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Purpose: To report successful corticosteroid treatment of optic disc neovascularization associated with uveitis., Methods: Retrospective review of medical records., Results: Nine patients were identified with chronic uveitis and optic disc neovascularization without clinical or angiographic evidence of retinal ischemia. Ages ranged from 14 to 37 years (median age, 27). All patients were treated with either oral and/or subtenon's corticosteroids. Partial regression of the neovascularization was observed in all patients within 2 to 6 weeks (median, 5 weeks) after initiating treatment. Eight of nine patients had complete resolution of disc neovascularization at a median of 3 months (range, 2 to 42 months) after initiation of treatment and a median follow-up of 24 months (range, 7 to 144 months). Recurrence of disc neovascularization occurred in two patients, but it regressed again after further corticosteroid therapy., Conclusions: Optic disc neovascularization may occur in patients with chronic uveitis in the absence of retinal ischemia. This neovascularization can be successfully treated with corticosteroids.

Purpose: To report the ophthalmic manifestations of neonatal onset multisystem inflammatory disease, a recently recognized, rare systemic disorder characterized by the triad of arthropathy, rash, and abnormal central nervous system development., Method: Case report., Results: A 2-year-old female with neonatal onset multisystem inflammatory disease presented with visual acuity of fix and follow with each eye, bilateral optic nerve head pallor and gliosis, as well as marked sheathing of the peripapillary vessels. No vitreous inflammation or macular edema was found. Visual acuity was stable from the neonatal period through the 3 months of follow-up after the changes involving the optic nerve heads and peripapillary vessels were observed (a total of 33 months)., Conclusions: This report provides a description of the ocular manifestations of neonatal onset multisystem inflammatory disease and supports earlier suggestions that swelling of the optic nerve heads can occur. In this case, optic nerve head pallor may have been a sequela of such swelling. The pathogenesis of neonatal onset multisystem inflammatory disease is unknown.

Purpose: To describe presumed activation of herpetic keratouveitis after argon laser peripheral iridotomy., Method: Case report., Results: A 68-year-old man developed chronic, unilateral, anterior uveitis associated with decreased corneal sensation, focal keratitis, and increased intraocular pressure after argon laser peripheral iridotomy. Treatment with oral acyclovir and discontinuation of topical latanoprost resulted in prompt and continued control of both the intraocular inflammation and pressure., Conclusion: Herpetic keratouveitis may occur after argon laser iridotomy, and it should be considered when postoperative inflammation persists despite appropriate use of topical corticosteroids, particularly in patients with a history of herpetic eye disease.

Aims: To describe the occurrence of spontaneous cataract absorption in patients with leptospiral uveitis., Methods: The records of patients with seropositive leptospiral uveitis seen in the uveitis clinic at Aravind Eye Hospital between January 1994 and December 1997 were reviewed retrospectively., Results: During the 4 years of the study, 394 eyes of 276 patients with seropositive leptospiral uveitis were identified. Of these, 54 eyes (13.7%) of 41 patients (14.9%) had a final visual acuity of 20/40 or worse attributable to cataract formation. Of these 54 eyes, 41 eyes (75.9%) had visually significant cataract on their first visit to the uveitis clinic, and 13 eyes (24.1%) were noted to have cataract 1-6 months after presentation. Spontaneous absorption was observed in 10 eyes (18.5%) of eight patients (19.5%), and occurred from 6 weeks to 18 months, with a median of 5 months, after the onset of cataract. Of 12 035 consecutive, non-leptospiral, non-traumatic, uveitic, control patients seen during the same 4 years of the study, none showed spontaneous cataract absorption., Conclusion: Spontaneous cataract absorption occurs in a significant number of patients with leptospiral uveitis, and appears to be unique to this form of non-traumatic uveitis.

Objective: To describe subretinal fibrosis as a long-term complication of Vogt-Koyanagi-Harada (VKH) disease., Design: Retrospective, clinic-based, cross-sectional study and clinical correlation., Participants: Ten patients with VKH disease and subretinal fibrosis were seen at two uveitis referral centers between 1977 and 1997., Intervention: A review of the historical, clinical, and fluorescein angiographic features was performed., Main Outcome Measures: The prevalence, demographic and clinical features, and time to development of subretinal fibrosis were summarized., Results: Subretinal fibrosis occurred in 20 eyes of 10 patients with VKH disease, an overall prevalence of 8% between the two institutions. Patient age ranged from 16 years to 48 years, with a median of 34.5 years. Five patients were Hispanic, one was mixed Hispanic and American Indian, three were Asian or mixed Asian and Caucasian, and one was African-American. Eight of the 10 patients were men. All patients were in the chronic, recurrent phase of their disease when they had subretinal fibrosis develop, and all patients had recurrent episodes of posterior uveitis. Presenting vision ranged from 20/20 to light perception, with a median acuity of 20/200. All patients were initially treated with oral and topical corticosteroids. Four patients required additional noncorticosteroid immunosuppressive therapy. Time from diagnosis of VKH disease to development of subretinal fibrosis ranged from zero (fibrosis present at time of diagnosis) to 27 years, with a median time of 10 months. The median time from diagnosis of VKH to development of subretinal fibrosis in Hispanic patients was 6.5 months, whereas in non-Hispanic patients it was 6.5 years. Final vision ranged from 20/25 to light perception, with a median acuity of 20/60. Seven of 20 eyes had a final visual acuity of 20/40 or better, and seven eyes saw 20/200 or worse. Five of the eyes with 20/200 or worse vision had fibrosis involving the fovea., Conclusions: Subretinal fibrosis occurs in a sizeable proportion of patients with VKH disease and may contribute to permanent loss of vision.

Purpose: To describe optic disk edema associated with peripapillary serous retinal detachment as an early sign of systemic Bartonella henselae infection., Methods: Multicentered, retrospective case series., Results: Five women and two men presented with optic disk edema producing peripapillary serous retinal detachment. Each patient had a markedly elevated serum anti-B. henselae antibody titer. Patient age ranged from 11 to 44 years, with a mean and median of 26.6 and 28 years, respectively. The time from the onset of systemic symptoms to the onset of visual symptoms varied from 3 days to 1 month. The peripapillary serous retinal detachment resolved within 1 to 3 weeks in each case, producing a macular star in four of seven patients. Initial vision was 20/200 or worse in five of seven patients and improved in four of these five patients to 20/30 or better., Conclusions: Systemic B. henselae infection should be considered in patients who develop optic disk edema associated with a peripapillary serous retinal detachment, even in the absence of classic neuroretinitis with a macular star.

Purpose: To review recent advances in the basic and clinical biology of Bartonella-related eye disease., Method: A review of the pertinent medical literature was performed., Results: A number of novel Bartonella species have been identified over the past decade. Of these, Bartonella henselae, the etiologic agent in cat scratch disease, is most often associated with ocular complications, which may include Parinaud oculoglandular syndrome, neuroretinitis, and focal retinochoroiditis. Although cat and flea exposure appear to be the main risk factors for contracting cat scratch disease, the diagnosis of ocular bartonellosis relies primarily on the recognition of suggestive clinical signs in conjunction with positive serologic testing. B. henselae-associated ocular complications are usually self-limited but may be treated with doxycycline or erythromycin, with or without rifampin, when the infections are severe or sight-threatening., Conclusions: B. henselae infection is common and should be considered in patients with Parinaud oculoglandular syndrome, neuroretinitis, or focal retinochoroiditis, particularly when there is a history of cat or flea exposure.

Infectious causes of uveitis are common in the developing world and include some causes that are rarely encountered in industrialized nations, such as tuberculosis, leptospirosis, leprosy, onchocerciasis, and cystercicosis. Ocular toxoplasmosis occurs in all countries but is more common in Central and South America, the South Pacific, and western Europe. AIDS-related opportunistic infections occur wherever HIV infection is prevalent, including North and South America, western and eastern Europe, the former Soviet Union, sub-Saharan Africa, and South and Southeast Asia. Physicians who care for patients in the developing world should consider these infectious possibilities whenever their patients develop uveitis.

Neovascularization is an infrequent but serious complication of uveitis. The retina and optic disk appear to be affected most often, although new blood vessels may arise from the iris, ciliary body, and choroid as well. Although neovascularization can usually be identified on careful clinical examination, some patients may require fluorescein angiography or UBM. Numerous neovascular growth and inhibitory factors have been identified experimentally. Clinically, however, uveitic neovascularization appears to be determined most directly by the severity of the inflammation and the presence of retinal nonperfusion. Virtually all patients with uveitic neovascularization deserve a trial of local or systemic corticosteroids. Laser photocoagulation can be considered in those patients who fail to respond to corticosteroid therapy, but only when retinal nonperfusion has been demonstrated on fluorescein angiography. Surgical excision of newly formed vessels is reserved for selected patients with CNV and uveitis, but should only be considered when corticosteroids and focal photocoagulation are ineffective or are otherwise contraindicated.

Herpetic eye disease is common and is frequently associated with intraocular inflammation or uveitis. Despite recent advances in measuring anti-herpes virus antibodies and viral DNA in ocular fluids, diagnosis remains largely clinical. The two more common syndromes include anterior uveitis, often associated with keratitis, and the acute retinal necrosis (ARN) syndrome. Treatment is complex and requires careful monitoring to provide the appropriate balance of antiviral medication and corticosteroids. Long-term prophylaxis with oral antiviral agents may be required in selected patients to help prevent the vision-compromising complications associated with recurrences.

Retrograde and anterograde axonal transport techniques were used to investigate the organization of inputs from the dorsomedial medulla, a region known to elicit patterned swallowing reflexes following focal stimulation, to the fifth (MoV), seventh (VII), tenth (nucleus ambiguus, NA), and twelfth (XII) cranial nerve motor nuclei in the rat, those motor nuclei most directly involved in the control of deglutition. The results may be summarized as follows. 1) Dorsal medullary inputs to MoV, VII, and XII arise primarily from an extended region of the caudal reticular formation immediately ventral to the nucleus of the solitary tract (NTS), which we term the dorsal medullary reticular column (DMRC). Projections from the DMRC are largely bilateral and are distributed preferentially to the ventral subdivision of MoV, to the dorsal and intermediate subdivisions of VII, and to both the dorsal and the ventral subdivisions of XII. In addition, a subpopulation of large multipolar neurons embedded within the DMRC gives rise to a primarily crossed input to the dorsal subdivision of MoV. 2) Dorsal medullary inputs to the NA arise from the NTS, are largely uncrossed, and are organized such that the ventrolateral, intermediate, and interstitial subdivisions of the NTS project to the semicompact formation and to the rostral extension of the compact formation (which supplies the pharynx) and to the loose formation (larynx), whereas the central subdivision of the NTS provides input to the compact formation (esophagus). 3) Neither the NTS nor the DMRC gives rise to significant projections to the central subnucleus of the NTS. Together, these results provide evidence for discrete medullary pathways subserving sequential activation of swallowing reflexes.

Objectives: To describe a patient with tuberculous neuroretinitis., Materials and Methods: Retrospective case report., Results: We describe a 43-year-old otherwise asymptomatic woman with a known exposure to tuberculosis who had unilateral optic disc edema and a partial macular star (neuroretinitis). This was followed approximately 1 year later by the development of an exudative retinal detachment in the setting of bilateral multifocal choroiditis. Laboratory testing revealed a marked positive cutaneous reaction to purified protein derivative (PPD). Treatment with antituberculosis medicine alone resulted in prompt resolution of the choroidal infiltrates and complete flattening of the exudative detachment., Conclusions: Tuberculosis should be considered in the differential diagnosis for patients with neuroretinitis.

Purpose: To investigate the rate of undiagnosed rheumatologic diseases and hepatitis C infection among patients with the clinical diagnosis of Mooren ulcer seen at Aravind Eye Hospital, Madurai, South India., Methods: Twenty-one patients with the clinical diagnosis of Mooren ulcer and 44 control patients underwent a complete ophthalmic history and examination, as well as serologic testing for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies., Results: There were no statistically significant differences in the rates of seropositivity for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies between patients with Mooren ulcer and control patients. Two patients with Mooren ulcer and four control patients were found to have a rheumatoid factor titer of greater than 1:20. One of the control patients, but none of the patients with Mooren ulcer, was found to have serologic evidence of hepatitis C infection. A history of corneal trauma, surgery, or infection was reported by 68% of patients with Mooren ulcer, compared with 20% of control patients (P < .001). Among patients with Mooren ulcer, bilateral disease occurred in 37% of patients, visual acuity was reduced to light perception in 15% of eyes, and perforation occurred in 19% of eyes., Conclusions: Nineteen (90%) of 21 patients with the clinical diagnosis of Mooren ulcer were found to have no evidence of an underlying rheumatologic disease by history, examination, or serologic testing, and none was seropositive for hepatitis C. However, patients with Mooren ulcer were more likely than control patients to report a history of corneal trauma, surgery, or infection.

The proto-oncogene Cot/Tpl-2 encodes a MAP3K-related serine-threonine kinase. Expression of wild type Cot activates the IkappaB kinases (IKK) leading to induction of NF-kappaB. Conversely, expression of kinase-deficient Cot inhibits CD3/CD28 but not TNF alpha induction of NF-kappaB. These findings suggest the selective involvement of Cot/Tpl-2 or a closely related kinase in the CD3/CD28 costimulatory pathway leading to induced nuclear expression of NF-kappaB. In contrast, a kinase-deficient mutant of the NF-kappaB-inducing kinase (NIK) inhibits both CD3/CD28 and TNF alpha signaling, indicating that these pathways converge at or prior to the action of NIK. Consistent with such a sequential function of these two kinases, Cot physically assembles with and phosphorylates NIK in vivo.

Tax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) that activates nuclear expression of the NF-kappaB/Rel family of transcription factors by an unknown mechanism. Tax expression promotes N-terminal phosphorylation and degradation of IkappaB alpha, a principal cytoplasmic inhibitor of NF-kappaB. Our studies now demonstrate that HTLV-1 Tax activates the recently identified cellular kinases IkappaB kinase alpha (IKKalpha) and IKKbeta, which normally phosphorylate IkappaB alpha on both of its N-terminal regulatory serines in response to tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) stimulation. In contrast, a mutant of Tax termed M22, which does not induce NF-kappaB, fails to activate either IKKalpha or IKKbeta. Furthermore, endogenous IKK enzymatic activity was significantly elevated in HTLV-1-infected and Tax-expressing T-cell lines. Transfection of kinase-deficient mutants of IKKalpha and IKKbeta into either human Jurkat T or 293 cells also inhibits NF-kappaB-dependent reporter gene expression induced by Tax. Similarly, a kinase-deficient mutant of NIK (NF-kappaB-inducing kinase), which represents an upstream kinase in the TNF-alpha and IL-1 signaling pathways leading to IKKalpha and IKKbeta activation, blocks Tax induction of NF-kappaB. However, plasma membrane-proximal elements in these proinflammatory cytokine pathways are apparently not involved since dominant negative mutants of the TRAF2 and TRAF6 adaptors, which effectively block signaling through the cytoplasmic tails of the TNF-alpha and IL-1 receptors, respectively, do not inhibit Tax induction of NF-kappaB. Together, these studies demonstrate that HTLV-1 Tax exploits a distal part of the proinflammatory cytokine signaling cascade leading to induction of NF-kappaB. The pathological alteration of this cytokine pathway leading to NF-kappaB activation by Tax may play a central role in HTLV-1-mediated transformation of human T cells, clinically manifested as the adult T-cell leukemia.

September 15, 1997 marked the golden anniversary of the Francis I. Proctor Foundation, which was established in affiliation with the University of California in San Francisco. Over 50 years, 182 fellows from 27 countries have been trained in programs focusing on the study of infectious and inflammatory eye disease, and the prevention of blindness worldwide. Many of the people and events that have contributed to the success of the Proctor Foundation are presented in this brief essay.

Objective: To describe ocular findings in 2 patients with disseminated coccidioidomycosis diagnosed by skin biopsy., Methods: The clinical and histopathologic findings of the 2 patients were reviewed retrospectively., Results: One patient had a unilateral, granulomatous iridocyclitis with multiple iris nodules and a large vascularized anterior chamber mass, in the setting of pulmonary, cutaneous, and skeletal infection by Coccidioides immitis. The second patient developed papilledema and multifocal chorioretinitis accompanied by pulmonary, cutaneous, and meningeal C immitis infection. In each case, examination of the skin biopsy specimen revealed C immitis spherules. Treatments included local and systemic amphotericin B and oral fluconazole., Conclusions: Although rare, intraocular involvement can occur in the setting of disseminated coccidioidomycosis. A thorough systemic evaluation and biopsy of suspicious skin lesions can aid in the diagnosis.

Purpose: To describe the clinical and fluorescein angiographic appearance of cystoid macular edema associated with cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS)., Methods: We retrospectively examined the clinical and photographic records of four patients with AIDS and cytomegalovirus retinitis who developed cystoid macular edema., Results: Seven eyes of four patients with AIDS and cytomegalovirus retinitis experienced decreased vision associated with cystoid macular edema. Vitreous inflammation was mild in each patient. In all eyes, the retinitis involved zone 1, and in all but one eye, the cytomegalovirus retinitis was inactive. In one eye, the cystoid macular edema was worsened by formation of a dense juxtafoveal epiretinal membrane., Conclusions: Although infrequently recognized, cystoid macular edema can cause visual loss in patients with AIDS and cytomegalovirus retinitis. Fluorescein angiography should be considered in any patient with cytomegalovirus retinitis and unexplained visual loss.

Objective: To describe the clinical and ocular histopathological findings in multiple members of a family with congenital Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss., Methods: We performed a retrospective review of the medical charts and the ocular histopathological material of multiple members of a family., Results: Congenital Axenfeld-Rieger anomaly and glaucoma were inherited by both the proband and her male half-sibling from a phenotypically positive father and 2 different phenotypically negative mothers, suggesting an autosomal dominant inheritance. The proband's male half-sibling and her father also had atrial septal defects and sensorineural hearing loss. The proband's paternal grandmother had severe glaucoma. Histopathological analysis of blind, painful eyes removed from the proband's father and paternal grandmother showed incomplete development of the anterior chamber angle with iris stromal hypoplasia, prominent posterior embryotoxon with iris adhesions, and abnormal position and insertion of the ciliary muscles., Conclusions: This is the first description of coexisting Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss in multiple members of a single family. The iris, trabecular meshwork, and large portions of the cardiac intraventricular septum all arise from neural crest anlagen, thus supporting the notion that anterior segment dysgenesis represents a developmental disorder of the neural crest.

Purpose: To describe a case of microsporidial keratoconjunctivitis in a patient without human immunodeficiency virus (HIV) infection., Methods: Case report. An epithelial corneal scraping from a woman with chronic bilateral keratoconjunctivitis was evaluated by Giemsa stain., Results: Giemsa stain of an epithelial corneal scraping disclosed intracellular and extracellular spores characteristic of microsporidia. An HIV enzyme-linked immunosorbent assay (ELISA) test was negative. The signs and symptoms of the bilateral keratoconjunctivitis resolved after treatment with albendazole., Conclusion: Microsporidia may cause a chronic epithelial keratoconjunctivitis in the absence of HIV infection.

Purpose: To describe the clinical presentation, ophthalmoscopic and fluorescein angiographic findings, and natural history of 14 eyes in nine otherwise healthy, young-to-middle-age adults with idiopathic, acute, multifocal retinitis., Methods: A retrospective review of the clinical and photographic records of nine patients., Results: Five of the nine patients reported a flu-like illness 1 to 2 weeks before the onset of visual symptoms. Ophthalmoscopic findings included mild vitritis (11 of 14), mild optic nerve edema (seven of 14), macular star (two of 14) or localized neurosensory retinal detachment (two of 14) caused by adjacent focus of retinitis, and small branch-artery occlusion (two of 14). Fluorescein angiography showed early blocking hypofluorescence with late staining hyperfluorescence of all areas of retinitis. In patients with optic nerve edema, the disk showed late leakage. Specific tests for collagen vascular disorders, as well as systemic syphilis and toxoplasmosis titers, were negative in all patients. Five of six patients with histories of cat exposure tested negative for systemic Bartonella henselae antibodies. One patient with a history of cat exposure refused testing. Clinical courses were self-limited, with complete return of vision without treatment in all but one eye, which developed a juxtafoveal scar and localized traction retinal detachment in an area of prior retinitis., Conclusions: Idiopathic acute multifocal retinitis should be considered in any otherwise healthy, young-to-middle-age adult with acute loss of vision in the presence of multifocal retinitis, particularly when accompanied by an antecedent flu-like illness. Patients with idiopathic acute multifocal retinitis usually have favorable clinical course.

Purpose: To investigate the distribution of p75 and p55 tumor necrosis factor receptor (TNFR) mRNA in normal mouse eyes and in mouse eyes acutely infected with McKrae strain herpes simplex virus (HSV)., Methods: In situ hybridization with antisense 35S-labeled riboprobes for p55 and p75 TNFR subtypes was used in uninfected and HSV-infected mouse eyes. Controls included the use of sense riboprobes and corneas inoculated with vehicle alone., Results: In uninfected and infected mouse eyes, in situ hybridization produced an autoradiographic signal for mRNA, encoding both p75 and p55 over the corneal endothelium, iris, ciliary body, choroid, and arachnoid layers of the optic nerve sheath. In addition, the signal was observed over scattered cells at the vitreoretinal interface. Signal for p75, but not p55, was observed over cells in the retinal ganglion cell layer. Acute HSV infection was accompanied by an intense leukocytic infiltrate in the conjunctiva, the corneal subepithelium and stroma, the anterior and posterior chambers, the iris root and ciliary body, and the vitreous cavity. In this setting, increased p75 and p55 mRNA signal was correlated closely with the number and location of receptor-bearing white blood cells. Signal over control sections hybridized with sense p75 and p55 TNFR cRNA probes was comparable to background. Signal over control eyes inoculated with sterile vehicle showed slight increased signal in the immediate vicinity of the traumatic keratitis, but otherwise it was comparable to that observed in uninfected animals., Conclusions: The observed distribution of p75 and p55 TNFR mRNA in normal and acutely infected mouse eyes, and particularly over the heavily vascularized uveal tract and over cells at the vitreoretinal interface, supports a role for TNF as a mediator of intraocular inflammation, perhaps as a key regulator of the blood-ocular barrier.

Purpose: To describe three patients with systemic lupus erythematosus in whom ophthalmoscopic and fluorescein angiographic evidence of central serous chorioretinopathy developed., Methods: The authors retrospectively reviewed the clinical and photographic records of three patients with systemic lupus erythematous in whom central serous chorioretinopathy developed., Results: Ophthalmoscopic changes observed in these patients with systemic lupus erythematosus included discrete areas of clumping and mottling of the retinal pigment epithelium (RPE), focal RPE detachments, serous elevations of the neurosensory retina, and late subretinal fibrosis with scar formation. Fluorescein angiographic findings included transmission hypofluorescence and hyperfluorescence corresponding to focal RPE alterations, early punctate intense hyperfluorescence corresponding to RPE leaks with progressive filling of sub-RPE detachment spaces, and slow late filing of subretinal detachment spaces., Conclusion: Patients with systemic lupus erythematosus are at increased risk to have central serous chorioretinopathy develop. The pathogenetic implications for an association between systemic lupus erythematosus and central serous chorioretinopathy as well as the similarity to the chorioretinopathy seen with accelerated hypertension, pregnancy, hemodialysis, organ transplantation, and exogenous and endogenous hypercortisolism are discussed. Focal choroidal vasculature compromise with secondary dysfunction of overlying RPE cells is the proposed common mechanism.

Purpose: To describe a case of bone marrow transplantation retinopathy in a patient in the absence of prior radiation therapy., Methods: Case report., Results: Bilateral scotomata developed in a 26-year-old woman because of a retinal microvasculopathy two years after receiving an autologous bone marrow transplantation for acute promyelocytic leukemia. No prior radiation therapy had been given., Conclusions: Certain combinations of antimetabolites used during induction and transplantation may themselves be toxic to the retinal microvasculature. Patients who undergo bone marrow transplantation would benefit from regular and complete eye examinations, even in the absence of prior radiation therapy.

Objectives: To describe 2 patients with acquired immunodeficiency syndrome who experienced a rapidly progressive, bilateral retinitis due to herpes simplex virus (HSV) (1 case due to HSV type 1 [HSV-1] and 1 case due to HSV type 2 [HSV-2] and to present a novel diagnostic polymerase chain reaction (PCR)-based assay., Methods: The presentation, clinical course, and diagnostic PCR-based assay used to make the diagnosis of HSV retinitis in 2 patients with acquired immunodeficiency syndrome are described., Results: Both patients experienced a rapidly progressive, bilateral retinal necrosis associated with intraretinal hemorrhages and a diffuse vasculitis. The PCR-based assays demonstrated HSV DNA in the vitreous specimens from the 2 patients. Restriction analysis on the amplified DNA showed HSV-1 in 1 patient and HSV-2 in the second patient. The diagnosis was supported in both patients by the occurrence of a herpes simplex-like encephalitis, and in 1 patient by a positive vitreous culture. The HSV-1-associated vasculitis affected primarily the retinal arterioles, with marked capillary dropout and occlusion of larger arcade vessels. In contrast, the HSV-2-associated vasculitis affected the retinal veins more than the arterioles, and was associated with an exudative retinal detachment., Conclusions: To our knowledge, these are the first 2 patients with acquired immunodeficiency syndrome in whom HSV has been implicated as the sole cause of a rapidly progressing, necrotizing retinitis. Combined PCR and restriction analysis of vitreous samples from such patients is a useful and highly specific means of diagnosing HSV-1 and HSV-2 retinitis.

Purpose: We studied a case of severe bilateral Vogt-Koyanagi-Harada syndrome in a 4-year-old boy., Methods: We evaluated the patient's clinical course., Results: The patient had severe bilateral, nongranulomatous uveitis and mild uveitic glaucoma. Initial examination and laboratory evaluation failed to provide a diagnosis. The patient subsequently developed areas of vitiligo, alopecia, and poliosis, suggesting the diagnosis of Vogt-Koyanagi-Harada syndrome. This diagnosis was confirmed by the eventual development of bilateral neurosensory retinal detachments. Vision was lost despite aggressive therapy with corticosteroids and chlorambucil., Conclusion: Although uncommon, Vogt-Koyanagi-Harada may affect young children, and may be severe.

NGF acts as a neurotrophic factor by binding and activating its receptor on certain neuronal populations in the CNS and PNS. TrkA is a receptor for NGF. Recent findings in vitro indicate that this NGF-activated receptor tyrosine kinase transduces the NGF signal. To further define NGF actions in the CNS, we examined trkA expression in the adult rat brain. We found that trkA mRNA and immunoreactivity (IR) coincided in specific, defined neuronal populations in the forebrain and brainstem. In addition to cholinergic neurons in the basal forebrain and neostriatum, trkA expression was found in noncholinergic neurons in (1) the paraventricular anterior and reuniens thalamic nuclei, (2) the rostral and intermediate subnuclei of the interpeduncular nucleus (IPN), (3) scattered neurons in the ventrolateral and paramedian medulla, (4) the prepositus hypoglossal nucleus, and (5) the area postrema. NGF responsiveness was demonstrated for each of these populations. In contrast to trkA, p75NGFR was found only in a minority of NGF-responsive populations. Our data provide further evidence that expression of trkA marks NGF-responsive CNS neurons and suggests novel roles for NGF in the brain.

We describe a 34-year-old man with acute, nontraumatic inferior branch oculomotor nerve palsy. Complete ophthalmologic, neurologic, and systemic examinations were otherwise normal. The oculomotor nerve palsy resolved, but the patient subsequently developed bilateral upper extremity numbness and painful dysesthesias in the distribution of the median nerves. These observations suggest that inferior branch oculomotor nerve palsy, although uncommon, may occur as part of a more generalized neurologic disorder, presumed in our patient to be either vasculitic or demyelinating in nature.

Immune activation is often accompanied by profound alterations in neurological and endocrine function, such as fever, increased somnolence, decreased appetite, activation of the hypothalamic-pituitary-adrenal axis, and suppression of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes. These well-recognized systemic responses to injury and infection have been attributed to circulating pro-inflammatory cytokines, the best characterized of which is interleukin 1 (IL-1). Here Emmett Cunningham and Errol De Souza discuss the mechanisms by which blood-borne IL-1 might affect such changes in the nervous and neuroendocrine systems.

The cytokine interleukin-1 (IL-1) has been reported to inhibit the hypothalamic-pituitary-gonadal axis, both through actions in brain and at the gonadal level. Recently, high affinity binding sites for 125I-recombinant human IL-1 alpha have been identified in the mouse testis with characteristics similar to those of type I IL-1 receptors on T lymphocytes and fibroblasts. The present study employed in situ hybridization histochemistry with 35S-labeled antisense cRNA probes derived from a murine type I IL-1 receptor cDNA to identify type I IL-1 receptor mRNA in the mouse testis. An intense signal was observed over interstitial cells, and over the cytoplasm of the epithelium of epididymal ducts, most prominently in the head region. The signal over seminiferous tubules, and over sperm cells within tubules and epididymal ducts, was comparable to background. This distribution of type I IL-1 receptor mRNA was similar to that recently reported for 125(I)I-IL-1-alpha binding sites, and supports evidence implicating IL-1 as a direct regulator of gonadal function.

The cytokine interleukin-1 (IL-1) has a number of biologic activities, including pronounced effects on the nervous and neuroendocrine systems. In this study, in situ histochemical techniques were used to investigate the distribution of cells expressing type I IL-1 receptor mRNA in the CNS, pituitary, and adrenal gland of the mouse. Hybridization of 35S-labeled antisense cRNA probes derived from a murine T-cell IL-1 receptor cDNA revealed a distinct regional distribution of the type I IL-1 receptor, both in brain and in the pituitary gland. In the brain, an intense signal was observed over the granule cell layer of the dentate gyrus, over the entire midline raphe system, over the choroid plexus, and over endothelial cells of postcapillary venules throughout the neuraxis. A weak to moderate signal was observed over the pyramidal cell layer of the hilus and CA3 region of the hippocampus, over the anterodorsal thalamic nucleus, over Purkinje cells of the cerebellar cortex, and in scattered clusters over the external-most layer of the median eminence. In the pituitary gland, a dense and homogeneously distributed signal was observed over the entire anterior lobe. No autoradiographic signal above background was observed over the posterior and intermediate lobes of the pituitary, or over the adrenal gland. This study therefore provides evidence for discrete receptor substrates subserving the central effects of IL-1, thus supporting the notion that IL-1 acts as a neurotransmitter/neuromodulator in brain. It also supports studies suggesting that IL-1-mediated activation of the hypothalamic-pituitary-adrenal axis occurs primarily at the level of the brain and/or pituitary gland.

We describe a patient with a left trochlear nerve paresis and a left relative afferent pupillary defect despite normal visual acuity, color vision, visual fields, and fundus examination. Magnetic resonance imaging revealed a lesion in the right dorsal midbrain extending from the brachium of the superior colliculus to the inferior colliculus. The anatomy and physiology of the pupillary light reflex are reviewed, as are possible mechanisms for the laterality of afferent pupillary defects with midbrain lesions. The presence of a trochlear nerve paresis with an ipsilateral relative afferent pupillary defect and an otherwise normal ophthalmic exam indicates a lesion in the contralateral dorsocaudal midbrain.

Reflex control of magnocellular vasopressin and oxytocin secretion has captured the curiosity and investigative imagination of neuroendocrinologists for nearly 50 years. While it may seem obvious that brisk elevations in circulating levels of vasopressin in response to hemorrhage, or of oxytocin in response to suckling, must of necessity arise from magnocellular neurosecretory neurons in the hypothalamus, the central pathways mediating these reflexes have, until quite recently, remained elusive. In this brief review, ongoing attempts to delineate these pathways are summarized. Evidence for plasticity and local modulation of magnocellular reflexes in response to prolonged stimulation, such as chronic dehydration and lactation, is also presented.

The cytokine interleukin-1 (IL-1) has numerous actions in brain, including pronounced neuroendocrine effects. Recent radioligand binding studies have identified high-affinity binding sites for 125I-recombinant human IL-1 alpha in the hippocampus with characteristics similar to those of IL-1 receptors in immune cells. The present study employed in situ hybridization histochemistry with 35S-labeled anti-sense cRNA probes derived from a full-length murine T-cell IL-1 receptor cDNA to identify cells producing IL-1 receptor mRNA in the murine hippocampus. An intense signal was observed over granule cells in the dentate gyrus. A weak to moderate signal was observed over the pyramidal cell layer of the hilus and CA3 region. Other aspects of the hippocampal formation, including the CA2 and CA1 regions, the subiculum, and the entorhinal area, displayed no signal above background. This distribution of IL-1 receptor mRNA was similar to that of 125I-IL-1 alpha binding sites and supports the growing body of evidence implicating IL-1 as a neurotransmitter/neuromodulator in brain.

The morphological maturation of cell suspension grafts of fetal striatal tissue (obtained from 14-15-day-old rat fetuses) was followed from two days to eight weeks after implantation into intact and ibotenic acid-lesioned striata of adult rats. The development of host afferent innervation of the grafts from the substantia nigra (tyrosine hydroxylase immunoreactive), mesencephalic raphe (serotonin immunoreactive), and the frontal cortex (anterogradely labelled with Phaseolus vulgaris leucoagglutinin) were revealed by immunohistochemistry. During the first weeks post-grafting, the striatal implants consisted of a mixture of mature- and immature-looking cell clusters. Grafts implanted into ibotenic acid-lesioned striatum grew rapidly (about five-fold) in volume over the first week. The areas of immature (probably proliferating) cells gradually disappeared, and by six to eight weeks the grafts had a fully mature appearance with patches of neurons which stained densely for DARPP-32 (i.e. were striatum-like) embedded within areas of essentially DARPP-32-negative (i.e. non-striatum-like) tissue. Peripheral clusters of grafted cells gradually intermingled with nearby areas of the surrounding lesioned host, and already by two to four days after implantation, coarse and densely immunoreactive host fibres from the substantia nigra, mesencephalic raphe and frontal cortex were present within the grafts. By four to five days the first DARPP-32-immunoreactive neurons appeared in patches within the mature portions of the grafts, and one to two days later the tyrosine hydroxylase-positive fibres began to sprout thin axons selectively within the DARPP-32-positive patches. Similarly, the serotonergic and cortical fibres in the grafts increased in number over the next two weeks, but they showed no preference for the DARPP-32-positive regions. Rich terminal networks were established by two to three weeks post-grafting, and by six to eight weeks the nigral, raphe and cortical afferents had reached terminal densities similar to those seen previously in long-term surviving grafts. Grafts implanted into dopamine-denervated hosts showed a normal morphological maturation of both DARPP-32-positive and -negative areas, although no tyrosine hydroxylase-positive innervation appeared within the grafts. Grafts implanted into non-lesioned striata did not grow beyond their initial size. The implanted cells showed less intermingling with the surrounding host striatum, thus resulting in sharply delineated graft-host borders. DARPP-32-positive patches developed, but they were smaller in size and generally present only in the most peripheral graft portions.(ABSTRACT TRUNCATED AT 400 WORDS)