Background
Criteria defined by the International headache Society are commonly used for the diagnosis of the different headache types in both adults and children. However, some authors have stressed ...some limits of these criteria when applied to preschool age.
Objective
Our study aimed to describe the characteristics of primary headaches in children younger than 6 years and investigate how often the International Classification of Headache Disorders (ICHD) criteria allow a definitive diagnosis.
Methods
This retrospective study analysed the clinical feature of 368 children younger than 6 years with primary headache.
Results
We found that in our patients the percentage of undefined diagnosis was high when either the ICHD-II or the ICHD-III criteria were used. More than 70% of our children showed a duration of their attacks shorter than 1 hour. The absence of photophobia/phonophobia and nausea/vomiting significantly correlate with tension-type headache (TTH) and probable TTH. The number of first-degree relatives with migraine was positively correlated to the diagnosis of migraine in the patients (p < 0.001).
Conclusions
Our study showed that the ICHD-III criteria are difficult to use in children younger than 6 years. The problem is not solved by the reduction of the lowest duration limit for the diagnosis of migraine to 1 hour, as was done in the ICHD-II.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heterozygous missense variants in the SPTBN2 gene, encoding the non‐erythrocytic beta spectrin 2 subunit (beta‐III spectrin), have been identified in autosomal dominant spinocerebellar ataxia type 5 ...(SCA5), a rare adult‐onset neurodegenerative disorder characterized by progressive cerebellar ataxia, whereas homozygous loss of function variants in SPTBN2 have been associated with early onset cerebellar ataxia and global developmental delay (SCAR14). Recently, heterozygous SPTBN2 missense variants have been identified in a few patients with an early‐onset ataxic phenotype. We report five patients with non‐progressive congenital ataxia and psychomotor delay, 4/5 harboring novel heterozygous missense variants in SPTBN2 and one patient with compound heterozygous SPTBN2 variants. With an overall prevalence of 5% in our cohort of unrelated patients screened by targeted next‐generation sequencing (NGS) for congenital or early‐onset cerebellar ataxia, this study indicates that both dominant and recessive mutations of SPTBN2 together with CACNA1A and ITPR1, are a frequent cause of early‐onset/congenital non‐progressive ataxia and that their screening should be implemented in this subgroup of disorders.
We report five patients with non‐progressive congenital ataxia and psychomotor delay, four of five harboring novel heterozygous missense variants in SPTBN2 and one patient with compound heterozygous SPTBN2 variants. With an overall prevalence of 5% in our cohort, the present study indicates that both dominant and recessive mutations of SPTBN2 are a frequent cause of early‐onset/congenital non‐progressive ataxia.
Prestatus and status dystonicus in children and adolescents Garone, Giacomo; Graziola, Federica; Nicita, Francesco ...
Developmental medicine and child neurology,
June 2020, 2020-Jun, 2020-06-00, 20200601, Letnik:
62, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Aim
To critically analyse the management of status dystonicus and prestatus dystonicus in children and adolescents, in order to examine clinical features, acute management, and risk of relapse in a ...paediatric cohort.
Method
Clinical, demographic, and therapeutic features were analysed according to disease severity. Risk of subsequent relapse was estimated through Kaplan–Meier curves.
Results
Thirty‐four patients (eight females, 26 males) experiencing 63 episodes of acute dystonia exacerbations at a tertiary referral Italian hospital were identified. Mean age at status dystonicus presentation was 9 years 11 months (11y at inclusion in the study). Onset of dystonia dated back to infancy in most cases. Fourteen patients experienced two or more episodes. Infections were the most common trigger (48%). Benzodiazepines were the most commonly used drugs for acute management. Stereotactic pallidotomy was performed in six cases during status dystonicus, and in two additional patients it was electively performed after medical management. The probability of survival free from status dystonicus relapses was 78% after 4 months and 61% after 27 months.
Interpretation
Dystonia exacerbations are potentially life‐threating emergencies, with a considerable risk of relapse. Nevertheless, no obvious factors for relapse risk stratification exist. Pallidotomy is a feasible option in medical refractory status dystonicus for patients with limited deep brain stimulation applicability, but the risk of recurrence is elevated.
What this paper adds
Acute exacerbations may affect up to 10% of children with dystonia.
Infections are the most common precipitant factor.
In about 30% of the cases, intensive care unit admission is needed.
Subsequent relapses are common, reaching 25% risk at 1 year.
Pallidotomy can be considered in medical‐refractory cases with no deep brain stimulation applicability.
What this paper adds
Acute exacerbations may affect up to 10% of children with dystonia.
Infections are the most common precipitant factor.
In about 30% of the cases, intensive care unit admission is needed.
Subsequent relapses are common, reaching 25% risk at 1 year.
Pallidotomy can be considered in medical‐refractory cases with no deep brain stimulation applicability.
This article is commented on by Lumsden on page 668 of this issue.
Next-generation sequencing, combined with international pooling of cases, has impressively enhanced the discovery of genes responsible for Mendelian neurodevelopmental disorders, particularly in ...individuals affected by clinically undiagnosed diseases. To date, biallelic missense variants in
gene, encoding a Krüppel-type zinc-finger protein, have been reported in three families with non-syndromic intellectual disability.
Here, we describe five individuals from four unrelated families with an undiagnosed neurodevelopmental disorder in which we performed exome sequencing, on a combination of trio-based (4 subjects) or single probands (1 subject).
We identified five patients from four unrelated families with homozygous
variants by whole exome sequencing. Four had variants resulting in truncation of ZNF526; they were affected by severe prenatal and postnatal microcephaly (ranging from -4 SD to -8 SD), profound psychomotor delay, hypertonic-dystonic movements, epilepsy and simplified gyral pattern on MRI. All of them also displayed bilateral progressive cataracts. A fifth patient had a homozygous missense variant and a slightly less severe disorder, with postnatal microcephaly (-2 SD), progressive bilateral cataracts, severe intellectual disability and unremarkable brain MRI.Mutant
zebrafish larvae had notable malformations of the eye and central nervous system, resembling findings seen in the human holoprosencephaly spectrum.
Our findings support the role of
biallelic variants in a complex neurodevelopmental disorder, primarily affecting brain and eyes, resulting in severe microcephaly, simplified gyral pattern, epileptic encephalopathy and bilateral cataracts.
Congenital ataxias associated with cerebellar atrophy are clinically heterogeneous conditions with a variable age of onset and a diverse molecular basis. The hypothesis-free approach of genomic ...sequencing has led to the discovery of new genes implicated in these disorders and the identification of unexpected genotype–phenotype correlations. Although a recurrent heterozygous mutation (p.Arg1715His) in CACNA1G is known to cause adult-onset spinocerebellar ataxia 42 (SCA42*616795), gain-of-function mutations in this gene have recently been identified by whole exome sequencing (WES) in four children with cerebellar atrophy and ataxia, psychomotor delay, and other variable features.
We describe four children from unrelated families with cerebellar anomalies on magnetic resonance imaging (atrophy or hypoplasia of the cerebellar vermis), hypertonia, psychomotor and speech delay, severe intellectual disability, ophthalmologic features and peculiar dysmorphic traits. All patients underwent a trio-based WES analysis. Clinical records were used to characterize the clinical profile of this newly recognized disorder.
Two previously reported de novo disease-causing mutations in CACNA1G (c.2881G>A, p.Ala961Thr and c.4591A>G, p.Met1531Val) were identified in these patients, providing further evidence of the specific impact of these variants. All four patients exhibit distinctive dysmorphic and ectodermal features which overlap those of the previously reported patients, allowing us to define the major features characterizing this homogeneous neurodevelopmental syndromic disorder associated with upregulated CACNA1G function.
Our findings confirm the specific association between a narrow spectrum of missense mutations in CACNA1G and a novel syndrome with infantile-onset cerebellar ataxiaand provide a dysmorphologic delineation of this novel neurodevelopmental trait.
ADAR1 variants are associated to rare and heterogenous neurological conditions, including Aicardi-Goutières syndrome type 6, bilateral striatal necrosis, and dyschromatosis symmetrica hereditaria. ...Movement disorders (MDs) commonly occur in ADAR1-related diseases although a complete overview on the phenomenology has not been provided yet. Here, a cohort of 57 patients with ADAR1-related diseases, including 3 unpublished patients and 54 previously reported cases, was reviewed. Data on demographics, clinical features of MDs, genetics and biomarkers were collected and descriptive statistics, group analysis for genotype and logistic regression were run. Manifestations of MD characterized the onset of ADAR1-related disease in 60% of patients. Specifically, dystonia occurred in 39% of cases, even as severe status dystonicus, while prevalence of other MDs was lower. Patients often presented brain lesions (>90%) and progressive disease course (43%), fatal in some cases. Clinical presentation and outcome differed among patients with distinct genotype. This review shows that phenomenology of MDs in ADAR1-related diseases is wide and heterogeneous, although a severe motor syndrome (often characterized by dystonia) secondary to brain lesions represents the most common manifestation. Waiting for future development of disease-modifying treatments, an appropriate symptomatic intervention is crucial for ADAR1 patients. Accordingly, a deeper knowledge of phenomenology is fundamental.
•ADAR1 variants cause heterogeneous diseases presenting with movement disorder.•Dystonia is the most common sign, even as severe status dystonicus.•Other motor disturbances may occur, requiring specific treatments.
Objective
We aimed to study the role of attachment style on headache severity and psychological symptoms in migraineurs children/adolescents. Moreover, we investigated the association between ...attachment style, migraine severity, and psychological symptoms.
Background
Attachment theory suggests that early interpersonal relationships may be important determinants of psychopathology and pain management. In particular, individuals with insecure attachment styles have been shown to experience more pain than people with secure attachment style. Few studies focused on headache and data on attachment style in pediatric headache are scarce.
Methods
We studied 90 migraineurs (mean age 12.2 ± 2.6 years; female: 54, male: 36). Patients were divided in two groups according to headache attack frequency: (1) high frequency (HF) patients, having from weekly to daily episodes and (2) low frequency (LF) patients, showing ≤3 episodes per month. According to headache attack intensity, patients were classified in two groups: (1) mild pain (MP), allowing the patient to continue his/her daily activities and (2) severe pain (SP), leading to interruption of patient activities or forcing the child to go to bed. The psychological screening was assessed by SAFA Anxiety, Depression, and Somatization questionnaires. Attachment style was measured by the semi‐projective test Separation Anxiety Test. Patients were divided into “secure,” “avoidant,” “ambivalent,” and “disorganized/confused” attachment patterns.
Results
We found a significant relationship between the attachment style and migraine features. The ambivalent attachment was the most common style among patients reporting high attack frequency (51%) and severe pain intensity (50%). Anxiety (SAFA‐A Tot: F = 23.3, P < .001), depression (SAFA‐D Tot: F = 11.8, P < .001), and somatization (SAFA‐S Tot: F = 10.1, P < .001) were higher in patients with ambivalent attachment style. Moreover, our results showed an association between high attack frequency and high anxiety levels, in children with ambivalent attachment style (F = 6.7, P < .002).
Conclusions
Ambivalent attachment style may be a common vulnerability factor that impacts on pain severity, anxiety, depression, and somatization symptoms in young migraineurs. In particular, the present study provides the first evidence of the role of insecure attachment on the relationship between pain severity and psychological symptoms in migraine children.
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