Abstract
Objective
Stroke incidence among young adults has risen in the last decade. This research attempts to determine the effect of substance use disorder (SUD) on the clinical characteristics of stroke, mortality, outcome after IV thrombolysis, and functional dependency after 1 month among young adults.
Methods
Through a retrospective study, data were extracted from the electronic medical records of stroke in young adults admitted to intensive care units in Kasr Al-Ainy Hospital (February 2018–January 2021). The National Institute of Health Stroke Scale (NIHSS) and the Modified Rankin Scale were documented at the onset and after 1 month.
Results
The study included 225 young adults with stroke (median age of 40, IQR: 34–44). Only 93 young adults (41%) met the criteria of SUD. Anabolic steroid use disorder was significantly associated with cerebral venous thrombosis (P-value = 0.02), while heroin use disorder was significantly associated with a hemorrhagic stroke (P-value = 0.01). Patients with tramadol, cannabis, and cocaine use disorders had significantly more frequent strokes in the posterior than the anterior circulation. Patients with heroin use disorders had significantly higher mortality than those without heroin use disorders (P-value = 0.01). The risk of poor outcomes was doubled by alcohol or heroin use disorder, while it was tripled by cocaine use disorder (P-value = 0.01 for each).
Conclusion
Forty-one percent of young adults diagnosed with a stroke had SUD, with a relatively higher posterior circulation involvement. Increased mortality was associated with heroin use disorder more than other substances. Poor stroke outcome was associated with alcohol, heroin, and cocaine use disorders.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
The worldwide prevalence of stroke in 2019 was 101.5 million people, whereas that of ischemic stroke was 77.2 million, that of intracerebral hemorrhage was 20.7 million, and that of subarachnoid hemorrhage was 8.4 million [1].
Strokes may affect people at the peak of their productive lives. Despite its enormous impact on countries' social and economic development, this growing crisis has not received much attention [2]. Although diagnosis and stroke management methods have significantly improved, undetermined etiology remains the main cause in this age group [3].
Substance use disorder (SUD), a risk factor for stroke, is a growing threat worldwide among young adults. Prevention is the primary treatment strategy. Disseminating awareness and promoting research on young stroke adults is essential to mitigate the burden of stroke [4].
As epidemiological studies of stroke in Egypt are scarce, accurate knowledge of stroke among young adults regarding the risk factors, especially SUD, its prevalence, and studying its effects on stroke outcome is crucial to establishing public health strategic and preventive plans to mitigate the stroke burden [5].
The primary aim of this study was to describe clinical and radiological characteristics in an Egyptian cohort of young stroke adults in relation to SUD. A secondary aim was to study the impact of SUD on mortality, stroke outcome following IV thrombolysis, and functional dependency outcome at 1 month of follow-up.
Methods
This retrospective observational study included all young adults with stroke consecutively admitted to the stroke unit of Cairo University Hospital between February 2018 and January 2021. Data from all young adults with stroke (age < 45 years) admitted to our institution were prospectively recorded. We exclude incomplete records and stroke-related head trauma cases. The ethical committee of the Neurology department-Faculty of Medicine-Cairo University approved the study.
These data were extracted from electronic stroke registries: demographics and medical conditions, such as hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, arrhythmias, obesity (body mass index ≥ 30), and others. Diagnosis of SUD was made according to the Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) [6] based on either urine drug testing or medical record history.
The severity of the neurological deficit on admission was evaluated by the National Institutes of Health stroke scale (NIHSS) [7] and The Modified Rankin Scale (mRS) [8].
At the initial presentation, all patients were investigated using brain computed tomography (CT) and magnetic resonance imaging (MRI). Further imaging modalities were performed case-by-case based on the physician's decision as computed tomography angiography (CTA) or magnetic resonance venography (MRV). Lesions in middle cerebral or anterior cerebral vascular territories denote anterior circulation involvement. In contrast, lesions in the territory of the vertebral artery, basilar artery, posterior cerebral artery, or their penetrating arteries were defined as posterior circulation [9].
Intravenous r-TPA was administered according to the American Heart Association/American Stroke Association (AHA/ASA) guidelines for the early management of acute ischemic stroke [10]. Brain CT was re-performed 48 h after the r-TPA bolus administration for patients with ischemic stroke or any neurological deterioration.
Study outcomes
-
Outcome after IV thrombolysis: was determined as favorable or unfavorable at 48 h after rtPA bolus administration. The favorable outcome was defined as a complete resolution of the neurological deficit or an improvement in the mRS score from baseline by two or more points 24 h after stroke onset.
-
Survival or mortality.
-
Functional stroke outcome was evaluated as either good or poor at a 1-month follow-up. A good outcome at a 1-month following stroke is defined as mRS scores of 0–2, whereas scores of 3–6 represent a poor outcome [11].
Statistical analysis
Data entries were carried out using SPSS (Statistical Package for Social Science) version 23.0 (IBM, SPSS, USA). The normality distribution of the data was tested by using the Shapiro–Wilk test. Categorical variables were expressed in numbers and percentages. Not normally distributed continuous variables were expressed as median and interquartile ranges. Chi-square and Fisher’s exact tests were used to compare the characteristics of stroke between young patients with SUD versus stroke in young adults without SUD; Mann–Whitney was used as appropriate for comparing and measuring the disability resulting from the stroke in young adults with SUD versus stroke in young adults without SUD. P-value < 0.05 was considered significant.
Results
Two-hundred-and-twenty-five strokes were identified in young adults (139 males & 86 females), with a median age of 40 (IQR: 34–44). Two hundred-six patients had an arterial stroke (179 with ischemic stroke, 13 with ICH, and 14 with SAH), while venous stroke was documented in 19 patients. Among the study population, 93 young adults (41%) met the criteria of SUD. The most frequently abused substance among the abusers was tramadol (54%), followed by cannabis (51%) (Fig. 1).
The frequency of some vascular risk factors, including diabetes, hypertension, dyslipidemia, and obesity, was significantly lower in adults with SUD than in those without SUD. Detailed demographics and vascular risk factors are illustrated in Table 1.
Substance use disorder and stroke pathology
It was found that cannabis use disorder was significantly associated with the arterial type of stroke, while anabolic steroid use disorder was significantly associated with the venous type (Table 2). Also, 60% of adults with heroin use disorder had a hemorrhagic stroke versus 40% who developed an ischemic type (P 0.01). Other substances showed no statistically significant difference between stroke types (Table 3).
Substance use disorder and stroke location
Patients with tramadol, cannabis, and cocaine use disorders had significantly more frequent strokes in the posterior than the anterior circulation (Table 4).
Regarding SAH, 10 cases were identified as aneurysmal SAH (6 with posterior communicating artery aneurysms, 3 with middle cerebral artery aneurysms, and one with anterior cerebral artery aneurysms), and 4 cases had peri-mesencephalic SAH. Mycotic aneurysms were identified in only two cases with heroin use disorder.
Among patients with SUD, intracranial stenosis was documented by CTA in nine cases (3 cases with cocaine use disorder, other 3 with cannabis cocaine use disorder, 2 cases with heroin use disorder, and only one had alcohol use disorder). All these cases had intracranial stenosis involving the anterior circulation, except for two cases (one with heroin use disorder and another with alcohol use disorder), in which posterior circulation was involved.
Substance use disorder and stroke disability
Patients with alcohol, heroin, and cocaine use disorders had significantly higher NIHSS and mRS scores at the onset. On the other hand, patients with tramadol and cannabis use disorders were significantly associated with higher mRS scores but not with NIHSS (Table 5).
Substance use disorder and IV thrombolysis outcome
Seventy-four young patients were eligible for r-TPA administration (19 were with SUD, and 55 were without SUD). Out of 19 patients with SUD, only one did not improve after receiving r-TPA. This patient met the criteria of SUD for three substances (alcohol, tramadol, and cannabis). There was no statistically significant difference between illicit substances regarding IV thrombolysis outcome.
Substance use disorder and mortality outcome
Among the whole study population, only eight cases died. Patients with heroin use disorders had significantly higher mortality than those without heroin use disorders (P-value = 0.01) (Table 6).
Substance use disorder and functional outcome at a 1-month follow-up
Poor outcome was significantly higher among patients with alcohol, cocaine, and heroin use disorder. The risk of poor outcomes among patients with alcohol or heroin use disorder was double that among the non-alcoholic or non-heroin use disorders (P-value = 0.01 for each). All patients with cocaine use disorder (4 patients) had a poor outcome, being at three times at risk of having a poor outcome than non-cocaine use disorder (P-value = 0.01) (Table 7).
Discussion
With the lack of detailed information about the effect of SUD among young adults on stroke characteristics and outcomes in Egypt, this study provided a better understanding of SUD-induced stroke in Egyptian young adults.
The co-existence of different comorbidities and SUD was investigated in this study; these comorbidities represent the main modifiable risk factors for stroke. It was noticed that most young stroke adults with different comorbidities developed stroke without SUD. This might denote that SUD, even without other comorbidities, is sufficient to be a risk factor for stroke.
Similar to our results, Chang, Münster [12] showed that anabolic androgenic steroids increased the risk of cerebral venous thrombosis. It is well-established that anabolic steroids cause an increase in prothrombin fragments and thrombin/antithrombin complexes, which leads to cerebral venous thrombosis [13, 14].
The present study showed that all cannabis abusers developed an arterial stroke predominantly of ischemic type (86%) involving the posterior circulation. This is in line with Middlekauff, Cooper [15], who found that cannabis-induced multifocal intracranial stenosis mostly involved the posterior circulation.
In contrast, the hemorrhagic type predominated over the ischemic stroke in heroin abusers. This could be explained by pyogenic arteritis or the rupture of mycotic aneurysms induced by heroin [16].
In light of the previous studies' agreement that cocaine-related stroke can be of any type and may happen in every brain region [16], the current study showed a significant preference for posterior circulation involvement among patients with cocaine use disorder. Potent cerebral vasospasm, cerebral vasculitis, and bradykinin-mediated endothelial dysfunction all have been demonstrated as consequences of cocaine abuse [17].
In 2016, a meta-analysis revealed that heavy alcohol consumption increases the risk for the hemorrhagic type, either ICH or SAH [18]. Regarding the ischemic events, alcohol-induced atrial fibrillation mainly contributes to cerebrovascular events [19], as the effects of alcohol on hemostatic and fibrinolytic factors are still doubtful [20]. However, we found no association between alcohol use disorder and any specific stroke type.
For tramadol, one of the most commonly abused substances by Egyptian youths [21, 22], data about its pathophysiological mechanisms of causing stroke is not settled yet [ This study concluded that 41% of young adults diagnosed with a stroke had SUD. Posterior circulation stroke was higher among patients with tramadol, cannabis, and cocaine use disorder. Cerebral venous thrombosis showed a higher frequency among anabolic steroid use disorders, whereas the frequency of hemorrhagic strokes was higher among heroin use disorder. High mortality was associated with heroin use disorder more than other substances. Poor stroke outcome was associated with alcohol, heroin, and cocaine use disorders. The current study emphasizes the importance of screening for SUD, especially among young adults with stroke, to improve the outcome.Conclusion
Data availability
Authors report that the datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
References
Krishnamurthi RV, Ikeda T, Feigin VL (2020) Global, Regional and country-specific burden of ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage: a systematic analysis of the Global Burden of Disease Study 2017. Neuroepidemiology 54:171–179
Johnson W, Onuma O, Owolabi M, Sachdev S (2016) Stroke: a global response is needed. Bull World Health Org 94:634-a
Yahya T, Jilani MH, Khan SU, Mszar R, Hassan SZ, Blaha MJ et al (2020) Stroke in young adults: current trends, opportunities for prevention and pathways forward. Am J Prev Cardiol 3:100085
Schulte MT, Hser YI (2014) Substance use and associated health conditions throughout the lifespan. Public Health Rev 35
Khedr EM, Elfetoh NA, Al Attar G, Ahmed MA, Ali AM, Hamdy A et al (2013) Epidemiological study and risk factors of stroke in Assiut Governorate, Egypt: community-based study. Neuroepidemiology 40:288–294
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. Arlington
National Institute of Neurological Disorders and Stroke (U.S.) (2011) NIH stroke scale. Dept of Health and Human Services, USA
Wilson JTL, Hareendran A, Grant M, Baird T, Schulz UGR, Muir KW et al (2002) Improving the assessment of outcomes in stroke. Stroke 33:2243–2246
Tang Y (2020) Ischemic stroke vascular territory. In: Tang Y (ed) Atlas of emergency neurovascular imaging. Springer International Publishing, Cham, pp 21–32
Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K et al (2018) 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 49:e46–e99
Banks JL, Marotta CA (2007) Outcomes validity and reliability of the Modified Rankin Scale: implications for stroke clinical trials. Stroke 38:1091–1096
Chang S, Münster AB, Gram J, Sidelmann JJ (2018) Anabolic androgenic steroid abuse: the effects on thrombosis risk, coagulation, and fibrinolysis. Semin Thromb Hemost 44:734–746
Roşca AE, Vlădăreanu AM, Mititelu A, Popescu BO, Badiu C (2021) Effects of exogenous androgens on platelet activity and their thrombogenic potential in supraphysiological administration: a literature review. J Clin Med 10:1–27
Hashmi A, Kim P, Ahmad SW, Faucheux J, Gandikal N (2019) Superior sagittal venous sinus thrombosis in a patient with illicit testosterone use. Cureus 11:e5491
Middlekauff HR, Cooper ZD, Strauss SB (2022) Drugs of misuse: focus on vascular dysfunction. Can J Cardiol 38:1364–1377
Tsatsakis A, Docea AO, Calina D, Tsarouhas K, Zamfira LM, Mitrut R et al (2019) A mechanistic and pathophysiological approach for stroke associated with drugs of abuse. J Clin Med 8(9):1295
Siniscalchi A, Bonci A, Mercuri NB, De Siena A, De Sarro G, Malferrari G et al (2015) Cocaine dependence and stroke: pathogenesis and management. Curr Neurovasc Res 12:163–172
Larsson SC, Wallin A, Wolk A, Markus HS (2016) Differing association of alcohol consumption with different stroke types: a systematic review and meta-analysis. BMC Med 14:178
Liang Y, Mente A, Yusuf S, Gao P, Sleight P, Zhu J et al (2012) Alcohol consumption and the risk of incident atrial fibrillation among people with cardiovascular disease. CMAJ 184:E857–E866
Salem RO, Laposata M (2005) Effects of alcohol on hemostasis. Am J Clin Pathol 123(Suppl):S96-105
Abolmaged S, Kodera A, Okasha T, Gawad T, Rawson R (2013) Tramadol use in EGYPT: emergence of a major new public health problem. Can J Addict 4:5
Bassiony MM, Salah El-Deen GM, Yousef U, Raya Y, Abdel-Ghani MM, El-Gohari H et al (2015) Adolescent tramadol use and abuse in Egypt. Am J Drug Alcohol Abuse 41:206–211
Li L, Marozoff S, Lu N, **e H, Kopec JA, Cibere J et al (2022) Association of tramadol with all-cause mortality, cardiovascular diseases, venous thromboembolism, and hip fractures among patients with osteoarthritis: a population-based study. Arthritis Res Ther 24:85
**e J, Strauss VY, Martinez-Laguna D, Carbonell-Abella C, Diez-Perez A, Nogues X et al (2021) Association of tramadol vs codeine prescription dispensation with mortality and other adverse clinical outcomes. JAMA 326:1504–1515
Rutten-Jacobs LCA, Arntz RM, Maaijwee NAM, Schoonderwaldt HC, Dorresteijn LD, van Dijk EJ et al (2013) Long-term mortality after stroke among adults aged 18 to 50 years. JAMA 309:1136–1144
Brgdar A, Gharbin J, Elawad A, Yi J, Sanchez J, Bishaw A et al (2022) Effects of substance use disorder on in-hospital outcomes of young patients presenting with a cardiovascular event: a nationwide analysis. cureus 14:e22737
Mahtta D, Ramsey D, Krittanawong C, Al Rifai M, Khurram N, Samad Z et al (2021) Recreational substance use among patients with premature atherosclerotic cardiovascular disease. Heart 107:650–656
Fernando SM, Qureshi D, Talarico R, Tanuseputro P, Dowlatshahi D, Sood MM et al (2021) Intracerebral hemorrhage incidence, mortality, and association with oral anticoagulation use. Stroke 52:1673–1681
Garg R, Biller J (2019) Recent advances in spontaneous intracerebral hemorrhage. F1000Research. https://doi.org/10.12688/f1000research.16357.1
Kwah LK, Harvey LA, Diong J, Herbert RD (2013) Models containing age and NIHSS predict recovery of ambulation and upper limb function six months after stroke: an observational study. J Physiother 59:189–197
Wouters A, Nysten C, Thijs V, Lemmens R (2018) Prediction of outcome in patients with acute ischemic stroke based on initial severity and improvement in the first 24 h. Front Neurol 9:308
Mahdy ME, Ghonimi NA, Elserafy TS, Mahmoud W (2019) The NIHSS score can predict the outcome of patients with primary intracerebral hemorrhage. Egypt J Neurol Psychiatry Neurosurg 55:21
Sheikh Andalibi MS, Rezaei Ardani A, Amiri A, Morovatdar N, Talebi A, Azarpazhooh MR et al (2021) The association between substance use disorders and long-term outcome of stroke: results from a population-based study of stroke among 450,229 urban citizens. Neuroepidemiology 55:171–179
Funding
Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no known competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Rizk, H.I., Magdy, R., Emam, K. et al. Substance use disorder in young adults with stroke: clinical characteristics and outcome. Acta Neurol Belg 124, 65–72 (2024). https://doi.org/10.1007/s13760-023-02317-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13760-023-02317-8