Lacunar syndromes are clinical manifestations of lacunar infarctions. Lacunar infarctions are defined as small subcortical lesions with a size of less than 15 mm in diameter caused by occlusion of a penetrating artery from a large cerebral artery, most commonly from the Circle of Willis. These penetrating arteries arise at sharp angles from major vessels and are thus, anatomically prone to constriction and occlusion. Other common sources of these penetrating arteries include the middle cerebral artery and the basilar artery.
The term “lacune” was first described in the late 19th and early 20th century based on pathologic analysis and adapted after imaging technology confirmed the initial hypothesis in the 21st century. A lacune usually describes a small, chronic cavity that represents the healed phase of lacunar infarction. However, there have been cases reported in which a lacune results from a larger infarct or intracerebral hemorrhage.
The anatomic distribution of lacunar syndromes and infarctions is most commonly the basal ganglia (globus pallidus, putamen, thalamus, and caudate), the pons, and the subcortical white matter structures (internal capsule and corona radiate). These anatomical sites correspond to lesions at the lenticulostriate arteries, the anterior choroidal artery, thalamoperforant arteries, paramedian branches of the basilar artery, and the recurrent artery of Heubner from the anterior cerebral artery.
Lesions at these specific sites account for many of the symptoms of lacunar syndromes. There are over 20 lacunar syndromes that have been described, but the most common ones are pure motor hemiparesis, pure sensory stroke, ataxic hemiparesis, sensorimotor stroke, and dysarthria-clumsy hand syndrome.
Multiple mechanisms have been proposed as the etiology of lacunar infarction. The usual etiology of small lacunar infarctions (between 3 mm and 7 mm) is lipohyalinosis of the small perforating arteries feeding deep subcortical structures. Another mechanism is micro-atheroma formation at the origin of penetrating arteries from major cerebral arteries like the middle cerebral artery, Circle of Willis, or the distal basilar artery. These first two mechanisms are proven pathologically and likely due to chronic hypertension and resulting in small vessel disease.
If the size of lacune is larger than 5 to 7 mm, it is often not caused by occlusion of 1 or 2 lenticulostriate arterial branches but from an atherothrombotic lesion involving the mainstem middle cerebral artery. These infarcts are named striatocapsular infarcts by Bladin and Berkovic.
Other proposed mechanisms that have been failed to be proven pathologically include tiny emboli causing obstruction and cerebral arteriolar and capillary endothelial dysfunction leading to small vessel disease as a result of extravasation of blood products.
Out of all the causes of Lacunar strokes, hypertension is the most common modifiable risk factor for stroke. For every 10mm hg decrease in blood pressure, there is a 1/3rd lowering of stroke risk in primary prevention. So it is extremely important to control the blood pressure effectively to prevent future strokes. Cigarette smoking doubles stroke risk.
One community-based study in Rochester, MN estimated that around 16% of first ischemic strokes in the United States are lacunar strokes.
In a similar community-based study of African-Americans in Cincinnati, lacunar infarctions accounted for 22% of first-time ischemic stroke events.
Data comparing the frequency of lacunar strokes among different sexes, races, and worldwide populations are not readily accessible. One study in Japan does state that the frequency of lacunar infarcts has decreased since the 1960s due to more aggressive control of risk factors, primarily hypertension.
The pathophysiology of lacunar syndromes is inherently linked to 2 vascular pathologies of the penetrating arteries from major intracranial and extracranial arteries: (1) thickening of the media resulting in decreased arterial diameter and (2) obstruction of the origins by microatheroma formation. Chronic hypertension, diabetes, and other genetic factors cause medial thickening by fibrinoid necrosis, smooth muscle hypertrophy, and other connective tissue elements. As a result, occlusive disease in these penetrating arteries causes a small infarct in the territory that the small vessel supplies. Since collateral circulation in these distant pontine and subcortical areas is so limited, and multiple penetrating vessels are likely affected in these patients, areas of infarct coalesce to form lake-like areas of infarcted/edematous brain tissue. Healing of this tissue ultimately forms "lacunes."
Dr. Miller Fisher first described arterial pathology under lacunes in the mid-1900s. These vessels contained focal enlargements and small hemorrhagic extravasations through the endothelium of the arteries. Fibrinoid tissue replaces subintimal foam cells that then obliterates the vascular lumens. This process was described as fibrinoid degeneration and lipohyalinosis.
Most commonly, lacunar syndromes affect the elderly with long-standing hypertension. Otherwise, younger patients with lacunar syndromes may have a diagnosis of rare genetic conditions, such as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The presenting complaint would usually not include cortical signs such as agnosia, aphasia, neglect, apraxia or hemianopsia. These lacunar infarcts usually cause symptoms over minutes to hours but may progress with a stuttering course. The clinical features and physical exam findings of lacunar syndromes are characteristic of the type of lacunar syndrome.
Pure motor hemiparesis: Patient presents with weakness on one side of the body (face, arm, and leg) without cortical signs and sensory symptoms.
Pure sensory stroke: Patient presents with unilateral numbness of the face, arm, and leg without cortical signs or motor deficits. All sensory modalities will be impaired.
Ataxic hemiparesis: These patients present with unilateral limb ataxia and weakness that is out of proportion to the strength/motor deficit. Patient’s may also exhibit other ipsilateral cerebellar signs such has dysarthria, dysmetria, and nystagmus without exhibiting cortical signs.
Sensorimotor stroke: Patients present with weakness and numbness of the face, arm, and leg without cortical signs. Cortical function testing must be done meticulously to distinguish between a frontoparietal lobe (MCA) stroke and a subcortical stroke (posterior thalamus and internal capsule).
Dysarthria-clumsy hand syndrome: This is the least common of all lacunar syndromes. Patients present with facial weakness, dysarthria, dysphagia and dysmetria/clumsiness of one upper extremity.
Initial evaluation of a suspected lacunar stroke involves brain imaging with a brain CT and MRI. Since small perforating arteries are hard to visualize with CTA and MRA, the diagnosis is made by matching a patient’s clinical features with a small, noncortical infarct seen on CT/MRI. The initial CT/MRI is also useful in ruling out life-threatening conditions such as intracerebral hemorrhage or herniation.
MRIs have been shown to have a higher sensitivity and specificity than CT. Diffusion-weighted imaging (DWI) is particularly important because it has higher sensitivity for acute infarcts when compared with T2 weighted MRI/FLAIR sequences.
In most cases, mapping a patient’s history of hypertension or diabetes and his/her clinical features with findings of acute ischemia on brain imaging is all that is needed for diagnosis of lacunar infarcts. However, if the patient is young and has no cerebral risk factors, further investigation may be required to determine if there is an embolic source. Vascular imaging and transcranial Doppler is warranted at the same time of initial CT/MRI to rule out large vessel ischemia.
The acute treatment of lacunar infarctions is like that of acute ischemic strokes. Within 4.5 hours of symptom onset, patients should receive intravenous (IV) alteplase therapy. The contraindications to IV thrombolysis is the same as those for other types of acute ischemic strokes, some of which include ischemic stroke/head trauma in the past 3 months, previous intracranial hemorrhage, gastrointestinal (GI) malignancy or hemorrhage in the past 21 days, intracranial/spinal surgery in the past 3 months, and intra-axial intracranial neoplasm. For those patients not eligible for IV alteplase therapy, aspirin therapy is recommended. Otherwise, the acute treatment involves stabilization and early involvement of rehabilitation with speech and physical therapy.
The most important aspect of treatment for these patients is preventative. Aggressive blood pressure control, early high-dose statin therapy, and antiplatelet therapy are crucial. Anti-platelet therapy with aspirin, clopidogrel, or fixed-dose aspirin with dipyramidal are all acceptable medications. With the results of the CHANCE trial and the POINT trial, dual antiplatelet therapy for 3 weeks followed by single antiplatelet will provide the best scheme of therapy. More prolonged dual antiplatelet therapy (clopidogrel + aspirin) has not been shown to decrease the risk of recurrent strokes and resulted in a significantly increased risk of bleeding and death. The present-day scheme of “aggressive medical therapy” with antiplatelet treatment, aggressive blood pressure control with a target of 120/80 mm Hg, high dose statin, good blood sugar control, stopping smoking, sodium reduction, and good weight control and lifestyle modification should be able to prevent at least 80% of strokes. The LDL should be lowered to less than 100 with a high-intensity statin. Usually a high-intensity statin decrease LDL approximately 50% on an average. Strategies to reduce HbA1C less than 7 are also very important.
The primary differential diagnoses that should be entertained are large vessel ischemic strokes (most commonly in the middle cerebral artery territory), intracranial hemorrhages (subarachnoid bleeds, subdural bleeds, intracerebral hemorrhage), seizures, and complicated migraine events.
As described earlier in the Evaluation section, large vessel ischemic strokes and intracranial hemorrhages are ruled out by brain imaging with CT and MRI. As described earlier, a large or giant lacune is pathophysiologically not a lacuna but rather, a striatocapsular infarct as described by Dr. Caplan resulting from atherothrombosis of the middle cerebral artery main-stem. If an acute lacunar infarction is not visible on initial DWI, seizures and complicated migraines should be entertained as possible differential diagnoses.
Seizures will present with cortical signs in addition to focal neurologic deficits. Usually, neurologic deficits will also improve after 24 to 48 hours after the seizure event and post-ictal phase. Lastly, an EEG may be used to further rule out a seizure as the cause of the patient’s symptoms.
The main adverse event to be hypervigilant for in patients with acute lacunar infarctions is a hemorrhagic transformation or adverse bleeding events after IV alteplase therapy. Close monitoring with frequent neurologic exams and a high degree of suspicion can prevent these devastating events.
Preventative treatment is generally well tolerated. However, patients should be notified that there is an increased risk of bleeding on long-term antiplatelet therapy. Side effects of antihypertensive therapy, such as orthostatic hypotension and an increased risk of falls should also be explained to the patient. No data exists that lacunar infarct patients are at increased risk of statin myopathy over the general population. These medications should be prescribed at the lowest therapeutic dose.
The short-term prognosis of lacunar infarctions is better than other infarcts due to other stroke mechanisms. Multiple population-based epidemiological studies on lacunar infarcts have shown significantly better survival among patients who suffered from lacunar infarctions compared to those who suffered from non-lacunar infarcts. These studies showed a case fatality of 0% to 3% within the first month and 3% to 9% within the first year, compared with 14% and 28%, respectively.
Though the short-term prognosis for patients with lacunar syndromes is better, there is not as stark a difference in the long-term prognosis when compared with non-lacunar events. Multiple studies have shown that the stroke recurrence rate and the risk of death between lacunar infarcts and non-lacunar infarcts are similar after 5 years. The main reason for the better 5-year survival rate in lacunar syndrome patients is attributed to the lower mortality within the first year of the ischemic event.
As expected, patients that suffered from a lacunar infarction with worse initial neurologic deficits had a worse functional outcome. However, data does not exist comparing patient functional outcome and long-term prognosis between different mechanisms of lacunar infarction production.
After initial stabilization and neurology evaluation, many consultations are not required in the acute phase setting. Physical therapy (PT), speech therapy (ST), occupational therapy (OT), and rehabilitation services led by a Physical Medicine and Rehabilitation (PM and R) physician must be made immediately. Lacunar syndrome patients must be initially evaluated in the hospital as well as followed closely in the outpatient setting to ensure that the patient recovers as quickly as possible.
Furthermore, close contact between the patient’s neurologist, primary care physician, PM and R physician, and PT/ST/OT providers after hospital discharge further aids in the prevention of recurrent lacunar/ischemic strokes.
Patients must be educated on the importance of compliance with preventative medical therapy after he/she suffers from a lacunar syndrome. The pathophysiology of their syndrome/infarct should be explained, emphasizing that the most common cause of lacunar infarctions is chronic, uncontrolled hypertension.
This includes antihypertensive, statin, and diabetic medication compliance, following up regularly with their primary care physician, neurologist, and physical therapist, and doing regular exercises provided through physical therapy to regain neurologic function and improve the standard of living.
As mentioned earlier in the treatment and consultations sections, patients with lacunar infarctions must be managed and seen by a neurologist, a PM and R physician, and physical, occupational, and social therapists to get total care. In the outpatient setting, a neurologist may treat neurologic deficits like ataxic and motor hemiparesis with muscle relaxants like baclofen, tizanidine, and/or botox. More importantly, preventative measures with intense antihypertensive therapy, high dose statin therapy, and strict control of blood sugars must be initiated immediately after a lacunar ischemic event. Finally, outpatient rehabilitation therapy must be continued until a patient’s neurologic function can be returned to as close to his/her baseline prior to the infarction.
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