Posted by CCF MD on September 22, 1997 at 16:07:12:

In Reply to: Recurrent Pontine Glioma treatment/trials posted by Mandy Wolfryd on September 10, 1997 at 18:08:13:

:
What follows is a history of my daughter Luanne's condition supported by scan reports and doctor's letters. I am unable to send any scans because we will need them in this country for the next 3 weeks so that comparisons can be made with the new scans Luanne is about to have. If at all possible could you advise me on what treatment and trials there are and if she could be treated at the clinic

History

After presenting with progressive symptoms over the course of a year, my daughter Luanne, was finally diagnosed as having a Brain stem Glioma in May 1994. Luanne received Radiotherapy at a dose of 5000 cGy in 30 fractions over 42 days. This finished on the 29th July 94. During this time she was also taking Dexamethasone at various doses ranging from 1.5 - 8mg per day and she had 10mg of Maxalon for her sickness. After radiotherapy she deteriorated rapidly and by the end of September was in a wheel chair. Luanne could no longer wash or dress herself, could not write, cut food, when eating she often choked on the food resulting in it coming out her nose. Her speech was slurred and she also got breathless just by trying to talk. Luanne had double vision over all fields of view and she was suffering from panic attacks as well as sickness each morning. On the 26th of September we went to Canada for 4 days treatment by a Dr. Rudi Falk. The drugs she had were 30 mg C-BPR , with 30mg Hyaluronic acid, and 20 mg Hyaluronic Acid with 30mg/1ml Toradol ( Votarol). They were given by I.V. on a daily basis for the 4 days. On returning home she continued on this treatment twice a week by I.V. However the drugs were unliceinsed in England so I was taught to use her line and for the following 11 months I gave her the treatments. During these 11 months Luanne improved tremendously and when we stopped the treatment at the beginning of August 95 the only problem Luanne had was her double vision.
In April 95 Luanne was well enough to return to school to complete her "A" levels. Her grades were high enough for her to get a place at Imperial College of London studying Biochemistry, and so in October 96 she started university.
Luanne remained stable until February/ March 97 at which time she gradually grew weaker on her right side. In April Luanne had another pet scan which was compared with her previous one that was taken when Luanne was at her best in August 95. The results of this latest scan shows some new tumour growth. At the same time Luanne had another M.R.I. scan, however this was also compared to her last M.R.I. which was taken when she had just started to walk again . Hence this report shows tumour shrinkage. Luanne never had an M.R.I. scan done when she was at her best (August 95 onwards).
Luanne has started back on the treatment she received in Canada, and if it were to work we would see some improvements by now but as yet all that can be said is that her symptoms have not progressed since being on the treatment. At this point in time Luanne still has a large tumour (although a fair amount of it is dead) which is continuing to grow. Her symptoms at the moment are:
Weakness in the right limbs with very little use of right arm and hand, although her physiotherapist feels she is gaining some strength back.
She has NO headaches or any other pains or stiffness.
Her double vision has been the same since 95
Emotional incontinence (laughs out for no reason and cannot control it)
Gets breathless just walking and talking, she only breathes very shallowly and does not use her diafram.
Her urgency and frequency in needing to pass water that she had prior to starting this latest course of Canadian treatment has subsided and the choking on food and it coming out of her nose that she had has also stopped.
Her speech is slurred when she tries to speak long sentences, (because she has trouble breathing and talking at the same time)

I realise that this is essentially a hopeless case, but at the moment my daughter doesn't. Any advice you could supply would be very much appreciated.

. All scan reports are listed below.

Scan Results

LUANNE WOLFRYD DOB 11.1.77

MRI SCAN OF BRAIN SCANNED 29.5.94

There ia a large T1 low,T2high signal mass showing minimal abnormal enhancement situated within and expanding the pons. There is an exophytic componant of the tumour extenting around the basilar artery. The tumour expands the pons, displacing the fourth ventricle posteriorly and the medulla inferiorly. There is downward herniation of the cerebella tonsils but there is no hydrocephalus. The tumour appears to be solid and there is no evidence of a major cystic change.
CONCLUSION: Large pontine glioma

MRI SCAN OF BRAIN SCANNED 12.9.94

The cranial MRI comparison is made with the study of May 1994. The tumour is virtually unchanged in overall size and extent. There is now considerably more enhancement after gadolinium, particularly in the exophytic part of the tumour extenting into the cerebello pontine angle. Thereis no hydrocephalus and the degree of tonsular depression is unchanged.

MRI SCAN OF BRAIN SCANNED 16.1.95

Comparison is made with the study of 12.9.94. The tumour has slightly decreased in bulk which is best appreciated in the sagittal images. The extent of the tumour however is unchanged. The enhancement which was present in 1994 is no longer evident.

CONCLUSION: Diminution in tumour size and regression of tumour enhancement.

Report done in Canada of the MRI scan done on January 16th 1995

MRI of the brain was performed in the high field supra-conducting magnet. T1 weighted sequences were performed pre-gallium in the sagittal plane and post gallium in the sagittal and axial planes. A T2-weighted double echo sequence was performed in the axial plane. Lastly there was a T2-weighted fast spin echo sequence performed in the axial plane of the posterior fossa. Comparison is made with the previous scans performed on 12.9.94.

There is a mass occupying the majority of the pons which extends posteriory into the anterior aspects of the inferior cerebellar peduncles more so on the left than on the right, superiorly into the central portion of both cerebral peduncles more so on the right than on the left side, and anteriorly it appears to encase the basilar artery at the level of the pons. This mass is expansile effacing the pre-pontine cistern. It does not appear to be significantly changed since the previous scan of September 94. As well it does not appear to extend into the medula.

OPINION: Expansile mass within the pons with extension into inferior cerebellar peduncles and cerebral peduncles unchanged in appearance from previous examination. This mass most likely represents a pontine glioma.

MRI SCAN OF BRAIN SCANNED 29.4.97

Comparison is made with the study of 16th January 1995. A large tumour remains centered in the left side of the pons and extending across the mid line. It is however considerably smaller and has less mass effect than on previous study. There is no longer any pathological enhancement.
CONCLUSION: considerable tumour regression.

Scans read by Dr Brian Kendall, Consultant Neuroradiologist

PET SCAN SCANNED 4.4.95
FDG/C11 PET Brain scan
Dosage 250MBq FDG + 135MBq C11 Methionine

RESULTS
Images were acquired from vertex to scull base.
The third ventricle appears enlarged. There is reduced uptake of FDG within the posterior fossa, in comparison with frontal cortex. On the Methionine scan, there is focal increased uptake on the left side of the pons, on the inferior surface.
INTERPRETATION
The reduced uptake of FDG is secondry to treatment. The absence of increased FDG uptake excludes a high grade tumour, however the presence of increased uptake of Methionine is indicative of either low grade tumour or possibly reactive gliosis in response to therapy. The enlarged third ventricle may be secondary to hydrocephalus.

PET SCAN SCANNED 30.8.95
FDG/C11 PET Brain scan
Dosage 259MBq FDG + 370 Mbq C11 Methionine

RESULTS
There is mild asymmetry in Methionine uptake in the pontine region with relatively greater uptake in the left side. Uptake of FDG in the pons is lower than in adjacent cerebral cortex. The distribution of radiotracer elsewhere in the study is physiological. Comparison to the previous study of 4.4.95 shows that the asymmetric Methionine uptake in the pontine region is less marked on this occasion. The pattern of FDG uptake remains unchanged.
INTERPRETATION
The mild degree of asymmetry in the pontine region may represent residuel low grade tumour, with gliosis being the less likely possibility. There has been some improvement in scan appearances in the interval period.

PET SCAN SCANNED 16.4.97
FDG/C11 PET Brain scan
Dosage 281MBq FDG + 295MBq C11 Methionine

RESULTS
There is C11 Methionine accumulation seen in the cerebellar pontine region with uptake to the left of midline, more marked than that on the right and comparable to the previous scan. The FDG uptake is reduced in this region.
INTERPRETATION: Scan findings are consistent with active low grade tumour in cerebellar pontine region.

Letters between doctors

Letters from Dr P. N. Plowman Consultant in Radiology and Medical Oncology
and
Dr John Jestico Consultant Neurologist

29 May 1994 (Dr Jestico writes)
Her symptoms started at least a year ago. She began to develop difficulty in lifting the right leg when walking and the left leg felt weak. More recently her parents have noticed that she has developed an unsteady gait disturbance. Over a similar period she has complained of dizziness by which she feels imbalanced. She feels secure when seated but when walking she has the sensation as if the floor is moving She is imbalanced and has a feeling that she will fall. She is no longer able to walk a straight line. She has double vision on gaze to the left side. This is binocular. Her writing has also been affected, and she has increasing difficulty manipulating her pen. In addition to this she has developed a slurring of speech. For about 3-4 months she has been dysarthric and she sometimes has difficulty swallowing and chokes. Throughout this time it has been noticed that she lacked energy. She has no bladder dysfunction. I have no doubt that her symptoms are progressive. She is otherwise well.
On examination she was rather euphoric, because of this her cooperation during examination was not entirely full. Following eye movements were broken up. She had partial left sixth nerve palsy, a mild bilateral lower neurone facial weakness, an obvious dysarthria and the jaw jerk was exaggerated. Otherwise the cranial nerve and fundoscopic examination was without note. There were no bruits in the head or neck. There was spasticity in both upper limbs, with a paucity of fine finger movements. There was a pyramidal weakness of elbow extension on the right side. She had an obvious ataxia. In the lower limbs she had sustained ankle clonus on each side, there was no weakness. There was heel-knee-shin ataxia and an ataxic gait disturbance. The reflexes were extremely brisk with bilateral extensor plantar responses. There was no sensory deficit, her abdomen was normal, chest was clear, heart normal. She complains of pains in head lasting a couple of minuits at a time.
She clearly has a progressive brain stem disorder. The presence of the sixth nerve palsy and bilateral lower motor neurone facial weakness suggests that this may well prove unfortunately to be a Pontine Glioma.

The MRI shows a Pontine Glioma which is partially exophytic anteriorly as it projects out in front of the Pons and envelops the basilar artery. It fills the Pons and extends up to the mid brain

9 August 1994 (Dr Plowman writes)
All went well with radiotherapy until the last week when she complained of being stiffer in the right side, being less able to feed herself with the right hand and seeing double not only to the left but also in central gaze. Her speech was more slurred. When I reviewed her today she does seem to have a more definite right spastic hemiparesis and diplopia on all eye movements towards the left.

13 September 1994 (Dr Plowman writes)
Subsequent to her last visit I was disappointed to see Luanne returning with worsening symptoms. I share her parents concern that her neurological signs are rapidly progressing despite increasing her steroids.
and on 26 October 1994 he writes
Subsequent to my letter of 13 September Luanne went to Canada for treatment. It remains to be seen if she will respond to this drug cocktail I will keep you informed.

24 October 1994 (Dr Jestico writes)
Since seeing me last time she has developed a variety of panic attacks which seem to be getting worse. She is not as giggly as Before. At times she will have nasal regurgitation of fluids, although this does seem to be improving. Her speech although variable is probably worse than before. Strength in her limbs tends to vary but she is certainly unsteady. She has great difficulty in controlling her upper limbs particularly on the right side because of an action tremor. She complains of persistent double vision Every morning she feels nauseated and this occurs when she gets up out of bed. She had a degree of emotional lability, a left sixth nerve palsy, her pupils were large but they reacted. There was nystagmus on gaze to the right side She was still dysarthric. There was pyramidal impairment of finger movement on each side, with spasticity at both wrists. Also pyramidal weakness affecting her right arm and right leg. She had a degree of cerebellar ataxia affecting both upper limbs, more marked on the right. There was clonus at the left ankle, reflexes were extremely brisk The plantar responses were extensor. There is no doubt that she has deteriorated. I suspect that her morning vomiting reflects the tumour involving the fourth of the fourth ventricle. This situation is essentially hopeless. I doubt that her present treatment is having any part to play in her symptoms.

7 Dec 1994 (Dr Jestico writes)
There seems to be an improvement over the past few weeks. Her walking seems steadier and she is not tripping up as much, there also is some improvement in her speech. Her breathing seems better than before, also there has been an improvement in the use of her hands, and her writing is better than before and certainly the strength in the right arm has improved. The morning vomiting has also subsided.
On examination she was bright and alert, she still has large pupils although they react. There was a complete left sided sixth nerve palsy and at times she alternated in fixation between the right and left eyes. There was nystagmus, particularly on gaze to the right. She has bilateral facial weakness, more marked on the left. She was still rather dysarthric although less than before. Surprisingly finger movement had improved, particularly on the left side and there is no further weakness in the right arm. She still has ataxia in the upper limbs although I felt this was less than before/Although she was able to walk on her own , she was circumducting the right leg more than before. The pains she was having in her head have subsided.
Her parents were obviously encouraged by her progress at this stage, although I am sure ultimately the situation is hopeless. I suggest she continue on her current treatment and I will see her after Christmas.

19 January 1995 (Dr Plowman writes)
I was delighted to find Luanne in good health today. All her neurological signs are improving. Her repeat MRI scan shows a slight improvement in the extensive brainstem glioma. I will review her again in another six weeks in which time she will continue on her Canadian treatment.

14 March1995 (Dr Plowman writes)
I reviewed our mutual patient today, all her neurological parameters have again improved. She gets occasional headaches which are transient. Her squint has virtually disappeared. Her handwriting is better and her gait is very much improved. Physical examination disclosed no new neurological signs

5 April 1995 (Dr Jestico writes)
Clinically she has continued to improve, squint virtually disappeared. She still has a degree of double vision although I suspect this is less than before. Her gait has certainly improved it was much steadier. On examination her dysarthria was less, she still has a left sixth nerve palsy, but there was some abduction of the left eye today. The facial weakness seemed less and there was less ataxia in the right arm. There is no doubt she is continuing to improve on her current treatment.
With regard to her scans, as you know she recently had a PET scan . T his apparently showed no evidence of a high grade tumour, however it was unable to distinguish low grade Neoplasm from reactive gliosis following treatment. My personal view is that PET scanning has no part to play in the assessment of this patient. I am also extremely worried by repeated MRI scans to review her progress. Her recent MRI scan really shows no change from previous studies and I would not expect this to do so. Unfortunately the parents would hope that the tumour would shrink in relation to her treatment. I suspect this will not prove to be the case. Therefore displaying serial scans may well be giving the parents and indeed Luanne false hopes or certainly cause disappointment when it is realised that the tumour is no different. My personal view is that no further scanning should be taken. The only yardstick is the patients obvious improvement and I am extremely pleased with this and hope that it will be maintained. However I still doubt that her final prognosis will be good.

28 August 1995 (Dr Jestico writes)
Luanne stopped Canadian treatment this month. Luanne has done extremely well. However she still complains of double vision in all directions of gaze, although she felt she was able to cope with this, and indeed double vision was present when she took her recent "A" level examinations. Close up and in the distance she will see a single image, however in between is double. On examination the eye movement disturbance was difficult to analyse, but there was no longer nystagmus. However she appeared still to have a left sixth nerve palsy. None the less she complained of double vision over all directions of gaze. There was no weakness in the limbs, indeed there was virtually no cerebellar deficit today which represented a considerable improvement. Her parents are pleased with her progress but I am sure it is too early to assess her future

29 November 1996 (Dr Plowman writes)
I am delighted to say Luanne has responded well to her treatment, and has just started studying chemistry at Imperial college and we are all very pleased with her progress. However she continues to have diplopia in most directions of gaze

2 April 1997 (Dr Jestico writes)
Over the last 3 months Luanne has felt she has deteriorated. She had a sensation of heaviness affecting the right arm and leg, rather similar to her initial symptoms several years ago. She also found her speech was rather worse although her parents did not agree. There have been times recently when she has had occasional episodes of nasal regurgitation of fluids. She felt her walking was slightly more unsteady than before. There are times she has had difficulty in coordinating respiration with her speech.
On examination she was bright and alert. She had a left sided sixth nerve palsy as before. I wondered whether she had a gaze palsy to the right side. There was only marginal facial weakness today. She was slightly dysarthric. Tongue movements were normal and she appeared to have normal palatal movement. There was a slight weakness of elbow extension on the right side but this was really the only weakness of the limbs. She had a mild cerebellar disturbance of the upper limbs and although her gait was extremely good, she was unable to walk heel to toe.

1 May 1997 (Dr Plowman writes)
Luanne now presents with a right sided weakness progressing since mid February ( which was a presenting feature in 1994), untidy handwriting and choking with reflux of food out of her nose. The MRI scan showed a predominantly left-sided pontine mass legion ( the original primary site) and a PET scan showed increased activity since August 1995. If we diagnose relapse ( which I fear we shall), Luanne wants to receive some more of the treatment she received in Canada. I would respect this as it disturbed her little and she wishes to take her exams in June. If, or when, this fails we have a very difficult choice of conventional chemotherapy versus some more radiotherapy. Bearing in mind the radical external beam dose she has received, this will prove very taxing for me.

Many thanks for your time.
Yours sincerely

Mandy Wolfryd

ABTA
2720 River Road
Des Plains, IL 60018
847 827-9910 800 886-2282
Fax 847 827-9918
web page www.abta.org

Good luck.