Idiopathic late-onset absence status epilepticus: A case report with an electroclinical 14 years follow-up

Late-onset absence status epilepticus (ASE) may be observed in adult and elderly patients as a late complication of idiopathic generalized epilepsy or de novo, usually related to benzodiazepines withdrawal, alcohol intoxication or psychotropic drugs initiation, but without history of epilepsy. EEG may be highly heterogeneous, varying from the 3 to 3.5 Hz spike-wave discharges typical of idiopathic generalized epilepsy to asymmetric irregular sharp and slow wave complexes. We report the clinical and neurophysiologic 14 years follow-up of a now 86 years-old woman, in whom we observed – at the age of 72 – an idiopathic late-onset ASE, with a good clinical response to lamotrigine monotherapy, but with the persistence over years of the same interictal 3–3.5 Hz spike-wave epileptic activity at EEG. This case is singular because, with the available long follow-up, indicates that idiopathic generalized epilepsy may also occur in the elderly, with a late-onset ASE presentation. In this condition, it is particularly important to underline the essential role of EEG (urgent and ambulatory) for the diagnosis, management and monitoring of the disease.     

In systemic sclerosis macrovascular damage of hands digital arteries correlates with microvascular damage

Objective

To assess morphology and blood flow of the proper palmar digital arteries (PPDA) by Color Doppler Ultrasonography (CDUS) and its relationship with nailfold videocapillaroscopy (NVC), skin blood perfusion and digital arteries pulsatility of hands in SSc patients and healthy controls.

Methods

CDUS, NVC, Laser Doppler Perfusion Imaging (LDPI) and photoplethysmography (PPG) were performed in 36 systemic sclerosis (SSc) patients and 20 healthy controls.

Results

CDUS was pathologic in 69% of patients with SSc and in none of healthy controls (p < 0.0001). SSc patients with low vascular damage (early capillaroscopic pattern) have a normal morphology of PPDA, but the blood flow, evaluated by peak systolic velocity (PSV) and end diastolic velocity (EDV), is reduced and vascular resistance, measured by resistive index (RI) and pulsatility index (PI), increased. At this stage the LDPI mean perfusion and digital artery pulsatility, evaluated by PPG, were reduced. The US changes appear with microvasculare damage progression (active and late capillaroscopic patterns), while the PPDA blood flow progressively decreases (PSV and EDV decreased, RI and PI increased). The macrovascular damage correlates with disease duration. Anti-topoisomerase I represents an independent predictive factor for macrovascular damage. We not observed any association between digital ulcer history, pulmonary fibrosis and US findings.

Conclusion

PPDA blood flow dysfunction is already present in early disease. Structural macrovascular damage progresses with worsening of SSc microangiopathy.     

Multiple drug delivery hydrogel system for spinal cord injury repair strategies

The multifactorial pathological progress of spinal cord injury (SCI) is probably the main reason behind the absence of efficient therapeutic approaches. Hence, very recent highlights suggest the use of new multidrug delivery systems capable of local controlled release of therapeutic agents. In this work, a biocompatible hydrogel-based system was developed as multiple drug delivery tool, specifically designed for SCI repair strategies. Multiple release profiles were achieved by loading gel with a combination of low and high steric hindrance molecules. In vitro, in vivo and ex vivo release studies showed an independent combination of fast diffusion-controlled kinetics for smaller molecules together with slow diffusion-controlled kinetics for bigger ones. A preserved functionality of loaded substances was always achieved, confirming the absence of any chemical stable interactions between gel matrix and loaded molecules. Moreover, the relevant effect of the cerebrospinal fluid flux dynamics on the drug diffusion in the spinal cord tissue was here revealed for the first time: an oriented delivery of the released molecules in the spinal cord tract caudally to the gel site is demonstrated, thus suggesting a more efficient gel positioning rostrally to the lesion.     

US-guided percutaneous radiofrequency thermal ablation for the treatment of solid benign hyperfunctioning or compressive thyroid nodules

The aim of the study was to define the effectiveness and safety of ultrasound-guided percutaneous radiofrequency (RF) thermal ablation in the treatment of compressive solid benign thyroid nodules. Thirty-one patients not eligible for surgery or radioiodine (¹³¹I) treatment underwent RF ablation for benign nodules; a total of 33 nodules were treated (2 patients had 2 nodules treated in the same session): 10 cold nodules and 23 hyperfunctioning. Fourteen patients complained of compressive symptoms. Nodule volume, thyroid function and compressive symptoms were evaluated before treatment and at 1, 3 and 6 mo. Ultrasound-guided RF ablation was performed using a Starbust RITA^® needle, with nine expandable prongs; total exposure time was 6 to 10 min at 95° C in one area or more of the nodule. Baseline volume (measured at the time of RF ablation) was 27.7 ± 21.5 mL (mean ± SD), but significantly decreased during follow-up: 19.2 ± 16.2 at 1 mo (–32.7%; p < 0.001), 15.9 ± 14.1 mL at 3 mo (–46.4 %; p < 0.001) and 14.6 ± 12.6 mL at 6 mo (–50.7%; p < 0.001). After treatment, all patients with cold nodules remained euthyroid: five patients with hot nodules normalized thyroid function, and the remaining sixteen showed a partial remission of hyperthyroidism. Besides a sensation of heat and mild swelling of the neck, no major complications were observed. Improvement in compressive symptoms was reported by 13 patients, with a reduction on severity scale from 6.1 ± 1.4 to 2.2 ± 1.9 (p < 0.0001). Radiofrequency was effective and safe in reducing volume by about 50% and compressive symptoms in large benign nodules. Hyperfunction was fully controlled in 24% of patients and partially reduced in the others. (E-mail: mdeandrea@libero.it)     

MLL-MLLT10 fusion in acute monoblastic leukemia: variant complex rearrangements and 11q proximal breakpoint heterogeneity

Cytogenetic studies of acute monoblastic leukemia cases presenting MLL-MLLT10 (alias MLL-AF10) fusion show a broad heterogeneity of chromosomal breakpoints. We present two new pediatric cases (French-American-British type M5) with MLL-MLLT10 fusion, which we studied with fluorescence in situ hybridization. In both we detected a paracentric inversion of the 11q region that translocated onto chromosome 10p12; one case displayed a variant complex pattern. We review the cytogenetic molecular data concerning the proximal inversion breakpoint of 11q and confirm its heterogeneity.     

Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis

Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity.     

Validity and reliability of the SPORTS score

Purpose  

Successful outcomes for an athlete usually consist of returning to their sport. The Subjective Patient Outcome for Return to Sports (SPORTS) score has been recently proposed as an easy to use score for evaluating an athlete’s ability to return to their sport. The aim of this study was to test the reliability and validity of the SPORTS score in athletes 5–10 years after anterior cruciate ligament reconstruction.     

In vivo monosomy 3 detection of posterior uveal melanoma: 3-year follow-up

Background Monosomy 3 is a highly specific marker for poor prognosis in posterior uveal melanoma. Unfortunately, cytogenetic prognostication is limited to enucleated eyes or resected tumors. The aim of this study was to evaluate mid-term natural history and safety of in vivo detection of chromosome 3 status in posterior uveal melanomas undergoing plaque brachytherapy. Methods A 25-gauge transscleral fine needle aspiration biopsy (FNAB) was performed in 32 eyes affected by posterior uveal melanoma undergoing plaque brachytherapy, just before applying the radioactive plaque. Sampled material underwent fluorescence in situ hybridization (FISH) with centromeric probes for chromosome 3. All patients had a follow-up of at least 36 months. Results Mean follow-up was 47.1 ± 8.5 months. Mean largest basal diameter and mean thickness of the tumors were 12.5 ± 2.7 mm and 8 ± 2.3 mm respectively. FNAB yielded sufficient material in 26 of 32 cases (81.2%). Adequacy of the sample ranged from 91.1% (ciliary body tumors) to 76.8% (choroidal tumors). Seventeen cases had monosomy 3 (65.3%). No correlation was found between monosomy 3 and tumor dimensions or location (ciliary body vs choroidal tumors). No early and mid-term local complications were documented. Seven patients (21.8%) died during follow-up: five (15.6%) of them died due to metastatic disease (all had monosomy 3 tumors). Conclusions Posterior uveal melanomas may be adequately and safely sampled, by intra-operative transscleral FNAB, to detect in vivo monosomy 3. The authors have no financial interest in the subject of this paper. The authors have full control of all primary data and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data if requested.