Seizures and tremors Flashcards
Give the definitions: Seizure Cluster seizure Epilepsy and its types Status epilepticus
Seizure: clinical manifestation of a paroxysmal cerebral disorder, caused by a synchronous and excessive electrical neuronal discharge, originating from the cerebral cortex.
Cluster seizure: 2 or more seizures within a 24-hour period.
Epilepsy and its types: is recurrent seizures of any type resulting from an intracranial cause.
- Idiopathic: seizures caused by a genetically determined intracranial disorder
- Symptomatic: caused by underlying intracranial disorder.
- Cryptogenic: cause of the seizures is suspected to be symptomatic, but an underlying cause is not found.
Status epilepticus: universally accepted definition does not exist in humans or animals but authors recommend the definition “Continuous seizures, or two or more discrete seizures between which there is incomplete recovery of consciousness, lasting at least 5 minutes”.
Classification of seizures
Partial or generalized. Based on clinical observation rather than EEG.
Partial originates originate from a focus in one cerebral hemisphere and usually manifest localized clinical signs. Usually have an acquired cause and maybe subdivided into:
- Simple: there is no alteration in consciousness, and the clinical signs are limited to isolated muscle groups. Additional clinical signs (e.g. autonomic signs) may be present.
- Complex partial seizures: are accompanied by an alteration in consciousness. There may be involuntary or compulsive actions such as chewing, licking and defensive or aggressive behaviour. They also have been referred to as psychomotor seizures.
Partial seizures may spread throughout the brain, causing generalized seizures.
Generalized seizures:
- Tonic-clonic: lose consciousness. Animal usually urinates, defecates and salivates
- Tonic: increased muscle tone results in limb and head extension, causing the animal to fall to the side.
- Clonic: alternating extension and flexion of the limbs and exaggerated chewing movements, occur.
- Myoclonic: Myoclonic seizures are brief shock-like jerks of a muscle or group of muscles. During a myoclonic seizure, the person is usually awake and able to think clearly.
What is Kindling and mirror focus?
Kindling: Experimentally, repeated stimulation of the rat cerebral cortex by a subconvulsive electrical stimulus caused generalized seizures over time.
Mirror focus: Following establishment of a focal seizure focus, abnormal electrical activity may be recorded over the contralateral cerebral cortex. Both focus can cause seizures.
What is the pathophysiology of seizures?
Seizures are caused by paroxysmal discharges from groups of neurons, which arise as a result of excessive excitation or loss of inhibition. The key unit of neurotransmission is the synapse, and the fundamental components of synapses are ion channels. Thus, the cause of seizures boils down to malfunction of ion channels. When the brain homeostasis is overcome, cerebrocortical excitability is altered and the seizure threshold is decreased. Normal animals can have a low threshold may be induced to have a seizure by many factors, including fatigue, fever, estrus, and photic stimulations.
What is the pathophysiology of cluster seizures?
There is a failure of the normal brain homeostasis mechanisms that work to stop seizures. Proposed mechanisms include persistent neuronal excitation, inadequate neuronal inhibition or both. Extrasynaptic factors may be important in spreading and maintaining the seizure. An excess of excitatory neurotransmitters such as glutamate, aspartate, or acetylcholine or antagonists of (GABA) may cause SE.
Give examples of progressive and a non- progressive intracranial disease
Progressive: Inflammation (MUA/Infectious), neoplasia, nutritional alterations, anomalous entities ( hydrocephalus) and trauma
Non-progressive: inherited epilepsy, previously active cerebral diseases no longer active (traumatic lesions, inflammation).
Describe your plan of diagnostics tests, differential diagnosis and initial emergency treatment for a 6y, MN Maltese that presents with acute onset of cluster seizures at 11am.
He has had in total 5 tonic –clonic seizures during the night is now circling to the left. During your physical exam he starts seizuring again. Explain your drugs of choice and their mechanism of action.
Maltese are predispose to MUA,
He is not normal between episodes, more likely to be intracranial progressive disease.
Diagnostic plan including full bloodwork, rule out PSS with bile acid stim/ammonia. Check triglycerides. Imaging (chest and abdo) to rule out metastatic disease.
Advanced imaging MRI (CT only if MRI unavailable) + CSF.
Consider EEG if concerned about other type of paroxysmal events.
Medication first line: benzos: Binds GABA receptor, enhances neuronal hyperpolarization reducing neuronal firing. Acts on Cl channels. Its lipid soluble, rapid absorption. Can be given IN, IV, IR. Boluses then CRI
Levetiracetam: Included with the barbiturates but The mechanisms by which LEV exerts its antiepileptic effects are not clearly defined. The most relevant mechanism of action is believed to be through binding to a unique protein known as synaptic vesicle protein 2A (SV2A). SV2A protein is a part of secretory vesicle membranes that mediates calcium-dependent vesicular neurotransmitter release. Binding of LEV to SV2A appears to decrease the rate of vesicle release.
Phenobarbital: potentiate the action of GABA by interfering with Na and K transmission in the neuronal membrane.
Propofol also has GABA agonist activity if needed.
Which one is true?
a. The cummulative success rate of Pheno as monotherapy in 8 studies was >80% seizure reduction, to improve seizure control was 70% and cummulative seizure – free rate of 50%. Failure rate was 5%
b. Potassium bromide monotherapy efficacy was found only in one study in which 73.9% of dogs had >50% seizure reduction, and 52% were seizure free during the 6 month treatment.
c. Primidone is the only anti-epileptic drug approved for dogs in the USA. It is rapidly metabolised to phenobarbital. For this reason comparative studies have shown very similar efficacy, tolerance and side effects.
d. The administration of Imepitoin twice daily was not as effective as phenobarbital controlling generalised seizures in dogs but the frequency of adverse events was significantly higher in the phenobarbital group.
Need to check! (not a. or c.)
b. Potassium bromide monotherapy efficacy was found only in one study in which 73.9% of dogs had >50% seizure reduction, and 52% were seizure free during the 6 month treatment.
d. The administration of Imepitoin twice daily was not as effective as phenobarbital controlling generalised seizures in dogs but the frequency of adverse events was significantly higher in the phenobarbital group.
a. The cummulative success rate of Pheno as monotherapy in 8 studies was >80% seizure reduction, to improve seizure control was 70% and cummulative seizure – free rate of 50%. Failure rate was 5% (F) >50%, 82%, 31%,5%
c. Primidone is the only anti-epileptic drug approved for dogs in the USA. It is rapidly metabolised to phenobarbital. For this reason comparative studies have shown very similar efficacy, tolerance and side effects.
How can the administration of phenobarbital affect T4?
Serum total and free T4 concentrations might be low resulting in a mistaken diagnosis of hypothyroidism.
Which one is true
a. Serum zonisamide concentration should be monitored 3-4 weeks after treatment initiation or dosage adjustment and any time seizure frequency increases.
b. Imepitoin does not need drug monitoring because it has short half-life (approximately 2 hours). Inter-individual differences are low and the therapeutic index is high. However, the therapeutic concentration range is not known.
c. Concurrent administration of phenobarbital does not alter the pharmacokinetics of Levetiracetam in dogs.
d. The therapeutic plasma concentration range of phenobarbitone is higher in dogs treated with primidone.
b. Imepitoin does not need drug monitoring because it has short half-life (approximately 2 hours). Inter-individual differences are low and the therapeutic index is high. However, the therapeutic concentration range is not known.
a. Serum zonisamide concentration should be monitored 3-4 weeks after treatment initiation or dosage adjustment and any time seizure frequency increases. (1-2 weeks)
c. Concurrent administration of phenobarbital does not alter the pharmacokinetics of Levetiracetam in dogs. (False it results in lower peak and more rapid elimination)
d. The therapeutic plasma concentration range of phenobarbitone is higher in dogs treated with primidone. (F)
What should be the objectives of monitoring through serum concentration of any AED?
Determine effective drug concentrations after initiation of successful treatment (as appropriate);
Determine if drug failure is because of pharmacokinetic factors so as to focus on a change in dose (metabolic tolerance) or pharmacodynamic factors so as to focus on a change of drugs (functional tolerance);
Determine if treatment failure is caused by poor compliance or an inadequate or changed drug concentration;
Prevent toxic effects;
Aid with individualization of treatment
What is the mechanism by which vagal nerve stimulation exerts its antiepileptic effect?
Not completely understood, but it I believed that stimulation of afferent vagal fibers influences brain activity by modulation of noradrenergic and cholinergic synaptic transmission in people. 50% of people treated responded with >50% decrease in seizure frequency with positive correlation with efficacy with duration of treatment.
Do you know any dietary treatment that has been suggested for human epilepsy?
Ketogenic diet: high fat, low protein and low carbs designed to mimic the biochemical changes of fasting to potentiate mitochondrial-dependent energy metabolism in neurons and inhibition of glutamatergic metabolic pathways and synaptic transmission. (Study failed to identify any difference between dog groups and 3/9 got pancreatitis.
In contrast, a medium chain triglyceride (MCT) based diet developed for treatment of cognitive dysfunction in dogs was evaluated in dogs with epilepsy and showed significantly lower seizure frequency and monthly seizure days compared to placebo.
What are tremors and what is the pathophysiology of tremors.
They are rhythmic oscillations created when neural membrane excitability increases or if inhibition is reduced.
Achieving coordinated movement required reciprocal innervation (Sherrington’s second law). This reciprocal innervation is controlled by neural circuits in the thalamus, inferior olive nucleus, cerebrum and cerebellum. These circuits with their complex feedback loops are inherently unstable.
Purkinje neurons in the cerebellum are implicated n many tremor syndromes as they are inhibitory and GABAergic, influencing the outflow of the deep cerebellar nuclei.
Also, it is suggested that decreased GABAergic inhibition of deep cerebellar neurons disinhibits their pacemaker activity, resulting in rhythmical activiy of the thalamic and thalamocortical circuits.
Define and Give an example of each type of tremor
Rest: tremor when body segment is at rest. Uncommon in vet medicine but very important in humans. E.g mycotoxicosis
(Action) - Postural: When a body part assumes a posture against gravity, In quadrupeds easy assessed in the head. E.g. physiological, cerebellar ataxias, idiopathic generalized tremor syndrome.
Kinetic simple: during entire movement trajectory. E.g cerebellar ataxias, mycotoxicosis, idiopathic generalized tremor syndrome.
Kinetic intention: progressively increases towards intended target. E.g cerebellar ataxias.
Kinetic task – specific — for example when writing, no vet examples.
Isometric: occurs during isometric muscle contractions (in which the muscle fires but no movement at a joint or change in length of the muscle (standing) E.g senile isometric limb tremor, orthostatic tremor in great danes and scottish deerhounds.
Tremor-like movement disorders: myokymia (rippling muscle contractions), myoclonus (brief involuntary twitching of a muscle or group of muscles) , dystonia (sustained involuntary contractions of a muscle or a group characterized by a repetitive patterned pulling or twisting movement
What treatments are discussed in Ettinger indicated for Mycotoxicosis?
Drugs vary between clinicians and are based in personal experience and anecdotal:
They mention dexmedetomidine followed by anticonvulsants. Dexmedetomidine is a central alpha-2–adrenoreceptor agonist with a site of action at the locus coeruleus, influencing Purkinje cell and GABAergic output. Use of the muscle relaxant methocarbamol in cases without seizures is described, but this concerns the intravenous preparation, which is not available in some countries. Mycotoxins are highly lipid soluble, which explains their excellent ability to penetrate the brain, and there is some evidence that using intravenous fat emulsion (i.e., Intralipid 20%) can be effective in management of nervous system toxicosis from lipophilic agents
Which breeds are more commonly affected by Idiopathic Generalized tremor syndrome (IGTS)?
Labrador Retriever. Maltese terrier West highland white terrier German shepherd German pointer
Name 5 differences between Isometric limb tremor and primary orthostatic tremor
Isometric: occurs in older dogs (senile tremor) vs young adults
Orthostatic Great Danes and scottish deerhounds vs any breed
Isometric muscle contraction (iso) vs standing or when moving from one static posture to another.
Isometric does not cause distress, can deteriorate with time but milder. In orthostatic the movement has a frequency of 13-16Hz. Also progressive but causes distress and function is compromised.
Isometric does not require treatment vs orthostatic can respond to pheno at low serum concentrations
True or false for idiopathic paroxysmal head tremor
a. Recognised in English bulldogs, boxers, dobermans and Staffordshire bull terrier
b. It is very usual to see both yes-yes or no-no action in an individual dog.
c. There may be a subtle head tilt (dystonia) and this syndrome may represent a dystonic tremor.
d. Duration is usually of several hours and the movement has variable frequency and amplitude
e. Anxiety may be a trigger in some dogs and owners may be able to interrupt mild episodes
f. The dog remains aware and might appear anxious. They might try to stop the action by pressing its head into an object or its paws.
a. Recognised in English bulldogs, boxers, dobermans and Staffordshire bull terrier (T)
b. It is very usual to see both yes-yes or no-no action in an individual dog. (F)
c. There may be a subtle head tilt (dystonia) and this syndrome may represent a dystonic tremor. (T)
d. Duration is usually of several hours and the movement has variable frequency and amplitude (F) from few seconds to several hours
e. Anxiety may be a trigger in some dogs and owners may be able to interrupt mild episodes (T)
f. The dog remains aware and might appear anxious. They might try to stop the action by pressing its head into an object or its paws. (T)
