A cerebrovascular accident, more commonly known as a “stroke,” is broadly classified as either ischemic or hemorrhagic. In either category, the end result is a loss of blood flow and nutrients and oxygen to a region of the brain, resulting in neuronal damage and subsequent neurological deficits. There are numerous causes of stroke, such as prolonged hypertension, arteriosclerosis, and emboli that have formed as a result of atrial fibrillation or rheumatic fever. In younger patients, the possible list of causes may be broadened to include clotting disorders and various forms of vasculitis. In the event of a possible stroke presentation, a precise history and physical must be performed alongside emergent neurological imaging before administering any form of treatment. With early, focused treatment based on the stroke etiology, rehabilitation programs, and long-term lifestyle changes, one can maximize his/her chances for a meaningful recovery.
There is a multitude of etiologies that can lead to a stroke. One of the most common causes is the formation of a plaque secondary to low-density lipoprotein cholesterol (LDL) build up. Some of the most common risk factors include hypertension, diabetes mellitus, and smoking. Thrombi can also develop at the bifurcation sites of the internal carotid, middle cerebral arteries, and the basilar arteries. Emboli commonly originate from the heart, especially in patients with preexisting heart arrhythmias (atrial fibrillation), valvular disease, structural defects (atrial and ventricular septal defects) and rheumatic fever. Emboli usually lodge in areas of preexisting stenosis.
Strokes that occur in small vessels are most commonly caused by chronic, uncontrolled hypertension and arteriosclerosis. These strokes occur in the basal ganglia, internal capsule, thalamus, and pons. Uncontrolled hypertension in these areas can also lead to small hemorrhages.
About 20% of all strokes are classified as hemorrhagic, with the etiology being most commonly uncontrolled hypertension. Other causes of hemorrhagic strokes include cerebral amyloid angiopathy, a disease in which amyloid plaques deposit in small and medium vessels, which causes vessels to become rigid and more vulnerable to tears. Deposition can occur anywhere, but they occur most commonly on the surfaces of the frontal and parietal lobes. The structural integrity of vessels is another important consideration in hemorrhagic stroke etiology, with aneurysms, arteriovenous malformations, cavernous malformations, capillary telangiectasias, venous angiomas, and vasculitis being more common reasons for stroke.
When a blockage or bleed occurs, the immediately adjacent neurons lose their supply of oxygen and nutrients. The inability to go through aerobic metabolism and produce ATP causes the Na+/K+ ATPase pumps to fail, leading to an accumulation of Na+ inside the cells and K+ outside the cells. The Na+ ion accumulation leads to cell depolarization and subsequent glutamate release. Glutamate opens NMDA and AMPA receptors and allows for calcium ions to flow into the cells. A continuous flow of calcium leads to continuous neuronal firing and eventual cell death via excitotoxicity.
In the first 12 hours, there are no significant macroscopic or microscopic changes. Twelve hours after the stroke, cytotoxic and vasogenic edema develop, neuronal cell bodies swell, and myelinated fibers disintegrate. Tissues swell as phagocytic cells clear away the dying cells. Extensive phagocytosis causes softening and liquefaction of the affected brain tissues, with peak liquefaction occurring 6 months post-stroke. Several months after a stroke, astrocytes form a dense network of glial fibers mixed with capillaries and connective tissue.
Hemorrhagic strokes lead to the same type of cellular dysfunction and concerted events of repair with the addition of blood extravasation and resorption.
A thorough history is an absolutely critical first step toward making a diagnosis. A stroke should be high on the differential for a patient presenting with sudden, focal neurological deficits and/or altered level of consciousness. Based on clinical presentation alone, it is almost impossible to differentiate between a hemorrhagic or ischemic stroke. The signs and symptoms elicited from the history and physical can aid in localizing the affected region. Common signs and symptoms include hemiparesis, sensory deficits, diplopia, dysarthria, and facial droop. Strokes that are more posterior present with a sudden onset of ataxia and vertigo. Symptoms commonly attributed to increased intracranial pressure, such as nausea, vomiting, headache, and blurred or double vision, may provide evidence supporting a hemorrhagic stroke. In addition to gathering information about the symptoms, one needs to establish the time of their onset to decide whether fibrinolytic therapy is an option once the diagnosis of ischemic stroke is confirmed.
A neurological exam is performed to ascertain stroke location, establish baseline function upon hospital admission, rule out a transient ischemic attack (TIA) and other stroke mimickers, and deduce potential comorbidities. It is composed of testing cranial nerve function, the range of motion and muscle strength, sensory integrity, vibratory sense, cerebellar function, gait, language, mental status, and level of consciousness. Baseline function is determined via the National Institutes of Health Stroke Scale (NIHSS), which focuses on the level of consciousness, visual and motor function, sensation and neglect, cerebellar function, and language capabilities.
In addition to the neurological exam, the neck is examined to rule out signs of meningitis via palpation of the paraspinal musculature and testing the range of motion. Besides testing extraocular muscle function and the visual field for visual defects, a fundus examination is performed to check for retinal hemorrhage, tears, and emboli. A peripheral vasculature exam includes palpation of the carotid, radial, femoral, and posterior tibial pulses. A cardiac exam is also performed to detect murmurs, rubs, gallops, or arrhythmias.
Emergency CT without contrast is one of the first diagnostic tools utilized to confirm the diagnosis and rule out any bleeds or a hemorrhagic stroke. Based on the CT results and symptom onset, a patient may be a candidate for fibrinolytic therapy. The diffusion-perfusion mismatch describes the area of tissue at risk ("penumbra") that can be saved with early treatment and identifies patients that benefit from reperfusion therapy. A diffusion-weighted MRI is obtained within the first 12 hours of patient presentation, but it is not considered to be the first line of imaging due to the time needed to obtain the images. There are also several contraindications for an MRI, with one of the most common ones being an implantable pacemaker. A CT angiogram aids in localizing the blockage in the vasculature. Doppler studies can also be utilized to determine the degree of carotid stenosis.
Labs are also drawn to determine the patient’s baseline health and provide potential clues toward stroke etiology. Some of the basic labs include a metabolic panel, complete blood count with differential, lipid profile, hemoglobin A1c (HbA1c), blood urine nitrogen (BUN), creatinine, albumin, and glomerular filtration rate (GFR). In younger patients presenting with stroke symptoms, other labs that might be ordered include a coagulation panel, rheumatoid factor (RF), anti-nuclear antibodies (ANA), and other markers for vasculitis.
An ECG and 24-hour ECG monitoring are performed to rule out a cardiac etiology. An EEG may also be warranted to rule out a post-seizure state.
Before any treatment can be administered, the patient must be assessed for stable airway, breathing, and circulation. The patient must also be assessed to determine whether he/she is a candidate for alteplase (rt-PA). The exclusion criteria are based on guidelines from the American Heart Association/American Stroke Association. Fibrinolytic therapy aims to dissolve the clot and restore blood flow to the affected regions. The fibrinolytic must be administered within 3 to 4.5 hours after symptom onset to be effective, depending on exclusion criteria. As with the treatment of myocardial infarction and sepsis care, during a stroke the "time is brain" approach is important and requires a fast treatment response. Mobile stroke units and telemedicine have evolved to reduce time to treatment onset. The time frame for treatment has recently been expanded due to the option of endovascular treatment.
A notable potential complication after fibrinolytic therapy is hemorrhagic transformation. Hemorrhagic transformation is classified as hemorrhagic infarction and parenchymal hematoma, each with 2 subsets. Hemorrhagic infarctions occur more often than parenchymal hematomas. Predictive factors for the occurrence of this complication include increased infarction area, gray matter location, atrial fibrillation, and cerebral embolism, acute hyperglycemia, low platelet count, and poor collateral circulation.
Within 24 to 48 hours of symptoms onset, patients should be placed on anti-platelet therapy, typically 325 mg of aspirin orally. Blood pressure should be maintained slightly elevated for the first few days after a stroke to counter vasoconstriction. Blood pressure should also be lowered by no more than 15% if diastolic blood pressure is over 220 mm Hg or if systolic blood pressure is over 120 mm Hg. Comorbidities also need to be addressed and managed during the patient’s hospital stay.
Patients are admitted to the stroke unit that is equipped and trained to treat and care for people with stroke. The superiority of stroke units compared to non-specialised units has been proven in studies.
The differential diagnosis is broad and can include stroke mimics such as TIA, metabolic derangement (in other words, hypoglycemia, hyponatremia), hemiplegic migraine, infection, brain tumor, syncope, and conversion disorder.
The prognosis after a stroke is multifactorial, with patient age, stroke severity, stroke etiology, infarct location, and associated comorbidities being significant contributing factors. Stroke complications can also impact a patient’s prognosis. Common complications include pneumonia, deep vein thrombosis, urinary tract infections, and pulmonary embolism. However, patients who do not experience any complications within the first week tend to experience steady neurological improvement. The majority of patients experience the most improvement during the first 3 to 6 months after a stroke.
During the time-dependent early stroke phase and rehabilitation, stroke care involves an interprofessional team to prevent the disease. Once the diagnosis of stroke is made, the patient may need extensive physical rehabilitation, speech therapy and/or a dietary consult. For those who recover function within 3 months, the prognosis is good, but for those with residual neurological deficits, the outcome is guarded.
|||Hankey GJ, Stroke. Lancet (London, England). 2017 Feb 11 [PubMed PMID: 27637676]|
|||Sarti C,Kaarisalo M,Tuomilehto J, The relationship between cholesterol and stroke: implications for antihyperlipidaemic therapy in older patients. Drugs & aging. 2000 Jul [PubMed PMID: 10933514]|
|||Shi Y,Wardlaw JM, Update on cerebral small vessel disease: a dynamic whole-brain disease. Stroke and vascular neurology. 2016 Sep [PubMed PMID: 28959468]|
|||Hanley DF,Awad IA,Vespa PM,Martin NA,Zuccarello M, Hemorrhagic stroke: introduction. Stroke. 2013 Jun [PubMed PMID: 23709734]|
|||Benjamin EJ,Blaha MJ,Chiuve SE,Cushman M,Das SR,Deo R,de Ferranti SD,Floyd J,Fornage M,Gillespie C,Isasi CR,Jiménez MC,Jordan LC,Judd SE,Lackland D,Lichtman JH,Lisabeth L,Liu S,Longenecker CT,Mackey RH,Matsushita K,Mozaffarian D,Mussolino ME,Nasir K,Neumar RW,Palaniappan L,Pandey DK,Thiagarajan RR,Reeves MJ,Ritchey M,Rodriguez CJ,Roth GA,Rosamond WD,Sasson C,Towfighi A,Tsao CW,Turner MB,Virani SS,Voeks JH,Willey JZ,Wilkins JT,Wu JH,Alger HM,Wong SS,Muntner P, Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017 Mar 7 [PubMed PMID: 28122885]|
|||Krishnamurthi RV,Moran AE,Feigin VL,Barker-Collo S,Norrving B,Mensah GA,Taylor S,Naghavi M,Forouzanfar MH,Nguyen G,Johnson CO,Vos T,Murray CJ,Roth GA, Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Adults Aged 20-64 Years in 1990-2013: Data from the Global Burden of Disease 2013 Study. Neuroepidemiology. 2015 [PubMed PMID: 26505983]|
|||Xing C,Arai K,Lo EH,Hommel M, Pathophysiologic cascades in ischemic stroke. International journal of stroke : official journal of the International Stroke Society. 2012 Jul [PubMed PMID: 22712739]|
|||Chung AG,Frye JB,Zbesko JC,Constantopoulos E,Hayes M,Figueroa AG,Becktel DA,Antony Day W,Konhilas JP,McKay BS,Nguyen TV,Doyle KP, Liquefaction of the Brain following Stroke Shares a Similar Molecular and Morphological Profile with Atherosclerosis and Mediates Secondary Neurodegeneration in an Osteopontin-Dependent Mechanism. eNeuro. 2018 Sep-Oct [PubMed PMID: 30417081]|
|||Mărgăritescu O,Mogoantă L,Pirici I,Pirici D,Cernea D,Mărgăritescu C, Histopathological changes in acute ischemic stroke. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2009 [PubMed PMID: 19690757]|
|||Aronowski J,Zhao X, Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 2011 Jun [PubMed PMID: 21527759]|
|||Yew KS,Cheng E, Acute stroke diagnosis. American family physician. 2009 Jul 1 [PubMed PMID: 19621844]|
|||Kwah LK,Diong J, National Institutes of Health Stroke Scale (NIHSS). Journal of physiotherapy. 2014 Mar [PubMed PMID: 24856948]|
|||Spader HS,Grossberg JA,Haas RA,Soares GM, Fundamentals of the neurologic examination for patients undergoing central nervous system interventional procedures. Seminars in interventional radiology. 2013 Sep [PubMed PMID: 24436545]|
|||Motta M,Ramadan A,Hillis AE,Gottesman RF,Leigh R, Diffusion-perfusion mismatch: an opportunity for improvement in cortical function. Frontiers in neurology. 2014 [PubMed PMID: 25642208]|
|||Heiss WD, The ischemic penumbra: correlates in imaging and implications for treatment of ischemic stroke. The Johann Jacob Wepfer award 2011. Cerebrovascular diseases (Basel, Switzerland). 2011 [PubMed PMID: 21921593]|
|||Birenbaum D,Bancroft LW,Felsberg GJ, Imaging in acute stroke. The western journal of emergency medicine. 2011 Feb [PubMed PMID: 21694755]|
|||Kisialiou A,Pelone G,Carrizzo A,Grillea G,Trimarco V,Marino M,Bartolo M,De Nunzio AM,Grella R,Landolfi A,Puca A,Colonnese C,Vecchione C, Blood biomarkers role in acute ischemic stroke patients: higher is worse or better? Immunity & ageing : I & A. 2012 Oct 31 [PubMed PMID: 23110752]|
|||Loftspring MC,Kissela BM,Flaherty ML,Khoury JC,Alwell K,Moomaw CJ,Kleindorfer DO,Woo D,Adeoye O,Ferioli S,Broderick JP,Khatri P, Practice Patterns for Acute Ischemic Stroke Workup: A Longitudinal Population-Based Study. Journal of the American Heart Association. 2017 Jun 23 [PubMed PMID: 28645938]|
|||Saver JL, Time is brain--quantified. Stroke. 2006 Jan [PubMed PMID: 16339467]|
|||Bowry R,Grotta JC, Bringing Emergency Neurology to Ambulances: Mobile Stroke Unit. Seminars in respiratory and critical care medicine. 2017 Dec [PubMed PMID: 29262428]|
|||Demaerschalk BM,Miley ML,Kiernan TE,Bobrow BJ,Corday DA,Wellik KE,Aguilar MI,Ingall TJ,Dodick DW,Brazdys K,Koch TC,Ward MP,Richemont PC, Stroke telemedicine. Mayo Clinic proceedings. 2009 [PubMed PMID: 19121244]|
|||Weimar C,Ziegler A,König IR,Diener HC, Predicting functional outcome and survival after acute ischemic stroke. Journal of neurology. 2002 Jul [PubMed PMID: 12140674]|
|||Wang W,Li M,Chen Q,Wang J, Hemorrhagic Transformation after Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke: Mechanisms, Models, and Biomarkers. Molecular neurobiology. 2015 Dec [PubMed PMID: 25367883]|
|||Musuka TD,Wilton SB,Traboulsi M,Hill MD, Diagnosis and management of acute ischemic stroke: speed is critical. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2015 Sep 8 [PubMed PMID: 26243819]|
|||Sun Y,Paulus D,Eyssen M,Maervoet J,Saka O, A systematic review and meta-analysis of acute stroke unit care: what's beyond the statistical significance? BMC medical research methodology. 2013 Oct 28 [PubMed PMID: 24164771]|
|||Allen CM, Differential diagnosis of acute stroke: a review. Journal of the Royal Society of Medicine. 1984 Oct [PubMed PMID: 6387114]|
|||Clarke DJ,Forster A, Improving post-stroke recovery: the role of the multidisciplinary health care team. Journal of multidisciplinary healthcare. 2015 [PubMed PMID: 26445548]|
|||Goyal M,Menon BK,van Zwam WH,Dippel DW,Mitchell PJ,Demchuk AM,Dávalos A,Majoie CB,van der Lugt A,de Miquel MA,Donnan GA,Roos YB,Bonafe A,Jahan R,Diener HC,van den Berg LA,Levy EI,Berkhemer OA,Pereira VM,Rempel J,Millán M,Davis SM,Roy D,Thornton J,Román LS,Ribó M,Beumer D,Stouch B,Brown S,Campbell BC,van Oostenbrugge RJ,Saver JL,Hill MD,Jovin TG, Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet (London, England). 2016 Apr 23; [PubMed PMID: 26898852]|
|||Nogueira RG,Jadhav AP,Haussen DC,Bonafe A,Budzik RF,Bhuva P,Yavagal DR,Ribo M,Cognard C,Hanel RA,Sila CA,Hassan AE,Millan M,Levy EI,Mitchell P,Chen M,English JD,Shah QA,Silver FL,Pereira VM,Mehta BP,Baxter BW,Abraham MG,Cardona P,Veznedaroglu E,Hellinger FR,Feng L,Kirmani JF,Lopes DK,Jankowitz BT,Frankel MR,Costalat V,Vora NA,Yoo AJ,Malik AM,Furlan AJ,Rubiera M,Aghaebrahim A,Olivot JM,Tekle WG,Shields R,Graves T,Lewis RJ,Smith WS,Liebeskind DS,Saver JL,Jovin TG, Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. The New England journal of medicine. 2018 Jan 4; [PubMed PMID: 29129157]|