62%), depression (36%), irritability (26%), as well as disinhibition and apathy (24% each). Twenty two patients (44%) had a score ≥ 4 on at least one of the NPI items: again, most frequently anxiety (17 patients; 34%), depression (13 patients; 26%) and apathy (9 patients; 18%). Therefore, even among stable, long-term treated patients with WD approximately 70% experienced psychiatric symptoms.     

晚发型帕金森病经颅超声的表现

目的 研究晚发型帕金森病(LOPD)患者经颅超声(transcranial sonography,TCS)的表现.方法 招募符合入选标准的LOPD患者和年龄匹配的正常对照者,分别进行TCS检测.对于检测成功的受试者的黑质异常信号进行半定量分级测评,同时测定第三脑室的宽度.结果 TCS检查在老年女性中成功率很低.两组间黑质强回声分级有极强的显著性差异.黑质强回声分级与患者的年龄、发病年龄、病程及病情严重程度不相关.两组间第三脑室宽度无显著性差异.结论 TCS检查在老年女性中应用受限制.明显的黑质异常强回声可能是LOPD患者的特征性表现.其强回声分级与患者年龄、发病年龄、病程及病情严重程度不相关.晚发型帕金森病患者组无明显第三脑室增宽.

Abstract：

Objective To investigate the characteristic features of transcranial sonography (TCS) in patients with late-onset Parkinson' s disease (LOPD). Methods We enlisted some LOPD patients and age-matched normal controls according to special criteria, and detected them by TCS. The obtained images of the subjects whose images could offer analyzing substantia nigra (SN) hyperechogenicity with sufficient resolution were evaluated. We used semi-qualitative estimation criteria to assess SN hyperechogenicity and also measured the widths of the third ventricles. Results There was a high rate of recording failure of the SN in older females. Significant SN hypereehogenicity was observed in LOPD patients group.There was no correlation between the degree of SN hyperechogenicity and patients' age, onset age, duration of illness, and the severity of condition. There was no significant difference of the widths of the third ventricles between groups. Condusions The recording failure in aged females may limit the clinical potential of TCS. SN hyperechogenicity maybe the characteristic features in LOPD patients. There was no correlation between the degree of SN hyperechogenicity and patients'age,onset age, duration of illness, and the severity of condition. The widths of the third ventricles in LOPD patients group were not increased significantly.