Jason H. Peragallo

Brain Imaging in Idiopathic Intracranial Hypertension.

Background: The primary role of brain imaging in idiopathic intracranial hypertension (IIH) is to exclude other pathologies causing intracranial hypertension. However, subtle radiologic findings suggestive of IIH have emerged with modern neuroimaging. This review provides a detailed description of the imaging findings reported in IIH and discusses their possible roles in the pathophysiology and the diagnosis of IIH. Evidence Acquisition: References were identified by searches of PubMed from 1955 to January 2015, with the terms “idiopathic intracranial hypertension,” “pseudotumor cerebri,” “intracranial hypertension,” “benign intracranial hypertension,” “magnetic resonance imaging,” “magnetic resonance venography,” “computed tomography (CT),” “CT venography,” “imaging,” and “cerebrospinal fluid (CSF) leak.” Additional references were identified by hand search of relevant articles. When possible, we extracted the number of patients and control subjects from each study for each radiological finding. When at least 2 studies used the same criteria to define a radiological finding, all patients from these studies were pooled to obtain a mean sensitivity and specificity with 95% confidence interval. Results: Specific neuroimaging findings may suggest long-standing IIH, including empty sella, flattening of the posterior globes, optic nerve head protrusion, distention of the optic nerve sheaths, tortuosity of the optic nerve, cerebellar tonsillar herniation, meningoceles, CSF leaks, and transverse venous sinus stenosis. Conclusion: Although IIH remains a diagnosis of exclusion, the most recently proposed diagnostic criteria have included neuroimaging findings to suggest IIH when major diagnostic criteria are not fulfilled. However, these findings are not diagnostic of IIH, and their presence is not required for the diagnosis of definite IIH. Their incidental discovery on brain imaging should not prompt invasive procedures, unless other signs of IIH, such as papilledema, are present.

Postoperative Drift in Patients with Thyroid Ophthalmopathy Undergoing Unilateral Inferior Rectus Muscle Recession

ABSTRACT Background: Extraocular muscles of patients with thyroid ophthalmopathy (TO) may respond differently to strabismus surgery than those of other strabismic patients. This study reports postoperative alignment changes in patients with TO compared with patients with non-restrictive strabismus following unilateral inferior rectus muscle recession (IRR). Methods: We reviewed records of patients with and without TO who underwent unilateral IRR. Group A had adjustable muscle sutures, while Group B had permanent or semi-adjustable sutures. Controls were patients undergoing adjustable unilateral IRR for other indications. Results: Mean preoperative hypotropias were 17 ± 9, 21 ± 7, and 11 ± 4 PD for groups A (n = 13), B (n = 14), and controls (n = 19), respectively. Postoperative day one (POD1) measurements after adjustment were 1.2 ± 2.5, 3.7 ± 4.9, and 0.3 ± 2.4 PD, respectively, representing overall undercorrections in all cases (the preoperative deviation was given a positive (+) value and overcorrections were deemed negative (−) deviations). Dose response from linear regression analysis of thyroid patients compared with control patients for IRR was 3.26 PD/mm (SE 0.18) vs 2.38 PD/mm (SE 0.18) (p = 0.001). Mean final measurements were −0.7 ± 5.6 (overcorrection), 2.7 ± 5.7, and 1.7 ± 5.7 PD of hypotropia, respectively. Final overcorrections occurred in 23%, 14%, and 16% of patients, for adjustables, permanent sutures, and control subjects, respectively. Drifts from POD1 measurements after adjustment to final measurements were −1.9 ± 4.3, −1.0 ± 4.6, and 1.4 ± 5.9 PD respectively (p = 0.05 for comparison between Group A and controls). Conclusions: TO patients with adjustable sutures drift toward postoperative overcorrection.

Is there treatment for Leber hereditary optic neuropathy

Purpose of review To discuss recent advances in potential treatments for Leber hereditary optic neuropathy (LHON), a typically visually devastating hereditary optic neuropathy caused by mutations in the mitochondrial genome. Recent findings Idebenone has been proposed as a means of bypassing defective complex I activity and a free radical scavenger to prevent oxidative damage. EPI-743 may have more potency than idebenone, but no clinical trials have been performed. Gene therapy techniques have advanced significantly, including allotopic expression and nuclear transfer. Successful rescue of animal models of LHON with both of these therapies has been demonstrated. Introduction of exogenous DNA into the mitochondrial genome with mitochondrial targeting of viral vectors is another promising technique. Summary There are currently no proven treatments for LHON. However, there are many promising novel treatment modalities that are currently being evaluated, with several clinical trials underway or in the planning stages. Supportive measures and genetic counseling remain of great importance for these patients.

Long-term follow-up of strabismus surgery for patients with ocular myasthenia gravis.

Background:Patients with ocular myasthenia gravis (OMG) may develop strabismus and diplopia. We completed a retrospective observational case series to evaluate long-term surgical outcomes in patients with OMG. Methods:The medical records of all patients with OMG who underwent strabismus surgery with at least 6 months of postoperative follow-up were reviewed. Nine patients met the study inclusion criteria. The main outcomes, including ocular alignment, number of surgeries, and sensory status were evaluated. Results:Of these patients, initially 2 had horizontal strabismus alone, 3 had vertical strabismus alone, 3 had both vertical and horizontal strabismus, and 1 patient had vertical and torsional strabismus. The length of preoperative stability was 2.0 ± 2.5 years (range: 0.1–8.0 years). The mean preoperative horizontal and vertical deviations were 40.5 ± 32.5 prism diopters (PD; range: 0–90 PD) and 25.6 ± 36.7 PD (range: 0–120 PD), respectively. The average length of the follow-up after the first surgery was 5.7 ± 4.2 years (range: 0.7–10.6 years). Four patients (44%) underwent 2 operations. For patients requiring a second operation, the time to second operation was 2.3 years (range: 0.4–5.0 years). Six patients (67%) were within 10 PD of orthotropia at distance in primary position at the final visit. Five patients (55%) had single vision after their surgeries. Conclusion:Strabismus surgery can achieve good long-term binocular alignment in patients with OMG.

Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene

ABSTRACT Background: Optic atrophy may be the sequela of optic nerve injury due to any insult, including isolated and syndromic genetic diseases. Alanyl-tRNA synthetase 2 (AARS2) pathogenic variants have been reported to cause leukodystrophy with ovarian failure, and cardiomyopathy (#615889) as well as combined oxidative phosphorylation deficiency-8 (#614096). We report a young child who presented with decreased vision due to optic atrophy and was found to harbor missense variants in the AARS2 gene expanding the phenotypic expression of the AARS2 gene.Materials and Methods: Single observational case report with genetic testing, laboratory testing, neurologic and ophthalmic clinical examinations, and neuroimaging performed at a tertiary academic medical center.Results: An 18-month old Korean boy was noted to have a progressive decline in visual function. The physical exam revealed bilateral optic atrophy, peripheral retinal bone spicule pigmentation, and absent patellar reflexes. Electromyography was consistent with demyelinating polyneuropathy. Magnetic resonance imaging (MRI) of the brain and spine showed cerebellar and supratentorial white matter multifocal changes with areas of restricted diffusion, and dorsal column signal abnormalities. Whole exome sequencing revealed two missense variants in the AARS2 gene [c.1519G>C (p.V507L) and c.2165G>A (p.R722Q)], found to be in trans on parental testing.Conclusions: Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene.

Imaging Features of Idiopathic Intracranial Hypertension in Children

Magnetic resonance imaging (MRI) signs of elevated intracranial pressure and idiopathic intracranial hypertension have been well characterized in adults but not in children. The MRIs of 50 children with idiopathic intracranial hypertension and 46 adults with idiopathic intracranial hypertension were reviewed for optic nerve head protrusion, optic nerve head enhancement, posterior scleral flattening, increased perioptic cerebrospinal fluid, optic nerve tortuosity, empty or partially empty sella, tonsillar herniation, enlargement of Meckel’s cave meningoceles, and transverse venous sinus stenosis(TSS). Compared to adolescents (11-17 years, n = 40) and adults (>17 years, n = 46), prepubescent children (<11 years, n = 10) had lower frequencies of scleral flattening (50% vs 89% and 85%, P = .02), increased perioptic cerebrospinal fluid (60% vs 84% and 89%, P = .08), optic nerve tortuosity (20% vs 46% and 59%, P = .07), empty or partially empty sella (56% vs 78% and 93%, P = .007), and TSS (67% vs 93% and 96%, P = .04). Children with idiopathic intracranial hypertension have similar MRI findings as adults, but they are less frequent in prepubescent children.

Ocular manifestations of drug and alcohol abuse.

Purpose of review The purpose of this study is to review commonly encountered adverse ocular effects of illicit drug use. Recent findings Drug and alcohol abuse can produce a variety of ocular and neuro-ophthalmic side effects. Novel, so-called ‘designer’, drugs of abuse can lead to unusual ocular disorders. Legal substances, when used in manners for which they have not been prescribed, can also have devastating ophthalmic consequences. Summary In this review, we will systematically evaluate each part of the visual pathways and discuss how individual drugs may affect them.

Relationship Between Age, Gender, and Race in Patients Presenting With Myasthenia Gravis With Only Ocular Manifestations.

Background: The demographic associations among patients presenting with myasthenia gravis with only ocular manifestations (OMG) is not clear. Methods: In this 5-center case series, we collected the race, gender, and age at diagnosis of patients diagnosed with myasthenia gravis who had no signs or symptoms of generalized myasthenia gravis (GMG). An a priori sample size calculation determined that 140 patients were required to accept that there was a ⩽10-year difference in mean age (equivalence testing: power 90%, &agr; = 0.05). Robust Bayesian analysis and linear regression were applied to evaluate whether age differed by gender or race. Results: Of 433 patients included, 258 (60%) were men. Mean age among men was 57 years (SD = 19) and 52 years (SD = 21) among women. The 95% credible interval (CI) (Bayesian equivalent of confidence interval) was 0.8–8.7 years for mean age, and there was a 99.6% probability that the mean difference in age between sexes was <10 years. Race was documented in 376 (68 [18%] non-Caucasian). Caucasians were 17.3 years older than non-Caucasians at diagnosis (95% CI, 12.2–22.3 y; P < 0.001) controlling for gender. There was no additive interaction of gender and race (P = 0.74). There was a bimodal distribution for women peaking around 30 and 60 years. Men had a left skewed unimodal age distribution peaking at age 70. Conclusions: The distribution of age at presentation in patients with OMG is different between men and women, similar to GMG. Non-Caucasian patients tend to develop OMG at a younger age.

Recent advances clarifying the etiologies of strabismus.

Background: Strabismus is commonly encountered in neuro-ophthalmology practice. Adult patients may present with symptoms including disabling diplopia and decreased quality of life. Although presentation to the neuro-ophthalmologist often prompts a thorough workup for a neurologic basis of ocular misalignment, advances in orbital imaging and understanding of orbital mechanics have revealed novel mechanical causes. A goal of this review is to clarify mechanical mechanisms of strabismus that were formerly assumed be neurologic in origin. Evidence Acquisition: The authors combine their own research and clinical experience with a literature review using PubMed. Results: Aberrant paths of the extraocular muscles can lead to strabismus. The extraocular muscles have connective tissue pulleys that control muscle paths and are, in turn, influenced by the extraocular muscle orbital layers. Orbital connective tissues, including the pulleys, constrain extraocular muscle paths. Abnormalities of these tissues may lead to strabismus that is not due to neurologic pathology. Some extraocular muscles are divided into independent neuromuscular compartments, so that partial motor nerve lesions may manifest as selective denervation of only 1 compartment, complicating the presentation of neuropathic strabismus. Conclusions: Strabismus in adults due to nonneurologic causes can result from recently described abnormalities of the orbital connective tissue pulley system. Advances in understanding of compartmental extraocular muscle anatomy and innervation can explain cyclovertical strabismus in partial nerve palsies. Recognition of the underlying pathogenesis of the strabismus can lead to improved treatments.

Pediatric Myasthenia Gravis

Myasthenia gravis is a disorder of neuromuscular transmission that leads to fatigue of skeletal muscles and fluctuating weakness. Myasthenia that affects children can be classified into the following 3 forms: transient neonatal myasthenia, congenital myasthenic syndromes, and juvenile myasthenia gravis (JMG). JMG is an autoimmune disorder that has a tendency to affect the extraocular muscles, but can also affect all skeletal muscles leading to generalized weakness and fatigability. Respiratory muscles may be involved leading to respiratory failure requiring ventilator support. Diagnosis should be suspected clinically, and confirmatory diagnostic testing be performed, including serum acetylcholine receptor antibodies, repetitive nerve stimulation, and electromyography. Treatment for JMG includes acetylcholinesterase inhibitors, immunosuppressive medications, plasma exchange, intravenous immunoglobulins, and thymectomy. Children with myasthenia gravis require monitoring by a pediatric ophthalmologist for the development of amblyopia from ptosis or strabismus.