Neurology

NEUROANATOMIC LOCALIZATION

Given neurological exam findings, be able to provide neuroanatomic localization for a small animal patient by:

Differentiate UMN vs. LMN weakness

• Deficits in Motor (strength)

  • 2 divisions making up motor systems

    • UMN →  conductor

    • LMN →  orchestra

  • UMN deficits →  Loss of SIGNAL

    • Increased stride length

    • Increased extensor tone (spastic)

    • Normal/Increased reflexes

    • Other evidence of UMN motor problems:

      • Standing or walking on the dorsum of the foot

      • Dragging or scuffing the dorsum of the foot → nail wear

  • LMN Deficits →  Loss of POWER

    • Decreased stride length

    • Decreased extensor tone (flaccid)

    • Decreased reflexes

Differentiate generalized NM disease vs. spinal cord disease

• Spinal cord localization

• As a rule: LMN signs will predominate. In UMN segments, GP ataxia will be seen. In LMN segments, LMN weakness will "mask" any ataxia

• Multifocal not as common

Differentiate cerebellar, vestibular, general proprioceptive ataxias

• Deficits in Sensory (coordination)

Recognize indications of multifocal lesion

• An attempt should be made to localize neurological deficits to 1 focal lesion within the nervous system

• Lesions that cannot be localized to 1 lesion are said to be multifocal

  • Multifocal lesions most common occur with infectious/non-infectious inflammatory diseases, metastatic neoplasia, or metabolic diseases

Forebrain Disease

Recognize the clinical signs and neurological exam findings associated with forebrain disease

Be familiar with the differential diagnoses of forebrain disease

• Degenerative - canine cognitive dysfunction

• Anomalous - congenital malformation, hydrocephalus

• Metabolic - hepatic encephalopathy, renal encephalopathy, hyper and hypo-natremia, hypoglycemia

• Neoplastic - extra or intra-axial neoplasia

• Inflammatory/Infectious/Idiopathic - meningoencephalitis of unknown origin (MUO)/ (Toxoplasmosis, Neosporosis, FIP, FeLV)/ Idiopathic epilepsy

• Trauma/Toxic - traumatic brain injury, toxicity

• Vascular - ischemic encephalopathy

• DON’T FORGET ABOUT SIGNALMENT

Be able to formulate a diagnostic plan for animals with forebrain disease

• Blood Tests

  • CBC and Chem (incl electrolytes, Ca, and Glu)

  • Liver function testing (bc PSS and hepatic encephalopathy)

    • Bile acid stimulation test

    • Ammonia

  • +/- Endocrine function tests

    • Fructosamine, insulin levels (insulinoma)

  • +/- Clotting function

  • +/- infectious disease testing

    • Dogs: Neospora caninum, Toxoplasma gondii, Rabies, Distemper, Cryptococcus, Tick bourne diseases (Ehrlichia canis, Rickettsia, borrelia burgdorfei, anaplasma), Bartonella, Coccidioidomycosis

    • Cats: Toxoplasma gondii, FIV, FeLV, FCoV, Cryptococcus, Coccidioidomycosis

• Urinalysis

  • USG, dipstick, sediment examination

  • +/- urine culture

  • +/- urine protein:creatinine ratio

  • +/- urine cortisol:creatinine ratio

  • When else is it useful?

    • Cerebrovascular accident

      • To assess for an underlying cause

        • Cushing's

        • Hypoproteinuria (PLN or hypertension)

    • Discospondylitis

      • Identify if UTI is underlying cause of infection

    • Paraparesis/urinary dysfunction

      • Increased risk of UTI

    • Inborn errors of metabolism or storage disease

      • To assess for unusual metabolites

• Thoracic radiographs and abdominal ultrasound

  • Consider based on results of blood work and signalment of patient

  • If older and more suspicion of neoplasia

  • If younger and increased suspicion of metabolic/congenital disease (PSS)

• MRI - Magnetic resonance imaging

  • Imaging modality of choice for brain

  • Contrast required

  • Disadvantages

    • Anesthesia

    • High cost

    • Limited availability

    • Artifacts (metal objects)

• Cerebrospinal Fluid (CSF) Analysis

  • Most useful to exclude INFECTIOUS/INFLAMMATORY conditions

  • Can be abnormal in neoplastic or traumatic condition

  • Limitations

    • May not be abnormal due to location (if parenchymal) or nature of the lesion (non-exfoliating)

    • Can have non-specific changes

    • Cell counts correlate with exfoliation into CSF not severity of disease

  • CONTRAINDICATED IN ABSENCE OF MRI

  • Contraindications

    • Increased ICP

      • Mental status

      • Pupil size and PLR

      • Abnormal postures

      • Vestibular eye movement

    • Coagulopathy

    • Cervical (cerebellomedullary cistern) collection contraindicated in some conditions (Chiari-like malformation, AA instability, cervical trauma)

  • Analysis - ideally should be done within 1 hour

    • Differential count, cytology, protein

    • +/- infectious disease testing

  • Equipment

    • Spinal needle

    • Collection pots (sterile plain +/- EDTA, extra for culture)

    • Clippers, scrub, gloves

  • Site

    • Cerebellomedullary cistern

      • Easier to obtain CSF

      • Blood contamination less likely

      • Greater risk

    • Lumbar cistern

      • L6-L7 (L5-L6 in larger dogs if no CSF obtained)

      • Can be more challenging to obtain CSF

    • Caudal to lesion

  • DO NOT ASPIRATE

  • Maximum volume - 1ml/5kg

• Abnormalities

• NOTE: SRMA does NOT result in forebrain disease but may cause CSF abnormalities

• Urine, Blood, or CSF culture (if appropriate)

  • When?

    • Bacterial meningitis/encephalitis

      • Infectious meningoencephalitis

      • Penetrating cranial injuries

      • Extension from otitis media/interna

    • Discospondylitis

      • Also +/- disc aspirate

• EEG - Electroencephalography

  • Assess forebrain activity

  • Identification of seizure activity

    • When used at the time of seizure

    • To identify abnormal activity between seizures

  • Can be useful in status epilepticus

Be able to formulate a treatment plan for the common differentials associated with forebrain disease

• Intracranial Neoplasia

  • Palliative

    • Meningioma and glioma - prednisolone 0.25-0.5 mg/kg BID initially tapering to the lowest effective dose

    • Pituitary - Trilostane

  • Surgery

  • Radiotherapy

• Canine Cognitive Dysfunction (CCD)

  • MCT diet/diet high in carnitine, omega 3-PFA, carnitoids, vitamin E & A

    • Purina neurocare or Hills b/d

  • Selegiline

    • Most show a positive response within the 1st month if they are going to improve

  • Cognitive enrichment

    • New toys, regular (and new) walks

  • Levetiracetam

    • ? Improved CNS mitochondrial function

• Hypernatremia

  • Half strength or normal saline, (5% dextrose)

  • Water deficit = 0.6 x BW (kg) x ([patient Na concentration/normal Na concentration]-1)

  • Acute hypernatremia

    • 5% dextrose

  • Chronic hypernatremia

    • CORRECT SLOWLY

    • CARE - over rapid correction = Brain edema

    • Deficits should be corrected gradually over 48-72 hours

    • Start with half or normal strength saline before switching to 5% dextrose

    • Should not be lowered faster than 0.5mEq/L/hr

    • Na levels should be monitored every 4 hours

• Hyponatremia

  • Sodium containing fluids normal (or hypertonic) saline

  • Na deficit = BW (kg) x 0.6 x (normal serum Na concentration - patient serum Na concentration)

  • CORRECT SLOWLY

  • Acute hyponatremia

    • Correct relatively quickly with normal saline (hypertonic saline only if acute and sever)

  • Chronic hyponatremia

    • CARE - over rapid correction = cell dehydration and hemorrhage; axonal shrinkage and demyelination - CENTRAL MYELINOLYSIS

    • Deficits should be corrected gradually over 48-72 hours

    • Normal saline

    • Should not be lowered faster than 0.5mEq/L/hr

    • Na levels should be monitored every 4 hour

• Hepatic Encephalopathy

  • Treatment Aimed at removal of underlying cause/precipitating causes

  • Medical management is usually required initially even if attenuation of a PSS is going to be attempted

  • IV Fluids

    • Restores euvolemia

    • Reduce NH3 concentrations - dilution and increases urinary excretion of both urea and NH3

  • Enemas

    • Physically removes colonic contents and so a source of nitrogen from urease producing bacteria

    • 1 lactulose:3 warm water at 10ml/kg, given by foley catheter to be retained for 30 min - 1 hour

  • Lactulose

    • Favors the production of NH4+, which are trapped in the colon

    • 0.5 ml/kg PO BID and titrate to produce 2 -3 soft stools per day

  • Diet

    • Highly digestible, high biologic value protein source

    • 4g protein/100kcal/day then titrated upwards

  • Antibiotics

    • Reduce the number of urease producing bacteria

    • Metronidazole or potentiated amoxicillin for 1 - 2 weeks, and only in cases of HE

  • Antiepileptic medication - if indicated

    • Levetiracetam 20-30mg/kg q 8h +/- loading dose 60mg/kg

• Hypoglycemia

  • Frequent feeding

  • Dextrose administration - CARE with insulinoma

• Hydrocephalus

  • Medical

    • Aimed at decreasing CSF production

    • Can stabilize or improve signs in the short term, but often not effective in the long term

    • Glucocorticoids - 0.25 - 0.5mg/kg BID initially before being tapered to the lowest effective dose

    • Furosemide - 1mg/kg SID- shown to decrease CSF production and ICP in rabbits

    • Omeprazole - 1mg/kg SID - has been shown to decrease CSF production (by 26% in 1 study) however it is debatble whether this translates to clinical practice

    • Acetazolamide - 10mg/kg TID shown to decrease CSF production by the choroid plexus, however this does not always correspond with a decrease in ICP

  • Surgical - Ventriculoperitoneal (VP) shunt placement

    • Success 72 - 100%

    • Seizures can resolve following surgery

    • High complication rate (22%)

      • Blockage - 10%

      • Pain - 5.5%

      • Infection - 4.1%

      • Mechanical failure - breakage, migration or disconnection (4.1%) of part of the shunt

      • Over-shunting - 2.7%

      • Kinking - 1.6%

Seizures

Recognize the different presentations of seizures, and the possible differential diagnoses

• Seizure: a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain

  • Occur due to a change in FOREBRAIN localization

  • Pathogenesis

    • Multifactorial

    • Imbalance in excitation and inhibition

      • Either excessive excitation OR decreased inhibition

        • Glutamate - EXCITATORY

        • GABA - INHIBITORY

      • Neurons become hypersynchronized

• Epilepsy = 2 or more unprovoked seizures in > 24 hours

• Stages of a seizure

  • Pre-ictal or prodrome => any predicting events

  • Aura => initial manifestation of a seizure

  • Ictal => seizure event, involuntary muscle tone or movement +/- abnormal sensations or behavior

    • Usually ~60-90s

    • Usually self terminate

    • Peracute in onset

    • Characteristics are the same for each event

    • Occurs most commonly at sleep or rest (bc decreased seizure threshold)

    • Autonomic signs

    • 2 major phenotypic categories

      • Generalized

        • Whole body affected

        • Involvement of both cerebral hemispheres simultaneously

        • CONSIOUSNESS IMPAIRED

        • May have 1 or several of the following phases:

          • Tonic-clonic: sustained increases in muscle contraction followed by repetitive involuntary muscle contractions at a frequency of 2-3 seconds

            • Most common

          • Tonic

          • Clonic

          • Myoclonic: sudden brief involuntary contraction of a muscle or group of muscles

          • Atonic: sudden loss of muscle tone

      • Focal

        • Initial activation of ONE part of ONE cerebral hemisphere or region in the forebrain

          • Most of the time consciousness remains normal

        • Complex focal seizure = altered consciousness

        • Forms of focal seizures

          • Motor: rhythmic movements of different parts of the body

            • Most common

          • Autonomic

            • Hypersalivation is v common

          • Behavioral

            • More common in cats

            • Hard to distinguish between behavior issue or seizure

  • Post-ictal => minutes to days, can have unusual behavior or neurological deficits

• Audiogenic reflex seizures

  • Cats (commonly have comorbidities, esp deafness)

  • Late onset (15yrs)

  • Reflex seizure - seizure that is consistently precipitated by environmental stimuli

  • Myoclonic seizures progressing to generalized tonic-clonic seizures in some

  • Levetiracetam to control

• Differential diagnosis

  • Narcolepsy/cataplexy - sudden onset & inappropriate sleep or loss of muscle tone

  • Neuromuscular collapse

  • Syncope

  • Movement disorder

    • Idiopathic head tremor syndrome

      • Reported in Doberman and English bull dogs and anecdotally in Boxers

    • Episodic falling of the CKCS

      • Genetic abnormality

      • Paroxysmal hypertonicity found in CKCS

  • Metabolic disease

    • Paroxysmal dyskinesia

      • Eg paroxysmal gluten sensitive dyskinesia in the Border Terrier

  • Vestibular disease

Be familiar with the differential diagnoses of seizures, including whether these seizures are likely to be epileptic (idiopathic v structural) or reactive in origin

• DAMNITV

  • Degenerative - not common

  • Anomalous - congenital malformation, hydrocephalus

  • Metabolic - hepatic encephalopathy, renal encephalopathy, hyper and hypo-natremia, hypoglycemia

  • Neoplastic - extra or intra-axial neoplasia

  • Inflammatory/Infectious/Idiopathic - meningoencephalitis of unknown origin(MUO)/(FIP, FeLV)/idiopathic epilepsy

  • Trauma/Toxic - traumatic brain injury, toxicity

  • Vascular - ischemic encephalopathy

• DON'T FORGET SIGNALMENT (and progression)

Be able to formulate a diagnostic plan for animals with seizures

• Idiopathic epilepsy = diagnosis of exclusion

  • Tier I confidence interval

    • 2 or more seizures (24 hrs apart)

    • Age of onset 6m - 6yrs

    • Normal inter-ictal examination

    • No clinically significant abnormalities on minimum database

      • CBC, Chem

      • Fasting bile acids +/- NH3

      • Urinalysis

    • Family history of IE

  • Tier II confidence interval

    • Unremarkable fasting and post-prandial bile acids

    • MRI of the brain

    • CSF analysis

  • Tier III confidence interval

    • Ictal or inter-ictal EEG abnormalities

  • When to MRI

    • Age of onset <6m or >6yr

    • Interictal neurological abnormalities consistent with intracranial neurolocalization

    • Status epilepticus or cluster seizure

    • Previous presumptive diagnosis of IE and drug resistance with a single AED titrated to the highest tolerable dose

  • Normal neurological exam between seizures

  • Types

    • Genetic epilepsy

      • A causative gene for epilepsy has been identified

        • Lagotto Romagnolo

        • Belgian Shepherd

        • Boerboels

    • Suspected genetic epilepsy

      • A genetic influence supported by a high breed prevalence (>2%)

    • Epilepsy of unknown cause

      • Epilepsy in which the nature of the underlying cause is as yet unknown

      • No indication of structural epilepsy

Be able to formulate a treatment plan for animals with seizures due to idiopathic epilepsy, or symptomatic control of seizures due to structural or reactive epilepsy

• When to start treatment

  • Structural epilepsy or reactive seizures

  • Status epilepticus or cluster seizures

  • 2 or more seizures in a 6m period

  • Post-ictal signs are severe or last >24h

• Idiopathic epilepsy cannot be cured with medication, but drugs are used to symptomatically suppress epileptic seizures

  • Primidone is the only AED FDA approved for use in dogs

  • No drugs licensed in cats

• As vets we have to consider

  • General health of the patient

  • Owner's lifestyle

  • Financial limitations

  • Owner compliance with the therapeutic regimen

• Phenobarbitone

  • Phenyl barbiturate

  • Longest history of use in vet med of all the ASDs

  • Effective in decreasing seizure frequency in 60-93% of dogs with idiopathic epilepsy

  • MOA: augments the inhibitory effect of GABA => prolonging the Cl channel opening at GABA-A receptor

  • Initial dose

    • Dogs - 2.5mg/kg BID

    • Cats - 2mg/kg BID

  • Steady state achieved after 2-3 weeks

    • Initial side effects (PU,PD, PP, ataxia) often reduce after this point

  • Monitoring

    • 2-3 weeks after any dose change (PLAIN SERUM)

    • 6 weeks (incl CBC, Chem, and ideally BAS)

      • Bile acids bc esp in 1st 3 months may get hepatic toxicity

    • 6 months (incl CBC, Chem, and ideally BAS)

      • phenobarb increases the metabolism of itself over time

    • AIM for levels between 25-35ug/ml (can be effective as low as 15ug/ml)

  • Side effects

    • Sedation, ataxia

    • Polyuria, polydipsia, polyphagia

    • Hepatotoxicity

    • Hematological abnormalities (neutropenia, anemia, thrombocytopenia)

  • Metabolism

    • Mainly via hepatic microsomal enzymes

      • ALP and ALT elevations without hepatotoxicity are common

    • Potent inducer of cytochrome P450 enzyme activity in the liver

      • Increases hepatic production of ROS

      • Increasing the risk of hepatic injury

    • Contraindicated in dogs with hepatic dysfunction

    • Also leads to accelerated clearance of itself over time

• Bromide (Br)

  • Usually administered as POTASSIUM (KBr)

  • MOA: competes with Cl transport across nerve cell membranes and inhibits Na transport => membrane hyperpolarization which raises the seizure threshold

  • Initial dose

    • Dogs - 40mg/kg SID; 30mg/kg SID in combination with phenobarb

    • NOT IN CATS

  • CONSISTENT DIET - diet is important because fluctuations in NaCl can cause fluctuations in Br levels

  • Steady state achieved after 12wks (2-3m)

    • Initial side effects (PU, PD, PP, ataxia) often reduce after this point

  • Monitoring

    • 12weeks - PLAIN SERUM (incl CBC, Chem)

    • 6 months (incl CBC, Chem)

    • Therapeutic interval

      • 800 - 2500ug/ml in combination with phenobarb

      • 1000 - 3000ug/ml as a monotherapy

  • Side effects

    • Sedation

    • Ataxia and pelvic limb weakness

    • May worsen with higher levels

      • May be sign of bromism (toxicity)

  • Metabolism

    • Excreted unchanged in the urine

    • Undergoes tubular reabsorption in competition with Cl

      • Contraindicated in patients with renal disease

• Levetiracetam

  • Unknown MOA

  • 30mg/kg QID immediate release or 45mg/kg BID extended release (initial loading of 60mg/kg can be considered)

    • Titrate dose up in cats

    • PO, IV

  • Long tern or pulse dose (IR for 3-5 following a seizure to prevent clusters)

  • AED of choice in PSS/liver disease

  • Minimal side effects (sedation)

  • Renal excretion

• Zonisamide

  • Blocks propagation of epileptic discharges

  • 5-10mg/kg BID PO

  • Side effects - ataxia, sedation, dry eye, inappetence

  • Reduce phenobarb doses by 25% when starting zonisamide

    • Due to enhanced enzyme induction and clearance of zonisamide

• Other drugs

  • Imepitoin - ONLY LICENSED FOR NOISE AVERSION IN THE USA, not readily available

    • Is licensed in Europe for use as a monotherapy in dogs with idiopathic epilepsy

  • Topiramate/Gabapentin/Pregabalin - minimal evidence for use as an anti-epileptic in dogs, licensed for use as adjunct seizure control in humans

• THINGS TO REMEMBER FOR CATS

  • Diazepam - fulminant hepatic necrosis associated with PO

  • Phenobarbitone - lower starting (2mg/kg) and loading doses (12-15mg/kg)

  • Potassium bromide contraindicated - eosinophilic bronchitis

  • Propofol - Heinz body anemia

Be familiar with emergency seizure management

• What is an emergency

  • Cluster seizures

    • 2 or more seizures within 24 hrs

    • Dogs with IE who suffer from CS:

      • Are less likely to achieve remission

      • Have decreased survival time

      • Are more likely to be euthanized

    • CS occur in 38-77% dogs with IE

  • Status epilepticus

    • Seizure lasting > 5min

    • >2 seizures without full recovery

      • Initial presentation with SE doesn't exclude IE as the cause

    • SE occurs in 16.5% of ALL dogs presented for seizures

• Why is it an emergency?

  • Irreversible neuronal damage occurs after 30-60min

  • Due to failure of the mechanisms that usually stop an isolated seizure

    • Abnormal excessive excitation

    • Ineffective inhibition

      • Excessive glutamate release

      • Excitotoxic cell injury

  • Stage 1: increased autonomic activity

    • Tachycardia

    • Hypertension

    • Hyperglycemia

  • Stage 2: irreversible neuronal damage (after ~30min)

    • Hypotension

    • Hypoglycemia

    • Hyperthermia

    • Hypoxia

• What is the 1st thing to do?

  • STOP THE SEIZURE

    • Diazepam 1-2mg/kg per rectum (0.5mg/kg IV)

    • Midazolam 0.2mg/kg IN

  • Get history

    • When? And how many?

    • Before, during, and after - what happens?

    • Autonomic signs

    • Other abnormalities

    • Any pre-existing diseases

    • Medication

    • Access to toxins

• Assessment

  • IV catheter placement

  • Examination

  • Baseline blood work as a minimum:

    • Glucose

    • Sodium, calcium

    • PCV

    • Hepatic (+/- renal) function

    • In existing epileptics:

      • Serum levels of AEDs

• Medication

  • Start AEDs: phenobarbital 2.5mg/kg BID

  • If clusters or status (or further seizure activity over the next few hours): phenobarbital IV loading (16mg/kg in 4mg/kg boluses)

  • If further seizures: levetiracetam loading (60g/kg) continue at 30mg/kg TID

• Infusions

  • For breakthrough seizures:

    • Diazepam - interacts with plastic and light

    • Midazolam - 0.3mg/kg IV bolus followed by 0.3mg/kg/h

      • NOT in hepatic dysfunction

      • Dogs in SE may become refractory

      • Ketamine may work better

    • Propofol - 6mg/kg IV bolus followed by 6mg/kg/h

      • CARE - Heinz body anemia in cats

      • Use preservative free formulation

  • Does the dog really need it? Increased M&M?

  • However - don't hesitate if it does!

• Monitoring

  • HR and RR

  • BP - systolic >90mmHg (MAP 70-80mmHG)

  • Urine production - 1-2ml/kg/h

  • Oxygenation/ventilation - pulse oximetry - >95%; end tidal CO2 35-40mmHg

  • Temp

  • Neuro exam - allow assessment for signs of improvement/deterioration

  • If on an infusion:

    • Pharyngeal tone - if risk of aspiration - intubation

• Management

  • Well padded cage - clean and adequate bedding

  • Monitor for pressure sores

  • Eye lubrication q 2-4h

  • Feeding/water

  • Thermoregulation

• Changes with prolonged status epilepticus

  • After 30 minutes in status

    • Altered GABA A receptor subunit expression

    • NMDA receptor activation is the major mediator of excitotoxicity

      • Increased calcium entry in to cells

      • Increased duration of status in rodents

  • NMDA receptor antagonists

    • Stop maintenance phase

    • Neuroprotective

    • (possible neuro-toxicity)

• Ketamine et al!

  • Ketamine

    • NMDA antagonist

    • 5mg/kg IV bolus followed by 5mg/kg/h

  • Ketamine and dexmedetomidine

    • Ketamine - 1mg/kg IV followed by 1mg/kg/h

    • Dexmedetomidine - 3ug/kg IV followed by 3-7ug/kg/hr

    • Mild hypothermia - 36.7-37.7C

• Other considerations

  • Potassium bromide rectal loading

    • 600mg/kg over a 24h period - as 6 rectal boluses of 100mg/kg q 4h

    • 200mg/kg/day for 4-5days divided into 4-6 doses a day

      • Sedation and ataxia

      • Often requires hospitalization

    • "mini" loading

      • 30-40mg/kg BID for 4-5days

  • Consider volatile anesthesia (required ventilation)

  • Zonisamide 10mg/kg q12h PO

• Take home points

  • INTERVENE if your patient is still seizing

  • CONTINUE with maintenance AEDs or loading doses

  • TREAT ALL SEIZURES including focal seizures

  • IF YOU ADMINISTER DIAZEPAM YOU PROBABLY ALSO NEED TO ADMINISTER OTHER AEDs

  • CHECK SERUM LEVELS REGULARLY in long term epileptics

  • IF STILL SEIZING - CHECK YOUR DIAGNOSIS

Myelopathies

Recognize the clinical signs and neurological exam findings associated with spinal cord and cauda equina disease

• Functional spinal cord localization

Be able to systematically evaluate gait abnormalities.

• Approach to spinal cord case?

  • We watch gait

    • Paresis and ataxia

      • What type of ataxia?

      • All 4 limbs, 2 limbs?

    • General proprioceptive ataxia and paresis

      • Spinocerebellar tracts = proprioception

      • Rubrospinal tract = motor (paresis)

      • Very difficult to effect 1 without the other. So with spinal cord injuries, usually have general proprioceptive ataxia AND UMN paresis

  • Then we do postural reactions IF motor present

    • Requires all PNS and CNS to be intact

  • Then reflexes to say if UMN vs LMN

    • Keep in mind withdrawal reflex is simply a reflex - you have to look for a response from the animal to assess nociception

    • UMN = normal to increased reflexes and tone

    • LMN = decreased to absent reflexes and tone

  • Functional loss

    • Proprioception

    • Weakness (paresis)

    • Motor (plegia)

    • Bladder

    • Nociception

      • Recovery occurs in reverse order

Be familiar with the differential diagnoses of spinal cord and cauda equina disease and how to prioritize them for individual clinical cases (those discussed in the mini-lectures).

• Intervertebral Disc Disease

  • Hansen Type I - Chondroid degeneration

    • Acute

    • Young, chondrodystrophic breeds

  • Hansen Type II - Fibroid degeneration

    • Any breed

      • Large non-chondrodystrophic

      • German Shepherd

    • Age > 7y old

    • Slower onset of signs

• Fibrocartilaginous Embolism (FCEM/FCE)

  • Acute

  • May be painful initially (hrs)

  • Non-progressive!

  • Localizes to area of cord affected

• Discospondylitis

  • Signalment

    • Medium to giant breed dogs

    • Young to middle aged

  • History

    • Acute to subacute to chronic

    • Spinal hyperesthesia

    • Systemic signs

      • Fever, inappetence, decreased mentation

    • Reluctance to move

• Degenerative Myelopathy

  • German Shepherds, Boxers, Corgis

  • Onset usually after 7 years of age

  • Insidious onset, slowly progressive

    • Over 6 - 12 months

  • Clinical Signs

    • Non-painful

    • T3 - L3 signs

      • GP ataxia/UMN paraparesis

      • Normal to increased tone and reflexes in the pelvic limbs

    • Degenerative process ascends and descends in the spinal cord

      • Will affect other areas

• Lumbosacral Syndrome

  • German shepherds most common breed

  • Middle-aged to older

• Caudal cervical spondylomyelopathy

  • 2 subtypes

    • Young Great Danes, Mastiffs, Borbels

      • Degeneration and thickening of the articular processes +/- laminae

      • Dorsolateral compression

      • Usually no disk degeneration

    • Older Doberman Pinschers

      • Type II disc protrusion

      • Hypertrophy of the articular processes, ligamentum flavum and the dorsal longitudinal ligament

      • Dorsal and ventral compression

• Atlantoaxial Instability (AA-Lux)

  • Luxation of C2 dorsal to C1

    • Congenital malformation of C2

      • Hypoplastic or aplastic dens

    • Trauma of dens, rupture of ligaments

Be able to formulate a diagnostic plan for animals with spinal cord disease.

• Diagnostic plan for spinal cord disease

  • Radiographs

    • Some neoplasias, bone lysis, fractures/subluxations, congenital malformations

  • Myelography

    • Helpful for certain lesions but inferior to advanced imaging

  • Advanced imaging (CT, MRI)

    • Cross sectional capabilities

  • CSF analysis

    • "blood" of the CNS

• Intervertebral Disc Disease

  • Hansen Type I - Chondroid degeneration

    • Radiographs not v helpful

    • Myelography

      • Allows visualization of spinal cord

      • Confirms compressive lesions

      • Targets specific location for surgery

    • CT - Computed Tomography

      • Sensitive and non-invasive

      • Can be used adjunctively with myelography OR by itself

      • Multi Planar Reformatting (MPR) - 3D images

      • If partially or not calcified at all, won't be able to see well or at all

    • MRI ⭐ - magnetic resonance imaging

      • Consistently more accurate than myelography and CT for determining site and side of lesion

      • Most $$$ and takes time

  • Hansen Type II - Fibroid degeneration

    • Generally not calcified - DO MRI

• Fibrocartilaginous Embolism (FCEM/FCE)

  • Radiographs: Area of hyperintensity within spinal cord itself

• Discospondylitis

  • Can be diagnosed with rads

    • Radiographic changes occur ~3wks after clinical signs start

  • Neurological exam

    • Pain (often severe!) alone or findings consistent with site of infection

  • Additional diagnostics

    • CBC, Chemistry

    • Urinalysis and urine culture

    • Blood cultures

    • Brucella canis serology (esp if intact dog)

    • Fluoroscopy-guided FNA of disc

• Degenerative Myelopathy

  • Diagnosis of exclusion

    • Normal MRI

    • Normal CSF analysis

  • DNA test

    • SOD1 genetic mutation

    • Joan Coates, University of Missouri

• Atlantoaxial Instability (AALux)

  • Lateral radiograph

  • DO NOT FLEX HEAD

  • Do radiographs awake so that normal muscle tone with help guard neck

  • Don't need MRI

Be able to formulate a treatment plan for the common differentials associated with spinal cord disease. *Dosages are not required, but you should be able to list the name of the medication used, if it is discussed in the class notes.

• Intervertebral Disc Disease

  • Hansen Type I - Chondroid degeneration

    • Conservative Treatment

      • Crate rest 4-8 weeks

      • Bladder management

      • Prevent continued extrusion through ruptured AF

      • Adjunctive therapy

        • Steroidal or Nonsteroidal anti-inflammatory drugs

        • Muscle relaxants (eg methocarbamol)

        • Opioids (eg tramadol)

        • Gabapentin/Amantidine

        • Acupuncture

        • Physical therapy

    • Surgical treatment

      • Recommended when

        • Persistent/recurrent pain

        • Unresponsive to conservative therapy

      • Surgery may offer

        • More completer (and faster) recovery

        • Lower probability of recurrence at that site

      • Definitely recommended if loss of nociception

        • Within 24-48 hours

      • Goals

        • Remove compression

          • Hemilaminectomy

          • Ventral slot for cervical discs

        • Remember

          • Surgery does not result in instant recover

          • Secondary spinal cord trauma/injury takes time to heal

          • Surgical decompression allows healing to begin

          • Functional recovery take weeks to months

        • Not all dogs recover

  • Hansen Type II - Fibroid degeneration

    • Conservative management vs surgery

      • Same options as we discussed for Type I disc herniations

      • But… prognosis with surgical intervention is difficult for Type II discs…

    • Sometime dogs are worse after surgery

    • Commonly don't recover

• Fibrocartilaginous Embolism (FCEM/FCE)

  • Supportive

  • Physical therapy

• Discospondylitis

  • Antibiotic therapy

    • Based on culture

    • Empiric - Cephalosporins

    • 8-12 months

  • Analgesics

• Degenerative Myelopathy

  • No definitive treatment

    • Only proven effective therapy is physical therapy

    • Can prolong disease progression

• Lumbosacral Syndrome

  • Treatment and Prognosis

    • Favorable with decompressive surgery

      • Dorsal laminectomy

    • Conservative therapy may help in some cases

      • Analgesics

      • Physical therapy

      • +/- steroids/NSAIDs

• Caudal cervical spondylomyelopathy

  • Various surgical approaches

    • Dorsal vs ventral

    • Fusion vs no fusion

    • Guarded prognosis

  • Conservative management

    • Generally continued deterioration or recurrence

  • Prognosis not as predictable as for IVDD

    • Relapse possible

• Atlantoaxial Instability (AALux)

  • Conservative therapy

    • Some dogs recover

    • Recurrence possible

    • Fusion does not occur

  • Surgical therapy

    • Goal is to fuse C1 - C2

MICTURITION AND NEUROGENIC BLADDER DYSFUNCTION

Explain the functional anatomy and innervation of the lower urinary tract

• Bladder innervation

  • Storage (Filling) Phase

    • Sympathetic system predominates

    • Thoracolumbar region

      • Hypogastric nerve (L1 - L4)

        • β receptor

          • Stimulation relaxes detrusor muscle to store urine

        • α receptor

          • Stimulation constricts internal urethral sphincter (smooth muscle)

    • Somatic component

      • Pudendal nerve (S1 - S3)

        • ACh receptor

          • Sensory and motor to external urethral sphincter (skeletal muscle)

          • Stimulation constricts external urethral sphincter

    • Pudendal nerve via ACh contracts external sphincter muscle

    • Hypogastric nerve via α receptors contract internal sphincter muscle

    • Inhibition of pelvic nerve to detrusor muscle to allow relaxation and filling

    • As bladder fills, pressure stimulates pelvic nerve sensory fibers which relay to beta receptors to relax further

    • Brain stem micturition centers facilitate and modulate these activities (helps decide whether it is good time to void/eliminate)

  • Micturition (Peeing) Phase

    • Parasympathetic system predominates

    • Cranial-sacral region

      • Pelvic nerve (S1 - S3)

        • ACh receptor

          • Stimulation contracts detrusor to evacuate urine

          • Sensory branch to complete an emptying reflex arc

    • Pelvic nerve sends sensory info up to brain stem, cerebellum, cerebrum

    • Activation of micturition via UMN pathways in pons and medulla; descends via spinal cord

    • Inhibition of hypogastric nerve (β receptors on detrusor, α receptors on internal sphincter muscle)

    • Inhibition of pudendal nerve to relax external sphincter

    • Facilitation of pelvic nerve to contract detrusor muscle

    • Part of coordination of these nerves is mediated reflexively within the sacral segments and from sacral to lumbar segments

    • Reflex bladder contractions

Combine this knowledge with neurological exam findings to accurately characterize the expected manifestations of bladder dysfunction

• As a general rule

  • If voluntary motor function is compromised to the muscles of the limbs

  • Voluntary motor function is likely compromised to a similar degree in the muscles of the lower urinary tract

• LMN Dysfunction => L4 - S3 spinal cord lesion

  • Hypotonicity of pelvic and pudendal nerves

  • Decreased external urethral sphincter tone

  • Decreased detrusor strength

  • Dysfunction due to

    • Inability to contract detrusor muscle

    • Dribbling due to inability to constrict sphincters

  • Passive dribbling because inability of muscle to contain contents

• UMN Dysfunction => T3 - L3 spinal cord lesion

  • Hypertonicity caudal to lesion

  • Increased external urethral sphincter tone

  • Increased resting tone to the detrusor muscle

  • Dysfunction due to :

    • Loss of higher level coordination of detrusor/sphincter

    • Detrusor cannot overcome resistance from external urethral sphincter

  • Difficult to express because increased tone, may have some leakage but not as much as LMN

• Autonomic Dysfunction

  • Pelvic and hypogastric (autonomic) decreased

  • Pudendal (somatic) preserved?

  • Loss of nerve function

    • Poor detrusor contraction

    • Poor internal sphincter control

  • Intact central integration

    • Aware bladder is full

    • Attempts to urinate (but not much urine will be evacuated)

  • Results: stranguria, dysuria with large residual volume

Create a prioritized list of differential diagnoses associated with abnormal micturition, including neurogenic and the common non-neurogenic causes

• Neurogenic Dysfunction

  • Brainstem

    • Loss of communication/coordination with micturition center

  • Spinal cord

    • Loss of communication or coordination with micturition center

    • Specific nerves based on lesion location

  • Cauda equina

    • Pelvic or pudendal nerve damage

  • Cerebral or cerebellar disease (rarely)

    • Loss of coordination with micturition center

    • Loss of voluntary control

  • Neuromuscular disease

    • Autonomic dysfunction (e.g., dysautonomia)

    • Other peripheral nerve, detrusor muscle, or NMJ effects (rare)

  • Detrusor-urethral dyssnergia

    • Lack of coordination between detrusor contraction and urethral relaxation

• Non-Neurogenic Dysfunction

  • Primary bladder pathology

    • Myopathic bladder disease

      • Detrusor atony

      • Bladder rupture

    • Mechanical outflow obstruction

      • Urolithiasis

      • Neoplasia or polyps

      • Prostatic disease

      • Urethral stricture

      • Extraluminal compression

  • Behavior, environmental

    • Pain upon urination

    • Hospitalized cats (or dogs) unwilling to urinate

    • Dogs unable/unwilling to posture due to other disease

      • Orthopedic disease, neurologic disease, other

    • Eventually these patients should urinate; concern is how long to wait if uncertain of ability

  • Pharmacologic effects

    • Opiates, antidepressants, anticholinergics

Be able to formulate a treatment plan for the medical management of UMN and LMN bladder dysfunction, which will reduce risk of complications

• Goals

  • Short term

    • Prevent infections, cystitis

    • Prevent detrusor atony

    • Prevent urine scald

  • Long term

    • Treat underlying cause of dysfunction

    • Improve function

• Bladder care

  • Evacuate bladder 2-4x a day

  • Manual expression

  • Catheterization

    • Intermittent

    • Indwelling

• Skin care

  • Keep skin clean and dry

  • Frequent baths

  • Baby powder, ointments to protect skin

  • Absorbent bedding

• Pharmacologic Intervention

  • UMN Dysfunction

    • α-antagonists

      • Reminder

        • Hypogastric n (L1 - L4)

          • α stimulation constricts internal sphincter

          • β stimulation relaxes detrusor

      • Phenoxybenzamine

        • 48 - 72h to onset of activity

      • Prazosin

        • Short onset of activity

      • Indications: UMN dysfunction to relax internal urethral sphincter

    • Striated muscle relaxants

      • Reminder

        • Pudendal n (S1 - S3)

          • Stimulation of pudendal n constricts external urethral sphincter

      • Diazepam (Valium)

        • Short duration of activity

      • Indications: UMN dysfunction to relax external urethral sphincter

  • LMN Dysfunction

    • Parasympathomimetics (ACh stimulation)

      • Reminder

        • Pelvic (S1 - S3) and Pudendal n(S1 - S3)

          • Stimulation of pelvic nerve contracts detrusor muscle

          • Stimulation of pudendal nerve constricts external urethral sphincter

      • Bethanechol

        • Short onset of activity

        • Stimulates detrusor contraction

        • Also stimulates contraction of external urethral sphincter muscle

        • USE CAUTIOUSLY

      • Indications: used in LMN dysfunction to assist with detrusor contraction

      • These patients are easily expressed… do they need medications?

        • Meds have side effects so tend not to use meds w LMN bladder

    • α-agonists

      • Reminder

        • Hypogastric n (L1 - L4)

          • α stimulation constricts internal sphincter

          • β stimulation relaxes detrusor

      • PPA

      • Estrogen

      • Indications:

        • Not typically used with neurogenic dysfunction

        • Could be used in LMN dysfunction to increase internal sphincter

        • Need to be cautious about outflow

Multifocal intracranial disease

Recognize the clinical signs and neurological exam findings associated with multifocal disease

• Paradoxical vestibular - Cerebellum

  • Head tilt and circling contralateral to the lesion

  • Dysmetria, head tremor, truncal sway

  • Postural deficits ipsilateral to lesion but contralateral to head tilt

Be familiar with the differential diagnoses of multifocal disease

• Degenerative (usually diffuse and symmetrical cf multifocal)

• Anomalous (usually diffuse and symmetrical cf multifocal)

• Metabolic (usually diffuse and symmetrical cf multifocal)

• Neoplastic - 1° (extra or intra axial); 2°

• Inflammatory/Infectious - meningoencephalitis of unknown origin (MUO)/Rabies, Distemper, Toxoplasma, Neospora, FIP, Bacterial

• Trauma/Toxic - traumatic brain injury

• Vascular (usually focal)

Be able to formulate a diagnostic plan for animals with multifocal disease

• Bloodwork +/- Thoracic and abdominal imaging

  • To rule out Metabolic disease - BUT usually diffuse and symmetrical cf multifocal

  • To confirm Inflammatory/Infectious

• MRI - to see…

  • Degenerative

  • Anomalous BUT usually diffuse and symmetrical cf multifocal

  • (Metabolic disease)

  • Neoplastic

  • Inflammatory/Infectious

  • Trauma/Toxicity

  • Vascular

• CSF

  • To confirm Inflammatory/Infectious and Neoplastic

Be able to formulate a treatment plan for the common differentials associated with multifocal disease

• Meningoencephalomyelitis of Unknown Origin (MUO)

  • Combination of immunosuppressive treatment

    • Prednisolone +/- other immunosuppressive medication

      • Cytosine arabinodise

      • Ciclosporin

      • Leflunomide

      • Lomustine

      • Procarbazine

      • Mycophenolate mofetil

      • Azathioprine

  • ALSO REMEMBER: Symptomatic treatment e.g. anti-convulsants

• Steroid Responsive Meningitis-Arteritis (SRMA)

  • 4 - 6 months of slowly tapering steroids

  • ANALGESIA

• Feline Infectious Peritonitis (FIP)

  • Remdesivir

  • Antiviral nucleoside analogue GS-441524 - for 12 weeks

    • NOT FDA APPROVED

    • 4 cats: survival 216-528 days

    • May have relapses

    • Doses required may be higher than with non-neurological disease

  • Corticosteroids may help reduce inflammation and edema

  • Symptomatic/supportive care

• Neospora Meningoencephalomyelitis

  • Clindamycin/TMPS + Pyrimethamine

  • Anti-inflammatory corticosteroids to reduce associated inflammation

  • Symptomatic treatment

  • PT if muscle involvement

• Canine Distemper Virus

  • Steroids - may reduce inflammation

    • Can also reduce viral clearance

  • No definitive treatment

  • Symptomatic/supportive treatment

• Bacterial meningoencephalitis

  • Antibiotics +/- surgical drainage

  • Guarded prognosis

FOREBRAIN | HEAD TRUMA AND TRAUMATIC BRAIN INJURY

Define the pathophysiology of brain injury

• Primary & Secondary Brain Injury

  •  Primary brain injury

    • Occurs at the time of the traumatic incident

    • => direct mechanical damage

      • Vascular compromise

      • Brain parenchyma damage

      • Skull fractures

    • Results in hemorrhagic &/or edema (vasogenic)

    • Initiates the processes causing secondary injury

    • Beyond the control of the clinician

    • Your role: understand, recognize, and treat secondary brain injury

    • Goal: combat factors contributing to rising ICP

  •  Secondary brain injury

    • Occurs in the minutes to days following the trauma

    • => biochemical changes/pathways

      • Excitotoxicity & depolarization

      • ATP depletion

      • ROS & inflammatory cytokines

    • Results in edema (cytotoxic) & cell death

    • Contributes to progressive increases in ICP

    • Where intervention is directed

• ICP Dynamics

  • ↑ ICP is a common and potentially deadly development of TBI

  • In order to treat it, you have to understand it

  • ICP = Intracranial pressure

    • The pressure exerted within the skull by the intracranial contents

    • Normal ICP in a dog is between 5-12mmHg

  • Normal Physiology

    • The brain receives 15 - 20% of the total cardiac output with each cardiac cycle

    • Adequate blood flow must be maintained

      • Brain has a ↑ metabolic rate

      • Dependence on nutrients (e.g. glucose, etc.)

    • Cerebral Perfusion Pressure (CPP)

      • The pressure of blood flowing to the brain

      • Reliant on a balance between MAP and ICP

        • ↓ CPP = ↑ MAP - ↑ ICP

      • The systemic circulation (MAP) must push against & overcome the blood & other tissues (CSF/brain) already in the skull (ICP) to get blood into the brain (CPP)

    • Cerebral Blood Flow (CBF)

      • The rate of blood delivery to the brain

      • Driven predominantly by CPP

      • CBF is regulated by cerebral vascular resistance (CVR)

        • Blood viscosity

        • Vessel diameter

          • Cerebral metabolic activity

          • Partial pressure of oxygen (O2)

          • Partial pressure of carbon dioxide (CO2)

        • ↑ CBF = ↑ CPP / CVR

      • CBF is kept constant by fluctuations in CVR to compensate for changes in CPP (↓ CBF = ↓ CPP /↑CVR)

  • Autoregulation

    • Autoregulation of blood flow occurs locally in the brain

    • The brain has an intrinsic ability to maintain CBF despite fluctuations in CPP

    • Chemical factors

      • Oxygen

        • ↑ PaO2 => vasoconstriction

        • ↓ PaO2 => vasodilation

      • Carbon dioxide

        • ↑ PaCO2 => vasodilation

        • ↓ PaCO2 => vasoconstriction

      • Nitric Oxide

        • ↑ NO => vasodilation

    • Myogenic factors

      • CBF remains constant when MAP = 50 - 150mmHg

      • Keeps CBF constant over a MAP range (50 - 150 mmHg)

    • Neurogenic factors

      • Parasympathetic = dilates

      • Sympathetic = constricts

• Monroe-Kelly Doctrine

  • Normal Physiology

    • 2 volume compartments

      • Brain tissue

      • CSF

      • Arterial and venous blood

  • Intracranial compliance (Monroe-Kellie Doctrine)

    • Fixed Calvarial Volume: V(brain) + V(CSF) + V(Blood) = constant

    • Intracranial compliance: ability of the intracranial contents to decrease in volume in an attempt to maintain normal ICP

    • ↑ ICP: compensation (i.e. "compliance") cannot occur to a sufficient degree

  • The skull is an enclosed space

  • There is only room for so many things: Brain, CSF, & blood

  • If 1 thing increases, 1 or more of the other things must decrease

  • If they can't => ICP will increase (& CPP & CBF will be compromised => brain tissue death/necrosis

  • With severe or ongoing injury (e.g. active cerebral bleeding), this can all happen very quickly

  • Summary

    • Trauma disrupts the BBB & autoregulation

    • CPP is compromised => more brain tissue death

    • If ICP rises too much => the brain will herniate (=> brain death & death of the individual)

    • All this mass pandemonium stabilizes after 72 hrs (the patient might worsen during that time) = get them through that & survival improves

• When autoregulation fails

  • Autoregulation requires functional and intact BBB

  • Trauma disrupts autoregulation, and affects CPP

  • ↑ ICP => Cushing's Reflex (hypertension and bradycardia)

  • What happens after ICP is elevated

    • Foramen magnum herniation

    • Rostral transtentorial herniation

    • Caudal transtentorial herniation

    • Transcalvarial/Herniation through a calvarial defect (e.g. fontanelle, fracture)

    • Subfalcine herniation

  •  Cerebral swelling can continue to worsen for up to 72 hours post-trauma

    • After 72 hours swelling will stabilize and begin to resolve over time

Adeptly assess a head trauma patient and diagnose traumatic brain injury (TBI)

• Head trauma

  • Epidemiology

  • Dogs and cats

    • Vehicular trauma

    • Missile injuries (e.g. gunshot wounds)

    • Animal bites

    • Falls

    • Crush injuries

    • Inadvertent or purposeful attacks from humans

  • ** consider polytrauma!!

• Traumatic Brain Injury

  • Can result from external injury, internal injury, or both (e.g. hemorrhage secondary to skull fracture)

  • High degree of morbidity & mortality

  • Fatality is due to progressive increases in ICP

  • TBI documented to occur in 25% of blunt trauma cases in dogs and cats

• Clinical Assessment

  •  Step 1: Initial Assessment = TRIAGE!!

    • Resuscitate and Re-evaluate

    • ABC's (Airway, Breathing, Cardiovascular)

    • Quick assessment tests (QATs)

      • Packed cell volume (PCV)

      • Total solids (TS)

      • Azostick (AZO)

      • Blood glucose (BG)

      • AFAST/TFAST*

    • Immediate assessment for

      • Hypo-/hyperthermia

      • Hypovolemic shock

      • Hypoxemia (PaO2 < 90 mmHg)

      • Hypotension (sysBP < 120mmHg)

    • Get these normalized first!

    • Modified Glasgow Come Score (MGCS)

• Step 2: Secondary Assessment

  • Assess for extent of injuries

    • Nervous system (e.g. vertebral fractures/luxations)

      • Increased ICP

      • fractures

    • Other body systems (lungs, abdominal organs, musculoskeletal system)

  • Complete physical assessment

    • Complete neurologic examination

    • Orthopedic examination

  • Additional bloodwork

  • Radiographs (thoracic/abdomen)

  • Imaging?

    • Neuroimaging

      • Skull radiographs (not very helpful)

      • Computed tomography (CT) - modality of choice

      • Magnetic resonance (MR) imaging

    • Imaging does NOT predict prognosis

    • No animal should die in radiology!!!

• Appearance of signs of ↑ ICP

  • Tachycardia, bradycardia

  • Ventricular arrhythmias

    • Catecholamine release (if CPP extremely low)

    • Results in myocardial ischemia

  • Abnormal respiratory rate and/or pattern

  • Deteriorating neurologic function

    • Biggest indicator of increased ICP

  • CUSHING'S REFLEX

    • Aka cerebral ischemic response

    • Indicates ↑ ICP (whether due to head trauma, mass effect, other causes)

    • Clinical manifestation

      •  Low or low-normal heart rate (< 60bpm), in the face of systemic hypertension (>250mmHg)

    • = the brain's "last ditch" effort for survival

Formulate a plan for stabilization and management, and recognize signs of increased intracranial pressure (ICP)

• Stabilize patient/Supportive care

  • ABC's (Airway, Breathing, Cardiovascular)

  •  Treatment of head trauma

    • Elevate head AND NECK/SHOULDERS to 30-45degree angle

    • Maximizes venous return without impairment of arterial flow to brain

      • To decrease ICP

    • AVOID JUGULAR COMPRESSION!! - jugular compression inhibits venous return from brain

      • ↑ ICP further

  • Fluid therapy

    •  Treat hypovolemic shock with fluid resuscitation

      • Restore NORMOVOLEMIA (and eventually euhydration)

      • Titrate all fluid administration to systemic blood pressure

      • Maintain MAP 80 - 120 mmHg to ensure CPP >60mmHg

      • Avoid overhydration

        • Can exacerbate cerebral edema

      • BUT, hypotension and cerebral ischemia are worse

        • DO NOT VOLUME-LIMIT FLUIDS TO VICTIMS OF SEVERE HEAD TRAUMA

    • Isotonic crystalloids (LRS or 0.9% saline)

      • 20 - 30ml/kg bolus over 15 - 20 min for shock; repeat PRN

    • Hypertonic saline (7% NaCl)

      • 4 - 5ml/kg over 3 - 5 mins for shock

    • Synthetic colloids (Hetastarch)

      • 10 - 20 ml/kg to effect (up to 40ml/kg/hr) for shock

    • Blood products

      • 1ml/kg of pRBCs or 2ml/kg of whole blood => increase PCV by 1%

        • Usually given over 4h (or faster if patient is unstable)

      • Coagulopathy: fresh froxen plasma (FFP)

        • 10 - 15 ml/kg, 2- 3 times per day until resolved

  •  Oxygenation

    • Maintain PaO2 > 90mmHg & PaCO2 > 30mmHg (on ABG)

    • Conscious patient, no neurologic deterioration - 40% [O2]

      • Facemask - used temporarily; used to stress patients

      • Oxygen cage/hood: generally ineffective; get rapidly depleted when opened => these patients need close observation

      • Nasal cannula or oxygen catheter (flow rate 100ml/kg/min): PREFERED

        • Apply topical lidocaine to avoid patient sneezing during placement => Valsalva maneuvers can ↑ ICP

      • Transtracheal oxygen catheter (flow rate 50ml/kg/min)

    • Unconscious patient, deteriorating neurologic status

      • Intubation and ventilation

      • Mechanical ventilation

      • +/- tracheostomy tube

    • Ventilatory rates: 15 - 20 breaths/min => PaCO2 levels 30 - 35 mmHg

• Medical treatment of head trauma

  • Osmotherapy

  • Mannitol (20 and 25%)

    • For treatment of ↑ ICP

    • Mechanisms of action

      • Increases IV osmolarity; result is osmotic shift of edema fluid (intracellular) into IV space

      • Decreases blood viscosity (& CVR) => reflex vasoconstriction (brain)

      • Free-radical scavenging

      • Reduction in CSF production

    • Concerns with mannitol

      • Use with ongoing brain hemorrhage (it's OK)

      • Other concerns: appropriate administration of mannitol makes these unlikely

        • "reverse osmotic shift"

        • Dehydration

        • AKI (due to renal vasoconstriction)

    •  Contraindication

      • Hypovolemia

      • Electrolyte imbalances

      • Use caution in renal failure/insufficiency, heart failure

    • Useful guidelines for mannitol

      • Reserved for the severe head trauma patient

        • MGCS < 8

        • Deteriorating neurologic patient

        • A patient failing to respond to other treatment

        • Positive response to initial mannitol dose

      • No more than 3 boluses within 24 hours and no CRIs => to avoid "reverse osmotic shift", AKI, etc.

      • Hemodynamically stable patient

    • 1g/kg IV over 15 minutes

      • +/- follow with 0.7 mg/kg furosemide IV 15 mins after mannitol administration finishes

        • To prolong and enhance the effect of mannitol

    • Onset: 3 - 30 minutes

    • Duration: 2 - 5 hours

    • Monitoring

      • Measured (not calculated) osmolality < 320mOsm/l

      • Serum electrolytes

  • Hypertonic saline (3, 7.5, 24%)

    • 7% NaCl: 4 - 6ml/kg IV x 15 - 20 min

    • Mechanisms of action

      • Improved hemodynamic status vis

        • Volume expansion

        • Positive inotropic effects

      • Beneficial vasoregulatory effects

      • Immunomodulatory effects

    • Contraindications

      • Significant sodium derangements (esp. hyponatremia)

      • Dehydration

• Analgesia

  • Pain will contribute to ↑ ICP

  • Analgesia must be provided to these patients

  • Options: opiates, gabapentin, NMDA antagonists, and injectable NSAIDs

    • Monitor for respiratory depression

    • May cause sedation and confound assessment of mental status

    • CRI administration is ideal

      • Minimize adverse effects like respiratory depression and breakthrough pain

      • Also allows for better control and titration of effect

• Steroids should NOT be given in head trauma cases!

  • They are no longer recommended and have been shown to be detrimental

  • Steroids have no benefit in head trauma

    • Any claim of promoting perfusion and improving mucous membrane color is purely due to vasodilatory effects, not true perfusion

• Glucocorticoid effect may exacerbate hyperglycemia, which is correlated with poor prognostic outcome in head trauma

• Hyperglycemia with cerebral ischemia => promotes an anaerobic glycolysis => increases lactic acid concentration (remember those secondary injury effects)

• Surgical treatment of head trauma

  • Craniectomy with durotomy

    • Surgical removal of bone, with durotomy

      • Reduces ICP by enlarging cranial vault

    • Must be large defect

      • Prevent brain tissue from herniating through craniectomy defect, cause entrapment, and impairment of local blood flow to tissue

    • Indications

      • Deterioration despite aggressive medical therapy

      • Subarachnoid/subdural hemorrhage

      • Imbedded or infected skull fracture fragments

• Additional therapy

  • Hyperventilation

    • May help decrease ICP by lowering CO2 (high CO2 => vasodilation)

    • Maintain PaCO2 between 30 - 35mmHg

      • CO2 < 30 mmHg => vasoconstriction => decreased CBF and ischemia

    • However it is NOT PRACTICAL in a non-anesthetized, non-intubated patient

  • Barbiturate coma

    • May be indicated in the most severe cases, refractory to other therapies

    • Used in hemodynamically stable patients

      • In humans, EEG is used to titrate level of sedation/anesthesia

  • Hypothermia

    • Was once thought to improve outcome

      • Thought to decrease ICP by decreasing cerebral metabolic demands

    • However, prognosis declined during rewarming phase

    • Personal opinion: do not actively warm patients who are hypothermic; but do not actively cool them

• Summary: treatment of a head trauma patient

  • Tier 1 therapies

    • Indications

      • All trauma patients

    • Always following triage and the ABCs

    • Treat hypovolemic shock

    • Normalize MABP

    • Improve oxygenation

      • Oxygen therapy

    • Elevate head/neck/shoulders

    • Analgesia

    • Give AEDs for seizures

  • Tier 2 therapies

    • Indications: ↑ ICP

      • Deterioration

      • MGCS < 8

    • Mannitol or hypertonic saline

  • NO STEROIDS!!!!!!!!!

  • Tier 3 therapies

    • Indications

      • Failed other aggressive therapy

        • Deteriorating patient

        • Failure to improve

      • Subarachnoid/subdural hemorrhage

      • Imbedded or infected skull fracture fragments

    • Craniectomy with durotomy

Predict prognosis of a patient based on the neurologic assessment

• Prognosis

  • Dependent on severity and response to treatment

  • Useful predictors:

    • Level of consciousness

    • Presence or absence of brainstem reflexes

    • Age and general physical status

    • Presence and extent of other concurrent injuries

  • Use the MGCS!

  •  The trend in the 1st 48hrs is more valuable than an isolated neurologic evaluation

    • PERFORM SERIAL NEUROLOGIC ASSESSMENTS: MGCS

  • Modified Glasgow Coma Score (MGCS)

    • Almost linear relationship => between score and probability of survival within the 1st 48 hrs

      • High score => high probability of survival

      • Low score => unlikely to survive

    • MGCS of >8 is associated with ~50% chance of survival

  • The recuperative ability of brain-injured dogs and cats is tremendous

  • Aggressive therapy may be successful in many hopeless cases

  • Severely affected animals can achieve a functional recovery with proper patient assessment and monitoring, appropriate aggressive treatment, and time

  • Hyperglycemia

    • A significant indicator of severity of injury

    • A potent predictor of the patient's outcome - in human's

      • Does not seem to be the same in dogs and cats

      • Nevertheless, iatrogenic hyperglycemia should be avoided in patients with head trauma

  • Complications of head trauma

    • Coagulopathies (e.g. disseminated intravascular coagulation; DIC)

    • Pneumonia

    • Fluid/electrolyte abnormalities (e.g. central diabetes insipidus)

    • Sepsis

    • Seizures

      • Around the time of trauma (suggesting intraparenchymal hemorrhage)

      • Months to years after trauma (development of a glial "scar" seizure focus)

• Summary: prognosis of a head trauma patient

  • Generally, prognosis = guarded/poor

    • More severe signs = less chance of recovery

  • Biggest predictor: LOC & brainstem reflexes, i.e. MCGS

  • The brain has large recuperative capabilities

  • 48 hrs trends of neurologic status are more predictive of outcome than a single timepoint

    • Use MGCS - provides a quantitative method for monitoring trends

  • Hyperglycemia and hypotension are associated with negative outcome

Equine Neurology

• Equine Neurology

  • Subtle deficits can be a problem

  • Safety

  • Liability

  • Diagnostic limitation

  • Return of function

  • Recovery and rehabilitation

• Diagnostic approach

  • History

  • Signalment

  • Physical examination

  • Neurologic examination

    • Observation in environment

      • Alertness; responsiveness

      • Symmetry

      • Body position

      • Abnormal movements

        • Local: muscle fasciculation/twitches

        • Whole body: seizures/head pressing/circling

    • Mentation and awareness

    • Cranial nerve examination

• Posture and proprioception

  • Walk

  • Trot

  • Under saddle

  • Challenging maneuvers

    • Head up, circling, tail pull, backing, over a curb, hill, blindfold

    • Goal: exacerbate subtle abnormalities

  • Ataxia

    • Loss of coordination

    • Truncal sway

    • General proprioceptive deficits

    • Inconsistent foot placement

    • Irregular irregularities

    • Interference

    • Excessive lifting of feet and uncontrolled placement

    • Does not seem to know where feet are placed

  • Paresis

    • Toe dragging

    • LMN vs UMN

    • Knuckling

    • Stumbling

    • Inability to resist tail pull

  • Dysmetria

    • Extent of joint movement

    • Hypometria: too little joint movement

      • Stiff

      • Tin soldier

    • Hypermetria: too much joint movement

      • Floating: lifting thoracic limbs too high

  • Proprioception

    • Recognize position in space

  • Spasticity - not really measured in horses

• Gait evaluation

• Tail and anus

• Ancillary diagnostics

  • Repeated neurologic exams

  • Diagnostic imaging

  • Lab analysis

    • Blood

    • CSF analysis

    • Infectious disease diagnostics

    • Histopathology

  • Electrodiagnostics (EEG)

• Neuroanatomic Localization

  • Central or peripheral

  • Focal or diffuse

  • Rostral or caudal to foramen magnum

  • CNS

    • Brain

      • Infectious

      • Seizures

      • Metabolic

      • Neoplasia

      • Trauma

      • Toxins

      • Foals: HIE

    • Cranial nerves

      • Trauma

      • Guttural pouch disease

        • Biggest reason

      • Otitis

      • Infectious

    • Foramen Magnum

    • Spinal cord

      • CVCM

      • EDM/eNAD

      • Infectious (EPM/EHM)

      • Trauma

      • Neoplasia

• Cranial nerve disease

  • Rostral to foramen magnum

  • Which ones affected?

  • How many affected?

  • Function can be disrupted anywhere between the cranial nerve nuclei in the brainstem to the nerve ending in the periphery

  • Many cranial nerves travel along the surface of the guttural pouches before termination in the periphery

  • VII dysfunction common after trauma (tight halter)

  • If CN V, VII, VII, IX, X are affected the guttural pouch on the affected side should be inspected

• Spinal Cord Disease

  • Normal mentation

  • Ataxia, dysmetria, paresis - most common: 4 limbs

  • Cervical Vertebral Compressive Myelopathy (CVCM)

    • Symmetrical ataxia, dysmetria, paresis; 4 limbs

    • Normal mentation, intact peripheral nerve function

    • Focal spinal cord compression

    • Affects primarily young, large breed, fast growing, male horses

    • Developmental orthopedic disease - multifactorial etiology; sometimes horses have OCD lesions elsewhere (esp distal limbs)

    • In older horses secondary to degenerative joint disease affecting articular process joints and possibly intervertebral disk space

    • Survey radiographs provide valuable info

    • Diagnosis by (CT) myelography

    • Dietary caloric restriction in growing horses (<1-2 yrs of age)

    • Cervical vertebral interbody fusion surgery: 65-70% of horses improve and return to athletic use

  • Equine Protozoal Myeloencephalitis (EPM)

    • Sarcocystis neurona; Neospora hughesi

    • Multifocal

    • Progressive disease

    • Geographic range of disease defined by range of opossum

    • Clinical signs

      • Variable

      • Spinal cord

        • Asymmetry

        • Muscle atrophy

        • Ataxia, dysmetria, paresis

      • Brainstem

        • CN VII, VIII

        • Seizures

        • Lethargy

    • Although EPM is characterized by asymmetric clinical signs, it can cause symmetric disease, and EPM is therefore a main differential diagnosis for CVCM

    • Diagnosis

      • Challenging

        • Variable clinical signs

        • High seroprevalence

      • Antemortem

        • SAG2,4/3 ELISA

        • (surface antigen)

        • Confirm intrathecal antibody production via serum:csf titer ratio

    • Presence of antibodies in CSF can occur via

      • Ab production in the CNS

      • Leakage over an intact BBB

      • Leakage over a diseased BBB

      • Iatrogenic contamination during CSF collection

    • Treatment

      • Ponazuril - Marquis

        • Disrupts the "apicoplast" organelle which is a chloroplast-related organelle important in energy metabolism and cell division

        • 28 day treatment duration

        • 63% efficacy

      • Sulfadiazine/pyrimethamine (ReBalance)

      • Diclazuril (Protazil)

  • Equine Degenerative Myelopathy (EDM)/Equine Neuronal Dystrophy (eNAD)

    • Diffuse neurodegenerative disease; EDM: More advanced form

    • Pathophysiology: genetic and environmental factors: predisposition to vitamin E deficiency

    • Clinical signs: symmetric ataxia, proprioceptive deficits; (decreased menace, lethargy, behavior change)

    • Onset: 1-12 months of age; then unchanged or progress before stabilizing within days to months

    • Occasionally: late-onset in older horses

    • Differential diagnoses: CVCM, EPM, EHM (equine herpes virus myeloencephalopathy)

    • Diagnosis

      • Suggestive

        • Exclusion other conditions

        • EDM confirmation in bloodline

        • Low serum vitamin E (<2.0ug/mL)

        • Deficient dietary vitamin E

      • Confirmation

        • Post-mortem

    • Treatment/prognosis

      • Vitamin E supplementation

      • Prognosis is poor: unlikely improvement of clinically affected animals is seen after supplementation

      • Supplementation of breeding stock and young horses can reduce incidence and severity of signs

  • Trauma (not very common)

• Peripheral Neuropathies

  • Affected motor nerve

    • Hypotonic/atonic effector muscle

    • Muscle atrophy

  • Classic

    • Radial n/brachial plexus

    • Suprascapular n

    • Femoral n

    • Obturator n

    • Sciatic n

  • Radial n paralysis

    • Non-weightbearing

    • Dropped elbow

    • Inability to advance limb

    • Humeral fx

    • Trauma

    • Post-anesthesia

  • Femoral n paralysis

    • Non-weightbearing

    • Flexion of stifle, hock, fetlock

    • Trauma

    • Post-anesthesia

    • Dystocia

  • Sweeney/Suprascapular n paralysis

    • Muscle atrophy

    • Abnormal gait with shoulder exo-rotation

    • Trauma to nerve at point of the shoulder

• American Association of Equine Practitioners

  • CORE

    • Rabies

      • Zoonotic! Causes progressive encephalomyelitis in mammals

      • Transmission through direct contact: saliva (biting) or nervous tissue

      • Virus remains infectious in a carcass < 24 hours

      • Reservoirs: bat, skunk, racoon, fox

      • Suspects:

        • Clinical signs

        • In endemic areas

        • Not vaccinated

      • Variable incubation period

      • Viral shedding prior to onset of clinical signs

      • Centripetal: virus travels in peripheral nerves to CNS at ~1cm/day

      • Central: CSF contains virus

      • Centrifugal: saliva contains virus

      • Post-mortem diagnosis: IFAT on brain tissue or presence of Negri bodies

      • Clinical signs in horses

        • Ataxia and paresis (43%)

        • Lameness (29%)

        • Recumbency (14%)

        • Pharyngeal paralysis (10%)

        • Colic (10%)

      • Fatal encephalopathy: 5-7 days

      • VACCINATE

    • Tetanus

      • Clostridium tetani

      • Tetanolysin: tissue destruction

      • Tetanospasmin: neurotoxin

        • Travels through lymphatics to NMJ and then to CNS

      • Renshaw cells of the spinal cord: Blocks GABA and glycine

      • Clinical signs

        • Within 5-10 days of infection

        • Increased sensitivity/anxiety

        • Stiff gait/sawhorse stance

        • Altered facial expression

          • Risus sardonicus

          • Protrusion of 3rd eyelid

          • Spasms of the masseter: lockjaw

        • Colic

      • Diagnosis

        • Clinical signs

        • Vaccination status

      • Prevention: tetanus toxoid

      • Treatment

        • Protection from loud noises and light

        • Antibiotics

        • Tranquilizers

        • Tetanus toxoid

        • Tetanus antitoxin

    • Equine encephalitis viruses:

      • Eastern Equine Encephalomyelitis

      • Western Equine Encephalomyelitis

      • West Nile Virus Encephalomyelitis

      • Clinical signs

        • EEE/WEE: inapparent infection with fever ~2 days after infection

        • WNV: 10% develop signs

        • WNV: incubation period 9-11 days

        • Generalized febrile illness

      • Clinical encephalomyelitis

        • ~5 days after infection

        • Changes in mentation

          • Obtundation

          • Dementia

            • Head-pressing

            • Irritability

            • Leaning

            • Teeth-grinding

            • Compulsive walking

            • Circling

        • Cranial nerve deficits

          • Blindness

          • Head tilt

          • Dysphagia

        • Muscle twitching

        • Recumbency

        • Death: 2-3 days later

      • Mortality

        • EEE: 75-95%

        • WEE: 19-50%

        • VEE: 19-83%

        • WNV: 30%

          • When recumbent: 80%

      • Diagnosis

        • IgM capture ELISA

          • IgM elevated for 4-6 weeks

          • Differentiate vaccine from disease

      • Control

        • Mosquito control

        • Vaccination

        • Surveillance

      • Treatment

        • Supportive care

        • Anti-inflammatories

        • Interferon

        • IgG

      • Prognosis

        • 30% can recrudesce within 2 weeks

        • 10% of recovered animals retain long-term complications

  • Risk based

    • Equine herpes virus 1/4

      • Equine herpes virus myeloencephalopathy

        • Equine herpes virus -1

        • Rare but severe

        • Contagious - outbreak scenarios

        • Impact on horse industry

        • Races, competitions, transport, quarantine

        • Pathogenesis

          • Primary infection at respiratory epithelium

          • Viremia

          • Infection of endothelial cells

          • Spinal cord grey and white matter

          • Infrequently brainstem

        • Clinical signs

          • Severity varies

          • Asymmetric ataxia, dysmetria, paresis

          • Recovery depends on extend of damage

        • Risk factors

          • Outbreak of fever & respiratory disease

          • Following return from an event

          • Fall-Winter-Spring

          • Tall breeds

        • EHM is an ascending myelopathy that typically results in a significant discrepancy between thoracic and pelvic limb signs resulting in dog-sitting, loss of tail tone and incontinence (UMN bladder)

  • No vaccine

    • Equine protozoal myeloencephalitis

Brainstem, Vestibular and Deafness

Recognize the clinical signs and neurological exam findings associated with brainstem and/or vestibular disease; and be familiar with those findings that discriminate between central and peripheral disease.

• Brainstem - clinical signs

  • General proprioceptive ataxia

  • Postural reaction deficits (ipsilateral)

  • UMN paresis (hemi or tetra)

  • Cranial nerve deficits (ipsilateral)

  • Change in mentation if ARAS affected

  • +/- vestibular signs

• Signs of vestibular disease

  • Ataxia

    • Lean, list, fall or roll

    • Loss of balance

  • Head tilt

  • Circle

  • Hemiparesis/postural reaction deficits

    • With central disease ONLY

  • Nystagmus

    • Peripheral disease

      • Horizontal or rotary

      • Fast phase ALWAYS away from lesion

      • Does not change fast phase direction with position changes

    • Central disease

      • Horizontal, rotary or vertical

      • May change +/- with position changes

  • Strabismus ("forced") - abnormal change in eye position

    • Usually ventral or ventrolateral

  • Horner Syndrome

    • Sympathetic trunk runs near bulla

  • Facial paresis/paralysis (CN VII)

    • Can see with peripheral or central

  • Paradoxical Vestibular Disease

    • Cerebellar involvement

      • Lack of inhibition

      • Caudal cerebellar peduncle

      • Flocculonodular lobe

    • Head tilt away

    • Falling, leaning away

    • Fast phase nystagmus towards

    • Postural reaction deficits on same side of lesion (only reliable way to localize lesion)

• Vestibular Disease Chart

Be familiar with the differential diagnoses of peripheral and central vestibular disease.

• Peripheral

  • Otitis media/interna

    • Bacterial, yeast, mites, foreign body

  • Idiopathic vestibular disease

    • "old dog vestibular disease"

    • Cause unknown

  • Congenital vestibular diseases

  • Hypothyroidism

    • Pathophysiology not known - theory: ischemic neuropathy of vestibulocochlear nerve

    • Signs usually resolve with treatment

  • Feline inflammatory polyps

    • Non-neoplastic masses

  • Aural neoplasia

    • Ceruminous gland adenocarcinoma, squamous cell carcinoma, fibrosarcoma

  • Trauma

  • Toxic (aminoglycosides)

• Central

  • Inflammation

    • Granulomatous Meningoencephalomyelitis (GME)

    • Breed-associated meningoencephalitis

  • Infection

    • Distemper, FIP, Ehrlichia canis, Neospora, toxoplasma, cryptococcus, anaplasma, bartonella

    • Cuterebra migration

  • Neoplasia

    • Cerebellopontine anglemeningioma

    • Fourth ventricular choroid plexus papilloma (carcinoma)

    • Lymphoma

    • Glioma

      • Astrocytoma

      • Oligodendroglioma

    • Metastatic disease

  • Drug toxicity

    • Metronidazole

      • Usually seen with higher doses for long period of time

      • DO NOT DOSE HIGHER THAN 15mg/kg BID

        • Signs of central vestibular disease

        • If severe - recumbent, opisthotonus, muscle tremors, spasms, severe nystagmus +/- seizures

        • Binds and blocks GABA receptors

  • Vascular events

    • Acute brainstem/cerebellar ischemic or hemorrhagic infarct

    • Central vestibular signs can be acute and severe

  • Congenital malformations

  • Thiamine deficiency

  • Trauma

Be able to formulate a diagnostic plan for animals with vestibular disease

• Do a thorough neurologic examination

  • This can help rule OUT peripheral disease

  • Remember: peripheral disease can mimic central disease so… CANNOT rule out central disease

• Peripheral

  • Otitis media/interna

    • Otoscopic exam, culture +/- radiographs, CT, MRI

    • Most common cause of VII and VIII dysfunction

      • But could be central (medulla)

    • Can also see Horner Syndrome

      • Sympathetic nerve involvement

  • Idiopathic vestibular disease

    • Geriatric dogs

    • Acute peripheral vestibular signs

    • No other cranial nerve deficits or Horner Syndrome

    • Signs can be severe - often difficult to examine

    • Diagnosis by exclusion

  • Congenital vestibular diseases

  • Hypothyroidism

    • Low serum total and free T4

    • Elevated endogenous TSH level

    • T4 alone is NOT diagnostic

  • Feline inflammatory polyps

    • Most commonly develop within tympanic cavity or in the pharyngeal region via eustachian tube

    • Visual inspection of both oropharynx and ear canals

    • MRI scan - best diagnostic tool if a bulla polyp is suspected

  • Aural neoplasia

  • Trauma

  • Toxic (aminoglycosides)

    • History of exposure to drugs that affect inner ear

    • Aminoglycosides

      • Streptomycin, amikacin, kanamycin, neomycin, gentamycin, vancomycin

    • Clinical signs usually unilateral

    • Recovery if rapid diagnosis and exposure is short

Be able to formulate a treatment plan for the common differentials associated with vestibular disease (those differentials listed in bold in the table). *Dosages are not required, but you should be able to list the name of the medication used, if it is discussed in the class notes.

• Peripheral

  • Otitis media/interna

    • Target underlying cause, based on culture/sensitivity

    • Anti-inflammatory doses of prednisone (0.5mg/kg BID) for 3-4days

    • Systemic antibiotics - Clavamox, Fluoroquinolones, Imipenem, Doxycycline

      • Long treatment (3 months or more) if intracranial extension

    • Myringotomy or bulla surgery if intracranial extension

    • Avoid flushing of the bulla/middle ear

  • Idiopathic vestibular disease

    • Supportive care

    • Diazepam

    • Meclizine or maropitant for nausea if necessary

    • Full recovery usually take 1-3 weeks (residual head tilt may persist)

    • Physiotherapy often speeds recovery

    • Prognosis - excellent with recurrence uncommon

  • Congenital vestibular diseases

  • Hypothyroidism

  • Feline inflammatory polyps

    • Surgical removal via bulla osteotomy

    • Surgical removal via the oropharyngeal route

    • If removed without bulla osteotomy - 50% recurrence

    • Prognosis - excellent

      • Recurrence possible

  • Aural neoplasia

    • Treatment and prognosis vary w tumor type and location

  • Trauma

  • Toxic (aminoglycosides)

• Central

  • Vascular events

    • Steroid therapy NOT recommended

      • No benefit, may be detrimental

    • Supportive care and intensive physiotherapy

    • Prognosis usually fair to good although recovery can take several weeks to months

    • Repeat infarcts can occur

  • Metronidazole toxicity

    • Discontinuation of the drug

    • Supportive care

    • Diazepam - normal neurotransmitter that binds GABA and blocks metronidazole

      • Shortens recovery time

        • Recovery 1-2 weeks

CEREBELLAR

WATCH MINIM LECTURE: TREMORS

Localize a patient’s neurologic dysfunction to the cerebellum based on a neurologic examination

• Clinical Signs of Cerebellar disease

  • Gait/posture: cerebellar ataxia

    • Dysmetria (hypermetria, hypometria)

      • Rate: onset of voluntary movement (protraction) is delayed

        • Followed by "bursty" movements

      • Range: greater movements of the limbs in all ranges of motion

      • Force: limb raised too high in protraction (excessive joint flexion)

        • Forcefully returned to the ground (excessive joint extension)

      • Hypermetria - overreaching ("toy soldier" with stiff hypermetric limbs)

      • Hypometria - underreaching

      • "hen-pecking" movements due to lack of fine motor control (overshoots target)

    • Truncal sway (truncal ataxia)

    • Base-wide stance/gait

    • Cerebellum does not initiate motor activity

      • Paresis is not a sign of (pure) cerebellar dysfunction

  • Multiplanar intention tremor (dysmetria of the head & neck)

    • At rest, tremor is absent; with initiation of movement, tremor appears

  • Weakness is NOT a characteristic of cerebellar disease

  • Postural reactions (paw placement, hopping)

    • Present, but may be "sloppy" or "choppy"

  • Cranial nerves (CNs)

    • Ipsilateral menace deficit

  • Paradoxical vestibular disease

Create a list of differential diagnoses based on the clinical presentation (signalment, history, and a cerebellar neuroanatomic localization), including the common types of tremors (those listed in bold in the table [see handout])

• Feline Cerebellar Hypoplasia

  • Clinical signs

    • Apparent at onset of locomotion

    • Cerebellar ataxia - symmetric

      • Truncal sway

      • Intention tremor

      • Hypermetria/dysmetria

• Cerebellar Abiotrophy

  • Normal at birth

  • Progressive disease; gradual loss of cells

  • Clinical signs first appear from 2-36 months

• Infarction

  • Predisposing factors/etiologies

    • Hypertension

    • Thromboembolic disease

    • Atherosclerosis

      • Hypothyroidism

    • Septic or neoplastic embolism

    • Aberrant parasite migration

    • Vasculitis

      • Rickettsial infections

    • Coagulation disorders

    • Neoplasia

    • Trauma

• Neoplasia

  • Primary

    • Meningioma

    • Glioma

    • Choroid plexus tumor

    • Medulloblastoma (Primitive neuroendocrine tumor; PNET)

    • Histiocytic sarcoma

    • Lymphoma

  • Secondary

    • Metastatic neoplasia

      • Hemangiosarcoma, lymphoma

    • Multilobular osteochrondrosarcoma (MLO)

    • Carcinomas & other sarcomas

• Corticosteroid-responsive tremor syndrome ("white shaker dog" syndrome)

  • Typically small breed dogs

  • Fine whole-body generalized tremor

  • May have other cerebellar signs: menace deficits, ataxia, possible head tilt/nystagmus

  • May have difficultly ambulating if tremor is severe

  • Elevated rectal temperature in some cases (due to muscle activity)

• Idiopathic head tremor syndromes

  • Episodic tremors of the head only

  • Equal oscillations (had should not be pulled toward one specific side)

  • May be side-to-side ("no") direction or up-down ("yes") direction

• Hypomyelination/dysmyelination

Formulate a diagnostic plan for animals with cerebellar disease, using the most likely diagnosis

• Cerebellar Abiotrophy

  • Diagnosis

    • Breed

    • Clinical history

    • DNA testing for some breeds

      • Autosomal recessive: Kerry Blue Terriers, Gordon Setters, Rough-Coated Collies

      • Arabian horses

    • Family history

    • MRI

    • Histopathology (post mortem)

Build a treatment plan for the common differentials associated with cerebellar disease (those differentials listed in bold in the table [see handout])

• Feline Cerebellar Hypoplasia

  • Treatment: None

  • Cats compensate; clinical signs may even improve slightly with time

• Cerebellar Abiotrophy

  • No treatment

• Infarction

  • Based on underlying disease if identified

    • Kidney, cardiovascular (hypertension, valvular disease), infection, coagulopathy (endocrinopathy)

  • Supportive care

• Neoplasia

• Corticosteroid-responsive tremor syndrome ("white shaker dog" syndrome)

  • Immuno-suppressive corticosteroids

    • Prednisone

  • Valium to minimize clinical signs in patients with hyperthermia or severe tremors

  • +/- doxycycline and Clindamycin in case of underlying infectious diseases

• Idiopathic head tremor syndromes

  • Often can be distracted out of episode with strong stimulus. Often petting is enough stimulus

  • Anti-convulsant medications if episodes are severe or frequent

 Neuromuscular Disease

Recognize the clinical signs and neurological exam findings associated with neuromuscular disease

• The neurological exam

  • Cranial nerve reflexes

  • Gait and postural reactions

  • Muscle bulk and tone

  • Spinal reflexes

    • Withdrawal

    • Patellar

• Tetraparesis, exercise intolerance and collapse

• Stiff/stilted gait, with reduced stride length, bunny hopping, may fatigue

  • Sensation/proprioception usually normal

• Narrow based stance

• Tremors/fasciculations

• Regurgitation/altered esophageal motility

• Myalgia

• Dysphoria

• Reduced reflexes and tone

• Muscle atrophy