Presentation of adult mitochondrial epilepsy

PurposeMitochondrial disorders (MIDs) frequently manifest phenotypically as epilepsy (mitochondrial epilepsy). Mitochondrial epilepsy occurs in early-onset as well as late-onset syndromic and non-syndromic MIDs. We were interested in the types of epilepsy, the prevalence of mitochondrial epilepsy, the type and effectiveness of treatment, and in the outcome of adult MID patients with epilepsy.MethodsWe retrospectively evaluated adult patients with syndromic or non-syndromic MIDs and epilepsy. MIDs were classified according to the modified Walker criteria as definite, probable, and possible.ResultsEpilepsy in adult patients with a MID was classified as “structural/metabolic” in two-thirds of the cases and as “genetic” in one-third of the cases. Although all types of seizures may occur in mitochondrial epilepsy, adult patients most frequently presented with generalised tonic–clonic seizures, partial seizures, convulsive status epilepticus, or non-convulsive status epilepticus. Cerebral imaging was normal in one-third of the patients. Two-thirds of the adult patients with mitochondrial epilepsy who took antiepileptic drugs received monotherapy, one-third combination treatment. The antiepileptic drugs most frequently administered included levetiracetam, lamotrigine, valproic acid, and gabapentin. Antiepileptic drugs were usually well tolerated and the outcome favourable.ConclusionsAdult mitochondrial epilepsy appears to be less frequent than previously believed but the prevalence strongly depends on patient selection. Mitochondrial epilepsy is most frequently “structural/metabolic”. AEDs recommended for mitochondrial epilepsy include levetiracetam, lamotrigine, gabapentin and lacosamide. The outcome of mitochondrial epilepsy may be more favourable if mitochondrion-toxic AEDs are avoided. Only if non-mitochondrion-toxic AEDs are ineffective, mitochondrion-toxic AEDs may be used.     

Short-term immunosuppression facilitates induction of mixed chimerism and tolerance after bone marrow transplantation without cytoreductive conditioning

BACKGROUND: Induction of mixed chimerism and tolerance usually requires cytoreduction or transplantation of high numbers of bone marrow cells (BMC). However, such protocols have only a suboptimal success rate and, more importantly, equivalent numbers of BMC cannot be routinely obtained in the clinical setting. The authors therefore evaluated whether a short-course of immunosuppression (IS) given in addition to co-stimulation blockade would facilitate chimerism induction and allow reduction of the minimally required number of BMC without cytoreduction. METHODS: B6 mice received 200, 100, or 50 x 10 unseparated BMC from Balb/c donors plus an anti-CD40L monoclonal antibody (mAb) and CTLA4Ig (without irradiation or cytotoxic drugs). Some groups were treated additionally with IS (rapamycin, methylprednisolone, and mycophenolate mofetil for 4 weeks after bone marrow transplantation), donor-specific transfusion (DST), or anti-OX40L mAb, as indicated. RESULTS: IS led to long-term multilineage chimerism in 9 of 10 mice receiving 200 x 10 BMC (without IS, 1 of 4; P<0.05), in all mice (n=10) receiving 100 x 10 (without IS, 6 of 9; P<0.05), and notably in 9 of 10 mice treated with 50 x 10 BMC (without IS, 4 of 10; P<0.05). With transient IS, donor skin grafts were accepted longer than 170 days in 9 of 10 mice receiving 200 x 10 (without IS, 0 of 5 mice; P<0.05), all mice receiving 100 x 10 (without IS, 6 of 9; P<0.05), and 6 of 11 mice receiving 50 x 10 BMC (without IS, 4 of 10). The use of DST or anti-OX40L mAb had no beneficial effect. CONCLUSIONS: Transient IS significantly improves rates of chimerism and donor skin graft survival, and allows lasting mixed chimerism after transplantation of only 50 x 10 BMC. Thus, IS might help in the further development of noncytoreductive chimerism protocols.     

High-dose intravenous immunoglobulin treatment in two patients with acquired factor V inhibitors

We report two patients who developed acquired factor V (FV) inhibitors not related to exposure to bovine thrombin. Associated conditions were found in one patient (surgery, antibiotic administration) but none in the other one. Bleeding complications occurred only in the patient with idiopathic FV inhibitor, leading to packed red cell infusion. Laboratory findings showed the presence of specific FV inhibitors with titers of 5.5 and 5 Bethesda units, respectively. These two patients received high-dose intravenous immunoglobulin and FV levels normalized within a few days with a concomitant disappearance of FV inhibitors.     

Differential detection of Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii in fecal samples by nested PCR in the United Arab Emirates (UAE)

Amoebiasis is one of the most important infectious diseases afflicting mainly tropical and subtropical countries. This study was carried out in the Sharjah Emirate, UAE in order to accurately detect and differentiate Entamoeba histolytica, Entamoeba dispar and E. moshkovskii in fecal samples collected from the Sharjah municipality public health clinic by ELISA and nested polymerase chain reaction (PCR). One hundred and twenty specimens were examined and the PCR was positive for E. histolytica, E. dispar and E. moshkovskii (collectively referred to as Entamoeba complex) in 19.2% (23 out of 120). Of those, 10% (12/120) were mono — infection with E. histolytica; 2.5% (3/120) with E. dispar; and 2.5% (3/120) E. moshkovskii. The nested PCR also detected mixed infections by both E. histolytica and E. dispar in 3.3% (4/120) and E. dispar and E. moshkovskii in 0.8% (1/120). The TechLab ELISA kit failed to detect E. histolytica in any of the E. histolytica PCR positive samples. Overall, the percentage of E. histolytica including those found in mixed infections was 13.3% (16/120). Compared to nested PCR, microscopy was found to have an overall sensitivity of 52.2% and a specificity of 75.2% for detection of Entamoeba complex. The present study indicates that E. histolytica is present in the UAE with an average incidence rate of 13.3%. However, larger studies need to be conducted in order to confirm these findings. We propose the use of PCR in both the routine diagnosis of amoebiasis and epidemiological survey in the UAE.