Continuing Education Activity

Wallenberg syndrome is also called lateral medullary and posterior inferior cerebellar artery syndrome. This neurological disorder is associated with various symptoms that result from damage to the lateral segment of the medulla posterior to the inferior olivary nucleus. It is the most common posterior circulation ischemic stroke syndrome. This activity explains when this condition should be considered as part of a differential diagnosis, articulates how to evaluate this condition, and highlight the role of an interprofessional team in caring for patients with this condition.

Objectives:

• Describe the pathophysiology of Wallenberg syndrome.
• Review the differential diagnosis of Wallenberg syndrome.
• Summarize how to evaluate for Wallenberg syndrome.
• Explain a well-coordinated, interprofessional team approach to effectively care for patients affected by Wallenberg syndrome.

Introduction

Wallenberg syndrome was first described in 1808 by Gaspard Vieusseux. However, a more detailed description given in 1895 by Adolf Wallenberg identified this condition as infarction of the lateral medulla oblongata following occlusion of the vertebral artery (VA) or Posterior inferior cerebellar artery (PICA). Wallenberg syndrome is also called lateral medullary or posterior inferior cerebellar artery syndrome. This neurological disorder is associated with various symptoms that result from damage to the lateral segment of the medulla posterior to the inferior olivary nucleus.[1][2]

Anatomy

The posterior inferior cerebellar artery (PICA) usually originates from the vertebral artery at an average distance of approximately 16 or 17 mm below the vertebrobasilar junction.[3][4] The vertebral artery, arising from the subclavian artery, is classically divided into four segments. The fourth segment of the vertebral artery gives off the PICA, the largest branch of the vertebral artery.[5][6] The trunk of PICA is divided into five segments:

1. The anterior medullary segment begins at the origin of the PICA. It ends at the level of a rostrocaudal line that passes through the most prominent part of the inferior olive.
2. The lateral medullary segment extends from the level of the most prominent point of the olive to the level of the origin of the glossopharyngeal (CN IX), vagus (CN X), and accessory (CN XI) rootlets.
3. The tonsillomedullary segment begins where the PICA passes posterior to the CN IX-XI and ends at the midpoint of the PICA's ascent toward the roof of the fourth ventricle along the medial surface of the tonsil.
4. The telovelotonsillar segment begins where the PICA ascends to the mid-level of the medial surface of the tonsil and ends where the artery exits the fissures between the tonsil, vermis, and hemisphere to reach the suboccipital surface.
5. The cortical segment begins where the PICA leaves the groove between the vermis, tonsil, and hemisphere and includes the terminal cortical branches.[3]

The trunk of PICA gives rise to perforating, choroidal, and cortical branches. The PICA supplies the medulla, the choroid plexus, the tela choroidea of the fourth ventricle, the tonsils, the inferior vermis, and the inferior aspects of the cerebellar hemispheres.[3][7] Furthermore, the PICA mostly supplies the choroid plexus on the roof and the median opening of the fourth ventricle and provides the majority of branches of the choroid plexus.[8]

Etiology

Wallenberg syndrome is commonly caused by atherothrombotic occlusion of the vertebral artery, followed by occlusion of the posterior inferior cerebellar artery and, least often, the medullary arteries. The PICA is of great clinical importance with its unique anatomical complexity and is involved in many diseases, including ischemic stroke, aneurysm, neurovascular compression syndrome (NVCS), arteriovenous malformation (AVM), brain tumor, etc. Besides, the PICA is exposed in many surgical approaches and is vulnerable to damage.[3][9] 

Hypertension is the most prevalent risk factor, followed by smoking and diabetes.[10] The other important cause is vertebral artery dissection, which may occur during neck manipulation or head injury, Marfan syndrome, Ehlers-Danlos syndrome, and fibromuscular dysplasia.[11] Vertebral artery dissection is the commonest cause of Wallenberg syndrome in younger patients.[12][13] 

Epidemiology

Wallenberg syndrome is the most prevalent posterior ischemic stroke syndrome. There are nearly 800,000 patients who suffer from acute stroke each year in the United States. Of these, 83% are ischemic strokes. Twenty percent of ischemic strokes occur in the posterior circulation. If clinicians assume that about half of these suffer from Wallenberg syndrome, it can be estimated that there are more than 60,000 new cases of Wallenberg syndrome each year in the United States.[14]

The condition shows a predominance for men in their sixth decade. Large artery atherothrombotic causes account for about 75% of the cases, followed by cardioembolism in 17% and vertebral dissection in 8%.[15]

Pathophysiology

The primary pathology of Wallenberg syndrome is occlusion of the posterior inferior cerebellar artery (PICA) or one of its branches.[16] The syndrome can also be due to occlusion of the vertebral artery or the inferior, middle, or superior medullary vessels. Anatomically the infarcted area in Wallenberg syndrome is supplied by the posterior inferior cerebellar artery (PICA). It turns out that occlusion of the PICA accounts for only a small number of cases. Most (80%) cases are caused by occlusion of the vertebral artery, which gives rise to the PICA and the anterior spinal artery before it joins with the opposite vertebral artery to form the basilar artery. The most common mechanism of occlusion of the vertebral artery or PICA is atherothrombosis.[17]

Atherosclerosis is the most common condition affecting the vertebrobasilar system, in which atheromatous plaques narrow and occlude large vessels. However, the pathology of small vessel disease differs from that of large vessels, which atherosclerosis affects. Small vessels are affected by lipohyalinosis, which is closely associated with hypertension. Ischemic infarctions of these small vessels lead to small round infarctions called lacunae, which are scattered throughout the brainstem.[18]

History and Physical

A typical patient with Wallenberg syndrome is an elderly patient with vascular risk factors. Like any stroke syndrome, the onset is acute. The most common symptoms of onset are dizziness with vertigo, loss of balance with gait instability, hoarseness of voice, and difficulty swallowing. The symptoms often progress over several hours to sometimes a couple of days.[10]

Usually, no weakness is associated with this syndrome, so this condition is often misdiagnosed or missed. A careful neurological examination is a key to the diagnosis. Complete Wallenberg syndrome is not common, yet partial syndromes are satisfactory for the diagnosis most of the time. The critical points in clinical diagnosis are a combination of crossed hemiparesis or hemianesthesia to indicate a brainstem lesion and the involvement of structures in the posterolateral medulla to localize, wherein the brainstem.

Different combinations of the following deficits may be elicited in Wallenberg syndrome:

On the side of the lesion:

• Vertigo with nystagmus (inferior vestibular nucleus and pathways): nystagmus is typically central, beating to the direction of gaze. Nausea and vomiting, and sometimes hiccups, are associated with vertigo. Hiccups can often be intractable.
• Dysphonia, dysarthria, and dysphagia (different nuclei and fibers of the IX and X nerves), often present with ipsilateral loss of the gag reflex
• Horner syndrome; miosis, ptosis, and anhydrosis (sympathetic fibers)
• Ipsilateral ataxia with a tendency to fall to the ipsilateral side (inferior cerebellar hemisphere, spinocerebellar fibers, and inferior cerebellar peduncle)
• Pain and numbness with impaired facial sensation on the face (descending trigeminal tract)
• Impaired taste sensation (involvement of nucleus tractus solitarius)

On the contralateral side:

• Impaired pain and temperature sensation in the arms and legs (spinothalamic tract)
• It is important to note that there is no or only minimal weakness of the contralateral side (corticospinal fibers are ventral in location)

It is clinically interesting to note that more rostral lesions tend to be more ventrally located. These patients present with significant dysphagia and dysphonia due to the involvement of the nucleus ambiguus. More caudal lesions involve more dorsolateral structures. These patients present with vertigo, ataxia, nausea/vomiting, and Horner syndrome.[19][20][15]

Evaluation

The clinical differential diagnoses include:

1. Other causes of vertigo, especially peripheral vertigo, such as acute labyrinthitis: the patient may be younger without any vascular risk factors. The nystagmus is peripheral and unidirectional or rotatory. There may be associated tinnitus without other brainstem signs. Head thrust test will be positive, which, if present, is most helpful in differentiating a central cause, such as Wallenberg syndrome, from a peripheral cause.[21][22]
2. Hemorrhagic stroke: much less common, and headache is much more prominent.
3. Acute demyelination in multiple sclerosis: patients are generally much younger, more likely female, and have a known history of demyelinating disease
4. Acute relapse/attack of neuromyelitis optica occurs, with the involvement of the area postrema. The patient is likely a young adult female, and the signs may suggest more than one central nervous system (CNS) lesion.

The diagnosis is usually made or suspected from a clinical exam and presentation history. MRI with diffusion-weighted imaging (DWI) is the best diagnostic test to confirm the infarct in the inferior cerebellar area or lateral medulla.[23] Up to 30% of patients with non-disabling stroke do not have a lesion on the DWI-MRI brain. These patients are DWI-negative stroke patients, and secondary prevention should be initiated to prevent future strokes.[24]

A CT or MR angiogram helps identify the site of vascular occlusion and rule out uncommon causes such as vertebral artery dissection.[25]

An ECG is useful in excluding any underlying atrial fibrillation or unexpected acute coronary syndrome. Checking the serum electrolytes is essential. The speech pathologist must assess patients with dysphagia or dysarthria before oral intake.

Treatment / Management

Similar to the management of any acute ischemic stroke, remember "TIME IS BRAIN." Rapid evaluation is essential to an orderly approach (algorithm) developed within each hospital or stroke center.[26] Management in certified stroke centers has been shown to improve overall patient outcomes.[27] Treatment aims to reduce the size of the infarction and prevent any medical complications with the final goal of improving patient outcomes and prognosis.

The management steps include:

1. Intravenous (IV) thrombolysis with IV tissue plasminogen activator (TPA) within 3 to 4 1/2 hours of the onset of the ischemic stroke with slightly different exclusion criteria: overall, IV thrombolysis, within this period, improves functional stroke outcomes by 30%. Studies have shown that the window for posterior circulation strokes may be longer than 4 1/2 hours.[28]
2. Endovascular revascularization: the newer devices have been shown to improve outcomes, with the number needed to treat as low as 3. These are indicated mainly for large vessel intracranial occlusion, which carries a poor prognosis without revascularization.
3. General medical therapy: patients are best monitored in the intensive care unit (ICU) for 24 hours after IV thrombolysis. Otherwise, managing the patients in dedicated stroke units should be an alternative.[26]

• IV fluid: avoid hypotonic solution to reduce risks of cerebral edema. Normal saline is generally preferred.
• Blood pressure (BP)management: cerebral autoregulation is impaired in the infarcted areas of the brain. Blood pressure often drops gradually without any drug treatment. BP generally does not need to be lowered unless the patient receives IV thrombolysis or when it is over 220/120 mmHg.[26]
• Speech therapy assessment is essential to assess swallow function and prevent any aspiration.
• Deep vein thrombosis prophylaxis: This is performed with sequential pressure devices and low-dose heparin or low molecular weight heparin (LWMH).
• Blood sugar: best to keep the patient normoglycemic.
• Antithrombotics: antithrombotic therapy with aspirin does improve the outcome.
• Early physical therapy and occupational therapy with a good rehabilitation plan.

Secondary stroke prevention is decided after each patient's primary prevention outcome; this involves a multimodality approach:

1. Carotid endarterectomy for significant large vessel extracranial stenosis
2. Oral anticoagulation for cardioembolic strokes
3. Antiplatelets such as aspirin, clopidogrel, or ASA/dipyridamole for other forms of stroke
4. Statins
5. Smoking cessation
6. Good control of diabetes
7. Good blood pressure control
8. Healthy diet and lifestyle with regular exercises

This multimodal approach can reduce the risk of subsequent stroke by 80%.[29][30][31]

Differential Diagnosis

• Chronic pain syndrome
• Lacunar stroke
• Middle cerebral artery stroke
• Migraine headache
• Multiple sclerosis
• Posterior reversible encephalopathy syndrome
• Subarachnoid hemorrhage
• Subdural hematoma
• Systemic lupus erythematosus
• Vertebrobasilar stroke

Prognosis

Overall Wallenberg syndrome has a better functional outcome than most other stroke syndromes. Most patients can return to satisfactory activities of daily living. The commonest sequel is gait instability.

Complications

Stroke syndromes, in general, can cause permanent disability and affect the normal functioning of the patient. The most common complications of posterior circulation strokes are aspiration pneumonia, deep vein thrombosis, pulmonary embolism, and myocardial infarction. Mechanical ventilation and the use of nasogastric tube further increase the risk of lung infections.[32]

Postoperative and Rehabilitation Care

Physiotherapy can be essential in helping those with Wallenberg syndrome regain their functional independence and reintegrate into their communities.[26] Considering Wallenberg syndrome is most commonly the result of a stroke in the lateral medulla, the condition is managed using traditional stroke rehabilitation protocols, individualized to each patient. 

The primary goal of any post-stroke rehabilitation program should be to:

1. Prevent complications
2. Minimize impairments
3. Maximize independence & function

Training is meant to be motivating, meaningful, engaging, and challenging. Instead of following a redundant mechanistic approach to rehabilitation, practitioners should use graded real-life activities that are purposeful and meaningful to every patient.[33] As a result, treatment of Wallenberg syndrome varies depending on the deficits each patient presents with. In many cases of Wallenberg syndrome, speech, language, and swallowing therapy may be beneficial.[34] A specialized form of neuromuscular electrical stimulation (NMES) has been cleared by the US Food and Drug Administration specifically for treating pharyngeal dysphagia when administered by appropriate healthcare professionals, though in practice, this is normally done by speech and language pathologists and occupational therapists.[35]

Physical therapy is used to combat balance, coordination, and movement deficits commonly associated with the disorder. Treatments should focus on task-oriented training, environmental adaptation, and motor retraining to improve functional ability. Furthermore, it has been found that electrical stimulation has a beneficial effect on improving muscle strength and balance in patients with stroke.[33] The current best evidence supports the use of electrical stimulation to facilitate motor recovery and should be incorporated early in the rehabilitation program.[33][34]

Deterrence and Patient Education

Patients need to understand the long-term sequelae of their condition and be reminded to adhere closely to all medication and therapy regimens to optimize their recovery.

Pearls and Other Issues

Hypertension is the most typical risk factor. Atherothrombosis of the vertebral artery is the most frequent underlying vascular cause. Vertebral artery dissection needs to be considered in younger patients, especially with a history of trauma, neck manipulation, or underlying collagen disorders such as Marfan syndrome. Head thrust (head impulse) test in the emergency department can differentiate peripheral vertigo due to acute labyrinthitis from central cause due to Wallenberg syndrome.[36]

The outlook for patients with Wallenberg syndrome depends on the infarct size. Still, most patients generally have a better outcome than other ischemic stroke syndromes, except for some lacunar syndromes. Gait instability or ataxia is the most typical sequelae. Sometimes hiccups can be intractable.

Enhancing Healthcare Team Outcomes

Treatment of Wallenberg syndrome requires a rapid response and coordinated interprofessional team approach involving clinicians, nurses, and pharmacists to provide the patient with the best possible outcome. Preferably, a specialty-trained neurologist and neurology specialty nurse should assist with coordinating patient care, monitoring, and patient education, keeping other team members apprised of findings and issues. Nursing will assist with patient assessment and counseling and coordinate activities among all involved healthcare professionals. The pharmacist should evaluate for potential drug-drug interactions and assist with appropriate dosing and patient education, coordinating with the clinical staff if any medication changes are necessary. Therapists (OT, PT, speech) are crucial to the rehabilitation of lost neural function. An interprofessional approach utilizing open communication between all team members and accurate record-keeping will improve outcomes.[26] [Level 5]