Objective
Antibodies to glutamic acid decarboxylase (GAD) have been described in a few patients with temporal lobe epilepsies consistent with limbic encephalitis (LE). We studied a cohort of patients with recent‐onset temporal lobe epilepsy caused by LE to test for GAD antibody positivity and response to immunotherapies.
Methods
Over a period of 3.75 years, 138 patients aged ≥18 years investigated at the Department of Epileptology, University of Bonn, for recent‐onset epilepsy were prospectively collected and studied for cliniconeuroradiological features of LE, autoantibodies, and treatment responses.
Results
Fifty‐three adult patients fulfilled the criteria for LE: (1) limbic signs and symptoms for ≤5 years and (2) brain MRI revealing mediotemporal encephalitis (T2/fluid attenuated inversion recovery hyperintensity without atrophy). Nine had high‐titer GAD antibodies; 10 had voltage‐gated potassium channel (VGKC) antibodies. Patients with GAD antibodies were younger (median age, 23 years; range, 17‐66 years) (p = 0.003) and presented with seizures only, whereas polymorphic limbic features were more common in the VGKC antibody‐positive group (p < 0.001). None had tumors. Patients with GAD antibodies more frequently had cerebrospinal fluid oligoclonal bands (p = 0.009) and intrathecal secretion of the specific antibody (p = 0.01). Following monthly intravenous methylprednisolone pulses, GAD antibodies remained highly elevated in 6/6 patients, whereas VGKC antibodies normalized in 6/9 patients (p = 0.03). Despite more intense anticonvulsive treatment in the GAD antibody‐positive group (p = 0.01), none of these patients became seizure free, unlike all of the patients with VGKC antibodies (p < 0.001).
Interpretation
High‐titer GAD antibodies define a form of nonparaneoplastic LE. This is a chronic, nonremitting disorder and should be included in the differential diagnosis of patients with TLE and mediotemporal encephalitis. Therapeutic trials of other immunotherapies should be undertaken. ANN NEUROL 2010;67:470–478
Pancytopenia is regularly encountered in hematology practice, yet there exist few published assessments of the frequencies of various etiologies, and these frequencies exhibit substantial geographic variation. We reviewed bone marrow specimens from pancytopenic adults to determine the most common etiologies and to identify associations with clinical and laboratory findings. Of 132 patients with no history of hematolymphoid neoplasia, no prior bone marrow study for pancytopenia and no recent cytotoxic chemotherapy, 64% had clonal hematopoietic disorders. Most common were myeloid processes: 26% of patients had acute myeloid leukemia, and 17% had myelodysplasia. Less common were lymphoid neoplasms such as non-Hodgkin lymphoma (6%), hairy cell leukemia (5%) and precursor B acute lymphoblastic leukemia (4%). Among non-clonal cases, the most common specific diagnoses were aplastic anemia (5%), megaloblastic anemia (2%) and human immunodeficiency virus (HIV)-related changes (2%). Clonal diagnoses were associated with more severe cytopenias than non-clonal cases. Circulating nucleated erythroid precursors, immature granulocytes and blasts were seen more frequently in clonal cases. Nearly two-thirds of cases of new onset pancytopenia in adults in our North American practice setting have a clonal etiology, with myeloid neoplasms being most common. Blood counts and peripheral smear findings can provide insights into the likelihood of a clonal etiology.
Context.-The College of American Pathologists published guideline recommending bone marrow synoptic reporting for hematologic neoplasms.Objective.-To evaluate the impact of pathology-driven algorithmic testing (PDAT) with integrated reporting for bone marrow examination on test utilization, ability to render a specific World Health Organization diagnosis, and clinician satisfaction 1 year after implementation.Design.-We reviewed the hematopathology reports, integrated synoptic reports, and ancillary test results generated during a 12-month period. The initial diagnosis from the hematopathology report was compared with the final diagnosis on the integrated synoptic reports. Test utilization data were compared with a previous year in which ancillary testing was ordered at clinician discretion. Clinicians were anonymously surveyed to assess their satisfaction with PDAT and integrated reporting.
A 66-year-old man with a history of hepatitis C virus and liver transplantation presented to the emergency department for shortness of breath. He had received weekly filgrastim for chronic neutropenia, and immediately before admission he had received 3 days of filgrastim and 1 day of pegfilgrastim. A hemogram showed a white blood cell count of 4.54 K/mL with 23% blastic cells. Emergent bone marrow specimen revealed 50% blasts and 43% promyelocytes with Auer rods (panel A). Flow cytometry demonstrated a predominant population expressing myeloid antigens, CD38, CD117, and dim CD7, but not HLA-DR or CD34. These features suggested acute promyelocytic leukemia (APL) and treatment with all-trans-retinoic acid (ATRA) was initiated. Subsequent fluorescence in situ hybridization testing for promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARa) with dual-fusion and RARa break-apart probes was negative (panel B). Molecular testing for PML/ RARa messenger RNA by reverse-transcriptase polymerase chain reaction was also negative, but FLT3-ITD was positive. Despite morphologic and immunophenotypic evidence for APL, confirmatory cytogenetic and molecular tests were negative; therefore, acute myeloid leukemia-not otherwise specified was the final diagnosis.Marrow specimens obtained after exposure to granulocyte colony-stimulating factor preparations should be interpreted cautiously because the features of AML may be altered, allowing confounding overlap with APL. This distinction must be made to avoid unnecessary risk of toxicity-although it is low-as a result of ATRA use in non-APL patients.For additional images, visit the ASH IMAGE BANK, a reference and teaching tool that is continually updated with new atlas and case study images. For more information visit http://imagebank.hematology.org.
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