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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 neuroclinical and neuroscience journals. Neuroscience Journals Reviewer: Syndee Givre, MD, PhD University of North Carolina at Chapel Hill Chapel Hill, North Carolina I. Neurogenesis in the Adult Brain Gage FH. Neurogenesis in the adult brain. JNeurosci 2002; 22: 612- 3. The Journal ofNeuroscience, Volume 22, Number 3, contains a review on neurogenesis in the adult mammalian brain, including a fine introduction by Fred H. Gage and several authoritative papers. Although neurogenesis is common in many adult vertebrates, neuroscience dogma has it that no new neurons are added to the mammalian CNS in adulthood. This dogma stemmed from early histologic studies showing a scarcity of mitotic figures and intermediate cell forms, from simple to more complex neurons, in adult brains. Furthermore, the intricacy of dendritic and axonal branching of neurons and the complexity of their interconnections made it difficult to conceive of how new neurons could functionally integrate into the mature brain. But about 40 years ago, evidence of new neurons in the adult brain began to accrue. After much initial skepticism, neurogenesis in adult mammals, including primates, is now accepted as fact. It occurs in the sub-ventricular zone adjacent to the olfactory bulb and in the dentate gyrus; it may occur in other regions of the brain as well. Some of the papers from this review are summarized below. Rakic P. Adult neurogenesis in mammals: an identity crisis. JNeurosci 2002; 22: 614- 8. This is an important review for those who wish to read original work on neurogenesis with an appropriately critical eye. The author outlines the common techniques used for demonstrating new neurons. The oldest method involves intraventricular injection of 3H- thymidine, which competes with endogenous thymidine for uptake by cells undergoing nuclear DNA synthesis in preparation for mitosis. 3H- thymidine is detected by autoradiography. More recently, another thymidine analogue, bromodeoxyuridine ( BrdU) has been used. The advantage of BrdU is that it is detected immunohistochemically and can be used in double labeling experiments with other immunohistochemical markers that are specific for neurons. The pitfalls of each technique, mainly those resulting in false labeling, are discussed in detail. Rakic proposes stringent criteria for asserting neurogenesis, including the demonstration of mitotic figures, unambiguous identification of new cells as neurons and precise definition of the term " adult." Gould E, Gross CG. Neurogenesis in adult mammals: some progress and problems. JNeurosci IQQlill'. bW- Ii. The authors review techniques used to demonstrate neurogenesis and their pitfalls. They also discuss other factors that can affect the number and survival rate of new neurons. Studies have shown that learning tasks, housing in enriched or natural environment settings, and ovarian steroids can enhance the proliferation and survival of new neurons in the hippocampus. Stress ( predator odor exposure in adult rats, for example) reduces new neuron proliferation in the dentate gyrus. Glucocorticoids ( released in stressful situations) produce a similar inhibition in the absence of stress. The authors conclude with a discussion of the possible role of new neurons in the adult brain. Because new neurons are so few in number, the authors speculate that these neurons would have to possess special properties to have any functional impact relative to mature neurons. Nottebohm F. Why are some neurons replaced in adult brain? JNeurosci 2002; 22: 624- 8. The author and his colleagues are responsible for pioneering work in elucidating the production and replacement of neurons in the adult avian brain. The avian system is an important model for adult mammalian neurogenesis. In adult birds, neurogenesis is relatively common but occurs only in restricted brain regions and only for certain neuronal types and therefore affects a small minority of cells. In songbirds, the spontaneous loss of neurons and neurogenesis occur continuously in the high vocal center ( HVC), a part of the cortex, such that the absolute number of neurons in HVC is constant. HVC controls song, a seasonal behavior. Changes in the light/ dark period lead to changes in testosterone levels and higher testosterone levels promote Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 164 JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 singing. Testosterone and singing additively promote the survival of new HVC neurons via a rise in brain- derived neurotrophic factor. If singing is discouraged, many of the new neurons in HVC disappear. The author concludes with a strong argument for studying adult neurogenesis in free- ranging animals leading relatively normal lives ( as has been done in birds). This may maximize our chance of observing what is likely an uncommon feature of brain functioning in mammals. Wilbrecht L, Crionas A, Nottebohm F. Experience affects recruitment of new neurons but not adult neuron number. JNeurosci 2002; 22: 825- 31. The authors studied the effect of deafening and denervation of the vocal organ of songbirds on adult neurogenesis as measured by BrdU labeling. Experimental groups consisted of deafened birds, unilaterally denervated birds ( able to hear and imitate song), bilaterally denervated birds ( able to hear but not imitate song), and deafened plus unilaterally denervated birds ( able to sing, but not hear and imitate song). The results showed that the absolute number of HVC neurons was no different in any experimental group compared with controls. Neither deafening nor bilateral denervation resulted in a significant change in the number of labeled ( new) neurons in HVC. In contrast, unilateral denervation nearly doubled the number of labeled neurons in the contralateral HVC as compared with the ipsilateral HVC 30 days after BrdU injection. This effect disappeared by 90 days after injection and was not seen if unilateral denervation was combined with deafening. These data suggest that, in the absence of learning of song ( in deafened and bilaterally denervated birds), there is continual and probably preprogrammed culling and replacement of neurons. With song learning ( normal birds), culling and replacement may be more selective and, as evidenced by the unilaterally denervated birds, may be based on activity in the particular circuits used to learn. Alvarez- Buylla A, Garcia- Verdugo JM. Neurogenesis in the adult subventricular zone. JNeurosci 2002; 22: 629- 34. The authors summarize recent work on the origin of new neurons in the adult subventricular zone ( SVZ), the mechanism of migration of these cells, and their potential functions. The subventricular zone lies along the lateral walls of the lateral ventricles. From there, new neurons migrate to the olfactory bulb, where they become mature in-terneurons. Regarding the origin of new neurons, work from several studies has surprisingly suggested that the neuronal precursor cell in the SVZ may be an astrocyte. In one experiment, SVZ astrocytes were labeled with a retrovirus. Later, labeled neurons were found integrated into the olfactory bulb. In adult rodents, new neurons must migrate from the SVZ to the olfactory bulb several millimeters away. These new neurons, with growth cones on their leading edges, move along each other in chains that are ensheathed by astrocytes. This phenomenon occurs in the absence of the olfactory bulb, implying that migration is not simply a response to a chemoattractant molecule secreted by this structure. Once the new neurons reach the edge of the olfactory bulb, they separate from the chain and individually move farther into the tissue, where a fraction differentiates into granule neurons. The recruitment of new neurons to the olfactory bulb is inhibited by naris closure. The authors propose that new neurons in the olfactory bulb participate in plasticity and learning and may improve olfactory discrimination. Similar proposals regarding learning and plasticity have been made about the function of new neurons in the mammalian adult hippocampus and the avian song nuclei. Kempermann G. Why new neurons? Possible functions for adult hippocampal neurogenesis. JNeurosci 2002; 22: 635- 8. In birds, studies have shown functional links between adult neurogenesis and specific behaviors, song learning being one example. In the hippocampus of adult mammals, similar neurogenesis occurs but its functional implications are less well understood. The author reviewed studies investigating the possible functions of neurogenesis in adult mammalian hippocampus. The function of the hippocampus itself is poorly understood but is thought to be related to learning and memory. Environmental enrichment, physical activity, and learning a task that relies on hippocampal functioning up-regulate adult hippocampal neurogenesis. Conversely, changes in the rate of neurogenesis and the survival of new neurons have been shown to affect subsequent learning of hippocampus- mediated behaviors. Mice that have received a cytostatic agent to inhibit neurogenesis perform worse on a hippocampus- dependent task. The author proposes that adult hippocampal neurogenesis enables this structure to continuously deal with novel and increasingly complex stimuli. The mere existence of neurogenesis in adult mammals has generated many important questions posed in this review. Given that mammals have a multitude of cell types that divide throughout life, why is it that most neurons in mammals do not replicate? Adult insects, fish, and amphibia can replicate neurons; why are there species- specific variations in this phenomenon? Furthermore, why is there variation in the degree of neurogenesis amongst different brain regions? What implications, if any, does this variation Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 165 JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 IN OTHER JOURNALS have with regard to the function of adult neurogenesis? Which cells are giving rise to the new neurons? Most importantly, for clinical purposes, can the phenomenon of neurogenesis be harnessed to reinstate brain function that has been lost by disease or other damage? n. Dyslexia Temple E. Brain mechanisms in normal and dyslexic readers. CurrOpinNeurobiol2QQ2;\ 2:\ l^-% 3. Dyslexia, characterized by reading difficulty in those who otherwise have normal intelligence, schooling, and motivation, affects 5% to 17% of people. The author reviews neuroimaging data that support a view of dyslexia as a problem of phonological and rapid auditory processing. Multiple positron emission tomography experiments have reported a reduction or absence of activity in the left temporoparietal cortex in dyslexic adults performing phonological processing of visually presented material. In one task, for example, subjects were asked to determine if a visually presented letter rhymed with the letter " B." The finding of similar results in functional magnetic resonance imaging ( fMRI) and magnetoencephalographic ( MEG) studies in children implies that, rather than being a marker for compensation for dyslexia in adults, reduced activity in temporoparietal cortex reflects the fundamental dysfunction in dyslexia. Reduced temporoparietal activity has also been found in dyslexic men from the United Kingdom, Italy, and France. The processing of rapid auditory stimuli is evaluated in tasks in which nonlinguistic stimuli designed to mimic the rapid temporal changes of speech syllables are presented. Both event- related potential ( ERP) and MEG studies have demonstrated abnormal brain processing of rapid auditory stimuli in dyslexics. Functional MRI studies have shown reduced activity in the left prefrontal cortex of dyslexics hearing rapidly presented auditory stimuli. Three dyslexic subjects underwent training to improve rapid auditory processing. After training, two of these subjects had significant improvement in rapid auditory processing tests, and these subjects had significantly increased activity in the left prefrontal cortex on fMRI compared with their pre-training scans. The third subject failed to improve behav-iorally on fMRI. These electrophysiologic and neuro- imaging experiments provide evidence that dyslexia is a dysfunction of auditory phonological processing. Having a better understanding of the fundamental dysfunction in dyslexia will ultimately lead to better treatment strategies and possibly prevention. Furthermore, the results of these studies can be passed on to patients, many of whom believe dyslexia to be a visual problem. III. Visual Perception Ward R, Jackson SR. Visual attention in blindsight: sensitivity in the blind field increased by targets in the sighted field. Neu-roReport 2002; l3: 30l^. Blindsight refers to the presence of residual visual abilities in areas of scotoma induced by damage to primary visual cortex. The existence of blindsight is not universally accepted; those who doubt its existence generally believe that residual vision results from incomplete damage to primary visual cortex. Proponents of blindsight believe that visual pathways not involving primary visual cortex, such as those involving the superior colliculus, pulvinar, and extrastriate cortex, mediate residual vision. In order to further investigate the mechanism of blindsight, an adult hemianope was asked to perform a divided attention task. The 41- year- old subject had had head trauma at age 8, leaving him with a right homonymous hemianopsia and 3.5 degrees of macular sparing. With central fixation maintained, stimuli were presented individually either in the blind or sighted hemifield or simultaneously in both hemifields outside of the spared area, at 10 degrees eccentricity. Blank trials with no target also occurred. The subject was instructed to indicate whether targets were detected in the seeing field, the blind field, both fields, or not at all. In normal subjects, it is well known that divided attention to multiple visual targets decreases performance in target detection tasks. For individually presented targets, accuracy of detection in the intact hemifield was perfect and accuracy of detection in the blind hemifield was significantly above chance. Simultaneous presentation of targets in the intact and blind hemifields dramatically and significantly increased the detection of targets in the blind hemifield. This effect was significantly increased when the target in the intact hemifield was in the same location with respect to the vertical meridian ( upper field, on the horizontal meridian or lower field) as the target in the blind hemifield. Thus, divided attention enhanced target detection in the blind field of this hemianope in contrast to the detrimental effect of divided attention in subjects with bilaterally intact primary visual pathways. This difference between normal subjects and the hemianopic subject suggests that blindsight is not likely to be the result of sparing of the primary visual pathways. Muckli L, Kriegeskorte N, Lanfermann H, et al. Apparent motion: event- related functional magnetic resonance imaging of perceptual switches and states. JNeurosci 2002; 22: RC219: 1- 5. Two spatially segregated, blinking visual stimuli can be presented simultaneously in such a way that an observer Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 166 © 2003 Lippincott Williams & Wilkins IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 will have two percepts, either of back- and- forth motion or of two stationary, blinking stimuli. Typically, the two percepts rapidly alternate. Previous studies have demonstrated that manipulating neuronal responses in monkey temporal areas MT and MST, known to be important in motion processing, can alter perception of such " bistable" images. In the current study, perception was allowed to alternate freely and brain activity was measured using fMRI in eight human subjects. Group and single- subject analyses revealed that hMT+, the human motion complex, an area that includes the homologue of monkey MT and associated regions, was the area most consistently activated during times when the stimulus was perceived as moving. Signals within hMT+ were subject to event- related time course analysis. Signal intensity in this region significantly rose after perception switched from stationary blinking to moving, and fell ( though this did not reach statistical significance) after perceptual transition from moving to stationary blinking. Thus, activity was associated with perception of motion despite the fact that the physical stimulus never changed. The authors demonstrated that hMT+ plays a role in the conscious perception of motion in humans. Other recent fMRI studies have stressed the importance of activation of visual areas of higher order than MT in initiating switches of perception. However, no such higher- order areas were consistently activated in the current study. The authors propose that, at least for the task they studied, activation of hMT+ alone may be sufficient for the perception of motion. Paradiso M. Perceptual andneuronal correspondence in primary visual cortex. Curr OpinNeurbiol2002; 12: 155- 61. According to most models, processing of visual information within either the dorsal ( motion) pathway or ventral ( form) pathway is serial. From VI, information is sent to increasingly complex visual areas and, at some point upstream of VI, perception is achieved. This review article summarizes several lines of data that support the concept that primary visual cortex plays an important role in visual perception. The first type of evidence comes from experiments measuring response latencies in various visual areas. Strictly serial processing would predict that response latencies are greater in higher- order visual regions. Although this holds true for the earliest responses in VI versus the earliest responses in upstream areas of the form pathway, the scatter of onset latencies in the form pathway would allow for some neurons in higher- order areas to be activated simultaneously with neurons in VI. In the motion pathway, the earliest onset latencies in areas upstream of VI, such as MT, are identical to those in VI. Second, some properties of primary visual cortex neurons argue for their role in perception. VI has the highest resolution retinotopic map of any visual area and the magnification factor for VI corresponds well with known visual acuities at varying eccentricities across the visual field. Thus, primary visual cortex may play a role in the perception of high acuity vision. The activity of some neurons in VI is related to perception during binocular rivalry. The relative number of these neurons found in VI is small as compared with higher order areas, but the absolute number may be higher as VI is the largest visual cortical area. Mental imagery is the perception of images without retinal stimulation and is thought to be a higher order visual function. However, mental imagery of gratings has been shown to activate primary visual cortex in PET studies. Furthermore, single neuron recordings from VI have shown that stimuli lying outside the classic receptive field can influence the response to stimuli within the classic receptive field in an orientation specific manner. Similarly, when a human subject viewing a stimulus is asked to imagine previously viewed flanking stimuli of a specific orientation, contrast threshold for the central stimulus is reduced. Two properties of this modulation in the human, imagined version of the task suggest that it is generated in early visual cortical regions. First, it is highly orientation specific, as are neurons in VI. Second, the effect is monocular- no reduction in contrast threshold is seen when the flanking stimuli to be memorized and later imagined are presented to one eye but the task is performed with the central stimulus presented to the other eye. Monocular cells are rare outside of VI. Finally, attention was previously thought to be a function of only higher order visual cortical neurons. It is now clear that attention modulates the responses of V1 neurons. This implies that primary visual cortex plays a greater role in vision than merely the detection and discrimination of visual stimuli. Taken together, these data support a role for primary visual cortex in certain types of perception, especially perception of features to which VI neurons are highly tuned. IV. Demyelination Boullerne AI, Rodriguez JJ, Touil T, et al. Anti- S-nitrosocysteine antibodies are a predictive marker for demyelination in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. JNeurosci 2002; 22: 123- 32. In an attempt to generate an easily measurable marker of disease activity in multiple sclerosis ( MS), the authors looked at antibodies to iS'- nitrosocysteine ( SNO- cysteine), a Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 167 JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 IN OTHER JOURNALS product of the reaction of cysteine and nitric oxide ( NO). Nitric oxide, which triggers axonal and oligodendrocyte degeneration, is proposed to be a contributor to tissue damage in MS. Since it is volatile, NO cannot be measured directly, but products of its reactions with amino acids can be measured. Serum antibodies to SNO- cysteine were measured in rats with experimental autoimmune encephalomyelitis ( EAE) and in 31 patients with definite MS. Cerebrospinal fluid antibodies to SNO- cysteine were measured in 25 patients with definite MS. Rats induced with EAE had antibodies to SNO-cysteine that peaked in concentration one week before the onset of clinical symptoms and well before the appearance of anti- myelin basic protein antibodies. Vehicle- injected rats had no anti- SNO- cysteine antibodies. Titers of anti- SNO- cysteine antibodies significantly correlated with the extent of histologic demyelination in the spinal cord. In patients currently in MS relapse, antibody titers directed against SNO- cysteine were significantly elevated as compared with MS patients in remission and normal controls. In two thirds of secondary progressive MS patients studied, anti- SNO- cysteine antibody titers were significantly elevated as compared with controls and MS patients in remission. Antibodies were detected in only one CSF sample from a patient with MS. The authors concluded that a rise in circulating anti- SNO- cysteine antibodies occurs before the clinical onset of EAE and that these antibodies are elevated in MS patients during relapse and progressive disease. Anti- SNO- cysteine antibodies may be a useful, easily measurable clinical marker of disease activity in MS. Sim FJ, Zhao C, Pendens J, Franklin RJM. The age- related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. JNeurosci 2002; 22: 2451- 9. Remyelination becomes less efficient with age. This phenomenon has implications for life- long demyelinating diseases such as MS. CNS remyelination involves recruitment of oligodendrocyte progenitors into the area of damage and subsequent differentiation of these progenitors into remyehnating oligodendrocytes. The goal of the authors was to determine which part of this process is affected by aging. The recruitment of oligodendrocyte progenitors after toxin- induced demyelination in the caudal cerebellar peduncle of young rats was compared with that of old rats. To assess differentiation, recruitment rates were then compared with the appearance of remyehnating oligodendrocytes. The absolute number of oligodendrocytes was similar in normal young and old rat caudal cerebellar peduncle. The demyelinating lesion depleted the involved area of oligodendrocytes, oligodendrocyte progenitors, and astrocytes. Oligodendrocyte progenitors appeared in the lesioned area at postlesion day 5 and, at all time points examined, were greater in density in young animals as compared with old animals. In addition, the appearance of markers for remyehnating oligodendrocytes was delayed in older animals as compared with younger animals. An important implication of these results is that therapeutic strategies aimed at enhancing remyelination in protracted demyelinating diseases such as MS will have to address both recruitment of oligodendrocyte progenitors and differentiation of these cells. V. Survival and Regeneration of Retinal Ganglion Cells Morimoto T, Miyoshi T, Fujikado T, et al. Electrical stimulation enhances the survival of axotomized retinal ganglion cells in vivo. NeuroReport 2002; 13: 227- 30. Transection of the intraorbital portion of the optic nerve leads to degeneration of the retinal ganglion cell population. Both in vivo and in vitro studies have demonstrated positive effects of neuronal activity and neuronal depolarization on axonal development and survival. The authors of the current study posited that electrical stimulation might improve the survival of axotomized retinal ganglion cells in vivo. To test this hypothesis, fluoro-gold was applied to the superior colliculus to mark retinal ganglion cells. Five days later, intraorbital optic nerve transection was performed. Electrical stimulation of the optic nerve stump with varying current strengths commenced 10 minutes after optic nerve transection and lasted for 2 hours. Seven days later, the retinas were evaluated for survival of retinal ganglion cells. Seven days after optic nerve transection, the mean density of retinal ganglion cells decreased significantly to 54% in unstimulated controls. Electrical stimulation significantly increased the density of surviving retinal ganglion cells in a dose- dependent fashion. The maximal response was to 50 LIA, which increased survival of retinal ganglion density to 83% of normal. Current intensities higher than 50 LIA yielded lower retinal ganglion cell densities. Sham stimulation showed no rescue effect. The authors found that electrical stimulation enhanced survival of axotomized retinal ganglion cells. The mechanism underlying this enhancement is unknown but cell depolarization is known to activate a number of neurotrophic signaling pathways. These results may have implications for repairing or saving damaged optic nerves. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 168 © 2003 Lippincott Williams & Wilkins IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 Inoue T, Hosokawa M, Morigiwa K, et al. Bcl- 2 overexpres-sion does not enhance in vivo axonal regeneration of retinal ganglion cells after peripheral nerve transplantation in adult mice. JNeurosci 2002; 22: 4468- 77. Optic nerve injury in adult mammals causes retinal ganglion cell death. Restoring function requires rescuing retinal ganglion cells and inducing regeneration of their axons. Axotomized retinal ganglion cells are rescued by bcl- 2, an antiapoptotic gene. However, the effect of bcl- 2 on axonal regeneration is less clear. In the current study, retinal ganglion cell survival and axonal regeneration through a peripheral nerve graft were compared in transgenic mice that overexpress bcl- 2 and wild- type mice after optic nerve transection. Enhancement of axonal regeneration has been shown in the presence of peripheral nerve transplants at the transection site. Bcl- 2 mice had a higher survival rate ( nearly 10 times greater) of retinal ganglion cells than wild- type mice after optic nerve transection. However, the axonal regeneration rate in bcl- 2 mice was unexpectedly much lower than that in wild- type mice. Even when corrected for the total number of retinal ganglion cells, the axonal regeneration rate in bcl- 2 mice did not exceed that in wild- type mice. This indicates that the majority of surviving retinal ganglion cells in bcl- 2 mice failed to regenerate their axons despite the peripheral nerve graft. Examination of the grafts revealed some retinal ganglion cell axons regrowing intraretinally and repulsed at the optic disc. The authors concluded that bcl- 2, an antiapoptotic gene, promotes retinal ganglion cell survival but not axonal regeneration after optic nerve transection. A combination of retinal ganglion cell survival and axonal regeneration is necessary to restore optic nerve integrity after physical damage. Further work on promoting axonal regeneration will be necessary if restoring optic nerve function after damage is to be achieved. Cheng L, Sapieha P, Kittlerova P, et al. TrkB gene transfer protects retinal ganglion cells from axotomy- induced death in vivo. JNeurosci 2002; 22: 3977- 86. Attempts to promote CNS recovery after injury are often limited by the death of large numbers of neurons soon after the damage. Various trophic factors have been used to prevent cell death after injury but their effects are transient. Brain- derived neurotrophic factor ( BDNF), for example, is a potent inhibitor of retinal ganglion cell death after optic nerve damage. However, even when BDNF is repeatedly or continuously applied, the neuroprotective result is not sustained and eventually retinal ganglion cells die. The authors hypothesized that the neuroprotective effect of BDNF is short- lived because the retinal ganglion cell response to this trophic factor is compromised by the injury. To investigate this, they first looked for changes in gene expression of the BDNF receptor, TrkB, after axotomy in rats. In an attempt to enhance retinal ganglion cell survival, copies of the TrkB gene were transfected into retinal ganglion cells to upregulate expression of this receptor. Retinal ganglion cell TrkB mRNA expression was significantly decreased after axotomy and this decrease occurred before the onset of retinal ganglion cell death. TrkB gene transfer to retinal ganglion cells before axotomy increased neuronal survival. Survival was further enhanced if BDNF was injected into the vitreous at the time of axotomy. These data show that the expression of TrkB is down-regulated in retinal ganglion cells after axotomy but before neuronal death. This downregulation may be the basis of the inability of BDNF to promote survival of injured neurons in a sustained fashion. When the expression of TrkB is augmented in vivo by transfecting retinal ganglion cells with its gene prior to axotomy, more ganglion cells survive. Ganglion cell survival is better still if TrkB gene transfection is combined with injection of BDNF into the vitreous. This strategy may have therapeutic potential in optic nerve and other CNS injuries. VI. Eye Movements Sato M, Hikosaka O. Role of primate substantia nigra pars reticulata in reward- oriented saccadic eye movements. JNeurosci 2002; 22: 2362- 73. Recent evidence suggests that activity of basal ganglia neurons is modulated by reward or motivation. The basal ganglia become involved with eye movements through a proposed pathway from the caudate nucleus to the substantia nigra pars reticulata ( SNr) to the superior collic-ulus. The caudate nucleus sends both direct inhibitory and indirect excitatory projections to SNr. SNr then exerts its effects on saccades via its strong inhibitory projections to the superior colliculus. Single cell recordings from the caudate nucleus have revealed neurons with saccadic and reward- predicting activity. Neuronal activity in SNr is also saccade related, especially when saccades are guided by memory, but whether activity in SNr is modulated by reward is unknown. This study tested the hypothesis that basal ganglia neurons participate in reward- oriented saccadic activity. Single cell recordings were obtained from SNr in primates performing a memory- guided saccade task. Monkeys had to make a saccade to a previously cued and memorized location that varied in position about a central fixation point. In some sets of trials, correct saccades to all locations were rewarded. In other sets, saccades to all locations were required but only those to a single location were rewarded. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 169 JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 IN OTHER JOURNALS Spike activity of SNr neurons after the cue was determined by the position of the cue and the reward that would be given after the trial. Baseline spike activity could either increase or decrease as a function of one or both of these factors. Some neurons, for example, exhibited decreased spike activity to a cue in a particular location in space. When that cue indicated an upcoming reward, the decrement in spike activity was even greater. This reward- related modulation of activity was greater in the task where only one location was rewarded than in the task where all locations were rewarded. The post- cue activity of most neurons ( whether inhibition or increase in spike activity) was larger for contralateral than ipsilateral cues. These results indicate that neuronal activity of SNr neurons is modulated by opportunity for reward. The most common type of neuron found in SNr had spike activity that was inhibited by a contralateral cue and more so when the cue signaled a reward. Via their inhibitory projections, such neurons would disinhibit neurons in the superior colliculus, leading to a saccade toward the position of the contralateral cue. The disinhibition would be greater in trials where the cue signaled a reward, possibly leading to an earlier and faster saccade. This study provides important insight into the mechanisms underlying saccadic eye movements and may have clinical implications for patients with basal ganglia disease. Neurodinical Journals Reviewer: David M. Katz, MD The Neurology Center Washington, DC I. Cerebrovascular Disorders Stiebel- Kalish H, Setton A, Berenstein A, et al. Bilateral orbital signs predict cortical venous drainage in cavernous sinus dural AVMs. Neurology 2002; 58: 1521^. Most cavernous sinus dural AVMs carry a relatively low morbidity and mortality. Conventional angiography is usually not necessary to diagnose the condition. In rare instances, however, the AVM may lead to intracranial hemorrhages or venous infarctions because of high pressure on cortical veins. The recommended treatment is then prompt angiographic confirmation and closure of the AVM. The authors retrospectively reviewed the records and cerebral angiograms of 118 patients with cavernous sinus dural AVMs to determine which signs and symptoms predicted the presence of cortical venous drainage ( CVD). They detected CVD in 22 of the 118 patients ( 19%). The three features associated with an increased risk of CVD were: 1) bilateral orbital congestion ( the presence of more than one of the following: proptosis, chemosis, increased IOP, venous stasis retinopathy, extraocular muscle dysfunction, choroidal effusions and optic neuropathy); a 2) a post- auricular bruit audible to the examiner; and 3) signs of CNS dysfunction. Bilateral orbital congestion was present in 28 patients, 43% of whom had CVD, whereas only seven of 80 patients ( 9%) with unilateral orbital signs had CVD. An audible postauricular bruit was present in four patients, two of whom had CVD. The seven patients presenting with CNS dysfunction ( intracerebral hemorrhages, transient ischemic episodes, or dizziness/ vertigo) had CVD. The authors recommend conventional angiography for patients with any of these three features. Those without them are at relatively low risk for the development of CVD and may be followed with conventional MRI and MRV studies. Of course, treatment might be indicated for other reasons, such as intractable pain, refractory high intraocular pressure, visual loss, or diplopia. Klijn C, Kappelle LJ, van Schooneveld MJ, et al. Venous stasis retinopathy in symptomatic carotid artery occlusion. Stroke 2002; 33: 695- 701. The authors evaluated 110 patients with symptomatic carotid artery occlusion ( CAO) for signs of venous stasis retinopathy ( VSR) and ocular ischemic syndrome ( OIS). All patients presented with a history of either a transient ischemic episode or minor stroke involving the brain or retina ipsilateral to the CAO. VSR was diagnosed if at least one of the following findings was present: midperipheral microaneurysms, dot- and- blot or splinter hemorrhages, cotton wool spots, or dilated or irregular retinal veins. OIS was diagnosed if at least one of the following was also present: neovascularization of the optic disc, retina, or iris or neovascular glaucoma. Cerebral blood flow was examined using cerebral arteriography, transcranial Doppler ( TCD), and magnetic resonance angiography ( MRA). Of the 110 patients, 32 ( 29%) had signs of VSR, including midperipheral hemorrhages in all 32, venous dilatation in 16, microaneurysms in three, and cotton wool spots in two. OIS was not found in any patient at the time of enrollment. There was no difference in visual acuity or intraocular pressure between patients with or without VSR. Transient monocular blindness or retinal infarction did not occur more frequently in patients with VSR. Retinal claudication, defined as transient blindness after exposure to bright light, was reported by only three patients, two with VSR. Reversal of blood flow in the ophthalmic artery as measured by TCD was no more common in patients with ( 94%) than without ( 84%) VSR. However, patients with VSR had a lower C02 reactivity and lower pulsatility index Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 170 © 2003 Lippincott Williams & Wilkins IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 of the cerebral arteries, indicating that the cerebral arteries in patients with VSR were compensating for impaired cerebral blood flow by maximal dilatation. During a mean follow- up period of 29 months ( range 2- 50 months), three of the 32 patients with VSR developed OIS, whereas none of the other 78 patients did. Unfortunately, the patients without VSR at enrollment were not reexamined unless they developed visual symptoms, so that some patients may have developed asymptomatic VSR or OIS. The authors recommended that patients with CAO undergo repeated ophthalmological examinations regardless of whether they have visual symptoms or not. If VSR is present, more careful follow- up is indicated to ensure that if OIS develops, it can be treated before irreversible retinal or optic nerve ischemic damage occurs. Because of the small number of patients with VSR and the lack of randomization of treatment, the authors could not determine whether surgical intervention ( contralateral internal carotid artery endarterectomy or EC/ IC bypass) prevents or treats VSR or OIS. n. Intracranial Hypertension King JO, Mitchell PJ, Thomson KR, Tress BM. Manometry combined with cervical puncture in idiopathic intracranial hypertension. Neurology 2002; 58: 26- 30. Corbett JJ, Digre K. Idiopathic intracranial hypertension. An answer to " the chicken or the egg?" Neurology 2002; 58: 5- 6. The cause of idiopathic intracranial pressure ( IIH) remains unknown, but recent evidence has suggested increased cerebral venous pressure ( CVP) as the underlying cause. Studies conducted on obese patients with IIH during gastric bypass surgery have shown increased intraabdominal pressure and increased CVP that may lead to increased right heart pressures and impaired cerebral venous drainage. The authors studied 21 patients diagnosed with IIH with cerebral dural sinus venography. They noted increased venous pressure within the superior sagittal sinus and a large pressure drop across the transverse sinus ( 9- 46 mmHg), supporting the theory that IIH is caused by increased cerebral venous pressure. The authors then studied eight additional IIH patients using dural sinus venography and CSF manometry before and after they lowered the intracranial pressure by removing 20- 25 mL of cerebrospinal fluid ( CSF) via C1- C2 cisternal puncture. They reported a dramatic decrease in pressure throughout the cerebral venous system after the intracranial pressure was lowered, indicating that the venous pressure elevation in IIH is secondary to increased ICP. In an accompanying editorial, Corbett and Digre state that " the chicken is the CSF pressure elevation and the egg is venous sinus pressure elevation." Lage JM, Panizo C, Masdeu J, Rocha E. Cyclist's doping associated with cerebral sinus thrombosis. Neurology 2002; 58: 665. The authors report a case of sagittal and transverse sinus thrombosis in a previously healthy 26- year- old professional cyclist who was illicitly injecting erythropoietin to enhance endurance by increasing packed cell volume ( PCV). He presented with headaches, mild papilledema, and increased CSF opening pressure. A cranial MRI revealed sagittal and transverse sinus occlusions. An extensive coagulopathy evaluation was negative, except for an increased red blood cell count ( 5.4xl012/ L ( normal 3.5- 5.0) and increased PCV of 0.51 ( normal 0.39- 0.49). He was treated with hydration and phlebotomy; within several months, the venous sinuses had recanalized and the headaches and papilledema had resolved. Clinical trials using erythropoietin to treat anemia in dialysis patients have shown an increased risk of cardiovascular and cerebral ischemic events even when the hematocrit remains within normal limit, suggesting that the drug itself is prothrombotic. The authors recommend adding this drug to the list of legal and illegal agents associated with CNS thrombotic events. III. Intracranial Tumors Liu JK, Forman S, Hershewe GL, et al. Optic nerve sheath meningiomas: visual improvement after stereotactic radiotherapy. Neurosurgery 2002; 50: 950- 7. The treatment of optic nerve sheath meningiomas ( ONSM) is controversial. Removal of the tumor and optic nerve en bloc has been recommended for significant prop-tosis and no light perception, intractable pain, or significant intracranial extension of the tumor. Attempts to strip an ONSM from the optic nerve almost always lead to severe optic nerve ischemia followed by a local recurrence years later. Stereotactic radiosurgery can be used only in sightless patients because the high dose radiation leads to radiation necrosis of the optic nerve. Several recent case reports have shown promising results using conformal fractionated radiotherapy, but follow- up has been 2 years or less. The authors report five patients with presumed ONSM treated with three- dimensional fractionated conformal radiotherapy ( the largest reported series to date). Baseline visual acuity ranged from 20/ 20- 20/ 40, and all five pa- Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 171 JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 IN OTHER JOURNALS tients had diminished color vision and visual field defects. One patient had either a unilateral ONSM that extended across the planum sphenoidale or a primary planum sphenoidale meningioma causing blindness in one eye and loss of acuity to 20/ 40 in the other. All five patients received 1.8 Gy/ session for 25- 30 daily sessions ( total dose of 45- 54 Gy) so that each patient's tumor was encompassed at the 90% isodense line. The patients were followed clinically and with fat- saturated, gadolinium- enhanced MRIs every 3 months for 1 to 7 years. Four patients improved and one remained stable 2 years after treatment. None developed radiation optic neuropathy or retinopathy. Follow- up is short and the series is small, but the preliminary data show great promise. Yeh DD, Warnick RE, Ernst RJ. Management strategy for adult patients with dorsal midbrain gliomas. Neurosurgery 2002; 50: 735- 40. Dorsal midbrain gliomas are rare in adults ( 1% of brain tumors) and more common in children ( 10% to 20%). Most brainstem gliomas in adults are aggressive, show marked enhancement on MRI, and are treated with radiation and chemotherapy with a poor prognosis; those in children tend not to enhance after gadolinium administration, are followed without intervention, and when studied pathologically are found to be low- grade gliomas. However, what treatment is most appropriate for adult patients with nonenhancing dorsal midbrain gliomas? The authors followed five patients with dorsal midbrain nonenhancing masses with increased T2 and decreased Tl signal on MRI consistent with low- grade gliomas ( one patient had a low grade glioma based on a biopsy taken during ventriculoperitoneal shunt placement). Two patients were diagnosed incidentally and three patients presented with signs and symptoms of obstructive hydrocephalus requiring ventriculoperitoneal shunt placement. The patients were observed for 2 to 9 years ( mean 4 years), and none deteriorated clinically or showed signs of tumor growth on MRI. These observations coincide with previous studies in children. The major shortcoming of this study is the relatively short follow- up period. Although the study supports conservative follow- up of low grade midbrain gliomas in adults, there is a reported case of an adult with a nonenhancing low- grade dorsal midbrain glioma that was not treated and remained unchanged for 5 years but later grew, developed gadolinium enhancement, and proved to be an anaplastic astrocytoma. ( Oka K, Kin Y, Go Y, et al. Neuroen-doscopic approach to tectal tumors: a consecutive series. JNeurosurg 1999; 91: 964- 70.) Nakamura M, Carvalho GA, Samii M. Abducens nerve schwannoma. A case report and review of the literature. Surg Neurol 2002; 57: 183- 9. The authors report a 42- year- old male presenting with headaches and vertigo who was found to have a large inhomogeneously enhancing mass centered in the prepon-tine cistern causing extrinsic brainstem compression. Apart from diminished hearing on the left, neurologic examination was unremarkable, including ocular motility. The mass was completely removed although adherent to the left sixth nerve and found to be a schwannoma. Immediately after surgery, the patient developed a partial sixth nerve palsy that resolved within 1 year. The authors point out that schwannomas affect cranial nerves in this decreasing order of frequency: eighth, fifth, seventh, ninth, tenth, eleventh, twelfth, third, and sixth nerves. They summarize ten other reported cases of sixth nerve schwannomas. The tumors have arisen either within the cavernous sinus or the prepontine cistern. All have presented with clinical deficits in other lower cranial nerves or the brainstem; three presented with signs of obstructive hydrocephalus. Posterior fossa schwannomas generally have different MRI and CT characteristics than meningiomas, such as inhomogeneous enhancement, cystic degeneration, lack of a dural tail, and lack of calcifications on non-contrast CT so common in meningiomas. Giannini C, Reynolds C, Leavitt JA, et al. Choristoma of the optic nerve: case report. Neurosurgery 2002; 50: 1125- 8. The authors report the case of a 21- year- old female with an 8- year history of painless, progressive visual loss OS, and evidence of an optic neuropathy without proptosis or impaired ocular motility. Serial non- fat saturated MRIs noted a nonenhancing high Tl signal mass involving the intracanalicular portion of the nerve with intracranial extension. The mass lost its increased Tl signal after fat saturation. The differential diagnosis included an optic nerve lipoma, choristoma, atypical meningioma, glioma, lymphoma, and a chronic inflammatory process. Surgery disclosed a fatty tumor interdigitating itself between optic nerve fascicles. It was resected with the optic nerve en bloc. Pathologically, the presence of adipose tissue and mature smooth muscle tissue indicated an optic nerve choristoma. The term choristoma refers to the proliferation of normal mature tissue in an abnormal location; most orbital choris-tomas involve the adnexa or choroid. The authors point out that five other reported cases of optic nerve choristoma have presented in a similar way with slowly progressive optic neuropathy. Three cases had involvement of the chiasm radiologically but not clinically. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 172 © 2003 Lippincott Williams & Wilkins IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 IV. Demyelinating Disease Wolinsky JS, Narayana PA. Magnetic resonance spectroscopy in multiple sclerosis: window into the diseased brain. Curr Opin Neurol 2002; 15: 247- 51. The authors discuss the potential uses of magnetic resonance spectroscopy ( MRS) in the diagnosis and treatment of MS. Unlike MRI, which measures nonspecifically altered tissue water properties, MRS assesses biochemical functions by measuring various bioactive compounds, including N- acetylaspartate ( NAA), a marker for neuronal or axonal integrity, choline, a marker of cell membrane turnover, lactate, a marker of anaerobic metabolism, glutamate, a marker of excitatory neurotransmitter function, and creatine, a reference marker. An acute, gadolinium- enhancing MS plaque has elevated choline and lactate peaks on MRS, indicating damage to myelin. The NAA peak is diminished, indicating axonal damage. After an acute plaque " heals" on MRI, the NAA, choline, and creatine peaks often normalize. If an MS plaque becomes a Tl " black hole," the MRS often shows a persistently depressed NAA peak, reflecting irreversible axonal loss. MRS has also been used to study " normal appearing white matter" on conventional MRI. An increase in the choline peak can precede the development of a visible MRI plaque by several months; depression of the NAA peak is often found in normal white matter surrounding plaques as an indication of more extensive axonal damage than visualized by MRI. Conventional MRI scans rarely detect cortical MS plaques ( although they are visible pathologically), whereas MRS often detects abnormal choline and lactate peaks involving the cortex. Reduced whole brain NAA levels also correlate well with T2 lesion load. MRS still remains a research tool, but it is likely to play an important role in the evaluation of patients early in the course of their illness, when conventional MRI may underestimate the extent of disease. MRS may also assist in the management of patients who are declining neurologi-cally but whose MRI scans show little or no change. Kupersmith MJ, Alban T, Zeiffer B, Lefton D. Contrast-enhanced MRI in acute optic neuritis: relationship to visual performance. Brain 2002; 125: 812- 22. The authors studied 107 patients presenting with acute, monocular optic neuritis who underwent fat-saturated, gadolinium- enhanced MRI of the orbits before being offered treatment with steroids. The mean time between symptom onset and MRI was 8.7 days ( range 1- 19 days). Enhancing optic nerves were found in 101 ( 94%) of the patients. Enhancement of the intracanalicular optic nerve correlated with worse baseline color vision ( P < 0.05), whereas enhancement of intraorbital, intracanalicular, and intracranial segments correlated with worse baseline threshold static perimetry ( P = 0.001) and color vision ( P < 0.01). Enhancement of > 10 mm of the optic nerve correlated with worse baseline threshold static perimetry ( P = 0.004), whereas enhancement of > 17 mm of the optic nerve correlated with worse baseline visual acuity ( P = 0.02), static perimetry ( P < 0.01), and color vision ( P = 0.01). Visual improvement occurred in all groups, and by 1 month there was no difference between the steroid- treated and untreated patients ( treatment was not randomized). The improvement also applied to those patients with intracanalicular enhancement or enhancement of > 17 mm of the nerve. This finding contradicts that of previous studies, which indicated that patients with intracanalicular or extensive optic nerve involvement tend to recover more slowly with more severe residual deficits. Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic' s neuromyelitis optica. Brain 2002; 125: 1450- 61. The authors presented the largest pathologic study to date of neuromyelitis optica ( NMO), or Devic disease, an often destructive form of demyelinating disease involving the optic nerves and spinal cord. They compared autopsy specimens from nine patients with NMO with 73 with multiple sclerosis ( MS). The mean age of the NMO patients was 50 years ( range 16 to 80 years), the mean disease duration was 2.4 years, and the mean interval between the development of optic neuropathy and transverse myelitis was 19 months ( range 4 to 41 months). All patients died of respiratory failure. Distinctive clinical features of NMO included normal brain MRI scans in the vast majority, longitudinally extensive signal abnormalities in the spinal cord during acute attacks ( extending over 3 to 4 spinal segments), occasionally prominent CSF pleocytosis with a polymorphonuclear predominance, and poorer clinical recovery from attacks compared with MS patients. A total of 82 lesions were examined from nine patients with NMO and were classified as " early active" if demyelinating lesions contained macrophages reactive to myelin oligodendrocyte glycoprotein ( MOG), " late active" if the lesions contained more myelin degradation and macrophages reactive to myelin basic protein ( MBP) and pro-teolipid protein ( PLP) but not MOG, " remyelinating" if lesions contained thin and irregularly arranged myelin sheaths, and " inactive" if lesions showed no evidence of remyelination. Twenty- one lesions were classified as early active, 18 late active, eight remyelinating and 35 inactive. Acute NMO lesions demonstrated extensive macrophage Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 173 JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 IN OTHER JOURNALS and microglial infiltration with necrosis of the optic nerves and spinal cord ( gray and white matter). The inflammatory infiltrates seen in acute NMO lesions were characterized by extensive perivascular infiltration by macrophages, microglia, B lymphocytes, eosinophils, and granulocytes. Acute MS lesions also showed macrophage and microglial infiltration but the inflammation was localized in oligodendrocytes along the active plaque margin rather than in a perivascular pattern as seen in acute NMO lesions. The authors reviewed autopsy specimens from 73 patients with MS and found that eosinophilic infiltration was rarely seen ( 4%) but was common in NMO lesions ( 56%). Chronic NMO lesions demonstrated extensive gliosis, cavitation, and atrophy of the optic nerves and spinal cord. The authors suggest that because acute NMO lesions show extensive eosinophilic and lymphocytic infiltration in a perivascular pattern, the disease may be caused by a primary vascular autoimmune disorder. They also report that rats sensitized with soluble MOG develop a chronic demy-elinating disease most prominent in the optic nerves and spinal cord. The active lesions contain lymphocytes and eosinophils and show signs of humoral immunity similar to NMO. The authors theorize that because the optic nerves and spinal cord have the weakest blood- brain barrier ( BBB), perhaps antigenic proteins preferentially cross the BBB in these areas in susceptible patients. Alternatively, CNS damage releases antigenic proteins, which reach the perivascular space and are recognized by immune cells within the circulation. V. Progressive supranuclear palsy Morris HR, Gibb G, Katzenschlager R, et al. Pathological, clinical and genetic heterogeneity in progressive supranuclear palsy. Brain 2002; 125: 969- 75. The authors studied the autopsy specimens of patients with typical ( 11) and atypical ( 15) progressive supranuclear palsy ( PSP) to determine if anatomic or genetic differences exist. They defined typical PSP by the presence of a supranuclear vertical gaze palsy, progressive gait disorder with a tendency to fall backwards, L- dopa unresponsive Parkinsonism, axial rigidity, and pseudobulbar palsy. They defined atypical PSP by the presence of prominent cortical dysfunction early in the course, idiopathic Parkinson disease- like presentation with asymmetric onset and a good response to L- dopa and relatively preserved balance and gait. Previous pathologic studies of PSP patients have revealed deposition of abnormally hyperphosphorylated tau-containing neurofibrillary tangles ( NFT) in the globus pal-lidus, subthalamic nucleus, substantia nigra, and reticular formation of the midbrain and pons. NFTs in the midbrain presumably cause the supranuclear vertical gaze palsy. Previous genetic studies of PSP patients have found a " PSP susceptibility gene" called the tau HI haplotype and the authors determined that all eleven of the typical PSP patients in their study were homozygous for the HI haplotype, whereas only eleven of the fifteen ( 73%) atypical cases were homozygous. Eight of the eleven patients ( 70%) with typical PSP had detectable levels of PSP tau protein in CNS tissue, whereas only five of the fifteen ( 33%) atypical PSP patients had PSP tau protein. The majority of the atypical patients had a tau deposition pattern indicative of Alzheimer disease: NFTs and plaques more extensively deposited within the cortex than in the basis pontis. The authors suggest that several discrete clinicopath-ologic entities may exist within the spectrum of clinical PSP. They believe that PSP- specific tau deposition and the PSP susceptibility genotype H1H1 indicate typical PSP. Lack of the tau susceptibility genotype HI HI indicates atypical PSP. This information is useful for diagnostic and research purposes but has little clinical utility. VI. Pregeniculate blindness and transcranial magnetic stimulation Gothe J, Brandt SA, Irlbacher K, et al. Changes in visual cortex excitability in blind subjects as demonstrated by transcranial magnetic stimulation. Brain 2002; 125: 479- 90. The authors used transcranial magnetic stimulation ( TMS) of the occipital lobes to study visual perception of patients with poor ( 20/ 400 to light perception) or absent vision of at least 10 years duration. TMS of the occipital lobes normally induces brief phosphenes. The authors hypothesized that a visually impaired patient's ability to experience phosphenes by TMS could be used as an indicator of the functional integrity of the visual cortex and might aid in the preoperative evaluation of patients considered for implantation of cortical stimulators. TMS was performed using a figure- of- eight shaped coil ( radius of one half coil = 6 cm) placed over various points on a surface grid overlying the occipital lobes. Seven consecutive impulses at 15 Hz were used with an intensity of 1.3 times the individual motor threshold. In normal control subjects, transcranial stimulation elicited white phosphenes, usually in the contralateral hemifield. All ten patients with acuities between 20/ 400 and counting fingers perceived the phosphenes, although at fewer locations than did the control group. Nine of the fifteen patients with hand motion to light perception vision perceived phosphenes but often required a higher stimulus intensity and responded at fewer stimulation sites. Only two of the ten patients with no light perception reported seeing phosphenes and then only at very high stimulus intensities. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 174 © 2003 Lippincott Williams & Wilkins IN OTHER JOURNALS JNeuro- Ophthalmol, Vol. 23, No. 2, 2003 This study shows that patients who are completely blind for more than 10 years are less likely to respond to TMS and theoretically less likely to respond to cortical stimulation by a visual prosthesis. VII. Leber Hereditary Optic Neuropathy Kim JY, Hwang JM, Park SS. Mitochondrial DNA C4171A/ ND1 is a novel primary causative mutation of Leber's hereditary optic neuropathy with a good prognosis. Ann Neurol 2002; 51: 630- 34. The authors found a novel mitochondrial DNA mutation ( 4171) in two Korean families with Leber hereditary optic neuropathy ( LHON) in the gene ND1 involved in the normal function of complex I of the electron transport chain. The three most common LHON mutations, 11778, 3460 and 14484, which account for 85% to 90% of cases worldwide, also encode proteins involved in complex I. One proband was a 17- year- old male with a history of painless, progressive vision loss to counting fingers, first affecting the OS and two weeks later, the OD. The right optic disc was slightly blurred and the left showed subtle temporal pallor. Eleven months later, visual acuity spontaneously improved to 20/ 200 OD and 20/ 30 OS and the dense bilateral cecocentral scotomas noted on initial Gold-mann kinetic visual fields decreased in size. The patient's maternal grandmother ( age 67) had developed bilateral vision loss at age 27 and recovered 3 years later. Her most recent ophthalmological examination revealed visual acuities of 20/ 40 OD and 20/ 25 OS with bilateral temporal disc pallor and pathologic cupping. The patient's maternal uncle ( age 46) had suffered acute bilateral vision loss at age 19 which improved 6 months later and on a recent examination had visual acuities of 20/ 20 OU with temporal disc pallor and pathologic cupping. The other proband was an 8- year- old boy who presented with painless progressive vision loss OD followed by similar loss OS 4 months later and visual acuities of 20/ 400 OU. Both optic discs were hyperemic with telangiectatic disc vessels and subtle temporal disc pallor. Two years later, visual acuity improved to 20/ 20 OD and 20/ 40 OS with normal color vision using Ishihara plates and essentially normal computerized static visual fields. Sequence analysis of the entire mtDNA of the first proband found one novel mutation at position 4171. The mutation was homoplasmic in all affected members of both families and the second proband's mother was heteroplas-mic ( 88%). The mutation substitutes a methionine for the normal leucine at codon 289 of the ND1 gene. Although both leucine and methionine are large, hydrophobic, non-polar amino acids, the substitution alters the aliphaticity of an extramembrane loop. The 4171 mutation was not found in 514 controls or 63 documented LHON lineages. All four patients with the 4171 mutation improved to > 20/ 40 in at least one eye. Fewer than 10% of patients with either the 11778, 3460 or 14484 mutations sustain this degree of visual improvement.. Perhaps the subtle molecular change in the ND1 encoded protein caused by the methionine for leucine substitution explains why these patients have a much better prognosis than the vast majority of LHON patients. VIH. Lagophthalmos Aramideh M, Koelman JH, Devriese PP, et al. Thixotropy of levator palpebrae as the cause of lagophthalmos after peripheral facial nerve palsy. J Neurol Neurosurg Psychiat 2002; 72: 665- 7. The authors hypothesized that the lagophthalmos sometimes found in patients with lower motor neuron facial nerve palsy is the result of stiffness of the levator palpebrae rather than weakness of the orbicularis oculi. Supportive evidence for their theory includes the observation that lagophthalmos persists during sleep and that the palpebral fissure widens during downward eye movements, indicating impaired relaxation of the levator palpebrae muscle. The authors consider this rigidity of the levator palpebrae muscle analogous to that of a skeletal muscle that has been splinted; the muscle becomes rigid due to the formation of tight crossbridges between actin and myosin fibers. The authors studied thirteen patients with lower motor neuron facial palsies ( nine due to Bell palsy) between 1 day and 6 months ( mean 18 days) after onset. They measured the degree of lagophthalmos before and again after passive closure of the eye for 15 seconds, an action that stretches the levator palpebrae muscle and breaks the actin-myosin crossbridges. The mean baseline degree of lagophthalmos was 7.0 mm ( range 5- 9 mm, standard deviation 1.2 mm) and the mean after passive eyelid closure decreased to 2.0 mm ( range 0- 3.0 mm, standard deviation 0.9 mm). The authors suggest that patients with facial nerve palsies should routinely stretch their levator palpebrae on the side of a facial nerve palsy several times per day to diminish the degree of lagophthalmos and lessen the chances of developing exposure keratopathy. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 175 |