[Comparison of 2 techniques for evaluating static monocular cyclotorsion with central visual field and scanning laser ophthalmoscope]. / Comparaison de deux techniques d'évaluation de la cyclotorsion monoculaire statique: le champ visuel central et l'ophtalmoscope laser à balayage.

OBJECTIVE: To compare the angles of cyclotorsion measured by central campimetry and scanning laser ophthalmoscopy. METHODS: Both methods were applied to each eye of 44 healthy volunteers, aged between 22 and 55 years. The line passing through the fovea and the center of the papilla was drawn on images from the scanning laser ophthalmoscope (SLO); the line passing through the fixing point and the center of the blind spot was drawn on the charts of the central visual field (VF). Torsion was estimated by the angle between these lines and the horizontal. RESULTS: With the VF method, the excyclotorsion was 5.6+/-2.9 degrees on the right eye and 7.2+/-2.9 degrees on the left eye. With the SLO method, these values were 4.7+/-2.6 degrees and 6.8+/-2.5 degrees , respectively. The measures obtained with both methods correlated significantly, for the right eye and the left eye, as well as for the difference between them. CONCLUSION: Data were in good agreement with the literature. Though slightly greater, values obtained with the scanning laser ophthalmoscope were coherent with campimetric measures. The origin of the greater excyclotorsion of the left eye remains an open issue. This phenomenon must be kept in mind when looking for a pathological between-eye difference.

[Quadruple sectoranopia]. / Quadruple sectoranopie.

Quadruple sectoranopia is a rare campimetric syndrome involving upper and lower, homonymous, congruent field blind sectors sparing a horizontal zone. Ischemia or infarction of the lateral parts of the lateral geniculate body, supplied by the distal part of the anterior choroidal artery, accounts for the visual field defect. Ganglionic nerve fiber atrophy matched to the visual field defect may be found if the lateral geniculate body dysfunction involves infarction. The four cases reported so far involve the following etiologies: a case of surgical ligation of the distal part of the anterior choroidal artery during cerebral meningioma removal, two cases of stroke with anterior choroidal artery infarction, and a case of vascular steal with anterior choroidal artery blood flow being shunted away from the lateral geniculate body by an arteriovenous malformation. If lateral geniculate body infarction is not solely involved, partial recovery may occur, ischemic quiescent neuronal areas being able to resume their activity following ischemia resolution.

[Congenital achromatopsia: electroretinogram in early diagnosis]. / Achromatopsie congénitale: interêt de l'électrorétinogramme pour le diagnostic précoce.

PURPOSE: Achromatopsia is a hereditary disease responsible for congenital low vision. Patients present with nystagmus, abnormal visual behavior or photophobia. Only the electroretinogram (ERG) can confirm the diagnosis in infants. PATIENTS AND METHODS: Thirty children referred for nystagmus or low vision were included in this retrospective study. A complete ophthalmological examination, an ERG and when possible a color vision test (Ishihara, Farnsworth 15 Hue test) was done. A Ganzfeld ERG was performed in accordance with ISCEV standards in patients more than 6 years of age. In younger patients, a simplified method using electroluminescent diode stimulation was used and a comparative ERG in accordance with ISCEV standards was performed when the patients were old enough. RESULTS: The ERG response was identical in children and adults. It confirmed the diagnosis of achromatopsia: the scotopic components obtained in dark adapted conditions were normal, (scotopic a-wave, b2 wave). The photopic components, recorded in light-adapted conditions, in order to inhibit the scotopic response (photopic wave, b1 wave), were not recordable. The color vision tests confirmed color blindness; however, in some patients color denomination was correct. CONCLUSION: The simplified ERG procedures performed in our series were reliable in detecting achromatopsia. However, it may not be sufficient to discriminate complete from incomplete achromatopsia.

[Up-dated ophthalmological screening and follow-up management for long-term antimalarial treatment]. / Surveillance ophtalmologique de la prise des antipaludéens de synthèse au long cours: mise au point et conduite à tenir à partir de 2003.

The early detection of macular toxicity linked to long-term antimalarial treatment requires regular ophthalmological screening based on patients'classification based on their results compared to successive controls. Patients are classified as "low risk" with screening every 18 months if all of the following criteria are met: age under 65 years, no associated renal, hepatic or retinal disease, treatment for less than 5 years, dose less than or equal to 6,5mg/kg/d for hydroxychloroquine and 3mg/kg/d for chloroquine (for a lean patient's weight); "at risk, without fundus findings" with screening every 12 months if one of the following criteria is met: age over 65 years (at the start of or during treatment), antimalarial treatment for more than 5 years, daily dose higher than recommended, presence of renal and/or hepatic disease; "at risk, with fundus findings" with screening every 6 months if a retinal dysfunction has been detected and even if treatment is established or followed. Screening consists of an in-depth clinical examination and at least two complementary tests of macular function: color vision (desaturated-Panel-D15 test) and/or static macular perimetry (central 10 degrees) and/or macular electroretinography (pattern ERG/multifocal ERG). If any changes or anomalies are found between two successive check-ups, the state of the retina can be assessed by angiography and global retinal function by full-field-ERG and electro-oculogram (EOG). The progression from one check-up to the next decides whether a course of treatment will be followed.

Autonomic and respiratory dysfunction in Charcot-Marie-Tooth disease due to Thr124Met mutation in the myelin protein zero gene.

OBJECTIVE: To report the clinical and electrophysiological characteristics of a family presenting Charcot-Marie-Tooth disease (CMT) associated with autonomic nervous system disturbances. METHODS: We studied nerve conduction values, postural adaptation, sympathetic skin reflex, the variation in heart rate by the Valsalva ratio and pupillometry in 7 members of a French family in which CMT due to a Thr124Met mutation in the myelin protein zero (MPZ) gene was diagnosed. RESULTS: Clinical and laboratory evidence of autonomic nervous system disturbances were found in the affected individuals. The clinical phenotype was characterized by sensorimotor peripheral neuropathy, defined as axonal type by electrophysiological studies, and was associated with severe pain, bladder dysfunction, sudorimotor disturbances and abolished pupillary reflex to light. Moreover, two patients had severe restrictive respiratory insufficiency requiring noninvasive mechanical ventilation. CONCLUSIONS: Our study demonstrates that autonomic disturbances may be one of the major clinical signs associated with CMT secondary to MPZ gene mutation in codon 124. Testing of pupillary reflex allows the discrimination of affected and unaffected subjects in our family. However, involvement of the autonomic nervous system in this type of neuropathy is unclear and further studies are required to elucidate the role of the MPZ gene in the autonomic nervous system.

Use of denaturing HPLC and automated sequencing to screen the VMD2 gene for mutations associated with Best's vitelliform macular dystrophy.

We identified three novel VMD2 mutations in patients with Best's macular dystrophy. DHPLC analysis of the 11 VMD2 exons revealed abnormal profiles in exon 8. Direct sequencing showed that these abnormal profiles were due to monoallelic transitions and transversions. We also found three polymorphic sequence changes that have been reported previously and annotated to an online database (http://www.uni-wuerzburg.de/humangenetics/vmd2.html).

[Dysfunction of the magnocellular pathway in Alzheimer's disease]. / Atteinte de la voie magnocellulaire dans la maladie d'Alzheimer.

Visual disturbances are a common feature of Alhzeimer's disease. They are related primarily to visuo-spatial deficits. The pathways mediating visuo-spatial and form identification are at least partially segregated in the brain. The magnocellular pathway has characteristics which make it more suitable for detecting dynamic form, motion and depth. We assessed by means of psychophysical and electrophysiological testings the properties of the parvo and the magnocellular pathways. We found contrast sensitivity deficits for the low and middle spatial frequencies, a significant reduction of the amplitude of the steady-state pattern VEP's at 16, 20 and 24 Hz, abnormal transient pattern VEP's only for the major positivity (P100) and abnormal flash VEP's (delayed P2) as previously observed. The temporal frequency deficits and other abnormalities pointed out in this study, could be related to a dysfunction of the M-pathways in Alzheimer's disease.

Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile.

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelitis without any other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom in 20% and 5% of MS cases, respectively. The aim of our study was to compare a new NMO cohort with recent studies and to try to determine the place of NMO in the spectrum of MS. We retrospectively studied 13 patients with a complete diagnostic workup for NMO. We compared our data with the most recent studies on NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999) 1107]. We also determined whether these patients fulfilled the diagnostic criteria for MS. Thirteen patients (10 women and three men, with a mean age of 37.4 years) were included in the study. We found similar results to previously published data, except for an association with vasculitis in 38% of our cases. All but three of the patients fulfilled the clinical criteria for MS and two patients fulfilled both clinical and MRI criteria for MS. However, if we applied more restrictive criteria concerning spinal cord and brain MRI and CSF, none of our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be differentiated from MS by the application of more stringent criteria. Furthermore, all NMO patients should be investigated for vasculitis, even those with no history of systemic disease.

Pupillary disturbances in multiple sclerosis: correlation with MRI findings.

UNLABELLED: Autonomic nervous system disturbances such as pupillary abnormalities have rarely been evaluated in multiple sclerosis (MS). However, pupillary impairment is not uncommon in MS and its origin is still unclear. The aim of this study was to investigate pupillary disturbances in MS and to try to correlate pupillary defects with spinal cord and brainstem magnetic resonance imaging (MRI) findings. We prospectively studied 45 MS patients and 30 normal subjects. METHODS: The pupillary contraction latency and the amplitude of contraction were recorded by pupillometry. We also determined afferent and efferent pathway defects by comparing the direct and consensual pupillary reflexes. We evaluated brainstem and spinal cord demyelinating lesions and spinal cord cross-sectional area on MRI. At least one pupillometric parameters were significantly impaired in 60% of patients and in none of the controls. We did not find any correlation between pupillary defect and demyelinating lesions on MRI. The most frequent abnormality was efferent pathway shift and this was correlated with spinal cord atrophy (P<0.02). These results confirm that the autonomic nervous system, and especially pupillary function, is frequently impaired in MS. The parasympathetic system is most commonly affected and this is most likely linked to axonal loss (demonstrated by spinal cord atrophy) rather than to demyelinating lesions.

[Kjellin syndrome]. / Syndrome de Kjellin.

A previously healthy 30-year-old woman who had cognitive impairment since childhood suddenly developed progressive spastic paraparesis. Visual impairment and characteristic retinal macular spots supported the diagnosis of Kjellin syndrome. This disease, probably transmitted by autosomal recessive inheritance, is seldom observed in clinical practice. We describe the characteristics of Kjellin syndrome and the differential diagnosis, including other macular changes associated with spastic paraparesis.

Identification of novel VMD2 gene mutations in patients with best vitelliform macular dystrophy.

ABSTRACT We report five novel VMD2 mutations in Best's macular dystrophy patients (S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8. Direct sequencing indicated that these shifts are caused by mono-allelic transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6. Five novel "silent" polymorphisms are also reported: 213T>C, 323C>A, 1514A>G, 1661C>T, and 1712T>C. Hum Mutat 17:235, 2001.

Visual evoked potentials study in chronic idiopathic inflammatory demyelinating polyneuropathy.

BACKGROUND: The frequency of the association between chronic demyelinating inflammatory polyneuropathy (CIDP) and central nervous system (CNS) demyelinating lesions is probably underestimated. OBJECTIVE: To investigate the occurrence of combined central and peripheral demyelination in CIDP patients and to correlate visual evoked potential (VEP) abnormalities with CNS demyelinating lesions, observed on brain magnetic resonance imaging, and antibodies against glycolipids. METHODS: Nerve conduction studies, brain MRI and antibodies against glycolipids were prospectively studied in 17 patients who fulfilled the diagnostic criteria proposed for CIDP (Cornblath DR, Asbury AK, Albers JW, Feasby TE, Hahn AF, McLeod JG, Mendell JR, Parry GJ, Pollard JD, Thomas PK. Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy. Neurology, 1991;41:617-618). VEPs were performed in each case before and after 6 months treatment with either intravenous immunoglobulins (IVIG) or steroids. RESULTS: Eight patients (47%) had increased latencies in at least one eye or showed increased interocular latency difference. Four patients (23%) presented a significant high signal intensity on T2-weighted brain MRI images. Of these 4 patients, 3 had prolonged VEP latency. Two patients with delayed VEP latency had antibodies against GM1, and SGLPG and anti-sulfatides, respectively. One patient with normal VEPs also had antibodies to GM1. VEP results were not significantly modified after treatment, either with steroids or IVIG. CONCLUSION: This study confirmed the high frequency of abnormal VEPs in CIDP patients, and found that they are poorly correlated with CNS demyelinating lesions and antibodies against glycolipids. The VEP abnormalities of these patients may be explained by the susceptibility to immune-mediated damage of both the peripheral nervous system and the optic nerve.

Atypical form of non-Langerhans histiocytosis with disseminated brain and leptomeningeal lesions.

An 18 year old girl presented with acute visual loss. T2 weighted brain MRI showed areas of hyperintensities in the thalamic nuclei, internal capsule, lentiform nuclei, the subarachnoidal spaces, and a retrobulbar infiltration. Analysis of CSF showed numerous foamy histiocytes without malignant cells, raised protein, and depressed glucose concentration. Biopsy of the right thalamus demonstrated aggregates of histiocytes with immunohistological and ultrastructural characteristics of non-Langerhans cell histiocytosis. The patient improved with chemotherapy and corticosteroids. After 3 months of treatment, CSF analysis showed no more histiocytes. Cytological examination of CSF can be helpful for the management of patients with extensive histiocytic infiltration.

[Quantitive evaluation of metamorphopsia in macular disease]. / Evaluation quantitative des métamorphopsies dans la pathologie maculaire.

INTRODUCTION: Visual acuity loss and scotoma are not the only functional consequence of macular disease. Frequently, patients also complain of metamorphopsia. Such visual distortion should be taken into account when evaluating the potential benefit of surgical procedures in macular disease. The Amsler grid does not allow any quantified analysis. In addition, a precise confrontation of the macular lesion with its functional consequences is not possible by this test. We present a new method for analyzing metamorphopsia in macular disease. METHODS: Opto-acustic modulation controlled laser emission allowed to generate a retinal image of 256 squares with an angular size of 1 degrees each. The subject was instructed to fixate the center of the grid and to push a handheld button every time he perceived abnormalities within the presented pattern. At the end of the procedure, the responses were represented on graph superimposed on the fundus image. 15 eyes of 15 successive patients complaining of metamorphopsia were included in this preliminary study. Informed consent was obtained prior to inclusion. All patients reported abnormalities on standard Amsler testing. The test-retest reliability was evaluated by repeating the same procedure between 2 hours and 7 days after the first procedure. RESULTS: The evaluation of 3 patients did not provide reliable information on metamorphopsia because of instable fixation. In 12 patients, a coherent response was obtained. In 9 eyes, the result was unchanged when repeating the procedure, concerning both the number of abnormal elements and their spatial distribution. CONCLUSION: The preliminary results appear to be encouraging, indicating a good reproducibility of the results of this method. They should be confirmed on a larger scale. Further work is necessary to evaluate the interest of this method in assessing functional results of macular surgery.

Multiple sclerosis with normal neuro-ophthalmological work-up: results of focal stimulations induced by a scanning laser ophthalmoscope.

OBJECTIVE: Visual evoked potentials (VEPs) are a very useful tool in diagnosis of multiple sclerosis (MS). Nevertheless, in some cases of the disease, VEPs are normal. The aim of this study was to evaluate the diagnostic value of focal checkerboard reversal stimulation based on opto-acoustic modulation generated by a scanning laser ophthalmoscope (SLO) in patients whose standard neuro-ophthalmological work-up was normal. METHODS: We prospectively studied 185 MS patients. In this cohort we found 30 patients with definite MS and normal neuroophthalmological work-up and we studied the diagnostic yield of focal visual stimulation in these patients. We performed focal SLO-elicited VEPs with two different spatial distributions: a central 8 x 8 degrees square field and a central 8 x 8 degrees exclusion square. The results were analysed in terms of age of the patient, course of the disease, and disability evaluated on the Expanded Disability Status Scale (EDSS). RESULTS: Mean latencies of focal VEPs were increased in MS patients compared to controls. In MS, focal stimulation allowed dysfunction of the visual system to be detected in 50% of patients who have been classified as normal according to conventional VEPs. VEP abnormalities were found to be correlated with the EDSS score (P<0.001) and the course of the disease (P<0.05). CONCLUSION: We have demonstrated the value of focal VEPs in MS diagnosis using SLO-based techniques. Further prospective work in patients with possible and probable MS should enable an evaluation of the sensitivity and specificity of this method in the early diagnosis of MS.

Working conditions and health effects of ethylene oxide exposure at hospital sterilization sites.

Ethylene oxide (EtO) is a powerful disinfectant and sterilant for heat-sensitive surgical items and instruments. Its use in hospitals constitutes an important source of occupational exposure that is sometimes underestimated, such as in cases of EtO device malfunction when the safety rules of procedure are not strictly followed or when individual or collective protective equipment is lacking. We carried out a descriptive study of the health care workers who were assigned to EtO sterilization units of the Lille University Hospital Centre in Lille, France (n = 16). Before the modification of the sterilization units in the development of a single, central sterilization site, we studied the workplaces, occupational conditions, and work procedures of the health care workers exposed to EtO. The aim was to assess the risk of EtO overexposure of the workers in order to improve workers' health and security in the future sterilization center. The study was based on a physical examination, a questionnaire covering each subject's personal and occupational history, and a complete ocular examination. For occupational conditions, the studies of each workplace were also performed by the occupational physician. Area and personal breathing air samplings were performed at each exposure site. Fourteen of the 16 operators had posterior and anterior subcapsular lens opacities, three of which seemed to be directly and primarily related to occupational exposure; the other ten seemed to be rather common and compatible with age. High levels of EtO exposure were reported in the oldest site (90 parts per million [ppm] during the changing of the gas bottle), where exposure often exceeded French threshold limits (permissible exposure limit: 1 ppm 8-hour time-weighted average (TWA) in air; short-term excursion limit: 5 ppm 15-minute TWA in air), or the current US recommended and legal exposure limits for EtO advocated by the Occupational Safety and Health Administration and the American Conference of Governmental Industrial Hygienists (permissible exposure limit: 1 ppm 8-hour TWA in air; excursion limit: 5 ppm 15-minute TWA in air), and the National Institute for Occupational Safety and Health standard (recommended exposure limits: 0.1 ppm 8-hour TWA in air; 5 ppm 10-minute TWA in air). The faults in the work processes, such as interruption of the sterilization cycle and disregard for the use of protective devices, were very common.

[Simplified electroretinography protocol and diagnosis of retinal dystrophies in children]. / Protocole simplifié d'électrorétinographie et diagnostic des dystrophies rétiniennes de l'enfant.

PURPOSE: To report results of a simplified electroretinogram in children. PATIENTS: 124 children under 6 years of age with nystagmus, blindness, neurological disease, cone rod dystrophy in the family, or abnormal fundus appearance were examined. METHOD: The electroretinogram was recorded by corneal electrodes in an awake state without sedation. A light-emitting orange diode stimulator was used. Stimulation was performed subsequently after 3 minutes of light adaptation and after 8 minutes of darkness. If the electroretinogram was abnormal, a second recording was done a few weeks later using the same method. In some cases, the children were re-examined, and a ganzfeld stimulation ERG was recorded. RESULTS AND DISCUSSION: This method allowed a reliable diagnosis of photoreceptor dystrophy: Leber's congenital amaurosis with or without rare metabolic diseases, X link pigmentary retinopathy or retinal dystrophy with general disease in children. It helped to differentiate isolated retinal pigment changes with normal electroretinogram from functional retinal impairment and rod-cone dystrophy from other retinal dystrophies.

Outer retinal dysfunction in patients treated with vigabatrin.

OBJECTIVE: To assess early visual impairment related to vigabatrin prospectively in patients with and without visual symptoms. BACKGROUND: Vigabatrin acts as an inhibitor of gamma-aminobutyric acid (GABA) transaminase. GABA-induced ion transport changes in the retinal pigment epithelium have been described. The electro-oculogram (EOG) is a clinical test that reflects photoreceptor and pigment epithelium function. PATIENTS AND METHODS: Of the 22 consecutive patients presenting with a history of partial seizures currently treated with vigabatrin, 20 were included in the study. A complete clinical ophthalmologic and neurologic examination was performed, including static 100-point perimetry, EOG, and electroretinogram (ERG). RESULTS: In 14 of 20 patients, the light/dark ratio (Arden ratio) of the standard EOG was reduced in at least one eye. The a- and b-wave amplitudes and implicit time of the ERG were within the normal range in all patients; however, ERG oscillatory potentials could not be recorded in 10 patients. Twelve patients had visual field constriction; five complained of visual symptoms. The most severe visual impairment was observed in patients treated with both vigabatrin and valproate. CONCLUSIONS: There is some evidence of outer retinal dysfunction in the patients treated with vigabatrin. EOG, a more sensitive diagnostic tool than ERG for screening vigabatrin-treated patients, also appears to be more specific.