Myoclonic encephalopathy in the CDKL5 gene mutation.

OBJECTIVE: Epilepsy with mutation of the CDKL5 gene causes early seizures and is a variant of Rett syndrome (MIM (312750), which is reported typically as infantile spasms. The purpose of this study was to analyze the epileptic histories and EEGs of patients with the CDKL5 mutation. METHODS: We reviewed the epilepsy histories and electroclinical analyses of three girls aged 9.5, 7.4, and 9.4 years, each with a mutation of the CDKL5 gene. RESULTS: We revealed the presence of an encephalopathy that started by 1.5 months of age. At first, seizures involved tonic spasms or complex partial seizures, and were complicated by the later appearance of complex partial, tonic, and unexpectedly, myoclonic seizures. This form of epilepsy was drug resistant. Routine and prolonged video EEGs both displayed a homogeneous electroclinical pattern consisting of (a) unique background with diffuse high voltage sharp waves of 6-7 Hz, and absence of the typical rhythmic frontal-central theta activity present in Rett syndrome; (b) unique awake and sleep background, with diffuse, high voltage, continuous sharp waves with multifocal and diffuse spikes; (c) rhythmic, diffuse, 15 Hz activity accompanied clinically by tonic seizures; (d) intercritical pattern with pseudoperiodic, diffuse, sharp waves or pseudoperiodic, diffuse spike and polyspike or wave discharges; and (e) diffuse, spike, polyspike and wave discharges accompanied by massive or focal myoclonias or both. CONCLUSIONS: Patients with the CDKL5 mutation have an early onset, epileptic encephalopathy in infancy that evolves into myoclonic seizures in childhood with a unique EEG pattern. SIGNIFICANCE: Recognizing this type of encephalopathy could be useful in prompting clinicians to proceed further with their diagnostic work in patients not fitting the criteria of classical Rett syndrome.     

Treatment of type B aortic dissection: endoluminal repair or conventional medical therapy?

OBJECTIVE: To evaluate the mid-term results of endovascular stent-grafting for type B aortic dissection, in comparison with those of standard medical therapy in uncomplicated cases. METHODS: Between January 1999 and 2004, among 56 patients (mean age 59.5+/-11.5 years) with type B aortic dissection, hypotensive medical therapy was the only treatment in 28 uncomplicated cases, (group A), while stent-graft implantation was performed in 28 patients with uncontrolled hypertension, persistent pain or evidence of dissection progression or complication (group B). In 14 cases (50%) the procedure was performed in an acute setting. Stent-grafting procedures were monitored with intraoperative trans-esophageal echocardiography and cine-angiography. CT scan and trans-esophageal echocardiography were performed before hospital discharge, at 6 and 12 months and then yearly. RESULTS: Follow-up (range 1-61 months, average 18.1+/-16.9 months) was 100% complete. In-hospital mortality was 10.7% (three patients, all belonging to Group B; P=0.24). No spinal cord injuries were observed. Early endoleak occurred in one patient (3.5%). Mid-term mortality was lower in Group B, although the difference was not significant (10.7 versus 14.3% in Group A, P=0.71). Follow-up CT scans evidenced complete thrombosis of the false lumen in 75% cases in Group B, 10.7% in Group A (P=0.0001), and an aneurismal dilatation of the descending aorta in 3.5% cases in Group B, 28.5% in Group A (P=0.02). CONCLUSIONS: Although with still considerable early mortality, endovascular stent-graft implantation is an effective option for the treatment of complicated type B aortic dissection. Endovascular treatment achieved a better mid-term fate of the descending thoracic aorta than medical therapy alone, even in patients with worse preoperative conditions.     

Towards improved clinical characterization of Leber congenital amaurosis: neurological and systemic findings

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy that presents in infancy. LCA is both clinically and genetically heterogeneous. The aim of our study was to clarify the clinical aspects of LCA and to contribute to improved characterization of the disorder. We studied 40 children affected by LCA (mean age at first observation: 19 months, range: 8-50 months), who underwent a comprehensive evaluation that included: neurophthalmological evaluation, electroretinogram (ERG), and visual evoked potentials (VEPs), general and neurological examinations, developmental assessment using scales for visually impaired children, neuroradiological examinations, hepatic and renal function and metabolic investigations, brainstem auditory evoked potentials (BAEPs), EEG, and hand radiographs. Analyses of known LCA genes are ongoing. The subjects are still being followed up at 6-/12-month intervals. All the subjects fulfilled De Laey's criteria for LCA. The neurological examination was abnormal in 31 cases (hypotonia, ataxia with/without associated cerebellar signs). Cognitive development was normal in 24 cases, borderline in five, and subnormal in 11. Mild and nonspecific alterations on MRI were present in seven cases, and "molar tooth" sign in four; all the others had a normal neuroradiological picture. Among the subjects presenting with neurological signs, a subgroup (13 patients) emerged that was characterized by systemic (skin, kidney, liver) involvement. Our data confirm that LCA is a heterogeneous entity that can present as an isolated ocular manifestation, or in association with neurological and systemic abnormalities and support the need for a multidisciplinary approach to this entity and for genotype-phenotype studies.     

Immunization of rabbits with a modified vaccinia Ankara recombinant virus bearing the HIV envelope antigen on its outer membrane

Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia virus, which propagates efficiently in chicken embryo fibroblasts but fails to complete its growth cycle in many types of mammalian cells. We constructed a recombinant virus MVA/EK5, which has a chimeric gene encoding for the extracellular domain of the HIV envelope protein fused to the cytoplasmic and transmembrane domain of the B5R protein of vaccinia virus. The fused HIV envelope antigen was expressed in the African green monkey kidney BS-C-1 cells infected with the recombinant virus. This virus, which had been grown in chicken embryo fibroblasts, induced in rabbits antibodies against the HIV envelope antigen, in addition to those against poxvirus.     

Micronuclei frequencies in hospital workers occupationally exposed to low levels of ionizing radiation: influence of smoking status and other factors

In the context of a medical surveillance program aimed at preventing cancer risk from exposure to ionizing radiation, we investigated chromosomal damage in peripheral lymphocytes from 37 hospital workers exposed to low levels of ionizing radiation and 37 controls. The micronuleus (MN) assay was used as a biomarker of genetic damage. The influence of confounding factors like smoking status, age and gender was investigated by multiple regression analysis. The results indicated that, overall, MN frequency was higher in exposed workers than in controls, although the difference was not statistically significant. Interestingly, smoking status significantly raised MN frequency among the exposed workers but not among controls. This suggests that smoking can influence chromosomal damage induced in humans by ionizing radiation. Among both exposed workers and controls, MN frequency was found to increase with age. Female gender influenced the increase in MN frequency in the exposed group. Our results suggest that the effect of cigarette smoking should be carefully factored into genetic monitoring studies assessing the risks associated with low level radiation exposure.     

Setting out the frame conditions for feasible use of FFPE derived RNA

Introduction

The usage of formalin-fixed paraffin embedded (FFPE) tissue is characterized by its long shelf-life and simple handling. Therefore it is the most commonly available tissue specimen in routine diagnostics and histological studies. Formaldehyde fixation may result in RNA degradation and cross linking with proteins, while storage conditions also affect RNA integrity. The present study was designed to investigate the influence of these factors on RNA analysis.