Daniel's Story
This is an ‘abridged’ version of Daniel’s rather complicated epilepsy journey – trying to reduce the length and still retain the context with the many, many turns his eventual road to recovery took was not an easy task, so I have had to resort to a bullet point type version…
The much (!) longer one I have written, something I have meaning to do for a long time, is more akin to a novel, ahem - and is somewhere in the vicinity of 18 (or more) pages long…… but in case other parents do want to take time to read it at some stage in the event it might be helpful, I will look into posting a link to it at a later date on Matthew’s Friends, and also on the MAE website.
- Daniel Richard Hill – born 29 November 1996 - only health issues were colic and silent reflux which resolved around 6 mths of age.
- All developmental milestones reached on or ahead of time.
- June 2000 - First seizure was a tonic clonic out of the blue at age 3 yrs 7 months.
- Myoclonics, drop attacks and absences crept in over ensuing weeks.
- Lennox Gastaut Syndrome Diagnosis given in July 2000, started on epilim (depakote) and clonazepam (rivotril, klonipin) but clonazepam induced violent/hyperactive behaviour, pulled on day 7 and replaced with clobazam (frisium).
- Still no seizure control, phenytoin added to epilim and clobazam during hospital admission, seizures still not controlled, actually worsened.
- Phenytoin replaced with tegretol a few weeks later, now on epilim, lamictal and tegretol, still no improvement, drop attacks escalating.
- August 2000 – 2 week course of ACTH (steroids) trialled – complete seizure control and normal EEG by day 3 but course stopped on Day 10 due to excessive fluid retention - hypersensitive reaction. Admitted to hospital for emergency diuretics, released 3 days later still with seizure control intact.
- 3 weeks later a cold turned to pneumonia, back to hospital, seizure control was then lost.
- Ethosuxomide (zarontin) added, now on epilim, clobazam, tegretol and ethosuxomide, still no control, very ‘toxic’.
- Ethosuxomide replaced with slowly incremented lamictal, now on epilim, clobazam, tegretol and lamictal, still no control so we requested a 2nd opinion on diagnosis and treatment.
- November 2000 – week long admission and EEG monitoring in Wellington Hospital, seen by pediatric neurologist recently arrived from Vancouver - diagnosis changed from LGS to MAE (Myoclonic Astatic Epilepsy of Early Childhood).
- Tegretol withdrawn cold turkey as it aggravates MAE (as does phenytoin and phenobarbitol), all seizures remitted within 3 days except for early am sleep tonic clonic seizure, discharged on epilim, lamictal and clobazam.
- All seizure types crept back within a few weeks, not as bad as when on tegretol but still not controlled – assumption in hindsight was that he was probably still toxic, tegretol had been inhibiting other medications, once removed the other levels ‘rose’ back to a toxic level.
- Not realizing this, agreed to lamictal then epilim increases (still with clobazam on board), seizures even worse, MAE diagnosis by then in doubt due to rapid cognitive deterioration, biopsies and other testing carried out for the metabolic/mitochondrial diseases.
- Late May 2001 - Chicken pox, minor spots wise (only a few isolated ones) but disturbance to Central Nervous System threw him into status – 2 week hospital admission with frequent high dose IV diazepam boluses.
- Discharged on epilim, lamictal and oral diazepam – the high dose diaz boluses had automatically replaced the previous clobazam.
- June 2001 – back to hospital, seizures out of control again, phenobarbitol IV load pushed him into electrical status (see above re adverse reactions in MAE…), unconscious for 26 hours.
- June 2001 - 2nd ACTH course administered as an inpatient so daily diuretics could be administered to counteract hypersensitivity reaction, repeat result of the first course – full seizure control but lost again a few weeks later a cold again turned to pneumonia (probably due to lowered immune system from steroids)
- July/August 2001 – another hospital admission when seizures started escalating to status, decision made to fast Daniel to insert a PIC line under general anesthetic ready for midazolam infusion in Intensive Care.
- Delay in theatre, 22 hours without food – woke from nap out of status for no apparent reason – no seizures at all, alert again, cognitively ‘intact’, released from hospital that night.
- Seizures returned the following day, escalated over next couple of weeks.
- Movie ‘First Do No Harm’ screened on TV during Epilepsy Awareness Week, realized the seizure cessation during previous admission may have been due to Daniel going into ketosis after being fasted.
- Sep 3rd 2001 – admitted to hospital again (practically in status again by then), this time to initiate the ketogenic diet – ‘awake’ seizure control within 3-5 days, alertness returned, discharged on day 6 with only intermittent early am sleep seizures remaining.
- Metabolic/mitochondrial disorder test results came back as negative, diagnosis changed back to MAE following return of cognitive function and positive seizure response to diet initiation
- 10 days later started acting ‘drunk’ – unsteady on feet, drooling, slurred speech but no seizures.
- Seizures returned a couple of days later, mainly myoclonic, back to hospital where seizures escalated into myoclonic status – no improvement with IV diazepam boluses.
- Declined recommendation to increase lamictal, requested decrease instead after seeking advice from Yahoo Ketogenic Diet support group – realized from there that the state of ketosis may have accentuated AED effects, potential toxicity again.
- Status broke 3 days after 50 mg lamictal reduction, second reduction of 25 mgs agreed to, daytime seizure control regained by the end of week, discharged back home again late September, so assumption was he had indeed gone toxic after diet initiation despite no actual med level increase.
- Started chipping away at oral diazepam dose at home following the realization that ‘less was more’ drug wise with Daniel and that he fared better when at less risk of toxicity.
- Stable until Dec 2001, breakthrough drop attack with no apparent cause until 7 days later when the chicken pox appeared again – assumption being the mild dose spots wise in June and the recent steroid courses affecting his immune system had allowed him to contract the illness a second time.
- Seizures escalated into status, horrendous month long hospital admission (including Christmas in Intensive Care) - midazolam infusion resulted in what had been by then low dose oral diazepam replaced with 10 mgs of nitrazepam (mogodon) as a weaning method from midaz infusion – back to square on with the benzodiazepines courtesy of the 2nd dose of the chicken pox.
- January 2002, discharged on epilim, lamictal and nitrazepam – bad drug for Daniel, very sedating and cognitive function markedly reduced.
- Chipped away at all 3 medications (in particular epilm and lamictal) during 2002, with the occasional daytime withdrawal seizures that always resolved once the blood levels had stabilized again.
- Relatively stable until March 2003 (but still unable to get rid of the early am sleep seizures), started carnitine supplement in an attempt to raise waking ketones to try and control sleep seizures – he was still on epilim, and recent blood testing had shown a deficiency. Incremented carnitine up to a dose of 50 mgs per kg per day as advised over a period of 2 weeks.
- Breakthrough daytime seizures started after another week, escalated into status, Intensive Care admission required with another midazolam infusion.
- Carnitine stopped in case it had provoked an adverse reaction seizure wise.
- Regular blood monitoring in PICU meanwhile showed high glucose levels after fasting, especially irregular for a child on the ketogenic diet where stored glycogen in the bloodstream would usually be at a minimum.
- Further investigations revealed calories had been too low – Daniel’s weight had been nearly at a standstill for the previous12 months and height had dropped from above the 90th percentile to below the 75th.
- Ree Dx test (resting energy expenditure measurement) revealed at least a 300 calorie shortfall, DEXA scan showed abnormally high fat composition and reduced muscle mass – result of him being in a catabolic state, hence the high glucose levels and loss of diet control
- Supposition was that introducing the carnitine and its effect of increased dietary fat metabolism had highlighted his (unbeknownst to us at the time) calorie deficit, possibly triggering the malnourishment/catabolic crisis.
- Meal plans altered with large calorie increase, but already addicted by then to high dose midazolam infusion – 60 mgs diaz per day used as oral weaning dose, reduced on the ward over the next week.
- Discharged in April 2003 on epilim, lamictal and 28 mgs per day diazepam - this replaced the previous nitrazepam which before the catabolic state was revealed we had previously managed to get down to only 2 mgs per day. Back to square one again with the benzodiazepines.
- Daytime control regained once diazepam brought below 20 mgs per day at home, did one more reduction to 16 mgs per day and left him on that dose to stabilize.
- August 2003 – Daniel slipped back into a catabolic state for the second time – this can occur relatively easily if not completely resolved the first time and despite the large calorie increase in March he was still apparently on insufficient calories (reflected in his continued lack of height growth which was by then had fallen further down to around the 50th percentile) and his blood sugar levels had once again risen to exceed ketone levels due to glucose being leeched from his muscle tissue.
- Seizure control therefore lost again, requiring another hospital admission, relatively short as this time we knew what had happened, so no high dose meds were added, instead his diet plan was corrected (calories and protein intake increased and ratio lowered) and he improved fairly rapidly.
- Stable until October 2003, when cognitive state and alertness gradually reduced, unsteady gait and showing signs of toxicity, but without any medication changes – all had been left alone including the 16 mg diaz dose since April as we had been concentrating on fine tuning the diet. EEG showed altered state not due to sub clinical seizure activity.
- A few days later the seizures did creep back in, we were sure as a result of the toxicity we were seeing.
- Decision was made to remove his remaining 400 mg epilim dose (had been gradually lowered down to that dose throughout 2002) as an inpatient and a few days afterwards, his seizures remitted and his cognitive functioning returned to it’s previous level.
- Discharged once the risk of withdrawal seizures had passed, started on carnitine again as another test had shown a marked deficiency again.
- November 2003 – re-emergence of altered cognitive state, and ‘toxic’ characteristics, re-admitted to hospital
- Hospital Metabolic Specialist ordered a MRI as he had found a journal case where a child on carnitine had suffered an adverse reaction to the supplement (bearing in mind his March experiences) but Daniel’s scan was clear, and showed none of the neurological signs that would have been obvious had this been the case.
- Carnitine stopped anyway as an urgent blood result showed his levels were now sky high, presumably a result of the October epilim removal meaning the previous depletion from that drug was no longer an issue and the 50 mgs per day supplement had taken the levels to the other extreme. Apparently not an issue though, as any excess carnitine is usually just peed out with other waste matter.
- Daniel’s cognitive state continued to decline with hallucinations, reduced mobility and speech and other increasingly worrying signs - his EEG at that stage was not reflecting status, which might otherwise have explained his rapid decline.
- Early am sleep seizures increased, very convulsive and prolonged, followed by the emergence of daytime seizures as well.
- Medications used on the ward, starting with IV loads of epilim in case he was suffering from some form of delayed withdrawal effect from October. No improvement, if anything he worsened.
- Paraldehyde tried without improvement, then IV boluses of clonazepam. This saw the beginning of many forms of ‘awake’ tonic seizures, initially mistaken for complex partials. Seizures spiraled into status and he was moved to Intensive Care on 17 November 2003 – by now unable to talk or move, only able to use eye movements and facial expressions to communicate with us.
- Recommendation was made by Intensive Care staff to start a midazolam infusion – we were totally opposed to this, as by now we had come to the conclusion that this is what had probably happened to Daniel :
An intolerance (so a step past ‘tolerance’) had formed to the benzodiazepine class of drugs that he had been on continually in one form or another, for 3 1/2 years since seizure onset, often at very high doses for a young child. Although this class of drug had never been one suited to him, for various reasons - mostly unfortunate twists of fate (as above!) we had never been able to quite complete the weaning process so by then he was very addicted to these meds.
We believe the prolonged midazolam infusion in March 2003 is the point at which the intolerance first started developing when we had seen his first tonic seizure emerge.
Those tonic seizures had persisted back then on the high 60 mg dose of weaning oral diazepam until we got it down to the 20 mgs, presumably the level he could cope with without invoking an adverse reaction.
Because of his catabolic state experiences, we had to concentrate on the diet aspects rather than medications from that point on, and we think that without continuing to chip away with decreasing the levels down, the intolerance continued to build during the latter half of 2003, in the same way that tolerance does in the opposite scenario where the level is not increased.
The ‘toxic’ episode that was resolved in October by removing his epilim we think was actually borne out of his growing benzodiazepine intolerance, but by removing the epilim (another CNS depressant) we may have applied a temporary ‘bandaid’ – removing the epilim may have in turn lowered his diaz levels to a point he could cope with, until the intolerance started ‘rising back’ again when no other reductions or adjustments were made.
We also think that adding the carnitine had an effect as well – whereby its introduction raised Daniel’s level of ketosis. We had already witnessed, especially at the beginning of the keto diet how being ketotic had altered the strength of Daniel’s AEDs, and the higher his ketones, the more the meds seemed to affect him. We had later found that a possible explanation for this was that as the state of ketosis places the body in a more acidic state, the protein binding mechanisms of many drugs can be altered – often resulting in higher medication levels. The increased acidity from the increased ketone level may have been the trigger that tipped his diaz over the intolerance level again, resulting in his altered state and subsequent onset of seizure activity.
I believe that when Daniel’s altered state started becoming obvious in early November, he was actually falling into a state of full blown CNS toxicity, hence his subsequent unresponsiveness and immobility, and EEG proven encephalopathy - the likes of which we had never seen in him before.
However the theories about ‘why’ this had all happened, culminating in this latest frightening admission were not given a lot of credibility. Understandably, the hospital’s main concern at that stage was to try and stabilise him through yet more medications, but because of what we believed about the cause of his condition, we were terrified that adding more drugs could worsen him even further, perhaps even kill him. At the stage of the midazolam infusion being planned, we sought help from the hospital patient advocacy staff to try and prevent it, requesting that Daniel be removed from our hospital and airlifted somewhere else. This request was declined on the basis that he was too medically fragile too move.
Faced with no other alternative, with Daniel’s heart rate increasing and his oxygen saturation level dropping markedly with each convulsive seizure, we had no choice but to watch the infusion begin. Our request to at least have the midaz administered under EEG guidance in case it exacerbated his seizures was declined – at this stage it was nearly 2.00 in the morning and there was apparently no one available to accommodate our request.
Back to the bullet points…..
- EEG finally ordered at 2.15 pm the next day, by which time Daniel was completely unconscious, with no signs of purposeful movement, the only activity we saw were the ever increasing convulsive seizures.
- Shortly afterwards we were taken aside and told that the EEG had confirmed that the midazolam infusion had pushed Daniel into tonic status and that not only were they stopping it, they were also planning to completely stop his oral diazepam from then on as well - that it did indeed appear Daniel was intolerant to the benzodiazepines and that his 3 ½ year addiction needed to be abruptly stopped.
- A thiepentone induced coma was required to try and ‘cover’ the abrupt withdrawal that ending such a long term addiction would cause, seizure wise and to his brain/body as a whole.
- Coma was induced that night, (18th Nov), very high levels of thiopentone needed to put our little ‘junkie’ lad into a comatose state, not achieved until the following day.
- On day 5 of the coma IV antibiotics were started, he had secretions on his lungs and developed a temperature.
- Still no improvement 2 days later so the antibiotic was changed to augmentin, an allergic reaction however developed it so was changed back to the original one. One of his lungs had meantime collapsed, a possible complication of prolonged ventilation.
- Thiopentone stopped on the 24th of Nov. Throughout the night before he had had many (almost continual) bowel movements. In hindsight I believe this was the beginning of Daniel’s ‘detox’ from the benzos, 6 days after his last dose had been given.
- An EEG on the 27th of Nov showed the return of sub clinical epileptic activity, but rather than being generalized MAE seizure activity, it was focal in nature. Daniel was therefore started on epilim, the reasoning being that the seizures may be benzo withdrawal related and if focal in nature, may respond to this med, even though his generalized MAE seizures never had done.
- He was still unconscious on the 28th of November, with blood tests showing this was probably because he still had fairly high levels thiopentone in his bloodstream – this was probably because his earlier catabolic periods that had resulted in abnormally high fat composition were ‘soaked’ with the high levels he had needed to induce the coma. Epilim was given in the morning and at night as regular AED doses, (400 mgs bd) and at about 1 am the next morning we saw his first convulsive (so probably generalized) seizure.
- The 29th of November saw Daniel still unconscious on his 7th birthday - his eyes were very slightly open but fixed straight ahead, with no response to any outside stimuli. Blood tests that day showed that he had shot back in ketosis (ketones had been lost over the previous week despite being given only ketogenic formula for nourishment and sugar free medications where required), with a high bhb reading of 6.0 mmol/L – he had lost a lot of weight whilst in intensive care and the fat burning process was contributing to the ketone level.
-This was reflected in his EEG that day, which saw the return of his 25-30 hz frequency ‘benzodiazepine’ spikes - it appeared that during the weight loss fat burning process stored medication was being leeched from his fatty tissues back into his bloodstream. That told us that the cold turkey withdrawal process was far from complete, and that he probably had a long way to go yet before he was free from the benzo class of drugs.
- The 30th of November saw his eyes open slightly more, but he was still unresponsive and during the day his mouth started twitching and his eyes started periodically rolling back in his head (we assume from seizure activity). That afternoon saw his first convulsive seizure since the coma had taken effect, followed by another one a couple of hours later. I believe they were induced from the combination of still some thiopentone in his bloodstream, along with the epilim, and the leeched benzodiazepine into his bloodstream – the feeling we had was that he was once again toxic, and still suffering from the abrupt initial withdrawal 2 weeks earlier.
- The following week was probably one of our worst – Daniel briefly spoke, his first words in 3 weeks were ‘help me Mum’ – if that wasn’t enough to drive us to absolute distraction, we realized he couldn’t see, his eyes were not following anyone, his head only turned towards the sound of voices. When asked if he could see anything he said ‘no, all dark, scared’.
- Seizures then got worse, he was basically back in status, and he didn’t really talk again during that period. The EEG showed that although his eyes were closed most of the time he was actually unable to sleep.
- Epilim was increased to a horrendous 2000 mgs a day – we were not really given much choice, we were told that it seemed the seizures were ‘attacking’ all parts of the brain one by one (the assumption was by then that a period of status stemming from the occipital lobe had blinded him) and that if they continued for many more days we should start preparing ourselves that we would probably shortly lose him.
- At that point, after knowing Daniel hadn’t slept for nearly 3 days, being told he would probably be blind and unable to ever have the life he had known before, possibly aware of what was happening but unable to communicate, I picked him up out of his hospital bed and rocked him for a very long time and then told him very quietly that if he was too tired he it was ok to stop fighting, that Mummy and Daddy would understand if he wanted to let go.
....and on that cliff-hanger we leave Daniel's story for now - come back in May to read the happy ending to this remarkable story. Just to give you a hint of what's coming, however, here's a more recent photo of Daniel!:
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