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### <code><font color="red">A Brief Presentation on Lacunar Infarcts</font></code>
#### <code><font color="red">with an emphasis on former and current clinical trials</font></code>
##### <code><font color="red">[Brian Muchmore | UVM Neurology | 07/11/2019]</font></code>

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# What is a lacunar stroke?

* Small (0.2 to 15 mm in diameter) non-cortical infarcts

* Infarcts result in a small cavity, or lacune

* Caused by occlusion of a single penetrating branch of a large cerebral artery

* Arise at acute angles from the
  + Large arteries of the circle of Willis
  + Stem of the MCA
  + Stem of the basilar 
  
* Thus, most lacunes occur in the
  + Basal ganglia (putamen, globus pallidus, thalamus, caudate)
  + Subcortical white matter (internal capsule and corona radiata)
  + Pons

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# What is the etiology?

* Lipohyalinosis

* Microatheroma

* Tiny emboli (never proven pathologically)

* Endothelial dysfunction

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# What is the epidemiology?

* Incidence is around 25-50 per 100,000 in the population

* Approximately 25% of all ischemic strokes

* Higher incidence among African-American and Hispanics

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# What are the risk factors and associations?

* Chronic vasculopathy associated with systemic hypertension

* Diabetes mellitus

* Smoking

* Age

* LDL

* Genetics (for example APOE e4 carriers)

* Hyperhomocysteinemia (for example, a *MTHFR* mutation). In addition
  + Developmental delay
  + Marfanoid appearance
  + Osteoporosis
  + Ocular abnormalities
  + Thromboembolic disease
  + Severe premature atherosclerosis

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# Clinically ABSENT signs

* Lack of cortical signs
  + Aphasia
  + Agnosia
  + Neglect
  + Apraxia
  + Hemianopsia
  
<br>
  
* Also typically absent
  + Monoplegia
  + Stupor
  + Coma
  + Loss of consciousness
  + Seizures

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# Clinically PRESENT signs

* Unlike large artery brain ischemia, symptoms usually develop over hours/days
  + A stuttering course similar to large artery thrombosis can also ensue
  
* More than 20 lacunar syndromes have been described

* Five have been validated as being clinically predictive of radiologic lacunes
  + Pure motor hemiparesis
  + Pure sensory stroke
  + Ataxic hemiparesis
  + Sensorimotor stroke
  + Dysarthria-clumsy hand syndrome

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# Pure motor hemiparesis

* ~50% of all lacunar syndromes

* Weakness of face, arm, and leg on one side of the body

* May have dysarthria/dysphagia

* If preceded by hemiplegic TIAs --> "capsular warning syndrome"
  
* Typical location:
  + Internal capsule
  + Corona radiata
  + Basal pons
  + Medial medulla
  
* Positive predictive value:
  + 52-85%
  
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# Pure sensory stroke

* Numbness of the face, arm, and leg on one side of the body 
  
* Typical location:
  + Thalamus
  + Pontine tegmentum
  + Corona radiata
  
* Positive predictive value:
  + 95-100%
  
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# Ataxic hemiparesis

* Ipsilateral weakness and limb ataxia that is out of proportion to the motor deficit

* Also may exhibit ipsilateral dysarthria, nystagmus and gait deviation
  
* Typical location:
  + Internal capsule-corona radiata
  + Basal pons
  + Thalamus
  
* Positive predictive value:
  + 59-95%
  
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# Sensorimotor stroke

* Weakness/numbness of the face, arm, and leg on one side of the body

* Ipsilateral sensory impairment
  
* Typical location:
  + Thalamocapsular
  + Basal pons
  + Lateral medulla
  
* Positive predictive value:
  + 51-87%
  
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# Dysarthria-clumsy hand syndrome

* No sensory deficits

* Facial weakness, dysarthria, dysphagia, and slight weakness/clumsiness of one hand
  
* Typical location:
  + Internal capsule
  + Corona radiata
  + Basal pons
  
* Positive predictive value:
  + ~96%

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# Diagnosis

* Clinical syndrome that is consistent with CT or MRI

* CT has low sensitivity for detecting lacunes (30 to 44 percent)

* MRI is better

* Both have difficulty differentiating between acute and chronic lesions

* DWI is great if multiple infarcts of different ages are present
  + DWI overestimates size by up to 40%

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# Treatment

* Lacunar stroke specific treatment does not exist

* Prevention is the best treatment

* Follow current stroke guidelines
  + Thrombolysis
  + Thrombectomy
  + Also Aspirin, VTE prophylaxis, statins, BP management, living zen

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# References

* Filho, JO. **Lacunar infarcts.** UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (Accessed on July 11, 2019.)

* Messe, S. **Lacunar stroke.** DynaMed Plus. Ipswich, MA: EBSCO Information Services. http://www.www.dynamed.com (Accessed on July 11, 2019.)

* Lavallée, P and Lacunar-B.I.C.H.A.T. Investigators. **Placebo-Controlled Trial of High-Dose Atorvastatin in Patients With Severe Cerebral Small Vessel Disease.** *Stroke* 2009;40:1721–1728

* The SPS3 Investigators. **Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke.** *N Engl J Med* 2012;367:817-825

* Olmestig, J. et. al. **Effect of Tadalafil on Cerebrovascular Response in Patients with Small Vessel Disease (ETLAS-STUDY).** *World Stroke Congress* 2018;225