Multimodal Regional Brain Monitoring of Tissue Ischemia in Severe Cerebral Venous Sinus Thrombosis.

BACKGROUND: Comatose critically ill patients with severe diffuse cerebral venous thrombosis (CVT) are at high risk of secondary hypoxic/ischemic insults, which may considerably worsen neurological recovery. Multimodal brain monitoring (MBM) may therefore improve patient care in this setting, yet no data are available in the literature. METHODS: We report two patients with coma following severe diffuse CVT who underwent emergent invasive MBM with intracranial pressure (ICP), brain tissue oximetry (PbtO2), and cerebral microdialysis (CMD). Therapy of CVT consisted of intravenous unfractionated heparin (UFH), followed by endovascular mechanical thrombectomy (EMT). EMT efficacy was assessed continuously at the bedside using MBM. RESULTS: Despite effective therapeutic UFH (aPTT two times baseline levels in the two subjects), average CMD levels of lactate and glucose in the 6 h prior to EMT displayed evidence of regional brain ischemia. The EMT procedure was associated with a rapid (within 6 h) improvement in both CMD lactate (6.42 ± 0.61 4.89 ± 0.55 mmol/L, p = 0.02) and glucose (0.49 ± 0.17 vs. 0.96 ± 0.32 mmol/L, p = 0.0005). EMT was also associated with a significant increase in PbtO2 (22.9 ± 7.5 vs. 30.1 ± 3.6 mmHg, p = 0.0003) and a decrease in CMD glutamate (12.69 ± 1.06 vs. 5.73 ± 1.76 µmol/L, p = 0.017) and intracranial pressure (ICP) (13 ± 4 vs. 11 ± 4 mmHg (p = 004). Patients did not require surgical decompression, regained consciousness, and were discharged from the hospital with a good neurological outcome (modified Rankin score 3 and 4). CONCLUSIONS: This study illustrates the potential utility of continuous bedside MBM in patients with coma after severe brain injury, irrespective of the primary acute cerebral condition. Despite adequate ICP and PbtO2 control, the presence of CMD signs of regional brain cell ischemia triggered emergent EMT to treat CVT, which was associated with a significant and clinically relevant improvement of intracerebral physiology.

A study of ER stress in rat model of cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is a rare form of stroke. The role of endoplasmic reticulum (ER) stress markers is well documented in arterial stroke but has not been evaluated in venous stroke. The present study has been undertaken to investigate the role of ER stress in rodent model of CVST. For inducing CVST, a cranial window was made to expose superior sagittal sinus (SSS). A strip of filter paper soaked with 40% ferric chloride was applied on exposed cranial window while in sham operated control 0.9% saline was used. Clinical evaluations were done on day 1, 2, and 7 for neurological deficit. Rota rod test and brain infarction volume were also measured. Brain tissue was collected from infarcted portion for further analysis using real time polymerase chain reaction and western blot technique for ER stress markers. Augmented expression of ER stress markers and up regulation of apoptotic genes were found in infarcted tissue. These markers improved on day 7. It is concluded that ER markers are up regulated at an early stage of CVST and may be important in pathophysiology.

Acquired and congenital risk factors associated with cerebral venous sinus thrombosis.

The mechanistic paradigm underlying venous thrombosis at atypical locations stems from the observation that most events occur as a result of pathology of the organ system drained by the involved venous segment. Cerebral venous sinus thrombosis stands apart as an exception to this general rule. Although brain and sinus pathology are well established causes, these combined variables account for approximately one third of cases. The marked female preponderance and strong association with gender specific risk factors including hormonal manipulation, pregnancy and the puerperium are particularly notable. Factor V Leiden and prothrombin G20210A mutations and hyperhomocysteinemia represent important risk factors particularly when combined with acquired variables. The association with oral contraception use and the prothrombin G20210A gene mutation may offer insights into the anatomic predilection for cerebral venous sinus involvement as compared to venous thrombosis of the lower extremities. The intent of this review is to summarize the corporate literature of both acquired and congenital risk factors associated with cerebral venous sinus thrombosis in order to assist clinicians in their search for underlying mechanisms and to risk stratify patients for anticoagulation treatment duration and risk of recurrent thrombosis.

Hemodynamic and metabolic changes in a patient with cerebral venous sinus thrombosis: evaluation using O-15 positron emission tomography.

The cerebral hemodynamics and oxygen metabolism before and after the recanalization of the occluded sinus were evaluated using O-15 positron emission tomography (PET) scanning in a 21-year-old woman with superior sagittal sinus thrombosis. During the initial presentation, there was increased regional cerebral blood volume (rCBV) in the left frontal and parietal lobes with moderately increased rCBV in the right parietal lobe. Recanalization of the occluded sinus resulted in a normalization of elevated rCBV in the frontal and parietal lobes and improvements of rCBF and regional cerebral metabolic rate for oxygen in the occipital lobe. Clinical improvement after recombinant tissue plasminogen activator therapy was accompanied by restoration of cerebral hemodynamics and oxygen metabolism, although magnetic resonance venography showed only partial recanalization of the occluded sinus. PET evaluation of the cerebral hemodynamics and oxygen metabolism may be of value in gaining further insight into pathophysiological characteristics of human cerebral venous sinus thrombosis.

Microvascular damage following experimental sinus-vein thrombosis in rats.

We evaluated effects of thrombosis of the superior sagittal sinus, its bridging and cortical veins (SVT) on the cerebral microvasculature in rats. Cryosections of brains ( n=7) were examined for venous infarction and microvascular basal lamina damage 3 h after SVT by immunohistochemical staining of microtubule-associated protein 2 and collagen type IV. Microvessels in the infarctions showed a decrease in the number (23.5+/-6.1%, P<0.002) and the total area (24.9+/-6.5%, P<0.011) of collagen type IV-positive vessels in contrast to control areas (21.7+/-12.4%, P<0.007; and 26.3+/-15.1%, P<0.026 in contrast to control areas of unoperated animals). This study showed a significant alteration of the cerebral microvasculature in SVT, which might contribute to edema and hemorrhagic transformation.

Cerebral venous sinus thrombosis in minimal change nephrotic syndrome.

Three cases of cerebral venous sinus thrombosis (CVST) occurring in patients with minimal change nephrotic syndrome (MCNS) are described. Personality change in two of these patients was wrongly attributed to steroid therapy prior to the discovery of the CVST. In addition, von Willebrand factor (vWF) levels were grossly elevated in one patient, during a previous relapse of MCNS, prior to developing CVST, and may be a useful prognostic tool in predicting thrombotic events in nephrotic patients.