Variant-specific in vitro neuronal network phenotypes and drug sensitivity in SCN2A developmental and epileptic encephalopathy.

De novo variants in the Na1.2 voltage-gated sodium channel gene SCN2A are among the major causes of developmental and epileptic encephalopathies (DEE). Based on their biophysical impact on channel conductance and gating, SCN2A DEE variants can be classified into gain-of-function (GoF) or loss-of-function (LoF).

The Q/R editing site of AMPA receptor GluA2 subunit acts as an epigenetic switch regulating dendritic spines, neurodegeneration and cognitive deficits in Alzheimer's disease.

Background: RNA editing at the Q/R site of GluA2 occurs with ~99% efficiency in the healthy brain, so that the majority of AMPARs contain GluA2(R) instead of the exonically encoded GluA2(Q). Reduced Q/R site editing infcreases AMPA receptor calcium permeability and leads to dendritic spine loss, neurodegeneration, seizures and learning impairments. Furthermore, GluA2 Q/R site editing is impaired in Alzheimer's disease (AD), raising the possibility that unedited GluA2(Q)-containing AMPARs contribute to synapse loss and neurodegeneration in AD.

Antisense oligonucleotide therapy for KCNT1 encephalopathy.

Developmental and epileptic encephalopathies (DEEs) are characterized by pharmaco-resistant seizures with concomitant intellectual disability. Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the most severe of these syndromes. De novo variants in ion channels, including gain-of-function variants in KCNT1, which encodes for sodium activated potassium channel protein KNa1.

Protective effects of medium chain triglyceride diet in a mouse model of Dravet syndrome.

Objective: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy with early childhood onset. Patients with DS do not respond well to antiepileptic drugs and have only a few treatment options available. Here, we evaluated the effect of medium chain triglyceride (MCT) diet therapy in a mouse model of DS.

HLA-DRB1*14 is a protective allele for multiple sclerosis in an admixed Colombian population.

Objective: The aim of this study was to determine ancestry informative markers, mitochondrial DNA haplogroups, and the association between HLA-DRB1 alleles and multiple sclerosis (MS) in a group of patients from Bogotá, Colombia.

Methods: In this case-control study, genomic DNA was isolated and purified from blood samples. HLA-DRB1 allele genotyping was done using PCR.

Cavernous sinus syndrome: need for early diagnosis.

Cavernous sinus syndrome (CSS) is a rare condition characterised by ophthalmoplegia, proptosis, ocular and conjunctival congestion, trigeminal sensory loss and Horner's syndrome. These signs and symptoms result from the involvement of the cranial nerves passing through the cavernous sinus. We report the case of a 53-year-old man with a history of daily stabbing headache associated with dizziness, progressive blurred vision, right ocular pain, ptosis and ophthalmoplegia.

Teaching case: a man with a progressive gait impairment and visual compromise.

Primary progressive multiple sclerosis can present with a wide variety of symptoms. We report a case of a 52-year-old man presenting with visual symptoms and gait impairment in whom a diagnosis of a primary progressive multiple sclerosis was established. Symptomatic treatment with dalfampridine was started but did not result in a considerable improvement.