Objective N/A. Background Neurochondrin is a cytoplasmic neuronal antigen that can be targeted by specific antibodies, resulting in an antigen-specific T-cell response and autoimmune cerebellar and brain stem degeneration.1 Previously reported cases of neurochondrin antibody positivity have been predominantly associated with rapidly-progressive rhombencephalitis, but various other neurological symptoms and signs may be present.1,2 Design/Methods N/A. Results 34-year-old woman presented with 2 years of constant numbness in her toes, gradually worsening to involve the entire lower and upper extremities. She also reported dysarthria, imbalance, and leg spasticity. Neurological examination showed a slow, wide-based gait, brisk reflexes bilaterally, and bilateral extensor plantar responses. MRI brain was normal and CSF analysis showed 7 oligoclonal bands. The patient was diagnosed with probable multiple sclerosis and steroids were initiated but resulted in no improvement of symptoms. Plasmapheresis was also ineffective. 3 months later, MRI showed subtly increased T2 signal of the central cord mainly involving the gray matter at the level of C5 and C6. CSF analysis showed 15 oligoclonal bands and an elevated IgG index of 1.39. VDRL was nonreactive. HTLV, ANCA, AQP4, CSF VZ PCR, HSV PCR, and HHV6 PCR were all negative. EMG showed mild length-dependent axonal sensory motor peripheral neuropathy. On neuro-ophthalmic examination, the patient showed slowed saccades with some preservation of optokinetic nystagmus (OKN) fast phases. Repeat MR showed abnormal T2 hyperintensity in the anterior horns of the gray matter from C1-2 to T1. Serum testing at that time showed a positive neurochondrin antibody. She was then started on cyclophosphamide and mycophenolate mofetil. 6 months after initiation of cyclophosphamide, dysarthria and upper limb mobility improved, and she had no further neurological deterioration at that time. Conclusions Neurochondrin IgG-related autoimmunity is rare and can result in a wide variety of neurological signs and symptoms. Ocular dysmotility, including slowed saccades, may be present.

Perioperative posterior ischemic optic neuropathy (PION) is a rare but potentially devastating condition. A correlation of PION with major surgical procedures has been established, particularly in cases of spine and cardiovascular surgery. The present case report describes a 72-year-old, male patient who developed PION after open aortic surgery, subsequently partially recovering from his visual deficit, which is an atypical feature for PION. Preventive measures as well as improvement of this condition's management depend on understanding its risk factors.

Disease terminology should convey an accurate and understandable picture, ideally with corresponding prognostic, therapeutic, and pathophysiologic utility.

The role of vitamin A-associated organic compounds such as retinol and retinoic acid in retinal photoreceptor metabolism is well understood. Vitamin A plays an important role for corneal and conjunctival development, prevention of xerophthalmia, and central nervous system function. Further properties of vitamin A and its metabolism are still unclear and subject to research [1]. Uptake from food sources and distribution is dependent of intact fat absorption mechanisms and cofactors such as retinol-binding protein [2]. Deficiency of vitamin A is the most common preventable cause of blindness in children and is associated with high mortality and morbidity in developing countries where the WHO is committed to treatment and prevention programs [3]. In industrialized countries, bariatric surgery has become an established treatment for obesity. Most of these procedures lead to the malabsorption of micro- and macronutrients and regular control, and substitution of vitamins and substrates is mandatory. However, a lack of regular substitution (i.e., when patients are non-adherent to treatment or lost to follow-up) can lead to severe vitamin deficiency states as shown in the following two case reports.

A 78-year-old woman with a history of hypertension and hypercholesterolemia presented with increasing shoulder, neck, and head pain. She described weight loss and listlessness. In the context of a CRP of 45 mg/L, her primary care doctor started the patient on prednisone 60 mg daily dosage. The pain subsided promptly, her CRP normalized, and she regained her original weight. Prednisone dosage was tapered slowly over a period of 3.5 months. As the daily dosage of prednisone reached 5 mg, she began to experience intermittent double vision [Fig. 1]. The prednisone daily dosage was increased to 25 mg. She was seen by neuro-ophthalmology 4 months after she had begun corticosteroid therapy, she was diagnosed with an abducens paresis, and a biopsy of the temporal artery was performed [Fig. 2]. It showed high-grade arteritis changes as well as multiple giant cells consistent with the acute stage of giant cell arteritis (GCA).

A 48-year-old man complained of tunnel vision after he experienced a cardiac arrest with out-of-hospital resuscitation. Best-corrected visual acuities were 20/15 OD and OS. Pupil responses were unremarkable. Goldmann perimetry showed bilateral homonymous hemianopia with central sparing and presence of temporal crescents (figure 1). Funduscopic examination was normal OU. MRI demonstrated bilateral posterior watershed infarctions (figure 2). This particular visual field pattern with sparing of 2 visual field regions located on opposite anatomic poles in the visual cortex is rare1 and presumably results from vascular redundancy and sparing of the anterior and posterior most aspects of the calcarine cortex.2

Background: Recurrent optic neuritis (rON) associated with myelin oligodendrocyte glycoprotein (MOG)-specific antibodies has been initially reported to show a better clinical outcome than aquaporin-4 (AQP4)-seropositive ON in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterize clinical and neuroimaging findings in severe cases of MOG antibody–positive and AQP4 antibody–negative bilateral rON. Methods: Three male adults with rON (ages 18, 44, and 63 years) were evaluated with optical coherence tomography (OCT), MRI, cerebrospinal fluid (CSF), and serological studies. Results: All patients experienced >7 relapses of ON with severe reduction of visual acuity and partial response to steroid treatment. Optic nerves were affected bilaterally, although unilateral relapses were more frequent than simultaneous bilateral recurrences. Patients were MOG-seropositive but repeatedly tested negative for AQP4 antibodies. OCT showed severe thinning of the peripapillary retinal nerve fiber layer. On MRI, contrast-enhancing lesions extended over more than half the length of the optic nerve. CSF analyses during ON episodes were normal. Severe visual deficits accumulated over time in 2 of 3 patients, despite immunosuppressive therapy. Conclusions: MOG-seropositive and AQP4-seronegative rON may be associated with an aggressive disease course and poor functional and structural outcomes. In contrast to previous reports, the severity and pattern of retinal and optic nerve damage closely resembled phenotypes commonly observed in AQP4-seropositive rON without fulfilling current diagnostic criteria for NMOSD.

Retinal optical coherence tomography (OCT) has recently become a vital tool for clinicians and researchers in ophthalmology and, increasingly, in neurology. Optical coherence tomography is quickly and easily performed, well-tolerated by patients, and allows high-resolution viewing of unmyelinated axons and other retinal structures in vivo. These factors have led OCT to find favor as a method of quantifying neuroaxonal loss in multiple sclerosis (MS), and the increasing acceptance of the anterior visual pathway as a model to investigate MS in humans.In this short review, the authors discuss OCT findings in MS research, and the relationships of these structural findings with established functional outcome measures such as visual acuity and electrophysiological examinations. The utility of OCT in patients with acute optic neuritis is emphasized. Optical coherence tomography is a particularly powerful tool when the individual retinal layers are visualized and quantified following the segmentation of scans; this technique shows promise as a method for defining novel MS phenotypes.

Cognitive operations can be detected by reduction of the pupillary light response. Neurophysiological pathways mediating this reduction have not been distinguished. We utilized selective blockade of pupillary sphincter or dilator muscles to isolate parasympathetic or sympathetic activity during cognition, without modifying central processes. Pupil diameter was measured during the light reaction in 29 normal adults under three processing levels: No Task, during an easy task (Add 1), or a difficult task (Subtract 7). At three separate sessions, the pupil was treated with placebo, tropicamide (blocking the muscarinic sphincter receptor), or dapiprazole (blocking the adrenergic dilator receptor). With placebo, pupil diameter increased with increasing task difficulty. The light reaction was reduced only in the Subtract 7 condition. Dapiprazole (which decreased overall diameter) showed similar task-related changes in diameter and light reflex as for placebo. Following tropicamide (which increased overall diameter), there was a further increase in diameter only in the difficult task. Findings suggest two separate inhibitory components at the parasympathetic oculomotor center. Changes in baseline diameter are likely related to reticular activation. Inhibition of the light reaction in the difficult task is likely associated with cortical afferents. Sustained sympathetic activity also was present during the difficult task.

The patient was a 58-year-old woman with left eye ptosis and vision loss. The patient had a history of Wegener's granulomatosis (WG) first diagnosed in 1995, 13 years before her presentation with the current illness. Her WG had been characterized by a migratory, pauciarticular arthritis; leukocytoclastic vasculitis of the skin; elbow nodules caused by cutaneous extravascular necrotizing granulomata (Churg-Strauss granulomas) (Figure 1); biopsy-proven pauci-immune glomerulonephritis; and necrotizing pulmonary vasculitis. The patient had been treated virtually continuously between 1995 and 2008 with a variety of agents, including several courses of high-dose glucocorticoids, oral cyclophosphamide, and azathioprine. Churg-Strauss granulomas. Cutaneous extravascular necrotizing granulomas are present on the patient's elbows (A), and knee (B) 4 months before presentation. The patient presented to the Rheumatology Clinic with symptoms for 2 weeks of impaired vision in her left eye and drooping of the left eyelid. In addition, the patient noted that she had had frequent low-grade migraine headaches for at least 6 months. The headaches had worsened over the 2 weeks that preceded her clinic visit and were accompanied by nausea, vomiting, and pain in the region of her left cheek. The headaches were cyclical in nature, worsening one day but subsiding the next. The patient believed that each headache cycle was accompanied by worsening of vision in the left eye and more severe drooping of her left upper eyelid. The patient denied any history of migraine headaches. The patient had had 2 similar episodes of vision loss in the left eye within 6 months of her presentation. On both occasions, she had presented with amaurosis fugax and vision loss in the left eye. She had been admitted to an outside hospital, undergone magnetic resonance imaging (MRI) studies that had been read as negative, and received the diagnosis of optic neuropathy secondary to WG. During both hospital admissions, the patient had been treated with methylprednisolone 1 gm/day for 3 days, with resolution of her headaches and subjective improvement in her vision. One month after her second admission for ocular dysfunction, the patient was evaluated as an outpatient by the Neuro-ophthalmology Service at our hospital. At that time, the patient was found to have normal afferent visual fields in both eyes except for a residual inferior arcuate scotoma in the left eye. WG had been diagnosed when the patient was age 45 years. Her most recent disease flare before the presumed optic neuropathy had occurred 2 years before presentation, at which time she had developed pulmonary infiltrates and undergone a lung biopsy that showed necrotizing, granulomatous inflammation. Over the previous 13 years, she had been treated with combinations of prednisone, azathioprine, and cyclophosphamide. She had no history of glucose intolerance. At the time of her hospitalization, she was receiving prednisone 10 mg/day. In addition, 3 months before admission she had undergone a course of treatment with rituximab (2 1-gm infusions separated by 2 weeks). This treatment had led to the depletion of circulating B cells. The patient was receiving trimethoprim/sulfamethoxazole as prophylaxis against Pneumocystis jiroveci pneumonia. The patient's family history was negative for rheumatic diseases, cancer, and ophthalmologic problems. She was receiving disability at the time of admission but had previously worked in social services, delivering meals to the elderly. She lived with her husband and had no children. She had an 18 pack-year smoking history and smoked approximately 10 cigarettes per day. She rarely drank alcohol. Her travel history was remarkable for a trip to Florida 10 months earlier, but otherwise she had traveled little outside of New England. The patient reported sinus congestion on the left side that was worse at night. She denied any bloody noses or nasal crusting, ocular erythema, oral ulcers, fevers, chills, neck stiffness, photophobia, hearing changes, cough, rhinorrhea, sore throat, or weakness. Upon admission to the floor, the patient had a temperature of 97.0°F. Her pulse was 108/minute and her blood pressure was 135/79 mm Hg. She was breathing at a rate of 20/minute and her oxygen saturation was 92% on room air. She was a thin woman who appeared older than her stated age. She had an obvious left ptosis. There was no tenderness over her frontal or maxillary sinuses and no neck stiffness. Her dentition was normal. The tympanic membranes and hearing were normal. No cervical or supraclavicular adenopathy was present. Examination of her heart revealed a normal S1 and S2 with no murmurs, rubs, or gallops. Her lungs were clear and her abdomen soft, without hepatosplenomegaly or masses. The radial and pedal artery pulses were normal. She had thin, fragile skin but no rash. The previous Churg-Strauss granulomas over the elbows and knees were not evident. Upon neurologic examination, the patient's pupils were both 4.5 mm in dim light, but the left pupil was poorly reactive and demonstrated an afferent pupillary defect. In addition to her left ptosis, the patient had severely impaired elevation, depression, abduction, and adduction of the ipsilateral eye, consistent with paresis of the left oculomotor (III), trochlear (IV), and abducens (VI) cranial nerves. Facial sensation was intact, with the exception of slightly impaired sensation in the distribution of the ophthalmic division of the left trigeminal nerve (V1). The patient was only able to detect the movement of large objects in the peripheral visual field of the left eye. The visual acuity and ocular movements of the right eye were normal, as was the remainder of the neurologic examination. The patient's erythrocyte sedimentation rate was 86 mm/hour (normal value <20) and her serum C-reactive protein level was 37.6 mg/liter (normal value <8.0). The serum creatinine and hematocrit levels were 1.1 mg/dl and 34.5%, respectively. The peripheral white blood cell count was 9,500/mm3. Other laboratory results are shown in Table 1. Flow cytometry was performed to assess the status of her B cells. Computed tomography (CT) scans of the brain, sinuses, and chest were performed. The brain and sinus CT scans demonstrated complete opacification of the left maxillary sinus with signs of chronic inflammatory changes (Figure 2A). The Otolaryngology Service performed a rigid fiberoptic examination that revealed no evidence of a bacterial or fungal infection in the nose. The left middle meatus was swabbed for cultures, which were negative for bacteria and fungi. A chest CT scan revealed multiple cavitary and non-cavitary lesions in all lung lobes, some with surrounding “ground glass” opacity (Figure 2B). A, Computed tomography (CT) scan of the sinuses shows complete opacification of the left maxillary sinus and signs of chronic inflammatory change. B, CT scan of the chest shows multiple cavitary and non-cavitary lesions in all lung lobes, some with surrounding “ground glass” opacity. MRI and MR venogram studies showed patent cavernous sinuses, but the tentorial and falcine dura had increased fluid-attenuated inversion recovery signal and enhanced abnormally following gadolinium administration (Figure 3). There was also a subtle signal abnormality in the left orbital apex (Figure 4). A lumbar puncture was performed. The cerebrospinal fluid (CSF) protein level was 61 mg/dl (normal range 15–45). Tubes 1 and 2 had 12 and 9 white blood cells, respectively, with a lymphocytic predominance. There were no red blood cells in the CSF. Coronal view of a T1-weighted magnetic resonance imaging study of the brain reveals increased fluid-attenuated inversion recovery signal in the falx. Subtle signal within the apex of the cavernous sinus. A serum assay for antineutrophil cytoplasmic antibodies (ANCAs) was positive by indirect immunofluorescence. An enzyme immunoassay for antibodies directed against proteinase 3 was positive at 326 units (normal value <20). This had increased from 102 units only 1 month before her admission. Antibodies to myeloperoxidase were negative, as was an assay for antibodies to Borrelia burgdorferi, a rapid plasma reagin assay, and blood cultures. A 58-year-old woman with a history of WG and 2 prior episodes of glucocorticoid-responsive left optic neuropathy presented with headaches, a central scotoma of the left eye, and cranial nerve dysfunction involving the left third, fourth, fifth, and sixth nerves. She had a lymphocytic pleocytosis in her CSF and multiple abnormalities on imaging studies of her sinuses, lungs, and meninges. The patient's left eye vision loss and cranial nerve abnormalities were consistent with localization of the lesion to the orbital apex (Figure 5). She was diagnosed as having an orbital apex syndrome. Orbital apex syndromes are constellations of neurologic findings that result from dysfunction of the optic, oculomotor, and abducens nerves, as well as involvement of the ophthalmic division of the trigeminal nerve. Some patients also have involvement of the vascular supply and drainage of the posterior orbital regions, the sympathetic innervation of the orbit, and the sensory nerves that supply the forehead. Orbital apex syndromes result from a variety of pathologic processes that lead to crowding or infiltration of the structures within the orbital apex. The cavernous sinus and orbital apex, with the location of the inflammatory lesion indicated. (Figure courtesy of Dr. John Stone.) The major diagnostic considerations for an orbital apex syndrome in an immunosuppressed patient are an opportunistic infection, a neoplasm, thrombosis of the cavernous sinus, or a space-occupying lesion of some other type (Table 2). We consider each of these major diagnostic possibilities in turn. Infections are common and potentially life-threatening complications of the treatment of WG. Indeed, infectious complications of therapy are now more likely to lead to death in this disorder than WG is itself (1). It is therefore essential to consider a broad differential of infectious etiologies and to approach the patient with a thoughtful diagnostic evaluation before initiating any immunosuppressive treatment. This patient's chronic course of WG and the consequent need for years of immunosuppression placed her at particular risk for an opportunistic infection. Moreover, damage to her sinuses and lungs from previous periods of active WG had created potential sites at which opportunistic microbes might thrive. The proximity of the maxillary sinus to the orbital apex was consistent with the spread of infection into the cavernous sinus from a focus within the sinuses. Cavitary pulmonary lesions are among the classic lung findings in WG but are also highly typical of a number of mycobacterial and fungal infections. Organisms commonly involved in cavernous sinus infections include Mucormycosis, Aspergillus, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Actinomyces, Treponema pallidum, herpes zoster, gram-negative bacilli, and anaerobes (2). Many patients with fungal rhinosinusitis are immunocompromised or have diabetes mellitus as an underlying risk factor. As an example, diabetes mellitus is a notorious predisposing condition for Mucormycosis infections. However, patients do not have to be overtly immunocompromised in order to develop a serious rhinosinusitis infection. The condition known as allergic fungal rhinosinusitis is a chronic disorder that can develop in immunocompetent individuals (3, 4). The lymphocytic pleocytosis and the meningeal enhancement on the MRI findings were concerning for the possibility of an infection in the orbital apex that had extended into the CSF. Our patient had negative sinus cultures and a negative rapid plasma reagin test result. In addition, her sinuses had been visualized by the Otolaryngology Service, which deemed the likelihood of infection low. Moreover, the patient's sinus imaging was also not consistent with an acute, invasive sinusitis. Nasopharyngeal cancer, lymphoma, pituitary adenoma, meningioma, and metastatic disease can all cause an orbital apex syndrome (2). Our patient had been treated intensively with cyclophosphamide and azathioprine, both of which are associated with secondary malignancies (5). Her previous hospital admissions for optic neuropathy might have been caused by a secondary malignancy that had regressed following high-dose glucocorticoid treatment. A lymphoma would be particularly likely to partially respond to such therapy. However, her brain CT scan did not demonstrate any mass lesions, and flow cytometry of her CSF was negative. A septic cavernous sinus thrombosis can occur in the setting of periorbital infections, leading to an orbital apex syndrome. An aseptic cavernous sinus thrombosis can also occur in the setting of idiopathic inflammation. Patients with WG are known to be at risk for venous thrombotic events, but these events are typically deep venous thromboses of the legs, frequently complicated by pulmonary emboli (6). Cavernous sinus thrombosis, in contrast, is not a complication that is common to WG. The patient's negative MR venogram result significantly decreased the possibility of this complication (7). WG can be associated with a host of ocular and orbital complications. These include inflammatory masses within the orbit, episcleritis, conjunctivitis, granulomatous inflammation of the tarsal conjunctivae, scleritis, peripheral ulcerative keratitis, uveitis, retinitis, retinal vascular disease, optic neuropathy, and oculomotor cranial neuropathy (8-13). Optic neuropathy, which had been diagnosed in our patient within 6 months of her admission, has been reported to occur in patients with WG in multiple case reports and pathology reviews (8, 14, 15-18). The optic neuropathy in patients with WG generally occurs either in isolation or with cranial nerve palsies, meningeal involvement, or ocular manifestations that extended to other portions of the eye. Three mechanisms leading to optic neuropathy in WG have been described: compression of the optic nerve from an inflammatory mass within the orbit, granulomatous inflammation of the optic nerve itself, and anterior ischemic optic neuropathy from vascular compromise of the posterior ciliary artery. The last mechanism is analogous to the most common pathway through which patients with giant cell arteritis lose vision. It was conceivable that our patient's orbital apex syndrome had been caused by WG-associated inflammation within her orbital apex, manifested by the very subtle signal observed on her MRI finding (Figure 4). This lesion, too small to be detected as a mass lesion on her brain CT scan, was situated as such that it could have accounted for all of the patient's cranial nerve lesions. WG can also cause chronic meningitis that is identical to that with which our patient presented: headache, low-grade lymphocytic pleocytosis, and meningeal enhancement upon MRI (19). In addition, cavitary pulmonary lesions and sinus disease are consistent with (although not diagnostic of) WG. Therefore, WG was a viable explanation for the patient's lymphocytic pleocytosis, dural enhancement, pulmonary cavitary lesions, and maxillary sinusitis, as well as her orbital apex syndrome (20, 21). One point arguing against WG as a cause of our patient's illness was the fact that she had been treated aggressively for this condition and had been treated with rituximab, an agent designed to deplete B cells, only 3 months earlier. Preliminary investigations of rituximab for the treatment of WG have been encouraging (22, 23), and the results of a randomized trial are awaited (Specks U: unpublished observations). Flow cytometry on the patient's peripheral blood indicated that she was still B cell depleted. Despite this, her serum ANCA titer had increased over the 1 month before admission. Infections, malignancies, cavernous sinus thrombosis, and WG were all carefully considered in this patient's differential diagnosis. The patient had had no fevers during either the 2 weeks since the recurrence of her ocular symptoms or over the 6 months that had preceded her presentation. This fact argued against infection, even though her glucocorticoids and other immunosuppressive therapies might have masked systemic signs of an infection. The 2 previous episodes of vision loss also argued against infection, as did the benign findings by the Otolaryngology Service upon examination of the patient's nose and sinuses. However, complete reassurance about an infection in this setting was not possible without surgical exploration of the cavernous sinus. Similar considerations held for malignancies that could have caused this problem. Cavernous sinus thrombosis appeared to be excluded with a reasonable degree of certainty by the negative MR venogram result (7). On the other hand, several features compellingly argued for WG as the cause of the patient's presentation. First, the 2 previous responses of her vision loss to high doses of glucocorticoids had not led to dissemination of the process, as one might anticipate in the setting of an infection. Furthermore, the patient had findings on her chest CT scan that were consistent with newly active disease in her lungs. Finally, her ANCA titer had risen significantly (despite the absence of peripheral B cells). In view of these considerations and the significant potential morbidity associated with performing a biopsy of the orbital apex region, the decision was made to treat the patient empirically for WG. The patient received 1 gm of methylprednisolone intravenously each day for 3 consecutive days, and was then discharged receiving prednisone 60 mg daily. Her headaches resolved completely and she recovered full extraocular muscle function, including resolution of her ptosis. However, the central scotoma remained unchanged. Followup visual fields testing 4 months after discharge showed a persistent central visual field defect of the affected eye. WG is an ANCA-associated necrotizing granulomatous disease that classically involves medium and small vessels. In the classic, disseminated form of the disease, both the renal and pulmonary vascular beds are involved. However, WG is a remarkably protean disorder that can present with neurologic, musculoskeletal, dermatologic, gastrointestinal, urologic, cardiac, or ophthalmologic symptoms. Among the multiple ocular complications of WG, orbital apex syndrome has been described (8, 12, 13). The rheumatologist should consider an orbital apex syndrome when a patient presents with deep, aching orbital pain, diplopia, conjunctival injection, proptosis, loss of vision, ocular motor dysfunction, or combinations of these features. In severe orbital apex syndromes, the patient presents with full ptosis, a dilated pupil, and a numb eye that does not move in any direction. Such a presentation localizes the lesion to the apex of the orbit adjacent to the carotid artery and cavernous sinus, the region through which cranial nerves II, III, IV, VI, and V1 course (Figure 5). More subtle presentations are challenging and are often missed. For instance, mild ptosis and diplopia in a patient with some orbital pain or the occurrence of a Horner's syndrome in a patient with an abducens neuropathy also suggests an orbital apical localization. In WG, orbital apex syndromes probably stem from a primary granulomatous process that is akin to the process leading to orbital pseudotumors. Alternatively, an orbital apex syndrome could result from the extension of inflammation that originates within a paranasal sinus. The timing of the patient's presentation with regard to her rituximab therapy is worthy of comment. She developed her full-blown orbital apex syndrome only 3 months after undergoing B cell depletion therapy with rituximab, and she remained B cell depleted at the time of her presentation. Perhaps paradoxically, however, her serum proteinase 3 ANCA assay actually indicated an increase in her ANCA titer at presentation compared with her titer at the time of the first rituximab infusion. These facts underscore some important points about the emerging potential role of rituximab therapy in WG. Although peripheral B cells are depleted by therapies directed against CD20, long-lived plasma cells (which do not bear CD20 on their surfaces) can continue to produce ANCA through stimuli that remain poorly understood. If rituximab proves to be effective in WG, the mechanism of its efficacy will require further elucidation (24). In addition, as our case illustrates, if rituximab is effective for some patients with WG, it is not likely to be effective in all patients. Additional studies will be required to understand the most appropriate clinical settings in which to employ B cell depletion as a treatment strategy. Orbital apex syndrome caused by Wegener's granulomatosis. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Stone had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. Cooley, Pless, Stone. Acquisition of data. Cooley, Pless, Stone. Analysis and interpretation of data. Cooley, Pless, Stone.

A 68-year-old man was admitted to the hospital because of headache and loss of vision in the right eye, 3 1/2 months after orthotopic liver transplantation. Four weeks after transplantation, headaches and jaw claudication developed, followed by blurred vision in the right eye. Two weeks before admission, an ophthalmologist began therapy with prednisone; symptoms improved and then worsened 2 days before admission. On admission, additional diagnostic studies were performed.

PURPOSE: To describe the pregnancy outcomes after the use of acetazolamide in pregnant patients with idiopathic intracranial hypertension (IIH).DESIGN: Observational case series.METHODS: SETTING: Two tertiary care academic neuro, ophthalmology units. PATIENT POPULATION: Patients with IIH treated with acetazolamide. OBSERVATION PROCEDURE: Documentation of pregnancy outcome. MAIN OUTCOME MEASURES: Normal pregnancy, fetal loss, or congenital malformation.RESULTS: Twelve patients were treated with acetazolamide for IIH during pregnancy, and there were no adverse pregnancy outcomes. A critical review of the English language literature on the subject failed to demonstrate any convincing evidence for any adverse effect on pregnancy for acetazolamide.CONCLUSIONS: Acetazolamide at high doses may produce birth defects in animals, but there is little clinical or experimental evidence to support any adverse effect of the drug on pregnancy outcomes in humans. If the clinical situation warrants the use of acetazolamide in IIH, then the drug probably can be offered after appropriate informed consent. (c) 2005 by Elsevier Inc. All rights reserved.

The contributions of separate sympathetic and parasympathetic pathways to pupillary dilation during a sustained processing task were studied through environmental and pharmacological manipulations. In Experiment 1, 22 healthy volunteers (11 female) performed a serial Subtract 7 task while pupil diameter was recorded both during moderate room light and in darkness. In a control for verbalization, subjects performed an easier Add 1 task. In all conditions, pupil diameter increased significantly during the response period as compared to a pre-verbalization baseline period. Pupillary dilation was increased for the difficult task, and further increase in dilation was associated with recording in light. This suggests a major differential contribution to task difficulty mediated through inhibition of the parasympathetic pathway. In Experiment 2, a subgroup of 12 volunteers (seven female) repeated all conditions at three additional sessions in which one eye was instilled with tropicamide (to block the parasympathetic sphincter muscle), dapiprazole (to block the sympathetic dilator muscle) or placebo. All pharmacological conditions resulted in overall dilation during task performance. Differential performance similar to the placebo condition was seen only in the dapiprazole condition, when parasympathetic activation was intact. The findings suggest that sustained performance during a difficult task is modulated by cortical inhibition of the parasympathetic pathway at the oculomotor nucleus. Moreover, modulation of both ambient light intensity and pharmacological blockade of the final pupillary musculature were observed to provide converging approaches for quantifying the activity of identifiable central autonomic pathways.

A 53-year-old man presented with optic neuritis, followed within 10 weeks by a subacute progression of weakness, ataxia, and multiple cranial nerve palsies. Cranial magnetic resonance imaging demonstrated multiple T2-hyperintense lesions extending from the ponto-medullary junction to the thalamus and internal capsule. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein content. A brain biopsy revealed inflammatory changes. After a month long period of inexorable worsening, the patient was treated with intravenous immunoglobulins (2 g/kg). He responded to treatment, and recovered over the subsequent 3 months. The patient's response to treatment suggests that intravenous immunoglobulins should be considered in patients with inflammatory brain disorders.

Four patients (age range 54-82, 1F 3M) diagnosed with non-arteritic ischemic optic neuropathy experienced acute worsening of visual function after instillation of phenylephrine for dilated funduscopic examination. They experienced decreased visual function immediately or shortly after administration of topical mydriatic drops given in preparation for funduscopy. In all cases one drop each of 2.5% phenylephrine and 0.5-1% tropicamide was used. Three patients had classical risk factors such as hypertension, diabetes, and had a contralateral "disc-at-risk". The female and youngest patient had ischemic optic neuropathy presumed secondary to lupus erythematosus. The time from acute visual loss to presentation to neuro-ophthalmic care ranged from 1-6 days. The time of onset of the decline in visual function varied from 45 minutes (patient with lupus) to 12 hours after instillation of mydriatic drops. Visual acuity at diagnosis ranged from 20/40-20/400. Phenylephrine is a mydriatic with vasoconstrictive properties, which may be absorbed through the cornea, thus yielding non-negligible intraocular concentrations. Vasoconstriction of the watershed posterior ciliary capillary beds may result in further precipitating infarction of already compromised circulatory territories in edematous optic nerves. Because phenylephrine is a known vasoconstrictor in vivo and in vitro, it is more likely to cause deleterious vasoconstriction and an acute decline in visual function in patients with acute ischemic optic neuropathy than tropicamide. The routine practice of using phenylephrine to prepare patients for funduscopic assessment should be re-examined, particularly in patients with ischemic optic neuropathy.