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Objective: 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., Methods: Temporal artery biopsy specimens were collected from patients at a single institution over a period of 4 years, and unbiased DNA sequencing was performed on 17 formalin-fixed, paraffin-embedded specimens. Twelve of the 17 patients fulfilled the clinical and histopathologic criteria for GCA, and the other 5 patients served as controls. Using PathSeq software, human DNA sequences were computationally subtracted, and the remaining non-human DNA sequences were taxonomically classified using a comprehensive microbial sequence database. The relative abundance of microbes was inferred based on read counts assigned to each organism. Comparison of the microbial diversity between GCA cases and controls was carried out using hierarchical clustering and linear discriminant analysis of effect size., Results: Propionibacterium acnes and Escherichia coli were the most abundant microorganisms in 16 of the 17 samples, and Moraxella catarrhalis was the most abundant organism in 1 control sample. Pathogens previously described to be correlated with GCA were not differentially abundant in cases compared to controls. There was not a significant burden of likely pathogenic viruses., Conclusion: DNA sequencing of temporal artery biopsy specimens from GCA cases, in comparison with non-GCA controls, showed no evidence of previously identified candidate GCA pathogens. A single pathogen was not clearly and consistently associated with GCA in this case series., (Copyright © 2014 by the American College of Rheumatology.)

Background: Dysfunction of regulatory T (Treg) cells has been detected in diverse inflammatory disorders, including chronic graft-versus-host disease (GVHD). Interleukin-2 is critical for Treg cell growth, survival, and activity. We hypothesized that low-dose interleukin-2 could preferentially enhance Treg cells in vivo and suppress clinical manifestations of chronic GVHD., Methods: In this observational cohort study, patients with chronic GVHD that was refractory to glucocorticoid therapy received daily low-dose subcutaneous interleukin-2 (0.3×10(6), 1×10(6), or 3×10(6) IU per square meter of body-surface area) for 8 weeks. The end points were safety and clinical and immunologic response. After a 4-week hiatus, patients with a response could receive interleukin-2 for an extended period., Results: A total of 29 patients were enrolled. None had progression of chronic GVHD or relapse of a hematologic cancer. The maximum tolerated dose of interleukin-2 was 1×10(6) IU per square meter. The highest dose level induced unacceptable constitutional symptoms. Of the 23 patients who could be evaluated for response, 12 had major responses involving multiple sites. The numbers of CD4+ Treg cells were preferentially increased in all patients, with a peak median value, at 4 weeks, that was more than eight times the baseline value (P<0.001), without affecting CD4+ conventional T (Tcon) cells. The Treg:Tcon ratio increased to a median of more than five times the baseline value (P<0.001). The Treg cell count and Treg:Tcon ratio remained elevated at 8 weeks (P<0.001 for both comparisons with baseline values), then declined when the patients were not receiving interleukin-2. The increased numbers of Treg cells expressed the transcription factor forkhead box P3 (FOXP3) and could inhibit autologous Tcon cells. Immunologic and clinical responses were sustained in patients who received interleukin-2 for an extended period, permitting the glucocorticoid dose to be tapered by a mean of 60% (range, 25 to 100)., Conclusions: Daily low-dose interleukin-2 was safely administered in patients with active chronic GVHD that was refractory to glucocorticoid therapy. Administration was associated with preferential, sustained Treg cell expansion in vivo and amelioration of the manifestations of chronic GVHD in a substantial proportion of patients. (Funded by a Dana-Farber Dunkin' Donuts Rising Star award and others; ClinicalTrials.gov number, NCT00529035.).

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.

We describe psychophysical, neuropsychological and neuro-ophthalmological studies of visual abilities in a patient who, following a right hemisphere stroke, had difficulty in combining parts of objects into a whole and in reading. Strikingly, her perceptual problems were accentuated when the objects moved or when she moved. Formal testing showed that her main deficits were in depth perception, various tasks of motion and object recognition of degraded stimuli. But low-level detection and discrimination of form and color were normal. Despite her deficits in visual motion and degraded static-object recognition, her visual recognition of 'biological motion' stimuli was normal. Structural magnetic resonance imaging revealed an infarct in the ventro-medial occipito-temporal region, extending ventro-laterally and leading to a 'kaleidoscopic disintegration of visible objects'.

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.

Background: Functional vision loss is a general term used to describe vision loss not associated with organic disease. Such cases are major challenges to the practitioner and demand a special workup., Methods: Patients may manifest symptoms in typical ways that should alert the examiner to the possibility of functional vision loss. In addition, a variety of techniques help distinguish functional from organic causes of vision loss. These techniques include standard tests that yield characteristic findings in functional vision loss, as well as problem-specific procedures that have the specific aim of detecting functional vision loss. Techniques are described according to whether they are useful in monocular or binocular vision loss and in cases of moderate or severe vision loss., Results: Three cases that illustrate the use of standard and select techniques to detect functional vision loss are presented. Differential diagnosis of functional from organic vision loss and special considerations in the management of patients with functional vision loss are also discussed., Conclusions: Although it is necessary to rule out underlying pathology in all cases of vision loss, a variety of techniques can provide positive evidence of functional vision loss.

Objective: To describe two patients with mesencephalic midline clefts and associated eye movement disorders., Design: Case reports., Results: The first patient developed bilateral internuclear ophthalmoplegia with exotropia, reduced convergence, right ptosis, right fourth-nerve palsy, and right elevator palsy several years after meningitis with hydrocephalus. The second patient had bilateral internuclear ophthalmoplegia with exotropia, reduced convergence, bilateral ptosis, limited upward gaze, and right hypertropia since childhood. In both patients, magnetic resonance imaging showed a midline cleft extending from the cerebral aqueduct into the midbrain., Conclusion: It is likely that the clefts affected the oculomotor nuclei and medial longitudinal fasciculi, accounting for the eye movement disorders.

We treated two patients with Crohn's 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 7-year-old boy developed a Horner's syndrome after falling on a stick that penetrated his peritonsillar soft palate. He did not suffer from any major vascular injury, and pharmacologic testing indicated a preganglionic lesion. We review previously reported cases of oculosympathetic paresis caused by surgical and nonsurgical intra-oral trauma. Because of the proximity between sympathetic and vascular structures in the lateral and parapharyngeal space, Horner's syndrome in the setting of intra-oral trauma should prompt evaluation of the internal carotid artery. Magnetic resonance imaging may be a reasonable noninvasive method for this investigation.

A series of psychophysical tests examining early and later aspects of image-motion processing were conducted in a patient with bilateral lesions involving the posterior visual pathways, affecting the lateral parietal-temporal-occipital cortex and the underlying white matter (as shown by magnetic resonance imaging studies and confirmed by neuro-ophthalmological and neuropsychological examinations). Visual acuity, form discrimination, color, and contrast-sensitivity discrimination were normal whereas spatial localization, line bisection, depth, and binocular stereopsis were severely impaired. Performance on early motion tasks was very poor. These include seeing coherent motion in random noise (Newsome & Paré, 1988), speed discrimination, and seeing two-dimensional form from relative speed of motion. However, on higher-order motion tasks the patient was able to identify actions from the evolving pattern of dots placed at the joints of a human actor (Johansson, 1973) as well as discriminating three-dimensional structure of a cylinder from motion in a dynamic random-dot field. The pattern of these results is at odds with the hypothesis that precise metrical comparison of early motion measurements is necessary for higher-order "structure from motion" tasks.

We report a case of a 47-year-old woman with rheumatoid arthritis who developed ocular myasthenia gravis during penicillamine treatment. Her serum contained elevated titers of acetylcholine receptor antibodies, and her symptoms resolved 8 weeks after discontinuation of penicillamine. We review the clinical and laboratory features of this syndrome of penicillamine-induced myasthenia gravis and discuss its pathophysiology and treatment.

We used electrooculography to study the saccadic velocities, smooth pursuit, and vestibular ocular reflex in a patient with an acute thalamic hemorrhage. Our findings confirmed what others have shown in that there were hypometric saccades contralateral to the lesion, impaired smooth pursuit ipsilaterally, and a preserved vestibular ocular reflex. In addition, we demonstrated an asymmetry with the contralateral eye being more affected. It is also shown that the "convergence" movements seen on attempted upgaze are typical of saccades and not vergence movements. A discussion of possible pathophysiologic mechanisms with review of other studies is presented.

The ocular side effects of carmustine (a nitrosurea) are not well established. Evidence of delayed bilateral ocular toxicity developed in two of 50 patients treated with high dose intravenous (IV) carmustine (800 mg/sq m) with autologous bone marrow rescue. Symptoms or signs of ocular toxicity became apparent four weeks following IV treatment. Evidence of delayed ocular toxicity ipsilateral to the side of the infusion developed in seven of ten patients treated with intra-arterial carotid doses of carmustine to a cumulative minimum of 450 mg/sq m in two treatments. The ocular toxicity began two to 14 weeks (mean, six weeks) following intra-arterial treatment. In three of these patients, the visual loss progressed over one week to no light perception. The funduscopic manifestations of both groups included arterial narrowing, nerve fiber-layer infarcts, and intraretinal hemorrhages. Fluorescein angiography demonstrated segmental perivascular staining, wide-spread late capillary leakage, and optic disc hyperfluorescence. One patient had light and microscopic confirmation of cilioretinal artery occlusion and choroidal fibrin thrombi.

Twelve patients with pituitary tumor whose prior treatment included surgery and radiotherapy in four, surgery alone in four, radiotherapy alone in one, and none in three were studied. Nine had hyperprolactinemia, two had elevated serum growth hormones, and one had no pituitary hormone excess. Visual field defects were present in six. All had pituitary-gonadal insufficiency manifested as impotence or amenorrhea. All were tested with bromocriptine, 7.5 to 25 mg daily, and followed up for eight to 27 (mean 15) months. Serum prolactin levels decreased to normal in seven of nine patients. Serum growth hormone values were normalized in both acromegalics. When hormone levels were reduced to normal, pituitary tumor size decreased. Vision was restored to normal in five of six patients, including one patient with pituitary tumor but no pituitary hormone excess. Bromocriptine corrects the physiological defects associated with pituitary tumors that have been incompletely treated with surgery, radiotherapy, or both and may be a useful primary treatment for patients with pituitary tumors.

An unusual case of severe head trauma is reported with postoperative 'total' ophthalmoplegia of the right eye. Subsequent recovery led to an apparent transposition of right medial and right lateral rectus function. Optokinetic stimulation induced convergence nystagmus when the target was moved to the patient's left, and a divergence nystagmus when the target was moved to the patient's right. In addition, attempted lateral gaze induced ipsilateral pupillary constriction. Aberrant regeneration involving the right abducens and right oculomotor nerves is proposed as the underlying mechanism.

Optic nerve sheath meningiomas, formerly thought to be rare, have been encountered with surprising frequency since the widespread use of computed tomography. Early diagnosis led to an enthusiastic surgical approach to these lesions, but this has been tempered by the realization that even in the best of hands, blindness followed such surgery with distressing frequency. Optic nerve sheath meningiomas may be divided into primary, secondary, and multiple meningioma groups. Five patients with primary optic nerve sheath meningiomas treated with irradiation therapy are presented in this report. Improvement in visual acuity, stabilization to increase in the visual field, and decrease in size to total regression of optociliary veins, have been documented following irradiation therapy of the posterior orbital and intracanalicular portions of the optic nerve in some of these cases. Although each patient must be carefully individualized, there is no question that visual palliation can be achieved in some cases of optic nerve sheath meningioma. Further investigation of this therapeutic modality in selected cases in advised.

Partial or complete occlusion of the internal carotid artery is a familiar consequence of severe atherosclerosis seen in the elderly. Complete obstruction of both internal carotids is rare, particularly in the young or middle-aged. The rapid onset of bilateral internal carotid occlusion would be expected to produce devastating neurological sequelae and probably not be compatible with survival. We present a case of a young man with complete obstruction of both internal carotid arteries whose presenting symptoms were those of a visual field cut. The history suggests that the carotid occlusion occurred as a result of blunt trauma. The patient had no known predisposition to vascular abnormalities (no history of hypertension, hyperlipidemia, signs of systematic arteriosclerosis or vasculitis, and an unremarkable family history for vascular abnormalities). Computerized tomography revealed an infarct in his right parietal lobe. Angiography demonstrated complete occlusion of both internal carotid arteries and the right posterior communicating artery and failed to disclose the development of extensive collatorals, adding further evidence to the acuteness of the occlusion. The patient was followed by noninvasive studies and in the subsequent year showed marked neurological and ophthalmological improvement.

We have used autoradiography (tritiated leucine) to investigate the projections of a number of nuclear groups of the cat pons. Some cells of the abducens nucleus have axons that cross the midline, ascend in the opposite median longitudinal fasciculus (MLF) and synapse on the cells of the oculomotor complex which have been identified by others as those innervating the medial rectus muscle.

The research presented in this paper studied the pathway taken by the crossed fibers of the third nerve nucleus in an animal whose nucleus has been well mapped and found to correlate well with higher mammals and man. Autoradiography using tritiated amino acid labeled the cell bodies an axons of the left side of the oculomotor nucleus of the cat. Axons so labeled could be seen emerging from the ventral portion of the left nucleus through the median longitudinal fasciculus (mlf) to join the left oculomotor nerve. Labeled axons were also seen to emerge from the medial border of the caudal left nucleus, cross the midline, and pass through the right nucleus and the right mlf to join the right oculomotor nerve. These latter axons must be the crossed axons of the superior rectus and levator palpebrae subnuclei. Since the path of these crossed axons is through the caudal portion of the nucleus of the opposite side, the destruction of one lateral half of the oculomotor nucleus would result in a bilateral palsy of the crossed subnuclei. Bilateral palsy of the superior rectus and bilateral assymetrical palsy of the levator palpebrae muscles would result.

The Richner-Hanhart syndrome with tyrosinemia was recognized in a mentally retarded adolescent boy. The clinical manifestations, including hyperkeratosis of the volar aspects of the hands and feet, thickening of the conjunctival epithelium, and corneal opacities, as well as biochemical aberrations of tyrosine metabolism, responded to specific treatment with a diet low in phenylalanine and tyrosine. Light and electron microscopical studies illustrate the underlying conjunctival pathologic changes.

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 passage of electric current. Ocular and orbital electric injuries of this severity have rarely been described.

We followed 210 cases of juvenile rheumatoid arthritis closely for eleven years. Thirty-six of the 210 patients (17.2%) developed iridocyclitis. Iridocyclitis was seen most frequently in young female patients (0 to 4 years) with the monoarticular or pauciatricular form of the arthritis. However, 30% of the patients developed uveitis after 16 years of age. Although 61% of patients had a noncontributory ocular history on entry, 42% had active uveitis on entry. Our approach was effective in detecting uveitis in new cases and exacerbations of uveitis in established cases. Forty-four percent of patients with uveitis had one or more identifiable signs or symptoms, such as red eye, ocular pain, decreased visual acuity, or photophobia, in order of decreasing frequency. Even after early detection and prompt treatment, 41% of cases of uveitis did not respond to more than six months of intensive topical treatment with corticosteroids and mydriatics. Despite this, there was a dramatic decrease in the 50% incidence of blinding complications of uveitis cited in earlier studies. Cataract and band keratopathy occurred in only 22 and 13% of our group, respectively. We used chloroquine or hydroxychloroquine in 173 of 210 cases and found only one case of chorioretinopathy attributable to these drugs. Systemically administered corticosteroids were used in 75 of 210 cases; a significant number of posterior subcapsular cataracts was found. Typical keratoconjunctivitis sicca developed in three of the uveitis cases. This association with uveitis and JRA was not noted previously. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results.

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.