pres syndrome/neurology

1. POSTERIOR REVERSIBLE ENCEPHALOPATHY
SYNDROME (PRES)
Dr. GOPIKRISHNAN R

2.  PRES –DEFINITION
ETIOLOGY &PATHOPHYSIOLOGY
PRESENTATION & APPROACH
RADIOLOGICAL FINDINGS
DIFERENTIAL DIAGNOSIS
MANAGEMENT & OUTCOME
MALIGNANT PRES

3. PRES
Clinicoradiological diagnosis based on a combination of typical clinical features and risk factors
and supported by radiological (MRI) findings
Symptoms may be multiple or isolated
Classical presentation-
Visual loss,headache,nausea
Altered mental function,seizures
Other FND-weakness,sensory or speech disurbances
It was initially described by Hinchey in 1996 and subsequently has subsequently gained
increasing attention

4. EPIDEMIOLOGY
At any age –most frequently affects young or middle aged adults- mean age of 45 years
Female predominance even excluding eclampsia patients
Associated with numerous conditions and iatrogenic causes –most freq with hypertension ,renal
failure, eclampsia , transplant and immunosuppressive ,sepsis, autoimmune disorders, cytotoxic
medications and toxins
In adults PRES is present in 98% of patients with eclampsia , 2.7 to 25% following bone marrow
transplantation, less commonly with solid organ transplantation , end stage renal failure and
auto immune diseases
The incidence of PRES in pediatric population is 0.04% and in pediatric intensive care unit is 0.4%
Incidence in general population is unkown.

5. Conditions associated with the development of PRES
General conditions
► Hypertension
► Sepsis
► Solid organ transplantation
► Eclampsia and pre-eclampsia
► Renal failure
► Malignancy (solid organ and haematological)
► Bone marrow transplantation
► Stem cell transplantation
► Hypomagnesaemia
► Hypercalcaemia
► Hypercholesterolaemia
► Late radiation-associated encephalopathy, for example, SMART
Autoimmune disorders
► Rheumatoid arthritis
► Crohn’s disease
► Systemic lupus erythematosus
► Scleroderma
► Vasculitis
► Neuromyelitis spectrum disorder
Toxins
► Scorpion poison
► LSD intoxication
► Ephedra overdose
► Alcohol intoxication
► Cocaine
Cytotoxic and immunosuppressive medications
► Hydroxydaunorubicin/adriamycin
► Vinblastine/vincristine
► Gemcitabine
► Platinum-containing drugs: cisplatin, oxaliplatin and carboplatin
► Bortezomib
► Cyclophosphamide
► Daunorubicin
► Interferon therapy
► Capecitabine, 5-fluorouracil
► Cytarabine
► Etoposide
► Corticosteroids
► Rituximab
► Ciclosporin
► Tacrolimus
► Sirolimus
► Mycophenolate mofetil
► Methotrexate
► Azathioprine
Other medications
► Lithium
► Linezolid
► Intravenous contrast
► Intravenous immunoglobulin

6. PATHOPHYSIOLOGY
Several theories have been proposed-leading theory is vasogenic theory
Activation and injury of endothelium(rapidly fluctuating BP
cytotoxins)impaired cerebral autoregulation
Activation of immune systemcytokine release
Breakdown of BBBcerebral hyperperfusion
vasogenic oedema

7. Posterior circulation is more vulnerable as it has less sympathetic innervation compared to anterior
circulation
So less counter reflex to parasympathetic vasodilation
Recently, activation of arginine vasopressin (AVP) axis by increase in AVP secretion or AVP receptor
density has been postulated in the development of PRES . Activation of cerebral AVP receptors (V1aR)
leads to cerebral vasoconstriction, endothelial dysfunction and cerebral ischemia and activation of
the peripheral (renal) receptors (V2R) may potentially lead to the development of hypertension, renal
impairment and is responsible for the symptoms and complications of PRES

8. APPROACH TO DIAGNOSIS
PRES similar to many acute neurological presentations- key to diagnosis is high index of suspicion with
consistent findings on MR brain scan.
Symptoms manifesting over several hours or days.
The symptoms are highly non-specific, with encephalopathy and seizures being the most common
symptoms followed by visual disturbances, headache, and focal neurological deficits.
Encephalopathy develops in 28 to 94% patients –ranges from min confusion and cognitive deficits to
stupor and coma
Seizures -74-87% within 24-48 hrs of presentation
Headaches in upto half of patients-dull,diffuse and gradual in onset
Visual symptoms -40% of patients-reduced visual acuity,diplopia,field defects,cortical blindness,visual
hallucinations and color vision abnormalities
FND –aphasia,hemiparesis only less than 20% patients

9. In rare occasions, myelopathic symptoms and signs from spinal cord involvement have been
demonstrated . Other uncommon presentations include abulia, agitation, delusions, ophisthotonus,
optic ataxia, ocular apraxia, and simultagnosia .
As diagnosis is challenging ,it is essential to review the patients current and past medical history ,
medication charts, examination findings including blood pressure variations
Also requires clear communication with radiologists

10. NEURODIAGNOSTICS
Serology
 deranged electrolytes like hypomagnesemia, hypercalcemia
 renal failure have abnormal electrolytes and renal function tests.
 PRES from underlying malignancy and preeclampsia, elevated lactate dehydrogenase levels
(LDH) have been reported, which supports endothelial dysfunction as the possible mechanism .
Elevated serum LDH levels have correlated with larger and more diffuse lesions on imaging
 Elevated C reactive protein (CRP) levels have been associated with increased mortality in PRES
patients.
 Low serum albumin levels have been observed in 70% of patients

11. Patients with significant unexplained hypertension specific testing for secondary causes of
hypertension( phaeochromocytoma, Conn’s syndrome or Cushing’s syndrome).
 A serum vasculitis screen( ANA, ANCA, extractable nuclear antigens, rheumatoid factor, complement,
lupus anticoagulant, anticardiolipin antibodies, paraproteins, ACE, HIV serology, ESR,CRP
Toxic screen (blood and urine)
Cerebrospinal Fluid
Cerebrospinal fluid (CSF) examination - atypical MRI patterns to exclude an alternative diagnosis such as
encephalitis or demyelination . Cerebrospinal fluid protein levels are elevated in 70% of patients

12. EEG PATTERNS IN PRES
Common indications of EEG were seizures and varying degrees of encephalopathy for
exclusion of non-convulsive status epilepticus .

13. NEUROIMAGING
Brain imaging is the cornerstone in confirming a diagnosis of PRES. Although vasogenic edema
can be visualized on non-contrast CT , brain MRI, especially the T2-weighted and FLAIR
sequences are much more sensitive esp of posterior fossa structures
• FLAIR detects cortical and a subcortical lesion related to PRES
• Diffusion weighted imaging combined with apparent diffusion coefficient (ADC) mapping
sequences  differentiates cytotoxic from vasogenic edema and thus may aid in the
differentiating PRES form ischemic lesions (absence of restricted diffusion)
•Post contrast enhancement occurs in 38 to 50%
•Intracranial haemorrhages in 10 t0 15%

14. IMAGING FINDINGS IN PRES
Common features
•Vasogenic cerebral edema
•Parieto-occipital pattern
•Holohemispherical watershed distribution
•Frontal and temporal lobe involvement
•Subcortical white matter
•Bilateral, frequently symmetric pattern
•Hyperintense T2 weighted and FLAIR sequences
•Isointense, hypointense, or hyperintense lesions on DWI
•Increased ADC values reflective of vasogenic cerebral edema
In practice patterns are commonly mixed.
Uncommon
• Brainstem (Central) variant
• Unilateral PRES
• Contrast enhancement
• Microhemorrhages
• Intracerebral hemorrhages
• Sulcal SAH
• Decreased ADC values indicative of ischemia
Grades of cerebral edema
• Mild
• Moderate
• Severe

15. Imaging findings in typical PRES. MR scan of the brain of a 39-year-old woman with PRES who presented with visual disturbance, seizure and fever. (A–C) Prominent cortical and
subcortical white matter signal hyperintensity on T2 FLAIR involving bilateral occipital and left anterior parietal lobe, left frontal lobe, and the splenium of the corpus callosum with
additional foci involving both the anterior left thalamus and posterior left putamen. There are also patchy hyperintense T2 FLAIR signal foci within the right cerebellar hemisphere. (D,E)
Areas of diffusion-weighted imaging hyperintensity and hyperintense apparent diffusion coefficient signal involving the occipital cortex bilaterally consistent with vasogenic oedema,
which corresponds to regions of high T2 signal on the FLAIR images. (F) There is a small focus of blooming within the left occipital lobe, in keeping with petechial haemorrhage
Most cases do not require further imaging.only needed in cases with possible cerebral vasculitis or RCVS-digital
substraction angiography is considered.

16. DIFFERENTIAL DIAGNOSIS
Most important differentials viral and autoimmune encephalitis,demyelinating disease, toxic
leucoencephalopathies, malignancy such as gliomatosis cerebri, CNS vasculitis, central/
extrapontine myelinolysis and acute stroke(cerebral venous thrombosis)
RCVS(reversible cerebral vasoconstriction syndrome)in context of similar risk factors
.distinguished by thunderclap headache,cerebral vasculopathy,infraction and intracranial
haemorrhage.

18. MANAGEMENT
SUPPORTIVE REMOVAL OR REVERSAL OF
CAUSE
1.Removal or reduction of the triggering factor (withdrawal of cancer chemotherapy or immunosuppressive
agents). In patients with PRES related to cancer chemotherapy or immunosuppressive agents, long term
management of immunosuppressive agents and chemotherapy remains a challenging issue and should be
individualized.
2. Supportive care with hydration, correction of electrolyte disturbances.
3. Monitoring of airway and ventilation. Intubation may be required in patients with altered mental status.
4. In pregnant women, prompt delivery should be considered.
5. In patients with renal failure, prompt dialysis should be performed.

19. 6.Patients with acute hypertension should have their blood pressure gradually reduced by no more
20%–25% in the first few hours to avoid the risk of cerebral, coronary and renal ischaemia.
 Aim for a mean arterial pressure of between 105 and 125 mm Hg.
 Once PRES is suspected, clinicians should consider transfer to an intensive care setting
 Up to 70% of patients ultimately require intensive care for symptom management
 35%–40% require mechanical ventilation for 3–7days.
 Intravenous agents are preferred to avoid fluctuations of blood pressure and the choice of agents
is left to the discretion of the physician.
 Continuous infusions are frequently required to avoid fluctuations of blood pressure and achieve
the goal blood pressure

21. MANAGEMENT IN SPECIFIC CONDITIONS
With intraparenchymal or SAH-gradual reduction of BP
With raised ICP-osmotherapy & neurosurgical measures
Status epilepticus-
1. Intravenous anticonvulsants (first line with diazepam, second line with fosphenytoin, phenobarbital.
2. In refractory cases propofol, pentobarbital, midazolam may be used.
3. Continuous EEG monitoring may be considered.
4. In pregnant women, magnesium sulfate is indicated to prevent seizures. It has cerebral vasodilatory
effects and reduces blood vessel permeability
Epilepsy is rare (1-3.9%).so long term antiseizure drugs not indicated
Steroid therapy not indicated-may contribute to PRES
Indications for transfer to an intensive care unit setting include encephalopathy, seizures, ventilatory
depression and the need for invasive blood pressure support.

22. NEW CRITERIA FOR PRES –ASSOCIATED HEADACHE
Headache attributed to hypertensive encephalopathy and PRES are not equalent
PROPOSED DIAGNOSTIC CRITERIA
Any new headache fulfilling the following criteria and continuous for more than or equal to 72
hrs without treatment or continuous for less than 72hrs with treatment
1.PRES diagnosed
2.evidence of causation demonstrated by either or both of the following:
a)headache has developed in close temporal relation to other symptoms and/or clinical signs
of PRES,or had led to diagnosis of PRES
b)headache significantly improved in parallel with stabilization or improvement of other
symptoms/clinical /radiological signs of pres
3)not better accounted for other like RCVS or arterial hypertension

23. COMPLICATIONS
Recurrent PRES
Recurrent PRES has been observed in 4% of patients in retrospective studies
It is not uncommon for patients to have recurrent episodes of PRES with persistent risk
factors sickle cell crisis, autoimmune conditions, hypertensive crisis, renal failure, and
multiorgan failure.

24. MALIGNANT PRES
Defined based on clinical criteria
Glasgow Coma Score <8 and clinical decline despite standard medical management for elevated
intracranial pressure
radiological criteria (edema with mass effect, intracerebral hemorrhage exerting mass effect,
effacement of basal cisterns, transtentorial, tonsillar, or uncal herniation)
Management of malignant PRES requires aggressive supportive care.
Besides routine care like mechanical ventilation, transfusion of blood products for reversal of
coagulopathy, steroids for autoimmune disorders, intracranial pressure monitoring is required in patients
with GCS of ≤8 .
Various interventions that have been undertaken in patients with raised ICP include osmotherapy,
draining of cerebrospinal fluid by external ventricular drain, craniectomy and evacuation of hematoma
A/c obstructive hydrocephalus-external ventricular drain

25. PROGNOSIS
•Although PRES was initially described as a benign entity that was reversible with a good
outcome, mortality has been observed in 19% of patients and functional impairments of varying
degree have been reported in 44% of patients
• Certain deficits that require long-term care include epilepsy and motor deficits.
•PRES is an acute neurotoxic syndrome and the prognosis is highly dependent on the etiological
factor.
•Studies have reported that patients with preeclampsia-eclampsia have less severe cerebral
edema, hemorrhage, contrast enhancement with a tendency for complete resolution on imaging
and good functional outcome.
• Residual structural lesions have been observed in 40% of cases on follow up imaging

26. FACTORS ASSOCIATED WITH POOR OUTCOME
Factors associated with poor outcomes include
severe encephalopathy
a hypertensive cause
 hyperglycaemia
a neoplastic cause
Various imaging features associated with poor outcome include corpus callosum involvement,
extensive cerebral oedema or worsening imaging severity, intracerebral haemorrhage,
subarachnoid haemorrhage and restrictive diffusion on imaging
a longer time to control the causative factor
the presence of multiple comorbidities
elevated C reactive protein,
low CSF glucose
coagulopathy.

27. FUTURE DIRECTIONS
Recent data from animal studies have demonstrated blood brain barrier disruption as a possible
mechanism for development of vasogenic cerebral edema from acute hypertension and thus
may be a target of future intervention .
Besides, based on the recent AVP theory, suppression of AVP the use of vaptans might play a
role in the treatment of PRES.
Currently, there is paucity of data on its clinical implications in PRES

28. REFERENCES
1. : Triplett JD, Kutlubaev MA, Kermode AG, et al. Pract Neurol 2022;22:183–189
2. Hinduja A (2020) Posterior Reversible Encephalopathy Syndrome: Clinical Features and
Outcome. Front. Neurol. 11:71. doi: 10.3389/fneur.2020.00071
3. Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and
radiological manifestations, pathophysiology, and outstanding questions.Lancet Neurol.(2015)
14:914–25.