Abstract
Limbic encephalitis is a rare complication reported in patients receiving an allogeneic hematopoietic stem cell transplant (HCT). It is characterized by a syndrome of short-term memory deficit, altered mental status, seizures and coma accompanied by characteristic MR imaging findings of abnormal high signal intensity on flair and T2 weighted images in the mesial temporal lobes. The incidence and risk factors for the development of of limbic encephalitis are not well studied in patients undergoing HCT. In this study we retrospectively reviewed the medical records of 399 allogeneic HCT recipients transplanted at our institution from June 1995 to June 2006 to determine the incidence of limbic encephalitis among these patients. Forty-nine of these patients received umbilical cord blood transplants (UCBT). We identified 66/399 patients who underwent MRI of the brain to evaluate neurologic symptoms; 28 patients had abnormal MRIs. The MRIs were then examined to determine if the findings were consistent with limbic encephalitis. Seven of the twenty-eight MRIs showed changes compatible with limbic encephalitis. Five of the seven patients with limbic encephalitis had undergone UCBT and 2 had received matched unrelated donor HCT. The median age of the patients was 44 years (range 32–54), 5 were female. Diseases treated were AML (3), Hodgkins disease (2), Burkitt’s lymphoma(1) and Multiple Myeloma (1). Four patients had failed prior autologous transplant. Six patients had persistent disease at the time of transplant. Total body irradiation based conditioning was given in 4 of 7 patients. All patients had received anti-thymocyte globulin (ATG) as a part of their conditioning. GVHD prophylaxis was with methylprednisolone + tacrolimus (5), mycophenolate mofetil + tacrolimus(1) and methotrexate + tacrolimus(1). The 2 patients that did not have methylprednisolone as part of GVHD prophylaxis received it as treatment for acute GVHD. All of the patients received prophylactic high dose acyclovir or valacyclovir. The median time from transplant to diagnosis was 39 days, (range 28–148). Symptoms included: short term memory deficit/confusion (6), seizures (5) and coma(4). SIADH was seen in 4 patients with a mean serum sodium of 125 mmol/L. Four patients had elevated CSF protein (median for the entire cohort 48 mg/dL; range 20–105) and glucose (82 mg/dL; 68–97). Three patients had an elevated CSF WBC count (4 cells/μL; 0–34) with lymphocyte pleocytosis (81%; 0–100). CSF bacterial and viral cultures were negative on all of the patients. Five patients had HHV-6 PCR performed; 4 of these had HHV-6 DNA detected in the CSF. Six of the seven patients recieved second line antiviral therapy with either ganciclovir or foscarnet. Three of the patients who had therapy started at the onset of symptoms had clinical improvement. Short term memory deficit persisted in all the patients. Six of the seven patients have died with the median survival of 39 days (range 4–110) from diagnosis of limbic encephalitis. One patient is alive 11 months after diagnosis with severe neurologic dysfunction. We describe a rare, but devastating complication of allogeneic transplantation affecting approximately 2% of our allografts and 10% of UCBT recipients. Heavily pretreated patients, and those receiving ATG and corticosteroids appear to have a higher risk of limbic encephalitis.
Down Syndrome and the Phonological Loop: The Evidence for, and Importance of, a Specific Verbal Short-Term Memory Deficit
