Continuing Education Activity

Brainstem stroke represents one of the most severe and lethal forms of cerebrovascular disease because even small ischemic or hemorrhagic lesions can disrupt vital autonomic, sensory, and motor pathways concentrated within the midbrain, pons, and medulla. The brainstem accounts for approximately 10% to 15% of all strokes. Ischemic events predominate, most commonly involving the pons, while hemorrhagic strokes frequently affect the dorsal pons. This course reviews the clinical manifestations of brainstem strokes, which vary widely by vascular territory and anatomical involvement, ranging from classic crossed syndromes and cranial nerve deficits to life-threatening disturbances of consciousness, respiration, and cardiovascular regulation. Early recognition, accurate localization, and timely intervention are critical to reducing morbidity and mortality in this high-risk population and are highlighted.

This activity outlines brainstem anatomy, vascular supply, stroke syndromes, and evidence-based acute and supportive management. Participants will also gain an in-depth understanding of brainstem stroke presentations, of interpreting diagnostic findings, of stratifying etiologies and risk factors, and of applying current medical, endovascular, and supportive care strategies. This activity for healthcare professionals is designed to enhance the learner's competence in identifying brainstem strokes, performing the recommended evaluation, and implementing an appropriate interprofessional approach to manage this condition, thereby improving outcomes.

Objectives:

• Identify common brainstem stroke syndromes based on clinical presentation.
• Interpret imaging findings to localize brainstem stroke lesions.
• Select appropriate therapies across the continuum of care for patients with brainstem stroke.
• Collaborate on management strategies with the interprofessional team to improve care coordination and patient outcomes in brainstem stroke. 

Introduction

Brainstem stroke represents one of the most devastating forms of cerebrovascular injury, with both ischemic and hemorrhagic subtypes contributing significantly to global morbidity and mortality.[1] Ischemic brainstem stroke occurs more frequently than hemorrhagic variants, yet both are associated with high lethality due to the extraordinary density of nuclei, tracts, and autonomic centers packed within this compact region.[2][3] Because even small lesions can produce catastrophic neurological deterioration, prompt recognition of brainstem stroke syndromes is essential for improving patient outcomes. Early diagnosis and intervention have been shown to dramatically reduce morbidity and mortality, reinforcing the value of detailed anatomical and clinical knowledge among frontline neurologists, emergency physicians, and neurocritical care teams.

The brainstem—comprising the midbrain, pons, and medulla oblongata—is positioned in the posterior cranial fossa and forms the primary conduit between the cerebrum, cerebellum, and spinal cord. Embryologically, it arises from the mesencephalon and portions of the rhombencephalon, originating from the neural ectoderm. Internally, the brainstem is functionally organized into 3 vertical laminae: the tectum, tegmentum, and basis. The tegmentum houses the cranial nerve nuclei, reticular formation, and numerous integrative centers, while the basis contains major ascending and descending white-matter tracts critical for sensorimotor relay. This arrangement allows the brainstem to regulate essential physiological functions—including respiration, cardiac rhythm, blood pressure, consciousness, and the sleep–wake cycle—while also supporting vision, hearing, balance, swallowing, taste, speech, and sensory-motor innervation of the face. The density of gray matter clusters and the compact organization of long tracts mean that even small ischemic lesions can disrupt multiple, simultaneous physiological functions.[3]

Because the brainstem’s vascular architecture is region-specific, the clinical manifestations of stroke depend heavily on which territorial distribution is compromised. Each brainstem segment is supplied by a predictable but intricately branching vascular network. For example, the medulla oblongata receives blood from the anterior spinal artery, vertebral artery, posterior inferior cerebellar artery, and posterior spinal artery; the pons receives perforators from the basilar artery as well as branches from the anterior inferior cerebellar and superior cerebellar arteries; and the midbrain is supplied by branches of the posterior cerebral artery, anterior choroidal artery, superior cerebellar artery, and related collicular and choroidal branches. These territories can be conceptualized through the following major groups:

• Medulla: Anteromedial, anterolateral, lateral, and posterior regions are supplied by the anterior spinal artery, vertebral artery, posterior inferior cerebellar artery (PICA), and posterior spinal artery.
• Pons: Anteromedial, anterolateral, and lateral pontine zones are supplied by basilar perforators, the anterior inferior cerebellar artery, and the superior cerebellar artery.
• Midbrain: Anteromedial, anterolateral, lateral, and posterior groups supplied by the posterior cerebral artery, anterior choroidal, superior cerebellar artery, and the collicular or choroidal branches.[2][4]

An understanding of this vascular topology is crucial for identifying lesion patterns, predicting clinical syndromes, and guiding acute management decisions.

Brainstem infarctions result from loss of oxygen supply to any of these territories and account for nearly one-third of all ischemic strokes. Pontine infarctions are the most common, whereas medullary infarctions account for approximately 7% of ischemic brainstem strokes, with lateral medullary (Wallenberg) syndrome the predominant subtype.[JAMP. Brainstem Infarcts: Imaging Features and Clinical Presentation] Overall, a notable male preponderance of brainstem stroke has been observed, with a male-to-female ratio of approximately 3:1. Large vessel atherosclerosis, small vessel disease affecting perforating arteries, cardioembolic, and vertebral artery dissection represent the leading etiologies, though basilar artery occlusion remains a critical cause of posterior circulation ischemic strokes.[5][6] 

Pontine strokes may be isolated or may occur as components of broader posterior-circulation infarctions. Ventral pontine infarcts are particularly common and frequently produce classic lacunar syndromes, eg, pure motor hemiparesis, dysarthria-clumsy hand syndrome, ataxic hemiparesis, and pure sensory stroke. In contrast, isolated midbrain infarctions are rare and typically present alongside involvement of adjacent structures, including the cerebellum, pons, or thalamus. Hemorrhagic brainstem stroke most commonly affects the dorsal pons, a region where dense perforator networks make small-vessel rupture particularly devastating.[2] 

Among these territories, the pons—the largest brainstem structure, situated between the midbrain and medulla—is especially vulnerable to ischemic injury because of its reliance on numerous small perforating vessels.[7] Disruption of blood flow to the pons can result in pontine infarction, a subtype of ischemic stroke with a broad spectrum of clinical manifestations. Patients may present with classical “crossed” neurological signs, characterized by ipsilateral cranial nerve palsy with contralateral motor or sensory impairment. However, presentations can be highly variable and may include pure motor hemiparesis or hemiplegia, pure sensory stroke, or mixed syndromes such as dysarthria-clumsy hand or ataxic hemiparesis. This heterogeneity directly reflects the tight anatomical juxtaposition of corticospinal tracts, cranial nerve nuclei, transverse pontocerebellar fibers, and reticular activating pathways.[8]

Collectively, brainstem strokes remain a uniquely challenging subset of cerebrovascular disease. Their clinical consequences stem from both the complexity of the neuroanatomy and the critical life-sustaining functions localized within this region. A detailed understanding of the structural organization, vascular supply, and clinical correlates is essential for clinicians involved in acute stroke care, neuroimaging interpretation, and neurocritical management. Continued advancements in acute therapy, imaging, and neurovascular intervention underscore the importance of early recognition and precise localization of brainstem infarction patterns to optimize outcomes for this high-risk population.

Etiology

Ischemic Brainstem Strokes

Brainstem infarction is the sequelae of ischemia to any part of the brainstem due to the loss of blood supply or bleeding. Posterior circulation occlusion and stenosis 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 vertebral artery stenosis, 26% are due to arterial dissection, and cardioembolic causes comprise the remainder.[9] However, the number of infarcts due to cardioembolic etiology increases to 8% in pontine infarcts and 20% to 46% in midbrain infarcts.[4] 

Large vessel atherothrombosis is the predominant cause of all ischemic strokes in all anatomical locations. Cardioembolic events are more common in mesencephalic infarcts, whereas dissections are common for medullary infarctions.[2] Approximately 25% of ischemic strokes occur within the posterior circulation, 60% in the brainstem, and 40% in the cerebellum.[2] According to the TOAST classification system, large-artery atherothrombosis is the primary underlying etiology of these strokes across all arterial territories (63% overall and 74% in the pons). Cardioembolism accounts for 15% to 30% of cases. Cardioembolic etiology accounts for 26% of midbrain infarctions and 31.5% of multiple concurrent infarctions. Dissection is more commonly involved in the lateral medulla supplied by the vertebral arteries.[6]

Risk factors for all types of stroke 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.[2][10][11] Ischemic brainstem stroke risk factors include:

• Atherosclerosis
• Hypertension
• Diabetes
• Smoking
• Atrial fibrillation
• Hyperlipidemia
• Ischemic heart disease
• Embolism, and
• Dissections.[2]

Hemorrhagic Brainstem Strokes

The etiologies for hemorrhagic brainstem strokes include:

• Hypertension (approximately 90% of cases)
• Anticoagulant therapy (7%)
• Arteriovenous malformations
• Occult vascular malformations (eg, cavernomas and capillary telangiectasia)
• Amyloid angiopathy.[2][12]

Epidemiology

Globally, lifestyle-related diseases, eg, cardiovascular disease, stroke, and diabetes mellitus, continue to rise across both developed and developing nations. The worldwide burden of stroke measures approximately 122 million disease-adjusted life years.[13] In the United States, a stroke occurs every 40 seconds.[14] Epidemiologic studies estimate that 10% to 15% of all strokes involve the brainstem.[10] Among individuals aged 25 years and older, the lifetime risk of stroke ranges from 23.3% to 26.0% in males and from 23.7% to 26.5% in females. Marked regional variation exists, with Eastern sub-Saharan Africa demonstrating the lowest lifetime risk at 11.8% and East Asia the highest at 38.8%. China carries the greatest estimated lifetime risk at 39.3%.[15]

The pons is the most common site of brainstem stroke, accounting for approximately 60% of infarctions (see Image. Pontine Infarction).[16] Ischemic vertebrobasilar strokes constitute 23% of cases, while ischemic brainstem infarctions account for 11% of all ischemic strokes. Distribution by anatomical region shows involvement of the pons in 27%, the medulla in 14%, and the midbrain in 7%. Cerebellar involvement occurs in 7%, posterior cerebral artery territory infarction in 36%, and concurrent involvement of multiple sites in 9%. Isolated pontine infarctions appear in 3% of all ischemic strokes. Lateral medullary infarctions occur nearly 5 times more frequently than medial variants, while the lateral midbrain represents the least frequently affected region.[16] Anteromedial, anterolateral, and lateral vascular territories demonstrate similar incidences overall, with posterior infarctions remaining the least common subtype. Anteromedial variants predominate in the midbrain, anteromedial and anterolateral variants in the pons, and lateral variants in the medulla.[16] Wallenberg syndrome, also termed posterior inferior cerebellar artery syndrome or lateral medullary syndrome, represents the most common brainstem stroke. Anterior inferior cerebellar artery syndrome, also known as lateral pontine syndrome, ranks as the second most common presentation.[16]

Primary brainstem hemorrhage accounts for approximately 10% of all intracerebral hemorrhages and carries an annual incidence of 2 to 4 per 100,000 individuals.[17] Pontine involvement predominates, reported in 60% to 80% of brainstem hemorrhages.[17] These events occur most frequently among males and individuals aged 40 to 60 years.[17] Female patients with brainstem stroke demonstrate higher survival rates despite a lower overall incidence.[17]

Pathophysiology

The pathophysiology underlying all infarcts involves deprivation of oxygen to neural tissue, culminating in cellular injury and death. The human brain consumes approximately 20% of total body oxygen despite comprising only 2% of total body weight.[18] Cerebral blood flow undergoes tight autoregulation to sustain constant perfusion and adequate venous outflow to meet metabolic demands. The cerebrum possesses minimal intrinsic energy reserves and relies primarily on glucose as its principal energy substrate, with distally produced ketone bodies used only during starvation.[19] This reliance on aerobic metabolism, combined with limited respiratory reserve, renders the brain highly vulnerable to ischemic injury and ultimately results in irreversible tissue damage (see Image. Brainstem Structures, Deficits, and Vascular Supply). The cellular cascade of events includes:

• Depletion of ATP due to a lack of aerobic respiration in the mitochondria
• Loss of function of membrane ion pumps and impaired voltage gradient across membranes, leading to cellular edema
• Neuronal excitotoxicity due to glutamate release and synaptosomal-associated protein release further deteriorates energy levels and membrane ion potentials.; reactive oxygen species and free radical production lead to cell death.[20] 

While the above apoptotic and necrotic pathway is in process, specific protective pathways are triggered, including:

• Expression of heat shock protein 70, B-cell lymphoma 2 gene family, and prion protein to prevent activation of the apoptotic cascade
• Release of Neurotrophin-3, interleukin-10, and granulocyte-colony stimulating factor, helping activate survival pathways and reduce proinflammatory cytokine activities

The cellular cascade is potentially reversible, which can lead to vasogenic edema over the next few hours. Vasogenic edema increases pressure in the surrounding tissue, leading to mass effects and worsening the situation.[21] The eventual release of matrix metalloproteinases leads to loss of structural integrity and dissolution of the blood-brain barrier.[22] 

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 the blood-brain barrier. Animal models of primary brainstem hemorrhage are primarily obtained via stereotactic collagenase injection or autologous blood injection.[17] The pathogenesis observed in animal models included erythrocyte lysis, heme oxygenase expression, iron deposition, and the release of reactive oxygen species, all of which are involved in the pathogenesis.[23] Anterior territory involvement is more common with stroke in the mesencephalon and pons, whereas posterior and lateral anatomical involvement occurs more frequently in strokes involving the medulla.[6]

History and Physical

Clinical Symptoms

Approximately 1.9 million neurons are lost each minute during an untreated stroke.[24] This rapid neuronal loss mandates a targeted clinical approach with clearly defined objectives. Initial evaluation focuses on airway, breathing, and circulation, followed by prompt stabilization, since patients with brainstem stroke may present with trauma, altered mental status, impaired respiratory drive, hypoxia, vomiting, or mechanical airway obstruction. Accurate determination of symptom onset remains critical. Patients, family members, attendees, coworkers, first responders, or other reliable witnesses may help establish the last known time without symptoms. When neurological deficits develop during sleep, the last known normal baseline corresponds to the time the patient went to bed. Clinical evaluation must also distinguish stroke from alternative conditions capable of producing acute neurological deficits.

Accurate documentation of current medications requires particular attention, including oral hypoglycemics, insulin, antiepileptics, neurologic or psychiatric agents, antiplatelet medications, anticoagulants, and any history of substance abuse or overdose. Assessment of comorbid conditions and vascular risk factors remains essential. Prompt recognition of hemorrhagic stroke features proves life-saving. A history of uncontrolled hypertension, sudden severe headache, vomiting, or clinical signs of elevated intracranial pressure should heighten suspicion for intracranial hemorrhage and warrant immediate noncontrast computed tomography (CT) imaging of the head.

In general, the region or function of the brainstem affected can be identified by the following presenting symptoms:

• Ascending and descending pathways: Weakness, loss of pain and temperature sensation, ataxia, Horner syndrome, loss of position and vibration sensation, gaze palsy
• Nuclei and cranial nerves: Ocular and extraocular muscle weakness, loss of sensation over the face, autonomic dysregulation, dysphagia, dysarthria, dysphonia, vertigo, alteration in taste and hearing
• Integrative and other functions: Choreoathetosis, tremors, ataxia, central dysautonomia, gaze paresis, lethargy, and locked-in syndrome [2][25]

Physical Examination

A focused physical examination should be performed to evaluate patients for signs of trauma, meningeal irritation, or neurological deficits. The following areas should be assessed during the neurological examination of patients with a brainstem stroke:

• Levels of consciousness and higher mental function
• Complete evaluation of cranial nerves and their functions
• Motor and sensory system examination, including reflexes, neglect, speech, and language
• Cerebellar signs, coordination, and gait
• Autonomic system

Clinical assessment of the 4 medial structures towards the midline, within the brainstem, including the motor tract (ie, corticospinal tract), medial lemniscus, medial longitudinal fasciculus, and motor nucleus of cranial nerves 3, 4, 6, and 12, and the 4 lateral structures, towards the sidelines, consisting of the spinocerebellar, spinothalamic, and sympathetic tracts as well as the sensory nucleus of the trigeminal nerve can help in the anatomical localization of the brainstem stroke.[26]

Evaluation

Evaluation of patients presenting with a suspected brainstem stroke includes vital signs, oxygen saturation, blood pressure, pulse rate, respiratory rate, fingerstick blood glucose levels, and a noncontrast CT scan of the head or brain magnetic resonance imaging (MRI). A noncontrast CT scan of the head is the preferred modality to evaluate brainstem stroke due to being a quick and widely available imaging method that is highly sensitive in detecting acute hemorrhage (see Image. Brainstem Stroke MRI). On a head CT scan, blood can be seen as a hyperdense lesion. Brain MRI can detect brain tissue infarction, with diffusion-weighted and fluid-attenuated inversion recovery images being highly sensitive in the hyperacute setting. Vascular imaging with either CT angiography or MR angiography of the head and neck vessels can be ideally included during the initial evaluation to assess vertebrobasilar occlusion, stenosis, or dissection.[27][28]

Blood workup should include a complete blood count, coagulation profile, serum electrolytes, renal function, lipid panel, hemoglobin A1c, thyroid function, vitamin B12, and vitamin D levels. Other blood investigations for hypercoagulability states, autoimmune conditions, liver pathologies, and genetic tests can be obtained. A cardiovascular workup for atrial fibrillation should include an electrocardiogram or Holter monitor, echocardiogram, cardiac enzyme levels, and chest x-ray. A multiphase CT angiography can assess the state of the vertebral and carotid arteries and inform any endovascular management. Sleep study or polysomnography is diagnostic for various sleep disorders and must be suspected in stroke cases with unknown etiologies. Additionally, evaluation of modifiable and non-modifiable risk factors for cardiovascular disease should be performed.

Brainstem Stroke Syndromes

Several syndromes may be classified based on the area of the brainstem affected. Because of the brainstem's high density of nuclei and fibers, lesions in different structures produce distinct signs and symptoms. Variously named stroke and stroke syndromes that have been described in the literature include:

• Top-of-the-basilar syndrome: Also known as the rostral brainstem infarction, this condition results in alternating disorientation, hypersomnolence, unresponsiveness, hallucination, behavioral abnormalities, visual and oculomotor deficits, and cortical blindness. Occurs due to occlusion of the distal basilar artery and its perforators.[29]
• Ondine syndrome: This condition affects the brainstem centers that control automatic breathing, resulting in complete breathing failure during sleep but normal ventilation when awake. The blood supply affected is the pontine perforating arteries, branches of the basilar artery, anterior inferior cerebellar artery, or the superior cerebellar artery.[29] 
• One-and-a-half syndrome: The paramedian pontine reticular formation and medial longitudinal fasciculus are affected, resulting in ipsilateral conjugate gaze palsy and internuclear ophthalmoplegia. The affected blood supply includes the pontine perforating arteries and branches of the basilar artery.[30] 

Midbrain syndromes

The following conditions are associated with abnormalities of the midbrain:

• Anteromedial midbrain syndrome: Affects the medial longitudinal fasciculus, cranial nerve (CN) IV, superior cerebellar peduncle, corticospinal tract, and medial lemniscus, resulting in ipsilateral internuclear ophthalmoplegia, contralateral superior oblique muscle palsy causing diplopia, contralateral hemiparesis, and contralateral ataxia. The blood supply involved is the proximal branches of the superior cerebellar artery and the paramedian branches of the basilar artery.[31]

• Claude syndrome: Affects the fibers from CN III, the rubrodentate fibers, corticospinal tract fibers, and corticobulbar fibers, resulting in ipsilateral CN III palsy, contralateral hemiplegia of lower facial muscles, tongue, shoulder, upper and lower limbs, and contralateral ataxia. The blood supply involved is from the posterior cerebral artery.[32]

• Dorsal midbrain syndrome (Parinaud syndrome): This affects the fibers from CN III, the rostral interstitial nucleus of the medial longitudinal fasciculus, the interstitial nucleus of Cajal, and the nucleus of Darkschewitsch. It results in ipsilateral CN III palsy, convergence-retraction nystagmus, vertical gaze paresis, and bilateral lid retraction. The blood supply is from the posterior cerebral artery and the paramedian branches of the basilar artery.[33][34]

• Paramedian midbrain syndrome (Benedikt syndrome): This affects the fibers from CN III and the red nucleus. It results in ipsilateral CN III palsy, contralateral choreoathetosis, tremor, and ataxia. The blood supply involved comes from the posterior cerebral artery and paramedian branches of the basilar artery.

• Nothnagel syndrome: Affects the fibers from CN III and the superior cerebellar peduncle, resulting in ipsilateral CN III palsy and ipsilateral limb ataxia. This syndrome can be due to quadrigeminal neoplasms and is often bilateral.[35]

• Ventral midbrain syndrome (Weber syndrome): This condition affects fibers from CN III, the cerebral peduncle (i.e., corticospinal and corticobulbar tracts), and the substantia nigra, resulting in ipsilateral CN III palsy, contralateral hemiplegia of the lower facial muscles, tongue, shoulders, and upper and lower limbs. The involvement of the substantia nigra can result in a contralateral movement disorder. The blood supply affected is the paramedian branches of the posterior cerebral artery.[36][37][38][39][40]

Pontine syndromes

The following conditions are associated with abnormalities of the pons:

• Brissaud-Sicard syndrome: Affects the CN VII nucleus and corticospinal tract, resulting in ipsilateral facial cramps and contralateral upper and lower limb hemiparesis. The blood supply affected is the posterior circulation. Rarely, the syndrome can arise due to a brainstem glioma.

• Facial colliculus syndrome: Affects the CN VI nucleus, the CN VII nucleus, fibers, and the medial longitudinal fasciculus, resulting in lower motor neuron CN VII palsy, diplopia, and horizontal conjugate. Facial colliculus syndrome can result from a neoplasm, multiple sclerosis, or a viral infection.

• Gasperini syndrome: This syndrome affects the nuclei of CN V, VI, VII, and VIII, as well as the spinothalamic tract, resulting in ipsilateral facial sensory loss, ipsilateral impaired eye abduction, ipsilateral nystagmus, vertigo, and contralateral hemi-sensory impairment. The blood supply derives from the basilar artery's pontine branches and the anterior inferior cerebellar artery's long circumferential artery.

• Gellé syndrome: Affects the CN VII, VIII, and corticospinal tract, resulting in ipsilateral facial palsy, hearing loss, and contralateral hemiparesis.

• Grenet syndrome: This syndrome affects the CN V lemniscus, CN VII fibers, and the spinothalamic tract, resulting in altered sensation in the ipsilateral face and the contralateral upper and lower limbs. Grenet syndrome can arise due to a neoplasm. 

• Inferior medial pontine syndrome: Also known as the lower dorsal pontine syndrome or Foville syndrome, this syndrome affects the corticospinal tract, medial lemniscus, middle cerebellar peduncle, and the nucleus of CN VI and VII, resulting in contralateral hemiparesis, contralateral loss of proprioception and vibration, ipsilateral ataxia, ipsilateral facial palsy, lateral gaze paralysis, and diplopia. The blood supply affected is from branches of the basilar artery.

• Lateral pontine syndrome: Also known as Marie-Foix syndrome, this affects the nuclei of CN VII and VIII, the corticospinal tract, the spinothalamic tract, and the cerebellar tracts, resulting in contralateral hemiparesis, contralateral loss of proprioception and vibration, ipsilateral limb ataxia, ipsilateral facial palsy, lateral hearing loss, vertigo, and nystagmus. The affected blood supply comprises the perforating branches of the basilar artery and the anterior inferior cerebellar artery.

• Locked-in syndrome: This syndrome is associated with lesions in the upper ventral pons, including the corticospinal and corticobulbar tracts, and the CN VI nuclei, resulting in quadriplegia, bilateral facial palsy, and horizontal eye palsy. The patient can move the eyes vertically, blink, and has intact consciousness. The blood supply affected is the middle and proximal segments of the basilar artery.

• Millard-Gubler syndrome: This syndrome is associated with lesions affecting the ipsilateral CN VII and the corticospinal tract in the ventral pons. Patients experience the classical crossed brainstem syndrome with ipsilateral facial palsy and contralateral hemiparesis. The blood supply involved is the paramedial pontine perforators from the basilar artery, especially the caudal branches.

• Raymond syndrome: Involves the CN VI fibers, corticospinal tract, and corticofacial fibers, resulting in an ipsilateral lateral gaze palsy, contralateral hemiparesis, and facial palsy. The blood supply involved is from the branches of the basilar artery.

• Upper dorsal pontine syndrome: This syndrome, also known as Raymond-Cestan syndrome, is associated with lesions affecting the longitudinal medial fasciculus, the medial lemniscus, the spinothalamic tract, the CN V fibers and nuclei, and the superior and middle cerebellar peduncles. It results in ipsilateral ataxia, coarse intention tremors, facial sensory loss, masticatory weakness, and contralateral loss of all sensory modalities. The blood supply involved is from the circumferential branches of the basilar artery.

• Ventral pontine syndrome: Also known as Millard-Gubler syndrome, this affects CN VI and VII and the corticospinal tract, resulting in ipsilateral lateral rectus palsy, diplopia, ipsilateral facial palsy, and contralateral hemiparesis of the upper and lower limbs. The blood supply involved derives from the branches of the basilar artery.[36][37][39][41][42][43][44][45][46][47]

Medulla oblongata syndromes

The following conditions are associated with abnormalities of the medulla oblongata:

• Avellis syndrome: Affects the pyramidal tract and nucleus ambiguus, resulting in ipsilateral palatopharyngeal palsy, contralateral hemiparesis, and contralateral hemi-sensory impairment. The blood supply affected is the vertebral arteries. 

• Babinski-Nageotte syndrome: Also known as the Wallenberg with hemiparesis, affects the spinal fiber and nucleus of CN V, nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, afferent spinocerebellar tracts, and corticospinal tract, resulting in ipsilateral facial loss of pain and temperature, ipsilateral palsy of the soft palate, larynx and pharynx, ipsilateral Horner syndrome, ipsilateral cerebellar hemi-ataxia, contralateral hemiparesis, and contralateral loss of body pain and temperature. The blood supply involved is from the intracranial portion of the vertebral artery and branches from the posterior inferior cerebellar artery.

• Cestan-Chenais syndrome: The condition affects the spinal fiber and nucleus of CN V, nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, and corticospinal tract and results in ipsilateral facial loss of pain and temperature, ipsilateral palsy of the soft palate, larynx and pharynx, ipsilateral Horner's syndrome, contralateral hemiparesis, contralateral loss of body pain and temperature, and contralateral tactile hypesthesia. The affected blood supply is the intracranial portion of the vertebral artery and its branches from the posterior inferior cerebellar artery.

• Hemimedullary syndrome: This condition, also known as Reinhold syndrome, affects the nucleus and fiber of CN V, CN XII nucleus ambiguus, lateral spinothalamic tract, sympathetic fibers, afferent spinocerebellar tracts, corticospinal tract, and medial lemniscus. Lesions in these areas result in ipsilateral Horner syndrome, ipsilateral loss of pain and temperature in the face, ipsilateral palsy of the soft palate, larynx, and pharynx, ipsilateral tongue weakness, ipsilateral cerebellar hemi-ataxia, contralateral hemiparesis, and contralateral face-sparing hemihypesthesia. The blood supply is from the ipsilateral vertebral artery, the posterior inferior cerebellar artery, and branches from the anterior spinal artery. 

• Jackson syndrome: Affects CN XII and the pyramidal tract, resulting in ipsilateral palsy of the tongue and contralateral hemiparesis. The blood supply involved is from the branches of the anterior spinal artery.

• Lateral medullary syndrome: Also known as Wallenberg syndrome, this syndrome is associated with lesions affecting the spinal nucleus and fibers of CN V, the nucleus ambiguus, the lateral spinothalamic tract, sympathetic fibers, the inferior cerebellar peduncle, and the vestibular nuclei. It results in ipsilateral Horner's syndrome, ipsilateral facial loss of pain and temperature, ipsilateral palsy of soft palate, larynx, and pharynx, ipsilateral cerebellar hemi-ataxia, contralateral loss of body pain and temperature, nystagmus, dysarthria, dysphagia, and hyperacusis. The blood supply affected is the vertebral artery and its branches from the posterior inferior cerebellar artery.

• Medial medullary syndrome: Also known as Dejerine syndrome, this condition affects the fibers of CN XII, the corticospinal tract, and the spinal medial lemniscus, resulting in ipsilateral tongue weakness, ipsilateral loss of proprioception and vibration, contralateral hemiparesis, and contralateral face-sparing hemihypesthesia. The affected blood supply is the branches of the vertebral artery and the anterior spinal artery.

• Schmidt syndrome: This syndrome is characterized by lesions affecting the fibers and nuclei of CN IX, X, and XI, and the pyramidal systems, resulting in ipsilateral palsy of the vocal cords, soft palate, trapezius, and sternocleidomastoid muscle, and contralateral spastic hemiparesis. The blood supply involves branches from the vertebral artery, the posterior inferior cerebellar artery, and the anterior spinal artery.

• Spiller syndrome: The fibers and nucleus of CN XII, corticospinal tract, medial lemniscus spinal, and medial hemi-medulla are affected, resulting in ipsilateral tongue weakness, ipsilateral loss of proprioception and vibration, contralateral hemiparesis, and contralateral face-sparing hemihypesthesia. The blood supply is from branches of the vertebral artery and the anterior spinal artery.

• Tapia syndrome: Affects the nucleus ambiguus, CN XII, and pyramidal tract, resulting in ipsilateral palsy of the trapezius, sternocleidomastoid muscle, and half of the tongue, dysphagia, dysphonia, and contralateral spasmodic hemiparesis. The blood supply is from branches of the vertebral artery, the posterior inferior cerebellar artery, and the anterior spinal artery.

• Vernet syndrome: Affects the CN IX, X, and XI and occurs due to compression in the jugular foramen.[36][37][48][49][50][51][52]

Brainstem stroke subgroups differ significantly only in the incidence of hemiparesis (74% in pontine but 30% with medullary or cerebellar strokes) and ataxia (97% and 95% of cerebellar and medullary but 74% in pontine strokes.[16] Convulsive-like movements have been observed in pontine strokes due to ischemia of the corticospinal tracts.[53] Restless leg syndrome has been observed in anteromedial pontine infarction.[54]

Diagnostic Imaging

CT scanning is the preferred method for radio imaging owing to its general availability. CT findings also closely correlate with prognosis in primary brainstem hemorrhage.[55] Computed tomography (CT) may paradoxically appear normal in the early course of the stroke. The "hyperdense basilar artery sign" may be observed. CT shows a nonenhancing hyperdense lesion. The formula ABC/2 can be used to calculate the volume of an ICH on CT, where "A" is the greatest hemorrhage diameter, "B" is the diameter 90 degrees to A, and "C" is the approximate number of CT slices containing hemorrhage multiplied by the slice thickness.[56] However, the 2/3SH formula is more accurate than ABC/2, with "S" representing the area of the largest axial hemorrhagic slice and "H" representing the hematoma height.[55] CT angiography (CTA) helps identify the level of occlusion and delineate the infarct size. The "spot sign" is not significantly related to hematoma expansion.[57] CT perfusion delineates the core and penumbra zones.[2]

MRI accurately depicts the location and extent of the stroke.[2] Diffusion-weighted magnetic resonance imaging is the recommended modality for visualizing irreversibly infarcted regions and has rapid acquisition. Magnetic resonance perfusion images are paramount in evaluating the penumbra zone.[2] Hemosiderin deposition on T2-weighted (T2W) and gradient-echo magnetic resonance images, with a characteristic "popcorn" appearance, is a radiological hallmark of cavernomas (see Image. Cavernoma Imaging Study).[2]

Classifications of Primary Brainstem Hemorrhage

Several methods have been used to classify primary brainstem hemorrhage. Chung and Park categorized pontine hemorrhage by the following anatomical landmarks:

• Dorsal group involving unilateral or bilateral tegmentum
• A ventral group involving the ventral basis pontis
• A massive group involving the basis pontis and tegmentum with extension into the midbrain.[2]

However, Kase and Caplan classified pontine hemorrhages as large paramedian, unilateral basal or basotegmental, or lateral tegmental subtypes.[2] The TOAST Classification System categorizes strokes according to etiologies, including:

• Large arterial atherothrombosis: >50% narrowing in CTA/MRA
• Cardioembolic: Atrial flutter on electrocardiogram, paroxysmal atrial flutter on Holter monitoring, akinetic segments or thrombus on transthoracic echocardiograms and transesophageal echocardiograms, history of rheumatic valve disease or prosthetic valves, monitoring, myocardial infarction within a month, or the presence of patent foramen ovale seen in transesophageal echocardiograms or Bubble test
• Small vessel disease: vessels <2 cm presenting as pure motor, pure sensory, ataxic, and dysarthria with clumsy hand patterns
• Other causes, eg, vasculitis, dissection, paraneoplastic syndrome, or stroke of unknown cause.[2]

Treatment / Management

Following stabilization of airway, breathing, and circulation, clinicians should establish a precise timeline of symptom onset. Vital signs and fluid status require continuous stabilization, while abnormalities in blood glucose, including hypoglycemia or hyperglycemia, require prompt correction. Febrile states warrant appropriate management to reduce secondary neurological injury. Blood pressure management should avoid aggressive lowering in ischemic stroke, allowing permissive hypertension when indicated to preserve cerebral perfusion.

Patients with a last known normal time within 4.5 hours qualify for consideration of intravenous thrombolysis, while individuals with symptom onset up to 24 hours may qualify for mechanical thrombectomy based on imaging and clinical criteria. When presentation occurs within 4.5 hours of symptom onset, administration of intravenous recombinant tissue plasminogen activator (tPA) significantly improves clinical outcomes.[58]

Tissue Plasminogen Activator Inclusion Criteria

The following clinical criteria should be met before tPA is administered:

• Clinical diagnosis of ischemic stroke
• <4.5 hours from symptom onset
• Age older than 18 and younger than 80 years
• Symptoms of stroke presenting for more than 30 minutes.[58][59]

Tissue Plasminogen Activator Exclusion Criteria

If the following clinical factors are present, tPA is not recommended:

• Unknown timeline of onset of patient symptoms
• Intracranial hemorrhage or any active bleeding
• Persistently elevated blood pressure ≥185 mm Hg systolic and ≥110 mm Hg diastolic
• Low platelets <100,000 cells/µL, altered international normalized ratio (INR) >1.7, prothrombin time >15 seconds, or partial thromboplastin time >40 seconds
• Current use of anticoagulant
• Severe hypoglycemia <50 mg/dL
• History of previous intracranial hemorrhage
• History of gastrointestinal bleeding in the past 21 days
• History of intracranial or intraspinal surgery in the past 90 days
• History of intra-axial intracranial neoplasm or gastrointestinal malignancy.[59][60]

Intravenous alteplase, a recombinant tissue plasminogen activator, should be given at 0.9 mg/kg with a maximum dose of 90 mg/kg; 10% of the recommended dose should be given as the loading dose in the first minute. The patient must be under continuous observation. Antiplatelet therapy must be withheld for at least 24 hours postthrombolysis and restarted after a head CT scan without evidence of bleeding. The time window for thrombolytic therapy in brainstem ischemic strokes has not been well defined.[61] 

Mechanical endovascular thrombectomy in patients with large anterior circulation occlusion is well documented; however, most brainstem strokes arise from posterior circulation perforating branches. Endovascular thrombectomy is recommended for successful revascularization and favorable outcomes in cases of occlusion in the main vertebral or basilar artery.[61][62][63][64][65][66][67][68] Other studies have found no difference in favorable outcomes between endovascular therapy and standard medical therapy alone.[69][70] Please see StatPearls' companion resource, "Thrombolytic Therapy," for further information.

Conservative Therapy

In many patients, primary brainstem hemorrhage is primarily treated conservatively with antiplatelet therapy using acetylsalicylic acid as monotherapy or dual therapy along with clopidogrel within 24 to 48 hours after the onset of symptoms, which significantly improved patient outcomes.[57] Conservative treatment of primary brainstem hemorrhage is generally recommended for patients with the following clinical features:

• Smaller hematomas >5 ml and <10 mL in size
• Glasgow Coma Scale (GCS) score of >6 and <8
• Age younger than 65 years
• A unilateral tegmental variant
• No extra-pontine extension.[57]

Surgical Management

The surgical treatment of primary brainstem hemorrhage is controversial. Brainstem hemorrhage has been excluded from previous ICH trials, eg, the Surgical Trial in Lobar Intracerebral Hemorrhage (STICH) and Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE).[57] The management of primary brainstem hemorrhage primarily involves conservative treatment, and surgery is generally not recommended.[55] In patients with the following features, surgery is not advocated:

• Hematomas <3 mL or >15 mL in size
• No evidence of ventricular dilatation and altered level of consciousness
• Severe irreversible brain damage
• Extreme hemodynamic instability.[57]

Surgical options for primary brainstem hemorrhage include craniotomy and microsurgical evacuation, stereotactic hematoma puncture and drainage, and endoscopic hematoma removal (eg, endoscopic endonasal transclival approach and external ventricular drainage).[55][57] Takahama et al performed stereotactic puncture and drainage in 1989. The aspiration group had a lower mortality rate than the microscopic surgery group (24.4% versus 31.6%). Precision can be critically aided by the application of newer armamentaria, eg, Stereotaxy, 3D printing, Robotics, and virtual and augmented reality.[57] Intraoperative neurophysiological monitoring is another helpful adjunct.[57] Hematoma aspiration is justifiable in older, fragile patients.[57] Intraventricular hemorrhage (IVH) occurs in almost 40% of patients with primary brainstem hemorrhage, so external ventricular drainage can effectively prevent the hazards of acute hydrocephalus.[57] The CLEAR III trial, however, has shown no significant advantage of ventricular irrigation with alteplase in IVH.[57]

Minimally invasive microsurgery serves as a rapid, effective, and safe treatment modality for brainstem hematomas with volumes less than 10 mL.[57] In 1998, Hong et al reported the first craniotomy performed for the evacuation of a brainstem hemorrhage. Microscopic craniotomy offers several advantages, including maximal hematoma removal under direct visualization, improved hemostasis, and simultaneous evacuation of ventricular blood to reduce the risk of secondary hydrocephalus.[57] Patients managed surgically demonstrate a 2-fold reduction in mortality risk and higher odds of functional recovery; however, surgical intervention also carries a 2-fold increased risk of persistent vegetative state or moderate to severe disability.[57]

Early microsurgical evacuation correlates with reduced mortality and improved overall prognosis.[57] Successful execution requires advanced microsurgical expertise and detailed anatomical knowledge of safe entry zones into the brainstem.[71][72] Experimental models demonstrate the development of brain edema and arterial necrosis predominantly after 6 hours following primary brainstem hemorrhage, supporting surgical intervention within a 6-hour window as the most practical theoretical approach.[57] In 2003, Takimoto et al. introduced neuroendoscopic techniques for evacuating brainstem hemorrhage. This approach favors ventral hematomas and exploits natural surgical corridors, minimizing brain retraction while allowing direct visualization of lesions, though a prolonged learning curve remains a primary limitation.[57]

Chinese researchers provided indicators for surgical intervention for primary brainstem hemorrhage to help identify appropriate candidates, including:

• Ictus for 6 to 24 hours
• Hematoma volume of >5 mL
• Hematoma diameter of >2 cm.[57]

Chinese surgeons are, however, compelled to operate even on moribund patients owing to the sociological issue of filial piety.[57] However, most of the included studies are of low to moderate quality and have minimal follow-up strategies. Moreover, almost 7% of these patients lacked integration of angiographic studies despite being normotensive.[57] None of the studies incorporated an anatomical classification system either.[57] 

Patient Care Considerations

In addition to conservative and surgical therapies, other aspects of patient care in individuals with primary brainstem hemorrhage are also essential. Class 1 evidence for nursing care and management includes:

• Clinicians should be highly trained in stroke care.
• Frequent, thorough neurological assessments should be performed.
• The patient’s head should be in neutral alignment with the body.
• Only non-dextrose, normotonic intravenous fluids (eg, normal saline) should be given.
• Intravenous rtPA should be administered without delay to all eligible candidates.
• Avoid temperatures >99.6 °F, serum glucose concentrations >140 mg/dL, infections, seizures, and constipation.
• Frequent hemodynamic and hydration assessments should be performed
• Measures to prevent aspiration pneumonia, falls, pressure sores, and deep vein thrombosis must be emphasized.
• Nurses should be familiar with bedside swallow assessments, and swallow screening ideally should be performed by the speech-language pathologist.[73]

Discharge Disposition

Before patients are discharged from the hospital, the following assessments and patient education should be considered:

• Use of statins
• Dysphagia screening
• Stroke education
• Smoking cessation advice and counseling
• Assessment for rehabilitation.[73]

Management of stroke risk factors, including 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 and rehabilitative strategies must start at the earliest and must be aggressively pursued as the brain loses its plasticity within 90 days. The vascular causes of brainstem hemorrhages (eg, cavernomas) also need to be properly addressed.[12] Nanoparticle and stem cell combined therapy are recent advances in the management of brainstem strokes.[74][75]

Differential Diagnosis

Differential diagnoses that should be considered during the evaluation of brainstem strokes include:

• Neoplastic and metastatic lesions
• Central pontine myelinolysis
• Acute disseminated encephalomyelitis
• Multiple sclerosis
• Diffuse axonal injury (see Image. Diffuse Axonal Injury III)
• Stroke mimics

  • Transient ischemic attack (TIA); Please see StatPearls' companion resource, "Transient Ischemic Attack," for further information.
  • Subarachnoid hemorrhage
  • Seizures
  • Basilar migraine
  • Basilar meningitis
  • Hypoglycemia
  • Electrolyte imbalance
  • Conversion disorder.[57]

Pertinent Studies and Ongoing Trials

The ongoing Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE) trial should provide newer insights into the role of surgical treatment of primary brainstem hemorrhage.[55] The inclusion criteria of the trial include:

• GCS <8
• Hematoma volume ≥5 mL
• New primary pontine hemorrhage (PPH) score of 2 to 4 points [55]

Prognosis

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 gradually increasing incidences.[13] Early diagnosis and management have a lower chance of permanent morbidity. 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 stroke's severity, etiology, location, structures involved, associated risk factors, comorbidities, and management. Variables prognosticating poor outcomes in brainstem strokes include:

• Old age
• Tachycardia (>110 beats/min)
• Systolic blood pressure <100 mm Hg
• Absence of a pupillary light reflex
• Pupillary abnormalities
• Low GCS score
• Large hematoma volume
• Central hyperthermia
• A need for mechanical ventilation
• History of diabetes mellitus
• Elevated platelet-to-lymphocyte ratio
• An elevated neutrophil-to-lymphocyte ratio.[55]

Conventional symptomatic basilar artery occlusion treatment yields poor results in almost 80% of cohorts.[76] Death and dependency were observed in nearly 95%. Both vertebral artery occlusion, primarily due to atherosclerosis, and basilar artery occlusion, due to cardio-embolic, have poor outcomes.[77] Time to therapy is better in the intravenous thrombolysis (IVT) group.[77] IVT is safer in posterior circulation ischemic strokes (PCIS) than anterior circulation ischemic strokes (ACIS).[78] This can be considered even in borderline cases, even after 4.5 hours of ictus. Time to IVT in PCIS seems to be a less crucial factor than in ACIS.[78] Reportedly, 38% to 49% have a favorable outcome after IVT.[78] The mortality rate following IVT is not significantly different between PCIS and ACIS.[78] Moreover, when comparing time to treatment, mortality, and favorable outcomes between intra-arterial thrombolysis (IAT) and endovascular thrombectomy (EVT), no significant differences are observed, likely owing to collateral flow from the posterior communicating arteries to the posterior circulation.[77]

Recanalization confers a 2-fold decrement in mortality and a 1.5-fold reduction in futile outcome rates.[77] Better recanalization and improved clinical outcomes in acute basilar occlusion are observed with endovascular thrombectomy compared with thrombolytic therapy (no difference between stent-retriever and thrombo-aspiration approaches).[77] Significant improvement in functional outcome and functional independence following thrombectomy, compared with best medical therapy alone, was observed. The mortality rate was significantly lower in the intervention group (RR 0.76).[79] A comparative study between different management modalities revealed the following outcomes:

• Mortality: 34.5%, 9.9%, and 28.9% in the mechanical thrombectomy, percutaneous transluminal angioplasty and stenting (PTAS), and mechanical thrombectomy plus PTAS groups
• Arterial dissection: 3.6% of the mechanical thrombectomy, 3.1% in the PTAS, and 16.7% of the mechanical thrombectomy plus PTAS group
• Distal embolization: 3.4%, 5.8%, and 9.5% of the mechanical thrombectomy, PTAS, and mechanical thrombectomy plus PTAS groups
• Favorable outcomes: 42.8% of the mechanical thrombectomy plus PTAS group, 64.7% of the PTAS, and 39.2% of the mechanical thrombectomy group
• Intracranial hemorrhage: 5.2%, 4.5%, and 15.3% in the mechanical thrombectomy, PTAS, and mechanical thrombectomy plus PTAS groups
• Successful recanalization: 85.3% of mechanical thrombectomy, 99.4% of PTAS, and 92.7% of the mechanical thrombectomy plus PTAS group

PTAS was, therefore, the most effective intervention for vertebrobasilar artery occlusion and was associated with a lower mortality rate than mechanical thrombectomy alone.[80] Almost 30% of these cohorts still possess some disabilities even at 1-year poststroke. Multiple infarctions and omissions in the use of statins have been associated with poor outcomes at 1 year.[81]

A worse prognosis is observed among patients with primary brainstem hemorrhage, having dysarthria, pupillary abnormalities, lower cranial nerve involvement, and diminished consciousness on admission.[13] Primary brainstem hemorrhage is the most fatal form of ICH.[55] The mortality rate can be as high as 30% to 88%.[82] In a study comprising 1437 pontine hemorrhages, the overall mortality observed was 48.1%.[83] Massive stroke subtypes with ventral or paramedian locations of involvement have a poor prognosis, with a survival rate of only 7.1%. The unilateral tegmental subtype has comparatively more favorable outcomes, with basotegmental variants having an intermediate prognosis (94.1% versus 18.2%).[55][57][82] Bilateral, ventral, and massive hematomas encompass the worst prognosis.[57] A brainstem stroke involving the medulla oblongata is the most serious type, harboring the risk of rapid death following the ataxic pattern of respiration.[55][57]

Predominant and consistent variables prognosticating outcomes include the presenting GCS score, location, and hematoma volume.[1][84] Additionally, a low GCS at presentation, a hematoma >4 mL in volume and 2 cm in diameter, a ventral subtype, and the need for mechanical ventilation indicate poor outcomes.[1][55][85]

A scoring system by Huang et al., incorporating hematoma volume and GCS, is the best, largest population-based, and best-evidence score for predicting mortality.[57] Almost 90% of patients in the study eventually developed hydrocephalus, causing 100% mortality in the conservative management group. However, early intervention for the same group markedly improved the clinical outcome.[82] In the study, age and intraventricular extension, though important predictive variables, were not independent determinants of early death in primary brainstem hemorrhage.[55][83] The surgical evacuation group had a mortality of 27.6% compared to 60.6% in the conservative management group.[82] Early tracheostomy, performed within 7 days of admission, was associated with a favorable 30-day functional outcome.[55] Quantitative electroencephalography (EEG) and neurophysiological monitoring, eg, brainstem auditory evoked potentials, somatosensory evoked potentials (SEPs), and motor evoked potentials, are reliable predictors of recovery and mortality in patients with primary brainstem hemorrhage.[57] Original and modified ICH scores may not apply well to PPH. Only 10% of primary brainstem hemorrhages were included in the ICH score.[57] The PPH score also lacks external validation, and the failure to consider early do-not-resuscitate orders (DNRs) was a major flaw.[57]

Complications

Complications associated with brainstem stroke include the following:

• Neurological deficits present characteristically as crossed signs, as in various brainstem stroke syndromes
• Dysautonomia due to involvement of the sympathetic tract
• Altered level of awareness and coma due to the involvement of the reticular activating system, as in the "locked-in" syndrome and the "top-of-the-basilar" syndrome
• Dysregulation of the respiratory control mechanism presents as central hypoventilation syndrome or Ondine syndrome due to the involvement of the dorsal and ventral respiratory group of neurons, pneumotaxic and apneustic respiratory centers
• Dysregulation of the blood pressure control mechanism due to the involvement of the Nucleus of tractus solitarius and neurons in the ventrolateral medulla
• Acute hydrocephalus
• Dysphagia
• Dysarthria
• Ataxia
• Central pain syndrome in 25% of cases of Wallenberg syndrome
• Restless leg syndrome
• Poststroke fatigue
• Depression
• Pulmonary aspiration, particularly in patients with medullary and cerebellar strokes 
• Deep vein thrombosis and pulmonary embolism
• Bed sores
• Contractures
• Sepsis
• Mortality.[16][29][86][87]

Postoperative and Rehabilitation Care

In a cohort study in a rehabilitation unit, ataxia (68%), hemiplegia (70%), and dysphagia (40%) were the most common neurological deficits. However, significant functional gains were observed across all these domains. Aspiration pneumonia and urinary tract infection were observed in 15% and 25% of patients. 96% were ultimately discharged home.[88] Functional recovery and long-term survival with brainstem stroke have been better than those observed in hemispheric stroke.[89] Approximately 35% of brainstem infarction survivors returned to living independently within the first year poststroke, compared to only 22% with hemispheric stroke survivors.[89]

Dysphagia is seen in approximately 47% of patients with brainstem stroke. Dysphagia is best evaluated with modified barium videofluoroscopy. Typically, dysphagia is initially managed by nasogastric tube feeding, though gastrostomy and jejunostomy feeding tubes are required in 20% of patients. Patients with this complication should receive appropriate swallowing instructions. Furthermore, oral and pharyngeal postures and biofeedback techniques are essential. Speech-language pathologists should also be consulted to help manage these cases. In most patients, the long-term result is favorable.

Ataxia is seen in 86% of patients with brainstem stroke due to gait initiation and patterning being governed by the pons and medulla. Gait training is promoted through the "use it to improve it" technique. Typically, ataxia can be managed through postural training, motor learning, and control and strengthening exercises. The Bobath treatment approach is also effective.

Dysarthria is observed in 49% to 89% of patients. Typically, dysarthria is managed by regaining tone and strength in the facial and buccal muscles. Reducing speech rate, pausing, deep breathing, and over-articulating can also help. Palatal lift and palatal augmentation have been effective. In 94% of patients with brainstem stroke, paresis is noted and is managed by task-related motor training and therapeutic approaches. Diplopia is seen in 38% of patients and can be treated with diachronic mirrors or integration of fogging, occlusion, and suppression. Surgical procedures are utilized only if rehabilitation has failed, usually 6 months poststroke.[89]

Deterrence and Patient Education

"ACT FAST" is an acronym suggested by the American Stroke Association to recognize the early symptoms of a stroke and consists of the following components:

• F-Face drooping
• A-Arm Weakness
• S-Speech
• T-Time to call 911

Along with the above, if the patient experiences any of the following symptoms, emergency medical services must be activated:

• Sudden confusion
• Sudden trouble seeing
• Sudden numbness
• Sudden trouble walking
• Sudden severe headache

Managing risk factors can significantly reduce future strokes, including:

• Smoking cessation
• Alcohol use
• Drug addiction and abuse
• Hypertension and diabetes control
• Obesity and a sedentary lifestyle
• Obstructive sleep apnea syndrome.[90]

Pearls and Other Issues

Key facts to bear in mind when managing brainstem strokes include the following:

• Early identification of stroke and its management; "time is brain."
• Avoiding pitfalls of stroke-like syndrome and stroke mimics (eg, migraine headache, seizure disorder, transient ischemic attack, and vertigo)
• Consider permissive hypertension to improve perfusion in ischemic stroke
• Patient education with the FAST acronym.

Enhancing Healthcare Team Outcomes

Brainstem stroke represents a highly complex and devastating form of cerebrovascular disease, producing substantial morbidity, mortality, and long-term disability for patients while imposing significant burdens on families and healthcare systems. The global burden of stroke continues to rise steadily, emphasizing the need for effective prevention, early recognition, and coordinated management. Brainstem involvement carries unique risks due to the dense concentration of vital autonomic and sensorimotor pathways, where small lesions can result in profound neurological deterioration. Prevention strategies must begin with patient and community education focused on modifiable risk factors, including smoking cessation, healthy diet, physical activity, and routine screening for hypertension and diabetes. Decentralized community-based models that emphasize primary and secondary prevention of noncommunicable diseases can meaningfully reduce stroke incidence.

Optimal diagnosis and management require a skilled, interprofessional approach across the continuum of care. Physicians, general practitioners, and advanced practitioners play central roles in early recognition, risk stratification, and acute decision-making, supported by standardized tools such as the National Institutes of Health Stroke Scale, the Modified Rankin Scale, or other standardized models and scales.[91] Nurses, pharmacists, physiotherapists, and allied health professionals contribute to stabilization, medication safety, rehabilitation, and prevention of complications. Effective interprofessional communication, supported by telemedicine, teleradiology, and rapid response systems, enables timely coordination and deployment of expertise. Structured teamwork, continuous protocol refinement, and coordinated rehabilitation involving occupational therapists, dietitians, and home support services collectively enhance patient-centered care, safety, outcomes, and overall team performance.

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Disclosure: Supreeth Gowda declares no relevant financial relationships with ineligible companies.

Disclosure: Sunil Munakomi declares no relevant financial relationships with ineligible companies.