Title | Literature Commentary |
Creator | Mark L. Moster, MD; M. Tariq Bhatti, MD |
OCR Text | Show Literature Commentary Section Editors: Mark L. Moster, MD M. Tariq Bhatti, MD Literature Commentary In this issue of the Journal of Neuro-Ophthalmology, Tariq Bhatti, MD and Mark Moster, MD, will discuss the following 6 articles: 1. Fisayo A, Bruce BB, Newman NJ, Biousse V. Overdiagnosis of idiopathic intracranial hypertension. Neurology. 2016;86:341-350. 2. Yang CP, Chen YT, Fuh JL, Wang SJ. Migraine and risk of ocular motor cranial nerve palsies: a nationwide cohort study. Ophthalmology. 2016;123:191-197. 3. Wu A, Andrew NH, McNab AA, Selva D. Bilateral IgG4-related ophthalmic disease: a strong indication for systemic imaging. Br J Ophthalmol. [published online ahead of print December 30, 2015] doi: 10.1136/ bjophthalmol-2015-307437. 4. Chin EK, Almeida DRP, Lam KV, Keltner JL , Charles E, Thirkill CE. Positive auto-antibody activity with retina and optic nerve in smokers and non-smokers: the controversy continues. Ophthalmic Surg Lasers Imaging Retina. 2015;46:1068-1070. 5. Valko Y, Rosengren SM, Jung HH, Straumann D, Landau K, Weber KP. Ocular vestibular evoked myogenic potentials as a test for myasthenia gravis. Neurology. 2016;86:660-668. 6. Butty Z, Gopwani J, Mehta S, Margolin E. Horner's syndrome in patients admitted to the intensive care unit that have undergone central venous catheterization: a prospective study. Eye (Lond). 2016;30:31-33. Fisayo A, Bruce BB, Newman NJ, Biousse V. Overdiagnosis of idiopathic intracranial hypertension. Neurology. 2016;86:341-350. Objective: To delineate the factors contributing to overdiagnosis of idiopathic intracranial hypertension (IIH) among patients seen in a neuro-ophthalmology service at a tertiary center. Methods: We retrospectively reviewed new patients referred with a working diagnosis of IIH over 8 months. The Diagnosis Error Evaluation and Research taxonomy tool was applied to cases referred with a diagnosis of IIH and a discrepant final diagnosis. Results: Of 1,249 patients, 165 (13.2%) were referred either with a preexisting diagnosis of IIH or to rule out IIH. Of the 86 out of 165 patients (52.1%) with a preexisting diagnosis of IIH, 34 (39.5%) did not have IIH. The most common diagnostic error was inaccurate ophthalmoscopic examination in headache patients. Of 34 patients misdiagnosed as having IIH, 27 (27/34 [79.4%]; 27/86 [31.4%]) had at least 1 lumbar puncture, 29 (29/34 [85.3%]; 29/86 [33.7%]) had a brain magnetic resonance imaging, and 8 (8/34 [23.5%]; 8/86 [9.3%]) had a magnetic resonance/computed tomography venogram. Twenty-six had received medical treatment, 1 had lumbar drain, and 4 were referred for surgery. In 8 patients (8/34 [23.5%]; 8/86 [9.3%]), an alternative diagnosis requiring further evaluation was identified. Conclusions: Diagnostic errors resulted in overdiagnosis of IIH in 39.5% of patients referred for presumed IIH, and prompted unnecessary tests, invasive procedures, and missed diagnoses. The most common errors were inaccurate ophthalmoscopic examination in headache patients and thinking biases, reinforcing the need for rapid access to specialists with experience in diagnosing optic nerve disorders. Indeed, the high prevalence of primary benign headaches and obesity in young women often leads to costly and invasive evaluations for presumed IIH. 216 Once again, the Emory group has provided us with a very practical and informative study on a very common neuroophthalmic disorder-idiopathic intracranial hypertension (IIH). Confirming the diagnosis of IIH can be challenging but there are firm criteria in place for making the diagnosis (1). This study explores the prevalence of overdiagnosing IIH and understanding the underlying errors resulting in the misdiagnosis. Patients were divided into 2 groups: 1. Previously diagnosed patients with IIH referred for further management 2. Patients with possible IIH referred to either confirm or refute the diagnosis I was astonished to see that nearly 40% (34/86) of the patients referred were overdiagnosed with IIH and 24% had an alternative diagnosis! Unfortunately, 26 of these patients received treatment for a diagnosis that was not correct. Interestingly, of those patients that were referred "to rule out" or confirm IIH, 81% did not have IIH. Table 1 breaks down very nicely where the error occurred in the diagnostic process and what exactly went wrong. Fortyfour percent of the patients were misdiagnosed because of inaccurate/misinterpretation of the physical examination findings (mostly the funduscopic examination). I was surprised to read that 30% of the misdiagnosis cases were from a neuroophthalmologist. I just hope that I wasn't one of them! This study reminds me of a book by Jerome Groopman titled "How Doctors Think" (2007, Houghton Mifflin, NY) that explores, in an intimate fashion, the medical decision making process physicians exercise on a daily basis (2). Moster and Bhatti: J Neuro-Ophthalmol 2016; 36: 216-220 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Here at Duke, I am often asked to evaluate patients for papilledema, who have been given the diagnosis of IIH. These referrals come from neurologists, ophthalmologists, optometrists, internists, and emergency room physicians. In a substantial proportion of these patients, I don't find papilledema and when I reviewed the history, I discovered that either the proper workup was not done or that the lumbar puncture (LP) was done incorrectly (3,4). I try to be diplomatic in my consultation note to the referring physician and alert them to the diagnostic criteria for IIH, proper technique for measuring the opening pressure (lateral decubitus position in a relaxed position), and outline what I typically do in my practice to confirm the diagnosis. -M. Tariq Bhatti, MD REFERENCES 1. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81:1159-1165. 2. Curry RH. How doctors think. N Engl J Med. 2007;356:2757- 2758. 3. Roos KL. Lumbar puncture. Semin Neurol. 2003;23:105-114. 4. Abel AS, Brace JR, McKinney AM, Friedman DI, Smith SD, Westesson PL, Nascene D, Ott F, Lee MS. Effect of patient positioning on cerebrospinal fluid opening pressure. J Neuroophthalmol. 2014;34:218-222. This is an important article that verifies something I have noted increasingly in my practice-an obese woman with headache is often presumed to have IIH by many practitioners, although headaches are very common and the prevalence of IIH in young women is likely less than 1/1,000. Fortunately, I evaluated such a patient last week before her LP was performed (already scheduled) and the history was one of common migraine, complete with photophobia, phonophobia, and motion sickness. I am not surprised or concerned about the large percentage of patients found without IIH in the group referred to rule out IIH. It is the job of neuroophthalmologists to exclude IIH. What is surprising is the percentages that were misdiagnosed who actually received medical or surgical treatments. -Mark L. Moster, MD Yang CP, Chen YT, Fuh JL, Wang SJ. Migraine and risk of ocular motor cranial nerve palsies: a nationwide cohort study. Ophthalmology. 2016;123:191-197. Purpose: To determine whether migraine is associated with an increased risk of developing ocular motor cranial nerve palsies (OMCNP). Design: Nationwide retrospective cohort study. Moster and Bhatti: J Neuro-Ophthalmol 2016; 36: 216-220 Participants: Medical records of patients with migraine who were entered in the National Health Insurance Research Database (NHIRD) between 2005 and 2009 were retrieved from the NHIRD in Taiwan. Two cohorts were selected: patients with migraine (n = 138,907) and propensity scorematched controls (n = 138,907). Main Outcome Measures: Cohorts were followed until the end of 2010, death, or occurrence of cranial nerve (CN)3, CN4, or CN6 palsies. A Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence intervals, which were used to compare the risk of developing CN3, CN4, and CN6 palsy between cohorts. Results: After a mean follow-up period of 3.1 years (range, 1-6 years), the migraine cohort exhibited a greater risk of developing subsequent CN3, CN4, and CN6 palsies compared with the control cohort (HR, 2.67, P , 0.001; HR, 4.23, P , 0.001; HR, 3.37; P , 0.001). This finding was maintained after excluding potential confounders during sensitivity tests. Moreover, the significant association between migraine and OMCNP remained after we adjusted for potential risk factors of microvascular ischemia. However, different migraine subtypes showed no significant differences. Conclusions: Migraine is an unrecognized risk factor for OMCNP development in adults. Further studies are needed to validate our findings, and to delineate the exact pathophysiologic mechanisms linking migraine and OMCNP. If you recall Mark, in the June 2015 issue of Literature Commentary (J Neuroophthalmol. 2015;35:220-225), we discussed a study from this same group in Taiwan which reported an association between migraine and Bell palsy. In that study, using the National Health Insurance Research Database from the Bell palsy study, 2 cohorts were analyzed- patients with migraine and patients without migraine/headache (control)-to determine if there is an association between migraine and OMCNP. The investigators found that patients with migraine had a greater risk of developing OMCNP with a HR of 2.67 for CN 3 palsies, 4.23 for CN 4, and 3.37 for CN 6. This increased risk was still present after controlling for diabetes mellitus and hypertension. As for the pathomechanism of migraine associated with OMCNP, the authors propose a microvascular ischemic etiology and a neurogenic inflammatory/vascular compromise theory based on the release of regional neuropeptides. To the credit of the authors, a relatively long paragraph is dedicated to the limitations of their study which includes the observational method of data retrieval, inability to exclude unknown confounding variables, lack of individual medical history verification, missing information (i.e., smoking and alcohol consumption), misdiagnosis of migraine, and a mean follow-up period of 3 years. -M. Tariq Bhatti, MD I agree with the authors about the limitations of this study. One other thing that seemed unusual is that the age at presentation was in the sixth decade, but the migraine 217 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary diagnosis was a mean of 1.4 years before the cranial neuropathy, quite an old age for diagnosis of migraine. Perhaps it is the diagnosis of migraine later in life that is the risk factor. Alternatively, perhaps a vasculopathy is contributing to headaches and cranial neuropathy, and this vasculopathy is misdiagnosed as migraine. -Mark L. Moster, MD Wu A, Andrew NH, McNab AA, Selva D. Bilateral IgG4-related ophthalmic disease: a strong indication for systemic imaging. Br J Ophthalmol. [published online ahead of print December 30, 2015] doi: 10.1136/bjophthalmol-2015-307437. Background/Aims: To investigate whether bilateral or unilateral IgG4-related ophthalmic disease (IgG4-ROD) is associated with extraophthalmic IgG4-related disease (IgG4-RD). Methods: Twin-center retrospective observational case series of biopsy-confirmed IgG4-ROD. Clinical and radiology data were reviewed for laterality of IgG4-ROD and presence of extraophthalmic disease. The literature was reviewed for case series of IgG4-ROD. Results: Forty IgG4-ROD cases were identified, with median follow-up of 36 months. At diagnosis of IgG4-ROD, all cases were screened for extraophthalmic disease with physical examination and blood testing. Systemic imaging was performed in 20 (50%) cases due to clinical suspicion of extraophthalmic disease. Of the 21 unilateral IgG4-ROD cases, 3 (14%) had extraophthalmic involvement. Of the 19 bilateral cases, 15 (79%) had extraophthalmic involvement. Extraophthalmic involvement was strongly associated with bilateral IgG4-ROD (P , 0.001). On pooling our data (n = 40) with previously published cases (n = 142), the association remained strong (P , 0.001). Conclusions: Bilateral IgG4-ROD is strongly associated with extraophthalmic IgG4-RD. We recommend that imaging of the neck, chest, abdomen, and pelvis be performed for all bilateral cases. Systemic imaging should also be considered in unilateral cases, because a significant proportion of these patients will also have extraophthalmic disease. Mark, as a neurology-trained neuro-ophthalmologist, you may not be as familiar with orbital disease compared with an ophthalmology/orbital-trained neuro-ophthalmologist. In that context, I chose this study to discuss because I think it provides some insight into what to do with a patient with IgG4-related disease beyond just the eye/orbit. The authors analyzed 40 of their own cases in addition to 142 cases from the literature for a total of 182 cases. They found that extraophthalmic involvement was much more common in bilateral ophthalmic cases (69%) compared with unilateral ophthalmic cases (29%). Extraophthalmic involvement occurred in the salivary gland, paranasal sinuses, lymph nodes, bile duct, retroperitoneum, aorta, lung, hard palate, pituitary gland, and infratemporal fossa. 218 The authors recommend a complete physical examination, laboratory testing, and imaging of the neck, chest, abdomen, and pelvis for both patients with bilateral and unilateral IgG4 ophthalmic disease. Although the authors discuss the various imaging modalities (computed tomography with contrast, magnetic resonance imaging with contrast, whole-body fludeoxyglucose positron emission tomography, and gallium scintigraphy), they do not make any recommendations as to what the best strategy would be. In addition, the only laboratory tests they mention is a complete blood count, serum electrolytes, renal and liver function tests that seems to me a bit scant. Despite these issues, I think it is important to remember that patients with IgG4 disease need a systemic workup. -M. Tariq Bhatti, MD I may not be an ophthalmologist, but common sense tells me that when the disease has gone beyond involvement of 1 orbit, it may well be systemic. Although, I believe the authors' conclusion that bilateral orbital disease is more often associated with systemic involvement, there are numerous problems with this study. First, only one-third of the unilateral cases had systemic workup, compared with two-third of bilateral cases. The decision to do systemic workup was made with the patient and driven by "the clinical suspicion of extraophthalmic disease." Other biases that affected patient evaluation included the statement that lesions which are silent "may not warrant specific treatment. their detection may not alter management" and patients who "well may be reluctant to pursue systemic imaging." -Mark L. Moster, MD Chin EK, Almeida DRP, Lam KV, Keltner JL, Charles E, Thirkill CE. Positive auto-antibody activity with retina and optic nerve in smokers and non-smokers: the controversy continues. Ophthalmic Surg Lasers Imaging Retina. 2015;46:1068-1070. Abstract: Auto-antibodies assist with the diagnosis of ocular paraneoplastic syndromes and autoimmune ocular conditions; however, the frequency of positive test results as a possible precursor to future disease is unknown. The frequency of positive antibodies in heavy smokers who may be at risk for autoimmune-related retinopathy and optic neuropathy was evaluated. Serum antibody activity was evaluated through the use of Western blot reactions from pig retina and optic nerve extract. Fifty-one patients were included. Thirty-five patients were smokers (average, 40.9 pack-year history) and 26 patients had no smoking history. None of the patients had any visual complaints or known eye disease. Of the patients studied, 76.5% (39 patients- 18 smokers, 21 nonsmokers) had positive antiretinal antibodies, and 19.6% (10 patients-3 smokers, 7 nonsmokers) had positive antioptic nerve antibodies. Antiretinal antibodies were seen in a majority of randomly selected patients Moster and Bhatti: J Neuro-Ophthalmol 2016; 36: 216-220 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary with and without a smoking history. Antioptic nerve bodies were less common, but more prevalent in those who never smoked. The specificity of these antibodies remains greatly uncertain and clinical correlation is warranted. This is a very sobering article. When we suspect a patient to have autoimmune retinopathy, we obtain and rely on the finding of antiretinal antibodies to support the diagnosis. A positive result often leads to various treatments including steroids, immunosuppression, plasma exchange, and intravenous immunoglobulin. And these treatments pose potential risk to the patient. This study, which was performed in one of the main goto labs for the diagnosis of autoimmune retinopathy, found that 46% of smokers and 81% of nonsmokers without visual symptoms had antibodies to retinal antigens. The authors conclude ". the detection of autoimmune reactions using Western blot reactions may for now be only a supplement to clinical findings.." This is a study on a small population sample. If borne out on further study, it would make the very costly and complicated process of obtaining retinal and optic nerve antibodies obsolete, and the diagnosis of autoimmune retinopathies more difficult. -Mark L. Moster, MD At a recent grand rounds, one of my residents presented a case of what I believed to be autoimmune-related retinopathy and optic neuropathy in a young woman with multiple auto-antibodies detected by Western blot analysis (the patient's sera was sent to Dr. Adamus' lab at Casey Eye Institute, Portland, OR). During the presentation, one of my astute retina colleagues brought up a very good point, which was that, to determine if any of these antibodies were possibly pathogenic (i.e., specific) requires further analysis with sophisticated immunohistochemical testing to known retinal/optic nerve antigens. I agree with you Mark that making the diagnosis of nonparaneoplastic (autoimmune) and paraneoplastic ophthalmic disorders is very challenging. We need to keep in mind that the mere detection of these auto-antibodies does not always give us the answer. -M. Tariq Bhatti, MD Valko Y, Rosengren SM, Jung HH, Straumann D, Landau K, Weber KP. Ocular vestibular evoked myogenic potentials as a test for myasthenia gravis. Neurology. 2016;86:660-668. Objective: To explore whether ocular vestibular evoked myogenic potentials (oVEMP) can be used to detect a decrement in the extraocular muscle activity of patients with myasthenia gravis (MG). Methods: Twenty-seven patients with MG, including 13 with isolated ocular and 14 with generalized MG, and 28 healthy controls participated. We applied repetitive vibration stimuli Moster and Bhatti: J Neuro-Ophthalmol 2016; 36: 216-220 to the forehead and recorded the activity of the inferior oblique muscle with 2 surface electrodes placed beneath the eyes. To identify the oVEMP parameters with the highest sensitivity and specificity, we evaluated the decrement over 10 stimulus repetitions at 3 different repetition rates (3, 10, and 20 Hz). Results: Repetitive stimulation at 20 Hz yielded the best differentiation between patients with MG and controls with a sensitivity of 89% and a specificity of 64% when using a unilateral decrement of $15.2% as cutoff. When using a bilateral decrement of $20.4% instead, oVEMP allowed differentiation of MG from healthy controls with 100% specificity, but slightly reduced sensitivity of 63%. For both cutoffs, sensitivity was similar in isolated ocular and generalized MG. Conclusion: Our study demonstrates that the presence of oVEMP decrement is a sensitive and specific marker for MG. This test allows direct and noninvasive examination of extraocular muscle activity, with similarly good diagnostic accuracy in ocular and generalized MG. Thus, oVEMP represents a promising diagnostic tool for MG. Classification of Evidence: This study provides Class III evidence that oVEMP testing accurately identifies patients with MG with ocular symptoms (sensitivity 89%, specificity 64%). Ocular vestibular myogenic potentials (oVEMP) are tests of the otolithic function that are used in vestibular testing. Because the potential is measured from skin electrodes and originates in the extraocular muscles (EOMs), this is a noninvasive way of measuring the EOM response. The authors used this with repetitive stimulation to generate a test similar to the repetitive nerve stimulation used in myasthenia gravis (MG). They studied patients with known ocular or generalized MG and compared with controls. They were able to identify MG with 89% sensitivity and 64% specificity. Some of the patients with positive oVEMP tests had negative antibodies and normal repetitive nerve stimulation tests. Further testing is necessary to determine whether this test can distinguish MG from other diseases in the differential diagnosis, including chronic progressive external ophthalmoplegia, cranial neuropathies, thyroid ophthalmopathy, and brainstem lesions. If so, this will be a nice addition to relative noninvasive testing for MG. -Mark L. Moster, MD As you said Mark, it is very early to know whether this test will be clinically useful or not, but if further studies do show it can be used in addition to or as a substitute for some of the tests we have for MG (in particular ocular MG) that would be wonderful. However, the bar is set pretty high in terms of sensitivity among the currently available diagnostic tests for MG. If you recall when we discussed the study by Peeler et al (J Neuroophthalmol. 2015;35:438-443), the relatively simple acetylcholine receptor antibody test had a sensitivity rate of 70% in ocular MG! -M. Tariq Bhatti, MD 219 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Butty Z, Gopwani J, Mehta S, Margolin E. Horner's syndrome in patients admitted to the intensive care unit that have undergone central venous catheterization: a prospective study. Eye (Lond). 2016;30:31-33. Purpose: Central venous catheterization (CVC) is estimated to be performed in millions of patients per year. Swan-Ganz catheters used for CVC are most often inserted into the internal jugular vein, and during this procedure they may come into contact with the sympathetic chain. This study aims to determine the incidence of Horner syndrome in patients admitted to intensive care unit (ICU) who have undergone internal jugular CVC insertion during their admission, and to determine whether ultrasonography-assisted insertion has decreased the frequency of this complication. Patients and Methods: A total of 100 prospective patients admitted to the ICU were examined for the presence of anisocoria and ptosis after undergoing recent CVC. Presence of Horner syndrome was confirmed by testing with 0.5% apraclonidine and looking for the reversal of anisocoria. Results: Frequency of Horner syndrome after CVC was 2% in a sample of 100 prospectively examined patients. Conclusion: Horner syndrome remains a relatively rare but definitive complication of CVC. ICU physicians should be educated about its existence and prevalence, and ophthalmologists should inquire about any history of ICU admission necessitating CVC insertion in any patient presenting with Horner syndrome. This study of 100 patients receiving Swan-Ganz catheters found a frequency of Horner syndrome of 2%. Interestingly, none of the patients with known local complications (4 with local bleeding and 2 with carotid puncture) had a Horner syndrome. Both of those with Horner syndrome had only 1 uncomplicated attempt at catheterization. The authors note that they may have underestimated the frequency, because of the difficulty in assessing Horner syndrome in intensive care unit patients with decreased levels of consciousness. One other issue is that they also relied on apraclonidine testing to exclude Horner syndrome in patients with isolated anisocoria. 220 However, there are numerous patients in the literature who at 5 days out, have had a negative apraclonidine test with Horner syndrome, because denervation sensitivity has not yet been established. Despite the limitations, this study confirms that Horner syndrome is a rare complication of Swan-Ganz catheterization. In this study, magnetic resonance imaging/magnetic resonance angiography and chest radiograph were performed. I do not think we know from this study whether vessel imaging is necessary, but I would still do it to be sure the carotid artery is patent and the vessel wall intact. -Mark L. Moster, MD Let me just say a few things about this article. As shown by the authors, the incidence of Horner syndrome from insertion of Swan-Ganz catheter is low. But did you notice that 9% of the patients had anisocoria greater than .1 mm but yet only 2% were pharmacologically confirmed to have a Horner pupil. It is not stated in the article if the anisocoria was greater in the dark or if there was any pupillary dilation lag to suggest an oculosympathetic pathway disruption. Therefore, I think it is incumbent on physicians to do a careful pupillary examination to search for clinical clues to support the diagnosis of a Horner syndrome (anisocoria greater in the dark, pupillary dilation lag, upside down ptosis, and facial anhydrosis). In addition, the authors used apraclonidine 0.5% to confirm a Horner pupil. I wonder what would have been if cocaine was used instead? As you know, there have been a few studies that have looked at the comparative sensitivity of apraclonidine to cocaine in the detection of a Horner pupil. In one study the sensitivity of apraclonidine was 87% (1). -M. Tariq Bhatti, MD REFERENCE 1. Koc F, Kavuncu S, Kansu T, Acaroglu G, Firat E. The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis. Br J Ophthalmol. 2005;89:1442- 1444. Moster and Bhatti: J Neuro-Ophthalmol 2016; 36: 216-220 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
Date | 2016-06 |
Language | eng |
Format | application/pdf |
Type | Text |
Publication Type | Journal Article |
Source | Journal of Neuro-Ophthalmology, June 2016, Volume 36, Issue 2 |
Collection | Neuro-Ophthalmology Virtual Education Library - Journal of Neuro-Ophthalmology Archives: https://novel.utah.edu/jno/ |
Publisher | Lippincott, Williams & Wilkins |
Holding Institution | Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E SLC, UT 84112-5890 |
Rights Management | © North American Neuro-Ophthalmology Society |
ARK | ark:/87278/s6c57f9q |
Setname | ehsl_novel_jno |
ID | 1276504 |
Reference URL | https://collections.lib.utah.edu/ark:/87278/s6c57f9q |