The brainstem is composed of the midbrain, the pons, and the medulla oblongata, situated in the posterior part of the brain. It is a connection between the cerebrum, the cerebellum, and the spinal cord. Embryologically, it develops from the mesencephalon and part of the rhombencephalon, all of which originate from the neural ectoderm. The brainstem is organized internally in three laminae: tectum, tegmentum, and basis. Gray matter in the brainstem is found in clusters all along the brainstem to forming mostly the cranial nerve nuclei, the pontine nuclei, and the reticular formation. White matter in the form of various ascending and descending tracts can be found mainly in the basis lamina, which is the most anterior part. The brainstem is responsible for multiple critical functions, including respiration, cardiac rhythm, blood pressure control, consciousness, and sleep-wake cycle. The cranial nerve nuclei that are present in the brainstem have a crucial role in vision, balance, hearing, swallowing, taste, speech, motor, and sensory supply to the face. The white matter of the brainstem carries most of the signals between the brain and the spinal cord and helps with its relay and processing.
The blood supply to the brainstem is mostly from the vertebrobasilar system. The blood supply can be divided into a group of arteries supplying each region:
Brainstem infarction is an area of tissue death resulting from a lack of oxygen supply to any part of the brainstem. The knowledge of anatomy, vascular supply, and physical examination can be life-saving in the setting of an acute infarct and provide precise diagnosis and management. Time becomes an essential factor in management. Early intervention has shown dramatically reduced morbidity and mortality.
Brainstem infarction refers to the sequelae of ischemia to any part of the brainstem, due to the loss of blood supply or bleeding. Occlusion and stenosis of the posterior circulation cause significant hypoperfusion in the brainstem. The most common etiologies for brainstem infarction are atherosclerosis, thromboembolism, lipohylanosis, tumor, arterial dissection, and trauma. In medulla oblongata infarcts, 73% are due to stenosis of the vertebral artery, 26% due to arterial dissection, and rest being caused by other causes like cardioembolic. However, the number of infarcts due to cardioembolic etiology increase to 8% in pontine infarcts and 20% to 46% in midbrain infarcts.
Risk factors for stroke, in general, include hypertension, diabetes mellitus, metabolic syndromes, hyperlipidemia, tobacco use, obesity, history of ischemic heart disease, atrial fibrillation, sleep apnea, lack of physical activity, use of oral contraceptives, fibromuscular dysplasia, trauma, and spinal manipulation.
Globally, there is a rise in lifestyle diseases like cardiovascular disease, stroke, diabetes mellitus, both in developed and developing nations. The global burden of stroke can be measured at 122 million disease-adjusted life years. In the US, a stroke is reported every 40 seconds. It has been estimated that the brainstem accounts for 10% to 15% of all strokes. The lifetime (age 25 and onwards) risk of stroke in males is between 23.3 to 26.0%, and in females is between 23.7% to 26.5%. There is variation between regions with Eastern Sub-Saharan Africa with the lowest lifetime risk of 11.8% to East Asia, with the highest risk of 38.8%. China has the most significant lifetime estimated risk of 39.3%.
The pathophysiology of all infarcts is the lack of oxygen in the tissue, leading to its death. The human brain requires 20% of oxygen consumption even though it accounts for only 2% of the body by weight. The cerebral blood flow is autoregulated to maintain a constant level of perfusion and adequate venous drainage to deal with all its needs. The cerebrum is also unique as it has little to no energy stores and uses glucose as its primary energy source, with distally produced ketone bodies being used only in starvation. Dependence on aerobic respiration and low respiratory reserve makes the brain susceptible to ischemia and eventually causing irreversible tissue death. The cellular cascade of events is as follows:
While the above apoptotic/ necrotic pathway is in process, specific protective pathways are triggered:
The cellular cascade is potentially reversible, which can lead to vasogenic edema over the next few hours. Vasogenic edema causes an increase in pressure in the surrounding tissue, leading to mass effect, and worsening the situation. The eventual release of matrix metalloproteinases causes loss of structural integrity and the dissolution of the blood-brain-barrier.
In the case of hemorrhagic etiology, the rupture of blood vessels causes hypoxia, pressure effects, and chemical irritation of brain tissue due to the disruption of blood-brain-barrier.
A loss of about 1.9 million neurons in the brain happens each minute in an untreated stroke. Hence a targeted approach must be followed with clear objectives. Assessment of airway, breathing and circulation, and its stabilization as a patient with brainstem stroke can present with trauma, altered mental status, altered respiratory drive, hypoxia, vomiting, and or mechanical airway obstruction.
Establishing the time of ischemic insult is critical. Patients, family members, attenders, co-workers, first responders, or any reliable witness can determine the time the patient was last known normal. If in the case of deficits arising in one's sleep, last known normal is the time the patient went to bed. A clinician needs to distinguish between ischemia and its differential diagnosis, causing various neurological deficits. Reliable information about the patient's current medication, especially with regards to oral hypoglycemic, insulin, anti-epileptics, neurological or psychological drugs, anti-platelets or blood thinners, drug abuse or overdose, and sleep apnea must be established. Co-morbidities and risk factors need to be assessed. Evaluation of signs and symptoms for hemorrhagic stroke is life-saving. Any history of uncontrolled hypertension, sudden onset of headache, vomiting, signs of raised intracranial pressure must raise high suspicion of hemorrhage and warrants an immediate non-contrast computed tomographic (CT) scan of the head.
A concise physical examination should evaluate any signs suggestive of trauma, meningeal irritation, or neurological deficits. Neurological examination of a brainstem infarct must include the following assessment:
The initial evaluation of patients presenting with a suspected stroke of the brainstem includes vital signs, oxygen saturation, blood pressure, pulse rate, respiratory rate, fingerstick blood glucose levels, non-contrast CT scan of the head or brain magnetic resonance imaging (MRI). Non-contrast CT scan of the head is a quick and widely available imaging modality, and it is highly sensitive for acute hemorrhage. On a head CT scan, blood can be seen as a hyper-dense lesion. Infarction of brain tissue can be detected by brain MRI diffusion-weighted images and fluid-attenuated inversion recovery images, which are highly sensitive in the hyper-acute setting.
Blood workup should including complete blood count, coagulation profile, serum electrolytes, renal function, lipid panel, hemoglobin-A1c level, thyroid function, vitamin B12 level, and vitamin D levels. Other blood investigation for hypercoagulability states, autoimmune conditions, liver pathologies, and genetic tests can be obtained. Cardiovascular workup for atrial fibrillation with either an electrocardiogram or Holter monitor, echocardiogram, cardiac enzyme levels, chest X-ray should be obtained. A multi-phase CT angiography can establish the state of vertebral and carotid arteries, along with assessment for any endovascular management. Sleep study or polysomnography is diagnostic for various sleep disorders and must be suspected in stroke cases with unknown etiologies. Evaluation of both modifiable and non-modifiable risk factors for cardiovascular disease must be done.
Due to the high density of nuclei and fibers running through the brainstem, the lesion in various structures gives rise to different signs and symptoms. Variously named stroke and stroke syndromes have been described in the literature.
After the patient's airway, breathing and circulation have been stabilized, a timeframe of the patient's symptoms is obtained. Vitals and fluid status must be stabilized. Hypo or hyperglycemia must be corrected. Fever, if present, should be managed accordingly. Blood pressure must not be aggressively controlled to allow permissive hypertension only in the case of ischemic injury. Patients with last known normal within 4.5 hours can be considered as candidates for thrombolysis, whereas a 24 hour last known normal can be candidates for mechanical thrombectomy. If it is a case presenting earlier than 4.5 hours of onset, thrombolysis with intravenous recombinant tissue plasminogen activator significantly improves the clinical outcome.
Tissue plasminogen activator (tPA)
Intravenous alteplase (recombinant tissue plasminogen activator) should be given at the dose of 0.9 mg/kg (maximum dose of 90 mg/kg) with 10% as the loading dose in the first minute. The patient must be under continuous observation. Anti-platelet therapy must be withheld for at least 24 hours post thrombolysis and restarted after a head CT scan without evidence of bleeding.
Mechanical endovascular thrombectomy in patients with large anterior circulation occlusion is well documented; however, most strokes affecting the brainstem arises from posterior circulation perforating branches. For those cases where the occlusion is at the main vertebral or basilar artery, endovascular thrombectomy is recommended for successful revascularization and favorable outcome. Other studies have shown no evidence of a difference in favorable outcomes between endovascular therapy when compared to standard medical therapy alone.
Antiplatelet therapy: The usage of acetylsalicylic acid as monotherapy or dual therapy along with clopidogrel within 24 – 48 hours after the onset of symptoms significantly improved patient outcomes.
Management of risk factors like hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, thyroid abnormalities, sleep apnea, malignancies, and hypercoagulable states should be treated accordingly. Dietary and lifestyle modification must be explained and discussed. Supplementation with vitamin B12 and vitamin D3 should also be considered. Physiotherapy, along with speech therapy, can be used if physical deficits arise due to infarct. Treatments must start at the earliest and must be aggressively pursued as the brain losses its plasticity within 90 days.
The differential diagnosis of brainstem infarction includes the following:
Metastatic disease of the brain
Central pontine demyelination
Cerebellopontine angle tumors
Supratentorial hemispheric mass effect with herniation and brainstem compression
Stroke is the primary cause of disability and a leading cause of mortality worldwide. Stroke has a burden of 122 million disease-adjusted life years, with gradual increasing incidences. Early diagnosis and management have a lower chance of permanent morbidity. Untreated acute basilar artery occlusion has extremely high mortality approaching 90%. For those patients who receive adequate treatment, the one-year survival rate is between 60 to 80%.
The risk of stroke recurrence is 10 to 15%; hence regular follow up is advised. Early initiation of rehabilitative care is also recommended. Patients with significant neurological deficits have a worse prognosis. The final prognosis depends on various factors including, age, the severity of the stroke, etiology of stroke, location, structures involved, associated risk factors, co-morbidities, and the management.
ACT FAST is an acronym suggested by the American Stroke Association to recognize the early symptoms of a stroke. It has the following components:
Along with the above symptoms, if the patient experiences any of the following, emergency medical services must be activated
Control of risk factors can significantly reduce future strokes:
Here are some important considerations:
The diagnosis and management of brainstem stroke bring a considerable burden to the healthcare system, the patient, the family members, and the society at large. The slow increase in the global burden of stroke has been steadily increasing.
The enhancement must start with proper patient education about the risk factors and how they can be modified. A simple community educational approach about smoking cessation, a healthy diet, an active lifestyle, regular health screening for diabetes mellitus and hypertension, drug addiction cessation, and rehabilitation can be undertaken. A decentralized model where a community-level assessment of primary and secondary prevention of non-communicable disease can result in a reduction in the incidence of stroke.
Acute management of stroke in a peripheral setting must be managed with skilled individuals; however, a complete and robust interdisciplinary team of neurologists, physicians, psychiatrists, nurses, physiotherapists, and other paramedical staff is necessary for the best patient outcome. A trained first responder who can immediately stabilize the patient and prevent the deterioration is critical. Usage of the National Institutes of Health Stroke Scale or the Modified Rankin Scale or other standardized models and scales help clinicians with their decision.
Constant root-cause analysis, frequent updates to local hospital protocol, and continued medical education should be implemented. The usage of telemedicine, teleradiology, and a rapid communication system can allow the various interprofessional to deploy rapidly and prevent long term complications. Examination of the patient must be done as a team, where each member can be delegated with certain aspects of evaluation and management. A multi-disciplinary approach has shown to prevent at least 80% of subsequent strokes. [Level I, II]
Post-stroke rehabilitation care must include inputs from the clinicians, nurses, pharmacists, to obtain the best outcome for the patient. A healthy support system of dieticians and therapists, along with adequate domiciliary support, must be provided.
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