Drugs & Leukoencephalopathy
Neurology. any of a group of diseases that affect the white matter of the brain, occurring especially in infants and children.
Drug reaction citations

Vaccines

Raptiva, a medication prescribed to treat Psoriasis, can cause viral infections. This is admitted by Raptiva's manufacturer, Genentech, and has been confirmed by the FDA. Indeed, the link between Raptiva and viral infections is so clear that Genentech recently agreed to withdraw all of the Raptiva on the U.S. market, based on the viral infections diagnosed in Raptiva patients in America and around the world.  Prescribed to treat psoriasis, Raptiva (efalizumab) is an injectable medication that is known to increase the risk of developing severe, life-threatening infections, including: bacterial sepsis (a blood infection), invasive fungal disease, progressive multifocal leukoencephalopathy/ PML (a type of Raptiva brain infection in which the white matter of the brain swells), viral meningitis (an infection that causes inflammation of the brain and/or spinal cord).  Deaths have been reported by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency, the FDA's counterpart for the EU (European Union). The Raptiva deaths were apparently due to PML (progressive multifocal leukoencephalopathy), a devastating and rare brain infection.

Beyenburg S, Scheid B, Deckert-Schluter M, Lagreze HL.Chronic progressive leukoencephalopathy in adult celiac disease.Neurology. 1998 Mar;50(3):820-2.PMID: 9521289 [PubMed - indexed for MEDLINE]

Critchley P, Abbott R, Madden FJ. Multifocal inflammatory leukoencephalopathy developing in a patient receiving 5-fluorouracil and levamisole.Clin Oncol (R Coll Radiol). 1994;6(6):406.PMID: 7873488 [PubMed - indexed for MEDLINE]
A single case of multifocal inflammatory leukoencephalopathy, which developed during a course of adjuvant chemotherapy with 5-fluorouracil (5FU) and levamisole is reported. Clinical features developed slowly and were not dramatic; this condition may therefore frequently be missed.

Enterline DS, Davey NC, Tien RD. Neuroradiology case of the day. Multifocal inflammatory leukoencephalopathy due to treatment with 5-fluorouracil and levamisole.AJR Am J Roentgenol. 1995 Jul;165(1):214-5. No abstract available.PMID: 7785607 [PubMed - indexed for MEDLINE]

Figueredo AT, Fawcet SE, Molloy DW, Dobranowski J, Paulseth JE. Disabling encephalopathy during 5-fluorouracil and levamisole adjuvant therapy for resected colorectal cancer: a report of two cases.Cancer Invest. 1995;13(6):608-11.PMID: 7583711 [PubMed - indexed for MEDLINE]

We observed leukoencephalopathy in 1 patient, and progressive dementia in another, during the administration of 5-fluorouracil (5-FU) and levamisole. A retrospective search, among 80 other patients with resected colorectal cancer receiving 5-FU and levamisole as adjuvant therapy, 166 resected malignant melanoma patients receiving adjuvant levamisole, and 254 advanced colorectal cancer patients receiving 5-FU often combined with leucovorin, for other cases of encephalopathy was negative. The frequency of this neurotoxicity is low (about 2% of patients receiving 5-FU and levamisole), but it appears specific for this combination of drugs. The lack of complete reversibility on stopping the drugs is worrisome, as this therapy is used to improve the curability of resected colon cancer.

Ferroir JP, Fenelon G, Beaugerie L, Avenin Recoing D.[Multifocal inflammatory leukoencephalopathy: a complication of chemotherapy by fluorouracil and levamisole]Rev Neurol (Paris). 1994 Jun-Jul;150(6-7):471-4. French.PMID: 7747017 [PubMed - indexed for MEDLINE]
Two female patients with an adenocarcinoma of the colon (Duke stages B and C) underwent colectomy followed by adjuvant chemotherapy combining 5 fluorouracil (5 FU) and levamisole. Secondary neurological manifestations occurred in both patients including vertigo, nausea and vomiting, dizziness with loss of balance, slow ideation, impaired memory, headache and, on one case, central origin facial paralysis. Symptoms appeared between the 11th and 34th week of treatment. The patients had received 9 to 30 g 5 FU and 2.7 to 7.6 g levamisole. CT scan and/or MRI first suggested cerebral metastases then demyelinisation. The clinical signs disappeared spontaneously in less than one month. The brain images were unchanged. The 5 FU/levamisole combination was undoubtedly responsible for the neurological manifestations. Levamisole may have potentialized the effect of 5 FU leading to demyelinisation. Whether chemotherapy should be stopped or not is debated.

Furuya A, Shiroyama H, Yano Y, Kishida S, Okeda R.  [Report on an autopsy of a cancer patient with Carmofur (HCFU) leukoencephalopathy]Rinsho Shinkeigaku. 1987 Nov;27(11):1430-40. Review. Japanese. No abstract available.PMID: 3329075 [PubMed - indexed for MEDLINE]

Fujikawa A, Tsuchiya K, Katase S, Kurosaki Y, Hachiya J. Diffusion-weighted MR imaging of Carmofur-induced leukoencephalopathy.Eur Radiol. 2001;11(12):2602-6.
Carmofur (1-hexylcarbamyl-5-fluorouracil), a derivative of 5-fluorouracil (5-FU), has been widely used in Japan as a postoperative adjuvant chemotherapy agent for colorectal and breast cancer. Periventricular hyperintensity on T2-weighted MR images in carmofur-induced leukoencephalopathy confront the physician with a broad range of differential diagnoses. We describe two cases of carmofur-induced leukoencephalopathy in which diffusion-weighted MR imaging revealed periventricular hyperintensity. We compared their findings with those of age-related periventricular hyperintensity in five patients and found discrepancies in signal intensity of periventricular areas. Our results suggest that diffusion-weighted MR imaging may be useful to differentiate carmofur-induced leukoencephalopathy from age-related periventricular hyperintensity.

Glass JP, Lee YY, Bruner J, Fields WS. Treatment-related leukoencephalopathy. A study of three cases and literature review.Medicine (Baltimore). 1986 May;65(3):154-62. Review.PMID: 3517552 [PubMed - indexed for MEDLINE]

The etiology and pathogenesis of treatment-related leukoencephalopathy remain obscure. The evidence is substantial, however, that radiation therapy in combination with higher cerebral concentrations of certain chemotherapeutic agents such as MTX increases the likelihood of permanent damage. There is no therapy of apparent benefit for treatment-related leukoencephalopathy, but reasonable alternatives include 1) withholding chemotherapy and/or radiation, 2) administering calcium leucovorin in high doses intravenously in methotrexate-induced leukoencephalopathy (26), or 3) perfusing the subarachnoid space (2) from above through an Ommaya reservoir and out from below through a lumbar puncture needle or lumbar subarachnoid catheter. Because CT scan abnormalities and subtle mental or intellectual changes are often noted before the full-blown clinical presentation, a prospective study involving periodic CT scanning as well as formal neuropsychologic testing appears worthwhile in all patients who are to receive cranial irradiation and/or chemotherapy in the prophylaxis or active treatment of CNS disease in order to detect and perhaps even to prevent this adverse side effect of cancer therapy.

Hoelzer D. [Leukoencephalopathy after the intrathecal administration of cytostatics in acute lymphatic leukemia]Dtsch Med Wochenschr. 1994 Nov 25;119(47):1637. German. No abstract available.PMID: 7982375 [PubMed - indexed for MEDLINE]

Hugonenq C, Lethel V, Chambost H, Michel G, Chabrol B, Mancini J.[Progressive multifocal leukoencephalopathy revealing AIDS in a 13-year-old girl]Arch Pediatr. 2002 Jan;9(1):32-5. French.PMID: 11865546 [PubMed - indexed for MEDLINE]
CASE REPORT: A 13-year-old girl with an immunosuppression developed a right hemiparesis and a cerebellar syndrome. She was seropositive for HIV. A progressive multifocal leukoencephalopathy (PML) was suspected because of white matter lesions (MRI) and established on detection of JC virus in CSF by polymerase chain reaction (PCR). In spite of highly active antiretroviral treatment (HAART) and cidofovir, she died three months later. CONCLUSION: Late AIDS diagnosis was established during a neurological complication, 13 years after a neonatal transmission. PML caused by JC opportunistic virus still has a poor prognosis.

Ito Y, Arahata Y, Goto Y, Hirayama M, Nagamutsu M, Yasuda T, Yanagi T, Sobue G. Cisplatin neurotoxicity presenting as reversible posterior leukoencephalopathy syndrome. AJNR Am J Neuroradiol. 1998 Mar;19(3):415-7.PMID: 9541291 [PubMed - indexed for MEDLINE]
Visual disturbance, hypertension, convulsions, and unconsciousness developed in a 70-year-old man after cisplatin chemotherapy and upper-limb amputation for osteosarcoma. MR imaging revealed bilateral reversible abnormalities in the occipital, parietal, and frontal white matter. Clinical and neuroradiologic features corresponded to reversible posterior leukoencephalopathy syndrome (RPLS), which some immunosuppressive and chemotherapeutic drugs have been reported to trigger. Cisplatin may be among these drugs. Our patient also had hypomagnesemia, which may have figured in the pathophysiology.

Ilhan I, Cila A, Buyukpamukcu M, Akyuz C, Kutluk T, Berberoglu S. Methotrexate-induced leukoencephalopathy. A case report. Turk J Pediatr. 1995 Jul-Sep;37(3):275-8.PMID: 7502368 [PubMed - indexed for MEDLINE]
A six-year-old girl with non-Hodgkin's lymphoma who was treated with both intravenous (IV) and intrathecal (IT) methotrexate and developed brain damage secondary to the cytostatic drug is described. This patient displayed hypertension, hypothermia/hyperthermia, lethargy, deterioration and coma as clinical findings, and bilateral, focal white matter hyperintensities in the occipital lobes were seen in her magnetic resonance imaging (MRI). Treatment-related leukoencephalopathy is one such adverse effect of IT methotrexate administration on the central nervous system and usually appears in a generalized form.

Kimmel DW, Schutt AJ.  Multifocal leukoencephalopathy: occurrence during 5-fluorouracil and levamisole therapy and resolution after discontinuation of chemotherapy.Mayo Clin Proc. 1993 Apr;68(4):363-5.PMID: 8455395 [PubMed - indexed for MEDLINE]

Kamata H, Murakami A, Miyagawa N, Yasui H, Nagano H, Abe S, Ueda K, Kisida S. [A case of leukoencephalopathy caused by HCFU]Gan No Rinsho. 1988 May;34(6):783-6. Japanese.PMID: 3379758 [PubMed - indexed for MEDLINE]
After a hysterectomy, a bilateral salpingo-oophorectomy, two courses of intra-peritoneal chemotherapy of Cisplatinum, Carmofur (HCFU, 600 mg/day [per os]) were given a patient who had ovarian granulosa cell tumor (malignant, stage Iai). Dizziness and loss of consciousness developed about 60 days after administration of HCFU, and leucoencephalopathy was diagnosed. A CT revealed a diffuse low density area in the white matter of the cerebrum. Myelin Basic Protein in the spinal fluid was found to amount to 9.8 mg/dl, which in norm. person is less than 4.0 mg/dl. Also, it showed parallel changes with the course of the clinical findings. HCFU easily dissolves to fat and changes to 5-FU without enzymes in the liver cell. Further HCFU also passes through Blood Brain Barrier to Produce 5-FU and its derivatives, in which the alpha-Fluoro-beta-Alanine is thought to be the culprit that brings on leucoencephalopathy. Even so, HCFU should be dosed when needed in spite of this risk. Other 5-FU modifiers also have been reported to produce the same effect in several cases.

Kuzuhara S, Ohkoshi N, Kanemaru K, Hashimoto H, Nakanishi T, Toyokura Y.   Subacute leucoencephalopathy induced by carmofur, a 5-fluorouracil derivative.J Neurol. 1987 Aug;234(6):365-70. Review.PMID: 3309192 [PubMed - indexed for MEDLINE]

Three cases of leucoencephalopathy induced by carmofur (1-hexylcarbamoyl-5-fluorouracil), an antineoplastic derivative of 5-fluorouracil are reported and the literature is reviewed. Initial symptoms were unsteady gait and dementia developing several weeks or months after carmofur had been started. Symptoms increased gradually even after stopping the drug. Severe encephalopathy with confusion, delirium or coma appeared frequently. Symptoms were usually reversible but death occasionally occurred. The EEG showed marked slowing. Computed tomography of the brains of severely intoxicated patients showed marked hypodensity of the entire cerebral white matter. Carmofur must be discontinued immediately if any psychomotor symptoms develop.

Lingesleben A, Hoffmann KT, Oppert M, Irlbacher K, Roricht S, Meyer BU.[Reversible cyclosporin A-induced leukoencephalopathy: a case report and differential diagnosis discussion]Rontgenpraxis. 2000;53(1):25-8. German.PMID: 10943139 [PubMed - indexed for MEDLINE]

The pathogenesis of Cyclosporin A (CsA) induced toxic leukoencephalopathy is unclear. CCT and CMRI reveal hypodense respectively hyperintense bilateral and symmetrical changes predominantly in the posterior white matter. We report a patient with a severe CsA induced toxic leukoencephalopathy in whom clinical symptoms (complete loss of brainstem functions, coma) and morphological changes in CCT and CMRI were completely reversible after immunosuppression with CsA has been stopped. We furthermore discuss the differential diagnoses of CCT and CMRI findings.

Luppi G, Zoboli A, Barbieri F, Crisi G, Piccinini L, Silingardi V. Multifocal leukoencephalopathy associated with 5-fluorouracil and levamisole adjuvant therapy for colon cancer. A report of two cases and review of the literature. The INTACC. Intergruppo Nazionale Terpia Adiuvante Colon Carcinoma.Ann Oncol. 1996 Apr;7(4):412-5. Review.PMID: 8805935 [PubMed - indexed for MEDLINE]

Osako Y.[A case of reversible carmofur-induced leukoencephalopathy]No To Shinkei. 2001 Oct;53(10):986-7. Japanese. No abstract available.PMID: 11725511 [PubMed - indexed for MEDLINE]

Okoshi Y, Itoh M, Okimoto Y, Horie H, Takashima S.  [A case of FK 506-induced leukoencephalopathy] No To Shinkei. 2002 Jan;54(1):51-5. Japanese. PMID: 11868353 [PubMed - in process]
We reported a 15-year-old boy with an acute myelomonocytic leukemia and FK 506-induced leukoencephalopathy. He was received FK 506 for graft versus host disease occurred after peripheral blood stem cell transplantation. He, four weeks later, had generalized seizures and consciousness disturbance. The serum level of FK 506 was high (27.5 ng/ml). His brain MRI showed abnormal high intensity areas in the frontal and parietal white matter lesions on T2-weighted images. Neuropathological studies revealed the destruction of myelin sheeths and axons in the cerebral white matter corresponded with abnormal lesions on MRI. There were calcification and mineralization in the small vessel walls of the cortex and white matter. Osteopontin immunoreactivity was detected in the endothelial cells of small vessels. These findings suggest that the vascular damage was involved in the FK 506-induced leukoencephalopathy.

Ohara S, Hayashi R, Hata S, Itoh N, Hanyu N, Yamamoto K. Leukoencephalopathy induced by chemotherapy with tegafur, a 5-fluorouracil derivative.Acta Neuropathol (Berl). 1998 Nov;96(5):527-31. Review.PMID: 9829818 [PubMed - indexed for MEDLINE]
We report an autopsy case of a 64 year-old Japanese man diagnosed as having leukoencephalopathy caused by tegafur, a 5-fluorouracil derivative, and review seven previous cases, mostly reported in Japan. In the present case, tegafur had been orally administered for the shortest period of 3 weeks in pre- and postoperative cancer chemotherapy. He died 2 years later after having made a slight recovery from a prolonged akinetic mute state. Unlike similar cases previously reported, the degeneration of the white matter was most prominent in the temporal lobes. Histologically, the severely involved white matter showed nearly complete myelin and axonal loss with a proliferation of hypertrophic astrocytes. In the less severely involved areas, such as in the frontal white matter where myelin was relatively well preserved, numerous activated microglial cells and a small number of T lymphocytes were identified immunohistochemically. The cerebral cortex, cerebellum and brain stem were well preserved, which is consistent with the previous reports. Literature review revealed that the histopathological features of the lesions reported in human cases are quite different from those reported in animal experiments.

Saitoh H, Shinohara Y, Fujita H, Aoki Y, Takagi S. A case of carmofur-induced leukoencephalopathy--MR images and CT findings.Tokai J Exp Clin Med. 1989 Sep;14(4):357-60.PMID: 2487975 [PubMed - indexed for MEDLINE]
In a patient with carmofur-induced leukoencephalopathy with a fairly good prognosis, serial MR images demonstrated reversible abnormal signal intensity areas located in the cerebral white matter surrounding the lateral ventricles. These findings suggested that the edematous change together with demyelination of the white matter is important in the pathogenesis underlying carmofur-induced leukoencephalopathy.

Shimizu C, Kimura S, Yoshida Y, Nezu A, Saitoh K, Osaka H, Aihara Y, Nagasaka Y. Acute leucoencephalopathy during cyclosporin A therapy in a patient with nephrotic syndrome.Pediatr Nephrol. 1994 Aug;8(4):483-5. Review.PMID: 7947043 [PubMed - indexed for MEDLINE]

A 13-year-old girl with nephrotic syndrome (NS) developed acute leucoencephalopathy during combination therapy with cyclosporin A (CyA) and prednisolone (PSL). The patient had a generalized motor seizure followed by coma at 19 days after CyA administration. Magnetic resonance scanning performed on the 1st hospital day revealed white matter lesions in the subcortices of the parietal and occipital lobes, brain stem and cerebellum. These lesions had completely resolved on the 10th hospital day. This episode might be caused by CyA because the clinical course and laboratory data revealed neither inflammation nor other causative factors. To our knowledge, this is the first report of acute leucoencephalopathy during combination therapy with CyA and PSL in a patient with NS.

Stone JA, Castillo M, Mukherji SK. Leukoencephalopathy complicating an Ommaya reservoir and chemotherapy.Neuroradiology. 1999 Feb;41(2):134-6. PMID: 10090607 [PubMed - indexed for MEDLINE]
We describe the imaging findings in an unusual case of biopsy-proven, methotrexate-induced leukoencephalopathy complicating a malfunctioning Ommaya reservoir in a patient with lymphoma.

Torocsik HV, Curless RG, Post J, Tzakis AG, Pearse L. FK506-induced leukoencephalopathy in children with organ transplants.Neurology. 1999 Apr 22;52(7):1497-500.PMID: 10227644 [PubMed - indexed for MEDLINE]
FK506-induced leukoencephalopathy is a well-known entity in adult organ transplant patients. The neurotoxicity of FK506 immunosuppression is frequently reversible, with either reduction or cessation of the drug. This neurologic syndrome is not well documented in children. We report the clinical and radiologic features in four pediatric cases of FK506 leukoencephalopathy. In two of the four patients this syndrome was reversible.

Thyagarajan GK, Cobanoglu A, Johnston W. FK506-induced fulminant leukoencephalopathy after single-lung transplantation.Ann Thorac Surg. 1997 Nov;64(5):1461-4.PMID: 9386723 [PubMed - indexed for MEDLINE]

FK506 is being used increasingly to prevent rejection after organ transplantation. Its use is associated with a wide spectrum of neurotoxicity, which has been described after most solid organ transplantations, but reports after lung transplantation are extremely rare. This is a report of the pathologic correlation of the clinical and radiologic features of delayed FK506-induced fulminant leukoencephalopathy after single-lung transplantation. The patient presented with neurologic symptoms that progressed to seizure activity. Neuroimaging showed diffuse changes in the brain, and results of a brain biopsy were consistent with leukoencephalopathy with microglial and astrocytic activation. The patient had a remarkable improvement in clinical status after discontinuation of FK506 administration, with resolution of the changes seen on neuroimaging.
Tomura N, Sashi R, Hashimoto M, Hirano H, Sato K, Hirano Y, Watarai J, Watanabe A. [MRI abnormalities of the brain in neurologic complications following treatment of cancer in children]No To Shinkei. 1996 Jul;48(7):623-30. Japanese.PMID: 8752996 [PubMed - indexed for MEDLINE]
During a 3-year period, 6 of 50 children with systemic malignacies developed neurologic complications such as hemiparesis, convulsions and loss of consciousness. The children consisted of 1 boy and 5 girls, from 3 to 12 years old, 3 with acute lymphoblastic leukemia and 3 with malignant lymphoma. Four patients received induction treatment that included intravenous administration of L-asparaginase and/or intrathecal administration of methotrexate. One patient received induction treatment and consolidation treatment that included intravenous administration of L-asparaginase. One patient received induction and consolidation treatment, and the protocol for peripheral blood stem cell transplantation. Laboratory examinations revealed coagulation dysfunction in 3 patients treated with L-asparaginase and 1 patient with disseminated intravascular coagulation (DIC). Magnetic resonance imaging (MRI) was performed on a 1.5-T unit, using spin-echo or fast spin-echo sequences. T1-weighted, T2-weighted, and proton density-weighted images were obtained in the axial and/or coronal plane (section thickness, 4 mm; inter-section gap, 2 mm). MRI was initially performed within 36 hours after the onset in all patients, and follow-up MRIs were performed for 6 months. MRI showed lesions involving the cortex and subcortex in 4 patients with coagulation dysfunction. In 2 of these 4 patients, Gd-enhanced T1-weighted images showed contrast enhancement in the surface of the gyrus, suggesting focal vascular stasis. Serial MRI revealed nearly complete resolution of the lesions. Symptoms were relieved in every case. The lesions on MRI were presumed to be due to venous thrombosis related to the coagulation dysfunction caused by L-asparaginase or DIC. On the other hand, in 2 patients with onset after intrathecal administration of high-dose methotrexate and cytarabine, MRI revealed multiple lesions involving the centrum semiovale and periventricular white matter. No Gd-enhancement of the lesion was detected. This MRI finding was consistent with leukoencephalopathy. As time passed, the symptoms improved completely, and the lesions became better demarcated. MRI is useful for differentiating lesions related to coagulation dysfunction from leukoencephalopathy.

Werring DJ, Chaudhuri KR. Human immunodeficiency virus-related progressive multifocal leukoencephalopathy presenting with an akinetic rigid syndrome.Mov Disord. 1996 Nov;11(6):758-61. No abstract available.PMID: 8914114 [PubMed - indexed for MEDLINE]

Yamada T, Okamura S, Okazaki T, Ushiroyama T, Yanagawa Y, Ueki M, Sugimoto O, Yamazaki H, Sugino M, Masui Y. Leukoencephalopathy following treatment with carmofur: a case report and review of the Japanese literature.Asia Oceania J Obstet Gynaecol. 1989 Jun;15(2):161-8. Review.PMID: 2667512 [PubMed - indexed for MEDLINE]

A 53-year-old woman was treated with 5 courses of CAP treatment following operation for FIGO Stage Ia cancer of the ovary in September 1986. And in April 1987, she started an oral adjuvant chemotherapy with 400 mg/day of carmofur. In early June, she developed vertigo and dysarthia and was hospitalized. A CT scan showed low-density areas adjacent to both lateral ventricles, and an EEG revealed abnormally slow waves. She improved gradually after carmofur was discontinued and left the hospital in October 1987. There have been 24 reported cases of leukoencephalopathy because of carmofur in Japan, but the pathophysiological mechanism involved is not known. Since it is more common in women than in men, its incidence will probably increase in gynecological patients. Therefore, we must be on the lookout for central nervous system signs and symptoms in patients receiving adjuvant chemotherapy with carmofur.

Yasue M, Ishijima B, Sato J, Mizutani T, Morimatsu Y.  [A case of toxic leucoencephalopathy induced by 5FU derivatives]No Shinkei Geka. 1985 Nov;13(11):1229-34. Japanese.PMID: 3937066 [PubMed - indexed for MEDLINE]
A case of toxic leucoencephalopathy induced by 5 FU derivatives is reported. A 46-year-old woman was diagnosed as having breast cancer, and radical mastectomy was performed on May, 1982. After operation, she was given irradiation and 5FU derivative (tegafur or carmofur) 600 mg and Nolvadex 20 mg (tamoxifen citrate) were administered every day. After taking the medication for a month, she began to stagger and developed a tremor in both arms. She was admitted to our hospital on August 16, because she showed evidence of dysarthria and memory disturbance in addition to her initial complaints. Soon after admission, she developed akinetic mutism, and metastasis in the brain stem was suspected. In spite of her severe condition, she was given radiation over the posterior fossa and continued the medication. On September 22, CT disclosed low density area in the centrum semiovale bilaterally. She died of DIC on November 30. An autopsy was performed. The brain weight was 1110 g and the outer surface of the brain was normal. In frontal cut surfaces stained with K.B., bilateral degeneration of the centrum semiovale was apparent. Microscopically, the degree of myelin degeneration was stronger than that of axon, and numerous fatty granular cells were found in the degenerated area. There were no bizarre shaped astrocytes, inclusion body or cellular infiltration. Fibrillary gliosis was scanty. No metastasis was found in the central nervous system or other organs. Based on these pathological findings and clinical history, toxic leucoencephalopathy induced by 5 FU derivatives was suggested.