Wednesday, 9 January 2013

Complete Remission of a Diffuse Pontine Glioma - with Homeopathy

A patient is described in whom a large diffuse glioma of the pons extending into the midbrain was diagnosed at the age of 2 years. Biopsy showed a fibrillary astrocytoma. After shunting of a hydrocephalus, the clinical symptoms abated without convencional therapy. Repeated MRI studies showed a continuous decrease of the tumour which was no longer visible when the patient was 6.6 years old.

In reviews on spontaneous remissions of oncologic disorders we were unable to find a case of a biologically benign brain stem tumour. There is one isolated report on a similar case, though without histologic documentation.

Gliomas of the brain stem can be classified according to their location and growth pattern as focal, dorsal exophytic, cervico-medullary, and diffuse intrinsic (6). Although a more active surgical approach has become feasible (3) the overall prognosis is still unfavourable with a 5-year survival rate in the range of 30 %. The prognosis is especially poor for the subgroup of diffuse intrinsic pontine gliomas resulting in "pontine hypertrophy". These tumours are not amenable to surgery. Treatment by radiotherapy (5, 7), by chemotherapy (1), or by a combination of both (11) mav induce short-term remissions but has up to now not improved a 2-4 year survival rate of less than 20% (4).
We report on a 2-years-old boy with a large diffuse fibrillary astrocytoma of the pons in whom the clinical symptoms abated without any conventional therapy other than shunting of an occlusive hydrocephalus. The tumour progressively decreased in size on repeated MRI scans, and was no longer visible after 5 years. Only one similar case has been published, though without histological documentation, by Rao et al (10).

Case report
The patient, the third of four children from a healthy family, was born without complications after an uneventful pregnancy. He developed normally until the age of 11 months when he was able to stand and to walk a few steps without support. He then stopped unaided walking, moved around only in a sitting position or by crawling without the use of his left leg.
He was seen by a child neurologist at the age of 20 months who described a broad-based ataxic gait, uncoordinated grasping, and intention tremor. Reflexes and cranial nerve functions were reported as normal.
At the age of 23 months, the boy was seen in our department. He could walk only when held on both hands. He showed muscular hypotonia, ataxia, and intention tremor. There were an alternating convergent strabism, bilateral weakness of the N. abducens, vertical gaze palsy, up-beat nystagmus, and pale optic discs without prominence. Reflexes were increased on the legs, pyramidal signs inconstantly positive. The boy appeared alert and attentive, but did not speak
Laboratory values from blood, urine and CSF were normal. On cranial CT a hypodense tumour without contrast enhancement was seen in the pons, compressing the 4th ventricle and causing a triventricular hydrocephalus. On MRI the tumour was hypointense on T1 and hyperintense on T2-weighed images, without enhancement after i.v. application of Gd-DTPA. The tumour was located in the pons extending into the midbrain. Both cerebral peduncles were involved, the right one slightly more than the left. Tumour margins were smooth within the pons with some small irregular tumour extensions into the adjacent brain at the level of the midbrain. A severe triventricular hydrocephalus with transependymal oedema was seen due to the tumour compression of the aquaeduct of the mesencephalon. A ventriculo peritoneal shunt was inserted and a stereotactic biopsy performed.

Histopathological investigation of the stereotactic biopsy specimens showed a diffusely infiltrating astrocytoma of low cellularity. Morphological signs of anaplasia, i.e., mitoses, necroses or microvascular proliferations, were absent. No Rosenthal fibres or eosinophilic granular bodies were seen. There were no inflammatory infiltrates. Immunohistochemically, the tumour cells strongly expressed glial fibrillary acidic protein. Individual tumour cells (< 1%) stained positive for the proliferation-associated nuclear antigen Ki-67 (MIB1). Nuclear immunoreactivity for the tumour suppressor protein p53 was noted in a considerable fraction of tumour cells while immunoreactivity for epidermal growth factor receptor was weak. Staining for leukocyte common antigen and CD68 revealed neither lynphocytic infiltrates nor evidence for microglial activation. The final neuropathological diagnosis was fibrillary astrocytoma of World Health Organisation (WHO) grade 11.

Surgical intervention, irradiation or chemotherapy appeared not feasible due to the location and extent of the tumour, the age of the patient, and the result of the biopsy. The boy therefore was discharged and the parents were informed about a dismal prognosis. Further care and treatment was taken up by another paediatric hospital where one of the authors (Ch. T.) is the responsible oncologist.

The parents, unable to accept the dismal prognosis, asked for therapeutic attempts, even if there would b e no scientific foundatioxi for the hope of a positive effect. Treatment was started with a mistletoe preparation (Iscador P 3%0) combined with homeopathic dilutions. After 3 months, Iscador was replaced by Helleborus 1 %', and these drugs were continued allernatiiigly in 3- months intervals. Already after six weeks of treatment, the boy started playing with other children and began to communicate verbally; there svere sWI few eye movements and barely any rriimic reactions. Improvement continued during the following months.

At 2.5 years, the boy was able to speak a few words and to walk some steps unaided. Neurological examination still showed generalized hypotonia, a broad-based ataxic gait, uncoordinated grasping, and a convergent strabism.

At 3.7 years, the motor functions had further improved. The boy could walk, stand on one leg, and had a normal neurological status except for a strabism.

At 6. 10 years, he had learned to ride a bike, to swim, and had to be rescued from the top of a cherry tree by the fire brigade.
Except for some behavioural problems at school there were no complaints, and the neurological examination was normal.

The first follow-up study by MRI, performed at the age of 3.5 years, revealed a clear shrinkage of the tumour. Hydrocephalus had regressed due to the ventriculo-peritoneal shunt. An additional MRI examination 11 months later showed an ongoing decrease of the tumour size with an incomplete tumour remission.
On the last MRI examination at the age of 6.6 years, the tumour was no longer visible. With the exception of two small CSF- isointense lesions within the pons which were assigned to the stereotactic biopsy, signal intensity in the pons and the midbrain was clearly normal.

Amongst paediatric patients with gliomas of the brain stem those with diffuse intrinsic gliomas of the pons have the worst prognosis. Though prolonged duration of brain stem symptoms and signs prior to diagnosis - more than 1 year in our patient - is considered prognostically favourable, pontine location, great tumour volume, and brain stem enlargement - as in our patient - correlate with a particularly adverse outcome (7). 3-year survival times in the literature vary between 3 and 21 % (for summary see Freeman and Farmer 1998 [61). The usual Kaplan- Meyer tables do not provide information concerning the further clinical and radiological course in the surviving patients. There is, however, no reason to assume that any one of those survived free of symptoms or even without a remaining tumour.

Langmoen et al (9) described a 2-year old boy with hypodense expansion of the pons who survived for 12 years without treatment. No information on neuroradiological follow-up is available to the authors (Langmoen, personal communication).

Rao et al (10) reported on spontaneous involution of an intrinsic brain stem lesion in a 4-year-old child. Though a histological diagnosis was not available, clinical and MRI findings were very similar to those in our patient and the authors' assumption that these characteristics "strongly suggest a tumour etiology" appears completely justified. We therefore refrain from presenting our patient as the first one with a complete remission of a diffuse pontine glioma, though he may be the first one in whom the diagnosis is morphologically documented.

According to sufficiently well documented case reports, spontaneous remission in oncologic disorders is considered to occur with a frequency of 1 in 60,000 to 100,000 cases (2) Reports concerns, besides the well known cases of neuroblastoma in infancy, metastasizing bronchial carcinomas, malignant melanomas, kidney carcinomas, and malignant lymphomas including certain forms of leukaemia. Brain-stem tumours, especially pontine gliomas, are not mentioned in extensive reviews (8).
The cause of the complete remission in our patient remains unknown. The effect which is to be attributed to the unconventional therapies applied is rated differently by the authors of this report according to their medical and philosophical background.

(1) Allen, J. C., Siffert, J. Contemporary chemotherapy issues for children with brainstem gliomas. Pediatr. Neurosurg. 24, 98-102 (1996).
(2) Cole W. H. Efforts to explain spontaneous regression of cancer., J. Surg. Oncol. 17, 201-209 (198 1).
(3) Constantini, S., Epstein, F Surgical indication and technical considerations in the management of benign brain stem gliomas. J Neuro-Oncol. 28, l93-205 (1996).
(4) Fischbein, N. J., Prados, M. D., Wara, W., Russo, C., Edwards, M. S. B., Barkovich, A. 1. Radiologic classification of brain stem tumors: Correlation of magnetic resonance imaging appearance with clinical outcome. Pediatr. Neurosurg. 24, 9-23 (1996).
(5) Freeman, C. R., Bourgouin, P. M., Sanford, R. A., Cohen, M. E., Friedman, H. S., Kurz, L. E. Long term survivors of childhood brain stem gliomas treated with hyperfractionated radiotherapy. Cancer 77, 555-562 (1996).
(6) Freeman, C. R., Farmer 1. P. Pediatric brain stem gliomas: a review. Int. J. Radiation Oncology Biol. Ph5,s. 40, 265-271 (1998).
(7) Kaplan, A. M., Albright, A. L., Zimmerman, R. A., Rorke, L. B., Li, H., Boyett, J. M., et al. Brainstem gliomas in children. Pediatr. Neurosurg. 24,185-192 (1996).
(8) Kappauf, H. Spontanmission bei Krebserkrankungen. Münch. Med.
Wschr. 139, 660-665 (1997).
(9) Langmoen, I. A., Lundar, T., Storm-Matheisen, I., Lie, S. 0., Hovind, K. H. Management of pediatric pontine gliomas. Child's nerv. Syst 7, 13-15 (1 99 1).
(10) Rao, 5., Constantini, S., Gomori, J. M., Siegal, T, Epstein, F. Spontaneous involution of an intraaxial brain stem lesion: A case report. Pediatr. Neurosurg. 23, 279-282 (1995).
(11) Walter, A. W, Gajjar, A., Ochs, J. S., Langston, J. W, Sanford, R. A., Kurz, L. E., et al. Carboplatin and etoposide with hyperfractionated radiotherapy in children with newly diagnosed diffuse pontine gliomas: A phase I/II study Med. Pediatr. Oncol. 30, 28-33 (1998).

Hans-Gerd Lenard, M. D.
Department of Paediatrics
Moorenstr. 5
D-40225 Düsseldorf


Medical Disclaimer
The content of this website is provided for general informational purposes only and is not intended as, nor should it be considered a substitute for, professional medical advice. Do not use the information on this website for diagnosing or treating any medical or health condition. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.

Dr JPB Prinsloo is the oldest homoeopathic practice in South Africa.
The practice, situated in Pretoria, was established in 1956.
To learn more about homeopathy, homeopathic treatment and the legal requirements for practising as a homeopath, visit: