Table 1.

Clinical observational studies of SDs following SAH

Study design	N of SAH patients	Outcomes assessed	Major findings	Ref
SDs and outcomes
Prospective multicenter study	18	Incidence and timing of SDs and DIND in patients with SAH	SDs occurred in 72% of patients with SAH. Patients with depression periods lasting > 10 min had worse outcomes, and all those with depression periods > 60 min had delayed infarctions	[18] Dreier et al., 2006
Prospective preliminary	6	SD cluster	Persistent depression during SD clusters suggests progressive damage	[19] Oliveira-Ferreira et al., 2010
Prospective case series	13	If SDs and DCI are abolished when vasospasm is not present	The cases that showed DCI in absence of angiographic VS have been reported. The number of SDs was significantly higher in these patients than in those without DCI	[20] Woitzik et al., JCBFM 2012
Prospective	25	SD, spreading convulsions, and epileptogenesis	SDs with prolonged depressions (high TDDD) were linked to worse outcome after SAH. Early SDs showed a significant association with the development of late epilepsy in patients with SAH	[21] Dreier et al., 2012
Pilot study	6	Duration of depolarization as measured by the negative DC shift in ECoG	Threshold of duration of a DC shift which distinguishes a normally distributed class of short CSDs with spreading hyperemia from prolonged CSDs with initial spreading ischemia is 3-3.5 min	[22] Hartings et al., 2013
Prospective	33 4 of the 33 cases were previously reported in a pilot study on correlates of SD in scalp EEG recordings (Drenckhahn et al., 2012)	Monitor SDs with an oxygen sensor	SDs with prolonged depressions (high TDDD) were linked to worse outcome after SAH	[23] Winkler et al., 2017
Prospective	23 8 cases were previously reported (Winkler et al., 2017)	Occurrence of spreading depolarizations and cortical lesions evaluated using MRI	The occurrence of isoelectric SDs and prolonged depression periods is related not only to DCI but also to the early brain injury after SAH	[24] Hartings et al., 2017
Prospective	11 7 cases were previously reported (Dreier et al., 2012; Winkler et al., 2017)	Occurrence of spreading depolarizations, negative ultraslow potential, and cortical lesions evaluated using MRI	The negative ultraslow potential is the electrophysiological correlate of infarction in the human cerebral cortex and a neuromonitoring-detected medical emergency	[25] Luckl et al., 2018
Observational	54	Occurrence of spreading depolarizations and cortical lesions evaluated using CT scan	Early focal brain injury after SAH is associated with early SDs SDs are a biomarker of focal brain lesions	[17] Eriksen et al., 2019
Mechanisms of injury
Prospective multicenter study	13	Inverse hemodynamic response occurs in human SAH brain	Spreading ischemia in patients. SDs were associated with either physiological, absent, or inverse rCBF responses	[26] Dreier et al., 2009
Prospective	9	If SDs can influence oxygen availability in patients with SAH	SD clusters can reduce oxygen availability and thereby promote DCI	[27] Bosche et al., 2010
Prospective	17	The dynamics of glucose, lactate, pyruvate, and glutamate using microdialysis during the occurrence of SDs in patients with spontaneous SAH	SD clusters are related to metabolic changes suggestive of ongoing secondary damage	[28] Sakowitz et al., 2013
Prospective	1	Continuous on-line microdialysis to observe the effects of spreading depolarizations on brain potassium, glucose, and lactate levels	Spreading depolarizations led to an increase in potassium, glucose, and lactate levels.	[16] Rogers et al. 2017
Prospective	21	Tested if episodes of spreading depolarization (SD) are reflected in compromised levels of extracellular glucose monitored by bedside microdialysis	The occurrence of SD was not linked to local deviations of extracellular glucose concentrations	[29] Sarrafzadeh et al., 2013
Case report	1	Monitor SDs with an intraparenchymal probe for combined intracranial pressure (ICP) and NIRS monitoring	3 out of 6 clustered SDs were associated with the hypoxic response, whereas all single SDs were associated with the hyperoxic response.	[30] Seule et al., 2015
Case report	1	Simultaneous electrocorticography and monitoring of the pressure reactivity index	Inverse neurovascular coupling to spreading depolarization might be related to impaired cerebrovascular autoregulation	[31] Sugimoto et al., 2016
Detection methodology
Prospective	5	If slow potential change or depression of spontaneous activity can be recorded using scalp EEG	Correlates of SD were identified in continuous scalp EEG recordings when performed simultaneously with subdural ECoG	[32] Drenckhahn et al., 2012
Prospective	2 SAH 6 TBI	Monitor SDs with intraparenchymal electrode array	SD can be detected using intracortical electrodes, opening the way for electrode insertion via burr hole	[33] Jeffcote et al., 2014
Retrospective and explorative analysis	SAH 20 Total 46	Frequency bands of electrocorticographic (ECoG) recordings were investigated with regard to SDs	Beta frequency might help to predict occurrence of SDs	[34] Hertle et al., 2016
Prospective observational studies	SAH 8 Total 27	Direct current-coupled recordings to detect SDs	Direct current electrocorticography should be used for SD detection	[35] Hartings et al., 2017