grand rounds vanderbilt eye institute 4/27/07 ryan tarantola m.d. pgy-2
TRANSCRIPT
Initial Evaluation 3/5/07
CC: Headache and acute bilateral vision loss
HPI:
• 43 year-old female
• 24 hour hx of HA, nausea/vomiting
• Awoke with bilateral NLP vision.
PMH: Relapsing B cell lymphoma dx 10/05 S/P multiple courses of chemo and recent BMT
POH: 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
VA sc at near:OD: NLP OS: NLP
General: Depressed level of consciousness Developed right gaze preference and seizure-like episode. Intubated and treated with IV Ativan at that time.
Localization?
Pen Light Exam: WNL OU
Dilated Fundus Exam:
Vitreous: Clear OU
Optic Nerves: C/D: 0.3 OU
Macula: WNL OU
Periphery: WNL OU
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
Acute onset of HA and N/V followed by bilateral post-geniculate visual loss, and SZ.
Differential Diagnosis?
Differential Diagnosis1. Vascular
a. Granulomatous angiitisb. SLEc. PANd. PRES: Posterior Reversible Encephalopathy Syndrome
2. Ischemic/Thrombotica. Ischemic stroke of posterior circulationb. Cerebral Venous Thrombosis
3. Infectiousa. Progressive Multifocal Leukoencephalopathyb. 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
FINDINGS:
• Patchy areas of increased signal on T2 and FLAIR involving the cortical and subcortical white matter of the occipital and parietal lobes bilaterally
• No associated restricted diffusion or enhancement
• Findings consistent with posterior reversible encephalopathy syndrome (PRES). Consider Cyclosporine toxicity
PRES: Posterior Reversible Encephalopathy Syndrome
• Described in 1996 by Hinchey et al in NEJM
• Transient, reversible, posterior cerebral edema
• Headache, nausea, vomiting, altered mental status, seizures, and visual disturbances
• Blurred vision, visual field loss, and complete cortical blindness
• MRI brain reveals characteristic findings
PRES: Posterior Reversible Encephalopathy Syndrome
• Involve the white matter > cortex
• Completely reversible when promptly recognized and treated
• Patients can progress to ischemia, massive infarction, and death
• Multiple systemic associations
PRES: Posterior Reversible Encephalopathy Syndrome
Associations: 1. Toxemia of Pregnancy
2. Drugs:CyclosporinTacrolimus (FK506)Interferon-alphaFlutarabineCisplatinGemcitabineErythropoietinIfosfamide
3. Secondary Hypertension:SLEAcute GlomerulonephritisHTN with CRF
4. Uncontrolled Essential Hypertension
5. Others:Hemolytic Uremic SyndromeHepatorenal SyndromeAcute Intermittent PorphyriaHIVBlood TransfusionPost-CEATTP
PRES: 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.
• Focal areas of blood-brain barrier breakdown and further fluid extravasation
PRES: Posterior Reversible Encephalopathy Syndrome
Radiologic Findings:
Vasogenic Edema:
• DWI shows parieto-occipital signal changes caused by fluid entrapment in the edematous region.
• ADC map removes the underlying T2 signal (T2 shine through) allowing distinction between vasogenic and cytotoxic edema.
MRI
• T1: Short TR, Short TE Fat>White Matter>Gray Matter>Vitreous/CSF>Air Demonstrates normal anatomy
• T2: Long TR, Long TE Vitreous/CSF>Gray Matter>White Matter>Fat. Demonstrates inflammation, ischemia, and neoplasia
• FLAIR: Very Long TR, Long TE Fat>Gray Matter>White Matter>Vitreous/CSF>Air Similar to T2 without CSF signal. Demonstrates demylelination
• DWI: Cellular swelling slow diffusion of molecules into cells Demonstrates regions of edema Reflects both diffusion weighting and T2 effects
• ADC: Constructed from diffusion data Removes underlying T2 signal
• CT, T2: Bilateral occipital lesions with a white matter predominance. • DWI: Slight hyperintensity, left more than right. ? cytotoxic edema due to infarction vs. T2 effects• ADC: Shows T2 shine through supporting a vasogenic pattern of edema
PRES
• T2: hyperintensity along the right calcarine cortex• DWI: Marked hyperintensity (lightbulb sign) characteristic of acute infarction• ADC:Hypointensity confirms that this is restricted diffusion related to cytotoxic edema
Acute Occipital Infarction
T2
DWI
ADC
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 drug-induced, 2/5 renal failure.
• Conclusions: Location of lesions and etiology are significant factor in reversibility of PRES.
How Reversible is PRES?
Cyclosporin and PRES
• Cyclosporin inhibits gene transcription of IL-2, IL-3, IFN- and directly inhibits activation / differentiation of T cells
• Most common medication associated with PRES
• Likely secondary to its ability to increase bp and cause 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
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
• ICU admission for monitoring and supportive care in severe cases
Our Patient
• Cyclosporin discontinued, IV antihypertensives, and seizures treated with IV Ativan
• 3/6/07: A+Ox3, HA and N/V resolved. C/O constant blurry vision, palinopsia (immediate type), and polyopia. Able to read
newspaper print with some difficulty
• 3/7/07: Vision returned to baseline per patient
• 3/8/07: Started on FK-506 to replace Cyclosporin
• 3/13/07: Va 20/20 OD, 20/20-1 OS at near, no field loss
Take Home Points
PRES should be considered in all patients with acute cerebral visual loss
Diffuse white matter hyperintensity on T2/FLAIR, DWI, and ADC are characteristic, and allow differentiation from ischemic cause
Treatment is aimed at controlling bp and determining underlying cause
ReferencesMiller et al. Walsh and Hoyt’s Clinical Neuro-Ophthalmology
Kline et al. Neuro-Ophthalmology Review Manual
Kahana et al. Cortical Blindness: Clinical and Radiologic Findings in Reversible PosteriorLeukoencephalopathy Syndrome. Ophthalmology. 2005;112:e7-e11.
Eckard et al. Cerebral Hemodynamics and Autoregulation in Reversible Posterior Leukoencephalopathy Syndrome. Cerebrovasc Dis. 2006;22:204-208.
Covarrubias et al. Posterior Reversible Encephalopathy Syndrome: Prognostic Utility of Quantitative Diffusion-Weighted MR Images. AJNR. 2002;23:1038-1048.
Pande et al. Clinicoradiological factors influencing the reversibility of posterior reversible Encephalopathy Syndrome: a multicenter study. Radiat Med. 2006;24:659-668.
Hinchey et al. A Reversible Posterior Leukoencephalopathy Syndrome. N Engl J Med. 1996;334:494-500
Ayoub, Mirza. Posterior reversible encephalopathy syndrome: A variant of hypertensive Encephalopathy. J of Clin Neurosci. 2006; 590-596.