Ocular motor and vestibular dysfunction in central nervous system lymphoma.

BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.

Biomarkers determining treatment interval of diabetic macular edema after initial resolution by anti-vascular endothelial growth factor.

PURPOSE: To identify predictive factors that help determine the interval of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection after the initial resolution of diabetic macular edema (DME). METHODS: This retrospective case-control study enrolled treatment-naïve DME patients who had achieved DME resolution after intravitreal anti-VEGF injections. Patients were classified into the recurrence and no-recurrence groups, depending on the development of recurrent DME after deferring intravitreal anti-VEGF injection. The demographics and clinical features, including optical coherence tomography findings, were compared between the two groups. RESULTS: We enrolled 105 eyes. Sixty eyes (57.1%) belonged to the no-recurrence group, and 45 (42.9%), belonged to the recurrence group. The severity of diabetic retinopathy at baseline was related to early DME recurrence (P = 0.009). At the treatment deferring point, the non-recurrence group had both thinner central subfield thickness (289.5 ± 27.2 µm vs. 307.0 ± 38.2 µm, P = 0.011) and thinner central retinal thickness (214.9 ± 41.4 µm vs. 231.8 ± 41.2 µm, P = 0.043) compared to the recurrence group. Intraretinal cyst was observed in 34 eyes (56.7%) in the no-recurrence group and 42 eyes (93.3%) in the recurrence group at the deferring point (P < 0.001). CONCLUSION: A low risk of early DME recurrence is anticipated in the eyes with foveal thinning and no intraretinal cyst when anti-VEGF injection is deferred. These predictive biomarkers can be useful for patient monitoring and determining treatment strategies for DME patients.

Macular hole with epiretinal proliferation: diagnostic value of en-face optical coherence tomography and clinical characteristics.

PURPOSE: To elucidate the clinical features and surgical outcomes of full-thickness macular hole (FTMH) with epiretinal proliferation (EP) diagnosed by both en-face and B-mode optical coherence tomography (OCT). METHOD: This retrospective cohort study classified idiopathic FTMHs into two groups, based on B-scan and en-face OCT imaging: FTMH with EP (EP group) and without EP (non-EP group). The preoperative features, as well as postoperative outcomes up to 12 months, were compared between the two groups. RESULT: Among 318 eyes of idiopathic FTMH that met the inclusion criteria, 59 eyes (18.6%) were in the EP group, and others were in the non-EP group. In 9 eyes (15.3%) out of the EP group, EP was not detected in the preoperative B-mode OCT but was identified through the en-face OCT. Baseline features showed a higher male proportion (47.5% vs. 27.8%, P = 0.005) and a lower incidence of vitreofoveal traction (P < 0.001) in the EP group than in the non-EP group. The EP group showed worse visual recovery than the non-EP group (- 0.23 vs. - 0.41 logarithm of the minimum angle of the resolution at 12 months, P = 0.001). CONCLUSION: The en-face OCT enhances diagnostic accuracy of EP in FTMH eyes, especially in the case with smaller extent of EP. Eyes with FTMH with EP showed a worse visual recovery than FTMH without EP.

RISK OF EXUDATION IN EYES WITH NONEXUDATIVE POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To investigate the characteristics and natural history of treatment-naive nonexudative polypoidal choroidal vasculopathy (PCV) and to determine biomarkers predicting exudative conversion. METHODS: Patients diagnosed with nonexudative PCV based on indocyanine green angiography and optical coherence tomography were included. Incidence of exudative conversion in nonexudative PCV patients and cumulative estimates for overall risk were assessed. Indocyanine green angiography and optical coherence tomography imaging-based features were analyzed to identify risk factors for exudative conversion. RESULTS: The study included 42 eyes of 40 patients with nonexudative PCV. The mean follow-up duration was 54.3 ± 35.5 months. Of the 42 eyes with nonexudative PCV, exudative conversion developed in 23 eyes (54.8%) after 42.2 ± 28.3 months (range, 8-103 months). Kaplan-Meier analysis showed that the exudation-free survival at 5 years after baseline was estimated to be 53.6%. Multivariate regression analysis showed that sequentially increased protrusion of retinal pigment epithelium in the polyp area was a significant risk factor for exudation in nonexudative PCV (odds ratio = 10.16; 95% CI 1.78-57.81; P = 0.01). CONCLUSION: Exudative conversion has been noted in nearly half of the nonexudative PCV cases in 5 years. The progressive protrusion of polypoidal lesions on optical coherence tomography examination may be a significant biomarker for predicting the near-term onset of exudation.

THE IMPACT OF EARLY SURGICAL INTERVENTION ON ANISEIKONIA IN PATIENTS WITH EPIRETINAL MEMBRANE: A Prospective Cohort Study.

PURPOSE: To investigate the efficacy of early surgical intervention in ameliorating aniseikonia among patients with epiretinal membrane. METHODS: This prospective cohort study enrolled patients who underwent surgery for epiretinal membrane. Patients were divided into early (symptom onset within 1 year) and late (symptom onset ≥1 year) treatment groups. Changes in aniseikonia, best-corrected visual acuity, and tangential retinal displacement were assessed and compared at 6 and 12 months postoperatively. RESULTS: Of the 56 patients, 30 (53.6%) belonged to the early treatment group and 26 (46.4%) to the late treatment group. The early treatment group demonstrated a significant reduction in aniseikonia score at 6- and 12-month follow-up visits (-1.10 ± 1.50 [P = 0.002] and -1.18 ± 1.79 [P = 0.003], respectively); however, no improvement was observed in the late treatment group (0.98 ± 4.62 [P = 0.310] and 1.52 ± 4.35 [P = 0.124], respectively). The early treatment group showed larger tangential retinal displacement at the 12-month postoperative follow-up visit. In addition, the amount of tangential retinal displacement was associated with postoperative changes in aniseikonia. CONCLUSION: Early surgical intervention is helpful in improving aniseikonia in patients with epiretinal membrane. The degree of recovery in inner retinal displacement was associated with the improvement of aniseikonia.

Genotypic and Phenotypic Spectrum of Foveal Hypoplasia: A Multicenter Study.

PURPOSE: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). DESIGN: Multicenter, observational study. PARTICIPANTS: A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384). METHODS: Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. MAIN OUTCOME MEASURES: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA). RESULTS: The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH. CONCLUSIONS: We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.

Episodic Vestibular Syndrome with Hyperventilation-Induced Downbeat Nystagmus.

Hyperventilation-induced downbeat nystagmus (HV-DBN) has been reported in cerebellar disorders and explained by a loss of the inhibitory cerebellar output via a metabolic effect on cerebellar Ca2+ channels. The aim of this study was to determine the clinical characteristics and underlying pathogenesis of episodic vestibular syndrome (EVS) with HV-DBN. Of 667 patients with EVS, we recruited 22 with HV-DBN and assessed their clinical characteristics, video-oculographic findings, and the results of molecular genetic analyses. The age at symptom onset was 47.5 ± 13.0 years (mean ± SD), and there was a female preponderance (n = 15, 68%). The duration of vertigo/dizziness attacks ranged from minutes to a few days, and 11 patients (50%) fulfilled the diagnostic criteria for vestibular migraine. HV-induced new-onset DBN in 8 patients, while the remaining 14 showed augmentation of spontaneous DBN by HV. The maximum slow-phase velocity of HV-DBN ranged from 2.2 to 11.9°/s, which showed a statistical difference with that of spontaneous DBN (median = 4.95, IQR = 3.68-6.55 vs. median = 1.25, IQR = 0.20-2.15, p < 0.001). HV-DBN was either purely downbeat (n = 11) or accompanied with small horizontal components (n = 11). Other neuro-otologic findings included perverted head-shaking nystagmus (n = 11), central positional nystagmus (n = 7), saccadic pursuit (n = 3), and horizontal gaze-evoked nystagmus (n = 1). Gene expression profiling with a bioinformatics analysis identified 43 upregulated and 49 downregulated differentially expressed genes (DEGs) in patients with EVS and HV-DBN and revealed that the downregulated DEGs were significantly enriched in terms related to the ribosome pathway. Our results suggest that the underlying cerebellar dysfunction would be responsible for paroxysmal attacks of vertigo in patients with EVS and HV-DBN.

Multi-Robot 2.5D Localization and Mapping Using a Monte Carlo Algorithm on a Multi-Level Surface.

Most indoor environments have wheelchair adaptations or ramps, providing an opportunity for mobile robots to navigate sloped areas avoiding steps. These indoor environments with integrated sloped areas are divided into different levels. The multi-level areas represent a challenge for mobile robot navigation due to the sudden change in reference sensors as visual, inertial, or laser scan instruments. Using multiple cooperative robots is advantageous for mapping and localization since they permit rapid exploration of the environment and provide higher redundancy than using a single robot. This study proposes a multi-robot localization using two robots (leader and follower) to perform a fast and robust environment exploration on multi-level areas. The leader robot is equipped with a 3D LIDAR for 2.5D mapping and a Kinect camera for RGB image acquisition. Using 3D LIDAR, the leader robot obtains information for particle localization, with particles sampled from the walls and obstacle tangents. We employ a convolutional neural network on the RGB images for multi-level area detection. Once the leader robot detects a multi-level area, it generates a path and sends a notification to the follower robot to go into the detected location. The follower robot utilizes a 2D LIDAR to explore the boundaries of the even areas and generate a 2D map using an extension of the iterative closest point. The 2D map is utilized as a re-localization resource in case of failure of the leader robot.

Development of livestock feed additives using porcine blood cells.

Livestock blood discarded during slaughtering has potentially valuable components such as plasma proteins and haemoglobin. Plasma is used as a feed additive following processing via different methods, including spray drying, whereas blood cells have been underutilized. In this study, we developed haemoglobin hydrolysate (HH) and iron-enriched residue (IER) from porcine blood cells and investigated whether their oral administration regulates the immune system and gut microbiota in growing rats. Twenty-one Sprague-Dawley male rats (n = 7) were used during a 4-week trial and were fed a control, HH or IER diet. The ratio of beneficial bacteria such as Lactobacillus and Akkermansia strains increased in rats fed HH or IER diets. Moreover, compared with the control group, the IER group had an elevated ratio of Lactobacillus to Enterobacteria, which is regarded as an index of beneficial aspect in the gut. Phagocytosis of peripheral blood leucocytes was higher in the HH and IER groups than in the control group. The level of plasma immunoglobulin G increased to approximately 72.7 mg/ml and 152.0 mg/ml in the HH and IER groups, respectively, which was significantly (p < 0.05) higher than that in the control group. These results confirm that HH and IER developed in this study may be a potential additive for animal feeds.

Conformer-specific VUV-MATI spectroscopy of methyl vinyl ketone: stabilities and cationic structures of the s-trans and s-cis conformers.

Methyl vinyl ketone (MVK), a volatile compound with photochemical activity, has received considerable attention in the fields of environmental chemistry and atmospheric chemistry. We explored the conformational stabilities of MVK in the neutral S0 and the cationic D0 states using conformer-specific vacuum ultraviolet mass-analyzed threshold ionization (VUV-MATI) spectroscopy, which provided identifiable vibrational spectra for cationic MVK conformers. Based on the origin bands of the two individual conformers of MVK identified in the MATI spectra under different supersonic expansion conditions, the accurate adiabatic ionization energies of the s-trans and the s-cis conformers were determined to be 77 867 ± 4 (9.6543 ± 0.0005 eV) and 78 222 ± 4 cm-1 (9.6983 ± 0.0005 eV), respectively. The identifiable vibrational spectra of the two cationic conformers were further confirmed using vibrational assignments based on the Franck-Condon fit. Accordingly, precise cationic structures of the MVK conformers could be determined. The structural changes of the two conformers upon ionization could be attributed to the removal of an electron from the highest occupied molecular orbital of each conformer, which consists of nonbonding molecular orbitals on the oxygen atom in the carbonyl group interacting with the σ orbitals in the molecular plane. Consequently, the s-trans conformer was preferred by 48 ± 18 and 403 ± 18 cm-1 in the neutral ground S0 and the cationic D0 states, respectively, which was supported by density-corrected density functional theory calculations and natural bond orbital analysis.

Comparison of Ocular Motor Findings Between Neuromyelitis Optica Spectrum Disorder and Multiple Sclerosis Involving the Brainstem and Cerebellum.

This study aimed to define the clinical features and involved structures that aid in differentiation of neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) involving the brainstem and cerebellum. We analyzed the clinical and ocular motor findings, and lesion distribution on brain MRIs in 42 patients with MS (17 men, mean age ± SD = 37 ± 12) and 26 with NMOSD (3 men, mean age ± SD = 43 ± 15) that were recruited from two university hospitals in South Korea (whole study population). An additional subgroup analysis was also conducted in 41 patients presenting acute brainstem or vestibular syndrome (brainstem syndrome population). Logistic regression analysis showed that bilaterality of the lesions (p = 0.012) and presence of horizontal gaze-evoked nystagmus (hGEN, p = 0.041) were more frequently associated with NMOSD than with MS in the whole study population. In the brainstem syndrome population, only hGEN (p = 0.017) was more frequent in NMOSD than in MS. The lesions specific for NMOSD were overlapped in the medial vestibular nucleus (MVN) and nucleus prepositus hypoglossi (NPH) at the pontomedullary junction. In conclusion, presence of hGEN and bilateral lesions involving the MVN and NPH favor the diagnosis of NMOSD rather than MS.

Atypical clinical manifestations of Miller Fisher syndrome.

Miller Fisher syndrome (MFS) is characterized by a clinical triad of ophthalmoplegia, ataxia, and areflexia, and is closely associated with serum anti-GQ1b antibody. Although the clinical triad is the cardinal diagnostic clue, a variety of other symptoms and signs beyond the triad have been reported. To elucidate the frequency and characteristics of atypical clinical manifestations of MFS, we recruited 38 patients with MFS and evaluated the symptoms or signs beyond the classic triad. Eleven (29%) of 38 patients had atypical clinical manifestations of MFS such as headache (n = 6), delayed facial palsy (n = 3), divergence insufficiency (n = 2), and taste impairment (n = 2). Headache was localized to the periorbital (n = 3), temporal (n = 2), or whole (n = 1) area. Only one of them showed bilateral papilledema and an elevated opening pressure in cerebrospinal fluid analysis. Delayed facial palsy developed after the other signs have reached nadir (n = 1) or started to improve (n = 2), and did not follow a pattern of descending paralysis with other cranial neuropathies. Two patients showed divergence insufficiency without external ophthalmoplegia, and another two had taste impairment over the entire tongue without the other signs of facial and glossopharyngeal nerve involvements. Our study shows that approximately 30% of MFS patients can have atypical clinical manifestations beyond the classic triad. These results reflect the broad clinical spectrum of MFS, and might be associated with the presence of additional antiganglioside antibodies besides anti-GQ1b in patients with MFS.

Acute Transient Vestibular Syndrome: Prevalence of Stroke and Efficacy of Bedside Evaluation.

BACKGROUND AND PURPOSE: The aim of this study was to determine the prevalence of stroke and efficacy of bedside evaluation in diagnosing stroke in acute transient vestibular syndrome (ATVS). METHODS: We performed a prospective, single-center, observational study that had consecutively recruited 86 patients presenting with ATVS to the emergency department of Pusan National University Yangsan Hospital from January to December 2014. All patients received a constructed evaluation, including HINTS plus (head impulse, nystagmus patterns, test of skew, and finger rubbing) and brain magnetic resonance imagings. Patients without an obvious cause further received perfusion-weighted imaging. Multivariable logistic regression was used to determine clinical parameters to identify stroke in ATVS. RESULTS: The prevalence of stroke was 27% in ATVS. HINTS plus could not be applied to the majority of patients because of the resolution of the vestibular symptoms, and magnetic resonance imagings were falsely negative in 43% of confirmed strokes. Ten patients (12%) showed unilateral cerebellar hypoperfusion on perfusion-weighted imaging without an infarction on diffusion-weighted imaging, and 8 of them had a focal stenosis or hypoplasia of the corresponding vertebral artery. The higher risk of stroke in ATVS was found in association with craniocervical pain (odds ratio, 9.6; 95% confidence interval, 2.0-45.2) and focal neurological symptoms/signs (odds ratio, 15.2; 95% confidence interval, 2.5-93.8). CONCLUSIONS: Bedside examination and routine magnetic resonance imagings have a limitation in diagnosing strokes presenting with ATVS, and perfusion imaging may help to identify strokes in ATVS of unknown cause. Associated craniocervical pain and focal neurological symptoms/signs are the useful clues for strokes in ATVS.

Late-onset episodic ataxia associated with SLC1A3 mutation.

Episodic ataxia type 6 (EA6) is caused by mutations in SLC1A3 that encodes excitatory amino acid transporter 1 (EAAT1), a glial glutamate transporter. EAAT1 regulates the extent and durations of glutamate-mediated signal by the clearance of glutamate after synaptic release. In addition, EAAT1 also has an anion channel activity that prevents additional glutamate release. We identified a missense mutation in SLC1A3 in a family with EA. The proband exhibited typical EA2-like symptoms such as recurrent ataxia, slurred speech with a duration of several hours, interictal nystagmus and response to acetazolamide, but had late-onset age of sixth decade. Whole-exome sequencing detected a heterozygous c.1177G>A mutation in SLC1A3. This mutation predicted a substitution of isoleucine for a highly conserved valine residue in the seventh transmembrane domain of EAAT1. The mutation was not present in 100 controls, a large panel of in-house genome data and various mutation databases. Most functional prediction scores revealed to be deleterious. Same heterozygous mutation was identified in one clinically affected family member and two asymptomatic members. Our data expand the mutation spectrum of SLC1A3 and the clinical phenotype of EA6.

Isolated optic neuritis associated with Mycoplasma pneumoniae infection: report of two cases and literature review.

Mycoplasma pneumonia is a major pathogen of primary atypical pneumonia and has been known to cause various kinds of extrapulmonary manifestations involving almost all organs of the human body. Optic neuritis associated with M. pneumoniae infection has rarely been described and mostly, it combined other neurological complications including meningitis, meningoencephalitis, myelitis, and peripheral neuropathy. We report two patients who presented with isolated optic neuritis due to M. pneumoniae infection, and reviewed the literatures on five additional patients. All patients are child or young adults, and optic neuritis was unilateral (n = 3) or bilateral (n = 4). Remarkably, four patients did not have preceding history of respiratory M. pneumonia infection, and ocular pain or headache was accompanied in only three. Although initial visual acuities were severely reduced in most cases, visual outcome was excellent after systemic steroid and/or antibiotics treatment. M. pneumonia infection should be considered in the differential diagnosis of isolated optic neuritis, especially when occurring in a child or young adults, even though there was no preceding pneumonia, accompanying ocular pain, or headache. Various mechanisms including direct local inflammation, vascular occlusion, or indirect immune modulation due to M. pneumonia infection can lead to isolated neurological manifestations without pneumonia.

Clinical and Oculographic Analysis of Inferior Oblique Myokymia.

A 63-year-old man experienced transient vertical oscillopsia lasting several seconds for 2 months. Examination disclosed paroxysmal excyclotorsion of the right eye, spontaneously or triggered by adduction. Eye movements using 3D video-oculography showed intermittent, monocular phasic movements which consisted of excyclotorsion of the right eye mixed with a small amount of supraduction and abduction, and a tonic movement with excyclotorsion and slight elevation. Orbital and brain MRI was unremarkable. Administration of oxcarbazepine markedly decreased the severity and frequency of the episodes. The oculographic characteristics in our patient may indicate that inferior oblique myokymia may be attributed to aberrant, spontaneous discharges in the inferior oblique motor unit.

Exercise-induced downbeat nystagmus in a Korean family with a nonsense mutation in CACNA1A.

Episodic ataxia type 2 (EA2) is characterized by recurrent attacks of vertigo and ataxia lasting hours triggered by emotional stress or exercise. Although interictal horizontal gaze-evoked nystagmus and rebound nystagmus are commonly observed in patients with EA2, the nystagmus has been rarely reported during the vertigo attack. To better describe exercise-induced nystagmus in EA2, four affected members from three generations of a Korean family with EA2 received full neurological and neuro-otological evaluations. Vertigo was provoked in the proband with running for 10 min to record eye movements during the vertigo attack. We performed a polymerase chain reaction-based direct sequence analysis of all coding regions of CACNA1A in all participants. The four affected members had a history of exertional vertigo, imbalance, childhood epilepsy, headache, and paresthesia. The provocation induced severe vertigo and imbalance lasting several hours, and oculography documented pure downbeat nystagmus during the attack. Genetic analyses identified a nonsense mutation in exon 23 which has been registered in dbSNP as a pathogenic allele (c.3832C>T, p.R1278X) in all the affected members. Ictal downbeat nystagmus in the studied family indicates cerebellar dysfunction during the vertigo attack in EA2. In patients with episodic vertigo and ataxia, the observation of exercise-induced nystagmus would provide a clue for EA2.