Cerebrovascular Disease

Mike Higginbotham, DVM, DACVIM (neurology)

BVNS - Richmond

CE event

November 1, 2015

“Barney”

• 12 yr MN Lab Mix

• Past medical

• Kidney disease, hypertension

• Pertinent history

• Normal at bedtime

• In AM – having difficulty walking

Neurological Exam

• Mentation: normal, alert, and appropriate • Posture: right head tilt, wide-based stance, titubation • Gait: ambulatory with a cerebello-vestibular ataxia, left-

sided hypermetria, slight tendency to circle right • Postural Reactions: delayed on left side, normal on right • Reflexes: normal • Cranial Nerves: right head tilt, horiz. nystagmus (f phase L),

positional strabismus OD, delayed menace response OS • Retina: normal fundic examination • Hyperesthesia: no pain involving head, neck or spine

Where is lesion? Why?

Neurolocalization?

• Central vestibular system (brainstem/cerebellum)

“Paradoxical”

CP angle

Differentials

• Neoplasia

Primary vs metastatic

• Inflammatory dz

Infectious vs. autoimmune vs. neoplasia

• Otitis media/interna

• Geriatric vestibular disease

• Vascular accident

Barney’s MRI

3-planes:

• Sagittal

• Transverse

• Dorsal

de Lahunta

Mid-sagittal

Transverse Images

Normal Barney

L L

Transverse – contrast

Pre - Post -

L L

Dorsal Images

L L

Dorsal – diffusion weighted images

DWI ADC T2 weighted image

L L L

So...

Barney had a left-sided cerebellar stroke

Goals today...

Definitions & Types

Clinical signs

Diagnostics

Discuss Treatment and Outcome

+/- cats

Fun Facts

• Brain has highest energy requirement • 2% of BW but 20% of cardiac output

• Critically dependent on adequate blood flow • Extremely susceptible to injury when oxygen,

glucose, or other nutrients are deprived

• Ischemia → necrosis of neurons and glia • Tissue dies → area referred to as an infarct

• +/- penumbra

Ahrens MB, Keller PJ.

Nature Method (2013).

Cerebrovascular disease - humans

• 2nd most common cause of death

6.7 million in 2012

• Major risk factors:

Smoking, obesity, hypertension, diabetes

• Secondary risk factors:

Age, genetics, race, gender

• All involve compromised blood flow

Cerebrovascular Disease - animals

• Do dogs have strokes?

• Stroke – “abrupt onset of focal neurologic deficits resulting from an intracranial vascular event with signs ≥ 24 hrs.”

• Transient ischemic attack (TIA) – “abrupt onset of neurologic deficits (of vascular origin) that resolves in 24 hrs. with no lasting signs.”

• Main Classifications of Strokes: • Hemorrhagic stroke

• Ischemic stroke

Ischemic vs. Hemorrhagic

23% 77%

Hemorrhagic Stroke

• Less common form. Results from rupture of intracranial blood vessels.

• Conditions thought to be associated:

neoplasia (1° or metastatic) coagulopathy

thrombocytopenia Angiostrongylus vasorum (~21%)

vasculitis DIC

idiopathic (~50%) vascular malformation

Hemorrhagic Stroke

• Diagnosis:

Time course of events

CSF may show xanthochromia or hemorrhage

CT can be used, but MRI far superior • CT can miss small amounts of

hemorrhage

Hemorrhage on MRI T2 weighted T1 weighted

Gradient echo

(T2*) Gradient echo

(T2*)

Microbleeds

Gradient echo (T2*)

Ischemic Stroke

• Much more common. Responsible for 87% strokes in humans and > 40% time no underlying cause found

• Conditions thought to be associated:

renal disease hyperadrenocorticism

endocarditis hypothyroidism

neoplasia (1° or 2°) diabetes mellitus

D. immitus hypercholesterolemia

FCE chronic hypertension

idiopathic PLE, PLN

Signalment

• Possibly higher frequency of males

58% in one K9 study (Garosi 2005)

• CKCS and Greyhounds overrepresented

(Kent 2014)

Ischemic Stroke

• Pathophys: Hypoperfusion → anaerobic metabolism → reduced

available ATP → Na+/K+ ATP pumps fail → cytotoxic edema → cells depolarize → excitatory nt → Ca2+ influx → nitric oxide and free radicals → cell death → release of inflammatory mediators

• Signs reflect area of infarction:

“Territorial” – 3 cerebral arteries, 2 cerebellar arteries

“Lacunar” – penetrating vessels

Ischemic Stroke

• Dx: Time course/history

CSF may be normal

MRI is very sensitive

• Location of lesion can be helpful

• Lack of mass effect

• DWI helpful in acute situations – Restricted diffusion

Common location of infarcts

• Cerebellum 45%

• Cerebrum 27.5%

• Thalamus 20%

• Multifocal 7.5% (thalamus and medulla)

How to Recognize???

Trauma or Vascular

Congenital /

Anomalous

Neoplasia

Degenerative

Time

Se

ve

rity

of

Clin

ica

l S

ign

s

Basic Sign-Time Graph

Clinical Signs

• Acute onset focal and asymmetric signs, minimally progressive

With hemorrhage may be somewhat progressive

• Seizures major finding

Forebrain= hemi-inattention, central blindness, head turn, disorientation, circling

Hind brain = torticollis, nystagmus, hypermetria

Diagnostics

• Imaging = key to confirming stroke in dogs

MRI, DWI

MRA, PWI, Proton MRS, PET (?)

CT

• *Warning – Some CVA may not show up on advanced imaging

Diffusion what?!

• Diffusion-weighted imaging (DWI)

• Evaluates “Brownian motion” of water

Restricted diffusion

Diffusion-weighted imaging (DWI)

• FACT: T2-weighted imaging detects fluid and displays it as white

Most fluid is extracellular.

vasogenic vs. cytotoxic

• FACT: Strokes develop VE at about 6-8 hrs after incident

Strokes result in CE as early as 20 minutes after incident

Diffusion-weighted images

DWI ADC T2 weighted image

L L L

Diffusion-weighted images

Diffusion-weighted images

DWI ADC T2 weighted image

“T2 Shine-through”

DWI ADC T2 weighted image

Magnetic Resonance

Angiography (MRA)

MRA

• Way to image vasculature

• Time-of-flight 3-D time-of-flight magnetic resonance angiography (3D TOF MRA)

+/- contrast

• New applications all the time Hepatic (evaluation of PSS) Intracranial Renal Cardiac

3D TOF-MRA

de Lahunta

3D TOF-MRA

• Used most extensively to assess

cerebrovascular accidents (CVA) or transient ischemic attacks (TIA)

• Can be added onto the end of any MRI study

Tufts & Cornell (circa 2001)

Kent et al. 2001. [Intravascular lymphoma]

de Lahunta

Computed Tomography (CT)

• Method of cross-sectional images using x-ray radiation and computers

• Good for bone...bad for brain

Types of CT

Multi-slice

Major Limitation

• Beam hardening artifact

MRI !!! CT

Gielen 2013

Diagnosis...“stroke”

• NOW WHAT ?!

• Look for that underlying cause!

• Additional testing

Full CBC / chem, thyroid panel, lipid panel, ACTH stim

Chest rads, ultrasound, echocardiogram

Serial BP

Treatment

• Both types: “tincture of time”

Treat any underlying diseases

Supportive care, manage ICP, anticonvulsants

Hypertension found on many occasions. Treatment is controversial = “chicken vs. egg”

• Reevaluate MAP in 5-7 days

Treatment

• Controversies

No evidence that steroids provide any benefit

Neuroprotective therapies for ischemic stroke

• Calcium channel blockers, NMDA antagonists, etc.

Thrombolytic therapy

• Conflicting results in human literature

• Could increase the risk of hemorrhage

• Low dose aspirin or Plavix® as a prophylactic?

Overall Prognosis

• In General:

Ischemic > hemorrhagic

Somewhat dependent on underlying etiology

• Worse when underlying cause found (Garosi 2005)

• Good-to-excellent in 61% of idiopathic cases (Fulkerson

2012)

And finally...CATS !!

Strokes

FIE

Post-anesthetic blindness

Strokes in Cats

• Median age 8.5 y

• 12/16 (75%) had ischemic

• 4/16 (25%) had hemorrhagic

• 15/16 cats had hyperthyroidism, heart disease, renal disease, or hepatic disease

Feline Ischemic Encephalopathy (FIE)

• Thought to be migrating Cuterebra larvae

• Path:

Direct trauma to tissue

Massive inflammation

Toxin released from larva?

Vasospasm (usually middle cerebral artery)

• Signs:

Acute to peracute onset forebrain signs

Usually behavioral change (depressed, fearful)

Feline Ischemic Encephalopathy (FIE)

• Tx:

Supportive care with anticonvulsants

Unapproved and anecdotal treatment • Diphenhydramine 4 mg/kg IM

• Ivermectin 200-500 mcg/kg SQ q24hrs x 3 days

• Prednisolone 5 mg PO q12hrs x 14 days

• +/- antibiotics

de Lahunta

Post-anesthetic Blindness

• Blood supply to feline brain unique

• Internal carotid not patent in adult cat

Ext carotid artery → maxillary artery

Anastomosis called rete mirabile

Branches form cerebral arteries

• Rete resides near TMJ and pterygoid mm

Post-anesthetic Blindness

Post-anesthetic Blindness

• 20 anesthetized cats went blind

65% had dentals

85% had mouth gags

• Factors/Variables • Comorbidities, drugs, anesthesia length, ↓ BP

• 14 cats recovered (70%)

Take Home Points

• Strokes should be a differential for acute onset intracranial signs

• MRI is the best test to diagnose

• Treatment is largely supportive

• Finding an underlying disease may alter prognosis

References • Altay U, et al. 2011. Feline cerebrovascular disease: clinical and

histopathologic findings in 16 cats. JAAHA 47(2):89-97 • Garosi L, McConnell LS. 2005. Ischaemic stroke in dogs and humans:

a comparative review. JSAP 46, 521-29. • Garosi L, et al. 2005. Results of diagnostic investigations and long

term outcome of 33 dogs with brain infarction (2000-2004). JVIM 19, 725-31.

• Garosi L, et al. 2006. Clinical and topographical magnetic resonance characteristics of suspected brain infarction in 40 dogs. JVIM 20, 311-21.

• Fulkerson C, et al. 2012. MRI characteristics of cerebral microbleeds in four dogs. Vet Radiol Ultrasound 53(4):389-93

References

• McConnell JF, et al. 2005. Magnetic resonance imaging findings of presumed cerebellar cerebrovascular accident in 12 dogs. Vet Radiol Ultrasound 46, 1-10.

• Platt SF, et al. 2003. Canine cerebrovascular disease: Do dogs have strokes? JAAHA 39, 337-42.

• Sager M, et al. 2009. Contrast-enhanced magnetic resonance angiography (CE-MRA) of intra- and extra-cranial vessels in dogs. Vet Journal 179, 92-100.

• Wessmann A, et al. 2009. Ischaemic and haemorrhagic stroke in the dog. Vet Journal 180, 290-303.

• Stiles J, et al. 2012. Post-anesthetic cortical blindness in cats-20 cases. Vet Journal 193:367-73.

• Gielen I, et al. 2013. Agreement between low-field MRI and CT for the detection of suspected intracranial lesions in dogs and cats. JAVMA; 243:367-375)