Hypertensive Encephalopathy – Causes, Symptoms, Treatment

A hypertensive emergency is a life-threatening condition where ongoing target-organ damage occurs due to markedly elevated blood pressure. Pulmonary edema?, cardiac ischemic events, acute renal failure?, aortic dissection, eclampsia?, retinopathy, and encephalopathy may present as a result of organ injury due to hypertension?.

Hypertensive encephalopathy is a less commonly encountered type of hypertensive emergency. It is characterized by signs of cerebral edema that occur after a severe? episode of hypertension. This condition is usually diagnosed retrospectively after symptoms dramatically resolve by lowering the patient’s blood pressure, and other causes of the neurologic disease have been ruled out. Symptoms of hypertensive encephalopathy include the gradual onset? of headache?, nausea?, and vomiting?, followed by neurologic symptoms such as restlessness, confusion?, seizures, and potentially coma. If hypertension is treated promptly, the symptoms of encephalopathy are usually reversible.[rx]

Causes of Hypertensive Encephalopathy

Hypertensive encephalopathy is triggered most commonly by inadequately controlled primary hypertension. Secondary causes of hypertension can also predispose patients to this condition.

Hypertensive encephalopathy shares multiple characteristics with other syndromes causing cerebral edema, such as posterior reversible encephalopathy syndrome? (PRES), hypertensive brainstem? encephalopathy, and eclampsia.

Evaluation for chronic? or acute? renal? disease, sympathomimetic ingestion (amphetamines, cocaine), side effects from drugs such as immunosuppressive agents, preeclampsia?, and eclampsia should be considered if primary hypertension has not been previously diagnosed.

Normally, the brain sustains blood flow within a narrow perfusion pressure range without being affected by fluctuations in systemic? arterial pressure. For healthy individuals, the pressure ranges are 50-150 mm Hg cerebral perfusion pressure (CPP) or 60 to 160 mm Hg mean arterial pressure (MAP).The CPP = MAP – intracranial pressure? (ICP?).[rx]

With increased MAP, cerebral arteriolar vasoconstriction occurs, and conversely, with decreased MAP, arteriolar dilation occurs to keep the CPP constant. This adaptive process maintains brain perfusion at a constant level despite systemic blood pressure changes. However, a sudden and severe increase in arterial pressure can exceed this autoregulatory mechanism because the arterioles are limited in their ability to constrict. The then intracerebral elevated blood pressure causes a breach in the blood-brain barrier, and vascular fluid diffuses across the capillary? membranes into the brain parenchyma. This leads to the development of cerebral edema, increased intracranial pressure, and neurologic deficits such as altered mentation, visual deficits, and seizures.

In patients with chronic hypertension, the cerebral vasculature undergoes adaptations, such as arteriolar hypertrophy?, to allow for a higher autoregulatory range. Lowering the blood pressure too quickly in these patients can produce cerebral ischemia? at a higher MAP compared to normotensive patients.

In previously normotensive patients, acute episodes of hypertension may induce hypertensive encephalopathy at diastolic blood pressures as low as 100 mm Hg. This scenario may be seen with patients that develop eclampsia or in patients receiving cytotoxic and immunosuppressive therapies.[rx][rx] It is hypothesized that these conditions directly elicit a toxic effect on the vascular endothelium and lead to dysfunction of the blood-brain barrier.

Symptoms Of Hypertensive Encephalopathy

The main symptoms of hypertensive encephalopathyare rapidly increasing blood pressure of 180/120 or higher and signs of organ damage. Usually, the damage happens to the kidneys? or the eyes.

Other symptoms depend on how the rise in blood pressure affects your organs. A common symptom is bleeding and swelling? in the tiny blood vessels in the retina?. The retina is the layer of nerves that line the back of the eye. It senses light and sends signals to the brain through the optic nerve?, which can also be affected by hypertensive encephalopathy. When the eye is involved,  can hypertensive encephalopathy cause changes in vision.

Other symptoms of malignant hypertension include

• Pheochromocytoma – Sweating, increased frequency or force of heartbeats, headache, anxiety
• Cushing’s syndrome – Weight gain, weakness, abnormal growth of body hair or loss of menstrual periods (in women), purple striations (lines) on the skin of the abdomen
• Thyroid problems – Fatigue (tiredness), weight gain or weight loss, intolerance to heat or cold
• Conn’s syndrome or primary aldosteronism – Weakness due to low levels of potassium in the body
• Obstructive sleep apnea – excessive fatigue or sleepiness during daytime, snoring, pauses in breathing during sleep
• Change in mental status, such as anxiety, confusion, decreased alertness, decreased ability to concentrate, fatigue, restlessness, sleepiness, or stupor
• Chest pain (feeling of crushing or pressure)
• Cough
• Headache
• Nausea or vomiting
• Numbness of the arms, legs, face, or other areas
• Reduced urine output
• Seizure
• Shortness of breath
• Weakness of the arms, legs, face, or other areas
• Blurred vision
• Chest pain (angina)
• Difficulty breathing
• Dizziness
• Numbness in the arms, legs, and face
• Severe headache
• Shortness of breath

In rare cases, hypertensive encephalopathy can cause brain swelling, which leads to a dangerous condition called hypertensive encephalopathy. Symptoms include:

• Blindness
• Changes in mental status
• Coma
• Confusion
• Drowsiness
• Headache that continues to get worse
• Nausea and vomiting
• Seizures

Diagnosis of Hypertensive Encephalopathy

A thorough physical exam and history are primarily used to diagnose hypertensive encephalopathy in patients presenting with elevated blood pressure in addition to altered mental status, visual abnormalities, headache, or seizures. Eliciting a thorough drug history is essential for identifying any previously used antihypertensive drugs. Typically, patients who develop hypertensive encephalopathy have chronic uncontrolled hypertension and may have recently discontinued their antihypertensive medication.[rx] Individuals that have rapidly developing and/or intermittent episodes of hypertension are also more at risk for developing hypertensive encephalopathy.

The majority of patients with this diagnosis have blood pressures in excess of 220/120 mm Hg.[rx] These patients should be evaluated for signs of organ damage that can be found during a hypertensive emergency. In particular, thoracic auscultation may reveal signs reflective of cardiac dysfunction, such as extra heart sounds or pulmonary edema, with rales heard on lung auscultation.[rx] Fundoscopy may show retinal hemorrhages and papilledema, which is a sign of severe hypertensive retinopathy. A complete neurologic exam can identify whether focal or non-focal deficits are present and may warrant other differential diagnoses for conditions that cause similar symptoms to be considered.

Lab Test and Imaging

A diagnosis of hypertensive encephalopathy is made in patients with severely elevated blood pressure plus neurologic symptoms by ruling out other conditions that may cause similar symptoms. Ischemic stroke and the intracerebral hemorrhage must be excluded in these patients because these conditions are treated differently and are not managed primarily or exclusively by lowering blood pressure.

Neuroimaging, such as computerized tomography (CT) or magnetic resonance imaging (MRI), should be performed to aid in identifying brain lesions responsible for neurologic signs or to exclude conditions such as ischemic stroke or intracerebral hemorrhage. CT may not be as sensitive as MRI in identifying regions of brain edema, but it is usually more readily available, and takes less time to perform, and is essential in ruling out some intracranial lesions. T2-weighted MRI can localize regions of cerebral edema found with hypertensive encephalopathy, which can then be characterized further as posterior reversible encephalopathy syndrome (PRES) or hypertensive brainstem encephalopathy. Bilateral white matter edema in the posterior cerebral hemispheres is characteristic of PRES.[11] The distribution of cerebral edema is localized, particularly to the parieto-occipital regions in PRES and the pontine region in cases of hypertensive brainstem encephalopathy. Although PRES can be associated with hypertensive encephalopathy, it can be found in normotensive individuals with conditions that cause vascular injuries, such as autoimmune disease, use of immunosuppressive drugs, and preeclampsia.

Lumbar puncture is not required for the diagnosis of hypertensive encephalopathy but may be performed when a patient is being evaluated for encephalopathy to determine etiology. In PRES, there may be a modestly elevated protein level without pleocytosis, i.e., an albuminocytologic dissociation.[12]

Other end-organ injuries in a hypertensive emergency may be present in addition to hypertensive encephalopathy. Heart failure, acute kidney injury, or retinopathy can be seen with this condition. Diagnostics such as ECG, thoracic radiography, urinalysis, cardiac enzymes, and a metabolic panel with electrolytes and creatinine should be pursued to evaluate for end-organ damage and potential causes of secondary hypertension. In female patients of childbearing age, urine pregnancy testing or serum human chorionic gonadotropin level can be measured to evaluate for eclampsia-related conditions. Toxicologic screening assays can be considered if there is clinical suspicion for the ingestion of sympathomimetic agents.

Treatment of Hypertensive Encephalopathy

Parenteral Antihypertensives

• Nicardipine: The initial dose is 5 mg/hour, and the usual maximum dose is 15 mg/hour.
• Labetalol: A 20 mg bolus is given initially, followed by subsequent boluses of 20 to 80 mg intravenously every 10 minutes to a maximum total dose of 300 mg in a day. Labetalol can also be given as a continuous infusion at 0.5 to 2 mg/min. Labetalol should not be used without prior adequate alpha blockade in patients with hyperadrenergic states (e.g., cocaine-induced hypertension)
• Fendolopam: The initial dose of infusion is 0.1 mcg/kg per min, and the dose is titrated at 15-minute intervals, depending upon the response. Especially beneficial in patients with kidney disease.
• Clevidipine: The initial dose is 1 mg/hour, and the usual maximum dose is 21 mg/hour.
• Sodium nitroprusside: The initial dose is 0.25 to 0.5 mcg/kg/min and the usual maximum dose is 8 to 10 mcg/kg/min. Not a first-line drug as it may cause cyanide toxicity. Use with caution in patients with kidney disease.

While the initial diagnosis and treatment of a hypertensive emergency may occur in the emergency department, definitive treatment for this condition is usually performed in an intensive care unit. The primary treatment for this condition involves administering antihypertensive drug therapy to lower the MAP by 10% to 15% during the first hour. The MAP should not be lowered by more than 25% of the original baseline MAP within the first day of treatment. This cautious reduction of blood pressure decreases the risk of ischemic events and allows for the healing of brain vasculature. If the MAP falls below the hypertensive-adapted autoregulatory range in the brain, as would occur with overaggressive hypertensive therapy, there is an increased risk of stroke as well as ischemic complications in other organs.[rx][rx] Exceptions to this conservative lowering of blood pressure include ischemic stroke, intracerebral hemorrhage, and aortic dissection.

Parenteral antihypertensive agents should be used initially. Oral antihypertensive agents should be avoided in this initial treatment phase because of the inability to titrate to effect, as well as a potentially slower onset of action. Parenteral antihypertensive drugs commonly used for this condition include nicardipine (5 mg/hour to the usual maximum dose 15 mg/hour), labetalol, fenoldopam, and clevidipine. Fenoldopam, a dopamine receptor agonist, may be preferential in patients with renal impairment as it has demonstrated a renal-protective effect.[rx]

Oral antihypertensives may be started as the initial intravenous therapy is tapered and discontinued after a suitable period (often 8 to 24 hours) of reaching the target blood pressure.

In pregnant patients with eclampsia, antihypertensive therapies are chosen based on concerns for the health of the placenta and fetus. Delivery of the infant and placental tissues may be instituted.

Antiseizure medication may be prescribed and continued until symptoms and neuroimaging findings begin to improve. The antiseizure medication can be tapered usually after one to two weeks, as continued seizure recurrence after resolution of encephalopathy is rare.[rx] Drug selection for seizure treatment may depend on other comorbidities the patient has, such as pregnancy or renal function impairment.

Patients with PRES that concurrently have hypertension are treated with antihypertensive drugs similarly as those with hypertensive encephalopathy.[rx] Immunosuppressive drug dosages may be reduced or discontinued in patients that develop symptoms of PRES. If a patient is changed to a different immunosuppressive drug, it is recommended that neuroimaging be performed if symptoms of PRES recur and to avoid using prior drugs that were associated with an encephalopathic episode. It has been reported that fluid therapy overload, MAP greater than 25% of baseline, and creatinine values greater than 1.8 mg/dL are risk factors for developing this condition in patients receiving cytotoxic and immunosuppressive drugs.[rx]

Blood Pressure Goals

• SHEP and HYVET trials have shown significant benefits of antihypertensive treatment in patients with the goal of SBP <150 mmHg[rx].
• The VALsartan in Elderly Isolated Systolic Hypertension (VALISH) trial showed no significant difference in the primary outcome of sudden death, fatal or nonfatal myocardial infarction and stroke, heart failure death, or other cardiovascular death among patients with strict (< 140 mmHg) and moderate (140 to 150 mmHg) SBP control[rx].
• However, the VALISH trial was underpowered due to the low number of events.
• Hence, the optimal SBP in patients with hypertensive disorder remained a controversial topic.
• The most recent Systolic Blood Pressure Intervention Trial (SPRINT) has shown that intensive SBP target of < 120 mmHg improved the cardiovascular outcomes and the overall survival compared to the standard SBP target of 135 to 139 mmHg[rx].
• However, aggressive SBP lowering may be harmful in the elderly and incite more adverse effects such as hypotension, end-organ hypoperfusion (causing acute kidney injury, and intracranial hypoperfusion which may link to cognitive decline), and polypharmacy.
• It is suggested that a goal blood pressure of < 130/80 mmHg is appropriate as long as the patient tolerates it.
• Otherwise, < 140/90 mmHg is considered reasonable in patients who are in the elderly population and patients with labile blood pressure or polypharmacy.
• Management strategies should always be patient-centered, with the aim of optimizing blood pressure control and avoiding polypharmacy, especially in the elderly.

J-curve Phenomenon

• Various studies have shown a J-curve association between blood pressure with risk of myocardial infarction and death.
• Patients with isolated systolic hypertension who receive antihypertensive treatment may precipitously drop their DBP as well.[rx][rx]
• As myocardial perfusion occurs mainly during diastole, an excessive drop in DBP may increase the risk of cardiovascular disease and death.

Lifestyle changes

You may also need to make some lifestyle changes as part of your ISH treatment plan. These can include:

• Losing weight. This can help lower your blood pressure. In fact, for every two pounds you lose, you could lower your blood pressure by about 1 mm Hg.
• Eating a heart-healthy diet. You should also aim to reduce the amount of sodium in your diet. Consider the DASH diet, which emphasizes eating:
  • vegetables
  •  whole grains
  •  low-fat dairy products
  •  fruits
• Exercising. Not only can exercise help you lower your blood pressure, but it can help you control your weight and stress levels. Aim to perform some sort of aerobic exercise for at least 30 minutes most days of the week.
• Decreasing alcohol consumption. Healthy alcohol intake is one drink per day for women and two per day for men.
• Quitting smoking. Smoking can raise your blood pressure and also contribute to a variety of other health problems.
• Managing stress. Stress can raise your blood pressure, so finding ways to relieve it are important. Examples of techniques to help lower stress are meditation and deep breathing exercises.