Intracranial Disease

Lectures 25 and 26

In general, which category of intracranial disease is described:

• actual time of onset may be young or old

• slow but steady progression without improvement

• signs often vague but forebrain in nature

• poor prognosis for recovery

degenerative

What is the age related syndrome similar to Alzheimer’s disease that occurs in dogs older than 9 years and cats older than 12 years?

cognitive dysfunction syndrome

What syndrome matches the following pathological findings:

• cerebral vascular changes, meningeal thickening, gliosis, and ventricular dilation

• progressive accumulation of a neurotoxic protein (beta-amyloid) which forms plagues in and around neurons

• intraneuronal accumulation of hyperphosphorylated tau protein (precursor to NFT)

• age associated decline in neurotransmitter activity

cognitive dysfunction sydrome

How can we diagnose cognitive dysfunction syndrome?

history

diagnosis of exclusion

How can we treat cognitive dysfunction syndrome?

pharmacologic —> selegilline

non-pharmacologic —> diet, supplements, environment

What behavioral changes can be associated with cognitive dysfunction sydrome?

change in obedience/response to commands

change in recognition of familiar people or pets

frequency of house soiling

change in excitement for walks or outings

frequency of walking during the night

avoiding being petted or touched

change in the frequency of house soiling

enthusiasm to greet the owner after a separation

What score on the purina canine cognitive dysfunction assessment tool is consistent with mild cognitive dysfunction syndrome?

4-15

What score on the purina canine cognitive dysfunction assessment tool is consistent with moderate cognitive dysfunction syndrome?

16-33

What score on the purina canine cognitive dysfunction assessment tool is consistent with severe cognitive dysfunction syndrome?

>33

The purina canine cognitive dysfunction syndrome evaluation tool is based on the acronym DISHAA, which stands for what?

disorientation

social interactions

sleep/wake cycles

housesoiling, learning, and memory

activity

anxiety

What score on the Hill’s cognitive assessment indicates your pet may not be showing signs of cognitive decline?

0-7

What score on the Hill’s cognitive assessment indicates your pet may be showing signs of moderate cognitive decline?

24-44

What score on the Hill’s cognitive assessment indicates your pet may be showing signs of early cognitive decline?

8-23

What score on the Hill’s cognitive assessment indicates your pet may have severe cognitive decline?

45-95

The Hill’s cognitive assessment tool is based on what factors?

spatial awareness

sleep wake cycles

social interactions

house soiling

What disease category is cognitive dysfunction sydrome?

degenerative

In general, which category of intracranial disease is described:

• signs usually present shortly after birth

• signs may remain static although many times they present after exacerbation

• treatments are aimed at reversing (or managing) nature

anomalous / structural

Which condition is defined as any increase in CSF volume within the ventricular system or subarachnoid space; typically classified as developmental or acquired?

hydrocephalus

Physical exam findings that include a dome shaped head, subset eyes, ± persistent fontanells with predominantly forebrain signs on neuro exam point towards which intracranial disease?

hydrocephalus

How can we diagnose obstructive (developmental) hydrocephalus?

often rpesumptive based on exam

imaging —> MRI preferred over CT or ultrasound

How can we medically treat hydrocephalus?

corticosteroids may decrease CSF production

diuretics may decrease volume of CSF

carbonic anhydrase inhibitor may decrease CSF production

proton pump inhibitor

anticonvulsants

How can we surgically treat hydrocephalus?

ventriculoperitoneal shunt

What is the prognosis for hydrocephalus cases?

overall guarded to poor

good chance of sustained clinical improvement following a successful shunting procedure

How do animals usually acquire obstructive hydrocephalus?

blockage of normal CSF flow

What is another name for Chiari like malformation?

caudal occipital malformation syndrome (COMS)

Which condition is thought to be a congenital occipital bone defect causing compression of cervicomedullary junction at the foramen magnum and may present in conjunction with variable degrees of syringomyelia?

Chiari-like malformation

What breeds are predisposed to chiari like malformation?

cavalier king charles spaniel

brussel griffon

yorkshire terrier

french bulldog

mini/toy poodle

maltese

pug dog

pomeranian

How can we diagnose chiari like malformation and syringomyelia?

MRI

What clinical signs can be associated with chiari like malformation?

cervical pain, scoliosis, phantom scratching

weakness and ataxia correlating to C1-5 or C6-T2 spinal segments

central vestibular signs

rarely seizures

What part of the brain is the problem in cases of chiari-like malformation?

caudal fossa

Medical treatment is generally recommended for mild or first time signs of chiari-like malformation. What can be used for medical treatment of this condition?

gabapentin

pregabalin

prednisone

amantadine

tramadol

Surgical treatment is considered for severe or recurrent signs of chiari-like malformation. What surgical treatment options are there for this condition?

foramen magnum decompression ± titanium mesh or cranioplasty

Why is re-operation rate high when using surgical treatment for cases of chiari like malformation?

scarring

What is the prognosis for cases of chiari like malformation?

fair to guarded for sustained relief of signs

What intracranial condition results from failure of the liver to remove toxic substances due to gut derived toxins or secondary to portosystemic shunts, end stage chronic liver disease, or acute, fulminant liver disease (lepto)?

hepatoencephalopathy

What clinical signs can be associated with hepatoencephalopathy?

symmetrical

depression

dementia

pacing

head pressing

stupor

coma

seizures

rarely cerebellar signs

ptyalism (excessive drooling) in cats

In general, which category of intracranial disease is described:

• most primary have a slow and insidious onset

• secondary can cause thrombosis and infarction, or hemorrhage resulting in significant deficits relativelt quickly

neoplasia

List examples of primary brain tumors.

meningioma (most common)

gliomas —> atrocytoma (GBM), oligodendroglioma

choroid plexus tumor —> papilloma/carcinoma

CNS lymphoma

malignant histiocytosis

ependymoma

medulloblastoma

primitive neuroectodermal tumor (PNET)

Primary brain tumors affect what components of the brain?

brain parenchymal cells (neurons, glial cells)

membranes (meninges, ependymal cells)

vascular elements (choroid plexus)

What causes clinical signs associated with primary brain tumors?

direct (invading) effects

secondary processes such as peritumoral edema/inflammation, ischemia, obstructive hydrocephalus, hemorrhage

What is the most common primary brain tumor seen in dolichocephalic breeds such as Golden Retrievers?

meningioma

What is the most common primary brain tumor seen in brachycephalic breeds such as Boxers?

glioma

What is the most common primary brain tumor seen in cats?

meningioma

In dogs with primary brain tumors, what is the most common presenting complant followed by behavioral change, circling, lethargy, visual deficits, and hemi-inattention (neglect) syndrome?

seizures

In cats with primary brain tumors, what is the number one presenting sign?

behavioral change

How can we diagnose primary brain tumors?

suspicion based on signs and susceptible breed

confident presumptive diagnosis can be made with imaging

definitive diagnosis only with biopsy —> surgical, CT guided, MR guided

How can we treat primary brain tumors?

surgery

radiationm

chemotherapy

What is the prognosis for cases of primary brain tumors?

guarded to poor

In general, which category of intracranial disease is described:

• many categories of disease; general classifications include infectious, autoimmune, neoplastic

• variable onset and severity of signs

• diseases will typically progress unless proper treatment is initiated

• rarely get antemortem definitive diagnosis

inflammatory

List examples of infectious inflammatory brain disease.

bacterial

viral —> rabies, CDV, FIP, FIV

fungal —> cryptococcus, blastomycosis, coccidiomycosis

protozoal —> Toxoplasma, Neospora

Rickettsial —> RMSF

Verminous

List examples of autoimmune inflammatory brain disease.

meningoencephalitis of unknown origin (MUO)

List examples of neoplastic inflammatory brain disease.

lymphoma

histiocytic disease

List examples of anomalous/structural intracranial disease.

hydrocephalus

chiari like malformation (COMS)

List an example of metabolic intracranial disease.

hepatoencephalopathy

List an example of nutritional intracranial disease.

thiamine deficiency

List examples of toxic intracranial disease.

tremorgenic mycotoxins

metronidazole

List examples of non-infectious inflammatory intracranial disease.

Steroid responsive meningitis-arteritis (SRMA)

granulomatous meningoencephalitis (GME)

necrotizing meningoencephalitis (NME)

necrotizing leukoencephalitis (NLE)

“white shaker dog”

List examples of vascular intracranial disease.

CVA and TIA

feline ischemic encephalopathy

A history of or concurrent extraneural signs are common in cases of intracranial disease caused by canine distemper virus. List examples of these extraneural signs.

hyperkeratosis

enamel hypoplasia

GI disease

mucopurulent nasal discharge and conjunctivitis

chorioretinitis

Young dogs <1 year of age with acute infections of canine distemper virus tend to get what form of intracranial disease?

polioencephalomyelopathy

Mature dogs >1 year of age with chronic infections of canine distemper virus tend to get what form of intracranial disease?

leukoencephalomyelopathy

Adult dogs >5 years of age may develop what rare intracranial condition associated with canine distemper virus?

old dog encephalitis

How can we diagnose intracranial disease caused by canine distemper virus?

frustrating —> usually done at necropsy

lymphopenia common, MRI/CT non specific, CDV tests available but flawed

How can we treat intracranial disease caused by canine distemper virus?

treat the symptoms as they appear, not the disease itself

What is the prognosis for cases of intracranial disease caused by canine distemper virus?

Largely dependent on patient’s immune response and whether signs stabilize or progress.

Most require humane euthanasia

What is the most common infection to affect the CNS of cats?

feline infectious peritonitis (FIP)

What clinical signs can be associated with intracranial disease caused by feline infectious peritonitis?

persistent fever

obtundation

myriad of neuro signs including cerebellovestibular, paraparesis, and seizures

What are the two forms of FIP?

wet/effusive —> immune complex

dry —> vasculitis and heavy accumulation of inflammatory cells

What is the virulent biotype of feline enteric coronavirus that hides in macrophages and forms immune complexes that deposit in a variety of tissues?

feline infectious peritonitis (FIP)

How can we diagnose intracranial disease caused by feline infectious peritonitis (FIP)?

no test is perfect

MRI and CSF analysis increase suspicion in cases with very high CSF protein

diagnosis made at necropsy

How can we treat intracranial disease caused by FIP?

immunosuppression may slow progression of disease

pentoxifylline supposedly improves circulation

feline omega-interferon seems promising (Virbagen)

polyprenyl immunostimulant

coronavirus protease inhibitor

What is the prognosis for cases of intracranial disease caused by FIP?

usually fatal

What is the adenoside nucleotide analog antiviral, similar to remdesivir (Veklury), that was patented in 2009 as an effective treatment for SARS-CoV?

GS-441524

Which form of fungal disease is carried in avian feces?

Cryptococcus neoformans

Which form of fungal disease is found in the southwest United States?

Coccidioides immitis (“Valley fever”)

Which form of fungal disease usually results in systemic involvement and may affect the eyes?

Blastomyces

Which form of fungal disease is fairly rare and located near river valleys?

Histoplasma

Which form of fungal disease more commonly causes discospondylitis and is likely fatal when it causes meningoencephalitis?

Aspergillus

What intracranial disease tyipcally affects Bernese mountain dogs, boxers, and beagles less than 2 years of age and is considered noninfectious and likely immune mediated?

steroid responsive meningitis-arteritis (SRMA)

What clinical signs can be associated with SRMA?

acute onset spinal pain, especially cervical

minimal to no neurologic abnormalities

Describe the pathogenesis of SRMA.

suppurative leptomeningitis with severe arteritis and fibrinoid necrosis of arterial wall

How can we diagnose SRMA?

rule out other causes like fracture, IVDD, etc

CBC shows leukocytsosi with mature neutrophilia

CSF shows elevated protein, neutrophilic pleocytosis (mature) without signs of infection/bacteria presence

How can we treat SRMA?

pain medications

immunosuppression with prednisone

elevate food/water dish

What is the prognosis for cases of SRMA?

excellent but relapse possible

What is the fairly common idiopathic inflammatory disease in young to middle aged female small breed dogs thought to be an autoimmune hypersensitivty reaction with potential triggers including previous infections and recent vaccination; 3 forms include ocular, focal, and multifocal/disseminated?

granulomatous meningoencephalitis (GME)

GME has a predilection for which parts of the brain?

cerebral white matter and the brainstem

What clinical signs are associated with GME?

largely dependent on location of disease but commonly seizures and cerebello-vestibular dysfunction

How can we diagnose GME?

histpathology is only definitive diagnostic

signs + suspicious MRI + characteristic CSF + negative infectious disease tests can provide a presumptive antemortem diagnosis

What do CSF results typically show in cases of GME?

moderately increased protein level

mixed cell pleocytosis —> macrophages/monocytes with evidence of reactivity

rarely results are normal

How can we treat GME?

multimodal immunosuppression recommended with corticosteroids

anticonvulsants if indicated

adjunctive therapy if indicated —> cyclosporine, cytarabine arabinoside, azathioprine, procarbazine, mycofenolate mofetil, lomustine, leflunomide

What is the prognosis for cases of GME?

overall guarded

What clinical signs are associated with NME/NLE?

acute to peracture onset of forebrain signs.

Seizures predominate, circling, visual impairment, head pressing, altered mentation

What non-infectious, idiopathic, potentially immune mediated encephalitis affects young to middle aged small breed dogs and has a genetic marker proving predisposition in pugs?

necrotizing meningoencephalitis / leukoencephalitis (NME/NLE)

How can we diagnose NME/NLE?

compatible signs

MRI/CT

CSF results

How can we treat NME/NLE?

multimodal immunosuppression recommended

anticonvulsants and adjunct therapies if indicated

What is the prognosis for cases of NME/NLE?

poor to grave

What intracranial disease is an action related repetitive myoclonus characterized by diffuse, whole body tremors that are rarely incapacitating?

“white shaker disease”

How can we diagnose “white shaker disease?”

MRI and CSF analysis

How can we treat “white shaker disease?”

prednisone

What is the prognosis for cases of “white shaker disease?”

excellent