Pediatric epilepsies misdiagnosed as gastrointestinal disorders.

In the last years, several cases of pediatric epilepsies misdiagnosed and treated as gastrointestinal (GI) disorders have been reported. The aim of this study was to evaluate both frequency and characteristics of these erroneous diagnoses. We identified children who had received a previous misdiagnosis of GI disorder out of 858 consecutive patients with a diagnosis of epilepsy at our hospital from 2010 to 2015. Misdiagnosis was observed in 21 patients (2.4%): 7 children with West syndrome, 10 with temporal lobe epilepsy, and 4 with Panayiotopoulos syndrome. The majority of children with a misdiagnosis (12/21) were younger than 1year at epilepsy onset, and median diagnostic delay was 15.5months. The most frequently diagnosed GI disorder was gastroesophageal reflux disease, especially in younger children. The study confirms that epilepsy in a significant percentage of children is wrongly identified and treated as GI disorders. In particular, epilepsy should be considered in the differential diagnosis of "atypical" gastroesophageal reflux in younger children in order to avoid serious prognostic consequences.

A mutation in PAK3 with a dual molecular effect deregulates the RAS/MAPK pathway and drives an X-linked syndromic phenotype.

Loss-of-function mutations in PAK3 contribute to non-syndromic X-linked intellectual disability (NS-XLID) by affecting dendritic spine density and morphology. Linkage analysis in a three-generation family with affected males showing ID, agenesis of corpus callosum, cerebellar hypoplasia, microcephaly and ichthyosis, revealed a candidate disease locus in Xq21.33q24 encompassing over 280 genes. Subsequent to sequencing all coding exons of the X chromosome, we identified a single novel variant within the linkage region, affecting a conserved codon of PAK3. Biochemical studies showed that, similar to previous NS-XLID-associated lesions, the predicted amino acid substitution (Lys389Asn) abolished the kinase activity of PAK3. In addition, the introduced residue conferred a dominant-negative function to the protein that drives the syndromic phenotype. Using a combination of in vitro and in vivo studies in zebrafish embryos, we show that PAK3(N389) escapes its physiologic degradation and is able to perturb MAPK signaling via an uncontrolled kinase-independent function, which in turn leads to alterations of cerebral and craniofacial structures in vivo. Our data expand the spectrum of phenotypes associated with PAK3 mutations, characterize a novel mechanism resulting in a dual molecular effect of the same mutation with a complex PAK3 functional deregulation and provide evidence for a direct functional impact of aberrant PAK3 function on MAPK signaling.

New patients with Temple syndrome caused by 14q32 deletion: Genotype-phenotype correlations and risk of thyroid cancer.

Temple syndrome (TS) is caused by abnormal expression of genes at the imprinted locus 14q32. A subset of TS patients carry 14q32 deletions of paternal origin. We aimed to define possible genotype-phenotype correlations and to highlight the prevalence of thyroid dysfunction, which is a previously unreported feature of TS. We described four new patients who carry deletions of paternal origin at 14q32 detected by array-CGH and reviewed nine patients reported in the medical literature. We compared clinical features with respect to deletion size and position. Expression of DLK1 is altered in all the patients with TS, but intellectual disability (ID) is present only in patients with larger deletions extending proximally to the imprinted locus. This study led to the identification of an ID "critical region" containing four annotated genes including YY1 as the strongest candidate. Furthermore, we described three patients with thyroid dysfunction, which progressed to papillary carcinoma at a very young age in two of them. We conclude that DLK1 loss of function is likely to be responsible for the core features of TS, while haploinsufficiency of a gene outside the imprinted region causes ID. Thyroid cancer may be an unrecognized feature and monitoring for thyroid dysfunction should thus be considered in TS patients.

Electroclinical features and long-term outcome of cryptogenic epilepsy in children with Down syndrome.

OBJECTIVE: To describe the electroclinical features and the long-term outcomes of epilepsy in a large cohort of males and females with Down syndrome who developed epilepsy in childhood. STUDY DESIGN: Subjects with Down syndrome and cryptogenic epilepsy with onset in childhood were identified retrospectively from the databases of 16 Italian epilepsy centers over a 40-year period. For each subject, age at onset of seizures, seizure semiology and frequency, electroencephalography characteristics, treatment with antiepileptic drugs, and long-term clinical and electroencephalography outcomes were analyzed. RESULTS: A total of 104 subjects (64 males [61.5%], 40 females [38.5%]) were identified. Seizure onset occurred within 1 year of birth in 54 subjects (51.9%), between 1 and 12 years in 42 subjects (40.4%), and after 12 years in 8 subjects (7.7%). Males had a younger age of seizure onset than females. Of the 104 subjects, 51 (49.0%) had infantile spasms (IS), 35 (33.7%) had partial seizures (PS), and 18 (17.3%) had generalized seizures (GS). Febrile seizures were recorded in 5 (4.8%) subjects. Intractable seizures were observed in 23 (22.1%) subjects, including 5 (9.8%) with IS, 8 (44.4%) with PS, and 10 (31.3%) with GS. CONCLUSION: Cryptogenic epilepsy in Down syndrome may develop during the first year of life in the form of IS or, successively, as PS or GS. Electroclinical features of IS resemble those of idiopathic West syndrome, with a favorable response to treatment with adrenocorticotropic hormone seen. Patients experiencing PS and GS may be resistant to therapy with antiepileptic drugs.

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.

Epilepsy and vaccinations: Italian guidelines.

Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination.

Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up.

INTRODUCTION: Corticosteroid treatment is the standard of care in Duchenne muscular dystrophy (DMD), but the optimal age to initiate treatment and dosage pattern remain a matter of discussion. METHODS: We performed a long-term study of alternate-day corticosteroids in five 2- to 4-year-old DMD patients. The primary outcome measure was prolongation of the ability to walk. RESULTS: One patient lost ambulation at age 10. Four patients, aged 16 to 18 were fully ambulant, and 3 of them could still climb stairs. Respiratory function was moderately reduced in 2. Left ventricular ejection fraction was > 45%. Short stature and delayed puberty were the most relevant side effects. Although the negative impact of corticosteroid treatment on growth rate remained their major concern, parents and patients stated that they preferred corticosteroid therapy. CONCLUSIONS: Long-term corticosteroid treatment is effective in prolonging function but not in recovering lost function, and its early use seems appropriate.

Status epilepticus as a main manifestation of posterior reversible encephalopathy syndrome after pediatric hematopoietic stem cell transplantation.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a severe neurological complication after pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). Seizures are a common manifestation of PRES. Status epilepticus (SE) is a potentially life-threatening event rarely described in this condition. The aim of this study was to describe the clinical and electroencephalographic features of SE as a manifestation of PRES in children after allo-HSCT. PROCEDURE: We retrospectively identified episodes of SE as a consequence of PRES out of 211 children who received allo-HSCT in the period January 2000 to June 2008. RESULTS: PRES was diagnosed in 11 patients. We identified 12 episodes of SE associated to PRES in 10 patients. Nonconvulsive SE (NCSE) involving posterior regions of the brain (confirmed by EEG monitoring) was observed in four cases; convulsive SE (CSE) was observed in eight cases. Gaze deviation, oculoclonic movements, nystagmus, and altered mental status were the main clinical signs during NCSE and preceded CSE in 5/8 cases. Most patients needed intensive care management. A complete normalization of neurological examination and EEG pattern was observed in all patients after SE and withdrawal of causative agent. Follow-up MRI showed complete resolution of brain edema in all patients. CONCLUSIONS: Our experience shows that SE is more frequent than previously reported and is often the main manifestation of PRES after pediatric allo-HSCT. Looking for suggestive clinical signs as well as routine use of EEG monitoring may allow prompt recognition of SE and therapy of both SE and PRES.

The characteristics and activities of child and adolescent mental health services in Italy: a regional survey.

BACKGROUND: To date, no studies have assessed in detail the characteristics, organisation, and functioning of Child and Adolescent Mental Health Services (CAMHS). This information gap represents a major limitation for researchers and clinicians because most mental disorders have their onset in childhood or adolescence, and effective interventions can therefore represent a major factor in avoiding chronicity. Interventions and mental health care are delivered by and through services, and not by individual, private clinicians, and drawbacks or limitations of services generally translate in inappropriateness and ineffectiveness of treatments and interventions: therefore information about services is essential to improve the quality of care and ultimately the course and outcome of mental disorders in childhood and adolescence.The present paper reports the results of the first study aimed at providing detailed, updated and comprehensive data on CAMHS of a densely populated Italian region (over 4 million inhabitants) with a target population of 633,725 subjects aged 0-17 years. METHODS: Unit Chiefs of all the CAMHS filled in a structured 'Facility Form', with activity data referring to 2008 (data for inpatient facilities referred to 2009), which were then analysed in detail. RESULTS: Eleven CAMHS were operative, including 110 outpatient units, with a ratio of approximately 20 child psychiatrists and 23 psychologists per 100,000 inhabitants aged 0-17 years. All outpatient units were well equipped and organized and all granted free service access. In 2008, approximately 6% of the target population was in contact with outpatient CAMHS, showing substantial homogeneity across the eleven areas thereby. Most patients in contact in 2008 received a language disorder- or learning disability diagnosis (41%). First-ever contacts accounted for 30% of annual visits across all units. Hospital bed availability was 5 per 100,000 inhabitants aged 0-17 years. CONCLUSION: The percentage of young people in contact with CAMHS for mental disorders is in line with those observed in previous epidemiological studies. The overall number of child psychiatrists per 100,000 inhabitants is one of the highest in Europe and it is comparable with the most well equipped areas in the US. This comparison should be interpreted with caution, however, because in Italy, child psychiatrists also treat neurological disorders. Critical areas requiring improvement are: the uneven utilisation of standardised assessment procedures and the limited availability of dedicated emergency services during non-office hours (e.g., nights and holidays).

Psychometric evaluation of SAFA P test for eating disorders in adolescents: comparative validation with EDI-2.

OBJECTIVE: This study evaluates the psychometric properties of self-administered psychiatric scale for children and adolescents with psychogenic eating disorders (SAFA P)--a brief self-report designed to screen and assess eating disorders (ED) in children and adolescents. Although SAFA P belongs to a broad battery of tests (SAFA) that explores different psychiatric conditions, it has not undergone appropriate validation until now. METHOD: We administered SAFA P and Eating Disorder Inventory 2 (EDI-2) to 87 ED patients, with an average age of 15.4 ± 1.6 years. RESULTS: The internal reliability of SAFA P is good (Cronbach α = .776). Convergent validity with EDI-2 was assessed: both SAFA P subscale P1 (p < .005) and EDI-2 subscale bulimia (p < .001) showed a statistically significant difference among the three diagnostic categories (anorexia nervosa, bulimia nervosa and eating disorder not otherwise specified). Sensibility and specificity range from 62 to 91%, depending on the subscales. McNemar's test did not reveal statistically significant differences in assessing the concordance of the two measures. Statistically significant correlations were found between specific couples of subscales (p < .001). CONCLUSIONS: Cross-validation with EDI-2 showed good results. SAFA P may be an alternative, useful and reliable instrument for assessing cursory ED in childhood and adolescence.

Eligibility criteria for pediatric patients who may benefit from anti SARS-CoV-2 monoclonal antibody therapy administration: an Italian inter-society consensus statement.

The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options.The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors.Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron).These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children.AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories.Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts' agreement.This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.

Long term outcome in children affected by absence epilepsy with onset before the age of three years.

OBJECTIVE: The goal of this study was to define the long-term outcome of absence epilepsy presenting before the age of 3 years. METHODS: We retrospectively studied the medical records of 40 children from eight neuropediatric centers in Italy with respect to the personal and family histories of epilepsy or febrile seizures, time of follow-up, cognitive functions, treatment, and outcome. RESULTS: Forty patients were enrolled in this study. They all fulfilled the criteria for absence epilepsy with 3-Hz spike-wave complexes on the EEG, normal neurological examination, and no other seizures types. Seizure onset occurred between 24.1 and 36.0 months. There was a family history of epilepsy in 28%, and of febrile seizures in 13%. Thirty-three patients were treated with valproic acid (VPA), mostly used in monotherapy (26 patients) or in association with ethosuximide. At final follow-up, 33 patients were seizure free and 29 had normal EEGs. Thirty-four patients had a normal intelligence quotient (IQ), whereas 6 had a decreased IQ, mainly associated with poor control of seizures. CONCLUSION: In our series, absence seizures presenting before the age of 3 appeared to have quite a good long-term clinical prognosis; the neuropsychological outcome was comparable to that of childhood epilepsy presenting after 3 years of age.

CDKL5 gene-related epileptic encephalopathy: electroclinical findings in the first year of life.

AIM: Cyclin-dependent kinase-like 5 (CDKL5) gene abnormalities cause an early-onset epileptic encephalopathy. We performed video-electroencephalography (video-EEG) monitoring early in the course of CDKL5-related epileptic encephalopathy in order to examine the early electroclinical characteristics of the condition. METHOD: We used video-EEG to monitor six infants (five females, one male) with CDKL5-related epileptic encephalopathy (five mutations; one deletion), at ages 45 days to 12 months and followed them up to the ages of 14 months to 5 years (mean age 23 mo). We focused our analysis on the first year of life. The results were evaluated against those of a comparison group of nine infants (aged below 1y) with epileptic encephalography who had tested negative for CDKL5 mutations and deletions. RESULTS: One infant exhibited normal background activity, three exhibited moderate slowing, and two exhibited a suppression burst pattern. Two participants had epileptic spasms and four had a stereotyped complex seizure pattern, which we defined as a 'prolonged' generalized tonic-clonic event consisting of a tonic-tonic/vibratory contraction, followed by a clonic phase with series of spasms, gradually translating into repetitive distal myoclonic jerks. Seizure duration ranged from 2 to 4 minutes. The EEG correlate of each clinical phase included an initial electrodecremental event (tonic vibratory phase), irregular series of sharp waves and spike slow waves (clonic phase with series of spasms), and bilateral rhythmic sharp waves (time locked with myoclonus). INTERPRETATION: Infants with CDKL5-related early epileptic encephalopathy can present in the first year of life with an unusual electroclinical pattern of 'prolonged' generalized tonic-clonic seizures.

FA2H-related disorders: a novel c.270+3A>T splice-site mutation leads to a complex neurodegenerative phenotype.

Homozygous mutations in the gene for fatty acid 2-hydroxylase (FA2H) have been associated in humans with three neurodegenerative disorders: complicated spastic paraplegia (SPG35), leukodystrophy with spastic paraparesis and dystonia, and neurodegeneration with brain iron accumulation. Here, we describe a novel homozygous c.270+3A>T mutation in an Italian consanguineous family. In two affected brothers (age at molecular diagnosis 22y and 15y; age at last follow-up 24y and 17y), altered FA2H function led to a severe phenotype, with clinical features overlapping those of the three FA2H-associated disorders. Both patients showed childhood onset progressive spastic paraparesis, mild pyramidal and cerebellar upper limb signs, severe cognitive impairment, white-matter disease, and cerebellar, brainstem, and spinal cord atrophy. However, absence of dystonia, drowsiness episodes, and a subtle globus pallidus involvement suggested that FA2H mutations result in a clinical spectrum, rather than causing distinct disorders. Although clinical heterogeneity is apparent, larger numbers of patients are needed to establish more accurate genotype-phenotype correlations.

Phonic and Motor Stereotypies in Autism Spectrum Disorder: Video Analysis and Neurological Characterization.

Stereotypies are among the core symptoms of Autism spectrum disorder (ASD) and can cause significant clinical impairment. At present, phonic stereotypies in ASD have been scarcely explored. This study investigates the frequency, variability, and typologies of phonic and motor stereotypies in children with ASD and their association with clinical neurological variables. We examined 35 patients by recording standardized video sessions and administering the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). Phonic stereotypies were present in 83.0% of the patients. The most prevalent subtypes were noncommunicative vocalizations (60.0%), single syllables (37.1%), and echolalic stereotypies (22.9%). Noncommunicative vocalizations were more frequent in nonverbal patients (OR = 4.629, p = 0.008), while echolalic stereotypies were more represented in verbal patients (OR = 0.279, p = 0.028). Patients with intellectual disability (ID) showed a higher number (F(1,26) = 9.406, p = 0.005) and variability (F(1,25) = 7.174, p = 0.013) of motor stereotypies, with a higher number (F(1,26) = 13.268, p = 0.005) and variability (F(1,26) = 9.490, p = 0.005) of stereotypies involving the head/trunk/shoulders category. Patients with guttural stereotypies showed a higher variability of total motor stereotypies (OR = 1.487, p = 0.032) and self-directed motor stereotypies (OR = 4.389, p = 0.042). These results, combined with a standardized video-analysis, document the frequency and variability of phonic stereotypies among children with ASD. Correlations between specific phonic stereotypies and verbal abilities should be investigated further.

Relationship between Sensory Alterations and Repetitive Behaviours in Children with Autism Spectrum Disorders: A Parents' Questionnaire Based Study.

The relationship between sensory profile and repetitive behaviours in autism spectrum disorder (ASD) has long been known. However, there is no consensus on the type of relationship that exists between them. This monocentric retrospective-prospective observational study aimed (a) to detect a clinical correlation between the severity of repetitive behaviours and the alterations of sensory profile in a sample of 50 children diagnosed with ASD; (b) to evaluate how different patterns of stereotypies and sensory alterations correlate with each other and with the main clinical-instrumental variables in the same sample. We enrolled 29 children in the retrospective phase of the study and 21 in the prospective phase. The Repetitive Behaviour Scale-Revised (RBS-R) and the Short Sensory Profile (SSP) were administered to the caregivers, and clinical-instrumental data were collected. SSP and RBS-R total scores directly correlated with a high significance rate. Among the subscales, the strongest correlations involved "Visual/Auditory Sensitivity", related to "Stereotyped Behaviour" and "Sameness Behaviour". "Under-Responsive/Seeks Sensation" related to "Stereotyped Behaviour". Sex and intellectual disability significantly influenced both the stereotypies and the sensory alterations of the examined population. In conclusion, this study provides new insights into the relationship between sensory alterations and repetitive behaviours in ASD children by using direct medical observation and parent observation.

Autism spectrum disorder and anorexia nervosa: an Italian prospective study.

BACKGROUND: Potential overlaps exist between psychopathological features of Anorexia Nervosa (AN) and Autism Spectrum Disorder (ASD). The impact of malnutrition on autistic traits in patients with AN should be considered. This study investigates possible associations among the psychopathology of Eating Disorders (EDs), ASD traits and BMI in a group of young patients with AN, using the EDI-3 (Eating Disorder Inventory-3) test and gold-standard measures for ASD. METHODS: Prospective study involving 23 inpatients admitted to an Italian Centre for paediatric ED. ASD traits and ED psychopathology were assessed administering the ADOS-2 (Autism Diagnostic Observation Schedule-2), AQ (Autism Quotient) and EDI-3 tests. Both present and past autistic traits were investigated using different versions of AQ. Correlations were adjusted for BMI, Obsessive Compulsive Disorder (OCD) comorbidity and concurrent antipsychotic treatments. RESULTS: An ASD diagnosis was possible in 22% of patients. Significant correlations were documented between ASD traits and ED psychopathology: AQ total-Interpersonal problems (IPC) (p = 0.041); AQ total-Global psychological maladjustment (GMPC) (p = 0.027); AQ social skills-Ineffectiveness (IC) (p = 0.018); AQ social skills-IPC (p = 0.019); AQ social skills-Affective problems (APC) (p = 0.025); AQ social skills-GMPC (p = 0.007); AQ attention switching-IPC (p = 0.020); ADOS-2 imagination-IC (p = 0.035). These correlations were independent of BMI, OCD and antipsychotic treatments. CONCLUSIONS: ASD traits presented high prevalence in a group of young inpatients with AN. These traits were significantly correlated to 4 specific EDI-3 subscales and independent of BMI. This is the first study to investigate the relationship between ASD traits as measured with gold-standard measures, EDI-3 scores, and BMI.

Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis.

AIM: To describe a spectrum of intracerebral large artery disease in Aicardi-Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1. METHOD: We used clinical and radiological description and molecular analysis. RESULTS: Five individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration. The cerebral vasculopathy was primarily occlusive in three patients (with terminal carotid occlusion and basal collaterals reminiscent of moyamoya syndrome) and aneurysmal in two. Three of the five patients experienced intracerebral haemorrhage, which was fatal in two individuals. Post-mortem examination of one patient suggested that the arteriopathy was inflammatory in origin. INTERPRETATION: Mutations in SAMHD1 are associated with a cerebral vasculopathy which is likely to have an inflammatory aetiology. A similar disease has not been observed in patients with mutations in AGS1 to AGS4, suggesting a particular role for SAMHD1 in vascular homeostasis. Our report raises important questions about the management of patients with mutations in SAMHD1.

A new case of idiopathic hemiplegia hemiconvulsion syndrome.

We report a new case of infantile idiopathic hemiconvulsion-hemiplegia syndrome (HH). A prolonged right-sided febrile convulsion was followed 4 days later, by right hemiconvulsive status epilepticus, documented by video-electroencephalogram (EEG) recording. The child developed an ipsilateral hemiplegia, partially improved during the first month of follow-up. Sequential cerebral magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) at 6, 15, 30 days of follow-up showed a cytotoxic edema in the left hemisphere and a subsequent necrosis. At 1-year of follow-up, we performed MRI control because of febrile convulsion lasting few minutes that confirmed a non-progressive left hemisphere atrophy. After 2 years, the patient was seizure-free, with a mild right hemiplegia and language skills deficit. We discuss the unclear pathogenesis of HH through sequential neuroradiological evaluation.

Bathing epilepsy: report of two Caucasian cases.

Bathing epilepsy, also known as water-immersion epilepsy, refers to a rare form of benign reflex epilepsy in which seizures are precipitated by the normal process of domestic bathing. This condition has been confused with true hot water epilepsy, even though bathing in water at normal temperature is the trigger. Focal seizures predominate with a staring gaze, pallor and generalised features followed by prolonged postictal somnolence. A variable percentage of patients may also show unprovoked seizures. The prognosis is usually favourable, and modifying bathing habits may prevent further seizures. We report two Caucasian patients with bathing epilepsy. In one, seizures were provoked by water immersion. In the other, we noted an unusual triggering factor; pouring of lukewarm water over the genitalia.