Wallenberg Syndrome – Causes, Symptoms, Treatment

Wallenberg syndrome is also known as lateral medullary syndrome or the posterior inferior cerebellar artery syndrome. Wallenberg described the first case in 1895. This neurological disorder is associated with a variety of symptoms that occur as a result of damage to the lateral segment of the medulla posterior to the inferior olivary nucleus. It is the most typical posterior circulation ischemic stroke syndrome in clinical practice. [rx][rx]

The vertebral arteries arise from the subclavian arteries. They enter the skull through the foremen magnum and merge to form the basilar artery at the pontomedullary junction. The posterior inferior cerebellar artery (PICA) is derived from each vertebral artery. PICA supplies the medulla and the suboccipital surface in the part of the cerebellum. When there is decreased blood flow to these regions, patients typically present with signs and symptoms of posterior circulation stroke which are discussed later.[rx]

Causes of Wallenberg Syndrome

Wallenberg syndrome is caused most commonly by atherothrombotic occlusion of the vertebral artery, followed most frequently by the posterior inferior cerebellar artery, and least often, the medullary arteries. Hypertension is the most prevalent risk factor, followed by smoking and diabetes. Cerebral embolism is a less frequent cause of the infarction. The other important cause to remember is vertebral artery dissection, which may have risk factors including neck manipulation or injury, Marfan syndrome, Ehlers Danlos syndrome, and fibromuscular dysplasia. Vertebral artery dissection is the commonest cause of Wallenberg syndrome in younger patients.[rx][rx]

Pathophysiology

The primary pathology of Wallenberg syndrome is occlusion of the posterior inferior cerebellar artery (PICA) or one of its branches[rx]. 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 occlusion of the PICA accounts for only a small number of cases. The majority (80%) of 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.[rx]

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 is different as compared to that of large vessels which are affected by atherosclerosis. Small vessels are affected by a process called 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.[rx]

Diagnosis of Wallenberg Syndrome

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 the 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.[rx][rx][rx]

The clinical differential diagnoses include:

• 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.[rx][rx]
• Hemorrhagic stroke – much less common, and headache is much more prominent.
• Acute demyelination in multiple sclerosis – patients are generally much younger, more likely female and known history of demyelinating disease
• 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.[rx] 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 started to prevent future strokes. [rx]

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[rx].

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.

Treatment of Wallenberg Syndrome

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:

• 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.[rx]
• 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.
• 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:

• Carotid endarterectomy for significant large vessel extracranial stenosis
• Oral anticoagulation for cardioembolic strokes
• Antiplatelets such as aspirin, clopidogrel, or ASA/Dipyridamole for other forms of stroke
• Statins
• Smoking cessation
• Good control of diabetes
• Good blood pressure control
• Healthy diet and lifestyle with regular exercises

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