Acute hypertensive encephalopathies

Acute hypertensive encephalopathies are a group of encephalopathies (global cerebral dysfunction) associated with malignant hypertension, with no other etiology identified. They can cause permanent brain damage, but are generally reversible (in >90% of cases) when blood pressure is reduced. These are medical emergencies.

They can affect all ages and both sexes. However, there is a discrete peak at 20-40 years of age, and a discrete preponderance of women, due to the involvement of gynecological causes (eclampsia, pre-eclampsia, HELPP syndrome).

Historically, the best-known form of this pathology is hypertensive PRES ("posterior reversible encephalopathy syndrome"). However, this name is a source of confusion.

Etiologies

The etiologies are those of arterial hypertension, but those most often found are :

• Eclampsia, pre-eclampsia, HELPP syndrome
• Renal hypertension: acute glomerulonephritis, HUS, PTT, renal artery stenosis
• Uncontrolled or poorly controlled chronic hypertension
• Pain, acute contexts, panic attacks

Certain rarer causes of malignant hypertension should be systematically investigated:

• Pheochromocytoma
• Toxic: cocaine, amphetamines, LSD, anorectics, etc.
• Iatrogenic: cyclosporine, MAOIs, EPO, nasal vasoconstrictors
• Withdrawal (generally due to therapeutic non-compliance) from an anti-hypertensive (central ++) or interaction with a non-steroidal anti-inflammatory drug (NSAID) or gastric dressing, etc.
• Vegetative dysautonomia

Elements of physiopathology

Classically, the syndrome is considered to arise when cerebral blood flow autoregulatory capacities are exceeded (generally when mean arterial pressure rapidly rises to > 150 mmHg), leading to vasodilation with disturbances in blood-brain barrier permeability, vasogenic cerebral edema, endothelial dysfunction, reactive vasospasm with diffuse arteriolar occlusions, etc.

Pathological findings include edema, petechial haemorrhages, disseminated micro-infarcts and fibrinoid necrosis lesions occluding small perforating vessels.

What about PRES?

PRES ("posterior reversible encephalopathy syndrome") or RPLS ("reversible posterior leukoencephalopathy syndrome") is a peculiar clinico-radiological presentation with lesions predominating in the parieto-occipital regions. Historically, it has been the archetypal acute hypertensive encephalopathy.

This name is confusing for several reasons:

• lesions are often not confined to the posterior regions ("atypical PRES") and may predominate in other brain regions
• the syndrome's name is deceptively reassuring, as lesions are not always reversible even with prompt treatment, and there may be clinical sequelae
• although hypertensive PRES is the most frequent, the same radiological picture may be observed in other conditions (metabolic and toxic), without any notion of hypertensive peaks.

In any case, clinicians and radiologists must be aware that this is a radiological rather than a clinical category, and not a pathology in itself.

Clinical

Blood pressure is usually > 180/110 mmHg (more important than absolute values, however, is the magnitude and rapidity of onset of the hypertensive spike) +.

• By definition, signs of global cerebral dysfunction should be observed: disorders of consciousness, confusion, multiple acute cognitive disorders, delirium, etc.
• Headache (~50%)
• Vertigo, tinnitus (~35%)
• Nausea and/or vomiting (~30%)
• Visual signs: reduced visual acuity, elementary hallucinations, hemianopia, cortical blindness
• Focal neurological deficits present in ~20% of cases
• Convulsive seizures,...

+- signs of other visceral damage.

Emergency investigations

Assessment of a suspected hypertensive emergency :

• Finger blood glucose
• Fundus → hypertensive retinopathy?
• Microscopic examination of urine + dipstick
• Biology (renal function, tropos, BNP, ionogram, blood glucose, hematocrit) → renal/cardiac involvement?
• Chest X-ray
• Systematic brain CT-scan → may show diffuse lesions or contribute to differential diagnosis
• Cerebral (angio)-MRI
  • Indispensable in case of doubt with ischemic stroke (to be justified to the radiologist by different blood pressure tolerance)
  • May be normal
  • Hypersignals possible in T2/ FLAIR :
    • diffuse, reversible brain lesions in cortex, white matter, brainstem, cerebellum
    • typical PRES lesions: edema of white matter in parieto-occipital regions
  • Diffusion: the most sensitive sequence, frequently showing vasogenic edema. No respect for vascular territories.
  • Possible signs (multiple vasospasms) of reversible acute cerebral angiopathy (complication).
• Electrocardiogram
• Cardiac ultrasound

Systematic search for remote secondary hypertension (up to 20-40% of patients presenting with hypertensive emergencies).

T2 MRI - hypertensive encephalopathy with lesions limited to the thalamus (total regression of lesions in this case after aggressive BP lowering)

FLAIR MRI - "Atypical PRES": predominantly parieto-occipital lesions co-existing with thalamic, internal capsule, corpus callosum and frontal lesions

Positive diagnosis and differential diagnosis

The diagnosis of hypertensive encephalopathy is one of exclusion. It presupposes the association of a sudden hypertensive peak, signs of global cerebral dysfunction and the exclusion of non-hypertensive etiologies. The association of other signs of hypertensive emergency (renal or cardiovascular damage) is frequent.

It is not uncommon for the diagnosis to be made retrospectively, due to the many difficulties encountered in the acute phase:

Lack of pathognomonic elements

• Identifying a hypertensive peak is generally not a problem. However :
  • It is more the speed of onset of blood pressure variations than their absolute value that is at issue. Untreated or poorly controlled patients may present with chronic severe hypertension that is very well tolerated, and then develop encephalopathy of another origin. Patients with ordinarily low blood pressure may present with a hypertensive emergency, with blood pressure values in moderate ranges, which will not usually attract attention.
  • Any acute pathology with the potential to cause encephalopathy, and any stressful context, can generate a reactive hypertensive spike that may falsely evoke the diagnosis.
• There is a wide overlap between differential diagnoses and complications of hypertensive emergencies. In some cases, it will be impossible to decide. For example
  • Cerebrovascular accident with reactive hypertensive peak or hypertensive emergency complicating a cerebrovascular accident? The same applies to myocardial infarction or aortic dissection.
• Frequently, the case occurs in patients already hospitalized in (semi)-intensive units and presenting multiple anomalies likely to lead to encephalopthy...

The differential diagnosis is wide-ranging and, depending on the clinical situation, may include..:

• Encephalopathies of other origins: hypoglycemia, toxic-metabolic encephalopathies, withdrawal, anoxic encephalopathies, etc.
• Meningitis and encephalitis
• Cerebrovascular accidents
• Non-convulsive status epilepticus
• Psychiatric pathologies and functional disorders

Therapeutic management - Treatments

In general :

• Monitoring, 2 IV infusions, diuretic monitoring, general management
• Anti-hypertensive drugs should not be administered prior to cerebral CT scan, except for vital indications (aortic dissection, myocardial infarction, acute heart failure).
• Blood pressure control:
  • In general :
    • reduce blood pressure slowly, aiming first for a 25% reduction and then gradually for values < 160/110 mmHg
    • prefer nicardipine or labetolol and avoid central antihypertensives
  • In association with
    • acute heart failure: prefer furosemide, nitrates, ACE inhibitors. Avoid beta-blockers.
    • myocardial infarction: prefer nitrates, beta-blockers and ACE inhibitors.
    • (pre)eclampsia: beta-blockers + magnesium preferred. Urgent gynaecological opinion.
    • acute renal failure: prefer ACE inhibitors
    • cerebrovascular accident: theoretically greater blood pressure tolerance, to be discussed according to the clinical situation:
      • Hemorrhagic stroke: tolerance up to 180 mmHg SBP (or 120 mmHg MAP).
      • Ischemic accident: tolerance up to 220 mmHg SBP (or 120 mmHg MAP). In the case of thrombolysis, however, obtain a pre-tension of < 180/105 mmHg.
• Specific management of other organ failures where appropriate. See corresponding chapters.
• Consider anxiolytics and/or morphine on a case-by-case basis.
• Etiological treatment if necessary. See relevant chapters.
• Hospitalization, ideally in a coronary or intensive care unit initially
• Consider (no EBM) the use of nimodipine (nimotop) 60 mg PO 6 x/day (or 1-2 mg/ hour IV if PO route not possible) to prevent vasospasm, depending on progression.

As a reminder, here is an example of an anti-hypertensive administration regimen, to be modulated according to tolerance:

• Nicardipine (Rydene): 10 mg/hour IV
• Nitroprusside: 0.5-10 µg/ kg/ minute IV
• Labetalol: 1 mg/ kg then 0.5-2 mg/ minute IV
• Furosemide: 40-80 mg IV (++ if OPH)
• Enalapril/ captopril: 1.25-5 mg IV every 6 hours
• Isosorbide dinitrate (cedocard): 2-10 mg/hour IV

Bibliography

Bradley WG et al., Neurology in clinical practice, 5th ed., Butterworth-Heinemann, e-dition, 2007

Cambier J et al., Neurologie, 13e édition, Masson, 2012

Elliott WJ et al., Evaluation and treatment of hypertensive emergencies in adults, 2023

Elliott WJ et al., Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults, 2022

Neill TA, Reversible posterior leukoencephalopathy syndrome, UpToDate, 2022

Osborn AG et al, Brain, Elsevier, 2018