Demographical domains and clinico-radiological characteristics of study cohorts with simultaneous multiple intracerebral hemorrhages in a tertiary neurosurgical center in Nepal: a cross-sectional study

Introduction

Simultaneous multiple intra-cerebral hemorrhages (SMICHs) are characterized by intracerebral hemorrhages within the two-or-more distinct and non-contiguous intracranial vascular territories visualized in the initial radiological imaging (Wu et al., 2017). Generally intracerebral hemorrhage (ICH) connotes high odds of continuum morbidity and mortality (Laiwattana et al., 2014). Among ICH patients, approximately 5% (1:20) have been identified as SMICHs (Renard et al., 2020).

Stroke ripples affect patients with continuum multi-spectral consequences (Gokce et al., 2016). Literature scarcity pertaining to SMICH paves the way for further research on the entity. Better knowledge and in-depth information pertaining to the incidence and patterns of SMICHs can help formulate treatment algorithms as well as provide newer reforms in patient management system.

Methods

The methodology for the research was focused to SMICH patients from the hospital medical record section of the College of Medical Sciences, in Bharatpur, Chitwan, Nepal, presenting between January 2019 to January 2021 (time we started recording and compiling data of patients with SMICHs). The outcomes were compiled to study the patterns through frequencies measures and analysis. The approval for the research conduction was obtained by the Institutional Review Committee (COMSTH-IRC/2021–56). Written informed consent was obtained from all the participants or their next of kin (in case their poor Glasgow coma scale did not allow taking consent from the patients themselves) at the time of their admissions.

Data collection

All data was taken from patient medical records.

Etiologic classification for the cause of ICH was stratified as per the SMASH-U classification into hypertensive angiopathy, cerebral amyloid angiopathy, structural vascular abnormalities, medication related, other systemic causes, and undefined causes respectively (Mosconi et al., 2021). The risk factors were defined as:

• 1. Arterial hypertension if blood pressure was above 160/90 mm Hg for more than two readings at the time of admission, on antihypertensive drugs or previous medical history of hypertension.

• 2. Diabetes mellitus if fasting glucose level was >120 mg/dL at the time of admission; hypercholesterolemia, and fasting cholesterol level >220 mg/dL.

• 3. Vascular lesion with pertinent radiological imaging at the site of the ICH was classified as the primary cause of the hematoma.

• 4. Cerebral venous sinus thrombosis was diagnosed on a cerebral venogram.

• 5. Drug associated ICH was considered in a patient on warfarin with international normalized ratio ≥2.0, novel oral anticoagulants within three days, full-dose heparin, or on systemic thrombolysis.

• 6. Cerebral amyloid angiopathy was classified in patients’ ≥55 years of age with predominant lobar bleeds with microbleeds on magnetic resonance imaging (MRI) sequences sparing the basal ganglion and the thalamus.

• 7. Tumor associated strokes was considered among patients with proven primary lesions with a histological diagnosis following either the therapeutic hematoma evacuation or minimally invasive biopsies.

The images of the varied etiological causes of SMICH are demonstrated in the Figure 1–Figure 3.

Figure 1. Hypertension and amyloid angiopathy as the cause of simultaneous multiple intracerebral hemorrhages.

All images are original, deidentified, and of our patients themselves.

Figure 2. Tumor associated simultaneous multiple intracerebral hemorrhages.

All images are original, deidentified, and of our patients themselves.

Figure 3. Miscellaneous etiological basis of simultaneous multiple intracerebral hemorrhages.

All images are original, deidentified, and of our patients themselves.

Results

The patients’ demographics and clinico-radiological based outcomes are provided in Table 1 (Munakomi, 2022).

Discussion

In a study by Yen et al. (2005), the mean age of the patients presenting with SMICH was 60.6 ±7.9 years with a male:female ratio of 1.5:1.The mean age of similar cohorts in another study was 68.5 ± 12.8 years (Yamaguchi et al., 2017). Comparatively, our study saw much younger patients with 32.5% of patients in the age groups of 36–45 years. The male to female ratio in our study was 1.66:1.

Contrary to single ICH, SMICH significantly showed lobar territorial preponderance (Wu et al., 2017) (Renard et al., 2020). Our study had cortical-cortical patterns of involvement in 60% of the patients and basal ganglion and thalamic involvement in 12.5% of cases. Putamen and thalamus patterns of involvement were the most common anatomical patterns of involvement in a study by Yamaguchi et al. (2017) whereas bilateral thalamic hemorrhages variants were the most common in a study by Yen et al. (2005).

The indication of surgery among patients with SMICH depends upon variables such as presenting GCS, location and size of the hematomas (Yi et al., 2013). Surgery has been advocated among patients with lobar or cerebellar hematomas (Yen et al., 2005). In a study by Yamaguchi et al. (2017), 35.3% of patients underwent craniotomy. Surgery was performed in only 12% of our cohort.

There are variables connoting clinical outcome among patients with SMICH. One study found low Glasgow Coma Scale (GCS) results, large hematoma and concurrent ventricular extension to be prognostic markers determining 90-day mortality (Wu et al., 2017). Unilateral supratentorial hematomas showed the most favorable outcomes (Zaorsky et al., 2019), while deep seated SMICH had the highest mortality (Renard et al., 2020). The SMICH mortality described in the literature is high, ranging from 37% to 50% (Wu et al., 2017) (Yen et al., 2005). The mortality in our study was comparatively low at 12%. 15% of the patients in our study were referred to appropriate oncology center while 35% of them left despite medical advice.

Hypertensive angiopathy and cerebral amyloid angiopathy accounted for more than 50% of cases in SMICH (Wu TY et al.) (Renard et al., 2020) (Stemer et al., 2010). They accounted for only 42.5% of the SMICH in our study. In total, 75% of our patients presenting with SMICH had a history of hypertension and were hypertensive on presentation. Paradoxically, 97.5% of diagnosed cases of hypertension lacked compliance to their medications.

The pathophysiology of SMICH was proposed to be due to degenerative alterations in the intraparenchymal arterioles caused by long-term, uncontrolled hypertension and the simultaneous rupture of bilateral charcot-bouchard microaneurysms (Yen et al., 2005). As per the “biphasic hypothetical mechanism," an initial ictal hematoma causes an adrenaline spike that disrupts the cerebral autoregulation thereby harbingering the rupture of already weakened arterioles (Yen et al., 2005). Primary SMICH characteristically showed high microhemorrhages burden of varying age in MRI studies. This also highlights the probable role of auto-regulatory dysfunction following the ictal bleed as the prime pathological genesis behind the SMICH (Stemer et al., 2010).

This real-world incidence, patterns and outcome of SMICH can only be validated following a nation-wide multicenter database study. Due to the location and specificity of our results they may not be generalizable to patients from other ethnic and geographic backgrounds. The recall bias (about the risk factors and the medical compliance by the patients when the information was provided by their kin) can be another limiting issue in this observational study.

Conclusions

This is one of the first observational studies pertaining to SMICH to be carried out within our subcontinent. This study proves the need fora national stroke data bank pertaining to SMICH. This will help foster effective patient education during preoperative counseling; as well as formatting a management algorithm combating them.

Data availability