Four Decades of Occipital Nerve Stimulation for Headache Disorders: A Systematic Review.

PURPOSE OF REVIEW: Chronic headaches are a significant source of disability worldwide. Despite the development of conventional strategies, a subset of patients remain refractory and/or experience side effects following these treatments. Hence, occipital nerve stimulation (ONS) should be considered as an alternative strategy for intractable chronic headaches. This review aims to provide a comprehensive overview of the effectiveness, safety, mechanisms and practical application of ONS for the treatment of headache disorders. RECENT FINDINGS: Overall response rate of ONS is 35.7-100%, 17-100%, and 63-100% in patients with cluster headache, chronic migraine and occipital neuralgia respectively. Regarding the long-term effectivity in all groups, 41.6-88.0% of patients remain responders after ≥ 18.3 months. The most frequently reported adverse events include lead migration/fracture (13%) and local pain (7.3%). Based on our results, ONS can be considered a safe and effective treatment for chronic intractable headache disorders. To support more widespread application of ONS, additional research with larger sample sizes should be conducted.

Cryptic protein-protein interaction motifs in the cytoplasmic domain of MHCI proteins.

BACKGROUND: Major histocompatibility complex class I (MHCI) proteins present antigenic peptides for immune surveillance and play critical roles in nervous system development and plasticity. Most MHCI are transmembrane proteins. The extracellular domain of MHCI interacts with immunoreceptors, peptides, and co-receptors to mediate immune signaling. While the cytoplasmic domain also plays important roles in endocytic trafficking, cross-presentation of extracellularly derived antigens, and CTL priming, the molecular mediators of cytoplasmic signaling by MHCI remain largely unknown. RESULTS: Here we show that the cytoplasmic domain of MHCI contains putative protein-protein interaction domains known as PDZ (PSD95/disc large/zonula occludens-1) ligands. PDZ ligands are motifs that bind to PDZ domains to organize and mediate signaling at cell-cell contacts. PDZ ligands are short, degenerate motifs, and are therefore difficult to identify via sequence homology alone, but several lines of evidence suggest that putative PDZ ligand motifs in MHCI are under positive selective pressure. Putative PDZ ligands are found in all of the 99 MHCI proteins examined from diverse species, and are enriched in the cytoplasmic domain, where PDZ interactions occur. Both the position of the PDZ ligand and the class of ligand motif are conserved across species, as well as among genes within a species. Non-synonymous substitutions, when they occur, frequently preserve the motif. Of the many specific possible PDZ ligand motifs, a handful are strikingly and selectively overrepresented in MHCI's cytoplasmic domain, but not elsewhere in the same proteins. Putative PDZ ligands in MHCI encompass conserved serine and tyrosine residues that are targets of phosphorylation, a post-translational modification that can regulate PDZ interactions. Finally, proof-of-principle in vitro interaction assays demonstrate that the cytoplasmic domains of particular MHCI proteins can bind directly and specifically to PDZ1 and PDZ4&5 of MAGI-1, and identify a conserved PDZ ligand motif in the classical MHCI H2-K that is required for this interaction. CONCLUSIONS: These results identify cryptic protein interaction motifs in the cytoplasmic domain of MHCI. In so doing, they suggest that the cytoplasmic domain of MHCI could participate in previously unsuspected PDZ mediated protein-protein interactions at neuronal as well as immunological synapses.

Racial Disparities in Acromegaly and Cushing's Disease: A Referral Center Study in 241 Patients.

CONTEXT: Acromegaly (ACM) and Cushing's disease (CD) are caused by functioning pituitary adenomas secreting growth hormone and ACTH respectively. OBJECTIVE: To determine the impact of race on presentation and postoperative outcomes in adults with ACM and CD, which has not yet been evaluated. METHODS: This is a retrospective study of consecutive patients operated at a large-volume pituitary center. We evaluated (1) racial distribution of patients residing in the metropolitan area (Metro, N = 124) vs 2010 US census data, and(2) presentation and postoperative outcomes in Black vs White for patients from the entire catchment area (N = 241). RESULTS: For Metro area (32.4% Black population), Black patients represented 16.75% ACM (P = .006) and 29.2% CD (P = .56). Among the total 112 patients with ACM, presentations with headaches or incidentaloma were more common in Black patients (76.9% vs 31% White, P = .01). Black patients had a higher prevalence of diabetes (54% vs 16% White, P = .005), significantly lower interferon insulin-like growth factor (IGF)-1 deviation from normal (P = .03) and borderline lower median growth hormone levels (P = .09). Mean tumor diameter and proportion of tumors with cavernous sinus invasion were similar. Three-month biochemical remission (46% Black, 55% White, P = .76) and long-term IGF-1 control by multimodality therapy (92.3% Black, 80.5% White, P = .45) were similar. Among the total 129 patients with CD, Black patients had more hypopituitarism (69% vs 45% White, P = .04) and macroadenomas (33% vs 15% White, P = .05). At 3 months, remission rate was borderline higher in White (92% vs 78% Black, P = 0.08), which was attributed to macroadenomas by logistic regression. CONCLUSION: We identified disparities regarding racial distribution, and clinical and biochemical characteristics in ACM, suggesting late or missed diagnosis in Black patients. Large nationwide studies are necessary to confirm our findings.

Administration of Sugammadex Intraoperatively in a Patient With a Congenital Myasthenic Syndrome: A Case Report.

Congenital myasthenic syndromes are a group of genetic neuromuscular disorders caused by mutations that impair synaptic transmission at the neuromuscular junction. Developing an anesthetic plan for patients with this diagnosis is difficult, as they are at risk for prolonged neuromuscular blockade. Sugammadex is an alternative to neostigmine for neuromuscular blockade reversal that does not produce muscarinic side effects, yet there is a little literature assessing sugammadex in congenital myasthenic syndromes. We present the case of a 6-year-old boy with a congenital myasthenic syndrome who received sugammadex without complication. This case provides support for clinicians to consider sugammadex in these patients.

Gender differences and temporal trends over two decades in acromegaly: a single center study in 112 patients.

PURPOSE: To evaluate the impact of gender and year at surgery on clinical presentation and postoperative outcomes in acromegaly. METHODS: Retrospective review of patients operated between 1994 and 2016 to compare presentation and outcomes in groups defined by gender and year of surgery. Kaplan-Meier survival analyses with a composite endpoint (recurrence, reoperation, and radiation) were used for gender comparison and Youden indices for biochemical remission rates changes during study period. RESULTS: Primary indications for evaluation were phenotype, neurological symptoms, incidentaloma, hypogonadism, and galactorrhea. At surgery, men (N = 54) were younger (43.6 ± 12.7 years) than women (N = 58, 48.7 ± 12.3, P = 0.04). Male:female ratios before and after age 50 were 1.4 and 0.6 respectively. Men had higher mean IGF-1 levels (874 ± 328 vs 716 ± 296, P < 0.01) and smaller tumors (1.8 ± 1.3 cm vs 2.3 ± 1.5, P = 0.04). Postoperative remission rates were comparable (51% men, 56% women) and inversely associated with cavernous sinus invasion and GH levels. Women had longer mean follow-up (5.2 ± 3.4 years vs 3.6 ± 3.6 men, P = 0.02) and longer endpoint-free survival (P < 0.01). At last follow-up, 89.6% women and 70% men had normal IGF-1 levels (P = 0.03). Postoperative remission rates were higher in patients operated after February 15, 2011 (67.35 vs 43.5% previously, P = 0.01). In late vs early surgery group, physical changes as main indication for screening decreased (54 vs 30%, P < 0.01), while incidentaloma and hypogonadism increased. Median GH levels were lower in late vs early surgery group (P = 0.03). CONCLUSION: We demonstrate gender-specific characteristics and an evolving spectrum of clinical presentation with implications for earlier diagnosis and personalized management of acromegaly.

Pre-operative MRI predictors of hormonal remission status post pituitary adenoma resection.

INTRODUCTION: Contrast-enhanced (CE) Constructive Interference in Steady State (CISS) and Volumetric Interpolated Breath-hold Examination (VIBE) are MRI sequences used to improve the detection of pituitary adenomas and adjacent cranial nerves. The purpose of this study was to assess image quality and identify imaging predictors of postoperative hormonal remission of functioning pituitary adenomas using CE-T1 weighted image (WI), T2WI, CE-CISS, and CE-VIBE MRI sequences. MATERIALS AND METHODS: Patients with pre-operative CE-T1WI, T2WI, CE-CISS, and CE-VIBE pituitary MRI sequences were included in this institutional retrospective review. Three raters independently reviewed randomized sequences in a blinded fashion for adenoma characteristics and parasellar invasion. Subgroup analysis of hormonal remission was performed. RESULTS: A total of 34 functioning pituitary adenoma patients were included (average age 39.3 ±â€¯12.2; female n = 27), 30 of which had post-operative hormonal remission (n = 34; 88.2%). Compared to CE-T1WI, CE-CISS has significantly higher number of sequences rated "good" image quality (p = 0.02). Hormone remission was associated with decreased degrees of pre-operative internal carotid artery (ICA) contact and Knosp score (p ≤ 0.02) on all sequences except for Knosp score on T2WI. On receiver operating characteristic analysis, the area under curve for differentiating endocrine remission ranged from 0.88 to 0.92 for Knosp score and 0.85-0.93 for ICA contact, depending on sequence. CONCLUSION: Extent of pituitary adenoma cavernous sinus invasion as measured by degrees of ICA contact and Knosp score is associated with postoperative endocrine outcomes. Given improved image quality, inclusion of CE-CISS may be helpful for pre-surgical planning.

Severe TSH Elevation and Pituitary Enlargement After Changing Thyroid Replacement to Compounded T4/T3 Therapy.

We present the first case of iatrogenic hypothyroidism as a result of compounded thyroid hormone (T4/T3) therapy. The thyroid replacement was changed from 175 µg levothyroxine (LT4) to 57/13.5 µg compounded T4/T3 daily in order to improve the T3 level, despite normal thyroid-stimulating hormone (TSH). This resulted in clinical manifestations of hypothyroidism and high TSH level (150 µIU/mL). Six months later, the patient was referred to our clinic for abnormal pituitary magnetic resonance imaging. On reinitiating a physiologic dose of LT4, clinical and biochemical abnormalities resolved and the pituitary gland size decreased. Our case emphasizes the importance of using TSH level to gauge dose adjustments in primary hypothyroidism. Also, it underscores the current American Thyroid Association recommendation against routine use of compounded thyroid hormone therapy.