Posterior Reversible Encephalopathy Syndrome - Diagnosis and Treatment

What Is Posterior Reversible Encephalopathy Syndrome?

It is an acute neurological condition with rapid onset of symptoms like seizures, headache, visual disturbances, impairment of consciousness, etc. In addition, associated conditions like renal failure, hypertension, eclampsia, autoimmune disorders, etc., trigger it. First described by Hinchey in 1996, PRES is characterized by specific neuroimaging findings. Typical features include bilateral subcortical vasogenic edema involving the parietal and occipital regions and occasional cortical involvement and hemorrhage. When recognized promptly, timely management of precipitating factors can achieve reversibility, although some cases might need aggressive therapy. Unfortunately, contrary to the name, PRES has caused the functional impairment, permanent brain damage, and mortality in a few patients.

Who Is Affected by Posterior Reversible Encephalopathy Syndrome?

It has been known to affect all age groups, from infancy to adulthood, the most common being middle-aged adults. This is because PRES has a slight female predilection, and not just because eclampsia is one of the triggers for PRES.

Patients with the below-mentioned comorbidities have higher chances of developing PRES-

1. Pre-eclampsia and Eclampsia- Both conditions are seen only in pregnant women; the former is characterized by high blood pressure and is caused due to fluid retention and proteinuria, and the latter is characterized by convulsions caused due to high blood pressure.

2. Blood Pressure Fluctuations- This includes conditions like hypertension, dysautonomia (for example- Guillain barre syndrome), drug withdrawal (like Clonidine, and Prazosin), stimulant drugs (like Cocaine and Ephedrine.), and post-carotid endarterectomy with reperfusion syndrome. It is a set of symptoms like headache and hypertension, that develop after successful carotid endarterectomy (a surgical procedure to remove fatty deposits in the carotid artery).

3. Infection- This can be sepsis or shock.

4. Renal Diseases- This includes hemolytic uremic syndrome, acute glomerulonephritis, acute and chronic renal failure, parenchymal diseases, and renal artery stenosis.

5. Immunosuppressive Drugs- These are usually given to lower the body’s ability to reject a transplanted organ. They include drugs like Cyclosporin A, intravenous immunoglobulin, and Sirolimus.

6. Chemotherapeutic Agents- These are commonly prescribed to cancer patients; a few examples of chemotherapeutic drugs are Cisplatin, Rituximab, and Thalidomide.

7. Autoimmune Disorders- These are conditions where the body’s natural defense system cannot tell the difference between its cells and foreign bodies. As a result, it starts attacking the normal cells instead of the pathogens. Some autoimmune conditions that can trigger PRES are systemic lupus erythematosus, Sjogren’s disease, vasculitis, and scleroderma.

8. Hematological Disorders- This includes conditions like thrombotic thrombocytopenic purpura, sickle cell anemia, and hemolytic uremic syndrome.

9. Endocrine Disorders- Patients suffering from endocrine conditions like pheochromocytoma and primary aldosteronism are susceptible to PRES.

10. Electrolyte Disturbances- This includes hypercalcemia and hypomagnesemia.

11. Others- Miscellaneous conditions that can precipitate PRES are acute porphyria, blood transfusion, and lithium.

What Happens During Posterior Reversible Encephalopathy Syndrome?

The most acceptable theory to explain PRES is the vasogenic theory. According to this theory, whenever there is a rapid rise in blood pressure, the auto (self) regulatory function of the cerebral vasculature (blood vessels) fails to cause the breakdown of the blood-brain barrier and leading to vasogenic edema (swelling). The posterior part of the brain is more affected because of its relative lack of sympathetic innervation. This theory is supported by the fact that there is a rapid clinical and radiological improvement when the underlying hypertension is treated.

This theory, however, does not explain the PRES in borderline hypertensive patients and normotensives (people with no blood pressure fluctuations). Therefore, additional theories like neuropeptide, cytotoxic, and immunogenic theories have been used to understand the underlying mechanisms. According to these theories, whenever the body is subjected to conditions like infection, immunosuppressant and chemotherapeutic drugs, etc., it goes through endothelial dysfunction because of the cytotoxic effects caused by these conditions. This endothelial dysfunction, when combined with cerebral vasoconstriction, cerebral ischemia, and potential activation of peripheral renal receptors, will potentially lead to the development of hypertension. This renal impairment is, in turn, responsible for the symptoms and complications of PRES.

What Are the Symptoms of Posterior Reversible Encephalopathy Syndrome?

Some of the commonly seen symptoms of PRES are-

1. Encephalopathy- Any condition that affects the brain's normal functioning is termed encephalopathy. The encephalopathy caused by PRES can manifest as mild confusion, stupor, somnolence, cognitive dysfunction, or coma. If not attended to immediately, the weakening mental status can lead to life-threatening respiratory failure.

2. Seizures- These are often seen in PRES; the most common type is the generalized clonic-tonic seizures; however, partial seizures and status epilepticus are not uncommon.

3. Headache- Seen in 50 % of the patients and is often dull, diffuse, and gradual in onset.

4. Ophthalmic Manifestations- These include decreased visual acuity, cortical blindness, diplopia (double vision), color vision abnormality, visual hallucinations, and visual field deficits.

Along with the above-mentioned symptoms, focal neurological deficits like aphasia (difficulty in the communication) and hemiparesis (inability to move one side of the body) have also been in patients suffering from PRES.

Some of the uncommon symptoms of PRES are-

1. Abulia- It is defined as the absence of willpower.

2. Agitation- It is the inability of a person to relax.

3. Delusions- Altered sense of perception.

4. Opisthotonus- It is the backward arching of the head, neck, and spine due to muscle spasms.

5. Optic Ataxia- It is the inability to accurately point or reach for objects under visual guidance with intact ability when directed by sound or touch despite normal strength.

6. Ocular Apraxia- It is the inability to perform voluntary eye movements.

7. Simultagnosia- It is the inability to perceive more than one object at a time.

How Is Posterior Reversible Encephalopathy Syndrome Diagnosed?

A detailed medical history, possible risk factors, clinical features, and investigations are crucial in diagnosing PRES. The necessary investigations to diagnose PRES are-

1. Serology Test- Patients with PRES have deranged electrolyte levels (like hypomagnesemia and hypocalcemia), elevated lactate dehydrogenase levels (LDH), elevated C reactive protein levels, and reduced serum albumin levels.

2. Cerebrospinal Fluid (CSF) Analysis- Most patients with PRES have elevated CSF protein levels.

3. Electroencephalogram (EEG)- The most common EEG pattern seen in patients with PRES is generalized slowing, focal slowing, epileptiform discharges, periodic lateral epileptiform discharges, and normal patterns.

4. Neuroimaging- It is the cornerstone in confirming PRES, a computed tomographic (CT) scan helps visualize vasogenic edema; however, a FLAIR (fluid-attenuated inversion recovery) MRI (magnetic resonance image) can detect cortical and subcortical lesions caused by PRES.

What Is the Treatment for Posterior Reversible Encephalopathy Syndrome?

Treatment primarily involves removing precipitating (risk) factors and providing supportive care. Most of the patients will need admission into the intensive care unit, where the following steps will be performed

• Stabilization of the airway, breathing, and circulation is given priority; if necessary, the patient may be intubated.

• Supportive care includes hydration and maintenance of electrolyte balance.

• The triggering risk factors should be removed or at least reduced.

• Dialysis should be performed in patients with renal failure.

• Delivery should be considered in pregnant women.

• Gradual reduction of hypertension with the help of first-line drugs (like Nicardipine and Nimodipine) and second-line drugs (like Diazoxide and Hydralazine) should be performed.

• Seizures are managed with the help of intravenous anticonvulsants (for normal patients) and magnesium sulfate (for pregnant women). Regular EEG monitoring should be considered to prevent refraction.

Conclusion:

PRES is a neurological condition characterized by encephalopathy, seizures, headache, and ophthalmic manifestations. Risk factors include fluctuating blood pressure levels, renal failure, immunosuppressive and chemotherapeutic drugs, pre-eclampsia, eclampsia, etc. Therefore, neuroimaging is important in diagnosing the condition, and prompt treatment can reverse the clinical features successfully.