Lecture 2: Forebrain Diseases

What is included in the forebrain?

- Cerebrum (telencephalon)

- Thalamus and hypothalamus (diencephalon)

What are the lobes of the cerebrum?

- Frontal (motor)

- Parietal (somatosensory)

- Temporal (auditory)

- Occipital (visual)

- Piriform (olfactory)

What are the 5 pairs of arteries that supply the brain?

- 4 from circle of Willis = rostral cerebral, middle cerebral, caudal cerebral, rostral cerebellar

- 1 from basilar artery = caudal cerebellar

dog blood supply forebrain

internal carotid artery

dog blood supply hindbrain

vertebral artery

cat ovine blood supply to brain

- Entire brain supplied by maxillary artery.

- In cats, the basilar carries arterial blood AWAY!

bovine brain blood supply

Entire brain supplied by a mixture of maxillary and vertebral blood.

What are the clinical signs of forebrain disease?

- Seizures

- +/- Altered mentation

- Behavioral change / dementia ****

- Loss of training

- Pacing/wandering

- Wide circles and head turn NOT TILT (towards the lesion)

- vision impaired

- postural reaction deficit

- Hemi-inattention/hemi-neglect

- Head pressing, star-gazing

- Seizures, fly-biting*

- "brain pain" painful/screaming with no obvious cause

(fyi) tilt indicates ?

vestibular

What direction are the circling and head turning with forebrain disease?

Towards the lesion

On what side are there postural reaction deficits with forebrain disease?

Contralateral

On what side is there visual impairment with forebrain disease?

Contralateral

T/F: animals with forebrain disease will typically have an abnormal gait.

False — they will have a normal gait, but may have proprioceptic ataxia

What are clinical signs not associated with forebrain disease?

- Head tilt

- Nystagmus

- Stupor, coma

- Ataxia

- Abnormal spinal reflexes

- Significant cranial nerve deficits

- Intention tremors

Decussation; where does it occur?

cross over of proprioceptive tracts occurs anatomically in medulla oblongata

What is the best mode of visualization during a diagnostic work-up?

MRI

other diagnostics for forebrain disease?

exam, MDB, CSF analysis, +/- infectious disease

Differentials for forebrain disease: degenerative

- Lysosomal storage disease (autosomal recessive = normal at birth, but progressive encephalopathy over first weeks/months, Metabolic by-products accumulate due to defective enzyme --> cellular dysfunction)

- Leukodystrophy (metabolic genetic disease than affects white matter)

- Cognitive dysfunctions CCDS

(older dogs >9 years ; accumulations of beta-amyloid)

Clinical signs of cognitive dysfunction (CD)?

- Progressive

- Inactivity, abnormal sleep/wake cycle

- Wandering/pacing

- Dementia

- Urinary/fecal incontinence, loss of training

- Anxiety

- Failure to recognize familiar people/animals/environments

- Decreased interaction

- Hearing loss, vocalization

- Cats = aggression

How is degenerative forebrain disease diagnosed?

- History, clinical signs

- Excluding other signs

- May or may not have abnormal MRI (chronic = cerebral atrophy, microhemorrhage/infarcts)

What is the treatment for degenerative forebrain disease?

- No known cure

- Supportive care = selegiline, SAM-e, holistic therapies

- prevent: make them play, do puzzles, walk, etc!

Differentials for forebrain disease: anomalous

Congenital hydrocephalus:

- Seen in toy and brachycephalic breeds

- Excessive CSF in ventricle (obstruction or insufficient absorption)

- Leads to destruction of ventricular lining and neuronal injury in the cerebral cortex

- Dogs often asymptomatic, but if progressive can cause dysfunction due to compression/stretching of the brain parenchyma

Primary epilepsy:

- Pure-breed dogs (1-5 years old) -- common in labs

- No identifiable brain abnormality

- Seizures (often at rest/sleep)

What are the exam findings with congenital hydrocephalus?

- Dome head

- Persistent fotanelle (soft spot) or argue calvarial defect

- Sun-set sign (ventrolateral strabismus)

- Apparent neurological changes by 6 months — behavior change, obtundation, dementia, circling, pacing, restlessness

What is the treatment for congenital hydrocephalus?

- Reduction of CSF production (prednisone, PPI-- omeprazole!!)

- Surgical (ventriculoperitoneal shunt)

- Cannot reverse cerebrocortical damage :(

What are the main drugs for primary epilepsy treatment? (4)

- Phenobarbital

- Potassium bromide (KBr)

- Levetiracetam (Keppra)

- Zonisamide

(drugs for life)

What are the emergency anticonvulsants for primary epilepsy? (3)

- Phenobarbital

- Diazepam IV/per rectum

- Levetiracetam

Differentials for forebrain disease: metabolic

- Hepatic encephalopathy (due to liver failure or PSS)

- Hypoglycemia (brain is completely dependent on glucose for metabolism)

What are the signs of hepatic encephalopathy?

- Behavioral changes

- Obtundation

- Pacing

- Head pressing

- Visual deficits

- Infrequent seizures

(Signs often associated with feedings)

How is hepatic encephalopathy diagnosed?

- History

- Pre- and post-prandial bile acids (>100)

- Elevated ALT, ALP

- Elevated ammonia

- Ammonium biurate crystals in urine

- Visualization of PSS on ultrasound

How is hepatic encephalopathy treated?

- Surgical shunt attenuation

- Low protein diet

- Lactulose

- Antibiotics

Brain COMPLETELY dependent on ? for metabolism

glucose

blood sugar too low (gave too much insulin for example) -->

seizure

What are the potential causes for metabolism problems — hypoglycemia?

- Glycogen depletion in very young, small puppies/kittens

- Excess insulin secretion (insulinoma)

- Insulin overdose in diabetic animals

- Addison's disease

- Liver failure

- Toxins (xylitol)

What are the signs of hypoglycemia?

- Behavioral changes

- Tremors

- Vocalization

- Altered mental status

- Seizures

- Visual dysfunction

(Usually no proprioceptive deficits because not a structural thing)

What are the most common primary neoplasia tumors?

- Meningioma (most common in cats and dogs) **** old long nose dog, can take out, benign in cats, from outside brain in

- Glioma #2 (from brain tissue itself, middle age brachiocephalic)

- Choroid plexus tumors

- Lymphosarcoma

- Histiocytic sarcoma

What are the most common secondary neoplasia tumors?

- Hemangiosarcoma

- Mammary, pulmonary, prostatic adenocarcinoma

- Lymphoma

- Melanoma

- Nasal and frontal sinus carcinoma

- Calvarial tumors

- Pituitary tumors

- Peripheral nerve sheath tumors (CN 5)

What is the only way to definitively diagnose a tumor?

Histopathology

neoplasia signalment

Typically older dogs (>5yrs), any breed

What are the signs seen with neoplasia?

- Highly variable — seizures often reported

- Behavior changes, circling, head pressing, visual deficits, hemi-inattention

- Proprioceptive deficits

- Endocrine signs (pituitary tumors)

What is the treatment for neoplasia?

- Palliative vs. definitive

- Surgery, radiation, chemotherapy (chemo not often, dont get in BBB)

Differentials for forebrain disease: nutritional.

- Thiamine deficiency (cats on an all-cold water fish diet

- Hypoglycemia

- Hypocalcemia

Differentials for forebrain disease: inflammatory

Immune-mediated:

- Meningoencephalitis of unknown etiology (MUE)****

- Necrotizing leukoencephalitis (Yorkies)

- Necrotizing meningoencephalitis (pugs)

- Granulomatous meningoencephalitis

(need histopath for all)

Differentials for forebrain disease: infectious

- Cats > dogs

- Usually protozoal, fungal (cryptococcus), viral

Differentials for forebrain disease: infectious (horses)

- Equine infectious encephalitidies: Mosquito-borne Alphavirus (family Togaviridae), horses don't become contagious; people can get from mosquitos) - EEE, WEE, VEE

- Equine protozoal myeloencephalitis (due to sarcocystis neurona)

- West Nile virus (Flavivirus)

- Equine herpes virus

- Rabies virus

How are infectious forebrain diseases diagnosed?

- CSF tap analysis (elevated WBCs and proteins)

- Serology

(CSF should have nothing; little cells and clear/colorless)

How are infectious forebrain diseases treated?

Drugs must cross the blood brain barrier

- Antibiotics

- Immune suppression (small dose)

Differentials for forebrain disease: toxins

- Xylitol

- Narcotic and "recreational" drugs (marijuana)

- Ivermectin

- Bromethalin rodenticide

- Metaldehyde snail bait

- Caffeine / methylxanthines

- Lead

- Strychnine

- Organophosphates

- Pyrethrins (cats)

- Ethanol glycol

multiple seizures

likely not a toxin; toxins are non-progressive

Differentials for forebrain disease: trauma

- Neonates = birthing

- Small breeds = fall, dropped, stepped on, HBC, blunt/penetrating trauma

- Large breeds = HBC, blunt/penetrating trauma

- Felines = high rise fall, HBC, blunt/penetrating trauma

Differentials for forebrain disease: vascular

Brain infarcts = strokes

- Can be hemorrhagic or ischemic

- Causes by hypertension or cardiac disease

Causes of vascular forebrain disease?

- Hypertension

- Cardiac disease

- Hypercoagulability

- Hyperviscosity

- Intravascular neoplasia

- Atherosclerosis (Schnauzer)

What are the signs of vascular forebrain disease?

- Typically per-acute or acute

- Signs may be transient

What is the treatment of vascular forebrain disease?

- Treat the underlying cause

- Supportive care