The ICU staff was now replaced on its annual rotation. Many of the replacement staff not familiar with the history, experience and elevation of Alina’s seizure intensity
01/02
Mum expressed that there was a conversation yesterday evening. Says that ICU fellow came into room and allegedly said that the anti-epileptic medications would be ceased and morphine commenced to make Ali comfortable and that it would take a few minutes for her to die. Mum expressed that she feels like this is “killing Ali” and that they would have to say goodbye to her within a few days. Parent very distressed about this conversation.
Has appeared to have been awake since I took over care, pupils equal and reactive, appears to be fixing on peoples faces however not following. Continues to have seizure activity, which at times involves all four limbs and mouth twitching. Remains on a midazolam infusion at 8micrograms/kg/minute and a ketamine infusion at 6micrograms/kg/minute via blue lumen of central line
Discussion of regarding second opinions. We have had a second opinion from Prof Ingrid Scheffer as well as Dr Deepak Gill, Prof Russell Dale, all the SCH neurologists: Hugo Sampaio, Annie Bye, John Lawson, Sekhar Pillai, Michelle Farrar, & Michael Cardamone. Reiterated that we are continuing to seek advice and opinions
Discussion that Alina has had opinions from many doctors. Many concerned that this process may be mitochondrial disorder.
02/02
Today Alina has bilateral jerking of hands, there is jerking of bilateral faces as well
—
A very abnormal EEG, with generalised slowing of the record and a focus of epileptiform activity at
least in the left occipital region. Muscle (EMG) activity corresponding to continuous jerking makes
further interpretation of the record difficult.
Reported by: PROF JAMES COLEBATCH/DR SUSAN WALKER
—
Today Alina has bilateral jerking of hands, there is jerking of bilateral faces as well
- Physiological artifacts may include cardiac, pulse, respiratory, sweat, glossokinetic, eye movement (blink, lateral rectus spikes from lateral eye movement), and muscle and movement artifacts
- Epileptiform: resembling that of epilepsy
Source: Merriam-Webster dictionary
In other words, artefacts are generally considered background interference, and epileptiform activity is the concerning evidence of epilepsy
03/02 more intense seizure activity
Alina has had increasing seizure activity overnight. Bilateral activity.
Phenobarb 5mg/kg given.
Discussion with family
Family are concerned about Alina’s suffering.
THey would like to give her an opportunity to breathe on her own.
Discussed the fulminating disease and her current clinical state. Discussed atrophy on the scan.
Discussed the extrapolated natural history of further seizures.
Discussed the possibility of any further clinical trials for example stem cells and neurology acknowledged that there is nothing currently available.
Emphasised the wide spread consultation within SCH, CHW, and a expert Melbourne opinion.
Further family members are coming on Monday and Tuesday. Dr Numa and ICU will document but talked about potential plan.
Currently over the weekend we will use midazolam to try to achieve better control of seizures.
Plan is to work towards an extubation in the earlier part of next week.
Skin biopsy discussed and will go ahead on Monday
Handed over by ICU team that family discussing withdrawal of care
– aware that family have fluctuated with their opinion and management requests over past 3 months
– aim to review at the same time for discussion with family regarding end of life measures
04/02
Discussion that Patrick was wondering about giving Alina rituximab.
Reading about FIRES.
Discussion that the process wasn’t behaving like FIRES in the progress of the disease.
Patrick discussed that she had ongoing cough during the time of seizures, wonders if this contributed to etiology of seizures
Continuing status no real improvement from yest
05/02
Parents did crowd enquiry
5 neurologists came back with a result of FIRES which has precondition and predisposition to it
high GAD is one of the features there is one drug which can be used to stop this inflammation which is Anakinra- Parents insisting to ave a trial for this medicine
Plasmapharesis was suggested also
Parents beleive that the history of cough over the last year is highly related to her current neurological status
06/02
Alina has super-refractory status. Would an immune modulating therapy be beneficial for her
Parents would like consult regarding the benefit of Anakinra
Dr Cardamone advised that Rituximab/Anakira is used but on the assumption that this is immune mediated. However, children using this medication would have a response to IVIG and steroids and would be used as a steroid sparer.
There is no indication that Alina responded to steroid or IVIG. Immune therapies have significant risks including risks of overwhleming immunosuppression and risk of sepsis. Risks of pursuing this medication outweigh benefits, and can lead to sepsis and death. We don’t want to harm her, by exposing her to medications that will possibly not benefit her.
Parents are prepared to take a chance that she may die as a result of this immunomodulatory treatment
Russell Dale, Neuroimmunologist has advised that this is not immune mediated. We have consulted widely on this subject, with several senior clinicans and neuroimmunologists and experience alongside the evidence base, that this is not immune mediated. We may not come to a diagnosis however
Dr Cardomone had the belief this disease more fitting to Pyruvate Dehydrogenase deficiency or Ring 20, “…because she has been so responsive to the ketogenic diet” [i.e. lack of sugar].
The mum expresses a lot of concern that “the communication [with external Immunological Doctors] did not mention to these people the fevers, the upper respiratory tract infections, or prone to croup… if that information is not there, then its mitochondrial, if you add this information, then you have some other diagnosis…. There could be a lot of missing information about her croup, and cough, and fevers!”
The Respiratory Specialist attending the meeting remarks “A Neurologist who doesn’t know much about respiratory disease, they might not have picked up on things I would consider important”
And they were all correct. Dr Sampaio had not picked up on the significance of Alinas history of chronic respiratory tract infections, croup and fevers, and he had not communicated these with external or internal Doctors. He had not even included the email contacts and pictures sent to him directly from the parents, or Alina’s medical history. He had weighted his assessment with quantitative data. Dr Sampaio had ignored qualitative data, such as the significance of excessive drooling, croup & stridor, rashes around the mouth and body, the low grade fevers, vomiting, and jerks on hearing loud noises. The indicators were all ignored, and there were a large number of them to ignore, and from parents who kept repeating them.
The parents had to summarise the history of symptoms (Parents statement, below), this time they were written and transcribed to the hospital notes. The parents were concerned as to why these notes weren’t on the hospital records already, they repeated these a number of times from December to multiple medical staff, believing they were in support of an even more detailed summary when the parents first met Dr Sampaio and Dr Sandi in November. The parents wanted a trial of Anakinra, as the symptoms were more closely related to an illness called FIRES than any other diagnosis presented. The Neurology department was trying to prove unknowns.
In fact mums suspicions were correct, in the entire Hospital notes any observations made by the parents and given to the Neurology department (the persons of contact), to include Alina’s medical history, were completely absent. Any observations mentioned to the nursing staff or ICU Doctors are often written “Parents feel that… “
A simplified proposal of why Alina was “so responsive to the ketogenic diet”:
- EV71-Viral infection hijacks UGGT (Glucose Transfer Protein) for replication. UGGT expression levels increase. Augmented AMP:ATP ratio activates AMPK, which enhances excessive glucose uptake into the cell. mTOR is deactivated. (*Insulin inhibits AMPK)
- UPR levels increase. Buildup of Interleukin -1B, (or Il-1) possibly as aggregates and unable to trigger an inflammation response*
- Tipping point of glucose saturation in cell
- mTOR is activated, AMPK is deactivated (Epilepsy)
* experimental design does not specify if this was a result of gene KO, or tissue sample location (Innate/Adaptive immunity)
In other words, the ketogenic diet, which was so effective; EV71 requires glucose to proliferate and so explaining why Alina was so reactive to glucose spikes, and responsive to the Ketogenic diet. Cortisol (or chronic stress) also increases circulatory glucose. EV71 encourages unwarranted uptake of glucose into the cell, (likely cyclic) once a threshold of Glucose/UPR is breached, the cells apoptosis quickly. This is presented as epilepsy.
Sources:
Substrate utilisation of cultured skeletal muscle cells in patients with CFS – Cara Tomas et al
The Intertwined Life Cycles of Enterovirus and Autophagy – Yasir Mohamud and Honglin Luo
UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication
- mTOR signaling was significantly increased in Knock Out mice accompanied with spontaneous epileptic discharge, and levels of upstream pMPK were decreased in these animals compared to control and KD-fed KO mice
- Collectively, either the KD or ketone not only reduces the severity of seizures in two different mouse models, but also attenuates mTOR signaling pathways
- Blocking EVA71-induced autophagy using 3-MA attenuates the disease symptoms and decreases the viral load in the brain tissues of the infected mice
- These results suggest that autophagy indirectly mediates neuronophagia Further study has shown that LY-55 and 3-MA synergistically inhibit EVA71 replication, suggesting that autophagy is a potential therapeutic target for the treatment of EVA71 infection
This model is an approximate guide. It is worth noting, this is not exclusive to EV71
- These results confirm that UGGT1 is a positive regulator of EVA71 and EVD68 replication, and suggest that it may be a commonly utilized host factor for viral replication in enteroviruses.
Source: UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication
Download Parents’ statement (PDF, 282kb)
A trial of Anakinra was approved after a week’s painful deliberation; On the 9th February. It was agreed to use a known protocol of trial dose (although a full trial is 24-48 weeks, this was 3 doses over 9 days). An EEG was used as the baseline marker of improvement.
07/02
I had the opportunity to revisit Alina's history with the family
Alina's parents feel that she was previously a completely well child with no developmental concerns.
She develoepd a cough in later 2016 (?Oct/Nov) mostly nocturnal but raely during the day.
The family had visited many doctors/GPS who reassured she was havign back to back viral infections realted to being in Day care.
Alina then developed croup and she had one admission requring adreanline nebs.
Her croup then became quite frequent and she would have a croup like cough at night.
Alina developed her first seizure 6 days after her 18 month MMR vaccination.
That week she was not eatign and not active, she was sleeping more and not herself.
Teh day of the first seizure – Mum and Alina had been at a party and she was unwell, not interested in eating.
She got home and Alina was drowsy, she started dribblign and her breath was abnormal and had been so for the week prior.
First seizure occured at home, it was a Sunday evening, Mum noted her teetch clenched and she was making clicking noises and her left side of the face was pulled and jerking.
The jerkign progressing down th eleft side of th ebody and she appeared ot be distressed byt he seizure
There was head and eye deviation to the left.
The focal motor seizure continued until she was given midzolam at Canterbury hospital ED about 55 minutes after its onset. She felt warm during this seizure. The parents recalled she had developed stridor and croup and she was also administered adrenaline.
Alina had post ictal drowsiness for about 2 hours and then within hours she had recovered and about 1/2 day later she was back to her playful self.
She was observed overnight and the family was discharged home.
The following day (Monday) she was well and she played
She was taken back to the day care.
The mondya night she had aother focal motor seizure- this time it was 1:30am in the morning and mum had woken to her making sighing respirations and then proceeded to have focal clonic hand jerking . This time they put he rint he car and drove to Canturbury hisptial. She was adminsitered midazolam IV which stopped the seizure – duration of seizure roughly 45 minutes. This time she was seen by the paedaitrician and transferred to SCh for further investigation. She met withthe Neurology team who organised a numbe rof tests including EEG and commenced her on Keppra. Then discharged home
About 1 week later Aina had a further seizure at home, this time her left foot was pulsating and she was taken back to Canturbury hospital, who transferred her to RPAH as they could not control the seizure with buccla and intranasal midazolam> RPAH then transferred Alina to SCH on the 25th November for management of status epilelpticus. Mum remmebers tha tshe has developed a fever on route to SCH.
She was taken to CICU an dthen placed on a midazolam infusion to try to control the prolonged seizure. With the seiuzre she continued ot have a croup like cough and stridorous breathing.
Mum also informed that the jerkign became intermiitent and at one stage she wasinformed that perhaps ALina had developed a movement disorder but the EEGs have always shown epielptic activity.
Alina was weaned off midazolam infusion and she was discharged to the Neurology ward after 6-7 days in the CICU.
On the ward it was clear that she was frightened and agitated after beign in CICU and unsettled.
Alina had a number of reviews by the Sleep and ENT teams, She was noted ot have desaturations on a overnght sats monitoring and she was thought to have an obstructive picture in keeping with her large tonsils. She was recommended for CPAP which ALina did not tolerate
09/02
EEG (Verified)
Clinical Neurophysiology Unit POWH/SCH
(MURTAGH, Alina MRN 10450683; EEG; Recorded: 09-Feb-2018)
Detail:
A ward portable EEG was performed.The patient was intubated.
The background activity consisted of delta (1-4Hz) rhythms, which
were symmetrical and continuous with some beta. Superimposed upon
this are focal epileptiform discharges arising from F4 and F3.
Hyperventilation not done.
Photic stimulation not done.
Conclusion:
A slow background (plus beta), likely to be medication-related. Epileptiform activity arises from two
independent frontal foci.
It is established that Alina has EPC epilepsy.
Trial of Anakinra is started.
- Anakinra (Kineret) is an IL-1 receptor antagonist that blocks the biologic activity of IL-1
- The finding that IL-1 induced IL-6 in monocytes may help in defining the spectrum of biologic activities of each of these interactive cytokines
Interleukin-6 (IL-6), a multifunctional cytokine produced in monocytes, fibroblasts, endothelial cells, and keratinocytes, is induced by a variety of stimulating signals, including lipopolysaccharide (LPS), poly (I), poly (C), IL-1, tumor necrosis factor (TNF)
- By specifically blocking IL-1, we have learned a great deal about the role of this cytokine in inflammation and, equally importantly, reducing IL-1 activity has lifted the burden of a broad spectrum of inflammatory diseases for many patients. Furthermore, blocking IL-1 activity has provided proof of concept for diseases that were not considered to be inflammatory, such as type 2 diabetes, heart failure and loss of hearing
- This propensity to produce higher IL-6 and IL-1β early in life is of particular interest given that these cytokines are associated with increased severity of EV71 infection
- Furthermore, this association with IL-1β suggests the possible benefit of anakinra, a synthetic IL-1Ra with cardioprotective effects, for the treatment of EV71-associated cardiopulmonary failure
- The Preferential Infection of Astrocytes by Enterovirus 71 Plays a Key Role in the Viral Neurogenic Pathogenesis
- After entry into the CNS, glial cells which constitute part of the CNS innate immune system, detect the intracellular viral nucleic acid, and stimulate the release of IFN-1, causing apoptosis and inhibit viral replication. It is, however, important to note that collateral damage incurred upon activation of cytolytic T cells during an adaptive immune response within the CNS may be more damaging to neurons than the infection. Furthermore, both greater cytokine induced tissue destruction due to higher systemic levels of proinflammatory cytokines like IL-6, IL-1β, and TNF
In other words, this was a chronic infection of Enterovirus, with multiple repeated assaults. The adaptive immune system had likely established a high level of Il-1 & Il-6 and TNF and antibodies in response, already in circulation. The adaptive immune system had likely resolved very effectively the EV71 infections. But not the Innate immunity (or sites of immune privilege) the Central Nervous System (Glial cells)
However, the sites infected, where the negative strand RNA was “seeding” repeated EV infections were propagating from sites of immune privilege; The central nervous system, the thyroid, the eye, the pancreas, the testicles, fetus; and to some extent the brain, cartilage (from low blood flow), and liver
- cytokine release syndrome is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ, and uncontrolled studies demonstrate that immunosuppression using tocilizumab, an anti-IL-6 receptor antibody, with or without corticosteroids, can reverse the syndrome
Source: Current concepts in the diagnosis and management of cytokine release syndrome – Daniel W. Lee et al
The EV infection had suppressed the immune response in particular areas of the body. Triggers that caused amplification of the -ve EV-RNA to +ve EV-RNA included elevated glucose, stress (elevated cortisol) and additional viral responses such as vaccines, or another viral infections. The virus used to propagate and spread amongst these organs, via the Central Nervous System and what seemed to be the primary source for Alina, the throat (the thyroid).
But the most likely trigger had occurred on the 12th January, an Adenovirus, that caused a cascade or cytokine release syndrome (sometimes known as the Cytokine storm), and the adaptive immune response caused a mass apoptosis of infected neurons, which had now spread to the brain in advance of glial clearance. The most likely explanation is the response to the Adenovirus is increased IFNy, which upregulates STAT1 protein, present in both the brain and lungs
- On the one hand, the activation of immune response, both in the brain and lung, could provide the mice with effective immune protection against EV71 infection; on the other hand, it might induce excessive cytokine production, which is consistent with “cytokine storm” in patients at severe and critical stages of HFMD
EEG (Verified)
Clinical Neurophysiology Unit POWH/SCH
(MURTAGH, Alina MRN 10450683; EEG; Recorded: 10-Feb-2018)
Detail:
The patients was intubated ans awake with bilateral limb and eye
twitching during the EEG.
Background is symetric and continuous with diffuse delata activity
and sustained superimposed beta activity.
Recurrent, predominantly unilateral frontal or bifrontal spike and
wave dischrges are noted.
No electrographic seizures were captured.
Conclusion:
Diffusely slow background with recurrent multifocal (predominantly frontal) epileptiform discharges.
Very similar to yesterday's EEG.
Reported by: DR. IAN ANDREWS
—
PArent feels she is fixing and perhaps tracking
Parent feel she is more more settled and not agitated
EEG unchanged from yesterday
No electrogrpahic seizures
Within a day, the parents could see the positive effect. Subtle, and something maybe only a parent would notice, especially ones who were very familiar with the seizure patterns, triggers and previous presentations
11/02
intractable seizures on multiple antiepileptics,ketogenic diet ,cannabinoids
day 2 Anakinra interleukin 1 (IL1) receptor antagonist
today ? not continious seizures on examination – ongoinf facial twich
12/02 Dr Cardamone advised Alina is currently half way through Anakinra treatment and we should see a response with 5mg/kg dose and if no response we then give 10mg/kg but should see improvement by 1 week
Discussed results of recent EEGs. Friday showed some reduced spike amplitude however today EEG was much worse with increased spike amplitude. Patrick feels the EEG was taken at the worst time, she had just woken up, was coughing and had lots of secretions at the time.
More settled overnight according to nursing staff
PArent feels she is more alert, able to fix and follow
Patrick expressed he wishes to continue Anakinra beyond the current treatment plan. Dr Cardamone explained we will finish the current treatment and go from there. Advised he will keep her other AEM stable whilst on Anakinra but will look to change vigabatrin once finished
13/02
Result type: EEG
Result date: 13 February 2018 08:50 AEDT
Result status: Auth (Verified)
Result title: EEG
Visit Info: Sydney Children's, Result/Historical Record, 01/01/2000 – 27/03/2018
Contributor system: Diagnostics
EEG (Verified)
Clinical Neurophysiology Unit POWH/SCH
(MURTAGH, Alina MRN 10450683; EEG; Recorded: 13-Feb-2018)
Detail:
Portable EEG performed in PICU. Patient intubated with ongoing
seizure activity throughout recording.
The background is continuous with predominantly diffuse delta
activity. Continous epileptic activity is seen in the left frontal
region. There is associated muscle artefact.
Conclusion:
Abnormal EEG consistent with status.
Reported by: OR HUGO SAMPAIO / DENISE CHAN
14/02/2018
Patrick would like to start a probiotic
EEG today: Looks much worse. Increase in number of epileptiform discharges. Anakinra appears not to have worked
The parents noticed and reported back that the seizures seemed to reduce further once she passed a stool and requested probiotics (as they believed there was some involvement with the gut). Alina was showing a significant lack of seizure activity, even when awake. But after a prolonged stay in hospital, pneumonia was causing significant breathing issues
Successfully extubated and PICC line in situ. Is now on high flow to support breathing 2l/kg but we will assess need for this over last 24 hours-may be able to get to low flow. PICU will review respiratory evolution over next few days.
Advised EEG has deterioated further. Many spikes in one second, and we feel that Anakinra has not worked. Almost a six fold increase in epileptiform activity. We will repeat EEG next monday. We feel that further Anakinra will not help.
Patrick feels Alina is more responsive over weekend – we feel this may be secondary to weaning off miadzolam and ketamine
15/02
Extubated yesterday
Increased secretions and desaturations
Required re-intubation overnight
mum visiablly upset when told new and need for reintubation – encouraged her to call Patrick or [Auntie] Faeza for support. Reassurance provided ++. She expressed how hard she found it to watch Alina go through this again and how she (Alina) can just not seem to catch a break. She also said it was hard to see her looking so well after extubation and then seeing her “back at the beginning” again.
Patrick also very upset – not saying much – after seeing Alina intubated mum encouraged Patrick to go back to bed.
Faeza coming to be with Alina at 0100hrs so that mum could go and get some sleep.
All very appreciative of care.
A meeting was held with the parents, Alina had to be intubated again and the parents felt defeated after a promising initial response to Anakinra
The parents made the choice that Alina had suffered enough and should be allowed to die peacefully
Parents wondering if this is going to be an ongoing cycle for Alina, and what is the best possible future for Alina.
Medical team want to do whats in Alina best interests for Alina. But we feel we have done the maximum for Alina. Alina is showing us that she is not able to function without alot of support and intervention.
mum asked about a further MRI. We have advised that this will not change management but this can be done
mum expressed that Alina is suffering and that she feels like she is suffering all the time, unless she is asleep
mum feels that Alina is no longer interactive and not the girl she knew; she cannot play/interact.
Medical team are feeling that there are few further approaches that would improve quality of life.
Palliative care will be involved and we will aim to take the breathing tube out and not reintubate. This is after some time after parents have thought about religious ceremonies/activities that they would like to complete with Alina. Parents happy for Palliative care to see them tomorrow
Patrick upset about Alina suffocating. We will talk with Palliative care about how to make Alina’s passing comfortable
17/02 Movements have generally settled over last 24-48hours Less prounounced in sleep
18/02 Appearing to respond to examination – attempting to push away stethoscope
—
Seizure activity is almost gone when asleep
—
19/02 Ongoing right eye deviation, and flickering movements of head, eyes and upper limbs which are partly suppressable by tactile stimulation which disappears when sleeping
21mths old girl, Intractable seizures since first sz onset in November 2017. Prior to this Alina was developing normally apart from a mild delay in gross motor skills
20/02 Patient appeared to be purposfully trying to hold onto toys with right hand
—
This EEG is abnormal. There is moderate generalised slowing, excessive fast activity and frequent
generalised epileptiform activity. Towards the end of the recording, the epileptiform activity stopped
and this coincided with the patient waking (cause or effect?). Some mouth twitching and right arm
movements at the end of the recording were not associated with any change in the EEG.
Reported by: PROF E SOMERVILLE
—
Following the EEG report, Dr Cardamone and Dr Eiyat held an unexpected meeting with the Father in the afternoon following the EEG. Dr Cardamone had seen the EEG reports and the clear improvements made by Alina, and was now saying “I think you’ve discovered a new disease!”, “they’ll make you a Doctor!”, “you’ll get a Nobel prize!” The visual aspect of Alinas improvement was undeniable, the heavy continuous seizures had, were now abated
Dr Cardamone explained EEG results from yesterday as below. Advised the EEG is worse than previous.
EEG results: moderate generalised slowing, excessive fast activity and frequent generalised epileptiform activity with temporalis twitching continuously 5 times every 1 second when awake, which lessens when asleep to one times every 5 seconds.
mum shocked she states she feels she is actually better since Anakinra, reaching out to relatives this morning, reacting to stimuli, and responding to her.
Dr Swil empathises that this isnt the result they were hoping for but asked Patrick & mum for their thoughts.
Patrick feels the intensity of the seizures has reduced from previous and despite EEG result he feels she is improving.
He is adamant they are not giving up on her and wishes to continue on the current path.
mum agrees she is improving and would like to see ongoing improvement in the next couple of weeks. She appreciates the results of the EEG but feels looking at her she is better.
Dr Cardamone explained the epileptic activity on the EEG will not always correlate clinically with clinical picture they are seeing.
The following day, Dr Cardomone dramatically changed his mind from his excitement the day before, and was now reporting to the parents that Alina had actually deteriorated. Immediately after the meeting (audio), a video of the “continuous seizure, every 5 seconds in Alina’s temple”. Dr Cardamone must now be able to see something very different to the clinical and parental observations who were with Alina around the clock.
Alina had very clearly improved as a result of Anakinra, the seizure activity had vastly reduced after just 10 days, and this clearly proved the Neurology team had made significant errors in diagnosis. You can only imagine that it may have come to his attention the liability and lifetime care the Doctors now faced for overlooking a very obvious illness and remedy. Alina was very sadly & clearly brain damaged as result from repeated viral assaults & overuse of medications, and this was likely irreversible.
From what Dr Cardomone was now reporting was in polar contrast to all videos, taken 2018.02.11, 2018.02.14 and 2018.02.18
Patrick discussed need to exclude autoimmune process for sytptoms, we discussed that LP is an invasive prcedure and ALina is not stable enough at this stage to perform procedure. Patrick enquiring about manangement of autoimmune cause of seizures, namely use of prednisolone, rituximab and plasmaphoresis, mechanism of action of these treatments were discussed.
It was elevated
The replacement (rotational) ICU team had no reference to the condition and improvement that Alina had made, their notes were generally copy/paste of the previous day.
The Neurology team were reluctant to discuss the ongoing treatment clearly observed by the parents from Anakinra, adamant there were no improvements.
Do compare the continuous seizure activity from mid-January to the trial and video taken on the 24th February
- A 9-month-old infant presented with lethargy and respiratory failure. He had been diagnosed of herpangina 4 days before admission. Initial examination revealed bulbar palsy and flaccid tetraparesis. Brain and spinal cord MRI showed dorsal brainstem and cervical T2-hyperintensities. CSF revealed pleocytosis, and enterovirus PCR was negative. EV-71 was isolated in throat and rectal specimens. Although methylprednisolone (30 mg/Kg/day, for 3 days) and IVIg (1 g/Kg/day for 2 days) were started, a few hours later he developed high fever, hemodynamic instability, and respiratory failure requiring mechanical ventilation. Due to the dramatic evolution, PEX was started 48 h after onset. Twelve hours later, a marked clinical response was observed and he was extubated after a second PEX session. Six PEX sessions were performed every other day. He continued to improve and no significant complications were observed. Two weeks later, he presented intention tremor that had disappeared at 3- and 12-month follow-up
- An 8-month-old infant with a viral exanthema presented with lethargy and hemodynamic instability requiring mechanical ventilation. An echocardiography showed reduced ejection fraction (40%). Brain and a spinal cord MRI demonstrated dorsal brainstem and cervical diffuse and poorly defined T2-hyperintensities, compatible with encephalomyelitis. CSF showed pleocytosis and enterovirus PCR was negative. EV-71 was isolated in throat and rectal specimen. Given the worsening of symptoms, PEX therapy was started, and four sessions were performed every other day. The consciousness status, muscular tone and motor function improved notably from the second day. At 12 months, cognitive and motor functions were normal except for mild axial hypotoni
- In the management of patients with enterovirus 71-related fulminant cardiopulmonary failure, early continuous veno-venous hemofiltration may be considered as an alternative treatment to improve patient survival and to prevent severe neurological disabilities
Seizures continuously despite maximal therapy – confirmed on recent awake and asleep EEG
– Ketogenic diet
– High respiratory secretion load – commenced on glycopyrrolate under guidance of palliative care team
– Extubated on to HFNP O2 (22/02/18) – ongoing at 2L/kg/min
Progress Has been relatively stable today with improving secretions
One documented febrile episode, cultures sent
Ongoing respiratory physio
Patrick also keen for further immune treatment/investigation re: immune route. Advised that hopefully formal genetic testing will be back soon