Update on Nystagmus and Other Ocular Oscillations

This review reports on recent advances in understanding nystagmus and other involuntary eye movements. Advances in quantitative evaluations of eye movements using oculography, computational model simulations, genetics, and imaging technologies have markedly improved our understanding of the pathophysiology of involuntary eye movements, as well as their diagnosis and management. Patient-initiated capture of eye movements, especially when paroxysmal, and the online transfer of these data to clinicians would further enhance the ability to diagnose involuntary eye movements.

Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact

Objective@#Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model. @*Methods@#Neurobehavior, neuroinflammation, and oxidative stress were assessed in a mouse model of controlled cortical impact (CCI) injury followed by HI. Mice underwent CCI alone, CCI followed by HI, HI alone, or sham operation. HI was induced by one-vessel carotid ligation with 1 hour of 8% oxygen in nitrogen. Learning and memory were assessed using the novel object recognition test, contextual and cued fear conditioning, and Barnes maze test. Brain cytokine production and oxidative stress-related components were measured. @*Results@#Compared to TBI-only animals, TBI followed by HI mice exhibited significantly poorer survival and health scores, spatial learning and memory in the Barnes maze test, discrimination memory in the novel object recognition test, and fear memory following contextual and cued fear conditioning. Malondialdehyde levels were significantly lower, whereas glutathione peroxidase activity was significantly higher in TBI followed by HI mice compared to TBI-only and sham counterparts, respectively. Interleukin-6 levels were significantly higher in TBI followed by HI mice compared to both TBI-only and sham animals. @*Conclusion@#Post-traumatic HI aggravated deficits in spatial, fear, and discrimination memory in an experimental TBI mouse model. Our results suggest that increased neuroinflammation and oxidative stress contribute to HI-induced neurobehavioral impairments after TBI.

Update on Nystagmus and Other Ocular Oscillations

This review reports on recent advances in understanding nystagmus and other involuntary eye movements. Advances in quantitative evaluations of eye movements using oculography, computational model simulations, genetics, and imaging technologies have markedly improved our understanding of the pathophysiology of involuntary eye movements, as well as their diagnosis and management. Patient-initiated capture of eye movements, especially when paroxysmal, and the online transfer of these data to clinicians would further enhance the ability to diagnose involuntary eye movements.

Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact

Objective@#Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model. @*Methods@#Neurobehavior, neuroinflammation, and oxidative stress were assessed in a mouse model of controlled cortical impact (CCI) injury followed by HI. Mice underwent CCI alone, CCI followed by HI, HI alone, or sham operation. HI was induced by one-vessel carotid ligation with 1 hour of 8% oxygen in nitrogen. Learning and memory were assessed using the novel object recognition test, contextual and cued fear conditioning, and Barnes maze test. Brain cytokine production and oxidative stress-related components were measured. @*Results@#Compared to TBI-only animals, TBI followed by HI mice exhibited significantly poorer survival and health scores, spatial learning and memory in the Barnes maze test, discrimination memory in the novel object recognition test, and fear memory following contextual and cued fear conditioning. Malondialdehyde levels were significantly lower, whereas glutathione peroxidase activity was significantly higher in TBI followed by HI mice compared to TBI-only and sham counterparts, respectively. Interleukin-6 levels were significantly higher in TBI followed by HI mice compared to both TBI-only and sham animals. @*Conclusion@#Post-traumatic HI aggravated deficits in spatial, fear, and discrimination memory in an experimental TBI mouse model. Our results suggest that increased neuroinflammation and oxidative stress contribute to HI-induced neurobehavioral impairments after TBI.

Usefulness of Squatting Combined with the Blood Pressure Measurement for Orthostatic Intolerance in Dizziness Clinic / 대한신경근육질환학회지

Background@#Orthostatic intolerance (OI) is a common clinical symptom in dizziness clinic. The head-up tilt table test (HUT) is one of the primary clinical examination for evaluating OI. There is no consensus on the optimum method for diagnosis of orthostatic hypotension (OH). Herein, we performed the additional squat combined with blood pressure (BP) monitoring for OI patients with normal HUT. @*Methods@#The study included 32 consecutive patients with orthostatic intolerance for 3 months since April, 2018 (Period I) and 27 patients with orthostatic intolerance for 3 months since April, 2019 (Period II) in dizziness clinic of Chungnam National University Hospital. During Period II, the additional squat combined with BP test was performed for normal HUT results in patients with OI. In squat combined orthostatic BP measurement, the first BP measurement was taken following 3 minutes of rest at the squat position; afterwards the patients were raised upright and the measurement was monitored for 2 minutes, using a continuous beat-to-beat BP monitoring. @*Results@#In this study, there was significant difference in OH diagnosis (p<0.001); 40.6% (13/32) by conventional HUT (Period I) vs. 92.5% (25/33) by conventional HUT and additional squat test for normal HUT (Period II). In patients with normal HUT, the positive OH was 86.7% (13/15) by the additional squat combined BP measurement (Period II). @*Conclusions@#In addition to HUT, squat test combined with BP measurement might be more informative for understanding and diagnosing the OH, particularly in patients with OI and normal HUT in dizziness clinic.

Usefulness of Squatting Combined with the Blood Pressure Measurement for Orthostatic Intolerance in Dizziness Clinic / 대한신경근육질환학회지

Background@#Orthostatic intolerance (OI) is a common clinical symptom in dizziness clinic. The head-up tilt table test (HUT) is one of the primary clinical examination for evaluating OI. There is no consensus on the optimum method for diagnosis of orthostatic hypotension (OH). Herein, we performed the additional squat combined with blood pressure (BP) monitoring for OI patients with normal HUT. @*Methods@#The study included 32 consecutive patients with orthostatic intolerance for 3 months since April, 2018 (Period I) and 27 patients with orthostatic intolerance for 3 months since April, 2019 (Period II) in dizziness clinic of Chungnam National University Hospital. During Period II, the additional squat combined with BP test was performed for normal HUT results in patients with OI. In squat combined orthostatic BP measurement, the first BP measurement was taken following 3 minutes of rest at the squat position; afterwards the patients were raised upright and the measurement was monitored for 2 minutes, using a continuous beat-to-beat BP monitoring. @*Results@#In this study, there was significant difference in OH diagnosis (p<0.001); 40.6% (13/32) by conventional HUT (Period I) vs. 92.5% (25/33) by conventional HUT and additional squat test for normal HUT (Period II). In patients with normal HUT, the positive OH was 86.7% (13/15) by the additional squat combined BP measurement (Period II). @*Conclusions@#In addition to HUT, squat test combined with BP measurement might be more informative for understanding and diagnosing the OH, particularly in patients with OI and normal HUT in dizziness clinic.

Exploratory, cognitive, and depressive-like behaviors in adult and pediatric mice exposed to controlled cortical impact

OBJECTIVE: Sequelae of behavioral impairments associated with human traumatic brain injury (TBI) include neurobehavioral problems. We compared exploratory, cognitive, and depressive-like behaviors in pediatric and adult male mice exposed to controlled cortical impact (CCI).METHODS: Pediatric (21 to 25 days old) and adult (8 to 12 weeks old) male C57Bl/6 mice underwent CCI at a 2-mm depth of deflection. Hematoxylin and eosin staining was performed 3 to 7 days after recovery from CCI, and injury volume was analyzed using ImageJ. Neurobehavioral characterization after CCI was performed using the Barnes maze test (BMT), passive avoidance test, open-field test, light/dark test, tail suspension test, and rotarod test. Acutely and subacutely (3 and 7 days after CCI, respectively), CCI mice showed graded injury compared to sham mice for all analyzed deflection depths.RESULTS: Time-dependent differences in injury volume were noted between 3 and 7 days following 2-mm TBI in adult mice. In the BMT, 2-mm TBI adults showed spatial memory deficits compared to sham adults (P < 0.05). However, no difference in spatial learning and memory was found between sham and 2-mm CCI groups among pediatric mice. The open-field test, light/dark test, and tail suspension test did not reveal differences in anxiety-like behaviors in both age groups.CONCLUSION: Our findings revealed a graded injury response in both age groups. The BMT was an efficient cognitive test for assessing spatial/non-spatial learning following CCI in adult mice; however, spatial learning impairments in pediatric mice could not be assessed.

Dizziness in Traumatic Brain Injury: Visual-Vestibular Dysfunction, Neurotological Approach / 대한평형의학회지

Traumatic brain injury (TBI) could give rise to variable clinical manifestations based on the involved structures of our bodies. Although there are no structural abnormalities proven, the patients with mild TBI suffer from chronic dizziness and imbalance. Herein, I will discuss the visuo-vestibular interaction and neurotological finding in TBI, which could demonstrate the clue to the diagnosis and management in dizzy patients with TBI.

Postprandial Dizziness/Syncope Relieved by Alfa-Glucosidase Inhibitor: A Case Report / 대한평형의학회지

A 74-year-old man presented with positional vertigo and prandial dizziness and syncope. He had experienced episodes of frequent dizziness and loss of consciousness for several months. He underwent total gastrectomy with esophagojejunostomy and brown anastomosis 30 years ago. Thirteen years ago, subtotal colectomy with ileo-descending colostomy was done due to colon cancer. And he also had mitral valve replacement and maze operation due to severe mitral valve stenosis and atrial fibrillation. After cardiac operation, he has suffered from sudden dizziness with diaphoresis and chalky face, which usually occurs especially within 30 minutes from the onset of eating. Sometimes, this event was followed by several seconds of loss of consciousness, which caused recurrent events of falling. Neurological examination showed positional nystagmus compatible with benign paroxysmal positional vertigo arising from posterior semicircular canal of the right ear. The positional vertigo disappeared immediately after canalith repositioning maneuver. We tried to monitor vital signs and serum level of glucose during eating. Hyperglycemia (range, 210–466 mg/dL) was noted during eating, which was accompanied by postprandial and prandial hypotension, up to 60/40 mmHg. The patient was prescribed 100 mg of the alfa-glucosidase, acarbose to be taken half an hour before each meal. Eventually, the treatment with acarbose ameliorated the prandial dizziness and hypotension associated with hyperglycemia. Our patient suggests the acarbose could prevent postprandial dizziness and hypotension.

Gaze-Evoked and Perverted Head-Shaking Nystagmus in a Patient with Polycythemia Vera / 대한평형의학회지

Polycythemia vera (PV) is well known chronic myeloproliferative neoplasm, caused by clonal expansion of an abnormal hematopoietic stem cell. Patients with PV may present diverse neurologic symptoms including headache, dizziness or vertigo, tinnitus. However, the attention has not been directed to the neurootological findings in patients with PV. Here, we present a 71-year-old male patient with PV suffered from vertigo and headache. He demonstrated gaze-evoked nystagmus and perverted head shaking nystagmus. Transcranial Doppler showed decrement of blood flow velocity in posterior circulation. The patient's neuro-otologic findings were normalized as polychethemia and blood flow improved with repetitive phlebotomy and medications such as hydroxyurea and aspirin. Considering the neurological and hemodynamic findings in our patient, the mechanism of vertigo in PV could be explained by central vestibulopathy because of vascular insufficiency rather than peripheral vestibulopathy because of inner ear blood hyperviscosity.

Factors Affecting Cognitive Impairment and Depression in the Elderly Who Live Alone: Cases in Daejeon Metropolitan City

BACKGROUND AND PURPOSE: With the rapid increase in the number of elderly people in Korea, multiple socio-economic problems have emerged. In 2015, 6.4 million people accounting for about 13% of the total population in Korea were aged 65 years and over. As the elderly population continues to grow, the elderly who live alone are also increasing. They have potential risks in medical and neuropsychological aspects. The purpose of this study was to investigate the association between cognition and socio-environmental status in the elderly who live alone. METHODS: This study was conducted on 512 people who live alone (equivalent to 1% of the total elderly people) in Daejeon Metropolitan City between April and November 2015. Structured questionnaires were used to investigate the general characteristics, socio-economic status, physical status, and mood for participants. Simple tests using Mini-Mental Status Examination-Demetia Screening, Geriatric Depression Scale and Korean-instrumental activities of daily living were also performed. RESULTS: Among the 512 participants, 109 participants (21.3%) had cognitive impairment, and 128 participants (25.0%) had depression. The number of daily meals, frequency of meeting with family, and depression were independent risk factors for cognitive impairment. Factors including the duration of living alone, cognitive impairment, poor self-perceived health status, frequency of meeting with family and duration of education were considered an independent risk factor for depression. CONCLUSIONS: This study showed that the elderly who live alone are susceptible to cognitive impairment and depression, and factors including the number of daily meals, social contact, and self-perceived health status may affect cognition and depressive mood. Thus, physicians need to pay attention to management of major factors that may cause cognition impairment and depression in the elderly who live alone; in addition, they require ongoing community interest and support.

A Case of Unilateral Internal Carotid Artery Stenosis Presenting with Chronic Isolated Dizziness / 대한평형의학회지

It is customary that the dizziness related to cerebral perfusion might be caused by insufficient posterior circulation. The occurrence and nature of dizziness originating from anterior circulation has not been well-known. Here, we report a chronic dizzy woman presenting with severe internal carotid artery stenosis, which improved after carotid artery stenting.

Preserved Ocular Vestibular Evoked Myogenic Potential to Head Tap in a Patient with Positive Head-Heave / 대한평형의학회지

Vestibular function can be evaluated using various clinical and laboratory findings. Among these, head heave and vestibular evoked myogenic potential (VEMP) represent the otolith-ocular response, which is dynamic rather than static. There have been no reports of tap-evoked VEMP and head-heave in dizzy patients. Here, we report dissociation between ocular VEMP to head tap and the head heave test in acute vestibulopathy.

Prevalence of Anti-Ganglioside Antibodies and Their Clinical Correlates with Guillain-Barre Syndrome in Korea: A Nationwide Multicenter Study

BACKGROUND AND PURPOSE: No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barre syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance. METHODS: Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody. RESULTS: Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) by a single electrophysiological study. CONCLUSIONS: Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.

Reversible Cerebellar Leukoencephalopathy Associated With Oral Methotrexate

Methotrexate (MTX)-induced leukoencephalopathy is the most often reported leukoencephalopathy following intrathecal or intravenous administration. A 72-year-old woman developed leukoencephalopathy localized to the cerebellum after treatment with oral MTX at a dose of 15 mg/week for 3 years. She complained of subtle imbalance during walking and reported having fallen. Her symptoms improved after discontinuation of MTX, and the leukoencephalopathy resolved. This is therefore a case report of selective cerebellar reversible leukoencephalopathy associated with oral MTX.

Diagnosis and Differential Diagnosis of Migrainous Vertigo / 대한평형의학회지

Migrainous vertigo is one of common recurrent vestibular disorders. Because the diagnostic criteria have not been yet settled internationally, we have a difficulty in both diagnosis and research in migraineurs with vertigo. Literature about the diagnostic criteria of migrainous vertigo and its differential diagnosis were reviewed. Until now, the criteria proposed by Neuhauser et al. is regarded as most adequate in diagnosis of migrainous vertigo. Differential diagnosis of migrainous vertigo should be guided by distinction of vestibular symptoms and nonvestibular dizziness and consider the common causes of recurrent vertigo. Just like migraine itself, migrainous vertigo is diagnosed on the basis of history and exclusion of other vestibular disorders mimicking migrainous vertigo. Therefore, delicate history taking is the most important in diagnosis and management of patients with migrainous vertigo.

Can Nitroglycerin Differentiate Benign Recurrent Vertigo From Vestibular Migraine? A Preliminary Study / 대한평형의학회지

BACKGROUND AND OBJECTIVES: Nitroglycerin (NTG), a donor of nitric oxide, is known to provoke migraine attacks in patients with migraine. However, this effect was not explored in patients with benign recurrent vertigo (BRV). To infer the mechanism of BRV, we evaluated provocative effects of NTG in patients with vestibular migraine (VM) and BRV compared with normal controls. MATERIALS AND METHODS: Thirteen patients with recurrent vertigo, 8 with VM and 5 with BRV, and 5 healthy controls received intravenous infusion of 0.5 microg/kg/min NTG over 20 minutes. Headache intensity (visual analog scale) and associated symptoms were recorded at baseline and every 10 minutes for an hour. And the subjects were also asked to complete a headache diary every hour for another 12 hours. RESULTS: In contrast to normal controls (2/5, 40%, p=0.035) and the patients with BRV (1/5, 20%, p=0.007), all patients with VM (8/8, 100%) had migraine attacks after NTG injection. However, there was no difference in the proportion of the patients with migraine attacks after NTG injection between normal controls and the patients with BRV. CONCLUSION: In contrast to the patients with VM, patients with BRV are not sensitive to nitric oxide. These results suggest that the pathophysiology of BRV may be different from that of VM.

Effect of Cardiac Function on Cognition and Brain Structural Changes in Dementia

BACKGROUND AND PURPOSE: Cardiovascular risk factors are considered to also be risk factors for dementia. Recent studies have shown that the prevalence of cognitive dysfunction is high in patients with cardiac diseases. However, few studies have investigated the influence of cardiac function on cognition and brain structural changes in dementia. The aims of this study were to determine the relationship between cardiac and cognitive function, and to characterize any structural changes in the brain that could be caused by cardiac function in patients with dementia. METHODS: Dementia patients (n=93) were recruited prospectively with checking for the presence of vascular risk factors such as hypertension. Cognitive function was measured by the Mini-Mental State Examination, modified Mini-Mental State test, and Korean version of the Dementia Rating Scale. Brain magnetic resonance imaging was conducted to evaluate the cerebral white-matter changes (WMC), ventricular dilation, and cortical and hippocampal atrophy. Cardiac function was evaluated using two-dimensional echocardiography. We divided the patients into two groups according to the presence (+) or absence (-) of WMC. RESULTS: In the entire cohort, the size of the left atrium (LA) was positively correlated with the degree of WMC, irrespective of age (p<0.05). The LA was larger in the WMC (+) group (n=42) than in the WMC (-) group. General cognitive function was significantly lower in the WMC (+) group than in the WMC (-) group. Subjects with an enlarged LA tended to exhibit lower cognitive function and more-severe cerebral WMC. CONCLUSIONS: Cardiac dysfunction represented by LA enlargement could be related to cognitive decline and WMC of the brain resulting from impairment of the cerebral hemodynamic process in dementia.

Medial Temporal Activation in Mal de Debarquement Syndrome Revealed by Standardized Low-Resolution Brain Electromagnetic Tomography

BACKGROUND: Mal de debarquement (MdD) literally means "sickness of disembarkation", and refers to the illusion of movement perceived as an after-effect of traveling on a boat, train, or airplane. The pathophysiology of MdD is currently unknown. CASE REPORT: A 20-year-old man presented with dizziness and swaying sensation for 3 days after a boat trip. Compared with the follow-up EEG without symptoms, the EEG recorded while having MdD symptoms disclosed a significantly decreased alpha-band current source density at the precentral gyrus of the left frontal lobe and increased beta-2 activity at the parahippocampal gyrus of right mesial temporal region. CONCLUSIONS: Our results provide evidence of deranged cortical activity in MdD. To the best of our knowledge this is the first study to document cortical correlates of MdD using an EEG source-localization method.

Prediction of Successful Repositioning of Horizontal Canal Benign Positional Vertigo in Gufoni's Maneuver: A Preliminary Study / 대한평형의학회지

BACKGROUND AND OBJECTIVES: Although several methods of repositioning maneuver have been introduced for the benign paroxysmal positional vertigo involving horizontal canal (HC-BPPV), no study has investigated the nystagmus pattern during the repositioning maneuver and its correlation with the repositioning results. Therefore, we evaluated the predictive value of the nystagmus for successful repositioning by studying the nystagmus pattern during the position of the Gufoni's maneuver. MATERIALS AND METHODS: Seventeen consecutive patients (age range=36~76 years, median age=64), with a diagnosis of HC-BPPV were recruited between July and August 2010. The Gufoni's maneuver for apogeotropic and geotropic nystagmus was performed. After 30 minutes, the treatment outcome was evaluated according to the nystagmus pattern at the individual stage of Gufoni's maneuver. Successful treatment was defined by the resolution of positional vertigo in geotropic HC-BPPV and nystagmus shifted from apogeotropic to geotropic in apogeotropic HC-BPPV. RESULTS: In the successfully treated patients, 4 of 6 patients had the contralesional nystagmus between 1st and 2nd position of Gufoni's maneuver. Ipsilesional nystagmus in 1st position of Gufoni's maneuver was observed in 1 patient with apogeotropic nystagmus. And the other 1 patient with Geotropic HC-BPPV showed no nystagmus in 2nd position after contralesional nystagmus in 1st position of Gufoni's maneuver. Unsuccessfully treated 11 patients had a conversion of nystagmus direction in 2nd position after 1st step. CONCLUSION: During the 2nd position of the Gufoni's maneuver, a nystagmus toward unaffected side predicts a successful repositioning, whereas reversed nystagmus is suggestive of poor response to repositioning.