Posterior reversible encephalopathy syndrome

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME

(PRES)

Dr Prashant Makhija

HISTORICAL BACKGROUND

In 1897, Vaquez and Nobecourt pointed out the correlation of toxemia of pregnancy and HTN

In1928, Oppenheimer and Fishberg introduced the term hypertensive encephalopathy

In 1996, Hinchey and colleagues first described the clinical condition- as reversible posterior leukoencephalopathy( RPLE)

1. Semin Neurol 2011;31:202–215

2. Crit Care & Shock (2009) 12:135-143

POSTERIOR REVERSIBLE ENCEPHALOPATHY

Is a Clinicoradiological entity Clinical features - headache, mental confusion, seizures and

visual disturbances Radiological features- pattern of bilateral white matter

abnormalities in the posterior regions of both cerebral hemispheres

Other terms reversible posterior leukoencephalopathy reversible posterior cerebral edema syndrome reversible occipital parietal encephalopathy “potentially reversible encephalopathy syndrome”

J Intensive Care Med 2012 27: 11

S. Legriel, F. Pico, and E. Azoulay. Annual Update in Intensive Care and Emergency Medicine 2011

Dynamics of Cerebral Blood Flow

The normal cerebral blood flow ~ 50 ml/100gm/min

Cerebral blood flow varies directly with the cerebral perfusion pressure and inversely with the cerebral vascular resistance

CPP = MAP – CVP CBF=(MAP – CVP) / CVR

Cerebral resistance arterioles respond to the MAP rises with compensatory vasoconstriction that maintains a relatively constant cerebral blood flow

There is relative paucity of sympathetic innervation in posterior circulation

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Wide range of mean arterial pressures (MAP; 50 mm Hg to 150 mm Hg)

With chronic HTN, the resistance arterioles undergo proliferation of the muscular media adapting to the chronically high perfusion pressures

This results in a shift of the autoregulation curve to the right

This adaptation allows the maintenance of normal CBF at higher mean arterial pressures

The shift also limits vascular dilation and makes the CBF vulnerable to rapid lowering of the MAP

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NORMAL CEREBRAL AUTOREGULATION

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DYNAMICS OF CBF IN PTS WITH CHRONIC HTN

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PATHOPHYSIOLOGY

Pathophysiology of PRES is poorly understood

Disruption of BBB → Vasogenic Edema

Cerebral Hyperperfusion- breakdown of Cerebral autoregulation due to rapid ↑ in BP

Cerebral Hypoperfusion- endothelial dysfunction

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Pathogenesis of PRES

COMORBID CONDITIONS/TRIGGERS

Pregnancy-related conditions Eclampsia Hydatidiform mole

Major medical illness Organ transplantation Thrombotic thrombocytopenic purpura Henoch-Scho¨nlein purpura Autoimmune inflammatory disease: systemic lupus, scleroderma,

Wegener’s, periarteritis nodosa Sepsis/systemic inflammatory response syndrome/multiple organ

failure Alcohol and drug withdrawal Hypomagnesemia, hypercalcemia, hypocholesterolemia

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Neurologic illness Guillain-Barre´ ’s syndrome Spinal cord injury with autonomic dysreflexia Head injury

Drugs that cause endothelial dysfunction Immunosuppressant agents - Cyclosporine A Chemotherapeutic agents, especially high-dose multidrug -

Tacrolimus (FK506), Cisplatin, Gemcitabine, Bevacizumab Erythropoietin Blood transfusion Indinavir Cytarabine IVIg

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CLINICAL FEATURES

Epidemiology Age- 4 to 90 years, most cases occur in young to middle-aged adults, the mean age

ranging across case series from 39 to 47 years Female predominance

Consciousness impairment severity from confusion, somnolence, and lethargy to coma reported in 13 % to 90 % of cases

Seizure Up to 92 % of cases rarely focal (23 %-28 %) ,Secondary generalized seizures are common (53–62 %) Status epilepticus, has been described in 3 % to 13 % of patients

Annual Update in Intensive Care and Emergency Medicine 2011

Headaches and nausea/vomiting were reported in 26 % to 53 % of patients

Visual abnormalities found in 26 % to 67 % of patients blurred vision (7 % -18 %) visual neglect (4 %-27 %) homonymous hemianopsia (4 % -20 %) visual hallucinations (3 % -5 %) cortical blindness (8 %-33 %)

Focal neurological signs None to 3-17% cases


Distribution of clinical features in cohort studies of PRES

Clinical Features

Hinchey1996 (N=13)

Bartynski2007(N=136)

McKinney2007(N=76)

Lee2008(N=36)

Burnett2010(N=79)

Consciousnessimpairment

10 (67 %) 39 (26 %) 10 (13 %) 34 (94 %) 76 (90 %)

Seizure 11 (73 %) 97 (71 %) 58 (76 %) 33 (92 %) 56 (70 %)

Headaches 8 (53 %) 39 (26 %) 3 (4 %) 19 (53 %) 26 (31 %)

Visual abnormalities

10 (67 %) 39 (26 %) 3 (4 %) 13 (36 %) 24 (29 %)

Nausea/vomiting

8 (53 %) 39 (26 %) NR NR NR

Focal neurological signs

NR NR 2 (3 %) 1 (3 %) 14 (17 %)

Acute hypertension

12 (80 %) 91 (67 %) NR NR 62 (78 %)


RADIOLOGICAL CHARACTERISTICS OF PRES

1. Holohemispheric watershed pattern (23 %) watershed zone between the anterior and posterior cerebral arteries,

on the one hand, and the middle cerebral artery, on the other confluent vasogenic edema extends through the frontal, parietal,

and occipital lobes


2. Superior frontal sulcus pattern (27 %) Patchy edema predominates in the frontal lobes along the superior

frontal sulci parietal and occipital lobes are variably involved


3. Dominant parietal-occipital pattern (22 %) previously thought to be typical of PRES posterior part of the parietal and occipital lobes is predominantly

involved


4. Partial / asymmetric expression of the primary patterns (28 %) absence of involvement of either the parietal or the occipital lobes

and asymmetric abnormalities in the affected parietal or occipital lobes


Complications diagnosed radiologically

Cerebral ischemia Reported to occur in 10 to 23% of pts. non-reversible damage associated with adverse outcomes

Cerebral herniation Posterior edema, particularly when located in the cerebellum and

brainstem, may cause transtentorial cerebral herniation


Cerebral hemorrhage uncommon in PRES- 5 to 17% of pts. parenchymal hematoma, subarachnoid hemorrhage, and focal

intraparenchymal hemorrhage measuring less than 5mm in diameter

more common among patients with allogeneic bone marrow transplantation or anticoagulant treatment


Radiological features in cohort studies of PRESRadiological Features

Hinchey1996 (N=13)

Casey2000N = 16

Bartynski2007(N=136

McKinney2007(N=76)

Lee2008(N=36)

Burnett2010(N=79)

Bilateral 15 (100 %) 11 (69 %) > 98 (> 72 %)

NR 36(100 %)

NR

Asymmetric 10 (67 %) NR 21 (15 %) 2 (3 %) NR NR

Confluent NR 2 (13 %) 31 (23 %) 44 (58 %) 2 (13 %) 12 (16 %)

Gray matter 4 (27 %) NR NR 22 (29 %) 16 (44 %) NR

Posterior > anterior

14 (93 %) 15 (94 %) 30 (22 %) NR NR NR

Occipital 14 (93 %) NR 134 (99 %) 75 (99 %) NR NR

Parietal 13 (87 %) 8 (50 %) 134 (99 %) 75 (99 %) NR 50 (67 %)

Frontal 7 (47 %) 14 (88 %) 93 (68 %) 60 (89 %) 22 (61 %) 61 (81 %)

Temporal 9 (60 %) 16 (100 %) 55 (40 %) 52 (68 %) NR 62 (83 %)

Brainstem 2 (13 %) NR 17 (13 %) 14 (18 %) 21 (58 %) NR

Cerebellum 1 (7 %) NR 41 (30 %) 26 (34 %) 21 (58 %) NR

Basal ganglia 1 (7 %) 3 (19 %) 19 (14 %) 9 (12 %) NR NR

DIFFERENTIAL DIAGNOSIS

Posterior circulation stroke usually no seizures infarction shows(cytotoxic oedema) hyperintensity on DWI with

low signal on the corresponding ADC map while, in contrast, PRES (vasogenic edema) shows the exact opposite on ADC mapping

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Reversible cerebral vasoconstriction syndrome Thunderclap headache PRES quickly progresses over a few hours, complications may

occur for several days with the RCVS Imaging PRES- Bilateral parieto-occipital lesions on MRI, typical

for PRES Imaging RCVS- classic pattern of ‘string of beads’ on

Angiography, at least two narrowings per artery on two different cerebral arteries at brain magnetic resonance angiography (MRA) or at conventional angiography

in about 10% of cases there seems to be overlap between this syndrome and PRES

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Primary CNS vasculitis Symptoms usually come on more insidiously CSF is abnormal, with more than 95% of cases showing an

inflammatory reaction MRI may show multiple infarcts of different ages

Encephalitis in PRES there are no systemic features of inflammation (fever,

blood tests, CSF)

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MANAGEMENT Principles of Management

General measures- aimed at maintaining ABC of the patient

Symptomatic therapy Antihypertensives Anticonvulsants

Correction/Removal of the underlying cause Withdrawl of offending drug Termination of pregnancy

MANAGEMENT OF BLOOD PRESSURE

No empirically established guidelines are available for the optimal degree of BP lowering

A 20% reduction in the MAP is a reasonable goal for immediate reduction in hypertensive crises

The above goal should be reached within the first 2 hours and to bring the blood pressure down to 160/100 mmHg within the first 6 hours

Ideal agent - IV administration, has a rapid onset and short duration of action allowing rapid titration to effect, and be free of limiting side effects- labetolol, hydralazine, nicardipine, or fenoldopam

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PROGNOSIS

Brain lesions are reversible

Most studies- excellent short term and long term outcome

symptoms usually seem to resolve in about 3–8 days while recovery of the MRI abnormalities takes longer—several days to weeks

The ideal timing of repeat MRI is about 7–10 days after onset of symptoms when there should usually be clear improvement of the MRI abnormalities

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Occasionally poor neurological outcome has been mentioned as being due to conversion from primary vasogenic into cytotoxic oedema

Poor outcome may also be related to associated comorbidity (sepsis) or intracerebral haemorrhage

A retrospective review of PRES cases between 1998 and 2005 suggested recurrent PRES episodes occur in ~ 4% of cases

Studies report up to 15 % mortality rate

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CONCLUSION

PRES is a clinicoradiological syndrome and its symptoms and signs develop over hours—a combination of seizures, disturbed vision, altered mental function and headache

MRI is the diagnostic gold standard. There is predominant affection of parieto-occipital subcortical white matter of both hemispheres.Typical PRES lesions on MRI are thought to represent vasogenic oedema

There are many different trigger factors, most commonly abrupt hypertension, renal failure, immunosuppressive therapy, eclampsia, autoimmune disease and infections

The prognosis is good and recurrence rare. Symptoms generally resolve within a week. MRI lesions resolve somewhat more slowly

Treatment consists of antihypertensive drugs, withdrawal of medication such as chemotherapy, and treatment of any underlying disease

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Posterior reversible encephalopathy syndrome

Health & Medicine

Transcript of Posterior reversible encephalopathy syndrome