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Egyptian Journal of Basic and Clinical Pharmacology

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ejbcp: Vol. 10
Review Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 10 (2020), Article ID 101500, 15 pages 
doi:10.32527/2020/101500

Pathophysiology, Complications and Management of Stroke: A review

Umme Habeeba A. Pathan1, Abdul Raheem Thayyil2, Thimmasetty Juturu2, and Shwetha Kamath2

1Department of Pharmacy Practice, Bapuji Pharmacy College, SS layout, Shamnur road, Davanagere-577004, Karnataka, India

2Faculty of Industrial Pharmacy, Bapuji Pharmacy College, SS layout, Shamnur road, Davanagere-577004, Karnataka, India

Received 09 August 2020; Accepted 04 September 2020

Editor: Hesham Hamed

Copyright © 2020 Umme Habeeba A Pathan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Stroke is the next foremost origin of death under Non-Communicable Diseases (NCD) after heart disease and cancer. Earlier, the detection of stroke was a failure due to its complexity in understanding. On the pages of history, it was a serious disease known as ‘Apoplexy’, which was later recognized as stroke. This review focuses on the updated definition, its types which are mainly two, ischemic and hemorrhagic stroke. It also covers the risk factors like age, genetics, cardiac diseases, and symptoms that differentiate the type of stroke which helps in diagnosing the mechanism correctly. The pathogenesis of stroke is summarized, which paves the path for the treatment regimen and if left untreated, possible complications can be seen. Finally, an attempt has also been made to brief the management including both non-pharmacological therapy with stem cell transplantation, surgical therapy, and pharmacological therapy.

1. Introduction

Stroke, commonly known as Cerebro-Vascular Accident (CVA), is stated as a sudden commencement of neurological discrepancy which is attributable to a pivotal vascular basis [1,2,3]. In modest words, it is a “brain attack�_, which occurs when the brain fails to get adequate blood circulation, as a result, brain cells do not get a sufficient amount of oxygen, and cells start dying ultimately. Stroke is an overwhelming public health concern [4]. Among 33 million stroke survivors worldwide, stroke is the second leading reason for death trailing ischemic heart disease, and the third steering foundation of disability [5, 6]. The World Health Organization (WHO) appraises that at regular intervals new patient gets cerebrum assault worldwide and encounters either demise or handicap like clockwork due to the stroke [7]. By 2025, the UN testimony summoned for a comparative reduction in hasty mortality by 25% from NCDs, including stroke [8]. In the year 2002, stroke was the seventh leading cause of the title `disability-adjusted life years lost' due to its immobile complications and this legacy will step up to the sixth position by the year 2030 [9].

The risk factors include advanced age [10], gender [3,11,12], race [13], hypertension [14], diabetic HbA1c [15], hyperlipidemia [16], atrial cardiopathy [17], cancer [18,19], genetic factors [20], walking pace [21], hyper viruses [22], and, cannabis abuse [23]. Signs and symptoms of stroke include multiple neurologic dysfunctions, hemiparesis, aphasia, dysarthria, blurred vision, and altered levels of consciousness [24]. Alone clinical features will not differentiate ischemic stroke from Intra-Cerebral Hemorrhage (ICH). Poorly performed scoring systems help to improve diagnose stroke with accuracy by introducing imaging techniques [25]. Stroke has got extremely complex pathophysiology which involves numerous processes, including atherosclerosis accumulation, hypertrophy of muscle, local occlusion leading to cerebral ischemia. This cerebral ischemia is a major culprit for a cascade of unwanted reactions leading to inflammation, mitochondrial damage, Blood-Brain Barrier (BBB) disruption, excitotoxicity, and cell death [26]. A serious and common complication in stroke patient includes Stroke-Associated Pneumonia (SAP) [27], followed by dysphagia [28], circulatory obstacles which are the second foremost source of post-stroke death [29], myocardial infarction [30], serotonin syndrome [31,32], post-stroke fatigue [33,34], post-stroke dementia [35,36,37], post-stroke epilepsy [38], post-stroke cognitive impairment [36,39], Post Stroke Cognitive Decline (PSCD) [36,40,41,42], post-stroke insomnia [43], and re-admission [44].

The goal of therapy includes recombinant tissue Plasminogen Activators (rtPA) which is a fibrinolytic therapy to improve BBB damage and reduce the hemorrhagic transformation in clinical practice [45]. To provide neuroprotection and aiming to avoid a series of Ischemic-Reperfusion (I/R) injury, U.S. Food and Drug Administration (USFDA) has permitted NADPH oxidase (NOX) inhibitors, and numerous drugs [46]. To protect against vascular endothelial dysfunction and alleviate ischemic injury, a new free radical called edaravone revealed better effect [47]. To overcome post-stroke complications, retrievals are established like involvement in the rehabilitation center [48]. Characteristic post-stroke care begins with hospitalization for a week and abides by some weeks of physiotherapy, occupational therapy, and speech-language pathology. Lifestyle modification includes exercise, which is essential for motor learning to reduce activity limitation [49], adopting the traditional Mediterranean Diet (MeD) [50], and having adequate sleep [51]. Stroke patients have a high mortality rate annually 30 to 50% [10].

2. Definition

The term stroke was initially proposed by William Cole in 1689 [52]. Before Cole, the stroke was described as `apoplexy' and it was first seen by Hippocrates around 400 BC [1,53].

Currently, WHO describes stroke as “quickly emerging clinical signs of focal disruption of cerebral event, durable more than 24 hours or directing to fatality, with no seeming reason other than that of vascular cause�_ [54].

3. Classification

3.1. Transient Ischemic Attack

In 2009, an expert committee of the American Heart Association/American Stroke Association (AHA/ASA) published a scientific statement defining Transient Ischemic Attack (TIA) and recommending evaluation. The definition proposed was “a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction�_ [55].

3.2. Etiological Classification of Ischemic and Hemorrhagic
3.2.1. Ischemic Stroke

Ischemic stroke classi�_cation is either phenotypic or causative, as per the present approaches. Phenotypic classi�_cation lean towards unfolding the agreeing fundamental pathologies, by not focusing on the most plausible ischemic stroke reason. While, causative classi�_cations accentuate on setting up the most probable reason, ignoring other related infections [56]. The classification is summarized in Table 1.

T1

Table 1: Ischemic stroke classi�_cation systems [34,56].

T2

Table 2: Causes of intracranial hemorrhages [58].

T3

Table 3: Symptoms associated with TIA [78]

T4

Table 4: Treatment of ischemic stroke.

3.2.2. Hemorrhagic stroke

Hemorrhages in hemorrhagic stroke are classified by their underlying vascular pathology and location. Important causes include aneurysmal Sub-Arachnoid Hemorrhage (SAH) [57]. Bleeding in the brain especially in the spaces of epidural and subdural is caused due to trauma and other major causes are listed in Table 2.

3.2.3. Classification based on mechanism

Classification is briefed in Figure 1 [24,59,60].

F1
Figure 1: Classification of stroke based on mechanism.

4. Risk factors

4.1. Single Risk Factors
4.1.1. Age

People over the age of 55 of either gender are in great jeopardy of getting a stroke. The likelihood of stroke doubles every decade among this age group [10,61].

4.1.2. Gender

Women are liable to get stroke than men because of high anxiety, depression, pain, discomfort, and decreased mobility leading to augmented frailty and low quality of life. Obstetric women are at high risk of developing ischemic stroke (RR=34), intracerebral hemorrhage (RR=95), and subarachnoid hemorrhage (RR=47). Epidemiologic studies chronicled preeclampsia and eclampsia credit for nearly 50% of obstetric strokes. Typical syndromes found in post-delivery women are Reversible Cerebral Vasospasm Syndrome (RCVS) and Posterior Reversible Encephalopathy Syndrome (PRES) [4]. As the age increases the risk of acquiring stroke shifts from women to men [62,63].

4.1.3. Genetic factors

Around 32 stroke risk loci are present in the brain which can get changed or mutated and lead to stroke [62]. It is a non-modifiable risk factor [63]. Genome-Wide Association Studies (GWAS) is the fronting methodology in genetics for finding an association between genetics and stroke [64]. Identifying stroke as a single-gene disorder has paved the path for enhancing its therapeutic outcome[65].

4.1.4. Hypertension

Rather than saying with increased or decreased BP, it would be best to define in terms of Blood Pressure Variability (BPV) and related metrics. The latest facts by a sequence of studies from Korea demonstrated the multifarious relationship between BP and Acute Ischemic Stroke (AIS). From these studies, it was noted that the tension of pulse had better prognostic powers rather than usual measures of BP metrics. The study by P B Gorelick et al. mentioned five systolic BP trajectory groups (low, moderate, rapidly stabilized, acutely elevated and, persistently high) within 24h onset of stroke among 8376 Acute Ischemic Stroke (AIS) patients. The risk worsened as vascular complications took over hypertension [14].

4.1.5. Cardiac disease

Atrial Fibrillation (AF), mitral stenosis, mitral annular calci�_cation, left atrial enlargement, structural abnormalities such as atrial-septal aneurysm, and myocardial disease can lead to stroke [24]. AF is more vulnerable to an embolic stroke [66]. Embolic Stroke of Undetermined Source (ESUS) which contributes to 30% of cryptogenic stroke has a stronger relationship with cardiac abnormalities especially AF and endocarditis [67].

4.1.6. Diabetes mellitus (DM)

One of the macrovascular complications of DM includes stroke, so DM is more prone to the high prevalence of getting a brain attack. In people with established DM, higher glycated hemoglobin values are strongly related to �_rst-ever stroke according to systemic review and meta-analysis [15].

4.1.7. Hyperlipidemia

It is a positive risk factor for extra-cranial atherosclerosis [3]. There exists an opposite relationship between total cholesterol in ICH and ischemic stroke. It is found that low levels of cholesterol increase the risk of ICH whereas high levels increase the risk of ischemic stroke [16].

4.1.8. Illicit drug use

Cannabis and its analogs are worldwide used illicit substances and drugs. The use of this violates and has a large impact on cerebrovascular events or stroke [23]. The violation is judged based on the hypothesis that cannabis induces transient vasoconstriction according to a systematic review of 18 case-reports by S.A Gomez Ochoa. According to this review, 9 case reports on the syndrome of vascular constriction allied with consumption of cannabis by Ducros et al., [68] revealed Magnetic Resonance Imaging (MRI) scans with inner and specific arterial constriction, Herning et al., [69] also revealed the similar findings regards with the high vascular defiance and rate of blood flow in substance abuser and non-abuser. Wolff et al., reinforced this above theory in his cohort analysis among young 48 patients revealing 21% of patients had multifocal intracranial stenosis with consumption of cannabis, and also the study supported for the fact that the stenosis is reversible. Hence due to investigative changes and hindrance in the normal mechanism of blood flow to the brain can associate the TIA and stroke in cannabis abusers [70].

4.1.9. Herpes virus

There is a greater risk of acquiring stroke due to herpesvirus infection as it provokes inflammatory actions in the body. The virus aid in the series of proactive consequences like thrombogenesis, atherosclerosis, damage to vessels, platelet aggregation, and, as a result of these inflammatory processes there lays a huge risk for stroke [22].

4.1.10. Smoking and alcohol abuse

Smokers risk increases by two or four folds of developing stroke than non-smokers [71]. It is found that there is a proof relating to the risk of stroke in young men through dose-response curve [72]. As per the alcohol is concerned, more than 5 drinks of alcohol per day can increase the risk of stroke than those who do not drink [73]. 20-30% of people are at risk to get stroke by living with smokers that are second-hand smokers [74].

4.2. Multiple Risk Factors

Stroke is increased by the presence of multiple risk factors. Framingham pro�_le also well known as Framingham Stroke Risk Profile (FSRP) is significant and easily available during an outpatient office visit. This gender-specific profile includes: Age, antihypertensive drugs, elevated systolic blood pressure, elevated serum cholesterol, glucose intolerance, cigarette smoking, presence of Coronary Vascular Disease (CVD), left ventricular hypertrophy, and AF [24,75]. The single and multiple risk factors are briefed in Figure 2.

F2
Figure 2: Risk factors.

5. Clinical Presentation

5.1. Signs and Symptoms

One of the earliest symptoms is detected by FAST which is shown in Figure 3 [76]. Signs and symptoms account for warnings due to brain injuries and precise discrepancies. The foremost sign is hemiparesis. Symptoms involved with vision and consciousness are diplopia and giddiness, which is due to the impaired circulatory involvement away from the brain. Symptoms involved with speech such as aphasia is because of circulatory dysfunction in the left hemisphere of the brain. Additional signs include dysarthria, optic chiasm defects, and stupor. Pain is commonly present in hemorrhagic stroke in the form of a severe headache than with ischemic stroke [24,77].

F3
Figure 3: FAST.

The symptoms of TIA are enumerated in Table 3.

5.2. Diagnosis
5.2.1. Clinical diagnosis

Knowledge plays a significant task in clinical diagnosis. The neuro-specialist who diagnoses and sets the treatment regimen should have sound knowledge in neuroanatomy and vascular anatomy [79]. During clinical diagnosis, three queries oblige a response and those are [80];

  • •:  The process is either of the vascular origin or it just mimics a stroke.
  • •:  Name of impaired blood vessel supply in the CNS.
  • •:  The mechanism involved, either ischemic or hemorrhagic.
5.3. Radiographic diagnosis

The radiological tests include [24,79]:

  • •:  X-Ray; Cerebral Angiography shown in Figure 4
  • •:  Computed Tomography (CT) scan
  • •:  Magnetic Resonance Imaging (MRI) scan
  • •:  Diffusion-Weighted Imaging (DWI)
  • •:  Carotid Doppler (CD)
  • •:  The Electro Cardio Gram (ECG)
  • •:  Trans Thoracic Echocardiogram (TTE)
  • •:  Trans Esophageal Echocardiogram (TEE)
  • •:  Trans Cranial Doppler (TCD)
F4
Figure 4: Cerebral angiography showing initial blockage and cerebral ischemia.
5.3.1. Diagnostic tools

Standardize neurologic evaluation is done by using stroke scales. Stroke scale is available and is evaluated based on two criteria;

  • •:  One which aims at cognitive and physical impairment.
  • •:  The second which regulates the impact of strokes based on day-to-day events and eminence of living throughout restoration from stroke [81].
5.3.2. Prognostic models

Prognostic Models can be precisely used for the purposeful sequel of a whole retrieval in patients with ischemic stroke might be useful to neural precaution practices for several following purposes;

  • •:  Developed prognostic model knowledge can be useful in selecting appropriate treatments and individualizing patient management, along with patient counseling.
  • •:  These models also improvise rehabilitation and discharge planning.
  • •:  In poor economical countries, the use of prognostic models would be the best clinical choice for patients concerning precise medical circumstances, which might decrease health concern charges and hospital stay.

But before the use of the prognostic model in the medical field, it is evaluated and the process of evaluation is known as model validation. Models are developed by predictor variables, for example, in a systemic review and meta-analysis done by Jampathong et al., [82] shows 23 prognostic tools.

5.4. Misdiagnosis

Many other neurologic conditions that depict the same symptoms as that of stroke are called Stroke Mimics (SM). Due to this condition often other conditions are misdiagnosed as stroke and some of them are listed below [83];

  • •:  Epilepsy
  • •:  Headache
  • •:  Metabolic abnormality
  • •:  Tumors
  • •:  Vertigo

6. Pathophysiology

6.1. Ischemic Stroke

The pathophysiology of ischemic stroke is exceptionally multifaceted. The processes involved are cerebral ischemia, inflammation/cytokines storm, oxidative stress, BBB disruption, excitotoxicity, necrosis, or apoptosis and circadian influence on the mechanism [84,85,86]. Cerebral ischemia is caused by thrombosis, embolism, focal hypoperfusion, lipid accumulation in the carotid artery, and inflammatory cells [24,77,86]. Cholesterol deposition in circle of Willis (coW) is shown in Figure 5.

F5
Figure 5: Circle of Willis of healthy brain v/s with atherosclerotic plaque.

Acute occlusion in the intracranial vessels leads to decreased blood flow to the brain resulting in three different scenarios based on the flow of blood to the brain. First, if the cerebral blood flow is zero then brain tissue dies within 4-10 min. Second, if the blood flow is < 16-18 ml min−1 for 100g tissue then there is infarction within an hour. Third, if the blood flow is < 20 ml min−1 for 100g tissue then ischemia is caused without infarction [3]. The process of atherosclerosis leads to cerebral ischemia and is summarized in Figure 6.

F6
Figure 6: Carotid atherosclerosis to cerebral ischemia.

Inflammation involves the accumulation of immune cells in certain regions [85]. The essential leukocyte sub-population that controls cascade of neuroinflammatory responses includes microglial cell instigation, brain leukocyte assault, lymphocytes, and pro-inflammatory cytokines [87,88]. It is seen that in experimental models of the brain as well as in patient with acute stroke are linked with increased production of pro-inflammatory cytokines and chemokines which contributes to cerebral infarct [89]. There are several cytokines which comes into play during the inflammatory response, like Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and Interleukin-18 (IL-18) [90].

When blood perfusion to the brain stops, the ischemic neurons become energy-deprived and necrosis happens. This event potentiates immune system activation causing the deposition of inflammatory cells in the vicinity of the ischemic region [91]. Earlier only bioenergetics of mitochondria was considered, however current knowledge focus on mitochondrial damage at a molecular level can lead to cerebral ischemia. Since mitochondria play a vital role in generating Reactive Oxygen Species (ROS), these further damage mitochondrial DNA and disrupt electron transport chain function causing inflammation and apoptosis [92]. Stroke, which is a result of neurological deficit have peculiar variations with the vascular system. They include altered BP, fibrinolysis, vascular tone, cerebral vasomotor regulation, hindering coagulation, and its factors. Day-to-day altered patterns of BP were noteworthy post-stroke because those patterns can monitor the duration of therapy, and help in averting initiation of stroke once again [84]. Oxidative stress results from a disparity in ROS production and competence to neutralize the free radical products in the human body [92].

The brain is considered an immune restricted site because the meninges especially BBB firmly confines the entrance of pro-inflammatory mediators from the periphery into the Central Nervous System (CNS) [93]. But when BBB is disrupted, then it facilitates the exchange of harmful substances like cytokines, C-Reactive Protein (CRP), matrix metalloproteinases (MMPs), and nitric oxide (NO) in the CNS, and scavenges crucial nutrients reaching the brain [45,91,94]. Hence, cytokines is crucial inflammatory factor which can be detected in serum and cerebrospinal fluid during acute phase of stroke making it as on road biomarker in early detection of stroke [95]. One such study included isolation of thrombus through standard thrombectomy procedure in post-stroke patients up to 24 hour onset. Later, the thrombus was studied at molecular and cellular level using machine learning that lead the way to find prognostic inflammatory biomarkers of stroke [96]. Due to lack of understanding in the mechanism of cytokines before and after stroke, it hinders the use of cytokine as biomarker or therapeutic target [97]. MicroRNAs have dual actions of pros and cons. Pros include that these help in nerve development, differentiation, synaptic plasticity, apoptosis, and degeneration. But the two among microRNAs namely microRNA-15a and microRNA-497 are pathophysiologically active. These microRNAs impair normal defense mechanisms and interfere in antiapoptotic action [85].

Due to increase accumulation of excitatory amino acids leads to excitotoxicity which paves a path for cellular calcium to increase to a toxic level. When toxic levels of calcium ions are present energy production system is imbalanced and so the Na�_�-K�_� ATPase enzyme is inhibited. As a result, there is a bulk entry of ions into the cell leading to either acute cell swelling or cell death [26]. Cell death can be categorized into two as necrosis and apoptosis. Necrosis is simple tissue death with minimal damage whereas apoptosis is programmed cell death. During necrosis, there is a chance of recovery of neuronal cells if the pressure of the mechanism is corrected at earliest. The apoptotic form can be severe and permanent injuries are seen due to the inability to reverse the programmed cell death [26,98,99,100]. The process of necrosis is summarized in Figure 7.

F7
Figure 7: Cerebral ischemia to cell death.
6.2. Hemorrhagic Stroke

Only 15% of stroke case accounts for a hemorrhagic one. Hence, the pathophysiology of hemorrhagic stroke is not well established as that of ischemic stroke. The only mechanism known is that the rupture of the blood vessel in the brain causes chaos in the brain and so the brain is posturized to be in the pool of blood. As the blood fills up in the cranium it creates increased intracranial pressure which is marked by severe headache and results can be fatal within hours if left untreated. The blood in brain parenchyma creates a mechanical effect that exhibits neurotoxicity and multiple organ failure due to severe internal bleeding. Sometimes hemorrhages can develop into secondary ischemia [3,24].

7. Complications

7.1. Stroke Associated Pneumonia (SAP)

It is the usual complications of a stroke. SAP is likely to develop inpatient with advancing age, increased hospital stay, and decreased human leukocyte antigen-DR isotype (HLA-DR), stroke-induced immune depression syndrome, and Chronic Obstructive Pulmonary Disease (COPD) [27].

7.2. Dysphagia

Post-stroke dysphagia can be seen in patients who are more prone to develop SAP. Early dysphagia screening can be assessed within 4 hours of hospital admission and evaluated by Speech and Language Pathologist (SLP) according to United Kingdom guidelines within 72 hours [28].

7.3. Cardiac Complications

The cardiovascular complication is one of the main reasons for death in stroke patients. It is well studied under a specialty called neurocardiology. The complications are mild to moderate such as Neurogenic Stress Cardiomyopathy (NSC) and Takotsubo cardiomyopathy. In the case of SAH, complications include cardiac arrhythmia associated with other heart abnormalities, and increased hospital stay. The mechanism involved in brain heart interaction is the stimulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, catecholamine surge, and sympathetic and parasympathetic regulations [29,101].

7.4. Depression

Post Stroke Depression (PSD) occurs around three months after the stroke, and around 12% of male and 16% of females suffer from depression due to stroke. Depression is likely due to decreased bioavailability of amines of several neurotransmitters like serotonin, dopamine, and norepinephrine in the brain [87].

7.5. Serotonin Syndrome (SS)

It is purely Adverse Drug Reaction (ADR) caused by an increased amount of serotonin in the brain which was earlier taken to enhance the activity of the brain. So it is necessary to have attention while prescribing dopaminergic drugs in stroke patients if not the stroke may worsen with life-threatening condition SS [31].

7.6. Fatigue

Post Stroke Fatigue (PSF) is also one of the consequences of stroke which is related to inactivity. PSF is assessed by different Patient-Reported Outcome Measures (PROMs) [33,34].

7.7. Dementia

Post Stroke Dementia (PSD) can be due to vascular dementia or Alzheimer's Disease (AD). Other contributing factors are recurrent stroke, severe neurologic deficits, multiple infarctions, cerebral atrophy, and cerebral micro-bleeds that can precipitate PSD [35,39].

7.8. Epilepsy

Post Stroke Epilepsy (PSE) is likely due to abnormal release of glutamate after stroke. These are the seizures arising from the neuronal deficit purely. According to Golvic et.al., 2018 [38] seizures can be seen post-stroke rather than because of 5 predictive factors and they are the severity of a stroke, large artery atherosclerosis, early seizures, cortical involvement, and Middle Cerebral Artery (MCA) territory infarct

7.9. Post Stroke Cognitive Decline (PSCD)

PSCD can be easily found in elderly, rural, fewer years of education, diabetes, recurrent stroke, physical inactivity, and smoking. This can be a lethal complication as cognitive decline will eventually take away sensory as well as motor actions leaving the patient to be bed-ridden and have increased morbidity and mortality [40].

7.10. Stroke related sarcopenia

There are several fragilities in muscles and progressive decline in muscle mass and its function which lead to sarcopenia with advancing age [102].

8. Management

8.1. Non- Pharmacological Treatment

Surgical intervention in the case of ischemic stroke, craniectomy is used to release high pressure due to cerebral edema by large ischemic infarction. To prevent the recurrence of stroke carotid endarterectomy of ulcerated narrowed carotid is the best option as secondary prevention of stroke. But compared to endarterectomy, carotid stenting is less invasive but investigational.In case of hemorrhagic rupture of aneurysm or Arterio-Venous Malformation (AVM) clips are placed to avoid re-bleeding. Surgical decompression of hematoma is considered only when pharmacological therapy fails or during life-threatening conditions [24]. Conventional therapies include speech therapy, mirror therapy, occupational therapy [103], and stem cell transplantation [104,105]. Particularly, Bone Marrow Mesenchymal Stem Cells (BMSCs) are frequently studied due to its paracrine effect and exosomes play vital role in paracrine effect. Compared to stem cell therapy, exosomes therapy has shown lesser risk of rejection and has novel approach of treatment in stroke [106]. The Chinese Cochrane databases include some herbs in prevention of stroke [107].

8.2. Pharmacological Treatment

The immediate drug of therapy given within hours of the onset of stroke is rtPA [108,109]. It reduces associated disability when given as early as possible but caution must be taken.When there is delayed administration of rtPA then other drugs like retinoic acid, ascorbic acid, etc. can alleviate the overdue adverse effects of rtPA [45].

Mechanism of Granulocyte-Colony Stimulating Factor (G-CSF) is the novel advancement in the therapy for stroke depicted in mouse model. The FDA approved G-CSF drugs has many neuroprotective actions like neurogenesis, angiogenic actions, and anti-apoptotic actions[110]. Another novel approach is nerinetide, which is aneicasopeptide that interferes with post-synaptic density protein 95 (PSD-95) resulting in neuroprotective action. Efficacy and safety of nerinetide for the treatment of acute ischemic stroke in patients who underwent endovascular thrombectomy was carried out by ESCAPE-NA1 randomized clinical trial [111].

The other treatments include antiplatelet agents, antihypertensive agents, statins, which are generally given to remove the threat in the form of a clot, hypertension, and cholesterol deposition, respectively. Neuro-protectants like antioxidants and FDA approved NADPH Oxidase inhibitors (NOX inhibitors) are also used. NOX inhibitors obstruct ROS production and prevent inflammatory processes. The drugs for ischemic stroke are listed in Table 4.

As of now, no confirmed pharmacologic treatment is there for ICH. Medical guidelines are there for monitoring BP, ICP (Intra-Cranial Pressure), other complications, and acutely ill patients in the neuro-intensive care unit [24].

9. Lifestyle Modification

9.1. Physiotherapy

Difficulty in walking or motor inactivity is majorly seen in a post-stroke patient. Stroke patients need to adapt `exercise' in their life provided with the true guidance of a physiotherapist. Rehabilitation after stroke has given significant outcomes in motor functions after stroke [49]. Gait training is done to improve walking post-stroke with the help of a treadmill [57,124,125,126].

9.2. Adequate Sleep

Damage to certain regions of the brain can interfere with sleep patterns. So, it is necessary to have an adequate amount of sleep for the improvement of sleep after stroke. Neuroplasticity and activity the of brain are improved by sleep [51].

9.3. Mediterranean Diet (MeD Diet)

It is a diet including a principal source of monounsaturated fats, vegetables, olive oil, limited consumption of meat and dairy products, and moderate use of fish and alcohol. This diet has attained greater attention with prolonged survival and a lower risk of neurodegenerative disorders. The benefit of the MeD diet is assessed by REGARDS (Reasons for Geographic And Racial Differences in Stroke) study. In this study, the inverse relationship between adherence to the MeD diet and the occurrence of ischemic stroke was documented [50].

9.4. Fasting for 11- 20 h

Changes in diet style during the holy month Ramadan that is no fluid or food intake affects 24-hourly rhythm pattern and influences the control of the appearance of stroke [84].

9.5. Dairy Products

Milk and other dairy product consumptions are inversely related to the occurrence of stroke [127].

10. Conclusion

Stroke which is also known as Cerebrovascular Disorder is a medical emergency. Despite people managing their physical and mental health through a workout, there are still more people like obese, altered food taste which is high in calories leading to devastating conditions like stroke. People should know the signs and symptoms of stroke since it is a medical emergency and to cope up earliest. The risk factors are the various entrances for the commencement of stroke through which one can be able to prevent if aware of it. In the section of risk factors of stroke, genetics are yet to be explored. The complication being disability is itself directing stroke patients mentally to die hence it is needed to look to remove this disability by various rehabilitation centers of stroke. The proper diagnosis is also needed for this condition as there are two main types, misdiagnosis can lead to the noxious effect. To be specific with the noxious effect is that the therapy given for ischemic stroke includes blood thinners if given for hemorrhage can kill patients in seconds. Lifestyle modifications should be followed by stroke hit patient as it is meant to ease the life after stroke and mostly towards the correction of symptoms like motor dysfunction.

Competing Interests

The authors declare no competing interests.

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Review Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 10 (2020), Article ID 101500, 15 pages 
doi:10.32527/2020/101500

Pathophysiology, Complications and Management of Stroke: A review

Umme Habeeba A. Pathan1, Abdul Raheem Thayyil2, Thimmasetty Juturu2, and Shwetha Kamath2

1Department of Pharmacy Practice, Bapuji Pharmacy College, SS layout, Shamnur road, Davanagere-577004, Karnataka, India

2Faculty of Industrial Pharmacy, Bapuji Pharmacy College, SS layout, Shamnur road, Davanagere-577004, Karnataka, India

Received 09 August 2020; Accepted 04 September 2020

Editor: Hesham Hamed

Copyright © 2020 Umme Habeeba A Pathan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Stroke is the next foremost origin of death under Non-Communicable Diseases (NCD) after heart disease and cancer. Earlier, the detection of stroke was a failure due to its complexity in understanding. On the pages of history, it was a serious disease known as ‘Apoplexy’, which was later recognized as stroke. This review focuses on the updated definition, its types which are mainly two, ischemic and hemorrhagic stroke. It also covers the risk factors like age, genetics, cardiac diseases, and symptoms that differentiate the type of stroke which helps in diagnosing the mechanism correctly. The pathogenesis of stroke is summarized, which paves the path for the treatment regimen and if left untreated, possible complications can be seen. Finally, an attempt has also been made to brief the management including both non-pharmacological therapy with stem cell transplantation, surgical therapy, and pharmacological therapy.

Review Article
Egyptian Journal of Basic and Clinical Pharmacology
Vol. 10 (2020), Article ID 101500, 15 pages 
doi:10.32527/2020/101500

Pathophysiology, Complications and Management of Stroke: A review

Umme Habeeba A Pathan1, Abdul Raheem Thayyil2, Thimmasetty Juturu2, and Shwetha Kamath2

1Department of Pharmacy Practice, Bapuji Pharmacy College, SS layout, Shamnur road, Davanagere-577004, Karnataka, India

2Faculty of Industrial Pharmacy, Bapuji Pharmacy College, SS layout, Shamnur road, Davanagere-577004, Karnataka, India

Received 09 August 2020; Accepted 04 September 2020

Editor: Hesham Hamed

Copyright © 2020 Umme Habeeba A Pathan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite this article

Umme Habeeba A. Pathan, Abdul Raheem Thayyil, Thimmasetty Juturu, and Shwetha Kamath, "Pathophysiology, complications and management of stroke: A review," Egyptian Journal of Basic and Clinical Pharmacology, Vol. 10, Article ID 101500, 15 pages, 2020. doi:10.32527/2020/101500.

EJBCP

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