Table 2: Self-controlled clinical trials (quasi experiment) of feasibility and efficacy of hypothermic intervention for stroke.

Reference Study designInterventionPatientsHypothermia inductionImpact on stroke severityMortality

[29] a Nonrandomized, open label, self-controlled, single-center (quasi-experiment)Mild hypothermia induced by external cooling within 4 to 24 hours of symptoms onset. Target temperature (33°C)25 patients with severe ischemic stroke, median SSS 24, mean GCS 9Target temperature reached in 3.5 to 6.2 h.
Does not clear report the % of patients reaching target temperature, apparently all of them.
Mean initial ICP mmHg and reduced to mmHg during hypothermia
Surviving patients displayed SSS 29 after 4 weeks and 38 three months after stroke
11/25 patients died

[28]bNonrandomized, open label, self-controlled, single-center (quasi-experiment)Mild hypothermia induced by external cooling within 6 hours of symptoms onset.
Target temperature (33°C)
20 patients with severe ischemic stroke, median SSS 27, mean GCS 9All patients reached target temperature in about 5-6 h.Mean SSS was , mean mRS 3 and mean BI 65 four weeks after stroke
ICP decreased with initiation of hypothermia
8/20 patients died

[27]Nonrandomized, open label, self-controlled, single-center (quasi-experiment)Mild hypothermia induced by external cooling as soon as possible (no mention of time delay after symptoms onset). Target temperature (33-34°C)6 patients with severe ischemic strokeMean duration of hypothermia 63.5 h Does not clear report the % of patients reaching target temperature, apparently all of them.Decreased CMRO2, transiently reduced CBF and controlled ICP2/6 patients died of intractable intracranial hypertension

[25]Nonrandomized, open label, self-controlled, single-center (quasi-experiment)Mild hypothermia induced by endovascular device within 3 h of symptoms onset Target temperature (33-34°C)10 patients with acute ischemic stroke NIHSS 4–12Temperature dropped from °C by a maximum of °C ( ) at 52±16 min after hypothermia induction.
Does not clear report the % of patients reaching target temperature, apparently all of them.
NIHSS at discharge (1) improved compared to admission (5.5) ( )NR

[26]Nonrandomized, open label, self-controlled, single-center (quasi-experiment)Mild hypothermia induced by external ( ) or intravascular ( ) cooling methods within 6 h of symptoms onset. Target temperature (33–34.5°C)18 acute stroke patients NIHSS 13 patients reached target temperature (mean latency 9h43, mean duration 19h48). 2 patients were not cooled due to catheter or machine failure.NIHSS 15 to 9 in 24 h
NIHSS 6 at discharge
2/18 patients died

(a) Published in Stroke. (b) Published in Acta Neurochirurgica Supplementum. BI: Barthel index; CBF: cerebral blood flow; CMRO2: cerebral metabolic rate of oxygen; GCS: Glasgow Come Scale; ICP: intracranial pressure; mRS: modified Rankin scale; NIHSS: NIH Stroke Scale; NR: not reported; SSS: Scandinavian Stroke Scale.