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Show IN OTHER JOURNALS Editor's Note: This section contains brief reviews of articles that have appeared in other journals within the past six months. From a comprehensive list of clinical and scientific medical journals, each reviewer has selected about 30 titles and reviewed the most pertinent articles. The March and September issues include reviews from ophthalmology and medicine journals; the June and December issues include reviews from neuroscience and neuroclinical journals. Neuroscience Journals Reviewer: Syndee Givre, MD, PhD I. Apoptotic Neuronal Death After Ischemia Formerly, necrosis was thought to be the process responsible for cell death after ischemia, hi the past several years, many studies have provided evidence that ischemia results in apoptosis as well as necrosis, and that apoptosis may be responsible for delayed neuronal loss after ischemic injury. Lievre V, Becuwe P, Bianchi A, et al. Intracellular generation of free radicals and modifications of detoxifying enzymes in cultured neurons from the developing rat forebrain in response to transient hypoxia. Neurosci 2001; 105: 287- 297. The goal of the authors was to investigate the role of free radicals and the enzymes that normally detoxify them in apoptotic neuronal death induced by hypoxia. Neuronal cell cultures isolated from developing rat brain were exposed to 6 hours of a 78% decrease in the partial pressure of oxygen, then reoxygenated ( experimental group), and were compared with identical cultures maintained at normoxia ( control group). Intracellular levels of reactive oxygen species were significantly increased in the experimental cultures as compared with controls up to 48 hours after reoxy-genation. Also in experimental cultures, the mRNA levels of Cu/ Zn- superoxide dismutase and Mn- superoxide dismu-tase, both active in detoxifying free radicals, were transiently depressed during hypoxia, and then increased after reoxygenation. At 96 hours after reoxygenation in the experimental cultures, there was a 37%> reduction in the number of living cells, and 23 %> of the living cells had nuclear morphology consistent with apoptosis. N- acetyl- L- cysteine ( NAC) is a precursor for the synthesis of reduced glutathione, an important part of the defense mechanism for detoxifying free radicals. If NAC was added to experimental cultures prior to hypoxia, the percentage of neurons displaying apoptotic characteristics decreased to 4.6%> but the percentage of necrotic cells was unaltered. NAC had no effect on the percentage of apoptotic or necrotic neurons in the control group. These results show that transient hypoxia is followed by intraneuronal free radical production that is detectable for several days after reoxygenation. Although there is a concomitant increase in the levels of mRNA encoding enzymes that detoxify free radicals, the anti- oxidant capacities of these enzymes may be overwhelmed, leading to apoptosis. NAC, a precursor of glutathione, appears neuroprotective. Elibol B, Soylemezoglu F, Unal I, et al. Nitric oxide is involved in ischemia- induced apoptosis in brain: a study in neuronal nitric oxide synthase null mice. Neurosci 2001; 105: 79- 86. The goal of the authors was to investigate the relationship between nitric oxide and apoptosis after ischemia. They compared the results of permanent, unilateral middle cerebral artery occlusion in normal mice to those of mutant mice lacking the gene for neuronal nitric oxide synthase ( those with a deficiency in neuronal nitric oxide production). The mean infarct area was significantly reduced in mutant mice at 6, 24, and 72 hours after artery occlusion. The number of apoptotic neurons as assessed by terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling ( TUNEL, a marker of DNA fragmentation) and by caspase- 3 mediated cleavage of actin to fractin was significantly reduced ( 50% o) in mutant mice as compared with wild type mice at 72 hours. This held true after normalization for the smaller infarct size in mutant mice. Also, the level of Bcl- 2, an anti- apoptotic protein, was significantly decreased ( 73 %>) in the ischemic hemisphere ( versus the nonischemic, control hemisphere) of wild type mice and was significantly increased ( 105% o) in the ischemic hemisphere ( versus the contralateral hemisphere) in mutant mice. Levels of the pro- apoptotic protein Bax were unchanged in the ischemic hemispheres of mutant and wild type mice. The authors propose that deficiency in neuronal nitric oxide production slows the development of apoptotic cell death after ischemia. Katchanov J, Harms C, Gertz K, et al. Mild cerebral ischemia induces loss of cyclin- dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal death. J Neurosci 2001; 21: 5045- 5053. Once terminally differentiated, neurons enter a resting state. Aberrant reentry into the cell cycle is believed to cause apoptosis. Such reentry may be induced by ischemia. The goal of the authors was to investigate the temporal relationship between the expression of various cell cycle ^ 134. DOL lp. l097/ 01. WNO, Q0Q001826L87375, CB . JNeuro- Ophthalmol. Vol. 22, No. 2,2Q02 , Copyright © Lip pincott Williams & Wilkins. Unauthorized reproduction oftnis article is prohibited. IN OTHER JOURNALS J Neuro- Ophthalmol, Vol. 22, No. 2, 2002 proteins and delayed neuronal death in mice after 30 minutes of reversible, unilateral occlusion of the middle cerebral and anterior choroidal arteries. Similar measurements were made in primary neuronal cultures after oxygen- glucose deprivation. Arterial occlusion led to cell death in the striatum but not the cortex. After 9 hours of reperfusion, before the appearance of any TUNEL staining, approximately half of the striatal neurons stopped expressing pl6INK4a, an inhibitor of cyclin- dependent kinase ( cdk). Cdkisa cell cycle protein. These pl6 negative neurons subsequently underwent cytoskeletal degradation and stained for TUNEL. TUNEL staining peaked at 72 hours after reperfusion and no TUNEL labeled cell expressed p 16. In contrast, virtually all neurons surviving at 72 hours did express pi 6. Similarly, in cultured neurons, pl6 and p27Kpl ( another inhibitor of cdk) were down-regulated after oxygen- glucose deprivation. Furthermore, cyclin Dl, an activator of cdk, was upregulated following cerebral ischemia and oxygen- glucose deprivation in vivo and in vitro, respectively. Such changes were not seen in control ( sham operated) mice and in control cultures. When added to cultured neurons prior to oxygen- glucose deprivation, olomoucine, an inhibitor of cdk, significantly protected neurons from damage. These results provide evidence that cell cycle proteins are altered in postmitotic neurons after ischemic insult as a prelude to apopto-sis. The authors hypothesize that these alterations represent attempts at cell cycle reentry. n. Apoptosis in Multiple Sclerosis Meyer R, Weissert R, Diem R, et al. Acute neuronal apoptosis in a rat model of multiple sclerosis. JNeurosci 2001; 21: 6214- 6220. Mechanisms of cell death resulting from inflammation in multiple sclerosis ( MS) and the animal model of MS, experimental autoimmune encephalomyelitis ( EAE), are not completely understood. The authors used electrophysi-ology and histology to investigate the function and morphology of retinal ganglion cells in rats after induction of EAE by intradermal injection of recombinant rat myelin oligodendrocyte glycoprotein. Of the 17 immunized rats, seven developed widespread, bilateral demyelination of the optic nerves and swollen, distorted axons on histology. These seven rats had absent flash and pattern evoked potentials, markedly reduced pattern ERGs and normal flash ERGs as compared with control ( sham injected) rats and experimental rats that did not develop demyelination on histology. Electrophysiological results were similar in control rats and experimental rats without demyelination. The density of retinal ganglion cells was evaluated by retrograde labeling using Fluorogold, a fluorescent dye that had been injected into both superior colliculi before induction of EAE or sham induction of controls. In rats with demyelination, the retinal ganglion cell density was significantly reduced at 50- 72 hours after the onset of clinical symptoms ( tail weakness). In EAE rats that did not develop demyelination, the retinal ganglion cell density varied greatly from normal ( similar to control rats) to greatly reduced ( as in EAE rats that did develop demyelination and symptoms). In rats with demyelination, some retinal ganglion cells stained positive for TUNEL and for caspase- 3 activation. In summary, EAE results in demyelination in rat optic nerve and a reduction in the number of retinal ganglion cells. The authors propose that the mechanism of retinal ganglion cell death is apoptosis and that their results give the molecular rationale for the early application of neuroprotective strategies in MS. However, given that markers for apoptosis were seen only in some remaining retinal ganglion cells, this proposal will require further investigation. III. Neurotrophic Factors Pencea V, Bingaman KD, Wiegand SJ, et al. Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci 2001; 21: 6706- 6717. Brain- derived neurotrophic factor ( BDNF) is known to promote survival and differentiation of neuronal progenitor cells in culture and generate new neurons and glia in selected areas of adult mammalian forebrain in vivo. In the current study, the authors examined the distribution and types of newly generated cells in the adult rat forebrain 16 days after a 12- day continuous administration of BDNF ( vehicle alone was administered in control rats) into the right lateral ventricle. To label the newly generated cells, the cell proliferation marker BrdU was administered intra-ventricularly, concurrent with BDNF ( another control group consisted of rats receiving intraperitoneal injections of BrdU without any intraventricular infusion). Newly generated, BrdU+ cells were present in the subventricular zone surrounding the infused lateral ventricle as shown in previous studies. New cells were also found in areas not previously thought to give rise to them including the parenchyma adjacent to the lateral ventricle, the striatum, septum, corpus callosum, cerebral cortex, thalamus and hypothalamus. In some areas, new cells were found in the brain parenchyma and not in the adjacent subventricular zone. Nuclear diameter and morphology of labeled cells varied with location. Cells were frequently aggregated in pairs, possibly indicating that cell division had occurred. In control rats infused intraventricularly with vehicle plus BrdU, the number of newly generated cells was substantially less, though the distribution was similar to the distribution of new cells in the experimental group. In control rats receiving only intraperitoneal BrdU, the number of new cells was substantially Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 IN OTHER JOURNALS less than in experimental animals and the distribution of new cells was restricted primarily to the subventricular zone adjacent to the lateral ventricle. In the experimental group, the distribution of BrdU labeling correlated well with labeling for TrkB, a high- affinity receptor for BDNF. However, TrkB labeling in infused hemispheres of experimental rats was not different from that in the uninfused hemispheres or from that in vehicle- infused controls. Thus, BDNF did not upregulate TrkB expression. Furthermore, TrkB+ cells were not themselves BrdU+ but were adjacent to Brdu+ cells. The percentage of BrdU labeled cells that co- labeled for a neuronal cell marker varied from 27 to 42 and in all regions was significantly higher than the number of new neuronal cells in rats infused with vehicle. The authors conclude that BDNF profoundly increases the cell proliferation and/ or survival of progenitor cells and their progeny. The fact that areas of higher new cell density were not necessarily closer to the subventricular zone may indicate that progenitor cells are normally present in situ. Variations in new cell density could be the result of variations in TrkB expression. Future studies will investigate whether BDNF can rescue degenerated neurons or replace neurons already lost as a result of disease. Akerud P, Canals JM, Snyder EY, et al. Neuroprotection through delivery of glial cell line- derived neurotrophic factor by neural stem cells in a mouse model of Parkinson's disease. JNeu-rosci 2001; 21: 8108- 8118. In recent years, therapeutic strategies for neurodegenerative diseases have been proposed that address cell loss rather than replacement of neurotransmitters. These strategies have included replacement of dead neurons with new ones via transplantation and prevention of neuronal death using trophic factors. Glial cell line- derived neurotrophic factor ( GDNF) is known to be a potent neurotrophic factor for substantia nigra dopaminergic neurons. The authors of the current study sought to determine if the delivery of GDNF by transplanted neural stem cells could exert a therapeutic effect in a mouse model of Parkinson's disease. A stable clone of mouse neuronal stem cells expressing GDNF and a mock- transfected clone were engineered and these cells were injected unilaterally into the striatum of mice. Graft survival was assessed histochemi-cally, by the presence of a marker present in both clones or by the presence of GDNF immunohistochemistry in GDNF clones. Engraftment was present in 100% of mice at 15 days but in only 12.5% of mice by 4 months. When the same clones were injected into the brains of CD- I nude mice there was engraftment of cells in 100% o of animals at 4 months. Using double labeling with markers for neurons, oligodendrocytes, or astrocytes, it was determined that most GDNF transplanted cells ( 81%) adopted an oligodendrocyte phenotype at 1 and 4 months and most ( 75.3%) integrated within the white matter and fiber bundles of the internal capsule that traverses the striatum. When the ventral midbrain was examined, an increase in GDNF immunoreactivity was found ipsilateral to the graft but not contralateral to the graft and not in mock grafted striatum. Double staining for GDNF and tyrosine hydroxylase ( TH) showed that GDNF was present in the substantia nigra and within dopaminergic neurons. Intrastriatal grafting of GDNF and mock clones was performed in a 6- OHDA lesion model of Parkinson's disease. Sixteen days after grafting, grafted and nongrafted control mice received a single intrastriatal injection of 6- OHDA. Thirty days after grafting, nongrafted control mice and mock grafted mice demonstrated a similar loss of substantia nigra dopaminergic neurons ( approximately 60%). Mice grafted with GDNF demonstrated a loss of only 21% of substantia nigra dopaminergic neurons. To determine if GDNF grafting conferred functional protection in the lesioned mice, two motor behavioral assays were performed 12 and 13 days after lesioning. Lesioned mice that had received GDNF grafts performed significantly better than lesioned mice that had received the mock graft or lesioned mice that had not received any graft. The delivery of genes by neural stem cells has the advantages that no genetic modification is introduced in the host cells and no viral particles are introduced into the nervous system. In grafting over 100 mice in these experiments, none developed a tumor. The results of the current study suggest that transplantation of genetically engineered neural stem cells could be an effective strategy to locally deliver trophic factors to the brain because GDNF-expressing neural stem cells integrated and differentiated well after grafting, dispersed within but remained restricted to the striatum, and maintained GDNF expression for at least 4 months. Furthermore, grafting afforded protection of dopaminergic neuron survival and prevention against motor disturbances in a mouse model of Parkinson's disease. Graft survival was greatly enhanced in nude mice, suggesting that some form of immunologic modulation may be necessary when applying this technique to immunologically normal subjects. Guan J, Miller OT, Waugh KM, et al. Insulin- like growth factor- 1 improves somatosensory function and reduces the extent of cortical infarction and ongoing neuronal loss after hypoxia-ischemia in rats. Neurosci 2001; 105: 299- 306. Insulin- like growth factor- 1 ( IGF- 1) is a potent neurotrophic factor that is present in brain. The goal of the authors was to determine the effects of IGF- 1 on long- term neuronal outcome and somatosensory function after right carotid artery ligation followed by short inhalational n136. , „ . . , „ . . © 2002 Lippincott Williams & Wilkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS J Neuro- Ophthalmol, Vol. 22, No. 2, 2002 asphyxia in rats. Two hours after the hypoxic- ischemic insult, the right lateral ventricle was infused with IGF- 1 or vehicle. Tactile stimulation tests were performed on days 3, 5, 10 and 20 after infusion and histology was obtained on day 20. Sham- operated rats showed no difference between right and left forelimb somatosensory function. At day 3, vehicle- treated rats had significantly worse ipsilateral somatosensory function as compared with sham operated controls. This improved by day 5. IGF- 1- treated rats had significantly better forelimb somatosensory function as compared with vehicle- treated rats but this was found only at the day 3 time point. On histology in the IGF- 1- treated group, the cortical infarct showed a trend towards an increased amount of surviving tissue but this did not achieve statistical significance. However, selective neuronal loss was significantly reduced in the IGF- 1- treated group as compared with the vehicle treated group. The authors propose that IGF- 1 improves somatosensory function by reducing the extent of cortical infarction and ongoing progressive neuronal death during brain recovery from hypoxic- ischemic insult. Romero MI, Rangappa N, Garry MG, et al. Function regeneration of chronically injured sensory afferents into adult spinal cord after neurotrophin gene therapy. JNeurosci 2001; 21: 8408- 8416. After injury, axons of the spinal cord dorsal root regenerate within the peripheral nervous system but stop abruptly at the central nervous system border, the dorsal root entry zone. Several strategies have been developed for reversing the nonpermissive nature of the adult central nervous system. These have included blocking inhibitory molecules and using grafts of growth- supporting glia. In the current study, recombinant adenoviruses conditionally expressing either nerve growth factor ( NGF), fibroblast growth factor- 2 ( FGF2), the cellular adhesion molecule LI, or a control marker gene were injected into the dorsal spinal cord after crush injury of the dorsal roots in rats. Specifically, dorsal roots L4 and L5 were lesioned by crushing approximately 5- 8 mm from the dorsal root entry zone. To prevent contamination of results by sprouting, dorsal roots L3 and L6 were completely cut. After 2 weeks, animals with complete sensory loss received eight injections of adenoviral vectors superficially, in the dorsal horn along L4- L5. The animals underwent behavioral testing 8 days after adenoviral vector injection. In animals killed before adenoviral injections, histology showed that crushing resulted in degeneration of all axons distal to the crush site. Rats receiving injections of the control marker displayed no regeneration of axons and nearly no collateral sprouting in to the L4 - L5 spinal cord. The vast majority of denervated rats that received FGF2 or NGF had a dramatic increase in the number of fibers regenerating into the dorsal horn as compared with animals receiving control injections. In addition, rats receiving injections of NGF had a dramatic increase in the amount of sprouting of spared axons from L3 and L6. Regenerated sensory afferents were observed in normal and abnormal laminae and both within gray and white matter of the dorsal spinal cord. Axonal growth was greatest within the regions surrounding the injection sites. Injections of LI did not induce axonal growth. Nociception and proprioception were tested in a double- blind fashion. After rhizotomy but before adenoviral vector injection, rats had a complete loss of thermal sensation ipsilaterally but not contralateral-ly. After injection of either control marker or LI in to the dorsal horn, rats showed no recovery of nociception or proprioception. Rats injected with either FGF2 or NGF gradually recovered nociceptive function. This was first apparent at one week after injection and reached statistical significance, achieving near- normal values by week 2 to 3. There was a correlation between the recovery of nociceptive function and the regeneration of axons on histology. Furthermore, cutting L4 and L5 after recovery abolished ipsilateral nociception, indicating that it was not due to collateral sprouting from L3 and L6.. Proprioceptive functioning was not improved after injection of control marker, NGF, FGF2orLl. The authors thus demonstrated that in vivo expression of NGF and FGF2 can induce axonal regeneration and functional recovery of nociception, supporting the use of in vivo gene therapy as a means of delivering molecules able to transform the adult CNS from inhibitory to growth-promoting. Ahuja P, Caffe AR, Holmqvist I, et al. Lens epithelium- derived growth factor ( LEDGF) delays photoreceptor degeneration in ex-plants of rd/ rd mouse retina. Neuroreport 2001; 12: 2951- 2955. Lens epithelium- derived growth factor ( LEDGF) is a transcription activator present in the nucleus of many cells types including the RPE and retinal photoreceptors. Previously, LEDGF had been shown to rescue damaged photoreceptors in chick and mouse models. The current study used a mouse retinal explant model to assess the rescue ability of LEDGF. At postnatal days 2 and 7 ( PN2 and PN7, respectively), retinal explants were obtained from rd/ rd mice, an animal model for the human recessive form of retinitis pigmentosa, and were compared with explants from wild type mice obtained on the same postnatal days. Wild type and rd/ rd explants were incubated both with and without LEDGF. Untreated PN2 and PN7 explants from rd/ rd mice had excessive loss of photoreceptors. LEDGF had no significant effect on wild type explants obtained from PN2 and PN7. LEDGF treatment significantly rescued the photoreceptors in both the PN2 and PN7- derived rd/ rd explants Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 IN OTHER JOURNALS when compared with untreated rd/ rd explants taken at the same age. The results were the same at PN2 and PN7. Im-munostaining for the photoreceptor proteins opsin and arrestin was unchanged by treatment with LEDGF in rd/ rd and wild type explants as compared with untreated explants. These data show that LEDGF has a protective effect on photoreceptors cells. The authors propose that, given the multitude of genes involved in various retinal degenerations, the use of survival factors may be a better strategy for preventing photoreceptor loss than gene therapy. IV. Electrophysiology Snodderly DM, Kagan I, Gur M. Selective activation of visual cortex neurons by fixational eye movements: implications for neural coding. Visual Neurosci 2001; 18: 259- 277. When the head is immobilized and a subject attempts to maintain fixation on an object, fixational eye movements maintain visibility of the object. These fixational eye movements consist of slow drifts interspersed with small, fixational saccades. Whether the slow drifts alone or the combination of slow drifts and fixational saccades is necessary to maintain visibility is not known. The goal of the authors was to investigate the effects of fixational eye movements on single neuron activity in area VI of macaque cortex. Subjects viewed a stationary stimulus on which they were trained to fixate. In addition to the temporal relationship between neuronal activity and fixational eye movements, the spatial relationship between the receptive- field activating region ( AR) and the stimulus that was established by the eye movement was investigated. Recordings revealed three types of neurons, position/ drift- activated cells, saccade-activated cells and mixed cells. Position/ drift- activated neurons were activated during the intersaccadic drift period when an optimal stimulus was within the cell's AR. This type of cell exhibited an increase or decrease in firing after a saccade, depending on whether the saccade moved the AR onto ( or better centered over) or off of ( or more poorly centered over) the stimulus, respectively. The activity of sac-cade- activated cells was complimentary to that of position/ drift- activated neurons. Saccade- activated neurons discharged when a fixational saccade moved the AR onto, off of or across the stimulus. Some saccade- activated cells were direction sensitive and were activated when the AR moved both off and onto the stimulus as long as the perceived retinal motion was in the cell's preferred direction. These cells were activated even by small saccades that moved the AR by only a fraction of its width. Direction selectivity for activation by a fixational saccade had not previously been found in VI. Mixed cells were the most numerous kind. They fired bursts of activity after saccades and exhibited more irregular, sustained activity during the intersaccadic drift periods. The authors hypothesize that, during natural viewing conditions, position/ drift- neurons may be important in signaling the position of stimulus features on the retina and may be refractory to the detrimental effects of saccades. The response of saccade- activated neurons, being ambiguous with respect to the spatial details of the retinal image, may be involved in constructing a stable world in spite of constant retinal image motion. Alternatively, saccade-activated neurons may be involved in the suppression of visual input associated with saccades. Jamison JA, Bush RA, Lei B, et al. Characterization of the rod photoresponse isolated from the dark- adapted primate ERG. Visual Neurosci 2001; 18: 445^ 155. The a- wave of the dark- adapted ERG is classically thought to represent the activity of rod photoreceptors but several studies have shown that the inner retina may also contribute to this potential. The goal of the authors was to use pharmacologic agents to determine if, in primates, the Ganzfeld ERG dark- adapted bright flash a- wave primarily reflects the activity of photoreceptors or whether it contains a component of inner retinal activity. ERGs were recorded from anesthetized macaque monkeys before and after intra-vitreal injections of 4- phosphono- butyric acid ( APB), which blocks depolarizing- bipolar cell activity and cis- 2,3- piperidine- dicarboxylic acid ( PDA), which blocks hyper-polarizing- bipolar cell, horizontal cell and amacrine cell activity. Light- adapted cone responses were subtracted from dark- adapted ERGs elicited over a 5- log- unit intensity range to isolate the rod ERG a- wave. The results showed that for bright, short flashes, the application of APB or PDA had no effect on the leading edge of the a- wave up to the point of intrusion of the b- wave. Therefore, the a- wave elicited by a bright, short flash is dominated by the activity of rod photoreceptors. APB reduced the dark- adapted maximum a- wave amplitude and PDA increased the dark-adapted a- wave maximum amplitude. Neither chemical changed the shape of the waveform. This suggests that APB and PDA can alter the maximum dark current flowing from the rod inner to outer segment. Since APB and PDA are not known to have any effect on photoreceptors themselves, this alteration of current may reflect feedback from postre-ceptor cells. Mizobe K, Polat U, Pettet MW, et al. Facilitation and suppression of single striate- cell activity by spatially discrete pattern stimuli presented beyond the receptive field. Visual Neurosci 2001; 18: 377- 391. The anatomic substrate for long- range interactions amongst single neurons in primary visual cortex exists in _ 13o. , . © 2002 Lippincott Williams & WUkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS J Neuro- Ophthalmol, Vol. 22, No. 2, 2002 the extensive dendritic and axonal arborizations of pyramidal cells. The physiologic and functional implications of these lateral connections are still not well understood. The goal of the authors was to study the nature of the modulation of the responses to stimuli in the classic receptive field ( CRF) by simultaneously presented remote stimuli. Single unit recordings were obtained from primary visual cortex of adult cats. Stimuli were composed of three distinct patches ( Gabor patches). The center patch ( target) matched the ret-inotopic location, orientation, size and spatial and temporal frequency selectivity of the classic receptive field of the neuron being recorded from. Two flanking patches were presented well outside the classic receptive field. In any given cell, the response to the target could either be facilitated or suppressed by the flankers when the orientation of the flankers matched that of the target. Rather than depending on the absolute contrast of the flankers, the sign of the modulation ( facilitation versus suppression) seemed to be determined by the contrast of the flankers relative to the threshold contrast of the target. At contrasts just above the neuron's firing threshold, facilitation most often occurred. At higher contrasts suppression most often occurred. Such modulation was obtained at 12 degrees or more of separation of the target and flankers. If the orientation of the flankers was made orthogonal to that of the target, facilitation was lost. These results were found in simple and complex cells and in cells in the supragranular, granular and infra-granular layers of cortex. The authors hypothesize that the effects of remote stimulation provide the basis for a neural mechanism for the perceptual grouping of stimulus features belonging to a large, complex scene. Ransom CB, O'Neal JT, Sontheimer H. Volume- activated chloride currents contribute to the resting conductance and invasive migration of human glioma cells. JNeurosci 2001 ; 21: 7674- 7683. Chloride channels are proteins known to be important in salt and fluid movement and cell volume regulation. Based on their previous work, the authors hypothesized that changes in cell shape and/ or volume are necessary for migration of human glioma cells and that CP currents may effect such changes. The current study used patch- clamp techniques to investigate CP currents, in particular volume-activated CP currents, in two human glioma cell lines. Also, an in vitro model of invasive migration was used to investigate the role of CI" currents in invasion. Exposure of the cells to hypotonic solutions led to swelling of the cells and activation of currents with electrical properties characteristic of CP currents. Such currents were > 80% inhibited by the application of several well known antagonists of the volume- activated CP channel including tamoxifen and 5- nitro- 2-( 3- phenylpropylamino)- benzoate ( NPPB). Furthermore, when the relative permeabilities of P and CP were compared, these currents had ion specificities similar to those of known volume- dependent CP channels. To look for resting CP currents, CP was replaced by poorly per-meant ions. This led to a reduction of outward current and a positive shift in the reversal potential of the cells, providing evidence for a resting CI" conductance. In the in vitro model of invasive migration, cells were plated on a plate with a filter consisting of pores that provide a three- dimensional constraint to movement. The pores were of such a size that cells were required to change their shape to navigate through them. Placement of a chemotactic agent on the side of the pores opposite the cells led to migration of the cells through the pores. This migration was reduced in a dose-dependent fashion after the application of NPPB. Spontaneous movement of glioma cells during patch- clamp recording was also observed using time- lapse video recording. This spontaneous movement was accompanied by an increase in the whole- cell current in a manner consistent with CP currents. Application of NPPB stopped the movement. The authors propose that volume- activated CI" currents are important in generating the cell size and volume changes necessary for the migration of glioma cells through the extracellular spaces in brain. Angelaki DE, Green AM, Dickman JD. Differential sensorimotor processing of vestibulo- ocular signals during rotation and translation. JNeurosci 2001 ; 21: 3968- 3985. The vestibulo- ocular reflexes ( VOR) are critical in maintaining stable image perception during motion. Previous studies have shown that, with regards to the rotational VOR ( RVOR), a disynaptic connection exists between the vestibular sensory organ and the ocular motor nuclei, with the initial synapse being in the rostral vestibular nuclei. The shortest latency RVOR pathways are mediated predominantly by excitatory projections to the contralateral sixth nerve nucleus. The pathways for the translational VOR ( Tr- VOR) are less well understood. The goal of the authors was to investigate the activity of single neurons in the rostral vestibular nuclei of rhesus monkeys during pursuit eye movements, RVOR, TrVOR ( with the subject fixating on an earth- fixed target) and suppression of the RVOR and TrVOR ( with the subject fixating on a head- fixed target). Based on their preferred stimulus patterns, neurons were classified into two broad categories, eye- contra cells and eye- ipsi cells that responded to contralateral and ipsilateral eye movements, respectively. Further subtypes of neurons Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 IN OTHER JOURNALS were then defined. Burst- tonic ( BT) neurons were sensitive to eye movements, behaving similarly during rotation and translation, but were inactive during VOR suppression. Vestibular- only neurons were insensitive to smooth pursuit eye movements in the absence of rotational or transla-tional head movement. Position- vestibular pause ( PVP) and position- vestibular ( PV) cells were sensitive to rotational head movement and eye movement in opposite directions ( with these movements performed either in isolation from each other or together). Eye- contra PVP and PV neurons exhibited no response to ipsilateral head translation when it was isolated from eye movement activity in the TrVOR suppression task whereas eye-ipsi PVP and PV neurons did respond to translational head movement without eye movement. Eye- head ( E- H) neurons were sensitive to rotational head movement and eye movement in the same direction ( with these movements performed either in isolation from each other or together). In contrast to the eye- contra PVP and PV cells that exhibited no response to TrVOR, 50% of E- H neurons exhibited activity when the animal suppressed its eye movements. In summary, most eye movement sensitive neurons exhibited activity during RVOR, RVOR suppression and TrVOR but only a subset, eye- ipsi PVP and PV neurons plus some of the E- H neurons, were activated during TrVOR suppression. This subset of neurons may be the recipient of more direct otolith signals and the authors suggest these neurons may form the cellular basis of the utriculoab-ducens pathway. A model of this pathway is constructed by the authors and discussed. V. Anatomy Yates PA Roskies AL, McLaughlin T, et al. Topographic-specific axon branching controlled by ephrin- As is the critical event in retinotectal map development. J Neurosci 2001; 21: 8548- 8563. The exact molecular mechanisms underlying the development of topographic connections in the visual system of chicks and mammals are controversial and not completely understood. Spatial concentration gradients of certain topographic guidance molecules play an important role. In chicks, EphA receptors and their ephrin- A ligands act as such guidance molecules in the development of connections between retinal ganglion cells ( RCG) and the tectum. The goal of the authors was to determine the mechanisms that chick RGC use to develop their topographic projections to the tectum. First, topographic specificity in growth cone targeting, axon branching and arborization were quantified in vivo. RGC axons were labeled by injection of dye into defined retinal locations on embryonic day 9 ( E9), when axons are initiating branching in the tectum, through E12, when definitive topographic organization can be identified. The retina and contralateral tectum of each subject were whole mounted and evaluated microscopically 12- 72 hours later. For each embryonic day, the termination zones ( TZ) of axons and their arbors in the tectum were compared with the predicted TZ based on the distance on the distance of the injection from the temporal edge of the retina. ( For subjects injected at E13, by which time topography is correctly established, the observed TZ was always found to be at the predicted TZ, confirming the accuracy of the method of prediction of the TZ.) Normally, RGC axons develop their topographic map along the anterior- posterior ( A- P) axis of the tectum with the temporal peripheral retina projecting to the anterior pole of the tectum. The labeling patterns revealed that retinal ganglion cell axons overshot the topographic location of their predicted TZ along the A- P tectal axis by a distance that varied with their origin along the temporal- nasal retinal axis ( temporal axons overshot by the greatest amount). In contrast, branches formed along the axons with a topographic bias for the correct A- P location of the predicted TZ. Both branch distribution and density increased in topographic specificity between E10 and E13. Even at E10, though, the topographic bias in branch distribution for the predicted TZ was statistically significant. Refinement of topographic specificity was achieved by both axonal branch addition and branch elimination. Next, an in vitro assay was set up in which explants of temporal or nasal retina from E6 chicks were placed on a substrate of alternating lanes of membranes prepared from anterior or posterior tectum from E9- E10 chicks. Using this assay, temporal retinal axons were shown to preferentially target anterior tectal membranes. Ephrin- As are normally present in a higher concentration in the posterior tectum and preferentially repel or collapse temporal RGC axon growth cones. After the addition of EphA3- Fc to the assay, which blocks ephrin- A function, temporal axons branched equally on anterior and posterior tectal membranes. Finally, time- lapse video microscopy was used to investigate axonal branching in vitro. Both de novo branching from the axon shaft and bifurcation of the growth cone occurred. Axons from temporal retina exhibited preferential extension of branches onto anterior membranes although a bias to retract branches from posterior membranes acted to sharpen the topographic specificity of branch distribution. These findings show that, rather than topographic growth cone targeting, topographic branching along the shaft of RGC axons is the critical event in the development of the retinotectal map in chicks. n 140 . , „.. , „ . . © 2002 Lippincott Williams & WUkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS J Neuro- Ophthalmol, Vol. 22, No. 2, 2002 Neuroclinical Journals Reviewer: Kathleen B. Digre, MD I. Wegener's Granulomatosis DeGroot K, Schmidt DK, Arlt AC, et al. Standardized neurologic evaluations of 128 patients with Wegener's Granulomatosis. Arch Neurol 2001 ; 58: 1215- 1221. The authors prospectively analyzed 128 patients with documented Wegener's granulomatosis diagnosed by American College of Rheumatology classification criteria. Internists, ophthalmologists, otorhinolaryngolo-gists, and neurologists examined all patients. All had serologic assessment, chest computed tomography ( CT), and cranial magnetic resonance imaging ( MRI). Sixty-four patients ( 50%) had central ( 9 patients) or peripheral ( 56 patients) nervous system involvement. In keeping with practical experience, but contrary to previous reports, cranial nerve involvement was rare, occurring in only 6 patients ( optic nerve 4, trigeminal and facial nerves 1 each). All cranial neuropathies were caused by infiltration originating in the paranasal sinuses. A distal symmetric peripheral neuropathy was the most common nervous system involvement. Patients with neurologic involvement were more frequently male, older at the onset, had a larger disease extent, and higher antineutrophil cytoplasmic antibody titers than those without neurologic involvement. Treatment with immunosuppression had a moderate effect. n. Anticonvulsant Toxicity Sills GJ, Patsalos PN, Butler E, et al. Visual field constriction. Accumulation of vigabatrin but not tiagabine in the retina. Neurology 2001; 57: 196- 200. The anticonvulsant vigabatrin is reported to constrict the visual field in 40% of treated adults and 65% of treated children. The drug increases the concentrations of the inhibitory neurotransmitter gamma- aminobutyric acid ( GABA). The mechanism of visual field constriction is not clear. Tiagabine, another new anticonvulsant, has also been reported to cause visual field defects. It may also increase GABA by inhibiting GABA reuptake. In this study, the authors measured GABA concentrations in the brain and retina in adult male rats after administration of vigabatrin or tiagabine. Vigabatrin accumulated in the retina and caused accumulation of GABA in the retina at 5- fold the amount in the brain. Tiagabine did not accumulate in the retina or affect GABA concentrations there. The authors concluded that vigabatrin accumulation and perhaps an increase in GABA concentration may be responsible for the visual field constriction. Tiagabine was considered unlikely to cause visual field defects in humans. Nousiainen I, Mantyjarvi M, Kalviainen R No reversion in vigabatrin- associated visual field defects. Neurology 2001; 57: 1916- 1917. The authors performed Goldmann perimetry on 60 adults who had been treated with vigabatrin for 7 months to 14 years as either single therapy or add- on therapy in partial epilepsy. Bilateral concentric visual field constriction was present in 40% and severe constriction in 13%. Follow- up visual fields after 4 to 38 months ( mean of over 12 months in 55 patients) showed no change. Ravindran J, Blumbergs P, Crompton J, et al. Visual field loss associated with vigabatrin: pathologic correlations. J Neurol Neurosurg Psychiatr 2001 ; 70: 787- 789. This is a postmortem case of a man who had taken vigabatrin 6 g/ d for 5 months, then 5 g/ d for 12 months, and finally 3g/ d for 7 months. Four months before his death, he developed trouble seeing houses along the street. He had bilateral concentric constriction of the visual fields with normal optic discs. On pathologic examination, the peripheral retina showed severe loss of ganglion cells and partial loss of nuclei from the inner nuclear layers. Macular fibers were preserved. There was no edema of the axon or myelin. The authors propose that the ganglion cell loss and damage to certain parts of the retina accounts for the variability of optic nerve atrophic changes seen and also the abnormality of the b- wave in the electroretinogram ( ERG) findings. These three studies strongly suggest that vigabatrin causes visual field constriction. The loss may be permanent in some cases. Ganglion cells appear to be damaged. Although tiagabine also affects GABA, there is no experimental animal evidence that it accumulates in the retina. III. Infectious Disease Chang GY, Keane JR. Visual loss in cysticercosis: analysis of 23 patients. Neurology 2001; 57: 545- 548. The authors analyzed the pattern of visual loss to the optic nerve, chiasm, and retro chiasmatic area in cysticercosis diagnosed by pathologic, imaging, and/ or cerebrospinal fluid ( CSF) examinations. Visual loss, defined as loss of acuity of 20/ 40 or worse, occurred in 23 ( 8%) of Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 IN OTHER JOURNALS 284 patients. Optic nerve damage ( 13) occurred most commonly from papilledema. Nearly all patients ( 12) had hydrocephalus. In four patients, chiasmal damage was caused by subarachnoid cyst or inflammation. Six patients showed retrochiasmal lesions due to parenchymal or subarachnoid cysts, or infarction of the visual radiations. The author recommended aggressive treatment of disc swelling by optic nerve sheath fenestration or correction of underlying hydrocephalus with shunting. V. Increased Intracranial Pressure Quattrone A, Bono F, Oliveri RL, et al. Cerebral venous thrombosis and isolated intracranial hypertension without papilledema in CDR. Neurology 2001; 57: 31- 36. The authors prospectively evaluated 114 patients with at least a 6- month history of chronic daily headache and 28 control subjects with other neurologic or psychiatric conditions. All patients underwent MRI and MRV; no patient had other confirming studies. Any patient with increased pressure of greater than 200 mm water had an ophthalmologic examination to exclude papilledema. The authors divided patients by MRV findings: group 1 ( 103) had normal MRV; group 2 ( 6) had irregular flow in the distal transverse sinus; group 3 ( 5) had irregular and absent flow in both sinuses. Then 30 patients were randomly selected from group 1 to undergo LP, as were all patients in groups 2 and 3. Not unexpectedly, group 1 and controls had normal lumbar puncture opening pressures (< 200 mm CSF), whereas patients in group 3, four of five patients had elevated intracranial pressure. The patients in groups 2 and 3 were presumed to have had cerebral venous thrombosis ( CVT). The headache characteristics in the 3 groups were indistinguishable; the CVT groups ( 2 and 3) were overweight compared with group 1 or controls. The authors concluded that CVT mimics idiopathic intracranial hypertension and that CVT should be looked for in all patients with chronic daily headache. The biggest problem with this study is that the authors assume that because there are MRV irregularities, the veins are occluded. In fact, one of the examples of irregularity of venous structure that they cite is an arachnoid granulation- a normal variant. Furthermore, in a recent study ( King JO, Mitchell PJ, Thomson KR, et al. Neurology 2002; 58: 26- 30.), increased intracranial pressure itself led to elevated venous pressures and apparent stricture within the transverse venous sinuses that reversed itself when the pressure was lowered. While we certainly want to exclude increased intracranial pressure in patients with chronic daily headache, accurate diagnosis of venous sinus obstruction still eludes us. Huna- Baron R, Landau K, Rosenberg M, et al. Unilateral swollen disc due to increased intracranial pressure. Neurology 2001; 56: 1588- 1590. Unilateral papilledema from increased intracranial pressure is rare. These authors found only 15 cases from a combined 24- year experience, and could only find 11 reported cases in the literature. All patients reported were studied with detailed ophthalmoscopy and indirect ophthalmoscopy, as well as perimetry. Ten of the 15 cases with unilateral papilledema had idiopathic intracranial hypertension ( IIH). The authors suggested that the symptoms and signs in patients with unilateral papilledema do not differ those in patients with bilateral papilledema. The authors propose that, in spite of its rarity, unilateral optic disc edema be considered as a manifestation of papilledema, and that an appropriate work- up be conducted. V. Myasthenia Gravis Yamamoto AM, Gajdos P, Eymard B, et al. Anti- titin antibodies in myasthenia gravis. Tight association with thymoma and heterogeneity of non- thymoma patients. Arch Neurol 2001; 58: 885- 890. Acetylcholine receptor antibodies are present in the serum of almost 85% of patients with myasthenia gravis ( MG). Anti- striated muscle antibodies have been a marker for thymoma, but are not specific for MG or thymoma. Antibodies to other antigens, including titin, one of the largest molecules in striated muscle, are being evaluated as markers for underlying thymoma. The authors studied a group of 398 patients with generalized MG ( 243 who had undergone thymectomy and 155 who had not) and 247 control patients ( including normal subjects and patients with other autoimmune or neurologic conditions). Titin antibodies were found in 80% ( 56/ 70) of MG patients with thymoma, but in only 11 % ( 17/ 165) of MG patients without thymoma. When titin antibodies were present in patients older than age 60 without thymoma, they were a marker for MG. In patients less than 60 years of age, the presence of titin antibodies increased the likelihood of thymoma. See also the editorial that accompanies this article, Aarli JA. Titin, thymoma and Myasthenia Gravis. Arch Neurol 2001; 58: 869- 70. Buckley C, Newsom- Davis J, Willcox N, et al. Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence? Neurology 2001; 57: 1579- 1582. In contrast to the above study, these authors studied titin and two cytokines, interferon a ( IFNa) and interleukin 12 ( IL12), in 191 patients with myasthenia gravis ( MG) ^ 142 „.. „ . . © 2002 Lippincott Williams & WUkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS J Neuro- Ophthalmol, Vol. 22, No. 2, 2002 who did and did not have thymoma, and compared them to 82 controls. Titin antibodies were uncommon in patients younger than 40 years of age. Although they were more common in older patients, titin antibodies did not distinguish between those with or without tumor. Titin antibodies were not present in controls, or sero- negative MG. Cytokine antibodies were more common in individuals with thymoma. Furthermore, these antibodies increased if thymoma recurred. The authors concluded that titin antibodies are of limited importance in predicting thymoma ( except in those younger than 60 years of age), but IFNa and IL12 may be important to predict recurrence in patients with MG who have thymoma. From the above studies, it appears that in a patient with MG who is younger than 60 years of age who has equivocal thoracic imaging, titin antibody may be suggestive of thymoma. IL- 12 and IFNa may be sensitive to recurrence of thymoma. VI. Multiple Sclerosis Evangelou N, Konz D, Esiri MM, et al. Size- selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis. Brain 2001; 124: 1813- 1820. In a postmortem study, the eight brains of patients who died of multiple sclerosis ( MS) disclosed smaller optic nerves and optic tracts and reduced axonal densities compared with normal brains. Although the size of the magno-cellular cells of the lateral geniculate nuclei was equal, the parvocellular cells were significantly smaller and contained atrophic neurons. The authors believe that their findings support the hypothesis that the smaller axons in MS patients are more susceptible to injury than are the larger axons. This fact might help to explain in part why color vision ( a parvocellular function) is preferentially affected over motion detection ( a magnocellular function) in MS. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50: 121- 127. This is a review by an international panel that convened in London in 2000 from several countries to review criteria for diagnosis of MS and incorporate modern imaging criteria. The clinical guideline of finding objective lesions in space and time is still essential. Clinical evidence cannot be based on history alone; there must also be objective evidence. Imaging criteria for a diagnosis of MS include 3 of 4 of the following: 1) one gadolinium enhancing lesion or 9 T2 hyperintense lesions; 2) at least one-infratentorial lesion; 3) at least one juxtacortical lesion; 4) at least 3 periventricular lesions. Cerebrospinal fluid ( CSF) evaluation is also of value for the presence of oligoclonal IgG bands. CSF should show less than 50 lymphocytes. VEP is helpful as an adjunctive test to supplement information or to look for objective evidence of a second lesion. The panel rejected the terms " definite MS," " probable MS" and substituted " MS", " possible MS" ( those at risk, but the diagnostic evaluation is not definite), or " not MS". VII. Vertigo Guerraz M, Yardley L, Bertholon P, et al. Visual vertigo: symptom assessment, spatial orientation and postural control. Brain 2001; 124: 1646- 1656. Visual vertigo, a frequent complaint, is characterized by symptoms provoked by visual contexts such as supermarkets, driving, or moving objects. In this study, 17 of 21 patients diagnosed with visual vertigo by history ( vertigo worsened by visual surroundings like crowds, grocery store aisles) were diagnosed as having a peripheral vestibular disorder ( history of vestibular neuritis, benign positional vertigo, basilar migraine). The 21 patients with visual vertigo were compared with 25 normal controls without history of neurologic or vestibular disease and 16 patients whose testing documented bilateral labyrinthine defect subjects ( LDS). Questionnaires showed that trait anxiety scores ( from the Spielberger Trait Anxiety Inventory) and childhood motion sickness were similar in all the three groups. However, vertigo symptom scales of autonomic symptoms were higher in both of the patient groups compared with controls. Furthermore, patients with visual vertigo had similar vertigo handicaps as those with bilateral labyrinthine defects. The three groups were next tested by psychophysical experimental stimuli including testing the subject's sense of visual vertical in darkness and on variously tilted frames and by measuring postural sway ( a standing platform that measured an individuals head and body movement) under different conditions ( eyes closed, eyes open, viewing a visual target on a tilted frame and on a rotating disc). Patients with visual vertigo and LDS both showed larger tilts of the visual vertical than normal controls. This indicates that those with visual vertigo as well as those with LDS are dependent on visual clues for perception. The postural sway patterns were expressed in quotients: The Romberg quotient was the sway path generated with eyes close divided by the sway path generated with eyes open. Patients with visual vertigo behaved like normal controls in that the sway path was almost equal in both conditions, whereas the patients with LDS had an increase in this quotient. However another quotient, the visual- kinetic quotient, which showed the sway path during the disc rotation divided by the sway path with the eyes open showed that patients with LDS Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 IN OTHER JOURNALS behaved more like normal controls whereas the disc rotation in patients with visual vertigo caused a much larger sway path. Visual vertigo patients therefore have larger perceptual and therefore postural responses to disorienting visual stimuli, and visual vertigo occurs when individuals have an over dependence on visual inputs. The authors suggest that patients with visual vertigo could be treated by visual motion desensitization. Visual vertigo is a common symptom presenting in neuro- ophthalmic and neuro- otologic clinics. This study begins to tease away at the complexity of the symptom. Further, it suggests that just as benign positional vertigo is treated with habituating exercises, visual vertigo may respond to motion desensitization exercises. VIII. Migraine Welch KMA, Nagesh V, Aurora SK, et al. Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Headache 2001 ; 41: 629- 637. The authors looked for non- heme iron deposition in the periaqueductal gray matter on 3.0 Tesla MRI in 17 patients with episodic migraine ( EM), 17 patients with chronic daily headache ( CDH), and control subjects. They found that there was a significant increase in iron in both of the EM and CDH patients as compared with control subjects. There was no difference between the CDH and EM patients and no difference between migraine patients with or without aura. The authors concluded that iron homeostasis in the periaqueductal gray area is progressively impaired by repeated attacks of migraine. They propose that the periaqueductal gray area is the " generator" of migraine attacks by loss of inhibitory control of nociceptive spinal affer-ents. Iron deposition, perhaps a marker of oxidative stress and free radical damage, may be the " burden of illness." This study is important because it not only corroborates earlier PET studies that showed increased regional blood flow to the midbrain structures ( periaqueductal gray, midbrain reticular formation and locus ceruleus) as a " generator" of migraine, but also because of the implications for the pathophysiology and long- term sequelae of migraine. Milhaurd D, Bogousslavsky J, van Melle G, et al. Ischemic stroke and active migraine. Neurology 2001; 57: 1805- 1811. The authors reviewed compared 130 patients with active migraine at the time of stroke to those with stroke without migraine from the Lausanne Stroke Registry. Among migraine patients, half were younger than 45 years of age; most were women ( 74%, younger; 63% older than 45). The prevalence of migraine in the younger stroke group was 23% in women and 8% in men. This rate reflects what is known about prevalence of migraine in the general population of this age group. The younger patients had mainly posterior circulation strokes and a patent foramen ovale, while the older patients had none of the usual vascular risk factors ( hypertension, ischemic heart disease or smoking). Compared with patients who had ischemic stroke without migraine, women with migraine were more frequently on oral contraceptives ( con- trols 30%, migraineurs 45%). Interestingly, in the younger group, arterial dissection was less frequent in patients with migraine than in controls. Only 9 patients developed stroke during a typical aura and 15 developed stroke during migraine without aura. These authors also found that a patent foramen ovale was four times more common in migraine- stroke patients. These authors reiterated that in older individuals, active migraine is infrequent as a cause of stroke. They suggested that in younger migraine- stroke patients, patent foramen ovale should be investigated, but do not provide any basis for concluding that this anatomic variant was associated with paradoxical embolism. IX. Visual Fields Lepore FE. The preserved temporal crescent: the clinical implications of an " endangered" finding. Neurology 2001; 57: 1918- 1921. The preserved temporal crescent on visual field examination is touted as a specific sign of contralateral occipital lobe pathology. The author reviewed 16 patients with a partial or complete monocular preserved temporal crescent as assessed by Goldmann perimetry. Imaging was performed in 15 patients. Lesions were due to stroke, birth injury, trauma, aneurysm and migraine. Most lesions were medial occipital lobe infarcts, but 19% ( 3/ 16) had lesions of the optic radiations. Spontaneous visual hallucinations were present in 44% ofpatients. The author asserts that the preserved temporal crescent is less likely to be diagnosed now that automated static perimetry- which usually samples only the central 30 degrees of field- has replaced kinetic Goldmann perimetry. X. Genetic Disorders Raffelsberger T, Rossmanith W, Thaller- Antlanger H, et al. CPEO associated with a single nucleotide deletion in the mitochondrial tRNA gene. Neurology 2001 ; 57: 2298- 2301. Napoli L, Bordoni A, Zeviani M, et al. A novel missense adenine nucleotide translocator- 1 gene mutation in a Greek adPEO family. Neurology 2001; 57: 2295- 2298. See also the editorial, „ 144 . , „ . , „ . . © 2002 Lippincott Williams & WUkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. IN OTHER JOURNALS J Neuro- Ophthalmol, Vol. 22, No. 2, 2002 Hirano M, DiMauro S. ANT1, Twinkle, POLG, and TP. New genes open our eyes to ophthalmoplegia. Neurology 2001; 57: 2163- 2165. Chronic progressive external ophthalmoplegia ( CPEO) is usually caused by large deletions in mitochondrial DNA, but point mutations have also been described. Several new genes have been linked to this disorder. One new gene, adenine nucleotide translocater 1 ( ANT1), has recently been associated with the autosomal dominant form of PEO ( adPEO). Found in 11% of patients with adPEO, it is responsible for transporting ATP across the inner mitochondrial membrane. Twinkle, another name for a gene associated with adPEO, is found in 15% of patients with adPEO and may be involved in mitochondrial replications. A third mutation, polymerase gamma ( POLG), is also responsible for mitochondrial DNA replication. How ANT1, Twinkle, or POLG cause PEO is unclear. The first of these three papers describes two further point mutations, including a single nucleotide in the tRNA in a single individual who exhibited CPEO, myopathy, exercise intolerance, and elevated serum lactate. The second report is of a mutation in L98PANT1 in a Greek family who had mild ptosis and PEO; one individual had pigmentary retinopathy. The accompanying editorial tries to synthesize what is known in PEO genetics. XI. Apraxia of Eyelid Opening Tozlovanu V, Forget R, Iancu A, et al. Prolonged orbicularis oculi activity. A major factor in apraxia of lid opening. Neurology 2001; 57: 1013- 1018. Apraxia of eyelid opening ( ALO) is the inability to open the eyes volitionally in the presence of intact spontaneous eye opening. While apraxia occurs most often in conjunction with blepharospasm, it can occur with other conditions such as progressive supranuclear palsy ( PSP) and Parkinson's disease. The authors studied 12 ALO patients ( 11 with blepharospasm) and 12 controls, using EMG of the orbicularis oculi and lid movement recordings. Not unexpectedly, lid opening latencies and lid movement duration were increased in ALO patients compared with controls. Persistent orbicularis oculi activity was detected by EMG in 11 ALO patients and thought to be the explanation for the delay in lid opening in these patients. This study suggests that ALO is a subclinical form of blepharospasm. XII. Pituitary Disease Biousse V, Newman NJ, Oyesiku. Precipitating factors in pituitary apoplexy. J Neurol NeurosurgPsychiat 2001; 71: 542- 545. The authors reviewed 30 patients with acute pituitary apoplexy who had undergone thorough neurologic and neuro- ophthalmologic examinations. Patients were divided into groups based on the presence or absence of precipitating factors. Only 6 of the 30 patients had a previously diagnosed pituitary adenoma. Conditions associated with apoplexy were found in 9 ( 30% o) patients, including recent anticoagulation ( 3), thrombolytic therapy ( 1), an antecedent surgical procedure ( 2), the postpartum state ( 1), treatment of cellulitis ( 1), and discontinuation of bromocriptine therapy ( 1). In addition to treatment of the underlying endocrine dysfunction, 27 patients underwent surgical decompression. The group with identifiable associations had more altered consciousness preoperatively than those who had no such associations. This study demonstrates two important points. First, most pituitary apoplexy does not occur in previously diagnosed adenomas. Second, pituitary apoplexy has few associated conditions, which makes this diagnosis unpredictable. Xin. Degenerative Conditions Warmuth- Metz, Naumann M, Csoti H, et al. Measurement of the midbrain diameter on routine magnetic resonance imaging. A simple and accurate method of differentiating between Parkinson's disease and progressive supranuclear palsy. Arch Neurol 2001; 38: 1076- 1079. The authors studied the MRI characteristics of the brain stem in patients with Parkinson's disease ( 20), progressive supranuclear palsy ( PSP) ( 16), and multiple system atrophy ( MSA) ( 14). The antero- posterior diameter of the midbrain was found to be the best separator. Parkinson's patients and controls were similar, while those with PSP had significantly lower diameters. Interestingly, the midbrain diameter in MSA was also lower than in controls and in Parkinson's disease, but not as low as in those with PSP. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. |