Cerebral disease: seizure disorders Flashcards
What are the two types of epilepsy and what are their characteristics
Primary (or idiopathic) epilepsy tends to be associated with a functional rather than a structural cerebral disorder and may have an inherited basis
- this is much less common in cats than dogs
- ideally should be diagnosed after structural lesions have been ruled out (CSF analysis and MRI)
- may manifest as either partial or generalized seizures in the cat
Secondary (or acquired/structural) epilepsy occurs after an acquired brain disease located in the forebrain (e.g., a traumatic or ischemic event) where the animal is left with a seizure focus
- other structural brain diseases such as neoplasia, inflammation, infection or degeneration may cause seizures, although these diseases commonly are progressive and cause other neurological signs (i.e., interictal neurologic abnormalities such as asymmetric menace deficits, paresis, circling)
How are seizures classified
Seizures can be classified as:
- generalized:
- characterized by a singificant tonic-clonic episode (can be very violent)
- accompanied by loss of consciouness
- partial (or focal):
- originate from abnormal activity in one region of a cerebral hemisphere, resulting in asymetric signs initially
- may involve the spontaneous motor activity of a particular part of the body (e.g., orofacial seizures (including twitching of the face, salivation, chewing, licking, lip smacking and swallowing) that may be associated with hippocmpal lesions in cats)
- circling, rapid running or climbing activity are common in cats with focal seizures and may suggest tempral lobe involvement
- simple partial seizures manifest as abnormal localized motor activity without alterations to mentation
- complex partial seizures are defined as localized motor activity accompanied by behavioral changes such as confusion, mania, aggression or a vacant expression, excessive vocalization, howling, hissing, growling and piloerection
- this type of seizure is seen more commonly in cats than dogs
- reflex seizures:
- occur immediately after a specific stimulus (e.g., auditory, tactile or visual)
- feline audiogenic reflex seizures have been described in older cats where the trigger was a high-pitched sound
- cats developed generalized tonic-clonic seizures or myoclonic jerks with the noise stimulus
- Birman cats are over-represented
What are the main differentials for seizures
It is essential that seizure activity is differentiated from syncope or fainting (which is usually a manifestation of cardiovascular disease)
- typically seizure activity will have a “pre-ictal” phase where the owner may notice subtle changes in behavior and a “post-ictal” phase that may last for seconds or days and sometimes manifests as changes in behavior, vision impairement and confusion
What are the causes of seizures activity in cats
Extra-cranial disease
- hepatic and renal disorders
- hyperosmolarity
- toxins (much less common than in dogs)
- hypoglycemia caused by insulinoma
- nutritional (e.g., thiamine or cobalamin deficiency)
Structural intra-cranial disease majority of etiologies in the cat):
- neoplasia (most commonly meningioma or lymphoma)
- meningoencephalitis
- vascular diseases (e.g., hypertension, polycythemia)
Functional intra-cranial diseases
- idiopathic epilepsy
What are the main characteristics of audiogenic seizures
Audiogenic seizures have been described in older cats (mean age 15 years) where the trigger was a high-pitched sound
Clinical manifestation:
- myoclonic jerks or seizures without apparent loss of consciousness were frequently reported but some degree of impairement could exist
- jerks were described as brief (<30s) commonly bilateral, rhythmic contractions that mainly started in the head and neck or occasionally in the back/abdomen
- the majority of the cats were normal immediately after a myoclonic episode
Birman cats of the seal and blue point variety may be overrepresented
Levetiracetam seems better than phenobarbital to reduce the frequency and progression of audiogenic seizures
When is it recommended to start treatment for seizures
The current recommendation is to begin treatment if there are two or more seizures within six months or any seizure lasting longer than 5 minutes
Likewise, if a cat is experiencing cluster seizures (i.e., several seizures within 24h) or has had an episode of status epilepticus (i.e., seizure activity lasting longer than 5 minutes), anticonvulsivant treatment should be commenced
What are the main facts to know about phenobarbitone
Phenobarbitone is the drug of choice for treatment of seizures in the cat
It exerts its effects by binding to the beta subunit of the GABA receptors in the brain
- it is also thought to block the receptors of an excitatory neurotransmitter (AMPA)
The recommended starting dose is 2-3 mg/kg, PO, q12h
- serum levels should be measured after 10-14 days (therapeutic drug levels of 15-45 µg/ml)
- transmucosal dosing at 9 mg/kg, q12h is effective
Serum drug levels should be measured:
- every 6 months
- 10-14 days after any dosage changes
- if the severity or frequency of the seizures increase
Unlike dogs, cats do not experience the enzyme induction that results in the necessity to increase the dose of phenobarbitone with long term use
Cats on phenobarbitone should have routine hemogram, serum biochemistries and bile acid levels checked after the first month then every 3-6 months
- hepatotoxicity has not been reported in cats, however cutaneous and bone marrow dyscrasia have
What are the main facts about potassium bromide
Due to the development of a severe and sometimes fatal eosinophilic bronchial disease that develops in some cats, the use of bromide cannot be recommended
What are the main facts about benzodiazepines
Benzodiazepines enhance the effect of GABA resulting in sedation, somnolence, as well as anti-seizure, muscle relaxant, and anxiolytic effects
Idiosyncratic drug reactions such as hepatic failure have been reported with the use of oral diazepam in cats
- it is not recommended for long-term treatment
What are the main facts about levetiracetam
Its mechanism of action is not entirely known:
- it is thought to bind to a synaptic vesicle receptor (SV2A) which regulates the release of excitatory neurtransmitters
- it is also believed to enhance the effects of GABA by suppressing the inhibitory effects of Zn2+ on this neurotransmitter
Levetiracetam appears to be safe ad effective at a dose of 20 mg/kg, PO, q8h
- it is usually used as an adjunct to phenobarbitone
It is not metabolized by the liver (most are excreted unchanged in the urine by glomeurlar filtration)
- dose should be reduced in cats with impaired renal function
Levetiracetam is the drug of choice for cats with audiogenic reflex seizures
What are the main facts about zonisamide
Zonisamide is a sulfonamide anticonvulsivant
Once to twice daily dose of 5-10 mg/kg, PO, is likely to be appropriate
- higher doses result in side effects such as anorexia, diarrhea, vomiting, somnolence and ataxia
It is thought that it may block repetitive voltage-gated sodium and T-type calcium channels in the brain
What are the main facts about gabapentin and pregabalin
Gabapentin is a structural analog of GABA that inhibits voltage-gated calcium channels
- it is used primarily to treat neuropathic pain in cats
Pregabalin is a more potent version of gabapentin
- it is used to treat chronic pain disorders and has anticonvulsivant activity
- doses of 1-2 mg/kg, q12h are suggested
They are excreted primarily via the kidneys
- thus, the dose should be reduced in cats with renal insufficiency
What would be your therapeutic plan for status epilepticus
Intially, a benzodiazepine is administered to try to arrest the seizure activity
- Iv or per rectal diazepam at 0.5-1.0 mg/kg
If multiple bolus administration is ineffective, then a CRI of midazolam can be administered 0.2-0.4 mg/kg/h
It is good to start injectable phenobarbitone therapy (2-4 mg/kg, q12h, IV) and then move on to oral phenobarbitone once the seizures are under control
What is feline temporal lobe epilepsy
Feline temporal lobe epilepsy is due to hippocampal and piriform lobe necrosis
This is an acute epileptic condition characterized by focal seizures consisting of uni- or bilateral orofacial or head twitching, hypersalivation, lip smacking, mydriasis, vocalization and motionless staring lasting 5-30s
Usually, there are inter-ictal behavioral changes such as significant unprovoked aggression or rapid running
- less frequently, pyrexia, urinary retention, ataxia, generalized hyperesthesia
What is the etiology for feline temporal lobe epilepsy
The etiology is unclear but growing evidence supports an autoimmune nature
- Autoantibodies are broadly divided into:
- cell-surface synaptic antigens and receptors
- proteins that stabilize voltage-gated potassium channel complex into the cell membrane (e.g., leucine-rich glioma inactivated protein 1)
- enzymes that catalyze the formmation of neurotransmitters
Disruption of hippocampal architecture secondary to brain neoplasia has also been found
How could you make a diagnosis of feline temporal lobe epilepsy
Neurological examination is commonly unremarkable or non-specific
Diagnosis is suspected based on clinical signs, supported by MRI and confirmed on post-mortem assessment
- the initial focal seizures described often progress to generalized seizures and status epilepticus, and tend to be refractory to antiepileptic treatment
- bilateral medial temporal lobe T2-weighted/FLAIR hyperintensity is suggestive for limbic encephalopathy
What is the treatment of feline temporal lobe epilepsy
Antiepileptic drugs seem to result in reduced seizure frequency and/or severity if associated with corticosteroids
- prednisolone 1-2 mg/kg, q12h then tapered
- phenobarbital combined with levetiracetam
Can the age at seizure onset be indicative of a cause for seizure
The age at seizure onset is significantly different between cats with idiopathic epilepsy and cats with symptomatic (structural) or reactive epilepsy
- cats younger than 7 years of age were more likely to have idiopathic epilepsy
- cats older than 7 years of age were more likely to have symptomatic (structural) or reactive epilepsy
What is a main difference between cats and dogs regarding the age of onset of seizure
Cats that developed seizures at < 12 months of age are more likely to have structural epilepsy than idiopathic epilepsy or reactive seizures
- therefore, advanced diagnostic imaging is recommended in cats with juvenile-onset seizures if metabolic and toxic causes are excluded
Compare and contrast syncope and seizure
The main similarity between seizures and syncope is that both affect regions of the forebrain and consciousness level. However, different mechanisms are recruited during each episode that eventually leads to collapse
Syncope is a paroxysmal event secondary to a short-term decrease in cerebral perfusion, oxygenation or essential nutrients delivery
- these changes result in a decreased function of the brain regions responsible for the level of consciousness
- excitement or strenuous exercise are the most commonly associated triggers
- a severe presentation of syncope can lead to the occurence of brief tonic-clonic activity (hypoxic convulsive syncope) and results from a diffuse cerebral hypoperfusion, secondary to severe hypotension, cardiac arrhythmia or asystole
Seizure activity is defined as the clinical manifestation of transient paroxysmal disturbances in brain function which are causes by an imbalance between excitatory and inhibitoory neurotransmission
- the brain region, within which seizure activity is triggered, is called epileptogenic zone
- at the neuronal level, seizure activity is characterized by two primary events:
- hyperexcitability which is responsible for the initiation of the seizures
- hypersynchronicity which is characterized by an increased excitability of neighbouring neurons
Clinical features helping in differentiation:
- precipitating events
- triggers factors for syncope
- spontaneous occurence mainly during sleep or resp for seizure
- signs preceding the episodes
- no preceding signs with syncope
- pre-ictal signs for seizures
- signs present during the main phase of the episode
- syncopal episode characterized by flaccid collapse
- signs last > 1minute with seizure and < 1 minute with syncope
- signs following the event
- no post-ictal signs with syncope with a rapid return to the normal pre-syncope stage
Give a definition for cluster seizures
More than one seizure in 24 hours
Give a definition for status epilepticus
Generalized seizure lasting > 5 minutes, or focal seizure lasting > 30 minutes, or repetitive seizures without returning to normal between seizures
List and characterize the four phases of a seizure
Prodrome (pre-ictal phase)
- precedes seizure onset and lasts hours to days, usually including attention-seeking or anxious behavior
Aura
- period at the beginning of a seizure lasting seconds to minutes where the animal may exhibit stereotypical sensory or motor activity (e.g., licking, swallowing, head turning), autonomic signs (e.g., salivation, vomiting) or abnormal behavior (e.g., hiding, agitation, attention seeking)
Ictus
- it is the seizure itself, when the animal exhibits a variety of signs that may include altered consciousness, altered muscle tone or movements (e.g., paddling of the limbs, jaw chomping, involuntary urination and defecation)
- this stage usually lasts seconds to 3 minutes in cats
Postictal
- immediately follows the seizure and reflects transiently abnormal brain function (seconds to many hours in duration) resulting from the seizure
- may exhibit abnormal behavior, disorientation, somnolence, blindness, polyphagia, polydipsia
