Thrombolysis for mild stroke

Table 1 Most commonly used definitions for mild stroke by literature

Based on baseline NIHSS	All patients with baseline NIHSS ≤ 3[6-9]
	All patients with baseline NIHSS ≤ 4[7,10]
	All patients with baseline NIHSS ≤ 5[4,11,12]
	All patients with baseline NIHSS ≤ 6[7,13]
	All patients with baseline NIHSS ≤ 9[14]
	All patients with a score 0 or 1 on every baseline NIHSS score item and normal consciousness[6,14]
Based on syndromes	All patients with a lacunar-like syndrome (presumed small vessel occlusive disease) such as pure sensory syndrome, pure motor hemiparesis, sensorimotor syndrome, ataxic hemiparesis, and dysarthria-clumsy hand syndrome[6,14]
	All patients with only motor deficits (can include dysarthria or ataxia) with or without sensory deficits. These patients can have only a combination of motor, coordination, and sensory deficits without any deficits in the spheres of language, level of consciousness, extinction or neglect, horizontal eye movements, or visual fields, deficits generally ascribed to larger territories of focal ischemia[6,14]
	All patients with baseline NIHSS in the lowest (least severe) quartile of severity (NIHSS ≤ 9), excluding all patients with aphasia, extinction, or neglect, or any points on the level-of-consciousness questions[6,14]
Based on imaging	Major stroke: A proximal cerebral artery occlusion on the CTA or MRA; if no occlusion, imaging evidence of significant parenchymal ischemia on NCCT or DWI[15]
	Minor stroke: all of the others except major stroke[15]

NIHSS: National Institutes of Health Stroke Scale; CTA: Computered tomography angiography; MRA: Magnetic resonance angiography; NCCT: Non-contrasted computered tomography; DWI: Diffusion-weighted imaging.

Table 2 Studies on thrombolysis in mild stroke

Ref.	Definition of mild stroke	Patients		Favorableoutcome(t-PA vs Placebo)	P	SICH(t-PA vs Placebo)	P
		rt-PA	Placebo
NINDS rt-PA Stroke Study Group[14]	Score ≤ 1 on each NIHSS item and normal consciousness	21	7	100% vs 86%	< 0.02	0% vs 0%	-
	Presumed small-vessel stroke	51	30	69% vs 60%	< 0.02	4% vs 0%	-
	Only motor deficits ± sensory deficits	220	219	61% vs 46%	< 0.02	3% vs 0.5%	-
	NIHSS score ≤ 9, minus all with aphasia, extinction/neglect, or any points on the level of consciousness questions	97	76	81% vs 74%	< 0.02	3% vs 0%	-
	NIHSS ≤ 9	99	78	82% vs 74%	< 0.02	3% vs 0%	-
Köhrmann et al[10]	NIHSS ≤ 4	32	-	94%	-	0%	-
Hassan et al[13]	NIHSS ≤ 6	27	24	92.6% vs 50%	< 0.03	3.7% vs 4.2%	1
Hassan et al[23]	NIHSS ≤ 10	52	98	74% vs 34%	< 0.009	2% vs 3%	-
1Steffenhagen et al[24]	NIHSS ≤ 5	78	16	74.7% vs 81.3%	0.75	2.6% vs -	0.572
2Khatri et al[25]	NIHSS ≤ 5	42	16	78.6% vs 81.3%	-	2.4% vs 0%	-
2Huisa et al[26]	NIHSS ≤ 5	59	74	57.6% vs 68.9%	0.871	5%	-
3Helsinki Stroke Thrombolysis Registry[7]	NIHSS 0-2	58	-	88%	-	0%	-
	NIHSS 3-4	194	-	86%	-	2.6%	-
	NIHSS 5-6	236	-	78%	-	2.1%	-
Greisenegger et al[27]	NIHSS ≤ 5	445	445	41% vs 29%	< 0.001	2.5% vs 0%	-
Urra et al28]	NIHSS ≤ 5	119	84	83% vs 81%	> 0.05	0% vs 0%	-
Logallo et al[29]	NIHSS ≤ 5	158	1633	38% vs 31%	0.07	1.9% vs 0.1%	< 0.001

¹Steffenhagen et al[24] compared the functional outcome of mild stroke patients using the modified Rankin scale (mRS) with severe (NIHSS score > 5) groups. Symptomatic intracerebral hemorrhage was low (2.6% vs 4.7%; P = 0.572). Favorable outcome (mRS score < 2) at 3 mo was more frequent (74.7% vs 34.7%; RR = 2.2, 95%CI: 1.8-2.5, P < 0.001) and mortality rate was lower (8% vs 22.9%; RR = 0.35, 95%CI: 0.16-0.76, P = 0.002). Favorable outcomes were not different (81.3% vs 74.7%, mRS score < 2, P = 0.75) compared to a placebo-treated group with baseline NIHSS scores ≤ 5 (n = 16) from the NINDS t-PA trial;

²In Khatri’s study, 4 of the 58 minor strokes had baseline disability (mRS > 2), and all were in the rt-PA group. In Huisa's study, the NIHSS score at admission was higher in the t-PA treated group compared to that in untreated group (3.4 ± 1.4 vs 1.9 ± 1.3; P < 0001). Thus the selective bias in the two studies might underestimate the effects of thrombolysis;

³In Helsinki Stroke Thrombolysis Registry, they did not give the definition of mid stroke. Fifty-eight mild stroke patients with NIHSS score 0-2 were treated with thrombolysis only when hyperdense cerebral artery sign, artery occlusion on computed tomography (CT) angiography, or perfusion deficit on perfusion CT scan presented. NIHSS: National Institutes of Health Stroke Scale; t-PA: Tissue plasminogen activator; SICH: Symptomatic intracranial hemorrhage.