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British Journal of Radiology (2006) 79, e196-e199
© 2006 British Institute of Radiology
doi: 10.1259/bjr/50789043
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Case report

Significant response of radiation induced CNS toxicity to high dose steroid administration

M Genc, MD1, E Genc, MD2, B O Genc, MD2 and D A Kiresi, MD3

Departments of 1 Radiation Oncology, 2 Neurology and 3 Radiology, Meram Medical Faculty, Selcuk University, Konya, Turkey

Correspondence: Dr Mine Genc, Department of Radiation Oncology, Selcuk University, Meram Medical Faculty, 42080, Akyokus, Konya, Turkey. E-mail: minegenc{at}yahoo.com


   Abstract
Top
 Abstract
Introduction
 Case report
 Discussion
 References
 
Treatment of radiation myelopathy remains a challenge. Supportive and rehabilitative therapy is the mainstay of treatment. This article describes a case of central nervous system (CNS) toxicity of radiation with a progressive improvement in the clinicoradiological picture following high dose steroid treatment. A female patient was admitted to the neurology department of our hospital 7 months after a course of radiotherapy in another centre for lingual epidermoid cancer. Neurological examination revealed a heavy spastic quadriplegia syndrome. On MRI examination, T2 weighted hyperintensities were observed in cerebral and cerebellar peduncles, periventricular regions and medulla spinalis at Th1-Th2 levels. The patient was treated with high dose methylprednisolone, 1 g day–1 for 5 days (pulse therapy) followed by oral methylprednisolone 80 mg day–1 for a week, tapered over 3 weeks. Within the first week of pulse therapy, she regained muscle strength of upper limbs against gravity. At the 2 year follow-up, MRI demonstrated obvious regression of the lesions in the medulla and cerebellum with disappearance of contrast enhancement. This case report is notable with the complete disappearance of MRI lesions at the 2 year follow-up after the treatment with high dose steroid.


   Introduction
Top
 Abstract
 Introduction
Case report
 Discussion
 References
 
Central nervous system (CNS) toxicity is a rare but serious complication of radiotherapy when the brain and spinal cord are included within the radiation field. The most important injuries are late syndromes. Typical radiation necrosis may become evident as early as 6 months, but may be delayed as long as 2–3 years [1]. Although ischaemia has been suggested as being responsible for the radiation necrosis, some cases are not associated with vascular changes [2]. Radiation also results in the loss of precursor cells of oligodendrocytes and causes demyelination [2]. Radiation tolerance of CNS depends on a number of factors, including total dose, dose per fraction, total time, volume, host factors like hypertension, diabetes, vascular disease and individual sensitivity, radiation quality, and concomitant use of drugs [2].

The aim of this report is to describe a case of CNS toxicity of radiation with a progressive improvement in the clinicoradiological picture following high dose steroid treatment.


   Case report
Top
 Abstract
 Introduction
 Case report
Discussion
 References
 
7 months prior to admission, a 55-year-old female underwent resection of a lingual epidermoid carcinoma and subsequently received adjuvant radiotherapy. The patient was treated with Cobalt-60 teletherapy machine using two lateral opposing portals and single anterior field. The prescribed tumour dose was 66 Gy in 2 Gy fractions. The lower part of the cerebellum and cervical cord between C1 and Th2 were included in the treated volume and received 46 Gy in 2 Gy fractions, over 5 weeks. The patient was admitted to hospital 7 months after the radiation with the complaint of ascending weakness of the extremities that progressed within several days. She complained of weakness of the upper and the lower extremities and urinary retention. Neurological examination revealed heavy spastic quadriplegia syndrome with distal pronounced paresis of her arms and legs. She had bilateral Hoffman and Babinski signs, T2 sensory level for all modalities and urinary retention. She had normal biochemical and serological tests including vitamin B12 and folic acid levels. Cerebrospinal fluid examination did not show any abnormality with normal protein and glucose levels, no white blood cells, and no oligoclonal bands. Visual and brainstem evoked potentials were unremarkable. However, somato-sensorial evoked potentials could not be elicited. MRI examination of the brain showed T2 weighted hyperintensities in the cerebellar peduncles (Figure 1aGo) and bulbus (Figure 1bGo). Linear contrast enhancement was observed in both cerebellar hemispheres and peduncles (Figure 2Go). There was spinal cord expansion at the medullary level. Spinal MRI revealed hyperintensity along the cervical cord between Th1 and Th2 levels on T2 weighted images (Figure 3Go).


Figure 1
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  		Figure 1. T2 weighted axial images demonstrate hyperintense lesions in (a) the cerebellum and (b) bulbus.

 

Figure 2
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  		Figure 2. Linear contrast enhancement is seen in the cerebellar hemispheres and peduncles on post-contrast T1 weighted image.

 

Figure 3
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  		Figure 3. T2 weighted sagittal image shows hyperintensities and expansion in the spinal cord.

 
The patient was treated with high dose methylprednisolone, 1 g day–1 for 5 days (pulse therapy), followed by oral methylprednisolone 80 mg day–1 for a week tapered over 3 weeks. Within the first week of pulse therapy, she regained muscle strength of upper limbs against gravity. Control MRI, taken 1 month later, showed minimal regression of the previous lesions. 2 months later, the patient was able to walk with assistance; however, bladder function did not improve. At the 2 year follow-up, she was able to use both her upper extremities and walk with assistance. Hoffman and Babinski signs continued to be positive on the right side, deep tendon reflexes were hypoactive and no sensory deficit could be elicited. Bilateral dysmetria and mild dysdiadochokinesia were recorded in both upper extremities. Her incontinence was replaced by urgency. Repeated MRI demonstrated obvious regression of the lesions in the medulla and cerebellum with disappearance of contrast enhancement. Lesions in the spinal cord were completely resolved.


   Discussion
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 Abstract
 Introduction
 Case report
 Discussion
References
 
The mechanism of CNS toxicity has not been clearly defined. The main target cells involved are vascular endothelial and glial cells. A vascular insult is the most commonly evoked mechanism [3]. Following radiotherapy, abnormal, rapidly growing cells replace the normal endothelial cells during the latent interval and induce an immunological response, leading to subintimal tissue swelling and narrowing of the lumen. This would lead to foci of ischaemic necrosis [4]. However, reports of radiation myelopathy without evidence of vascular damage suggest involvement of the oligodendrocytes or glial progenitor cells [5].

Myelopathy is an uncommon complication of radiotherapy. The radiation tolerance dose of the spinal cord in adults is approximately 4500 cGy in 5–6 weeks, depending on the level and volume of the cord being irradiated [6–8]. The myelopathy is mainly influenced by fraction size, the total radiation dose, the length of spinal cord and individual patient sensitivity [6–9]. In addition, a total dose of radiation ranging from 4500 cGy to 6000 cGy delivered at 180 cGy per day–1 represents the optimal dose of irradiation, with clinically acceptable incidence of adverse effects ranging from 3% to 5% in the brain [10]. Incidence of radiation necrosis is higher in patients treated with higher fraction doses and the time of onset was found to be shorter [10].

In this case, we have observed CNS injury despite the conventional fractionation and relatively low dose. However, there are also other cases observed following radiation doses which are considered as safe [9–12]. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation. However, imaging and clinical changes are observed generally only above 50 Gy [13]. Moreover, neurocognitive effects are observed at lower doses, especially in children.

In the present case, the spinal cord was spared after 46 Gy. Although this is a relatively low dose, there is no precise safe radiation tolerance dose for the spinal cord. The majority of myelopathy cases with doses ≤45 Gy were reported to be associated with high fraction sizes [12]. In the cases of radiation-induced myelitis described in the literature following a total radiation dose lower than 45 Gy or with daily fractions lower than 2 Gy, some technical error (e.g. dosimetry errors) or a particular sensitivity of the spinal cord have been considered responsible [9, 14]. Overlap may occur at the match-line junction of the three fields when head and neck cancer is often irradiated using parallel opposed lateral fields and an anterior low neck field, resulting in an increased risk of radiation myelitis [15]. In our case, the patient has no other known disease which may cause hypersensitivity. However, one can not exclude individual hypersensitivity or technical errors (e.g. dosimetry).

The diagnosis of radiation-induced CNS toxicity is often made by excluding other possible causes. Pallis et al [16] established the diagnostic criteria for radiation-induced spinal cord injury: (1) the spinal cord must have been included in the radiation field, (2) the main neurological lesion must be within the segments of cord exposed to radiation, and (3) other causes of neurological dysfunction were excluded. We believe that our patient satisfies these criteria. Latency periods of 1 month to 13 years have been described [17], with the shorter intervals usually seen at higher radiation doses and in the paediatric age group. Cerebrospinal fluid analysis of the spinal tap may either be normal or characterized by a mild increase in protein concentration [18]. Findings of swelling of the spinal cord, abnormal MR signal intensity and intramedullary contrast enhancement are similar to those seen in myelitis of other aetiology [19]. These abnormalities seen on MRI have been attributed to blood–brain barrier (BBB) breakdown due to vascular endothelium damage [20, 21]. The obliteration of vessels would very likely give rise to the permeability of the BBB which was observable by MRI as delayed radiation myelitis. Radiological findings were found to correspond to the irradiated field. The present case also demonstrated similar MRI findings compatible with radiation myelitis. Atrophy appears only in the long term (≥3 years) if myelitis does not ameliorate [20]. Even in cases of over-irradiation, only contrast enhancement and signal changes were seen on MRI in delayed phase [21].

Late CNS toxicity is usually permanent. It is usually fatal in about 50% of cases, most often because of infection [22]. Supportive and rehabilitative therapy remains the mainstay of treatment. Hyperbaric oxygen therapy (HBO) is effective in the treatment of osteoradionecrosis and radionecrosis of soft tissues. Although there are several cases of radiation myelitis that benefited from HBO in the literature, its role is still controversial [2, 11, 23, 24]. Glantz et al [25] reported partial neurological function recovery using anticoagulation therapy for myelopathy and cerebral necrosis. Innovative prevention strategies for radiation necrosis of CNS include treatment with growth factors as well as neural stem cell transplantation and neoangiogenesis [26].

Initial medical management involves corticosteroids, which are known to decrease cytokines and reduce inflammation. Steroids were reported to delay the progression of radiation myelitis for a short period of time [18]. However, Lee et al [27] have treated 72 patients with temporal lobe necrosis due to radiation with a tapering dose of dexamethasone, with 35% achieving a durable response. In their report, dexamethasone was found to be most beneficial when used in the early stages of radiation necrosis, when there is marked reactive oedema. Steroid treatment has not only an oedema-reducing effect, but it also modifies subsequent development of vascular and inflammatory changes [28]. The present case with both brain and spinal cord involvement demonstrated dramatic response to high dose steroid therapy. We were able to follow the clinical and radiological evolution for a relatively extended period of time after the end of steroid therapy. This case report is notable with the complete disappearance of MRI lesions including contrast enhancement at the 2 year follow-up after the diagnosis of radiation toxicity. Partial regression of neurological findings suggests that clinical evolution does not correlate with radiological findings.

Received for publication August 15, 2005. Revision received November 21, 2005. Accepted for publication January 24, 2006.


   References
Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 

  1. Hall EJ. Clinical response of normal tissues. Philadelphia, PA: Lippincott Williams & Wilkins Press, 2000:340–60
  2. New P. Radiation injury to the nervous system. Curr Opin Neurol 2001;14:725–34.[CrossRef][Medline]
  3. Kristensson K, Molin B, Sourander P. Delayed radiation lesions of the human spinal cord. Report of five cases. Acta Neuropathol 1967;9:334–44.
  4. Howell DA. Radiation myelopathy. Dev Med Child Neurol 1979;21:653–6.[Medline]
  5. Rampling R, Symonds P. Radiation myelopathy. Curr Opin Neurol 1998;11:627–32.[CrossRef][Medline]
  6. Cohen L, Creditor M. An iso-effect table for radiation tolerance of the human spinal cord. Int J Radiat Oncol Biol Phys 1981;7:961–6.[Medline]
  7. Abbatucci JS, Delozier T, Quint R, Roussel A, Brune D. Radiation myelopathy of the cervical spinal cord: time, dose and volume factors. Int J Radiat Oncol Biol Phys 1978;4:239–48.[Medline]
  8. Kim YH, Fayos JV. Radiation tolerance of the cervical spinal cord. Radiology 1981;139:473–8.[Abstract/Free Full Text]
  9. Barontini F, Cionni L, Maurri S, Grappi C, Sita D. Late myelopathy caused by ionizing radiation. Considerations on 3 cases. Riv Patol Nerv Ment 1984;105:119–26.[Medline]
  10. Safdari H, Fuentes JM, Dubois JB, Alirezai M, Castan P, Vlahovitch B. Radiation necrosis of the brain: time of onset and incidence related to total dose and fractionation of radiation. Neuroradiology 1985;27:44–7.[CrossRef][Medline]
  11. Calabro F, Jinkins JR. MRI of radiation myelitis: a report of a case treated with hyperbaric oxygen. Eur Radiol 2000;10:1079–84.[CrossRef][Medline]
  12. Goldwein JW. Radiation myelopathy: a review. Med Pediatr Oncol 1987;15:89–95.[Medline]
  13. Schultheiss TE, Kun LE, Ang KK, Stephens LC. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys 1995;31:1093–112.[CrossRef][Medline]
  14. Marcus RB, Million RR. The incidence of myelitis after irradiation of the cervical spinal cord. Int J Radiat Oncol Biol Phys 1990;19:3–8.[Medline]
  15. Meeks SL, Williams RO, Bova FJ, Mendenhall WM, Buatti JM. The midline dose distribution for a three-field radiotherapy technique. Med Dosim 1999;24:91–8.[CrossRef][Medline]
  16. Pallis CA, Louis S, Morgan RL. Radiation myelopathy. Brain 1961;84:460–79.[Free Full Text]
  17. Schultheiss TE, Higgins EM, El-Madhi AM. The latent period in clinical radiation myelopathy. Int J Radiat Oncol Biol Phys 1984;10:1109–15.[Medline]
  18. Schultheiss TE, Stevens LC. Radiation myelopathy. Am J Neuroradiol 1992;13:1056–8.
  19. Hirota S, Soejima T, Higashino T, et al. A case of chronic progressive radiation myelitis treated with long-time corticosteroid administration. Jpn J Clin Radiol 1998;43:649–52.
  20. Alfonso ER, De Gregorio MA, Mateo P, et al. Radiation myelopathy in over-irradiated patients: MR imaging findings. Eur Radiol 1997;7:400–4.[CrossRef][Medline]
  21. Wang PY, Shen WC, Jan JS. MR images in radiation myelopathy. Am J Neuroradiol 1991;13:286–9.
  22. Schultheiss TE, Stephens LC, Peters LJ. Survival in radiation myelopathy. Int J Radiat Oncol Biol Phys 1986;12:1765–9.[Medline]
  23. Chuba PJ, Aronin P, Bhambhani K, Eichenhorn M, Zamarano L, Cianci P, et al. Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer 1997;80:2005–12.[CrossRef][Medline]
  24. Leber KA, Eder HG, Kovac H, Anegg U, Pendl G. Treatment of cerebral radionecrosis by hyperbaric oxygen therapy. Stereotact Func Neurosurg 1997;70:229–36.
  25. Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW, Schold SC Jr. Treatment of radiation induced nervous system injury with heparin and warfarin. Neurology 1994;44:2020–7.[Abstract/Free Full Text]
  26. Nieder C, Andratschke N, Price RE, Rivera B, Ang KK. Innovative prevention strategies for radiation necrosis of the central nervous system. Anticancer Res 2002;22:1017–23.[Medline]
  27. Lee AW, Kwong DL, Leung SF, Tung SY, Sze WM, Sham JS, et al. Factors affecting risk of symptomatic temporal lobe necrosis: significance of fractional dose and treatment time. Int J Radiat Oncol Biol Phys 2002;53:75–85.[CrossRef][Medline]
  28. Tada E, Matsumoto K, Kinoshita K, Furuta T, Ohmoto T. The protective effect of dexamethasone against radiation damage induced by interstitial irradiation in normal monkey brain. Neurosurg 1997;41:209–17.[CrossRef][Medline]




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