Andrew Wilner, MD, Neurology, 09:10PM Sep 24, 2012
Neurohospitalist and Author of Bullets and Brains
In these days of multitudinous, multi-author, multi-center, multi-national, randomized, double blind, placebo controlled trials*, I stumbled upon a gem of an article from the Department of Ophthalmology, Nationaal Multiple Sclerosis Centrum, Melsbroek, Belgium (Roodhooft 2012). Dr. Roodhooft, an experienced clinician, personally examined 284 adults (173 females, 111 males) referred to the multiple sclerosis (MS) clinic between 2007-2010. Dr. Roodhooft summarized his observations in an easy to read, single author article.
Most of the MS patients had an ophthalmologic examination to assess for refractive errors. Other indications included headache, diplopia, acute optic neuritis, blepharoconjunctivitis, visual failure, diabetes, arterial hypertension, intraocular pressure, cataracts, nystagmus, uveitis, photophobia, anisocoria, and dry eye.
Of the 284 patients, 51 (27 females, 24 males) had functional visual loss (<6/20). There were 129 eyes with temporal pallor of the optic nerve head, 110 with global pallor, 70 with pathological excavation, and 29 with a chalky white color. None of the patients had papilledema. Nystagmus of various types (e.g., gaze-evoked, rotatory, pendular, jerk) was observed in 104 patients, with primary gaze nystagmus in 28 patients. Diplopia occurred in 51 and oscillopsia in 17 patients. Two patients had bilateral active uveitis. In addition, 65 patients had facial palsy and 19 had trigeminal neuralgia.
Dr. Roodhooft noted that 4-aminopyridine may cause diplopia "either by itself or through an overdose or a change in dose." Given the widespread use of 4-aminopyridine marketed as dalfampridine (Ampyra) to improve walking in MS, physicians should be alert to this possibility. This observation deserves more attention as diplopia is not listed as one of the "common adverse events" on the Ampyra website or in the package insert.
The paper discusses, "How to help MS patients with ocular problems." Practical recommendations include:
1. Treat acute optic neuritis with steroids.
2. Correct refractive errors.
3. Treat dry eyes and evaluate for causes, such as anticholinergic medications or poor blinking.
4. Heat, exercise, fever and stress may temporarily worsen vision, diplopia and oscillopsia, and patients should be counseled accordingly.
5. Fresnel lenses may correct diplopia.
6. Gabapentin or memantine may help nystagmus.
7. Sunglasses may be a simple solution for photophobia.
8. Cataracts secondary to steroid use or other causes may be a correctable form of decreased vision.
9. Uveitis may cause blindness and needs to be diagnosed and treated.
10. Fatigue in MS patients is multifactorial (e.g., depression, medications, sleep disturbances) and may affect vision.
The article does not include data from optical coherence tomography (OCT), which may soon become part of the routine evaluation of patients with MS. Follow-up regarding the clinical course of individual patients is not provided.
New Journals for Case Reports
Detailed clinical observations such as these, as well as case reports (long denigrated as "anecdotal)," may be experiencing a renaissance. As new treatments enter clinical practice, it is important to publish case reports of successes, failures, and idiosyncratic reactions. The management of complex patients and complications related to new therapies may also lend itself to publication. A new journal, Neurology: Clinical Practice, was recently launched as a "spoke" journal of Neurology. According to editor John R. Corboy, MD, FAAN, Neurology: Clinical Practice includes peer-reviewed articles targeted at clinical practitioners, including images and full case reports. The first edition of Neurology: Clinical Practice, was published in December 2011. The most recent issue included 5 cases (September 2012).
In the field of epilepsy, a new clinical journal has also recently been created. According to the publisher, Elsevier, "Epilepsy & Behavior Case Reports is a new, online-only, Open Access journal devoted to the rapid publication of case reports on the behavioral aspects of seizures and epilepsy."
Epilepsy & Behavior Case Reports is a companion journal to Epilepsy and Behavior, which has achieved high standing in the epilepsy community since it's first publication a dozen years ago. Similar journals focusing on clinical cases may evolve in other specialties as well.
Whether the eye represents a "window to the soul" may be debated, but it certainly serves as a convenient portal to inspection of the optic nerve and many critical central nervous system pathways. While large, controlled trials are essential to test new therapies and establish an evidence base for clinical practice, it is a breath of fresh air to see that one needn't participate in a research juggernaut in order to make useful academic contributions. At least two new journals, Neurology: Clinical Practice and Epilepsy & Behavior Case Reports offer platforms for publication of case reports and may lead to a resurgence of academic interest in clinical phenomena. Dr. Roodhooft's well organized observations are testimony that skilled examination of individual patients in the hospital or clinic, coupled with intellectual curiosity, can still yield useful scientific information. Bravo Dr. Roodhooft!
*There has been an explosion of articles on MS, including 2 important randomized, clinical trials just published in the New England Journal of Medicine on dimethyl fumarate (BG-12) (Fox et al. 2012, Gold et al. 2012). These positive trials suggest imminent Food and Drug Administration (FDA) approval of BG-12 for relapsing MS, and are worth a look, as is the accompanying editorial by Ropper (Ropper 2012).
1. Fox RJ, Miller DH, Phillips JT et al. New England Journal of Medicine 2012; 367:1087-97.
2. Gold R, Kappos L, Arnold DL et al. New England Journal of Medicine 2012;367:1098-107.
3. Roodhooft JM. Summary of eye examinations of 284 patients with multiple sclerosis. Int J MS Care 2012;14:31-38.
4. Ropper AH. The "Poison Chair" treatment for multiple sclerosis. New England Journal of Medicine 2012;367:1149-50.