Risk factors for developing multiple sclerosis after childhood optic neuritis.

We reviewed the records of all children (younger than 16 years of age) who presented with a diagnosis of optic neuritis (ON) identified through the comprehensive records-linkage system at the Mayo Clinic and identified 94 cases between 1950 and 1988 with a documented history of idiopathic ON. Detailed follow-up information was available on 79 patients, with a median length of follow-up of 19.4 years. Life-table analysis showed that 13% of the 79 patients with isolated ON had progressed to clinically or laboratory-supported definite multiple sclerosis (MS) by 10 years of follow-up, 19% by 20 years, 22% by 30 years, and 26% by 40 years. Gender, age, funduscopic findings, visual acuity, or family history of either ON or MS did not predict the development of MS. The presence of bilateral sequential or recurrent ON increased the risk of developing MS (p = 0.002; hazard ratio = 5.09), whereas the presence of infection within 2 weeks before the onset of ON decreased the risk of developing MS (p = 0.060; hazard ratio = 0.24). This study of childhood ON supports the lower risk of recurrence and progression to MS compared with adults.

A randomized trial of intravenous immunoglobulin in inflammatory demyelinating optic neuritis.

OBJECTIVE: To determine whether IV immunoglobulin (IVIg) reverses chronic visual impairment in MS patients with optic neuritis (ON). METHODS: In this double-blind, placebo-controlled Phase II trial, 55 patients with persistent acuity loss after ON were randomized to receive either IVIg 0.4 g/kg daily for 5 days followed by three single infusions monthly for 3 months, or placebo. RESULTS: The trial was terminated by the National Eye Institute because of negative results when 55 of the planned 60 patients had been enrolled. Fifty-two patients completed the scheduled infusions, and 53 patients completed 12 months of follow-up. Analysis of this data indicated that a difference between treatment groups was not observed for the primary outcome measure, improvement in logMAR visual scores at 6 months (p = 0.766). Exploratory secondary analyses suggested that IVIg treatment was associated with improvement in visual function (including logMAR visual scores at 6 months and visual fields at 6 and 12 months) in patients with clinically stable MS during the trial. CONCLUSIONS: IVIg administration does not reverse persistent visual loss from ON to a degree that merits general use.

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.

Xp22.3 microdeletion syndrome with microphthalmia, sclerocornea, linear skin defects, and congenital heart defects.

We report on an infant girl with congenital erythematous, linear skin lesions on face and neck, bilateral microphthalmia, sclerocornea, cataracts, and a complex cardiac anomaly including atrial septal and ventricular septal defects. This patient had an Xp22.3 microdeletion and a chromosome satellite on the abnormal X p-arm. The abnormal X chromosome was late replicating in peripheral blood lymphocytes and cultured skin fibroblasts. Four other patients with similar congenital anomalies and Xp deficiency have been reported previously and are compared with this patient. One patient had an interstitial or terminal deletion, but in others the material translocated to Xp22.3 was variable (Yq material in two patients, and Yp material and an unidentifiable satellite in one patient each). Several mechanisms are suggested by which this chromosome abnormality might produce this phenotype in these patients. Our patient is the first with this syndrome to have a congenital heart defect.

Hypertensive retinopathy mimicking neuroretinitis in a twelve-year-old girl.

Bilateral disk swelling and marked peripapillary and macular exudates were found on routine ophthalmologic examination in a 12 1/2-year-old girl. Eleven months later, with persistent findings, her blood pressure was found to be extremely elevated. She had an Ask-Upmark kidney, a rare form of segmental renal hypoplasia. The Ask-Upmark kidney abnormality occurs primarily in young women and is associated with hypertension. The disk edema and retinopathy resolved after the hypertension was controlled. Hypertensive retinopathy can sometimes resemble neuroretinitis.

Intracranial plasma cell granuloma presenting as an optic neuropathy.

A 40-year-old man presented with a left optic neuropathy. Magnetic resonance imaging demonstrated a contrast-enhancing mass along the course of the left trigeminal nerve and in the region of the left cavernous sinus with suprasellar extension. Preoperatively, he had a serum polyclonal gammopathy. Pathologic diagnosis was an intracranial plasma cell granuloma. The patient responded to high-dose steroids with resolution of his optic neuropathy, marked decrease in the size of the mass, and resolution of the serum polyclonal gammopathy. Intracranial plasma cell granuloma is a rare lesion; only 11 cases have been described in the literature. Almost half of the patients presented with vision loss as their chief complaint.

Incidence of nonarteritic anterior ischemic optic neuropathy.

PURPOSE: Nonarteritic anterior ischemic optic neuropathy is the most common acute optic nerve disease of adults over age 50 years. This study determined the incidence of acute nonarteritic anterior ischemic optic neuropathy in the circumscribed population of Olmsted County, Minnesota. METHODS: This was a retrospective study of the incidence of acute nonarteritic anterior ischemic optic neuropathy between 1981 and 1990. The Rochester Epidemiology Project medical records linkage system facilitates identification of the medical records of virtually all Olmsted County residents with a given diagnosis. All cases of acute nonarteritic anterior ischemic optic neuropathy that fulfilled certain inclusion and exclusion criteria were identified. RESULTS: Twenty-two cases in 21 patients (11 men and 10 women) were recorded. The crude annual incidence rate was 10.3 per 100,000 individuals (95% confidence interval [CI] = 5.1 to 18.4). When adjusted to the age and sex distribution of the 1990 United States white population, the incidence rate was 10.2 per 100,000 (95% CI = 6.5 to 15.6). At diagnosis, the median age was 72 years, mean visual acuity was 20/200 in the affected eye, and the most common visual field defect was an altitudinal deficit (10 cases). CONCLUSIONS: Although results of this small study should be interpreted cautiously, extrapolation of our findings to the United States white population indicates that nearly 5,700 new cases of acute nonarteritic anterior ischemic optic neuropathy may be expected to occur each year in this group.

Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients.

OBJECTIVE: To determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery. METHODS: One hundred ninety consecutive patients with 206 meningiomas underwent radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20-90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1-5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm(3) (range, 0.5-50.5 cm(3)), and the median tumor margin dose was 16 Gy (range, 12-36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively. RESULTS: Overall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications. CONCLUSION: Radiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.

Wegener's granulomatosis presenting as dacryoadenitis.

Wegener's granulomatosis is a life-threatening condition characterized by the triad of necrotizing granulomatous inflammation of the respiratory tract, vasculitis, and glomerulonephritis. During early stages of the disease, some patients may present with only one or two components of the triad. Other patients may be affected by the limited form of Wegener's which lacks the renal involvement. We report an 18-year-old female who initially presented with bilateral dacryoadenitis. A lacrimal gland biopsy was consistent with Wegener's granulomatosis. A few months later she developed glomerulonephritis and responded well to cyclophosphamide treatment. Wegener's granulomatosis remains a diagnostic challenge and is frequently underdiagnosed. Early diagnosis is crucial in saving many lives because the disease is potentially curable with cytotoxic therapy. Dacryoadenitis may be one of the initial presentations of Wegener's granulomatosis.

Reproducibility of the catecholamine response to serial exercise testing in normals.

Plasma norepinephrine (NE) and epinephrine (E) increase with exercise but the reproducibility of their response to short-term serial exercise testing has not been established. Therefore, NE and E were measured at rest, 6 minutes, peak exercise, and 5 minutes postexercise in 10 normal subjects undergoing three identical exercise tolerance tests within 4-13 days. Norepinephrine and E were also measured in tests 2 and 3 at the time equivalent to the peak exercise duration in test 1 (peak--equivalent). Exercise duration increased slightly from test 1 (15.6 +/- 0.7 min) to test 2 (16.5 +/- 0.5 min; p = 0.07) but no further on test 3 (16.2 +/- 0.9 min). Norepinephrine and E did not differ across the three tests at rest, 6 minutes, peak test or posttest, but a significant decrease in both NE and E was seen at peak-equivalent by test 3 (p less than 0.05). Heart rate decreased across the three tests at 3, 6, 9, and 12 minutes (p less than 0.02 for each) and peak equivalent (p less than 0.005) but was unchanged at rest, peak exercise and postexercise. Thus, plasma catecholamines and heart rate decrease at high levels of exercise with repeated, short-term exercise testing, possibly due to familiarity with the protocol. These results suggest that control groups are important when measuring the effects of short-term pharmacologic intervention by serial exercise tests.

Systemic amyloidosis with temporal artery involvement mimicking temporal arteritis.

A 77-year-old man presented with jaw claudication, arthralgias and myalgias, weight loss, marked fatigue, and thickened temporal arteries. No vasculitis was seen on the temporal artery biopsy specimen, but amyloidosis was suspected and confirmed with Congo red staining. Subsequent bone marrow biopsy revealed multiple myeloma. Although the patient initially was thought to have temporal arteritis, the results of temporal artery biopsy directed further investigations that led to the diagnosis of systemic amyloidosis. Systemic amyloidosis should be considered in the differential diagnosis when patients, especially men, present with clinical findings suggestive of temporal arteritis but without evidence of vasculitis in temporal artery biopsy specimens.

Myasthenia gravis with a paraneoplastic marker.

Ocular manifestations of myasthenia gravis are very common. Myasthenia gravis may be associated with lung carcinoma. Lambert-Eaton syndrome is also commonly associated with lung carcinoma and can have ocular manifestations. Overlap of these two entities has been described. The case of a patient with fatigable diplopia and ptosis 3 years after removal of a large-cell lung carcinoma is presented. Tests results for acetylcholine receptor binding and modulating antibodies were positive for myasthenia gravis. Test results for presynaptic voltage-gated calcium channel antibodies of the N-type were also positive. However, test results for the P/Q-type voltage-gated calcium channel antibodies, which are consistent with Lambert-Eaton syndrome, were negative. Autoantibodies can be used to serologically distinguish paraneoplastic myasthenia gravis from Lambert-Eaton syndrome.

Cost-effectiveness in the diagnosis of sarcoidosis: the conjunctival biopsy.

PURPOSE: Sarcoidosis is a multi-system disease that often affects ocular structures. The definitive diagnosis of sarcoidosis requires tissue biopsy for confirmation. Conjunctival biopsy is a simple and relatively inexpensive diagnostic tool. This study was undertaken to determine the utility and cost of conjunctival biopsy for the diagnosis of sarcoidosis compared with other diagnostic biopsy sites. METHODS: A retrospective study was performed of all conjunctival biopsies taken for sarcoidosis at the Mayo Clinic Rochester between 1982 and 1995. All case histories were reviewed. Data regarding biopsy of tissues confirming sarcoidosis was collected. The costs of performing and evaluating all biopsy techniques were obtained from the estimating department. RESULTS: Forty-one cases of sarcoidosis were identified that had undergone conjunctival biopsies. Twenty-one patients had a positive conjunctival biopsy for sarcoidosis, and 20 patients had a negative conjunctival biopsy but a positive biopsy of another organ. In all positive biopsies, special stains for acid fast organisms and fungi were negative. CONCLUSIONS: Conjunctival biopsy is a simple, relatively inexpensive procedure that may be helpful in establishing the diagnosis of sarcoidosis with a negligible complication rate. Positive results are similar for conjunctival biopsy and mediastinoscopy. About 10 patients can be evaluated with conjunctival biopsy for the cost of one patient undergoing mediastinoscopy. Multiple levels of the tissue must be examined, as distribution of the granulomas may be random. Also, bilateral conjunctival specimens should be obtained to increase the positive yield.

Internuclear ophthalmoplegia in sickle cell trait.

An 8-year-old boy presented with symptoms compatible with a right internuclear ophthalmoplegia. Magnetic resonance imaging showed a high-intensity signal on T2-weighted images at the level of the medial longitudinal fasciculus. Laboratory evaluation was positive only for sickle cell trait. Sickle cell trait is an uncommon cause for brainstem infarction.

Direct observation of myelination in vivo in the mature human central nervous system. A model for the behaviour of oligodendrocyte progenitors and their progeny.

We studied patches of CNS myelin in human retina in vivo to determine the pattern of myelination and the local influence of axons. We analysed the position, area and thickness of the nerve-fibre layer in 60 patches of retinal myelin in 47 eyes (in 37 adults and two adolescents). Five patches in four eyes were studied serially over 6-11 years. Nerve-fibre layer thickness was obtained from an atlas of primate retina, and volumes of myelinated tissue were then estimated for each patch. Retinal myelination occurred in three patterns: thick patches contiguous with the optic disc (type I); thin, striated patches detached from the disc (type II); or massive myelination of the posterior pole associated with severe amblyopia (type III). The papillomacular bundle did not myelinate in types I and II and was relatively spared in type III patches, suggesting that migratory oligodendrocyte progenitors are not supported by these axons. The local nerve-fibre layer determined patch size, and quantal myelination was evident with modal peaks of patch volume at 0.16 and 0.64 mm3. Myelination advanced at patch edges when observed over time, consistent with the hypothesis that new oligodendrocytes are produced in adulthood. We propose a theoretical model where patches of retinal myelination are the clonal progeny of a few oligodendrocyte progenitors exhibiting two different behaviours. First, a highly migratory, nonmyelinating progenitor uses larger, phylogenetically older axons as the substrate for movement. Secondly, a more mature progenitor generates myelinating oligodendrocytes well into adult life, but traverses only short distances. Using this data, we can estimate the number of oligodendrocytes in these clones and population doubling-time. This study supports a role for axon-derived signals in the regulation of human oligodendrocyte progenitor behaviour and myelination in vivo.

Steroid treatment of radiation-induced choroidopathy.

Irradiation has been an important form of treatment of both ocular and cerebral neoplasms for decades. We report the case of a patient who underwent external beam irradiation to treat an astrocytoma of the left parietotemporal region. Sixteen months later, the patient developed radiation choroidopathy OS. Although not spontaneously resolvable, this case suggests that radiation choroidopathy can be treated successfully by the prompt and repeated application of both local and systemic corticosteroid preparations.

Ophthalmic manifestations of vertebral artery dissection. Patients seen at the Mayo Clinic from 1976 to 1992.

PURPOSE: To determine the ophthalmic manifestations of vertebral artery dissections. METHODS: Fifty-one separate episodes of vertebral artery dissections evaluated at the Mayo Clinic from 1976 through 1992 were studied. In all cases, the diagnosis had been documented with angiography. RESULTS: There were 28 men and 19 women (mean and median age, 39 and 40 years, respectively; range, 8-61 years). There were ophthalmic findings in 86% of the episodes. Visual symptoms, in decreasing order of frequency, were diplopia (45% of the episodes), blurred vision (14%), transient visual dimming (8%), oscillopsia (4%), photophobia (4%), upside-down vision (2%), positional transient visual obscuration (2%), and unilateral dry eye (2%). Ophthalmic signs in decreasing order of frequency were nystagmus (37% of the episodes), ocular misalignment (cranial nerve palsy or skew) (33%), Horner syndrome (27%), decreased corneal sensation (22%), ptosis (16%), visual field defect (10%), abnormal pursuits and saccades (6%), ocular bobbing (4%), internuclear ophthalmoplegia (4%), anisocoria (4%), and pinpoint pupils (2%). CONCLUSION: Vertebral artery dissections occur in a relatively young population. Most of the patients in our study had ophthalmic manifestations at the time of diagnosis. Heightened awareness of this entity should enable the consulting ophthalmologist to have a role in the diagnosis and treatment of vertebral artery dissection.

Carotid cavernous fistula associated with persistent primitive trigeminal artery.

A patient with diplopia had a carotid cavernous fistula associated with a persistent primitive trigeminal artery that was seen with angiography. Balloon occlusion of the carotid cavernous fistula resulted in flow stasis of the persistent primitive trigeminal artery and resolution of the symptoms. Persistent primitive trigeminal artery may be associated with a carotid cavernous fistula.