METHODS: Twenty-eight patients with severe TBI (GCS ≤ 8, three patients had initial GCS = 9-10, but rapidly deteriorated to ≤8) were recruited. CSF was collected from admission to day 5 post-injury. TRP, kynurenine (KYN), kynurenic acid (KYNA), QUIN, anthranilic acid (AA) and 3-hydroxyanthranilic acid (3HAA) were measured in CSF. The Glasgow Outcome Scale Extended (GOSE) score was assessed at 6 months post-TBI. Post-mortem brains were obtained from the Australian Neurotrauma Tissue and Fluid Bank and used in qPCR for quantitating expression of KP enzymes (indoleamine 2,3-dioxygenase-1 (IDO1), kynurenase (KYNase), kynurenine amino transferase-II (KAT-II), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3HAO) and quinolinic acid phosphoribosyl transferase (QPRTase) and IDO1 immunohistochemistry.
RESULTS: In CSF, KYN, KYNA and QUIN were elevated whereas TRP, AA and 3HAA remained unchanged. The ratios of QUIN:KYN, QUIN:KYNA, KYNA:KYN and 3HAA:AA revealed that QUIN levels were significantly higher than KYN and KYNA, supporting increased neurotoxicity. Amplified IDO1 and KYNase mRNA expression was demonstrated on post-mortem brains, and enhanced IDO1 protein coincided with overt tissue damage. QUIN levels in CSF were significantly higher in patients with unfavourable outcome and inversely correlated with GOSE scores.
CONCLUSION: TBI induced a striking activation of the KP pathway with sustained increase of QUIN. The exceeding production of QUIN together with increased IDO1 activation and mRNA expression in brain-injured areas suggests that TBI selectively induces a robust stimulation of the neurotoxic branch of the KP pathway. QUIN's detrimental roles are supported by its association to adverse outcome potentially becoming an early prognostic factor post-TBI.
METHODS: PubMed and Scopus electronic databases were searched based on the guidelines established by PRISMA to obtain studies investigating the integration of DTI in intracranial RT/RS treatment planning. References and citations from Google Scholar were also extracted. Eligible studies were extracted for information on changes in dose distribution, treatment parameters, and outcome after DTI integration.
RESULTS: Eighteen studies were selected for inclusion with 406 patients (median study size, 19; range: 2-144). Dose distribution, with or without DTI integration, described changes of treatment parameters, and the reported outcome of treatment were compared in 12, 7, and 10 studies, respectively. Dose distributions after DTI integration improved in all studies. Delivery time or monitor unit was higher after integration. In studies with long-term follow-up (median, >12 months), neurologic deficits were significantly fewer in patients with DTI integration.
CONCLUSIONS: Integrating DTI into RT/RS treatment planning improved dose distribution, with higher treatment delivery time or monitor unit as a potential drawback. Fewer neurologic deficits were found with DTI integration.
MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify eligible reports on cognitive changes following PT of PBT according to PRISMA guidelines. Reports were extracted for information on demographics and cognitive outcomes. Then, they were systematically reviewed based on three themes: (1) comparison with photon therapy, (2) comparison with baseline cognitive measures, to population normative mean or radiotherapy-naïve PBT patients and (3) effects of dose distribution to cognition.
RESULTS: Thirteen reports (median size (range): 70 (12-144)) were included. Four reports compared the cognitive outcome between PBT patients treated with proton to photon therapy and nine compared with baseline/normative mean/radiotherapy naïve from which two reported the effects of dose distribution. Reports found significantly poorer cognitive outcome among patients treated with photon therapy compared with proton therapy especially in general cognition and working memory. Craniospinal irradiation (CSI) was consistently associated with poorer cognitive outcome while focal therapy was associated with minor cognitive change/difference. In limited reports available, higher doses to the hippocampus and temporal lobes were implicated to larger cognitive change.
CONCLUSION: Available evidence suggests that PT causes less cognitive deficits compared with photon therapy. Children who underwent focal therapy with proton were consistently shown to have low risk of cognitive deficit suggesting the need for future studies to separate them from CSI. Evidence on the effect of dose distribution to cognition in PT is yet to mature.
METHOD: Seven volunteer post-call doctors were recruited to go through an EEG recording before and after their on-call rotation while at rest and subsequently while carrying out Stroop Test, putting their cognitive function at work.
RESULTS: The doctors have worked up to 33 hours in a row and have had sleep of an average of 1.5 hours. It is found that during task there is a statistically significant increase in theta (frontal and occipital regions) and beta (occipital region) band power while at task post-call. Alpha band power is increased in the frontal and reduced in other regions. Correlation with Stroop Test results indicated that those who have higher alpha, beta, and lower relative theta powers at the frontal region at post-call rest have higher percentage of correct congruent trials.
CONCLUSION: The results objectively imply that these fatigue doctors are under more strain while carrying out a task and corresponds to the implicated regions of brain stimulated by the task accordingly.