Can we do better at measuring patient-reported outcomes after cranioplasty? A systematic review.

Measuring quality of life (QOL) after cranioplasty is increasingly evident as a necessary component of patient-centered care. For data to be useful in clinical decision-making and approval of new therapies, studies must utilize valid and reliable instruments. Our objective was to critically appraise studies evaluating QOL in adult cranioplasty patients and determine validity and relevance of the patient-reported outcome measures (PROMs) used. Electronic databases of PubMed, Embase, CINAHL, and PsychINFO were used to identify PROMs measuring QOL in adult patients with cranioplasty. The methodological approach, cranioplasty outcomes, and domains measured by the PROMs were extracted and summarized descriptively. A content analysis of the identified PROMs was completed to identify the concepts measured. From 2236 articles identified, 17 articles containing eight QOL PROMs met the inclusion criteria. None of the PROMs was specifically validated or developed for adults undergoing cranioplasty. The QOL domains included physical health, psychological health, social health, and general QOL. These four domains encompassed 216 total items among the PROMs. Appearance was only assessed in two PROMs. To our knowledge, there are currently no validated PROMs that comprehensively measure appearance, facial function, and adverse effects in adults undergoing cranioplasty. There is an urgent need to develop PROMs to measure QOL outcomes rigorously and comprehensively in this patient population to inform clinical care, research, and quality improvement initiatives. Findings from this systematic review will be used to derive an outcome instrument containing important concepts related to QOL in patients who undergo cranioplasty.

Deep Brain Stimulation for the Management of AIFM1-Related Disabling Tremor: A Case Series.

The AIFM1 gene encodes a mitochondrial protein that acts as a flavin adenine dinucleotide-dependent nicotinamide adenine dinucleotide oxidase and apoptosis regulator. Monoallelic pathogenic AIFM1 variants result in a spectrum of X-linked neurological disorders, including Cowchock syndrome. Common features in Cowchock syndrome include a slowly progressive movement disorder, cerebellar ataxia, progressive sensorineural hearing loss, and sensory neuropathy. We identified a novel maternally inherited hemizygous missense AIFM1 variant, c.1369C>T p.(His457Tyr), in two brothers with clinical features consistent with Cowchock syndrome using next-generation sequencing. Both individuals had a progressive complex movement disorder phenotype, including disabling tremor poorly responsive to medications. Deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus ameliorated contralateral tremor and improved their quality of life; this suggests the beneficial role for DBS in treatment-resistant tremor within AIFM1-related disorders.

The Transverse Facial Artery as a Recipient Artery in Neuroplastic Surgery Microvascular Reconstruction.

Microvascular reconstruction in the craniofacial region is particularly challenging due to a paucity of adequate recipient vessels. The facial vessels are commonly utilized; however, in neurocranial reconstruction, the distance from the defect to the vessels may require the use of interposition vein grafts. The superficial temporal vessels, which have the benefit of closer proximity, are often compromised or injured in patients with previous neurosurgical procedures or radiation therapy. Here, we describe the use of the transverse facial artery as a recipient for a latissimus dorsi free flap for scalp reconstruction in a 63-year-old man with a compromised scalp from multiple surgeries and radiation therapy for glioblastoma multiforme. The patient had extensive scarring, temporalis muscle wasting, thinning of the overlying scalp, and notable alopecia. On surveillance imaging, he was found to have an area on the brain concerning for tumor recurrence, for which a surgical biopsy was recommended, with a significant risk of postoperative wound healing complications. We present the use of the transverse facial artery in this case as a recipient artery for free flap reconstruction of the scalp.

Development of CHARMM Additive Potential Energy Parameters for α-Methyl Amino Acids.

Potential energy parameters for α-methyl amino acids were generated with ab initio calculations on α-methyl-N-acetylalanyl-N'-methylamide (the α-methyl "alanine dipeptide") which served as an input to a grid-based correction to the backbone torsional potential (known as CMAP) consistent with the CHARMM36m additive protein force field. The new parameters were validated by comparison with experimentally determined helicities of the 22 residue C-terminal peptide (H10) from apolipoprotein A1 and five α-methylated variants in water and 0.3:0.7 trifluoroethanol (TFE)/water. Conventional molecular dynamics simulation totaling 30 µs for each peptide is in overall good agreement with the experiment, including the increased helicity in 30% TFE. An additional 500 ns of simulation using two-dimensional dihedral biasing (bpCMAP) replica exchange reduced left-handed conformations, increased right-handed helices, and thereby mostly decreased agreement with the experiment. Analysis of side chain-side chain salt bridges suggests that the overestimation of the helical content may be, in part, due to such interactions. The increased helicity of the peptides in 30% TFE arises from decreased hydrogen bonding of the backbone atoms to water and a concomitant increase in intramolecular backbone hydrogen bonds.

Incorporation of α-methylated amino acids into Apolipoprotein A-I mimetic peptides improves their helicity and cholesterol efflux potential.

Apolipoprotein A-I (ApoA-I) mimetic peptides are potential therapeutic agents for promoting the efflux of excess cellular cholesterol, which is dependent upon the presence of an amphipathic helix. Since α-methylated Ala enhances peptide helicity, we hypothesized that incorporating other types of α-methylated amino acids into ApoA-I mimetic peptides may also increase their helicity and cholesterol efflux potential. The last helix of apoA-I, peptide 'A' (VLESFKVSFLSALEEYTKKLNT), was used to design peptides containing a single type of α-methylated amino acid substitution (Ala/Aα, Glu/Dα, Lys/Kα, Leu/Lα), as well as a peptide containing both α-methylated Lys and Leu (6α). Depending on the specific residue, the α-helical content as measured by CD-spectroscopy and calculated hydrophobic moments were sometimes higher for peptides containing other types of α-methylated amino acids than those with α-methylated Ala. In ABCA1-transfected cells, cholesterol efflux to the peptides showed the following order of potency: 6α>Kα≈Lα≈Aα≫Dα≈A. In general, α-methylated peptides were resistant to proteolysis, but this varied depending on the type of protease and specific amino acid substitution. In summary, increased helicity and amphilicity due to α-methylated amino acid substitutions in ApoA-I mimetic peptides resulted in improved cholesterol efflux capacity and resistance to proteolysis, indicating that this modification may be useful in the future design of therapeutic ApoA-I mimetic peptides.