Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most frequent non-hereditary autoinflammatory disorder in childhood: Its onset is usually observed ...before 5 years, though reports regarding adulthood are increasing. The pathogenesis of the syndrome is not completely understood, but a multifactorial origin, probably based on a polygenic pattern of susceptibility, is the most probable rational pathogenetic hypothesis. Treatment of PFAPA syndrome relies on the administration of low-dose corticosteroids, which promptly abort flares but cannot prevent subsequent disease episodes over time. Tonsillectomy with or without adenoidectomy has proved to be successful in some pediatric patients, as proven by different studies. On the other hand, colchicine, cimetidine, nonsteroidal anti-inflammatory drugs, and interleukin-1 inhibitors have shown efficacy, which require further definite confirmations. This review is aimed at summarizing all the recent evidence about treatment options available for PFAPA syndrome both in pediatric and adult patients.
Coffin-Siris syndrome is a rare genetic disorder defined by the presence of particular facial traits, congenital malformations, intellectual disability, and speech impairment. Epilepsy in ...Coffin-Siris syndrome has only occasionally been reported, and its features are poorly defined. We provide a detailed description of the clinical and instrumental findings of three patients with Coffin-Siris syndrome and epilepsy. The clinical diagnosis in our patients was confirmed by molecular analysis, which identified the presence of de novo mutations of ARID1B and SMARCB1 genes, in two patients and one patient, respectively. All the patients presented with epilepsy, with a mean age of seizure onset of 5.5 years. Seizures were brief and had a focal onset with secondary generalization. Electroencephalographic recording documented a unilateral, and less commonly bilateral, paroxysmal activity in the temporal, parietal, and occipital regions. Clinical response to anticonvulsive therapy was satisfactory, with a low rate of seizure recurrence. Our case series contributes to delineate the phenotype of Coffin-Siris syndrome. We wish this report could pave the way for further studies that will better define the prevalence and clinical manifestations of epilepsy in this rare syndrome.
Introduction
The short arm of chromosome 17 is characterized by a high density of low copy repeats, creating the opportunity for non-allelic homologous recombination to occur. Microdeletions of the ...17p13.3 region are responsible for neuronal migration disorders including isolated lissencephaly sequence and Miller-Dieker syndrome.
Case report
We describe the case of a 4-year and 2-month-old female with peculiar somatic traits and neurodevelopmental delay. At the age of 6 months, she started to present with infantile spasms syndrome; therefore, we administered vigabatrin followed by two cycles of adrenocorticotropic hormone, with good response. The coexistence of epileptic activity, neuropsychological delay, brain imaging abnormalities, and peculiar somatic features oriented us towards the hypothesis of a genetic etiology that could explain her clinical picture. Array CGH identified a 730 Kb deletion in the p13.3 region of the short arm of chromosome 17 including eleven genes, among these are YWHAE and CRK.
Discussion
Microdeletions of the 17p13.3 region involving only YWHAE and CRK, sparing PAFAH1B1, result in neurodevelopmental delay, growth retardation, craniofacial dysmorphisms, and mild structural brain abnormalities. Differently from the previously described patients carrying YWHAE and CRK deletions, the main complaint of our patient was represented by seizures. The absence of clear neuronal migration defects and mutations of the PAFAH1B1 gene in our patient underlines the central role of additional genes located in the 17p13.3 chromosomal region in the pathogenesis of epilepsy and helps to expand the phenotype of 17p13.3 microdeletion syndrome.
MECP2 duplication syndrome (MECP2 DS) is an X-linked disorder characterized by early-onset hypotonia, poor speech development, recurrent respiratory infections, epilepsy and progressive spasticity. ...Epilepsy occurs in more than 50% of the affected patients. Generalized tonic-clonic seizures (GTCS) are the most common seizure-type described but atonic seizures, absences and myoclonic seizures have also been reported. Electroencephalographic (EEG) and seizure types occurring in MECP2 DS have been poorly investigated. Here we report on two male siblings carrying a maternally-inherited MECP2 duplication. Patients underwent several EEG recordings and long-lasting video-EEG monitoring. The most represented seizure types were myoclonic and atonic seizures. GTCS were rarely observed. In patients, we found a slowing of the background activity with multifocal paroxysmal activity, prominent on the frontal areas. In conclusion, our observations seem to suggest that MECP2 syndrome seem to have a peculiar epileptic pattern mainly characterized by the occurrence of myoclonic seizures, the recognition of which is important in order to undertake an appropriate treatment.
Chronic anterior uveitis is the most frequent among extra-articular manifestations of juvenile idiopathic arthritis (JIA) and a relevant cause of ocular morbidity in children. Asymmetric arthritis, ...early onset disease, female sex, and anti-nuclear antibody (ANA) positivity are counted among risk factors for developing this complication. It usually has insidious onset and asymptomatic chronic-relapsing course, but the persistence of low-grade chronic inflammation can lead to irreversible structural ocular damage and to vision-threatening complications. For such reasons, achieving a complete absence of inflammation through early targeted and aggressive treatments is a primary therapeutic goal in these patients. This review is aimed at summarizing scientific evidence about biologic rescue therapy of JIA-related uveitis in patients who fail to achieve clinical remission, in spite of being treated with conventional disease-modifying anti-rheumatic drugs (cDMARDs) and at least one biologic tumor necrosis factor (TNF)-α inhibitor. Interleukin (IL)-6 inhibition appears a promising and safe option for refractory JIA-related uveitis. Abatacept and rituximab proved to be beneficial as well, but their efficacy together with some safety concerns needs to be more extensively evaluated.
We report the case of a 3.6-year-old male child who developed progressive hyposthenia of the left lower limb. Symptoms were preceded by rhinitis, malaise, and fever. Brain and spinal magnetic ...resonance imaging revealed diffuse signal abnormalities compatible with a subacute myeloencephalitis. A diagnostic lumbar puncture was performed and followed by an empirical therapy including Acyclovir, Ceftriaxone, and Clarithromycin. The cerebrospinal fluid analysis revealed clear fluid, glucose, proteins, albumin within the reference range, and 144 leukocytes/mm
3
. Oligoclonal bands were absent and a search for viruses was negative. Wide microbiological surveillance was performed on surface swabs, blood, urine, and stool. Both nasal and pharyngeal swabs were positive for PicoRNAvirus: sequencing identified Rhinovirus A44. This virus has been detected in association with acute flaccid paralysis in only a few patients worldwide, whereas in the great majority of patients with acute flaccid paralysis other Enterovirus species were identified. The most appropriate therapeutic approach towards acute flaccid paralysis is still a matter of debate in the scientific community, with no current definitivere commendations available. With a combined immunosuppressive and anti-inflammatory therapy including intravenous immunoglobulins, intravenous Methylprednisolone, oral Prednisone, and oral Ibuprofen, we experienced a positive outcome both from the clinical point of view and from three-month follow-up imaging studies. Given the rarity and the complexity of this condition, additional studies are needed to better define the potential role of Rhinovirus A44 in the pathogenesis of the disease and the efficacy of any therapeutic measure in the management of acute flaccid paralysis.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the pathogen responsible for the pandemic health emergency declared by the World Health Organization in March 2020. ...During the first part of the pandemic, adults showed mild to severe respiratory symptoms. Children seemed initially exempt, both from acute and subsequent complications. Hyposmia or anosmia were promptly identified as the main symptoms of acute infection, so neurotropism of SARS-CoV-2 was immediately suspected. (1, 2). As the emergency progressed, post infectious neurological complications were described also in pediatric population (3). Cases of cranial neuropathy in connection with acute SARS-CoV-2 infection have been reported in pediatric patients, as an isolate post infectious complication or in the context of the multisystem inflammatory syndrome in children (MIS-C) (4-6). Neuroinflammation is thought to be caused by several mechanisms, among which immune/autoimmune reactions (7), but so far, no specific autoantibody has been identified. SARS-CoV-2 can enter the central nervous system (CNS) directly and/or infect it retrogradely, through the peripheral nervous system (PNS), after replicating peripherally; several factors regulate invasion and subsequent neuroinflammation. Indeed, direct/secondary entry and replication can activate CNS-resident immune cells that, together with peripheral leukocytes, induce an immune response and promote neuroinflammation. In addition, as we will discuss in the following review, many cases of peripheral neuropathy (cranial and non-cranial) have been reported during or after SARS-CoV-2 infection. However, some authors have pointed out that the increase of cranial roots and ganglia in neurological imaging is not always observed in children with cranial neuropathy. (8). Even if a variety of case reports were published, opinions about an increased incidence of such neurologic diseases, linked to SARS-CoV-2 infection, are still controversial (9-11). Facial nerve palsy, ocular movements abnormalities and vestibular alterations are among the most reported issues in pediatric population (3-5). Moreover, an increased screen exposure imposed by social distancing led to acute oculomotion's disturbance in children, not primarily caused by neuritis (12, 13). The aim of this review is to suggest food for thought on the role of SARS-CoV-2 in neurological conditions, affecting the peripheral nervous system to optimize the management and care of pediatric patients.
Cyclic Vomiting Syndrome in Children Raucci, Umberto; Borrelli, Osvaldo; Di Nardo, Giovanni ...
Frontiers in neurology,
11/2020, Volume:
11
Journal Article
Peer reviewed
Open access
Cyclic Vomiting Syndrome (CVS) is an underdiagnosed episodic syndrome characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. It is often misdiagnosed due to the ...unappreciated pattern of recurrence and lack of confirmatory testing. CVS mainly occurs in pre-school or early school-age, but infants and elderly onset have been also described. The etiopathogenesis is largely unknown, but it is likely to be multifactorial. Recent evidence suggests that aberrant brain-gut pathways, mitochondrial enzymopathies, gastrointestinal motility disorders, calcium channel abnormalities, and hyperactivity of the hypothalamic-pituitary-adrenal axis in response to a triggering environmental stimulus are involved. CVS is characterized by acute, stereotyped and recurrent episodes of intense nausea and incoercible vomiting with predictable periodicity and return to baseline health between episodes. A distinction with other differential diagnoses is a challenge for clinicians. Although extensive and invasive investigations should be avoided, baseline testing toward identifying organic causes is recommended in all children with CVS. The management of CVS requires an individually tailored therapy. Management of acute phase is mainly based on supportive and symptomatic care. Early intervention with abortive agents during the brief prodromal phase can be used to attempt to terminate the attack. During the interictal period, non-pharmacologic measures as lifestyle changes and the use of reassurance and anticipatory guidance seem to be effective as a preventive treatment. The indication for prophylactic pharmacotherapy depends on attack intensity and severity, the impairment of the QoL and if attack treatments are ineffective or cause side effects. When children remain refractory to acute or prophylactic treatment, or the episode differs from previous ones, the clinician should consider the possibility of an underlying disease and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities and specific sub-phenotype. This review was developed by a joint task force of the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) to identify relevant current issues and to propose future research directions on pediatric CVS.
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