Dyke-Davidoff-Masson Syndrome: An unusual cause of status epilepticus

The Dyke-Davidoff-Masson Syndrome (DDMS) results from an insult to the growing brain in utero or early infancy, which lead to loss of neurons compromising the growth of the brain. Clinical presentation includes seizures, hemiparesis, facial asymmetry, and learning disability. Radiological findings include cerebral atrophy on one side. Here, we present a case with status epilepticus who had underlying DDMS. It is a rare syndrome and uncommon cause for status epilepticus. Infections of CNS, hypoxic ischemic encephalopathy, intracranial bleed, trauma, congenital vascular malformations are the common causes of this syndrome. Diagnosis is established after clinical history, examination, and MRI. Intractable seizures can be controlled with appropriate anticonvulsants. Subsequently, these children may require physiotherapy, speech therapy, and occupational therapy in addition to the anticonvulsant medication. Outcome is better if the seizures are controlled.The Dyke-Davidoff-Masson syndrome (DDMS) was presented for the first time in 1933 by Dyke, Davidoff, and Masson who reported a series of 9 cases.1-4 The syndrome results from an insult to the growing brain in utero, or during the early years of life.5 The insult to the developing brain results in loss of neurons compromising the growth of the brain.6 Hence, patients suffering from DDMS present with contralateral hemiparesis, seizures, mental retardation, facial asymmetry, learning disability along with radiographic findings of cerebral hemispheric atrophy on one side.2,3 It is a relatively rare syndrome, and since 1933 less than 100 cases have been reported. It may present at any age including children, adolescents, and adults.1,3 Albert Zilkha’s study comprising of 5,000 head CT scans showed 10 cases of cerebral hemiatrophy.4 Trauma, infection, stroke, ischemia, intracranial bleed, perinatal hypoxia, inflammation or congenital abnormalities including vascular anomalies are believed to be the common causes of this syndrome.2,7 These children may present with mental retardation, cerebral palsy, and epilepsy. Presentation is quite variable and they rarely present with status epilepticus (SE).8 Our objective in presenting this particular case is to highlight clinical significance of DDMS as an underlying cause of statue epilepticus.     

Prior treatment with alpha interferon does not adversely affect the outcome of allogeneic transplantation for chronic myeloid leukaemia

Summary. The timing of transplantation in chronic myeloid leukaemia is still debated and previous treatment with interferon (IFN) alpha has been reported to be deleterious. We have analysed the outcome of 438 allogeneic transplants performed between 1984 and 1995 and reported to the Société Française de Greffe de Moelle (SFGM) registry. One hundred and two patients (group I) received IFN for more than 6 weeks (median = 9 months) before transplant. Their outcome was compared with 336 other patients (group II) not pretreated with IFN. There were no significant differences between the groups for engraftment and chronic graft‐versus‐host disease (GVHD) incidence. However, other significant differences included the incidence of acute GVHD ≥ 2 at 3 months which was higher in group I (65 ± 10%) than in group II (38 ± 5%; P = 0·01). Moreover, disease‐free survival (DFS) and overall survival (OS) at 5 years were significantly shorter for group I than for group II (33 ± 10% vs. 41 ± 6%; P = 0·005)(95% CI) and (41 ± 10% vs. 55 ± 6%; P = 0·002)(95% CI) respectively. After adjustment for patient and transplant covariables in a multivariate analysis, prior IFN was not found to adversely affect transplant outcome.     

Impact of disease status and stem cell source on the results of reduced intensity conditioning transplant for Hodgkin’s lymphoma: a retrospective study from the French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

The role of reduced intensity allogeneic stem cell transplantation for the treatment of relapsed/refractory Hodgkin’s lymphoma remains controversial. We retrospectively analyzed 191 patients who underwent reduced intensity allogeneic stem cell transplantation between 1998 and 2008 for relapsed or refractory Hodgkin’s lymphoma and whose data were reported to the French registry. The median follow-up was 36 months. The estimated 3-year overall survival rate, progression-free survival rate, cumulative incidence of relapse and cumulative incidence of non-relapse mortality were 63%, 39%, 46%, and 16%, respectively. There was no difference in outcome between patients in complete response and in partial response at the time of transplantation with regards to overall survival (70% versus 74%, no significant difference) and progression-free survival (51% versus 42%, no significant difference). Patients with chemoresistant disease had a shorter overall survival (39% at 3 years; P=0.0003) and progression-free survival (18% at 3 years; P=0.001) than patients in complete remission. The use of umbilical cord blood as the source of stem cells was associated with a poor outcome with an increased risk of death with a hazard ratio of 3.49 (95% confidence interval: 1.26 to 9.63; P=0.016). The use of peripheral blood was associated with a better outcome for patients who where alive 1 year after transplantation with a hazard ratio of 0.38 (95% confidence interval: 0.17 to 0.83; P=0.016). Disease status at transplantation remains the most important risk factor for outcome. Our data suggest that the use of peripheral blood should be preferred whereas umbilical cord blood should be used with caution.     

Double intensive consolidation chemotherapy in adult acute myeloid leukemia

Of 115 adult patients with de novo acute myeloid leukemia (AML), 87 (75.5%) achieved complete remission (CR) after induction treatment with zorubicin and conventional doses of cytarabine (Ara-C). Patients under age 45 years with histocompatibility locus antigen-identical sibling underwent bone marrow transplantation (BMT). The others were treated with two courses of intensive consolidation chemotherapy (ICC): course 1 with 4 days of high-dose Ara-C and 3 days of amsacrine (m-AMSA); course 2 with carmustine (BCNU), Ara-C, cyclophosphamide, and etoposide. Forty-two patients received both planned courses, 15 received only the first, and 13 patients could only support conventional maintenance therapy. Four patients died during consolidation. With a median follow-up of 60 months, the disease-free survival (DFS) after ICC at 5 years is 40.3% (+/- 6.5%), with no statistically significant difference between patients receiving one or two courses. The DFS for the 17 transplanted patients is comparable (P = .72) and is lower for the 13 excluded patients (23% +/- 11.5%, P = .046). Age did not influence the probability of remaining in CR. In univariate analysis, three parameters had a negative impact on the 5-year DFS: a high initial WBC count (52% for patients with less than 30 x 10(9) WBC/L v 12% for patients with greater than 30 x 10(9) WBC/L, P = .01), a long delay between induction treatment and course 1 (+/- 60 days; 63% v 29%, P = .01), and a long delay between course 1 and course 2 (+/- 60 days, 61.5% v 28.5%, P = .05). In multivariate analysis (Cox model), only the WBC count remained significant. This study confirms the value of intensive postremission chemotherapy, which can be compared in AML with allogeneic or autologous BMT. It also demonstrates the prognostic value of the initial WBC count. The optimal modalities of ICC remain to be defined by further studies.     

Spontaneous remission in adult acute leukemia

A spontaneous complete remission of 34 months' duration was observed in an adult patient with acute myeloblastic leukemia. The remission occurred after a severe febrile pneumonia, which was treated with leukocyte transfusions. At relapse, chromosomal abnormalities reappeared slowly. Such spontaneous complete remissions, almost always associated with bacterial infections and blood transfusions, are extremely rare, and are usually of short duration. Previous cases are summarized, and the role of etiologic factors, including those related to the leukemic proliferation, are discussed.     

Digital scrapbooking as a standard of care in neonatal intensive care units: initial experience

In this article, we describe a digital photo scrapbooking project as a standard of care for the parents of infants admitted in a neonatal intensive care unit (NICU). Photographs were taken from birth until discharge or expiry at special moments during the infant's hospitalization and used to create a digital scrapbook with daily notes by the parents. The scrapbook and original photos were provided on a CD at discharge or at expiry. Parents and their families unanimously appreciated the photos and the opportunity to record their thoughts, and considered the CDs as a lifetime treasure. Digital photo journaling could be implemented as a standard of care at other institutions with a commitment from the nursing and ancillary staff of the NICU and labor and delivery department, with possible support from volunteers.     

Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities

The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics. CK was observed in 129 patients (69%), and 110 exhibited abnormalities according to the definition of MK (59%). MK(+) patients had a complete response rate significantly lower than MK(-) patients: 37% vs 64% (P = .0008), and their 2-year overall survival was also decreased at 7% vs 22% (P < .0001). In multivariate analysis, MK appeared as the major independent prognostic factor related to complete remission achievement (odds ratio = 2.3; 95% confidence interval, 1-5.4, P = .05) and survival (hazard ratio = 1.7; 95% confidence interval, 1.1-2.5, P = .008). In the subgroup of 129 CK(+) patients, survival was dramatically decreased for MK(+) patients (8% vs 28% at P = .03). These results demonstrate that MK is a major independent factor of very poor prognosis in elderly AML.     

Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia

The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia is of growing interest as a prognostic marker of patients' outcome. Multiparameter flow cytometry (MFC), tracking leukemia‐associated immunophenotypic patterns, has been shown in several studies to be a useful tool to investigate MRD. Here, we report a multicenter prospective study which allowed to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to predict outcome. This study included 276 patients, in 10 different MFC centers, of whom 268 had at least 1 MRD check point. The combination of a CD45, CD34, and CD33 backbone, with the addition of CD117, CD13, CD7, and CD15 in 2 five‐color tubes allowed to define each patient's multiparameter immunophenotypic characteristics at diagnosis, according to a Boolean combination of gates. The same individual diagnosis gating strategy was then applied at each MRD time point for each patient. MRD levels were stratified according to log by log thresholds, from 5 × 10^?2 (the classical morphological threshold to define remission) down to <5 × 10^?5. MRD was found to be constantly negative (<5 × 10^?5) for 148 patients. Survival analyses significantly associated MRD negativity with a good prognosis and any positive value with poorer outcome. All P values were <0.0001 both for disease‐free and overall survival at the earliest time point (post‐induction, MRD1) as well as when considering all time points together. Finally, MRD levels were independent of cytogenetics and allowed in fact to further stratify all cytogenetics risk groups. In summary, this multicenter study demonstrates that a simple combination of immunophenotypic markers successfully allows for the detection of MRD in acute myeloblastic leukemia patients, with a strong correlation to outcome.     

Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database

The place of allogeneic bone marrow transplantation (BMT) in the treatment of aggressive non-Hodgkin's lymphoma (NHL) remains controversial. We conducted a retrospective study of French experience in allografting NHL between 1984 and 1994. To improve the homogeneity of the study population, cases of low-grade, Burkitt and lymphoblastic NHL were excluded. 73 patients were included in the analysis. Median age at transplantation was 35 years (range 9-61 years); 64 patients were in stage IV and 45 had bone marrow involvement at diagnosis. At the time of transplantation, 46 patients had sensitive disease (25 in complete remission; CR). The overall survival (OS) and progression-free survival (PFS) rates were 41% and 40% respectively at 5 years (median follow-up of survivors 90 months). The probability of disease progression was 30% at 5 years, and only one relapse occurred after 15 months. 32 patients died of transplantation-related complications. In multivariate analysis, pretransplant complete remission was the main factor associated with longer survival (OS at 60 months of 76% among the 25 patients in CR at transplant and of 23% among the 48 patients not in CR at transplant). Neither acute nor chronic graft-versus-host disease (GvHD) influenced the relapse rate. In conclusion, in this high-risk population the overall results of allogeneic BMT were encouraging, despite a high transplant-related mortality rate. We believe this procedure should be studied further in prospective controlled trials.     

Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01) and interferon alpha-2b for the treatment of chronic myelogenous leukemia patients in chronic phase.

Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials.