Visual dysfunction in multiple sclerosis. / Synsproblemer ved multippel sklerose.

Multiple sclerosis can give rise to signs and symptoms from the entire nervous system, including visual impairments. Visual impairments often go unreported because they are not obvious to patients, which means that doctors must ask about them specifically. Regular monitoring of vision is important, however, to provide personalised rehabilitation and assistive technologies, and thereby improve patients' functioning and quality of life.

The Development of a Nystagmus-Specific Quality-of-Life Questionnaire.

PURPOSE: To develop a nystagmus-specific quality-of-life (QOL) questionnaire derived from patient concerns based on eudaimonic aspects of well-being. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 206 participants with nystagmus for factor analysis phase and an additional 42 participants with nystagmus for construct validity phase. METHODS: Questionnaire items were written on the basis of the 6 domains of everyday living affected by nystagmus that were elicited by previous semistructured interviews conducted with 21 people with nystagmus. After consultation with 8 nystagmus experts, 37 items were administered to 206 people with nystagmus. Factor analysis was used to identify latent factors among the items and identify items to propose new nystagmus QOL scales. Cronbach's alpha was used to assess the internal reliability of the new scales. To assess for discriminate and concurrent validity between the new nystagmus scales and an existing vision-related QOL tool, the Visual Function Questionnaire-25 (VFQ-25) was administered to 42 additional participants. MAIN OUTCOME MEASURES: Questionnaire response scores on nystagmus-specific QOL items. RESULTS: The factor analysis revealed the retention of 29 items to form a measure comprising 2 distinct subscales reflecting "personal and social" and "physical and environmental" functioning as relating to nystagmus-specific QOL. The Cronbach's alpha coefficients for the "personal and social" functioning scale and "physical and environmental" functioning were 0.95 and 0.93, respectively. Tests for validity of the measure, consistent with a priori predictions, when compared with the VFQ-25, revealed the "physical and environmental" subscale showed concurrent validity (0.88), whereas the "personal and social" subscale was demonstrated to have discriminative validity (0.81). CONCLUSIONS: We have developed a 29-item, nystagmus-specific QOL questionnaire (NYS-29) based on eudaimonic aspects of well-being with subscales that address not only physical functioning but also psycho-social issues. The NYS-29 is grounded in the perspectives and concerns of those who have nystagmus and can be used to determine the impact of nystagmus on daily living in terms of both physical and psychosocial aspects.

Negative prognostic factors for psychological conditions in patients with audiovestibular diseases.

OBJECTIVE: To examine the backgrounds of patients with audiovestibular disease regarding what influences their psychological state. METHODS: During a 12-year period, 375 successive patients with audiovestibular diseases were enrolled in this study. Diseases included unilateral (n=174) and bilateral (n=51) Menière's disease, sudden deafness with vertigo (n=70), and vestibular neuritis (n=80). Diagnosis, sex, age, duration of disease, vertigo frequency, persistent nystagmus, and ipsilateral/contralateral hearing levels were recorded. Cornell Medical Index (domains III-IV=neurosis) and Self-Rating Depression Scale (score>40=depression) were applied during acute vertigo remissions in all patients. RESULTS: Neurosis and depression, respectively, were diagnosed in 62.7% and 82.4% of bilateral Menière's, 32.7% and 48.9% of unilateral Menière's, 15.7% and 38.6% of sudden deafness/vertigo, and 12.7% and 31.3% of vestibular neuritis patients. Multivariable logistic regression analysis showed that Menière's disease with longer disease duration (Oz 1.212; P=0.021) and worse hearing in the secondary affected ear (Oz 1.131; P=0.042); sudden deafness/vertigo with persistent nystagmus (Oz 1.895; P=0.005); and vestibular neuritis with longer disease duration (Oz 1.422; P=0.019) and persistent nystagmus (Oz 1.950; P=0.0003) had mental illness significantly more often than those with shorter-duration disease, better hearing and no persistent nystagmus. CONCLUSION: Mental disorder increased in accordance with solo vertigo, vertigo/hearing loss, repeated symptoms, and bilateral lesions. Treatment strategies should be carefully constructed for patients with persistent nystagmus, long disease duration, and hearing loss in the secondary affected ear to avoid psychological disorders.

Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS.

OBJECTIVE: To elucidate the neuropathology in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS), a novel cerebellar ataxia comprised of the triad of cerebellar impairment, bilateral vestibular hypofunction, and a peripheral sensory deficit. METHOD: Brain and spinal neuropathology in 2 patients with CANVAS, together with brain and otopathology in another patient with CANVAS, were examined postmortem. RESULTS: Spinal cord pathology demonstrated a marked dorsal root ganglionopathy with secondary tract degeneration. Cerebellar pathology showed loss of Purkinje cells, predominantly in the vermis. CONCLUSION: The likely underlying sensory pathology in CANVAS is loss of neurons from the dorsal root and V, VII, and VIII cranial nerve ganglia-in other words, it is a "neuronopathy" rather than a "neuropathy." Clinically, CANVAS is a differential diagnosis for both spinocerebellar ataxia type 3 (or Machado-Joseph disease) and Friedreich ataxia. In addition, there are 6 sets of sibling pairs, implying that CANVAS is likely to be a late-onset recessive or autosomal dominant with reduced penetrance disorder, and identification of the culprit gene is currently a target of investigation.

Motion perception without Nystagmus--a novel manifestation of cerebellar stroke.

OBJECTIVE: The motion perception and the vestibulo-ocular reflex (VOR) each serve distinct functions. The VOR keeps the gaze steady on the target of interest, whereas vestibular perception serves a number of tasks, including awareness of self-motion and orientation in space. VOR and motion perception might abide the same neurophysiological principles, but their distinct anatomical correlates were proposed. In patients with cerebellar stroke in distribution of medial division of posterior inferior cerebellar artery, we asked whether specific location of the focal lesion in vestibulocerebellum could cause impaired perception of motion but normal eye movements. METHODS/RESULTS: Thirteen patients were studied, 5 consistently perceived spinning of surrounding environment (vertigo), but the eye movements were normal. This group was called "disease model." Remaining 8 patients were also symptomatic for vertigo, but they had spontaneous nystagmus. The latter group was called "disease control." Magnetic resonance imaging in both groups consistently revealed focal cerebellar infarct affecting posterior cerebellar vermis (lobule IX). In the "disease model" group, only part of lobule IX was affected. In the disease control group, however, complete lobule IX was involved. CONCLUSIONS: This study discovered a novel presentation of cerebellar stroke where only motion perception was affected, but there was an absence of objective neurologic signs.

An eye for an I: a 35-year-old woman with fluctuating oculomotor deficits and dissociative identity disorder.

Physiologic changes, including neurological or pseudo-neurological symptoms, occur across identity states in dissociative identity disorder DID) and can be objectively measured. The idea that dissociative phenomena might be associated with changes in brain function is consistent with research on the brain effects of hypnosis. The authors report a case of psycho-physiologic differences among 4 alter personalities manifested by a 35-year-old woman with DID. Differences in visual acuity, frequency of pendular nystagmus, and handedness were observed in this patient both when the alter personalities appeared spontaneously and when elicited under hypnosis. The authors consider several diagnostic possibilities for these findings and discuss whether prevailing treatment recommendations for DID patients could possibly be modified to ameliorate such visual and neurologic symptoms.

Quality of life is decreased in patients with paragangliomas.

CONTEXT: Germline mutations in succinate dehydrogenase (SDH) genes predispose carriers for developing paragangliomas, and studies on their quality of life (QoL) are scarce. OBJECTIVES: The objectives of this study were to assess QoL in patients with paragangliomas (PGL), to evaluate long-term QoL, and to explore potential differences in QoL between SDH mutation carriers and paraganglioma patients without an SDH mutation. DESIGN: Cross-sectional, case-control study. SETTING: Tertiary referral center. SUBJECTS: ONE HUNDRED AND SEVENTY FOUR PARAGANGLIOMA PATIENTS WERE INCLUDED: 25 SDHB, two SDHC, and 122 SDHD mutation carriers and 25 patients without an SDH mutation. They provided 100 peers as control persons. Furthermore, patients were compared with age-adjusted reference populations. MAIN OUTCOME MEASURES: QOL WAS ASSESSED USING THREE VALIDATED HEALTH-RELATED QOL QUESTIONNAIRES: the Hospital Anxiety and Depression Scale, the Multidimensional Fatigue Index 20, and the Short Form 36. RESULTS: Patients reported a significantly impaired QoL compared with their own controls, mainly on fatigue and physical condition subscales. Compared with age-adjusted literature values, patients had significantly impaired scores on physical, psychological, and social subscales. A decreased QoL was mainly related to paraganglioma-associated complaints. There was no difference in QoL between the various SDH mutation carriers or paraganglioma patients without an SDH mutation. QoL in asymptomatic mutation carriers, i.e. without manifest disease, did not differ from QoL of the general population. Long-term results in 41 patients showed no alteration in QoL besides a reduced level of activity. CONCLUSION: QoL is decreased in paraganglioma patients but stable when measured over time.

Living with nystagmus: a qualitative study.

BACKGROUND/AIMS: To identify aspects of daily living affected by nystagmus. METHODS: Semistructured interviews were conducted at the University of Leicester, UK with participants with acquired and infantile nystagmus. In total 21, participants were purposively sampled and recruited. Transcript analysis was conducted using constant comparative technique, based upon the grounded theory, to identify specific areas of living affected by nystagmus. RESULTS: Analysis identified six domains that were adversely affected by nystagmus; visual function, restriction of movement, standing out/not fitting in, feelings about the inner self, negativity about the future and relationships. Cosmetic appearance of nystagmus, including others' avoidant response to this, was described (n=18), as was others' failure to recognise what it is like to have nystagmus (n=18). Driving issues were frequently raised (n=19) and restrictions in occupation choice/opportunities (n=17) were highlighted. Reliance on others (n=16) also emerged. Additional to other categories was an overarching and universal distress arising from nystagmus affecting every aspect of everyday life. CONCLUSION: Interviews revealed universally negative experiences of living with nystagmus that are previously unreported. Findings are similar to studies conducted for strabismus, in particular with respect to cosmetic impact. This study provides the content that is required to develop a nystagmus-specific quality of life tool.

Improved visual acuity and recognition time in nystagmus patients following four-muscle recession or Kestenbaum-Anderson procedures.

PURPOSE: Many patients describe more rapid recognition of objects after surgical procedures for nystagmus; however, this "recognition time" is not reflected in the parameters typically studied in these patients. The purpose of this study is to assess the effect of nystagmus surgery on visual acuity and recognition time. METHODS: In this prospective, interventional, comparative case series, patients with nystagmus were divided into two groups. group A (n = 13) underwent four-muscle retroequatorial recession; group B (n = 8) underwent the Kestenbaum-Anderson procedure. Visual acuity, binocularity, and recognition time were assessed before and after surgery. Recognition time was measured in a routine examination setting using specially designed software that controlled the time of appearance of optotypes in 0.1 second increments. RESULTS: A total of 21 patients were enrolled. The entire group experienced significant postoperative improvement in visual acuity (P = 0.002) and recognition time (P = 0.005). The mean improvement in recognition time was 0.3 seconds at maximum preoperative visual acuity level. A trend toward more improvement in group A than in group B was not statistically significant. CONCLUSIONS: Both the four-muscle recession and the Kestenbaum-Anderson procedures resulted in a 1- to 2-line improvement in visual acuity and a 0.3 second improvement in optotype recognition time.

A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias.

OBJECTIVE: The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus. METHODS: After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis. RESULTS: The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects. Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p = 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p = 0.08). The VDADL score decreased from 6.00 to 1.50 (p = 0.02). 4AP was well-tolerated. CONCLUSIONS: This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life. LEVEL OF EVIDENCE: This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias.

Acquired pendular nystagmus in multiple sclerosis and oculopalatal tremor.

OBJECTIVE: Acquired pendular nystagmus occurs mainly in multiple sclerosis (MS) and focal brainstem lesions. In the later case, it is part of the syndrome of oculopalatal tremor. Even though pathophysiology of acquired pendular nystagmus has been clearly characterized experimentally in both etiologies, there is a persisting ambiguity in clinical literature, which leads one to consider both clinical conditions as a common entity. The objective of our work was to compare in a prospective study clinical features, eye movement recording, and functional consequences of acquired pendular nystagmus in 14 patients with oculopalatal tremor and 20 patients with MS. METHODS: Besides complete neurologic evaluation, evaluation of visual function, 3-dimensional eye movement recording, and functional scores of the Visual Function Questionnaire were recorded. RESULTS: One patient with oculopalatal tremor and 15 patients with MS disclosed signs of optic neuropathy. The nystagmus in the oculopalatal group showed significant larger mean amplitude (8 deg vs 1 deg), higher mean peak velocity (16 deg/s vs 6 deg/s), lower mean frequency (1-3 Hz vs 4-6 Hz), and larger asymmetry and irregularity of ocular oscillations compared to the MS group. The vision-specific health-related quality of life was more deteriorated in the oculopalatal tremor group than in the MS group. CONCLUSIONS: This study emphasizes the need to consider acquired pendular nystagmus in MS and oculopalatal tremor as 2 different clinical entities. This is of particular importance regarding the future evaluation of potential specific effects of pharmacologic agents.

Phenotypical characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7.

Idiopathic infantile nystagmus (IIN) consists of involuntary oscillations of the eyes. The familial form is most commonly X-linked. We recently found mutations in a novel gene FRMD7 (Xq26.2), which provided an opportunity to investigate a genetically defined and homogeneous group of patients with nystagmus. We compared clinical features and eye movement recordings of 90 subjects with mutation in the gene (FRMD7 group) to 48 subjects without mutations but with clinical IIN (non-FRMD7 group). Fifty-eight female obligate carriers of the mutation were also investigated. The median visual acuity (VA) was 0.2 logMAR (Snellen equivalent 6/9) in both groups and most patients had good stereopsis. The prevalence of strabismus was also similar (FRMD7: 7.8%, non-FRMD7: 10%). The presence of anomalous head posture (AHP) was significantly higher in the non-FRMD7 group (P < 0.0001). The amplitude of nystagmus was more strongly dependent on the direction of gaze in the FRMD7 group being lower at primary position (P < 0.0001), compared to non-FRMD7 group (P = 0.83). Pendular nystagmus waveforms were also more frequent in the FRMD7 group (P = 0.003). Fifty-three percent of the obligate female carriers of an FRMD7 mutation were clinically affected. The VA's in affected females were slightly better compared to affected males (P = 0.014). Subnormal optokinetic responses were found in a subgroup of obligate unaffected carriers, which may be interpreted as a sub-clinical manifestation. FRMD7 is a major cause of X-linked IIN. Most clinical and eye movement characteristics were similar in the FRMD7 group and non-FRMD7 group with most patients having good VA and stereopsis and low incidence of strabismus. Fewer patients in the FRMD7 group had AHPs, their amplitude of nystagmus being lower in primary position. Our findings are helpful in the clinical identification of IIN and genetic counselling of nystagmus patients.

Social and visual function in nystagmus.

AIM: To investigate the influence of nystagmus on visual and social function and determine if parents are able to assess visual and social function in children with nystagmus. METHOD: A postal questionnaire comprising 14 questions related to visual function (VF-14) and questions pertaining to social function were sent to all 1013 members of the Nystagmus Network-a UK based organisation for nystagmus sufferers and their families. Visual and social function scores were compared by regression analysis. RESULTS: 180 adult, 233 parent, and 124 child questionnaires were returned. Idiopathic nystagmus was the most common cause. In adults the mean VF-14 score indicated very low visual function, in the same range as patients assessed in low vision services. Children's visual function scored better than adults, between scores of patients with age related macular disease and corneal grafts. There was a strong correlation between perceived visual and social function for adults (p<0.001) and parental assessment of their children (p<0.001), but not between child self assessment of visual and social function. There was strong correlation between parental and child assessment of visual and social function (p<0.001, p<0.001) CONCLUSION: Questionnaires indicated that nystagmus is associated with very low visual function. There is a strong correlation between visual and social impairment. The authors have shown for the first time in an ophthalmic disease that parents are able to estimate the impact of nystagmus on their child both in terms of visual and social functioning, although they underestimate the impact of nystagmus on emotional aspects of wellbeing.

Congenital nystagmus: control of slow tracking movements by target offset from the fovea.

Patients with congenital nystagmus (CN) are unable to respond adequately to optokinetic stimuli. This suggests that patients with CN do not use the movement of images (slip) across the retina as a control variable for their eye movements. Nevertheless, they are capable of tracking moving targets with slow eye movements. Experiments using paracentral afterimages as targets for fixation suggest that these slow tracking movements may be executed by the control of target position on the retina rather than slip across the retina: all seven patients with CN produced slow tracking movements, superimposed on nystagmic cycles. The fact that the basic parameters of the CN waveform remained unchanged under the open-loop condition constituted by afterimage tracking (only the amplitude was reduced in four out of seven patients) indicates that the timing and direction of slow and rapid components of CN do not depend on retinal feedback. During refixations between stationary targets, some patients with CN occasionally acquired the target with a slow, rather than a saccadic movement. This finding further supports the notion that patients with CN use target offset from the fovea as a very effective control variable not only for rapid, but also for slow eye movements.

Functional disease in neuro-ophthalmology.

Techniques for assessment of the functional basis for neuro-ophthalmic complaints are given. By use of these techniques, most neurologists will discover that the majority of patients will resolve their symptoms without unwarranted medical procedures.

Influence of vestibular and cerebellar dysfunction on the performance of alcoholics on the Rod-and-Frame Test.

The hypothesis of vestibuloocular or cerebellooccular motor dysfunction as a possible cause of the field-dependent behavior of alcoholics on the Rod-and-Frame Test could not be verified.