Autoimmune encephalitis and CSF anti-AMPA GluR3 antibodies in childhood: a case report and literature review.

Acute autoimmune encephalitis is a severe neurological disorder presenting with altered level of consciousness, confusion, irritability, headache, vomiting, and in some cases seizures. An infective event precedes by 1-2 weeks the onset of the symptoms. Cognitive impairment is considered the cardinal symptom. The autoimmune encephalitis comprises an increasingly group of inflammatory brain disorder caused by an underlying abnormal immune response to the CNS to the infective agent. In children, several antibodies have been recorded as causative agent. Among these, GAD65, MOG, and NMDAR antibodies are more commonly reported and with less frequency, the Dopamine-2 receptor, GABA A receptor, GABA B receptor, and Glycinereceptorandm-GluR5. We report here a 10-year-old male with acute autoimmune encephalitis with altered status of consciousness and severe cerebral involvement at the brain-MRI. Serum and cerebrospinal fluid disclosed the presence of anti-AMPA-GluR3 antibodies suggesting a possible pathogenetic correlation with the disorder presented by the proband. Precocious treatment with intravenous methylprednisolone and immunoglobulin resulted in progressive but constant improvement. At 3-month follow-up, the clinical condition of the child and the neuro-radiological brain anomalies returned to the normal. At the 2-year follow-up, no recurrence or other disturbances were reported.

Benign Acute Childhood Myositis: Our Experience on Clinical Evaluation.

BACKGROUND: Benign acute childhood myositis (BACM) is a transient condition mainly affecting children of school age characterized by muscle pain, typically localized to the calf muscle with symmetrical lower extremity pain and difficulty in walking. Usually, the symptomatology is preceded by a viral infection including influenza, parainfluenza, rotavirus, and mycoplasma. METHODS: The case series was conducted in four pediatric hospitals in Catania, Italy, over a 12-year observational period. Clinical examination, laboratory data, course, treatment, and complications of the affected children were extracted from electronic medical records of each hospital. RESULTS: For the case series, 50 children diagnosed with BACM were enrolled: the mean age of affected children was 5.35 years, 86% of were males, and in 56% the affections occurred during the winter. In the affected children, the clinical picture was characterized by previous fever and/or symptoms of inflammation of the upper airways, and followed by pain in the lower extremities up to uncoordinated gait. In 17 cases the etiological agent was isolated, including the influenza virus type B as the most frequent and influenza virus type A, Mycoplasma pneumoniae, beta-hemolytic streptococcus, and herpes simplex virus. Children were treated with supportive therapy. In all the children the muscular symptomatology had a good evolution with progressive marked reduction of pain and of the high level of CKemia. Neither clinical recurrences nor sequelae were reported. CONCLUSION: BACM shows to have in most of the cases a favorable evolution, a spontaneous remission of symptoms, and a good prognosis. However, the disorder generates parental distress for the acute presentation and the striking muscle dysfunction. It is worthy a rapid and early diagnosis to avoid unnecessary diagnostic investigations and a careful follow-up necessary to exclude persistence of symptoms or creatine kinase elevation.

Pure Interstitial 7q21.3-q 31.1 Duplication: A Rare Segmental Genomic Aneuploidy: Case Report and Review of Cases with Distal and Similar Segment Involved.

In children with developmental delay (DD) and neurologic impairment, diagnosis can be challenging because of the wide spectrum of causes. Since the last decade, the use of array comparative genomic hybridization (CGH) offered a great contribution to get a diagnosis in complex phenotypes. The chromosome 7 is subject of interest in medical genetics because of its frequent association with chromosome aberrations, rearrangements, and deletions involving clinical manifestations. We hereby reported a 3-year-old male child patient with severe neuro-DD, craniofacial dysmorphisms, and pulmonary stenosis, whose array CGH analysis disclosed a duplication of 14.4 Mb on chromosome 7 (7q21.3-7q31.1). By reviewing the current literature to date, we first reported on neurologic and dysmorphic anomalies related to this rearrangement which was not previously reported.

Malformations of Cortical Development, Cognitive Involvementand Epilepsy: A Single Institution Experience in 19 Young Patients.

BACKGROUND: Malformations of cortical development (MCD) include a wide range of congenital disorders mostly causing severe cognitive dysfunction and epilepsy. OBJECTIVE: to report on clinical features including cognitive involvement, epileptic seizures with response to antiseizure medications, comorbidities in young patients affected by MCD and followed in a single tertiary hospital. PATIENTS AND METHODS: A retrospective review of the medical records and magnetic resonance images (MRI) of 19 young patients with an age ranging between eight days and fifteen years affected by MCD and admitted to Pediatrics Department University of Catania, Italy from October 2009 and October 2020 were selected. Patients were distinguished in three groups following the Barcovich et al. 2012 classification for MCD: 4 (21%) in Group I; 8 (42%) in Group II; and, and 7 (37%) in Group III. Clinical features and MRI of the patients including cognitive involvement, epilepsy type and response to drugs treatment were analyzed. RESULTS: In Group I, two patients showed cortical dysplasia and two dysembryoplastic neuroepithelial tumors plus focal cortical dysplasia; developmental delay/intellectual disability (DD/ID) was severe in one, moderate in one and absent in two; the type of seizures was in all the cases focal to bilateral tonic-clonic (FBTCs), and drug resistant was found in one case. In Group II, three patients showed neuronal hetero-topias and five had pachygyria-lissencephaly: DD/ID was severe in four, moderate in two, and absent in two; the type of seizure was focal (FS) in five, focal to bilateral tonic-clonic (FBTCs) in two, infantile spasms (IS) in one, and drug resistant was found in three. In Group III, six showed polymicrogyria and one schizencephaly: DD/ID was found severe in five, moderate in two, and the type of seizure was focal (FS) in five, FBTCS in two, and drug resistance was found in three.

On clinical findings of Bickerstaff's brainstem encephalitis in childhood.

A short review on the clinical presentation of pediatrics cases of Bickerstaff brain encephalitis emphasizing the broad clinical spectrum of the disease. Cases of pediatric Bickerstaff's brainstem encephalitis collected on three electronic medical databases (PubMed, Cochrane Library and Scopus Web of Science) are reviewed. The inclusion criteria of the cases were based on the clinical characteristics of the disorder in the pediatric age. We reviewed 20 articles on Bickerstaff's brainstem encephalitis, identifying 40 pediatric cases focused on the clinical symptoms. We saw that the prevalence was higher in male subjects, and the median age at diagnosis was 8 years. The phenotype of pediatrics patients was similar to previously published literature. We identify three cases of overlapping forms between Bickerstaff brain encephalitis and Guillain-Barré Syndrome in patients with lower limbs weakness and typical signs of Bickerstaff brain encephalitis, suggesting a combined involvement of the central and peripheral nervous system. Although there is no defined data on incidence and prevalence in the literature, Bickerstaff's brainstem encephalitis appears to be a rare disorder, especially in children. The incidence of Bickerstaff brain encephalitis and Guillain-Barré Syndrome, and Miller Fisher Syndrome has been underrated in the past, primarily due to an underestimation of the forms with a Peripheral Nervous System involvement. Bickerstaff brain encephalitis usually has a rapid and acute onset within 2-4 weeks, characterized by a typical picture of ophthalmoplegia, hyperreflexia, cerebellar symptoms as ataxia. The subsequent manifestations of hyperreflexia or consciousness disturbances as drowsiness, sleepiness, or coma, indicative of central involvement, suggest a Bickerstaff brain encephalitis clinical diagnosis.

Non-Epileptic Paroxysmal Events: Clinical features and diagnostic differences with epileptic seizures. A Single Tertiary Centre Study.

BACKGROUND: Non-Epileptic Paroxysmal Events (NEPE) are common clinical manifestations in pediatric age presenting with dysfunction of motor and behavioral activity mimicking features of epileptic seizures. OBJECTIVE: To present and analyze number and clinical characteristic of a group of children/adolescents presenting with various types of NEPE; to compare clinical data of this group of NEPE affected children/adolescents with a group of children/adolescents affected by Epileptic Seizures (ES). METHODS: The retrospective study was conducted at the Pediatric Clinic of University of Catania, Catania, Italy, in a period ranging from January 2005 and January 2018. Two groups of children/adolescents, aged from 1 month to 15 years, were selected: 312 affected by NEPE and 192 by ES. Number and percentage of the single type of NEPE were reported. Then, demographic characteristics, clinical manifestations, duration of the events, time of diagnosis, and age of onset of each type of NEPE and ES affected children/adolescents were analyzed and compared. Results of statistical analysis of the data were carried out between ES and some type of NEPEs including Sandifer syndrome, breath-holding spells, paroxysmal tremors, vertigo, and syncope. RESULTS: Among the group of NEPE, vertigo, type of paroxysmal event clinically not classifiable, syncope, and Sandifer syndrome were the most common events; In the comparative analyzed samples, variability between NEPE and ES was found in the duration of the paroxysmal events, in number of episodes, in lag-time between the onset of symptoms and the diagnosis, and in age of onset. Analyzing clinical data of ES with some type of NEPE, statistical significant results were obtained in vertigo as regards the duration and average duration event, in paroxysmal tremors as number of events, in Sandifer syndrome as lag-time of diagnosis, and finally in all the types of NEPE as regards the age of onset, and loss of consciousness. CONCLUSIONS: Analyzing the clinical features of each type of NEPE differences with ES are found. However, globally considered diagnostic differences between NEPE and ES remain difficult, questionable, and unrealizable without the support of correct parental report, direct clinical observations, and video-EEG monitoring.

Previously Unreported COL7A1 Mutation in a Somali Patient with Dystrophic Epidermolysis Bullosa.

Epidermolysis bullosa (EB) encompasses a group of inheritable skin disorders characterized by various degrees of epithelial fragility that lead to cutaneous and mucosal blistering following negligible mechanical traumas. These disorders are clinically and genetically heterogeneous, ranging from mild skin involvement to severe disabling conditions with associated manifestations affecting the gastrointestinal and vesico-urinary tracts. EB may be classified into 4 main categories: simplex, junctional, dystrophic, and Kindler syndrome. Clinically, EB may present as syndromic or nonsyndromic forms. EB subtypes have mainly reported a number of mutations in the candidate COL7A1 gene encoding type VII collagen, a major stabilizing molecule of the dermoepidermal junction. Herein, we report a Somali girl with dystrophic EB who showed a previously unreported missense variant c.6797G>T in exon 86 in COL7A1.

Poland Syndrome with Atypical Malformations Associated to a de novo 1.5 Mb Xp22.31 Duplication.

Poland's syndrome (PS; OMIM 173800) is a rare congenital syndrome which consists of absence or hypoplasia of the pectoralis muscle. Other features can be variably associated, including rib defects. On the affected side other features (such as of breast and nipple anomalies, lack of subcutaneous tissue and skin annexes, hand anomalies, visceral, and vertebral malformation) have been variably documented. To date, association of PS with central nervous system malformation has been rarely reported remaining poorly understood and characterized. We report a left-sided PS patient carrying a de novo 1.5 Mb Xp22.31 duplication diagnosed in addiction to strabismus, optic nerves and chiasm hypoplasia, corpus callosum abnormalities, ectopic neurohypophysis, pyelic ectasia, and neurodevelopmental delay. Since, to our knowledge, this features' association has not been previously reported, we argue that this case may contribute to further widening of the variability of PS phenotype.

Secondary Scoliosis as a Complication of Acute Transverse Myelitis in a Child.

Acute transverse myelitis (ATM) is a rare neurological condition that affects the spinal cord. Several events, including infections, autoimmune conditions, inflammatory, and drug-induced factors, may cause this disorder. Correct and rapid etiological diagnosis is necessary in order to start appropriate treatment that mainly consists of immunomodulating therapy, high dose intravenous corticosteroids, and in plasma exchange in noninfectious cases. The outcome is varied and depends on several factors. In children, the prognosis is usually good. We report a case of an 11-year-old boy who presented with interscapular pain, right leg steppage, homolateral hyposthenia of the upper limb, and signs of autonomic dysfunction. After performing specific and instrumental exams, a diagnosis of transverse myelitis was reached, and appropriate therapy was performed. A few days post-treatment, the child developed a secondary scoliosis, involving a thoracolumbar curve with loss of cervical and lumbar lordosis. After rehabilitative treatment was undertaken for 12 months, a complete recovery and normal restoration of spinal physiological curves was obtained. The pediatric cases of ATM have a good response to steroid therapy combined with physiotherapy. Collaboration among the various specialists is worthwhile, in order to lead to a correct and rapid diagnosis.

Grisel syndrome, sigmoid sinus thrombosis and rheumatic carditis: Case report of a rare association.

Grisel's syndrome (GS) is a non traumatic atlanto-axial rotatory subluxation of C1-C2 joint. A six year old girl, 20 days after an episode of fever, developed a torticollis and a 3/6 heart murmur. The echocardiography showed a Rheumatic Carditis. The Brain and cervical spine Magnetic resonance imaging (MRI) and the Computerized Tomography (CT) showed rotary dislocation of C1-C2 vertebrae, compatible with GS, and cerebral venous thrombosis (CVT). An antibiotic therapy, Prednisone and a low molecular weight heparin for 7 days was prescribedfollowed by an oral anticoagulant for 6 months. After a month the MRI showed a reduction of the dislocation and cerebral venous recanalization.

Optic Neuropathy, Secondary to Ethmoiditis, and Onodi Cell Inflammation during Childhood: A Case Report and Review of the Literature.

Optic neuropathy consists of several etiological events. The primary etiologies of its acute form include optic neuritis, ischemic optic neuropathy, inflammatory (nondemyelinating) disorders, and trauma. Its subacute and chronic forms are most often linked to compressive, toxic, nutritional, or hereditary-genetic causes. Visual loss, dyschromatopsia, and visual field defects are the presenting symptoms. The Onodi cell (sphenoethmoidal air cell) is an anatomic variant located laterally and superior to the sphenoid sinus; it is closely related to the optic nerve. Onodi cell disorders are rare and may be unnoticed in differential diagnoses of patients with ocular and neurological manifestations. Here, we present the case of a 12-year-old boy with headache and acute loss of sight characterized by hemianopsia in the left eye and retrobulbar optic neuropathy caused by left sphenoethmoidal sinusitis with the presence of Onodi cell inflammation. The diagnosis was confirmed by multilayered paranasal computed tomography and cerebral magnetic resonance imaging. Therapeutic treatment resulted in gradual improvement: at the 2-week follow-up, the patient no longer had headaches and his visual acuity returned to normal. Inflammation of Onodi cells should be considered in children with headache and abnormal vision.

Focal Neuropathy Mimicking Focal Dystonia in a Child: Diagnostic and Rehabilitative Tools.

OBJECT: Focal neuropathy results from an injury of any etiology that occurs in a peripheral nerve. The lesion may be followed by alteration of the sensory sphere (either dysesthesia or paresthesia with or without neuropathic pain), or by compensatory attitudes that are attributable to the altered contraction in muscles that are innervated by the injured nerve. METHODS: We describe the case of a 13-year-old boy who attended our hospital for a focal neuropathy of the radial nerve. CONCLUSION: This neuropathy was revealed after the removal of a plaster Zimmer splint that was applied following a post-traumatic subluxation of the metacarpal-trapezoid joint.

Arterial ischemic stroke (AIS) in childhood: clinical report from a single control center.

INTRODUCTION: Stroke is the clinical designation for a rapidly developing loss of brain function due to an interruption in the blood supply to all or part of the brain. It is the third cause of death in adults and one of the top 10 causes in pediatric age. The perinatal period of onset is the second only to adult age group in the incidence of stroke. Arterial ischemic stroke during childhood occurs most frequently in the perinatal period with an incidence of 1 out 2300-5000 live infant births. MATERIALS AND METHODS: This is a retrospective study that includes 28 patients affected by perinatal arterial ischemic stroke. Family and gestational history, risk factors of perinatal stroke, gender and clinical data of affected children and outcome are reported. RESULTS: A stroke family history was registered in three unrelated families. Gestational history disclosed cases of threats of abortion, preterm delivery, hyperthermia, gestosis, and placental disorders. In the children, onset of seizures were reported within 3 days of life and diagnosis of stroke was confirmed by brain MRI which disclosed involvement of the middle cerebral artery in all the cases. Hemilateral cerebral palsy, epileptic seizures, and intellectual disability from mild to severe were the most frequent complications. CONCLUSION: Stroke is still a common and dreadful events in perinatal period as this disorder is often unpredictable and cause of severe neurological impairment.

Pott Disease in a 14-year-old Girl Affected by Congenital Lamellar Ichthyosis Type 3 and Diabetes Mellitus.

Extrapulmonary manifestations of tuberculosis (TB) are particularly frequent during childhood, and usually involve the lymph nodes and the skull. They are related to predisposing immunosuppression conditions. A patient affected by diabetes mellitus type 1 (DMT1) and congenital lamellar ichthyosis type 3 came at our attention with a 4-year history of recurrent parotitis and severe back pain and inferior limb hypomobility, which had lasted for 6 months. A diagnosis of chronic TB parotitis combined with Pott disease was performed after a suggestive spinal magnetic resonance imaging, and positive culture and polymerase-chain reaction examination. Surgical aspiration of the fluid collection and a 12-month antitubercular treatment resulted in complete resolution of the symptomatology. This is the first report of a Pott disease in a patient affected by the two co-occurrences of two immunosuppression diseases such as DMT1 and congenital lamellar ichthyosis type 3.

Hypoglossal nerve paralysis in a child after a dental procedure.

Unilateral palsy of the hypoglossal nerve is a rare complication of orthodontic procedures. The main reported causes of HNP are: orthopedic and otorhinolaryngology surgical interventions, and in particular maneuvers involving compression or overstretching of the hypoglossal nerve, dental procedures and traumas, and also infections, motoneuron disorders, tumors, vascular diseases. Diagnosis is usually performed by electrophysiology studies (EMG-VCN), and brain magnetic resonance imaging (MRI) is useful to exclude other causes. The prognosis depends on the location and extension of the damage. Currently there is not a standardized treatment approach except the speech therapy, although, in some cases, the high-dose steroid treatment could be useful. We describe the case of a ten-year-old female, who was admitted in our Unit after a deviation of the tongue associated with dysarthria and dysphagia, occurred after the application of a mobile orthodontic device.

Erythema Nodosum and Mycoplasma pneumoniae Infections in Childhood: Further Observations in Two Patients and a Literature Review.

Erythema nodosum (EN) is the most frequent panniculitis in childhood and has been associated with various conditions, such as infectious and autoimmune disorders, medications, and malignancies. The author reports on two children affected with EN associated with Mycoplasma pneumoniae infection, which occurred in one patient without pulmonary detection. The available literature on EN and M. pneumoniae infection in childhood is also reviewed.

Congenital portosystemic shunt: our experience.

Introduction. Congenital portosystemic venous malformations are rare abnormalities in which the portal blood drains into a systemic vein and which are characterized by extreme clinical variability. Case Presentations. The authors present two case reports of a congenital extrahepatic portosystemic shunt (Type II). In the first patient, apparently nonspecific symptoms, such as headache and fatigue, proved to be secondary to hypoglycemic episodes related to the presence of a portosystemic shunt, later confirmed on imaging. During portal vein angiography, endovascular embolization of the portocaval fistula achieved occlusion of the anomalous venous tract. In the second patient, affected by Down's syndrome, the diagnosis of a portosystemic malformation was made by routine ultrasonography, performed to rule out concurrent congenital anomalies. Because of the absence of symptoms, we chose to observe this patient. Conclusions. These two case reports demonstrate the clinical heterogeneity of this malformation and the need for a multidisciplinary approach. As part of a proper workup, clinical evaluation must always be followed by radiographic diagnosis.

Rhabdomyomas and tuberous sclerosis complex: our experience in 33 cases.

BACKGROUND: Rhabdomyomas are the most common type of cardiac tumors in children. Anatomically, they can be considered as hamartomas. They are usually randomly diagnosed antenatally or postnatally sometimes presenting in the neonatal period with haemodynamic compromise or severe arrhythmias although most neonatal cases remain asymptomatic. Typically rhabdomyomas are multiple lesions and usually regress spontaneously but are often associated with tuberous sclerosis complex (TSC), an autosomal dominant multisystem disorder caused by mutations in either of the two genes, TSC1 or TSC2. Diagnosis of tuberous sclerosis is usually made on clinical grounds and eventually confirmed by a genetic test by searching for TSC genes mutations. METHODS: We report our experience on 33 cases affected with rhabdomyomas and diagnosed from January 1989 to December 2012, focusing on the cardiac outcome and on association with the signs of tuberous sclerosis complex. We performed echocardiography using initially a Philips Sonos 2500 with a 7,5/5 probe and in the last 4 years a Philips IE33 with a S12-4 probe. We investigated the family history, brain, skin, kidney and retinal lesions, development of seizures, and neuropsychiatric disorders. RESULTS: At diagnosis we detected 205 masses, mostly localized in interventricular septum, right ventricle and left ventricle. Only in 4 babies (12%) the presence of a mass caused a significant obstruction. A baby, with an enormous septal rhabdomyoma associated to multiple rhabdomyomas in both right and left ventricular walls died just after birth due to severe heart failure. During follow-up we observed a reduction of rhabdomyomas in terms of both number and size in all 32 surviving patients except in one child. Eight patients (24,2%) had an arrhythmia and in 2 of these cases rhabdomyomas led to Wolf-Parkinson-White Syndrome. For all patients the arrhythmia spontaneously totally disappeared or was reduced gradually. With regarding to association with tuberous sclerosis, we diagnosed tuberous sclerosis clinically in 31 babies (93,9%). CONCLUSION: Rhabdobyomas are tumors with favorable prognosis because they frequently do not cause symptoms and they often regress in numbers and size. Nevertheless, due to frequent association with tuberous sclerosis complex and the resulting neurological impairment, the prognosis can result unfavorable.