Pyridoxine-dependent seizures caused by alpha amino adipic semialdehyde dehydrogenase deficiency: the first polish case with confirmed biochemical and molecular pathology

Pyridoxine-dependent seizures are a rare condition recognized when numerous seizures respond to pyridoxine treatment and recur on pyridoxine withdrawal. For decades the diagnosis was confirmed only with pyridoxine treatment withdrawal trial. Recently described biochemical and molecular pathology improved the diagnostic process for those cases in which seizures are caused by alpha amino adipic semialdehyde dehydrogenase deficiency. This article presents a girl with recurrent status epilepticus episodes resistant to phenobarbital and phenytoin and partly responding to midazolam. Eventually the seizures were completely controlled with pyridoxine; however, due to the severe condition of this child when seizing, no trial of withdrawal has been performed. The diagnosis of pyridoxine-dependent seizures was confirmed with biochemical and molecular testing revealing elevated alpha-AASA excretion and the presence of 2 different mutations in the antiquitin ( ALDH7A1) gene. Due to the availability of reliable laboratory testing, confirmation of the diagnosis was made without the life-threatening trial of pyridoxine withdrawal.     

Factors affecting the health-related quality of life of patients with cervical dystonia and the impact of botulinum toxin type A injections

The purpose of this study was to analyze the health-related quality of life (HRQL) of patients with cervical dystonia (CD) and the impact of botulinum toxin A (BTX-A) therapy in these patients. The authors recruited 101 patients with CD, all previously treated with BTX-A. Both before and 4 weeks after injection of BTX-A the patients were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), a Visual Analogue Scale for pain (VAS: 0-100%), the Short Form 36 health survey questionnaire (SF-36), and the Montgomery-Asberg Depression Rating Scale (MADRS). A control group of 84 healthy volunteers was also evaluated. The patients? baseline SF-36 scores were worse in all the domains when compared with those of the controls. Depression was found in 47.5% of the patients. Improvements were noticed 4 weeks after the single BTX-A injections in all the SF-36 domains, and in the VAS, TWSTRS and MADRS scores. The TWSTRS results did not correlate with any of the SF-36 subscores. Stepwise backward regression analysis revealed depression as the main predictor of poor HRQL, as well as female sex, poor financial situation, and living alone. On contrary, longer treatment with BTX-A was associated with better scores. Cervical dystonia has a marked impact on HRQL and treatment with BTX-A injections has a beneficial effect, seen both in objective and in subjective measures. Depression in CD patients is a main predictor of worse HRQL.     

Aspirin treatment influences platelet-related inflammatory biomarkers in healthy individuals but not in acute stroke patients

Objectives

Platelet-leukocyte aggregation is believed to contribute to acute thrombotic events. While the effect of aspirin on platelet-to-platelet aggregation is well established, the impact of the drug on pro-inflammatory platelet function remains equivocal. Thus we investigated the effect of aspirin on selected platelet-related inflammatory biomarkers in both acute ischaemic stroke patients and healthy volunteers.

Methods

Using five-colour flow cytometry the platelet surface expression of CD62P and CD40L and subpopulations of leukocyte-platelet aggregates were assessed in 63 acute stroke patients and 40 healthy volunteers at baseline and after a 10-day period of aspirin intake at a daily dose of 150 mg. Simultaneously the plasma levels of soluble CD62P and CD40L, serum level of TxB₂, and whole blood impedance platelet aggregation under arachidonic acid (AA) stimulation were investigated.

Results

No differences in values of studied platelet-related inflammatory biomarkers in both resting platelets and those activated with TRAP after 10-day treatment with aspirin were confirmed in stroke subjects. In healthy individuals the resting platelet expression of CD62P, plasma level of soluble CD62P and percentage of circulating monocyte-platelet aggregates were lower after the aspirin intake period (P = 0.009; P = 0.04; P = 0.004, respectively). In both studied groups serum level of TxB₂ and platelet aggregation under AA stimulation were lower than before treatment (P < 0.001).

Conclusion

Despite effective inhibition of COX-1-dependent platelet aggregation, aspirin does not influence the platelet α-granule-derived inflammatory mediators and monocyte-platelet aggregation in acute stroke subjects, although it does in healthy individuals.     

EVER2 Deficiency is Associated with Mild T-cell Abnormalities

Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by persistent flat warts or pityriasis versicolor-like lesions caused by betapapillomaviruses (EV-HPVs). Autosomal recessive EVER1 and EVER2 deficiencies account for EV in most patients. The mechanisms by which mutations in these partners of the Zinc transporter ZnT1 impair host defense against EV-HPVs are still poorly understood. Keratinocytes of EVER-deficient patients display an alteration of zinc homeostasis and an enhanced proliferative activity. Since EVER proteins are highly expressed in T lymphocytes, we aimed to assess the impact of EVER2 deficiency on T-cell development and function. We studied circulating lymphocyte populations in three adult EV patients sharing the same EVER2 mutation (T150fsX3). We found a normal count of CD4⁺ and CD8⁺ T cells and a normal proliferative capacity in response to anti-CD3 stimulation. However, we observed a significant increase of memory CD4⁺ and effector memory CD8⁺ T cells, a bias of the TCR Vαβ and Vγδ repertoires and an increase of skin-homing CD4⁺ T-cell subsets. Our findings suggest that EVER2-deficient patients display mild T-cell abnormalities. It remains unclear whether these abnormalities result from EVER deficiency, chronic EV-HPV infection, or both.     

Pregnancy After Kidney Transplantation: A Single-Center Experience and Review of the Literature

After kidney transplantation (KT), pregnancy is possible, although the risk of maternal and fetal complications is much higher than in the general population. Outcome of 22 pregnancies in 17 patients transplanted in the Gdańsk center in the period 1980–2012 was studied. Mean maternal age at pregnancy was 30 ± 5 (range, 23–39) years, interval between transplantation and conception 3.4 ± 2.5 (range, 0.6–11) years. Mean creatinine concentration before conception was 1.29 ± 0.36 (range, 0.8–2.45) mg/dL and was stable during 1 year preceding pregnancy (mean increase, 0.01 mg/dL). Nine of the 17 patients received 1 and 4 received ≥2 antihypertensive drugs, and 1 had proteinuria. Twelve of the 17 patients were primagravidas, 1 was pregnant 3 times, and 14 times. At the time of conception, 20 patients received CNI (14 cyclosporine, 6 tacrolimus), 15 antimetabolites (3 mycophenolate mofetil [MMF], 12 azathioprine), 1 mammalian target of rapamycin inhibitor (mTORi; sirolimus), and all prednisone. MMF and mTORi were discontinued before or during the 1st weeks of pregnancy. Maternal outcome: all survived the pregnancy. None experienced rejection or graft loss as a direct result of pregnancy. Maternal complications included edema (5/17), worsening of blood pressure control (5/17), and worsening (1/17) or new onset of proteinuria (2/17). Mean creatinine decrease during pregnancy was 0.06 mg/dL. Mean creatinine 1 year after pregnancy was 1.49 ± 0.53 mg/dL. There were 12 cesarean sections. Fetal outcomes: 17 live births (2 with serious congenital defects), 2 spontaneous and 1 induced abortion, 2 stillbirths. Mean pregnancy age and neonate birth weights were 35 ± 4 (range, 23–39) weeks and 2,552 ± 629 (range, 1,480–3,420) g, respectively. During mean 8.5 (range, 1–25) years of follow-up after pregnancy, 4/17 patients lost grafts. Grafts were lost in the 3rd to 7th years after pregnancy. We conclude that pregnancy does not exert a direct negative influence on patient and graft survivals; 68% of all pregnancies resulted in delivering healthy neonates.