PRES posterior reversible encephalopathic syndrome

(Posterior Reversible
Encephalopathy Syndrome)

J. Ryan Altman, MD
AM Report
15 July 2008

 A clinical radiologic syndrome of heterogenic
 Many Names
   Posterior Reversible Encephalopathy Syndrome
   Reversible Posterior Cerebral Edema Syndrome
   Posterior Leukoencephalopathy Syndrome
   Hyperperfusion Encephalopathy
   Brain Capillary Leak Syndrome

 Epidemiology
   All age groups susceptible (ages 2-90)
   More common in women, even when
    eclampsia excluded
   Risk Factors
     Hypertensive disorders
     Renal disease
     Immunosuppressive therapies
 Pathogenesis—unclear
   Autoregulatory Failure
      Normal autoregulation maintains constant cerebral blood
       flow over range of systemic BP by arteriolar constriction
       and dilatation.
      As upper limits of cerebral autoregulation exceeded,
       arterioles dilate and cerebral blood flow increases. Results
       in brain hyperperfusion, and may lead to breakdown of
      Chronic HTN
          Vascular changes “reset” range of autoregulation
          As a result, pts with PRES in setting of longstanding HTN
           may have markedly elevated BP, while less severe
           elevations, even nl BP, are associated with PRES in other
 Pathogenesis—unclear
   Endothelial dysfunction
      Cytotoxic therapies
          may have direct toxicity on vascular endothelium, leading to capillary
           leakage, and BBB with axonal swelling, triggering vasogenic edema.
          may occur in normotensive individuals with nontoxic levels of these
      Preeclampsia
          PRES best dx by elevated markers
      Elevated endothelial cell markers: fibronectin, tPA,
       thrombomodulin, endothelin-1, von Willebrand factor
          Markers also elevated in PRES associated with chronic renal failure,
           lupus nephritis, HUS
   Other possible causes: uremia, sepsis, hypomagnesemia, fluid
 Anatomy
   Combination of acute HTN and endothelial damage results in
    hydrostatic edema (type of vasogenic edema characterized by
    forced leakage of serum through capillary walls and into the
    brain interstitium)
   The cortex, structurally more tightly packed than the white
    matter, resists accumulation of edema, hence predilection of
    abnormalities in white matter
   Primary involvement of posterior brain regions not well
    understood. (One thought is regional heterogeneity of
    sympathetic nerve innervation of intracranial arterioles, which
    protects the brain from marked increases in BP, have greater
    concentration around pial and intracerebral vessels in anterior
 Associated Conditions
   Comorbidities that exacerbate neurologic
    deterioration: ischemic bowel disease, sepsis,
    hyponatremia, fever, proteinuria
   Hypertensive Encephalopathy
      PRES likely caused by vasogenic edema from
       breakthrough of autoregulation
      Risk for HE: rapidly developing, fluctuating, or intermittent
          May be seen in pts with chronic HTN, renal failure, or
      Percent elevation of BP above baseline as well as severity
       of HTN are associated with development of PRES.
       Therefore, it may occur in normotensive pts.
 Associated Conditions
   Immunosuppresive Therapy
      Toxic levels of meds NOT required for development of
       PRES and prior Rx exposure does NOT appear to be
      Cyclosporine
          Exacerbates HTN by inhibiting nitric oxide production and
           thought to mediate cellular injury through mitochondrial
          Systemic HTN was only major factor associated with
           neurotoxic effects (MAHA, thrombocytopenia, and
           hypoalbuminemia were common thought)
          Elevated levels NOT related to onset of neurologic sx
      Other Rx: Tacrolimus, Sirolimus, Cisplatin, Interferon
       therapies, Bevacizumab
     Headache
         Typically constant, nonlocalized, mod to sev, unresponsive to analgesia
     Altered Consciousness
         Ranged from mild somnolence to confusion and agitation, progressing to stupor or
     Seizures
         Usually generalized tonic clonic. May begin focally and often recur. Status epilepticus
          has been reported. Preceding visual loss/hallucinations suggest occipital lobe origin.
         Minority of pts may be seizure free.
     Visual Distubances
         Hemianopia, visual neglect, auras, visual hallucinations, cortical blindness
         Cortical blindness may be associated with denial of blindness (Anton’s syndrome)
         Fundoscopic exam often normal. May find papilledema with accompanying flame-
          shaped retinal hemorrhages or exudates
     Other findings
         DTR may be brisk with Babinski signs present
         HTN is frequent but not invariable. The hypertensive crisis may precede the
          neurologic syndrome by 24h or longer.

 DDx
     Stroke
     Venous thrombosis
     Toxic or metabolic encephalopathy
     Demyelinating disorders
     Vasculitis
        Bilateral posterior cerebral a. infarctions (“top of
         the Basilar syndrome”)
   Encephalitis
 Neuroimaging
   Symmetrical white matter edema in posterior cerebral
    hemispheres, particularly in parieto-occipital regions
   With tx, resolution of findings expected within days to weeks.
   Important localizations
       Calcarine and paramedian parts of occipital lobe are usually
        spared: this distinguishes PRES from bilat post cerebral a.
       Involvement of cerebellum and brainstem is common
       Lesions are usually in anterior cortex occur in more severe cases
       Although abnormalities primarily affect subcortical white matter,
        cortex and basal ganglia may be involved.
       Distribution is NOT usually confined to a single vascular territory.
 Neuroimaging 2
   FLAIR sequences improve sensitivity and detect
    subtle peripheral lesions
   Gyriform signal enhancement, reflecting disruption
    of BBB, can be present following administration of
   Petechial and large parenchymal hemorrhages have
    been described
   DWI aids to distinguish PRES from a top of the
    basilar stroke
   The anatomical extent of MRI findings have been
    shown to correlate with patient outcome.

                         Resolution after 2 weeks
  Gyriform enhancement

 Treatment
   HTN
      Lower diastolic BP to 100-105 mmHg within 2-6 hrs. Max
       initial fall of BP should not exceed 25% of presenting value.
      More aggressive tx may reduce beyond autoregulatory
       range and possibly lead to ischemic event
      Use of IV Labetalol or Nicardipine to attain desired BP. If
       neither agent effective, may consider nitroprusside, with
       caveat of theoretical concern of paradoxically increasing
       intracranial pressure through vasodilatation.

 Treatment
   Seizures
     Phenytoin
        Can probably be safely tapered as sx and
         neuroimaging findings resolve, usually after 1-2 wks.
     In setting of eclampsia: Delivery of baby and
      placenta are usually sufficient, but if not tx with
      Mg as opposed to Phenytoin or Diazepam
     No indication pts at long-term risk for sz
      recurrence or epilepsy (although long term
      studies are lacking)
 Treatment
   Cytotoxic Immunosuppressive Therapy
      Reduce dose or remove agent
          Not recommended that agents known to induce PRES be
      In setting of cytotoxic agent, pt with one or more are at risk
       for PRES (based on 2 case studies and lit review)
          Significant fluid overload (>10% baseline weight)
          Mean BP >25% baseline
          Cr >1.8 mg/dL
   Note: Decadron NOT recommended given
    associated risk of HTN, fluid overload, and
    electrolyte disturbance.

 Prognosis
   Death may result from progressive cerebral edema,
    intracerebral hemorrhage or as complication of
    underlying condition.
   In one series, elev Cr levels were a risk factor for
    death, but neither BP levels or percent elevation
    from baseline values appeared to correlate with
   More extensive brain involvement, particularly in
    brainstem correlates with worse prognosis.

  Reversible Posterior
   Leukoencephalopathy Syndrome. 14 July 2008.