Journal of Neuro-Ophthalmology, June 1984, Volume 4, Issue 2

Neuro-ophthalmology in the recent European literature. Part I. The visual system.

J. elin. Neuro-ophthalmol. 4: 115-128, 1984. Neuro-ophthalmology in the Recent European Literature Part I. The Visual System AVINOAM B. SAFRAN, M.D. A number of papers of interest to neuro­ophthalmologists have recently been published in European journals, including non-ophthalmo­logical and non-neurological periodicals. Some of them are reviewed here in an effort to bring to clinicians information that is not always readily available, especially in countries where European journals are read less frequently. As in the excel­lent "Information Summaries" published in this journal by Dr. McCrary, the name and address of the corresponding author of these recent papers are provided with each reference when indicated in the original paper, in order to facilitate reprint requests. Studies that appeared from January to June 1983 are reviewed in this paper and in parts 11 and III. Unfortunately, some publications could not be retained, because of lack of space. Excep­tionally, recent European articles published be­fo! e January 1983 are included when they deal with matters considered here. The articles will be arranged (sometimes rather arbitrarily) under the following headings: I. The Visual System Developmental abnormalities Optic nerve: hereditary, ischemic, and toxic changes Optic neuritis, multiple sclerosis, and Creutzfeldt-Jakob disease The chiasma The retrochiasmatic visual pathways Higher visual functions II. Eyelid Motor Disturbances and Extrapyr­amidal Disorders III. The Ocular Motor System Supranuclear and nuclear disorders Infranuclear disorders IV. The Autonomic Nervous System V. Heredodegenerative Disorders VI. Retinal and Cerebral Stroke VII. Pain VIII. Diagnostic Techniques Automated perimetry Contrast sensitivity measurement From Clinique d'ophtalmologie, Hopital Cantonal Universi­lalre, Geneva, Switzerland. June 1984 Visual-evoked potentials Evaluation of visual function in patients with cataract Conventional radiology Nuclear magnetic resonance In Part I, the visual system will be discussed. The Visual System Developmental Abnormalities Since 1968,1 there has been increasing evidence that alcohol abuse during pregnancy is harmful to the offspring. One teratogenic effect of alcohol is hypoplasia of the optic nerve, which has been observed in as many as nine of a group of 30 children presenting with the so-called "fetal al­cohol syndrome." If little doubt remains about the danger of heavy drinking during pregnancy, much controversy has arisen about the minimal amount of alcohol that may represent a real dan­ger. It has been suggested that even moderate or social levels of drinking in pregnancy may also be detrimental to the fetus. The rate of congenital a~norn,:ali~ies has been shown repeatedly to be higher In Infants born to moderate drinkers than in those born to light drinkers or nondrinkers, although it is difficult to exclude the possibility that the background characteristics of the studied population account for a part of these findings. A recent editorial in Tile Lancet3 addressed this problem under the explicit title"Alcohol and the fetus: Is zero the only option?", and provided a synthesis of the matter. In the same issue of Tile Lancet, vyrig~t et ~l. -l I?ublished the findings of a prospective investigation of 900 pregnancies in London. The women who, before diagnosis of pregnancy, commonly had 10 or more drinks a week were more than twice as likely to have a low-birthweight baby as those who normally had less than five drinks a week. This is of particular concern, especially when one takes into account the fact that for example, in England and Wales 10% of women aged from 1~ to 24 years take more than three drinks a day.' It is even more so if the assumption is true that the critical period is the first weeks after conception, when pregnancy may not yet be diagnosed in many women.3 115 Recent Literature: Part I Major developmental failures of optic nerve and retinal vessels have been observed by Ro­chels et al.b in a premature infant showing serol­ogical evidence of cytomegalovirus infection. Such developmental failures could result from a cytomegaly infection prior to the fourth month of pregnancy. Rochels et al. gave credit to Hittner et al. 7 and to Hotchkis and Green,8 for having pre­viously reported five cases with association of optic nerve dysplasia and cytomegaly. Correla­tion between optic nerve defects and congenital cytomegaly is noteworthy when one considers that this type of infection is known to be one of the most common that occur in utero. Association of morning glory syndrome and contractile peripapillary staphyloma has been re­ported by Cennamo et al.9 It was observed in the left eye of a 20-year-old man. Visual acuity in that eye was 20/200 with -2/-2 X 180°. Ophthalmoscopic examination demonstrated that each contraction lasted about 20 seconds. No correlation was found between staphyloma con­tractions and either respiratory or ocular move­ments. However, contractions were occasionally initiated by finger pressure on the globe, and then they repeated rhythmically. Staphyloma contrac­tions have been documented by means of serial fundus photographs, M-mode and B-scan ech­ography. The latter technique made it possible to determine that the staphyloma was 2.5 mm in depth. Morning glory syndrome, like most congenital abnormalities of the optic nerve head, can occur in conjunction with basal encephalocele and other midline abnormalities. 10, II This was recalled by Caprioli and Lesser, 12 with their description of a child showing cleft lip and palate and a morning glory dysplasia in the left eye. At 16 months of age, when admitted for repair of the cleft palate, he was found to have a soft pulsatile mass of the posterior pharynx extending through the palatal defect. Plain skull films and laminography of the base of the skull disclosed the midline bony de­fect. Association of midfacial and optic nerve abnormalities should alert the physician to the possible presence of an unrecognized basal en­cephalocele. The Chediak-Higashi's syndrome is a rare form of partial albinism, which is associated with in­creased susceptibility to infections and a hemor­rhagic tendency. If affected patients survive the recurrent infections of childhood, they often de­velop a progressive cranial and peripheral poly­neuropathy, muscle weakness, and ataxia. Ap­parent hypopigmentation is the result of the ag­gregation of abnormally large melanosomes. Al­though this syndrome is considered a type of oculocutaneous albinism, hair, skin, and irises are relatively well-pigmented. Creel et al. 13 investi-gated visual and auditory functions of affec~ed patients to determine if misrouting of de~ussatm.g retinal fibers and anomalies of decussatmg audi­tory pathways could be found, as they are known to occur in conjunction with ocular and oculocu­taneous albinism. Indeed, three of four patients studied showed abnormal stereoscopic vision, as evaluated by means of the Titmus test, and hemispheric asymmetry of monocular visual­evoked potentials, which provided evidence that most humans with this syndrome probably have misrouted retinogeniculostriate projections. Fur­thermore, all patients produced asymmetric au­ditory brain stern responses similar to those re­ported for albinos. Normal infants who fail to demonstrate visual responsiveness in early infancy and later develop normal visual function exhibit what has been termed delayed visual maturation. At the time these infants are still unresponsive to visual stim­uli, electroretinograms are characteristically nor­mal, whereas visual-evoked potentials are al­tered. The clinical importance of this delay has been reemphasized by Harel et al.,14 who pro­vided visual electrophysiological findings of three new cases. Evidence of both prolonged latencies and immature wave form responses in visual­evoked potentials led the authors to favor a phy­siopathological hypothesis based on delay of both myelination and synaptic development. It was suggested by Hoyt et al. 15 that children with delayed visual maturation actually present with widespread maturational delay of cortical function, and that portions of both the sensory and the motor systems account for this condition. Eight infants presenting with clinical and electro­physiological features of this phenomenon were studied. The patients were first examined be­tween 5 and 11 weeks of life. It was noted that six of the eight infants initially could not generate saccadic eye movements by means of vestibular stimulation. Eventually, all infants presented nor­mal vestibulo-ocular responses. When first seen, seven of the eight infants also showed obvious delays in their general motor development. Optic Nerve: Hereditary, Ischemic, and Toxic Changes In an histological study that is apparently the most extensive performed in a patient with dom­inant optic atrophy, Kjer et al. 16 found a decreased number of neurofibrils and myelin sheets in the intracranial segments of vestibulocochlear nerves. During his life, the studied patient had never complained of auditory symptoms. In dominant optic atrophy, anomalies outside the visual sys­tem do not characteristically occur, although sev- Journal of Clinical Neuro-ophthalmology eral families have been reported who also exhib­ited deafness, asymmetry of the face, and defor­mation of the ears. In addition, Kjer et a1. 16 noted heavy fibrosis of the ganglion cell layer in the eyes, and the inner limiting membrane was highly condensed. There was a partial atrophy of the optic nerve, and in the lateral geniculate body massive loss of ganglion cells, fibrillary gliosis, and a great quantity of fine granular lipid in the cytoplasm of the ganglion cells were demon­strated. No change was observed in the calcarine cortex. In a group of 53 patients with ischemic optic neuropathy studied by Eckardt et al., 17 average life expectancy was not found to be significantly different from that of the general population of corresponding age. These findings are in agree­ment with Boghen and Glaser'sls statement that, in patients with nonarteritic ischemic optic neu­ropathy, there appears to be no increased inci­dence of stroke over long follow-up periods. Fur­thermore, based on a study of 44 patients suffer­ing from central or branch retinal artery occlu­sion, Eckardt et al. agreed with Savino et a1. 19 that patients with retinal artery occlusion show a statistically significant increase in mortality rate. They finally indicated that no excess mortality was found in a group of 53 patients with central retinal vein occlusion. Nonarteritic posterior ischemic optic neuropa­thy has aroused a ~rowing interest since Hayreh's 1981 publication.2 Blood supply of the posterior optic nerve was investigated by Isayama et al. 21 in 10 monkeys, by means of resin injection into the carotid arteries. The authors first demon­strated the existence of superior and inferior vas­cular semicircles around the intracanalicular optic nerve. Furthermore, they confirmed previous ob­servations about the blood supply of the intraor­bital, intracanicular, and intracranial segments of the optic nerves. Ischemic changes in the posterior part of the optic nerve were found at necropsy in 12 of 33 cases with medical history of cerebrovascular de­ficiency, by Isayama and Takahashi. 22 The loca­tions of the lesions were the transverse, periph­eral, altitudinal, and (in one case) axial areas of the optic nerves. These were in orbital, intracan­alicular, and intracranial segments. Occlusion of vessels due to atherosclerosis, arteriolosclerosis, capillarosclerosis, and emboli were demonstrated in association with the ischemic lesions of the optic nerves. No histopathological changes of giant cell arteritis were encountered. Unfortu­nately, no clinical data could be provided about the visual function before death. Early reports on posterior ischemic optic neu­ropathy offered little clinical information on ar­teriosclerotic forms of the disease. This prompted June 1984 Safran Cullen and Duval23 to present a detailed account of a 61-year-old patient who presumably suffered from posterior ischemic neuropathy. One eye demonstrated an altitudinal field defect, going on to total visual loss and normal disc appearance until 6 weeks after the onset. The fellow eye showed a similar, but less severe involvement several weeks after the onset of the visual symp­toms, with a loss of temporal field. The defect eventually reversed in part, and essentially left an inferior bundle defect. Ophthalmodynamo­graphy showed a marked reduction of diastolic pressure. Diagnosis of giant cell arteritis was dis­carded after repeated sedimentation rate evalua­tion and temporal biopsy. That ischemic optic neuropathy can also be a feature of pulseless disease was indicated by Leonard and Sanders.2~ It was shown in a 67­year- old female who also complained of faint­ness. Beside characteristic fundoscopic features of right anterior ischemic optic neuropathy, both fundi exhibited vascular signs of chronic retinal ischemia. At operation, a narrowed internal ca­rotid artery was found to be the only main vessel to the head. With a Dacron graft between the aorta and the right internal carotid artery, general condition dramatically improved, but visual func­tion remained essentially unchanged. Seventy percent of patients suffering from pulseless dis­ease present with anterior segment and/or fun­dus signs of chronic ischemia, including optic atrophy. However, acute ischemic neuropathy has apparently never been described before. Also noteworthy in this case report was that ischemic optic neuropathy occurred in the eye that was previously the better supplied of the two, accord­ing to data collected during an ocular examination performed prior to the disc infarction. Leonard and Sanders hypothesized that the fellow eye survived because it was supplied by an adequate collateral circulation resulting from marked chronic ischemia. Papilloarterial ischemia is the result of circula­tory insufficiency of both optic disc and retinal vascular networks. Clinical features of this syn­drome were described 2 years ago by Kottow20i and reported in this journal in the "Information Summaries" by McCrary.~6 These include mainly altitudinal field defects, pale disc edema, constric­tion of emerging arteries with occasional staining of walls during fluorescein angiography, peripa­pillary hemorrhages, and cotton-wool spots. Kottow27 recently published an extended series covering 10 eyes presenting with this syndrome. Papilloarterial ischemia occurred more frequently in young females, in whom fundoscopic findings, elevated sedimentation rates, and clinical remis­sions with systemic corticosteroids suggested an inflammatory origin. 117 Recent Literature: Part I The latest drugs to be abused because of their euphoric effects include volatile complex hydro­carbons, in particular those found in adhesives, spot removers, and aerosols. Glues and other common sources of volatile hydrocarbons often contain mixtures of organic compounds, and, therefore, it may be difficult to identify individual chemicals responsible for damage. However, the most commonly abused substance is toluene. The occurrence of retrobulbar optic neurogathy has been reported following toluene abuse.-8 This was confirmed by Ehyai and Freemon29 in a 27-year­old patient who also exhibited dramatic sensori­neural hearing loss. Fornazzari et al. 30 indicated that optic atrophy occurred in two out of 24 studied toluene abusers. Other neurological find­ing included cerebellar symptoms, memory loss, and peripheral neuropathy. Impairment was sig­nificantly correlated with computerized tomog­raphy scanning measurements of cerebellum, ventricles, and cortical sulci. Little evidence of reversibility of neurological defects was shown over a 2-week follow-up. Fornazzari et al. were surprised by the lack of correlation of either chronicity or level of current abuse with neuro­logical findings. The authors suggested that im­pairment could also be the result of associated factors, such as malnutrition or periods of anoxia. Possible neuro-ophthalmological side effects of tiliquinol and tilbroquinol were debated in the correspondence section of The Lancet. Soffer et al. 31 first wrote to the Editor to describe the his­tory of a 60-year-old man who received tiJiquinol and tilbroquinol (lntetrix®) continuously for 4 years at average doses of 80 mg and 200 mg, respectively, because of alternating constipation and diarrhea. The patient presented with loss of temperature, pain, paresthesia of the arms and legs, impairment of thermic sensibility in the dis­tal parts of the legs, cerebellar ataxia, and poor memory. Ophthalmological findings were de­scribed as right scotoma, bilateral papilloedema, and color vision disturbance. Computerized to­mography and cerebral angiogram were normal. Drugs were withdrawn, and 6 months later the general condition dramatically improved, but there was no change in visual function. The au­thors suggested that clinical findings were com­parable to those of subacute myelo-optic neurop­athy (SMON) syndrome, and that changes could originate in consumption of tilbroquinol and tili­quinol, a drug combination with worldwide sales. This hypothesis was, however, criticized 3 weeks later in a letter to the Editor by Rose,32 who stated that several clinical features exhibited by this patient were not typical of the subacute myelo­optic neuropathy syndrome, and that he doubted that the patient showed oxyquinoline toxicity. Hypozinchemia has repeatedly been correlated 11 ~ with optic atrophy, includin~ in cases of etham­butol or disulfiram toxicity. 3 Furthermore, pa­tients with alcohol and tobacco abuse demon­strate low blood zinc concentration, whereas lead concentration is higher than in the general pop­ulation. 34 Effects of zinc administration on visual function were evaluated by Bechetoille et al. 35 in patients showing bilateral retrobulbar axial optic neuropathy in conjunction with excessive smok­ing and consumption of wine and/or beer. In a double-blind study eight patients received zinc sulfate, 400 mg daily per os, and a control group of nine other patients received placebos. After 1­month therapeutic trial, when considering the four paracentral points of the Friedmann ana­lyzer, some improvement was observed in the zinc-treated group. Based on these findings Be­chetoille et al. suggested that zinc therapy could be helpful in the management of the so-called tobacco-alcohol ambylopia. Clinicians should be aware that, beside chelating drugs such as etham­butol, isoniazide, bisulfiram, diiodohydroxyquin, and iodochlorhydroxyquin, various substances contribute to reducing the biological availability of zinc. These include dietary fiber, phytic acid, iron, and calcium. 33 * Artificial increase of intraocular pressure in man causes the appearance of a certain amount of pallor of the optic disc. However, with intra­ocular press,ure values higher than 40 mm Hg, Robert et al. >0 described a fluctuation of the pallor and even, in some subjects, a substantial decrease of the pallor. This was demonstrated by compar­ing with a photoscanner one small square of the temporal rim of the optic disc with a second square on the retina adjacent to the rim, on neg­atives of orthochromatic film. They suggested that the paradoxical response observed with higher intraocular pressure may be due to an autoregulatory process in optic nerve head circu­lation. Optic Neuritis, Multiple Sclerosis, and Creutzfeldt-Jakob Disease Hyperbaric oxygen therapy is now receiving an enthusiastic welcome among British multiple scle­rosis patients. Fund raising has begun to enable self-help groups to have their own treatment centers. This wave of excitement was triggered by experimental data and theoretical considera­tions published in the medical literature, essen­tially since 1980.37 The trend was further en­hanced by the findings of a study conducted by the Action for Research into Multiple Sclerosis in 38 self-selected British patients, published re- • For prescribing the drugs mentioned in this article, please refer to the authors' original articles. Journal of Clinical Neuro-ophthalmology cently in London,38 which also suggested some benefits from oxygen therapy. Fisher's recent double-blind study39 demonstrating improve­ment from hyperbaric oxygen in patients with advanced chronic multiple sclerosis heightened this enthusiasm. The matter was synthesized in a recent editorial in The Lancet.4o Beneficial results were attributed to the reduction of edema and the immunosuppressive effects of oxygen ther­apy, as well as to the raising of partial venous oxygen pressure and reduction of damage in hy­poxic oligodendrocytes. James' suggestion41 that fat embolisms could account for formation of plaques in multiple sclerosis patients and his ra­tionale of hyperbaric oxygen therapy were also :onsidered. Recent advances in interferon and nonspecific immunosuppressive treatment were also reviewed in the editorial. One month later, in a letter to the Editor of The Lancet, James40 commented further on his hypothesis that sub­acute fat embolism caused the initial lesion in multiple sclerosis. High doses of intravenous methrl prednisolone were administered by Goas et al.4 in 13 patients exhibiting acute exacerbations of multiple scle­rosis. Beneficial results were obtained, as noted also in two other recent reports. 44.45 All studied patients received 1 g of the drug daily for 5 days. Ten of the 13 patients improved quickly, often during the time of perfusion. The first two pa­tients of the therapeutic trial were administered adrenocorticotropic hormone (ACTH) upon with­drawal of methyl prednisolone. No relapses were observed upon withdrawal or during the months following the treatment. One patient showed a new exacerbation 45 days after discontinuation of the drug, in another location. Great commitment is required from patients involved in therapeutic trials, particularly when repeated extensive and somewhat invasive ex­aminations are performed to assess clinical evo­lution. Confavreux4b raised the difficult ethical issue of double-blind studies in patients with multiple sclerosis, especially problematic when the trial encompasses a several-yearlong evalua­tion. Confavreux reviewed the too many incon­clusive studies that have been conducted, and urged researchers to start clinical trials only when chosen evaluation criteria lead to a high level of certainty. He indicated that, for studying diseases with a remittant onset, at least 540 patients are required in a placebo-controlled trial to demon­strate a decrease from 20% to 10% in the 5-year worsening of the disability. Arsenic therapy was tried in the management of multiple sclerosis in the 1940s and 1950s, but was eventually discarded for various reasons, in­cluding frequent toxic side effects. Long-term consequences of arsenic treatment for multiple June 1984 Safran sclerosis were reported by Robertson and Low­Beer. 47 These authors observed a patient who presented in 1957 with clinical signs of multiple sclerosis. He was entered into an arsenic thera­peutic trial, and subsequently developed transi­tional cell tumor of the bladder, and noncirrhotic portal hypertension. The diseases were ascribed to the previous arsenical treatment, and it was suggested that other patients similarly treated in this trial could develop such lesions. In patients with clinically isolated unilateral optic neuritis, occurrence of oligoclonal bands in cerebrospinal fluid significantly increased the risk of subsequent development of multiple sclerosis. This was demonstrated in 1981 by Nikoskelainen et al. 48 and recently confirmed by Stendahl-Bro­din and Link. 49 The latter studied 30 patients over a mean follow-up period of 11 years. Nine of the 11 patients with oligoclonal bands developed multiple sclerosis, whereas only one of the 19 patients without these cerebrospinal fluid abnor­malities eventually exhibited signs of multiple sclerosis. It has been established that, in multiple scle­rosis, old age at onset is associated with a more rapid evolution of the disease. It has also been reported that chronic progressive forms bear a more unfavorable prognosis than relapsing re­mitting forms. However, since chronic progres­sive disease course is generally encountered in conjunction with late onset, it has remained un­clear whether age of onset or progressive form of the disease was the determining factor for prog­nosis. This problem was approached by Verjans et al. 50 in a study of 200 consecutive patients with definite multiple scerlosis. It was clearly demon­strated that chronic progressive course per se was associated with a more rapid deterioration. In contrast, age per se had no effect on the rate of progression of the chronic progressive form. When individual patients were concerned, how­ever, the prognostic value of age at onset and evolution type is limited. Prognostic significance of intrathecal IgG synthesis in the course of mul­tiple sclerosis was evaluated in the same study. 50 Occurrence of a large number of oligoclonal bands was significantly greater in the patients with the most rapid progression rate. IgG indices, however, did not correlate with disease progres­sion when the whole population was evaluated. It tended to correlate only when the most benign and most malignant forms were compared. Significance of certain HLA antigens in multi­ple sclerosis patients remained controversial. HLA antigens were studied in 200 definite mul­tiple sclerosis patients by Dejaegher et al. 51 The authors were unable to confirm previous reports correlating occurrence of HLA-DR2 and severity of the disease, although highly significant con- 119 Recent Literature: Part I junction of this antigen with multiple sclerosis was found again. Dejaegher determined, appar­ently for the first time, that occurrence of HLA­DR2 was more frequent in the group of patients with onset after the age of 31. This may indicate that age of onset is influenced by genetically determined characteristics. Ilonen et a1. 52 suggested that, in multiple scle­rosis, the difficulty of correlating immune system responsiveness with clinical remissions and ex­acerbations could be due to the existence of large "silent" areas in the central nervous system. These authors studied the follow-up results of lympho­cyte blast transformation responses in individual patients with multiple sclerosis, and found that some of the patients had a regular pattern of decreasing responses during disease relapses, whereas others had more irregular fluctuations of these responses. Contrary to a frequently held view, it was shown by Edward J. Thompson et a1. 53 that changes occur in the oligoclonal patterns of in­dividual patients with multiple sclerosis at suc­cessive examinations of the cerebrospinal fluid. This statement was based on a longitudinal study of 25 patients. The authors, therefore, suggested that the "fingerprint" concept of oligoclonal pat­tern in individual patients with this condition was spurious. They indicated that in all the previous studies supporting the "fingerprint" hypothesis, concentrated cerebrospinal fluid was used for electrophoresis. In addition, methods have been used that did not involve separation on the basis of protein charge as well as size. Thompson et a1.'s research was performed with polyacrilamide electrophoresis of unconcentrated cerebrospinal fluid. The importance of methodologies was dis­cussed in that paper. Vervliet et a1. 54 showed that in patients with multiple sclerosis, interferon production of pe­ripheral blood lymphocytes in response to mito­gens: 1) has a certain prognostic value, and 2) is a criterion for selecting patients for possible treat­ment with interferon. Decrease in interferon re­sponsiveness of patients with multiple sclerosis may also be related to occurrence of HLA-DR2 phenotype. It has been shown that gamma-type interferon production of peripheral blood leuco­cytes in response to mitogens is often reduced in multiple sclerosis patients. In addition, presence of HLA-DR2 phenotype in these patients seems to further reduce the already diminished inter­feron responsivene?s.55 In contrast with a pre­vious observation,'h Vervliet et a1. 54 recently found positive correlation between decreased in­terferon responsiveness and both disability and progression rates of the disease in multiple scle­rosis patients. There is increasing interest in changes of lipid 120 metabolism in multiple sclerosis, because of the presumed fatty acid regulatory. fun~tion. in. the immune system,57 and the pOSSible implIcations for diet regulation in the management of affected patients:b Neu58 reassessed essenti~l fatty. acid levels in the serum and cerebrospmal flUId of multiple sclerosis patients. He found minor dif­ferences of fatty acid levels in serum of these patients as compared to normals, but in the cere­brospinal fluid he demonstrated that multiple sclerosis patients had a clear decrease in fatty acid levels, especially linoleic and arachidonic acid levels. Alteration of lipid metabolism in multiple sclerosis and in other neurological conditions was discussed. Zinc metabolism is also altered in patients with multiple sclerosis. This was demonstrated in a paper by Wong et a1.,59 which summarized recent metallochemical and biochemical studies and in­dicated trends of ongoing research on the subject. Double-blind randomized tests showed low plasma zinc levels in fasting multiple sclerosis patients as compared with normal subjects. De­creased plasma zinc level in these patients is associated with a functional abnormality in plasma membranes of erythrocytes, which are unable to maintain the zinc gradient between the extracellular and the intracellular compartments. Multiple sclerosis can be discovered unexpect­edly at necropsy. Phadke and BestbO reviewed previously reported cases and found that 18 had been clinically silent. They described 12 addi­tional cases of multiple sclerosis discovered at necropsy. In all 12, the diagnosis was either ig­nored or had been considered, but was subse­quently discarded. Analysis of these cases dis­closed that in four of them, intellectual deterio­ration had been a misleading clinical feature. Epileptiform attacks are uncommon in multiple sclerosis, and, therefore, can also be misleading clinical clues, as happened in two other cases of this series. In one case, a ruptured aneurysm was considered to be the likely cause of neurological involvement. Two patients had suffered isolated optic neuritis, 4 years and 22 years before death, respectively. In one case, urinary symptoms were probably erroneously attributed to urethral stric­ture. In another case, 16 years after an episode of optic neuritis, major neurological abnormalities arose, but they were considered a result of cere­brovascular disease. In one case with cervical cord involvement, cervical spondylotic myelopathy was diagnosed. Pain down both arms, lack of neurological signs above the neck, and obstruc­tion of the flow of myodil in the cervical region favored the diagnosis of spondylotic myelopathy. Of course, these conditions may coexist and pro­duce a mixed neurological disorder. In Aberdeen Royal Infirmary, Aberdeen, Scotland, where this Journal of Clinical Neuro-ophthalmology study was carried out, an average of one case of multiple sclerosis per year was discovered only at necropsy. Other misleading signs in multiple sclerosis diagnosis are unusual computerized tomography scanning appearances of enhancing lesions with edema suggesting cerebral tumors. In the corre­spondence section of the Journal of Neurology, Neurosurgery, and Psychiatry, Vannest and Daviesbl added a new case to the eight recently reported in that journal by Sagar et a1.b~ All patients presented with "cerebral" form of the disease, and computerized tomography scanning demonstrated lesions with mass effect. Although they were aware that use of corticosteroids in multiple sclerosis was controversial, Vannest and Davies felt that dexamethasone could be benefi­cial in the case of large cerebral lesions with edema. In their reply, Sagar et a1. 63 drew attention on the fact that such scan appearances could also result from lesions other than multiple sclerosis, including infections. The risk of patients with optic neuritis devel­oping multiple sclerosis may be related to geo­graphical factors. This prompted Landy64 to con­duct a prospective study in tropical and subtrop­ical areas of Queensland and northern New South Wales, Australia. The authors felt that the pro­portion of patients with optic neuritis who sub­sequently developed multiple sclerosis was simi­lar to that reported in temperate climates. Several reviews have recently appeared on multiple sclerosis and related matters. A review of the present state of research in multiple scle­rosis with regard to epidemiology, genetics, virol­ogy, and immunology of the disease, was pro­vided by Lhermitte and Lyon-Caen.65 Biblio­graphical data were extensive and up-to-date. A useful introduction to neuroimmunology was prepared by Aarly,b6 and Lassman67 published a synthesis on the value of experimental allergic encephalomyelitis as an experimental mode for multiple sclerosis. Occurrence of extensive white matter degen­eration (with optic atrophy) in patients with Cruetzfeldt-Jakob disease significantly altered clinical evolution of the disease. Kitagawa et a1.6~ studied 109 autopsy proven cases of Cruetzfeldt­Jakob disease reported in Japan, and one personal additional case. They found that in only 4 months the stage of appalic syndrome was reached in the 14 patients who presented with white matter involvement, whereas in patients with no or min­imal white matter deterioration it took an average of 11 months to reach that stage. Nevertheless, the interval between onset of the disease and end of life was not significantly different in the two groups of patients. Finally, Kitagawa et a1. noted that white matter involvement was more frequent June 1984 Safran in the cases of Creutzfeldt-Jakob disease de­scribed in Japan than in those reported in Amer­ican or European literature. The Chiasma An uncommon case of multiple fibrosclerosis with macular and suprasellar lesion was de­scribed by Brazier and Sanders.69 It occurred in a 26-year-old male, who also showed retroperito­neal and testicular involvement. The patient first presented with left gynecomastia and right testis enlargement. Elevated sedimentation rate was demonstrated. Furthermore, fibrosis around the pelviureteric junction was disclosed by means of pyelography and diagnosed with biopsy. Six months later, the patient complained of progres­sive visual loss in the right eye, and of generalized headache. Fundoscopy showed some swelling of the right optic disc and extensive serous detach­ment of the retina at the posterior pole; retinal pigment epithelium was atrophic and elevated in some areas. On skull x-rays, abnormal calcifica­tion was seen within the pituitary fossa, which was not, however, enlarged. Computerized to­mography scanning showed a calcified mass aris­ing from the pituitary fossa. With right frontal craniotomy, the right optic nerve was surgically decompressed. Tissue from the intracranial lesion showed nonspecific chronic inflammation. The authors found only one previously reported case of multiple fibrosc1erosis presenting with visual disturbances and intrasellar lesion. Metastasis to the pituitary region is rarely di­agnosed before death. Clinical features of two patients presenting with malignant melanoma metastasis to the pituitary gland and chiasmal syndrome were described by Hirst et a1. 70 Meta­static cells presumably originated from skin and from choroidal lesions, with a symptom-free pe­riod of 5-10 years. As soon as clinical and radio­logical diagnosis of suprasellar mass was estab­lished, surgical decompression of the anterior vis­ual pathway was performed. In both patients, dramatic visual improvement was obtained and lasted for the remainder of the patient's lives. In spite of poor general prognosis in these patients, indication of neurosurgical intervention is war­ranted by the remarkable recovery of visual func­tion. The Retrochiasmatic Visual Pathways Visual symptoms are important clues for diag­nosis of Lafora's disease. This recessively inher­ited condition bears a poor life prognosis. It ap­pears in 6- to 20-year-old children, and manifests mainly with myoclonic jerks, grand mal seizures, and progressive dementia. Early clinical diagnosis 121 Recent Literature: Part I is often difficult. Transient visual phenomena might help to distinguish this condition from primary generalized epilepsy and other progres­sive myoclonic epilepsies. This was indicated in a study by Roger et al. 71 in which paroxystic visual manifestations were found and analyzed in 17 out of 31 affected subjects. Visual phenomena were elementary or complex. Thirteen patients complained of elementary visual hallucinations, which were described as sparklings, rainbows, blue lights, etc. These were occasionally followed by transitory loss of vision. Their early occurrence in the course of the disease was noteworthy. In three patients, the hallucinations were isolated presenting symptoms, and in nine others were present at onset of the disease. Complex visual phenomena were experienced by seven patients; in four, they were associated with elementary positive visual phenomena. Complex visual hal­lucinations included perception of people and animals in a background that often was terrifying for the patient. In contrast to elementary phe­nomena, complex visual hallucinations only oc­curred late in the course of the disease, when mental state was often altered. Skin biopsy is invaluable in the diagnosis of Lafora's disease. Infantile epilepsy with occipital focus and good prognosis was described as a primary benign epileptic entity by Beaumanoir,n who also re­ported related ocular changes. The paper was based on a long-term follow-up of 18 patients. These presented with infantile epilepsy which generally began between the ages of 4 and 8 and disappeared before adulthood. Epilepsy, with re­peated uni- or bilateral occipital paroxysms, was suppressed by visual stimulation and enhanced by slow sleep. Seizures varied according to the state of vigilance. When they occurred in awake patients, symptomatology was mainly sensorial, including micropsias (in four patients), macro­psias (in one), loss of vision (in two), and visual hallucinations (in three). One child complained of intense photophobia during almost every sei­zure. In three patients, visual phenomena were followed by tonicoclonic seizures of the eyes. When seizures happened in the sleeping state, opening of the eyelids, tonic deviation of the eyes, occasionally associated with head deviation, and ocular clonia occurred successively. In certain cases, face, neck, and limbs were involved. Visual function was altered in half of the patients stud­ied. Five patients had strabismus, which was as­sociated with amblyopia in three of them. One patient showed severe myopia. Unilateral macu­lar changes were noted in one and partial optic atrophy in another. Also important was the fact that in five patients occipital focuses were already recorded before the appearance of seizures. Beau­manoir suggested that these data supported the assumption that development of the focuses and convulsive phenomena described could be related to cerebral maturation process and udisuse sensi­tivity." Although postictal complete blindness has ap­parently been reported in only one adult patient, this condition was found by Sadeh et aJ.73 not to be so rare among adults. These authors provided us with the observation of five adults who devel­oped total blindness immediately after grand mal seizures of various origins. Four patients regained visual function after 5 hours, 2, 3, and 4 days, respectively. In one, vision did not return before the patient died 3 months later. The authors noted that visual problems were denied by two patients, while a third appeared undisturbed by visual loss. They suggested that postictal blindness occurs more frequently than has been reported, but goes unrecognized because of associated unawareness of the visual impairment. A case of transient homonymous hemianopia occurring as the earliest symptom of subacute sclerosing panencephalitis was described by Ken­nedy et aJ.7-1 The visual defect resolved within 6 weeks. This seems to be the first report of a transient homonymous hemianopic defect as pre­senting symptom of subacute sclerosing panen­cephalitis. Also remarkable in this case history were relatively late onset of the disease (17 years of age) and delay of nearly 2 years between the onset of the hemianopia and the subsequent de­velopment of classical symptoms of the disorder. Lengthy survival and spontaneous remissions are unusual in subacute sclerosing panencepha­litis. The possibility of both should, however, be borne in mind when evaluating therapeutical trials in this condition, as was stressed by Parra­clough, 75 who described a patient showing such an atypical clinical course. A 12-year-old boy first presented with a 2-year-long characteristic course of the disease. Diagnosis was supported by an increased level of gammaglobulin in the cerebro­spinal fluid, typical changes in electroencephalo­gram, high serum and raising cerebrospinal fluid, measles antibody titers, and brain biopsy. Over the next 5 years, however, there were signs of mild, but sustained clinical improvement, disap­pearance of generalized repetitive complexes from electroencephalogram, and marked fall in the serum titers of measles antibody. The author suggested that these were not just signs of remis­sion, but that the pathological process could well have ceased. Such a well-documented case dem­onstrating prolonged survival in this disease has rarely been reported. Visual hallucinations are common features of chronic solvent encephalopathy secondary to glue sniffing. Channer and Stanley7!> demon­strated that they were not always transitory as Journal of Clinical Neuro-ophthalmology might have been believed. A 16-year-old boy was reported to first experience bright colored lights and zigzag shapes in the visual field when sniff­ing glue. Hallucinations initially lasted a few hours. Then, progressively, after each intoxication they persisted longer, until they remained con­stant. Visual acuity, color vision, fundi, and elec­troretinogram were normal, over a 3-month pe­riod following drug withdrawal. Pattern visual­evoked potential repeatedly showed delayed re­sponses and electroencephalogram demonstrated generalized alterations. After a follow-up period of 4 months, hallucinations consisted of a con­stant looping pattern. Dopamine treatment was apparently beneficial in a patient presenting with delayed blindness following carbon monoxide poisoning. Duncan and Gumpert77 reported the case history of a 28­year- old man who was accidentally exposed to carbon monoxide. He first fell unconscious, and when he regained consciousness visual acuity was reduced to light perception. Twenty hours later, he could read a newspaper and was dis­charged. Five days after the accident, he devel­oped bitemporal headache, photophobia, and blurring of vision. The next day, vision was again reduced to light perception. The regional cerebral blood flow was decreased in both temporal areas. Patients who have been exposed to carbon mon­oxide can first recover from neurological impair­ment and subsequently develop neurological dys­function, including cortical blindness, within the next few weeks. Improvement may occur over 3 years. Since this delayed neurological dysfunction could be due to elevated vascular resistance, Dun­can and Gampert chose to treat the patient with intravenous infusion of dopamine to increase the systemic arterial pressure. The latter was in­creased from 130/80 to 180/85 mm Hg with 17 Jig/kg/minute. After receiving the dopamine in­fusion for 6 hours, the patient could read the top line of a Snellen chart held at 70 cm. At 36 hours, he had 20/20 visual acuity and normal visual field. This case history warrants consideration, bearing in mind, however, that slow spontaneous recovery from delayed blindness in carbon mon­oxide intoxication has been reported. 78 Review papers on plasticity in visual systems were provided by Vital-Durand/9 . 80 and Hyvari­nen and Hyvarinen.81 Studies on morphological development of the primary visual pathway in infants recently conducted at the Institute of Anatomy at the University of Lausanne, Switz­erland, under the direction of L. J. Garey, were summarized in a paper by DeCourten and Garey.82 Two stages in the development of corti­cal area 17 were defined. The first was character­ized by a rapid growth to its adult volume by about the age of 4 months, and by intense syn- June 1984 Safran aptogenesis reaching a peak value at about 8 months. In the second stage, volume was stabi­lized and synaptic density was progressively re­duced to reach the adult level at about 11 years of age. Higher Visual Functions A remarkable case of highly selective disturb­ance of movement vision after bilateral posterior damage was reported by Zihl et al. 83 This peculiar visual impairment had striking effects on the everyday life of the patient. A 43-year-old woman presented with neurological symptoms and angiographic data indicating a superior sag­ittal sinus thrombosis. When examined 19 months after the onset of her illness, she mainly com­plained of a loss of movement vision in all three dimensions. She explained that, for example, she had difficulty in pouring tea into a cup. The fact that she did not perceive the rise of liquid level in the cup made her unable to stop pouring in time. She also experienced difficulty in following a discussion because she was disturbed by her inability to perceive the movements of a speaker's mouth. Being in a crowded place was almost unbearable to her, because people were suddenly here or there, without her realizing that they were moving. This made her feel quite insecure, and she avoided being with more than two persons at a time. Similarly, she could not evaluate the speed of vehicles in the street, and this made crossing a road a real problem to her: she first noted a car in the distance, then, when she started to cross the street, the car was there, in front of her. She finally got used to judging the movement of cars by means of changes in sounds. Detailed examination disclosed that visual acuity, static and kinetic visual fields, color vision, and critical flicker frequency were normal. Visual localization accuracy was not impaired. Conversely, move­ment vision in depth was apparently abolished, although the patient reported some impression of stimulus movement when the target moved along the horizontal or vertical axes, up to about 15° excentricity with relatively low velocity. Zihl et al. suggested that this selective alteration in visual movement perception could be due to a lesion of a cortical area functionally equivalent to that of the posterior third of the superior temporal sulcus in the monkey. This cortical area was found to contain movement-sensitive cells in heavy con­centration. An alternative explanation would be the disconnection of this cortical area from the striate cortex. Decreased ability to indicate which of two clearly visible gratings has the higher spatial fre­quency was described by Regan et al.84 in patients with multiple sclerosis. This was a form of dete- 123 Recent Literature: Part I rioration of size discrimination. Vision was dis­torted rather than blurred. Regan et al. believed that alteration in spatial frequency discrimination was due to relative changes in activities of differ­ent spatial frequency channels. This hypothesis could involve an opponent processing mecha­nism analogous to that attributed to color discrim­ination. A visual discrimination loss somewhat similar to that described by Regan et al. has also recently been reported in amblyopia.85 Alexia without agraphia is not always associ­ated with impairment of music reading. This was emphasized in a paper by Judd et al.,86 who described the case of a composer with severe reading impairment resulting from a left occipi­totemporal hematoma. Noteworthy was his re­tention of the ability to read music. The authors suggested that three levels of differences between music and text reading could explain the dissocia­tion of the patient's reading disorder: English text and staff music notation differ: 1) graphically, with regard to the relative spatial placement of symbols; 2) symbolically, in the use of nominal, ordinal, and intervallic modes of representation; and 3) functionally, i.e., in the output and processing strategies needed. Still, the present clinical features are exceptional since in the 35 previously published cases of musical alexia, Judd et al. noted that music reading was disturbed in most cases of alexia without agraphia. In addition, review of the literature did not reveal any con­vincing case of isolated disturbances of music reading. Music probably involves a complex of related, but distinct skills, which may concern many brain areas of both hemispheres. Optic ataxia is a disturbance of the activity of reaching under visual control. It may concern one or both hands, in a part of, or the whole visual field. Splenium of a patient with crossed optic ataxia was examined at necropsy by Ferro et aLB? A lesion was found in the dorsal part of the posterior two-fifths of the callosum. Ferro et al. proposed that the pathway that serves crossed visual reaching passes through the dorsal part of the posterior callosum. They agreed with the previously held opinion that fibers in the corpus callosum are distributed topographically in both anterior and ventrodorsal arrangement.88 Fur­thermore, they suggested that, in the posterior callosum, fibers conveying information about let­ters, colors, and visuospatial localization were respectively distributed from bottom to top. A paper by LhermitteB9 reported in patients with frontal lesions a type of behavior which was termed "utilization behavior." Visual, visuotactile, and tactile presentation of objects compelled the patients to grasp and use them. Lhermitte sug­gested that the balance between dependence on and independence from the outside world was 124 altered. I believe this paper could be correlated with the recent findings of Guitton et al. 90 about ocular motor behavior of patients with removed frontal lobes. Guitton et al. found in these pa­tients an inability to suppress a disallowed reflex glance at the visual stimulus. This is in agreement with the observation that plotting visual field isopters in patients with frontal lesions is often difficult because of the patients difficulty in keep looking at the central fixation point. In man, many visually responsive cells were found in the posterior parahippocampal gyrus, a structure that is known to be important for visu­ally determined memory tasks. Wilson et al.91 had the opportunity to obtain recordings from elec­trodes placed in patients with medically intract­able temporal lobe epilepsy. Some of the units in this posterior parahippocampal gyrus displayed receptive field characteristics similar to those re­ported in lower primates. The heterogeneity of receptive field types in this area suggested the influence of more than one source of visual af­ferents. Wilson et al. hypothesized that this con­vergence of visual information would play a prominent role in the complex memory process occurring in the human hippocampal formation. Like medial temporal lobe, medial thalamus is involved in visual object recognition. Clinical data in man and experimental findings in monkeys have indicated that bilateral damage in either of the two regions may result in anterograde am­nesia. 92 For the first time in the monkey, Aggelton and Mishkin93 demonstrated that a limited lesion of the medial thalamic region may produce a marked impairment in visual object recognition. This experiment reproduced the main features of "diencephalic amnesia." Pulvinar nuclei have been recognized as a part of the extrageniculostriate visual pathways. In man, visual dysfunctions have been attributed to lesions of the pulvinar.94 Although a retinotopic organization has been reported in the pulvinar of macaque monkeys, experimental observations regarding retinopulvinar projections in primates were felt to be inconclusive. To clarify conflicting results of these studies, Itaga and Van Haesen95 applied recently improved techniques of horse­radi. sh peroxidase and wheat germ agglutinine conjugated horseradish peroxidase. They thus demonstrated a retinofugal pathway to inferior pulvinar and a projection to medial pulvinar in macaque monkey. The fact that similar results were obtained with both horseradish peroxidase and wheat germ agglutinine conjugated horse­r~~ ish peroxidase seemed to preclude the possi­bIlIty that transsynaptic transport was responsible for their findings. Inferior pulvinar of macaque is not a homoge­neous structure as was believed previously. It Journal of Clinical Neuro-ophthalmology contains several subdivisions which project pri­marily to specific functional subdivisions in the visual cortex. Standage and Benevento96 discov­ered in the macaque monkey pulvinar one such region, which was topographically organized and projected to MT visual area in the superior tem­poral sulcus. MT area is also known as the mo­tion- sensitive area. References 1. 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(Reprints: Mr. M.D. Sand­ers, Department of Neuro-Ophthalmology, Na­tional Hospital for Nervous Diseases, Queen Square, London WClN, United Kingdom) 25. Kottow, M.H.: Papilloarterial ischemia. AllIl. Ophthall/lol. 13: 963-969, 1981. 26. McCrary, '.A, III: Information summaries. f. Gill. Nellro-ophthall/lol. 2: 65-71, 1982. 27. Kottow, M.: Papilloarterielle Ischamie. Klill. MOIl­ats/ ll. Allgellheilkd 182: 200-202, 1983. (Reprints: Dr. M. Kottow, Elisabethenstrasse 15, 0-7000 Stuttgart 1, Federal Republic of Germany) 125 Recent Literature: Part I 28. Keane, J.R.: Toluene optic neuropathy. Ann. Neu­ral. 4: 390, 1978. 29. Ehyal, A, and Freemon, F.R.: Progressive optic neuropathy and sensorineural hearing loss due to chronic glue sniffing. f. Neurol. Neurosurg. Psychia­try 46: 349-351, 1983. (Reprints: Dr. F.R. Freemon, Veterans Administration Medical Center, 1310 Twenty-first, South, Nashville, Tennessee 37203) 30. 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