Hypertensive encephalopathy

Historical note and nomenclature
  The term “hypertensive encephalopathy” was introduced by Oppenheimer and Fishberg (Oppenheimer and Fishberg 1928). They described essential clinical characteristics of acute malignant hypertension. Ten years prior, Volhard was the first to separate clearly acute hypertension-induced neurologic dysfunction from a uremic state and introduced the term “pseudouremia” to refer to hypertensive encephalopathy (Volhard 1918).

  Although the association of eclampsia and elevated blood pressure has been known since the turn of the century, it was not until 1935 that Volhard suggested “eclamptic uremia” in a woman who had identical clinical and pathologic changes and the same underlying pathophysiology as hypertensive encephalopathy (Volhard 1935). This has been further confirmed by modern neuroimaging techniques (Schwartz et al 1992). Recognition of this association of cerebral edema and eclampsia led to the first effective surgical treatment of craniotomy and dural incision in 1911 (Zangemeister 1911). Subsequently, less drastic measures of venesection and repeated spinal taps were used to relieve the effects of cerebral edema.

Clinical manifestations
  Hypertension-induced neurologic signs and symptoms can be broadly divided into either focal deficits associated with chronic hypertension (eg, lacunar stroke or hypertensive basal ganglia hemorrhage) or more diffuse cerebral dysfunction related to acute hypertension, termed hypertensive encephalopathy. Additional clinical features of chronic hypertension may simulate encephalopathy due to bilateral multiple cerebral insults (eg, multi-infarct dementia). In contrast, acute hypertensive encephalopathy may present with subtle focal deficits on the background of diffuse cerebral symptoms. Unfortunately, the term hypertensive encephalopathy has been used in the past to describe any cerebral event occurring in a hypertensive patient. This chapter will only discuss the clinical entity of acute hypertensive encephalopathy.

  The level of blood pressure elevation that will result in hypertensive encephalopathy is variable but generally requires a diastolic pressure of greater than 130 mm Hg. A rapid rise in blood pressure in a previously normotensive patient is more likely to result in manifestations of hypertensive encephalopathy than a similar elevation in a chronically hypertensive person. This explains why a pregnant woman with a diastolic blood pressure of 100 mm Hg or lower may have hypertensive encephalopathy in contrast to the absence of symptoms in a patient with long-standing hypertension and a diastolic blood pressure greater than 150 mm Hg. Despite the lower blood pressure level that triggers hypertensive encephalopathy in previously normotensive patients, the vast majority of patients have a history of hypertension. Typically, the patient with chronic hypertension has not been taking medication as prescribed.

  Clinical presentation typically includes headache, nausea, vomiting, confusion, drowsiness, and possibly an epileptic event. These symptoms are manifested over several days in various combinations and degrees and may progress to stupor, coma, and death if left untreated. Such overt focal complaints as an aphasia or a transient hemiparesis are uncommon, but visual complaints such as blurriness, scotoma, or visual field defects are frequently encountered during the clinical evolution. Headache is the most common symptom, occurring in greater than 75% of hypertensive encephalopathy patients (Clarke and Murphy 1956). Gradual onset of morning headaches accompanied by nausea and vomiting is typical. If accompanied by an overt focal neurologic disturbance, a localized hemorrhage or an ischemic stroke should be suspected.

  Visual disturbance is common, occurring in 4 out of 11 cases (Jellinek et al 1964), even in absence of funduscopic abnormalities. The presence of cortical visual symptoms remains a helpful diagnostic feature corresponding to occipital lobe involvement. Retinal or optic disc ischemia and papilledema have been implicated for frequent visual complaints (Beck et al 1980), but more often, occipital lobe involvement is suggested by normal-appearing fundi and brisk pupillary constriction to light in addition to occasional accompaniment of cortical visuospatial or speech disturbance (Jellinek et al 1964). Typical visual symptoms may range from a nonspecific blurriness with normal acuity to color-blindness, hemivisual field defects, and even cortical blindness. Visual hallucinations, impairment of facial recognition (prosopagnosia), parietal lobe dysfunction with inappropriate behavior, denial of blindness (Anton syndrome), and blindness with intact pupillary light constriction may simulate drug ingestion or withdrawal, complex migraine, or even a psychiatric illness. Isolated cortical blindness or occipital lobe seizures as a manifestation of hypertensive encephalopathy has also been reported (Marra et al 1993; Bakshi et al 1998). Thus, the presence of predominantly global or diffuse symptoms with frequent visual complaints and markedly elevated blood pressure, followed by rapid recovery with lowering of blood pressure, constitutes the frequently seen clinical scenario of hypertensive encephalopathy.

  Nondiagnostic clinical presentation with nonspecific laboratory or neuroimaging studies may pose difficulty in arriving at the correct diagnosis. Markedly elevated blood pressure, relative absence of focal neurologic signs, and funduscopic abnormalities of retinal arteriolar narrowing or disc edema in a drowsy or confused patient are suggestive but unfortunately not diagnostic. Laboratory tests may reveal renal insufficiency or proteinuria; if these are new, their presence is helpful in pointing to a renovascular etiology of hypertension or leakage of protein from renal tubules secondary to elevated blood pressure. Spinal fluid examination, likewise, may reveal nonspecific abnormalities. Despite the uniform appearance of cerebral swelling and edema in patients dying of hypertensive encephalopathy, elevated CSF opening pressure is only found in about two thirds of cases. Mild elevation in CSF protein due to blood-brain barrier leakage is seen in only 20% of cases. Lymphocytic pleocytosis is unusual, and neutrophilic pleocytosis is distinctly rare (McDonald et al 1993). Its presence should suggest a separate underlying infectious or inflammatory disorder. EEG recordings have been frequently abnormal but nondiagnostic, ranging from slowing of the background activity to epileptiform transients in up to 80% of patients (Thomas et al 1995).

  Imaging studies with CT or MRI scans have been particularly helpful in suspected cases if bilateral posterior cortical lesions are detected that extend beyond a posterior cerebral artery territory.  Lesions beyond the occipital lobes to the areas such as the thalamus, basal ganglia, cerebellum, or brainstem generally reflect extension of the primary occipital lobe lesions. Predominant lateralized vasogenic edema from underlying arterial stenosis accompanied by minimal occipital lobe involvement can be difficult to recognize (Chang 2008). Primary brainstem involvement without occipital lobe involvement may rarely occur (Nakano et al 1997; Chang and Keane 1999). In exceptional cases, complete recovery after a transient brainstem areflexia (Keswani and Wityk 2002) or predominant unilateral cerebellar edema simulating a tumor may be seen (Lin et al 2006). These “brainstem hypertensive encephalopathy” are important to recognize because a decompressive ventriculostomy (Adamson et al 2005) and cerebellar resection (Chang 2004) may be life-saving. Despite these rare cases, bilateral, predominantly posterior cerebral lesions remain the hallmark of hypertensive encephalopathy, and this characteristic feature has been further emphasized by phrases such as “a reversible posterior leukoencephalopathy syndrome” (Hinchey et al 1996) or an “occipital-parietal encephalopathy syndrome” (Pavlakis et al 1997). A T2-weighted or fluid-attenuated inversion-recovery MRI scan is particularly helpful in disclosing the full extent of the signal abnormality. The relative absence of mass effect or enhancement helps to differentiate hypertensive encephalopathy from a tumor or an abscess. Bilateral posterior cerebral artery distribution infarction can be excluded by frequent sparing of calcarine and paramedian occipital lobe structures and normal appearance on diffusion-weighted images. Rapid clinical recovery following lowering of blood pressure and characteristic MRI signal changes are compatible with vasogenic edema being the main underlying mechanism in hypertensive encephalopathy (Schaefer et al 1997).