scholarly journals Elevated Cerebrospinal Fluid Tau Protein Concentrations on Admission Are Associated With Long-term Neurologic and Cognitive Impairment in Ugandan Children With Cerebral Malaria

2019 ◽  
Vol 70 (6) ◽  
pp. 1161-1168 ◽  
Author(s):  
Dibyadyuti Datta ◽  
Andrea L Conroy ◽  
Peter F Castelluccio ◽  
John M Ssenkusu ◽  
Gregory S Park ◽  
...  

Abstract Background Elevated concentrations of cerebrospinal fluid (CSF) tau, a marker of axonal injury, have been associated with coma in severe malaria (cerebral malaria [CM]). However, it is unknown whether axonal injury is related to long-term neurologic deficits and cognitive impairment in children with CM. Methods Admission CSF tau concentrations were measured in 145 Ugandan children with CM and compared to clinical and laboratory factors and acute and chronic neurologic and cognitive outcomes. Results Elevated CSF tau concentrations were associated with younger age, increased disease severity (lower glucose and hemoglobin concentrations, malaria retinopathy, acute kidney injury, and prolonged coma duration, all P < .05), and an increased CSF:plasma albumin ratio, a marker of blood–brain barrier breakdown (P < .001). Admission CSF tau concentrations were associated with the presence of neurologic deficits at hospital discharge, and at 6, 12, and 24 months postdischarge (all P ≤ .02). After adjustment for potential confounding factors, elevated log10-transformed CSF tau concentrations correlated with worse cognitive outcome z scores over 2-year follow-up for associative memory (β coefficient, –0.31 [95% confidence interval [CI], –.53 to –.10]) in children <5 years of age, and for overall cognition (–0.69 [95% CI, –1.19 to –.21]), attention (–0.78 [95% CI, –1.34 to –.23]), and working memory (–1.0 [95% CI, –1.68 to –.31]) in children ≥5 years of age (all P < .006). Conclusions Acute axonal injury in children with CM is associated with long-term neurologic deficits and cognitive impairment. CSF tau concentrations at the time of the CM episode may identify children at high risk of long-term neurocognitive impairment.

2017 ◽  
Vol 23 (4) ◽  
pp. 332-340 ◽  
Author(s):  
Mira Karrasch ◽  
Petri Tiitta ◽  
Bruce Hermann ◽  
Juho Joutsa ◽  
Shlomo Shinnar ◽  
...  

AbstractObjectives: Little is known about the very long-term cognitive outcome in patients with childhood-onset epilepsy. The aim of this unique prospective population-based cohort study was to examine cognitive outcomes in aging participants with childhood-onset epilepsy (mean onset age=5.3 years) five decades later (mean age at follow-up=56.5 years).Methods: The sample consisted of 48 participants with childhood-onset epilepsy and 48 age-matched healthy controls aged 48–63 years. Thirty-six epilepsy participants were in remission and 12 continued to have seizures. Cognitive function was examined with 11 neuropsychological tests measuring language and semantic function, episodic memory, and learning, visuomotor function, executive function, and working memory. Results: The risk of cognitive impairment was very high in participants with continuing seizures; odds ratio (OR)=11.7 (95% confidence interval [CI] (2.8, 49.6), p=.0008). They exhibited worse performances across measures of language and semantic function, and visuomotor function compared to participants with remitted epilepsy and healthy controls. In the participants with remitted epilepsy, the risk of cognitive impairment was somewhat elevated, but not statistically significant; OR=2.6 (95% CI [0.9, 7.5], p=.08).Conclusions: Our results showed that the distinction of continued versus discontinued seizures was critical for determining long-term cognitive outcome in childhood-onset epilepsy. Few participants in remission exhibited marked cognitive impairment compared to age-matched peers. However, a subgroup of participants with decades long active epilepsy, continuous seizure activity and anti-epileptic drug (AED) medication, showed clinically significant cognitive impairment and are thus in a more precarious position when entering older age. (JINS, 2017, 23, 332–340)


2009 ◽  
Vol 15 (3) ◽  
pp. 344-353 ◽  
Author(s):  
JÖRN PROHL ◽  
SEBASTIAN BODENBURG ◽  
STEPHAN JEFF RUSTENBACH

AbstractThis prospective study evaluated the prognostic value of early neurobiochemical markers, neuron-specific enolase and astroglial protein S-100B, for long-term cognitive outcome after cardiac arrest. Six months after admission of a cohort of 80 consecutive patients, 26 survivors were able to undergo a neuropsychological test battery. Survivors showed low test performances in attention, learning/memory, and executive functioning. Neuropsychological bedside screening during the first month significantly differentiated between patients with and without long-term cognitive impairment. The neurobiochemical marker S-100B at day 3 after admission was found to predict significant proportions of variance in specific cognitive domains (learning/memory and executive functioning). The results indicate that early neuropsychological assessment might help identify patients who run at risk of long-term neuropsychological dysfunction. This study also suggests that especially the protein S-100B provides valuable information on long-term cognitive outcomes. To understand the exact relationship, results have to be replicated in larger trials. (JINS, 2009,15, 344–353.)


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Max Borsche ◽  
Dirk Reichel ◽  
Anja Fellbrich ◽  
Anne S. Lixenfeld ◽  
Johann Rahmöller ◽  
...  

AbstractNeurological long-term sequelae are increasingly considered an important challenge in the recent COVID-19 pandemic. However, most evidence for neurological symptoms after SARS-CoV-2 infection and central nervous system invasion of the virus stems from individuals severely affected in the acute phase of the disease. Here, we report long-lasting cognitive impairment along with persistent cerebrospinal fluid anti-SARS-CoV-2 antibodies in a female patient with unremarkable standard examination 6 months after mild COVID-19, supporting the implementation of neuropsychological testing and specific cerebrospinal fluid investigation also in patients with a relatively mild acute disease phase.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Andrea L. Conroy ◽  
Robert O. Opoka ◽  
Paul Bangirana ◽  
Ruth Namazzi ◽  
Allen E. Okullo ◽  
...  

Abstract Background In 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM. Methods From 2008 to 2013, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up. Results 346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07–0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children <6 years of age at severe malaria exposure following adjustment for child age, sex, socioeconomic status, enrichment in the home environment, and the incidence of hospitalizations over follow-up. Children receiving artesunate had the greatest reduction in mortality and benefit in behavioral outcomes and had reduced inflammation at 1-month follow-up compared to children treated with quinine. Conclusions Treatment of severe malaria with artemisinin derivatives, particularly artesunate, results in reduced in-hospital mortality and neurologic deficits in children of all ages, reduced inflammation following recovery, and better long-term behavioral outcomes. These findings suggest artesunate has long-term beneficial effects in children surviving severe malaria.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
George Wong ◽  

Objectives: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid haemorrhage (SAH). Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale. Cognitive function is another important dimension of outcome assessment and yet had not been investigated in statin studies for aneurysmal subarachnoid hemorrhage. We therefore explored whether acute simvastatin treatment would improve cognitive outcomes. Methods: The study recruited SAH patients with acute simvastatin treatment enrolled in a randomized controlled double-blinded clinical trial (ClinicalTrials.gov Identifier: NCT01038193). A control cohort of SAH patients without simvastatin treatment was identified with propensity score matching of age and admission grade. Primary outcome measure was Montreal Cognitive Assessment (MoCA). Secondary outcome measures were delayed ischaemic deficit (DID), delayed cerebral infarction, modified Rankin Scale (mRS), and Mini-Mental State Examination( MMSE). Results: Fifty-one SAH patients with acute simvastatin treatment and 51 SAH patients without simvastatin treatment were recruited for analysis. At 3 months, there were no differences in MoCA scores (MoCA: 21+/-6 vs. 21+/-5, p=0.772). MoCA-assessed cognitive impairment (MoCA<26) was not different (75% vs. 80%, OR 0.7, 95%CI 0.3 to 1.8, p=0.477). There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups. Conclusions: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.


Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 264-265
Author(s):  
Molly E Hubbard ◽  
Abdullah Bin Zahid ◽  
Gabrielle Meyer ◽  
Kathleen Vonderhaar ◽  
David Y Balser ◽  
...  

Abstract INTRODUCTION Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US. The effects of TBI on quality of life may not become apparent for years after the injury. There are conflicting reports in the literature regarding long term outcomes. Physicians are often asked to predict long term functional and cognitive outcomes, with limited data available. METHODS Patients with severe TBI (GCS = 9) who previously participated in a clinical trial during the 1980s were followed up with and compared to healthy controls without history of TBI. A health questionnaire, sports concussion assessment tool version 3 (SCAT3) and the Telephone Interview for Cognitive Status-modified (TICS-m) were completed over the phone and compared with controls using t-test. GCS at admission and 12-month GRS were used to predict to TICS-M at 30 years using linear regression. RESULTS >45 of the initial 168 subjects were confirmed alive, and 37 (13 females; mean age: 52.43 years S.D. 10.7) consented. Controls (n = 58; 23 females; mean age = 54 years, S.D. 11.5) had lower symptom severity score (6.7 S.D. 12.6 versus 20.6 S.D. 25.3; P = 0.005), lower total number of symptoms (3.4 S.D. 4.7 versus 7.12 S.D. 6.5; P = 0.006), higher standardized assessment of concussion score (25.6 S.D. 2.8 versus 21.2 S.D. 6.9; P = 0.001), and lower corrected MPAI-4 (22.3 S.D. 17.0 versus 43.7 S.D. 12.8; P < 0.001). GCS at admission did not predict cognitive status at 30-years assessed using TICS-M (P = 0.345). The Glasgow Outcome Scale score at 12-months was correlated to TICS-M at 30 years (R = 0.548, P < 0.001); each point decrease in GOS decreasing the score at TICS-M by 5.6 points. CONCLUSION Remote history of TBI disrupts the lives of survivors long after injury. Admission GCS does not predict cognitive status 30 years after TBI. The GOS at 12-months predicted the cognitive status assessed using TICS-M score at 30 years.


PEDIATRICS ◽  
2008 ◽  
Vol 122 (1) ◽  
pp. e92-e99 ◽  
Author(s):  
C. C. John ◽  
P. Bangirana ◽  
J. Byarugaba ◽  
R. O. Opoka ◽  
R. Idro ◽  
...  

This case focuses on long-term cognitive impairment after critical illness by asking the question: What is the prevalence of long-term cognitive impairment after critical illness, and does the duration of delirium and use of sedative or analgesic medications affect cognitive outcomes? This study demonstrated that 74% of adult patients with critical illness experience delirium during their hospital course. Furthermore, patients in the intensive care unit (ICU) setting commonly experience global cognition and executive function deficits at 3 and 12 months following hospitalization. These findings highlight the importance of careful delirium surveillance in ICU patients.


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