Robin Bhatia

Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain

OBJECTIVE To test the co-occurrence and interrelation of ictal activity and cortical spreading depressions (CSDs) - including the related periinfarct depolarisations in acute brain injury caused by trauma, and spontaneous subarachnoid and/or intracerebral haemorrhage. METHODS 63 patients underwent craniotomy and electrocorticographic (ECoG) recordings were taken near foci of damaged cortical tissue for up to 10 days. RESULTS 32 of 63 patients exhibited CSDs (5-75 episodes) and 11 had ECoGraphic seizure activity (1-81 episodes). Occurrence of seizures was significantly associated with CSD, as 10 of 11 patients with seizures also had CSD (p=0.007, 2-tailed Fishers exact test). Clinically overt seizures were only observed in one patient. Each patient with CSD and seizures displayed one of four different patterns of interaction between CSD and seizures. In four patients CSD was immediately preceded by prolonged seizure activity. In three patients the two phenomena were separated in time: multiple CSDs were replaced by ictal activity. In one patient seizures appeared to trigger repeated CSDs at the adjacent electrode. In 2 patients ongoing repeated seizures were interrupted each time CSD occurred. CONCLUSIONS Seizure activity occurs in association with CSD in the injured human brain. SIGNIFICANCE ECoG recordings in brain injury patients provide insight into pathophysiological mechanisms, which are not accessible by scalp EEG recordings.

Spreading depolarizations cycle around and enlarge focal ischaemic brain lesions

How does infarction in victims of stroke and other types of acute brain injury expand to its definitive size in subsequent days? Spontaneous depolarizations that repeatedly spread across the cerebral cortex, sometimes at remarkably regular intervals, occur in patients with all types of injury. Here, we show experimentally with in vivo real-time imaging that similar, spontaneous depolarizations cycle repeatedly around ischaemic lesions in the cerebral cortex, and enlarge the lesion in step with each cycle. This behaviour results in regular periodicity of depolarization when monitored at a single point in the lesion periphery. We present evidence from clinical monitoring to suggest that depolarizations may cycle in the ischaemic human brain, perhaps explaining progressive growth of infarction. Despite their apparent detrimental role in infarct growth, we argue that cycling of depolarizations around lesions might also initiate upregulation of the neurobiological responses involved in repair and remodelling.

Persisting Depletion of Brain Glucose following Cortical Spreading Depression, despite Apparent Hyperaemia: Evidence for Risk of an Adverse Effect of Leão's Spreading Depression

Rapid sampling microdialysis (rsMD) directed towards the cerebral cortex has allowed identification of a combined time-series signature for glucose and lactate that characterizes peri-infarct depolarization in experimental focal ischaemia, but no comparable data exist for ‘classical’ cortical spreading depression (CSD) associated with hyperaemia in the normally perfused brain. Here, we examined the rsMD responses of dialysate glucose and lactate to five hyperaemic spreading depressions induced with intracortical microinjections, typically of 1 mol/L KCl, in open-skull preparations in five cats under chloralose anaesthesia. Depolarization was verified with microelectrodes, and laser speckle flowmetry was used to examine propagation of the events and perfusion responses near the MD probe. Ten minutes after depolarization, dialysate glucose fell and lactate rose by 28% and 58% respectively. There was no recovery of dialysate glucose 30 mins after depolarization. Mean baseline indicative cerebral blood flow was 25.5 ± 4.1 mL/100 g/min and mean maximum hyperaemic increase was by 29.6 ± 6 mL/100 g/min; hyperaemia remained present 30 mins after CSD. As CSD events are repetitive, frequent, and often clustered temporally in human acute brain injury, these results indicate a high risk of depletion of extracellular glucose in association with depolarization events of a pattern previously thought to be largely benign.

Application Of Rapid-Sampling, Online Microdialysis To The Monitoring Of Brain Metabolism During Aneurysm Surgery

OBJECTIVE: To introduce rapid-sampling microdialysis for the early detection of adverse metabolic changes in tissue at risk during aneurysm surgery. METHODS: A microdialysis catheter was inserted under direct vision into at-risk cortex at the start of surgery. This monitoring was sustained throughout the course of the operation, during which intraoperative events, for example, temporary arterial occlusion or lobe retraction, were precisely documented. A continuous online flow of dialysate was fed into a mobile bedside glucose and lactate analyser. This comprises flow-injection dual-assay enzyme-based biosensors capable of determining values of metabolites every 30 seconds. RESULTS: Eight patients underwent clipping or wrapping of intracranial aneurysms and were monitored. Time between events and detection: 9 minutes. Mean change in metabolite value ± standard deviation: temporal lobe retraction lactate, +656 ± 562 &mgr;mol/L (n = 7, P < 0.05); glucose, -123 ± 138 &mgr;mol/L (n = 6, P = 0.08). Glucose intravenous bolus infusion glucose, +512 ± 244 &mgr;mol/L (n = 5, P < 0.01); peak at mean time after bolus, 16 minutes. Temporary proximal clip lactate, +731 ± 346 &mgr;mol/L (n = 6, P < 0.01); glucose, -139 ± 96 &mgr;mol/L (n = 5, P < 0.05); mean clip time, 8.6 minutes. CONCLUSION: The technique detects changes 9 minutes after intraoperative events occur (limited only by probe-to-sensor tubing length and dialysate flow rate). This provides reliable information to the surgeon and anesthetist promptly. It is a useful method for monitoring glucose and lactate in dialysate, particularly when rapid, transient changes in brain analyte levels need to be determined and the alternative offline methodology would be inadequate.

The application of near-infrared oximetry to cerebral monitoring during aneurysm embolization: a comparison with intraprocedural angiography.

Near-infrared spectroscopy (NIRS) has been used to monitor regional cerebral oxygen saturation (rSO2) in patients at risk of cerebral desaturation during surgical and neurointerventional procedures. However, the quantitative capabilities of the method have been questioned, as has its validation compared with jugular bulb oximetry. Here, we compare NIRS data acquired during coil embolization procedures with incidence of vasospasm as detected from angiography. Thirty-two subarachnoid hemorrhage patients underwent embolization. Bilateral SomaSensor strips (Invos 4100, Somanetics) were affixed to the forehead at constant anatomic positions, avoiding frontal sinuses and scalp hair. Mean arterial pressure, SaO2, end-tidal pCO2, temperature and Hb were held within a narrow range during the procedure. Ipsilateral angiography was performed every 10 to 15 minutes. An independent neuroradiologist classified any vasospasm in the parent vessel as mild (25% baseline), moderate (50%), severe (75%), or total (100%). Of all, 15/32 (46.9%) patients developed spasm; in 2 it was severe or total. There was no significant association between World Federation of Neurological Surgeons grade and baseline rSO2 signal (either ipsilateral or contralateral to the side of the aneurysm) (P=0.598). There was no significant association between side of aneurysm and baseline rSO2 signal (P=0.243). However, episodes of angiographic spasm were strongly associated with reduction in trend ipsilateral NIRS signal (P<0.001); furthermore, the degree of spasm (especially more than 75% vessel diameter reduction) was associated with a greater reduction in same-side NIRS signal (P<0.001) (2-level random effects regression model, Stata 8.2, Stata Corp, TX). NIRS may have a useful role to play in the detection of cerebral desaturation secondary to vasospasm during neuroendovascular procedures.

Clusters of cortical spreading depression are the electrocorticographic correlate of delayed ischemic neurological deficits after subarachnoid hemorrhage

difference higher than 1.86 ms. Method: Thirty-eight patients with the clinical suspect of a piriform muscle-syndrome were examined. The test if performed in belly position, using the same experimental setting as known from the H-reflex, the leg is on time inclined and other time stretched. Results: None of the examined patients met the criteria of a positive FAIR-test with a H-reflex latency lengthening higher than 1.86 ms. 5% of the patients showed an amplitude decrease of more than 50%, 10% of the patients showed less than 50% decrease. Another 15% revealed no amplitude changes at all. Due to low amplitude or missing H-answer 55% of the patients were not FAIR-tested. Conclusion: Our data suggested that latency differences in FAIR-test are not suitable in detecting a piriform musclesyndrome.