Don C. Bienfang

Ocular Manifestations of Juvenile Rheumatoid Arthritis

We followed 210 cases of JRA closely for 14 years. Thirty-six patients (17.2%) developed iridocyclitis; it most frequently occurred in young females (0-4 years) with monarticular or pauciarticular form of the disease. In 30% of the patients iridocyclitis was first detected after 16 years of age. Forty-two percent had active iridocyclitis on entry. By combining quantitative antinuclear antibody titers with age, sex, and time on onset of arthritis, it has been possible to define the risk of developing iridocyclitis in individual patients. Our approach was effective in detecting iridocyclitis in new cases and exacerbations of the disease in established cases. Forty-four percent of patients with iridocyclitis had one or more identifiable early signs or symptoms. Iridocyclitis in 36% of patients did not respond to more than 6 months of intensive topical treatment with corticosteroids and mydriatics. Despite this statistic, patients had a better outcome than those experiencing the 50% incidence of blinding complications cited in earlier studies. Cataract and band keratopathy occurred in only 19% and 11% of our group, respectively. Only one case of chorioretinopathy was found in 173 patients who had received antimalarials; a significant number of posterior subcapsular cataracts were found in 75 patients who had received systemic corticosteroids. Keratoconjunctivitis sicca developed in 3 patients with iridocyclitis. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results.

Pseudotumor Cerebri Associated With Corticosteroid Withdrawal in Inflammatory Bowel Disease

We treated two patients with Crohns disease and one patient with ulcerative colitis who developed headache, papilledema, and intracranial hypertension (pseudotumor cerebri) during corticosteroid withdrawal. One had four separate episodes with corticosteroid withdrawal, which suggested a causal relationship. This association between pseudotumor cerebri and corticosteroid withdrawal has been documented in children, but is rare in adults with inflammatory bowel disease.

A lesion of cortical area V2 selectively impairs the perception of the direction of first-order visual motion.

Lesions of area MT/V5 in monkeys and its presumed homologue, the motion area, in humans impair motion perception, including the discrimination of the direction of global motion in random dot kinematograms. Here we report the results of similar tests on patient TF, who has a discrete and very small, unilateral infarct in the medial superior part of the right occipital cortex. Structural MRI, co-registered in software with a standardized human brain atlas, reveals that the lesion involves area V2. The patient was impaired in his retinotopically corresponding left lower quadrant on several motion tasks including discrimination in random dot kinematograms of direction, speed and motion-defined discontinuity. He was also impaired on tasks selectively involving first-order motion based on luminance contrast but not on second-order motion based on texture contrast. The results show that even though area MT/V5 is intact, motion perception is abnormal and, in particular, his perception of first-order motion is impaired.

Can spatial and temporal motion integration compensate for deficits in local motion mechanisms

We studied the motion perception of a patient, AMG, who had a lesion in the left occipital lobe centered on visual areas V3 and V3A, with involvement of underlying white matter. As shown by a variety of psychophysical tests involving her perception of motion, the patient was impaired at motion discriminations that involved the detection of small displacements of random-dot displays, including local speed discrimination. However, she was unimpaired on tests that required spatial and temporal integration of moving displays, such as motion coherence. The results indicate that she had a specific impairment of the computation of local but not global motion and that she could not integrate motion information across different spatial scales. Such a specific impairment has not been reported before.

In search of a candidate pathogen for giant cell arteritis: sequencing-based characterization of the giant cell arteritis microbiome.

To characterize the microbiome of the temporal artery in patients with giant cell arteritis (GCA), and to apply an unbiased and comprehensive shotgun sequencing‐based approach to determine whether there is an enrichment of candidate pathogens in the affected tissue.

Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial

BACKGROUND: Animal and cellular studies support the importance of autophagy inhibition in lymphangioleiomyomatosis (LAM). In a cohort of subjects with LAM, we tested the hypothesis that treatment with sirolimus and hydroxychloroquine (an autophagy inhibitor) at two different dose levels is safe and well tolerated. Secondary end points included changes in lung function. METHODS: This 48‐week, two‐center phase I trial evaluated the safety of escalating oral hydroxychloroquine doses (100‐200 mg) given twice a day in combination with sirolimus to eligible patients ≥ 18 years old with LAM. Subjects received combination therapy for 24 weeks followed by an observation phase without taking study drugs for an additional 24 weeks. RESULTS: Fourteen patients provided written informed consent. Thirteen were treated in cohorts of three patients each with escalating hydroxychloroquine doses (200 and 400 mg) and an extension phase at the 400‐mg dose. The most common adverse events were mucositis, headache, and diarrhea. No drug‐related serious adverse events were reported. Secondary end points showed improvement in lung function at 24 weeks, with a decrease in lung function at the 48‐week time point. When the higher dose of hydroxychloroquine was analyzed separately, FEV1 and FVC remained stable at 48 weeks, but the 6‐min walk distance showed a decrease toward baseline. CONCLUSIONS: The combination of sirolimus and hydroxychloroquine is well tolerated, with no dose‐limiting adverse events observed at 200 mg twice a day. Potential effects on lung function should be explored in larger trials. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01687179; URL: www.clinicaltrials.gov

Loss of the ocular pulse in the acute phase of temporal arteritis.

Abstract Severe cases of temporal arteritis often have infarctions of the optic nervehead. Such cases frequently have a decrease in the amplitude of the ocular pulse. This is in contrast to cases of anterior ischemic optic neuropathy not due to temporal arteritis. In addition to aiding in the diagnosis of temporal arteritis, monitoring of the ocular pulse may help in following the course of this disease.

Clinical course and management of a consecutive series of patients with "healed temporal arteritis"

Objective. To describe the clinical course and management of patients with a pathologic diagnosis of “healed” giant cell arteritis (GCA), and to determine whether previously published histological descriptions of healed arteritis can identify patients with a greater likelihood of clinically significant arteritis. Methods. All temporal artery biopsy reports between 1994 and 2003 were examined for a diagnosis of “healed arteritis.” Two rheumatologists abstracted the medical record for presenting features, physical findings, comorbid conditions, and data on treatment and outcomes. One pathologist, blinded to the clinical data, reviewed all specimens and reinterpreted the biopsies according to published histological descriptions of healed arteritis. Results. Forty-seven patients with an initial pathologic diagnosis of healed arteritis were identified. In 54% of these patients, corticosteroid therapy did not change after the diagnosis of healed arteritis was documented in the pathology report. Seventy percent were ultimately treated with no corticosteroids or low-moderate corticosteroid regimens. Only 32% of the initial cases were confirmed upon review of the biopsies using standardized histological criteria. Patients with confirmed healed arteritis were more likely to have a documented history of polymyalgia rheumatica/GCA and a longer duration of corticosteroid treatment before biopsy. These patients were not more likely to have adverse outcomes. Conclusion. In this case series, the diagnosis of healed arteritis had little effect on treatment decisions. In most cases, the initial pathologic diagnosis of healed arteritis was not confirmed when biopsies were reviewed by a single pathologist using uniform histological criteria.

Severe electrical burn of the eye

The clinical and histopathologic findings in an 18-year-old male who sustained a severe orbital and ocular electrical burn as a result of contact with a “third rail” are described. The third rail was 600 volts positive with respect to the ground, and a maximum of 50,000 amperes was available as current. The anterior segment changes described are considered secondary to heat, as well as electrical energy; whereas the more discrete pathology in the posterior retina and optic nerve was thought to be caused by the passage of electrical current. Ocular and orbital electrical injuries of this severity have rarely been described.

A Pain in the Brain

This interactive feature presents the case of a 54-year-old woman with a history of mild, intermittent headaches who awoke from sleep with a squeezing, stabbing pain around her entire head. Test your diagnostic and therapeutic skills at NEJM.org.