Cerebrovascular Disease. Mike Higginbotham, DVM, DACVIM (neurology) BVNS - Richmond CE event September 27, 2015

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1 Cerebrovascular Disease Mike Higginbotham, DVM, DACVIM (neurology) BVNS - Richmond CE event September 27, 2015

2 Barney 12 yr MN Lab Mix Past medical Kidney disease, hypertension Pertinent history Normal at bedtime In AM having difficulty walking

3 Neurological Exam Mentation: normal, alert, and appropriate Posture: right head tilt, wide-based stance, titubation Gait: ambulatory with a cerebello-vestibular ataxia, leftsided 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?

4 Neurolocalization? Central vestibular system (brainstem/cerebellum) Paradoxical CP angle

5 Neurological Exam Mentation: normal, alert, and appropriate Posture: right head tilt, wide-based stance, titubation Gait: ambulatory with a cerebello-vestibular ataxia, leftsided 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 Why paradoxical?

6 Mid-sagittal

7 Transverse Images L L Normal Barney

8 Dorsal diffusion weighted images L L L T 2 weighted image DWI ADC

9 So... Barney had a left-sided cerebellar stroke

10 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 energy requirement Critically dependent on adequate blood flow Extremely susceptible to injury when oxygen,

11 Fun Facts Brain has highest energy requirement 2% of BW but 20% of energy requirement 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 (noun) +/- penumbra Ahrens MB, Keller PJ. Nature Method (2013).

12 Cerebrovascular Accident 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: Hemorrhagic stroke Ischemic stroke

13 Ischemic vs. Hemorrhagic 77% 23% McConnell Vet Rad 2005

14 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

15 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

16 Hemorrhage on MRI T 2 weighted T 1 weighted Gradient echo (T 2 *) Gradient echo (T 2 *)

17 Ischemic Stroke Much more common. Responsible for 78% strokes in humans. > 40% time no underlying cause found Conditions thought to be associated: renal disease endocarditis neoplasia (1 or 2 ) hyperadrenocorticism hypothyroidism diabetes mellitus D. immitus hypercholesterolemia FCE idiopathic chronic hypertension PLE, PLN

18 Signalment Possibly higher frequency of males Both humans and dogs 58% in one K9 study (Garosi 2005) CKCS and Greyhounds overrepresented (Kent 2014)

19 Ischemic Stroke Pathophys: Hypoperfusion anaerobic metabolism reduced available ATP Na + /K + ATP pumps fail cytotoxic edema cells depolarize excitatory nt Ca 2+ 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

20 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 Garosi 05

21 Common location of infarcts Cerebellum 45% Cerebrum 27.5% Thalamus 20% Multifocal 7.5% (thalamus and medulla)

22 How to Recognize???

23 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

24 Diagnostics Imaging = key to confirming stroke in dogs MRI, DWI MRA, Proton MRS, PET (?) CT *Warning Some CVA may not show up on advanced imaging

25 CT has major limitations Beam hardening artifact CT MRI!!!

26 Gielen 2013

28 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

29 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 7-10 days

30 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?

31 Overall Prognosis In General: Ischemic > hemorrhagic Somewhat dependent on underlying etiology Worse when underlying cause found (Garosi 2005) Idiopathic cases have fair to good prognosis for recovery given enough time Good-to-excellent in 61% of dogs (Fulkerson 2012)

32 And finally...cats!! Strokes FIE Post-anesthetic blindness

33 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

34 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)

Diphenhydramine 4 mg/kg IM Ivermectin 200-500 mcg/kg SQ

35 Feline Ischemic Encephalopathy (FIE) Tx: Supportive care with anticonvulsants Unapproved and anecdotal treatment Diphenhydramine 4 mg/kg IM Ivermectin mcg/kg SQ q24hrs x 3 days Prednisolone 5 mg PO q12hrs x 14 days +/- antibiotics

36 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

37 Post-anesthetic Blindness

38 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%) Stiles J, et al Post-anesthetic cortical blindness in cats-20 cases. Vet Journal 193:

39 Take Home Points Strokes should be a differential for acute onset neuro signs MRI is the best test to diagnose Treatment is largely supportive Finding an underlying disease may alter prognosis

40 References Altay U, et al Feline cerebrovascular disease: clinical and histopathologic findings in 16 cats. JAAHA 47(2):89-97 Garosi L, McConnell LS Ischaemic stroke in dogs and humans: a comparative review. JSAP 46, Garosi L, et al Results of diagnostic investigations and long term outcome of 33 dogs with brain infarction ( ). JVIM 19, Garosi L, et al Clinical and topographical magnetic resonance characteristics of suspected brain infarction in 40 dogs. JVIM 20, Fulkerson C, et al MRI characteristics of cerebral microbleeds in four dogs. Vet Radiol Ultrasound 53(4):389-93

41 References McConnell JF, et al Magnetic resonance imaging findings of presumed cerebellar cerebrovascular accident in 12 dogs. Vet Radiol Ultrasound 46, Platt SF, et al Canine cerebrovascular disease: Do dogs have strokes? JAAHA 39, Sager M, et al Contrast-enhanced magnetic resonance angiography (CE-MRA) of intra- and extra-cranial vessels in dogs. Vet Journal 179, Wessmann A, et al Ischaemic and haemorrhagic stroke in the dog. Vet Journal 180, Stiles J, et al Post-anesthetic cortical blindness in cats-20 cases. Vet Journal 193: Gielen I, et al Agreement between low-field MRI and CT for the detection of suspected intracranial lesions in dogs and cats. JAVMA; 243: )

Cerebrovascular Disease. Mike Higginbotham, DVM, DACVIM (neurology) BVNS - Richmond CE event November 1, 2015

Cerebrovascular Disease. Mike Higginbotham, DVM, DACVIM (neurology) BVNS - Richmond CE event November 1, 2015 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