Charcot-Bouchard aneurysms are minute aneurysms (microaneurysms) in the brain that occur in small penetrating blood vessels with a diameter that is less than 300 micrometers. The most common vessels involved are the lenticulostriate branches (LSA) of the middle cerebral artery (MCA). LSAs originate from the MCA just before its bifurcation, and they can vary between 2 to 12 in number (average 8.1). Most branches arise medially (99.2%), close to the internal carotid artery. They supply the basal ganglia, and more specifically the putamen and caudate, followed by the thalamus, pons, and the cerebellum.
Charcot-Bouchard aneurysms are named after the French physicians Jean-Martin Charcot and his student Charles Joseph Bouchard. In the 19th century, Bouchard discovered these aneurysms during his research under Charcot. Cole and Yates strengthened Charcot and Bouchard's work by demonstrating that aneurysms truly exist using microangiographic techniques in the 1960s. However, it has been a topic of lively debated if it is, in fact, the rupture of these aneurysms that are responsible for the intracerebral bleeds.
Individuals with chronic systemic hypertension are at high risk of developing atrophy of the outer muscular layer. With the loss of integrity of the vessel wall, microaneurysms develop in LSA, which are at high risk of rupture. Bleeding of aneurysms into the deep structures of the brain parenchyma is also referred to as intraparenchymal hemorrhage or, more broadly, as intracerebral hemorrhage. Clinically the deficits that present can point towards the location of the bleed. The first line diagnostic modality for these patients is a non-contrast computed tomography (CT) of the head to visualize the bleed. Depending on the severity and location of the hemorrhage the treatment options vary from observation to neurosurgical intervention.
Chronic systemic hypertension is the most critical risk factor for developing Charcot Bouchard aneurysms that subsequently rupture and cause hemorrhage. The risk factors broadly classify as follows:
Systemic diseases such as chronic kidney disease, cerebral amyloid angiopathy, vascular malformations, and coagulopathies either hereditary, acquired, or due to drugs such as warfarin and antiplatelet medications also increase the risk of development of microaneurysms and intracerebral hemorrhages.
Intracerebral hemorrhage contributes to 10 to 20% of all strokes worldwide and about 8 to 15% of all strokes in the United States. The lifetime risk of stroke in individuals 25 years and older in 2016 was estimated to be 24.7% among men and 25.1% in women. The overall risk is thus, an estimated 24.9% compared to 22.8% in 1990. The highest risk is in East Asia and Europe and the lowest risk in countries with a low sociodemographic index such as Sub-saharan Africa. Similarly, the incidence and mortality of stroke are highest in Asia, especially China, and East European countries. Although the rates are declining, the absolute number of incidence cases in 2016 has doubled since 1990, with the majority of individuals being under the age of 70. The estimated case fatality of intracerebral at one month is 40% and at one year is 54%. Long term functional independence occurs in only 13 to 49% of the patients.
LCAs branch-off at right angles from the MCA, rendering the blood flow through the LCA disturbed and non-laminar. The friction between the blood flow and lateral walls of the blood vessels gives rise to a sheer force. Furthermore, the changes in blood pressure, velocity, and diameter that occurs at the branching of arterioles to capillaries increase the sheer force in LCAs. Over time the increase in blood pressure and wall stress upregulates atherogenic factors and smooth muscle cell proliferation, causing abnormality in the cell junctions and formation of microaneurysms. Rupture of the microaneurysms leads to bleeding and hematoma formation in the deep structures of the brain - commonly in the basal ganglia.
Following this sequence of events is the disruption of the surrounding parenchymal structure, mass effect on surrounding structures, disruption in neurotransmitter release, and membrane depolarisations. Through different mechanisms, several inflammatory pathways become activated. Some of these mechanisms include:
Most of the hematoma enlargement occurs within the first 3 hours of onset, but it can continue to expand post 12 hours of onset. The perihematomal edema peaks at five days from onset. With increased intracranial pressure the cerebral perfusion decreases, and patients are at risk of global cerebral hypoxia.
Like in any other blood vessel, the wall comprises of, from inside out, the tunica intima, media, and adventitia. The intima layer is sensitive to endothelial nitric oxide synthase, which produces potent vasodilation in response to acetylcholine, substance P, and bradykinin. The nerve fibers, the majority of which are sympathetic, are distributed in the tunica media and adventitia layers.
Chronic hypertension causes hypertrophy of the smooth muscle layer in response to the consistently higher pressures within the vessel lumen. Hypoxia to the outer smooth muscle layers leads to their degeneration and fibrinoid necrosis. Following this is sclerosis of the media layer and overtime of the entire vessel wall.
A similar sequence of events occurs in cerebral amyloid angiopathy, where there is a deposit of beta-amyloid in the vessel wall that leads to hypoxia and fibrinoid necrosis.
Finally, the collagen fiber network then gets replaced with hyalin. These hyalinized areas are points of low resistance and are thus susceptible to aneurysmal dilatation and rupture with sudden increases in blood pressure. The size of the hematoma correlates with the size of the ruptured aneurysm. The LCAs are especially vulnerable since the deep structures in the brain surrounding these arterioles and capillaries do not allow them to withstand high-pressure variations.
The history should begin with asking the patient about the time of symptom onset and progression of symptoms. Intracerebral hemorrhage could present during physical activity, emotional stress, or even at rest in individuals with risk factors. General symptoms that the patient (or accompanying bystanders) complain of at presentation include
Also, screening for risk factors such as systemic hypertension, as well as medications such as anticoagulant drugs, antiplatelet drugs, is crucial. Important comorbid states to look for in these patients include liver disease and malignancies as they are associated with coagulopathies. In patients with cerebral amyloid angiopathy, cognitive dysfunction might be additionally present.
Accurate measurement of vital signs, a baseline GCS score, and a complete physical exam with a structured neurological exam is required. With the worsening of cerebral edema and an increase in the size of the hematoma, neurological symptoms progress within minutes to hours. The specific neurological deficits seen reflect the location of hemorrhage, such as:
Management of intracerebral hemorrhage begins with securing the airway, breathing, blood pressure control, and maintaining circulation using pressors. Patients with a Glasgow Coma Scale less than 8 often require intubation and ventilation. An anticoagulation reversal would follow this if the patient were on any pertinent medications. The risk of rapid deterioration in patients with intracerebral hemorrhage is maximum in the first 24 hours and requires intensive care unit monitoring.
The blood pressure should be lowered cautiously in these patients. For patients with initial systolic blood pressure between 150 and 220 mm Hg, without contraindications to acute lowering of the blood pressure, the target systolic blood pressure should be between 140 mm Hg and lower. For patients with systolic blood pressure over 220 mm Hg, the blood pressure goal should be between 140 to 160 mm Hg. However, lowering of blood pressure must be balanced with maintaining adequate cerebral perfusion pressure, and blood pressure should be monitored closely (every 5 minutes) in these patients. Appropriate antihypertensives include nicardipine, clevidipine, labetalol, esmolol, enalaprilat, fenoldopam, and phentolamine.
After stabilization of the patient, a neurosurgical consult is necessary to evaluate for intracranial hypertension. Short-term intravenous mannitol boluses, hypertonic saline, or hyperventilation could be considered in acutely worsening cerebral edema to maintain cerebral perfusion greater than 70 mm Hg. Surgical procedures such as decompressive craniectomy for intracerebral hemorrhages merit consideration for two purposes, firstly to decrease the mass effect of the hematoma, thereby improving cerebral perfusion and second, to halt the inflammatory processes caused by the breakdown of blood. In patients with lobar hematomas of 10 to 100 mL located within 1 cm from the brain surface, and without intraventricular hematomas or coma, early surgical intervention has a favorable outcome at six months.
Lastly, the management of concomitant intraventricular hemorrhage and obstructive hydrocephalus with ventriculostomy and external ventricular drainage is warranted in patients with enlarging ventricles on CT scan and neurological deterioration. If the patient is experiencing seizures or has cortically located lobar hemorrhages, seizure prophylaxis with anti-seizure medications such as phenytoin can be administered.
Other important therapeutic interventions include:
In summary, the key to management is stabilizing the patient, cautious lowering of blood pressure, and maintaining adequate cerebral perfusion while actively managing complications as they arise.
It is critical to differentiate intracerebral hemorrhage from lacunar hemorrhages. Intracerebral hemorrhages occur due to microaneurysm formation in the LCAs versus lacunar hemorrhages that occur secondary to ischemia and reperfusion injuries. Although they both have systemic hypertension as an important predisposing risk factor, patients with lacunar hemorrhage are more likely to have type 2 diabetes mellitus and a higher body mass index.
The following are relevant studies for the management of intracerebral hemorrhage and its complications:
Determining prognosis in patients with intracerebral hemorrhage is critical. Underestimation of the prognosis would lead to unnecessary procedures and prolonged hospitalization, while overestimation would lead to a limitation of care. Three important independent prognostic indicators of early neurologic deterioration and mortality are hematoma expansion with perihematomal edema, intraventricular hemorrhage, and hyperglycemia.
Complications of intracerebral hemorrhage secondary to rupture of Charcot-Bouchard aneurysms are as follows,
Hematoma expansion, also referred to as rebleeds, is an independent predictor of early neurological deterioration and mortality. Maximal hematoma expansion occurs in the first 3 hours and can occur up 24 hours from symptom onset. The "spot sign" or contrast extravasation into the hematoma is seen on the CT angiogram and is an indication of the expansion of the hematoma. The spot sign has been described as a heterogeneous marker due to its different shapes and sizes, depending on the timing of imaging relative to the onset of symptoms. Management of hematoma expansion includes administering hemostatic therapy with recombinant factor VIIa, cautious lowering of blood pressure, and craniotomy with surgical evacuation.
Perihematomal edema develops secondary to vasogenic and cytotoxic effects due to the hematoma formation and exerts a mass effect on surrounding structures. It is maximal at two weeks from the onset of symptoms. The management goal is to minimize any increase in the intracranial pressure by elevating the head to 20 to 30 degrees, analgesics for pain, infection control, sedatives, osmotic diuretics such as mannitol, and hyperventilation.
Seizures can be either a presenting symptom or complication of intracerebral hemorrhage. Treatment includes antiepileptic drugs based on the patient's medication regimen and contraindications.
IVH is also an independent predictor of early neurological deterioration and mortality due to IVH-induced inflammation and damage to periventricular structures, the brain stem, and leading to hydrocephalus with subsequent herniation. Relieving the IVH with external ventricular drainage is a life-saving procedure. For stable clots, intraventricular fibrinolytic (low-dose alteplase) can be administered. Lumbar drainage is less invasive, with a lower complication rate for communicating hydrocephalus.
Other complications include:
It is critical to set age-appropriate blood pressure goals for patients and motivate them to be compliant with their medications. Counseling regarding modifiable risk factors such as smoking, excessive alcohol consumption, and high-fat diets must be pursued when appropriate.
Since the initial symptoms of a stroke are non-specific, patients (and caregivers) might delay getting medical attention, which limits their treatment options. Ischemia greater than 4 to 6 hours can produce permanent damage to the neurovascular tissue, and yet a study found only half the patients present within the first 24 hours of the onset of stroke. It is essential to educate them (and reiterate for patients with uncontrolled hypertension and multiple risk factors) on the presenting symptoms of headache with nausea and vomiting to encourage them to come to the hospital sooner.
It is imperative to have a multi-specialty interprofessional team approach to care for patients with Charcot-Bouchard aneurysms and intracerebral hemorrhage.
Optimizing management for hypertension and other risk factors by the primary care team is the first step, along with adequate patient education about the signs and symptoms of a stroke to encourage early presentation to the emergency department.
Next, a baseline severity score must be established in the emergency department for patients with spontaneous intracerebral hemorrhage followed by rapid neuroimaging with CT or MRI to distinguish an ischemic and hemorrhagic stroke.
Initial management of patients with intracerebral hemorrhage must be in intensive care set up or stroke unit with neuroscience expertise amongst physicians and nursing staff.
Management of hemostasis should be as follows:
Patients presenting with systolic blood pressure between 150 to 200 mm Hg and without contraindications to acute lowering of blood pressure, should have systolic blood pressure lowered to 140 mm Hg.
Monitoring of glucose to avoid hyper- or hypoglycemia, treatment of seizures, and assessment of dysphagia to prevent aspiration pneumonia should be performed in all patients.
All medications, including IV fluids, should have the pharmacist examine them in the context of the patient's entire medication record, ruling out interactions, verifying dosing and administration, and consulting with the team in the event there are any issues in the regimen. Nursing needs to be aware of proper administration and also the adverse events associated with the drugs given so that they can alert the clinicians of any concerns. These interprofessional interactions can help drive improved patient outcomes. [Level 5]
Lastly, patients requiring surgical interventions due to neurological deterioration should be referred to neurosurgery as early as possible to improve results.
Patients with intracerebral hemorrhage must have not only access to interprofessional rehabilitation as an inpatient but also have continued rehabilitation services available in the community and at home to promote recovery. [Level 1]
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