Development Of Neuropsychiatric Symptoms Research Articles

Evaluation of Neurological Manifestations of Systemic Lupus Erythematosus

Abstract Background: Neuropsychiatric symptoms are typical consequences in patients with systemic lupus erythematosus (SLE). There is no apparent link between the clinical parameters of SLE patients and the development of neuropsychiatric symptoms. Objectives: to determine the incidence of neurological manifestations and the risks associated with them in SLE patients. Patients and Methods: This is a case-series study comprised 65 patients who visited the rheumatology Department at Baghdad Teaching Hospital/Medical City between January 2022 and February 2023. All patients' demographic and clinical data, including age, gender, disease duration, type and duration of treatment, general signs of the disease, and neurological and psychiatric manifestations of SLE, were collected. Laboratory data comprised plasma anti-phospholipid antibodies (aPL), anti-double stranded DNA (anti-dsDNA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The cognitive dysfunction was assessed using the six-item cognitive impairment test (6CIT). Results: Out of 65 patients, 34 (52.3%) were found to have at least one neuropsychiatric SLE (NPSLE) manifestation. Headache and depression were the most common NPSLE manifestation encountered in 36 patients (55.4%) followed by psychosis (21.5%), neuropathy (16.9%) and stroke and seizure (13.5%). In multivariate analysis, each of age >35 years (OR= 2.92, 95%CI= 1.12-34.2, p= 0.10), disease duration >5 years (4.45, 95%CI=1.23-28.43, p= 0.001), anti-phospholipid Abs (OR= 4.22, 95%CI= 1.17-89.38, p= 0.036), lupus nephritis (OR= 6.34, 95%CI= 1.27- 64.98, p= 0.029) and 6CIT>3 (OR= 5.83, 95%CI= 1.55- 21.87, p= 0.009) are independent predictors for NPSLE in patients with SLE. Conclusions: Neuropsychiatric manifestations developed in more than half of the SLE cases studied within up to six-year of disease duration. Headache and depression, psychosis and neuropathy are the most common NPSLE manifestations. Older age and longer disease duration are risk factors for development of NPSLE. Clinically, anti-phospholipid antibodies, lupus nephritis and a high score of the six-item cognitive impairment test (>8) are predictors for NPSLE. Received: May, 2023 Accepted: Sept., 2023 Published: Jan., 2024

Clinical Manifestations.

Previous studies have shown that microglial activation (MA) plays a key role in the physiopathology and progression of Alzheimer's disease (AD). Unpublished data suggest that MA is highly associated with the development of neuropsychiatric symptoms (NPS) in patients with AD. Thus, we aim to investigate here the contribution of each NPS domain to this association across individuals in the AD continuum. We assessed 132 individuals (86 cognitively unimpaired (CU), 28 MCI, and 18 AD dementia) from the TRIAD cohort who underwent clinical assessments with the Neuropsychiatry Inventory Questionnaire (NPI-Q), and had positron emission tomography (PET) for amyloid-β (Aβ) ([18F]AZD4694), tau tangles ([18F]MK6240) and MA ([11C]PBR28) at the same visit. Regions were tailored using Desikan-Killiany (DK) atlas. SUVRs were calculated using the cerebellum gray matter as a reference. Linear regression tested the association between biomarkers accounting for age, sex, and cognitive status. NPI-Q total score was significantly associated with [11C]PBR28 in the cingulate, inferior temporal, and precuneus accounting for age, sex, and after false discovery rate (FDR) correction for multiple comparisons (Figure 1A). This association was independent of Aβ and tau levels (Table 1). When we stratify NPI-Q domains (agitation, irritability, motor disturbance, disinhibition, elation, delusion, hallucinations, nighttime disturbance, depression, anxiety, apathy, and appetite disturbance) severity score, we found that the hyperactivity subdomain (agitation, irritability, motor disturbance, disinhibition, and elation) showed the larger contribution to the results (Figure 1B). Bootstrapping each NPI-Q domain from the NPI-Q total score, linear regression analysis reveals that irritability, nighttime disturbance, and agitation are the main contributors to the association between NPS and MA (Figure 1C). Removing these domains, but no other combination of two or three NPI-Q domains, from the NPI-Q total score, abolishes this association (Figure 1D). Our results suggest that MA is associated with neuropsychiatric dysfunction in AD. Notably, we found that irritability, nighttime disturbance, and agitation drive the association between NPS and MA.

Neuroinflammation Exacerbates Irritability and Agitation in Alzheimer’s Disease

AbstractBackgroundPrevious studies have shown that microglial activation (MA) plays a key role in the physiopathology and progression of Alzheimer’s disease (AD). Unpublished data suggest that MA is highly associated with the development of neuropsychiatric symptoms (NPS) in patients with AD. Thus, we aim to investigate here the contribution of each NPS domain to this association across individuals in the AD continuum.MethodWe assessed 132 individuals (86 cognitively unimpaired (CU), 28 MCI, and 18 AD dementia) from the TRIAD cohort who underwent clinical assessments with the Neuropsychiatry Inventory Questionnaire (NPI‐Q), and had positron emission tomography (PET) for amyloid‐ß (Aß) ([18F]AZD4694), tau tangles ([18F]MK6240) and MA ([11C]PBR28) at the same visit. Regions were tailored using Desikan‐Killiany (DK) atlas. SUVRs were calculated using the cerebellum gray matter as a reference. Linear regression tested the association between biomarkers accounting for age, sex, and cognitive status.ResultNPI‐Q total score was significantly associated with [11C]PBR28 in the cingulate, inferior temporal, and precuneus accounting for age, sex, and after false discovery rate (FDR) correction for multiple comparisons (Figure 1A). This association was independent of Aß and tau levels (Table 1). When we stratify NPI‐Q domains (agitation, irritability, motor disturbance, disinhibition, elation, delusion, hallucinations, nighttime disturbance, depression, anxiety, apathy, and appetite disturbance) severity score, we found that the hyperactivity subdomain (agitation, irritability, motor disturbance, disinhibition, and elation) showed the larger contribution to the results (Figure 1B). Bootstrapping each NPI‐Q domain from the NPI‐Q total score, linear regression analysis reveals that irritability, nighttime disturbance, and agitation are the main contributors to the association between NPS and MA (Figure 1C). Removing these domains, but no other combination of two or three NPI‐Q domains, from the NPI‐Q total score, abolishes this association (Figure 1D).ConclusionOur results suggest that MA is associated with neuropsychiatric dysfunction in AD. Notably, we found that irritability, nighttime disturbance, and agitation drive the association between NPS and MA.

Evaluation of Neuropsychiatric Effects of Montelukast-Levocetirizine Combination Therapy in Children with Asthma and Allergic Rhinitis.

Drug-induced neuropsychiatric effects are important for disease management. We aim to evaluate the neuropsychiatric effects of montelukast-levocetirizine combination therapy in children. This descriptive study was conducted with children aged 2-5 years, diagnosed with asthma and allergic rhinitis, who began to receive montelukast and levocetirizine combination therapy. The respiratory and asthma control test for children (TRACK), Rhino Conjunctivitis Scoring System (RCSS), and common neuropsychiatric effects (irritable behavior, hallucinations, headaches, nightmares, sleep disorders, behavioral and mood disorder, restlessness, depression) were ascertained by the questionnaire applied before and 4 weeks after the treatment. Parents answered on behalf of their children. The most common finding before and after treatment was irritable behavior. While irritable behavior was observed in 82.4% (n = 56) of children before the treatment, this percentage was 63.2% (n = 43) after the treatment (p = 0.004). The percentage of children who developed at least one neuropsychiatric symptom after treatment was 22.1% (n = 15). There was no significant effect of age, gender, RCSS, TRACK, or allergy test positivity on the development of neuropsychiatric symptoms (p > 0.05). According to the results, at least one neuropsychiatric finding developed in approximately one in five children. Identifying risk factors will enable more careful treatment or consideration of alternative treatments for children at higher risk in the clinical follow-up period.

Can Pyridoxine Successfully Reduce Behavioral Side Effects from Levetiracetam? A Critically Appraised Topic.

Levetiracetam is a commonly used anti-seizure medication, with the development of neuropsychiatric symptoms being the most common side effect. Preliminary literature describes the improvement of these symptoms with pyridoxine, mostly within the pediatric population. However, randomized control trial data investigating this relationship is sparse. The objective of this study was to critically assess evidence regarding the role of pyridoxine in the treatment of neuropsychiatric symptoms from levetiracetam. The objective was addressed through the development of a structured, critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, medical librarians, clinical epidemiologists, and content experts in the field of epilepsy. A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared pyridoxine versus placebo for the treatment of neuropsychiatric symptoms from levetiracetam in a pediatric population and included 105 patients (46/105 received pyridoxine, 59/105 received placebo). It found that both groups had a significant reduction in behavioral symptoms at the 2-,4-and 6-week time points (P<0.05). However, the authors noted that the pyridoxine group had almost double the relative reduction when compared with the placebo group at all time points: 1.9 at 2 weeks, 2.0 at 4 weeks, and 1.8 at 6 weeks (P=0.001). This study suggests that pyridoxine for the treatment of levetiracetam-induced behavioral side effects may result in modest improvement, although many limitations prevent conclusive results. There remains a need for a double-blinded, randomized control trial in both the adult and pediatric populations.

Association of Traumatic Brain Injury Severity and Self-Reported Neuropsychiatric Symptoms in Wounded Military Service Members.

The impact of traumatic brain injury (TBI) severity and loss of consciousness (LOC) on the development of neuropsychiatric symptoms was studied in injured service members (SMs; n = 1278) evacuated from combat settings between 2003 and 2012. TBI diagnoses of mild TBI (mTBI) or moderate-to-severe TBI (MS-TBI) along with LOC status were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes and the Defense and Veterans Brain Injury Center Standard Surveillance Case Definition for TBI. Self-reported psychiatric symptoms were evaluated for post-traumatic stress disorder (PTSD) with the PTSD Checklist, Civilian Version for PTSD, the Patient Health Questionnaire-9 for major depressive disorder (MDD), and the Patient Health Questionnaire-15 for somatic symptom disorder (SSD) in two time periods post-injury: Assessment Period 1 (AP1, 0.0-2.5 months) and Assessment Period 2 (AP2, 3-12 months). mTBI, but not MS-TBI, was associated with increased neuropsychiatric symptoms: PTSD in AP1 and AP2; MDD in AP1; and SSD in AP2. A subgroup analysis of mTBI with and without LOC revealed that mTBI with LOC, but not mTBI without LOC, was associated with increased symptoms as compared to non-TBI: PTSD in AP1 and AP2; MDD in AP1; and SSD in AP1 and AP2. Moreover, mTBI with LOC was associated with increased MDD symptoms in AP2, and SSD symptoms in AP1 and AP2, compared to mTBI without LOC. These findings reinforce the need for the accurate characterization of TBI severity and a multi-disciplinary approach to address the devastating impacts of TBI in injured SMs.

Anosognosia in Early- and Late-Onset Dementia and Its Association With Neuropsychiatric Symptoms.

Background: The symptom anosognosia or unawareness of disease in dementia has mainly been studied in patients with late-onset dementia (LOD, ≥65 years), whereas little is known on whether it is also present in patients with early-onset dementia (EOD, <65 years). We aimed at investigating differences in anosognosia between LOD and EOD, by also studying its association with different clinical variants of EOD and the presence of neuropsychiatric symptoms.Methods: A total of 148 patients, 91 EOD and 57 LOD, were recruited and underwent extended clinical assessment and caregiver interview that included questionnaires aimed at measuring anosognosia and neuropsychiatric symptoms. Differences in anosognosia between EOD and LOD and between subgroups with different clinical variants were investigated, as well as correlation between anosognosia and neuropsychiatric symptoms. A regression analysis was applied to explore the association between anosognosia and development of neuropsychiatric symptoms during disease progression.Results: Median levels of anosognosia were not significantly different between EOD and LOD. Anosognosia increased overtime with disease progression and was higher in frontotemporal dementia patients or, more precisely, in frontotemporal dementia and Alzheimer's disease variants associated with involvement of the frontal lobes. Higher levels of early anosognosia were associated with higher frequency and severity of subsequent neuropsychiatric symptoms, in particular apathy, later in the course of the disease.Conclusion: Anosognosia is a frequent symptom of EOD, occurring in 94.5% of all-cause EOD, and it is associated with higher risk of developing neuropsychiatric symptoms during disease progression. Recognising anosognosia may be helpful for clinicians and families to reduce diagnostic delay and improve disease managment.

Immunological and behavioral responses to in vivo lipopolysaccharide administration in young and healthy obese and normal-weight humans

Obesity is associated with an increase prevalence of neuropsychiatric symptoms and diseases, such as depression. Based on the facts that pro-inflammatory cytokines are able to modulate behavior, and that obesity is characterized by a chronic low-grade inflammatory state, inflammation has been hypothesized to contribute to the neuropsychiatric comorbidity in obese individuals. However, a causal link between inflammation and the development of neuropsychiatric symptoms is hard to establish in humans. Here, we used an inflammatory stimulus, i.e. the intravenous injection of lipopolysaccharide (LPS), in a double-blind placebo-controlled design, to determine the vulnerability of obese individuals to inflammation-induced behavioral changes. The hypothesis was that obese individuals would show heightened behavioral response compared to normal-weight subjects for the same inflammatory stimulus, reflecting an increased sensitivity to the behavioral effects of pro-inflammatory cytokines. LPS (dose 0.8 ng/kg body weight, adjusted for estimated blood volume in obese subjects) and placebo (saline) were intravenously injected in 14 obese healthy subjects and 23 normal-weight healthy subjects in a within-subject, randomized, crossover design. LPS administration induced, in both groups, an acute increase in blood concentrations of cytokines (interleukin-6, tumor necrosis factor-α, and IL-10), as well as in body temperature, cortisol, norepinephrine, sickness symptoms, fatigue, negative mood, and state anxiety. There were little differences in the immune and behavioral responses to LPS between obese and normal-weight subjects, but the cortisol response to LPS was strongly attenuated in obese individuals. Higher percentage of body fat was related to a lower cortisol response to LPS. Taken together, the population of young and healthy obese individuals in this study did not exhibit an increased behavioral sensitivity to cytokines, but an attenuated cortisol response to the immune challenge. Future studies will need to determine whether additional physiological and psychological factors interact with the state of obesity to increase the risk for inflammation-induced neuropsychiatric symptoms.

The Effect of Type 2 Diabetes Mellitus on Neuropsychological Symptoms in Chinese Early Alzheimer's Disease Population.

ObjectiveTo explore the effect of Type 2 diabetes mellitus (T2DM) on the development of neuropsychiatric symptoms (NPS) in early Alzheimer’s disease (AD).MethodsFrom September 2017 to March 2019, a cross-sectional study was conducted on the clinical data of 158 early AD patients over 65 years old in the Department of Neurology of Daping Hospital. All early stage of AD patients were divided into early stage of AD with NPS group and early stage of AD without NPS group according to the presence or absence of NPS. Clinical data of age, sex, body mass index (BMI), smoking and alcohol consumption, history of hypertension, hyperlipidemia, white matter leisure (WML) and T2DM, MMSE, CDR and NPI-Q scores were collected. Multivariate logistic regression analyses were performed to examine the relationship between T2DM and NPS in early AD.ResultsCompared with the early stage of AD group without NPS, the early stage of AD group with NPS was older, the proportion of women was higher, the proportion of T2DM, hypertension, hyperlipidemia and WML was higher, and the MMSE score was lower (P< 0.05). T2DM was an independent risk factor for NPS in early stage of AD patients (OR 3.48, 95% CI 2.91–3.84). The incidence of T2DM in AD patients with depression, anxiety, nighttime behavioral disturbances, and appetite disturbances was significantly higher than in AD patients without these symptoms. T2DM was an independent risk factor of depression (OR 2.04, 95% CI 1.71–2.38), anxiety (OR 1.69, 95% CI 1.38–1.97), nighttime behavioral disturbances (OR 1.95, 95% CI 1.75–2.13) and appetite disturbances (OR 1.62, 95% CI 1.33–1.94) in early AD patients.ConclusionT2DM was an important independent risk factor for NPS in early AD, which promotes the occurrence of depression, anxiety, nighttime behavioral disturbances and appetite disturbances in early AD.

Limited preventive effect of prednisone on neuropsychiatric symptoms in murine systemic lupus erythematosus.

To investigate whether glucocorticoids, the hallmark medication for systemic lupus erythematosus (SLE), could prevent the development of neuropsychiatric SLE (NPSLE). The protective effects of prednisone on NPSLE were tested using the open field, object recognition/placement, forced swim, tail suspension, and sucrose preference tests in MRL/lpr mice. Auto-antibody titres and the weight of lymph nodes were also measured. MRL/lpr mice exhibited mild depression at the age of 8weeks before progressing with spatial cognitive impairment and severe depression-like behaviour at the age of 16weeks. Treating MRL/lpr mice with prednisone (5mg/kg) from the age of 8weeks decreased anti-cardiolipin and anti-N-methyl-D-aspartate (NMDA) receptor antibody titres in the brain, reduced the weight of lymph nodes, and prolonged the floating latency in the forced swim test. However, prednisone (3 or 5mg/kg) had no preventive effect on the development of spatial cognitive impairment and other depression-like behaviours in MRL/lpr mice. The dose of prednisone had a positive correlation with the floating latency in the forced swim test, while it offered no effects on all other behavioural tests. Our results provide evidence that early treatment with prednisone had a limited effect on the development of neuropsychiatric symptoms in MRL/lpr mice. Further work is needed in other models beyond NPSLE in MRL/lpr mice before any definitive conclusions are made on the efficacy of prednisone in human NPSLE.

Steroid-induced psychiatric syndromes: A case report and a review of the literature

IntroductionGlucocorticoids are widely prescribed for a variety of diseases and are known to cause neuropsychiatric as well as somatic side effects.ObjectiveTo review the incidence, clinical characteristics, course and treatment of neuropsychiatric effects of glucocorticoids.AimWe have described the case of a 86-year-old woman. She had no personal and no psychiatric medical history in her family. She presented wrist arthritis requiring high doses of an oral corticoid treatment (prednisona 20 mg/d). After a week, she started with symptoms characterised by persecutory and surveillance delusions. Organicity was ruled out. The patient got a progressive recovery after starting anti-psychotic medication and progressive reduction of the steroid drugs.MethodsWe have performed a literature review of the neuropsychiatric complications of glucocorticoids using the PubMed database.ResultsNeuropsychiatric effects of glucocorticoids involve affective, behavioural, and cognitive manifestations. The incidence is variable, between 2 and 60% of patients who receive steroids. Although the effects of glucocorticoids are unpredictable, the administered dose is the most significant risk factor for the development of neuropsychiatric symptoms. Dosage reduction typically results in clinical recovery. Although the limited data on this subject, it is a problem that clinicians face on their regular basis. The administration of anti-psychotics or mood stabilizers may be beneficial in the prevention and treatment of this syndrome.ConclusionThe neuropsychiatric effects of glucocorticoids are unpredictable and non-specific. More controlled trials are needed in order to perform evidence-based clinical guidelines for the treatment with glucocorticoids and for the prevention of neuropsychiatric manifestations.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Subjective sleep problems in Huntington's disease: A pilot investigation of the relationship to brain structure, neurocognitive, and neuropsychiatric function

Subjective reports of sleep disturbance are a common feature of Huntington's disease (HD); however, there is limited research investigating the relationship between sleep problems with changes in brain and behaviour. This study aimed to investigate whether subjective reports of sleep problems in HD are associated with brain volume, neurocognitive decline, and neuropsychiatric symptoms. This retrospective pilot study used brain volume, neurocognitive and neuropsychiatric data from premanifest (pre-HD) and symptomatic HD (symp-HD). Subjective sleep problem was measured using the sleep item of the Beck's Depression Inventory-II (BDI-II). Pre-HD individuals reporting sleep problems had significantly poorer neuropsychiatric outcomes compared to those not reporting sleep problems. In the symp-HD group, those with sleep problems had significantly accelerated thalamic degeneration and poorer neuropsychiatric outcomes compared to those without sleep problems. There was no relationship between subjective sleep problems and neurocognitive measures. These findings suggest an association between subjective sleep disturbance, neuropathology, and development of neuropsychiatric symptoms in HD. Further studies using quantitative EEG-based monitoring of sleep in HD and changes in the brain and behaviour will be necessary to establish the causal nature of this relationship.

Apolipoprotein E-ε4 deficiency and cognitive function in hepatitis C virus-infected patients.

Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.

Liver Transplantation for Liver Malignancies in Wilson’s Disease

Liver Transplantation for Liver Malignancies in Wilson’s Disease

Anti-nuclear antibodies positive serum from systemic lupus erythematosus patients promotes cardiovascular manifestations and the presence of human antibody in the brain.

Background:Systemic lupus erythematosus (SLE) is characterized by the presence of anti-nuclear antibodies (ANAs) in the serum of patients. These antibodies may cross over into the brain resulting in the development of neuropsychiatric symptoms and result in abnormal pathology in other organs such as the heart and kidneys.Objective:The objective of this study was to determine if SLE pathology could be detected in the hearts and brains of rats injected with positive human ANA serum.Materials and Methods:Lewis rats (n = 31) were selected for this study due to documented research already performed with this strain in the investigation of serum sickness, encephalitis and autoimmune related carditis. Rats were injected once a week with either ANA positive or negative control serum or saline. Hearts were examined for initial signs of heart disease including the presence of lipid deposits, vegetation, increased ventricular thickness and a change in heart weight. Brains were examined for the presence of human antibody and necrotic lesions. Animals were observed for outward signs of neuropathy as well. Blood samples were taken in order to determine final circulating concentrations of IgG and monitor histamine levels.Results:Animals injected with ANA were significantly higher for lipid deposits in the heart and an increased ventricular thickness was noted. One animal even displayed Libman-Sacks endocarditis. Brains were positive for the presence of human IgG and diffuse internal lesions occurred in 80% of the ANA positive serum injected animals examined. Blood histamine levels were not significantly different, but actually lower than controls by the end of the experiment.Conclusion:Since human antibodies were detected in the brain, further studies will have to identify which antibody cross reactions are occurring within the brain, examine cell infiltration as well as characterize the antibodies associated with more destructive consequences such as lesion formation.

F07 Cross-sectional and longitudinal associations between CRP and neuropsychiatric symptoms in HD

Background There is a growing body of evidence that inflammatory processes play a role in the development of neuropsychiatric symptoms in Huntington9s disease (HD). Aims To investigate the relationship between C-reactive protein (CRP) concentration in blood on the one hand and neuropsychiatric symptoms on the other hand in HD mutation carriers compared to non-mutation carriers, both cross-sectionally and longitudinally. Methods In 2003, a longitudinal cohort study was initiated in Leiden, The Netherlands, comprising 154 mutation carriers and 56 non-carriers. In 2005–2007 and 2009–2011 a first and second wave of follow-up was conducted. Blood samples for the assessment of CRP were obtained during the first and second wave of follow-up, in addition to a battery of psychometric measures, cognitive functioning tests, and a neurological examination. Multivariate regression analyses to associate neuropsychiatric symptoms with CRP and analyses of (co)variance for comparisons between different stages of HD and controls will be used. Results We will present the results regarding associations between CRP on the one hand and HD disease stage and several neuropsychiatric symptoms on the other hand, both cross-sectionally and longitudinally.

Rapid resolution of akinetic mutism in delayed post-hypoxic leukoencephalopathy with intravenous magnesium sulfate

Delayed post-hypoxic leukoencephalopathy is a rare condition marked by the development of neuropsychiatric symptoms, parkinsonism and akinetic mutism days to weeks after an individual has recovered from a prolonged cerebral hypoxic event. This syndrome can cause significant long-term neurologic dysfunction. At present there are no acute treatment strategies that have been identified that have been shown to alter the natural course of this disorder. In most instances all that can be offered to patients is early supportive care and then subsequent rehabilitation services. Case Report. A patient is presented who developed new onset encephalopathy, extrapyramidal symptoms and akinetic mutism three weeks after being discharged for a respiratory arrest from a drug overdose. MRI showed the development of extensive white matter and bilateral globus pallidus lesions. She had rapid resolution of akinetic mutism with intravenous magnesium sulfate as well as improvement in her other associated neurologic symptoms. The case report suggests the use of intravenous magnesium sulfate as an acute treatment for the akinetic mutism associated with delayed post-hypoxic leukoencephalopathy. In addition it also may improve the extrapyramidal and neuropsychiatric symptoms associated with this syndrome. This may be the first potential acute treatment for this rare neurologic condition.

The Development of Infective Endocarditis and Oral Dyskinesia in a Type 2 Diabetic Patient

The group A streptococcus infection has been reported to be associated with the development of neuropsychiatric symptoms in children such as Sydenham’s chorea and pediatric autoimmue neuropsychiatric disorders associated with streptococci, possibly due to autoimmunity. However, there are very few literatures discuss the association between neuropsychiatric manifestations and Streptococcus viridians infection, especially in the elderly people. Here, we show a 74-year-old type 2 diabetic woman who developed infective endocarditis infected by Streptococcus viridans and oral dyskinesia. doi:10.4021/jmc286w

Proinflammatory cytokines, sickness behavior, and Alzheimer disease

In Alzheimer disease (AD), systemic inflammation is known to give rise to a delirium. However, systemic inflammation also gives rise to other centrally mediated symptoms in the absence of a delirium, a concept known as sickness behavior. Systemic inflammation is characterized by the systemic production of the proinflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) that mediate immune to brain communication and the development of sickness behavior. To determine if raised serum TNFα or IL-6 are associated with the presence of sickness behavior symptoms, independent of the development of delirium, in a prospective cohort study of subjects with AD. A total of 300 subjects with mild to severe AD were cognitively assessed at baseline and a blood sample taken for inflammatory markers. Cognitive assessments, including assessments to detect the development of a delirium, and blood samples were repeated at 2, 4, and 6 months. The development of neuropsychiatric symptoms in the subject with AD over the 6-month follow-up period was assessed independently by carer interview at 2, 4, and 6 months. Raised serum TNFα and IL-6, but not CRP, were associated with an approximately 2-fold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior. These relationships are independent of the development of delirium. Increased serum proinflammatory cytokines are associated with the presence of symptoms characteristic of sickness behavior, which are common neuropsychiatric features found in AD. This association was independent of the presence of delirium.

Depression in chronic hepatitis: the virus, the drug, or the ethnic background?

Depression in chronic hepatitis: the virus, the drug, or the ethnic background?