|Year : 2014 | Volume
| Issue : 1 | Page : 41-44
Super refractory epilepticus in a patient with post-ictal psychosis
Aghukwa Nkereuwem Chikaodiri
Department of Psychiatry, Bayero University/Aminu Kano Teaching Hospital, Kano, Nigeria
|Date of Web Publication||7-Apr-2014|
Aghukwa Nkereuwem Chikaodiri
Bayero University/Aminu Kano Teaching Hospital, Kano
Source of Support: None, Conflict of Interest: None
Post-ictal psychosis occurring with super refractory epilepticus is an uncommon neuropsychiatric phenomenon. The purpose of this article is to describe the clinical management in an adult male of a protracted post-ictal psychotic disorder, which complicated a super-refractory status epilepticus in a resource poor country. The case describes the clinical presentation of a young man on an anti epileptic drug, diagnosed with secondarily generalized complex partial seizure disorder following a head injury. The index episode, which the patient presented days later for orthodox care, manifested after some days with post-ictal psychotic mental disturbances. Despite the cautious use of antipsychotic and antiepileptic drugs, super-refractory status epilepticus complicated seizure. On admission to the ICU, intravenous midazolam was given to the patient, but could not be maintained due to unavailability and substituted with magnesium sulphate infusion.The magnesium sulphate infusion was maintained due to break through seizures on return of patient to the psychiatric ward. The psychosis and refractory seizures were controlled after 8 weeks by joint magnesium titration, intravenous diazepam, high dose oral anti epileptics, and atypical antipsychotic drugs. A combined therapy of magnesium, benzodiazepine, and atypical antipsychotics might be an effective treatment option in post-ictal psychosis with super- refractory status epilepticus.
Keywords: Epilepsy, post-ictal psychosis, super refractory epilepticus
|How to cite this article:|
Chikaodiri AN. Super refractory epilepticus in a patient with post-ictal psychosis. Niger J Basic Clin Sci 2014;11:41-4
| Introduction|| |
Attacks of mental disturbance sometimes complicate a fit or bouts of fit few hours or days after.  This disturbance presents as post-ictal psychosis (PP), if following a lucid period of 2 hours to 7 days, the sufferer experience changes like auditory and visual hallucinations, delusions, paranoia, affective change and aggression, with a degree of confusion and delirium lasting a few hours to 3 months.  Identification and management of status epilepticus in resource-poor countries (RPCs) like Nigeria, are problematic.  Although status fits are common in such countries, problems arise in case identification by primary physicians who treat the majority of the patients.  Some of the reasons for this are: Improper accounting of seizure presentations, inadequate anti-epileptic drug (AED) treatment, and difficulty accessing some of the drugs used for its treatment. , It is important that physicians identify status epilepticus early because of the risk of treatment non-response and subsequent morbid neuronal damage to the brain. , Seizures tend to become resistant to AEDs after an appropriate use of two or more of such drugs fails, probably to alterations in the GABAergic and NMDA neuronal systems.  PP is claimed to be the outcome of over activation of the central nervous system following depressants withdrawal there from, such as in sudden anti-convulsant stoppage. , In like manner, one of the major causes of status seizure in a patient on anti-convulsants is sudden stoppage. Besides this, erratic use of medications, neurological and physical illnesses such as encephalitis/encephalopathies, stroke, haemorrhages and intoxicants are also other causes.  Treatments of pharmaco-resistant seizures require aggressive supportive care and prompt termination with intravenous anti-convulsants. If the seizures persist, the patient is anesthetised while monitoring the airways and cardiovascular functions. Intravenous lorazepam or diazepam is the first line drug. Where this fails, intravenous phenytoin or fosphenytion is given and if the seizure persists, cautious use of intravenous phenobarbital is instituted. Status epilepticus is super refractory when it continues or recurs 24 hours or more, and after the institution, reduction or withdrawal of anaesthetic therapy.  In refractory situations where seizure does not respond to the earlier treatments, infusions of diazepam, midazolam, propofol or pentobarbital could be used. , Where intravenous valproate is available, it is an effective alternative with lesser risk of respiratory compromise to phenobarbital.  Use of magnesium salts in refractory or super refractory seizures is sparsely reported, and treatment outcome is based on clinical and case reports. , Identifying status seizures may be no simple matter in patients with post-ictal psychotic mental disturbances, yet cases describing the co-occurrence of both conditions appear scanty. The study aims to highlight the management of complicating refractory seizures in a Nigerian patient with PP. Although there are literature reports on refractory status epilepticus, this is the first on its management in a post-ictal psychotic situation, in the present area of study.
| Case Report|| |
The patient was a 20-year-old single unemployed secondary school educated Nigerian Moslem man. He presented with 7 days history of laughing to self, poor night's sleep, restlessness and saying about meaningless things. He fitted during a mid-day prayer in a mosque 5 days prior to the abnormal behaviours. The fits, which had been recurrent, usually manifest with strange behaviours, loss of consciousness, sudden falls and jerky movements of the limbs. His first experience of fit was 3 years ago, 2 years after a road traffic accident that left him unconscious for 10 days , from which the relatives claimed he had full recovery afterwards. Before the recent fit, he was on a prescribed AED for complex seizure with secondary generalisation. He had a recurrence of seizure episodes in the past due to irregular use of his anti-epileptic medication. His father died 3 months prior to the present episode of seizure and there is a family history of epilepsy in a half male sibling. The pregnancy, labour and delivery were uneventful. Milestone, infancy and childhood progressed normally. The patient's relatives denied any family history of mental illness but a history of hypertension in the late father , and his forensic records were uneventful. He lived with his mother and other siblings in a three-bedroom apartment, and was described as quiet, affable and loved singing. Before the last fit at home, he was preparing to attend for the University Matriculation Examinations, with an intent to study law if successful. Not known to use alcohol, tobacco or illicit drugs, he was dark complexioned, tall, neatly dressed in a blue T-shirt and a pair of black trousers, conscious but restless; speech was disorganised with meaningless words and phrases (neologisms). He appeared suspicious of both people and things happening around him with inappropriate responses to questions. Though he was restless and unco-operative most of the time, he identified himself and the relatives around, but was neither oriented to time nor place and was unable to state the days of the week forward and backward. A positive finding on physical examination was an old left ankle scar, and baseline laboratory tests like complete blood count and electrolytes were normal . An initial diagnosis of PP was based on the following: The lucid interval following the last episode of recurring fits, followed by bizarre behaviours, disorganised speech and an impaired cognitive state with possible delirium. A post-ictal delirium was an alternative diagnosis at this stage of illness had the criteria for PP not been fulfilled in the case.  An electroencephalographic investigation showed epileptiform activities from the left superior-frontal/mid-temporal lobes, while a computed tomographic scan reported features of mild cerebral atrophy in the patient. Serial reports of some of the previous laboratory investigations in the course of his treatment revealed no abnormalities. The patient was previously stable on 200 mg twice daily oral carbamazepine; on admission, this was increased to 300 mg bd, with an addition of 2.5 mg twice daily oral haloperidol. Two days of admission, he had repeated abrupt episodes of tonic clonic jerks that lasted 45 seconds on the average. A typical episode usually starts with stiffening and the extension of the right upper limb of the ambulatory patient, which spreads to all limbs within seconds, grunting and clenching of the teeth and this is followed by the few seconds of mild twitchy movements that are more apparent in his upper limbs and toes. The patient responds to no form of relational contact within this period but a couple of minutes later, he becomes restless, confused, uttering meaningless phrases while tending to leave his bed and physically aggressive. Due to an increase in the frequency of occurrence of fits at about every 1-2 hours and the worsening of the patient's behaviours afterwards, intravenous 20 mg diazepam and intramuscular 5 mg haloperidol were introduced for both tranquilisation and seizure control. Although the jerks abated within 24 hours of tranquillising the patient, physical restraint was used because of the heightened agitation and bizarre behaviours. Brief but repeated fits re-occurred 2 days later, and following this, oral carbamazepine was increased to 300 mg tds, oral haloperidol was replaced with 5 mg bd olanzapine and prn diazepam (20 mg IV not more than 3 doses in 24 hours) was instituted. The fits became intermittent, occurring in a few seconds with hours in-between episodes, hence 500 mg bd oral sodium valproate was added to the treatment but this did not abort the brief attacks. Due to the more frequent brief fits with heightened restlessness in the patient, sodium valproate was gradually stepped up to 2 g and carbamazepine was reduced to 600 mg in two divided daily doses, respectively . A reviewing neurologist made an impression of an impending status epilepticus in the patient, requested for some investigations, and instituted 8 hourly 20 mg diazepam in 1 litre of normal saline while maintaining the oral medications. Though the patient's psychosis persisted, clinical seizure episodes stopped within 24 hours of the infusion and he was maintained on oral AEDs. The convulsive manifestation of the fits re-started 5 days later, but was not controlled with the diazepam titration; hence he was given 4 mg IV lorazepam while on artificial oxygen. The fits persisted despite a repeat of lorazepam; 20 mg/kg intravenous bolus of phenobarbitone was given to the patient since parenteral phenytoin was unavailable. The patient's fits were considered refractory when it did not stop with phenobarbitone, and he was transferred to the intensive care unit (ICU) for further care. While in the ICU, the frequency of seizure was controlled with a 4 g IV bolus dose of magnesium sulphate, and abated with10 mg of intravenous midazolam after intubation. Continual titration of midazolam was not done because it ran out of stock; hence alternative titration with magnesium sulphate (MgSO4) infusion at 1 g/hour. The infusion was instituted and maintained when the patient returned to the ward, because of breakthrough seizures that occurred almost every day. Clinical monitors for signs of magnesium toxicity in the patient while on the ward were, respiratory rate at less than 12 cycles per minute and 4 hourly check for presence of hyporeflexia at the Achilles tendon. He made a remarkable recovery by the 8 th week of admission, and the magnesium sulphate infusion was gradually withdrawn. He remained fit free and without agitations on oral 2 g sodium valproate, 300 mg bd carbamazepine and 10 mg nocte olanzapine. In addition, he was very ambulant while on this regimen, and attended occupational therapy sessions. Although he recognised familiar faces and was able to follow instructions, his gross motor condition for tasks was poor, and with perseveration.
| Discussion|| |
The neuropathological factors in the occurrence of psychosis in epilepsy remain unresolved. PP in epilepsy has been linked to, temporo-frontal lobe abnormalities, and improper use or withdrawal of anti-convulsants among other propositions. , Similar to the noted findings in the present patient, among Nigerians,  cortical atrophy is a commonly associated risk factor for epilepsy. Just as bilateral cortical abnormalities, head injuries and epilepsies with temporal lobe foci are commonly associated with PP. , However, the problem of universal identifiers for status epilepticus particularly when co-existing with psychotic illnesses makes its identification difficult. ,
The unavailability of essential drugs, adequate manpower and facilities are major hindrances to effective management of refractory status epilepticus in an underdeveloped society.  In such countries, intravenous diazepam and phenobarbitone have been the most common drugs available for treating such patients.  Despite this shortfall, barbiturate anaesthetics are recommended alternatives to midazolam or propofol in refractory generalised convulsive status and complex partial status epilepsies. , Magnesium, which has been effectively used in eclamptic fits, shows a potential application in refractory status epilepticus.  Magnesium acts to increase the seizure threshold by blocking the NMDA-receptors, unlike barbiturates and benzodiazepines, which act majorly to enhance GABAergic receptor functions.  Status epilepticus becomes super refractory with persistence despite therapy with general anaesthesia for 24 hours or more. Although the present case study applied clinical monitory for magnesium toxicity in the patient, it might support an earlier claim that; gradually achieving a serum level of 3.5 mmol/l after an initial bolus dose of intravenous magnesium is beneficial in super refractory status epilepticus without significant toxicity or drawbacks.  This is usually augmented with preferably two oral high doses of anti-epileptics with less GABAergic and low interaction potentials throughout the treatment.  Despite potentiating GABAergic actions, carbamazepine and valproate also inactivate membrane channels, which reduce neuronal firing, thereby enhancing stabilisation.  This potentiates the actions of the titrated anaesthetic agents in reversing the distorted membrane GABAergic receptor sensitivity in refractory status epilepticus.
The delay in coming to the hospital from the onset of the patient's psychotic manifestations contributed to not start an early intervention of the PP that subsequently deteriorated to pharmaco-resistant seizures. In addition, the underlying cerebral atrophy, and poor compliance with AED medication use were possible markers to the earliest manifestations in him. The unavailability of conventional medications for refractory status epilepticus prompted the use of magnesium, its use demonstrated an alternative efficacy that deserves further evaluation in future randomised studies.
| Conclusion|| |
The implication of this report in the care of patients with super refractory epilepticus in a RPC like Nigeria is that doctors, especially primary physicians, who are usually the first to treat such patients may apply this line of management in such critical situations where facilities, drugs and adequate man-power are limited. In addition, unavailability of monitors for blood magnesium titres may not be a hindrance to its use since effective clinical observations for its toxicity could be relied upon as being done in obstetric use. Epilepsy patients should be made to understand the need for strict treatment adherence and the hazards that come with in appropriate compliance or sudden drug stoppage. A universally accepted definition of status epilepticus, which puts into cognizance such situations that are complicated by ictal psychoses should be adopted by International League Against Epilepsy (ILEA) in the near future. This is a single report on the use of magnesium in status epilepticus, therefore findings cannot be generalised. Further studies on the efficacy of magnesium in refractory seizures, especially in RPCs with limited treatment options in epilepsy with psychosis, is a vital future research, which is supported by this case report.
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