Summary:We prospectively evaluated the neuropathological complications of 180 patients who underwent autopsy studies following bone marrow transplantation (BMT) (177 allogeneic, three autologous). The most frequent underlying disorders included severe aplastic anemia (n = 55), chronic myelogenous leukemia (n = 53), acute myelogenous leukemia (n = 24) and Fanconi anemia (n = 16). There were 114 males and 66 females. Neuropathological findings were detected in 90.55% of the patients. The most frequent findings were subarachnoid hemorrhages (SAH) (n = 57), intraparenchymal hemorrhages (IHP) (n = 49), fungal infections (n = 16), Wernicke's encephalopathy (n = 10), microglial nodular encephalopathy (n = 10) and neurotoxoplasmosis (n = 8). In only 17 patients was the brain within normal limits. Survival time after BMT averaged 5.4 months and the majority of patients died in the first 3 months post BMT (n = 105). Central nervous system (CNS) pathology was the main cause of death in 17% of the patients (n = 31), with a predominance of IHP in this particular group. Furthermore, the survival time of these patients who died of CNS causes (96.3 days) was almost half of the survival time of those who died of extra-cerebral causes (177.8 days) (P = 0.0162). IHP (70.96 vs 27.22%) (P Ͻ 0.001), fungal infections (25.8 vs 8.88%) (P Ͻ 0.001) and toxoplasmosis (9.67 vs 4.44%) (P Ͻ 0.001) were significantly more frequent in the group of patients who died due to CNS causes than in the control group. The findings of this work provide a possible guide to the possible causes of neurological syndromes following BMT. Bone Marrow Transplantation (2000) 25, 301-307. Keywords: central nervous system; bone marrow transplantation; cerebrovascular disorders; infections Bone marrow transplantation (BMT) is used to treat several malignant diseases, severe aplastic anemia, immunodeficiencies and metabolic disorders.1,2 It allows use of potentially lethal doses of chemotherapy and/or irradiation to eradicate systemic malignancy or poorly functioning con-

Toxoplasma infection following bone marrow transplantation (BMT) is infrequently reported. We report 9 cases of disseminated Toxoplasma gondii infection in BMT recipients documented during an 11-year period at our institution. The incidence of T. gondii infection in our institution (1.14 per 100 allogeneic BMT) is higher than previously reported. The most frequently affected sites were the brain, lungs, and heart. Findings common to most patients who developed toxoplasmosis were positive pre-transplant serology, allogeneic transplant and graft-versus-host disease and its treatment, as well as BMT from matched unrelated donors. All 9 patients died and 8 were diagnosed only after autopsy. Heightened awareness of the occurrence of toxoplasmosis in marrow recipients, especially in highly endemic areas, and early diagnosis and therapy are needed for a better outcome.

A chromosomal translocation involving the MYC gene is characteristic of Burkitt lymphoma (BL) and represents a molecular disease marker with diagnostic and clinical implications. The detection of MYC breakpoints is hampered by technical problems, including the distribution of the breakpoints over a very large genomic region of approximately 1,000 kb. In this article, we report on the testing and validation of a segregation fluorescence in situ hybridization (FISH) assay for MYC breakpoints on a large series of BLs. A contig of overlapping genomic clones was generated, and two probe sets flanking the MYC gene were selected. Both probe sets were tested in an interphase FISH segregation assay on 8 B-cell lymphoma cell lines and 32 lymphoma samples with proved 8q24/MYC abnormalities and validated in 47 BLs from The Netherlands, Brazil, and Uganda. MYC translocation breakpoints were identified in 98% of the tumors of the test series and in 89% of the cases of the validation series. In 89% of all positive samples, the breakpoints were located between 190 kb 5' and 50 kb 3' of MYC. Nine cases had more distant breakpoints, and in one patient an insertion of MYC into the IGH region was detected. In two of the three BLs lacking CD10 expression, no breakpoint could be detected, suggesting that CD10 is a discriminative marker of BL. We did not find consistent differences between BL and atypical BL in incidence of an MYC breakpoint.

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Summary:to carbohydrate metabolism, any increase in carbohydrate intake will also raise the need for thiamine to metabolize it, and may constitute an immediate precipitating factor for Wernicke's encephalopathy (WE) is a neuropsychiatric condition generally caused by acute thiamine deficiency some syndromes such as WE. First described by Carl Wernicke, in 1881, 7 WE is an acute neuropsychiatric condition and classically involves the triad of altered mentation, ataxia and ophthalmoplegia. It is most common among caused by thiamine deficiency. It classically involves the triad of ataxia, ophthalmoplegia and altered mental state. 6-8 alcoholics, but several other causes have been identified, including total parenteral nutrition (TPN) use. We It may be followed by a state of amnesia and confabulation, known as Korsakoff psychosis 8 which may cause death in present eight cases of WE in patients undergoing allogeneic BMT, where thiamine deficiency was caused by some patients. We present eight cases of iatrogenic WE in patients undergoing allogeneic BMT. These patients a lack of vitamin supplementation during TPN administration. Clinically, WE presented as a severe refractory presented with severe metabolic acidosis, preceded by a 'raspberry tongue' and followed by the subclinical findings metabolic acidosis, preceded by 'raspberry tongue', and ophthalmologic and neurologic dysfunction. The sites of WE. The final diagnosis was made only after autopsy examination. Data presented here represent the largest sermost affected were the periventricular structures and the thalamus, and no mammilary bodies lesions were ies in the literature and should alert physicians to this unusual entity in BMT patients, alerting them to WE as a found. Keywords: Wernicke's encephalopathy; leukemia; allopossible BMT complication. 9,10 geneic bone marrow transplantation; thiamine deficiency Patients and methods BMT is the treatment of choice for a wide variety of hema-A total of 96 allogeneic BMT were undertaken from Janutological, non-hematological, genetic and immune disary 1988 to May 1990. Autopsy materials from the fatal eases. 1 However, aside from the prolonged neutropenia and cases were studied, and eight cases with WE-like neurorisk of opportunistic infection, 2,3 conditioning may cause pathological abnormalities were diagnosed. There were five several side-effects including nausea, vomiting, mucositis females and three males with ages ranging from 14 to 37 and diarrhea, 4 leading to a reduced caloric intake and malyears (median 25 years). Diagnoses were AML in four, absorption. These complications necessitate TPN regimens CML in two and ALL in two patients. Medical records and their attendant complications. Thiamine, also known as were reviewed for conditioning regimen, clinical course vitamin B1, is a water soluble vitamin, formed by a pyrimand neuropathological features. idine and a thiazole ring linked through a methylene group. 5 In the tissues, thiamine is phosphorylated to its most active BMT procedures coenzyme form, thiamin...