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Background Invasive fungal sinusitis carries high morbidity and mortality and often poses a diagnostic challenge. Orbital apex syndrome (OAS) is not an uncommon presentation in the setting of invasive fungal sinusitis. Delays in diagnosis and appropriate treatment can result in permanent visual dysfunction and, potentially, death. We present 2 cases of OAS secondary to invasive sinus aspergillosis, detailing the diagnostic process, treatment, and outcome for both patients. Subsequently, we present a review of the literature and combined analysis of our 2 patients plus 71 cases from previously published reports. Methods Literature review was performed to identify demographic, diagnostic, clinical, and treatment data of patients with OAS caused by Aspergillus species. Results The review resulted in 52 included articles with 71 patients, plus our 2 reported patients, leading to a total of 73 subjects included in the analysis. The average age of patients at presentation was 59.9 years. A combination of visual disturbance and pain (headache and/or periocular pain) was the most common presentation reported (46 cases; 63%). Diabetes mellitus was reported in 15 cases (21%), with more than half specifically noted to have poorly controlled diabetes. After diabetes, the second most common cause of immunocompromise was chronic steroid use (n = 13; 18%). Empiric antifungal treatment was started in 10 patients (14%), while 25 patients (34%) were first treated with systemic steroids due to a concern for an inflammatory etiology. Time to diagnosis from initial presentation was on average 7.4 weeks (range of 0.3-40 weeks). Approximately 78% of the cases (57 of 73) had biopsies with histology that confirmed Aspergillus fungal morphology, and 30/73 (41%) had diagnostic fungal cultures. The majority of the cases received monotherapy with intravenous (IV) amphotericin B (36 patients; 49%) and IV voriconazole (19 patients; 26%), with a combination of the 2 or more antifungal agents being used in 11 patients (15%). Forty patients (55%) showed signs of clinical improvement with treatment, while 33 (45%) patients did not experience any improvement or continued to deteriorate, and 23 (32%) died in the course of their reported follow-up. Conclusions The present cases illustrate well the challenge in the diagnosis and treatment of OAS due to invasive sinus aspergillosis. Our review and analysis of 73 cases support the notion that a high index of suspicion leading to early biopsy with histology and fungal culture is paramount for diagnosis. Early empiric antifungal treatment and debridement can potentially reduce morbidity and mortality.

Visual complaints are commonly encountered by the practicing neurologist. We review assessment of vision loss, diplopia, and positive visual phenomena, all of which require a thoughtful evaluation to localize disease and refine management. While many causative entities are unlikely to cause poor visual outcomes, including dry eyes, migraine, and congenital strabismus, others may threaten vision, life, or both, such as posterior communicating artery aneurysms, pituitary apoplexy, or temporal arteritis. A systematic approach to vision loss and diplopia is reviewed along with focused differential diagnoses.

Neurologic complications of COVID-19 are not well described. We report 2 patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.

INTRODUCTION: Multi-domain intervention for Alzheimer’s disease (AD) risk reduction is an emerging therapeutic paradigm. METHODS: Patients were prescribed individually-tailored interventions (education/pharmacologic/non-pharmacologic) and rated on compliance. Normal cognition/subjective cognitive decline/preclinical-AD were classified as Prevention. Mild cognitive impairment due to AD/mild-AD were classified as Early Treatment. Change from baseline to 18-months on the modified-Alzheimer’s Prevention Cognitive Composite (primary outcome) was compared against matched historical control cohorts. Cognitive aging composite (CogAging), AD/cardiovascular risk-scales, and serum biomarkers were secondary outcomes. RESULTS: 174 were assigned interventions (age 25–86). Higher-compliance Prevention improved more than both historical cohorts (P=.0012,P

Decades of research suggests nutritional interventions can be an effective tool for reducing risk of Alzheimer’s disease (AD), especially as part of an individualized clinical management plan. This review aims to emphasize new findings examining how specific dietary changes may delay or possibly prevent AD onset, and highlight how interventions can be adopted in clinical practice based on emerging principles of precision medicine. Specific dietary patterns and varied nutrient combinations can have a protective effect on brain health, promote cognitive function, and mediate the comorbidity of chronic conditions associated with increased AD risk. Individuals at risk for AD may see a greater impact of evidence-based dietary changes when initiated earlier in the AD spectrum. Depending on individual clinical profiles, incorporation of nutrition strategies is an essential component of an AD risk reduction plan in clinical practice.

A 22-year old male with a history of B-cell acute lymphoblastic leukemia with recent bone marrow transplantation and on immunosuppressive therapy presented with painless, subacute vision loss of two weeks duration. He exhibited a horizontal gaze palsy, nystagmus, and mildly swollen and hyperemic optic discs with peripapillary flame hemorrhage on retinal exam. He had bilateral cecocentral scotomas on visual field exam, and MRI of his brain/orbits demonstrated hyperintensities in the hypothalamus, periaqueductal gray, and dorsal rostral medullary regions. After continued progression of symptoms despite discontinuation of the patient’s tacrolimus, an empiric trial of IV thiamine treatment was started before the patient’s lab vitamin levels were available, given strong clinical suspicion for a nutritional etiology. The patient’s clinical presentation improved dramatically, and he achieved a final visual acuity of 20/20, full visual fields bilaterally, and resolution of nystagmus. A final diagnosis of Wernicke’s encephalopathy was supported by his clinical course, imaging findings, and further confirmation with blood thiamine levels. This case presents unique ocular manifestations of Wernicke’s encephalopathy and highlights the importance of early diagnosis in this potentially reversible condition.

Purpose Myopathic blepharoptoses (ptoses) is a complex group of disorders. To date, no formal categorization scheme has been developed based on associated ocular and systemic findings, genetic fingerprint, treatment, and prognosis for each ptosis in this group. We report a new classification scheme for myopathic ptoses. Methods Literature review and classification development. Results A new classification scheme of myopathic ptoses includes isolated static myopathic ptosis (congenital ptosis), static myopathic ptosis associated with aberrant innervation and those associated with periocular abnormalities, and progressive myopathic ptoses that affect the levator muscle and other muscle groups in childhood and adulthood. Conclusions Making the distinction of myopathic ptosis type early will maximize patient outcomes by optimizing surgical and systemic management and facilitating the recruitment of subspecialists to care for patients with these challenging conditions.The authors present a comprehensive and effective myopathic ptosis classification scheme to optimize surgical management and facilitate subspecialty care.

We appreciate Dr. Machado's insightful comments regarding our case series1 describing cranial neuropathies in 2 patients with COVID-19. The triad of progressive ophthalmoplegia, ataxia, and areflexia in our first case suggested Miller Fisher syndrome (MFS), despite the negative ganglioside panel, although we were surprised by the short interval of 4 days between respiratory and neurologic symptoms. However, in 2 cases of COVID-19-associated MFS, latencies were similar (5 and 3 days),2 suggesting that the postinfectious interval is shorter for COVID-19 than for other infections. In fact, in a recent case of Guillain-Barre syndrome associated with COVID-19, neurologic symptoms preceded the respiratory symptoms by 1 week.3 The authors noted that lymphopenia was present on admission, indicating the presence of COVID-19 long before systemic symptoms began. This is in line with recent observations that 10/13 nursing home residents only developed symptoms 7 days after testing positive.4 Our second case may reflect direct viral invasion because there were no signs of MFS. Transfer of the virus through the olfactory bulbs is supported by recent evidence of olfactory bulb edema5 and hyperintensity of the adjacent gyrus rectus6 in patients with COVID-19-associated anosmia, although our patient never developed anosmia. The rapid recovery of anosmia observed in most COVID-19 cases argues for olfactory epithelial dysfunction as opposed to olfactory nerve damage, and we agree with Dr. Machado that hematogenous spread of virus may also play a role in CNS disease.

Alzheimer's disease (AD) is the most common neurodegenerative cause of dementia and is responsible for significant individual morbidity and mortality, and economic impact on the health care system. Neurodegeneration (including neuronal atrophy and/or loss) are attributed to extraneuronal toxic amyloid oligomers and proteins, intraneuronal neurofibrillary tangles consisting of hyperphosphorylated tau, region-specific diminished cerebral glucose metabolism, synaptic dysfunction, and mitochondrial dysfunction. Several of these pathologic changes may occur decades before symptom onset, leaving ample time for implementing prevention strategies that target the earliest stages of the disease. In recent years, a myriad of modifiable and nonmodifiable risk factors have been elucidated. We describe the latest criteria for the diagnosis of AD, including earliest diagnostic stage of preclinical AD, which has the highest potential for research, including diagnosis and disease modification. We discuss both FDA-approved pharmacologic treatments, as well as nonpharmacologic strategies for AD therapeutics, including prevention via evidence-based, low-risk interventions. Genotype is an important consideration in managing patients on the AD continuum, as presence of the APOE ε4 allele may influence response to treatment. We present the most current evidence relating to pharmacogenomics, nutrigenomics, and distinctive nutritional requirements targeted toward AD.

Epicardial adipose tissue has been linked to cardiovascular metabolism and inflammation and has been shown to predict prevalence and progression of coronary artery disease. Only limited data are available on the role of epicardial fat in patients with heart failure (HF). We analyzed cardiac adiposity and its relation to markers of morbidity and clinical outcome in patients with normal and impaired left ventricular (LV) function. Epicardial fat volume (EFV) and coronary artery calcium were measured in 381 patients (210 women and 171 men, mean age 55 ± 10 years) who underwent low-dose computed tomography. HF was defined by LV ejection fraction (EF)55%. Three hundred twenty-one patients had an EF55% (mean 63 ± 6) and 60 patients had an EF55% (mean 41 ± 12). Subgroup analysis was performed according to degree of LV dysfunction in patients with HF (LVEF 35% to 55% or35%). Mean EFVs were 114.5 ± 98.5 cm(3) in patients with normal EF and 83.5 ± 67.1 cm(3) in those with decreased EF (p0.05). Mean EFVs were 96.1 ± 73.9 cm(3) in patients with moderate HF and 52.2 ± 29.7 cm(3) in patients with severe HF (p0.05). Subgroup analysis revealed a persistently smaller EFV in patients with HF regardless of coronary artery calcium scores, markers of renal function, lipid metabolism, fasting blood glucose, or body mass index. In conclusion, our data demonstrate a stepwise decrease in EFV in patients with impaired cardiac function.

Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm(3), 156.4 ± 121.9 cm(3), and 96.3 ± 102.1 cm(3), respectively (P 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm(3); P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm(3); P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease.

Natural menopause is a sentinel event in the female life course that marks the cessation of reproductive functioning and impacts the risks of several serious conditions in maturing women. The onset of menopause is considered a marker of overall aging and health that is associated with risks of coronary artery disease, osteoporosis, and all-cause mortality.1–3 The reported typical menopause age of approximately 51 years has been highly reproduced in series across time, both domestically and globally.4–7 Those entering menopause earlier than the age of 45 years experience higher-than-average menopause-related disease risks and mortality.8–10 More than 20 million women in the United States currently smoke—a figure that represents nearly 18% of the adult female population.11 Globally, it is estimated that more than 200 million women are smokers.12 Smoking has repeatedly been identified as a risk factor for earlier time to menopause (TTM), hastening its onset by approximately 1 to 2 years.4–7,13–18 Of the more than 4,000 chemicals found in tobacco smoke, a subset contributes to the development of hypoestrogenism through mechanisms that include oxidative metabolism of estrogens and inhibition of aromatase.19–21 In addition, polyaromatic hydrocarbons (PAHs) are a powerful class of carcinogens in cigarettes that are cytotoxic to both murine and human oocytes in vitro.14,22–26 Many PAHs are protoxins that require bioactivation by enzymes in the cytochrome P450 (CYP) superfamily to exert their toxic effects.27,28 A prevailing theory of reproductive senescence is that women are born with a complete complement of oocytes, which can never be replenished,29 and that chemicals in tobacco that hasten the natural trajectory of oocyte atresia increase the risk of menopause entry and hasten TTM. Factors that enhance the toxicity of these chemicals could increase the risk of menopause further. A comprehensive assessment of potential modifiers of the risk of smoking in relation to menopause timing is currently lacking in the literature. Of great importance is that smoking and menopause have overlapping negative health consequences that could worsen health outcomes in aging women.30 We have recently described that the effects of smoking on the prevalence and severity of hot flashes vary according to the presence of specific single nucleotide polymorphisms (SNPs) in genes responsible for the metabolism of sex steroids and/or the bioactivation of PAHs.31 In the current investigation, we hypothesized that genetic variation in these pathways is associated with further acceleration of onset of menopause in smokers. To test this hypothesis, we examined the risk of menopause in smokers from a population-based cohort of reproductive-age women and evaluated whether the risk of menopause entry in smokers was modified by the presence of relevant gene variants. A candidate gene approach was used to select variants that (1) could potentiate the effects of tobacco-related ovotoxins such as PAHs through mechanisms such as increased bioactivation (CYP1B1 and CYP3A4) and/or (2) had a known association with menopause onset or menopausal symptoms (COMT, CYP1B1, and CYP3A4).32–34