Choline acetyltransferase (ChAT; EC 2.3.1.6) catalyzes synthesis of acetylcholine from acetyl-CoA and choline in cholinergic neurons. Mutations in CHAT (MIM # 118490) cause potentially lethal congenital myasthenic syndromes associated with episodic apnea (ChAT-CMS) (MIM # 254210). Here we analyze the functional consequences of 12 missense and 1 nonsense mutations of CHAT in 11 patients. Nine of the mutations are novel. We examine expression of the recombinant missense mutants in Bosc 23 cells, determine their kinetic properties and thermal stability, and interpret the functional effects of 11 mutations in the context of the atomic structural model of human ChAT. Five mutations (p.Trp421Ser, p.Ser498Pro, p.Thr553Asn, p.Ala557Thr, p.Ser572Trp) reduce enzyme expression to <50% of wild-type. Mutations with severe kinetic effects are located in the active-site tunnel (p.Met202Arg, p.Thr553Asn and p.Ala557Thr) or adjacent to the substrate binding site (p.Ser572Trp), or exert their effect allosterically (p.Trp421Ser and p.Ile689Ser). Two mutations with milder kinetic effects (p.Val136Met, p.Ala235Thr) are also predicted to act allosterically. One mutation (p.Thr608Asn) below the nucleotide binding site of CoA enhances dissociation of AcCoA from the enzyme-substrate complex. Two mutations introducing a proline residue into an α-helix (p.Ser498Pro and p.Ser704Pro) impair the thermal stability of ChAT.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen and naproxen sodium, are effective yet nonspecific analgesic and anti-inflammatory drugs, which work for a variety of pain and inflammatory syndromes, including migraine. In migraine, their analgesic effect helps relieve the headache, while their anti-inflammatory effect decreases the neurogenic inflammation in the trigeminal ganglion. This is the hypothesized mechanism by which they prevent the development of central sensitization. Triptans, including sumatriptan, work early in the migraine process at the trigeminovascular unit as agonists of the serotonin receptors (5-HT receptors) 1B and 1D. They block vasoconstriction and block transmission of signals to the trigeminal nucleus and thus prevent peripheral sensitization. Therefore, combining these two drugs is an attractive modality for the abortive treatment of migraine. Sumatriptan–naproxen fixed combination tablet (Treximet® [sumatriptan–naproxen]) proves to be an effective and well tolerated drug that combines these two mechanisms; yet is far from being the ultimate in migraine abortive therapy, and further research remains essential.

Dyslipidemia and hypertriglyceridemia may be more prevalent in children with arterial ischemic stroke compared with stroke-free children.

Advanced practice providers (APPs) are qualified medically licensed health care providers, including nurse practitioners (NPs), physician assistants (PAs), nurse anesthetists, certified nurse-midwives, and clinical nurse specialists, who can function either independently or alongside a physician in populationcentered care models, disease management integration, care coordination, or in the provision of direct patient care. They also can improve revenue and reduce physician burnout. The use of APPs in the practice of neurology is still in its infancy, and many neurologists are not sure how to integrate an APP in their practice. This article addresses some concerns related to integrating an APP in the inpatient and outpatient settings. Neurol Clin Pract 2016;6: 538-542 A recent position paper by the American Academy of Neurology states that advanced practice providers (APPs) "will be crucial to improving access and continuity of care" in neurologic practice.1 APPs are qualified medically licensed health care providers. As medicine becomes more focused on quality and value, new population-centered care models are developing. APPs can play an important role in disease management integration and care coordination, and can provide added value to the entire spectrum of neurologic care. They also can improve revenue and reduce physician burnout. Training and certificationTo meet growing physician shortages, nurse practitioners (NPs) and physician assistants (PAs) were introduced into American medicine in 1965 by 2 divergent pathways.To become an advanced practice registered nurse (RN) (NP), students must complete a nursing-related 4-year bachelor's degree and become licensed RN by passing the National Council Licensure Examination for Registered Nurses. Then, to be certified as an NP, either a Master of Science in Nursing or a Doctor of Nursing Practice degree is required, with 2-4 additional years of advanced education.2 The 2 major national certifying agencies are the American

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