Pres

Neurology Topic 1 Ismail Penukonda MD PGY 1 LSUHSC-S, Alexandria, LA

Pre Test CC: 17 yr old AAF with New Onset of Seizures – 5 days Post C-section. Tonic-Clonic Seizure * 3 with urinary incontinence and 30 min post-ictal period after the third seizure. Headache and AMS- Screaming loudly instructing “turn the noise down”. After her fourth seizure in the hospital, the patient was forgetful and seemed to “revert back to

Hx Contd… PMH: Anemia PSH: C-section secondary to IUGR and non-reassuring fetal pattern. First pregnancy. Allergies: NKDA MEDS: Albuterol inhaler PRN & Iron  SH: Senior in High School, No smoking/alcohol/illicit drug use.  FH: Paternal GF and uncle have ‘seizure disorder’ since childhood.

PE       

Vitals: Afebrile, HR: 110, BP: 162/87, RR: 16,Oxygen Sat: 100% on RA. PE: Normal except increased DTR’S. Labs: H/H: 8.1/ 26.9 Platelets: 375 Potassium: 2.5 EKG: Sinus Tachycardia

CXR

MRI

???



What is the Diagnosis?

Clue No.1

Clue No.2

Clue No.3

Common factor



PRESident of USA.

S: Posterior Reversible Encephalopathy Syndrome

ribed in 1996 by Hinchey et al in NEJM

sient, reversible, posterior cerebral edema

dache, nausea, vomiting, altered mental status, seizures, visual disturbances

red vision, visual field loss, and complete cortical blindness

brain reveals characteristic findings

S: Posterior Reversible Encephalopathy Syndrome

• Involve the white matter > cortex

• Completely reversible when promptly recognized and tre

• Patients can progress to ischemia, massive infarction, an • Multiple systemic associations

PRES - Associations:

Toxemia of Pregnancy

Drugs: Cyclosporin Tacrolimus (FK506) Interferon-alpha Flutarabine Cisplatin Gemcitabine Erythropoietin Ifosfamide

5. Others: Hemolytic Uremic Syndrome Hepatorenal Syndrome Acute Intermittent Porphyria HIV Blood Transfusion Post-CEA TTP

Secondary Hypertension: SLE Acute Glomerulonephritis HTN with CRF

Uncontrolled Essential Hypertension

S: Posterior Reversible Encephalopathy Syndrome Pathophysiology: • Posterior cerebral circulation has reduced perivascular sympathetic activity. • Autoregulation in response to hemodynamic challenge (HTN) is insufficient. • Local increases in hydrostatic pressure cause extravasation of fluid. • Regions of vasoconstriction and vasodilatation develop  hypoperfusion.

CT 



The computed tomography finding is the presence of bilateral and symmetric hypodense areas in the posterior parietal and occipital lobes. This finding can be misdiagnosed as posterior cerebral artery territory infarcts, venous thrombosis, demyelinating disorders, vasculitis and encephalitis.

CT

MRI     

Magnetic resonance imaging has important role for diagnosis. MRI show hyperintense lesions on T2weighted images and FLAIR FLAIR: Fluid attenuated inversion recovery. These lesions don’t show enhancement after gadolinium administration. Lesions are typically symmetrical, located in the subcortical white matter and occasionally in the cortex of the occipital and parietal lobes.

MRI

MRI 



 

Diffusion-weighted MR imaging (DWI), including quantification of ADC, is the imaging modality of choice. Cytotoxic edema is caused by acute ischemia, with subsequently decreased ADC (Apparent Diffusion Coefficient) High ADC values are consistent with highly mobile water in areas of vasogenic edema. Quantification of ADC (ADC mapping) is necessary to differentiate cytotoxic edema from vasogenic edema.

DWI

ADC

MRI

CT

Treatment of PRES 

Reduction of BP and removal of causative agent.



IV Nicardipine and Labetalol are 1st line agents.



Avoid: Clonidine  CNS depression. NTG  aggravation of edema due to cerebral vasodilatation.



Identify and treat any systemic disease that may be underlying etiology.



In eclampsia delivery and IV magnesium typically rapid improvement.

 

Seizure management.

How Reversible is PRES? 

Pande et al, 2006



Multicenter retrospective study



53 patients July 1999-June 2003



PRES lesions in the subcortical white matter showed significantly higher reversibility (76-91%) than those in the brain stem (44%), deep white matter (47%) and thalamus (60%).



Complete resolution of radiographic findings occurred in 12/12 with eclampsia, 7/11 with hypertension, 12/21 druginduced, 2/5 renal failure.



Conclusions: Location of lesions and etiology are significant factor in reversibility of PRES.

BEFORE

FLAIR

AFTER 6 D

PRES - Associations:

Toxemia of Pregnancy

Drugs: Cyclosporin Tacrolimus (FK506) Interferon-alpha Flutarabine Cisplatin Gemcitabine Erythropoietin Ifosfamide

5. Others: Hemolytic Uremic Syndrome Hepatorenal Syndrome Acute Intermittent Porphyria HIV Blood Transfusion Post-CEA TTP

Secondary Hypertension: SLE Acute Glomerulonephritis HTN with CRF

Uncontrolled Essential Hypertension

Case 2 CC: Headache and acute bilateral vision loss HPI:  43 year-old female  24 hour hx of HA, nausea/vomiting  Awoke with bilateral NLP (No Light Perception) vision.

Hx Contd… 

    

PMH: Relapsing B cell lymphoma dx 10/05 S/P multiple courses of chemo. Wears glasses, No eye disease, No trauma or surgeries Allergies: Codeine, PCN FH: No eye disease SH: Married with 2 children. No tobacco, alcohol, or drug use. ROS: +HA, N/V Meds: Levaquin, Mycofungin, Valtrex, Nystatin, Cyclosporin, Prednisone, Zyrtec, Effexor, Prevacid, MVI



General: Depressed level of consciousness  Developed right gaze preference and seizure-like episode. Intubated and treated with IV Ativan at that time.



Labs: Toxicology Screen: Negative CSF: clear, cell count wnl, protein: 43, gram stain -, culture CBC c differential, CMP: WNL



Imaging: CT Head s Contrast: No acute intracranial abnormality

MRI

Cyclosporin: PRES 

 



Cyclosporin inhibits gene transcription of IL-2, IL-3, IFN-g and directly inhibits activation / differentiation of T cells Most common medication associated with PRES Likely secondary to its ability to increase BP and fluid retention Toxic effect on vascular endothelium



Low magnesium, aluminum overload, and high-dose steroids also potentiate toxicity of cyclosporin



Frequently causes hypomagnesaemia and lower seizure threshold

Follow Up 

Cyclosporin and Levaquin discontinued, IV antihypertensives, and seizures treated with IV Ativan



Day 3: A+Ox3, HA and N/V resolved. C/O constant blurry vision, Able to read newspaper print with some difficulty



Day 4: Vision returned to baseline per patient



Day 5: Started on FK-506 to replace Cyclosporin



Day 10: Vision 20/20 , no field loss

Case 3 





 

46 y/o woman with recent liver/kidney transplant for EtOH cirrhosis presents to ER with seizures. Seizure at home described as tonic clonic lasting 15 minutes, in ED 2 more focal seizures Associated diffuse headache, visual loss, and tongue biting Not feeling well the day before 2 days prior change in Prograf (Tacrolimus)3 mg bid to 4 mg bid and

Physical Exam       

VS: HR 120, BP 157/97, RR 16, T 99.6, Sat 100% GEN: NAD HEENT: MMM CV: Sinus Tachy RR LUNGS: CTAB ABD: Mild pain to palpation diffusely, +BS NEURO: A&Ox2, not following verbal command consistently, poor coordination, visual field deficits and left hemineglect, sensation: left body numbness, reflexes normal

MRI

Management & Follow Up   

  

HTN: Labetalol Seizures: Keppra, Phenytoin Tacrolimus d/c , started on Sirolimus Clinically Improved MRI Improved Discharged , repeat MRI on 1 Month.

Case 3

Back to Case 1: MRI 



1. Diffuse bilateral Subdural enhancement suggestive of meningitis. 2. Abnormal T2 and FLAIR signal hyper intensity involving the subcortical white matter and cortex of the post. Parietal and occipital lobes. Clinical correlation for PRES is recommended as follow up. Was the patient hypertensive or eclamptic during

DDx: T2-bright white matter     

      

Neoplastic - glioma, lymphoma, gliomatosis cerebri, metastasis Vascular - arterial or venous thrombosis, anoxia, vasculitis, amyloid angiopathy Demyelination - MS, acute hemorrhagic encephalomelitis, Schilder’s disease, concentric sclerosis Dysmyelination - leukodystrophies, PKU, MSUD Infection Viral - HIV, VZV, JC (PML), measles (SSPE), rubella Bacterial - Lyme, neurosyphilis Parasitic - toxoplasmosis Inflammatory - neurosarcoid, SLE, Behcet’s, Sjogren’s, Wegener’s, polyarteritis nodosa, scleroderma Hydrocephalus - early and normal-pressure Trauma - diffuse axonal injury Seizure Toxic - radiation therapy, antineoplastics, immunosuppressants, drugs of abuse, environmental exposures Posterior Reversible Encephalopathy Syndrome (PRES) Other genetic: NF2, Hurler’s syndrome, mytonic dystrophy

Differential Diagnosis 





 



1. Vascular a. Granulomatous angiitis. b. SLE c. PAN d. PRES: Posterior Reversible Encephalopathy Syndrome 2. Ischemic/Thrombotic a. Ischemic stroke of posterior circulation b. Cerebral Venous Thrombosis 3. Infectious a. Progressive Multifocal Leukoencephalopathy b. Infectious Encephalitis 4. Inflammatory/Demylenating a. Acute Disseminated Encephalomyelitis 5. Mitochondrial Disease a. MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like episodes 6. Non-Organic

Back to Case 1  



  

Blood C/S: No growth LP was done with normal CSF studies. CSF C/S : Negative for Malignant Cells/ AFB/Fungal/Viral/Bacterial pathogens. RF: Negative CSF Viral Serology: Negative MS Battery: Negative.

Treatment   



Labetalol, Nifedipine, Hydralazine are used to control BP. Seizure control: Depakote and IV Magnesium sulfate. Clinically Improved, Potassium corrected on repletion. Seizure free for 3 days and BP is well controlled and discharged home on Nifedipine. After 2 months she is seizure free and her labs look great.

Post Test 





CC: 24 yr old Asian Indian Primi with PIH and started seizing right after delivery and on day 2 has complete bilateral visual loss. Continued to seize for 2 week despite being on Phenytoin and IV MgSo4. BP is tigthly controlled and on third week stopped seizing and regained vision with in a week and discharged home.

Question???

What is the Diagnosis?

Ans: PRES 

Thanks!