Common Neurological Sequelae Research Articles

Evaluation and outcome of hearing in meningitis patients

Background: Meningitis remains the most common cause of acquired severe to profound SNHL in childhood. Likewise, deafness is the most common long-term neurological sequelae of the disease. Important consideration following meningitis is the development of labyrinthitis ossificans in which there is new bone formation within the lumen of the otic capsule. Ossification of the labyrinth can develop within a few days of meningitis which can make cochlear implantation difficult. Every newborn should be promptly screened for any hearing deficit along with the patients having meningitis. The most easily available investigation are OAE and BERA. Methods: Our ambispective study of 25 patients was undertaken in a duration of 2 years in ENT department of civil hospital, Ahmedabad. All the patients underwent a detailed clinical examination and all routine audiological, and radiological investigations. Results: The prevalence of hearing loss in post meningitis pediatric age group is 40%. Females are affected more than males. Median age group of presentation with hearing deficit is 4 years. Patients with complete immunization history have lower incidence of hearing loss associated with meningitis than incomplete immunization. Ossification of the cochlea can develop as early as 6 days from the development of first symptom. Conclusions: Ossification of the cochlea can develop as early as 6 days from the development of first symptom. These are the candidates who should be prioritized for cochlear implant surgery. Patients with mild hearing loss recovered completely whereas those with profound hearing loss underwent cochlear implant surgery and were benefited with it.

Correlation between clinical-laboratory profile and outcome of AES cases in children: A hospital-based study

Objective: This study aims to determine the correlation between clinical as well as laboratory profile changes with the outcome of acute encephalitis syndrome (AES) cases. Materials and Methods: This prospective observational study was conducted in the Department of Pediatrics at Jorhat Medical College and Hospital, Assam over a period of 1 year where 49 diagnosed cases of AES in children aged between 1 month and 12 years were enrolled. Results: The study found that fever (100%) and altered sensorium (100%) were the most common clinical presentations in AES cases, followed by seizure (63%), headache (34.7%), vomiting (26.5%), diarrhea (22.4%), etc. Japanese encephalitis (JE) was the most common cause of AES (28.6%), followed by herpes simplex virus (4.1%), pyogenic meningitis (4.1%), and tubercular meningitis (2%), etc. However, the majority of cases (61.2%) were found to have an unknown etiology. Among the 49 cases, 27 (55.1%) recovered without neurological sequelae, 8 (16.8%) had neurological sequelae, and 14 (28.6%) died during the course of treatment. The most common neurological sequelae observed were motor deficit (37.5%), behavioral disorders, aphasia (25% each), and cranial nerve palsy. Glasgow coma scale (GCS) at the time of admission and during the time of hospital stay was found to have a significant (p<0.05) correlation with outcome in AES patients. Conclusion: The study concludes that AES cases commonly present with fever, altered sensorium, seizure, headache, vomiting, and signs of meningeal irritation. JE remains a major known cause of AES in children in this region of India. GCS at the time of admission and during the time of hospital stay were found to have a significant correlation with outcome. The neurological sequelae highlight the need for global attention to combat them save the lives of children.

Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review.

Spasticity is a very common neurological sequelae that significantly impacts the quality of life of patients, affecting more than 12 million people worldwide. Botulinum toxin is considered a reversible treatment for spasticity, but due to the large amount of available evidence, synthesis seems necessary. Therefore, we conducted an overview of existing systematic reviews and meta-analyses to evaluate the effect of botulinum toxin injections in the treatment of spasticity of different etiologies. A systematic search of different databases, including Pubmed, Scopus, the Cochrane Library, and Web of Science, was performed from inception to February 2024. Standardized mean differences (SMDs) and their respective 95% confidence intervals (CIs) were calculated to assess the effect of botulinum toxin compared to that of the control treatment using the Modified Ashworth Scale (MAS). All the statistical analyses were performed using STATA 15 software. 28 studies were included in the umbrella review. The effect of botulinum toxin injections on spasticity, as measured by the MAS, was significantly lower in all but three studies, although these studies also supported the intervention. The SMDs reported by the meta-analyses ranged from -0.98 to -0.01. Botulinum toxin injections were effective at treating spasticity of different etiologies, as indicated by the measurements on the MAS. This implies an improvement in muscle tone and, consequently, in the patient's mobility and quality of life.

Powassan virus persistence after acute infection.

Survivors of Powassan encephalitis often have persistent neurological disease. A new mouse model replicates some elements of the human disease and demonstrates the presence of viral RNA in the brain as well as myelitis more than 2 mo after the acute infection. The related tick-borne encephalitis and West Nile Neuroinvasive Disease (WNND) also have common neurological sequelae, and models for these better-studied diseases provide evidence for prolonged virus, RNA, and inflammation in some cases, in addition to damage from the acute encephalitic disease. A better understanding of the biological basis for persistent signs and symptoms after Powassan encephalitis, currently a rare disease, could benefit from further studies of the more prevalent flaviviral encephalitides.

0301 Associations between sleep and cognitive function in patients with Neurological post-acute sequelae of SARS-CoV-2 infection

Abstract Introduction Fatigue and sleep disturbance are among the most common neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). We tested the hypothesis that impaired sleep and disrupted rest-activity rhythms are associated with impaired cognitive performance and greater burden of self-reported Neuro-PASC symptoms. Methods Forty adults (mean age 45 years, 69% female, 15% hospitalized post COVID) recruited from the Neuro-COVID-19 Clinic at Northwestern Memorial Hospital. Patients were evaluated via clinical assessment/history, chart review, patient reported outcomes for symptom severity (PROMIS cognitive function, fatigue, sleep disturbance, anxiety, depression), cognitive performance tests (NIH Toolbox modules for processing speed, attention, executive function, working memory), and 7 days of wrist actigraphy with a sleep log. We tested associations between objective and subjective measures using Pearson’s correlation and difference from population normative data using Student’s t test. Results 39 participants provided sufficient data for analysis. The median number of discrete neurologic symptoms attributed to PASC was 6 with 87% reporting ≥4 neurologic symptoms. Fatigue, insomnia, and depression were common (~70% reporting each). Participants reported significant symptom burden in all PROMIS domains, and had measurably worse attention function along with borderline executive function, compared to population normative data (all p< 0.001 except executive cognition p=0.056). Actigraphy showed Neuro-PASC patients had lower sleep efficiency and greater sleep latency (both p< 0.001) but similar wakefulness after sleep onset (WASO) compared to age-matched population controls. Self-reported cognitive symptoms were correlated with severity of fatigue (p< 0.001), anxiety (p=0.05), and depression (p< 0.01), but not subjective sleep disturbance. There were no associations between actigraphy-measured sleep or rest-activity characteristics and self-reported symptoms. Patients with abnormal sleep characteristics (WASO, sleep efficiency, sleep latency) demonstrated impaired objective attention and executive function. Conclusion Neuro-PASC patients presenting to a post-COVID clinic have a significant burden of subjective mental health, sleep, fatigue and cognitive impairment symptoms, along with objectively abnormal cognitive performance and sleep, compared to population controls. Interventions to improve sleep could benefit cognitive performance. Prospective studies including larger populations of patients are needed to fully determine the interplay of sleep/circadian rhythm disruption on the cognitive function and quality of life in patients with PASC. Support (if any) Center for Circadian and Sleep Medicine

Urogenital dysfunction and quality of life in women after stroke: Pilot study

Introduction: Research shows that urinary and sexual dysfunction is very common neurological sequelae of stroke with a markedly significant impact on body self-image and quality of life. Still, there is a lack of recent research to address this problem in female stroke survivors. The study aimed to examine the existence and level of urinary and sexual dysfunction, quality of life, and self-reported body image in a group of women after stroke and compare findings with those found in a group of women with other chronic non-neurological diseases. Methods: This study’s sample consisted of 30 females; two groups composed of 15. The stroke group consisted of subjects after stroke and the non-neurological group with different chronic non-neurological, mainly muscle-skeletal conditions. This study’s specific interest data were collected from respondents through pelvic floor distress inventory (PFDI-20), the pelvic floor impact questionnaire (PFIQ-7), female sexual function index (FSFI), and an eight-item body image scale (BIS). The SPSS v.26 program was used for statistical processing. Results: Results show a statistically higher scores in stroke group (M = 219.65 ± 34.573) on PFDI-20 than in non-neurological group (M = 118.54 ± 27.734). Furthermore, statistically significant higher scores were found in stroke group in PFIQ-7 (Mdn = 233.33) and BIS (Mdn = 16.00) than in non- neurological group (Mdn = 28.57) – PFIQ-7; (Mdn = 11.00) – BIS. Also, statistically significant lower scores were found in stroke group (Mdn=10.40) on FSFI index than in non-neurological group (Mdn=24.60). Conclusions: Women after stroke show significantly more urinary and sexual dysfunction, lower quality of life, and poorer body self-image than the non-neurological group of chronic non-neurological conditions. There is a clear need for research on this issue in women after stroke.

Potential Therapeutic Benefits of Brahma Rasayana in the Management of Tuberculous Cerebrovascular Disease - A Case Report

Tuberculous meningitis (TBM) is an air-borne infectious disease caused by the bacteria Mycobacterium tuberculosis that affects the central nervous system (CNS). Among all the incident cases of TB, CNS TB represents approximately 1% with TBM as the most grievous among all. The basic pathology in TBM is the inflammation of the arachnoid membrane, the pia mater and the cerebrospinal fluid (CSF). It typically presents as mild fever, headache, anorexia and general debility that progress over one to two weeks to cause severe headache, fever, vomiting, confusion, meningismus and cranial nerve deficits. The most common complications of TBM include hydrocephalus, optico-chiasmatic arachnoiditis, seizures and stroke. Out of these, tuberculous cerebrovascular disease is a common neurological sequelae. This case study elaborates the treatment line and observations made in a 29 year old male patient who presented with hemiparesis and significant sensory deficit following an event of tuberculous meningitis. MRI brain was suggestive of basilar meningitis, optico-chiasmatic arachnoiditis, infarcts and tuberculoma with chest X-ray revealing increased bronchovascular markings in bilateral lung fields. Initially on admission, Deepana-pachana was done followed by snehapana with Shadpala ghrta and Virechana as Sodhana karma. Abhyanga, Ushma Sweda, Churna pinda sweda and Jambeera pinda sweda were successively done allied with physiotherapy. Yogavasti with Vedanasthapana gana as Kashaya and Kalka was done intervened by Anuvasana vasti. Succeedingly, Murdhni taila prayoga and Marsha nasya were also incorporated with periodical neurological, hematological and biochemical assessment. On discharge, Brahmi kalyanaka ghrta and Brahma Rasayana were advised inclusive of physiotherapy.

Neurological Sequela of Acute Pesticide Poisoning Among Adults in Central Taiwan.

Background and Purpose: Cases of acute pesticide poisoning account for significant morbidity and mortality in developing countries; however, its burden in Taiwan remains unknown. The study examined acute pesticide poisoning (APP) involving adults in the central region of Taiwan, which is a mainly agricultural sub-urban area.Methods: The retrospective study evaluated the outcome and neurological sequelae of patients with APP in a Taiwanese cohort between April 2002 and February 2019. The pesticides were classified according to the Insecticide Resistance Action Committee Mode of Action (MoA) classification. The clinical characteristics, duration of hospitalization (days), follow-up duration (years), in-hospital mortality, neurological sequela, and imaging findings were recorded. Furthermore, multivariate logistic regression analyses were performed.Results: We identified 299 patients with APP comprising 206 (68.9%) adult men with a mean exposure age of 56.4 ± 16.8 years. Paraquat, organophosphates, pyrethroids, carmabates, and phosphinic acid were the most commonly known reported poisoning agents. The mortality rate was highest in users with paraquat (77.1%), followed by phosphinic acid (22.2%), carbamates (16.7%), and organophosphates (15.8%). After a mean follows up of 3.69 ± 2.26 years, the most common neurological sequela was a cognitive decline (56 among 225 survivors, 24.89%), peripheral neuropathy (11 among 225 survivors, 4.89%), tremor (10 among 225 survivors, 4.44%), ataxia (3/225, 1.33%), and parkinsonism feature (2/225, 0.89%). Brain imaging studies revealed basal ganglion lesions on CT or hyperintensity on T2-weighted MRI images in 26 among 46 patients (56.5%). The basal ganglion lesions on brain imaging had a positive correlation with neurological sequelae.Conclusion: Acute pesticide poisoning (APP)-related mortality is high especially paraquat intoxication, and cognitive decline, as well as peripheral neuropathy, were the most common neurological sequelae among survivors, which is highly correlated with basal ganglia lesions on brain imaging.

Prevalence and pattern of hearing loss among meningitis survivors in the Pacific Islands: a prospective, observational study protocol

Background Permanent hearing loss is the most common neurological sequelae among meningitis survivors in low- and middle-income countries. It is preventable through the availability and optimal population coverage of immunization programs. The most recent Global Burden of Disease Project reported that mortality and morbidity rates associated with meningitis are in decline in the Pacific Islands. While the report is encouraging, clinical and rehabilitation services for meningitis survivors remain important for regions where immunization delivery is unable to reach optimal levels. The aim of the proposed study is to assess the prevalence and pattern of hearing impairment among meningitis survivors in Samoa, a Polynesian nation of the Pacific Islands. Methods and analysis This will be a prospective observational study design. All patients admitted to Tupua Tamasese Meaole Hospital with a meningitis diagnosis from January 2021 to December 2022 will be eligible for the study. All meningitis survivors will be referred to the Ear, Nose and Throat (ENT)/audiology clinic prior to discharge for an ear and hearing assessment. The dependent variables will be otoscopic result and audiometry result for each ear. The independent variables will be age, gender, causal meningitis pathogen, and place of residence (urban/rural/remote). Ethics and conclusions We publish this protocol to facilitate similar research studies, especially among our Pacific Island neighbours. This research protocol may be a useful resource for the development of clinical procedures for routine ENT/audiology assessments for patients following infection with known causes of hearing loss. This study was approved by the Government of Samoa Ministry of Health Ethical Research Committee and the University of Queensland Medical Ethics Research Committee.

Increased Sestrin3 Contributes to Post-ischemic Seizures in the Diabetic Condition.

Seizures are among the most common neurological sequelae of stroke, and diabetes notably increases the incidence of post-ischemic seizures. Recent studies have indicated that Sestrin3 (SESN3) is a regulator of a proconvulsant gene network in human epileptic hippocampus. But the association of SESN3 and post-ischemic seizures in diabetes remains unclear. The present study aimed to reveal the involvement of SESN3 in seizures following transient cerebral ischemia in diabetes. Diabetes was induced in adult male mice and rats via intraperitoneal injection of streptozotocin (STZ). Forebrain ischemia (15 min) was induced by bilateral common carotid artery occlusion, the 2-vessel occlusion (2VO) in mice and 4-vessel occlusion (4VO) in rats. Our results showed that 59% of the diabetic wild-type mice developed seizures after ischemia while no seizures were observed in non-diabetic mice. Although no apparent cell death was detected in the hippocampus of seizure mice within 24 h after the ischemic insult, the expression of SESN3 was significantly increased in seizure diabetic mice after ischemia. The post-ischemic seizure incidence significantly decreased in SESN3 knockout mice. Furthermore, all diabetic rats suffered from post-ischemic seizures and non-diabetic rats have no seizures. Electrophysiological recording showed an increased excitatory synaptic transmission and intrinsic membrane excitability in dentate granule cells of the rat hippocampus, together with decreased IA currents and Kv4.2 expression levels. The above results suggest that SESN3 up-regulation may contribute to neuronal hyperexcitability and seizure generation in diabetic animals after ischemia. Further studies are needed to explore the molecular mechanism of SESN3 in seizure generation after ischemia in diabetic conditions.

Associations of cigarette smoking with gray and white matter in the UK Biobank

Cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. In the current study, we assessed the relationship of cigarette smoking with gray matter (GM) and white matter (WM) in the UK Biobank, controlling for numerous confounding demographic and health variables. We used negative-binomial regression to model the association of cigarette smoking (having ever smoked regularly, cigarettes per day, and duration smoked) with GM and WM (GM N = 19,615; WM N = 17,760), adjusting for confounders. Ever smoked and duration were associated with smaller total GM volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum and elevated WM hyperintensity volume. Smoking duration was associated with reduced total WM volume. Regarding specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation, and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. This study identified significant associations of cigarette exposure with global measures of GM and WM, and select associations of ever smoked, but not cigarettes per day or duration, with specific GM and WM regions. By controlling for important sociodemographic and health confounders, such as alcohol use, this study identifies distinct associations between smoking and brain structure, highlighting potential mechanisms of risk for common neurological sequelae (e.g., dementia).

Stroke and Lower Urinary Tract Symptoms

Lower urinary tract symptoms (LUTSs) are common neurological sequelae of stroke, which negatively impact the mortality of patients with stroke and the quality of life of both patients and their caregivers. There are three hierarchical micturition centers: the sacral spinal center, subconscious structures, and conscious structures. Several brain imaging modalities for micturition studies on humans and animals and neuroanatomical studies on animals have facilitated a better understanding of LUTSs. The urodynamic findings in patients with stroke may vary and tend to evolve with time; the identification of the underlying cause of poststroke voiding dysfunction helps optimize the management of these patients. For patients with stroke with overactive bladders, the first-line treatments include behavioral therapies and the second-line therapies include the use of drugs. Intermittent or indwelling catheterization can be used for patients with stroke with detrusor underactivity. In this article, we discuss the current consensus, relevant assessment modalities, and management of LUTSs in patients with stroke.

Follow-up study on Chinese children with relapsing MOG-IgG-associated central nervous system demyelination

BackgroundSome studies have reported clinical features of relapsing MOG-IgG-associated CNS demyelination principally in Caucasians children. It is not clear whether Chinese children share the same phenotype. ObjectiveTo delineate the clinical characteristics in Chinese children with relapsing MOG-IgG-associated demyelination. MethodsA follow-up study on 23 Children with relapsing MOG-IgG-associated demyelination from two Chinese tertiary hospitals was performed. Phenotypic features at each demyelinating attacks, neuroimaging characteristics, autoimmune antibodies in CSF/serum, response to disease modifying drugs and functional deficits during the disease course were analyzed. ResultsThe median age at disease onset was 5.38 (2.33–12.75) years. The male to female ratio was 1:1.30. The disease duration was 2.33(1.00–8.92) years at the last follow-up. (1) Clinical phenotypes: ADEM was the most common initial presentation (12/23, 52.17%). In 82 attacks during disease course, ADEM was also the most common phenotype (30/82, 36.59%), followed by ON (24/82, 29.27%). (2) Imaging findings: 57/70 (81.43%) brain MRI scans during acute attacks showed new lesions. The most common location of new lesions in brain was the juxtacortical white matter (45/57, 78.95%). In 46 brain MRI scans with supratentorial white matter lesions, ADEM-like patterns were most common (25/46, 54.35%), and 5/46 (10.87%) scans exhibited leukodystrophy-like patterns. (3) Laboratory examinations: Anti-NMDA receptor IgG in CSF was detected in two patients (2/12, 16.67%), with one patient presented with anti-NMDAR encephalitis associated symptoms. (4) Therapeutic responses and outcomes: In 19 patients treated with disease-modifying drugs (including rituximab, mycophenolate mofetil, azathioprine and so on) longer than 6 months, median annualised relapse rates decreased from 1.71 before treatment to 0.44 during treatment (P < 0.05), with eleven patients (11/19, 57.89%) having no relapses. Median EDSS score at the last follow-up was 1.0(0–3.5). Visual dysfunction (12/23, 52.17%) was the most common neurological sequela, with cognitive dysfunction and epilepsy in some of patients. ConclusionsThe phenotypic features of Chinese children with relapsing MOG-IgG-associated CNS demyelination were similar to that in Caucasian children. ADEM was the most common phenotype in all demyelinating attacks, followed by ON. Cerebral lesions were common and extensive, manifested as ADEM-like or even leukodystrophy-like patterns. Visual dysfunction was the most common neurological sequela. Although some disease-modifying drugs could reduce ARR, optimal treatment needs future study.

Does a Rehabilitation Program of Aerobic and Progressive Resisted Exercises Influence HIV-Induced Distal Neuropathic Pain?

Distal symmetrical polyneuropathy is a common neurological sequela after HIV, which leads to neuropathic pain and functional limitations. Rehabilitation programs with exercises are used to augment pharmacological therapy to relieve pain but appropriate and effective exercises are unknown. This study explored the safety and effect of moderate-intensity aerobic exercises and progressive resisted exercises for HIV-induced distal symmetrical polyneuropathy neuropathic pain. A randomized pretest, posttest of 12 wks of aerobic exercise or progressive resisted exercise compared with a control. Outcome measures were assessed using the subjective periphery neuropathy, brief peripheral neuropathy screening, and numeric pain rating scale. Pain was assessed at baseline, 6 and 12 wks. Data between groups were compared using Kruskal-Wallis, Mann-Whitney U test, and within-groups Friedman and Wilcoxon signed rank tests. There were 136 participants (mean [SD] age = 36.79 [8.23] yrs) and the exercise groups completed the protocols without any adverse effects. Pain scores within and between aerobic exercise and progressive resisted exercise groups showed significant improvement (P < 0.05) from baseline to 6 and 12 wks compared with the control (P > 0.05). This study supports a rehabilitation program of moderate-intensity aerobic exercise and progressive resisted exercise being safe and effective for reducing neuropathic pain and is beneficial with analgesics for HIV-induced distal symmetrical polyneuropathy.

Neurological Sequelae and Clinical Outcomes After Lung Transplantation.

BackgroundNeurological complications are common after lung transplantation. However, no large cohort studies have examined the incidence, predictors, and clinical significance of neurological events sustained by lung transplant recipients.MethodsWe conducted a retrospective cohort analysis of a consecutive series of lung transplant recipients, transplanted at Duke University Medical Center between May 2014 and February 2017 (n = 276). Early neurological complications (ie, occurring during the first week after transplant) were documented by transplant mental health specialists and included delirium, ischemic injury, and posterior reversible encephalopathy syndrome. Analyses accounted for age, native disease, sex, type of transplant, lung allocation score, and primary graft dysfunction. The objectives of the study were to characterize the prevalence and predictors of early neurological sequelae (NSE), occurring during the first week posttransplant, and the association between NSE and subsequent clinical outcomes, including length of stay and mortality.ResultsNeurological sequelae were common, occurring in 123 (45%) patients. Fifty-seven patients died over a follow-up interval of 2.1 years. The most common NSE were postoperative delirium (n = 110 [40%]) and posterior reversible encephalopathy syndrome (n = 12 [4%]), followed by stroke/transient ischemic attack and neurotoxicity. Higher lung allocation score was the strongest predictor of delirium. The presence of a NSE was associated with longer length of hospital stay (32 days vs 17 days, P < 0.001) and greater mortality (hazard ratio, 1.90; 95% confidence interval, 1.09-3.32], P = 0.024), with the greatest mortality risk occurring approximately 2 years after transplantation.ConclusionsNeurological events are relatively common after lung transplantation and associated with adverse clinical outcomes.

Citalopram restores short-term memory deficit and non-cognitive behaviors in APP/PS1 mice while halting the advance of Alzheimer's disease-like pathology

Alzheimer's disease (AD) is the most common cause of dementia. In addition to cognitive impairments, deficits in non-cognitive behaviors are also common neurological sequelae in AD. Here, we show that complex behavioral deficits in 7-month-old APPswe/PSEN1dE9 (APP/PS1) mice include impairments in object recognition, deficient social interaction, increased depression and buried marbles. Citalopram, one of the selective serotonin reuptake inhibitors (SSRIs), ameliorated the amyloid deposition in AD patients and transgenic animal models. After treatment for 4 weeks, citalopram rescued the deficits in short-term memory, sociability and depression in these mice. Further immunohistochemical analysis showed chronic citalopram treatment significantly attenuated β-amyloid deposition and microglial activation in the brains of APP/PS1 mice as demonstrated previously. Parvalbumin (PV) interneurons, which are the primary cellular subtype of GABAergic neurons and considered indispensable for short-term memory and social interaction, also contributed to the progress of depression. Additionally, we found the citalopram could significantly increase the PV-positive neurons in the cortex of APP/PS1 mice without alteration in the hippocampus, which might contribute to the improvement of behavioral performance. Our findings suggest that citalopram might be a potential candidate for the early treatment of AD.

N-Butylphthalide Improves Cognitive Function in Rats after Carbon Monoxide Poisoning.

Cognitive impairment is the most common neurologic sequelae after carbon monoxide (CO) poisoning, and the previous investigations have demonstrated that N-Butylphthalide (NBP) could exert a broad spectrum of neuroprotective properties. The current study aimed to investigate the effect of NBP on cognitive dysfunction in rats after acute severe CO poisoning. Rats were randomly divided into a normal control group, a CO poisoning group and a CO+NBP group. The animal model of CO poisoning was established by exposure to CO in a chamber, and then all rats received hyperbaric oxygen therapy once daily, while rats in CO+NBP group were administered orally NBP (6 mg/ 100g) by gavage twice a day additionally. The results indicated that CO poisoning could induce cognitive impairment. The ultrastructure of hippocampus was seriously damaged under transmission electron microscopy, and the expressions of calpain 1 and CaMK II proteins were significantly elevated after CO exposure according to the analysis of immunofluorescence staining and western blot. NBP treatment could evidently improve cognitive function, and maintain ultrastructure integrity of hippocampus. The expression levels of both calpain 1 and CaMK II proteins in CO+NBP group were considerably lower than that of CO poisoning group (P < 0.05). Taken together, this study highlights the molecular mechanism of cognitive dysfunction in rats after CO exposure via the upregulation of both calpain 1 and CaMK II proteins. The administration of NBP could balance the expressions of calpain 1 and CaMK II proteins and improve cognitive function through maintaining ultrastructural integrity of hippocampus, and thus may play a neuroprotective role in brain tissue in rats with CO poisoning.

Treatment of brain metastases.

Brain metastases are a very common neurological sequela in cancer patients. The ability of current anti-cancer therapies to prolong overall survival is beleaguered by this development in the case of a number of different cancers. This review provides a general overview of relevant treatment modalities, highlights major decision strategies used in selecting the optimal treatment algorithm and summarizes important steps necessary before initiating therapy. A PubMed database search was done to identify publications describing the treatment of brain metastases including surgery, radiotherapy and symptomatic care. Patient performance status and extent of disease play the most important roles in selecting between an aggressive or more conservative approach. As several other options are available, treatment decisions should be made in cooperation with multiple medical specialties and the involvement of multidisciplinary teams. In the future, brain metastases could become less of a treatment obstacle than they are today.

Assessment of ataxia phenotype in a new mouse model of galactose-1 phosphate uridylyltransferase (GALT) deficiency.

Despite adequate dietary management, patients with classic galactosemia continue to have increased risks of cognitive deficits, speech dyspraxia, primary ovarian insufficiency, and abnormal motor development. A recent evaluation of a new galactose-1 phosphate uridylyltransferase (GALT)-deficient mouse model revealed reduced fertility and growth restriction. These phenotypes resemble those seen in human patients. In this study, we further assess the fidelity of this new mouse model by examining the animals for the manifestation of a common neurological sequela in human patients: cerebellar ataxia. The balance, grip strength, and motor coordination of GALT-deficient and wild-type mice were tested using a modified rotarod. The results were compared to composite phenotype scoring tests, typically used to evaluate neurological and motor impairment. The data demonstrated abnormalities with varying severity in the GALT-deficient mice. Mice of different ages were used to reveal the progressive nature of motor impairment. The varying severity and age-dependent impairments seen in the animal model agree with reports on human patients. Finally, measurements of the cerebellar granular and molecular layers suggested that mutant mice experience cerebellar hypoplasia, which could have resulted from the down-regulation of the PI3K/Akt signaling pathway.

Enhanced autophagy signaling in diabetic rats with ischemia-induced seizures

Seizures are among the most common neurological sequelae of stroke, and ischemic insult in diabetes notably increases the incidence of seizures. Recent studies indicated that autophagy influences the outcome of stroke and involved in epileptogenesis. However, the association of autophagy and post-ischemic seizures in diabetes remains unclear. The present study aimed to reveal the involvement of autophagy in the seizures following cerebral ischemia in diabetes. Diabetes was induced in adult male Wistar rats by intraperitoneal injection of streptozotocin (STZ). The diabetic rats were subjected to transient forebrain ischemia. The neuronal damage was assessed using hematoxylin-eosin staining. Western blotting and immunohistochemistry were performed to investigate the alteration of autophagy marker microtubule-associated protein light chain 1B (LC3B). The results showed that all diabetic animals developed seizures after ischemia. However, no apparent cell death was observed in the hippocampus of seizure rats 12h after the insult. The expression of LC3B was significantly enhanced in naïve animals after ischemia and was further increased in diabetic animals after ischemia. Immunofluorescence double-labeling study indicated that LC3B was mainly increased in neurons. Our study demonstrated, for the first time, that autophagy activity is significantly increased in diabetic animals with ischemia-induced seizures. Further studies are needed to explore the role of autophagy in seizure generation after ischemia in diabetic conditions.