Clinical Program for Cerebrovascular DisordersPresented by Clara Raquel Epstein, MD, Fellow

Aneurysms ~ Factor VIII Deficiency

Neurosurgical/Neurological Management and Intervention

Introduction

Aneurysm Incidence and Location

Epidemiology

•Ratio of ruptured:unruptured (incidental) is 5:3 to 5:6

•Ratio of autopsy prevalence is 0.2 – 7.9%

•Only 2% present in childhood

Aneurysm Incidence and Location

Giant Aneurysms

•>2.5 cm (= 1 inch) diameter

•Two types – saccular and fusiform

•Comprise 3-5% of intracranial aneurysms

•Peak age of presentation 30-60 years

•Female:Male Ratio = 3:1

Aneurysm Incidence and Location

Giant Aneurysm Evaluation –

•Definitively via operative visualization

•Angiogram – underestimates the size secondary to thrombosed regions of the aneurysm that do not fill with contrast

•CT Scan – significant edema seen surrounding the aneurysm due to increased vascularity secondary to inflammatory reaction to the aneurysm

•MRI Scan – Turbulence within leads to complicated signal on T1 image. Pulsation artifact (linear distortion radiation thru aneurysm) on MRI helps differentiate giant aneurysms from solid or cystic lesions

Aneurysm Incidence and Location

Location•90-95% in Carotid system

•ACoA (single most common): 30%

•Pcomm: 25%

•MCA: 20%

•5-15% in Posterior Circulation (Vertebro-basilar)

•10% on Basilar Artery:Basilar bifurcation/tip, followed by BA-SCA

•5% on Vertebral artery, VA-PICA junction is most common

•20-30% of Aneurysm patients have multiple aneurysms

Aneurysm Incidence and Location

Etiology

•Congenital predisposition (arterial wall defect)

•“atherosclerotic” or hypertensive:presumed etiology of most saccular aneurysms

•Embolic (atrial myxoma)

•Infectious (mycotic)

•Traumatic

•Other

Aneurysm Incidence and Location

Presentation•Rupture – most frequently

•SAH

•Intracerebral hemorrhage in 20-40% (especially when distal to the Circle of Willis)

•Intraventricular hemorrhage in 15-20% (especially with PICA)

•Subdural blood in 2-5%

•Mass Effect

•Giant aneurysms

•Compression of neural structures (non pupil sparing 3rd nerve palsy with enlarging PCOM aneurysm)

•Small Infarcts due to distal embolization

•Seizures

•Incidentally found

Conditions Associated with Aneurysms

•Polycystic kidney disease

•Fibromuscular dysplasia (FMD)

•Arteriovenous Malformations (AVM) including Moyamoya disease

•Connective Tissue Disorders – Ehlers-Danlos type IV (deficient collagen type III), Marfan’s syndrome, pseudoxanthoma elasticum

•Multiple other family members with intracranial aneurysms

•Coarctation of the Aorta

•Osler-Weber-Rendu Syndrome

Treatment Options for Aneurysms

Non-Surgical Treatment

•Medical Management –

•control hypertension

•continue calcium-channel blockers

•stool softeners

•bed rest

Treatment Options for Aneurysms

Surgical Treatment

•Clipping – across the neck of the aneurysm to exclude the aneurysm from the circulation

•Wrapping – with cotton or muslin, muscle, plastic resin or other polymer

• Trapping – distal and proximal arterial interruption by direct surgical means (ligation or occlusion with a clip), placement of a detachable balloon, or EC-IC bypass

Treatment Options for Aneurysms

•Proximal Ligation (Hunterian ligation) - especially with Giant aneurysms

•Thrombosing Aneurysm – with coils of wire placed either during open surgery or via endovascular techniques

•Intra-aneurysmal Placement of Detachable Balloon by interventional neuroradiologist – disadvantages include possible subsequent aneurysm growth, hemorrhage during balloon inflation , and embolization of thrombus

Presentation

A 61 year old Peruvian male with a history of hypertension, type II diabetes, hypothyroidism and a recent 30 pound weight loss, investigated with upper and lower endoscopies which were negative, presented to St. Joseph’s hospital in New Jersey, with complaints of headache, nausea and vomiting, and double vision with upward gaze. The patient was also found to have upon further investigation a factor VIII deficiency reflected by an elevated PTT. In July, 1999, an MRI was obtained which demonstrated a giant L ICA cerebral aneurysm (figure 1).

Hospital Course

The patient was transferred to Mt. Sinai Hospital, initially assessed in the ER, and subsequently admitted to the NSICU for further management and pre-operative evaluation for surgical correction.

On admission the patient presented with a left third nerve palsy, decreased sensory in the V2 and V3 distribution, diplopia with upward gaze, and was otherwise neurologically intact.

Hematology was consulted and the pre-operative treatment plan included correction with Recombinant Factor VIII replacement and close monitoring of levels with a goal of raising the Factor VIII to 60% (previously reported as low as 15%).

Diagnostic Procedures

Surgical Procedure

On the second hospital day, the patient was deemed stable for intraoperative intervention. A left ICA occlusion via proximal clipping, with an ECA-MCA bypass with saphenous vein grafts from the right leg were performed by Joshua Bederson, MD. Intraoperative neurophysiological monitoring of the nervous system was concurrently performed by Isabelle Germano, MD using continuous recording of somatosensory evoked potentials. Of note was that the patient did require large amounts of Factor VIII in order to control bleeding parameters intraoperatively.

Postoperative Course

The patient tolerated the surgical procedure well. Postoperative recovery included close hematologic monitoring and continued therapy, including FFP, Vitamin K and PRBC replacement as well as continued recombinant Factor VIII replacement throughout the remainder of the hospital course. The patient postoperatively did not have obvious bleeding problems.

On POD #2, the patient was noted to have hyponatremia with slight deterioration of mental status presumably related to this. After correction, improvement was evident.

Postoperative Course

On POD # 6 a follow-up MRI/MRA was obtained which demonstrated a patent MCA to ECA bypass with some residual aneurysm filling, in addition to a hyperemic temporal area suggesting an ischemic region.

Neurology was consulted to evaluate the patient in light of this new finding. At that time, the patient’s neurologic condition remained unchanged with the exception of a mild right upper extremity weakness and slight pronator drift noted.

The remainder of the postoperative recovery was unremarkable and the patient was deemed stable for transfer back to St. Joseph’s for further postoperative rehabilitation on the 8th postoperative day. A follow-up MRI has been recommended at two weeks postoperatively for further evaluation.

Postoperative Course

Discussion

SAH

•Estimated Annual rate of aneurysmal SAH in North America is 10-28/100,000, or 28,000 aneurysmal ruptures per year

•10% Die prior to receiving medical attention

•Rebleeding is the major cause of morbidity and mortality: risk is 38%

•8% Die from progressive deterioration from the original bleed

•Of those receiving neurosurgical intervention, vasospasm kills 7% and causes severe deficit in another 7%

•1/3 of the patients will have “good” results

Discussion

•Peak age for aneurysmal SAH is 55-60 years, 20% between 15-45 years

•30% occur during sleep

•50% of patients with aneurysms have warning symptoms, usually 6-20 days prior

•Headache is lateralized in 30%, most to side of aneurysm

Discussion

•SAH is complicated by:

•intracerebral hemorrhage in 20-40%

•Intraventricular hemorrhage in 15-35%

•Subdural blood in 2-5%

•SAH is seen more frequently in Spring and Fall

Discussion

Risk Factors for SAH

•Hypertension

•Cigarette Smoking

•Oral Contraceptives, Pregnancy and Parturition

•Alcohol Consumption

•Diurnal Variations in Blood Pressure

•Increased Risk with Lumbar Puncture &/or Cerebral Angio

•Increased Risk with Age

•Cocaine Abuse

Discussion

SAH Clinical Features

•Sudden Onset of Severe H/A

•Vomiting

•Syncope (Apoplexy)

•If LOC, patient may recover consciousness

•Focal Cranial Nerve Deficits (Especially 3rd Nerve causing Diplopia)

•Low Back Pain may develop via lumbar nerve root irritation from dependant blood