Epilepsy

Find out all the details of previous medications used – doses, durations, and why stopped. Ask what the patient thinks about previously used agents, and the impact of the medications themselves on quality of life. Explore adherence in detail. Also find out about work: driving or using dangerous machinery or working on tall buildings are all activities that can be dangerous for both patients and those around them.

Seizures – who needs a CT scan?

In the situation of new onset fits, CT scanning is performed to help determine if there is any correctable intra-cranial pathology rather than to demonstrate that there is a lesion that can cause a fit. Demonstrating pathology does not necessarily mean that management will change – very many of the intra-cranial pathologies detected by CT scanning are old – they may cause fits, but there is no treatment for them other than the treatment of the fits. Locally, there is a very high prevalence of organic causes for fits, such as neurocysticercosis and recent head trauma.

In the following situations it is clearly desirable to obtain a CT scan:

• When the fit(s) is part of a more widespread pathology – e.g. the patient has new onset lateralising signs.
• Where there are other worrying features – e.g. persistent headache or visual disturbances.
• When status epilepticus appears refractory to treatment.
• History of recent trauma.
• Any evidence of raised intra-cranial pressure.
• New onset focal fits.

There are also a number of situations where on probability a CT scan is unlikely to demonstrate remediable pathology:

• Abrupt onset, with a clear history, of lateralising weakness in an elderly person. (This is most likely to be a cerebrovascular event and in all likelihood nothing can be done for it other than conventional medical management for a stroke.)
• Long-standing epilepsy of unchanged pattern. (Years.)
• Seizures occurring in the setting of other serious medical illnesses – e.g. hyperosmolar pre-coma or profound hyponatraemia.
• When there is a clear history of heavy ethanol ingestion, no focal signs, and the patient is waking up or already fully conscious (beware lucid phase of subdural haemorrhage – usually will have headache or some head ‘discomfort’)

Most adults with new onset seizures warrant a CT scan, particularly if HIV positive, because of the high value of finding remediable pathology. It is appropriate to temporise in the context of another ‘medical’ explanation, e.g. binge alcohol use with a clear temporal relationship to the fit and no features suggestive of a subdural, hypoglycaemia, or strongly positive syphilis serology.

Management of epilepsy – outpatients

The history is essential. Don’t just take it for you own interest – document the salient features. This may involve a fair amount of writing, but there aren’t any short cuts. This information is essential if you want to be able to manage the issue. Key points include:

• Precipitating features (fatigue, missed meals, alcohol, flashing lights/TV
• Prodrome – get the details
• Eye witness description of the event, if available
• Course of events – what happens first, and then next and then next
• Associated features such as tongue biting and incontinence
• What happens afterwards – confusion, automatic behaviour, residual lateralising weakness, sleepiness
• Frequency
• Possibility of missed nocturnal fits (odd behaviour in the morning, wet bed)
• Occupational history – risk to self, risk to others.
• Previous medications used if any, and doses, and obviously adherence issues. Because most anti-epileptic agents have some neurocognitive impact, achieving concordance between what the patient can tolerate and the prescriber’s wishes is essential.

Life style issues

This is important. It is not just about stopping alcohol abuse, but also involves getting enough sleep, reducing stressors, regularising meals, adapting occupation (and giving advice about driving), and addressing social and family stigma and perceptions

Medication

Most seizures will respond to most available medications. There are a few exceptions, but in general most first and second generation agents are worth considering. A key issue is potential for drug interactions – in general avoid first line agents (phenytoin, carbamazepine and phenobarbitone) in patients on anti-retrovirals, and monitor INR carefully if starting any of these agents in a patient on warfarin. Lamotrigine is fairly cheap and effective, and should be considered before valproate – both medicines require dose escalation for efficacy, and lamotrigine should also be escalated carefully for safety reason (skin rashes with too rapid increments in dosing)

Status epilepticus

This is conventionally defined as a series of fits without regaining consciousness between seizures, or as fits lasting more than 30 minutes. Some authors⁹ would add the rider that this pattern should be new or atypical for the patient, but in practice this information is often unavailable when initially assessing a fitting patient.

Aim to stop seizures in all patients with status within one hour of presentation. Without prompt treatment there is a high probability of permanent neurological sequeli.

Initial management of status epilepticus

Check the finger prick glucose and treat hypoglycaemia if found.

Airway. Don’t try to secure the airway during the fit – either you or the patient will be traumatised. Wait until the fit is over, and then turn the patient into the left lateral position and suction/intubate as necessary.

Give diazepam 10 mg I.V. over 2 minutes, watching respiration. Repeat once if fits continue. An alternative is lorazepam 0.1 mg/kg¹⁰ to a total of 6-8 mg at a maximum rate of 2 mg per minute. (Give a first dose of 2 mg then wait 10 minutes before repeating.) Another possibility with a similar long biological effect to lorazepam, but without the requirement for refrigeration, is clonazepam 1 mg slowly IV, repeat once or twice if necessary (max 4 mg). Benzodiazepines will stop 60-80% of seizures. (Although not entirely predictable from their elimination kinetics, the ‘effect half lives’ seem to favour lorazepam or clonazepam, with the duration of fit control varying from 2-4 hours for diazepam to 24 hours for clonazepam, and up to 72 hours for lorazepam¹¹ Options if there is no venous access are clonazepam 1 mg IM or midazolam 5 mg buccally or IM.

Phenytoin loading (will stop seizures in another 28%¹²). Doing this incorrectly is the commonest cause for poor control. The dose is 20 mg/kg lean body mass, diluted in 200 ml of normal saline (NOT dextrose!) and given at a rate of 50 mg/minute. i.e. for a 75 kg man, give 1500 mg over at least 30 minutes. The vials usually contain 250 mg in 5 ml, so for 1500 mg, six vials will be required.

Ideally, monitor BP and pulse every 15 minutes. Give the phenytoin in a place where you can keep an eye on the patient. (e.g. keep the patient in casualty until the infusion is finished and the fits have stopped. Do not assume that it will be given if you don’t supervise personally – sending the patient to the ward while the infusion is still running almost predicts you will find it half -finished on the post-intake ward round the next morning.

You can top up to a total dose of 30 mg/kg of phenytoin by giving an extra infusion of 5-10 mg/kg but in practice this extra bit is seldom helpful. Knowing the safety margin is most useful if you are trying to calculate an acceptable increment in a patient where there is doubt about whether the load was truly given or may have been given incompletely.

Give a second dose (4 mg/kg) of phenytoin orally or via NGT 12 hours after the loading dose. This can serve as evening maintenance if given after 16H00 ( i.e. if the load was given early that morning), but if given before then (because 12 hours after the load ends up as being in the morning, say), then a second dose for that day should be given at 22H00. All doses after the load can be given via NGT, but no enteral feed should be given for 2 hours before or 4 hours after the NGT phenytoin (it may impairs absorption).

If the patient is still fitting after the phenytoin infusion is completed:

Re-consider the possibility of subdural or other structural cause for status epilepticus.
If the fits aren’t controlled immediately after the end of the phenytoin infusion, then transfer the patient to a place where you can monitor breathing and intubate and ventilate if necessary (e.g. ICU)

Thiopentone for status epilepticus

Thiopentone is loaded at 15 mg/kg (e.g. 750 – 1000 mg) in 200 ml normal saline over 60 minutes. Maintenance infusion of thiopentone 1-5 mg/kg/hour in normal saline thereafter. (An alternative to the initial loading dose is to give boluses of 50-100 mg at a time until the fits are controlled.) Ventilation will be required. Hypotension is very common with higher doses, and autonomic instability has been reported¹³. An inotrope infusion may be needed.

Propofol for status epilepticus

If thiopentone is unavailable or not preferred, other options are propofol or midazolam infusions. Propofol is usually given as a 2 mg/kg bolus followed by an infusion of 1-5 mg/kg/hr. Propofol can sometimes cause myoclonus that should not be confused with a return of seizure activity. Another caution concerns the propofol infusion syndrome (fever, metabolic acidosis, rhabdomyolysis and ECG abnormalities.) The cut-offs of infusion rates of less than 5mg/kg/hr and total infusion times of less than 48 hours may induce a false sense of security – the syndrome can occur with lower doses for shorter times. Blue or green urine only occurs in 10% and its absence does not exclude the syndrome. Incidence is about 1% of patients given the agent in ICU. Mortality is influenced by co-morbidities, but reported to range from 20% to 50%.¹⁴.

Midazolam for status epilepticus

Midazolam – 10 mg bolus and then 0.05 – 0.4 mg/kg/hr. (Effective ness of midazolam declines with time as tachyphylaxis tends to develop after 24 to 48 hours of use¹⁵

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6. Baykan B, Wolf P.  Juvenile myoclonic epilepsy as a spectrum disorder: A focused review. Seizure. European J of Epilepsy. 2017,49:36-41. https://doi.org/10.1016/j.seizure.2017.05.011  ↩

7. Sillanpaa M, Jelava M, Kaleva O, et al. Long-term prognosis of seizures with onset in childhood. N Engl J Med. 1998;338:1715-22  ↩

8. Duncan JS, Shorvon SD, Fish DR. Clinical Epilepsy. Churchill Livingstone 1995 p304.  ↩

9. Cruz, J. Neurological and neurosurgical emergencies. WB Saunders. 1998 p56  ↩

10. Treimann DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalised convulsive status epilepticus. N Engl J Med. 1998;339:792-798  ↩

11. Rey E, Treluyer J, Pons G. Pharmacokinetic optimisation of benzodiazepine therapy for acute seizures. Clin Pharmacokinet 1999;36:409-24.  ↩

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13. Ghosh IR, Langford RM, Nieminen K, et al. Repetitive synchronized cyclical oscillations of multisystem parameters subsequent to high-dose thiopental therapy for status epilepticus secondary to herpes encephalitis. Br J Anaesthesia. 2000; 85: 471-81  ↩

14. Hemphill S, McMenamin L, Belamy MC, Hopkins PM. Propofol infusion syndrome: a structured literature review and analysis of published case reports. British J Anaesthesia. 2019;122:448-459  ↩

15. Lawn ND, Wijdicks EF. Status epilepticus: A critical review of management options. Can J Neurol Sc. 2002;29:206-215..  ↩

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