The complete mutational spectrum of dystrophinopathies and limb-girdle muscular dystrophy (LGMD) remains unknown in Mexican population. Seventy-two unrelated Mexican male patients (73% of pediatric age) with clinical suspicion of muscular dystrophy and no evidence of DMD gene deletion on multiplex polymerase chain reaction (mPCR) analysis were analyzed by multiplex ligation-dependent probe amplification (MLPA). Those with a normal result were subjected to Sanger sequencing or to next-generation sequencing for DMD plus 10 selected LGMD-related genes. We achieved a diagnostic genotype in 80.5% (n = 58/72) of patients with predominance of dystrophinopathy-linked genotypes (68%, n = 49/72), followed by autosomal recessive LGMD-related genotypes (types 2A-R1, 2C-R5, 2E-R4, 2D-R3 and 2I-R9; 12.5%, n = 9/72). MLPA showed 4.2% of false-negatives for DMD deletions assessed by mPCR. Among the small DMD variants, 96.5% (n = 28/29) corresponded to null-alleles, most of which (72%) were inherited through a carrier mother. The FKRP p.[Leu276Ile]; [Asn463Asp] genotype is reported for the first time in Mexican patients as being associated with dilated cardiomyopathy. Absence of dysferlinopathies could be related to the small sample size and/or the predominantly pediatric age of patients. The employed strategy seems to be an affordable diagnosis approach for Mexican muscular dystrophy male patients and their families.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common autoimmune encephalitides. The frequency of anti-NMDAR encephalitis is known to exceed the frequency of any individual viral encephalitis in young subjects. Epileptic seizures are a cardinal symptom in anti-NMDAR encephalitis; a significant amount of pediatric patients exhibit seizures as the first symptom of the disease, and most of them will develop them during the acute phase. The use of antiepileptic drugs (AEDs) is a cornerstone of the treatment of these patients, but the choice of agent and duration of treatment is currently unknown. This was a single-center retrospective review case series of all pediatric patients with a confirmed diagnosis of anti-NMDAR encephalitis and epileptic seizures admitted to the National Institute of Pediatrics in Mexico City from January 2012 to July 2019. We included a total of 31 patients (males 64.5%, median age: 10 years). No patient showed evidence of teratoma; only 38% of cases had a viral prodrome. Most patients initially exhibited psychiatric symptoms (51%), but the leading cause in soliciting medical assistance was the presence of epileptic seizures (71%). About 85% of patients presented epileptic seizures during the course of the illness, predominantly focal onset seizures (42% focal to bilateral tonic-clonic seizures, 32% focal seizures with impaired awareness). Electroencephalogram (EEG) was abnormal in 97% of patients; the characteristic extreme delta brush pattern was found in 9% of patients. Two AEDs on average were required to control seizures during the acute stage. In six (19%) patients, human herpesvirus (HHV) was detected in cerebrospinal fluid (CSF); all of them had epileptic seizures, which were more resistant to pharmacological treatment during the acute phase, requiring a higher number of AED (median 2.5 vs. 2). The development of epilepsy after acute encephalitis was uncommon; at 24 months, only one patient continued to have epileptic seizures. One of the factors most closely related to the persistence of epileptic seizures was the inadequate response to immunotherapy after four weeks. The functional prognosis was generally good; at a two-year follow-up, only two (10%) patients had a significant disability [modified Rankin Scale (mRS) score: 3-5]; both patients had seizures at a one-year follow-up. Sustained use of AEDs after the acute phase of anti-NMDAR encephalitis is controversial. We found that the continuation of AEDs after the acute phase could be considered in the following scenarios: status epilepticus (SE), inadequate response to immunotherapy at four weeks, and a high mRS score at discharge and during follow-up. In other cases, discontinuation of AED may be warranted. More studies are needed in our country to replicate these results.

Epilepsy is a chronic neurological disease characterized by the presence of spontaneous seizures, with a higher incidence in the pediatric population. Anti-seizure medication (ASM) may produce adverse drug reactions (ADRs) with an elevated frequency and a high severity. Thus, the objective of the present study was to analyze, through intensive pharmacovigilance over 112 months, the ADRs produced by valproic acid (VPA), oxcarbazepine (OXC), phenytoin (PHT), and levetiracetam (LEV), among others, administered to monotherapy or polytherapy for Mexican hospitalized pediatric epilepsy patients. A total of 1034 patients were interviewed; 315 met the inclusion criteria, 211 patients presented ADRs, and 104 did not. A total of 548 ASM-ADRs were identified, and VPA, LEV, and PHT were the main culprit drugs. The most frequent ADRs were drowsiness, irritability, and thrombocytopenia, and the main systems affected were hematologic, nervous, and dermatologic. LEV and OXC caused more nonsevere ADRs, and PHT caused more severe ADRs. The risk analysis showed an association between belonging to the younger groups and polytherapy with ADR presence and between polytherapy and malnutrition with severe ADRs. In addition, most of the severe ADRs were preventable, and most of the nonsevere ADRs were nonpreventable.

ANTECEDENTES: La atrofia muscular espinal es la principal causa de muerte por enfermedad genética en lactantes. Es un trastorno degenerativo de las neuronas del asta anterior de la médula espinal. Según la edad de presentación se clasifica en 5 tipos. Las manifestaciones clínicas son: debilidad, hipotonía, atrofia muscular y retraso psicomotor. OBJETIVO: Conocer las características clínicas de pacientes mexicanos con atrofia muscular espinal (AME) que permitan el reconocimiento oportuno de la patología y el inicio de medidas terapéuticas. PACIENTES Y MÉTODOS: Estudio retrospectivo, retrolectivo, observacional y descriptivo al que se incluyeron pacientes con diagnóstico clínico y/o molecular de atrofia muscular espinal.RESULTADOS: Se estudiaron 31 pacientes, 15 de ellos con atrofia muscular espinal I, 13 con AME II y 3 con AME III. Todos los pacientes iniciaron con debilidad muscular, hipotonía y retraso del desarrollo psicomotor. El diagnóstico se estableció a una edad promedio de 30.81 meses, mediana de 23, mínima 2 y máxima 108 meses. Se estableció el diagnóstico genético en 23 de los 31 pacientes. Los de la clasificación AME I fallecieron.CONCLUSIONES: La AME I es el tipo más frecuente. La debilidad severa y las infecciones de las vías respiratorias son los motivos de consulta más comunes. Las manifestaciones clínicas de la AME III son de inicio más tardío y son ortopédicas que generan discapacidad. Existe retraso en el diagnóstico de esta enfermedad y limitaciones importantes en México para el tratamiento y aplicación de la terapia modificadora, lo que limita la calidad de vida y pronóstico de los pacientes.