Exploding head syndrome: new observations.

BACKGROUND AND PURPOSE: The etiology of 'exploding head syndrome' (EHS) is currently highly controversial and its management is unknown. The object was to explore these. METHODS: This observational study describes my personal experience of EHS and discusses its implications. RESULTS: I experienced, while suffering from EHS, recurrent episodes of transient cardiac arrests due to sick sinus syndrome. Implantation of a cardiac pacemaker resulted in immediate, dramatic, permanent cessation of both cardiac arrest episodes and EHS. This has not been reported previously. CONCLUSIONS: This striking temporal relationship indicates a possible association between EHS and sick sinus syndrome.

The blood supply of the optic nerve head and the evaluation of it - myth and reality.

Evidence has gradually emerged that there is vascular insufficiency in the optic nerve head (ONH) in both anterior ischemic optic neuropathy (AION) and glaucomatous optic neuropathy (GON); thus both represent ischemic disorders of the ONH. Together these diseases constitute a major cause of blindness or seriously impaired vision in man. Consequently there has recently been great interest in the ONH circulation in health and disease and in how to evaluate it. Many studies of the subject have been published, with conflicting interpretations and claims. The basis of the inconsistent information seems to be confusion on some fundamental issues concerning the ONH circulation itself. The objective of this paper is to differentiate myths and misconceptions from reality about the ONH blood supply; to elucidate the reasons for disagreement on the blood supply of the ONH; and to evaluate the reliability and validity of various methods currently used to measure ONH blood flow.

Blood flow in the optic nerve head and factors that may influence it.

In the recent past there has been great interest in the blood supply of the optic nerve head (ONH), how to evaluate ONH blood flow, and what factors influence it, in health and disease. This is because evidence has progressively accumulated that there is vascular insufficiency in the ONH in both anterior ischemic optic neuropathy (AION) and glaucomatous optic neuropathy (GON)-two major causes of blindness or of seriously impaired vision in man. For the management and prevention of visual loss in these two disorders, a proper understanding of the factors that influence the blood flow in the ONH is essential. The objective of this paper is, therefore, to review and discuss all these factors. The various factors that influence the vascular resistance, mean blood pressure and intraocular pressure are discussed, to create a better basic understanding of the ONH blood flow, which may help us toward a logical strategy for prevention and management of ischemic disorders of the ONH.

Retinal and optic nerve head ischemic disorders and atherosclerosis: role of serotonin.

Ischemic disorders of the retina and optic nerve head (OPH) constitute a common cause of visual loss in the middle-aged and elderly population. These disorders have a high association with atherosclerosis. This review has considered the various aspects of atherosclerosis and its role, as well as that of serotonin, in the development of ischemic disorders of the retina and ONH. It is known that when platelets aggregate on an atheromatous plaque, serotonin is one of the agents released. Studies in experimental atherosclerotic monkeys have shown that, although serotonin has no effect on ocular vasculature in normal monkeys, in atherosclerotic monkeys it produces vasopasm of the central retinal artery (CRA) and/or posterior ciliary artery (PCA) in various combinations but not vasopasm of the arterioles in the retina; vasospasm of the CRA and/or PCA(s) can consequently cause transient, complete occlusion or impaired blood flow in these arteries. It is postulated that in some atherosclerotic individuals this mechanism may play an important role in the development of ischemic disorders of the retina and ONH, including amaurosis fugax, (CRA) occlusion and anterior ischemic optic neuropathy, and possibly also glaucomatous optic neuropathy, particularly in normal tension glaucoma. Studies have also shown that dietary treatment of atherosclerosis abolishes or markedly improves the serotonin induced vasoconstriction within a few months. All these considerations may have important implications for our understanding of the pathogenesis and management of these blinding disorders.

Anterior ischemic optic neuropathy.

Though anterior ischemic optic neuropathy (AION) has been widely reported, it is not fully appreciated as one of the commonest causes of impaired vision in persons past middle age. These patients are not infrequently suspected of having an intracranial tumor. This article reviews the clinical features of AION and discusses its pathogenesis and treatment.

Experimental allergic encephalomyelitis. II. Retinal and other ocular manifestations.

Experimental allergic encephalomyelitis (EAE) was produced in 6 adult rhesus monkeys. All the animals developed acute EAE. Optic neuritis developed in all eyes. A vasculo-occlusive retinopathy was seen in five of the 12 eyes. Conjunctivitis and iridocyclitis were seen in some eyes. The available evidence indicates that the retinopathy is secondary to the optic nerve changes and represents central retinal vein occlusion by intraneural compression. Histopathologic studies revealed no evidence of inflammatory infiltration in the retina or around the retinal vessels.

Influence of experimental chronic high-pressure glaucoma on age-related macular degeneration in rhesus monkeys.

PURPOSE: To assess prospectively whether development of age-related macular degeneration is influenced by experimentally induced chronic high-pressure glaucoma, and whether age-related macular degeneration influences the appearance of the optic nerve head in experimental chronic high-pressure glaucoma in older rhesus monkeys. METHODS: The longitudinal study included 102 eyes of 52 rhesus monkeys. The total study group was divided into a group with experimentally induced unilateral chronic high-pressure glaucoma (n = 40 eyes) and a normal control group (n = 62 eyes). Additionally, arterial hypertension and atherosclerosis were experimentally induced in both study groups in a similar percentage of monkeys. Mean monkey age at the end of the study was 19.6 +/- 3.1 years (range, 13-24 years). The macular region, optic disc, and retinal nerve fiber layer were morphometrically evaluated by color wide-angle fundus photographs taken at baseline and at the end of the study. RESULTS: The degree of age-related macular degeneration, measured as number and area of drusen in the foveal and extrafoveal region of the macula, did not differ significantly between the two study groups. In the glaucomatous group, the degree of macular degeneration was statistically independent of the development of parapapillary atrophy, loss of neuroretinal rim, and decrease in the visibility of the retinal nerve fiber layer. CONCLUSIONS: Development of age-related macular degeneration in rhesus monkeys is independent of concomitant chronic high-pressure glaucoma, including the development of glaucomatous parapapillary chorioretinal atrophy. Conversely, age-related macular degeneration does not markedly influence the course of experimental chronic high-pressure glaucoma or the development of parapapillary atrophy in monkeys.

Ophthalmoscopic appearance of the normal optic nerve head in rhesus monkeys.

PURPOSE: To evaluate the ophthalmoscopic appearance of the normal optic disc, parapapillary region, and retinal nerve fiber layer in rhesus monkeys. METHODS: Color stereo fundus photographs of 17 normal eyes of 17 rhesus monkeys aged between 13 and 23 years were morphometrically evaluated. RESULTS: The neuroretinal rim was significantly (P: < 0.008) broadest in the inferior disc region followed by the superior disc region, the nasal region, and the temporal region. Retinal nerve fiber layer visibility was significantly highest in the inferior temporal fundus region followed by the superior temporal fundus region, the superior nasal fundus region, and the inferior nasal fundus region. It decreased significantly (P: < 0.001) with increasing age. The retinal arterioles were significantly (P: < 0.01) wider in the inferior temporal and superior temporal fundus regions than in the superior nasal and inferior nasal fundus regions. The alpha zone of parapapillary atrophy (14/17 or 82.4%) occurred significantly (P: < 0.001) more often than the beta zone (2/17 or 11.8%). In 15 eyes (88. 2%), the foveola was located inferior to a horizontal line drawn through the center of the optic disc. Neuroretinal rim shape and area and size of alpha and beta zones of parapapillary atrophy were independent of age. CONCLUSIONS: As in humans, in normal rhesus monkeys the neuroretinal rim has a typical physiologic configuration that spatially correlates with the retinal arteriole diameter, retinal nerve fiber layer visibility, and position of the foveola inferior to the center of the optic disc. Neuroretinal rim shape is independent of age. Retinal nerve fiber layer visibility decreases significantly with increasing age. These findings may be useful for the early detection and differentiation of experimental optic nerve damage in rhesus monkeys.

Parapapillary chorioretinal atrophy in chronic high-pressure experimental glaucoma in rhesus monkeys.

PURPOSE: To evaluate in rhesus monkeys parapapillary chorioretinal atrophy in chronic high-pressure glaucoma and the effects of age, atherosclerosis, and chronic arterial hypertension in a prospective, planned study. METHODS: Seventy-six eyes from 38 monkeys were studied. First, experimental atherosclerosis and chronic arterial hypertension were produced in 24 animals. Then experimental high-pressure glaucoma was produced by laser photocoagulation of the anterior chamber angle in 38 eyes from the 38 animals. Intraocular pressure measurements and fundus photography were serially performed. The photographs were morphometrically analyzed. RESULTS: In the glaucomatous eyes, area and frequency of beta zone of parapapillary atrophy were significantly (P < 0.0001) larger at the end of the study than at baseline. Area of beta zone was significantly (P < 0.0001) and negatively correlated with neuroretinal rim area. In an intraindividual intereye comparison, beta zone was significantly (P < 0.0001) larger in the glaucomatous than in the contralateral nonglaucomatous eyes. Increase of beta zone and loss of neuroretinal rim were independent of presence and size of beta zone at start of the study. Beta zone was significantly (P = 0.036) greater in older than in younger monkeys; however, atherosclerosis-arterial hypertension had no significant influence on frequency and size of beta zone. Area and frequency of alpha zone showed no significant change between baseline values and those at the end of study. CONCLUSIONS: In experimental chronic high-pressure glaucoma in monkeys, beta zone of parapapillary atrophy was positively correlated with glaucomatous optic nerve damage. This confirms previous biomorphometric and histomorphometric studies on patients with glaucoma. In chronic experimental high-pressure glaucoma, neuroretinal rim loss and an increase of beta zone may be independent of preexisting parapapillary atrophy. Increase of beta zone may be independent of concomitant atherosclerosis-arterial hypertension.

Experimental allergic encephalomyelitis. I. Optic nerve and central nervous system manifestations.

Experimental allergic encephalomyelitis (EAE) was produced in six adult rhesus monkeys. The animals were evaluated serially by ocular, ophthalmoscopic, fluorescein fundus angiographic, pupillary, visual evoked potential, neurologic, cerebrospinal fluid (CSF), and hematologic examinations and by postmortem detailed histopathologic examination. All the animals developed acute EAE. Four of the monkeys, surviving longer than 1 month, developed chronic relapsing EAE and were sacrificed 3 to 14 months after sensitization. All 12 eyes developed acute optic neuritis (with variable degrees of optic disc edema and visual loss). Later on, all the eyes of animals with chronic EAE developed optic atrophy with total or almost total blindness. Histopathologic examination of the optic nerve and central nervous system revealed inflammatory infiltrates, extensive demyelination, and axonal degeneration, without inflammation in the retina or optic nerve head (i.e., nonmyelinated neural tissue). Relapsing EAE was reflected in episodic increases of CSF proteins and pleocytosis. The various findings are correlated.

Optic disc edema in raised intracranial pressure. VI. Associated visual disturbances and their pathogenesis.

The pattern and pathogenesis of nonlocalizing visual disturbances, associated with optic disc edema (ODE). raised cerebrospinal fluid pressure, and intracranial space-taking lesions were investigated experimentally in rhesus monkeys with simulated progressive brain tumor and clinically in patients with benign intracranial hypertension. The visual disturbances occurring in one of both eyes were of three types: recurrent attacks of transient obscuration, permanent blindness, and various types of visual field defects. The studies indicate that the visual disturbances are usually due to two mechanisms. The most common is ischemia of the optic disc secondary to ODE. The other, rarer mechanism probably consists of the space-taking lesion causing downward herniation of the parahippocampal gyrus into the tentorial notch, producing compression of the lateral geniculate body and optic tract.

Optic disc edema in raised intracranial pressure. V. Pathogenesis.

The pathogenesis of optic disc edema (ODE) in raised intracranial pressure is discussed in the light of recent observations on the subject. The findings indicate that ODE is a mechanical phenomenon. The raised cerebrospinal fluid pressure (CSFP) in the sheath of the optic nerve produces axoplasmic flow stasis in the optic nerve head. This results in swelling of the axons, which manifests as early ODE and secondarily produces the well-known optic disc and retinal vascular changes associated with ODE. The pathogenesis of ODE seen in different conditions without raised CSFP cannot be explained by any single mechanism in spite of the occurrence of axoplasmic flow stasis in most cases, because the stasis in different situations has different mechanisms.

Anterior ischemic optic neuropathy. V. Optic disc edema an early sign.

Four unusual patients had bilateral anterior ischemic optic neuropathy (AION). In all four cases, AION developed in the first eye with the classic presentation. The fellow eye had symptomless optic disc edema (ODE) with no subjective or objective visual loss initially, but the classic AION clinical picture developed later on. The findings indicate that symptomless ODE may precede the visual loss in AION and could constitute the earliest sign of this disease. Since ODE in AION is due to axoplasmic flow stasis that, by itself, does not produce visual loss (this is produced by disruption of visual impulse transmission), this would suggest that mild optic nerve head ischemia interferes with axoplasmic flow without disrupting the visual impulse; however, more severe ischemia would disrupt both. Possible effects of various grades of acute optic nerve head ischemia are discussed.

Anterior ischemic optic neuropathy. IV. Occurrence after cataract extraction.

Findings are described from 13 eyes in which post-cataract-extraction anterior ischemic optic neuropathy (PCE-AION) developed immediately after an uncomplicated cataract extraction. During the early stages of the disease, the disc is edematous, with optic disc-related visual-field defects, but after about two months, the disc is pale. The almost invariable high rise of intraocular pressure during the immediate postoperative period plays a critical role in production of PCE-AION in eyes with vulnerable optic nerve head circulation. There is a high risk of development of PCE-AION in the second eye in patients with PCE-AION in the first eye, but this can be prevented by prophylactic measures. Post-cataract-extraction AION needs to be differentiated from ordinary AION seen in aphakic eyes months or years after the cataract extraction.

Optic disc edema in raised intracranial pressure. III. A pathologic study of experimental papilledema.

Optic nerve heads of 21 eyes from 13 rhesus monkeys that had developed papilledema secondary to chronically raised intracranial pressure from balloon implantation in the subarachnoid space were studied by light and electron microscopy. Nine eyes were also examined with the horseradish peroxidase tracer technique. The pathologic changes in the optic nerve head included severe axonal changes and mild interstitial edema. Axonal alteration ranged from axonal swelling to formation of cytoid bodies. Interstitial edema and vascular leakage of horseradish peroxidase were noted in the posterior lamina retinalis, lamina choroidalis and lamina scleralis (prelaminar and lamina cribrosa regions), as well as in the retrolaminar myelinated optic nerve. No intracellular edema of the glial elements was noted. Axonal swelling was so prominent that it appeared to be primarily responsible for the overall swelling of the optic disc observed ophthalmoscopically.

Optic disc edema in raised intracranial pressure. IV. Axoplasmic transport in experimental papilledema.

Tritiated leucine was injected intravitreously into the eyes of rhesus monkeys that had developed papilledema secondary to implantation of intracranial balloons. Autoradiographic studies of the optic nerve head showed that six hours after intravitreous injection of the isotope the fast component of axoplasmic transport accumulated in the regions of the lamina choroidalis and lamina scleralis. The slow component arrived at the optic nerve head two to four days after injection, and the swollen axons of the entire optic nerve head were filled with radioactive isotopes. Twelve days after injection of isotope, the axons in the optic nerve head were still diffusely labeled. Disturbance of axoplasmic transport was one of the primary events resulting in swelling of axons in papilledema. The pattern of axoplasmic disturbances in papilledema secondary to raised intracranial pressure was similar to that observed in papilledema secondary to ocular hypotony or increased intraocular pressure. Ocular hypotony, raised intracranial pressure, and increased intraocular pressure appear to share a final common pathway. All these conditions apparently converge into this final common pathway of disturbance of axoplasmic transport to give rise to papilledema.

Optic disc edema in raised intracranial pressure. I. Evolution and resolution.

Progressively growing intracranial space-taking lesions were simulated in 32 rhesus monkeys by balloons introduced into the subarachnoid space of the temporal region. Optic disc edema (ODE) first appeared at the lower pole, then the upper pole, then the nasal part, and last the temporal part of the disc; severity of edema generally followed sult, most severe at the lower pole (P less than .005). Fluorescein fundus angiography showed that swelling of the optic disc preceded the vascular changes associated with ODE. Raised intracranial pressure for 24 hours, or less, could cause ODE. The atrophic part of the optic disc did not develop ODE. The studies indicate that swelling of the optic disc is the first sign of raised intracranial pressure and is due to swelling of the nerve fibers in the optic disc; the various associated vascular changes are secondary.

Optic disc edema in raised intracranial pressure. II. Early detection with fluorescein fundus angiography and stereoscopic color photography.

Optic disc edema (ODE) due to chronic intracranial hypertension was produced experimentally in rhesus monkeys. Serial studies of fundus changes at frequent intervals, by routine ophthalmoscopy, steroscopic color photography, and fluorescein angiography, revealed that swelling of the optic disc was the first sign of ODE. Other early signs were striation of nerve fibers on the optic disc margins and peripapillary retina, blurring of the disc margins, hyperemia of the disc and capillary dilation, hemorrhages, and other retinal vascular changes; these usually appeared in that sequence. The classically described signs of early ODE were almost always absent. A normal fluorescein fundus angiogram during the incipient stage did not rule out ODE. Stereoscopic color fundus photography was the most sensitive means of detecting early ODE. Fluorescein angiography did not show changes till edema was of a mild to moderate degree; routine ophthalmoscopy was the least reliable method.

Fluorescein iris angiography. I. Normal pattern.

Fluorescein iris angiography was performed in 42 normal blue or green human eyes to investigate the normal angiographic pattern and in vivo circulation of the iris. Brown irides were unsuitable for the angiography because the brown pigment masked fluorescence. The pattern in the iris was much more complex than in the retina when seen on fluorescein angiography, with interindividual variations in its filling, and these physiological variations may erroneously be considered pathological. Radial arteries of the iris filled rather sluggishly and the circulation in the pupillary and peripupillary region was often much slower than in the peripheral part of the iris. Various segments of the iris usually filled in an irregular order. There was no distinct venous phase, but it merged with the arteriovenous phase. The pupillary region of the iris between the collarette (which contained a fragmented and incomplete minor circle of vessels) and the pupillary margin contained a dense plexus of capillaries. The normal vessels usually showed no fluorescein leakage.

Fluorescein iris angiography. II. Disturbances in iris circulation following strabismus operation on the various recti.

Iris circulation was investigated by fluorescein iris angiography in 33 human eyes before and after tenotomy of one or more recti for correction of strabismus. Tenotomy of one or both horizontal recti produced no appreciable circulatory disturbance in the iris, but tenotomy of superior or inferior rectus produced circulatory delay in superior temporal or inferior temporal sectors, respectively, of the iris. When tenotomies of a horizontal and one or two vertical recti were combined, the defect occurred in the region of the vertical rectus only. Blood supply of the nasal half of the iris was usually not disturbed by tenotomy of the vertical and/or medial rectus. The findings indicate that the blood supply of the iris is segmental and suggest that, in strabismus surgery, cutting the two vertical recti along with the lateral rectus may subject the eye to the risk of anterior segment ischemia. In the light of the present findings, physiological anatomy of the blood supply of the iris and role of the major arterial circle of the iris are discussed.