Continuing Education Activity

Ischemic strokes are due to the occlusion of vascular supply to a specific part of the brain leading to tissue hypoxia and damage. Lacunar stroke is a common occlusive stroke with significant morbidity and mortality. Advancement in knowledge about modifying risk factors and early diagnosis has led to a favorable outcome. Most lacunar strokes remain asymptomatic due to the involvement of small vessels causing small-sized infarcts. However, accumulating multiple small lacunar infarcts can lead to significant physical and cognitive disabilities. This article reviews the pathophysiology, diagnosis, and management options and highlights the role of the interprofessional team in treating patients suffering from a lacunar stroke.

Objectives:

• Summarize the pathophysiology of lacunar stroke.
• Review history and physical examination findings of patients suffering from lacunar infarctions.
• Outline various treatment options, including medications and rehabilitation for managing lacunar stroke.
• Describe the importance of improving care coordination among interprofessional team members to ensure the best outcomes.

Introduction

Stroke is one of the most common illnesses causing functional impairment and disability. According to American Stroke Association data, ischemic stroke accounts for 87 percent of all strokes, while hemorrhagic stroke accounts for the rest. Lacunar strokes, a type of ischemic stroke, are small and located in non-cortical areas.[1]

Lacunar infarctions are caused by the occlusion of small deep penetrating branches of the cerebral vessels from the circle of Willis, including branches from the middle cerebral artery, anterior cerebral artery, posterior cerebral artery, or basilar artery.[2]

Most lacunar strokes remain asymptomatic due to the involvement of small vessels causing small-sized infarcts. However, accumulating multiple small lacunar infarcts can lead to significant physical and cognitive disabilities. 

Etiology

Ischemic strokes are due to the occlusion of vascular supply to a specific part of the brain leading to tissue hypoxia and damage. In lacunar infarction, the small penetrating cerebral vessels supplying the subcortical areas are occluded due to various vascular pathologies, including lipohyalinosis and microatheromas.[3]

In some cases, small embolic fragments from a cardiac source or large vessel disease can cause deep penetrating artery occlusion.[4][5][6]

The development of small vessel disease, causing a lacunar stroke, is mainly due to underlying medical conditions such as hypertension and diabetes mellitus. Other risk factors include smoking, LDL levels, carotid artery atherosclerosis, peripheral artery disease, previous TIA, and hyperhomocysteinemia.[7][3]

Certain genetic factors also increase the risk of developing small vessel disease. APOE e4 alleles and carriers are at increased risk of developing white matter lesions. Also, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the rare genetic disorders that can cause small vessel arteriopathy.[8]

Epidemiology

Stroke is the fifth leading cause of death in the United States.[9][10] Lacunar strokes are the most common among ischemic strokes; they constitute 25% of ischemic strokes.[11][12]

According to the Global Burden of Disease (GBD) 2016 lifetime risk of stroke, the estimates include almost equivalent risk of stroke among women and men. GBD estimated lifetime risk of 18.3% with ischemic stroke and 8.2% risk of hemorrhagic stroke. [10]

In a community-based study, the incidence rate of lacunar infarct in a predominantly White community was 29 per 100,000 population, while in another community-based research with a mostly Black population, the incidence rate of lacunar infarct was 52 per 100,000 people.[13][14]

In a follow-up study, patients with lacunar infarcts are diagnosed with dementia 4 to 12 times more frequently than the average population.[15] Post-stroke dementia in accumulated lacunar infarct is common despite their small size and association with small vessel disease.[16] Also, lacunar stroke at an older age is associated with worse long-term disability.[17]

Pathophysiology

Cerebral circulation mainly comprises the arterial system, which forms the circle of Willis.[18] The main cerebral branches include the middle cerebral artery, anterior cerebral artery, posterior cerebral artery, basilar artery, and vertebral arteries that supply the cerebrum, cerebellum, and brainstem. These arteries have deep branches that penetrate and feed deep gray and white matter of the cerebrum, cerebellum, and brainstem.[18]

Occlusion or blockage of the small penetrating arteries causes small lacunar strokes. Their size varies from 3 mm to 20 mm in dimension. However, only 17% of lacunar strokes are less than 10 mm in size.[3]

Small arterial occlusion is the fundamental pathogenesis for lacunar strokes. The primary underlying pathophysiological process is lipohyalinosis and micro-atheroma formation.[19]

In lipohyalinosis, the media of small vessels thickens, followed by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements. This arterial pathology is caused by hypertension, diabetes, and other risk factors, including hyperlipidemia and hyperhomocysteinemia. Such segmental arteriolar disorganization causes a significant reduction in the luminal diameter of small arteries (less than 200 μm in diameter) and causes hypoperfusion to subcortical areas.[3]

Microatheroma is an atheromatous arterial lesion within the brain parenchyma. They cause occlusion or stenosis of a deep penetrating brain artery. Histologically, microatheroma is identical to large-vessel atheroma. Microatheroma has the subintimal deposition of lipids and proliferation of fibroblasts, smooth muscle cells, and lipid-laden macrophages. Microatheroma is generally located in the proximal region near the origin of the parent artery.[19]

Other mechanisms can cause small vessel arteriopathy, which can cause subcortical strokes. Sometimes arterial media may get foreign deposits, as in amyloid angiopathy and genetic conditions like cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).[8]

APOE gene is responsible for making apolipoprotein; it helps transport cholesterol across different tissues and cells. APOE represents three alleles, e2, e3, and e4. The APOE e4 allele may confer some risk of developing small vessel pathology. There is evidence that APOE e4 carriers are at increased risk for atherosclerosis. APOE is responsible for clearing beta-amyloid from the brain; e4 may be less efficient, causing atherosclerosis.[20]

Deep penetrating branch occlusion via direct emboli or thrombus from a cardiac or large artery source, micro atheroma involving the lenticulostriate branch, or macroatheroma caused by parent artery occlusion can also cause a lacunar stroke.

Other rare postulated reasons for small cerebral infarcts include embolism, vasculitis, infections, and vasospasm, which are not proven by autopsy.

Histopathology

A lacune is generally identified on autopsy as a fluid-filled cavity that marks the healed stage of small infarcted brain tissue. There are three types of lacunes, as described per histopathology. Type 1 is classified as an ischemic infarct, type 2 is a small hemorrhage, and type 3 includes dilated perivascular space.[21][22]

Atherosclerosis of small cerebral arteries originating from the brain's base is involved in subcortical ischemia and lacunar syndromes.

On autopsy, Miller Fisher observed specific pathological changes in lacunar infarcts. It showed a characteristic histopathological finding of segmental arterial disorganization, fibrinoid degeneration, and lipohyalinosis (hyaline wall thickening).[23]

Lipohyalinosis is described as microangiopathy with loss of normal arterial architecture with mural foam cells and fibrinoid necrotic changes in the vessel wall.[24][19]

Histologically, microatheroma is very much like a large-vessel atheromatous plaque. It involves the subintimal deposition of lipids, a proliferation of fibroblasts and smooth muscles, and lipid-laden macrophages.[23]

Hyaline atherosclerosis of small cerebral vessels is a common finding in patients with lacunar infarcts.

History and Physical

As with ischemic strokes, lacunar infarcts usually present with sudden onset neurological deficits. However, a subset of lacunar infarctions may present in a stepwise pattern and are known to worsen even during admission. Lacunar infarcts are common in the deep brain nuclei, including the thalamus, basal ganglia, pons, and white matter of the internal capsule. Lacunar infarcts can be asymptomatic and are noted on imaging as incidental findings. Silent lacunar infarcts are more common than symptomatic lacunar infarcts.[25]

Clinical presentation depends on the area of brain involvement. Lacunar infarcts in the centrum semiovale may present without symptoms and can be found incidentally on brain imaging for some other cause. However, certain lacunar infarcts, like in the posterior limb of the internal capsule or the pons, can present with severe hemiplegia. Often, cortical findings, such as neglect, visual disturbances, aphasia, and behavioral changes, are absent in the clinical presentation of lacunar stroke as they occur in subcortical areas of the brain.

Lacunar strokes seldom affect memory, language, and judgment. There are about 20 different types of lacunar syndromes described in the literature. The most common lacunar syndromes are described below:

1. Pure motor hemiparesis involves the posterior limb of the internal capsule, corona radiata. This type presents with contralateral hemiparesis of the face, arm, and leg. Mild dysarthria may be present with the absence of sensory symptoms. These are the most common lacunar syndromes. They account for 45% of cases of lacunar strokes. Cortical signs like aphasia, cognitive deficit, or visual symptoms are always absent. Pure motor stroke can be a combination of weakness in the arm, leg, or face on one side or any of these parts alone.
2. Ataxic hemiparesis comprises 10 to 18% of cases. It involves the internal capsule, pons, or corona radiata. It causes hemiparesis of the contralateral face and leg and ataxia of the contralateral limb. Ataxia is the prominent feature of this stroke.
3. Pure sensory stroke involves the thalamus or corona radiata; it presents with the absent or abnormal sensation of the contralateral of the face, arm, and leg. It accounts for 7% of cases of lacunar strokes. The sensations affected are pain, temperature, touch, pressure, vision, hearing, and taste. A common form of thalamic lacunar stroke is known as Dejerine Roussy syndrome.[26]
4. Dysarthria: clumsy hand syndrome involves the pons or internal capsule and presents with dysarthria and problems pronouncing words due to voice box muscle weakness, including tongue, larynx, and other facial muscle weakness. Contralateral clumsiness of the upper extremity is present with preserved motor strength. There may be difficulty with subtle fine movements such as writing or tying a shoelace.
5. A sensory: motor stroke involves the thalamus, internal capsule, or putamen-capsule-caudate and presents clinically with a combination of contralateral sensory and motor loss. Sensory-motor lacunar strokes are the second most common type of lacunar strokes. They account for 20% of cases.[27][28][29]

Most penetrating branches arise from the middle cerebral artery; the intracranial non-stenotic atheroma in the large vessel may cause a lacunar stroke by blocking the penetrating branch artery at its takeoff point.[30]

Neurological fluctuation and deterioration is a common feature of subcortical strokes. More than 40% with subcortical infarct deteriorate neurologically within the first week of onset of stroke symptoms. One-third of the deteriorated patients reverse spontaneously. The rest of them suffer a physical disability.[31] Lacunar strokes are a common cause of vascular dementia and mild cognitive impairment, often overlooked in clinical practice. Multiple silent lacunar strokes are documented on brain MRI, with patients presenting with mild cognitive impairment and early dementia.[32]

Evaluation

Sudden onset neurological deficit requires emergent neuroimaging. An initial non-contrast head CT scan is preferred in an acute setting as it is readily available, quick, and useful to rule out life-threatening conditions such as intracerebral bleeding or herniation and clear the patient for possible intervention.

CT scan seldom identifies lacunar ischemic insult within the first 24 hours due to its small size. If seen, lacunar strokes are ill-defined hypodensities on CT scans unless there is a hemorrhagic component to the acute stroke. A hyperdensity of a large artery on non-contrast head CT indicates the presence of a thrombus inside the arterial lumen or vessel calcification. Early infarct signs on non-contrast CT include loss of gray-white differentiation and focal hypoattenuation of brain parenchyma. These details are difficult to read in small subcortical strokes. Chronic lesions may appear as hypodense foci.

CT angiogram of the head and neck can also be done. This can show a filling defect consistent with a thrombus blocking a specified vessel. It may also show arterial narrowing, and extensive vessel disease, like in the carotid arteries, which may be a source of an embolus or the middle cerebral artery features consistent with an atheroma. Neurovascular imaging modality is essential to determine the presence of large artery occlusion as it helps determine the need for catheter-guided thrombolysis.

MRI is a superior imaging modality in acute and subacute settings to detect lacunar infarction. In the acute stage, the MRI diffusion-weighted image (DWI) has the most diagnostic accuracy. MRI-DWI helps to differentiate between acute and chronic infarction.[33] In an acute setting, on T1-weighted images, lacunes appear as focal areas of decreased signal intensity and as focal areas of hyperintensity on T2-weighted images. Chronic lesions are isointense to CSF on all sequences.

In cases where a neck angiogram is not done, carotid ultrasound helps diagnose an atherosclerotic narrowing of the extracranial carotid artery. The risk of stroke is higher in patients with severe carotid artery stenosis (CAS). The U.S. Preventive Services Task Force considers 70%-99% of carotid stenosis clinically significant. Carotid artery intervention is recommended in clinically significant lesions.

Extensive embolic workup, including echocardiography and vascular imaging evaluation, is very low yield in cases of lacunar strokes.[34] However, this may be necessary in some cases, like in young patients with no apparent medical issues.

Other immediate tests to be performed include blood glucose levels, electrocardiogram, complete blood count including platelets, troponin, prothrombin time, and international normalized ratio (INR), activated partial thromboplastin time, and a complete metabolic panel and lipid panel. These tests are helpful in the assessment of underlying stroke risk factors.

Treatment / Management

Treatment principles for acute lacunar stroke are similar to any acute ischemic stroke. The initial goal of acute-stage treatment is ensuring medical stability and determining candidacy for thrombolysis. Tissue plasminogen activator (TPA) improves outcomes for patients with ischemic stroke if administered within 4.5 hours of symptom onset. Once intracerebral bleed is ruled out, intravenous thrombolysis is an important step in the treatment. An acute lacunar infarct is efficiently treated with TPA.[35][36]

If symptom onset duration is more than 4.5 hours and there is suspicion of intracranial arterial occlusion in the anterior circulation, CTA/MRA is useful for selecting candidates for mechanical thrombectomy between 6 to 24 hours from the last known well.

Management of a patient who presents with acute lacunar infarct out of TPA window consistent with a non-cardioembolic stroke includes dual antiplatelet therapy (DAPT) with aspirin and clopidogrel within 24 hours of symptom onset and continued for 21 days. DAPT in the acute phase effectively lowers recurrent ischemic stroke for 90 days from symptom onset. Antiplatelet therapy should be delayed for 24 hours in patients who received TPA.

Management of hypertension includes allowing for permissive hypertension unless the blood pressure is markedly elevated (i.e., more than 220/120 mmHg); in this case, lower blood pressure by 15% during the first 24 hours, hold any outpatient antihypertensive medications at admission for the early 24 hours, unless other comorbid conditions require the immediate lowering of blood pressure. In patients where TPA is given or who undergo thrombectomy, lowering the blood pressure below 185/110 mmHg is ideal.

Blood sugar management is done to maintain euglycemia with recommended blood glucose levels at 60–180 mg/dL. Both hypoglycemia and hyperglycemia should be monitored and corrected. The recommended HbA1c goal is 6.5 to 7.

Correct volume status by giving isotonic saline as stroke patients tend to be volume depleted. Keep oxygen saturation above 90%. Continue statin therapy with a goal LDL of less than 70 mg/dl. Assess swallowing function before advancing diet. VTE prophylaxis and early mobilization efforts are essential parts of the treatment plan.[37]

Stroke Prevention 

Primary and secondary stroke prevention remains an essential part of the treatment plan. Primary prevention includes the prevention of the first episode of stroke, and secondary prevention includes the prevention of recurrence.

Primary stroke prevention measures include risk factor management that uses antihypertensive medications, diabetes control, cholesterol-lowering agents, smoking cessation, dietary intervention, weight loss, and exercise.

Secondary prevention includes antithrombotic agents like aspirin, clopidogrel, extended-release dipyridamole, and ticlopidine and managing underlying risk factors. Antiplatelet agents reduce the risk of recurrence in patients with lacunar strokes.[38] Blood pressure control, diabetes control, lipid management, smoking cessation, weight loss, and regular exercise are included in secondary prevention strategies. Blood pressure reduction at a systolic blood pressure target of less than 130 mmHg is beneficial.[39]

Dual antiplatelet therapy (clopidogrel and aspirin) for secondary prevention has not shown a further reduction in the risk of recurrence in lacunar stroke.[40] Secondary stroke prevention is an essential strategy; it can prevent as much as 80% of all recurrent strokes.[41]

Oral anticoagulants are not considered for small cerebral vessel disease-related stroke prevention, including recurrent lacunar infarcts, as they disproportionately increase intracranial cerebral hemorrhage risk.[42]

Physical therapy and rehabilitation are essential steps for managing patients who suffer lacunar strokes that cause physical disability. These patients require rehabilitation. The goal of rehabilitation is to optimize functional recovery after a stroke and level of independence and maintain quality of life.

Differential Diagnosis

Differential diagnoses of lacunar infarcts include the following:

• Large vessel ischemic stroke in the middle cerebral artery territory: it is clinically differentiated from lacunar strokes by the presence of cortical signs, including altered mental status, aphasia, hemineglect, etc.
• Intracranial hemorrhages can be easily seen on neuroimaging modalities like brain CT scans.
• Seizures are caused by excess neuronal activity and can be differentiated clinically by their tonic-clonic activity and postictal state after having seizures.
• Complicated migraine: symptoms are usually accompanied by headache and aura. A typical aura may involve visual disturbances, sensory symptoms, motor weakness, or speech disturbances.
• Brain tumors: are distinguished by their characteristic appearance on MRI.
• Multiple sclerosis (MS): can cause paroxysmal attacks of ataxia and dysarthria. MRI helps distinguish the presence of plaques due to MS from a stroke. Further cerebral vasoreactivity measured by transcranial Doppler (TCD) sonography can be used for differentiating ischemic and demyelinating lesions. The presence of oligoclonal bands on lumbar puncture is characteristic of multiple sclerosis.

Prognosis

Earlier studies suggested that lacunar stroke has a better prognosis compared to other strokes. It has a high survival rate, a low recurrence rate, and a relatively good functional recovery. In general, lacunar infarcts have a relatively favorable prognosis.[43]

However, recent studies showed that in the earlier stages of the disease, the prognosis of lacunar stroke appears to be benign. Still, long-term prognosis with lacunar stroke constitutes an increased risk of death, mainly from cardiovascular causes. The risk of stroke recurrence is similar to any other type of stroke. Patients with recurrent small vessel disease are at increased risk of developing cognitive decline and dementia.[44][16]

Complications

Lacunar strokes are thought to be the leading cause of vascular dementia and cognitive impairment.[16] Accumulated lacunar infarcts can lead to other disease-related complications due to physical disability, including, but not limited to, aspiration pneumonia, deep vein thrombosis, pulmonary embolism, urinary tract infection, depression, and decubitus ulcers.

Postoperative and Rehabilitation Care

Most patients with lacunar infarctions have significant improvements in neurologic deficits. Physical therapy, speech therapy, occupational therapy, and rehabilitation services remain essential after hospital care to regain maximum strength and functional level after stroke.

Deterrence and Patient Education

Patients need to be aware of risk factors that increase stroke risk. Compliance with antithrombotic agents to prevent the recurrence of stroke is essential. Patients are advised to maintain a healthy diet, exercise regularly, avoid smoking, and avoid excessive alcohol use. Together, these habits reduce the risk of having strokes in general. If patients have high blood pressure, lipid disorder, or diabetes, regular follow-up with their primary care provider is essential to keep these risk factors optimally controlled.

The timeline of recovery from a lacunar stroke is different for everyone. Home safety is essential. Fall risk due to physical disability is common. Depression is common in people who have experienced a stroke and should be addressed if present. Cognitive impairment due to multiple subcortical strokes can progress to vascular dementia and should be monitored.

Enhancing Healthcare Team Outcomes

Patients with lacunar infarctions must be managed by a neurologist, family clinicians, nursing staff, and physical, occupational, and social therapists, all operating as an interprofessional team, to receive comprehensive care. Physical deficits like ataxia and motor hemiparesis are managed with physical therapy, while muscle relaxants like baclofen and tizanidine can be used for spasticity. Pharmacists remain crucial in patients receiving multiple medications to check drug interactions. Rehabilitation therapy must be continued to maximize the patient’s neurologic function to bring them close to their baseline before the infarction. All interprofessional team members must maintain open communication lines with each other and maintain accurate and updated patient records to serve as an accurate information source for everyone involved in care. This interprofessional approach to care will result in the best possible patient outcomes. [Level 5]

Long-term care coordination is the responsibility of the primary care provider. Emphasis on managing stroke risk factors includes intense antihypertensive therapy, lipid management, and strict control of blood sugars after the lacunar ischemic event.