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World Neurosurgery Aug 2023A 72-year-old female with a history of hypertension and hyperlipidemia presented to the emergency department from an outside hospital with acute confusion and global...
A 72-year-old female with a history of hypertension and hyperlipidemia presented to the emergency department from an outside hospital with acute confusion and global amnesia immediately following cervical epidural steroid injection with fluoroscopic guidance for radiculopathy relief. On exam, she was oriented to self, but disoriented to place and situation. Otherwise, she was neurologically intact with no deficits. Head computed tomography (CT) revealed diffuse subarachnoid hyperdensities most prominent in the parafalcine region concerning for diffuse subarachnoid hemorrhage and tonsillar herniation concerning for intracranial hypertension. CT angiograms of head and neck were negative for vascular abnormalities. Dual-energy head CT was subsequently performed 4 hours later without IV contrast. The 80 kV sequence revealed prominent diffuse hyperdensity throughout the cerebrospinal fluid spaces in bilateral cerebral hemispheres, basal cisterns, and posterior fossa consistent with the initial CT, but these corresponding regions were relatively less dense on the 150 kV sequence. These findings were consistent with contrast material in the cerebrospinal fluid spaces without evidence of intracranial hemorrhage or transcortical infarct. Three hours later, the patient's transient confusion resolved, and she was discharged home the next morning without any neurological deficit.
Topics: Female; Humans; Aged; Subarachnoid Hemorrhage; Head; Confusion; Intracranial Hemorrhages
PubMed: 37207723
DOI: 10.1016/j.wneu.2023.05.043 -
Neurology Nov 2023Blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have recently been Food and Drug Administration approved as...
BACKGROUND AND OBJECTIVES
Blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have recently been Food and Drug Administration approved as predictors of intracranial lesions on CT after mild traumatic brain injury (mTBI). However, most cases with mTBI are CT negative, and no biomarkers are approved to assist diagnosis in these individuals. In this study, we aimed to determine the optimal combination of blood biomarkers to assist mTBI diagnosis in otherwise healthy adults younger than 50 years presenting to an emergency department within 6 hours of injury. To further understand the utility of biomarkers, we assessed how biological sex, presence or absence of loss of consciousness and/or post-traumatic amnesia (LOC/PTA), and delayed presentation affected classification performance.
METHODS
Blood samples, symptom questionnaires, and cognitive tests were prospectively conducted for participants with mTBI recruited from The Alfred Hospital Level 1 Emergency & Trauma Center and uninjured controls. Follow-up testing was conducted at 7 days. Simoa quantified plasma GFAP, UCH-L1, tau, neurofilament light chain (NfL), interleukin (IL)-6, and IL-1β. Area under the receiver operating characteristic (AUC) analysis assessed classification accuracy for diagnosed mTBI, and logistic regression models identified optimal biomarker combinations.
RESULTS
Plasma IL-6 (AUC 0.91, 95% CI 0.86-0.96), GFAP (AUC 0.85, 95% CI 0.78-0.93), and UCH-L1 (AUC 0.79, 95% CI 0.70-0.88) best differentiated mTBI (n = 74) from controls (n = 44) acutely (<6 hours), with NfL (AUC 0.81, 95% CI 0.72-0.90) the only marker to have such utility subacutely (7 days). Biomarker performance was similar between sexes and for participants with and without LOC/PTA, with the exception at 7 days, where GFAP and IL-6 retained some utility in female participants (GFAP: AUC 0.71, 95% CI 0.55-0.88; IL-6: AUC 0.71, 95% CI 0.55-0.87) and in those with LOC/PTA (GFAP: AUC 0.73, 95% CI 0.59-0.86; IL-6: AUC 0.71, 95% CI 0.57-0.84). Acute IL-6 ( = 0.50, 95% CI 0.34-0.64) outperformed GFAP and UCH-L1 combined ( = 0.35, 95% CI 0.17-0.50), with the best acute model featuring GFAP and IL-6 ( = 0.54, 95% CI 0.34-0.68).
DISCUSSION
These findings indicate that adding IL-6 to a panel of brain-specific proteins such as GFAP and UCH-L1 might assist in the acute diagnosis of mTBI in adults younger than 50 years. Multiple markers had high classification accuracy in participants without LOC/PTA. When compared with the best-performing acute markers, subacute measures of plasma NfL resulted in minimal reduction in classification accuracy. Future studies will investigate the optimal time frame over which plasma IL-6 might assist diagnostic decisions and how extracranial trauma affects utility.
Topics: Adult; Humans; Female; Brain Concussion; Interleukin-6; Brain; Biomarkers; Glial Fibrillary Acidic Protein; Ubiquitin Thiolesterase; Tomography, X-Ray Computed; Brain Injuries, Traumatic
PubMed: 37788938
DOI: 10.1212/WNL.0000000000207881 -
Journal of Complementary & Integrative... Sep 2023The most common human neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) etc. have been recognized to result... (Review)
Review
The most common human neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) etc. have been recognized to result from a complex interplay between genetic predisposition and defective cellular dynamics such as inappropriate accumulation of unfolded proteins, oxygen free radicals and mitochondrial dysfunction. The treatment strategies available today for these neurodegenerative ailments are only palliative and are incapable of restraining the progression of the disease. Hence, there is an immense requirement for identification of drug candidates with the ability to alleviate neuronal damage along with controlling progression of the disease. From time immemorial mankind has been relying on plants for treating varied types of dreadful diseases. Among the various medicinal plants used for treating various neurological ailments, (CP) popularly known as Jyotishmati or Malkangni is well known in the Ayurveda system of Indian Traditional Medicine whose seeds and seed oil have been used for centuries in treating epilepsy, dementia, facial paralysis, amnesia, anxiety, sciatica, cognitive dysfunctions etc. This review apart from specifying the phytochemical characteristics and traditional uses of seeds and seed oil also exemplify the comprehensive data derived from various research reports on their therapeutic potential against some common neurological disorders.
PubMed: 35005853
DOI: 10.1515/jcim-2021-0448 -
Biomedicine & Pharmacotherapy =... Sep 2023Albizia adianthifolia (Schumach.) (Fabaceae) is a medicinal herb used for the treatment of epilepsy and memory impairment. This study aims to investigate the...
Ameliorative effects of Albizia adianthifolia aqueous extract against pentylenetetrazole-induced epilepsy and associated memory loss in mice: Role of GABAergic, antioxidant defense and anti-inflammatory systems.
Albizia adianthifolia (Schumach.) (Fabaceae) is a medicinal herb used for the treatment of epilepsy and memory impairment. This study aims to investigate the anticonvulsant effects of Albizia adianthifolia aqueous extract against pentylenetetrazole (PTZ)-induced spontaneous convulsions in mice; and determine whether the extract could mitigate memory impairment, oxidative/nitrergic stress, GABA depletion and neuroinflammation. Ultra-high performance liquid chromatography/mass spectrometry analysis was done to identify active compounds from the extract. Mice were injected with PTZ once every 48 h until kindling was developed. Animals received distilled water for the normal group and negative control groups, doses of extract (40, 80, or 160 mg/kg) for the test groups and sodium valproate (300 mg/kg) for the positive control group. Memory was measured using Y maze, novel object recognition (NOR) and open field paradigms, while the oxidative/nitrosative stresses (MDA, GSH, CAT, SOD and NO), GABAergic transmission (GABA, GABA-T and GAD) and neuro-inflammation (TNF-α, IFN-γ, IL- 1β, and IL-6) were determined. Brain photomicrograph was also studied. Apigenin, murrayanine and safranal were identified in the extract. The extract (80-160 mg/kg) significantly protected mice against seizures and mortality induced by PTZ. The extract significantly increased the spontaneous alternation and the discrimination index in the Y maze and NOR tests, respectively. PTZ kindling induced oxidative/nitrosative stress, GABA depletion, neuroinflammation and neuronal cells death was strongly reversed by the extract. The results suggest that the anticonvulsant activity of Albizia adianthifolia extract is accompanied by its anti-amnesic property, and may be supported by the amelioration of oxidative stress, GABAergic transmission and neuroinflammation.
Topics: Mice; Animals; Pentylenetetrazole; Antioxidants; Anticonvulsants; Albizzia; Neuroinflammatory Diseases; Plant Extracts; Epilepsy; Seizures; Kindling, Neurologic; Memory Disorders; Oxidative Stress; Amnesia; Water; gamma-Aminobutyric Acid; Anti-Inflammatory Agents
PubMed: 37392651
DOI: 10.1016/j.biopha.2023.115093 -
BioRxiv : the Preprint Server For... Sep 2023Memories involving the hippocampus can take several days to consolidate, challenging efforts to uncover the neuronal signatures underlying this process. Using calcium...
Memories involving the hippocampus can take several days to consolidate, challenging efforts to uncover the neuronal signatures underlying this process. Using calcium imaging in freely moving mice, we tracked the hippocampal dynamics underlying memory formation across a ten-day contextual fear conditioning (CFC) task. We found that cell turnover between the conditioning chamber and a neutral arena even to learning predicted the accuracy of subsequent memory recall the next day. Following learning, context-specific place field remapping correlated with memory performance. To causally test whether these hippocampal dynamics support memory consolidation, we induced amnesia in a group of mice by pharmacologically blocking protein synthesis immediately following learning. We found that halting protein synthesis following learning paradoxically accelerated cell turnover and also arrested learning-related remapping, paralleling the absence of remapping observed in untreated mice that exhibited poor memory expression. Finally, coordinated neural activity that emerged following learning was dependent on intact protein synthesis and predicted memory-related freezing behavior. We conclude that context-specific place field remapping and the development of coordinated ensemble activity require protein synthesis and underlie contextual fear memory consolidation.
PubMed: 36778486
DOI: 10.1101/2023.02.02.526824 -
Experimental Brain Research Aug 2023Is retrograde amnesia associated with an ability to know who we are and imagine what we will be like in the future? To answer this question, we had S.G., a patient with...
Is retrograde amnesia associated with an ability to know who we are and imagine what we will be like in the future? To answer this question, we had S.G., a patient with focal retrograde amnesia following hypoxia, two brain-damaged (control) patients with no retrograde memory deficits, and healthy controls judge whether each of a series of trait adjectives was descriptive of their present self, future self, another person, and that person in the future, and later recognize studied traits among distractors. Healthy controls and control patients were more accurate in recognizing self-related compared to other-related traits, a phenomenon known as the self-reference effect (SRE). This held for both present and future self-views. By contrast, no evidence of (present or future) SRE was observed in SG, who concomitantly showed reduced certainty about his personality traits. These findings indicate that retrograde amnesia can weaken the self-schema and preclude its instantiation during self-related processing.
Topics: Humans; Amnesia, Retrograde; Memory Disorders; Brain Injuries; Language; Neuropsychological Tests
PubMed: 37450003
DOI: 10.1007/s00221-023-06661-2 -
Journal of Translational Autoimmunity Dec 2023The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as... (Review)
Review
The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches.
PubMed: 37859804
DOI: 10.1016/j.jtauto.2023.100218 -
Neurological Research Oct 2023Agitation and aggression are common following traumatic brain injury. The challenges related to these disorders affect all stages of recovery, from the acute hospital to... (Review)
Review
OBJECTIVES
Agitation and aggression are common following traumatic brain injury. The challenges related to these disorders affect all stages of recovery, from the acute hospital to the community setting. The aim of this literature review is to provide an updated overview of the current state of post-traumatic agitation research.
METHODS
We performed a PubMed literature review which included recent confirmatory and novel research as well as classic and historical studies to integrate past and future concepts.
RESULTS
Areas explored include the personal and societal effects of post-traumatic agitation, methods for defining and diagnosing several neurobehavioral disorders, and pathophysiology and management of agitation and aggression. Target areas for future study are identified and discussed.
DISCUSSION
While much progress has been made in understanding post-traumatic agitation, there remain several key areas that require further elucidation to support the care and treatment for people with traumatic brain injury.
Topics: Humans; Brain Injuries; Psychomotor Agitation; Brain Injuries, Traumatic; Anxiety; Aggression
PubMed: 32706643
DOI: 10.1080/01616412.2020.1797374 -
Revista de Neurologia Jul 2023Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with... (Review)
Review
INTRODUCTION
Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with heterogeneous neurological manifestations. However, LE is not considered a typical presentation of neuro-Behcet's disease (NBD).
CASE REPORT
A 40-years-old male presented with new-onset subacute headaches, memory problems and apathy. A review of systems revealed an unrecorded past history of recurrent oral sores for years, recent malaise and fever, as well as an episode of bilateral panuveitis four months before presentation. His general and neurologic examination revealed slight fever, an isolated oral aphtha, anterograde amnesia and signs of bilateral retinal vasculitis. Brain magnetic resonance imaging displayed a pattern of limbic meningoencephalitis, and his cerebrospinal fluid showed mononuclear inflammation. The patient met BD diagnostic criteria. Considering LE is a very rare presentation of NBD, alternative etiologies were thoroughly assessed and excluded, including infectious, autoimmune and paraneoplastic encephalitis. Therefore, he was diagnosed with NBD, and he recovered well after immunosuppression.
DISCUSSION
Only two cases of NBD presenting with LE have been previously reported. We report a third case of this rare presentation and compare it with the previous two. We aim to highlight this association and contribute to enlarge the rich clinical spectrum of NBD.
Topics: Humans; Male; Adult; Behcet Syndrome; Limbic Encephalitis; Brain; Magnetic Resonance Imaging; Headache
PubMed: 37403244
DOI: 10.33588/rn.7702.2022049 -
Neuropsychologia Aug 2023Disorientation is a frequent consequence of acute brain injury or diffuse disorders, such as confusional states or dementia. Its anatomical correlates are debated.... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
Disorientation is a frequent consequence of acute brain injury or diffuse disorders, such as confusional states or dementia. Its anatomical correlates are debated. Impaired memory as its commonly assumed mechanism predicts that disorientation is associated with medial temporal damage. The alternative is that disorientation reflects defective orbitofrontal reality filtering (ORFi) - a specific failure to identify whether thoughts or memories refer to present reality or not. The latter is a function of the posterior orbitofrontal cortex and connected structures. This study examined the mechanisms and anatomical basis of disorientation in an unselected group of patients with first-ever subacute brain injury.
METHODS
Participants hospitalized for neurorehabilitation were asked to participate in this observational cohort study if they had first-ever organic hemispheric brain dysfunction as evident in a localizable brain lesion or verbal amnesia (often without localizable brain damage). Orientation to time, place, situation and person was tested with a 20-items questionnaire. To identify the mechanisms of disorientation, we determined its correlations with executive tasks, verbal episodic memory, and ORFi in all patients. ORFi was examined with a continuous recognition task, which measures learning and item recognition in the first run, and ORFi as reflected in the increase of false positive responses in the second run (temporal context confusion). Lesions of patients having localizable brain damage were manually delineated and normalized before entering multivariate lesion-symptom-mapping (LSM) to determine anatomical predictors of orientation.
RESULTS
Eighty-four patients (61.1 ± 14.4 years, 29 women) were included. Among measures of memory and executive functioning, a step-wise regression retained temporal context confusion (R = -0.71, p < 0.0001), item recognition (R = 0.67, p < 0.0001) and delayed free recall (R = 0.63, p < 0.0001) as significant predictors of orientation. LSM was possible in 67 participants; it revealed an association of disorientation with damage of the right OFC and the bilateral head of the caudate nucleus.
CONCLUSION
Disorientation in non-confused, non-demented patients with first-ever brain damage is associated with impaired orbitofrontal reality filtering and memory dysfunction, but not with executive dysfunction. Its main anatomical determinant is damage to the orbitofrontal cortex and its subcortical relay, the head of the caudate.
Topics: Humans; Female; Confusion; Recognition, Psychology; Brain Injuries; Prefrontal Cortex; Memory, Episodic
PubMed: 37263576
DOI: 10.1016/j.neuropsychologia.2023.108601