1. POSTERIOR REVERSIBLE ENCEPHALOPATHY
SYNDROME
(PRES)
Dr Prashant Makhija

2. 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.
2.
Semin Neurol 2011;31:202–215
Crit Care & Shock (2009) 12:135-143

3. 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

4. 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
Semin Neurol 2011;31:202–215

5.  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
Semin Neurol 2011;31:202–215

6. NORMAL CEREBRAL AUTOREGULATION
Semin Neurol 2011;31:202–215

7. DYNAMICS OF CBF IN PTS WITH CHRONIC HTN
Semin Neurol 2011;31:202–215

8. 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
Pract Neurol 2011; 11: 136–144
S. Legriel, F. Pico, and E. Azoulay. Annual Update in Intensive Care and Emergency Medicine 2011

9. Pathogenesis of PRES

10. 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
Semin Neurol 2011;31:202–215

11.  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
Semin Neurol 2011;31:202–215

12. 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

13.  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
Annual Update in Intensive Care and Emergency Medicine 2011

14. Distribution of clinical features in cohort studies of PRES
Clinical
Features
Hinchey
1996
(N=13)
Bartynski
McKinney
2007(N=136) 2007(N=76)
Lee
2008(N=36)
Burnett
2010(N=79)
Consciousness
impairment
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/vomiti
ng
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 %)
Annual Update in Intensive Care and Emergency Medicine 2011

15. 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
S. Legriel, F. Pico, and E. Azoulay. Annual Update in Intensive Care and Emergency Medicine 2011

16. 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
S. Legriel, F. Pico, and E. Azoulay. Annual Update in Intensive Care and Emergency Medicine 2011

17. 3. Dominant parietal-occipital pattern (22 %)
 previously thought to be typical of PRES
 posterior part of the parietal and occipital lobes is predominantly
involved
S. Legriel, F. Pico, and E. Azoulay. Annual Update in Intensive Care and Emergency Medicine 2011

18. 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
S. Legriel, F. Pico, and E. Azoulay. Annual Update in Intensive Care and Emergency Medicine 2011

19. 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
S. Legriel, F. Pico, and E. Azoulay. Annual Update in Intensive Care and Emergency Medicine 2011

20.  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
S. Legriel, F. Pico, and E. Azoulay. Annual Update in Intensive Care and Emergency Medicine 2011

21. Radiological features in cohort studies of PRES
Radiological
Features
Hinchey
1996
(N=13)
Bilateral
Bartynski
McKinney
2007(N=136 2007(N=76)
Lee
2008(N=36)
Burnett
2010(N=79)
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
3 (19 %)
19 (14 %)
9 (12 %)
NR
NR
Basal ganglia 1 (7 %)
Casey
2000
N = 16

22. 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
Pract Neurol 2011; 11: 136–144

23.  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
Pract Neurol 2011; 11: 136–144

24.  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)
Pract Neurol 2011; 11: 136–144

25. 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

27. 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
Semin Neurol 2011;31:202–215
Annual Update in Intensive Care and Emergency Medicine 2011

29. 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
Pract Neurol 2011; 11: 136–144

30.  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
Pract Neurol 2011; 11: 136–144
Annual Update in Intensive Care and Emergency Medicine 2011

31. 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

32.  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

33. THANK YOU