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The |
Early days |
March to November 1996. Pregnancy, birth trauma, early symptoms, development of infantile spasms, drug treatment with vigabatrin and ACTH.
Pregnancy
At three months, a high AFP level was recorded. A subsequent scan showed no abnormality.
At 8½ months Sue had a watery discharge from her vagina. This was reported to her doctor. Subsequent examination showed a lack of amniotic fluid. During the birth process, the waters were broken and the midwife expressed surprise at the small quantity of amniotic fluid.
Birth, 27 March 1996
The birth was at full term, to the day. First contractions were about 8am, they were regular at three minutes. the hospital was called, and Sue driven to hospital, arriving around 10:00. Sue had severe contractions on the way to hospital (car delayed by launch of the Matthew), and on arrival, before admission.
Gas and air used for pain relief. The midwife noticed a reduction in heart rate to 44 at 12:30 and the labour was slowed down. Subsequently a fentanil epidural was administered; a second dose was given later in the labour.
Stage 2 labour commenced at 16:00. The waters were broken (see above) and a monitor attached to Marchant’s scalp. During the final stages of labour the midwife appeared agitated, but perhaps that was normal. Marchant was born at 16:27 (nurse recorded as 16:32) . He did not cry at birth.
This birth was part of a study (HOOPS - hands off or poised) to evaluate the effect of interference in the birth process on tearing of the perineum. Sue signed a disclaimer on consequences before the birth; the birth was hands off, so the midwife did not assist in the final stages of birth.
At birth the baby appeared a reasonable colour (greyish). The midwife was clearly concerned, she administered two doses of naloxone, and called the paediatrician, who was subsequently joined by other doctors. We were not told what was happening, and in response to questions, the only answer was that the baby was "floppy". After about 30 mins, the baby was taken to SCBU (Special Care Baby Unit, subsequently renamed NICU - Neonatal Infant Care Unit). No information was given to us.
Because the birth process had been going so well, it had been the intention to film Sue breast feeding the baby after the birth for a Royal College of Nursing training programme, but this was cancelled after the birth.
The medical records reported:
1min 5 min 10 min 15 min Heart rate 1 2 2 2 Respiration 1 0 0 1 Muscle tone 1 0 0 1 Colour 1 2 2 2 Total 5 4 4 7
Problems
The baby was put into an incubator. The medical record states that at that time the posture was abnormal, but that there was no overt evidence of fits. Marchant had at least two significant fits in the evening and one further during the night. He was put on phenobarbitone, with a saline drip and was fed through a stomach tube. He had further fits over the next 3 days. After 36 hours on phenobarbitone, Marchant was put onto paraldehyde for four days.
According to the medical record, the parents were talked to by Mr J Dudley on 30 March, who said:
We have no recollection that the birth situation was reported.
The medical record states that Marchant had some renal impairment (this is a frequent consequence of hypoxia, the kidneys are even more sensitive to a lack of oxygen than the brain). As parents, we were never made aware of this.
After 4 days in an instrumented incubator, Marchant was transferred to a simpler incubator. He started to feed from the breast, and also took some milk from a bottle. Sue stayed with him in the hospital, although in a separate room. During this time, Marchant had a CT and an EEG.
The CT was reported as normal. The medical record of the EEG states:
This is a grossly abnormal EEG, with bursts of moderately high amplitude, mixed slow and faster frequencies separated by periods of relative suppression. Both the bursts and the periods of suppression last from approximately one to five seconds. The discharges appear synchronous as well as independently over both hemispheres. Changes in the constituent frequencies of the bursts at one stage during recording probably represent an alteration from the waking to the sleeping state. The appearance of the trace indicates severe cerebral dysfunction, presumably of a hypoxic origin, and recent medication as well as metabolic disturbance will have a contributory effect. There is no evidence of seizure during the recording.
After 2 weeks, Marchant was discharged. At discharge, we were talked to by Dr Speidal. The medical record states:
I have discussed the CT and EEG with both parents.
I have talked about the risk of neurological handicap, but emphasised that we cannot predict outcome accurately, and that the best option is careful follow up and a wait and see attitude.
It is our recollection that Dr Speidal said that the EEG was abnormal, but that this might be due to the drugs, and that while no conclusions could be drawn, it was possible that Marchant might be damaged and have some degree of cerebral palsy.
The discharge summary, written by Dr Hartnoll, and dated 21 June 1996 (sic), states
Apparently normal labour and delivery, but baby was born in poor condition with low heart rate and no respiratory effort and poor tone. Prior to the arrival of the paediatrician, baby had been given 2 doses of naloxone by midwife as mother had had fentanil epidural. On arrival of the paediatrician, the baby had a good heart rate but was still floppy and not making any respiratory effort. He was given bag and mask ventilation by the midwife which was continued by the paediatrician and by the age of 25 minutes, Marchant was making good respiratory effort. Because of this amount of resuscitation and his condition at birth, Marchant was transferred to Special Care for further observation.
When on NICU, Marchant was very irritable with abnormal posture suspicious of fits early on. However, there was no overt seizure activity. He was given a full septic screen which proved negative. Over the next 24 hours, Marchant developed overt fitting for which he was treated with anticonvulsants, initially given phenobarbitone, but then started on a paraldehyde infusion.
Over the first few days, Marchant also had renal impairment, which was consistent with a diagnosis of hypoxic ischaemic encephalopathy. Thereafter, Marchant made general improvement and we were able to wean him off his anticonvulsant and stop his antibiotics when his septic screen was negative.
Marchant was a little slow to establish full feeding which was not surprising given his history, but by discharge was fully brestfed. Whist on the unit, Marchant also had an EEG, which was grossly abnormal, the appearance of the trace indicating severe cerebral dysfunction, presumably of hypoxic origin and recent medication. There was no evidence of seizure activity during the recording. CT scan on 02 04 96 was essentially normal. There are no contraindications to immunisation and we will review Marchant in 6 weeks time.
At no time were we told what had happened at the birth, nor how serious the situation had been. We were not told about the renal impairment. We were not told how bad the EEG was.
More seriously, we were not warned about the possibility of further fits, and were given no guidance about what signs to look for. Clearly, a further EEG should have been scheduled as soon as the possible perturbing effect of the drugs was eliminated.
Early development to three months
Marchant was very alert and active throughout the day, and slept well at nights, waking for one feed.
Almost from his return from hospital, Marchant was difficult to breast feed. When presented with the breast, he would arch his back and neck away from the breast and scream. It was necessary to forcibly hold his mouth to the breast and then, after several attempts, he would start to feed. If he came off the breast, it was usually necessary to repeat the sequence.
Initially, Marchant was breast fed in the day, and fed by bottle at night, because Sue had insufficient milk. With increased milk, the bottle feeding was discontinued. Later Sue had problems with milk again, but Marchant then refused to accept bottle feeding. He would accept the teat being put into his mouth, but he would not suck.
At about ten weeks feeding became very difficult, and Marchant was started on solid foods. He accepted these immediately, seemingly determined to eat in a chair, from a spoon, like big people. He had strong likes and dislikes in terms of food, the favourites being banana and fromage frais.
Marchant experienced pain after feeding - initially, we thought that was the reason why he reacted to the breast as he did. It became clear that the pain was associated with an umbilical lesion. When he feed, his gut popped through the lesion and became obstructed (hard). He would scream, but would stop if the gut was pushed back through the lesion and massaged to remove the obstruction. Because of the level of discomfort, Marchant was taken to see the doctor (Dr Elphick). She did not accept that there was any problem with the lesion, and said that Marchant was just a bit colicky. The discomfort continued, and Marchant was again taken to see the doctor (Dr Cox) Eventually, Marchant saw Dr Speidal on a hospital visit; he thought the problem was reflux and he suggested the use of gavascon. The problem eventually (5 to 6 months) went away as the lesion healed.
Marchant did not cry at birth, and did not cry at all until he was 4 weeks. He was a good natured and happy baby, but occasionally his behaviour would change, and he would scream and would not stop. This seemed to more than a temper tantrum, as though he was in pain. We said we had two babies - baby one and baby two.
His physical development was slow, with his weight and head size below the 95th percentile. At birth, it was noted that his right ankle was twisted (talipes). This was rectified by wearing a constraining boot for the first 6 weeks or thereabouts.
His mental development seemed satisfactory. He was fascinated by music from an early age, 3 or 4 weeks, particularly liking clear tones like the french horn. He was very alert and attentive, fixing on objects and following. He could recognise people and objects. However, there appeared to be something wrong with his vision - he did not look in the right direction. Normally, rather than looking at a person, he would turn his head upwards, or away, although his head control was good and he was clearly interested in the person. He started to smile at 6 weeks and was a charming baby and generally very happy. By three months he appeared able to understand words like ba-na-na and hello, and would respond by trying to say hello and wave. The intent was clearly there, although he could not enunciate "hello", and could not move his arm properly. He was also fascinated by books, liking to be "read to" attending closely to the page, and attempting to turn the pages. This was surprising, since he did not normally see either of us reading, so it was not just imitation.
His posture was still abnormal, often arching his back and putting his head right back, so that he was looking at the ceiling. He also wanted to stand; his body would go rigid and he would insist on being held upright. Marchant usually screamed when he was put into a restraint, eg a car seat, arching his back. It is possible that he was frightened of the restriction this imposed. He was able to roll onto his side, by had no useful movement in his arms.
He also had spasms, single twitches of the upper body. These probably occurred with increasing frequency to several a day, although we did not attach any significance to them.
All the abnormal aspects of his development were seen by the health visitor Sylvia Guest, who did not make any significant comments or recommendations. Marchant had a routine checks at six weeks (7 May, Dr Hartnoll) and three months (9 July, Dr Speidal) at Southmead Hospital. We had been told that he would have a further EEG at six weeks, but Dr Hartnoll said it was unnecessary.
Early development, 3 to 6 months
In retrospect, Marchant regressed over the next three months, although we did not appreciate this at the time.
Feeding continued to be very difficult. To provide more liquid intake, the solids were mixed with formula milk. The problem with the umbilical lesion reduced. He continued to wake once each night, and did not sleep much during the day.
His physical development continued to be slow.
| Weight | Height | Head | |
| 21 May | 9.5 | 35.9 | |
| 18 June | 10.13 | 56.5 | |
| 3 July | 11.6 | ||
| 9 July | 11.13 | 60.4 | |
| 6 August | 12.4 | 60.5 | |
| 20 August | 12.11 | ||
| 3 September | 13.0 | ||
| 8 October | 13.11 | ||
| 15 October | 13.12 | 65.0 | 39.7 |
Marchant visited a cranial osteopath, Kate Burns. She noticed a problem with his vision and "twitches" and suggested we saw an eye specialist. She phoned the health visitor, who agreed something was wrong with his sight, and referred him to Bristol Eye Hospital.
Marchant was given his DTP inoculation in September. Dr Watkins had clearly been concerned about this, and had queried its advisability several times with Southmead Hospital. When the inoculation was given he disclaimed all responsibility, saying to Sue that Marchant was possibly brain damaged, and that there was a risk that the pertussis vaccine could cause brain damage.
We were given no advice about the risks, or the appropriateness of the vaccination, and only became aware of the reservations about it use on babies with fits afterwards.
By six months, Marchant had less body movement than at three months, and had stopped rolling. The tendency to arch his back was reduced, but he still tended to look at the ceiling (this action appeared purposeful). His hand and arm movement did not develop. He was unable to move his arms purposefully, and his hands were always clenched. He would try to hit the sound buttons on a play bench, but was not very successful, and this activity decreased.
The abnormality with his vision in terms of the direction in which he looked persisted, and he was taken to Bristol Eye Hospital for evaluation (25 September 1996). The tests concluded that there was nothing significantly wrong with the mechanics of his vision - he had a squint, and was slightly long sighted. No comment was made about the abnormality in direction of attention, even though we drew attention to this repeatedly.
He lost the ability to respond to "hello" with an attempt to speak and wave, although he would still respond by smiling.
The spasms continued, and probably increased in frequency and magnitude.
October 1996
Around 5 October, Marchant developed a cold, which became increasingly worse throughout the week. Associated with the cold, he developed high spiking temperatures, and with these he started to have increased spasms, involving all four limbs simultaneously and the spasms became clonic, with two or three cycles; his eyelids also fluttered, but there was no movement of his eyes. Unfortunately, although we were concerned, we did not recognise these as fits. On Thursday 10 October, Sue became so concerned about the severity of the spasms that she phoned Dr Hartnoll of SCBU at Southmead Hospital. Dr Hartnoll said that all babies twitched, and that it would do no harm, recommending that Sue wait for the routine hospital visit on 15 October. On Sunday evening, 13 October, Marchant had a very high temperature at 38.8 and was shaking badly. Sue rang the emergency doctor and told the receptionist of the situation and that Marchant had a history of fits. The doctor did not come out, but relayed a message via the receptionist that Sue should continue to treat Marchant with calpol. Marchant continued to be ill; each time that his temperature rose, he had clonic spasms.
At this time we noticed that he had improved in other ways. He was now able to control his hands, opening them and touching things, and he had better control over his arms. He also started to babble and he even tried to wave. But at the same time he had started to make movements with his tongue, pushing it forwards and out of his mouth.
On Tuesday 15 October, Marchant attended Southmead Hospital for a routine examination. He was seen by Dr Amos Burke who immediately identified his spasms as myoclonic jerks, and said that he was having salaam attacks, and that his EEG would exhibit hypsarrhythmia. He explained that the situation was very serious, and that he wanted to have Marchant to have an EEG and be admitted immediately.
Marchant was admitted to Victor Neale (a children's’ ward) because the was no room in the babies ward He was attended to by Dr Amanda Leaf, who had no specific experience of treating infantile spasms. It was arranged that Marchant should have an urgent EEG. This was scheduled for 4pm, and Marchant was taken from Southmead Hospital to Frenchay Hospital by ambulance. The ambulance was late arriving, and had to go onto another call, after the EEG, we had to wait another hour + for a second ambulance. The consequence of all this was that the staff had to keep the unit open from 5:30pm to 7pm, so the efficiency of the ambulance system cost gross inefficiency elsewhere.
The EEG report from Dr Hilary Morgan said:
The EEG is grossly abnormal with multifocal slow waves, episodic runs of slow activity, and lack of normal background frequencies. In addition, there are frequent brief runs of pulsed [?] slow and fast activity with sharp waves which are increased during sleep. The latter coincide with myoclonic or tonic spasms and are ictal. Apart from the episodic episodes, the sleeping record, at normal gain, justifies the term hypsarhythmia
After consultation with Dr Sharples (the neurological consultant at Bristol Children’s Hospital), Dr Leaf prescribed a course of vigabatrin, and Marchant was put onto a steadily increasing dose, starting at 50mg twice a day rising to 250mg twice a day over 6 days
Because the doctors at Southmead obviously had little knowledge of the condition, Iann started to access information from the Internet.
The vigabatrin had almost immediate effect, in relieving the salaam attacks at elevated temperatures. However, Marchant developed a pattern of increasingly frequent fits, several an hour while awake, which were not so violent, but had the same form, a tremor of all four limbs; also, the number of oscillations increased from 2 or 3 up to 7 or 8. The nurses were recording the tremors as lasting 5 seconds, when actually they usually lasted less than a second - 4 or 5 oscillations to a second.
Over the next three days, Marchant continued to have a variable temperature, with excessive spikes. Marchant became increasingly distressed. Eventually he had a discharge from his ear. Sue thought he had a bacterial infection, but the doctor would not accept this, variously arguing that the marks on the pillow were not a discharge, that Marchant was crying because he was hungry, and that Sue had poked Marchant’s ear. Eventually, there was a large discharge from Marchant’s left ear, and an antibiotic, amoxycillin, was prescribed.
Marchant was discharged from hospital on Saturday 19 October, because the bed was required for someone else; also there was no point in keeping him in hospital, Sue could care for him better at home, and the doctors had little relevant experience.
When Marchant left hospital, he still had a spiking temperature, and frequent fits. He was taking a course of amoxycillin and was still on an increasing dose of vigabatrin.]
Marchant’s fits continued and Sue became very concerned. Sue tried to telephone Dr Sharples, but she was away on holiday. Sue then telephoned Dr Leaf, who wanted Marchant readmitted to Southmead. Finally, Sue rang Werner Schutt who said that Marchant’s condition was serious and that he should be seen by Dr Jardine.
Marchant was taken to the outpatients clinic at Bristol Children’s Hospital on Monday, where he saw Dr Jardine. Dr Jardine said that Marchant was very ill, but that he would be better cared for at home. He increased the vigabatrin dose to 300mg twice a day.
By Wednesday, Marchant was having very frequent fits (up to one every 2 minutes at the worst times) of the same form, but with an increasing number of oscillations - up to 12 per fit. He was seen by the health visitor, Ula Keeling, who suggested that Sue telephone Dr Jardine; he arranged that Marchant should be admitted to Bristol Children’s’ Hospital immediately. He was admitted at 5.30pm, but was not allowed onto the ward, because the procedure was that he had to be seen by the Casualty Doctor, who was very busy. He was eventually examined very thoroughly by Dr Sandhu and was transferred to ward 37 at 8.30pm; by that time, Dr Jardine had left.
We were now very concerned, and thought that Marchant’s fits were being caused by the Vigabatrin (it increases fits in some 25% of infantile spasms cases). Accordingly we wanted Marchant to be taken off the drug, to see what his fit level would be under no medication. This was explained to the Doctor, Dr Megan Eaton, but she would not agree. She was prepared to taper down the Vigabatrin, but wanted to replace it by ACTH. Since the ACTH had to be couriered down from Essex, the treatment did not start until Friday night, 25 October. During the intervening period, the frequency of fits, and the duration increased, with up to 18 oscillations per fit.
Marchant responded quickly to the ACTH, all evidence of fits disappearing within 2 days, except that he continued to have some fits as he became drowsy; eventually these stopped as well. He was, however, distressed and unhappy. On Thursday, Marchant was taken to Bristol Royal Infirmary and given an MRI scan. He also had several urine samples and a blood sample taken. Marchant was very poorly on Monday, and Dr Jardine stopped the Vigabatrin.
His discomfort gradually increased, until, by Wednesday, he had periods when he was writhing in agony. At this time, he was seen by Dr Jardine, who agreed to stop the ACTH. By now, Marchant had completely stopped having the salaam fits. By the evening his pain was worse, and Dr Eaton agreed to put Marchant onto chloral hydrate as a sedative. This was partially effective on the Thursday, but the pain level gradually increased. The pain could be relieved by moving Marchant from the horizontal to the vertical; he would then immediately stop crying, only to resume gradually. If put back to the horizontal position for a while, it was then possible to go through the cycle again. The pain appeared to come in spasms; Marchant would tense, and start to cry, then scream and go into tonic spasm, arching his back.
On Friday, we had heard nothing from the various tests. The doctor (Dr Eaton) was asked, and she then looked up the results. She said the blood test and urine tests were negative, but the faeces had shown Marchant had got a rotovirus; he might have had this for three weeks (cause of temperature?) and would have to build antibodies naturally. Marchant’s temperature continued to spike; it also dropped, and at one point went down to 35.7 and his mouth went blue (not his lips - ie failure of secondary circulation, not primary). The temperature variations were many more than recorded, since the nurses only checked every 4 hours, or when requested by Sue because she was concerned.
On Friday night, the registrar considered a lumbar puncture to check whether Marchant had a brain virus, but this was not done.
This pattern persisted through to Sunday, except that, it became impossible to relieve his pain as previously. For a period, it was possible to reduce the pain by resisting the spasm, when he would stiffen, and then relax without crying out. Finally, even this became impossible. The pain came in cycles, possibly related to feeding, He might have an hour after waking up before the pain occurred, and it would then continue until he was totally exhausted and went to sleep.
Over Friday to Sunday, the pain became slightly less severe, although this might have been due to exhaustion or sedation.
On Sunday evening, we asked whether Marchant could be given a muscle relaxant, because it looked as though the pain might be caused by the muscle spasm, rather then the converse. The sister said that the nurses had wondered why this had not been prescribed, and that a doctor had said on Friday that Marchant needed a muscle relaxant , but had not done anything about it. The nurses also said that they did not understand why the dosage level for chloral was so low. The sister arranged for a prescription from the casualty doctor. Diazepam was administered rectally at 11pm, and relieved the pain almost immediately. Marchant slept throughout the night, and was quieter on Monday morning.
Marchant lost 1lb in weight (from 13lb) over the three days from Friday to Monday.
Marchant had a further EEG on 5 November, with similar results to the previous EEGs. Dr Hillary Morgan wrote:
This grossly abnormal EEG shows a marked lack of normal background frequencies and the trace consists of generalised fast activity, being relatively featureless for much of the time - only intermittent runs of rhythmic slow waves occur during presumed drowsiness when feeding. However, there are no 'paroxysmal' complex discharges on this occasion.
Marchant gradually improved over the week and was discharged on Friday 8 November. He was now feeding better, taking milk from a bottle, and the breast, but not taking solid food. His fits had returned at a low level on Sunday, single shakes at three or four an hour, but he was not in discomfort. It was agreed that if the fits returned, he should be treated with phenobarbitone and lamotrigine.
The discharge report by Dr Megan Eaton says:
Whilst an inpatient Marchant had a number of investigations, including Chromosomes of which the result is still outstanding. We also extracted DNA and have stored this. A Woods Light examination showed no evidence of tubero sclerosis. A urine for amino and organic acids have been repeated after unusual first result. A torch screen showed, Rubella Serology negative; CMV negative; insufficient for oxo-plasmosis. . . At the time of discharge, Marchant was much more responsive and beginning to look at his hands although he was not bringing them to the mid line or putting objects to his mouth. He was not able to sit but he was fixing, following and laughing. His head circumference remains well below the 3rd percentile. . .
During the next week, Marchant’s fit level increased, perhaps to 20 or 30 minor spasms per hour. He was generally happy, and not disturbed by the fits. He had increased movement in his left hand, which now succeeded in touching things which interested him, although not strong enough to grasp properly. His tongue movements had largely stopped. His head movements were improved, and he was looking in the correct direction. His feeding was satisfactory, and he was now accepting a bottle, although this still needed persuasion.
Marchant was seen at Bristol Children’s Hospital on Wednesday 13 November by all the neurological doctors - Drs Jardine, Sharples, Eaton and Patel. They agreed with our proposal that he should go onto a ketogenic diet, after a period to assess his fit rate, also that he should have a further EEG as a reference (EEG finally done in April 197). Dr Jardine also wanted him to be given a course of vitamin B6 injections, to check against a possible vitamin deficiency. It was agreed that we should see the notes, but they were not available. The results of various metabolic test were still awaited, and we did not know the result of the last EEG.
Marchant was admitted to hospital on Tuesday 19 November for the pyridoxine (B6) injection. He had to have a cannula inserted, which took the doctor three attempts, and the injection was done while he was having an EEG. If there had been a vitamin deficiency, the effect should have been immediate, but nothing happened, and he was sent home with the instruction to continue with the vitamins, although this seemed rather pointless.
[Results of MRI scan]
continue to Start
of the ketogenic diet
return to Medical notes
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(update 1.1: 18 July 2002)
(issue 1: 24 December 1997)