Intracranial Disease Flashcards

Question

Current recommendations of when to treat cats with seizures - JFMS 2018

Answer 1

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

Answer 2

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

Answer 3

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

Answer 4

increase in CSF, brain or blood components within the calvarium

Answer 5

↑ in systemic BP to maintain cerebral perfusion. This can result in reflex ↑ in vagal tone → ↓ HR and RR --> Cushing's reflex

Answer 6

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

Answer 7

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

Answer 8

More general diffuse symptoms, symmetrical in most cases Often affect forebrain most as is the most metabolically demanding area

Answer 9

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

Answer 10

Excessive blood flow - hypertension Rupture of vasculature - haemorrhagic infarction Reduction in blood flow - ischaemic infarction (vascular occlusion)

Answer 11

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

Answer 12

cerebral cortex (especially the gray matter of the hippocampus), cerebellar cortex, and basal and thalamic nuclei are more prone to ischemic damage

Answer 13

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

Answer 14

thromboembolism, haemodynamic (hypertension) and local vasospasm (feline ischaemic encephalopathy from larval migration)

Answer 15

intra-axial in the brain parenchyma or extra-axial in the intraventricular, subdural or subarachnoid space

Answer 16

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

Answer 17

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

Answer 18

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

Answer 19

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

Answer 20

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

Answer 21

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.

Answer 22

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

Answer 23

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.

Answer 24

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

Answer 25

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.

Answer 26

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

Answer 27

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

Answer 28

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

Answer 29

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

Answer 30

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.

Answer 31

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

Answer 32

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.

Answer 33

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

Answer 34

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

Answer 35

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

Answer 36

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.

Answer 37

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

Answer 38

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

Answer 39

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

Answer 40

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

Answer 41

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

Answer 42

Sx resection and adjunctive fractionated radiation Palliative - adress the secondary effects of tumour such as vasogenic oedema, seizures --> corticosteroids, mannitol and AEDs

Answer 43

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

Answer 44

Can disrupt BBB with use of mannitol to improve penetration, Cytosine also enters For lymphoma L-asparaginase and cytosine are used along with nitrosurea

Answer 45

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

Answer 46

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

Answer 47

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

Answer 48

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)

Answer 49

Stenotic mesencephalic aqueduct Other causes are in utero teratogenic factors, intra-arachnoid cysts

Brainscape's Knowledge GenomeTM

Intracranial Disease Flashcards

Brainscape's Knowledge Genome^TM