Prevalence of ocular morbidities among school children in Raipur district, India.

Purpose: To estimate the prevalence of various ocular morbidities in school children (5-15 years) utilizing a comprehensive mobile eye unit in Central India. Methods: A prospective, cross-sectional, school-based observational study was carried out in Raipur, Chhattisgarh, India between December 2017 and September 2018. A total of 1557 eligible school-going children in the age group 5-15 years were evaluated. Random sampling was done to allocate schools (n = 29) and children from various urban and rural (836 vs 721) schools. The primary objective was to estimate the prevalence of ocular morbidities in school-going children in Raipur district, India. The secondary objective was to analyze whether geographical location (rural vs urban), age group, and gender led to any differences in ocular morbidity patterns. Results: The mean age of the study population was 10.3 ± 2.4 years. There were 691 (44.4%) boys and 866 (55.6%) girls. Ocular morbidity was present in a total of 331 (21.2%) children. Vitamin A deficiency was the most common cause of ocular morbidity, noted in 156 (10%) children, followed by refractive error (81, 5.2%). Myopia was significantly higher in urban school children (4.3%) compared to rural children (1.9%) (P = 0.002). The older age group had a higher prevalence (7.6%) of refractive error, especially myopia, compared to the younger age group (2.2%) (P < 0.001). Conclusion: Vitamin A deficiency prevalence was much higher indicating missed opportunities for vitamin A supplementation at a younger age. Refractive error was more prevalent in the urban population as well in the older age group (11-15 years), indicating a need for frequent eye screening.

Prevalence and Improvement of Caine-Positive Wernicke-Korsakoff Syndrome in Psychiatric Inpatient Admissions.

BACKGROUND: Wernicke-Korsakoff Syndrome (WKS) resulting from thiamine deficiency is classically defined as including encephalopathy, ataxia, and ophthalmoplegia. Only 16% of autopsy-confirmed patients with WKS exhibit all three signs. Caine-positive WKS criteria include two or more of the following: nutritional deficiency, delirium or mild memory impairment, cerebellar dysfunction/ataxia, and oculomotor abnormalities. OBJECTIVE: We describe Caine-positive WKS prevalence among psychiatric inpatients and compare pretreatment-versus-posttreatment neurocognitive improvement to an unaffected group. METHODS: This 6-month quality-improvement evaluation included two-stage screening for Caine-positive WKS, administering high-dose intravenous thiamine (day 1: 1200 mg; days 2-4: 200 mg) with reexamination on day 5. We used descriptive statistics and fitted random effects models to examine rate-of-change differences in pre-/posttreatment Montreal Cognitive Assessment (MoCA), delayed 5-item recall, and gait/coordination scores between treated Caine-positive patients with WKS and untreated Caine-negative patients. RESULTS: Of 262 patients, 32 (12%) had Caine-positive WKS; 17 (53%) used alcohol currently. Treated Caine-positive WKS (n = 26) versus Caine-negative comparison (n = 34) before and after treatment observed a mean change (standard deviation) in the MoCA score of 3.6 (2.5) versus 1.8 (2.5) (P < 0.01); 5-item recall: 1.8 (1.4) versus 0.5 (1.4) (P < 0.001); gait/coordination scores: -0.6 (1.2) versus -0.1 (0.6) (P < 0.001). Oculomotor abnormalities were infrequent (n = 4 in Caine-positive WKS, n = 2 in Caine-negative comparison groups). CONCLUSIONS: Caine-positive WKS prevalence among psychiatric inpatients was 12%; only half used alcohol. Patients treated with high-dose thiamine demonstrated clinically significant neurocognitive improvement.

Age-related deficits in voluntary control over saccadic eye movements: consideration of electrical brain stimulation as a therapeutic strategy.

Sudden changes in our visual environment trigger reflexive eye movements, so automatically they often go unnoticed. Consequently, voluntary control over reflexive eye movements entails considerable effort. In relation to frontal-lobe deterioration, adult aging adversely impacts voluntary saccadic eye movement control in particular, which compromises effective performance of daily activities. Here, we review the nature of age-related changes in saccadic control, focusing primarily on the antisaccade task because of its assessment of 2 key age-sensitive control functions: reflexive saccade inhibition and voluntary saccade generation. With an ultimate view toward facilitating development of therapeutic strategies, we systematically review the neuroanatomy underpinning voluntary control over saccadic eye movements and natural mechanisms that kick in to compensate for age-related declines. We then explore the potential of noninvasive electrical brain stimulation to counteract aging deficits. Based on evidence that anodal transcranial direct current stimulation can confer a range of benefits specifically relevant to aging brains, we put forward this neuromodulation technique as a therapeutic strategy for improving voluntary saccadic eye movement control in older adults.

Impairment of saccade adaptation in a patient with a focal thalamic lesion.

The frequent jumps of the eyeballs-called saccades-imply the need for a constant correction of motor errors. If systematic errors are detected in saccade landing, the saccade amplitude adapts to compensate for the error. In the laboratory, saccade adaptation can be studied by displacing the saccade target. Functional selectivity of adaptation for different saccade types suggests that adaptation occurs at multiple sites in the oculomotor system. Saccade motor learning might be the result of a comparison between a prediction of the saccade landing position and its actual postsaccadic location. To investigate whether a thalamic feedback pathway might carry such a prediction signal, we studied a patient with a lesion in the posterior ventrolateral thalamic nucleus. Saccade adaptation was tested for reactive saccades, which are performed to suddenly appearing targets, and for scanning saccades, which are performed to stationary targets. For reactive saccades, we found a clear impairment in adaptation retention ipsilateral to the lesioned side and a larger-than-normal adaptation on the contralesional side. For scanning saccades, adaptation was intact on both sides and not different from the control group. Our results provide the first lesion evidence that adaptation of reactive and scanning saccades relies on distinct feedback pathways from cerebellum to cortex. They further demonstrate that saccade adaptation in humans is not restricted to the cerebellum but also involves cortical areas. The paradoxically strong adaptation for outward target steps can be explained by stronger reliance on visual targeting errors when prediction error signaling is impaired.

The visual system in eyelid myoclonia with absences.

OBJECTIVE: To investigate the functional and structural brain correlates of eyelid myoclonus and absence seizures triggered by eye closure (eye closure sensitivity [ECS]). METHODS: Fifteen patients with eyelid myoclonus with absences (EMA, Jeavons syndrome), 14 patients with idiopathic generalized epilepsies (IGE) without ECS, and 16 healthy controls (HC) underwent an electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) and voxel brain morphometry (VBM) protocol. The functional study consisted of 30-second epochs of eyes-open and eyes-closed conditions. The following EEG events were marked and the relative fMRI maps obtained: (1) eye closure times, (2) spontaneous blinking, and (3) spontaneous and eye closure-triggered spike and wave discharges (SWD; for EMA and IGE). Within-group and between-groups comparisons were performed for fMRI and VBM data as appropriate. RESULTS: In EMA compared to HC and IGE we found: (1) higher blood oxygenation level-dependent (BOLD) signal related to the eye closure over the visual cortex, the posterior thalamus, and the network implicated in the motor control of eye closure, saccades, and eye pursuit movements; and (2) increments in the gray matter concentration at the visual cortex and thalamic pulvinar, whereas decrements were observed at the bilateral frontal eye field area. No BOLD differences were detected when comparing SWD in EMA and IGE. INTERPRETATION: Results demonstrated altered anatomo-functional properties of the visual system in EMA. These abnormalities involve a circuit encompassing the occipital cortex and the cortical/subcortical systems physiologically involved in the motor control of eye closure and eye movements. Our work supports EMA as an epileptic condition with distinctive features and provides a contribution to its classification among epileptic syndromes.

Ocular vestibular evoked myogenic potentials are abnormal in internuclear ophthalmoplegia.

OBJECTIVE: The cervical vestibular evoked myogenic potential (cVEMP) is sensitive to lower brainstem lesions affecting the vestibulo-collic pathway. We wished to determine whether the ocular VEMP (oVEMP), a recently-described otolith-ocular reflex, is also abnormal in patients with brainstem lesions. We tested patients with internuclear ophthalmoplegia (INO), caused by a brainstem lesion in the medial longitudinal fasciculus (MLF), to investigate whether the oVEMP is abnormal in patients with a lesion of the otolith-ocular pathway. METHODS: We describe a patient who developed a right INO during his first episode of demyelination, and report results from 12 additional patients, most of whom had multiple sclerosis. All subjects were stimulated with air-conducted tone bursts. cVEMPs and oVEMPs were measured using surface electrodes placed over the neck and beneath the eyes. RESULTS: Overall, oVEMPs showed significantly more abnormalities (69%) than cVEMPs (8%). Ocular VEMPs were absent with stimulation of 13/26 ears, significantly delayed in 5/26 cases and normal in only 8/26 cases. CONCLUSION: Ocular VEMPs are often abnormal in patients with multiple sclerosis who have an INO, while cVEMPs are usually normal. SIGNIFICANCE: Ocular VEMPs provide a new, non-invasive method for examining central vestibular pathways in humans and are sensitive to lesions of the MLF.

Integrated center for research and treatment of vertigo, balance and ocular motor disorders.

The German BMBF (German Ministry of Education and Research) has decided to establish an Integrated Center for Research and Treatment (IFB(LMU)) of Vertigo, Balance and Ocular Motor Disorders in Munich in 2010. With funding of 50 euros million over a ten-year period, the long-term continuation of the IFB(LMU) is envisioned.

Institutional profile: integrated center for research and treatment of vertigo, balance and ocular motor disorders.

In 2009 the German BMBF (German Ministry of Education and Research) established an Integrated Center for Research and Treatment (IFB(LMU)) of Vertigo, Balance and Ocular Motor Disorders in Munich. After the 10-year period of funding by the BMBF, it is envisioned that the (IFB(LMU)) will continue over the long term with the joint support of the University Hospital, the Medical Faculty, and the Bavarian State. Vertigo is one of the most common complaints in medicine. Despite its high prevalence, patients with vertigo generally receive either inappropriate or inadequate treatment. This deplorable situation is internationally well known and its causes are multiple: insufficient interdisciplinary cooperation, no standardized diagnostics and therapy, the failure to translate findings of basic science into clinical applications, and the scarcity of clinical multicenter studies. The (IFB(LMU)) will constitute a suitable tool with which these structural, clinical, and scientific deficits can be overcome. It will also make possible the establishment of an international interdisciplinary referral center. Munich has become the site of a unique concentration of leading experts on vertigo, balance and ocular motor disorders, both in the clinical and basic sciences. Academic structures have paved the way for the creation of an interdisciplinary horizontal network that also allows structured, vertical academic career paths via the Bachelor's and Master's degree programs in Neuroscience, a Graduate School of Systemic Neurosciences, and the Munich Center for Neurosciences - Brain and Mind. The (IFB(LMU)) has the following objectives as regards structure and content: to create an independent patient-oriented clinical research center under the auspices of the Medical Faculty but with autonomous administration and budget; to overcome existing clinical and academic barriers separating the traditional specializations; to establish a standardized interdisciplinary longitudinal and transversal network at one site for the management of patients. This should professionalize both the management and the international recruitment of patients (integrated care, telemedicine); to organize the study infrastructure for prospective multicenter clinical studies as well as to free clinical scientists from administrative tasks; to promote translational research with a focus on the innovative topics of molecular, functional and structural imaging, experimental and clinical pharmacotherapy, clinical research of vertigo and balance disorders, mathematical modelling, interaction between biological and technical systems (robotics), and research on functionality and the quality of life; to offer new attractive educational paths and career images for medical doctors, students of the natural sciences, and engineers in clinical research in order to overcome traditional hierarchical structures. This should promote the principles of efficiency and self-reliance; to supplement the existing excellence with up to eight groups of young scientists and up to eight professorships (tenure track). This should also be seen as an incentive that will attract the best young scientists; to incorporate (IFB(LMU)) competence into the existing medical and biological graduate schools. The (IFB(LMU)) is a unique center - worldwide.

[Ocular tilt reaction in thalamic infarct]. / Reacción ocular de inclinación en infarto talámico.

Ocular tilt reaction (OTR) includes skew deviation, eye torsion and head tilt. It is usually accompanied by a tilt in the subjective visual vertical. OTR seems to reflect an otolithic dysfunction. This case report shows an OTR of central origin as a result of simultaneous paramedial thalamic and mesencephalon rostral infarcts.

Rehabilitation approaches to hemineglect.

BACKGROUND: Hemineglect is a difficult neurologic condition to rehabilitate. It arises predominantly from right brain injury, and manifests heterogeneously in clinical deficits such as poor visual exploration to the left, inaccurate assessment of the midpoint of a line, left limb hypokinesis, and anosognosia. Most of the cognitive dysfunction produced by hemineglect is because of an asymmetric distribution of attention, either with respect to extrapersonal space or to an object being viewed. Many treatments draw on hemineglect theory to attempt to mediate the basic asymmetry of attention. REVIEW SUMMARY: Treatment approaches can be divided into 2 main categories. Extrinsic or "top-down" approaches require active participation of the patient under the guidance of a therapist. The most common approach of this type is visual scanning therapy in which the patient is continually instructed to move the gaze leftward into the neglected space. Intrinsic or "bottom-up" approaches manipulate stimulus characteristics, sensory input, or the brain directly in an attempt to alter the interhemispheral attentional imbalance. Examples of this approach include vestibular stimulation of the left side, sensory activation of the left limb, and transcranial magnetic stimulation of the overactive left hemisphere. Combined approaches such as prism adaptation have also shown good results. CONCLUSIONS: Hemineglect is a complicated disorder that poses challenges to treatment. A paucity of clinical trial evidence limits our ability to extrapolate experimental mediation of hemineglect to globally improved functioning. Nonetheless, many treatment approaches appear promising. Underlying neuroscience may help guide future treatment approaches.

Bimedial rectus hypermetabolism in convergence spasm as observed on positron emission tomography.

A 52-year-old man developed vertical gaze palsy, convergence spasm, and convergence-retraction nystagmus due to glioblastoma of the right thalamus. 18F-fluorodeoxyglucose positron emission tomography (PET) inadvertently demonstrated markedly increased metabolism in the medial rectus muscles. The hypermetabolism indicates active contraction of these extraocular muscles due to excessive convergence drive attributed to inappropriate activation or disrupted inhibition of convergence neurons by the diencephalic lesion.

Neurophysiological endophenotypes across bipolar and schizophrenia psychosis.

The search for liability genes of the world's 2 major psychotic disorders, schizophrenia and bipolar disorder I (BP-I), has been extremely difficult even though evidence suggests that both are highly heritable. This difficulty is due to the complex and multifactorial nature of these disorders. They encompass several intermediate phenotypes, some overlapping across the 2 psychotic disorders that jointly and/or interactively produce the clinical manifestations. Research of the past few decades has identified several neurophysiological deficits in schizophrenia that frequently occur before the onset of psychosis. These include abnormalities in smooth pursuit eye movements, P50 sensory gating, prepulse inhibition, P300, mismatch negativity, and neural synchrony. Evidence suggests that many of these physiological deficits are distinct from each other. They are stable, mostly independent of symptom state and medications (with some exceptions) and are also observed in non-ill relatives. This suggests a familial and perhaps genetic nature. Some deficits are also observed in the BP-I probands and to a lesser extent their relatives. These deficits in physiological measures may represent the intermediate phenotypes that index small effects of genes (and/or environmental factors). The use of these measures in genetic studies may help the hunt for psychosis liability genes and clarify the extent to which the 2 major psychotic disorders share etio-pathophysiology. In spite of the rich body of work describing these neurophysiological measures in psychotic disorders, challenges remain: Many of the neurophysiological phenotypes are still relatively complex and are associated with low heritability estimates. Further refinement of these physiological phenotypes is needed that could identify specific underlying physiological deficits and thereby improve their heritability estimates. The extent to which these neurophysiological deficits are unique or overlap across BP-I and schizophrenia is unclear. And finally, the clinical and functional consequences of the neurophysiological deficits both in the probands and their relatives are not well described.

Modeling Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis.

OBJECTIVE: The goal of this investigation was to demonstrate that internuclear ophthalmoparesis (INO) can be utilized to model the effects of body temperature-induced changes on the fidelity of axonal conduction in multiple sclerosis (Uhthoff's phenomenon). METHODS: Ocular motor function was measured using infrared oculography at 10-minute intervals in patients with multiple sclerosis (MS) with INO (MS-INO; n = 8), patients with MS without INO (MS-CON; n = 8), and matched healthy controls (CON; n = 8) at normothermic baseline, during whole-body heating (increase in core temperature 0.8 degrees C as measured by an ingestible temperature probe and transabdominal telemetry), and after whole-body cooling. The versional disconjugacy index (velocity-VDI), the ratio of abducting/adducting eye movements for velocity, was calculated to assess changes in interocular disconjugacy. The first pass amplitude (FPA), the position of the adducting eye when the abducting eye achieves a centrifugal fixation target, was also computed. RESULTS: Velocity-VDI and FPA in MS-INO patients was elevated (p < 0.001) following whole body heating with respect to baseline measures, confirming a compromise in axonal electrical impulse transmission properties. Velocity-VDI and FPA in MS-INO patients was then restored to baseline values following whole-body cooling, confirming the reversible and stereotyped nature of this characteristic feature of demyelination. CONCLUSIONS: We have developed a neurophysiologic model for objectively understanding temperature-related reversible changes in axonal conduction in multiple sclerosis. Our observations corroborate the hypothesis that changes in core body temperature (heating and cooling) are associated with stereotypic decay and restoration in axonal conduction mechanisms.

Skew deviation as the initial manifestation of left paramedian thalamic infarction.

We describe a 73-year-old man who developed diplopia as the initial manifestation of a left thalamic infarction. By the time he reached the emergency department, clouded consciousness precluded localization of the lesion. Results of brain MRI were initially interpreted as negative. Ophthalmologic examination several hours later disclosed a small vertical ocular misalignment attributed to skew deviation. This finding led to careful scrutiny of the upper brainstem on MRI. Comparison of the diffusion, apparent diffusion coefficient, and exponential apparent diffusion coefficient MRI studies allowed a diagnosis of subtle left thalamic infarction. The recognition of skew deviation in this setting is important because it may be the most specific indicator of a brainstem lesion.

A new familial disease of saccadic oscillations and limb tremor provides clues to mechanisms of common tremor disorders.

Tremor disorders pose fundamental questions about disease mechanisms, and challenges to successful neurotherapeutics: What causes motor circuits to oscillate in disorders in which the central nervous system otherwise seems normal? How does inheritance 'determine' the clinical phenotype in familial tremor disorders? Here, we address these questions. Analogies between the neural circuits controlling rapid eye movements (saccades) and those controlling limb movements allow us to translate the interpretations from the saccadic systems to the limb movement system. Moreover, the relatively well understood neurophysiology of the ocular motor system offers a unique opportunity to test specific hypotheses about normal and abnormal motor control of both eye and limb movements. We describe a new familial disorder--'micro-saccadic oscillations and limb tremor (microSOLT)'--in a mother and daughter who had tiny saccadic oscillations of the eyes and tremor of the hands. This unique oscillatory movement disorder resembles other common tremor disorders (such as essential tremor) that occur in patients who have an otherwise normally functioning central nervous system. We hypothesize that microSOLT is caused by an inherited abnormality that results in abnormal membrane properties causing reduced external inhibition in the premotor neurons that generate the high-frequency discharge (burst) for saccades and for ballistic limb movements. To test this hypothesis, we recorded hand tremor and eye movements in two patients with microSOLT and particularly during natural circumstances when inhibition of the premotor saccadic burst neurons is removed (e.g. eye closure). We then simulated a conductance-based model for the premotor commands which included excitatory and reciprocally inhibitory burst neurons. The structure of this physiologically realistic model was based upon known cell types and anatomical connections in the brainstem (for saccades) and the thalamus (for limb movements). The physiological phenomenon of post-inhibitory rebound in premotor burst neurons makes the circuit inherently unstable and prone to oscillate unless prevented by external inhibition. Indeed, with simulated reduction of external inhibition (in this case glycinergic), saccadic oscillations and limb tremor were reproduced. Our results suggest that a single-inherited deficit can alter membrane properties, which impairs inhibition in an inherently unstable neural circuit causing the eye and limb oscillations in microSOLT. This concept has broad implications for understanding the mechanism and designing rationale pharmacotherapy for abnormal oscillations and may be applicable to other common disorders in which there are no structural abnormalities in the brain such as essential tremor.

Infective endocarditis presenting with Parinaud's dorsal midbrain syndrome.

We present a case of vertical gaze palsy in a 13-year-old girl caused by underlying infective endocarditis, secondary to an infected navel piercing. This case illustrates that infective endocarditis does not always present with classic signs.

The syndrome of combined polar and paramedian thalamic infarction.

BACKGROUND: Occlusion of the polar or the paramedian arteries of the thalamus usually leads to distinct infarcts with specific clinical and imaging correlates. However, vascular variation is such that in up to one third of humans, the polar artery is missing and its territory taken over by the paramedian arteries. OBJECTIVE: To provide attention to the corresponding stroke syndrome of combined polar and paramedian thalamic infarction. METHODS: We studied combined polar-paramedian thalamic infarction in 12 patients (6 right-sided lesions, 3 left-sided lesions, and 3 bilateral lesions) who were selected from 208 consecutively registered patients with thalamic strokes in the Lausanne Stroke Registry. RESULTS: The clinical manifestation included executive dysfunction, apathy, and memory impairment in all patients, with eye movement disturbances in 10 patients (5 with right-sided lesions, 2 with left-sided lesions, 3 with bilateral lesions); acutely impaired consciousness in 11 patients (5 with right-sided lesions, 3 with left-sided lesions, 3 with bilateral lesions); aphasic disturbances in 8 patients (2 with right-sided lesions, 3 with left-sided lesions, 3 with bilateral lesions), including nonfluent aphasia in 1 patient (with left-sided lesions); dysarthria in 5 patients (4 with right-sided lesions, 1 with bilateral lesions); constructional apraxia in 5 patients (with right-sided lesions); mild hemiparesis in 4 patients (2 with right-sided lesions, 2 with left-sided lesions); dyscalculia in 3 patients (1 with left-sided lesions,1 with right-sided lesions, 1 with bilateral lesions); limb dystonia or asterixis in 2 patients (1 with right-sided lesions, 1 with bilateral lesions); mild hemisensory loss in 2 patients (1 with right-sided lesions, 1 with left-sided lesions); hemiataxia in 1 patient (with right-sided lesions); and ideomotor apraxia in 1 patient (with left-sided lesions). Follow-up showed severely disabling, persistent amnesia in 7 patients (4 with right-sided lesions, 3 with bilateral lesions) and persistent eye movement dysfunction in 5 patients (2 with right-sided lesions, 1 with left-sided lesions, 2 with bilateral lesions). The most common etiology appeared to be cardioembolism, followed by artery-to-artery embolism and presumed small-artery disease. CONCLUSIONS: Key features of this syndrome included amnesia preceded by a period of altered consciousness, and vertical eye movement disturbances. The severe and persistent amnesia may be due to coexisting damage to the anterior and dorsomedial nuclei.