Case presentation

Dr Aysha Alshareef Neurology consultant, Assistant

professor

history

the case was referred to neurology team from ob ward

she was 34 y old chadian F, P1+0 ,2 days post CS Acute Confusion ,recurent generalized GTC seizure

? headache, h/o other neurological symptoms? No fever.

No similar attak in the pastDrugs: unremarkableSocial:married ,living in JeddahNo h/o hypertension, or other medical illness

O/E

Vital sign :BP 189/88, afebrile General : no lower limb edema Neurological: no neck stifness She was disoriented ,no papilledeomaNo focal neurological signs,moving all limbs,hyper reflexea,planter were bilaterally down going

Other systems :unremarkable.

Differential diagnosis

Post partum +Recurrent seizure +encephalopathy

Eclampsia

Hypertensive encephalopathy

Cerebral venous thrombosis

Arterial stroke

Others :metabolic , encephalities…

Work up

CBC

U&E

LFT

Urine for protien: -ve

MRI

P : posterior

R : Reversible

E : encephalopathy S : syndrome

RPES

is a clinical radiologic syndrome of heterogeneous etiologies that are grouped together because of similar findings on neuroimaging studies.

Posterior reversible leukoencephalopathy syndromeIt is also often referred to as:

Reversible posterior cerebral edema syndrome

RPLS (reversible posterior leukoencephalopathy syndrome) Hyperperfusion encephalopathy

Brain capillary leak syndrome

it was first codified as a single named syndrome in a 1996 .

This described a clinical syndrome of insidious onset of headache, confusion or decreased level of consciousness, visual changes, and seizures, which was associated with characteristic neuroimaging findings of posterior cerebral white matter oedema. N Engl J Med 1996 Feb 22;334(8):494-500.

EPIDEMIOLOGY

(RPES) is increasingly recognized and reported in case reports and case series

however, the incidence of RPES is not known.

Patients in all age groups appear susceptible AJNR Am J Neuroradiol 2002 Jun-Jul;23(6):1038-48.

reported cases exist in patients as young as two years and as old as 90 years.

Case series suggest that PRES is more common in women, even when patients with eclampsia are excluded .

Neurology 1998 Nov;51(5):1369-76

PATHOGENESIS

  The pathogenesis of PRES remains unclear, but it appears to be related to:

disordered cerebral autoregulation and

endothelial dysfunction.

Autoregulatory failure Endothelial dysfunction

vasodilatation capillar leakage

hyperperfusion disruption BBB

Vasogenic edeoma

Anatomic distribution :

WHY WHITE MATTER DISEASE? The cortex, structurally more tightly packed than the white matter, resists accumulation of edema, hence predilection of abnormalities to be seen in the white matter

WHY POSTERIOR REGION ? A histochemical study revealed a greater concentration of adrenergic nerves around pial and intracerebral vessels in the anterior circulation than posteriorly . This observation may explain why the hyperperfusion and edema is mainly seen in the posterior circulation in RPLS. Acta Physiol Scand 1981 Feb;111(2):193-9

Clinical presentation

 The clinical syndrome of reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by:

Headaches Altered consciousness Visual disturbances Seizures The headache is typically constant, nonlocalized, moderate to severe, and unresponsive to analgesia .Altered consciousness ranges from mild somnolence to confusion and agitation, progressing to stupor or coma in extreme cases .Seizures are usually generalized tonic clonic; they may begin focally and often recur. Status epilepticus has been reported Preceding visual loss or visual hallucinations suggest occipital lobe origin in some patients.

Intern Med J 2005 Feb;35(2):83-90

Signs

Visual perception abnormalities are often detectable. Hemianopia, visual neglect, auras, visual hallucinations, and cortical blindness may occur . The latter may be accompanied by denial of blindness (Anton's syndrome).The funduscopic examination is often normal, particularly in eclamptic and chronically hypertensive patients, but papilledema may be present with accompanying flame-shaped retinal hemorrhages and exudates.

The deep tendon reflexes are frequently brisk with Babinski signs often present . . Other focal neurologic deficits are rare.Hypertension is frequent but not invariable. The hypertensive crisis may precede the neurologic syndrome by 24 hours or longer .

Intern Med J 2005 Feb;35(2):83-90

Risk factors

Common:

Hypertension encephalopathy

Eclampsia

Acute and chronic renal failure

Immunosuppressive agents and cytotoxic drugs

Acta Physiol Scand 1981 Feb;111(2):193-9

Immunosuppressive and immunomodulatory drugsCyclosporine A , Bevacizumab, Cisplatin Combination chemotherapy, Cytarabine GemcitabineInterferon-alpha Intravenous immunoglobulinMethotrexate Rituximab Sirolimus Sorafenib Sunitinib TacrolimusVincristine

Risk factors

Other reported causes:Hemolytic and uremic syndrome Collagen vascular disordersleukemiaBehcets syndrome TTPHIVAcute intermittent prophyriaHypercalcemia,hypomagnesmiaContrast media exposureCryoglobulinemia

Hypertensive encephalopathy 

• sever hypertension, Rapidly developing, or intermittent hypertension carries a particular risk for hypertensive encephalopathy .

•untreated or under treated chronic hypertension also carry risk of PRES

• PRES is more common, in patients with comorbid conditions

•

Eclampsia 

Some suggest that PRES (typical clinical syndrome and neuroimaging findings) could be considered an indicator of eclampsia, even when the other features of eclampsia (proteinuria, hypertension) are not present .

Br J Obstet Gynaecol 1997 Oct;104(10):1165-72.

Immunosuppressive therapy:

 The neurotoxic effects of these therapies are well known but still poorly understood.

Toxic levels of medications are not required for the development of PRES

prior exposure to the drug does not appear to be protective .

Even after several months of exposure to the drug, patients with therapeutic levels can be symptomatic .

Mol Interv 2004 Apr;4(2):97-107.

Cyclosporine is one of the more common cytotoxic therapies associated with PRES.

After renal toxicity, neurotoxicity is the most serious side effect with cyclosporine.

affecting 25 percent to 59 percent of transplant patients.

Hypomagnesemia, and hypertension have all been implicated in facilitating cyclosporine neurotoxicity . J Biol Chem 2002 Aug 16;277(33):29669-73. Epub 2002 Jun 5.

DIFFERENTIAL DIAGNOSIS :

Arterial stroke , Particularly in cases with a sudden onset of neurologic symptoms, the presentation can mimic bilateral posterior cerebral artery infarctions ("top of the basilar syndrome"). cerebral venous thrombosis Others :demyelinating toxic or metabolic encephalopathy, , vasculitis, or encephalitis , ,among others .

It is important to distinguish between PRES and ischemic stroke, as the treatment of hypertension may be very different in these conditions.

J Neurol Neurosurg Psychiatry 2000 Aug;69(2):248-5

NEUROIMAGING:

Neuroimaging is essential to the diagnosis of reversible posterior leukoencephalopathy syndrome (PRES)

magnetic resonance imaging (MRI) is the best modalities .

Typical findings are symmetrical white matter edema in the posterior cerebral hemispheres, particularly the parieto-occipital regions, but variations do occur .

Complete resolution of neuroimaging findings within days to weeks is expected.

J Neuroimaging 2004 Apr;14(2):89-96.

DIAGNOSIS :

 There are no specific diagnostic criteria for reversible posterior leukoencephalopathy syndrome (RPLS).

clinical and radiological findings.

PREVENTION AND TREATMENT

  (PRES) should be promptly recognized, since it is usually reversible.

Treating clinicians should have a high clinical suspicion in the appropriate settings

Treat underlying risk factors( hypertension,eclampsia, stop immunosupression )

Hypertension 

with lowering blood pressure , patients will often improve dramatically.

For patients with lower levels hypertension, lowering blood pressure is also recommended to treat PRES

this goal should be achieved within two to six hours, with the maximum initial fall in BP not exceeding 25 percent of the presenting value.

Lancet 2000 Jul 29;356(9227):411-7

IV drugs such as nicardipine

, labetalol, and nitroprusside are effective and safe in reducing the blood pressure to a desirable range] .

Oral antihypertensive are not usually effective to treat PRESS.

PROGNOSIS: Most case series and case reports suggest that (PRESS) is often benign.

In many cases,PRES seems to be fully reversible within a period of days to weeks, after removal of the inciting factor and control of the blood pressure.

However, one of the largest case series reported highlights the potential grave consequences of this disorder; among 22 patients studied, six died and many survivors had permanent neurologic disability

. Death may result from progressive cerebral edema, intracerebral hemorrhage, or as a complication of the underlying condition . Arch Neurol. 2008 Feb;65(2):205-10

SUMMARY AND RECOMMENDATIONS

(PRES) is a neurologic syndrome defined by clinical and radiologic features.

The typical clinical syndrome includes headache, confusion, visual symptoms, and seizures. Typical MRI findings are consistent with vasogenic edema and are predominantly localized to the posterior cerebral hemispheres. DWI can be helpful in distinguishing PRES from stroke.

Prompt reduction of blood pressure or withdrawal of immunosuppressive agents leads rapid reversal of the syndrome

It is important to distinguish between PRES and ischemic stroke, as the treatment of hypertension may be very different in these conditions.,