Efek terapi oksigen hiperbarik terhadap nilai Montreal Cognitive Assesment Indonesia (MoCA-INA) pada pasien cedera otak traumatik ringan

Hyperbaric oxygen therapy (HBOT) uses 100% oxygen at a pressure of more than 1 ATM in a chamber, therefore, it can improve the state of tissue hypoxia. This study was aimed to prove that TOHB could increase the MoCA-INA score in mild traumatic brain injury (mTBI). This study was carried out at the Surgery Department of Prof. Dr. R. D. Kandou Hospital, Manado using the pre and post trial design. Subjects were 20 patients with mTBI divided into two groups: treated with HBOT and control group (without HBOT). Each patient involved would be examined for MoCA-INA before and after treatment or with HBOT added. The results showed that before treatment, the MoCA-INA scores tended to be evenly distributed around 36 (SD 5). The score increased to 71 (SD 10) at post-injury management or a mean increase of 35 points (p<0.001 in the paired two-sample t-test). However, there was no significat difference in MoCA-INA scores between the first and the second measurements. The density of the two groups clearly overlapped even though the variation of MoCA-INA scores of the HBOT group was much wider than that of the control group (p=0.302 and 0.297 in the first and second measurements, respectively). There was no cognitive disturbance either mild, moderate, or severe in all patients. In conclusion, there was an increase of the MoCA-INA value in mTBI patients after treatment. The patients treated with HBOT showed wider variation of MoCA-INA score of pre and post HBOT than those without HBOT Keywords: HBOT; mTBI; MoCA-INA; cognitive function Abstrak: Terapi oksigen hiperbarik (TOHB) menggunakan oksigen 100% pada tekanan lebih dari 1 ATM dalam sebuah chamber sehingga dapat memperbaiki keadaan hipoksia jaringan. Penelitian ini bertujuan untuk membuktikan bahwa TOHB dapat meningkatkan nilai MoCA-INA pada pasien cedera otak traumatik ringan (COTr). Penelitian dilaksanakan di Bagian Bedah RSUP Prof. Dr. R. D. Kandou, Manado dengan menggunakan pre and posttrial design. Subyek penelitian ialah 20 pasien COTr dibagi dalam dua kelompok: dengan dan tanpa TOHB (kelompok kontrol). Setiap subyek diperiksa MoCA-INA sebelum dan sesudah penatalaksanaan cedera/disertai TOHB. Sebelum penatalaksanaan cedera, rerata skor MoCA-INA sekitar 36 (SD 5) dan nilai tersebut meningkat menjadi 71 (SD 10) pasca penatalaksanaan cedera atau kenaikan rerata 35 poin (p<0,001 pada uji t dua sampel berpasangan). Tidak tampak perbedaan skor MoCA-INA baik pada pengukuran pertama maupun kedua. Densitas kedua kelompok terlihat jelas tumpang tindih sekalipun variasi skor MoCA-INA group TOHB jauh lebih lebar daripada group kontrol (p=0,302 dan 0,297 masing-masing pada pengukuran pertama dan kedua). Tidak terlihat adanya gangguan kognitif ringan sedang maupun berat pada semua pasien. Simpulan penelitian ini ialah terdapat peningkatan nilai MoCA-INA pada pasien COTr. Pasien dengan TOHB memperlihatkan variasi skor MoCA-INA yang lebih besar pada pre dan pasca TOHB.Kata kunci: TOHB; COT; MoCA-INA; gangguan kognitif

Effect of Anesthesia/Surgery on Gut Microbiota and Fecal Metabolites and Their Relationship With Cognitive Dysfunction

Aims: Post-operative cognitive dysfunction (POCD) is the decline in cognitive function of the central nervous system (CNS) after anesthesia/surgery. The present study explored whether anesthesia/surgery altered gut microbiota and fecal metabolites, examining their associations with risk factors of cognitive dysfunction in aged mice.Methods: Sixteen-month-old C57BL/6 mice underwent abdominal surgery under isoflurane anesthesia to establish an animal model of POCD. The Morris water maze test (MWMT) was used as an indicator of memory after surgery. The effects of anesthesia/surgical interventions on gut microbiota, fecal metabolites, hippocampus, and serum levels of inflammatory factors were examined.Results: The anesthesia/surgery induced more serious POCD behavior, increasing brain interleukin (IL)-6, and IL-1β levels than sham control mice. The relative abundance of bacterial genera Bacteroidales_unclassified, Mucispirillum, and Clostridiales_unclassified declined, whereas that of Escherichia–Shigella, actinomyces, Ruminococcus_gnavus_group, and Lachnospiraceae_FCS020_group were enriched after anesthesia/surgery compared to the baseline controls. Liquid chromatography–mass spectrometry (LC–MS) showed that the metabolites differed between post-anesthesia+surgery (post_A + S) and baseline samples and were associated with the fecal metabolism of tryptophan, kynurenic acid, N-oleoyl γ-aminobutyric acid (GABA), 2-indolecarboxylic acid, and glutamic acid. Furthermore, the differential metabolites were associated with alterations in the abundance of specific bacteria. These results indicate that the POCD intervention may be achieved by targeting specific bacteria associated with neurotransmitter metabolism.Conclusions: A transient cognitive disturbance induced by anesthesia/surgery may be associated with unfavorable alterations in gut microbiota and fecal metabolites, thereby contributing to the POCD development.

Cushing’s disease presenting with psychosis

Cushing’s disease is a rare endocrine condition in which a pituitary corticotroph adenoma drives excess adrenal cortisol production, and is one cause of endogenous Cushing’s syndrome. We present a young woman with 3 weeks of headaches and cognitive disturbance who subsequently developed florid psychosis requiring multiple admissions under neurology and psychiatry. Her clinical stigmata of hypercortisolism and biochemical abnormalities prompted an MR scan of the pituitary, which confirmed a pituitary microadenoma. Treatment with metyrapone and subsequent surgery led to complete recovery within 2 months. Cushing’s disease commonly causes neuropsychiatric symptoms and can present with psychosis. Diagnosing Cushing’s disease can be challenging, but with early diagnosis and treatment it has an excellent prognosis.

Clinical Character of CASPR2 Autoimmune Encephalitis: A Multiple Center Retrospective Study

ObjectiveTo examine the clinical characteristics of autoimmune encephalitis associated with the contactin-associated protein-2 (CASPR2) antibody.Materials and MethodsMedical records of all patients diagnosed with CASPR2 antibody-associated encephalitis were retrospectively analysed. Data regarding demographic features, neurological symptoms and signs, laboratory tests, imaging results, treatments, and prognosis were collected.ResultsA total of 25 patients aged from 3 to 79 years old were enrolled in this study, with a median age of 43. Eight of 25 (32%) were female, and 17 of 25 (68%) were male. The median age of symptom onset was 42 years old with the course of disease from onset to hospital admission ranging from 2 days to 6 months (median was 17 days). Six patients (6/25) had fever as an onset symptom. During the course of disease, cognitive disturbance was the most common symptom, which was observed in 17 patients (17/25) in total. Eight patients (8/25) met the criteria for limbic encephalitis. Epileptic seizure occurred in six of these eight patients. Four patients (4/25) were diagnosed as Morvan syndrome. All patients were positive for anti-CASPR2 antibody in the serum (1:10–1:300). In six patients, antibodies were detected both in the blood and CSF (1:32–1:100). White blood cell (WBC) counts in the CSF were elevated in eight patients (8/25). The concentration of proteins in CSF increased in 10 patients (ranging from 480 to 1,337.6 mg/dl), decreased in seven patients (ranging from 23.2 to 130.5 mg/dl) and remained at a normal range in the other eight patients (ranging from 150 to 450 mg/dl). Abnormal electroencephalogram (EEG) activities included slow background activity and epileptic patterns. Abnormal signals in the bilateral hippocampus were detected by magnetic resonance imaging (MRI) in three patients presenting cognitive disturbance. In one patient who had limbic encephalitis, increased metabolism of bilateral basal ganglia and the mesial temporal lobe was revealed by PET-CT. Eleven of 15 patients receiving immunotherapy experienced varying degrees of improvement. Relapse occurred in four of 25 patients (4/25) after 2 months.ConclusionCASPR-antibody-mediated autoimmune encephalitis is characterized by diverse clinical manifestations. The most prominent conclusion revealed by this retrospective analysis is the involvement of both central and peripheral nerve systems, as well as a lower relapse rate, a good response to immunotherapy, and favorable short-term prognosis after treatment was also demonstrated. Besides, additional work is necessary to evaluate the long-term prognosis.

Impact of Hyperbaric Oxygen Therapy on Cognitive Functions: a Systematic Review

Hyperbaric oxygen therapy (HBOT) is a modality of treatment in which patients inhale 100% oxygen inside a hyperbaric chamber pressurised to greater than 1 atmosphere. The aim of this review is to discuss neuropsychological findings in various neurological disorders treated with HBOT and to open new perspectives for therapeutic improvement. A literature search was conducted in the MEDLINE (via PubMed) database from the inception up 10 May 2020. Eligibility criteria included original articles published in English. Case studies were excluded. Full-text articles were obtained from the selected studies and were reviewed on the following inclusion criteria (1) performed cognitive processes assessment (2) performed HBOT with described protocol. Two neuropsychologists independently reviewed titles, abstracts, full texts and extracted data. The initial search retrieved 1024 articles, and a total of 42 studies were finally included after applying inclusion and exclusion criteria. The search yielded controversial results with regard to the efficiency of HBOT in various neurological conditions with cognitive disturbance outcome. To the best of our knowledge this is the first state-of-the art, systematic review in the field. More objective and precise neuropsychological assessment methods are needed to exact evaluation of the efficacy of HBOT for neuropsychological deficits. Future studies should widen the assessment of HBOT effects on different cognitive domains because most of the existing studies have focussed on a single process. Finally, there is a need for further longitudinal studies.

Celecoxib in a Preclinical Model of Repetitive Mild Traumatic Brain Injury: Hippocampal Learning Deficits Persist with Inflammatory and Excitotoxic Neuroprotection

Repetitive mild traumatic brain injuries (mTBIs) contribute to inflammation-induced neurodegeneration. Cycloxygenase (COX) enzymes produce inflammatory cytokines that influence the microglia response to neurotrauma. Celecoxib is a selective COX-2 inhibitor that is prescribed in some conditions of mTBI to alleviate symptoms of concussion, and has shown benefits in neurodegenerative conditions. We investigated molecular pathways of neuroinflammation in response to celecoxib treatment in a mouse model of repetetive mTBI. Fifteen mTBIs were delivered over 23 days in adult male C57BL/6J mice in one of four groups (control, celecoxib without impact, celecoxib with impact, and vehicle with impact). Cognitive function was assessed at 48 h and three months following the final mTBI. Morris Water Maze testing revealed impaired hippocampal spatial learning performance in the celecoxib treatment with the impact group compared to the vehicle with impact control in the acute phase, with celecoxib treatment providing no improvement compared with the control at chronic testing; mRNA analysis of the cerebral cortex and hippocampus revealed expression change, indicating significant improvement in microglial activation, inflammation, excitotoxicity, and neurodegeneration at chronic measurement. These data suggest that, in the acute phase following injury, celecoxib protected against neuroinflammation, but exacerbated clinical cognitive disturbance. Moreover, while there was evidence of neuroprotective alleviation of mTBI pathophysiology at chronic measurement, there remained no change in clinical features.

The role of epigenetic modifications in Alzheimer’s disease

Aging is the primary risk factor for various neurodegenerative diseases, including Alzheimer’s disease (AD), which is the most frequent form of Dementia. AD is progressive neurodegenerative disease with abnormal protein production, inflammation and memory deterioration. The main clinical manifestations of this illness are cognitive disturbance and memory deficit. Abnormal of beta-amyloid (Aβ), neurofibrillary tangles (NFTs) and tau deposition are the most common findings pathology in this disease. Recent studies indicate that epigenetic modifications strongly correlate in developing these pathology and disease progression. The hallmarks of epigenetic modifications are DNA (deoxyribonucleic acid) methylation, histone modifications, chromatin remodeling and ncRNA (non-coding ribonucleic acid) expressions. This review aims to explain the potential mechanisms of epigenetic modifications associate with this disease. The general conclusion of this review is that epigenetic modifications play an ultimate role in AD and there are potential biomarkers of AD and future novel treatment of AD based on epigenetics.

ENSEFALITIS ANTIRESEPTOR NMDA: ENSEFALITIS DENGAN GEJALA AWAL PSIKOSIS

ANTI-NMDA RECEPTOR ENCEPHALITIS: ENCEPHALITIS PRESENTING WITH EARLY PSYCHOSIS SYMPTOMSABSTRACTAnti N-methyl-D-aspartate (NMDA) receptor encephalitis is seldom found in Indonesia. The atypical initial presentation of psychosis and cognitive disturbance results in underdiagnosed, or even undiagnosed case. This report described a 12-year-old girl presenting with initial psychiatric symptom followed by seizure and oropharyngeal dystonia. Anti-NMDA receptor antibody test carried out on both serum and cerebrospinal fluid (CSF) were positive and no other pathogen was detected in the CSF. Clinical improvement was seen following the third day of methylprednisolone administration. This case demonstrates the importance of considering anti-NMDA receptor encephalitis or the other autoimmune encephalitis as the differential of infective encephalitis. Anti-NMDA receptor antibody test, which can already be performed in Indonesia, will greatly guide to the definitive diagnosis.Keywords: Encephalitis, NMDA, oropharyngeal dystonia, psychiatricABSTRAKEnsefalitis antireseptor N-metil-D-aspartat (NMDA) masih jarang ditemukan di Indonesia. Gejala awal yang tidak khas berupa psikosis dan gangguan kognitif menyebabkan keterlambatan diagnosis, atau bahkan tidak terdiagnosis, ensefalitis jenis ini. Berikut dilaporkan kasus seorang perempuan 12 tahun dengan gejala awal berupa gejala psikiatrik yang diikuti dengan kejang dan munculnya distonia orofaring. Pemeriksaan antibodi antireseptor NMDA pada serum dan cairan serebrospinal (CSS) positif dan tidak ditemukan patogen lain pada pemerikaan CSS. Perbaikan klinis terlihat setelah pemberian metilprednisolon selama 3 hari. Kasus ini memperlihatkan pentingnya mempertimbangkan diagnosis ensefalitis antireseptor NMDA atau ensefalitis autoimun lainnya sebagai diagnosis banding pada kasus ensefalitis infeksi. Oleh karena itu, pemeriksaan antibodi antireseptor NMDA yang telah dapat dilakukan di Indonesia akan sangat membantu proses penegakan diagnosis.Kata kunci: Distonia orofaring, ensefalitis, NMDA, psikiatrik

Systematic Review of the Kynurenine Pathway and Psychoneurological Symptoms Among Adult Cancer Survivors

The co-occurrence of multiple psychoneurological symptoms, including pain, sleep disturbance, fatigue, depression, anxiety, and cognitive disturbance among adult cancer survivors led us to question which common biological mechanisms are shared among these conditions. Variances in tryptophan (Trp) levels and downstream metabolites of the kynurenine (Kyn) metabolic pathway are known to affect immune response and psychoneurological symptoms. The objective of this systematic review was to help us (a) better understand the role of the Kyn pathway in psychoneurological symptoms among adult cancer survivors and (b) identify common significant biomarkers across psychoneurological symptoms as a guide for future research. Some evidence has shown that decreased Trp levels and increased Kyn, Trp/Kyn ratio, and kynurenic acid/Trp ratio in parallel with immune activation are correlated with some psychoneurological symptoms among people undergoing cancer treatment, although discrepancies exist between studies. Kyn pathway activation could also be associated with psychoneurological symptoms among adult cancer survivors, but further research is needed to confirm its exact etiological role with respect to psychoneurological symptoms.