A peculiar family with recurrent self-limited epileptic syndrome and associated developmental disorders in six girls.

We describe a complex family with two couples (two sisters who married two brothers) with consistent social and neuropsychiatric problems, originally from Sardinia. Each couple had three daughters, which shared electroclinical epileptic syndrome and developmental disorders. All patients suffered from mild to moderate intellectual disability, speech difficulties and behavioural disorders. Four out of six patients had epilepsy onset between 3 and 4 years of age. The epileptic history almost reflected the typical clinical course of a self-Limited Focal Epilepsy of Childhood. However, our patients don't have the complete features characteristic of one of the four specific self-Limited Focal Epilepsies of Childhood; a progressive evolution into a Developmental and/or Epileptic Encephalopathy with spike-wave activation in sleep was observed in the two older sister of the first family, which developed more severe developmental disorder too. In the other epileptic patients, improvement of EEG pattern was not coincident with an improvement of the developmental disorders. Brain MRI, performed in three patients, showed normal findings. Genetic analysis carried out so far (SNP-array, study of Runs of homozygosity, FMR1 triplet-repeat primer-PCR assay, Next Generation Sequencing based gene panel for epilepsy and neurodevelopmental disorders and Exome Sequencing), did not provide useful elements for an aetiological diagnosis.

De novo Absence Status Epilepticus in a pediatric cohort: Electroclinical pattern in a multicenter Italian patients cohort.

PURPOSE: Absence Status epilepticus (AS) is a form of Non Convulsive Status Epilepticus defined as a prolonged, generalized and non-convulsive seizure, with an altered content of consciousness. We aim to describe a group of healthy children, who presented recurrent and unprovoked de novo AS as the only manifestation of their epilepsy, with an excellent response to antiepileptic drugs. METHOD: We retrospectively reviewed the electroclinical and genetic features of 13 pediatric patients, referring to our epilepsy centers from 2005 to 2019, on the following criteria: (1) regular psychomotor development, (2) one or more unprovoked AS as the only epileptic manifestation, (3) normal blood testing, (4) normal neuroimaging, (5) EEG recording, (6) available follow-up (1-14 years). RESULTS: Patients are 7 females and 6 males, aged 7-22, with a mean age at AS onset of 9,3 years. All of them started an antiepileptic therapy, with an excellent response to Valproic Acid (VPA) or Ethosuximide (ETS). 5 patients did not start the therapy immediately after the first AS and they presented recurrent AS (from 2 to 4 episodes). 10 of them performed aCGH, karyotype, NGS panel or Whole Exome Sequencing. CONCLUSIONS: We suggest that de novo AS may be a well-defined age-related and self-limited epilepsy syndrome, with a good prognosis and excellent response to therapy, but it comes with a high risk of relapsing if not adequately treated with antiepileptic drugs.

Novel NALCN biallelic truncating mutations in siblings with IHPRF1 syndrome.

Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. It is caused by mutations in the NALCN gene that encodes a voltage-independent, cation channel permeable to NM, K+ and Ca2+ and forms a channel complex with UNCSO and UNC79. So far, only 4 homozygous mutations have been found in 11 cases belonging to 4 independent consanguineous families. We studied a Sardinian family with 2 siblings presenting dysmorphic facies, hypotonia, psychomotor retardation, epilepsy, absent speech, sleep disturbance, hyperkinetic movement disorder, cachexia and chronic constipation. Polymorphic generalized seizures started at 4 and 6 years, respectively. Anti-epileptic drugs (AEDs) therapy was efficient for female proband's epilepsy, but the male still has weekly seizures. Whole exome sequencing identified 2 novel truncating mutations in NALCN allowing to assess the clinical phenotype to IHPRF1. This is the fifth family reported worldwide, and these are the first European cases with IHPRF1 syndrome with biallelic truncating mutations of NALCN.

Chiral Hexahalogenated 4,4'-Bipyridines.

The preparation of 27 isomers of chiral hexahalogeno-4,4'-bipyridines by means of two complementary methods is described. The first one is convergent and based on the LDA-induced 4,4'-dimerization of trihalopyridines, whereas the second method is divergent and achieved through regioselective halogenation reactions of 4,4'-bipyridine-2,2'-diones. Iodine in 2,2'-positions of the 4,4'-bipyridines was introduced by a copper-catalyzed Finkelstein reaction (Buchwald procedure) performed on 2,2'-dibromo derivatives. Selected compounds of this new family of atropisomeric 4,4'-bipyridines were enantioseparated by high performance liquid chromatography on chiral stationary phases, and the absolute configurations of the separated enantiomers were assigned by using X-ray diffraction analysis. The latter revealed that various halogen bond types are responsible for crystal cohesion.

Kikuchi-Fujimoto disease with lateral neck localisation: a case report.

The case is described of a Kikuchi-Fujimoto disease, in a 22-year-old female, onset of which was characterised by rapidly evolving lateral neck lymphadenopathy. Since clinico-radiological findings suggested a lymphoproliferative disease, it was mandatory, in order to establish the diagnosis and programme a suitable treatment protocol, to collect a lymph node biopsy specimen. The histological pattern was characteristic of Kikuchi-Fujimoto disease necrotizing lymphadenitis. Bearing in mind the difficulties encountered in the diagnosis of Kikuchi-Fujimoto disease, due not only to lack of a characteristic clinical pattern but also to the generic and aspecific findings emerging from radiological evaluation, the Authors stress the important role of histological examination in establishing the nature of the disease. In their opinion, onset of a rapidly evolving lateral neck lymphadenopathy, in a young patient, in the absence of well-defined disorders possibly responsible for the condition, and in order to establish a correct diagnostic approach, should induce the ENT specialist to take into consideration the possible presence of Kikuchi-Fujimoto disease, even if this is to be considered a rare finding.

Supraventricular tachyarrhythmias involving the sinus node: clinical and electrophysiologic characteristics.

Supraventricular tachyarrhythmias occur quite commonly and are now evaluated more often because of technological advances in the field of electrophysiology. Arrhythmias that involve the sinus node, namely, the syndrome of inappropriate sinus tachycardia and sinus node reentry, are rare. Because of their origin in the sinus node, the surface electrocardiogram (ECG) in these patients can present a diagnostic challenge to the clinician and in fact may elude recognition as an abnormal heart rhythm. Presented in this review are the clinical characteristics of these arrhythmias, as well as the mechanisms of action. Pharmacotherapy may be therapeutic in certain patients in preventing recurrences; however, radiofrequency catheter ablation offers a lifelong curative effect for these patients.

Acantholytic dyskeratotic epidermal naevus localized unilaterally in the cutaneous and genital areas.

A 38-year-old woman presented with unilateral lesions on the left side of the body and in the genital area. Clinically, the lesions showed a polymorphic pattern: brownish papules in the axilla, keratotic comedo-like papules on the hand and foot, and whitish papular plaques on the labia majora and anal canal. There was no family history of skin diseases. Histologically, cutaneous and mucosal specimens were characterized by acantholytic and dyskeratotic cells, corps ronds and grains in the parakeratotic zone, and by hyperkeratosis and parakeratosis. A diagnosis of epidermal naevus with acantholytic dyskeratosis was made.

[Kikuchi's disease and proteinaceous lymphoadenopathy in 4 patients with HIV infection]. / Malattia di Kikuchi e linfoadenopatia proteinacea in quattro pazienti on infezione da HIV.

In the lymphadenopathy occurring in the acquired immunodeficiency syndrome (AIDS) and the AIDS related complex (ARC), consistent histologic patterns have been described with some variants thereof, such as angioimmunoblastic lymphadenopathy-like or Castleman disease-like. In four such patients we have observed two other types of nodal lesions. Three patients had lymph node biopsies showing the characteristic histologic and immunophenotypic features of histiocytic necrotizing lymphadenitis (Kikuchi's disease). These were two males, 26 and 35-year old, with bilateral axillary and cervical lymphadenopathy, respectively, and one female, 29-years old with peripheral and abdominal lymphadenopathy. One patient had proteinaceous lymphadenopathy. This was a 26-year old man with disseminated lymphadenopathy and a small monoclonal IgG/k peak in the serum. Whether these two processes are direct effects of the HIV virus on the immune system or due to intercurrent etiologic factors, has to be determined. These observations, however, indicate that the range of nodal lesions (that the pathologist may encounter) in AIDS/ARC is wider than previously reported.

Radiofrequency catheter ablation of postinfarction ventricular tachycardia: long-term success and the significance of inducible nonclinical arrhythmias.

BACKGROUND: Radiofrequency (RF) catheter ablation is effective therapy for monomorphic ventricular tachycardia (VT) in patients without structural heart disease. In patients with postinfarction VT; however, this procedure has been used predominantly as adjunctive therapy, targeting only the patient's clinically documented arrhythmia. By targeting all inducible, sustained VT morphologies, we sought to determine the utility of RF catheter ablation as a primary cure in patients who present with hemodynamically tolerated VT. METHODS AND RESULTS: RF ablation was attempted in 35 patients with a previous myocardial infarction and recurrent, hemodynamically tolerated VT. A mean of 3.9+/-2.7 VTs were induced per patient (range, 1 to 10). The clinically documented arrhythmia was successfully ablated in 30 of 35 patients (86%), and on follow-up electrophysiological testing, 11 patients had no inducible VT and were discharged without other therapy. Nineteen patients had inducible "nonclinical" arrhythmias on follow-up testing, and the majority underwent cardiac defibrillator implantation. Freedom from recurrent arrhythmias, including sudden death, was 91% in patients without inducible VT and 53% in patients with persistently inducible "nonclinical" arrhythmias (P<.05; mean follow-up, 17+/-12 and 12+/-11 months, respectively). CONCLUSIONS: In patients with well-tolerated VT, RF catheter ablation may be useful as a primary cure if no other ventricular arrhythmias are inducible on follow-up testing. Ablation of all hemodynamically tolerated arrhythmias should be attempted in patients with multiple inducible VT morphologies because of the high rate of recurrence of unablated VTs in these patients.

Inappropriate pauses during bradycardia pacing in a third-generation implantable cardioverter defibrillator.

Many ICD devices have the capability for back up bradycardia pacing. Because of the use of a single sensing algorithm for both bradycardia and tachycardia functions, they may be prone to certain "sensing errors." Following implantation of an ICD in a patient with long QT syndrome, "inappropriate" pauses were noted during bradycardia pacing, which were exactly twice the programmed pacing cycle length. This was due to an automatic increase in the device's sensitivity during pacing, a characteristic of the automatic gain control of this particular ICD. Proper recognition of this ICD's special features, known as "lower threshold crossing," allowed noninvasive rectification of the problem and prevented these pauses.

The effects of isoproterenol on the cardiac conduction system: site-specific dose dependence.

INTRODUCTION: Isoproterenol is used to assess and facilitate AV nodal conduction, and thus potentiate the induction of supraventricular arrhythmias. It is commonly administered in increasing doses until a predetermined decrease in sinus cycle length, usually 20% to 30%, occurs. This regimen may result in undesirable side effects. We have observed that effects of isoproterenol on the AV node may occur prior to achieving the target sinus cycle length. The purpose of this study was to determine whether the sinus and AV nodes have equal sensitivity to isoproterenol. METHODS AND RESULTS: Thirty-eight consecutive patients, who underwent electrophysiologic evaluation for a variety of indications, were given incremental doses of isoproterenol at 0.007, 0.014, 0.021, and 0.028 microgram/kg per minute. Sinus cycle length and AV node function were assessed at baseline and after 5 minutes at each dose. The percent change from baseline in AV node function was compared with the change in sinus cycle length at each dose interval. Significantly greater decreases were observed in the anterograde and retrograde AV nodal Wenckebach cycle length (P < 0.0001) than in the sinus cycle length at the lowest isoproterenol dose (0.007 microgram/kg per min). These differences were not apparent at higher doses. A sustained supraventricular tachycardia was inducible in 15 of 38 patients in the presence of isoproterenol, of which 40% occurred at the lowest dose. CONCLUSIONS: The AV node is more sensitive than the sinus node to the effects of isoproterenol. Lower doses of isoproterenol than those commonly used may often facilitate the induction of a supraventricular tachyarrhythmia, thus reducing side effects.

Lymphangioma-like variant of Kaposi's sarcoma: clinicopathologic study of seven cases with review of the literature.

The clinical and pathological features of seven cases of lymphangioma-like Kaposi's sarcoma (KS) are reported. As with the other subtypes of KS, the lymphangioma-like variant occurs more often in men aged 59-80 years. Clinically, the lesion appears intermingled with the classical forms of KS, but a "bulla-like" appearance recognized in seven of 13 cases has been considered as a clinical hallmark of this variant. Although occasional cases have shown aggressive behavior, the most frequent clinical course is slowly progressive with localized or diffuse involvement of lower limbs. The histological pattern, characterized by permeation of dermal collagen by labyrinthine vascular channels lined by a flattened endothelium, must be differentiated from spindle cell hemangioendothelioma, low-grade angiosarcoma, targetoid hemosiderotic hemangioma, and benign lymphangioendothelioma.

Primary ablation of atrial flutter and atrial fibrillation.

Direct treatment of atrial flutter and atrial fibrillation--that is, attempting to prevent arrhythmia recurrences by ablating atrial tissue--has been a challenge because of uncertainty about the location of optimal target tissues as well as the amount of atrial tissue requiring destruction to effect cure. Advances have yielded success rates for ablation of the common form of atrial flutter comparable to those for other types of supraventricular tachycardia and provide reason for optimism about the use of catheter techniques, to treat atrial fibrillation definitively. This article discusses some of these advances as well as the current status of catheter ablation for atrial flutter and atrial fibrillation and, finally, what the future may bring.

Primary spindle cell tumor of lymph node with "amianthoid" fibers: a histological, immunohistochemical and ultrastructural study.

A primary mesenchymal spindle cell tumor with amianthoid fibers was observed in an inguinal lymph node of a 70-year-old woman. With immunohistochemical stains the cells were positive for muscle actin and negative for desmin. Transmission electron microscopy (TEM) showed intracytoplasmic bundles of microfilaments with focal densities, profiles of rough endoplasmic reticulum, and basementlike material indicative of myofibroblastic and/or smooth-muscle cell differentiation. At scanning electron microscopy (SEM) the tumor was organized into slitlike spaces containing red blood cells. Amianthoid fibers showed a strong positivity for actin at their edge with a central negative core; by TEM they appeared to be formed of 200 nm thick crystallized collagen fibers surrounded by actin microfilaments arranged in a palisading fashion. The immunohistochemical and ultrastructural findings of the proliferating myoid cells suggest a possible derivation from smooth-muscle vascular cells. Collagen fiber aggregation and actin filament dismission might be secondary to anoxia due to vascular obliteration or disruption.

Rhabdoid tumours of the central nervous system. Report of three cases with immunocytochemical and ultrastructural findings.

Three cases of rhabdoid tumour of the central nervous system arising in a supratentorial location are reported. The patients were 18, 14, and 7 years old. All three tumours showed a common morphology. The neoplastic cells were usually globoid with round nuclei and prominent nucleoli and large acidophilic, cytoplasmic inclusions were present in many of them. These inclusions showed strong immunoreactivity for vimentin, weak immunoreactivity for epithelial membrane antigen and focal immunoreactivity for cytokeratins. Ultrastructurally they were made up of whorls of intermediate filaments, 8-10 nm in thickness. Rhabdoid tumours of the central nervous system, whatever the cell of origin, appear to be an independent entity with identifiable histology and aggressive behaviour.

Familial insulinoma: description of two cases.

We describe cases of isolated functioning insulinoma occurring in two members of the same family (father and daughter). The father had a first encapsulated insulinoma diagnosed at 14 years of age and at the age of 33 years he was operated on for a second insulinoma infiltrating the exocrine pancreas with lymph node metastases. The daughter was operated on for an encapsulated insulinoma in the tail of the pancreas when she was 6 years old. No clinical and laboratory signs of other endocrine disturbances have so far been detected in either care or in any other members of the family. Our report suggests the possibility of multiple familial insulinoma, although this is an extremely rare condition. Our data also indicate that insulinomas, even if well controlled by medical treatment, should always be removed by surgery because malignancy cannot be excluded with certainty. Moreover, patients should be closely followed up, as recurrence may develop up to 15 years after surgery.