Post on 23-Sep-2019
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?
Differentials
• Neoplasia
Primary vs metastatic
• Inflammatory dz
Infectious vs. autoimmune vs. neoplasia
• Otitis media/interna
• Geriatric vestibular disease
• Vascular accident
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
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
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)
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
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
• Used most extensively to assess
cerebrovascular accidents (CVA) or transient ischemic attacks (TIA)
• Can be added onto the end of any MRI study
Computed Tomography (CT)
• Method of cross-sectional images using x-ray radiation and computers
• Good for bone...bad for brain
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)
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
• 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)