Lindsey B. De Lott

Brainstem infarction and sleep-disordered breathing in the BASIC sleep apnea study

BACKGROUND Association between cerebral infarction site and poststroke sleep-disordered breathing (SDB) has important implications for SDB screening and the pathophysiology of poststroke SDB. Within a large, population-based study, we assessed whether brainstem infarction location is associated with SDB presence and severity. METHODS Cross-sectional study was conducted on ischemic stroke patients in the Brain Attack Surveillance in Corpus Christi (BASIC) project. Subjects underwent SDB screening (median 13days after stroke) with a well-validated cardiopulmonary sleep apnea-testing device (n=355). Acute infarction location was determined based on review of radiology reports and dichotomized into brainstem involvement or none. Logistic and linear regression models were used to test the associations between brainstem involvement and SDB or apnea/hypopnea index (AHI) in unadjusted and adjusted models. RESULTS A total of 38 participants (11%) had acute infarction involving the brainstem. Of those without brainstem infarction, 59% had significant SDB (AHI⩾10); the median AHI was 13 (interquartile range (IQR) 6, 26). Of those with brainstem infarction, 84% had SDB; median AHI was 20 (IQR 11, 38). In unadjusted analysis, brainstem involvement was associated with over three times the odds of SDB (odds ratio (OR) 3.71 (95% confidence interval (CI): 1.52, 9.13)). In a multivariable model, adjusted for demographics, body mass index (BMI), hypertension, diabetes, coronary artery disease, atrial fibrillation, prior stroke/transient ischemic attack (TIA), and stroke severity, results were similar (OR 3.76 (95% CI: 1.44, 9.81)). Brainstem infarction was also associated with AHI (continuous) in unadjusted (p=0.004) and adjusted models (p=0.004). CONCLUSIONS Data from this population-based stroke study show that acute infarction involving the brainstem is associated with both presence and severity of SDB.

DNA methylation analysis of the temporal artery microenvironment in giant cell arteritis

Objective To investigate the inflammatory response in giant cell arteritis (GCA) by characterising the DNA methylation pattern within the temporal artery microenvironment. Methods Twelve patients with non-equivocal histological evidence for GCA and 12 age-matched, sex-matched and ethnicity-matched controls with normal biopsies were studied. DNA was extracted from the affected portions of temporal artery tissue in patients with GCA and from histologically confirmed normal arteries in controls. Genome-wide DNA methylation status was evaluated using the Illumina Infinium HumanMethylation450 BeadChip Array. Differentially methylated loci between affected and unaffected arterial tissues were identified, and subsequent bioinformatic analysis performed. Immunohistochemistry was used to examine tissue expression patterns in temporal artery biopsies. Results We identified 1555 hypomethylated CG sites (853 genes) in affected temporal artery tissue from patients with GCA compared with normal controls. Gene ontology enrichment analysis of hypomethylated genes revealed significant representation in T cell activation and differentiation pathways, including both TH1 and TH17 signatures. Our DNA methylation data suggest a role for increased activity of the calcineurin/nuclear factor of activated T cells (NFAT) signalling pathway in GCA, confirmed by immunohistochemistry showing increased expression and nuclear localisation of NFAT1. NFAT signalling downstream targets such as interleukin (IL)-21/IL-21R and CD40L were overexpressed in GCA-affected arteries. Further, proinflammatory genes including TNF, LTA, LTB, CCR7, RUNX3, CD6, CD40LG, IL2, IL6, NLRP1, IL1B, IL18, IL21, IL23R and IFNG were hypomethylated in the cellular milieu of GCA arteries. Conclusions We characterised the inflammatory response in GCA-affected arteries using ‘epigenetic immunophenotyping’ and identified molecules and pathways relevant to disease pathogenesis in GCA.

Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis

IMPORTANCE The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. OBJECTIVES To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. DESIGN, SETTING, AND PARTICIPANTS A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. MAIN OUTCOMES AND MEASURES Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. RESULTS Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). CONCLUSIONS AND RELEVANCE We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalized myasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease.

Papilledema and Vision Loss Caused by Jugular Paragangliomas.

Paragangliomas that arise from the jugular bulb are known to present as masses in the neck or with hearing loss, pulsatile tinnitus, and lower cranial nerve palsies. Much less recognized is their tendency to cause increased intracranial pressure and papilledema by obstructing jugular venous outflow. Only 7 such cases have been reported and with minimal ophthalmic documentation. We describe 3 more cases to provide additional documentation and to emphasize that paragangliomas are a potential cause of the pseudotumor cerebri syndrome, and that papilledema may be overlooked when a jugular paraganglioma is diagnosed or after it has been treated. Such lapses have led to disabling vision loss from damage to the optic nerves in long-standing papilledema.

Neurology Choosing Wisely recommendations: 74 and growing

AbstractTo increase neurologist awareness and inform future efficiency efforts, we identified all neurology-related Choosing Wisely items. Items were categorized by neurologic specialty, disease/symptom, and test/treatment. Of 370 items provided by 65 medical societies, 74 (20%) items were relevant to neurologists. Twelve were duplicated by multiple societies. Items pertaining to 10 neurologic subspecialties were identified, but none for movement disorders and neuromuscular disease. While many recommendations question the use of imaging, few address other high-cost neurologic tests such as EMG/nerve conduction studies and EEG. A rapidly growing number of neurology-related Choosing Wisely recommendations exist including areas of consensus and areas with few recommendations despite high costs. Consensus items should be prioritized for near-term interventions, while areas with few recommendations represent opportunities for future research.

Use of Laboratory Markers in Deciding Whether to Perform Temporal Artery Biopsy

Temporal artery biopsy (TAB) can confirm the diagnosis of giant cell arteritis (GCA), but it is not without risk.1 Therefore, markers of inflammation such as the erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP), and platelet counts are often used to select patients for TAB.2–4 Our aim was to investigate which demographic and laboratory data predict biopsy-proven GCA in patients undergoing biopsy to generate hypotheses about how physicians integrate this information into TAB decisions.

Restricted Diffusion of the Superior and Inferior Ophthalmic Veins in Cavernous Sinus Thrombosis.

Two previous reports have described restricted diffusion in thrombosed superior ophthalmic veins (SOVs) in patients with cavernous sinus thrombosis (CST). We report a patient who displayed restricted diffusion in both the SOV and inferior ophthalmic vein in CST consequent to a masticator space abscess. The orbital vascular imaging findings added support to the cavernous sinus findings in making the diagnosis of CST. Diffusion-weighted imaging of the orbit is a valuable asset in this setting.

Prevalence of pre-stroke sleep apnea risk and short or long sleep duration in a bi-ethnic stroke population

BACKGROUND The ethnic disparity in ischemic stroke between Mexican Americans (MAs) and non-Hispanic whites (NHWs) may be partly attributable to disparities in sleep and its disorders. We therefore assessed whether pre-stroke sleep apnea symptoms (SA risk) and pre-stroke sleep duration differed between MAs and NHWs. METHODS MA and NHW ischemic stroke survivors in the Brain Attack Surveillance in Corpus Christi (BASIC) project reported sleep duration and SA symptoms on the validated Berlin questionnaire, both with respect to their pre-stroke baseline. Log binomial and linear regression models were used to test the unadjusted and adjusted (demographics and vascular risk factors) associations of high-risk Berlin scores and sleep duration with ethnicity. RESULTS Among 862 subjects, 549 (63.7%) were MA and 514 (59.6%) had a high risk of pre-stroke SA. The MA and NHW subjects showed no ethnic difference, after adjustment for potential confounders, in pre-stroke SA risk (risk ratio (95% confidence interval (CI)): 1.06 (0.93, 1.20)) or in pre-stroke sleep duration (on average MAs slept 2.0 fewer minutes than NHWs, 95% CI: -18.8, 14.9 min). CONCLUSIONS Pre-stroke SA symptoms are highly prevalent, but ethnic differences in SA risk and sleep duration appear unlikely to explain ethnic stroke disparities.

Ethambutol optic neuropathy in a hemodialysis patient receiving a guideline-recommended dose.

W e read with interest the review of mitochondrial optic neuropathies by Wang and Sadun (1). We report a case of ethambutol optic neuropathy in a patient receiving maintenance hemodialysis, who was treated with an ethambutol dose of 20 mg/kg 3 times per week. Other published reports of ethambutol optic neuropathy in patients receiving hemodialysis cite a daily ethambutol dose (2,3). The dose in this case was prescribed 3 times per week according to the Centers for Disease Control and Prevention (CDC), in conjunction with the American Thoracic Society and the Infectious Diseases Society of America, tuberculosis treatment guidelines for patients with renal dysfunction (4). A 79-year-old woman weighing 60 kg presented to our outpatient ophthalmology clinic with progressive visual difficulty occurring over 4 weeks. Her medical history included atrial fibrillation, diabetes mellitus, and chronic kidney disease requiring hemodialysis three times per week. Approximately 1 year previously, evaluation of dyspnea included chest computed tomography (CT) that showed multiple calcified lung nodules, thickening of the interlobular septae and pleural fissures on the right, opacities in the right upper lobe with tree-in-bud appearance, and multiple borderline enlarged mediastinal lymph nodes. QuantiFERON-TB Gold testing was positive. Initial results from a bronchoalveolar lavage showed acid-fast bacilli, and cultures from these samples grew Mycobacterium tuberculosis. The patient began tuberculosis treatment with isoniazid 300 mg daily, pyridoxine 25 mg daily, rifampin 600 mg daily and pyrazinamide 1500 mg (25 mg/kg) three times per week. The medications were given after hemodialysis and followed the recommendations of the CDC (4). Within 24 hours of treatment initiation, she developed confusion and somnolence that worsened over the next 7 days. She was admitted into the hospital for further evaluation. Cerebrospinal fluid, blood, and urine cultures did not reveal an infectious cause of her symptoms. A noncontrast brain CT was normal. Isoniazid-induced central nervous system toxicity was suspected, and her medications were changed to an alternative CDC-recommended regimen that included ethambutol 1200 mg (20 mg/kg), rifampin 600 mg, and pyrazinamide 1500 mg (25 mg/kg),

Vision Loss After Central Retinal Artery Occlusion Secondary to Orbital Sarcoid Mass.

The authors describe the first report in the literature of central retinal artery occlusion as the presenting manifestation of sarcoidosis. A 33-year-old man with asthma, headache, and 6 days of intermittent, transient vision loss in the OS presented with persistent vision loss in the OS. Ophthalmic examination was consistent with diagnosis of central retinal artery occlusion in the OS. Vascular imaging with CT angiography revealed an incidental finding of an intraconal mass surrounding the left optic nerve and hilar lymphadenopathy. Broncho scopic lymph node biopsy demonstrated noncaseating granulomas consistent with sarcoidosis. This case proffers a unique mechanism of vision loss in sarcoidosis and highlights that atypical causes of central retinal artery occlusion must be considered in patients without typical risk factors.