Reversible
posterior leukoencephalopathy syndrome (RPLE)
- Term
first coined by Hinchey et al. in 1996 who reported on a series of 15
patients
- Has been
described both in children and adults
Clinical
features
- Acute to
subacute onset
-
Neurological symptoms:
Headache
Altered mental status / confusion / drowsiness
Visual disturbance
Hemianopsia, visual neglect, cortical blindness or Anton’s syndrome (denial of blindness,
confabulation)
Seizures
Often
precede other symptoms
Usually
generalized tonic-clonic
May be
preceded by visual aura/hallucinations
Single
seizure infrequent, usually multiple
- Systemic
signs
Hypertension
Usually
acute onset
Can be mild
to moderate OR severe (depending on patient’s usual BP)
Metabolic derangements
Hypomagnesemia
Hypocholesterolemia
Both of
above present in > 50% patients with RPLE secondary to cyclosporin A
Aluminum overload
Elevated drug levels
Present in 50% patients with RPLE secondary to cyclosporin A
(rate of rise may be important)
Renal failure
Worsens hypertension
Can cause
fluid overload
Etiologies
Most
commonly reported:
-
Hypertensive encephalopathy
- Renal failure with hypertension,
these patients appear to be more susceptible
- Eclampsia
(pregnancy or puerpurium)
-
Immunosuppressive agents and cytotoxic drugs (see below)
- Drug withdrawal (esp clonidine)
Case
reports:
- Collagen
vascular disorders, including SLE, PAN, Behcet’s
- TTP
- Acute
porphyria
- Post
organ transplantation
- Post-carotid
endarterectomy (unilateral hemispheric) with reperfusion syndrome
- GBS with autonomic
hyperactivity
Immunosuppressive
and cytotoxic agents
-
cyclosporin A
-
tacrolimus / FK-506
- IFN-a
- cisplatin
-
cytarabine
- IVIg
-
Erythropoietin
Pathogenesis
- Not
precisely known
- Rapid
rise in blood pressure overwhelms normal autoregulatory mechanisms
- Leads to
dilatation and leakage of cerebral arterioles causing vasogenic edema
- Posterior
circulation has less sympathetic adrenergic innervation, and therefore is
thought to be more susceptible to effects of rapid rise in blood pressure
Alternative hypotheses (which have
largely fallen out of favor):
- Vasospasm
secondary to sudden severe rise in pressure or toxin leads to ischemia and
cytotoxic and vasogenic edema
- Toxic damage
to blood brain barrier or vascular endothelium
Differential
diagnosis
- Vascular
Infarct, especially
“top-of-the-basilar syndrome” (with bilateral PCA ischemia)
Hemmorhage (congophilic
parieto-occipital lobar ICH etc)
- Infection
Encephalitis, meningitis
-
Inflammatory / Autoimmune
- Postinfectious encephalomyelitis
- Vasculitis e.g. SLE
Investigations
CSF
- Usually
normal
- May have
mild elevation in protein
Imaging
- Changes
noted below are seen in bilateral occipital and parietal lobes
- Often
symmetrical but can be asymmetrical
- Primarily
affects white matter, but grey can also be involved
*** Calcarine / paramedian occipital lobe is
spared
- More
rarely may involve brain stem, cerebellum, basal ganglia, frontal lobes
- Imaging
findings are REVERSIBLE with prompt successful treatment (may take days to weeks
for full reversal)
- If
treatment is not promptly initiated, may progress to infarction or hemorrhage
CT / MRI
CT
Hypodense lesions
MRI
Iso- / Hypo-intense on T1
Hyperintense on T2
Iso- / Hypo-intense on DWI
Treatment
- Control
blood pressure
- 10-20% decrease in MAP is usually
sufficient to terminate process
-
Discontinue or decrease dose of offending agents (immunosuppressive, cytotoxic)
- Treat
hypomagnesemia
- Treat
seizures with anticonvulsants
- Note: Phenytoin also induces
metabolism of cyclosporin and FK-506
Prognosis
- Most
patients recover completely with prompt treatment within hours (12-24h) to days
- Imaging
findings may persist for weeks
- Can lead
to poterior circulation infarction or hemorrhage if not treated promptly
- Patients
do not require chronic antiepileptic treatment once imaging abnormalities have
resolved
Differentiating
top-of-the-basilar syndrome from RPLE
-
Appropriate clinical scenario
e.g. acute hypertension, renal
failure, transplant, use of immunosuppressive agent etc.
- Seizures
Uncommon in stroke, common and
multiple in RPLE
- CT / MRI
Sparing of paramedian and calcarine
occipital lobe in RPLE
Top-of the basilar syndrome often
also involves thalamus and midbrain
Infarct is bright on DWI, whereas
RPLE is iso or hypointense
- Rapid
clinical / imaging resolution with appropriate treatment in RPLE
References:
Postgrad
Med J 77:24-28, 2001
J. Neurol.
246:339-346, 1999
Neuroradiology
39:711-715, 1997
NEJM
334:494-500, 1996
Last update: August 2004
Reviewed by: pending
review
Neurological Medicine Pocketbook
© 2003-2004 UWO Neurology Residents
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