SA Neuro Flashcards
Limitations of MRI?
Many diseases have normal MRI
Anatomical imaging often lacks specificity - e.g. infiltrative neoplasia and lymphoma may look identical to inflammatory disease
High cost
Limited availability
Indications for aural radiography? View used? Limitations?
Chronic otitis
Peripheral vestibular disease
Facial nerve paralysis
Horner’s syndrome
Rostral-caudal (open mouth)
GA required
Often limited value in large dogs
CT preferred in available
Principles of CT?
X ray Contrast based on physical density Cross sectional No superimposition Better ST contrast (not as good as MRI) Excellent for bone For brain CT need to give iodinated contrast in most cases (potentially nephrotoxic)
MRI principles?
Imaging net magnetic vectors of spins of hydrogen protons
Strong magnetic field with varying gradients
Apply RF pulses at Lamour frequency
Turn off RF pulse
Spins rephrase and lose energy emitting RF signal
MRI safety?
Magnet extremely strong - need to be careful when taking objects into room, act as projectiles (can be fatal)
Acoustic damage - ear plugs and defenders for patients
Patient temperature:
- SAR effects: patient heating
- prolonged GA: patient cooling
What are the MRI contrasts?
T2W: fluid and fat are hyperintense (bright)
T1W: fluid is hypointense (dark, depends on protein content), fat is hyperintense
T2 FLAIR: fluid is hypointense, fat is hyperintense
STIR: fluid is hyperintense, fat is hypointense
Which MRI sequence to use?
T2W sequences most sensitive
If T2W normal consider additional sequences
STIR screening for pathology
T2* GRE bone lesions and haemorrhage
What to assess on MRI of the brain (T2W sequence)?
Look for abnormal signal intensity Symmetry on transverse and dorsal plane images Mass effect or atrophy Grey/white matter contrast Ventricles - size, shape Enhancement pattern Assess extracranial soft tissues
What is myelography? When is it used? Contraindications?
Injection of non-ionic low osmolar iodinated positive contrast (iohexol) into subarachnoid space
Outline surface of spinal cord on radiographs or CT - highlights extradural or bony lesions
Always take CSF first
Used to:
- localise spinal lesions
- surgical planning
- rule out surgical disease
- assessment of dynamic spinal cord lesions
Contraindications:
- coagulopathy
- spinal instability
- cloudy/turbid CCSF (suggests inflammatory process)
Complications of myelography?
Exacerbation of neurological signs Seizures Brainstem injection Central canalogram Spinal cord haematoma Epidurogram Rapid movement of contrast Subdural injection Infection Dysrhythmias Death
What to assess on spinal images?
Roentgen signs - shape, size etc Alignment Disk spaces Endplates Foraminal changes Facets Soft tissues
What incidental findings could there be with spinal images?
Spondylosis deformans (very rarely clinically significant)
Facet OA
Congenital anomalies common
What are the main alignment problems of the spine seen by imaging?
Atlanto-axial subluxation
Congenital malformations (e.g. hemivertebra causing kyphosis or compressive myelopathy)
Trauma
“Wobbler” - Dobermans and larger breeds
What is the most common cause of extradural compression? Other causes?
(Extradural is most common form of compression)
Disk herniation
Others:
- vertebral tumour
- superiosteal haemorrhage
- extradural cysts
- vertebral stenosis
- disk extrusion
- disk protrusion
How does intervertebral disk disease (IVDD) appear on imaging? Pitfall with radiography?
Narrowed disk space
Reduced size of foramina
Endplate changes (chronic)
Mineralised material in vertebral canal
Pitfall with radiography = artifactual narrowing further away from centre of beam
Differentials for destructive changes of spine seen on imaging?
Diskospondylitis - centred on disk space
Neoplasia - may see changes if involve bone
Which imaging is needed for intramedullary disease?
Not visible on radiographs and poorly seen on CT
MRI required in most cases
History and CSF often important for diagnosis
Causes of intramedullary disease?
Neoplasia Myelitis Ischaemic myelopathy Syrinx Contusion Haemorrhage
Causes of intradural-extramedullary disease?
Subarachnoid diverticulae/cyst
Masses - meningioma, peripheral nerve sheath tumour
What are the 3 localisations of spinal disease?
Intramedullary
Intradural-extramedullary
Extradural
Tests to rule out non neurological diseases causing neurological signs?
Haematology and biochemistry
Electrolytes
Liver function testing - e.g. for PSS (BAST, ammonia)
Endocrine function tests (hypothyroidism, addison’s, cushings, diabetes)
Clotting function - stroke
Anti-gluten antibodies (anti-gladin IgG, anti-transglutaminase 2 IgA)
Immune mediated disease - acute phase proteins, specific autoantibodies
Infectious diseases (quite uncommon with neurological signs in UK) - Toxoplasma, Neospora
Urinalysis - renal disease, electrolyte abnormalities, hypertension (PLN), UTI
Bacteriology
Why is urinalysis important for patients with paraparesis/urine dysfunction?
Increased risk of UTIs
What infectious CNS conditions could be find by bacteriology?
Encephalitis - penetrating cranial injuries (cats), extension from otitis media/interna Bacterial meningitis (CSF degenerative neutrophils) Empyema, paraspinal abscessation
Significance of bridging spondylosis below vertebrae?
Often doesn’t cause neurological signs as not affecting vertebral canal
May cause pain due to impingement on nerves
How do extradural, intradural-extramedullary and intramedullary lesions appear with myelography?
Extradural:
- axial displacement of 1 or more contrast columns
- columns often thin or partially disrupted at the site of the
lesion
- most common
Intradural- extramedullary
- filling defect within the contrast column
- ‘Golf tee’ sign or widening of subarachnoid space due to a arachnoid diverticulum
Intramedullary
- divergence of contrast columns
What is CSF analysis useful for? Limitations? Contraindications?
Most useful for infectious/inflammatory conditions
Can be abnormal in neoplastic or traumatic conditions
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
Contraindications:
- increased intracranial pressure (mental status, pupil size and PLR, abnormal postures, vestibular eye movement)
- coagulopathy
- cervical collection contraindicated in some conditions (Chiara-Like malformation, AA instability, cervical trauma)
How to take a CSF sample? Needle? Site? Volume? Analysis?
Spinal needle
Site caudal to lesion:
- cerebellomedullary cistern: easier, blood contamination less likely, greater risk
- lumbar cistern: L6-L7 (L5-L6 in larger dogs if none obtained), can be more challenging to obtain
Do not aspirate
Max volume 1ml/5kg
Analyse within 1 hour - differential count, cytology, protein, infectious disease testing
Normal analysis of CSF?
Clear
No RBCs, WBCs <6
Cervical protein <30
Lumbar protein <45
How does blood contamination affect CSF analysis?
Falsely increases WBC count by 1 per 500 RBC
Falsely increases protein by 1 per 1000 RBC
What is albuminocytological dissociation of CSF? What does it indicate?
= increased protein without increased WBC
Non specific
Extradural compression (disc disease), neoplasia, infection, vasculitis, trauma, springomyelia, degenerative myelopathy
What is pleocytosis of CSF? What could cause neutrophilic and mononuclear pleocytosis? Mixed? Eusinophilic?
Increased WBCs Neutrophilic pleocytosis: - SRMA - bacterial (intracellular) - GME/NE - fungal - FIP - post myelography, haemorrhage, trauma, neoplasia Mononuclear pleocytosis: - GME/NE - CNS lymphoma - viral (CDV) - bacterial and SRMA (chronic) Mixed pleocytosis: - GME - bacterial and SRMA (chronic) - fungal - protozoal - non inflammatory disease (infarct) Eosinophilic: - eosinophilic ME - fungal - protozoal - parasitic
What can Pilocarpine be used to test?
Functional test of autonomic NS 0.1% topical administration to the cornea -> miosis Rapid constriction (<30mins) suggestive of denervation hypersensitivty Supportive finding of dysautonomia (definitive diagnosis requires PME)
What is the Edrophonium response test?
Functional test
“Tension test”
For junctionopathies - acquired and some congenital myasthenia gravis
IV administration of edrophonium chloride (fast acting cholinesterase inhibitor)
Care for cholinergic crisis:
- bradycardia
- salivation
- miosis
- dyspnoea
- tremors
(Have incubation kit on stand by and atropine drawn up)
What are electrodiagnostics useful for?
Identifying denervated muscles
Extent and severity
Treatment monitoring
What can be seen with electromyography?
Normal muscle silent except in end-plate region
Spontaneous activity is abnormal
10-14 days to be apparent
What is motor nerve conduction velocity used for? How is it done?
Investigate suspected peripheral neuropathies
Stimulate a motor nerve at a minimum of 2 sites and record the
evoked electrical activity (CMAP)
Patient age and limb temperature should be taken into account
What are F-waves used for?
Assess the nerve roots
F wave latency or F ratio (polyradiculoneuritis)
What is repetitive nerve stimulation used for?
Assess neuromuscular junction
High repetition rate (3-5 per second)
Myasthenia gravis - consistent 10% decrease or more in the CMAP
What is electroencephalography (EEG) used for?
Assess forebrain activity
Identification of seizure activity (when used at the time of the
seizure)
Can be useful in status epilepticus
What does the brainstem auditory evoked response (BAER) screen for?
Congenital sensorineural deafness
Localise acquired deafness
Access hearing threshold
What type of problems are most likely with focal and lateralised, multifocal and diffuse and symmetrical brain lesions?
Focal and lateralised - neoplasia, vascular
Multifocal - inflammatory/infectious
Diffuse and symmetrical - metabolic, toxic
What controls the rate of blood flow through the brain? What is this controlled by?
Rate of blood flow is controlled mainly by CPP (cerebral perfusion pressure)
CPP is controlled by MABP and ICP
CPP = MABP - ICP
Compensatory mechanism of the ICP of the brain? What happens if exceeded?
If one component of the brain (tissue, blood, CSF) increases, another has to decreases
= Compliance
Once limit exceeded, ICP can rise precipitously -> brain herniation:
- forebrain herniates underneath tentorium
- or cerebellum herniates through foramen magnum
Signs of raised ICP?
Mental status - depression, stupor, coma
Cushing’s reflex:
- bradycardia and hypertension
- ICP increases above MAP resulting in cerebral ischaemia
- a1 adrenergic sympathetic activation -> systemic vasoconstriction -> hypertension
- carotid artery baroreceptors detect hypertension -> vagal activation -> bradycardia
Pupils:
- PLR
- aniscoria
- miosis
- mydriasis (worst sign)
Reduced physiological nystagmus (early sign of raised ICP)
Abnormal postures - decerebrate (seen with cerebrum herniation), decerebellate (seen with cerebellar herniation)
Differentials for raised ICP?
V: CVA - ischaemic or haemorrhagic strokes
I: MUOs, bacterial ME, protozoal MEs, viral MEs (CDV, FIP, FIV)
T: head trauma, toxins
A: hydrocephalus, lisencephaly, hydranencephaly and porencephaly, CCA
M: hepatic encephalopathy, hypoglycaemia, electrolyte imbalances
I
N: meningiomas, gliomas, pituitary tumours, lymphoma, metastases, MPNS T
D: lysosomal storage diseases, cognitive dysfunction, many degenerative GM and WM disorders
What types of meningoencephalitis are there? How do they present? Diagnosis?
GME (granulomatous
NME (necrotising)
NLE (necrotising leukoencephalitis
Usually acute and progressive, often multifocal
Diagnosis - advanced imaging, CSF analysis, sometimes biopsy
What is idiopathic tremor syndrome? Signs? Diagnosis? Treatment? Prognosis?
Mostly small breed dogs Fine tremor - rapid, low amplitude, worse with stress/excitement \+/- head tilt, reduced menace, ataxia Diagnosis: - CSF: very mildly inflammatory - +/- MRI to rule out other problems - no other condition causes this type of tremor Treatment: - corticosteroids for 4-6m - +/- other immunosuppressive drugs - diazepam initially Fair-good prognosis but possibility of relapse
What are the 3 main routes of infection for Bacterial ME? Signs? Diagnosis? Treatment? Prognosis?
3 main routes = haematogenous, direct invasion (inner ear, eyes, nasal sinuses or bone infection, trauma), CSF
Signs:
- usually acute CNS signs
- obtundation and CN deficits most common signs
- pyrexia
- neck pain
Diagnosis:
- CSF: increased protein concentration and pleocytosis (rare phagocytksed organisms)
- CSF/blood culture (positive 30%): inside abscess or in small amounts
Treatment = antibiotics +/- surgical drainage
Guarded prognosis
Clinical signs of CNS intoxications? Possible causes?
Acute (<24h) onset
Seizures (approx 40% of all reactive seizures)
Often GI, CV or resp signs before or at same time
Muscle tremors and fasciculations often seen
Status epilepticus (SE) common - infusions usually needed to control seizures
Toxins:
- organophosphates
- pyrethrin
- lead
- avermectins
- medications
- etc
Difference between primary and secondary head trauma?
Primary injury: - physical disruption of parenchyma: concussion, contusion, laceration - no intervention possible Secondary injury: - release of inflammatory mediators - continued haemorrhage - leads to increased ICP - can intervene
Assessment of head trauma? When is surgery needed?
Modified Glascow Coma Scale (useful for serial monitoring, high score is better prognosis)
Imaging: MRI or CT (need for decompressive surgery)
Surgery if fractures compressing brain parenchyma or contaminated fragments, haematomas or severe raised ICP
Medical management of head trauma?
Fluids
- restore IV volume to ensure adequate CPP
- hypotension significantly increases mortality
- resuscitation then maintenance
- isotonic or hypertonic crystalloids, colloids and blood products
- avoid glucose as hyperglycaemia associated with poorer outcome
ICP management
- Mannitol: reduces blood viscosity, increases CBF an oxygen delivery, free radical scavenger, osmotic effect, contraindicated in hypovolaemia, can become refractory
- hypertonic saline: contraindicated if hyponatraemia or cardiac/respiratory disease
Oxygen
- establish clear airway
- essential for brain (high CO2 increases CBF)
Temperature
- avoid hyperthermia (affects metabolic rate) and hypothermia (shivering oxygen demands)
BP:
- maintain between 90-140mmHg
- cerebral blood flow is affected outside this range
- avoid hypotension to maintain CPP
Pain
- pain increases BP and therefore ICP
- caution as morphine may cause emesis and result in increased ICP
General care
- keep head elevated
- avoid jugular compression
- turn every 4-6h
- catheterise bladder every 6h
- nutritional support
Are steroids good for head trauma?
No
Associated with hyperglycaemia and production of lactic acid -> cell death
Increased risk of infection
Affects metabolism
What is hydrocephalus? Which breeds and age usually? Signs?
= Abnormal dilation of ventricular system within cranium Toy breeds, young age Signs: - domed shaped head - persistent fontanelle - abnormal behaviour - cognitive dysfunction - obtundation - circling/pacing - seizures(?) - vestibular signs
What are corpus callus anomalies? Signs? Which breeds?
Corpus callous = white matter that connects cortex of one hemisphere with the other Anomalies = hypogenesis, agenesis Signs: - adipsia associated with hypernatremia - seizures - abnormal behaviour - tremors - circling Min Schnauzer, SBT
What are arachnoid diverticulae?
Prevalence of supracollicular fluid accumulations
What are hydranencephaly and porencephaly? Signs?
= presence of cerebral cavities, usually communicating with subarachnoid space and/or lateral ventricles
Signs in first few months (circling, abnormal behaviour) or up to years (seizures_
Most common cause of hepatic encephalopathy? Pathogenesis?
Most common cause = secondary to PSS Pathogenesis: - hyperammonaemia - neuroinflammation - deranged neurotransmission - cerebral oedema
Signs of hepatic encephalopathy?
Vague signs - failure to thrive, weight loss, PUPD, GI signs
Forebrain signs - behaviour changes, pacing, blindness, seizures
Rare brainstem or cerebellar signs in older dogs
Neuro signs may develop after surgery
Diagnosis and treatment of hepatic encephalopathy?
Diagnosis - BAST, fasting ammonia, US, CT angiography
Treatment:
- lactulose: traps ammonia in intestine, decreases absorption, inhibits uptake of glutamine by intestinal wall
- antibiotics: reduce ammonia producing bacteria in gut
- diet: reduce gut derived ammonia, low protein, aromatic amino acids and short chain fatty acids
- minimise factors causing increased ammonia (constipation, GI bleeding, azotaemia, infection, hypokalaemia)
- minimise factors causing reduced toxin clearance (dehydration, hypotension, anaemia)
- reduce factors affecting neurotransmission (benzodiazepines)
- seizure control: levetiracetam first choice
What is the primary source of energy for the brain?
Glucose oxidation
Brain consumes 25% of total blood glucose
Brain has 3x metabolic rate of peripheral tissues but 10-30% less extracellular glucose
Lack of glycogen ctores
Underlying causes of hypoglycaemia?
Insulinoma Liver disease Insulin overdose Glycogen storage diseases Juvenile hypoglycaemia
Clinical signs and diagnosis of hypoglycaemia?
Clinical signs: - lethargy, ravenous appetite, anxiety - depression - weakness and tremors - reduced vision - seizures Diagnosis: - low glucose levels (typically <3mmol/l) - clinical signs
Causes of hypernatraemia?
Excess water loss (e.g. diabetes insipidus, osmotic diuresis, diarrhoea)
Excess salt intake (e.g. salt poisoning, administration of IV hypertonic solutions, hyperadrenocorticism)
Insufficient water intake (e.g., lack of access, inability to drink or CNS disease resulting in primary adipsia)
Causes of hyponatraemia?
Hypovolemic (e.g., renal and GI disease, third space or cutaneous losses)
Hypervolemic (e.g. congestive heart failure, liver failure, nephrotic syndrome, hypoalbuminemic states)
Normovolemic (e.g., primary polydipsia, water intoxication, hypothyroidism, adrenal insufficiency or renal failure
Signs of sodium derangements?
Altered mentation Blindness Seizures Coma Death
What happens with chronic Na abnormalities? What happens with rapid correction?
In chronic Na abnormalities, there is active movement of electrolytes (Na, K and Cl) followed by “idiogenic osmoles”
With rapid correction, the compensatory influx of electrolytes is not matched by the slower moving organic osmolytes
Signs of hypocalcaemia?
Excitability due to increased neuronal permeability to Na -> nerve fibre discharges spontaneously -> muscle contraction and tetany
Muscle spasm, cramping, muscle twitching, trembling, stiffness, tonic-clonic spasms, episodic rigidity, tetraparesis, seizures
Types of brain neoplasia?
Primary:
- intra-axial: gliomas
- extra-axial: meningiomas, choroid plexus tumours
Secondary:
- metastases e.g. haemangiosarcoma
- direct extension of neoplasia outside brain e.g. nasal tumours, pituitary macro adenoma
Most common clinical signs of brain neoplasia? Which animals? Treatment?
More common in older and larger breed dogs
Most common signs:
- seizures in suratentorial tumours
- central vestibular dysfunction in infratentorial tumours
Treatment:
- less sedative AEDs
- anti-inflammatory doses of prednisolone
- analgesia: paracetamol, gabapentin
What degenerative disorders of the brain are there?
Storage diseases - defect of a lysosomal hydrolase enzyme
Accumulation and storage of substrate(s) within the cytoplasm of neurons - early onset, diffuse neurological dysfunction, progessive course leading to death
Cognitive dysfunction
Signs of cognitive dysfunction? Why does it happen? Treatment?
Changes in behaviour, memory and learning ability: - disturbances in sleeping - staring into space - getting stuck in corners - loss of house training - pacing or vocalising at night - newly developed behaviour problems Due to: - accumulation of beta-amyloid with senile plaque formation and neurofibrillary tangles Treatment: - selegiline - nutritional supplementation with antioxidants and other brain protective compounds - behaviour modification
What makes up the vestibular system?
Peripheral:
- 3 semicircular ducts at right angles to each other, rotation of head makes endolymph flow
- vestibulocochlear nerve (CN8) in connection with hair cells of each receptor, movement of endolymph causes bending of hair cells
Central:
- brainstem: 4 nuclei receive information from nerve and pass to brain and spinal cord
- cerebellum: inhibits vestibular nuclei
Clinical signs of vestibular disease?
Ispilateral head tilt Head sway if affecting both sides Ataxia and wide based stance Leaning and falling Less commonly tight circling Nystagmus - horizontal, rotatory or vertical - lesion on side of slower phase - vertical suggests central - may be positional Positional strabismus
When is a paradoxical head tilt seen?
= contralateral head tilt
Lesion of flocculonodular lobe or caudal cerebellar peduncle
Have other cerebellar signs
Cerebllum inhibits ipsilateral vestibular nuclei -> disinhibition:
- inhibition of ipsilateral extensors
- facilitation of contralateral extensors
What is convergence-related nystagmus?
Seen with small dorsal midbrain lesions - mostly infarcts
Irregular, jerky nystagmus in which both eyeballs rhythmically converge and retract into orbit
Which is opsoclonus nystagmus?
Seen with cerebellar disease
Bursts of rapid multidirectional eye movements without an interval between saccades
How to differentiate between central and peripheral vestibular disease?
Central - paresis possible, proprioceptive deficits possible, mentation may be affected, may be CNV-XII deficits, Horner’s rare, nystagmus can be vertical, horizontal or rotatory and may change direction
Peripheral - no paresis, no proprioceptive deficits, alert mentation, may be VII CN deficit, Horner’s possible, nystagmus is horizontal or rotatory, fast phase away from lesion
Causes of central vestibular disease?
V: cerebrovascular disease I: MUEs, FIP T: head trauma, metronidazole A: brain malformation M: hypothyroidism I N: brain tumours, thiamine deficiency D: lysosomal storage diseases, degenerative diseases
Causes of peripheral vestibular disease?
V I: otitis media/interna T: trauma to middle/inner ear, ototoxic drugs A: congenital vestibular disease M: hypothyroidism N: middle ear tumours D
Which vestibular diseases are acute?
Idiopathic vestibular disease
Cerebrovascular disease
Head trauma
Trauma to middle/inner ear
Acute or chronic:
Hypothyroidism
Metronidazole
Ototoxic drugs
What cerebrovascular diseases are there?
= abnormality of brain caused by disruption of blood supply
Strokes - ischaemic (arterial or venous obstruction) or haemorrhagic (rupture of blood vessel)
Infarct - area of necrotic tissue resulting from ischaemia
Signs of cerebrovascular disease (e.g. stroke)? Appearance on MRI?
Clinical signs vary but acute and non- progressive
Signs of central vestibular disease
MRI:
- well-defined, sharply demarcated lesions with minimal to no mass effect
- limited to vascular territory of a main cerebral or perforating artery
- hyperintense on T2WI and FLAIR
What concurrent medical conditions can cause cerebrovascular disease (stroke)?
Present in approx half of cases
CKD Hypertension HAC Protein losing enteropathy Cardiac disease Neoplasia Angiostrongylus vasorum DM, hypothyroidism
Treatment for cerebrovascular disease (strokes)? Prognosis?
Supportive
Treat underlying disease
Fair-good prognosis
Shorter survival time and more recurrence if concurrent medical condition
GME: Which dogs? Signs?
Young adults, toy and terrier breeds Multifocal signs: - often caudal fossa (vestibular and cerebellar) but anywhere - may affect spinal cord - may just cause acute blindness
What are the 3 forms of GME?
- Disseminated - most common, multifocal signs involving forebrain, brainstem, cerebellum, spinal cord
- Focal - can be confused with neoplasia
- Ocular - acute onset visual impairment, dilated and non-responsive pupils and optic disc oedema
What is seen on MRI and CSF analysis with GME?
MRI:
- multiple hyperintensities on T2WI and FLAIR
- irregular margins
- predilection for WM but in both GM and WM
- variable degrees of contrast enhancement
CSF analysis:
- pleocytosis (lymphocytic, neutrophilic or mixed)
- increased protein concentration
- occasionally can be normal
Which breeds get NE? Presentation? What happens? Signs? Treatment?
Mostly pug, chihuahua, yorkie Acute onset and progressive signs Worse prognosis than GME Areas of necrosis mostly in cerebral cortex often coalesce to form large areas of cavitation Signs: - seizures - blindness - altered behaviour - circling - depression Can potentially stabilise but often permanent deficits (e.g. will still be blind/circle) Treatment = immunosuppression: - high dose of corticosteroids plus: - cytosine arabinoside - azathioprine - ciclosporine - lomustine
Why do 30% of cats with clinical FIP have CNS involvement -> vestibular disease? What signs?
Lesions result from immune-complex mediated vasculitis
Neurological signs:
- insidious signs, progressive, can be focal, diffuse or multifocal
- more commonly localise to the cerebellomedullary region (tetraparesis, ataxia, nystagmus and loss of balance)
- occasionally only progressive spinal cord disease
- sometimes also behavioural changes, seizures
- +/- iritis, anterior uveitis, chorioretinitis
Diagnosis of FIP?
Clinical signs +/- ocular changes
Lymphopenia, neutrophilia, non-regenerative
anaemia
Increased serum a-1-acid glycoprotein (AGP)
High serum titres of FCoV Ab
Albumin to globulin ratio <0.8g/dL
CSF (variable): usually high protein and pleocytosis (mononuclear or mixed)
RT-PCR for FCoV RNA on CSF
MRI or CT:
- periventricular contrast enhancement
- ventricular dilation and hydrocephalus
Why can hypothyroidism cause vestibular disease?
Poss:
- thyroid supports metabolism so normal axonal function and transport
- aberrant lipid metabolism and atherosclerosis
- formation of xanthomata
Can cause peripheral or central vestibular disease
Reversible with supplementation of levothyroxine
Possible CNS signs from metronidazole toxicity? When seen? Mechanism? Treatment?
Uncommon
Signs of CVS, seizures, tremors, rigidity
Usually when doses ≥60mg/kg/day
Mechanisms of neurotoxicity suggested:
- RNA and DNA binding
- modulation of inhibitory neurotransmitter GABA receptor
Treatment - discontinuation of drug, faster improvement with diazepam
When is thiamine deficiency seen? Why can it cause CNS signs? What CNS signs seen?
Low amount in food - overcooked
Cats fed all fish diet
Destroyed by sulfites used as a preservative
Essential for oxidation of glucose in Krebs cycle
Tissues dependent on glucose more affected (brain, heart)
Signs:
- anorexia, lethargy
- vestibular signs
- seizures
- reduced VOR, mydriasis with reduced PLR
What is the most common brain tumour causing vestibular signs?
Caudal fossa menigiomas
What CNS signs may be seen with otitis media/interna? Why?
CNVII, CNVIII and sympathetic supply to eye pass by middle ear Signs: - facial paralysis - peripheral vestibular signs - horner's syndrome - pain opening mouth
Idiopathic vestibular disease - How do they present? Diagnosis? Treatment?
= acute onset of PVD, non progressive, spontaneous recovery, improving over 2-4 weeks More common in dogs Unknown aetiology Acute onset of peripheral signs: - rolling, falling, vomiting, ataxia - head tilt - nystagmus (horizontal or rotatory) Can be bilateral Can happen simultaneously with facial paralysis Middle to older age dogs Diagnosis of exclusion Some contrast enhancement of CNVIII sometimes seen on MRI No need to treat
What is the atypical form of idiopathic vestibular disease?
Acute onset of PVD but clinical signs progressive over 3 week period
Recovery over 3 months
Residual deficits (mild head tilt) not common
More common in cats
Causes of facial nerve paresis/paralysis? Signs? Treatment? Prognosis?
Causes: - idiopathic most common - brainstem lesions (+ other signs) - middle ear disease Clinical signs: - drooping of face - widening of palpebral fissure - food and saliva may drop from side of mouth - absence/reduction of palpebral and corneal reflexes Treatment: - avoid KCC (eye lubrication) Prognosis (Idiopathic): - extent of recovery variable (permanent deficits 50% cases), over several weeks (~8 weeks)
Mechanism of hearing?
- sound wave
- external ear canal and tympanum
- 3 ossicles (malleus, incus, stapes)
- oval window
- perilymph in scala vestibuli
- wave flow is reflected to basilar membrane
- movement of hair cells
- impulse in cochlear neurons
- CnVIII goes through internal acoustic meatus
- cochlear nucleus in medulla
- pass many nuclei in pons and midbrain
- cerebral cortex (temporal lobe) bilaterally
How is deafness classified?
Age of onset - congenital, late onset
Underlying cause - inherited, acquired
Location of defect - peripheral, central
Sensorineural (from cochlea to brain) or conductive (failure to conduct sound from outer to inner ear)
What are the most common types of deafness in dogs? Causes?
Congenital sensorineural deafness (dog and cat breeds with white pigmentation and blue eye colour, merle and piebald genes)
Acquired sensorineural deafness (chronic otitis interna, ototoxicity, noise trauma, presbycusis)
Acquired conductive deafness (otitis externa and media)
What an Otoacoustic Emission test (OAEs)?
Low level sounds produced by inner ear as part of normal hearing that can be measured with the use of a microphone
Less expensive, quicker and easier to interpret than BAER
But less reliable
How does the BAER test work?
Brainstem auditory evoked responses
Click stimuli generated by either headphones or insert earphones
3 SC needle electrodes sample electrical responses of CNVIII and auditory portion of the brainstem and result in up to seven (I-VII) positive waves
Important history for spinal disease?
Onset
Progressive or not
Pain
Which spinal diseases have a peracute/acute, subacute and chronic onset?
Vascular and trauma/tocic - acute, static/improving
Inflammatory, infectious, degenerative (IVDD) - subacute, progressive
Degenerative, neoplastic, anomalous, inflammatory/infectious - chronic, progressive
Which spinal diseases are painful?
Inflammation
Space occupying
Trauma
Steroid responsive meningitis-arteritis (SRMA): Which dogs? Cause? Clinical signs? Diagnosis? Treatment? Prognosis?
Young dogs (6-18mo)
Most common cause of neck pain in young dogs
Immune mediated cause suggested
Clinical signs:
- lethargy and anorexia
- stiff gait
- fever
- cervical rigidity and spinal hyperaesthesia
- neurological deficits possible with chronic form
- often concurrent IMPA
Diagnosis:
- CSF analysis: neutrophilic pleocytosis in acute form, mononuclear pleocytosis in chronic form
- +/- spinal radiographs, CT, MRI
Treatment:
- corticosteroids for 6-9m
- +/- azathioprine or cyclosporine
- monitoring with repeated CSF analysis or CRP
Prognosis - very good but potential relapse
What is discospondylitis? Signs? Diagnosis? Treatment?
= Infection of IVD and adjacent vertebrae, most common at L7-S1 Signs: - Marked spinal pain - Systemic signs of illness Diagnosis: Radiography (can only see after 2-4w), MRI or CT: - narrowing of IVD space - roughening of endplates - proliferation of adjacent bone Bacteriology: blood, urine, CSF, IVD Treatment: - antibiotics for at least 8 weeks - analgesia
Meningomyelitis of unknown origin (MUO): Presentation? Diagnosis? Treatment?
(Sub)acute, progressive, can be symmetrical, can be painful
Often multifocal (sometimes affect brain)
Care as same breeds and often similar presentation to IVDD
Diagnosis:
- MRI: variable findings
- CSF: mononuclear or mixed pleocytosis
Treatment: corticosteroids +/- other immunosuppressive drugs
Causes of spinal fractures and luxations? Diagnosis?
Causes: - RTA, bite wounds, falling from height TL spine most commonly Diagnosis: - careful neurological exam - thoracic and abdominal radiography - survey lateral radiographs of spine - orthogonal views essential - care with sedation and manipulation (don't want complete muscle relaxation as may be stabilising fracture) - CT/MRI may be indicated
What is the 3 compartment model of vertebral fractures?
Dorsal = articular processes, laminae, pedicles, spinous processes and supporting soft tissue structures Middle = dorsal longitudinal ligament, dorsal vertebral body and dorsal annulus fibrosus Ventral = rest of vertebral body, lateral and ventral annulus fibrosus, nucleus pulposus and ventral longitudinal ligament
Treatment and prognosis of vertebral fractures and luxations?
Initial treatment: stabilise trauma patient and analgesia (NSAIDs)
Use 3 compartment rule -> if unstable needs surgery or splint
Decompression if fragments compressing spinal cord
Splint if transporting patient
Prognosis:
- lack of deep pain perception <5% recovery (usually associated with spinal cord laceration)
- severe cerebral displacement, other injuries, weight and age, time to referral
Atlantoaxial (AA) instability: Which animals? Presentation? Cause? Clinical signs? Treatment?
Young dogs, toy breeds
Associated with aplasia/hypoplasia of dens in toy breeds
Acute or chronic, often with waxing and waning
Sometimes associated with trauma
Clinical signs:
- neck pain
- ataxia or tetraparesis
Treatment:
- conservative splint for 6-12w has 60% success
- surgery has high preoperative morbidity and mortality (problems with respiration when manipulating) but success up to 90%
What is Chiari-like malformation? Which breeds? What does it cause? Signs?
= mismatch between caudal fossa volume and its contents (cerebellum and brainstem) with caudal displacement through foramen magnum
All CKCS have this but only about 30% get springomyelia
It can cause:
- hydromyelia = dilatation of central canal
- springomyelia = fluid filled cavitation
- springohydromyelia = both
Signs:
- neck pain
- neck scratching
- torticollis/scoliosis
- thoracic limb weakness and atrophy
Treatment of Chiari-like malformation?
Medical: - gabapentin, amantadine - NSAIDs - furosemide, omeprazole, acetazolamide - corticosteroids, paracetamol, opioids Surgical: - results in clinical improvement in 50% cases - does not correct syrinx, high recurrence rate of clinical signs
Ischaemic myelopathies - Presentation? What causes it?
Peracute, non painful signs often very lateralised
Usually at exercise
Fibrocartilage from nucleus pulpous embolisms in spinal cord vasculature (fibrocartilagenous embolism (FCE))
Traumatic disc extrusion - Presentation? Cause?
Following traumatic events (RTA, fall from height) or just exercise
Acute onset, non-painful, non-progressive
Herniated nucleus pulposus is non-mineralised, causing mainly cord contusion with minimal compression
Non surgical as no compression to remove
Treatment of FCE and traumatic disc extrusions?
Supportive care and physiotherapy
Median time to ambulation is 2 weeks
Time to maximal recovery is 3m
Difference between intervertebral disc degeneration (IVDD) in chondrodystrophic and non chondrodystrophic breeds?
Chondrodystophic breeds:
- during first 2 years
- chondroid metamorphis
- IVD dehydrates and nucleus is invaded by hyaline cartilage, nucleus can mineralise
Non chondrodystrophic breeds:
- after middle age
- fibroid metamorphosis
- IVD dehydrated and nucleus is invaded by fibrocartilage, mineralisation less common
What is type I IVDD? breeds and age? Signs?
= extrusion
Herniation of nucleus pulposus through annular fibres and extrusion of the nuclear material into the spinal canal
3-6y chondrodystrophic and 6-8y non- chondrodystrophic breeds
Peracute/acute onset, progressive
Typically painful
What is type II IVDD? Breeds and age? Signs?
= protrusion Annular protrusion caused by shifting of central nuclear material, commonly associated with fibroid disc degeneration Older, non-chondrodystrophic breeds Slowly progressive, chronic onset Spinal pain may or may not be present Typically less severe signs
Grades of IVDD? Prognosis?
Grade 1: no deficits, just pain Grade 2: paresis, ambulatory Grade 3: paresis, non ambulatory Grade 4: paralysis Grade 5: no pain sensation
Very good prognosis for grades 1-4
Grade 5 5% with conservative, 50-60% with surgery
Treatment for IVDD?
Conservative: - strict rest for 4-6 weeks - analgesia Surgical: - if severe neurological deficits (grades 3-5) - if severe or recurrent pain - if lack of improvement with rest
Cervical spondylomyelopathy (CSM) “Wobblers”: Signs? Treatment?
Signs worse in pelvic limbs - paresis, ataxia
Short stilted gait and muscle atrophy in thoracic limbs
Conservative treatment: anti-inflammatories, rest
Surgery:
- decompression vs distraction-stabilisation
- 80% success
What causes CSM (Wobblers)?
Multifactorial:
- protrusion of IVD (type II IVDD)
- hypertrophy of ligament flavum and dorsal longitudinal ligament
- hypertrophy of synovial membrane
- stenosis of spinal canal
- degenerative joint disease of facets
Signs of lumbosacral degenerative stenosis?
Reluctance to exercise, rise, jump into car, do stairs
Lameness - nerve root signature
Lumbosacral pain
Monoparesis/paraparesis
Proprioceptive deficits, reduced withdrawal reflex, muscle atrophy
Urinary and/or faecal incontinence
What causes lumbosacral degenerative stenosis?
- type II I VDD
- sclerosis of vertebral endplates and
articular processes - hypertrophy of ligaments
- hypertrophy of synovial membranes
- foraminal stenosis
- ventral subluxation of sacrum
Treatment for lumbosacral degenerative stenosis?
Conservative treatment: anti-inflammatories, gabapentin Surgical treatment: - dorsal laminectomy - dorsal fusion-fixation - foraminotomy
What vertebral anomalies are there? How do they present? Diagnosis? Treatment?
Butterfly vertebrae Block vertebrae Transitional vertebrae Hemivertebrae Spinal stenosis
Chronic onset, slowly progressive
Typically non-painful
Myelography (+/- CT), MRI
Surgical decompression +/- stabilisation
Degenerative myelopathy: presentation? Diagnosis? Treatment?
Insidious, progressive ataxia and paresis of pelvic limbs, ultimately leading to paralysis (over 6-18m)
Typically T3-L3 myelopathy
Usually asymmetrical
Not painful
Diagnosis of exclusion, genetic test
No treatment but physiotherapy prolongs QOL
What is a hemilaminectomy?
Removal of one half of the vertebral arch (lamina, articular process and pedicle)
Mainly used in TL spine
Access to lateral and ventral SC
Allows for IVD fenestration
What is a dorsal laminectomy? When used?
Removal of the dorsal spinous process and laminae
Can be used anywhere, most commonly performed at the LS area
Access to dorsal and dorsolateral SC
IVDD at LS, congenital malformations, neoplasia
What is a ventral slot?
Slot-like opening ventrally through the IVD and cranial and caudal endplates of cervical vertebrae
Access to ventral SC (IVDD)
Limited view
UMN and LMN incontinence?
UMN:
- lesions cranial to sacral SC that interrupt afferent sensory and efferent motor pathways
- impair voluntary micturition, distended bladder difficult to express
LMN:
- lesions in sacral SC, sacral spinal nerves and plexus, pelvic and pudendal nerves
- distended bladder, continually overflowing and dribbling
Which drugs can be used for urinary incontinence?
Bethanecol, cisapride - increase detrusor contraction by cholinergic stimulation
Propantheline bromide - reduce detrusor hyperreflexia as anticholinergic
Phenylpropanolamine - increases urethral tone as a-adrenergic agonist
Phenoxybenzamine, prazosin - redce urethral tone as a-adrenergic antagonist
What are non specific signs of generalised neuromuscular disease?
Tetraparesis and exercise intolerance/collapse
Stiff-stilted gait with reduced stride length, bunny hopping
+/- Proprioceptive deficits
Muscle atrophy and tremors/fasciculations (especially when weight bearing)
May have dysphonia, regurgitation, difficulty chewing/opening mouth
What are the general signs of lesions in motor units?
Reduced/absent reflexes
Muscle atrophy
Reduced tone
Clinical signs of neuropathies?
Can be cranial and/or spinal nerves and mono, multiple mono or generalised
Motor +/- sensory deficits (proprioception, nociception, hypo- or para-esthesia)
Severe flaccid paresis, neurogenic atrophy and reduced-absent reflexes
Clinical signs of junctionopathies?
Always generalised
Classicaly exercise intolerance with fatigue
Normal sensory function
Often intact tendon reflexes unless severe weakness
Clinical signs of myopathies?
Generalised or focal (usually symmetrical)
Atrophy or hypertrophy
Specific features:
- dimple contractures (myotonia)
- myalgia
- restricted joint movement (contracture)
Normal sensory function
Often normal tendon reflexes but exceptions
Definition of paresis/plegia?
= Reduced/absent voluntary movement
Clinical signs of UMN and LMN dysfunction?
UMN: (wobbly)
- long strided, incoordinated, irregular, ataxic gait
- slow postural reactions
- normal/increased reflexes
- none/disuse muscle atrophy
- normal/increased muscle tone
LMN: (weak)
- short strided, appears stiff/lame, difficulty supporting weight, bunny hopping
- normal postural reactions if supported
- reduced reflexes
- neurogenic muscle atrophy (rapid and severe)
- reduced muscle tone
How to localise
Slide 13
General diagnostic approach to neuromuscular problems?
Haematology Biochemistry: - CK and AST - electrolytes K+, Ca2+, Na+ - glucose - cholesterol Urinalysis: - myoglobinuria (muscle damage) Chest radiography (conscious): - megaoesophagus +/- aspiration pneumonia Endocrine tests Serology for infectious diseases CSF Electrodiagnostics Muscle biopsy Nerve biopsy
Avoid GA/sedation - risks
Specific diagnostic tests for neuromuscular problems?
Specific auto-antibodies (nAChR Ab in acquired myasthenia gravis, 2M Ab in masticatory myositis)
Edrophonium response test
Lactate and pyruvate (exercise testing for mitochondrial dysfunction)
Genetic testing:
- Labrador centronuclear myopathy
- Leonberger polyneuropathy
- etc
Muscle biopsies for neuromuscular problems - Preparation?
Formalin-fixed samples:
- histological stains such as H&E
- can diagnose inflammatory infiltrates, fibrosis
- but will miss a lot of info if just use these
Fresh-frozen samples (cryosections):
- histological stains
- enzymatic reactions
- immunohistochemistry
Electron microscopy:
- rapid fixation in formalin or glutaraldehyde
Nerve biopsy?
Muscle biopsy – denervation changes – intrafascicular nerve branches Fascicular nerve biopsy – Axon structure and density – Myelin sheath thickness and integrity – Schwann cells, support tissues, infiltrates Specialist laboratory required for analysis
What is polyradiculitis? Cause? Presentation? Signs? Natural disease progression?
Relatively common (dogs>cats affected)
Inflammation of nerves and roots:
- idiopathic/vaccine (rabies)/contact with racoons
- breed predisposition in Bengal cats
- demyelination (axon damage in severe forms)
Most pathology is in ventral spinal roots so usually pure motor deficits
CN not affected other than mild facial paresis
No sensory deficits
Acute onset, rapidly progressive (days):
- tetra/paraparesis -> non ambulatory tetaparesis/plegia
- flaccid, markedly reduced motor function (inc absent reflexes)
- can affect respiratory muscles
Natural disease progression:
- inflammation is of short duration
- recovery over days-weeks (demyelination)
- more prolonged if axonal damage
Diagnosis, treatment and prognosis of polyradiculoneuritis?
Diagnosis:
- clinical signs and history
- F waves and CSF analysis (lumbar) supportive)
Treatment:
- supportive (recumbent care, physiotherapy, poss ventilatory support)
- specific (human IV Ig?)
Prognosis = fair (guarded if respiratory dysfunction
What is myasthenia gravis? Types?
A junctionopathy
D/t reduced neuromuscular transmission
Acquired:
- immune mediated: Abs against nAChR in majority
- can be paraneoplastic, especially thymoma in cats
- generalised most common in dogs (cats less likely to have megaoesophagus)
- fulminant: acute onset, rapidly progressive
- focal: facial, pharyngeal, laryngeal, megaoesophagus
- megaoesophagus in >80% of dogs with MG
- thymoma in 25% of cats
Congenital: AR inheritence
Diagnosis of myasthenia gravis? Prognosis?
Diagnosis:
- clinical signs
- nAChR Ab test is gold standard (slow to get results)
- electrodiagnostic tests (repetitive nerve stimulation)
- “Tension” edrophonium response test
Treatment:
- anti-cholinesterase (pyridostigmine p/o, neostigmine i/m)
- immunosuppression (pros and cons, better in cats than dogs)
- thymectomy?
- postural feeding if megaoesophagus
Appears to be self limiting in some dogs so monitor nAChR Ab titres
Prognosis guarded
- fulminant forms can be difficult to treat
- poor if aspiration pneumonia
What causes botulism? Clinical signs?
Ingestion of contaminated food (esp animal carcasses) - Clostridium botulinum exotoxins
Rare in dogs and cats
Toxin absorbed from the gut and blocks vesicle fusion with the presynaptic membrane and ACh release
Clinical signs due to nicotinic ACh synapses (junctionopathy):
- acute onset rapidly progressive tetraparesis (2-3d)
- may affect CNs: jaw tone, facial paralysis, gag reflex, megaoesophagus
- may affect respiratory muscles
Clinical signs due to muscarinic ACh synapses (dysautonomia):
- urinary dysfunction
- GI dysmotility
- mydriasis
- reduced tear production
Diagnosis, treatment and prognosis of botulism?
Diagnosis:
- clinical signs
- electrophysiology
- demonstrate toxin (usually not possible) or serology (retrospective exposure)
Treatment:
- supportive care (bladder management, recumbency care, megaoesphagus management, physiotherapy)
- (anti-toxin)
Prognosis
- depends upon severity of clinical signs
- generally poor if impaired ventilation/aspiration pneumonia
Causes of myositis?
Generalised inflammatory: - IM polymyositis - dermatomyositis (familial in collies, shelties) - prominent skin lesions - polysystemic IM diseases Focal myositis: - masticatory - extra-ocular - vizsla polymyositis Paraneoplastic: - thymoma - lymphoma Infectious: - Neospora - Toxoplasma - etc
Clinical signs of infectious myositis due to Neospora in puppies? Diagnosis? Treatment? Prognosis?
Clinical signs: - radiculoneuritis and polymyositis - pelvic limb hyperextension (usually starts in one limb and progresses to other) - ascending paralysis of pelvic limbs with muscle contracture and arthrogryposis Diagnosis: - clinical signs - CK/AST - EMG - biopsy - serology Treatment: - clindamycin/TMPS + pyrimethamine Poor prognosis with contractures
Clinical signs, diagnostic tests and treatment of immune mediated polymyositis?
Clinical signs – Acute or chronic onset, variable signs – Exercise intolerance, generalised weakness, muscle atrophy – Pyrexia, stiffness, non-ambulatory tetraparesis, reluctance to move, lowered head carriage, myalgia – +/- oesophageal involvement Diagnostic tests – H+B: Inflammatory leucogram, elevated CK/AST (acute typically +++) – Electrodiagnostics: marked EMG abnormalities, normal MNCV – Muscle biopsy for diagnosis – Rule out infectious diseases and tumours Treatment – Prednisolone – +/- other immunosuppressives
Masticatory myositis - Cause? Clinical signs? Diagnosis? Treatment?
Dogs only Antibodies to 2M myosin isoform Juvenile form in CKCS Clinical signs: - acute or chronic - swollen/painful MM, exophthalmos - trismus (pain/fibrosis), MM atrophy Diagnosis - imaging (muscles + TMJ) - CK (may be normal or slightly elevated) - 2M antibodies - EMG - biopsy temporal muscles Treatment - prednisolone +/- other IM drugs - physiotherapy
Trigeminal neuritis - What is it? What happens? Clinical signs? Diagnosis? Treatment?
Dogs»_space; cats
Inflammation throughout trigeminal nerves including ganglia bilaterally
Demyelination -> axon degeneration
Clinical signs:
- acute onset paresis/plegia of masticatory
muscles -> dropped jaw
- normal gag and tongue tone and movements (Horner’s or facial paresis can be seen)
- sensory deficits in ~30% pf cases
- masticatory muscle atrophy
Diagnosis
- MRI: swollen, inflamed nerves
- CSF
Treatment
- resolves usually within 3weeks with supportive care
Traumatic neuropathies: What are neuropraxia, axonotmesis and neurotmesis? Prognosis of each?
Neuropraxia = temporary nerve damage (conduction block) but no disruption of the nerve or myelin sheath
- prognosis for return of function is good, often within a few days
Axonotmesis = disruption of axon but intact basal lamina and myelin sheath
- prognosis is variable, but rate of axonal regrowth is only 1 to 4 mm per day, recovery will be slow
Neurotmesis = partial or complete transection of the nerve (axon and supporting structures)
- partial recovery is possible, but complete recovery is unlikely
Clinical signs and prognosis of brachial plexus avulsion?
Monoparesis, cutaneous truancy absent ipsilaterally, Horner’s syndrome
Radial function necessary for gait
Poor prognosis with loss of nociception
Clinical signs, diagnosis and treatment of brachial plexus tumours?
Most are intrinsic e.g. malignant peripheral nerve sheath tumour Clinical signs: - chronic progressive thoracic limb lameness, pain, muscle atrophy - neuro deficits: partial/complete plexus involvement, monoparesis-plegia, progression to myelopathy, palpable mass Diagnosis: - electrodiagnostics - imaging - US - CT - MRI best Treatment and definitive diagnosis: - surgery Prognosis poor if spinal involvement
Definition of a seizure?
= A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain
Localisation of seizures?
Always forebrain
Pathogenesis of seizures?
Imbalance in excitation and inhibition
Balance moves towards excessive excitement or decreased inhibition
Stages of a seizure?
- Prodrome - any predicting events
- Aura - initial manifestation of a seizure
- Ical - seizure event, involuntary muscle tone or movement +/- abnormal sensations or behaviour
- Post-ictal - minutes to days, can have unusual behaviour or neurological deficits
What happens with the ictal event of a seizure? How long does it last? Phenotypic categories?
Usually around 60-90 seconds
Peracute onset
Characteristics are the same for each event
Occurs most commonly at sleep or rest
Autonomic signs
2 major phenotypic categories:
- generalised: involvement of both cerebral hemispheres simultaneously, consciousness impaired
- focal: initial activation of one part of one cerebral hemisphere or region in the forebrain, complex focal seizures have altered consciousness
What phases may a generalised seizure have?
May have one or several:
- Tonic-clonic (most common)
- Tonic
- Clonic
- Myoclonic
- Atonic
Forms of focal seizures?
- Motor
- Autonomic
- Behavioural
What are audiogenic reflex seizures? How to control?
Cats
Late onset (15y)
Reflex seizure = seizure that is objectively and consistently precipitated by environmental or internal stimuli
In response to noise
Myoclonic seizures progressing to generalised tonic/clonic seizures in some
Levetiracetam to control
What can look like seizures but isn’t?
Narcolepsy/cataplexy Neuromuscular collapse Syncope Movement disorder Metabolic disease Vestibular disease
How can idiopathic head tremor syndrome be differentiated form a seizure?
Can distract and stop it with a treat etc
Conscious throughout
Lasts too long
Acts normal afterwards
Causes of seizures?
- Reactive seizures:
- occurs as a natural response from the normal brain to a transient disturbance in function
- concurrent neurological signs usually present
- metabolic or toxic - Idiopathic epilepsy:
- genetic or presumed genetic in origin
- no inter-ictal neurological signs - Structural epilepsy:
- epileptic seizures which are provoked by intracranial or cerebral pathology
- concurrent neurological signs usually present
- inflammatory, neoplastic, traumatic
What causes episodic falling of the CKCS? what does it look like?
Paroxysmal hypertonicity found in CKCS
Conscious and aware throughout
What is dyskinesia? What is the most common one?
Abnormal movement
Most common is paroxysmal gluten sensitivity in Border terrier - presumed problem in basal nuclei
Conscious and aware throughout
Idiopathic epilepsy - Age affected? Presentation? Types?
Dogs 6m-6y
Normal neurological exam between seizures
- Genetic epilepsy: causative gene has been identified:
- Logotto Romagnolo (protein truncating mutation in LGI2 gene)
- Belgian shepherd
- Boerboels - Suspected genetic epilepsy: a genetic influence supported by a high breed prevalence (>2%)
- Epilepsy of unknown cause: epilepsy in which the cause in unknown, no indication of structural epilepsy
Diagnosis of idiopathic epilepsy?
Diagnosis of exclusion Tier 1 confidence interval: - 2 or more seizures 24h apart - age of onset 6m-6y - normal inter-ictal examination - no clinically significant abnormalities on minimum database (haematology, biochemistry, fasting bile acids, urinalysis) Tier 2 confidence interval: - unremarkable fasting and post-prandial bile acids - MRI of brain - CSF analysis - as well as tier 1 factors Tier 3 confidence interval: - ictal or inter-ictal EEG abnormalities - as well as tier 1 and 2 factors
When to MRI a dog with seizures as less likely idiopathic epilepsy?
Age of onset <6m or >6y
Interictal neurological abnormalities (consistent with intracranial neurolocalisation)
Status epileptics or cluster seizure
Previous presumptive diagnosis of IE and drug resistance with a single AED titrated to the highest tolerable dose
When would you start treatment for idiopathic epilepsy?
Structural or metabolic epilepsy
Status epileptics or cluster seizures
An interictal period of 6m or less
Post-ictal signs are severe or last longer than 24h
The seizure frequency and/or duration is increasing and/or seizure severity deteriorating over 3 interictal periods
The first seizure is within 1 month of a traumatic event
Treatment for epilepsy?
Epilepsy cannot be cured with medication but drugs can be used to symptomatically suppress epileptic seizures
3 licensed maintenance treatments in dogs:
- phenobarbitone
- bromide
- imepitoin
No drugs licensed in cats
Phenobarbitone for epilepsy - How effective? Mechanism of action? Initial dose? Monitoring? Aim?
Effective in decreasing seizure frequency in 60-90% of dogs with idiopathic epilepsy
Mechanism = augments the inhibitory effects of GABA -> prolonging the chloride channel opening at GABAA receptor
Initial dose:
- dogs 3mg/kg BID
- cats: 2mg/kg BID
Monitoring:
- 2 weeks after any dose change (plain serum)
- 3 months (inc haematology and biochemistry)
6 months (haematology and biochemistry)
Aim = levels between 25-30mg/L
Takes about 10-14d for peak effects
Side effects of phenobarbitone?
Sedation, ataxia (most adapt after 2 weeks)
PUPDPP
Hepatotoxicity - always get increased ALP (and poss ALT, don’t worry unless very high)
Haematological abnormalities (neutropenia, anaemia, thrombocytopenia)
How is phenobarbitone metabolised? When contraindicated?
Mainly via hepatic microsomal enzymes
Potent inducer of cytochrome P450 enzyme activity in the liver:
- increases hepatic production of reactive oxygen species
- increasing the risk of hepatic injury
Contraindicated in dogs with hepatic dysfunction
Also leads to accelerated clearance of itself over time
Bromide for epilepsy - Form given in? How given? Mechanism? Initial dose? Monitoring? Therapeutic range?
Usually KBr or NaBr salts
Not licensed as a monotherapy
Can be used in combination
mechanism of action = competes with Cl- transport across nerve cell membranes and inhibits Na+ transport -> membrane hyper polarisation which raises the seizure threshold
Initial dose:
- dogs 30mg/kg SID
- NOT cats
Monitoring:
- 12 weeks plain serum (inc haematology and biochemistry)
Therapeutic interval:
- 10-15mmol/L in combo with phenobarbitone
- or 12.5-37.5mmol/L as mono therapy
Takes 12 weeks for peak effects
Must be on consistent diet to be effective
Side effects of bromide?
Sedation
Ataxia and pelvic limb weakness
Metabolism of bromide?
Excreted unchanged in urine
Undergoes tubular reabsorption in competition with chloride
Imepitoin for epilepsy - Licensing? Mechanism? Dose? Monitoring? Side effects? Metabolism?
Not licensed for cluster seizures or structural epilepsy
Only licensed as monotherapy
mechanism = low affinity partial agonist for benzodiazepine binding sire of GABAA receptor
Dose:
- dogs 10-30mg/kg BID
No monitoring required
Side effects - similar but fewer than phenobarbitone
Metabolism:
- metabolised by liver
- excreted in faeces
What non licensed drugs are used in dogs for epilepsy? Doses? Side effects?
Levetiracetam: - 20mg/kg TID (initial loading dose of 60mg/kg can be considered) - titrate dose up in cats - minimal side effects (sedation) - PO, IV Zonisamide: - 10mg/kg BID - side effects: ataxia, sedation, dry eye, inappetance - reduce phenobarbitone doses by 25%
Drugs used for epilepsy in cats?
Nothing licensed
Diazepam - fulminant hepatic necrosis associated with oral administration
Propofol - Heinz body anaemia
Potassium bromide - eosinophilic bronchitis
Phenobarbitone - lower starting (2mg/kg) and loading doses (12-15mg/kg)
What seizures are emergencies?
Cluster seizures: - 2 or more in 24h - dogs with IE who suffer from CS are less likely to achieve remission, have decreased survival time, are more likely to be euthanised Status epilepticus: - seizure lasting >5 mins - or >2 seizures without full recovery
Why are cluster seizures and status epilepticus emergencies?
Irreversible neuronal damage occurs after 30-60 minutes
Due to failure of the mechanisms that usually stop an isolated seizures -> abnormal excessive excitation or ineffective inhibition
-> excitotoxic cell injury due to excessive glutamate release
What are the stages of cluster seizures or status epilepticus causing brain damage?
Stage 1 - increased autonomic activity: - tachycardia - hypertension - hyperglycaemia Stage 2 - irreversible neuronal damage (after 30 mins): - hypotension - hypoglycaemia - hyperthermia - hypoxia - excessive electrical activity results in brain damage
Causes of status epilepticus?
Idiopathic epilepsy Neoplasia CNS inflammatory disease Trauma Metabolic disorders Toxicities
How to treat emergency seizures (cluster seizures or status epilepticus)?
First stop the seizure! - Diazepam 1mg/kg per rectum Take history IV catheter placement Examination Baseline blood work - minimum = - glucose - sodium - calcium - renal and hepatic function In existing epileptics - check serum levels of anti epileptic drugs
If not already on AEDs:
Start AEDs: phenobarbital 3mg/kg BID
If further seizure activity over next 1-3h or if seizures do not stop: phenobarbital loading (18-21mg/kg in 3mg/kg boluses)
If further seizures: levetiracetam loading (60mg/kg)
Other meds based on individual:
- KBr rectal loading (600mg/kg over 24h as 5 rectal boluses of 100mg/kg q4h
- consider volatile anaesthesia
- zonisamide 10mg/kg PO
- dexmedetomidine CRI (can be considered for management of agitation on recovery from CRI)
What to do for breakthrough seizures (emergency seizures still going despite emergency treatment)?
Diazepam - interacts with plastic and light Midazolam: - 0.3mg/kg IV bolus followed by 0.3mg/kg/hr - not in hepatic dysfunction - dogs in SE may become refractory Propofol: - 6mg/kg IV bolus followed by 6mg/kg/hr - care Heinz body anaemia in cats
Ensure dog needs it - don’t hesitate if does!
Also although idiopathic epilepsy likely, consider underlying causes and treat (e.g won’t stop hypoglycaemic seizure without correcting glucose!)
Monitoring of emergency seizures while on treatment?
HR and RR
BP - systolic >90mmHg (MAP 70-80)
Urine production - 1-2ml/kg/hr
Oxygenation/ventilation - pulse oximetry >95%, ETCO2 35-40mmHg
Temperature
Neurological exam - allow assessment for signs of improvement/deterioration
If on an infusion:
- pharyngeal tone - intubation if risk of aspiration
Management of emergency seizures while treating?
Well padded cage - clean and adequate bedding Monitor for pressure sores Eye lubrication q2-4h Feeding/water Thermoregulation
What must be ruled out in a young dog with seizures, sleeping more after eating?
PSS
