RESUMEN
By converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of stretch-activated ion channels with human disease is limited. Here, we describe 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes carrying ten distinct heterozygous variants of TMEM63B, encoding for a highly conserved stretch-activated ion channel. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense, including the recurrent p.Val44Met in 7/17 individuals, or in-frame, all affecting conserved residues located in transmembrane regions of the protein. In 12 individuals, hematological abnormalities co-occurred, such as macrocytosis and hemolysis, requiring blood transfusions in some. We modeled six variants (p.Val44Met, p.Arg433His, p.Thr481Asn, p.Gly580Ser, p.Arg660Thr, and p.Phe697Leu), each affecting a distinct transmembrane domain of the channel, in transfected Neuro2a cells and demonstrated inward leak cation currents across the mutated channel even in isotonic conditions, while the response to hypo-osmotic challenge was impaired, as were the Ca2+ transients generated under hypo-osmotic stimulation. Ectopic expression of the p.Val44Met and p.Gly580Cys variants in Drosophila resulted in early death. TMEM63B-associated DEE represents a recognizable clinicopathological entity in which altered cation conductivity results in a severe neurological phenotype with progressive brain damage and early-onset epilepsy associated with hematological abnormalities in most individuals.
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Encefalopatías , Discapacidad Intelectual , Humanos , Encefalopatías/genética , Canales Iónicos/genética , Encéfalo , Discapacidad Intelectual/genética , FenotipoRESUMEN
PURPOSE: RNF213, encoding a giant E3 ubiquitin ligase, has been recognized for its role as a key susceptibility gene for moyamoya disease. Case reports have also implicated specific variants in RNF213 with an early-onset form of moyamoya disease with full penetrance. We aimed to expand the phenotypic spectrum of monogenic RNF213-related disease and to evaluate genotype-phenotype correlations. METHODS: Patients were identified through reanalysis of exome sequencing data of an unselected cohort of unsolved pediatric cases and through GeneMatcher or ClinVar. Functional characterization was done by proteomics analysis and oxidative phosphorylation enzyme activities using patient-derived fibroblasts. RESULTS: We identified 14 individuals from 13 unrelated families with (de novo) missense variants in RNF213 clustering within or around the Really Interesting New Gene (RING) domain. Individuals presented either with early-onset stroke (n = 11) or with Leigh syndrome (n = 3). No genotype-phenotype correlation could be established. Proteomics using patient-derived fibroblasts revealed no significant differences between clinical subgroups. 3D modeling revealed a clustering of missense variants in the tertiary structure of RNF213 potentially affecting zinc-binding suggesting a gain-of-function or dominant negative effect. CONCLUSION: De novo missense variants in RNF213 clustering in the E3 RING or other regions affecting zinc-binding lead to an early-onset syndrome characterized by stroke or Leigh syndrome.
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Enfermedad de Leigh , Enfermedad de Moyamoya , Accidente Cerebrovascular , Humanos , Niño , Enfermedad de Moyamoya/genética , Enfermedad de Leigh/complicaciones , Factores de Transcripción/genética , Ubiquitina-Proteína Ligasas/genética , Zinc , Predisposición Genética a la Enfermedad , Adenosina Trifosfatasas/genéticaRESUMEN
Ketogenic diet therapy (KDT) is a safe and effective treatment for epilepsy and glucose transporter type 1 (GLUT1) deficiency syndrome in infancy. Complete weaning from breastfeeding is not required to implement KDT; however, breastfeeding remains uncommon. Barriers include feasibility concerns and lack of referrals to expert centres. Therefore, practical strategies are needed to help mothers and professionals overcome these barriers and facilitate the inclusion of breastfeeding and human milk during KDT. A multidisciplinary expert panel met online to address clinical concerns, systematically reviewed the literature, and conducted two international surveys to develop an expert consensus of practical recommendations for including human milk and breastfeeding in KDT. The need to educate about the nutritional benefits of human milk and to increase breastfeeding rates is emphasized. Prospective real-world registries could help to collect data on the implementation of breastfeeding and the use of human milk in KDT, while systematically including non-seizure-related outcomes, such as quality of life, and social and emotional well-being, which could improve outcomes for infants and mothers.
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Febrile seizures (FS) are usually self-limiting and cause no morbidity. Nevertheless they represent very traumatic events for families. There is a need to identify key messages that reassure carers and help to prevent inappropriate, anxiety-driven behaviors associated with "fever phobia." No recommendations have been proposed to date regarding the content of such messages. Using a Delphi process, we have established a consensus regarding the information to be shared with families following a FS. Twenty physicians (child neurologists and pediatricians) from five European countries participated in a three-step Delphi process between May 2018 and October 2019. In the first step, each expert was asked to give 10 to 15 free statements about FS. In the second and third steps, statements were scored and selected according to the expert ranking of importance. A list of key messages for families has emerged from this process, which offer reassurance about FS based on epidemiology, underlying mechanisms, and the emergency management of FS should they recur. Interestingly, there was a high level of agreement between child neurologists and general pediatricians.Conclusion: We propose key messages to be communicated with families in the post-FS clinic setting. What is Known: ⢠Febrile seizures (FS) are traumatic events for families. ⢠No guidelines exist on what information to share with parents following a FS. What is New: ⢠A Delphi process involving child neurologists and pediatricians provides consensual statement about information to deliver after a febrile seizure. ⢠We propose key messages to be communicated with families in the post-FS clinic setting.
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Convulsiones Febriles , Niño , Consenso , Fiebre , Humanos , Padres , Recurrencia , Convulsiones Febriles/etiología , Convulsiones Febriles/terapiaRESUMEN
Children with unilateral cerebral palsy (UCP) have complex health, education and social care needs. Delayed gross motor milestones are the most common presenting feature, and much of the early management focuses on gross motor skills and lower limb management. In later childhood, adolescence and adulthood, upper limb function has significant impact on activity, participation and independence. There is clear pathophysiological rationale and emerging clinical evidence that earlier intervention to improve upper limb function is beneficial. Whereas most children with UCP are managed in secondary care, it is recommended that the assessment and delivery of specialist intervention for the upper limb occurs at a regional centre.
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Parálisis Cerebral/fisiopatología , Parálisis Cerebral/terapia , Hemiplejía/terapia , Extremidad Superior/fisiopatología , Instituciones de Atención Ambulatoria , Toxinas Botulínicas/uso terapéutico , Niño , Hemiplejía/fisiopatología , Humanos , Anamnesis , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/fisiopatología , Examen Neurológico , Procedimientos Ortopédicos , Modalidades de Fisioterapia , Férulas (Fijadores)RESUMEN
Perampanel is an adjunctive treatment for epilepsy that works through the direct inhibition of AMPA receptors. The same molecular mechanism has recently been shown for a fatty acid, decanoic acid, prescribed in the medium chain triglyceride ketogenic diet for the treatment of patients with drug-resistant epilepsy. Because each compound has been proposed to act through a distinct AMPA receptor binding site, we predicted that perampanel and decanoic acid would act synergistically against AMPA receptors and, consequently, seizures. Here, we show a synergistic interaction between perampanel and decanoic acid in direct AMPA receptor inhibition, in an ex vivo model of seizure activity, and against seizure-induced activity in human brain slices. These data support a potential role for combination treatment using perampanel and dietary decanoic acid to provide enhanced seizure control.
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Anticonvulsivantes/farmacología , Encéfalo/efectos de los fármacos , Ácidos Decanoicos/farmacología , Piridonas/farmacología , Receptores AMPA/metabolismo , Animales , Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Potenciales Evocados/efectos de los fármacos , Hipocampo/efectos de los fármacos , Humanos , Técnicas In Vitro , Nitrilos , Oocitos , Pentilenotetrazol/toxicidad , Ratas , XenopusAsunto(s)
Epilepsia , Neoplasias , Complicaciones del Embarazo , Embarazo , Femenino , Humanos , Niño , Ácido Fólico/efectos adversos , Madres , Epilepsia/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Neoplasias/tratamiento farmacológico , Suplementos Dietéticos , Complicaciones del Embarazo/tratamiento farmacológicoRESUMEN
OBJECTIVE: The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation. METHOD: Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained. RESULTS: Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases. SIGNIFICANCE: Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males.
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Proteínas de Ciclo Celular/genética , Proteínas Cromosómicas no Histona/genética , Epilepsia/genética , Mutación/genética , Convulsiones/genética , Niño , Preescolar , Electroencefalografía , Epilepsia/complicaciones , Femenino , Heterocigoto , Humanos , Masculino , Convulsiones/complicacionesRESUMEN
There are difficulties inherent in measuring Quality of life (QoL) in patients with chronic illness, including agreement on definitions of quality of life and the type of measure used, disease specific or generic. Well validated QoL instruments for epilepsy exist but focus on capturing common themes pertinent to children and families as a group instead of focusing on themes important to individual patients and their families/carers. In addition, it is common for numerous items on these inventories to be left incomplete or responded to with "not applicable" since many of the items are not suitable for children with disabilities and their families. This led us to devise a way to capture individual quality-of-life measures that are linked to parental/carer expectations in families of children undergoing ketogenic diet therapy for epilepsy. As part of our routine clinical assessment, parents/carers were asked to describe what they would like to see happen or change as a result of their child being on ketogenic diet therapy. A simple unstructured form was designed to facilitate the assessment process. Parents were then asked to rate their own QoL against these criteria on a Likert scale of 0-10 prior to commencement of the diet. This assessment was repeated at subsequent visits with parents/carers initially blinded to their original responses. Our assessments indicated that ketogenic diet therapy improves quality of life over a twelve-month period when measured against parental expectations. This ideographic approach has demonstrated changes in parental Qol and parental perceptions of their child's quality of life that would not have been captured by other validated measures. A lengthy questionnaire is avoided and is replaced by a skilled supportive conversation that identifies goals for treatment that are important to parents. This helps parents to reflect on the progress their child makes on the diet by revisiting their previously stated aspirations, and assessing whether they have been achieved. This is particularly helpful for those parents who express a sense of failure or helplessness relating to their child's intractable epilepsy. As a result, future work will center on developing this approach as a clinical tool.
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Dieta Cetogénica/psicología , Dieta Cetogénica/tendencias , Epilepsia Refractaria/dietoterapia , Epilepsia Refractaria/psicología , Calidad de Vida/psicología , Encuestas y Cuestionarios , Cuidadores/psicología , Niño , Enfermedad Crónica , Epilepsia Refractaria/diagnóstico , Femenino , Humanos , Masculino , Padres/psicología , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate incorporating a ready-to-use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. METHODS: Following a three-day baseline, patients (n = 19; age: 19 years [SD 13], range: 8-46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready-to-use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß-hydroxybutyrate (BHB) concentration, seizure outcomes, health-related quality of life (HRQoL), acceptability and safety. RESULTS: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (<50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p < 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p < 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). SIGNIFICANCE: These findings provide an evidence-base to support the effective management of children and adults with drug-resistant epilepsy following a KD with the use of a ready-to-use, nutritionally complete, 2.5:1 ratio feed including MCTs. PLAIN LANGUAGE SUMMARY: This study examined the use of a ready-to-use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively.
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Dieta Cetogénica , Epilepsia Refractaria , Niño , Adulto , Humanos , Adulto Joven , Dieta Cetogénica/efectos adversos , Dieta Cetogénica/métodos , Calidad de Vida , Triglicéridos , Convulsiones , CarbohidratosRESUMEN
BACKGROUND: Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy. METHODS: In this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding. FINDINGS: Between Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to a ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1·33, 95% CI 0·84-2·11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee. INTERPRETATION: In this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite previously trying two antiseizure medications. FUNDING: National Institute for Health and Care Research.
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Dieta Cetogénica , Epilepsia Refractaria , Epilepsia , Niño , Adulto , Humanos , Masculino , Lactante , Femenino , Preescolar , Dieta Cetogénica/efectos adversos , Epilepsia Refractaria/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Reino Unido , Resultado del TratamientoRESUMEN
Isolated complex I deficiency is the most frequently observed oxidative phosphorylation defect in children with mitochondrial disease, leading to a diverse range of clinical presentations, including Leigh syndrome. For most patients the genetic cause of the biochemical defect remains unknown due to incomplete understanding of the complex I assembly process. Nonetheless, a plethora of pathogenic mutations have been described to date in the seven mitochondrial-encoded subunits of complex I as well as in 12 of the nuclear-encoded subunits and in six assembly factors. Whilst several mitochondrial DNA mutations are recurrent, the majority of these mutations are reported in single families. We have sequenced core structural and functional nuclear-encoded subunits of complex I in a cohort of 34 paediatric patients with isolated complex I deficiency, identifying pathogenic mutations in 6 patients. These included a novel homozygous NDUFS1 mutation in an Asian child with Leigh syndrome, a previously identified NDUFS8 mutation (c.236C>T, p.P79L) in a second Asian child with Leigh-like syndrome and six novel, compound heterozygous NDUFS2 mutations in four white Caucasian patients with Leigh or Leigh-like syndrome. Three of these children harboured an identical NDUFS2 mutation (c.875T>C, p.M292T), which was also identified in conjunction with a novel NDUFS2 splice site mutation (c.866+4A>G) in a fourth Caucasian child who presented to a different diagnostic centre, with microsatellite and single nucleotide polymorphism analyses indicating that this was due to an ancient common founder event. Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes.
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Enfermedad de Leigh/genética , Mitocondrias/genética , Mutación/genética , NADH Deshidrogenasa/genética , Electroforesis en Gel de Poliacrilamida , Femenino , Haplotipos , Humanos , Lactante , Masculino , Proteínas Mitocondriales/genética , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: The evidence base to guide the pharmacological management of tone and abnormal movements in cerebral palsy (CP) is limited, as is an understanding of routine clinical practice in the UK. We aimed to establish details of motor phenotype and current pharmacological management of a representative cohort across a network of UK tertiary centres. METHODS: Prospective multicentre review of specialist motor disorder clinics at nine UK centres, collecting data on clinical features and pharmacological management of children and young people (CYP) with CP over a single calendar month. RESULTS: Data were collected from 275 CYP with CP reviewed over the calendar month of October 2017. Isolated dystonia or spasticity was infrequently seen, with a mixed picture of dystonia and spasticity ± choreoathetosis identified in 194/275 (70.5%) of CYP. A comorbid diagnosis of epilepsy was present in 103/275 (37.4%). The most commonly used medications for abnormal tone/movement were baclofen, trihexyphenidyl, gabapentin, diazepam and clonidine. Medication use appeared to be influenced separately by the presence of dystonia or spasticity. Botulinum toxin use was common (62.2%). A smaller proportion of children (12.4%) had undergone a previous neurosurgical procedure for tone/movement management. CONCLUSIONS: CYP with CP frequently present with a complex movement phenotype and comorbid epilepsy. They have multiple therapy, medical and surgical management regimens. Future trials of therapeutic, pharmacological or surgical interventions in this population must adequately encompass this complexity in order to be translatable to clinical practice.
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Parálisis Cerebral/epidemiología , Relajantes Musculares Centrales/uso terapéutico , Adolescente , Baclofeno/uso terapéutico , Toxinas Botulínicas/uso terapéutico , Parálisis Cerebral/tratamiento farmacológico , Parálisis Cerebral/fisiopatología , Niño , Servicios de Salud del Niño , Preescolar , Clonidina/uso terapéutico , Diazepam/uso terapéutico , Distonía/tratamiento farmacológico , Distonía/fisiopatología , Femenino , Humanos , Lactante , Masculino , Registros Médicos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/fisiopatología , Estudios Prospectivos , Medicina Estatal , Trihexifenidilo/uso terapéutico , Reino Unido/epidemiologíaRESUMEN
A 15-week old male infant presented with bilateral lower motor neuron facial palsy of unknown cause. Subsequently his growth deteriorated and he developed progressively worsening cough and wheeze. A diagnosis of cystic fibrosis was confirmed and hypovitaminosis A detected. Improvement of the facial palsy was noted following standard management of cystic fibrosis including vitamin A supplementation.
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Fibrosis Quística/complicaciones , Fibrosis Quística/fisiopatología , Parálisis Facial/etiología , Suplementos Dietéticos , Humanos , Lactante , Masculino , Vitamina A/uso terapéutico , Deficiencia de Vitamina A/complicacionesRESUMEN
An 11-month-old infant with a 5-month history of seizures and a 3-month history of infantile spasms is described. EEG showed epileptic encephalopathy. The infantile spasms were resistant to treatment with clobazam. Following the introduction of levetiracetam, there was clinical cessation of seizures with resolution of seizure activity on the EEG. This is the second report in the literature of effective treatment of infantile spasms with levetiracetam.
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Anticonvulsivantes/uso terapéutico , Piracetam/análogos & derivados , Piracetam/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Electroencefalografía , Humanos , Lactante , Levetiracetam , Masculino , Espasmos Infantiles/fisiopatologíaRESUMEN
Autonomic instability is well recognized in Guillain-Barré syndrome (GBS), particularly in the acute inflammatory demyelinating polyneuropathy subtype. Hypertension occurs in up to two-thirds of children with GBS but is rarely the main presenting feature. We describe a teenager who presented with tachycardia, dizziness, flushing, and significant hypertension as well as ascending limb weakness and sensory disturbance with areflexia. Because the predominant initial concern was hypertension, she was referred to pediatric nephrology and appropriate investigations for hypertension were conducted. Her neurologic findings prompted a neurology referral, and a diagnosis of GBS was made. The investigations for hypertension subsequently revealed increased urinary normetadrenaline levels in a range consistent with pheochromocytoma, prompting the question of dual pathology. Both autonomic symptoms and urinary metadrenaline levels subsided with GBS resolution, and further investigations excluded the diagnosis of pheochromocytoma. Our case highlights that significant dysautonomia can occur in children with GBS, with hypertension being a prominent early feature. Recognition that urinary metadrenalines can increase to levels seen in pheochromocytoma is important in avoiding diagnostic confusion.
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Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/diagnóstico , Feocromocitoma/complicaciones , Feocromocitoma/diagnóstico , Adolescente , Neoplasias de las Glándulas Suprarrenales/orina , Femenino , Síndrome de Guillain-Barré/orina , Humanos , Feocromocitoma/orinaRESUMEN
BACKGROUND: Hyperthyroidism is rare in pre-school children. Untreated, it can have a profound effect on normal growth and development, particularly in the first 2 years of life. Although neurological manifestations of dysthyroid states are well known, specific expressive speech and language disorder as a presentation of hyperthyroidism is rarely documented. METHODS: Case reports of two children with hyperthyroidism presenting with speech and language delay. RESULTS: We report two pre-school children with hyperthyroidism, who presented with expressive speech and language delay, and demonstrated a significant improvement in their language skills following treatment with anti-thyroid medication. CONCLUSIONS: Hyperthyroidism must be considered in all children presenting with speech and language difficulties, particularly expressive speech delay. Prompt recognition and early treatment are likely to improve outcome.
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Hipertiroidismo/complicaciones , Trastornos del Desarrollo del Lenguaje/etiología , Antagonistas Adrenérgicos beta/uso terapéutico , Carbimazol/uso terapéutico , Preescolar , Femenino , Humanos , Trastornos del Desarrollo del Lenguaje/tratamiento farmacológico , MasculinoRESUMEN
Blister formation and eccrine sweat gland necrosis have been recognized to occur in states of impaired consciousness and were first reported following barbiturate intoxication. Their etiology is complex and cannot simply be explained by pressure effects. Now that barbiturates are less frequently used, clinicians are likely to be less aware of the phenomenon of coma blister formation; however, newer drugs have also been associated with the occurrence of coma blisters. We describe 2 new associations of coma blisters and anticonvulsants in children. In the first child, blisters recurred on multiple occasions along with obtundation and edema. Our aims are to alert clinicians to the occurrence of coma blisters in children sedated on anticonvulsant medications and to report the new finding of recurrent coma blisters.