Small Animal Neurology Flashcards
What are the 4 questions you should ask when dealing with a neurological patient
1) Is it neurologic?
2) Where is it?
3) What is it?
4) How bad is it?
What are your two options for neuroanatomic diagnosis
Is it
a) Intracranial or
b) Extracranial
What are the different 5 different spinal cord segments
1) C1-C5
2) C6-T2
3) T3-L3
4) L4-S3
5) Caudal
What are the components of the CNS
a) Brain (intracranial)
b) Spinal cord (extracranial)
What are the components of the peripheral nervous system (PNS)
a) Cranial nerves (Intracranial)
b) LMN (Neuron cell body, spinal nerves, peripheral nerves, NMJ, muscle) - extracranial
What are the components of a neurologic exam
1) Onset and progression
2) Mental status and behavior
3) Cranial nerves
4) Postural reactions
6) Spinal reflexes, muscle mass, and tone
7) Perception of sensory stimuli and pain
How is gait generated
Motor: Initiation and Strength
*Cerebrum (primary motor cortex; parietal lobe) + brainstem (red nucleus and reticular formation
Sensory: Coordination
Where is the primary motor cortex?
in the parietal lobe of the cerebrum
What are the components of spinal cord segments (UMN)
1) Neuron cell bodies (grey matter in brain)
2) Axons descend all spinal cord segments
3) Synpase on LMNs (all spinal cord regions)
What are the functions of UMN and spinal cord segments
1) initiate voluntary motor function
2) Maintain tone to antigravity muscles -> posture
3) Inhibit to extensor muscles -> moderate activity
What are the components of LMN and spinal cord segments
1) Neuron cell bodies (grey matter all levels and intumescence)
2) Spinal nerve, nerve root, nerve
3) Neuromuscular junction
4) Muscle
What are the functions of LMN and spinal cord segments
link between CNS (UMN) and effector muscles
direct innervation of effector muscles
What spinal cord segments are associated with UMN
C1-C5
T3-L3
What spinal cord segments are associated with LMN
C6-T2
L4-S3
efferent motor tracks
caudally direct tracts from the brain (UMN) to the muscles (LMN) to produce movement
afferent sensory tracks
cranially directed tracts from muscles (LMNs) to brain (UMNs) to produce coordination
How is coordination produced
afferent sensory tracks- cranially directed tracts from muscles (LMNs) to brain (UMNs)
Partial efferent block
a lesion that some signal gets through but there is a block to the signal to the LMNs/muscles (effector organ)
What sign might you see if something goes wrong with the motor tracts
Weakness
What will you see if there is a lesion that blocks the signal getting to the UMNs
Sensory deficits
What sign might you see if something goes wrong with the sensory tract
Ataxia
How do motor gait deficits present, how about sensory gate deficits
Motor: Weakness
Sensory: Ataxia
When can you see both weakness and ataxia together
UMN spinal cord region
hemi-
word to describe which limbs are affected
Just one side
A word to describe only the 2 pelvic limbs being affected
Para-
What changes to the stride do you see with UMN deficits
Increased stride length
Increase extensor tone (spastic)
Normal/Increased reflexes
Standing or walking on dorsum of foot
Draggin or scuffin the dorsum of foot (nail wear)
What changes to the stride do you see with LMN deficits
Decreased stride length
Decreased extensor tone (flaccid)
Decreased reflexes
Is increased stride length seen with UMN or LMN deficits
UMN
Is decreased extensor tone seen with UMN or LMN deficits
LMN
Do you see decreased reflexes with UMN or LMN deficits
LMN
Do you see flaccid paresis/ paralysis with LMN or UMN
LMN
Do you see spastic paresis/paralysis with LMN or UMN
UMN
Do you see normal to increased reflexes in LMN or UMN deficits
UMN
Do you see rapid muscle atrophy in LMN or UMN deficits
LMN- severe (rapid 5-7 days) denervation atrophy
What muscle atrophy is seen in UMN deficits
None/mild
occurs slowly
disuse atrophy
What is the muscle tone of LMN deficits
Hypotonic/flaccid
What is the muscle tone of UMN deficits
Normal to hypertonic/spastic
T/F: Paresis localizes to LMN lesions and paralysis localizes to UMN
False- they dont localize to any part of system, just describe severity
T/F: paresis is more muld and paralysis is more severe but both are signs of weakness
True
Neurogenic atrophy
muscle atrophy from UMN deficit, occurs slowly
disuse atrophy
foot placement that is regularly irregular
lameness
foot placement that is irregularly irregular
ataxia
What are the 3 different types of ataxia
1) Cerebellar ataxia (cerebellum)
2) Vestibular ataxia (vestibular system)
3) General proprioceptive ataxia- caudal brainstem and spinal cord
What do you see with cerebellar ataxia
Hypermetria
Overflexion of joints (carpi)
What do you see with general proprioceptive (GP) ataxia
Over-reaching
over extension of joints (carpi)
Do you see over flexion or extension with cerebllar ataxia
over flexion of joints (carpi)
Do you see over flexion or extension with GP ataxia
Over extension of joints
What limbs are affected with general proprioceptive ataxia
All limbs caudal to the lesion
What limbs are affected with cerebellar ataxia
all limbs
What limbs are affected with vestibular ataxia
all limbs
What is the stride length of a patient with cerebellar ataxia
Hypermetria/overflexion of joints or hypometria/underflexion
T/F: patients with cerebellar ataxia have proprioceptive deficits and paresis
False
T/F: patients with vestibular ataxia have proprioceptive deficits and paresis
True- for centra
False- for peripheral
Do patients with cerebellar ataxia have symmetric or asymmetric gait symmetru
Symmetric but focal lesions are asymmetric
Where might there be a lesion if the patient has vestibular ataxia
1) CN VII
2) Brainstem
3) Cerebellum
What is the stride length of patients with general proprioceptive ataxia
longer (over-reaching, solder marching)
UMN hypermetria
Where might there be a lesion if the patient has general proprioceptive
1) Brainstem
2) Spinal cord (C1-C5, T3-L3)
What do postural reactions tell us
not much, just that the nervous system isnt normal
What the the transmission route when you test proprioception with the patient’s foot
1) Muscle and joint receptors
2) Nerves (LMNs)
3) Dorsal root ganglia
4) Spinal cord (dorsal column/medial lemniscus pathways)
5) Brainstem (medulla, pons, midbrain)
6) Thalamus
7) Cerebral somatosensory cortex (parietal lobe)
What would you see with a C1-C5 spinal cord lesion
Thoracic limbs: UMN + GP ataxia
Pelvic Limbs: UMN +GP ataxia
What would you see with a C6-T2 spinal cord lesion
Thoracic limbs: LMN (no ataxia)
Pelvic limbs: UMN +GP ataxia
What would you see with T3-L3 spinal cord lesion
Thoracic limbs: Normal
Pelvic Limbs: UMN + GP ataxia
What would you see with L4-S3 spinal cord lesion
Thoracic limbs: normal
Pelvic limbs: LMN (no ataxia)
Myotatic reflexes of the thoracic limbs
Triceps
Biceps
Extensor carpi radialis
Myotatic reflexes of the pelvis limbs
Patellar
Cranial tibial
Gastrocnemius
What is another name for Acute polyradiculoneuritis
Coonhound paralysis
Acute polyradiculoneuritis
“Coon hound paralysis”
affects predominantly the ventral (motor) nerve roots and nerves and thus causes profound weakness
*Will have better sensory function (paw placement) than motor function (hopping which requires more strength0
Idiopathic or can occur following exposure to antigenic stimulation
Lesions that are rostral to midbrain create _______ deficits
contralateral
Lesions that are caudal to midbrain create _________ deficits
ipsilateral
What is the syndromes name of only reacting to one half of the environemt
Hemineglect
Hemineglect Syndrome
“Hemi-inattention” “Unilateral neglect” “hemi-spatial neglect”
Gait is generated in the
Brainstem and cerebrum
Proprioception is sensed in the
brainstem and cerebellum
What are the clinical signs of forebrain disease
Mental: Altered (confusion)/ behavior change
Cranial nerves: Contralateral blindness and decrease/absent menace
Posture: Ipsilateral head/body turn, head press, pacing, circling
Postural reactions: deficits in contralateral limbs, normal gait
Normal tin increased spinal reflexes and muscle tone in contralateral limbs
Sensation: contralateral facial hypoalgesia, hypoaesthesia on contralateral half body
Seizures, hemi-neglect syndrom
T/F: you get a normal gait with forebrain lesion
True
Causes of forebrain disease
Degenerative: canine cognitive dysfunction
Anomalous: congenital malformation, hydrocephalus
Metabolic: hepatic encephalopathy, renal encephalopathy, hyper and hyponatremia, hypoglycemia
Neoplastic: extra or intra-axial neoplasia
Inflammatory: meningoencephalitis of unknown origin, Toxoplasmosis, Neosporosis, FIP, FeLV)
Trauma: traumatic brain injury, toxicity
Vascular: Ischemic encephalopathy
What blood tests are important for working up forebrain disease
1) CBC/Chem (including electrolytes Ca and Glucose
2) Liver function testing- Bile acid stimulation test and ammonia
3) +/- Endocrine function tests: fructosamine, insulin levels (insulioma)
4) +/- clotting function
What are some common forebrain infectious diseases in cats
1) Toxoplasma gondii
2) FIV
3) FeLV
4) Cryptococcus
5) Coccidioidomycosis
Why might a urinalysis be useful in your workup of forebrain disease
1) Cerebrovascular accident: to assess for an underlying cause (Cushings, Hypoproteinuria- PLN or hypertension)
2) Discospondylitis - identify if UTI is underlying cause of infection
3) Paraparesis/ urinary dysfunction- increased risk of UTI
4) Inborn errors of metabolism or storage disease- to assess for unusual metabolites
What is the imaging modality of choice for the brain
MRI - contrast required
What are the disadvantages of MRI
1) Anesthesia
2) High cost
3) Limited availability
4) Artifacts (metal objects)
What is the most useful test to exlude infectious/inflammatory conditions of the forebrain
CSF analysis
Limitations: May not be abnormal due to location (if parenchymal) or nature of lesion, can have non-specific changes, cell counts correlate with exfoliation into CSF not severity of disease
What are the limitations of CSF analysis
1) May not be abnormal due to location (if parenchymal) or nature of lesion (non-exfoliating)
2) can have non-specific changes, cell counts correlate with exfoliation into CSF not severity of disease
When is CSF analysis contraindicated
1) Increased intracranial pressure (mental status, pupil size and PLR, abnormal postures, vestibular eye movement)
2) Coagulopathy
3) Cervical (Cerebellomedullary cistern) collection contraindicated in some conditions (chiari-like malformation, AA instability, cervical trauma)
Analysis of CSF fluid should be done within
1 hour
-differential count, cytology, protein
+/- infectious disease testing
What equipment is needed for CSF collection
spinal needle, collection pots (sterile plain +/- EDTA, clippers, scrub, gloves)
What is the preferred site for CSF collection
1) Cerebellomedullary cistern
2) Lumbar cistern
What is the max volume of CSF you can collect
1ml/5kg
What should you not do when collecting CSF fluid
1) Do no aspirate
2) Max volume of 1ml/5mg
Is it easier to obtain CSF from the lumbar cistern or cerebellomedullary cistern
Cerebellomedullary cistern (cistern magna)
Is there a greater risk to collect from the lumbar cistern or cisterna magna
cisterna magna
Is blood contamination less likely in the cisterna magna or lumbar cistern
cisterna magna
Where do you collect CSF from the lumbar cistern
L6-L7 (L5-L6 for larger dogs if no CSF obtained) - aim for subarachnoid space
*can be more challenging to obtain CSF, more blood contamination but less risk
Should CSF protein content be higher in cervical or lumbar area
lumbar
Blood contamination in CSF
can falsely increase WBC count by 1/uL per 500 RBC
protein by 1mg/dl per 1000 RBC
What is Albuminocytological dissociation
increased protein without increased WBC
-Nonspecific
-Extradural compression (disc compression), neoplasia, infection, vasculitis, trauma, syringomyelia, degenerative myelopathy
When might you see albuminocytological dissociation
Extradural compression (disc compression)
neoplasia
infection
vasculitis
trauma
syringomyelia
degenerative myelopathy
increased protein in CSF without having an increased WBC
albuminocytological dissociation
CSF pleocytosis
increased WBC in CSF
When might you see CSF with neutrophilic pleocytosis
1) GME/ NE
2) bacterial meningitis/ meningoencephalitis
3) Fungal
4) FIP
5) Post myelography, hemorrhage, trauma, neoplasia
6) SRMA (no forebrain disease by CSF abnormalities)
When might you see a mononuclear pleocytosis
1) GME, NE
2) CNS lymphoma
3) Viral (CDV)
4) Bacterial meningitis/ meningoencephalitis
5) SRMA (chronic)- CSF abnormalities but no forebrain disease
How might an animal get bacterial meningitis/encephalitis
Infectious meingoencephalitis
Penetrating cranial injuries
Extension from otitis media/ interna
*Culture of urine, blood or CSF is appropriate
When might a culture of urine, blood, or CSF form working up forebrain disease be appropriate?
Bacterial meningitis/ encephalitis
Discospondylitis
used to assess forebrain activity
idenfication of seizure activity- when used at time of seizure or identify abnormal activity between seizures
*useful in status epilepticus
Electroencephalography
Is intracranial neoplasia more likely to be primary or secondary
Primary
What are the neurological signs of intracranial neoplasia
Seizures
Change in mentation
Vestibular signs
Circling
*depends on the localization of the lesion
What are common intracranial neoplasias
1) Meningioma (most common)
2) Glioma
3) Histiocytic sarcoma
4) Choroid plexus tumor
5) CNS lymphoma
How do you diagnose intracranial neoplasia
1) Magnetic resonance imaging
2) Histopathology (brain biopsy or post mortem examination)
How do you treat intracranial neoplasia
1) Palliative:
Meningioma and glioma - prednisolone 0.25-0.5mg/kg BID initially tapering to the lowest effective dose
Trilostane (pituitary)
2) Surgery
3) Radiotherapy
Analogue to Alzheimers disease
thought to be due to
1) cerebrovascular disease
2) oxidative brain damage
3) Neuronal mitochondrial dysfunction
4) impaired neuronal glucose metabolism
Canine Cognitive dysfunction
What might be the cause to canine cognitive dysfunction
1) cerebrovascular disease
2) oxidative brain damage
3) Neuronal mitochondrial dysfunction
4) impaired neuronal glucose metabolism
What are the clinical signs of canine cognitive dysfunction
*Slowly progressive
-apparent confusion
-anxiety
-loss of sleep-wake style
-decreased pet owner interaction
Behaviors:compulsive wandering and pacing, excessive vocalization ,decreased interaction with family, attempting to pass through inappropriately narrow spaces, urinary +/- fecal incontinent, inability to recognize familar people or animals
What is the typical signalment of canine cognitive dysfunction (CCD)
Dogs >8 years old
14-35% of canine population
Female and smaller dogs
How do you diagnose Canine cognitive dysfunction
signalment and clinical signs
MRI
food searching tasks
How do you treat canine cognitive dysfunction
1) MCT diet/ diet high in carnitine, omega 3-PFA, carnitoids, Vitamin EandA (Purina neurocare or Hills b/d)
2) Selegiline (most show a positive response within the first month if they are going to improve)
3) Cognitive enrichment- new toys, regular and new walks
4) Levetiracetam (improved CNS mitochondrial function)
What drug might help with CCD by improving CNS mitochondrial function
Levetiracetam
What diet is recommended for patients with CCD
MCT diet/ diet high in carnitine, omega 3-PFA, carnitoids, Vitamin EandA (Purina neurocare or Hills b/d)
What drugs might help treat canine cognitive dysfunction?
-Selegiline
-Levetiracetam
usually due to water loss, rather than salt gain
commonly seen in critically ill and hospitalised patients
hypernatremia
What might cause hypernatremia
1) Hypovolemia- CKI, nonoliguric AKI, GI disease, burns, DM/ DKA
2) Normovolemia: Hypodypsia, fever, reduced access to water, DI
3) Hypervolemia: Hypertonic saline/ bicarbonate, hyperadrenocorticism, salt intoxication
How might an animal have hypernatremia due to hypovolemia
1) CKI
2) Nonoliguric AKI
3) GI disease
4) Burns
5) DM/DKA
How might an animal have hypernatremia and normovolemia
1) Hypodypsia
2) Fever
3) Reduced access to water
4) Diabetes insipidus
How might an animal have hypernatremia and hypervolemia
1) Hypertonic saline/ bicarbonate
2) Hyperadrenocorticism
3) Salt intoxication
How does acute vs chronic hypernatremia differ
*relatively rapid onset
Acute: shrinkage of brain parenchyma, results in stretching and tearing of small intracranial vessels and hemorrhage
Chronic (>2-3 days): Parenchyma will produce idiogenic osmoles to compensate for increased extracellular osmolarity
What are the clinical signs of hypernatremia
Anorexia
Lethargy
Vomiting
Muscular weakness
Behavioral change
Disorientation
Ataxia
Seizures
Coma
Death
> 170mEq/L Na+ Dogs
175mEq/L Na+ Cats
Hypernatremia
How do you treat hypernatremia
half strength or normal saline, 5% dextroses
Water deficits = 0.6 x BW (kg) x [patient Na concentration / normal Na concentration] - 1)
Acute: 5% dextrose
Chronic: correct over 48-72 hours, should not be lowered faster than 0.5mEq/L/hr
over rapid correction can lead to brain edema
Why do you need to correct chronic hypernatremia slowly
Must be over 48-72 hours or else you can cause brain edema
Why might an animal have hyponatremia and hypovolemia
1) Hypoadrenocorticism
2) Na losing nephropathy
3) GI fluid losses
4) Shock
5) Renal insufficiency
Why might an animal have hyponatremia and normovolemia
1) Hypotonic fluid admin
2) Hypothyroidism
3) Glucocorticoid insufficiency
4) Psycogenic polydipsia
5) SIADH (Syndrome of inappropriate antidiurectic secretion
Why might an animal have hyponatremia and hypervolemia
1) Acute or chronic renal failure
2) Nephrotic syndrome
3) CHF
4) Hepatic cirrhosis
5) Accidental ingestion or injection of water
How does acute vs chronic hyponatremia differ
Acute: Osmotic gradient created, water will enter brain parenchyma cells- increasing their volume, brain edema
Chronic (>2-3days): Parenchyma will actively extrude electrolytes and idiogenic osmoles
Is brain edema seen in acute or chronic hyponatremia
acute hyponatremia
What are the clinical signs of hyponatremia
-GI signs (nausea and vomiting)
-Lethargy
-Disorientation
-Decreased reflexes
-Seizures
-Coma
-Respiratory arrest
What is the treatment for hyponatremia
Sodum contain fluids - normal or hypertonic saline
Na deficit= BW(kg) x 0.6 x (normal serum Na concentration - patient serum Na concentration)
Acute: correct relatively quickly with normal saline
Chronic: Correct slowly or you can cause cell dehydration and hemorrhage, axonal shrinkage and demyelination (Central myelinolysis)
Why do you need to correct chronic hyponatremia slowly *
Central Myelinolysis- axonal shrinkage and demyelination
*cell dehydration and hemorrhage
need to correct gradually over 48-72 hours
should not be faster than 0.5mEq/L/hr
monitor every 4 hours
Central Myelinolysis
axonal shrinkage and demyelination
*cell dehydration and hemorrhage from not correcting chronic hyponatremia gradually
What are the neurologic signs seen with hepatic encephalopathy
Grade 0: Asymptomatic
Grade I: Mild decrease in mobility, apathy, or other
Grade II: Severe apathy, mild ataxia
Grade III: Combination of hypersalivation, severe ataxia, head pressing, circling, blindness
Grade IV: Stupor/coma, seizures
*bilaterally symmetrical
Hepatic encephalopathy affects the forebrain _________
bilaterally and symmetrically
What is seen diagnostically with hepatic encephalopathy
CBC: microcytosis
Chem:
ALT and ALP (possibly only mildy elevated in PSS)
Hypoalbuminemia
Hyperbilirubinemia
Low urea
Bile Acid Stimulation Test
NH3
Abdominal Ultrasound (or CT)
+/- liver biopsy
How do you treat hepatic encephalopathy
1) IV Fluids- restores euvolemia, reduce NH3 concentration - dilution and increases urinary excretion of both urea and NH3
2) Enemas: removes colonic contents and source of nitrogen from urease producing bacteria
3) Lactulose: favors production on NH4+ which are trapped in the colon
4) Diet: highly digestible, high biologic value protein source
5) Antibiotics- reduce number of urease producing bacteria (metronidazole or amoxicillin for 1-2 weeks)
6) Antiepileptic medication: levetiracetam
What causes hepatic encephopathy
1) Hepatic dysfunction
2) Porto-systemic shunt
*Acute liver disease is uncommon
What are the clinical signs of hypoglycemia
Lethargy, ravenous appetite, anxiety
weakness and tremors
reduced vision and seizures
What are some causes of hypoglycemia
1) Severe liver disease
2) Portosystemic shunt
3) Insulinoma
4) Hypoadrenocorticism
5) sepsis
6) Pancreatic tumors
7) Glycogen storage dusease
8) Neoantal/ juvenile hypoglycemia
9) extreme exercise
10) malnutrition
11) insulin overdose
12) xylitol toxicity
13) oral hypoglycemics
14) beta blockers
How do you diagnose hypoglycemia
low blood glucose
check insulin at same time
identify underlying cause
How do you treat hypoglycemia
frequent feeding
dextrose administration- care with insuloma
What precaution should you take with treating hypoglycemia insuloma
care dextrose administration with insulinoma
What will you see on CBC in a dog with portosystemic shunt
Microcytosis
What Biochem results will you see in a patient with hepatic encephalopathy
ALP +ALP (mildly in PSS)
Hypoalbuminemia
Hyperbilirubinemia
Low urea
a congenital defect where there is an active dilation of the ventricular system
hydrocephalus
What is the difference between hydrocephalus and ventriculomegaly
Hydrocephalus: active dilation of ventricular system
Ventriculomegaly: nonactive increase of ventricular system
How might an animal have hydrocephalus
1) Accumulation of CSF within the ventricular system (internal)
2) Accumulation of CSF within the subarachnoid space (external)
3) ObstructiveL Ventricular dilation due to a lesion causing obstruction of the CSF before it enters the subarachnoid space
4) Communicating: CSF in ventricular system communicates with the subarachnoid space
5) Due to loss of CNS parenchyma. CSF volume increases to take up the space formerly occupied by the lost parenchyma
What is the typical signalment of hydrocephalus
toy breeds
What are the clinical signs of hydrocephalus
-Domed shaped head and fontanelles
-Obtundation, behavioral abnormalities
-Difficulties in training
-Decreased vision
-Circling, pacing
-Seizuring
How do you diagnose hydrocephalus
1) MRI - periventircular hyperintensities to distinguish between ventriculomegaly and hydrocephalus
2) Ultrasound- identify large ventricles in presence of persistent fontanelle
3) CT- allows visualization of entire ventricular system - may allow identification of site of stenosis (cant tell hyperintensities)
How do you treat hydrocephalus
Aimed at decreasing CSF production - can improve signs in short term but not effective long term
1) Glucocorticoids
2) Furosemide
3) Omeprazole
4) Acetazolamide
Surgically - but can have blockage, pain, infection, mechanical failure, overshunting, or kinking
What drugs might help to decrease CSF
1) Glucocorticoids
2) Furosemide
3) Omeprazole
4) Acetazolamide
abnormal excessive or synchronous neuronal activity in the forebrain
isolated event
seizure
How is epilepsy defined
2 or more unprovoked seizures in >24 hours
What is seen with forebrain localization seizures
behavior change
circling
head turn to the side of lesion
loss of vision on opposite side
seizures are multifactorial but they are primarily due to
either excessive excitation or decreased inhibition
glutamate - excitatory
GABA- inhibitory
neurons become hypersynchronized leading to a seizure
behavioral phenomenon which proceeds the seizure by minutes, hours, or days
examples: anxiety, reluctance to perform normal behaviors, and hiding (cats)
Prodome / Pre-ictal stage
the initial manifestation of a seizure. a feeling. difficult to recognize in dogs and cats
Aura
the actual seizure event. usually lasts 60-90 seconds. per-acute in onset. characterisitics are generally the same in each event, Often accompanied by autonomic signs such as urination, defecation, and hypersalivation
Ictal
can last minutes to days, can include abnormal periods such as pacing, aggression, disorientation, excessive thirst or appetite, or neurological deficits such as menace deficits- usually bilateral and symmetrical
Post-ictal
What are the stages of seizures
1) Pre-ictal/ prodrome
2) Aura
3) Ictal
4) Post-ictal
how long is the ictal event
60-90 seconds
peracute in onset
The ictal event occurs most often during
sleep or rest- seizure threshold decreases during sleep due to hypersynchrony of sleep facilitating the initiation and propagation of seizures in the parietal and occipital lobe
What are the 2 major phenotypical characteristics of seizures
1) Generalized - both cerebral hemispheres and therefore both sides of the body - can occur alone or evolve from a focal seizure
2) Focal - lateralized or regional signs. consciousness often unimpaired. can be motor, autonomic, or behavioral.
seizures where there is involvement of both cerebral hemispheres simultaneously
consciousness is impaired
Generalized seizures
tonic phase of seizure
sustained increase in muscle contraction lasting a few seconds to minutes
myoclonic phase of seizure
sudden, brief, involuntary contraction of a muscle or group of muscles
clonic phase of seizure
regularly repetitive myoclonus, involving the same muscle groups at a frequency of 2-3 seconds
atonic seizure
sudden loss of muscle tone
What is the most common activity in generalized seizures
tonic-clonic activity
a sequence of movements- a tonic (sustaicned increase in muscle contraction) followed by a clonic phase (regularly repetive myoclonus, involving the same muscle groups at a frequency of 2-3 seconds
Are dramatic generalized seizures more common in dogs or cats
cats- smaller body size, able to move limbs more dramatically
When do focal seizures occur
when there is initial activation of one part of one cerebral hemisphere or region in the forebrain
What is a complex focal seizure
a focal seizure where consciousness is impaired (typically focal seizures do not impair consciousness)
What are the 3 forms of focal seizures
1) Motor (most common)
2) Autonomic - eg. hypersalivation
3) Behavioral
What are Audiogenic reflex seizures
A seizure that is a reflex to environmental stimuli
occurs in cats (late onset- 15 years)
Myoclonic seizures progressing to generalized tonic-clonic seizures in some
Levetiracetam to control
What is the best drug to control audiogenic reflex seizures in old cats?
Levetiracetam
What kind of seizures do you see in Audiogenic reflex seizures
myoclonic seizures progressing to generalized tonic-clonic seizures
What are you differentials for seizures (resemble seizures)
Narcolepsy/ cataplexy
Neuromuscular collapse
Syncope
Movement disorder
Metabolic Disorder
Vestibular Disease
What breeds are affected by idiopathic head tremor syndrome
Doberman
English bull dogs
Boxers (ancedotally)
Idiopathic Head Tremor Syndrome
head tremors that is idiopathic. patients will stop tremoring head when you get their attention.
remain conscious
common in Doberman, English bulldog, and boxer
What is Episodic falling of the CKCS
Paroxysmal hypertonicity found in the CKCS due to genetic abnormality
remains conscious throughout
can be tx with acetazolamide or benzo
What breed has episodic falling due to paroxysmal hypertonicity
CKCS
Paroxysmal hypertonicity found in the CKCS due to genetic abnormality
remains conscious throughout
can be tx with acetazolamide or benzo
What is paroxysmal Dyskinesia?
paroxysmal gluten sensitive dyskinesia that occurs in the border terrier
(Canine Epileptoid Cramping)
respond to a gluten free diet
What breed is typically affected by paroxysmal dyskinesia
Border terrier
How do you treat paroxysmal dyskinesia in the border terrier
gluten free diet
often caused by a gluten sensitive dyskinesia
What are the 3 main causes of seizures
1) Reactive seizures- occurring as a natural response from the normal brain to a transient disturbance in function. concurrent neurological signs usually present
Metabolic or toxic
2) Structural epilepsy- provoked by intracranial or cerebral patholgoy. concurrent neurological signs usually present. can be inflammatory, neoplastic, or traumatic
3) Idiopathic epilepsy- genetic or presumed genetic in origin. No inter-ictal neurologic signs
Seizures that occur as a natural response from the normal brain to a transient disturbance in function.
concurrent neurological signs usually present
typically metabolic or toxic
Reactive Seizures
Seizures provoked by intracranial or cerebral pathology. concurrent neurological signs usually present. can be inflammatory, neoplastic, or traumatic
Structural epilepsy
Seizures that are genetic or presumed genetic in origin
no inter-ictal neurological signs
diagnosis of exclusion. Six months to 6 years
Idiopathic epilepsy
What are the criteria for diagnosis idiopathic epilepsy
1) 2 or more seizures (24 hours apart)
2) Age of onset 6m to 6 years
3) Normal inter-ictal examination
4) No clinically significant abnormalities on minimum database,
5) Family history of IE
Tier II Confidence
6) Unremarkable fasting and post-prandial bile acids
7) MRI of brain
8) CSF analysis
Tier III Confidence
9) Ictal or inter-ictal EEG abnormalities
When should you perform MRI for a patient with seizures
1) Age onset <6 months or >6 years
2) Interictal neurological abnormalities consistent with intracranial neurolocalization
3) Status epilepticus or cluster seizure
4) Previous presumptive diagnosis of IE and drug-resistance with a single AED titrated to the highest tolerable dose
What breeds have a causative gene for genetic epilepsy
1) Lagotto Romagnolo
2) Belgian Shepherd
3) Boerboels
When should you start treatment for seizures
1) Structural epilepsy or reactive seizures
2) Status epilepticus or cluster seizures
3) 2 or more seizures in a 6 month period
4) Post-ictal signs are severe and last longer than 24 hours
T/F: Idiopathic epilepsy can be cured with medication
False- but drugs are used to symptomatically suppress epileptic seizures
Primidone is only approved but not as affected as phenobarbital
What is the only AED FDA approved drug for use in dogs
Primidone
not as affective as Phenobarbitone
(no drugs licenced in cats)
What must you consider when choosing a drug to manage epilepsy
1) General health of the patient
2) owners lifestyle
3) Financial limitations
4) Owner compliance with the therapeutic regimen
What is the mechanism of action of phenobarbital
augments the inhibitory effect of GABA
prolongs the chloride channel opening at GABAa receptor
allows GABA to work for longer times to stop seizures
What are the side effects of managing a patient with Phenobarbitone?
Initial side effects, which subside in 2-3 weeks: PU/PD, PP, ataxia)
Side effects: sedation, ataxia, PU/PD. polyphagia, hepatotoxicity, hemological abnormalities (neutropenia, anemia, thrombocytopenia)
When should you do bloodwork to monitor a patient that is on phenobarbital
1) 2-3 weeks after any dose change (plain serum)
2) 6 weeks (including CBC, Chem, and ideally BAS)
3) 6 months (including CBC, Chem, and ideally BAS)
Why do you need to monitor a patient that is on phenobarbital
1) Hepatotoxicity
2) Increases metabolism of itself over time, decreasing its levels
3) Hemotological abnormalities (neutropenia, thrombocytopenia, anemia)
What levels do we aim for in a patient on phenobarbital
25-35ug/ml (can be effective as low as 15ug/ml)
How is phenobarbital hepatoxic
Potent inducer of cytochrome P450 enzymes activity which increases ROS generation and risk of hepatic injury
metabolized via hepatic microsomal enzymes- ALP and ALT elevations without hepatoxicity are common
How is phenobarbital metabolized
via hepatic microsomal enzymes-
ALP and ALT elevations without hepatoxicity are common
Phenobarbital is contraindicated in which patients
dogs with hepatic dysfunction
Phenobarbital is a potent inducer of ________
cytochrome P450 enzymes activity which increases ROS generation and risk of hepatic injury
and accelerated clearing of itself over time
Bromide for seizures is typically administered as
Potassium Bromide (KBr)
What is the mechanism of action of Bromide (Br)
Competes with Cl- transport across nerve cell membranes and inhbits Na+ transport leading to membrane hyperpolarization which raises the seizure threshold
Competes with Cl- transport across nerve cell membranes and inhbits Na+ transport leading to membrane hyperpolarization which raises the seizure threshold
Bromide (Br)
What could result if Potassium Bromide is given to cats
Eosinophilic bronchitis
Potassium Bromide but be given along side a
consistent diet
When should you monitor a patient on potassium bromide
1) 12 weeks- when steady state is reached, use plain serum (include CBC, chem)
2) 6 months (including CBC, chem)
What kind of patients is potassium bromide contraindicated in?
Patients with renal disease
excreted unchanged in urine and undergoes tubular reabsorption in competition with chloride
What is the mechanism of action of Levetiracetam?
unknown MOA
What is the anti-epileptic drug of choice for patients with liver disease or portosystemic shunts
Levetiracetam (Keppra)
What kind of patients should you use Levetiracetam (Keppra) with caution
Those with kidney disease (renal excretion)
What is the mechanism of action of Zonisamide
blocks propagation of epileptic discharges
What can help reduce phenobarbital doses 25% when used in combination due to enhanced enzyme induction and clearance
Zomisamide
a drug that has a low affinity partial agonsit for benzo binding site of GABAa receptor
FDA approved for noise aversion only but licensed in Europe as a monotherapy
Metabolized by the liver
Imepitoin (Pexion)
What are inflammatory/infectious differentials for seizures in cats
FIP
FIV
FeLV
Toxoplasmosis
What are neoplastic differentials for seizures in cats
1) Meningioma
2) Lymphoma
3) Glioma
How is idopathic epilepsy different in cats
we do not think that it has the same genetic basis as with dogs (called epilepsy of unknown cause)
What is a degenerative cause of seizures in cats
Hippocampal necrosis
up to 30% of cats which seizure
-Clusters and complex focal seizures- hypersalivation and lipsmacking
Idiopathic epilepsy in cats is most common when they are _____ years of age
1-5 years of age
seizures last 1-3 minutes
What is the most common causes of reactive seizures in cats
Hypoglycemia
Hepatic encephalopathy
Intoxication
What is Hippocampal necrosis
can occur in up to 30% of cats which seizure
clusters and complex focal seizures that present with hypersalivation and lipsmacking
What anti-seizure drug can cause fulminant hepatic necrosis when given orally to cats
Diazepam
What might occur if you give Diazepam orally to cats
fulminant hepatic necrosis
What can occur with propofol administration in cats
Heinz Body anemia
What is a precaution when using phenobarbitone in cats
lower starting (2mg/kg) and loading (12-15mg/kg) in cats
because less likely to get sedation
Why is potassium bromide contraindicated to use in cats
eosinophilic bronchitis
Dogs with idiopathic epilepsy who suffer from cluster seizures are
less likely to achieve remission
Decreased survival time
more likely to be euthanized
Cluster seizure
2 or more seizures within 24 hours
What is Status Epilepticus
Seizures lasting >5 minutes
>2 seizures without full recovery
What defines an emergency seizure
1) Cluster seizure: 2 or more within 24 hours
2) Status Epilepticus: Seizure lasting >5 minute or >2 seizures without full recovery
*Irreversible neuronal damage occurs after 30-60 minutes
What two things can define Status Epilepticus
1) Seizure lasting >5 minutes
or
2) >2 seizures without full recovery
How can a seizure cause irreversible neuronal damage
it can occur after 30-60 minutes
due to failure of mechanisms that usually stop an isolated seizure (abnormal excessive excitation or ineffective inhibition)
-Excessive glutamate release
-Excitotoxic cell injury
Why can seizures be an emergency
1) Stage 1: Increased autonomic activity- tachycardia, hypertension, hyperglycemia
2) Stage 2: Irreversible neuronal damage (after 30 minutes)- hypotension, hypoglycemia, hyperthermia, hypoxia
What are the effects of increased autonomic activity during a seizure (stage 1)
tachycardia
hypertension
hyperglycemia
What are the effects of irreversible neuronal damage (after 30 minutes of seizure)
hypotension
hypoglycemia
hyperthermia
hypoxia
Why might a dog be in seizure status
1) Idiopathic epilepsy
2) Toxicity
3) Metabolic disease
4) Neoplasia
5) CNS inflammatory disease
6) Trauma
What is the first thing you should do when a dog is having a seizure
STOP THE SEIZURE
1) Diazepam 1-2mg/kg per rectum (0.5mg/kg IV)
2) Midazolam 0.2mg/kg intranasalaly
-GET the history
What questions should you ask when getting a history for a seizure
-When, how many
-Before, during and after
-Autonomic signs
-Other abnormalities
-Any pre-existing disease
-Medication
-Access to toxins
What should you do for assessment of an animal that had a seizure
IV catheter placement
Examination
Baseline blood work- minimum: GLucose, sodium, calcium, PCV, Hepatic +/- renal function
In existing epileptics: Serum levels of antiepileptic drugs
What order of anti epileptic drugs should you use (assuming idiopathic)
1) Phenobarbital 2.5mg/kg q12h
2) If clusters of status (or futher seizure activity over the next few hours: Phenobarbital IV loading
3) If further seizures - Levetiracetam loading (60mg/kg)
What should you use for breakthrough seizures
1) Diazepam- interacts with plastic and light
2) Midazolam - not in hepatic dysfunctions, dogs in SE may become refractory
3) Propofol- 6mg/kg IV bolus followed by 6mg/kg/h
care heinz body anemia in cats , use preservative free formation
When should you not use midazolam for breakthrough seizures
1) Hepatic dysfunction
2) Dogs in status epilepticus may become refractory
What should you be careful about with propofol in cat
CARE- heinz body anemia
use preservative free formation
What should you monitor while a dog is on infusion for seizures
1) Heart rate and respiratory rate
2) Blood pressure (systolic >90mmHg (MAP 70-80mmHg)
3) urine production 1-2 ml/kg/hr
4) Oxygenation/ventilation- pulse oximetry >95%; end tidal CO2 35-40mmHg
5) Temperature
6) Neurological examination- allow assessment for signs of improvement or eterioration
7) If on infusion assess pharyngeal tone- if risk of aspiration- intubate
What are changes with prolonged status epilepticus after 30 minutes
1) Altered GABA A receptor subunit expression
2) NMDA receptor activation is the major mediator of excitotoxicity - increased calcium entry into cells, increased duration of status in rodents
*Need NMDA receptor antagonist (ketamine) to stop maintenance phase and neuroprotective
Why is ketamine neuroprotective in patients in prolonged status epilepticus (>30min)
There is altered GABA A receptor subunit expression and NMDA receotir activator is major mediator of excitotoxicity
Ketamine is an NMDA receptor antagonist to stop the maintenance phase alongside dexmedetomidine
What is a NMDA receptor antagonist
Ketamine
If you administer diazepam you probably also need to administer
other AEDs
The storage (filling) phase of the bladder is predominated by the
Sympathetic nervous system
1) Thoracolumbar region (Hypogastric nerve)
2) Somatic component- Pudendal nerve
What are the two nerves dealing with the storage (filling) phase of the bladder
1) Hypogastric nerve (thoracolumbar region)
2) Pudendal nerve (somatic)
Micturition phase is predominated by the
Parasympathetic system
Cranial-sacral region - Pelvic nerve
Is the pelvic nerve associated with filling of the bladder or micturition
Micturition
- cranial sacral region
What receptors does the hypogastric nerve stimulate
B-receptor: Stimulation relaxes muscle to store urine
a- receptor: Stimulation constricts internal urethral sphincter (smooth muscle)
*Promotes storage of urine)
Where does the hypogastric nerve come off of the spinal cord
L1-L4
Where does the pudendal nerve come off of the spinal cord
S1-S3
What receptor does the pudendal nerve stimulate
ACh receptor
1) Sensory and motor to the external urethral sphincter
2) Stimulation constricts external urethral sphincter
*Promotes storage of the urine
Stimulation of pudendal nerve on ACh receptors results in __________ (sensory and motor) of the external urethral sphincter
Constriction
Where does the pelvic nerve come off of the spinal cord
S1-S3
Stimulation of the hypogastric nerve on beta receptors results in ________ of the detrusor muscle and the alpha receptor results in _________ of the internal urethral sphincter
relaxation of detrusor
constriction of the internal urethral sphincter
The pelvic nerve stimulates ACh receptor to ___________ detrusor muscle
contract the detrusor to evacuate urine
*Sensory branch to complete an emptying reflex arch
What is the purpose of the sensory branch in the pelvic nerve
to complete an empyting reflex arch and prevent over contraction of detrusor
What are the steps of filling and storage of the bladder
1) Pudendal nerve (somatic) leads to contraction of external sphincter muscle
2) Hypogastric nerve (L1-L4) via a receptor contracts internal sphincter muscle
3) Inhibition of pelvic nerve to detrusor muscle to allow relaxation
4) As bladder fills, pressure stimulates pelvic nerve sensory fibers which relay to B-receptors to relax further
5) Brain stem micturition centers facilate and modulate these activityes
What are the steps of the micturition phase
1) Pelvic nerve sends sensory info up the brain stem, cerebellum, cerebrum
2) Activation of micturition via UMN pathways in pons and medulla; descends via spinal cord
3) Inhibition of L1-L4 sympatheics (B receptors on detrusor, a receptors on internal sphincter muscle
4) Inhibition of pudendal n to relax external sphincter
5) Facilitation of pelvic nerve to contract detrusor m
*Part of coordination of these nerves is mediated reflexively within the sacral segments and from sacral to lumbar segments -> reflex bladder contractions
What are causes of neurogenic bladder dysfunction
1) Brainstem: Loss of communication/coordination with micturition center
2) Spinal cord: loss of communication or coordination with micturition center or specific nerves based on lesion location
3) Cauda equina: Pelvic or pudendal nerve damage
4) Cerebral or cerebellar disease (rare)- loss of comm with micturition, loss of voluntary control
5) Neuromuscular disease- dysautonomia, other peripheral nerve, detrusor muscle, or NMJ effects (rare)
6) Detrusor-urethral dyssnergia: lack of coordination between detrusor contraction and urethral relaxation
a form of neurogenic bladder dysfunction where there is a lack of coordination between detrusor contraction and urethral relaxation
Detrusor-urethral dyssnergia
Detrusor-urethral dyssnergia
a form of neurogenic bladder dysfunction where there is a lack of coordination between detrusor contraction and urethral relaxation
How might an animal have non-neurogenic bladder dysfunction
1) Primary bladder pathology: a) Myopathic bladder disease- Detrusor atony or bladder rupture
b) Mechanical outflow obstruction (Urolithiasis, neoplasia/polyps, prostatic disease, urethral stricture, extraluminal compression
2) Behavioral, environmental
a) Pain upon urination
b) Hospitalized cats or dogs unwilling to urinate
c) Posture- orthopedic or neurologic disease
3) Pharmacologic effects: opiates, antidepressants, anticholingers
Causes of primary bladder pathology leading to non-neurogenic bladder dysfunction
a) Myopathic bladder disease- Detrusor atony or bladder rupture
b) Mechanical outflow obstruction (Urolithiasis, neoplasia/polyps, prostatic disease, urethral stricture, extraluminal compression
Causes of behavioral, environmental non-neurogenic dysfunction
a) Pain upon urination
b) Hospitalized cats or dogs unwilling to urinate
c) Posture- orthopedic or neurologic disease
What drugs might lead to non-neurogenic bladder dysfunction
1) Opiates
2) Antidepressants
3) Anticholinergics
As a general rule of thumb, if voluntary motor function is compromised to the muscles of the limbs then
it is likely compromised to a similar degree in the muscles of the lower urinary tract
With LMN, reflexes to the bladder are ____________ while with UMN, reflexes to the bladder are _________
LMN: decreased to absent
UMN: Normal to increased- can account for overflow
With LMN, muscle tone to the bladder is __________ while in UMN, reflexes to the bladder are
LMN: Hypotonic, flaccid bladder
UMN: Normal to hypertonic/spastic firm bladder
Do you see a hypotonic/flaccid bladder with LMN or UMN
LMN
Do you see a normal to hypertonic/spastic firm bladder with LMN or UMN
UMN
With LMN, expression of the bladder is ________ while with UMN expression of the bladder is ______
LMN: very easy
UMN: can be difficult
IS expression of the bladder easy or difficult with UMN
difficult
IS expression of the bladder easy or difficult with LMN
easy
You have hypotonicity of the pelvic and pudendal nerves, decreased external urethral sphincter tone, and decreased detrusor strength, where is the lesion
These are all LMN signs leading to the inability to contract the detrusor muscle and dribbling due to inability to constrict sphincters
*L4-S3 spinal lesion
How will a L4-S3 spinal lesion affect the bladder
Hypotonicity of pelvic and pudendal nerve leading to decreased external urethral sphincter tone and decreased detrusor strength
1) Inability to contract detrusor muscle
2) Dribbling due to inability to constrict sphincters
How will a T3-L3 spinal cord lesion affect the bladder
Hypertonicity caudal to lesion leading to increased external urethral sphincter tone and increased resting tone to the detrusor muscle
1) Loss of higher level coordination of detrusor/sphincter
2) Detrusor cannot overcome resistance from external urethral sphincter
What would be the result of pelvic and hypogastric decreased but pudendal (somatic) is preserved
1) Loss of nerve function leading to poor detrusor contraction and poor internal sphincter control
2) Intact central integration- aware bladder is full and attempts to urinate
*Stanguria, dysuria, with large residual volume
What are potential sequelae to bladder dysfunction
1) Bacterial infection/ cystitis from residual volume remaining, (higher incidence of IVDD dogs)
2) Urine scald from overflow dribbling or reflex contractions
3) Bladder atony- from prolonged distension (>24-48 hours)
4) Bladder rupture- uncoommon with functional problems and more of concern with mechanical obstruction (or during expression)
What is bladder atony
Where there is stretch injury to the detrusor muscle leading to the detrusor muscle cells not functioning
dysfunction due to
1) inability to contract detrusor
2) May have some overflow dribbling
from prolonged distension >24-48 hours
When does urine overflow occur
when the bladder is distended to the point of overstretching the muscle
UMN dysfunction: protective mechanism local reflex arc to release small amounts of urine
LMN dysfunction: tone of sphincters is reduced leaving an open pathway for urine to leak out (Not over-distension but may indicate incomplete emptying which can lead to UTI and continuous leaking can lead to severe urine scalding and cutaneous infections)
What are the goals when managing bladder
Shortterm: Prevent infections, detrusor atony, and urine scald
Longterm: Treat underlying cause of dysfunction and improve function
What should you do when managing the bladder
1) Evacuate bladder 2-4 times a day via manual expression or catherization (intermittent or indwelling)
2) Skin care: keep skin clean and dry, frequent baths, baby powder, ointments to protect skin, absorbent bedding
Pros and cons of manual bladder expression
Pros: inexpensive, can be performed by some owners
Cons: Usually only evacuate 50% of volume, stressful for patient, abdominal soreness, risk for bladder rupture
