Gaetano Cantalupo

• MD
• Professor (Associate) at University of Verona

Benign childhood epilepsy with centrotemporal spikes (BECTS) has been investigated through EEG–fMRI with the aim of localizing the generators of the epileptic activity, revealing, in most cases, the activation of the sensory–motor cortex ipsilateral to the centrotemporal spikes (CTS). In this case report, we investigated the brain circuits hemodyna...

It has been documented that anteromedial temporal lobe dysfunction can cause impairment in emotional intelligence. In particular, medial temporal lobe epilepsy (MTLE) is associated with disorders in emotion recognition from facial expressions. About one-third of patients with MTLE experienced febrile seizures (FSs) during childhood. In the present...

We present the response pattern of intracranial event-related potentials (ERPs) recorded from depth-electrodes in the human amygdala (four patients) to faces or face parts encoding fearful, happy or neutral expressions. The amygdala showed increased amplitude ERPs (from 200 to 400 ms post-stimulus) in response to the eye region of the face compared...

Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanops...

The terms “epileptic encephalopathy” (EE) and “developmental and epileptic encephalopathy” (DEE) are used to describe complex neurological conditions characterized by seizures, severe EEG abnormalities, and developmental impairments. EE, as initially defined, describes epilepsy-related disruptions in cerebral function, while DEE incorporates develo...

Polygraphic investigations provide a correlation between a behavioral manifestation and a variable set of physiologic parameters. In the study of epilepsy, polygraphic recordings can be essential to identify and describe the occurrence and characteristics of changes occurring in various physiologic functions in concomitance with epileptic abnormali...

Electroencephalography (EEG) has evolved significantly since its origins with Richard Caton and Adolf Beck, culminating in Hans Berger’s first human EEG recording in 1924. This breakthrough marked a paradigm shift in neuroscience, leading to the development of a “new language” to describe the characteristic waveforms observed in EEG recordings. As...

Objective Dravet syndrome (DS) is a developmental and epileptic encephalopathy with a wide spectrum of comorbidities comprising sleep disorders, reported in up to 85% of cases. For this, a sleep study is recommended in patients with a sleep complaint. However, no data are available on sleep architecture in DS or on the impact of seizures on sleep q...

Most practicing neurologists will have seen patients with reflex epilepsies—in other words, patients with seizures induced by light stimuli or by sudden, unexpected noises. In some patients, seizures may be triggered by more complex precipitants such as reading, emotion or certain movements or activities. The neurophysiological bases and clinical m...

Background Sturge–Weber Syndrome (SWS) is a rare, sporadic neurocutaneous disorder affecting the skin, brain, and eyes, due to somatic activating mutations in GNAQ or, less commonly, GNA11 gene. It is characterized by at least two of the following features: a facial capillary malformation, leptomeningeal vascular malformation, and ocular involvemen...

Background and Clinical Significance: Acute necrotizing encephalopathy (ANE) represents a severe complication, mainly described in children, of influenza virus infection. We report the cases of two young girls with ANE associated with influenza virus infection who were diagnosed by MRI cerebral scan. Case Presentation: A 7-year-old girl with a hist...

Background We aimed to estimate real-world evidence of the prevalence rate of genetic developmental and epileptic encephalopathies (DEEs) in the Italian population over a 11-year period. Methods Fifteen paediatric and adult tertiary Italian epilepsy centres participated in a survey related to 98 genes included in the molecular diagnostic workflows...

Objective Few studies have evaluated the efficacy of antiseizure medications (ASMs) according to the etiology of neonatal acute provoked seizures. We aimed to investigate the response to ASMs in term/near term neonates with acute arterial ischemic stroke (AIS), as well as the type of seizure at presentation and the monitoring approach. Methods We...

Background and Clinical Significance: Acute necrotizing encephalopathy (ANE) represents a severe complication of influenza virus infection, mainly described in children. We report the cases of two young girls with ANE associated with influenza virus infection, diagnosed by MRI cerebral scan. Case Presentation: A 7-year-old girl with a history of a...

Objective EEG patterns and quantitative EEG (qEEG) features have been poorly explored in monogenic epilepsies. Herein, we investigate regional differences in EEG frequency composition in patients with STXBP1 developmental and epileptic encephalopathy (STXBP1‐DEE). Methods We conducted a retrospective study collecting electroclinical data of patien...

Myoclonus has multiple clinical manifestations and heterogeneous generators and etiologies, encompassing a spectrum of disorders and even physiological events. This paper, developed from a teaching course conducted by the Neurophysiology Commission of the Italian League against Epilepsy, aims to delineate the main types of myoclonus, identify poten...

Objectives People with neurodevelopmental disorders frequently experience sleep disturbances, negatively impairing their quality of life. We aimed to determine the prevalence and nature of sleep disturbances in patients with SCN8A ‐related disorders. Methods Through a collaborative network of caregivers and clinicians, we collected data about epil...

Objective: The clinical spectrum of SMA has changed due to advances in the treatment with disease-modifying therapies, which should be started as soon as possible to improve therapy efficacy and the disease's prognosis. This work aims to present the state of the art of the SMA clinical pathway, outlining the importance of newborn screening (NBS) in...

A 7-year-old right-handed girl presented to the pediatric neurology outpatient clinic after 5 episodes of headache over the previous 3 months. Her family history was positive for migraine in the mother and maternal grandmother and for febrile seizures in the older sister. The neurologic examination and cognitive profile were normal. Five seconds af...

COL4A1/2 variants are associated with highly variable multiorgan manifestations. Depicting the whole clinical spectrum of COL4A1/2 ‐related manifestations is challenging, and there is no consensus on management and preventative strategies. Based on a systematic review of current evidence on COL4A1/2 ‐related disease, we developed a clinical questio...

Objective DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1‐related epilepsy has been reported in small cohorts. We dissect the electroclinical features of 34 patients harboring de novo DYNC1H1 pathogenic variants, identify subphenotypes on the DYNC1H1‐related epilepsy spectrum...

Introduction. AADCd is an ultrarare, underdiagnosed neurometabolic disorder for which a screening test (3-OMD dosing on dried blood spot (DBS)) and targeted gene therapy (authorized in the EU and the UK) are available. Therefore, it is mandatory to raise awareness of presenting symptoms and signs among practitioners. Delivering scientifically sound...

Content available: Video.

In epilepsy with myoclonic-atonic seizures (EMA), status epilepticus (SE) may occur during the onset phase, uncommonly in post-puberal patients. We report a post-puberal patient with EMA who presented SE with insidious onset and catamenial recurrence. She had a stormy epilepsy onset at 4 years, with tonic seizures, atypical absences, and myoclonic-...

High-density EEG (hdEEG) is a validated tool in presurgical evaluation of people with epilepsy. The aim of this national survey is to estimate diffusion and knowledge of hdEEG to develop a network among Italian epilepsy centers. A survey of 16 items (and 15 additional items) was distributed nationwide by email to all members of the Italian League A...

Objective Variants in GABRA1 have been associated with a broad epilepsy spectrum, ranging from genetic generalized epilepsies to developmental and epileptic encephalopathies. However, our understanding of what determines the phenotype severity and best treatment options remains inadequate. We therefore aimed to analyze the electroclinical features...

Backgroud SARS-Cov2 infection began to spread worldwide since December 2019; on March 2020, the World Health Organization characterized its related disease, named COVID-19, as a pandemic. In Italy, to contain the spread of infection a severe lockdown in the spring 2020 was instituted. Other less severe restrictions were imposed in the winter 2020–2...

Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be i...

Purpose: Heterozygous variants in PRRT2 are mostly associated with benign phenotypes, being the major genetic cause of benign familial infantile seizures (BFIS), as well as in paroxysmal disorders. We report two children from unrelated families with BFIS that evolved to encephalopathy related to status epilepticus during sleep (ESES). Methods and...

Gelastic seizures are rare epileptic manifestations characterized by laughter or a smile. The main etiology is represented by hypothalamic hamartoma, but also focal localization of the epileptogenic zone is described. We reviewed a group of patients with gelastic seizures to describe the semiology and to establish any difference related to diverse...

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is a childhood epilepsy syndrome characterized by the appearance of cognitive, behavioral, and motor disturbances in conjunction with a striking activation of EEG epileptic abnormalities during non-REM sleep. After more than 50 years since the first description, the pathophysiolo...

Background and Objectives We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Methods In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs rela...

Aim To explore the feasibility of using an adaptive behaviour profile (ABP) assessment generated from a well‐known measure—the Vineland Adaptive Behavior Scales, Second Edition (VABS‐II)—as an instrument for outcome measures in adolescents and adults with Dravet syndrome. Method We administered the VABS‐II to 35 adolescents and adults with Dravet...

Purpose To perform a systematic review searching for differences in the side effects of antiseizure medications (ASMs) with respect to sex in pediatric patients with epilepsy. Methods We carried out a comprehensive literature search of the PubMed database and all results up to April 2020 were included. Titles, abstracts, and full texts of the arti...

Objective Febrile status epilepticus evolves from a febrile seizure (FS) in 5% of cases. Its prompt recognition is challenging, especially when motor manifestations are absent or subtle. We describe the ictal electroclinical features of non‐convulsive febrile status epilepticus (NCFSE) following an apparently concluded FS, initially misinterpreted...

Background and objectives Pathogenic STXBP1 variants cause a severe early-onset developmental and epileptic encephalopathy (STXBP1-DEE). We aimed to investigate the natural history of STXBP1-DEE in adults focusing on seizure evolution, presence of movement disorders and the level of functional (in)dependence. Methods In this observational study, p...

Background and Objectives Clinical manifestations in STXBP1 developmental and epileptic encephalopathy (DEE) vary in severity and outcome, and the genotypic spectrum is diverse. We aim to trace the neurodevelopmental trajectories in individuals with STXBP1 -DEE and dissect the relationship between neurodevelopment and epilepsy. Methods Retrospecti...

SYNGAP1-developmental and epileptic encephalopathy (SYNGAP1-DEE) has been recently featured as a distinct genetic disease characterized by global psychomotor delay mainly involving language, moderate-to-severe cognitive impairment, autism spectrum disorder, and a generalized epilepsy with spontaneous and reflex seizures. The severity and variabilit...

BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. We identified, by whole exome-sequencing analysis, the p.His162Gln variant of the BCKDK gene in a neonate,...

Objective. Coffin‐Siris syndrome (CSS) is a rare congenital malformation syndrome, caused by mutations in the ARID1B gene in over half of the cases. While the clinical characteristics of the syndrome have been increasingly described, a detailed evaluation of the epileptic phenotype in patients with ARID1B alterations and CSS has not been approached...

Background and Objectives Purine-rich element-binding protein A ( PURA ) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotyp...

PURA syndrome is a distinct form of developmental encephalopathy, characterized by early‐onset hypotonia, severe developmental delay, intellectual disability, epilepsy and respiratory and gastrointestinal disorders. We report a child with PURA syndrome, harbouring a previously described mutation, whose phenotype included two peculiar aspects: (1) h...

CHD2 encodes the chromodomain helicase DNA‐binding protein 2, an ATP‐dependent enzyme that acts as a chromatin remodeler. CHD2 pathogenic variants have been associated with various early onset phenotypes including developmental and epileptic encephalopathy, self‐limiting or pharmacoresponsive epilepsies and neurodevelopmental disorders without epil...

Background and purpose: The core manifestations of leucine-rich glioma-inactivated 1 (LGI1) autoantibody-mediated encephalitis are limbic encephalitis and faciobrachial dystonic seizures. Agrypnia excitata (AE) is a rare syndrome characterized by sleep-wake cycle disruption, autonomic hyperactivation and episodes of oneiric stupor. Only a few dise...

Objective To report longitudinal clinical, EEG, and MRI findings in 2 sisters carrying compound heterozygous ARV1 mutations and exhibiting a peculiar form of developmental and epileptic encephalopathy (DEE). Neuropathologic features are also described in one of the sisters. Methods Clinical course description, video-EEG polygraphic recordings, bra...

Background: Purified cannabidiol (CBD) was administered to highly refractory patients with Dravet (DS) or Lennox–Gastaut (LGS) syndromes in an ongoing expanded access program (EAP). Herein, we report interim results on CBD safety and seizure outcomes in patients treated for a 12-month period. Material and Methods: Thirty centers were enrolled from...

Monoallelic mutations on TMEM63A have been recently reported as cause of a previously unrecognized disorder named “infantile-onset transient hypomyelination”. Clinical and neuroradiological presentation is described as highly similar to Pelizaeus-Merzbacher Disease but evolution over time was surprisingly benign with a progressive spontaneous impro...

The aim of this work is to establish inclusive guidelines on electroencephalography (EEG) applicable to all neonatal intensive care units (NICUs). Guidelines on ideal EEG monitoring for neonates are available, but there are significant barriers to their implementation in many centres around the world. These include barriers due to limited resources...

New-Onset Refractory Status Epilepticus (NORSE) is rare condition and sharing knowledge is vital in its management, based on strict collaboration between multiple specialists, continuous EEG (c-EEG) monitoring and prompt therapy modification. The COVID-19 pandemic challenged many of these established practices, due to “social distancing” measures,...

Autozygosity-driven exome analysis has been shown effective for identification of genes underlying recessive diseases especially in countries of the so-called Greater Middle East (GME), where high consanguinity unravels the phenotypic effects of recessive alleles and large family sizes facilitate homozygosity mapping. In Italy, as in most European...

Congenital glycosylation disorders (CDG) are inherited metabolic diseases due to defective glycoprotein and glycolipid glycan assembly and attachment. MOGS-CDG is a rare disorder with seven patients from five families reported worldwide. We report on a 19-year-old girl with MOGS-CDG. At birth she presented facial dysmorphism, marked hypotonia, and...

Lipopolysaccharide responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disorder (PID) that can cause a common variable immunodeficiency (CVID)-like disease. The typical features of the disease are autoimmunity, chronic diarrhea, and hypogammaglobulinemia. Neurological complications are also reported in patients affe...

Objective: To verify safety and efficacy of the corticosteroid-sparing drug Azathioprine (AZA) in Rasmussen syndrome (RS), we retrospectively analyzed a cohort of RS patients recruited in a single pediatric neuroscience center. Methods: We compared outcomes in 30 RS patients who received AZA with 23 patients who were not treated with this drug....

Introduction Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years'...

Objective To analyse autoantibody status in a well-defined European multicentre cohort of patients with epilepsy of unknown aetiology and to validate the recently proposed Antibody Prevalence in Epilepsy (APE2) and Response to ImmunoTherapy in Epilepsy (RITE2) scores. Methods We retrospectively collected clinical and paraclinical data of 92 patien...

Intrinsically photosensitive melanopsin retinal ganglion cells (mRGCs) are crucial for non-image forming functions of the eye, including the photoentrainment of circadian rhythms and the regulation of the pupillary light reflex (PLR). Chromatic pupillometry, using light stimuli at different wavelengths, makes possible the isolation of the contribut...

Background: Xq duplication is a rare condition with a very variable phenotype, which could mimic other genetic syndromes involving the long arm of chromosome X. Sometimes short stature and diminished ovarian reserve (DOR) may be present. Treatments with rGH (Recombinant growth Hormon) or with fertility preservation strategies have not been previou...

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of “self-limited focal epilepsies.” In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological d...

Circulating and cerebrospinal fluid (CSF) neurofilament light chain (NfL) levels represent a reliable indicator of disease activity and axonal damage in different neuroinflammatory conditions. Recently, high CSF NfL levels have been detected in active autoimmune encephalitis, as opposed to significant lower levels after clinical improvement. The ai...

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is a peculiar electro‐clinical condition, with variable etiologies, characterized by an age‐dependent phenomenon of extreme activation of epileptic activity during sleep, i.e. “status epilepticus during sleep”, that is strictly associated with the appearance of cognitive and beha...

Under the old term of focal “idiopathic” epilepsies of infancy are comprised a group of epilepsy conditions characterized by localization-related-onset seizures and a relatively “benign” course. These conditions account for about the 20% of children with non febrile seizures. The electro-clinical syndromes recognized by the International League Aga...

Background Acute rheumatic fever (ARF) is a nonsuppurative sequaela that can occur two to four weeks after group A beta-hemolytic Streptococcus pharyngitis. Despite its decline in incidence in modern countries, ARF still represents worldwide a serious healthcare concern. The most common manifestations are arthritis and carditis, followed by chorea,...

Since its first description, quantifying the burden of epileptiform abnormalities in sleep EEG has played a fundamental role in the diagnosis of Encephalopathy related to Status Epilepticus during slow Sleep (ESES). In fact, in the 1971 seminal paper by Tassinari's group and in the following studies on this syndrome, the amount of epileptiform disc...

Aims. Epilepsy with auditory features (EAF) is a focal epilepsy syndrome characterized by prominent auditory ictal manifestations. Two main genes, LGI1 and RELN, have been implicated in EAF, but the genetic aetiology remains unknown in half of families and most sporadic cases. We previously described a pathogenic SCN1A missense variant (p.Thr956Met...

We describe the case of an otherwise healthy 3-year old girl who suffered from anti-NMDA receptor encephalitis dominated by a peculiar gait disorder. At onset, she presented with unsteadiness during walking, which was rapidly followed by prolonged epileptic convulsive seizures, treated with intravenous midazolam and valproic acid. On admission, fac...

The polyglandular autoimmune syndrome type I is a rare hereditary autosomal recessive disease. We describe a child with the classic triad of the disease and her sister with pure red cell aplasia and cerebellar hypoplasia. The latter received two haematopoietic stem cell transplantations, complicated by an acute disseminated encephalomyelitis.

Background: Overgrowth syndromes are known as a heterogeneous group of conditions characterized by a generalized or segmental, symmetric or asymmetric, overgrowth that may involve several tissues. These disorders, which present a wide range of phenotypic variability, are often caused by mosaic somatic mutations in the genes associated with the PI3...

Fixation-off sensitivity (FOS) refers to seizures or EEG abnormalities elicited by the elimination of central vision/fixation, even in the presence of light. Typically, a paroxysmal discharge occurs within 1–3 seconds of eye closure, persists throughout the eye-closed state, and disappears immediately on eye opening. FOS occurs mainly in childhood...

Mutations in the CDKL5 (cyclin-dependent kinase-like-5) gene are known to determine early-onset drug resistant epilepsies and severe cognitive impairment with absent language, hand stereotypies, and deceleration of head growth. Reflex seizures are epileptic events triggered by specific stimuli and diaper changing is a very rare triggering event, pr...

Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as a potential biomarker in patients with inflammatory demyelinating diseases of the central nervous system. We here compare the clinical and laboratory findings observed in a cohort of MOG-Ab seropositive and seronegative cases and describe IgG subclass analysis results....

Type 1 narcolepsy is a central hypersomnia due to the loss of hypocretin-producing neurons and characterized by cataplexy, excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. In children, close to the disease onset, type 1 narcolepsy has peculiar clinical features with severe cataplexy and a compl...

Poretti-Boltshauser syndrome (PBS) is a recently described cerebellar disorder characterized by cerebellar dysplasia with cysts and an enlarged and square-like shaped fourth ventricle.¹ The clinical phenotype includes nonprogressive cerebellar ataxia, ocular motor apraxia (OMA), intellectual disability, and frequent high myopia or retinal dystrophy...

Photosensitivity is a condition in which lights induce epileptiform activities. This abnormal electroencephalographic response has been associated with hyperexcitability of the visuo-motor system. Here, we evaluate if intrinsic dysfunction of this network is present in brain activity at rest, independently of any stimulus and of any paroxysmal elec...

Background: A growing number of studies have disclosed the myriad of features that can suggest the diagnosis of a Glucose-transporter-1 deficiency (GLUT1D). The occurrence of paroxysmal movement disorders such as exercise-induced dystonia and non-kinesigenic dyskinesia, received considerable emphasis, while limited attention has been paid to other...

Seizures are a frequent acute neurological event in the neonatal period. Up to 12 to 18% of all seizures in newborns are due to perinatal stroke and up to 39% of affected children can then develop epilepsy in childhood. We report the case of a young patient who presented stroke-related seizures in the neonatal period and then developed focal sympto...

Background: Children with achondroplasia often have breathing problems, especially during sleep. The most important treatments are adenotonsillectomy (for treating upper obstruction) and/or neurosurgery (for resolving cervicomedullar junction stenosis). Data sources: We reviewed the scientific literature on polysomnographic investigations which...

Objective: To describe the clinical, neuropsychological, and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at time of recruitment and through the first month. The selected population will be followed for 2-5 years after enrollment to investigate the epilepsy course and...