Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis.

BACKGROUND AND PURPOSE: Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. METHODS: Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. RESULTS: The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. CONCLUSION: In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability.

Perifocal and remote blood-brain barrier disruption in cortical photothrombotic ischemic lesion and its modulation by the choice of anesthesia.

We assessed blood-brain barrier (BBB) disruption in early stage of photothrombotic focal cerebral ischemia in the rat. We specifically looked for contralateral changes in BBB permeability and tested the influence of two anesthetics on the results. Adult Wistar rats were randomly anesthetized with pentobarbital (PB) or ketamine-xylazine (KX). Rats received intravenously (i.v.) Rose Bengal followed by Evans Blue (EB). Stereotactically defined spots on denuded skull were irradiated by laser (532 nm) for 18 min. Twenty four hours later, rats were killed, brains perfused, fixated, sectioned and slices analyzed by fluorescence microscopy. Volume of necrosis and volume of EB-albumin extravasation were calculated. Evidence of BBB breakdown in remote brain areas was sought and compared to sham handled controls. BBB disruption was consistently present, frequently with EB-albumin accumulating cells. Total lesion volume did not significantly differ among groups (TLVPB=9.4±1.3 mm³ vs. TLVKX=8.3±2.1 mm³); same was true for the volume of necrosis (NVPB=5.1±0.7 mm³ vs. NVKX=6.3±1.9 mm³). However, volume of EB-albumin extravasation area was significantly smaller in KX group (EBEVPB=4.3±0.8 mm³ vs. EBEVKX=2.0±0.5 mm³; p=0.0293). Median background EB-fluorescence signal density was higher in PB group (p<0.0001). Furthermore, regional increase in EB-fluorescence was found in two animals in PB group. Our study shows that anesthesia with NMDA-antagonist ketamine and α2-adrenergic agonist xylazine may reduce BBB breakdown in photothrombosis. Pentobarbital anesthesia lead to increased BBB permeability in the contralateral hemisphere.

The MRI volumetry of the posterior fossa and its substructures in trigeminal neuralgia: a validated study.

PURPOSE: Our aim was to determine whether the anatomical configuration of the posterior fossa and its substructures might represent a predisposition factor for the occurrence of clinical neurovascular conflict in trigeminal neuralgia (TN). METHODS: We used MRI volumetry in 18 patients with TN and 15 controls. The volume of the pontomesencephalic cistern, Meckel's cave and the trigeminal nerve on the clinical and non-affected sides was compared. The reliability has been assessed in all measurements. RESULTS: The posterior fossa volume was not different in the clinical and control groups; there was no difference between the affected and non-affected sides when measuring the pontomesencephalic cistern and Meckel's cave volume either. The volume of the clinically affected trigeminal nerve was significantly reduced, but with a higher error of measurement. CONCLUSIONS: We did not find any association between the clinical neurovascular conflict (NVC) and the size of the posterior fossa and its substructures. MRI volumetry may show the atrophy of the affected trigeminal nerve in clinical NVC.

Influence of melatonin pretreatment and preconditioning by hypobaric hypoxia on the development of cortical photothrombotic ischemic lesion.

Photothrombotic model of ischemia (PT) is based on free radical-mediated endothelial dysfunction followed by thrombosis. Free radicals are also involved in hypoxic preconditioning. We tested the sensitivity of PT to preconditioning with hypobaric hypoxia and to pretreatment with melatonin. In adult Wistar rats, after intravenous application of Rose Bengal, a stereo-tactically defined spot on the denuded skull was irradiated by a laser for 9 min. The first experimental group underwent hypobaric hypoxia three days before irradiation. In the second experimental group, melatonin was applied intraperitoneally one hour before irradiation. Three days after irradiation, animals were sacrificed, the brains perfused, and stained with TTC. Ischemic lesions were divided into grades (I, II, III). In the control group (where no manipulation preceded photothrombosis), most animals displayed deep damage involving the striatum (grade III). The group pre-exposed to hypoxia showed similar results. Only 28.57 % of the melatonin pretreated animals exhibited grade III lesions, and in 57.14 % no signs of lesions were detected. Pre-exposure to hypoxia was not protective in our model. Pretreatment with melatonin lead to a significant reduction of the number of large ischemic lesions. This result is probably caused by protection of endothelial cells by melatonin.