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Survivor Issues: Leukoencephalopathy

Note: This section has health/medical information. It was not written by a health care professional. The medical references are listed in the text below (Merck Manual, The Myelin Project web site, Childhood Leukemia by Pui, Childhood Cancer Survivors by Nancy Keene et al.

Leukoencephalopathy is the destruction of the myelin sheaths that cover nerve fibers. These sheaths, composed of lipoprotein layers, promote the transmission of a neural impulse along an axon. In cancer patients, especially leukemia patients, leukoencephalopathy is a rare side effect, caused by methotrexate and/or radiation. The symptoms of leukoenceopalopathy include seizures, mental dysfunction, and ataxia.

Leukoencephalopathy, also called multifocal demyelinating disease, is not at all unique to patients treated with chemotherapy and radiation. Online, most discussions of this condition are found on AIDS web sites. It can also be caused by "local injury, ischemia, toxic agents, or metabolic disorders" (Merck manual). Multiple Sclerosis (MS) is a demyelinating disease.

A link to demyelinating diseases:

According to the Merck Manual, the demyelinating process can be reversed.

Progressive Multifocal Leukoencephalopathy, or PML, is a progressive disease caused by a slow virus in immune-compromised patients. Here is a description of PML:

The following paragraph is directly from the Royal Belgian Radiological Society web site:

"PML is an uncommon demyelinating disease that occurs in immuno-compromised patients (lymphoma, leukemia, carcinomatosis, AIDS). The incidence of PML in adult AIDS-patients has been estimated to be up to 4%. PML is caused by central nervous system infection by group B Human Papovaviruses (Jacob-Creutzfeldt virus, simian virus 40), destroying principally oligodendroglia, thus resulting in extensive demyelination. The clinical manifestations are those of multiple, progressively enlarging lesions of the cerebral and cerebellar fiber systems: motor system abnormalities, visual loss, dementia and ultimately death, occur four to six months after onset."

The following paragraphs have been copied directly from published books, as referenced.

Principles and Practice of Pediatric Oncology, 3rd ed. Chapter 17.

"Necrotizing leukoencephalopathy, a particularly severe form of delayed neurotoxicity, is relatively uncommon. It occurs most frequently in patients who have received large cumulative doses of cranial irradiation and intrathecal and systemic methotrexate (eg: treatment of recurrent meningial leukemia) but also has been observed in patients who have not received cranial irradiation.

Leukoencephalopathy is characterized pathologically by multifocal demyelination. Patients with this syndrome may present with a variety of clinical findings ranging from poor school performance and mild confusion to lethargy, dysarthria, dysphasia, ataxia, spasticity, or progressive dementia."

Childhood Cancer Survivors by Nancy Keene, Wendy Hobbie, and Kathy Ruccione. 2000, O'Reilly, p. 238.

"A rare effect from radiation to the brain is leukoencephalopathy. Children who develop this disorder may have problems with balance (ataxia), difficulty swallowing (dysphagia), or speach problems (dysarthria). Other symptoms are seizures, blindness, and coma. Leukoencephalopathy usually occurs in children or teen swho relapsesd and recieved crania radiation plus high total doses of IV and/or intrathecal methotrexate."

Childhood Leukemias, Ching-Hon Pui, editor. 1999, Cambridge University Press, p 470.

"Leukoencephalopathy has been primarily attributed to injury of white matter from chronic methotrexate toxicity. Cranial radiation therapy may exacerbate leukoencephalopathy by compromising the blood-brain barrier and permitting increased concentratis of drug into the CNS."

Journal Abstracts on Leukoencephalopathy found from a search on PubMed 6/01.

Toxic Leukoencephalopathy. Christopher M. Filley, M.D., and B.K. Kleinschmidt-DeMasters, M.D. New England Journal of Medicine. Volume 345:425-432 August 9, 2001 Number 6.

Reversible posterior leukoencephalopathy during the treatment of acute lymphoblastic leukemia. Shin RK, Stern JW, Janss AJ, Hunter JV, Liu GT. Neurology 2001 Feb 13;56(3):388-91. PubMed Abstract.

Leukoencephalopathy after CNS prophylaxis for acute lymphoblastic leukaemia. Spencer MD. Pediatr Rehabil 1998 Jan-Mar;2(1):33-9. PubMed Abstract.

Pure methotrexate encephalopathy presenting with seizures: CT and MRI features. Lovblad K, Kelkar P, Ozdoba C, Ramelli G, Remonda L, Schroth G. Pediatr Radiol 1998 Feb;28(2):86-91. PubMed Abstract.

Coexistence of life threatening chemotherapy related leukoencephalopathy, saggital sinus thrombosis and multiple organ failure in a child with acute lymphoblastic leukemia: an unusual case with clinical recovery. Duru F, Ertem U, Dagdemir A, Kunak B, Keskin T, Saatci I, Gundogdu S, Cila A. Leuk Lymphoma 1997 Jul;26(3-4):377-85. PubMed Abstract.

CNS late effects after ALL therapy in childhood. Part I: Neuroradiological findings in long-term survivors of childhood ALL--an evaluation of the interferences between morphology and neuropsychological performance. The German Late Effects Working Group. Hertzberg H, Huk WJ, Ueberall MA, Langer T, Meier W, Dopfer R, Skalej M, Lackner H, Bode U, Janssen G, Zintl F, Beck JD. Med Pediatr Oncol 1997 Jun;28(6):387-400. PubMed Abstract.

Treatment-related disseminated necrotizing leukoencephalopathy with characteristic contrast enhancement of the white matter. Laxmi SN, Takahashi S, Matsumoto K, Higano S, Kurihara N, Imaizumi M, Abe K, Itoyama Y, Sakamoto K. Radiat Med 1996 Nov-Dec;14(6):303-7. PubMed Abstract.

Reversal of CNS-prophylaxis-related leukoencephalopathy after CSF shunting: case histories of identical twins. Tekkok IH, Carter DA, Robinson MG, Brinker R. Childs Nerv Syst 1996 Jun;12(6):309-14. PubMed Abstract.

Childhood leukemia: central nervous system abnormalities during and after treatment. AJNR Am J Neuroradiol 1996 Feb;17(2):295-310. PubMed Abstract.

Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy--an MR analysis. Matsumoto K, Takahashi S, Sato A, Imaizumi M, Higano S, Sakamoto K, Asakawa H, Tada K. Int J Radiat Oncol Biol Phys 1995 Jul 15;32(4):913-8. PubMed Abstract.

A list member wrote the following summary of her son's leukoencephalopathy, in hope of helping other parents in the same situation. Many thanks to her!! The child's name has been changed for privacy reasons.

"Mike was 8 years old when diagnosed with ALL. Shortly after beginning chemotheraphy treatments Mike had a generalized seizure which warranted a CT scan and MRI.

Ten days into treatment we learned Mike's scans were showing signs of early leukoencephalopathy.

At week 7 of treament Mike had cranial radiation (1800 cGy).He also had 10 TIT's and 3 double IT's during the course of his treatment.

8 months into treatment Mike developed an unusual gait and another MRI was done. This MRI found leukoencephalopathy had intensified and there was also a finding of white matter atrophy.

Two further MRI's during treatment showed leukoencephalopathy was not progressing and was in fact stable.

Mike had two neuropsychological assessments done during the course of his treatment.The first set of tests showed Mike's intelligence to be in the normal range although there were several areas of concern. Recommendations were made to assure Mike would continue to make academic progress.We had an IEP drawn up and Mike received resource help through the school board. He was successful in completing grade 4 and 5.

Towards the end of grade 5 we noticed changes in Mike. His balance and coordination were poor. His listening skills were declining and his memory was poor.It was difficult at times to carry on a conversation with Mike, he had a hard time concentrating on what was being said to him and he would often ask us to repeat things for him. At this time we requested a repeat neuropsychological assesment.

We received results of this assessment when Mike was in grade 6 and really struggling to keep up to his peers. The results were devastating. His intelligence was now in the low normal/borderline range and significant difficulties in a number of cognitive and academic functions were evident. We were advised to apply for a full time teachers aid to help him in the classroom.We are in the midst of waiting to hear if this will be granted.

We have been told by his oncologists and the neuropsychologist that 'our goal' for Mike is to have him stay in school in the hopes that he will eventually become an 'independant adult who can balance a cheque book'. Very hard to hear.

Mike's life has been profoundly affected by the very chemo and radiation that saved him. We are deeply saddened by his losses but we have also set our hopes much higher for our son. The tests Mike underwent do not take into consideration his determination and terrific sense of humour. Mike may not grow up to be a rocket scientist but he has much to offer the world and I know he will be successful~in his own way.My hope is that he follows his dreams wherever they may take him.With a heart as big as his he will make a difference in this world."

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