Clinical features and long-term prognosis of trochlear headaches.

BACKGROUND AND PURPOSE: Trochlear headaches are a recently recognized cause of headache, of which both primary and inflammatory subtypes are recognized. The clinical features, long-term prognosis and optimal treatment strategy have not been well defined. METHODS: A cohort of 25 patients with trochlear headache seen at the Mayo Clinic between 10 July 2007 and 28 June 2012 were identified. RESULTS: The diagnosis of trochlear headache was not recognized by the referring neurologist or ophthalmologist in any case. Patients most often presented with a new daily from onset headache (n = 22, 88%). The most characteristic headache syndrome was reported as continuous, achy, periorbital pain associated with photophobia and aggravation by eye movement, especially reading. Individuals with a prior history of migraine were likely to have associated nausea and experience trochlear migraine. Amongst individuals with trochleitis, 5/12 (41.6%) had an identified secondary mechanism. Treatment responses were generally, but not invariably, favorable to dexamethasone/lidocaine injections near the trochlea. At a median follow-up of 34 months (range 0-68), 10/25 (40%) of the cohort had experienced complete remission. CONCLUSIONS: Trochlear headaches are poorly recognized, have characteristic clinical features, and often require serial injections to optimize the treatment outcome. The identification of trochleitis should prompt neuroimaging to look for a secondary cause.

Adenoid cystic carcinoma of the lacrimal gland is frequently characterized by MYB rearrangement.

PurposeAdenoid cystic carcinoma (ACC) represents ~10-15% of salivary neoplasms and almost universally exhibits a lethal clinical course. ACC is also known to occur in the lacrimal gland. ACC is characterized by its heterogeneous morphology and may demonstrate tubular, cribriform, and/or solid architectural patterns. Unfortunately, these histopathological features are not specific to ACC and can be seen in other salivary gland-type neoplasms, introducing a diagnostic dilemma. The discovery of fusion transcripts has revolutionized the diagnosis, surveillance, and treatment of epithelial malignancies. In several anatomic subsites ACC is frequently characterized by a fusion transcript involving genes MYB and NFIB; more specifically, t(6;9)(q22-23;p23-24). This study explores the incidence of MYB rearrangement in cases of lacrimal gland ACC using fluorescent in situ hybridization.Materials and methodsRetrospective clinical and histopathological review of 12 cases of lacrimal gland ACC seen at Mayo Clinic over a 25-year period (1990-2015) was performed. Demographic and clinical data were obtained from medical records. Surgical pathology archival material including H&E slides and immunostains was re-examined. Formalin-fixed paraffin-embedded material was further evaluated using immunohistochemistry when appropriate. Fluorescent in situ hybridization (FISH) using a MYB break-apart probe was applied to all histologically confirmed cases of ACC and benign salivary gland parenchyma.ResultsThe median patient age was 53.6 years (range 12-64) and distributed equally by gender (six male and six female). Rearrangement of MYB was identified using FISH in seven cases (58%). Twenty-five sections of benign salivary gland parenchyma showed no evidence of MYB rearrangement. Primary surgical resection was most common treatment, and 78% of the patient received adjuvant radiation therapy. Median overall survival (OS) was 11 years. Rearrangement of MYB did not affect OS.ConclusionsIn summary, our results indicate that the MYB rearrangement defines a significant subset of lacrimal gland ACCs. Importantly, FISH for MYB rearrangement may be used as a diagnostic tool during pathological examination of lacrimal gland neoplasms. Our results showed no relationship between rearrangement status and clinical outcome. Lastly, the presence of t(6;9) in ACC may provide a platform for molecular-targeting strategies in the future.

Clinical review 13: Diagnosis and management of Graves' ophthalmopathy.

Although Graves ophthalmopathy is a potentially sight threatening and disfiguring condition that can be frightening for the patient to experience, there are effective means of management. At the present time, treatment is based on the relief of excessive intraorbital pressures and is accomplished either by shrinking the orbital contents or by expanding the orbital volume. The most effective treatment modality or combination of modalities is an area of controversy. However, it must be remembered that the approach to management undertaken should be finely tuned to the needs of the particular individual afflicted with the condition. Perhaps with a greater understanding of pathophysiology, more reliable and effective treatments, based on specific pathophysiological mechanisms, may be developed. In addition, tests to reliably predict those patients most likely to progress in their disease might be developed, allowing preventive measures to be taken.

Ocular motor nerve palsies in spontaneous dissections of the cervical internal carotid artery.

Cranial nerve palsies affecting ocular motor function in patients with spontaneous cervical internal carotid artery dissections are rare. Among 155 patients with spontaneous dissections of the cervical internal carotid artery, four (2.6%) had transient third, fourth, or sixth cranial nerve palsy. The third nerve was involved in two patients, the fourth nerve in one, and the sixth nerve in one. Three patients had ipsilateral headache or facial pain, one had bilateral headaches, and three had oculosympathetic palsy. None had any associated cerebral or retinal ischemic symptoms. Cervical internal carotid artery dissection should be included in the differential diagnosis of palsies of the third, fourth, or sixth cranial nerve, especially when associated with ipsilateral headache or facial pain. Interruption of the nutrient arteries supplying these cranial nerves could explain their involvement by internal carotid artery dissection.

Local control and complications after radiation therapy for primary orbital lymphoma: a case for low-dose treatment.

Orbital involvement at the time of initial presentation is unusual in non-Hodgkin's lymphoma. In an effort to identify potential ways of improving the radiotherapeutic management of this disease, the records of 22 patients were reviewed retrospectively. All had biopsy-proven orbital non-Hodgkin's lymphoma, and the minimal, median, and maximal durations of follow-up in surviving patients were 4.8 years, 7.0 years, and 17.4 years, respectively. Permanent local control was achieved in 21 of the 22 patients (96%). Complications were scored according to a grading scheme in which grade 1 was the least significant complication and grade 4 was blindness as a result of radiation therapy. Of the 12 patients who received a radiation dose less than 35 Gy, 6 developed a grade 1 or grade 2 complication. Of the 10 patients treated with greater than or equal to 35 Gy, 6 experienced a complication, 1 of whom had a grade 4 complication resulting in blindness and another who developed a severe keratitis, which was scored as a grade 3 complication resulting in decreased visual acuity. At last follow-up, 10 patients were alive at 4.8 to 17.4 years after completion of radiation therapy, 4 had died of intercurrent disease at 3 months to 10.6 years, and 8 had died of disease at 3 months to 15.8 years. Actuarial survival for the entire group was 75% at 5 years and 48% at 10 years. Survival in patients with Stage I AE disease (lymphoma confined to orbit) at presentation was 87% at 5 years and 50% at 10 years, and survival in patients with Stage II A through Stage IV disease was 36% at 5 years and at 10 years. Primary orbital lymphoma is an indolent disease characterized by prolonged survival after radiation therapy. Excellent local control can be achieved with radiation doses of 20 Gy to 35 Gy. Higher doses may result in an increased risk of complications.

Diagnostic evaluation of Graves' ophthalmopathy.

The important questions to be answered in the course of decision-making in patients with Graves' ophthalmopathy include the following: 1. Is the eye problem owing to Graves' ophthalmopathy? If not, the cause of the eye problem must be sought. 2. Does the patient have serious medical problems apart from the thyroid and the eyes? Define type and severity, and risk to life and well-being. Do they preclude anesthesia or steroid therapy? 3. Is the patient euthyroid? Define thyroid abnormality and treat. 4. Is the eye problem the highest medical priority for the patient and the physician? If not, treat the highest priority, then return to the eyes. 5. Which particular manifestations of Graves' ophthalmopathy are the most troublesome to the patient? Establish priorities according to need and rational order for surgical procedures. 6. How have the eyes been treated in the past? What has been successful? What side effects have resulted? In the evaluation of a patient with possible Graves' ophthalmopathy, no single clinical or laboratory feature is necessary or pathognomonic of the disorder. The sufficient findings for a diagnosis are a matter of clinical judgment. Several diagnostic tools including CT scanning, various ophthalmologic examinations, and studies of thyroid function are available. The physician must use these tools, along with clinical judgment, to establish the diagnosis with maximum certainty. Following this, the particular manifestations of the disease that are most troublesome to the patient must be carefully defined and assessed. Only then can the treatment be optimally tailored to the patient's needs.

Orbital lymphoma: radiotherapy outcome and complications.

BACKGROUND AND PURPOSE: Orbital non-Hodgkin's lymphomas (NHL) have traditionally been treated with radiation. Forty-eight patients presenting with orbital NHL were treated with radiation and were evaluated for local control, overall survival, cause-specific survival, and complications. MATERIALS AND METHODS: Forty-five patients had low-grade and 3 patients had intermediate-grade histologic findings. Orbit-only disease occurred in 22 patients, the conjunctiva in 16, both in five, and lacrimal gland only in five. Patient age ranged from 35 to 94 years (median, 68). Ann Arbor stages were cIEA (34), cIIEA (six), cIIIEA (two), and cIVEA (six). Radiation doses ranged between 15 and 53.8 Gy (median, 27.5 Gy). RESULTS: Follow-up ranged from 0.14 to 18.23 years (median, 5.35). Median overall survival and cause-specific survival were 6.5 and 15.5 years, respectively. Patients with clinical stage I or II disease had significantly better overall and cause-specific survival than patients with stage III or IV disease. Ten-year relapse-free survival in 41 patients with stage I or II disease was 66%. However, there was continued downward pressure on relapse-free survival out to 18 years. One local failure occurred. Twenty-five patients sustained acute complications. There were 17 minor and four major late complications. All major late complications occurred with doses more than 35 Gy. CONCLUSIONS: Excellent local control with radiation doses ranging from 15 to 30 Gy is achieved. Patients with stage I or II disease have better overall and cause-specific survival than patients with stage III or IV disease. Late relapse occurs in sites other than the treated orbit, even in patients with early-stage disease. Doses 35 Gy or higher result in significant late complications and are therefore not indicated for patients with low-grade tumors.

The differential diagnosis of orbital calcification as detected on computed tomographic scans.

We reviewed 350 orbital computed tomographic scans to determine the frequency, significance, and differential diagnosis of calcified lesions. Of 171 suitable scans that fulfilled the study criteria, 37 (22%) showed calcific densities. The most common intraocular lesion that contained calcium was retinoblastoma, and the most frequently calcified extraocular masses were vascular lesions (hemangioma, lymphangioma, and varix). We describe two orbital tumors--metastatic colonic carcinoma and primary orbital malignant melanoma--that previously have not been reported as having calcification. The presence of calcification within lesions of the lacrimal gland fossa usually, but not always, portends malignant disease.

Idiopathic intracranial hypertension.

OBJECTIVE: This review was undertaken to summarize the significant progress that has been made in the epidemiology of idiopathic intracranial hypertension (IIH), the changing nosology, and the diagnostic criteria and therapeutic strategy. DESIGN: We reviewed the pertinent literature on IIH published in major English-language journals for the last 20 years. MATERIAL AND METHODS: The diagnosis, epidemiology, pathophysiology, complications, and treatment of IIH are described. RESULTS: IIH occurs at an average annual incidence rate per 100,000 persons of 1 to 2 for the total population and 19 to 21 in obese females of the reproductive age-group. IIH is a recognized cause of reversible vision loss in adult obese women. The diagnosis of IIH requires a documented elevation of intracranial pressure, normal cerebrospinal fluid (CSF) composition, and normal findings on neuroimaging studies. At least two primary mechanisms for the development of increased CSF pressure in IIH have been postulated and supported by experimental data: vasogenic extracellular brain edema and a low conductance of CSF outflow at the arachnoid villi. This condition may be secondarily exacerbated by compression of intracranial venous sinuses by the increased intracranial pressure, resulting in a further reduction of flow across the arachnoid villi. The therapeutic strategy is determined by visual status, which needs close monitoring. CONCLUSION: Although medical measures to lower the intracranial hypertension are successful in the majority of patients, surgical therapy should not be delayed in those with significant or progressive vision loss. Based on recent advances, a practical approach has been described for the diagnosis, early detection of visual impairment, and targeting therapy to preserve the vision or to reverse recent loss of vision in patients with IIH.

Sarcoid masquerading as optic nerve sheath meningioma.

Sarcoid manifesting as an optic nerve tumor without evidence of systemic disease is uncommon. Throughout a 2-year period, a 22-year-old white woman had progressive monocular loss of vision to the level of no light perception. Optic atrophy but no uveitis was noted in the affected eye. Magnetic resonance imaging revealed thickening and enhancement of the apical optic nerve, with "tram-tracking." The presumptive diagnosis was optic nerve sheath meningioma; however, a biopsy specimen from the optic nerve revealed sarcoid. Extensive postoperative investigations revealed no systemic sarcoidosis. To our knowledge, 17 cases similar to ours, with the diagnosis proved by optic nerve biopsy, have been previously reported in the English-language literature. Most of these were mistaken preoperatively for optic nerve sheath meningioma. None of the patients had evidence of systemic sarcoidosis on initial postoperative testing. Neuroimaging, serum level of angiotensin-converting enzyme, and clinical characteristics such as age, race, sex, and optochoroidal collaterals do not distinguish optic nerve sheath meningioma from sarcoid of the optic nerve. In the absence of uveitis or systemic involvement, optic nerve sarcoid manifesting as an orbital tumor is virtually impossible to diagnose without results of biopsy.

Traumatic carotid artery dissection causing blindness.

A case of delayed postoperative visual loss due to bilateral traumatic carotid artery dissection is presented. In patients with a major craniofacial injury due to a high-speed motor vehicle accident, we suggest that carotid artery duplex ultrasonography be used in the initial evaluation for possible carotid artery dissection. Magnetic resonance imaging of the head and neck with magnetic resonance angiography should be performed subsequently if indicated. Early diagnosis and initiation of therapy can minimize complications.

Role of testing for anticytoplasmic autoantibodies in the differential diagnosis of scleritis and orbital pseudotumor.

Wegener's granulomatosis is a multisystem disease often with protean manifestations. Eye signs and symptoms can be prominent and may be the patient's initial complaint. For a definitive diagnosis of Wegener's granulomatosis, a tissue biopsy specimen must show vasculitis and necrotizing granuloma. The presence of anticytoplasmic autoantibodies in the serum of patients has been found to be highly specific for Wegener's granulomatosis and can considerably facilitate early diagnosis and be used to monitor disease activity. In two illustrative cases, the utility of this laboratory test in the differential diagnosis of scleritis and orbital pseudotumor is demonstrated.

Transfrontal orbital decompression after failure of transantral decompression in optic neuropathy of Graves' disease.

Transantral and transfrontal orbital decompression procedures are effective for treating optic neuropathy of Graves' disease. We studied 10 patients with Graves' disease to clarify whether transfrontal decompression is effective after prior failure of transantral orbital decompression. All patients had persistent or recurrent optic neuropathy after transantral decompression and had failed to respond to systemic corticosteroid therapy. After transfrontal decompression, visual acuity improved in 70% of the eyes, and visual field scotomas decreased in 80%. No major intraoperative or postoperative complications occurred. We conclude that in optic neuropathy of Graves' disease, transfrontal orbital decompression after failure of transantral decompression is an acceptable and beneficial salvage procedure.

Predictors of response to transantral orbital decompression in severe Graves' ophthalmopathy.

OBJECTIVE: To identify factors that may help predict the outcome after transantral orbital decompression in Graves' ophthalmopathy. DESIGN: A retrospective study was conducted of 428 patients who had undergone an initial transantral orbital decompression for severe Graves' ophthalmopathy at the Mayo Clinic between November 1969 and May 1989. MATERIAL AND METHODS: With use of logistic regression analysis, we assessed the preoperative characteristics, the early postoperative results, and the follow-up questionnaire data (obtained a median of 9.5 years postoperatively) from 304 female and 124 male patients with Graves' ophthalmopathy who had undergone transantral orbital decompression at a median age of 53 years. RESULTS: On multivariate stepwise regression analysis, young age, male sex, and long duration of eye symptoms were predictors of severe initial proptosis (P < 0.001). The only independent predictors of greater postoperative recession of proptosis were severity of initial proptosis and longer interval between operation and postoperative examination (P < 0.001). Patients with the most reduction of proptosis had the greatest improvement in visual acuity but more chance for postoperative development of continuous diplopia. Failure of prior corticosteroid or orbital radiation therapy did not affect the degree of recession of proptosis or improvement in visual acuity. On multivariate analysis for predictors of long-term overall patient satisfaction, only young age of the patient was of borderline significance (P = 0.05), and the only significant predictor of satisfaction with the postoperative eye appearance was an operation done primarily for cosmetic purposes (P = 0.012). CONCLUSION: Although various factors may influence the outcome of orbital decompression in patients with Graves' ophthalmopathy, this study showed that the more pronounced the initial proptosis, the greater the degree of recession postoperatively. A higher degree of reduction of proptosis is associated with better visual acuity but also a greater likelihood of development of continuous diplopia.

Visual impairment due to macular disciform scars in a 20-year-old man with Smith-Magenis syndrome: another ophthalmologic complication.

We describe a 20-year-old man with Smith-Magenis syndrome and a 46,XY,del(17)(p11.2p11.2) karyotype. The interstitial deletion was confirmed by metaphase analysis using the fluorescent in situ hybridization probe (D17S29) for the Smith-Magenis region. The patient had hypertelorism, exotropia, and high myopia. Examination under anesthesia showed a lacquer crack near the right macula and a disciform scar of the left macula. Six months later, the patient presented with subacute visual loss. Examination demonstrated end-stage macula degeneration with bilateral disciform scars. There was no evidence of retinal detachment. Prior reports of Smith-Magenis syndrome mention telecanthus, ptosis, strabismus, iris anomalies, cataract, microcornea, optic nerve hypoplasia, myopia, retinal detachment, and lattice retinal degeneration. Bilateral macular degeneration has not been reported previously, and it may be an additional ophthalmologic manifestation of Smith-Magenis syndrome, either as a primary manifestation or as a direct consequence of high myopia.

Treatment of Graves' orbitopathy in 1990.

In a mechanical sense, we understand how the orbital changes and the symptoms of endocrine ophthalmopathy develop. Expansion of the retrobulbar tissues results in forward displacement of the globe beyond the protective cover of the eyelids. Lymphocytic infiltration, followed by fibrosis of the extraocular muscles and the eyelid retractors, leads to diplopia and corneal exposure. Glycosaminoglycans, which are water binding molecules, accumulate in the retrobulbar tissues of patients with orbitopathy and add to the bulk to the retrobulbar tissues. Proptosis at first serves to relieve retrobulbar pressure but eventually the restrictive action of the extraocular muscles and the orbital septum limits protrusion of the globe. As forward motion is restricted, pressure from the expanded tissues rises in the confined retrobulbar space, and the optic nerve may be compressed and functionally impaired. If one thinks of the central problem in orbitopathy as being a discrepancy between the volume of the bony orbit and the bulk of the tissues it is supposed to contain, then it follows that effective treatment must either shrink the swollen tissues or make more space available for them. Medical therapy attempts to shrink the swollen tissues by steroids, radiotherapy or cyclosporin. Surgery relies on making more space available for the swollen tissues and can be modified for each patient. Further rehabilitation for diplopia can be managed with prisms or extraocular muscle surgery. Non-urgent eyelid surgery follows completion of extraocular muscle surgery. Close collaboration with an interested endocrinologist is essential.

Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging.

OBJECTIVE: To demonstrate spontaneous regression of large, clinically symptomatic optic pathway gliomas in patients with and without neurofibromatosis type 1 (NF-1). METHODS: Patient cases were collected through surveys at 2 consecutive annual meetings of the North American Neuro-Ophthalmology Society (NANOS) and through requests on the NANOSNET Internet listserv. Serial documentation of tumor signal and size, using magnetic resonance imaging in 11 patients and computed tomography in 2 patients, was used to evaluate clinically symptomatic optic pathway gliomas. All tumors met radiologic criteria for the diagnosis of glioma and 4 patients had biopsy confirmation of their tumors. In 3 patients, some attempt at therapy had been made many years before regression occurred. In one of these, radiation treatment had been given 19 years before tumor regression, while in another, chemotherapy had been administered 5 years before signal changes in the tumor. In the third patient, minimal surgical debulking was performed 1 year before the tumor began to shrink. RESULTS: Spontaneous tumor shrinkage was noted in 12 patients. Eight patients did not have NF-1. In an additional patient without NF-1, a signal change within the tumor without associated shrinkage was detected. Tumor regression was associated with improvement in visual function in 10 of 13 patients, stability of function in 1, and deterioration in 2. CONCLUSIONS: Large, clinically symptomatic optic gliomas may undergo spontaneous regression. Regression was seen in patients with and without NF-1. Regression may manifest either as an overall shrinkage in tumor size, or as a signal change on magnetic resonance imaging. A variable degree of improvement in visual function may accompany regression. The possibility of spontaneous regression of an optic glioma should be considered in the planning of treatment of patients with these tumors.

Edema of the corneal stroma induced by cold in trigeminal neuropathy.

A patient with a left sensorimotor trigeminal neuropathy was found to have edema of the corneal stroma induced by cold. Examination at room temperature demonstrated an anesthetic left cornea with minimal injection of the left eye and multiple punctate epithelial erosions. Corneal thickness, mean endothelial cell size, coefficient of variation of cell size, endothelial permeability to fluorescein, and aqueous humor flow rate, measured at room temperature were similar in the two eyes. After 47 minutes in a cold room at 4 C, the corneal thickness in the left eye increased from 0.55 to 0.65 mm, whereas that of the right eye remained at 0.55 mm. During the period of maximum swelling, the left cornea had clinical stromal edema with folds in Descemet's membrane but no epithelial edema. After return to room temperature there was a gradual return to normal corneal thickness over three hours. Fluorophotometry showed no evidence of increased endothelial permeability during corneal swelling in the left eye. Specular microscopy after 15 minutes of cold exposure demonstrated many swollen and irregular endothelial cells with darkened areas between cells in the left eye. Sensory nerve deficiency in the human cornea can produce an abnormal sensitivity to cold, resulting in defective control of corneal hydration. This study suggests that this effect may be on the endothelium.

A review of 340 orbital tumors in children during a 60-year period.

We reviewed cases of histopathologically verified orbital tumors in children at our institution over 60 years to determine the distribution of various pathologic processes and trends over time. We studied the medical records and pathology specimens from 340 patients aged 18 years or younger who underwent biopsy for orbital mass from 1932 through 1991. The most common tumors were cysts (79 of 340, 23.2%), vascular lesions (60 of 340, 17.6%), optic nerve and meningeal neoplasms (56 of 340, 16.5%), inflammatory masses (29 of 340, 8.5%), osseous and fibrocystic lesions (27 of 340, 7.9%), and rhabdomyosarcomas (24 of 340, 7.1%). The overall frequency of malignancies was 18.2% (62 of 340): 11.5% (39) were primary tumors and 6.8% (23) were secondary and metastatic. The frequency of orbital malignancies was 25.4% (36 of 142) in the first 30 years (1932 through 1961) and 13.1% (26 of 198) in the second 30 years (1962 through 1991). The percentage of primary orbital malignancies was almost identical during the first and second periods (11.9% [17 of 142] and 11.1% [22 of 198], respectively). However, secondary and metastatic orbital neoplasms occurred in 13.4% (19 of 142) of the patients during the first 30 years and in only 2.0% (four of 198) during the second 30 years. The frequency of primary orbital malignancies in biopsy material remained the same over 60 years. However, the overall incidence of orbital biopsy specimens containing a malignancy decreased as a result of a reduction in the number of secondary and metastatic neoplasms that underwent biopsy.

Optic nerve sheath decompression for visual loss in patients with acquired immunodeficiency syndrome and cryptococcal meningitis with papilledema.

Visual dysfunction developing in association with acquired immunodeficiency syndrome (AIDS) can be multifactorial. Two patients with this syndrome and cryptococcal meningitis had papilledema and visual loss. Both were treated by optic nerve sheath fenestration. One patient had bilateral nonsimultaneous optic nerve sheath fenestrations; visual function improved in one eye. The other patient had bilateral visual improvement after a unilateral optic nerve sheath fenestration. Cryptococcal organisms were present in the dural sheath specimens of both patients despite ongoing therapy with antifungal medication. Postoperative orbital infectious complications did not occur. Autopsy examination of one patient showed that the sites of fenestration were patent. Medical treatment of cryptococcal meningitis associated with AIDS has a guarded prognosis. Optic nerve sheath fenestration offers a treatment alternative for papilledema and visual loss that occur with cryptococcal meningitis.