Visual search in Alzheimer's disease and amnestic mild cognitive impairment: An eye-tracking study.

INTRODUCTION: Visual search impairment is a potential cognitive marker for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). The aim of this study is to compare eye movements during visual tracking in AD and aMCI patients versus healthy controls (HCs). METHODS: A prospective cohort study included 32 AD and 37 aMCI patients, and 33 HCs. Each participant was asked to look at the target object in a visual stimulus containing one target and eight distractors, and eye movements were recorded with EyeLink 1000 Plus. RESULTS: AD patients had fewer fixations and shorter target fixation duration than aMCI patients and HCs. Fixation durations were also shorter in aMCI patients compared to HCs. Also, AD patients were more fixated on distractors than HCs. DISCUSSION: Our findings revealed that visual search is impaired in the early stages of AD and even aMCI, highlighting the importance of addressing visual processes in the Alzheimer's continuum. HIGHLIGHTS: AD patients looked to distractors more and longer than the target compared to aMCI patients and older healthy individuals. aMCI patients had an impaired visual search pattern compared to healthy controls, just like patients with AD. The visual search task differentiated AD and aMCI patients from healthy individuals without dementia.

Optical Coherence Tomography Angiographic Follow-Up in a Case of Subacute Sclerosing Panencephalitis and Unilateral Necrotising Retinitis.

We present a 20-year-old woman who was diagnosed with subacute sclerosing panencephalitis (SSPE) 20 months after presenting with unilateral retinitis. At presentation, the patient had two inferotemporal macular lesions in her left eye. Corresponding to these areas, optical coherence tomography (OCT) showed hyporeflective spaces with loss of nearly all of the retinal layers. OCT-angiography (OCTA) demonstrated some flow deficit areas with a reduction in the vessel density. Her serum measles antibody titre was high (IgG >5000.0 mIU/ml). Twenty months later the macular lesions had diminished in size, and there was some focal retinal thinning with interruption of the ellipsoid zone. OCTA showed that the flow deficit areas were diminished in size together with the relatively improved perfusion density. Neurological examination disclosed myoclonic jerks. Neuropsychological assessment demonstrated impaired executive function, attention, and narrowed lexical fluency. Measles IgG antibody was high in the cerebrospinal fluid (>230.0 U/ml). Brain magnetic resonance imaging demonstrated bilateral, non-specific, small foci of T2 hyperintensity in the frontoparietal subcortical white matter and centrum semiovale. The present case is the first where OCTA findings of SSPE-related retinal lesions have been described.

Cognitive function in Meniere's disease.

Meniere's disease is an otological disease characterized by various symptoms that include episodic peripheral vertigo, sensorineural hearing loss, tinnitus, and aural fullness, all of which deteriorate the maintenance of daily activities. We aimed to investigate cognitive function in Meniere's disease patients and compare their results to those of healthy controls. Eighteen patients diagnosed with definite Meniere's disease without any psychiatric, neurological or otological comorbidity, and 30 healthy controls with normal cognitive functions were included in the study. General cognitive status, attention, verbal memory, visual memory, executive and visuospatial function were measured by detailed neuropsychological tests in both groups. In the patients with Meniere's disease, pure-tone hearing thresholds, and speech discrimination scores were also measured. Patients with Meniere's disease showed lower levels of performance in the trail making test, Oktem verbal memory processes, Rey Complex Figure Test, Wisconsin Card Sorting Test, semantic and phonemic fluency than did healthy controls. In other words, there were deficits in attention, recognition and recall in verbal memory, recall in visual memory, visual spatial construction, and planning skills in patients with Meniere's disease. Education years and depression scores of participants had a significant effect on cognitive function in all groups. This study is an update and confirmation of the findings of studies showing cognitive impairment in patients with Meniere's disease. In addition to previous findings, this study found a decrease in executive function performance in patients with Meniere's disease compared to healthy controls. Unlike previous studies, this study comprehensively addressed all cognitive functions and included a control group. Our results emphasize that executive functions, which are high-level cognitive processes, may affect the compliance of patients with Meniere's disease treatment and follow-up processes.

The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice.

BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.

Modeling the interaction among three cerebellar disorders of eye movements: periodic alternating, gaze-evoked and rebound nystagmus.

A woman, age 44, with a positive anti-YO paraneoplastic cerebellar syndrome and normal imaging developed an ocular motor disorder including periodic alternating nystagmus (PAN), gaze-evoked nystagmus (GEN) and rebound nystagmus (RN). During fixation there was typical PAN but changes in gaze position evoked complex, time-varying oscillations of GEN and RN. To unravel the pathophysiology of this unusual pattern of nystagmus, we developed a mathematical model of normal function of the circuits mediating the vestibular-ocular reflex and gaze-holding including their adaptive mechanisms. Simulations showed that all the findings of our patient could be explained by two, small, isolated changes in cerebellar circuits: reducing the time constant of the gaze-holding integrator, producing GEN and RN, and increasing the gain of the vestibular velocity-storage positive feedback loop, producing PAN. We conclude that the gaze- and time-varying pattern of nystagmus in our patient can be accounted for by superposition of one model that produces typical PAN and another model that produces typical GEN and RN, without requiring a new oscillator in the gaze-holding system or a more complex, nonlinear interaction between the two models. This analysis suggest a strategy for uncovering gaze-evoked and rebound nystagmus in the setting of a time-varying nystagmus such as PAN. Our results are also consistent with current ideas of compartmentalization of cerebellar functions for the control of the vestibular velocity-storage mechanism (nodulus and ventral uvula) and for holding horizontal gaze steady (the flocculus and tonsil).

The effect of directional social cues on saccadic eye movements in Parkinson's disease.

There is growing interest in how social processes and behaviour might be affected in Parkinson's disease. A task which has been widely used to assess how people orient attention in response to social cues is the spatial cueing task. Socially relevant directional cues, such as a picture of someone gazing or pointing to the left or the right have been shown to cause orienting of visual attention in the cued direction. The basal ganglia may play a role in responding to such directional cues, but no studies to date have examined whether similar social cueing effects are seen in people with Parkinson's disease. In this study, patients and healthy controls completed a prosaccade (Experiment 1) and an antisaccade task (Experiment 2) in which the target was preceded by arrow, eye gaze or pointing finger cues. Patients showed increased errors and response times for antisaccades but not prosaccades. Healthy participants made most anticipatory errors on pointing finger cue trials, but Parkinson's patients were equally affected by arrow, eye gaze and pointing cues. It is concluded that Parkinson's patients have a reduced ability to suppress responding to directional cues, but this effect is not specific to social cues.

Adult Spinal Primary Leptomeningeal Medulloblastoma Presenting as Pseudotumour Cerebri Syndrome.

A previously well 34-year-old man presented with severe pseudotumour cerebri. Imaging showed that he had a cauda equina tumour which proved to be a medulloblastoma. There was no tumour mass in the posterior fossa so we assume that this was a primary leptomeningeal medulloblastoma. In patients with somewhat atypical pseudotumour, spinal imaging should always be considered.

Plasma levels of inflammatory mediators in vestibular migraine.

Objectives: Vestibular migraine (VM) is an under-recognized entity with substantial burden for the individual and society. The underlying mechanism of VM and its distinction from other migraine mechanisms still remain unclear. Inflammatory pathways have been suggested to contribute to vestibular migraine. Our aim was to further investigate the possible role of inflammation in the pathophysiology of VM.Methods: We recruited 30 patients with VM diagnosed according to ICHD-3 criteria and 50 gender- and age-matched controls. Blood samples were obtained from 11 VM patients during an attack and from 13 VM patients under prophylactic treatment. Plasma levels of calcitonin gene related peptide (CGRP), neurokinin A (NKA), substance P (SP), NLRP1, NLRP3, caspase-1, IL-1ß, IL-6, TNF-α and NFκB were measured by ELISA.Results: IL-6 levels were significantly reduced in VM patients, whereas levels of other inflammation parameters were comparable to those of healthy controls. Levels of inflammatory mediators were not correlated with clinical parameters. Likewise, there were no significant differences among VM patients with and without headache attack and prophylactic treatment.Conclusion: Our results argue against involvement of systemic inflammation in the pathophysiology of VM.

Search for SCA2 blood RNA biomarkers highlights Ataxin-2 as strong modifier of the mitochondrial factor PINK1 levels.

Ataxin-2 (ATXN2) polyglutamine domain expansions of large size result in an autosomal dominantly inherited multi-system-atrophy of the nervous system named spinocerebellar ataxia type 2 (SCA2), while expansions of intermediate size act as polygenic risk factors for motor neuron disease (ALS and FTLD) and perhaps also for Levodopa-responsive Parkinson's disease (PD). In view of the established role of ATXN2 for RNA processing in periods of cell stress and the expression of ATXN2 in blood cells such as platelets, we investigated whether global deep RNA sequencing of whole blood from SCA2 patients identifies a molecular profile which might serve as diagnostic biomarker. The bioinformatic analysis of SCA2 blood global transcriptomics revealed various significant effects on RNA processing pathways, as well as the pathways of Huntington's disease and PD where mitochondrial dysfunction is crucial. Notably, an induction of PINK1 and PARK7 expression was observed. Conversely, expression of Pink1 was severely decreased upon global transcriptome profiling of Atxn2-knockout mouse cerebellum and liver, in parallel to strong effects on Opa1 and Ghitm, which encode known mitochondrial dynamics regulators. These results were validated by quantitative PCR and immunoblots. Starvation stress of human SH-SY5Y neuroblastoma cells led to a transcriptional phasic induction of ATXN2 in parallel to PINK1, and the knockdown of one enhanced the expression of the other during stress response. These findings suggest that ATXN2 may modify the known PINK1 roles for mitochondrial quality control and autophagy during cell stress. Given that PINK1 is responsible for autosomal recessive juvenile PD, this genetic interaction provides a concept how the degeneration of nigrostriatal dopaminergic neurons and the Parkinson phenotype may be triggered by ATXN2 mutations.

Antisaccade error rates in first-episode psychosis, ultra-high risk for psychosis and unaffected relatives of schizophrenia: A systematic review and meta-analysis.

BACKGROUND: Antisaccade, which is described as looking at the opposite location of the target, is an eye movements paradigm used for assessing cognitive functions in schizophrenia. Initiation and sustainment of saccades in antisaccade are managed by frontal and parietal cortical areas. Antisaccade abnormalities are well-established findings in schizophrenia. However, studies in the early phases of psychotic disorders and clinical/familial risk for psychosis reported inconsistent findings. The current systematic review aimed to review the results of studies investigating antisaccade error rates in first-episode psychosis (FEP), individuals with ultra-high-risk for psychosis (UHRP), and familial-high-risk for psychosis (FHRP) compared to healthy controls. METHOD: A meta-analysis of 17 studies was conducted to quantitatively review antisaccade errors in FEP, UHR-P and FHRP. The error rate (Hedges'g) was compared between the total of 860 FEP, UHRP, FHRP, and 817 healthy controls. Hedges' g for effect size, I2 for estimating the percentage of variability, and publication bias were evaluated through the R software. RESULTS: The outcomes of this meta-analysis suggested that FEP is associated with a robust deficit in the antisaccade error rate (g = 1.16, CI = 0.95-1.38). Additionally, both the clinical and familial high-risk groups showed small but significant increases in AS errors (g = 0.26, CI = 0.02-0.52 and g = 0.34, CI = 0.13-0.55, respectively). CONCLUSION: The large effect size estimated for FEP was compatible with previously reported results in chronic schizophrenia patients. Additionally, relatives had abnormalities with small to medium effect sizes and significant differences. The current findings suggest that antisaccade errors might be a potential endophenotype for psychotic disorders.

One simple question detects motion sickness susceptibility in migraine patients.

OBJECTIVE: To find out if motion sickness susceptibility (MSS) of vestibular migraine (VM) patients and migraine only (MO) patients can be reliably detected with a single simple question: "Can you read while travelling in a car without getting motion sick?". METHOD: Ninety-two definite VM and 58 MO patients and 74 healthy control (HC) subjects were asked about their MSS and about being able to read while riding in a car without becoming motion sick. A Motion Sickness Susceptibility Questionnaire (MSSQ-Short) including childhood (MSA), adulthood (MSB) and total (MST) parts was also administered to all participants. ROC curves of MSSQ-Short were prepared for "not being able to read in a car" as the gold standard. RESULTS: Mean MSA scores were significantly higher in both VM and MO patients than in HCs (p < 0.001), but their scores were not significantly different (p = 0.171). Mean MSB and MST scores were significantly higher in VM than in MO patients (p < 0.001) and both VM and MO patients had significantly higher scores than HCs (p < 0.001). MSA scores were significantly higher than MSB scores in MO patients (p < 0.001). All sections of the questionnaire were associated with high area-under-curve values for MSS detected by the question about being able to read in a car without becoming motion sick. CONCLUSION: We propose that all migraine patients could have the same level of MSS in childhood but MO patients are able to compensate over years, but VM patients are not. A quick way to determine MSS is to ask about the ability to read without becoming motion sickness while riding a car.

Uncorrected errors and correct saccades in the antisaccade task distinguish between early-stage Alzheimer's disease dementia, amnestic mild cognitive impairment, and normal aging.

Alzheimer's disease (AD) dementia is a degenerative illness that is characterized by a gradual decline in cognitive abilities. Amnestic mild cognitive impairment (aMCI) is seen as a precursor to AD. The changes in antisaccade performance that can be seen in MCI may provide important clues in the early detection of AD. Therefore, the antisaccade deficits in AD and aMCI remain a research question. This study aimed to examine antisaccade responses and the relationship between antisaccade and cognitive function in AD, aMCI, and healthy controls (HC). This study included 30 patients with early-stage AD, 34 with aMCI, and 32 HC. Patients with AD showed higher rates of uncorrected error, anticipatory saccades and corrected errors, as well as decreased correct saccade rates, and shortened saccade latency compared to aMCI and HC in this study. Patients with aMCI exhibited increased rates of express saccades relative to HC. The antisaccade task and cognitive domains were found to be significantly related. Our study showed that the rate of correct saccades has the capacity to distinguish AD from HC with 87% sensitivity and 86% specificity (AUC = 0.93, p < 0.001). In addition, the rate of uncorrected errors was found to be capable of distinguishing AD from HC with 84% sensitivity and 83% specificity (AUC = 0.91, p < 0.001). This study presented promising findings that these parameters can be used clinically to differentiate AD and aMCI from healthy older individuals.

Visual search for real-world scenes in patients with Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND: Visual attention-related processes that underlie visual search behavior are impaired in both the early stages of Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), which is considered a risk factor for AD. Although traditional computer-based array tasks have been used to investigate visual search, information on the visual search patterns of AD and MCI patients in real-world environments is limited. AIM: The objective of this study was to evaluate the differences in visual search behaviors among individuals with AD, aMCI, and healthy controls (HCs) in real-world scenes. MATERIALS AND METHODS: A total of 92 participants were enrolled, including 28 with AD, 32 with aMCI, and 32 HCs. During the visual search task, participants were instructed to look at a single target object amid distractors, and their eye movements were recorded. RESULTS: The results indicate that patients with AD made more fixations on distractors and fewer fixations on the target, compared to patients with aMCI and HC groups. Additionally, AD patients had longer fixation durations on distractors and spent less time looking at the target than both patients with aMCI and HCs. DISCUSSION: These findings suggest that visual search behavior is impaired in patients with AD and can be distinguished from aMCI and healthy individuals. For future studies, it is important to longitudinally monitor visual search behavior in the progression from aMCI to AD. CONCLUSION: Our study holds significance in elucidating the interplay between impairments in attention, visual processes, and other underlying cognitive processes, which contribute to the functional decline observed in individuals with AD and aMCI.

Neuro-ophthalmology of invasive fungal sinusitis: 14 consecutive patients and a review of the literature.

BACKGROUND: Invasive fungal sinusitis is a rare condition that usually occurs in immunocompromised patients and often presents as an orbital apex syndrome. It is frequently misdiagnosed on presentation and is almost always lethal without early treatment. DESIGN: Retrospective case series of 14 consecutive patients with biopsy-proven invasive fungal sinusitis from four tertiary hospitals. PARTICIPANTS: Fourteen patients (10 men and 4 women; age range 46-82 years). METHODS: Retrospective chart review of all patients presenting with invasive fungal sinusitis between 1994 and 2010 at each hospital, with a close analysis of the tempo of the disease to identify any potential window of opportunity for treatment. MAIN OUTCOME MEASURES: Demographic data, background medical history (including predisposing factors), symptoms, signs, radiological findings, histopathological findings, treatment approach and subsequent clinical course were recorded and analysed. RESULTS: Only one patient was correctly diagnosed at presentation. Only two patients were not diabetic or immunocompromised. The tempo was acute in two patients, subacute in nine patients and chronic in three patients. In the subacute and chronic cases, there was about 1 week of opportunity for treatment, from the time there was a complete orbital apex syndrome, and still a chance for saving the patient, to the time there was central nervous system invasion, which was invariably fatal. Only two patients survived - both had orbital exenteration, as well as antifungal drug treatment. CONCLUSIONS: Invasive fungal sinusitis can, rarely, occur in healthy individuals and should be suspected as a possible cause of a progressive orbital apex syndrome.

Video head impulse and suppression head impulse test in vestibular migraine.

BACKGROUND: Vestibular Migraine (VM) is a frequent cause of recurrent spontaneous vertigo. While some report a normal Video Head Impulse Test (vHIT) in VM, others observed abnormal results on this test. Whether or not methodological discrepancies could be the cause of these differences is not known. There are 2 vHIT methods: subjects fixating an earth-fixed target (HIMP paradigm) or a head-fixed target, the suppression head impulse test (SHIMP paradigm). OBJECTIVES: The present study aimed to compare VM patients against healthy controls on both HIMP and SHIMP in order to unravel any differences between them. METHODS: Forty-eight VM patients and 27 healthy controls tested with both the HIMP and SHIMP paradigm. Results: Our 48 VM patients showed mean VOR normal range gains in both the HIMP and SHIMP paradigms, although there were some VOR impairments in individual semicircular SCCs. VM patients with motion sickness had lower horizontal VOR gain than those without motion sickness, with the HIMP, but not the SHIMP paradigm. CONCLUSION: VM patients have normal VOR gain with either vHIT paradigm. SIGNIFICANCE: The clinical significance of this observation is that a definitely abnormal vHIT with either method is unlikely to be due to vestibular migraine and an alternative diagnosis should be sought.

Neurological update: neuro-otology 2023.

Much has changed since our last review of recent advances in neuro-otology 7 years ago. Unfortunately there are still not many practising neuro-otologists, so that most patients with vestibular problems need, in the first instance, to be evaluated and treated by neurologists whose special expertise is not neuro-otology. The areas we consider here are mostly those that almost any neurologist should be able to start managing: acute spontaneous vertigo in the Emergency Room-is it vestibular neuritis or posterior circulation stroke; recurrent spontaneous vertigo in the office-is it vestibular migraine or Meniere's disease and the most common vestibular problem of all-benign positional vertigo. Finally we consider the future: long-term vestibular monitoring and the impact of machine learning on vestibular diagnosis.

Saccadic Eye Movements in Patients with Mild Cognitive Impairment: A Longitudinal Study.

Saccadic eye movements are one of the sensitive and noninvasive methods to help monitor the cognitive course of mild cognitive impairment (MCI). The study aimed to evaluate both pro and anti-saccade longitudinally and the relationship between cognitive functions and eye movements in MCI subgroups and healthy controls (HCs) at a two-year follow-up. This study revealed that the anti-saccade anticipatory responses decreased in amnestic MCI (aMCI). Correct vertical pro-saccades increased in non-amnestic MCI (naMCI), while the express saccades decreased. Our study demonstrated that longer than two years of follow-up is necessary to monitor the course of MCI. Findings of the relationships between longitudinal changes of saccades and cognitive measurements demonstrated the usability of eye movements in evaluating the process of MCI.

Examination of eye movements during visual scanning of real-world images in Alzheimer's disease and amnestic mild cognitive impairment.

Available evidence shows that Alzheimer's disease (AD) patients display inefficiencies in visual scanning of their surroundings, directing their attention towards non-relevant aspects of scenes. Not much is known about eye movements during visual scanning in individuals with amnestic mild cognitive impairment (aMCI). Notably, a consensus has yet to be reached on this issue. Furthermore, prior research has indicated the existence of visual attention deficits in individuals diagnosed with AD and aMCI. The objective of this study was to examine the visual scanning patterns of individuals diagnosed with AD, aMCI, and healthy controls (HC) when viewing various scenes. Thirty patients with AD, 32 aMCI, and 32 HC were included in the study. A set of 30 real-life scene images were presented to the participants in the visual scanning task. Participants' eye events were monitored using the EyeLink 1000 Plus in this task. The results indicate a significant reduction in total fixation duration, number of scanned areas, fixation counts, and saccade counts in AD as compared to those with aMCI and HC. The research did not reveal any significant statistical differences in eye parameters between the aMCI and HC groups. This study found abnormalities in visual scanning in AD compared to aMCI and HC. Visual scanning patterns of aMCI patients were not different from HC. Previous studies have specifically shown visual attention difficulties in AD and MCI. Our findings may be related to visual attention difficulties in AD. In addition, this study is the first to examine visual scanning behaviour with real-world images in AD and aMCI.

Eye movement patterns during viewing face images with neutral expressions in patients with early-stage Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND: Alzheimer's disease (AD) neuropathology affects the brain regions responsible for visuospatial skills. Accumulating evidence points to visual difficulties involving face processing in AD and amnestic mild cognitive impairment (aMCI). No study has so far examined eye movement patterns when viewing faces with neutral expressions in patients with AD. AIM: The objective of this study aimed to examine the eye movements of patients with early-stage AD, aMCI, and healthy controls (HC) during viewing face images. MATERIALS&METHODS: Thirty-one AD, 37 aMCI, and 33 HC were included in the study. Eye movements in facial stimuli were recorded with the EyeLink 1000 Plus eye-tracker. RESULTS: Our findings showed that AD patients looked less at the eye area of interest than the nose and mouth areas of interest compared to aMCI and HC. Regardless of the group, all participants looked at the eye and nose areas of interest more and longer in the mouth area of interest. In addition, the first fixation duration to the eye area of interest of all participants was shorter than that of the nose and mouth. DISCUSSION: Consistent with our study, studies in healthy adults revealed eye movement patterns that focused more on the eyes and nose. AD patients are unable to pay attention to the salient parts of faces, tending to focus instead on the non-informative parts. CONCLUSION: Our study is the first to reveal eye movement differences in face processing in AD.