Intracranial Disease Flashcards
DDx for syncope/weakness
Structural intracranial disease
Reduced O2 or nutrient delivery to brain (cardiac, resp, metabolic)
Impaired blood flow (ischaemic event)
Altered muscle function
Toxins
Systems to be considered in any patient with history of collapse, weakness or seizure: CVS, NS, MSK, metabolic (electrolytes, glucose, endogenous toxins), respiratory.
Differentials for persistent vs episodic weakness
PERSISTENT - most presentations in cats are persistent
Peripheral neuropathy
Muscle dysfunction
NMJ abnormalities (MG)
Hyperviscosity syndrome
Anaemia
K or Ca derangements
Endogenous toxaemia
EPISODIC
NMJ abnormalities (MG)
CV disorders
Exercise induced hyperthermia
Respiratory disease (HT, HWD, lar par)
Metabolic disturbance (hypoglycemia or K+)
Cataplexy/Narcolepsy
Common causes of stupor/coma
Increased ICP
(encephalitis, meningitis, masses, vascular events, trauma, SHT)
Cerebral oedema
Vasogenic vs cytotoxic (metabolic disturbance) vs interstitial (hydrocephalus)
Herniation
caudal transtentorial herniation or foramen magnum herniation
Differentials for Coma/Stupor
Diffuse bilateral forebrain disease
Metabolic or toxic encephalopathy
Lesions of rostral brainstem
An anatomic diagnosis can be made based on: content of consciousness/level of consciousness, neuro ophthalmic signs, alterations in respiratory pattern and skeletal motor responses.
Localisation for comatose/stuporous patient with tetraparesis, postural deficits, absent vision, normal pupil size and normal eye movement but does not track objects
Stupor/coma and tetraparesis with postural deficits = forebrain or brainstem
Absent vision with normal pupils implies lesion caudal to optic chiasm (less likely brainstem)
Implies Forebrain, metabolic disease could also be cause especially if depressed spinal reflexes also (implying more generalised effects)
Localisation for comatose/stuporous patient with tetraparesis, postural deficits with increased reflexes
normal vision, dilated pupil size and abnormal eye movement (vestibulo-ocular reflex) with strabismus
Stupor/coma with UMN tetraparesis implies brainstem lesion as UMN signs not expected in forebrain lesion
Altered PLR implies
Abnormal vestibulo-ocular movements suggests brainstem injury as the CN III, IV. VI and VIII all closely located together.
Brainstem compression → pupillary changes and disruption of UMN and respiratory pathways
Diagnostic approach to comatose patient
Look for metabolic cause: BG, BP, thiamine
Imaging of thorax/abdo to look for neoplastic infiltation or evidence of infectious disease
Monitor BP and HR for Cushing’s reflex that could indicate increased ICP
CSF collection for determination of presence of inflammatory or infectious cause
How does systemic hypertension cause neurological signs
Most often cause injury to forebrain or cerebellum thought to be due to a failure of the autoregulatory capacity of the brain vasculature
–> hyperperfusion and breakdown of BBB –> vasogenic oedema
Chronic hypertension can cause remodelling of cerebral vasculature (through persistent constriction to regulate cerebral blood flow). These changes can make the vessels more prone to leakage and rupture causing microhaemorrhage
definition of epilepsy and proposed pathogenesis for IE
> 2 seizures > 24 hours apart
Transient paroxysmal disturbance in brain function due to an imbalance of excitatory and inhibitory neurotransmission.
Ineffective termination of seizure activity by the normal mechanisms (GABA and glutamate derangements are fundamental to this)
during ictus there is dysfunction of one or more of: muscle tone, involuntary movement, autonomic NS, loss of consciousness
What NTs are deranged primarily in IE
Glutamate - activates Ca channel and a metabotropic R that mediates Na and Ca influx –> hyperexcitability.
Increased in CSF of cases with IE
GABA- normally causes Cl influx and hyperpolarisation of neurons.
A different R also increases K conductance and reduces Ca.
Found to be reduced in Epilepsy CSF
Difference between focal and generalised seizures
Generalised seizures originate from both cerebral hemispheres at the onset of the episode
–> symmetric tonic clonic contractions
Focal seizures originate within a discrete region of the cerebrum or thalamus and manifest as motor or behavioural signs without loss of consciousness. More likely to be associated with structural intracranial disease (though this is not absolute)
3 classifications of seizures
Idiopathic
Symptomatic (structural disease, storage disease, trauma, inflammatory)
Reactive (metabolic disease such as hypoglycemia, thiamine deficiency, toxins)
the latter 2 have neuro exam deficits b/w episodes most often
Pathophysiological consequences of repeat seizures
Neuronal cell loss
Neuroinflammation -> can cause changes on MRI for up to 8 weeks post seizure, and mild pleocytosis on CSF (usually normal w/in 3 days if IE)
BBB dysfunction
Altered NT receptor expression
Increasing intrinsic disease severity
reduced response to therapeutics
Suspect lifespan is impaired -not proven
Breeds with higher prevalence of IE - and is there a cause identified
most studies have not yet identified causative gene mutations. In breeds, which are predisposed to idiopathic epilepsy, considerable higher prevalence rates are reported
Aust Shepherds
- also poor Tx response
Belgian Shepherd
- Generally good Tx response
Border Collie
- reported poor Tx response
CKCS
- DDx episodic falling syndrome (exercise induced dyskinesia), COMS
Golden Retriever
- males higher prevalence
Lagotto
- much younger age of onset (6w) and spontaneous resolution
- genetic test available
Beagles, Dachshund, Basset hound
–> consider Lafora disease
GSD
- increased cluster seizure risk
Collie
Dalmatian
English Springer Spaniel
Irish Wolfhound
Labrador
Differentiating seizure from movement disorder
Paroxysmal movement disorder dogs continue to perform the activity they were doing prior to onset (ie keep playing)
Owner intervention may also alter the course of the episode in a paroxysmal movement disorder.
Age cut off for IE diagnosis in dogs
<1y an infectious cause is more likely
1-5y most likely IE if no interictal symptoms and normal bloods
(does not 100% rule out structural disease)
> 5y structural disease such as neoplasia, CVD have greater prevalence and should be investigated.
Initial diagnostics for seizures
CBC, Bio, UA, BATT/Ammonia
FIV and FeLV and Toxo titres in cats
+/- LCAT
If concerned for metabolic cause: fructosamine, B12, iCa and thiamine levels
Inborne metabolism defects: genetic testing if breed appropriate (Beagle Lafora Dz, Lagotto juvenile seizure disorder), amino acid serum levels
IVETF tier based confidence of diagnosis of IE
Tier I (low) - age 1-6y, >2 unprovoked seizures 24 hours apart, normal neuro exam and no abnormalities on bloods
Tier II - a/a + BATT and MRI and CSF
Tier III - I + II + EEG abnormalities consistent with seizure
Indications to perform CSF and MRI in seizure patient
Age <6 months (30% have structural disease)
> 6y (11x increase of intracranial disease)
Interictal neurological abnormalities –> indicates abnormal MRI in up to 90%
Status epilepticus or cluster seizures
(45% structural, 30% reactive)
Previous IE diagnosis not responsive to highest dose of AE drug
Indications to start AED in any patient
Frequency >4-6weeks
Interictal period of <6 months
Seizure duration, frequency is worsening
Hx of cluster seizures
Severe seizures or postictal signs
Symptomatic epilepsy where underlying cause not being treated
Risk factors for poorer seizure control
Seizure density
Clusters
Male dogs
Certain breeds: Aust Shep, Border Collie, GSD, Irish Setter, Staffordshire bull terriers, Italian Spinoni
Causes of seizures in cats
Reactive - extracranial metabolic or toxic disease 15-25%
- Hypoglycemia from insulin overdose most common.
- hypertension,
hepatic encephalopathy, uraemia
Thiamine deficiency
Structural 40-70%
Interictal abnormalities in 75%
NEOPLASIA - meningioma, lymphoma
INFLAMMATORY
- FIP is main one
Other infections: Toxoplasma, Cryptococcus and Bartonella species, feline immunodeficiency virus (FiV), FeLV, West Nile virus, bacterial agents and rabies virus have all been reported to cause seizures in cats
- Non infectious non-suppurative meningoencephalitis of unknown origin reported in a small number (acute and rapidly progressive)
VASCULAR
- Hypertension can cause ischaemic CVA or haemorrhagic
- Hypertension, neoplasia or thiamine deficiency
–> Intraparenchymal haemorrhage
- Thromboembolism
DEGENERATIVE
Feline hippocampal necrosis
ANOMALOUS
Hydrocephalus, lissencephaly etc
TRAUMATIC
What is feline hippocampal necrosis
Hippocampal neurons are very sensitive to hypoxia, hypoglycemia, hyperglycemia and glutamate excitotoxicity, potentially leading to ischemic injury and necrosis following severe seizures
occurs in 6–30% of seizuring cats and is most prevalent in cats with severe seizure disorders that have had at least one observed episode of cluster seizures or status epilepticus
Many epileptic cats with FHN have no other structural brain disease identified, suggesting either that the FHN is causing their seizures or that they have iE and secondary hippocampal ischemia and necrosis
One large study evaluating 93 cats with epilepsy, however, the risk of FHN was highest in cats with inflammatory or neoplastic causes for their severe seizure disorder
In some cats with clinical and MRi features of FHN, antibodies could be detected against proteins of the voltage-gated potassium channel complex, suggesting that the disorder could be a manifestation of autoimmune limbic encephalitis. Ten of 14 cats experienced full remission (ie, became seizure-free) after antiepileptic, supportive and corticosteroid treatment
Significance of feline hippocampal necrosis
Most cats with FHN are presented because of a rapidly progressive acute cluster of generalized or complex focal seizures together with interictal abnormalities, suggesting a fore-brain lesion
Even when seizures can be controlled acutely, the neurologic and behavioral abnormalities may persist for several months and recurrent seizures can be a problem
There are a few reports of cats with FHN that gradually returned nearly to normal, with few neurologic deficits and well controlled seizures, suggesting that the long-term outcome can occasionally be good to excellent
Current recommendations of when to treat cats with seizures - JFMS 2018
more frequently than once every 12–16 weeks,
All cats whenever seizures occur in a cluster (>1 seizure/24 h), when status epilepticus occurs, or when seizure frequency increases over time
whenever seizures occur post-trauma
when potentially progressive structural forebrain disease
Are AEDs recommended in cats following CVA causing seizures
Chronic AEd therapy is also recommended following initial AEd loading and stabilisation (as for status epilepticus)in cats presenting with acute onset of repetitive seizures caused by a non-pro-gressive intracranial disorder such as a CVA - but may be tapered after weeks/months without any additional episodes
Oral anti-epileptics that have reported efficacy in cats
Phenobarbitone - considered most effective, low incidence of serious adverse effects and reaches therapeutic serum concentrations relatively quickly
60-90% seizure control reported, some have good control at subtherapeutic levels
Levetiracetam - rapidly absorbed and excreted by kidneys. Good adjunctive choice, reduced seizure frequency in 70% of cats on PB.
Imepitoin - small rial demonstrating efficacy in 4/8 cats
Zonisamide - used anecdotally. May see GI AEs.
Gabapentin/Pregabalin as adjunctive Tx
diazepam - long half life and does not cause drug tolerance in cats
JFMS - pheno as first line with leve or imepitoin as reasonable 2nd lines
Broad causes of increased ICP
increase in CSF, brain or blood components within the calvarium
Effect of increased ICP on systemic BP
↑ in systemic BP to maintain cerebral perfusion. This can result in reflex ↑ in vagal tone → ↓ HR and RR
–> Cushing’s reflex
