Rare clinical findings in a patient with sporadic hemiplegic migraine: FDG-PET provides diminished brain metabolism at 10-year follow-up.

BACKGROUND: Sporadic hemiplegic migraine (SHM) is defined as migraine attacks associated with some degree of motor weakness during the aura phase and where no first-degree relative has identical attacks. SHM has a wide inter- and intraindividual clinical spectrum and, in case of prolonged aura symptoms and disturbed consciousness, can mimic several other acute neurological diseases. CASE: In 1996, during his wedding night, a 28-year-old man developed left face, arm and leg weakness, nausea and a throbbing headache. Neurological examination on presentation revealed stupor, fever, meningism and left hemiplegia. There were no abnormalities on emergency magnetic resonance. Lumbar puncture showed mild lymphocytic pleocytosis and slightly elevated protein. He received symptomatic treatment. Subsequent genetic analysis revealed the T666M mutation in the CACNA1A gene of chromosome 19. He was diagnosed with SHM. In 2005, at the end of another episode of hemiplegic migraine (HM), he for the first time developed an episode of paranoid psychosis with anxiety and visual hallucinations. The psychiatric symptoms resolved within a week. DISCUSSION: All perfusion SPECT and transcranial Doppler studies performed in the first days of HM attacks were consistent with hyperemia of the hemisphere contralateral to the neurological signs. FDG-PET/CT in January 2013 revealed a diffusely reduced glucose metabolism of the supratentorial cortex and marked asymmetric hypometabolism of the left cerebellum. The finding of progressive cortical metabolic dysfunction over years appears as a new finding. Glucose hypometabolism may indicate primary neuronal dysfunction as the cause of the prolonged deficits.

Heparin treatment in acute cerebral sinus venous thrombosis: a retrospective clinical and MR analysis of 42 cases.

The only randomized data on heparin treatment in acute cerebral sinus venous thrombosis (CSVT) are derived from a small number of patients. The rate of intracranial hemorrhages as a complication of high-dose heparin treatment is still unknown. This retrospective study evaluates the clinical features, neuroimaging monitoring and outcome of 42 patients with proven CSVT. Diagnosis was established by DSA, CT, MR tomography and MR angiography. All patients received heparin intravenously guided by doubling the aPTT value for 3 weeks, followed by oral anticoagulation. Partial or complete recanalization was found in 36 cases. 40 patients improved clinically, in 26 of them complete recovery was observed. One patient deteriorated and developed an apallic syndrome, one further patient died of septic multiorgan failure. Only in one patient was hemorrhagic transformation of infarcted brain tissue observed but without clinical deterioration.

Posttransplant T-cell lymphoproliferative disorders--an aggressive, late complication of solid-organ transplantation.

T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid-organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid-organ transplants. The patients ranged in age from 31 to 56 years (median, 43). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4,880 IU/L; median, 1,220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T-PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.

BCR/ABL-negative primitive progenitors suitable for transplantation can be selected from the marrow of most early-chronic phase but not accelerated-phase chronic myelogenous leukemia patients.

We have previously reported that selection of marrow cells on the basis of the CD34+HLA-DR- phenotype (34+DR-) may result in the recovery of Philadelphia chromosome (Ph)- and BCR/ABL-negative long-term culture-initiating cells (LTC-IC) in selected patients with chronic myelogenous leukemia (CML). We now present data on 27 early chronic-phase ([ECP] studied within 1 year after diagnosis) and 23 advanced-phase ([AP] late chronic phase, ie, studied >1 year from diagnosis, or accelerated phase) CML patients. Fluorescence-activated call-sorting (FACS)-selected 34+DR- and 34+DR+ cells were subjected to reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization. These cells were also cultured in long-term bone marrow culture for 1 to 5 weeks to examine the number of LTC-IC and the presence or absence of the BCR/ABL gene rearrangement in progeny of primitive LTC-IC. The number of 34+DR- cells and LTC-IC present in ECP CML marrow was similar to that in normal (NL) marrow, whereas the numbers were reduced in AP CML. Furthermore, 34+DR- cells from more than 80% of ECP CML patients were BCR/ABL mRNA- and Ph-negative and contained only BCR/ABL mRNA- and Ph-negative LTC-IC, whereas 34+DR- cells and LTC-IC from less than 40% of AP CML patients were BCR/ABL mRNA- and Ph-negative. In contrast to NL marrow, 34+DR+ cells from CML marrow, irrespective of clinical stage, contained large numbers of LTC-IC. CML 34+DR+ cells and LTC-IC were BCR/ABL mRNA- and Ph-positive. Since these studies suggested that a population of primitive progenitors that are Ph-negative can be selected from steady-state marrow in some ECP CML patients, we determined if similar results could be obtained when large quantities of marrow sufficient for transplantation are processed. We demonstrate that 1 to 3 x 10(5) BCR/ABL mRNA-negative 34+DR- cells/kg recipient body weight, containing only BCR/ABL mRNA-negative LTC-IC, can be obtained from a 2- to 2.5-L marrow collection by sequential COBE Spectra apheresis (COBE BCT, Lakewood, CO), CD34+ enrichment using the CEPRATE SC Cell-Concentrator (CellPro, Bothell, WA), and high-speed FACS. Thus, large-scale selection of a BCR/ABL mRNA- and Ph-negative 34+DR- cell population is possible in a fraction of chronic-phase CML patients, in whom these cells could be used to reconstitute the hematopoietic compartment following autologous transplantation.

Elevated serum antibody response to toxin A following splenic abscess due to Clostridium difficile.

Splenic abscess and segmental small-bowel infarction were documented in a patient from whose splenic culture Clostridium difficile was isolated. A week and a half after splenectomy and partial bowel resection, diarrhea developed and stool cultures yielded an isolate of C. difficile that was identical to the abscess isolate when subjected to restriction endonuclease analysis. The level of IgG antibody to toxin A was markedly higher in serum from this patient than in sera from patients with C. difficile diarrhea alone. This case illustrates a rare but serious extraintestinal manifestation of infection with C. difficile and suggests a correlation between serum levels of IgG antibody to toxin A and systemic exposure to C. difficile, a typically noninvasive enteric pathogen.

Functional effect of IL-7-enhanced CD19 expression on human B cell precursors.

We have previously demonstrated that IL-7 can sustain the growth of normal human B cell precursors (BCP) for several weeks on bone marrow-derived stromal cells. Flow cytometric analysis of BCP recovered from IL-7 supplemented cultures revealed two- to threefold higher levels of cell surface CD19, compared with BCP maintained without IL-7. Short term culture of BCP showed that IL-7 enhancement of CD19 was dose-dependent, with increases detected by day 1 and plateauing by days 3 to 4. IL-7 increased cell-surface CD19 on small lymphoid cells, and to a greater degree on lymphoblasts, whereas cell-surface CD10 was unchanged. The CD34+/CD19+ pro-B cell population showed a greater increase in cell-surface CD19 compared with pre-B and immature B cells. IL-1, IL-3, IL-4, IL-6, and stem-cell factor had no effect on CD19. The potential functional significance of IL-7-enhanced cell-surface CD19 was examined using a F(ab')2 fragment of anti-CD19. This reagent had no effect on [3H]TdR incorporation in BCP cultured in the absence or presence of IL-7 for 5 days, but homotypic adhesion of BCP was induced at a concentration as low as 1.0 ng/ml F(ab')2 anti-CD19. IL-7 enhanced the F(ab')2 anti-CD19 induced homotypic adhesion of BCP in a dose-dependent manner. Blocking antibody studies indicated that members of the beta 1 or beta 2 integrin families did not mediate anti-CD19-induced homotypic adhesion, even though the adhesion was completely ablated by 10 mM EDTA. The pre-B and immature leukemic B cell lines NALM-6 and 1E8 expressed comparable levels of cell-surface CD19, and exhibited comparable increases after IL-7 stimulation. However, their homotypic adhesion responses to anti-CD19 were different. NALM-6 cells exhibited a strong homotypic adhesion response to anti-CD19 that was EDTA-resistant, and beta 1/beta 2 integrin independent. 1E8 cells only responded to anti-CD19 after IL-7 stimulation; this response was EDTA-sensitive and beta 1/beta 2 integrin independent. These collective results indicate that IL-7 not only acts as a growth factor for human BCP, but also regulates signal transduction through cell-surface CD19.

Isocitrate dehydrogenase kinase/phosphatase exhibits an intrinsic adenosine triphosphatase activity.

In Escherichia coli, isocitrate dehydrogenase (IDH) is regulated by reversible phosphorylation. The bifunctional enzyme which catalyzes this phosphorylation cycle, IDH kinase/phosphatase, also exhibits a specific ATPase activity. Mutant derivatives of this protein which are nearly devoid of IDH phosphatase activity retain both IDH kinase and ATPase activity, indicating that ATP hydrolysis does not result from the cyclic phosphorylation of IDH. However, the IDH kinase and ATPase activities of these mutant proteins differ significantly from those of the wild-type IDH kinase/phosphatase expressed from the parental allele. This observation suggest that IDH kinase and IDH phosphatase do not reside on structurally independent domains. In contrast to many enzymes which catalyze kinetically unfavorable side reactions, the maximum velocity of the ATPase substantially exceeded those of IDH kinase and IDH phosphatase. ATP hydrolysis was only partially inhibited by phospho- and dephospho-IDH, with saturating levels of phospho-IDH decreasing the rate of ATP hydrolysis by a factor of approximately 5. Even in the presence of near-saturating concentrations of phospho-IDH, the rate of ATP hydrolysis was 4-fold greater than the rate of the cyclic phosphorylation of IDH.