A typical patient with Wallenberg syndrome is an elderly patient with vascular risk factors. Like any acute 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.

Usually, there is no weakness associated with this syndrome and so this condition is often misdiagnosed or missed. A careful neurological examination is a key to the diagnosis. A complete Wallenberg syndrome is not common, yet partial syndromes are satisfactory for the diagnosis most of the time. The important 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 all be found in Wallenberg syndrome:

On the side of lesion:

• Vertigo with nystagmus (inferior vestibular nucleus and pathways). The 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 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 marked 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.[10][11][6]

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.[12][13]
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 known history of demyelinating disease
4. Acute relapse/attack of neuromyelitis optica with the involvement of the area postrema. The patient is most 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 history of presentation. MRI with diffusion-weighted imaging (DWI) is the best diagnostic test to confirm the infarct in the inferior cerebellar area or lateral medulla.[14] Up to 30% of patients with nondisabling stroke do not have a lesion on the DWI-MRI brain. These patients are DWI-negative stroke patients, and secondary prevention should be started to prevent future strokes. [15]

A CT angiogram or MR angiogram is very helpful in identifying the site of vascular occlusion and to rule out uncommon causes such as vertebral artery dissection[16].

An ECG is useful in excluding any underlying atrial fibrillation or unexpected acute coronary syndrome. Checking the serum electrolytes is essential. Patients with dysphagia or dysarthria need to be assessed by the speech pathologist before any food or medicine can be given orally.

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. Management in certified stroke centers has shown to improve overall patient outcomes. Treatment aims at reducing the size of infarction and preventing any medical complication with the final target of improving patient outcome 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 time period, improves functional stroke outcomes by 30%. There have been studies showing that the window for posterior circulation strokes may be longer than 4 1/2 hours.[17]
2. Endovascular revascularization: the newer devices have been shown to improve outcome with the number needed to treat to be as low as 3. These are indicated mainly for large vessel intracranial occlusion which carries a very 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, it will be best to manage the patients in dedicated stroke beds or units.

• 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 comes down gradually without any drug treatment. In general, BP does not need to be lowered unless the patient receives IV thrombolysis or when it is over 220/120 mmHg.
• Speech therapy assessment: very important to prevent aspiration.
• Deep vein thrombosis prophylaxis: with sequential pressure devices and low dose heparin or low molecular weight heparin (LWMH).
• Blood sugar: best to keep the patient normoglycemic.
• Fever: the source of fever needs to be identified and treated. A simple antipyretic with acetaminophen is helpful.
• Antithrombotics: numerous more recent clinical trials failed to show any benefit or anticoagulants in acute stroke even in atrial fibrillation. Antithrombotic therapy with aspirin does improve the outcome.
• Early physical therapy and occupational therapy with a good plan for rehabilitation.

Secondary stroke prevention is decided after the outcome of the primary prevention of each patient. This will again include 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%.[18][19][20]

• 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

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.

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.[21]

Hypertension is the commonest 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.[22]

The outlook for patients with Wallenberg syndrome depends on the size of the infarct, but in general, most patients have a better outcome compared with other ischemic stroke syndromes with the exception of some lacunar syndromes. Gait instability or ataxia is the most typical sequelae. Sometimes hiccups can be intractable.

Treatment of Wallenberg Syndrome requires a rapid response and coordinated 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 the coordination of care of the patient, monitoring, and patient education, keeping other team members apprised of findings and issues. The pharmacist should evaluate for potential drug-drug interactions and assist with appropriate dosing as well as with patient education, coordinating with the clinical staff if any medication changes are necessary. An interprofessional approach will lead to improved outcomes. [Level 5]