First-ever acute ischemic strokes in HIV-infected persons: A case-control study from stroke units.

OBJECTIVE: The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. METHODS: AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score. RESULTS: Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated. INTERPRETATION: The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

MRI spot sign in acute intracerebral hemorrhage: an independent biomarker of hematoma expansion and poor functional outcome.

BACKGROUND: In acute intracerebral hemorrhage (ICH), the prognostic value of the MRI spot sign on hematoma expansion (HE) and poor functional outcome is poorly known. METHODS: We retrospectively included patients admitted over a 4-year period for an acute ICH in a single institution using MRI as the first-line imaging tool. The presence and number of MRI spot signs on contrast-enhanced T1-weighted imaging was evaluated by one neuroradiologist, blinded from outcomes. The primary outcome was HE, defined as > 6 mL or > 33% ICH volume growth from initial MRI to 24-48 h follow-up imaging; the secondary outcome was poor 3-month modified Rankin score (4-6). RESULTS: Overall, 147 patients were included, and 62% had a spot sign. Among the 130 patients with follow-up imaging, 24% experienced HE. HE occurred in 6%, 21% and 43% patients with 0, 1 and ≥ 2 spots, respectively (P < 0.001). The MRI spot sign was independently associated with HE (adjusted OR 6.15 [95% CI 1.60-23.65]; P = 0.008), with a dose-dependent effect. The negative and positive predictive values of the spot sign for HE were 0.94 and 0.35, respectively. Poor functional outcome occurred in 27%, 32% and 71% patients with 0, 1 and ≥ 2 spots, respectively (P < 0.001). In multivariable analysis, the presence of ≥ 2 spots was independently associated with poor functional outcome (adjusted OR 3.67 [95% CI 1.21-11.10]; P = 0.024). CONCLUSION: The MRI spot sign is an independent biomarker of HE, and the presence of ≥ 2 spots is independently associated with poor 3-month outcome. The lack of spot sign is highly predictive of a favorable evolution.

Heterozygous HTRA1 nonsense or frameshift mutations are pathogenic.

Heterozygous missense HTRA1 mutations have been associated with an autosomal dominant cerebral small vessel disease (CSVD) whereas the pathogenicity of heterozygous HTRA1 stop codon variants is unclear. We performed a targeted high throughput sequencing of all known CSVD genes, including HTRA1, in 3853 unrelated consecutive CSVD patients referred for molecular diagnosis. The frequency of heterozygous HTRA1 mutations leading to a premature stop codon in this patient cohort was compared with their frequency in large control databases. An analysis of HTRA1 mRNA was performed in several stop codon carrier patients. Clinical and neuroimaging features were characterized in all probands. Twenty unrelated patients carrying a heterozygous HTRA1 variant leading to a premature stop codon were identified. A highly significant difference was observed when comparing our patient cohort with control databases: gnomAD v3.1.1 [P = 3.12 × 10-17, odds ratio (OR) = 21.9], TOPMed freeze 5 (P = 7.6 × 10-18, OR = 27.1) and 1000 Genomes (P = 1.5 × 10-5). Messenger RNA analysis performed in eight patients showed a degradation of the mutated allele strongly suggesting a haploinsufficiency. Clinical and neuroimaging features are similar to those previously reported in heterozygous missense mutation carriers, except for penetrance, which seems lower. Altogether, our findings strongly suggest that heterozygous HTRA1 stop codons are pathogenic through a haploinsufficiency mechanism. Future work will help to estimate their penetrance, an important information for genetic counselling.

Clinical Scales Do Not Reliably Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion.

BACKGROUND AND PURPOSE: It remains debated whether clinical scores can help identify acute ischemic stroke patients with large-artery occlusion and hence improve triage in the era of thrombectomy. We aimed to determine the accuracy of published clinical scores to predict large-artery occlusion. METHODS: We assessed the performance of 13 clinical scores to predict large-artery occlusion in consecutive patients with acute ischemic stroke undergoing clinical examination and magnetic resonance or computed tomographic angiography ≤6 hours of symptom onset. When no cutoff was published, we used the cutoff maximizing the sum of sensitivity and specificity in our cohort. We also determined, for each score, the cutoff associated with a false-negative rate ≤10%. RESULTS: Of 1004 patients (median National Institute of Health Stroke Scale score, 7; range, 0-40), 328 (32.7%) had an occlusion of the internal carotid artery, M1 segment of the middle cerebral artery, or basilar artery. The highest accuracy (79%; 95% confidence interval, 77-82) was observed for National Institute of Health Stroke Scale score ≥11 and Rapid Arterial Occlusion Evaluation Scale score ≥5. However, these cutoffs were associated with false-negative rates >25%. Cutoffs associated with an false-negative rate ≤10% were 5, 1, and 0 for National Institute of Health Stroke Scale, Rapid Arterial Occlusion Evaluation Scale, and Cincinnati Prehospital Stroke Severity Scale, respectively. CONCLUSIONS: Using published cutoffs for triage would result in a loss of opportunity for ≥20% of patients with large-artery occlusion who would be inappropriately sent to a center lacking neurointerventional facilities. Conversely, using cutoffs reducing the false-negative rate to 10% would result in sending almost every patient to a comprehensive stroke center. Our findings, therefore, suggest that intracranial arterial imaging should be performed in all patients with acute ischemic stroke presenting within 6 hours of symptom onset.