Piero Pavone

Hepatic echinococcosis: Clinical and therapeutic aspects

Echinococcosis or hydatid disease (HD) is a zoonosis caused by the larval stages of taeniid cestodes belonging to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated into alveolar and cystic forms, associated with Echinoccus multilocularis (E. multilocularis) and Echinococcus granulosus (E. granulosus) infection, respectively. Cystic echinococcosis (CE) has a worldwide distribution, while hepatic alveolar echinococcosis (AE) is endemic in the Northern hemisphere, including North America and several Asian and European countries, like France, Germany and Austria. E. granulosus young cysts are spherical, unilocular vesicles, consisting of an internal germinal layer and an outer acellular layer. Cyst expansion is associated with a host immune reaction and the subsequent development of a fibrous layer, called the pericyst; old cysts typically present internal septations and daughter cysts. E. multilocularis has a tumor-like, infiltrative behavior, which is responsible for tissue destruction and finally for liver failure. The liver is the main site of HD involvement, for both alveolar and cystic hydatidosis. HD is usually asymptomatic for a long period of time, because cyst growth is commonly slow; the most frequent symptoms are fatigue and abdominal pain. Patients may also present jaundice, hepatomegaly or anaphylaxis, due to cyst leakage or rupture. HD diagnosis is usually accomplished with the combined use of ultrasonography and immunodiagnosis; furthermore, the improvement of surgical techniques, the introduction of minimally invasive treatments [such as puncture, aspiration, injection, re-aspiration (PAIR)] and more effective drugs (such as benzoimidazoles) have deeply changed life expectancy and quality of life of patients with HD. The aim of this article is to provide an up-to-date review of biological, diagnostic, clinical and therapeutic aspects of hepatic echinococcosis.

Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection

The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fishers exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection.

The neurology of coeliac disease in childhood: what is the evidence? A systematic review and meta‐analysis

Aim  The aim of this article was to review and conduct a meta‐analysis of the paediatric literature on the neurology of coeliac disease.

Infantile spasms syndrome, West syndrome and related phenotypes: What we know in 2013

The current spectrum of disorders associated to clinical spasms with onset in infancy is wider than previously thought; accordingly, its terminology has changed. Nowadays, the term Infantile spasms syndrome (ISs) defines an epileptic syndrome occurring in children younger than 1 year (rarely older than 2 years), with clinical (epileptic: i.e., associated to an epileptiform EEG) spasms usually occurring in clusters whose most characteristic EEG finding is hypsarrhythmia [the spasms are often associated with developmental arrest or regression]. The term West syndrome (WS) refers to a form (a subset) of ISs, characterised by the combination of clustered spasms and hypsarrhythmia on an EEG and delayed brain development or regression [currently, it is no longer required that delayed development occur before the onset of spasms]. Less usually, spasms may occur singly rather than in clusters [infantile spasms single-spasm variant (ISSV)], hypsarrhythmia can be (incidentally) recorded without any evidence of clinical spasms [hypsarrhythmia without infantile spasms (HWIS)] or typical clinical spasms may manifest in absence of hypsarrhythmia [infantile spasms without hypsarrhythmia (ISW)]. There is a growing evidence that ISs and related phenotypes may result, besides from acquired events, from disturbances in key genetic pathways of brain development: specifically, in the gene regulatory network of GABAergic forebrain dorsal-ventral development, and abnormalities in molecules expressed at the synapse. Children with these genetic associations also have phenotypes beyond epilepsy, including dysmorphic features, autism, movement disorders and systemic malformations. The prognosis depends on: (a) the cause, which gives origin to the attacks (the complex malformation forms being more severe); (b) the EEG pattern(s); (c) the appearance of seizures prior to the spasms; and (d) the rapid response to treatment. Currently, the first-line treatment includes the adrenocorticotropic hormone ACTH and vigabatrin. In the near future the gold standard could be the development of new therapies that target specific pathways of pathogenesis. In this article we review the past and growing number of clinical, genetic, molecular and therapeutic discoveries on this expanding topic.

Increased antistreptococcal antibody titers and anti-basal ganglia antibodies in patients with Tourette syndrome: controlled cross-sectional study.

The association between Tourette syndrome, attention-deficit hyperactivity disorder (ADHD), and obsessive-compulsive disorder following streptococcal infections has been documented, but with conflicting reports. We thus felt it was important to investigate this association in a group of Italian patients not previously documented. We took blood on 69 patients with Tourette syndrome and 72 age- and sex-matched tic-free controls. Laboratory staff were blind to the diagnostic status of the subjects. Evidence of recent streptococcal infection was defined using antistreptolysin titers. Anti-basal ganglia antibodies were determined using human basal ganglia sections. Statistical analysis was conducted using analysis of variance and chi-square tests. Raised antistreptolysin titers were found in 41 of 69 (59%) patients with Tourette syndrome and 14 of 72 (19%) controls (P = .000). Positive anti-basal ganglia antibodies were found in 22 of 69 (32%) subjects with Tourette syndrome compared with 7 of 72 (10%) controls, which was also significant (P = .002). Raised antistreptolysin titers were detected in 18 of 22 (82%) patients with Tourette syndrome with positive anti-basal ganglia antibodies and 22 of 47 (47%) patients with negative anti-basal ganglia antibodies (P = .01). These results support the reported association between streptococcal infection and anti-basal ganglia antibodies and some patients with Tourette syndrome.

Ohtahara syndrome with emphasis on recent genetic discovery

Ohtahara syndrome or Early Infantile Epileptic Encephalopathy (EIEE) with Suppression-Burst, is the most severe and the earliest developing age-related epileptic encephalopathy. Clinically, the syndrome is characterized by early onset tonic spasms associated with a severe and continuous pattern of burst activity. It is a debilitating and early progressive neurological disorder, resulting in intractable seizures and severe mental retardation. Specific mutations in at least four genes (whose protein products are essential in lower brains neuronal and interneuronal functions, including mitochondrial respiratory chains have been identified in unrelated individuals with EIEE and include: (a) the ARX (aristaless-related) homeobox gene at Xp22.13 (EIEE-1 variant); (b) the CDKL5 (SYK9) gene at Xp22 (EIEE-2 variant); (c) the SLC25A22 (GC1) gene at 11p15.5 (EIEE-3 variant); and (d) the Stxbp1 (MUNC18-1) gene at 9q34-1 (EIEE-4 variant). A yet unresolved issue involves the relationship between early myoclonic encephalopathy (EME-ErbB4 mutations) versus the EIEE spectrum of disorders.

Acute Disseminated Encephalomyelitis: A Long-Term Prospective Study and Meta-Analysis

BACKGROUND There are only a few series in the literature on acute disseminated encephalomyelitis (ADEM) in children. OBJECTIVES AND METHODS the aims of this study were to perform (i) a prospective clinical/imaging study (1992-2009) on ADEM in children consecutively referred to our institution in Catania, Italy, and (ii) to undertake a systematic review and meta-analysis of published ADEM pediatric cohorts (>10 cases). RESULTS We identified 17 patients with ADEM (incidence <10 years of age=1.1 per 100 000 person-years). 15 previously published cohorts were compared with our cohort: (i) systematically reviewed (750 cases); and (ii) meta-analyzed (492/750 cases). The 17 patients had the following characteristics: (a) male-to-female ratio, 1.4 (vs. 1.2-1.3 in previous cohorts); (b) mean age at presentation, 3.6 years (vs. 7.1 years in previous cohorts); (c) specific preceding triggering factor, 88% (vs. 69-79% in previous cohorts); (d) the most common initial signs were ataxia, seizures, headache, and thalamic syndrome; (e) brain imaging revealed >3 lesions in 100% (vs. 92% in previous cohorts); (f) the outcome was good in 94% (vs. 70-75% in previous cohorts); and (g) 12% relapsed once (vs. 18% in previous cohorts). CONCLUSIONS ADEM is generally a benign condition that mosly affects boys more than girls and rarely recurs.

Ophthalmological manifestations in segmental neurofibromatosis type 1

Aims: To study the ophthalmological manifestations in individuals with the typical features of neurofibromatosis type 1 (NF1) circumscribed to one or more body segments, usually referred to as segmental NF1. Methods: Visual acuity and colour tests, visual field examination, slit lamp biomicroscopy of the anterior segment, and a detailed examination of the retina by indirect ophthalmoscopy were performed at diagnosis and follow up in 72 consecutive subjects (29 males, 43 females; aged 1–64 years; mean age 14.6 years) seen at the university departments of paediatrics in Catania and Rome, Italy, during years 1990–2003, who had in restricted body areas: (1) typical pigmentary manifestations of NF1 (café au lait spots and freckling) only (n = 48); (2) NF1 pigmentary manifestations and neurofibromas alone (n = 2); (3) neurofibromas only (n = 15); and (4) plexiform neurofibromas only (n = 7). Results: None of the 72 patients had Lisch nodules in the iris irrespective of age at eye examination or hypertelorism (a “minor” NF1 feature) and none developed typical associated ophthalmological NF1 complications. An additional child had an isolated optic pathways glioma (OPG), which behaved both biologically and radiographically as an NF1 associated OPG. Conclusions: This represents the first systematic study reporting on eye involvement in the largest series of individuals at different ages having segmental NF1. As one of the postulated mechanisms to explain segmental NF1 is somatic mosaicism for the NF1 gene (so far demonstrated only in two patients) the present findings could be explained either by the fact that the eye is too far from the mutated area with NF1 lesions in most cases or by the NF1 (or other “predisposing” or “cooperating”) gene mutation restricted to too few cellular clones or to tissues embryologically different from the eye.

Lacosamide in pediatric and adult patients: comparison of efficacy and safety.

PURPOSE This multicenter, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in pediatric and adult patients with uncontrolled epilepsy. METHOD This study was carried out between September 2010 and December 2011 at 16 Italian and 1 German neurologic centers. Lacosamide was added to the baseline therapy at a starting dose of 1 mg/kg/day in patients aged <16 years (group A) and 100 mg daily in subjects aged 16 and older (group B), and titrated to the target dose, ranging from 3 to 12 mg/kg/day or from 100 to 600 mg daily, respectively. After completing the titration period, patients entered a 12-month maintenance period and they were followed up at 3, 6 and 12 months. The primary assessment of efficacy was based on the change from baseline in seizure frequency per 28 days and was evaluated at 3, 6 and 12 months as follows: number and proportion of 100% responders, 50% responders, non-responders and worsening patients. Safety evaluation was also performed at 3, 6 and 12 months. RESULTS A total of 118 patients (59 group A, 59 group B) with uncontrolled generalized and focal epilepsy were enrolled. Patient mean±SD age was 15.9±6.80 years and the age range was 4-38 years. At 3-month evaluation, of 118 treated patients 56 subjects (47.4% group A; 47.4% group B; p=0.8537) experienced at least a 50% reduction in seizure frequency. At 6 and 12-month follow-up, the 50% responders were 57 (52.5% group A; 44.1% group B; p=0.4612) and 51 (47.4% group A; 39% group B; p=0.4573), respectively. Thirty-five subjects (30.5% group A; 28.8% group B; p=1) experienced side effects during the treatment period. The most common adverse events were dyspepsia for group A and dizziness for group B. CONCLUSION Lacosamide may be a useful and safe pharmacological treatment option for both pediatric and adult patients with uncontrolled seizures.

Headache in pediatric patients with celiac disease and its prevalence as a diagnostic clue.

Objectives: To establish the prevalence of headache in children with celiac disease (CD), the response to a gluten-free diet, and the prevalence of CD in children affected by headache. Methods: This hospital-based study included 2 steps. In the retrospective part, 354 children with CD answered a questionnaire investigating the presence of headache before and after the gluten-free diet. The same questionnaire was administered to 200 healthy children matched for sex and age. In the prospective part, 79 children affected by headache were screened for CD by antitransglutaminase IgA. Diagnosis of CD was confirmed by duodenal biopsy; before starting a gluten-free diet patients underwent a brain positron emission tomography study. After 6 months of follow-up children were reevaluated for the presence of headache. Results: Overall, 88 patients with CD complained of headaches before the diagnosis of CD as compared with 16 in the control group (24.8% vs 8%, P < 0.001). After the institution of a gluten-free diet, the headaches significantly improved in 68 children (77.3%), of whom 24 (27.3%) were headache-free during the study period. Four of 79 (5%) headache patients were found to have CD compared with 0.6% of the general population (P = 0.005). The brain positron emission tomography studies did not show any anomalies. During the follow-up, headaches improved in all 4 children with CD. Conclusions: We recorded—in our geographical area—a high frequency of headaches in patients with CD and vice versa with a beneficial effect of a gluten-free diet. Screening for CD could be advised in the diagnostic work-up of patients with headache.