3-4. intracranial / CNS disease differentials

general signs localizing to the brain

• mentation change

  • cerebrum, thalamus, or brainstem

• vestibular syndrome

  • brainstem and cerebellum, (inner ear, CN VIII)

• ataxia, paresis

  • brainstem

• CN signs

  • brainstem (or PNS)

• circling

  • toward lesions

  • large circles — cerebral lesion

  • small circles — brainstem (vestibular)

brain diseases — degenerative

• lysosomal storage disease

• cerebellar abiotrophy

• cognitive dysfunction

lysosomal storage disease — pathogenesis

• metabolic disorder

• accumulation of substrates in neurons → degeneration of neurons

• autosomal recessive

lysosomal storage disease — clinical presentation / diagnosis

• puppies to young animals

• progressive neurological signs

• systemic signs

• diagnosis with genetic testing or histopathology

cerebellar abiotrophy — pathology

• inherited in some breeds

• animals are born normal → cerebellum degenerates

cerebellar abiotrophy — clinical presentation / prognosis

• age of degeneration varies between breeds

  • 5 months to several years

• mainly cerebellar signs

• poor prognosis, although some breeds can live with mild signs

cognitive dysfunction syndrome — clinical presentation

• older patients: dogs >9 y/o, cats >12 y/o

• clinical signs similar to other brain disorders

  • change in sleep/wake cycle

  • decreased interaction with family members

  • vocalization at night

  • pacing

  • loss of house training

cognitive dysfunction syndrome — pathophysiology

• accumulation of toxic protein (β amyloid) in frontal cerebral cortex & hippocampus

• neurochemical changes

  • ↓ activity of ACh, norepinephrine, dopamine

  • increased activity of monoamine oxidase B (MOAB), which catalyzes breakdown of dopamine

cognitive dysfunction syndrome — diagnosis

• r/o other brain diseases (tumor, infection, inflammation)

• MRI — sometimes atrophy, periventricular edema

• histopathology: demonstration of beta protein

cognitive dysfunction syndrome — treatment / prognosis

• treatment: symptomatic only

  • L-deprenyl (selegiline) — MOAB inhibitor

• poor prognosis (but can live with disease for months-years)

brain diseases — anomalous

• caudal occipital malformation syndrome (COMS)

• hydrocephalus

• quadrigeminal cyst = supracollicular fluid accumulation = intracranial intra-arachnoid cyst (ICIAC)

• cerebellar hypoplasia

• lissencephaly

• etc.

caudal occipital malformation syndrome — pathogenesis

• occipital bone malformation (skull too small for brain)

• crowding of caudal fossa

• cerebellar herniation

• change in CSF flow

• syringomyelia (CSF in spinal cord)

caudal occipital malformation syndrome — signalment

• young small breed dogs

• cavalier king charles spaniel

caudal occipital malformation syndrome — clinical signs

• cervical pain

• intense neck pruritus

• seizures, ataxia, tetraparesis

caudal occipital malformation syndrome — diagnosis / treatment

• diagnosis: MRI

• medical treatment

  • prednisone or NSAID — ↓ inflammation

  • gabapentin or pregabaline for pain

  • amitriptyline — for nerve pain later?

• surgical treatment

  • suboccipital craniectomy and durotomy

caudal occipital malformation syndrome — prognosis

fair with surgery, but pruritus usually does not resolve

congenital hydrocephalus — signalment

• toy breeds, brachycephalic breeds

• clinical signs when young

congenital hydrocephalus — pathophysiology

• stenosis of mesencephalic aqueduct

• failure of lateral aperture formation

• idiopathic

congenital hydrocephalus — clinical signs / diagnosis

• clinical signs

  • dome-shaped head

  • open fontanelles

  • ventrolateral strabismus

  • altered mental status

  • seizures

  • blindness

• diagnosis

  • U/S if open fontanelles

  • MRI, CT

congenital hydrocephalus — medical treatment

• prednisone (0.5 mg/kg PO BID)

  • reduce CSF production & inflammation

• acetazolamide (10 mg/kg PO TID)

  • increase CSF reabsorption

  • side effect: K⁺ depletion

• anticonvulsants

• mannitol for emergencies (0.5-1 g/kg over 20 mins; can repeat after 6 hrs)

prognosis: variable, usually guarded

congenital hydrocephalus — surgical treatment

• ventriculoperitoneal shunt

• complications

  • shunt too small when animals grows

  • obstruction of shunt

  • infection

  • falling out

• expensive

• prognosis variable

acquired hydrocephalus — causes & treatment

• pathophysiology

  • neoplasia

  • infection, inflammation

• treat underlying cause

• prognosis variable

quadrigeminal cyst — clinical presentation

• signalment: usually young animals, occasionally older

• clinical signs

  • may be non-clinical

  • seizures

  • vestibular signs

quadrigeminal cyst — diagnosis & treatment

• diagnosis: MRI

• medical treatment

  • prednisone to reduce edema & inflammation

• surgical removal

brain diseases — metabolic

• hepatic / renal encephalopathies

  • hypertension also with renal encephalopathy

• hypoglycemia

• hyper- or hypothyroidism

• diabetes mellitus

• hyperadrenocorticism

• electrolyte abnormalities

• acid-base disturbances

causes of hypoglycemia

• insulinoma

• hepatic failure

• sepsis

• iatrogenic (insulin overdose)

• hunting dog hypoglycemia

• addison’s

• small immature animals

how do different endocrine diseases contribute to brain disease?

(hyperthyroidism, hypothyroidism, diabetes mellitus, cushing’s)

• hyperthyroidism

  • neurotransmitter imbalance

  • hypertension

• hypothyroidism

  • brain myxedema coma: accumulation of water-retaining extracellular mucoplysaccharide substance

  • atherosclerosis

  • demyelination

• diabetes mellitus

  • hyperosmolality

• cushing’s disease

  • neurotransmitter imbalance

  • systemic hypertenion

  • atherosclerosis

brain tumor — signalment

• more frequent in dogs > cats

• incidence increases in dogs > 5 yrs

• more common in certain breeds

  • golden retriever

  • boxer

primary & secondary effects of brain tumors

• primary

  • infiltration of nervous tissue

  • compression of adjacent structures

  • disruption of circulation

  • local necrosis

• secondary

  • peritumoral edema (vasogenic)

  • obstructive hydrocephalus

  • increased intracranial pressure — brain herniation

types of primary brain tumors

• parenchyma

  • astrocytoma

  • oligodendroglioma

• inner & outer lining

  • meningioma

  • ependymoma

• vascular structures

  • choroid plexus (papilloma / carcinoma)

types of secondary brain tumors

• metastatic

  • many, including hemangiosarcoma, lymphoma, mammary carcinoma, pulmonary carcinoma, etc.

• local extension

  • nasal & frontal sinus carcinoma

  • multilobular osteochondrosarcoma — tumors of the calvarium

  • pituitary tumors (adenomas / adenocarcinomas)

  • nerve sheath tumors

brain tumors — medical (palliative) treatment

• glucocorticoids → reduce peritumoral edema

  • prednisone (0.5 mg/kg BID)

  • dexamethasone (0.1-0.25 mg/kg BID)

• anticonvulsants to treat seizures

• poor long-term prognosis

brain tumors — surgical & chemotherapy treatment

• surgical

  • complete removal

  • debulking

  • often combined with radiation therapy

• chemotherapy

  • ineffective, most drugs do not cross BBB

    • palliative alone

    • better in combination with surgery

MUE — clinical presentation

• signalment: any breed and age; more common in small terrier breeds

• can affect brain, spinal cord, or both

• clinical signs depend on localization of inflammation

  • vestibular signs common

  • seizures if forebrain lesions

  • myelopathic signs if in spinal cord

MUE — diagnosis

clinical (presumptive) diagnosis

• MRI (half are normal)

• CSF — usually lymphocytic pleocytosis

• rule out infectious encephalitides

MUE — treatment

• immunosuppression

  • prednisone 2 mg/kg/day for 4-6 weeks; taper based on neurologic improvement and ideally normal CSF analysis

  • ± chemotherapeutic drugs

• 80% of dogs respond to treatment and can do well for many years

• relapse is common — 30% at any time during treatment

idiopathic tremor syndrome — clinical presentation

• signalment: middle-aged small breed dogs (not only white!)

• acute onset whole body tremor, intention tremor

  • worse with excitement

aka idiopathic cerebellitits / little white shaker syndrome

idiopathic tremor syndrome — diagnosis & treatment

• diagnosis: clinical signs & CSF (lymphocytic pleocytosis, but not always)

• treatment: immunosuppressive therapy

  • prednisone 2 mg/kg/day x 4wks then taper slowly

• prognosis is good

canine distemper — acute form clinical presentation

• usually young dogs <1 yr old

  • poor to absent antiviral response — immature immune system

• often with systemic disease

canine distemper — chronic form clinical presentation

• mature animals, 4-8 yrs old

• adequate vaccination history

• no systemic signs; non-specific neurological signs

• delayed antiviral immune response

canine distemper — diagnosis

• CSF

  • mild lymphocytic pleocytosis, protein elevation

• RT-PCR

  • urine, CSF, serum

  • false positive within 3 weeks of vaccination

• histology, IHC

  • intracytoplasmic & intranuclear inclusion bodies

canine distemper — treatment

• palliative

  • prednisone 0.5 mg/kg PO BID x 7-10d (controversial)

  • antiepileptic drugs if seizures

• prognosis: guarded to poor

rabies — clinical presentation

• any animal with acute onset, rapidly progressive neurologic disease, unvaccinated or exposure to wildlife or other rabid animals

• clinical signs

  • furious syndrome (forebrain signs)

  • paralytic syndrome (LMN signs ascending from site of bite)

  • progression is rapid and death occurs within several days

• diagnosed post-mortem (fluorescent antibody staining of brain tissue)

• no treatment; fatal disease

FIP — signalment

• most common infectious CNS disease in indoor cats

  • mostly indoor cats

  • age: 6 mo—2yrs and > 14 yrs

FIP — pathophysiology

• replicates in macrophages → distribution to entire body

• immune-complex mediated vasculitis

• pyogranulomatous inflammatory response

• 30% develop CNS signs

FIP — diagnosis

• MRI — often hydrocephalus

• CSF

  • high viscosity

  • neutrophilic pleocytosis

  • elevated total protein

• definitive diagnosis: post-mortem

bacterial meningoencephalitis — pathogenesis

• abscess

  • bite wounds

  • otitis media / interna — extension into brain

• hematogenous

  • bacterial endocarditis

bacterial meningoencephalitis — diagnosis

• MRI

• CSF

  • high TNCC

  • neutrophils with intracellular bacteria

  • high protein

bacterial meningoencephalitis — treatment

• selective antibiotics or ampicillin 5-10 mg/kg IV q6hrs

• surgery for abscess

fungal meningoencephalitis — treatment

• fluconazole penetrates CNS well (5-15 mg/kg PO BID)

• itraconazole (5-10 mg/kg PO BID)

• treat 6-12 months

• prognosis: usually poor, 25% recurrence rate with CNS disease

protozoal agents of neurological disease

• toxoplasma gondii (dog, cat)

• neospora caninum (dog)

protozoal disease — clinical signs

• mutlisystemic

• CNS: encephalitis, myelitis

• PNS: radiculitis, myositis, muscle fibrosis and inflammation causes contractions and muscle pain

protozoal disease — treatment

• clindamycin

  • 25-40 mg/kg/day PO divided into 2 doses; treat until 2 weeks after resolution of clinical signs

• prognosis

  • cat: fair

  • dog: guarded to poor

brain trauma — pathogenesis of primary & secondary injuries

• primary injury

  • contusion, compression, reduced blood flow, laceration

• secondary injury

  • ischemia, necrosis, hemorrhage

  • release of free radicals, cascade of reactions with increase of intracellular calcium and glutamate — toxic to neurons

head trauma management

• IV fluids

  • colloids — hetastarch

  • crystalloids — 0.9% NaCl, LRS

• O₂ therapy + prevent hypercapnea

  • PaCO₂ at 30-35 mmHg

  • do not hyperventilate

• mannitol or hypertonic saline

  • osmotic diuretic (↓ ICP)

• steroids are contraindicated in head trauma

  • cause hyperglycemia → increase lactic acid, neurotoxic

• elevate head 20-30 degrees above pelvis

serial neurological evaluations for monitoring deterioration or improvement

brain vascular disorders

• brain infarct

  • ischemic

  • hemorrhagic

• sometimes underlying cause — try to r/o endocrinopathies, renal disease, hypertension, hypercoagulability,etc.

brain infarct — clinical presentation & diagnosis

• acute onset, non-progressive, focal or mutlifocal signs

• diagnosis:

  • MRI → well demarcated lesion

  • CSF:

    • mild increase in protein

    • xantocromia

    • RBCs within macrophages

    • inflammatory response

brain infarct — therapy & prognosis

• no specific therapy

• treat underlying problem (hypertension, hypothyroidism, infection, renal disease, cushing disease)

• prognosis: usually favorable