BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) is widely 
used to measure neurological deficits, evaluate the effectiveness of treatment 
and predict outcome in acute ischemic stroke. It has also been used to measure 
the residual neurological deficit at the chronic stage after ischemic events. 
However, the value of NIHSS in ischemic cerebral small vessel disease has not 
been specifically evaluated. The purpose of this study was to investigate the 
link between the NIHSS score and clinical severity in a large population of 
subjects with CADASIL (cerebral autosomal dominant arteriopathy with subcortical 
infarcts and leukoencephalopathy), a unique model to investigate the 
pathophysiology and natural history of ischemic small vessel disease.
METHODS: Demographic and clinical data of 220 patients with one or more lacunar 
infarcts confirmed by MRI examination and enrolled from a prospective cohort 
study were analyzed. Detailed neurological examinations, including evaluation of 
the NIHSS and modified Rankin Scale score (mRS) for evaluating the clinical 
severity, were performed in all subjects. The sensitivity, specificity, positive 
and negative predictive values of various NIHSS thresholds to capture the 
absence of significant disability (mRS <3) were calculated. General linear 
models, controlling for age, educational level and different clinical 
manifestations frequently observed in CADASIL, were used to evaluate the 
relationships between NIHSS and clinical severity.
RESULTS: In the whole cohort, 45 (20.5%) subjects presented with mRS ≥3, but 
only 16 (7.3%) had NIHSS >5. All but 1 subject with NIHSS >5 showed mRS ≥3. 
NIHSS ≤5 had an 85.3% positive predictive value for no or slight disability with 
only 33.3% specificity. The NIHSS, MMSE score and presence or absence of gait 
disturbances were found to be strongly and independently correlated with 
disability (all p < 0.001). Altogether, they accounted for 73% of the variance 
of mRS in contrast with the NIHSS alone accounting for only 50% of this 
variance. Among patients with NIHSS ≤5, subjects with mRS ≥3 showed a lower MMSE 
score than those with mRS <3 (p < 0.001). All patients with NIHSS ≤5 but with 
mRS ≥3 presented either with gait disturbances or MMSE score <25.
CONCLUSIONS: The present results suggest that the NIHSS cannot reflect the 
extent of neurological deficit and clinical severity in subjects with lacunar 
infarctions in the context of a chronic and diffuse small vessel disease. A 
specific and global neurological scale, including the assessment of cognitive 
and gait performances, should be developed for ischemic cerebral 
microangiopathy.