Intracranial Disease Flashcards

1
Q

DDx for syncope/weakness

A

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.

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2
Q

Differentials for persistent vs episodic weakness

A

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

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3
Q

Common causes of stupor/coma

A

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

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4
Q

Differentials for Coma/Stupor

A

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.

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5
Q

Localisation for comatose/stuporous patient with tetraparesis, postural deficits, absent vision, normal pupil size and normal eye movement but does not track objects

A

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)

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6
Q

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

A

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

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7
Q

Diagnostic approach to comatose patient

A

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

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8
Q

How does systemic hypertension cause neurological signs

A

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

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9
Q

definition of epilepsy and proposed pathogenesis for IE

A

> 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

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10
Q

What NTs are deranged primarily in IE

A

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

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11
Q

Difference between focal and generalised seizures

A

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)

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12
Q

3 classifications of seizures

A

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

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13
Q

Pathophysiological consequences of repeat seizures

A

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

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14
Q

Breeds with higher prevalence of IE - and is there a cause identified

A

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

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15
Q

Differentiating seizure from movement disorder

A

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.

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16
Q

Age cut off for IE diagnosis in dogs

A

<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.

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17
Q

Initial diagnostics for seizures

A

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

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18
Q

IVETF tier based confidence of diagnosis of IE

A

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

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19
Q

Indications to perform CSF and MRI in seizure patient

A

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

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20
Q

Indications to start AED in any patient

A

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

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21
Q

Risk factors for poorer seizure control

A

Seizure density

Clusters

Male dogs

Certain breeds: Aust Shep, Border Collie, GSD, Irish Setter, Staffordshire bull terriers, Italian Spinoni

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22
Q

Causes of seizures in cats

A

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

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23
Q

What is feline hippocampal necrosis

A

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

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24
Q

Significance of feline hippocampal necrosis

A

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

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25
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
26
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
27
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
28
Broad causes of increased ICP
increase in CSF, brain or blood components within the calvarium
29
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
30
3 types of brain oedema and their pathogenesis
CYTOTOXIC accumulation of fluid within the neurons due to energy depletion and failure of the normal process that maintain the electrochemical gradient. VASOGENIC The result of physical or functional disruption of the endothelium of the BBB --> fluid accumulates extracellularly in the white matter (around the axons). INTERSTITIAL Occurs following obstructive hydrocephalus --> increased pressure of CSF --> extracellular oedema in the periventricular region
31
Indications of a focal brain disease process on neurological exam
Strongly lateralised signs (will be contralateral to lesion if forebrain sensory/motor function) NB can cause diffuse signs if secondary hydrocephalus or increase in ICP
32
Expected presentation of metabolic disease causing CNS signs
More general diffuse symptoms, symmetrical in most cases Often affect forebrain most as is the most metabolically demanding area
33
Main DDx for multifocal neurolocalisation
Inflammatory Vascular Neoplastic (metastasis) Infectious Waxing/waning signs are more consistent with inflammatory and metabolic disease Acute onset of signs is most likely to occur with vascular disease, trauma, toxins and infectious/inflammatory
34
Different types of cerebrovascular accident
Excessive blood flow - hypertension Rupture of vasculature - haemorrhagic infarction Reduction in blood flow - ischaemic infarction (vascular occlusion)
35
difference b/w ischaemia and infarction and how does progression occur
Ischemia = Perfusion reduction sufficient to induce dysfunction in the affected tissue Infarction = Perfusion reduction that causes irreversible injury and eventually necrosis Both the severity and the duration of perfusion reduction influence progression from ischemia to infarction. 5 hours at <40% CBF results in permanent dysfunction Irreversible damage can occur after just 4-5 minutes of complete obstruction
36
Sites at high risk of CVA
cerebral cortex (especially the gray matter of the hippocampus), cerebellar cortex, and basal and thalamic nuclei are more prone to ischemic damage
37
Pathophysiology of CVA brain damage
Primary injury is due to energy failure from reduced blood supply, to which neurons are most sensitive. - The ↓ blood supply → lack of O2 or glucose → neuronal ischaemia or death. - Failure of Na/K ATPase pumps → cytotoxic edema Failure of aerobic metabolism → lactic acidosis → cytotoxicity - Loss of ionic gradients → depolarization of resting potential → increased Ca release → activation of proteases and phospholipases → membrane damage and free radical formation Secondary injury due to compromise of local vascular endothelium and supporting cells and begins to develop in 4 to 6 hours following the onset of hypoperfusion, with progression for 24 to 48 hours Damage to the BBB → vasogenic edema and inflammatory cell infiltration In very severe endothelial injury, hemorrhagic conversion occurs (extravasation of all blood components, including RBCs, through compromised capillaries) The area of infarcted brain has an ischaemic core with permanent loss of blood flow, surrounded by penumbra which has ↓ but still viable neurons at risk of irreversible damage
38
Major differential categories for ischaemic CVD
thromboembolism, haemodynamic (hypertension) and local vasospasm (feline ischaemic encephalopathy from larval migration)
39
Locations that haemorrhagic CVD can occur
intra-axial in the brain parenchyma or extra-axial in the intraventricular, subdural or subarachnoid space
40
Progression of damage from primary injury of haemorrhagic CVD
Primary injury occurs from compressive effects of expanding haematoma, Elastic resistance of the surrounding parenchyma and increasing ICP limit hematoma expansion. Hematoma and edema cancause increased ICP and risk of brain herniation, obstructive hydrocephalus Secondary injury breakdown of blood products → Heme which is damaging to neuronal parenchyma through several mechanisms: proinflammatory and prooxidant activities, and stimulation of excessive glutamate release Takes 3-7d
41
DDx for Haemorrhagic CVD
Most are caused by trauma, but intraprenchymal is the most common in non-traumatic haemorrhage Published associations between hypertension and intracranial haemorrhage (ICH) in dogs and cats are limited to cases with one or more <5 mm T2*-weighted signal voids termed microbleeds which are of unknown significance Secondary causes of ICH include: coagulopathy; vascular malformation; vasculopathy; neoplasia; septicemia; haemorrhagic conversion of ischaemic insult
42
What is global ischaemia
watershed infarction develops when cerebral blood flow is lowered below the point of compensation by cerebral autoregulatory mechanisms → widespread bilateral brain dysfunction Most often seen post resus mild diffuse T2W hyperintensity in the gray matter of the cerebrum, thalamus, and cerebellum, with mild contrast enhancement of the same regions
43
MRI appearance of ischaemic vs haemorrhagic CVD
ISCHAEMIC well demarcated wedge shaped lesions with minimal mass effect. Intra Axial lesion is hyperintense on T2W and FLAIR and hypointense on T1W. HAEMORRHAGIC imaging characteristics on MRI are dependent on the reduction-oxidation state of iron and the oxygen content of Hgb CT highly sensitive for acute bleeds --> hyperdense
44
Additional testing if CVD suspected
BP, fundic exam for hypertension Evaluate for hypercoagulability - TEG, AT3 levels, UPC, endocrine testing, echo in cats (or hypocoagulable if haemorrhagic --> plt, PT/APTT, TEG, PIVKA, BMBT) Hyperlipidemia testing Sepsis --> echo, blood cultures HW testing, Angiostrongylus vasorum Neoplasia - imaging
45
Treatment for CVD
Supportive --> seizure control. Maintenance of ICP and systemic BP --> rapid drop in systemic BP may affect cerebral perfusion pressure. Only lower systemic BP if >180mmHg and suspect target organ damage based on retinal exam. Mannitol or hypertonic saline to manage increased ICP Thrombolytic agents - not been evaluated throughly, and difficult to know if thromboembolic cause in most cases without rapid access to MRI -contraindicated if haemorrhagic infarction. Antithrombotic therapy - indicated if underlying hypercoagulability causing ischaemic infarct. Not been evaluated in vet med. Steroids - no proven benefit in either type.
46
Prognosis for CVD
In cat hypertensive study 15/25 had neurological signs resolve with management of underlying hypertension Recent case series in 66 dogs --> 23% died within 30days, remainder had MST >500d Single large non-traumatic haemorrhage had better long term prognosis than multiple small lesions Likely largely dependent on underlying disease process
47
Function of microglia and 2 possible activation outcomes
Microglia are the most prominent MHC-expressing cells in the CNS and are capable of processing and presenting antigen by expression of MHC classes I and II, and thereby have a bidirectional interaction with neurons and other microglia Cytokine mediated phenotype switch: M1 if IFNy, TNFa, IL17 usually due to acute injury (from Th1 Th17 or CD8 cytotoxic T cells) --> activated phagocytic state and production of proinflammatory cytokines (IL6, IL1B, TNFa), ROS and reduced neurotrophic factor pproduction --> cytotoxicity, astrocyte activation (amplification of microglial response) and neurodegeneration M2 (response to IL10 and TGF-B from Th2 or Treg cells) --> produced antiinflammatory cytokines (IL10, IL4) and neurotrophins.
48
Current theory for pathogenesis of MUO
Multifactorial response to genetic and environmental trigger factors Possibly molecular mimicry or cryptic antigen unmasking --> autoimmune response to CNS antigens normal immune regulatory mechanisms of the CNS are rendered dysfunctional, for instance by age, pathogen exposure, or neurodegeneration, the threshold to initiate CNS inflammation is altered
49
Characteristics of GME
MRI - T2W/FLAIR hyperintense lesions with T1W variable contrast enhancement. Affecting grey and white matter in acute disease but just white in chronic disease. May have mass effect Localisation: multifocal (forebrain and brainstem), 50% focal forebrain, 8% spinal, ocular only also reported Histo: Perivascular mononuclear infiltration, predominance of CD3 T cells; parenchymal granulomas; anti-astrocyte AB are demonstrated in some.
50
Characteristics of NME
Pug, Maltese, Chihuahua, Shih tzu, Papillon, Pekingese, and Staffys. MRI - T2W/FLAIR hyperintense lesions with T1W variable contrast enhancement. Affecting grey and white matter and also meningeal enhancement. No mass effect Localisation: multifocal (forebrain and brainstem), focal forebrain Histo: Necrosis and cavitation that is asymmetric, mononuclear cell infiltrates CD3 lymphocytes predominating but less than in GME. Anti-astrocyte Ig
51
Characteristics of NLE
Yorkshire terrier, French Bulldog MRI - T2W/FLAIR hyperintense lesions with no contrast enhancement Affects cerebral white matter predominantly No mass effect Localisation: multifocal (forebrain and brainstem), focal forebrain. Many present with vision loss seizures or central vestibular signs Histo: Necrosis and cavitation that is asymmetric, prominent reactive astrogliosis IgG and other Ig deposits in white matter reported
52
Diagnostic Criteria of TVJ 2018 MUO review
1. Age >6mo 2. MRI hyperintense intra-axial lesions Although some MR imaging features are common to the NEs and GME, none are considered specific for the diagnosis of any disease process --> normal MR reported in up to 25% --> contrast enhancement is variable and depends on BBB disruption --> overall sensitivity is 60-70% --> no information on ability to differentiate different MUO types but likely poor as large overlap 3. CSF pleocytosis and increased protein (leaky BBB or increased Ig intrathecal production) --> most often lymphocytes predominating (neutrophilic occurs in <10%) 4. Infectious disease testing negative (Toxo, Neo, Ehrlichia, Anaplasma, Coccidioides) 5. Brain Biopsy - Accuracy 82-100% reported. highly specialised. Imaging guided
53
TVJ MUO Biomarker review key points
Acute phase proteins - seem of limited utility, CRP increase uncommon and more likley SRMA Antibodies - antiGFAP Ab in CSF have sens 91% and Spec 73% for MUO Cytokines - IFNy higher in NME - IL17 in GME Measured in tissue limiting their clinical use Neurofilament light chain - higher in MUO dogs than healthy controls and declined with response to treatment. Plasma concentration is proportional to aging so need more investigation to determine appropriate cut offs and if affected by neoplasia or infection Lactate increases in CSF of 50% of dogs with various inflammatory brain disorders miRNA - possible future marker of immune dysregulation which can be measured in CSF. Further investigations needed PET - functional imaging using radiotracers to assess metabolic tracers. Limited availability but may be able to detect areas of necrosis in NME Biome significant relationship between high Prevotella spp. abundance and reduced risk for developing MUO was found --> possible interaction of SCFA production and reducing the TH17 production of inflammatory cytokines --> or tryptophan metabolite interaction with astrocytes
54
Evidence for MUO Tx protocols and recommendation for monitoring
Several treatment protocols using different inclusion criteria resulting in different long-term survival times have been reported as a result with efficacy assessed by clinical response (or in smaller studies by repeat MRI and CSF analysis) combination of MR imaging and CSF analysis provided greater sensitivity for prediction of relapse than one modality alone. However, repeating those examinations might be difficult to justify because of the risks associated with anaesthesia and CSF collection.
55
Genetic mutation in Pugs
NME-assoc susceptibility variant Mutation in dog leukocyte antigen - associative mutation not causative homozygous 12.5x increased risk of NME development heterozygotes have low risk of disease 2 additional mutations known to be regulators of immune system dysfunction also identified in toy breeds
56
Recommended Tx of MUO
Prednisolone is mainstay with most evidence Combination with: Cytarabine - infusions every 3 weeks for 8h Procarbazine only small retro study demonstrating efficacy Cyclosporine - only small retro study demonstrating efficacy in AVJ Also Leflunomide and MM reported in TVJ review.
57
Prognosis in MUO
Variable depending on Tx, dz type and severity MST of <30d to >3y reported Good prognostic factors: younger, focal forebrain disease, resolution of MRI changes within 3 months Abnormal CSF at 3 months poor prognostic indicator Lack of validated outcome measures make comparison challenging. Also lack definitive Dx in many
58
Eosinophilic ME findings, DDx and Tx
Characterised by meningeal inflammation and an eosinophilic pleocytosis with >10-20% eosinophil count in CSF Usually large breed dogs Thought to be idiopathic, may be associated with fungal or parasitic dz (Crypto, Toxo, Neo) Tx same as for MUO
59
Sources of bacterial meningitis common clinical signs of bacterial meningitis
Haematogenous Traumatic direct extension from middle ear disease acute onset neurological dysfunction with neck pain and fever Suppurative CSF, possible toxic/degenerate neuts MRI may identify abscesss or site of extension
60
Optimal Tx of Bacterial meningitis
Ideally low protein binding, lipophilic and not Pgp substrate so can cross BBB High dose ampicillin - can cross inflamed BBB TMS - good penetration Enrofloxacin Metronidazole - good penetration and anaerobe cover Median duration in recent case series was 8 (2-16 weeks) Low dose glucocorticoids may aid in reducing associated swelling from BBB breakdown and vasogenic oedema.
61
Reported causes of Fungal encephalitis Recommended Tx
Fungal organisms reported to invade CNS: Cryptococcus, Coccidioides, Blastomyces, Histoplasma, Aspergillus. CSF and serum may also be tested for antibodies to fungal antigens. Most reliable for Cryptococcus, coccidioides, and blastomyces but not Aspergillus. Cats should be tested for FeLV and FIV if fungal disease is suspected Fluconazole (10mg/kg total daily (split) for 2-3 months beyond resolution) and flucytosine are the antifungals most able to cross the BBB Amphotericin has poor penetration into CSF which is why it is not chosen as a single agent but combination therapy with Flucytosine can be effective for C. neoformans
62
Viral causes of Meningitis
Canine Distemper virus - has preceding GI and respiratory signs. chronic distemper causes encephalomyelitis after survival of acute disease. Dx with IFA on tissue FIP - usually non-effusive form. FPV - cerebellar hypoplasia in kitttens FeLV and FIV
63
Vet J biomarker review for SRMA findings
CRP - increased in serum and CSf, non-specific biomarker as elevated in many disease processes but does help differentiate from MUO May be used as monitoring biomarker as tends to follow disease course. IgA serum and CSF levels combined sens 91% Spec 78% for differentiating from other inflammatory brain disease (but not if there is other systemic disease) Does not resolve with treatment. More information needed on heat shock protein in CSF Cytokine levels appear non specific for SRMA Imaging - tends to be leptomeningeal enhancement
64
Common Brain tumours in dogs and breed predilections
30-40% Gliomas - more common in brachycephalic breeds (French BD, Boxer, Boston Terrier) 50% Meningioma - more common in doliocephalic, and Golden Ret overrepresented Most common in cat
65
MRI findings of different tumour types
Meningioma - broad base, dural tails that invade into adjacent parenchyma Gliomas - intra-axial masses. Widely variable appearance Choroid plexus tumour Pituitary tumours Metastatic - more often located in grey-white interface matter Dx HSA, histiocytic sarcoma Lymphoma - multifocal indistinct margins
66
Tx options for intracranial neoplasia
Sx resection and adjunctive fractionated radiation Palliative - adress the secondary effects of tumour such as vasogenic oedema, seizures --> corticosteroids, mannitol and AEDs
67
Prognosis for primary brian tumours
Cats with meningiomas - 21mo with surgery alone depending on location. Dogs MST for meningiom is shorter 7mo Low proliferation fraction assoc with longer survival Gliomas and other intra-axial tumours are less amenable to surgical resection RT can extend survival time 17-30mo as adjunct, or as palliative Tx
68
Chemotherapeutics that cross the BBB
Can disrupt BBB with use of mannitol to improve penetration, Cytosine also enters For lymphoma L-asparaginase and cytosine are used along with nitrosurea
69
Types of hydrocephalus
Distension of the ventricular system of the brain Usually impedance to flow rather than increased production Can be congenital or acquired Obstructive or non-obstructive
70
How does hydrocephalus develop and what occurs to mmitigate it
when rate of formation of CSF is greater than rate of removal Generally formation is constant and independent of ICP (relies on oncotic pressure) Hydrocephalus occurs when there is an obstruction to CSF flow --> pressure difference before and after obstruction With chronicity alternate pathways of CSF drainage can develop to reduce pressure within the ventricles --> flow of CSF across ependyma with absorption by periventricular capillaries or across the cribriform plate and absorption by nasal lymphatics
71
What factors determine if hydrocephalus causes increased ICP
1) size of pressure gradient determined by severity of obstruction and ability of alternative pathways to manage the overflow. (acute severe obstruction will be worse than gradual onset obstruction which may not increase pressure) 2) Efficiency of transmission of pressure to the surface of the brain - in early stages brain is incompressible so only coping mechanism is movement of venous blood into systemic circulation - with chronicity brain becomes more compressible as interstitial pressure increases and interstitial fluid is absorb by capillaries 3) Ventricular size - smaller ventricles mean thicker cortical mantle better able to absorb pressure against the ventricle wall
72
Pathological effects of hydrocephalus
1) direct effects of compression on neurons and damage to blood vessels 2) compression of the ependyma in the lateral ventricles --> alterations to lining and loss of integrity --> water leaks into periventricular white matter --> vasogenic oedema 3) ventricular enlargement compresses white matter and causes demyelination and axonal degeneration --> thinning of cortex due to loss of neurons in severe cases (results in reduced ability to recover after shunt correction) 4) loss of septum pellucidum (separates ventricles)
73
Most common cause of congenital hydrocephalus
Stenotic mesencephalic aqueduct Other causes are in utero teratogenic factors, intra-arachnoid cysts