Seizures & Sleep Disorders Flashcards
Define the following: Epilepsy, epileptic seizure, status epilepticus, convulsions
Epilepsy: A disorder of the brain characterised by an enduring predisposition to generate epileptic seizures (recurrent seizures).
Epileptic seizure: A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Status epilepticus: A condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures after time point 1, and can have long-term consequences after time point 2, whereby time point 1 is considered 5 mins and time point 2 is considered 30 minutes.
Convulsions are seizures accompanied by tonic-clonic muscle activity and loss of consciousness.
Differentiate partial from generalised seizures
Partial seizures involve a discrete area of cerebral cortex and cause localised clinical signs (facial twitch, limb twitching etc).
Generalised seizures affect the whole body with loss of consciousness. They can be primary (generalised from the onset) or secondary (progression from partial seizures).
Describe the pathogenesis of a seizure
Abnormal hypersynchronous electrical activity of neurons caused by imbalance between excitation and inhibition in the brain. If the balance shifts towards excitation a seizure might occur.
List the differentials for seizure in a horse under 1 year old
Congenital: hydrocephalus, hydranencephaly, idiopathic epilepsy.
Metabolic: hypoxia, hyponatremia, hypoglycemia, hyperkalemia.
Toxic: Organophosphates, strychnine, metaldehyde, moldy corn, locoweed.
Traumatic: brain trauma, lightning.
Vascular: NMAS
Infectious: Septicemia, hyperthermia, bacterial meningitis, cerebral abscesses, rabies, viral encephalitis.
Most common in foals under 2 weeks: NMAS, HIE, trauma and bacterial meningitis.
List the differentials for seizure in a horse older than 1 year
Metabolic: HE, hypocalcemia, ureamia, hyperlipidaemia
Toxic: organophosphates, strychnine, metaldehyde, moldy corn, locoweed, bracken fern, lead, arsenic, mercury, rye grass
Traumatic: brain trauma.
Vascular: Strongylus vulgaris, cerebral thromboembolism, intracarotid injection, neoplasia, haemarthroma, cholesterol granuloma
Infectious: cerebral abscess, rabies, arbovirus encephalitis, mycotic cryptococcosis, EPM.
Most common in adults: brain trauma, HE and toxicity. Tumours such as melanoma, pituitary adenoma, cholesteatoma and rarely glioma can cause seizures.
Describe the roles of NMDA receptors and GABA in the pathogenesis of seizure development
NMDA: binding of glutamate to NMDA receptors opens Na and Ca channels causing post-synaptic depolarisations. If exacerbated, intracellular Ca overload causes neuronal necrosis by activation of lytic enzyme systems and nitric oxide synthase with generation of free radicals.
GABA: in response to the above depolarisation shift GABA-ergic inhibitory zones are established to prevent spread of epileptic activity. This can be pre or post synaptic. If this system fails, the abnormal depolarisation shift will continue and once a critical mass is reached uncontrolled spread over the cerebral cortex may occur and can result in a seizure.
What are the electrolyte derangements noted during the inter-ictal period
Increased potassium concentration, decreased intracellular calcium, magnesium and chloride. Alterations in sodium conductance, particularly rapid influx into the neuron, may also be involved.
What changes on EEG do you expect to see with seizures
Spikes, sharp waves, spike-and-wave discharges and other transient events.
List the treatments (short term) for seizure, including the benefits and contraindications for each
Benzodiazepines (diazepam, midazolam) - bind to GABA receptors, hyperpolarising neuronal cells therefore decreasing electrical activity of the seizure focus and increasing the seizure threshold. They have a short half life (10-15 min for diazepam), prolonged use can result in respiratory depression/arrest and drug accumulation in foals; phenobarbital - rapidly provides high serum concentrations; reduces cerebral metabolic rate, facilitates inhibitory neurotransmission by GABA receptors, inhibits post-synaptic potentials produced by glutamate and inhibits the voltage gated Ca channels at excitatory nerve terminals. Lower doses should be used in foals, including the loading dose. Sodium pentobarbital - more useful in foals due to anaesthetic effects but may be helpful in adults with status epilepticus (as well as propofol and ketamine); primidone (metabolised to phenobarbital and to a lesser extent phenylethylmalonamide which might potentiate effects of phenobarbital) has been advocated for foals. Phenytoin inactivates voltage-dependent neuronal sodium channels, preventing depolarisation hence reducing release of glutamate. Adverse effects are prolonged depression in foals, AV block and decreased blood pressure in adults. ACP may reduce seizure threshold. Ketamine may exacerbate seizures due to increased cerebral blood flow, O2 consumption and intracranial pressure, but also antagonises NMDA receptors hence may be useful.
List the treatments (long term) for seizure, including the benefits and contraindications for each
Phenobarbital (drug of choice) - remember it induces cytochrome P450 enzyme complex therefore increased its own metabolism so therapeutic monitoring is required (every 60 days once stable). Adverse effects include excessive sedation, respiratory depression, bradycardia, hypotension and hypothermia in neonates. Avoid drugs with interactions such as ivermectin. Tetracyclines and chloramphenicol inhibit microsomal emzymes therefore prolonging effects of phenobarbital.
Potassium bromide - competes with Cl to hyperpolarise neuronal membranes and enhances GABA-activated Cl conductance. Takes a few weeks to reach steady state so shouldn’t be used alone. Can reduce dose of phenobarbital by 20% and add Potassium bromide.
Phenytoin - inactivates voltage-dependent neuronal sodium channels, preventing depolarisation hence reducing release of glutamate. Adverse effects are prolonged depression in foals, AV block and decreased blood pressure in adults.
Primidone - metabolised to phenobarbital and to a lesser extent phenylethylmalonamide which might potentiate effects of phenobarbital; has been advocated for foals.
Other drugs used in other species: felbamate, gabapentin, clorozepate, toparimate, levetiracetam and zonisamide. These potentially have improved therapeutic indices.
List the breeds associated with familial narcolepsy
Shetland, Suffolk, American miniatures and Lippizaners.
List the described triggers for an episode of narcolepsy and cataplexy
Initiation of eating or drinking, petting/stroking the head or neck, hosing with cold water after exercise and leading out of a stable.
Differentiate narcolepsy from other causes of collapse
Narcolepsy: gradual lowering of the head precipitates a collapse episode. Neurologically and cardiovascularly normal between episodes.
Sleep deprivation: may also include gradual lowering of the head and buckling; no cataplexy.
Syncope: Not preceded by lowering of the head or drowsiness.
Seizure: loss of consciousness and tonic-clonic activity in generalised seizures.
Botulism: Additional neurological signs (progressive weakness, dysphagia, weak tongue tone etc).
HYPP: remain alert, often anxious and may have prolapse of the third eyelid.
List treatments for narcolepsy
Drugs that stimulate monoamine systems (dopamine, noradrenaline, serotonin) should be effective narcolepsy suppressors; those that stimulate cholinergic activity exacerbate narcolepsy.
- Atropine sulphate reduces the severity of cataplectic attacks and can prevent reoccurrence for 12-30 hours.
- Imiprimine (tricyclic antidepressant) blocks uptake of serotonin and noradrenaline and decreases REM sleep. Oral Tx produces inconsistent results, although no adverse results. Adverse effects of IV tx exceeding 2mg/kg include muscle fasciculations, tachycardia, hyperresponsiveness to sound and haemolysis.
List differentials for a collapsing horse
- Seizure
- Sleep deprivation
- Narcolepsy
- Syncope
- Hypersomnia
- REM disorders
