Primary headache with onset in childhood and adolescence: natural history and prognostic factors in a Portuguese population.

Introduction: Headaches are the most frequent neurological disorder in the pediatric population, with great impact on quality of life. This study aims to characterize a cohort of patients followed at a pediatric neurology unit between January 1st 2013 and December 31st, 2021.

Materials And Methods: We reviewed medical records and selected patients with primary headaches and a minimum follow-up of 12 months.

Congenital ataxia due to novel variant in ATP8A2.

Congenital ataxias are a heterogeneous group of disorders characterized by congenital or early-onset ataxia. Here, we describe two siblings with congenital ataxia, who acquired independent gait by age 4 years. After 16 years of follow-up they presented near normal cognition, cerebellar ataxia, mild pyramidal signs, and dystonia.

Cardiac phenotype in -related syndromes: A multicenter cohort study.

Objective: To define the risks and consequences of cardiac abnormalities in -related syndromes.

Methods: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an knock-in mouse (Mashl) to determine the sequence of events in seizure-related cardiac death.

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur.

[Tuberous sclerosis: clinical characteristics and their relationship to genotype/phenotype].

Introduction: Tuberous sclerosis (TS) is an inherited disorder with multisystemic involvement and a high phenotypic variability. There are two genes that cause this condition: TSC1 and TSC2.

Objectives: Our goal was to clinically characterize patients with TS followed up in the Pediatric Neurology Clinic of a tertiary hospital during the last 10 years, and correlate the genotype with the severity of neurological manifestations and imaging studies.

The expanding clinical and genetic spectrum of ATP1A3-related disorders.

Objective: We aimed to delineate the clinical and genetic spectrum of ATP1A3-related disorders and recognition of a potential genotype-phenotype correlation.

Methods: We identified 16 new patients with alternating hemiplegia of childhood (AHC) and 3 new patients with rapid-onset dystonia-parkinsonism (RDP) and included these as well as the clinical and molecular findings of all previously reported 164 patients with mutation-positive AHC and RDP in our analyses.

Results: Major clinical characteristics shared in common by AHC and RDP comprise a strikingly asymmetric, predominantly dystonic movement disorder with rostrocaudal gradient of involvement and physical, emotional, or chemical stressors as triggers.

Progressive encephalomyelitis with rigidity and myoclonus: the first pediatric case with glycine receptor antibodies.

Importance: Progressive encephalomyelitis with rigidity and myoclonus is characterized by rigidity, painful muscle spasms, hyperekplexia, and brainstem signs. Recently, glycine receptor alpha 1 antibodies have been described in adult patients with progressive encephalomyelitis with rigidity and myoclonus. We describe a pediatric case.

[Sturge-Weber syndrome -clinical and neuroimaging variability].

Sturge Weber Syndrome is a rare neurocutaneous syndrome in which the severity is determined by degree of brain involvement and control of epilepsy. The authors describe and analyse clinical and imaging features of this syndrome, through a retrospective study of 13 patients (8 girls; aged between 15 days and 9 years at first visit). Twelve had facial angioma and one had atrichia corresponding to the area of brain involvement.

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder.

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members.

Rett syndrome with and without detected MECP2 mutations: an attempt to redefine phenotypes.

Background: The diagnosis of Rett syndrome (RTT) is based on a set of clinical criteria, irrespective of mutation status. The aims of this study were (1) to define the clinical differences existing between patients with Rett syndrome with (Group I) and without a MECP2 mutation (Group II), and (2) to characterize the phenotypes associated with the more common MECP2 mutations.

Patients And Methods: We analyzed 87 patients fulfilling the clinical criteria for RTT.

Mutations in the MECP2 gene are not a major cause of Rett syndrome-like or related neurodevelopmental phenotype in male patients.

Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls, but mutations in the causative MECP2 gene have also been identified in boys with classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome-like phenotype; the patients had diverse clinical presentations that included perturbations of the autistic spectrum, microcephaly, mental retardation, manual stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2 gene, including the detection of large rearrangements, and we did not detect any pathogenic mutations in the MECP2 gene in these patients, in whom the genetic basis of disease remained unidentified.

Neurodegeneration associated with genetic defects in phospholipase A(2).

Objective: Mutations in the gene encoding phospholipase A(2) group VI (PLA2G6) are associated with two childhood neurologic disorders: infantile neuroaxonal dystrophy (INAD) and idiopathic neurodegeneration with brain iron accumulation (NBIA). INAD is a severe progressive psychomotor disorder in which axonal spheroids are found in brain, spinal cord, and peripheral nerves. High globus pallidus iron is an inconsistent feature of INAD; however, it is a diagnostic criterion of NBIA, which describes a clinically and genetically heterogeneous group of disorders that share this hallmark feature.

Evaluation of CSF neurotransmitters and folate in 25 patients with Rett disorder and effects of treatment.

Background: Rett disorder (RD) is a progressive neurodevelopmental entity caused by mutations in the MECP2 gene. It has been postulated that there are alterations in the levels of certain neurotransmitters and folate in the pathogenesis of this disease. Here we re-evaluated this hypothesis.

Mitochondrial diseases mimicking neurotransmitter defects.

Objectives: Mitochondrial disorders are clinically heterogeneous. We aimed to describe 5 patients who presented with a clinical picture suggestive of primary neurotransmitter defects but who finally fulfilled diagnostic criteria for mitochondrial disease.

Methods: We report detailed clinical features, brain magnetic resonance findings and biochemical studies, including cerebrospinal fluid (CSF) biogenic amine and pterin measurements, respiratory chain enzyme activity, and molecular studies.

Movement disorders in Rett syndrome: an analysis of 60 patients with detected MECP2 mutation and correlation with mutation type.

Rett syndrome (RS) is one of the best human models to study movement disorders. Patients evolve from a hyperkinetic to a hypokinetic state, and a large series of abnormal movements may be observed along their lives such as stereotypies, tremor, chorea, myoclonus, ataxia, dystonia, and rigidity. The aim of this work was to analyze movement disorders in RS patients with a detected MECP2 mutation, as well as their correlation with genotype, in a clinically and genetically well-characterized sample of patients, and thus contribute to redefine the clinical profile of this disease.

Infantile neuroaxonal dystrophy: what's most important for the diagnosis?

Background And Aims: Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder, with onset in the first 2 years of life. Mutations in the PLA2G6 gene were identified in patients with infantile neuroaxonal dystrophy. Our purpose was to review clinical, neurophysiologic, neuroradiologic and neuropathological features of our patients in order to identify the earliest signs of disease.

Bilateral perisylvian polymicrogyria and chromosome 1 anomaly.

Polymalformative syndromes are always a clinical challenge for their complexity and sometimes for their rarity. Authors present the case of a girl with peculiar facies, macrocephaly, axial hypotonia, and severe development delay. Cerebral magnetic resonance showed polymicrogyria.

One year of Lamivudine therapy for portuguese patients with chronic hepatitis B.

Objective: To assess the efficacy of lamivudine treatment on hepatitis B e antigen (HBeAg) and/or hepatitis B surface antigen (HBsAg) seroconversion, on other virological and serological markers of response including hepatitis B virus (HBV) DNA and serum aminotransferases, and the safety of lamivudine treatment in hepatitis B patients.

Patients: This phase III open-label study evaluated the virological and biochemical response to lamivudine in 70 Portuguese patients with HBeAg positive chronic hepatitis B. Patients were treated with lamivudine 100mg once daily for 12 months.

Stereotypies in Rett syndrome: analysis of 83 patients with and without detected MECP2 mutations.

Background: Hand stereotypies are considered a hallmark of Rett syndrome (RTT) and are usually described as symmetric movements at the midline. However, related pathologies may show the same type of involuntary movement. Furthermore, patients with RTT also have stereotypies with other localizations that are less well characterized.

Novel L2HGDH mutations in 21 patients with L-2-hydroxyglutaric aciduria of Portuguese origin.

We studied 21 patients, from 18 families, with L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic disorder with a homogeneous presentation: progressive neurodegeneration with extrapyramidal and cerebellar signs, seizures, and subcortical leukoencephalopathy. Increased levels of L-2-hydroxyglutaric acid in body fluids proved the diagnosis of L-2-HGA in all 21 patients. We analyzed the L-2-HGA gene (L2HGDH), recently found to be mutated in consanguineous families with L-2-HGA, and identified seven novel mutations in 15 families.