Variabilità clinica, in particolare riguardo all'epilessia, in pazienti affetti da Sindrome di Angelman con differenti anomalie genetiche nella regione 15q11-q13
Blink induced epileptiform EEG activity in a patient with chromosomopathy | [Anomalie EEG indotte da ammiccamento palpebrale in paziente con cromosomopatia]
Narcolepsy in childhood-adolescence is characterized by a high occurrence of psychiatric comorbid... more Narcolepsy in childhood-adolescence is characterized by a high occurrence of psychiatric comorbidities. The most frequent psychiatric disorders reported in these patients are attention deficit/hyperactivity disorder, depression, anxiety disorder, and schizophrenia. However, narcolepsy can be associated also with introversion, sorrowfulness, feelings of inferiority, impaired affectivity modulation, emotional lability, irritability, aggressiveness, and poor attention, that have been pooled by some authors under a definition of “narcoleptic personality.” Some aspects of this “narcoleptic personality,” and in particular introversion, impaired affectivity modulation, irritability, and poor attention, partially overlap with the clinical features of the individuals with autism spectrum disorder, considering also those that are not regarded as core autism symptoms. Till now, in literature the number of cases affected by both narcolepsy and autism spectrum disorder (seven patients) has been clearly too small to demonstrate the presence of a pathogenetic link between these two conditions, but this possible connection has not yet been adequately investigated, despite the presence of several points in common. The finding of a connection between narcolepsy and autism spectrum disorder could boost the study of possible etiopathogenetic mechanisms shared between these two apparently so distant disorders. Basing on the literature data summarized in this paper, in the diagnostic work-up of a child with narcolepsy it is essential to evaluate also the social-communicative behavior using standardized tools in order to detect the real recurrence of clinical features suggesting an autism spectrum disorder. At the same time, it appears necessary to screen in the individuals with autism spectrum disorder for the possible presence of evoking symptoms of narcolepsy.
Some considerations about the association between autism spectrum disorder and epilepsy
Türk Pediatri Arşivi
From a clinical perspective, the possible scenarios of this association are very heterogeneous. T... more From a clinical perspective, the possible scenarios of this association are very heterogeneous. The first and most frequent scenario is represented by an individual with ASD presenting epilepsy with very heterogeneous features (with two onset peaks, respectively in early childhood and towards adolescence): focal forms prevail, often benign, with good response to antiepileptic drugs and high chances of suspending the therapy without seizure relapse. Note that epilepsy diagnosis can be complex in individuals with ASD, particularly if an intellectual disability coexists, due to the difficulties in history taking. The main factor favoring the appearance of epilepsy in these individuals is the comorbidity with an intellectual disability. Other favoring factors include cerebral lesions, comorbid rare diseases, and pre-/peri-/neonatal personal antecedents. In this scenario, seizures impact negatively on the quality of life of affected individuals and their families, but do not substantially modify ASD evolution.
Italy is one of the few countries in the world where pediatric neuropsychiatry is still a united ... more Italy is one of the few countries in the world where pediatric neuropsychiatry is still a united discipline not following the separation that has been underway for several years between adulthood neurology and psychiatry. However, in practice, many pediatric neuropsychiatrists here operate as if this separation was present, dealing with either neurologic or psychiatric pathologies of the developmental age. Indeed, due to the increasing hyperspecialization of skills, there are some pediatric neuropsychiatrists, in the field of neurology, who deal almost only with epilepsy or neuromuscular diseases, while there are others, in the field of psychiatry, who deal almost only with autism spectrum disorder (ASD). At least partially, this trend towards the hyperspecialization of skills is inevitable due to the recent great progress of neurosciences, but at the same time, this situation entails serious risks for adequate patient care. Each individual, particularly during development, should be considered as a single entity both in physiologic and pathologic situations. A clear distinction between normal neurologic and psychic development is very difficult and probably pointless, especially in the earliest stages of life. This distinction becomes almost impossible when, for some reason, the development of the individual shows domain-specific or global deficits. In this regard, there would be innumerable examples of pathologic conditions whose clinical picture at onset may appear misleading and requires a global neuropsychiatric approach; here we will mention only a few. The first example: a child aged around 2 years showing language delay, potentially the prelude to a specific language disorder, who unfortunately in the following months begins to present a series of signs such as epileptic seizures, ataxia, as well as cognitive, motor, and visual deterioration, leading then, based on the results of instrumental tests, to a diagnosis of neuronal ceroid lipofuscinosis type 2 disease. It is known that the first sign of this disease can be language delay (1). The second example: a boy aged 15 months presenting a mild motor developmental delay, but who after a few months starts to show the classic signs of ASD. A consistent series of data shows that, in ASD, motor type signs, including a delay in the gross motor and fine motor acquisitions, may occur even before the impairment of social communication skills (2, 3). The third example: a girl aged 18 months showing an apparently non-specific global developmental delay, whose clinical picture subsequently becomes more complicated following the loss of acquired skills and the appearance of symptoms including handwashing stereotypies, breathing abnormalities during wakefulness (hyperventilation alternating with apnea), and others, leading to a diagnosis of atypical Rett syndrome, whose onset is often difficult to identify (4, 5). These examples highlight that an overall picture of the developing individual, through a global approach combining both the neurologic and psychiatric perspective, facilitates an adequate diagnostic framework and therefore a correct management. The fact that pediatric neuropsychiatry remains a united discipline is not a legacy of the past, but reflects a modern way of dealing with the neuropsychiatric disorders of the developing individual.
Duplications of chromosome 16p11.2, even though rare in the general population, are one of the mo... more Duplications of chromosome 16p11.2, even though rare in the general population, are one of the most frequent known genetic causes of autism spectrum disorder and of other neurodevelopmental disorders. However, data about the neuro-behavioral phenotype of these patients are few. We described a sample of children with duplication of chromosome 16p11.2 focusing on the neuro-behavioral phenotype. The five patients reported presented with very heterogeneous conditions as for characteristics and severity, ranging from a learning disorder in a child with normal intelligence quotient to an autism spectrum disorder associated with an intellectual disability. Our case report underlines the wide heterogeneity of the neuropsychiatric phenotypes associated with a duplication of chromosome 16p11.2. Similarly to other copy number variations that are considered pathogenic, the wide variability of phenotype of chromosome 16p11.2 duplication is probably related to additional risk factors, both geneti...
We examined the potential benefits of neuroimaging measurements across the first 5 years of life ... more We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans of a group of 117 ASD children younger than 5 years old. These data were compared to those reported in typically developing (TD) children. MRI findings in children with ASD were analyzed in relation to their cognitive level, severity of autistic symptoms, and the presence of electroencephalogram (EEG) abnormalities. The MRI was rated abnormal in 55% of children with ASD with a significant prevalence in the high-functioning subgroup compared to TD children. We report significant incidental findings of mega cisterna magna, ventricular anomalies and abnormal white matter signal intensity in ASD without significant associations between these MRI findings and EEG features. Based on these resu...
Background Autism spectrum disorder is characterized by impairment in social interaction and comm... more Background Autism spectrum disorder is characterized by impairment in social interaction and communication along with repetitive, restricted, and stereotyped behaviors, interests and activities. It is important to detect this condition as soon as possible and promptly begin targeted treatments. This study aimed to report on age at onset, early signs, and mode at onset in 105 Italian patients with autism spectrum disorder, searching for correlations with a series of clinical and instrumental variables. Methods This retrospective cross-sectional study considered the following five categories of symptoms at onset: language, social interaction and relationships, stereotyped behavior and activities, motor skills, and regulation. Three modes of presentation were considered: a delay, a stagnation, or a regression of development, which were defined modes of onset of autism spectrum disorder. The age at onset, the category of clinical features, and the mode at onset were considered in the en...
Variabilità clinica, in particolare riguardo all'epilessia, in pazienti affetti da Sindrome di Angelman con differenti anomalie genetiche nella regione 15q11-q13
Blink induced epileptiform EEG activity in a patient with chromosomopathy | [Anomalie EEG indotte da ammiccamento palpebrale in paziente con cromosomopatia]
Narcolepsy in childhood-adolescence is characterized by a high occurrence of psychiatric comorbid... more Narcolepsy in childhood-adolescence is characterized by a high occurrence of psychiatric comorbidities. The most frequent psychiatric disorders reported in these patients are attention deficit/hyperactivity disorder, depression, anxiety disorder, and schizophrenia. However, narcolepsy can be associated also with introversion, sorrowfulness, feelings of inferiority, impaired affectivity modulation, emotional lability, irritability, aggressiveness, and poor attention, that have been pooled by some authors under a definition of “narcoleptic personality.” Some aspects of this “narcoleptic personality,” and in particular introversion, impaired affectivity modulation, irritability, and poor attention, partially overlap with the clinical features of the individuals with autism spectrum disorder, considering also those that are not regarded as core autism symptoms. Till now, in literature the number of cases affected by both narcolepsy and autism spectrum disorder (seven patients) has been clearly too small to demonstrate the presence of a pathogenetic link between these two conditions, but this possible connection has not yet been adequately investigated, despite the presence of several points in common. The finding of a connection between narcolepsy and autism spectrum disorder could boost the study of possible etiopathogenetic mechanisms shared between these two apparently so distant disorders. Basing on the literature data summarized in this paper, in the diagnostic work-up of a child with narcolepsy it is essential to evaluate also the social-communicative behavior using standardized tools in order to detect the real recurrence of clinical features suggesting an autism spectrum disorder. At the same time, it appears necessary to screen in the individuals with autism spectrum disorder for the possible presence of evoking symptoms of narcolepsy.
Some considerations about the association between autism spectrum disorder and epilepsy
Türk Pediatri Arşivi
From a clinical perspective, the possible scenarios of this association are very heterogeneous. T... more From a clinical perspective, the possible scenarios of this association are very heterogeneous. The first and most frequent scenario is represented by an individual with ASD presenting epilepsy with very heterogeneous features (with two onset peaks, respectively in early childhood and towards adolescence): focal forms prevail, often benign, with good response to antiepileptic drugs and high chances of suspending the therapy without seizure relapse. Note that epilepsy diagnosis can be complex in individuals with ASD, particularly if an intellectual disability coexists, due to the difficulties in history taking. The main factor favoring the appearance of epilepsy in these individuals is the comorbidity with an intellectual disability. Other favoring factors include cerebral lesions, comorbid rare diseases, and pre-/peri-/neonatal personal antecedents. In this scenario, seizures impact negatively on the quality of life of affected individuals and their families, but do not substantially modify ASD evolution.
Italy is one of the few countries in the world where pediatric neuropsychiatry is still a united ... more Italy is one of the few countries in the world where pediatric neuropsychiatry is still a united discipline not following the separation that has been underway for several years between adulthood neurology and psychiatry. However, in practice, many pediatric neuropsychiatrists here operate as if this separation was present, dealing with either neurologic or psychiatric pathologies of the developmental age. Indeed, due to the increasing hyperspecialization of skills, there are some pediatric neuropsychiatrists, in the field of neurology, who deal almost only with epilepsy or neuromuscular diseases, while there are others, in the field of psychiatry, who deal almost only with autism spectrum disorder (ASD). At least partially, this trend towards the hyperspecialization of skills is inevitable due to the recent great progress of neurosciences, but at the same time, this situation entails serious risks for adequate patient care. Each individual, particularly during development, should be considered as a single entity both in physiologic and pathologic situations. A clear distinction between normal neurologic and psychic development is very difficult and probably pointless, especially in the earliest stages of life. This distinction becomes almost impossible when, for some reason, the development of the individual shows domain-specific or global deficits. In this regard, there would be innumerable examples of pathologic conditions whose clinical picture at onset may appear misleading and requires a global neuropsychiatric approach; here we will mention only a few. The first example: a child aged around 2 years showing language delay, potentially the prelude to a specific language disorder, who unfortunately in the following months begins to present a series of signs such as epileptic seizures, ataxia, as well as cognitive, motor, and visual deterioration, leading then, based on the results of instrumental tests, to a diagnosis of neuronal ceroid lipofuscinosis type 2 disease. It is known that the first sign of this disease can be language delay (1). The second example: a boy aged 15 months presenting a mild motor developmental delay, but who after a few months starts to show the classic signs of ASD. A consistent series of data shows that, in ASD, motor type signs, including a delay in the gross motor and fine motor acquisitions, may occur even before the impairment of social communication skills (2, 3). The third example: a girl aged 18 months showing an apparently non-specific global developmental delay, whose clinical picture subsequently becomes more complicated following the loss of acquired skills and the appearance of symptoms including handwashing stereotypies, breathing abnormalities during wakefulness (hyperventilation alternating with apnea), and others, leading to a diagnosis of atypical Rett syndrome, whose onset is often difficult to identify (4, 5). These examples highlight that an overall picture of the developing individual, through a global approach combining both the neurologic and psychiatric perspective, facilitates an adequate diagnostic framework and therefore a correct management. The fact that pediatric neuropsychiatry remains a united discipline is not a legacy of the past, but reflects a modern way of dealing with the neuropsychiatric disorders of the developing individual.
Duplications of chromosome 16p11.2, even though rare in the general population, are one of the mo... more Duplications of chromosome 16p11.2, even though rare in the general population, are one of the most frequent known genetic causes of autism spectrum disorder and of other neurodevelopmental disorders. However, data about the neuro-behavioral phenotype of these patients are few. We described a sample of children with duplication of chromosome 16p11.2 focusing on the neuro-behavioral phenotype. The five patients reported presented with very heterogeneous conditions as for characteristics and severity, ranging from a learning disorder in a child with normal intelligence quotient to an autism spectrum disorder associated with an intellectual disability. Our case report underlines the wide heterogeneity of the neuropsychiatric phenotypes associated with a duplication of chromosome 16p11.2. Similarly to other copy number variations that are considered pathogenic, the wide variability of phenotype of chromosome 16p11.2 duplication is probably related to additional risk factors, both geneti...
We examined the potential benefits of neuroimaging measurements across the first 5 years of life ... more We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans of a group of 117 ASD children younger than 5 years old. These data were compared to those reported in typically developing (TD) children. MRI findings in children with ASD were analyzed in relation to their cognitive level, severity of autistic symptoms, and the presence of electroencephalogram (EEG) abnormalities. The MRI was rated abnormal in 55% of children with ASD with a significant prevalence in the high-functioning subgroup compared to TD children. We report significant incidental findings of mega cisterna magna, ventricular anomalies and abnormal white matter signal intensity in ASD without significant associations between these MRI findings and EEG features. Based on these resu...
Background Autism spectrum disorder is characterized by impairment in social interaction and comm... more Background Autism spectrum disorder is characterized by impairment in social interaction and communication along with repetitive, restricted, and stereotyped behaviors, interests and activities. It is important to detect this condition as soon as possible and promptly begin targeted treatments. This study aimed to report on age at onset, early signs, and mode at onset in 105 Italian patients with autism spectrum disorder, searching for correlations with a series of clinical and instrumental variables. Methods This retrospective cross-sectional study considered the following five categories of symptoms at onset: language, social interaction and relationships, stereotyped behavior and activities, motor skills, and regulation. Three modes of presentation were considered: a delay, a stagnation, or a regression of development, which were defined modes of onset of autism spectrum disorder. The age at onset, the category of clinical features, and the mode at onset were considered in the en...
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