MRI findings in people with epilepsy and nodding syndrome in an area endemic for onchocerciasis: an observational study

Background

Onchocerciasis has been implicated in the pathogenesis of epilepsy. The debate on a potential causal relationship between Onchocerca volvulus and epilepsy has taken a new direction in the light of the most recent epidemic of nodding syndrome.

Objective

To document MRI changes in people with different types of epilepsy and investigate whether there is an association with O. volvulus infection.

Methods

In a prospective study in southern Tanzania, an area endemic for O. volvulus with a high prevalence of epilepsy and nodding syndrome, we performed MRI on 32 people with epilepsy, 12 of which suffered from nodding syndrome. Polymerase chain reaction (PCR) of O. volvulus was performed in skin and CSF.

Results

The most frequent abnormalities seen on MRI was atrophy (twelve patients (37.5%)) followed by intraparenchymal pathologies such as changes in the hippocampus (nine patients (28.1%)), gliotic lesions (six patients (18.8%)) and subcortical signal abnormalities (three patients (9.4%)). There was an overall trend towards an association of intraparenchymal cerebral pathologies and infection with O. volvulus based on skin PCR (Fisher''s Exact Test p=0.067) which was most pronounced in children and adolescents with nodding syndrome compared to those with other types of epilepsy (Fisher''s Exact Test, p=0.083). Contrary to skin PCR results, PCR of CSF was negative in all patients.

Conclusion

The observed trend towards an association of intraparenchymal cerebral pathological results on MRI and a positive skin PCR for O. volvulus despite negative PCR of CSF is intriguing and deserves further attention.     

Primary Immunodeficiency Diseases in Latin America: The Second Report of the LAGID Registry

This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reveals that from a total of 3321 patients registered, the most common form of primary immunodeficiency disease was predominantly antibody deficiency (53.2%) with IgA deficiency reported as the most frequent phenotype. This category was followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune dysregulation, and 2.8% complement deficiencies. All countries that participated in the first publication in 1998 reported an increase in registered primary immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease, and severe combined immunodeficiency between the first report and the present one shows an increase in the reporting of these diseases in all countries. In this report, the estimated minimal incidence of chronic granulomatous disease was between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica, and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and 3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these diseases are underreported in other participating countries. In addition to a better diagnosis of primary immunodeficiency diseases, more work on improving the registration of patients by each participating country and by countries that have not yet joined LAGID is still needed. Latin American Group for Primary Immunodeficiency Diseases     

Fracture healing following high energy tibial trauma: Ilizarov versus Taylor Spatial Frame

Introduction

The optimal treatment of high energy tibial fractures remains controversial and a challenging orthopaedic problem. The role of external fixators for all these tibial fractures has been shown to be crucial.

Methods

A five-year consecutive series was reviewed retrospectively, identifying two treatment groups: Ilizarov and Taylor Spatial Frame (TSF; Smith & Nephew, Memphis, TN, US). Fracture healing time was the primary outcome measure.

Results

A total of 112 patients (85 Ilizarov, 37 TSF) were identified for the review with a mean age of 45 years. This was higher in women (57 years) than in men (41 years). There was no significant difference between frame types (p=0.83). The median healing time was 163 days in both groups. There was no significant difference in healing time between smokers and non-smokers (180 vs 165 days respectively, p=0.07), open or closed fractures (p=0.13) or age and healing time (Spearman''s r=0.12, p=0.18). There was no incidence of non-union or re-fracture following frame removal in either group.

Conclusions

Despite the assumption of the rigid construct of the TSF, the median time to union was similar to that of the Ilizarov frame and the TSF therefore can play a significant role in complex tibial fractures.     

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfan-based reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P=0.006 for PFS and P=0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versus-myeloma effect with an acceptable incidence of toxicity and TRM.     

Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase

In chronic myelogenous leukemia (CML) imatinib mesylate has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic bcr-abl fusion protein. Using this agent alone high rates of cytogenetic responses were recorded. However, several mechanisms of resistance have been described. In vitro studies examining the effects of imatinib mesylate plus cytarabine have shown synergistic antiproliferative effects of this combination. Thus, the CML French Group decided to perform a phase 2 trial testing a combination of imatinib mesylate and low-dose cytarabine in 30 previously untreated patients in chronic phase. Treatment was administered on 28-day cycles. Patients were treated continuously with imatinib mesylate orally at a dose of 400 mg daily. Cytarabine was given on days 15 to 28 of each cycle at an initial dose of 20 mg/m2/d via subcutaneous injection. Adverse events were frequently observed with grade 3 or 4 hematologic toxicities and nonhematologic toxicities in 53% (n = 16) and 23% (n = 7) of patients, respectively. The cumulative incidence of complete cytogenetic response (CCR) at 12 months was 83% and at 6 months 100% of the patients achieved complete hematologic response (CHR). We concluded that the combination was safe and promising given the rates of response.