Vertical Gaze Research Articles

Isolated Vertical Gaze Palsy due to Unilateral Rostral Midbrain Stroke.

Isolated Vertical Gaze Palsy due to Unilateral Rostral Midbrain Stroke.

The overestimation of gaze for horizontal, vertical, and diagonal fixation points.

A widely known result from gaze-perception research is the overestimation effect where gaze endpoints are seen farther to the side than they actually are. While horizontal gaze directions have been studied repeatedly, there is scarce research on other directions after early reports that vertical gaze is perceived accurately. It is argued that if participants base their judgment on the movements of the iris-pupil-complex in relation to eye size, vertical gaze should be overestimated similarly as horizontal gaze. This is what was found in the reported experiment. However, horizontal gaze was actually overestimated more than diagonal and vertical gaze. The small difference in overestimation between the axes may be explained by the horizontal-vertical illusion, entailing that horizontal extensions are seen as shorter than vertical extensions.

Conjugate Vertical Gaze Palsy Related to Unilateral Midbrain Infarction

Conjugate upward and downward gaze palsy related to unilateral midbrain infarction is a rare neurological symptom, as there were few reported cases worldwide. Here, we report a case of 55-year-old male patient presenting with conjugate vertical gaze palsy. In this case, diffusion-weighted magnetic resonance images demonstrated a localized infarction in the right rostral midbrain.

An Indirect Pathway from the Rat Interstitial Nucleus of Cajal to the Vestibulocerebellum Involved in Vertical Gaze Holding.

The neural network, including the interstitial nucleus of Cajal (INC), functions as an oculomotor neural integrator involved in the control of vertical gaze holding. Impairment of the vestibulocerebellum (VC), including the flocculus (FL), has been shown to affect vertical gaze holding, indicating that the INC cooperates with the VC in controlling this function. However, a network between the INC and VC has not been identified. In this study, we aimed to obtain anatomical evidence of a neural pathway from the INC to the VC (the INC-VC pathway) in rats. Injection of dextran-conjugated Alexa Fluor 488 or adeno-associated virus 2-retro (AAV2retro) expressing GFP into the FL or another VC region (uvula/nodulus) did not reveal any retrogradely labeled neurons in the INC, suggesting that INC neurons do not project directly to the VC. Rabies virus-based transsynaptic tracing experiments revealed that the INC-VC pathway is mediated via synaptic connections with the prepositus hypoglossi nucleus (PHN) and medial vestibular nucleus (MVN). The INC neurons in the INC-VC pathway were mainly localized bilaterally within the rostral region of the INC. Transsynaptic tracing experiments involving the INC-FL pathway revealed that INC neurons connected to the FL via the bilateral PHN and MVN. These results indicate that the INC-VC pathway is not a direct pathway but is mediated via the PHN and MVN. These findings can provide clues for understanding the network mechanisms responsible for vertical gaze holding.

Beyond Vertical: Unraveling The PSP Enigma

Progressive Supranuclear Palsy (PSP) is an aberrant type of Parkinsonian disorder that cognates with progressive axial rigidity, vertical gaze palsy, dysarthria and dysphagia. It is supposed to affect movement, gait, balance, speech, swallowing, vision, movements, mood, behavior and cognition. PSP increases as per age and its prevalence is 7% per 1 lakh, as reported. PSP is often misdiagnosed with Parkinson’s disease, however, PSP progresses more rapidly than Parkinson’s. people with PSP develop unique eye movement problems with looking up and down, speech and swallowing problems are much more common and severe in PSP than PD, leaning backwards and extend their neck in PSP (axial rigidity) while in PD -bending happens in forward direction than backward. Tremors are rare for PSP but very common in PD. The three most important primary motor symptoms are: tremors, bradykinesia, and rigidity (parkinsonism). Since this disease is termed as tauopathy, 4R-tau isoforms aggregate into straight filaments and appear as a major tau doublet (tau64 & 69). The differential diagnosis is very difficult for PSP because many neurodegenerative disorders have similar symptoms and very less discrimination between PSP and other disorders. The main objective of our study is to create awareness about PSP and its overlapping symptoms with PD as well as other and other neuro-degenerative disorders. However, based upon detailed investigations about, tau and its isoforms, these clinical features may be distinguished. However, it would require abundant knowledge of the molecular functioning and structure of tau proteins. Keywords: tauopathy, parkinsonism, progressive axial rigidity, neuro-degenerative disorders

Dopaminergic neurodegeneration in Gerstmann-Sträussler-Scheinker (P102L) disease: insights from imaging and pathological examination.

Gerstmann-Sträussler-Scheinker (GSS) disease is an inherited prion disease characterized by dementia, cerebellar ataxia, and painful sensory disturbances. GSS is pathologically defined by the presence of amyloid plaques comprised of prion protein predominantly localized in the cerebral cortex, cerebellar cortex, and basal ganglia, resulting from mutations in the prion protein gene. This study investigated five cases of GSS P102L [GSS caused by a leucine (L) substitution of proline (P) at position 102 of the prion protein gene] with L-dopa-resistant extrapyramidal symptoms and reduced dopamine transporter single-photon emission computed tomography (DAT-SPECT) uptake. Clinical findings revealed diverse manifestations, with all cases exhibiting parkinsonism, and four patients had a vertical gaze palsy. Notably, all patients showed reduced striatal DAT-SPECT uptake, indicating neurodegeneration of the nigrostriatal system. Autopsy findings in one case confirmed prion protein plaques and dopaminergic neuron loss in the substantia nigra of a patient with GSS P102L. Additionally, reduced DAT immunostaining was observed in the putamen compared with a control. While previous studies have identified reduced DAT-SPECT and positron emission tomography uptake in Creutzfeldt-Jakob disease and fatal familial insomnia owing to nigrostriatal neurodegeneration induced by abnormal prion protein deposition, similar phenomena in GSS P102L have not been reported. This study provides support for a correlation between abnormal prion protein deposition and nigrostriatal system degeneration in GSS P102L. Our results reveal the importance of considering GSS P102L in cases of atypical Parkinsonism and abnormal DAT-SPECT results, which would serve as a valuable indicator for subsequent prion genetic testing.

Collective vulnerability between the researcher and the researched: a reflection on researcher positionality and ‘safety’ in the study of Islamophobia in economic Muslim migrants

ABSTRACT This paper reflects on collective vulnerability shared between the researcher and the researched, specifically in relation to studying the impact of Islamophobia in South Asian Muslim women in Britain. I reflect on my PhD study, and explore the tensions within the research space vis-à-vis researcher positionality. Puwar’s ‘Space Invaders’ is employed to explore the possibilities of disrupting power within research. This paper, therefore, reflects on the role of ‘collective vulnerability’ as a key to creating and maintaining a ‘safe’/ ‘counterspace’ to dislodge the trappings of employing a vertical gaze on data.

Alzheimer's Disease-Related Cerebrospinal Fluid Biomarkers in Progressive Supranuclear Palsy.

Progressive Supranuclear Palsy (PSP) is the most common four-repeat tauopathy. PSP cases are typically characterized by vertical gaze palsy and postural instability; however, various phenotypes have been reported, making antemortem diagnosis based on clinical symptoms challenging. The development of biomarkers reflecting brain pathology and the ability to diagnose patients based on these biomarkers are essential for developing future intervention strategies, including disease-modifying therapies. However, despite many dedicated efforts, no highly specific fluid biomarker for PSP has yet been established. Conversely, several cerebrospinal fluid (CSF) biomarkers of Alzheimer's Disease (AD) have been established, and an AT(N) classification system has been proposed. Typically, among patients with AD, CSF amyloid β42 (Aβ42), but not Aβ40, is decreased, resulting in a reduction in the Aβ42/Aβ40 ratio, while tau phosphorylated at threonine 181 (p-tau181) and total tau (t-tau) are increased. Interestingly, the core CSF AD biomarkers show unique patterns in patients with PSP. Furthermore, reports have indicated that the CSF levels of both Aβ42 and Aβ40 are decreased independently of Aβ accumulation in PSP. Therefore, the Aβ42/Aβ40 ratio could potentially be used to differentiate PSP from AD. Additionally, studies have reported that CSF p-tau and t-tau are reduced in PSP, and that the neurofilament light chain is remarkably increased compared to healthy controls and patients with AD, even though PSP is a neurodegenerative disease associated with tau accumulation. These PSP-specific changes in AD-related core biomarkers may reflect the pathology of PSP and contribute to its diagnosis. As such, elucidating the mechanisms underlying the observed decreases in Aβ and tau levels could facilitate a better understanding of the pathogenesis of PSP.

Dopa-responsive Rest Tremor Preceding Tachyphemia in Progressive Supranuclear Palsy: A Case Report.

Progressive supranuclear palsy (PSP) is characterized by progressive postural instability, falls, and supranuclear vertical gaze abnormalities. In this report, we present the case of a 71-year-old woman with dopa-responsive rest tremor followed by tachyphemia and postural instability. She initially presented with dopa-responsive slowness and tremor in the right hand. Two years later, she developed speech difficulties (tachyphemia) and a propensity for falls. Based on the diagnostic criteria for PSP, the patient was diagnosed with probable PSP-RS. The clinical manifestations observed in our patient are unique and are considered important for illustrating a broad spectrum of PSP syndrome.

Clinical and genetic analysis of Niemann-Pick disease type C with a novel NPC1 variant

BackgroundNiemann-Pick disease type C poses a significant challenge within the landscape of rare genetic disorders, marked by its connection to variants in the NPC1 or NPC2 genes. This autosomal recessive lipid storage disorder unfolds with a relentless progression of neurological deterioration and a distinctive hallmark of hepatosplenomegaly.Case presentationThis case report delves into the intricate presentation of a 9-year-old Iraqi boy exhibiting heightened walking instability and speech slurring. His medical history unfolds a series of challenges, including neonatal hyperbilirubinemia, hepatosplenomegaly, and recurrent nasal bleeding. A comprehensive physical examination reveals motor and neurological abnormalities such as an inability to squat and rise, vertical gaze palsy, and dysdiadochokinesia. Further investigations, encompassing laboratory tests and imaging studies, coupled with the identification of foamy cells in bone marrow smears, raise significant concerns about Niemann-Pick disease type C. By utilizing whole exome sequencing, we pinpointed a previously unreported homozygous variant—c.2925_2928delCTGC; p.Cys976PhefsTer6—found within exon 20 (NM_000271.5) of the proband’s NPC1 gene.ConclusionsThis study significantly advances our understanding of the c.2925_2928del (C976Ffs*6) variant in the NPC1 gene, shedding light on the complexities of Niemann-Pick disease type C. Beyond its scientific significance, the findings provide crucial insights for familial genetic counseling and prenatal diagnoses. This research expands our knowledge of the variant’s genetic landscape, making it a valuable resource in both academic and clinical settings, particularly for families dealing with Niemann-Pick disease type C.

Patterns of brain volume and metabolism predict clinical features in the progressive supranuclear palsy spectrum.

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that presents with highly heterogenous clinical syndromes. We perform cross-sectional data-driven discovery of independent patterns of brain atrophy and hypometabolism across the entire PSP spectrum. We then use these patterns to predict specific clinical features and to assess their relationship to phenotypic heterogeneity. We included 111 patients with PSP (60 with Richardson syndrome and 51 with cortical and subcortical variant subtypes). Ninety-one were used as the training set and 20 as a test set. The presence and severity of granular clinical variables such as postural instability, parkinsonism, apraxia and supranuclear gaze palsy were noted. Domains of akinesia, ocular motor impairment, postural instability and cognitive dysfunction as defined by the Movement Disorders Society criteria for PSP were also recorded. Non-negative matrix factorization was used on cross-sectional MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) scans. Independent models for each as well as a combined model for MRI and FDG-PET were developed and used to predict the granular clinical variables. Both MRI and FDG-PET were better at predicting presence of a symptom than severity, suggesting identification of disease state may be more robust than disease stage. FDG-PET predicted predominantly cortical abnormalities better than MRI such as ideomotor apraxia, apraxia of speech and frontal dysexecutive syndrome. MRI demonstrated prediction of cortical and more so sub-cortical abnormalities, such as parkinsonism. Distinct neuroanatomical foci were predictive in MRI- and FDG-PET-based models. For example, vertical gaze palsy was predicted by midbrain atrophy on MRI, but frontal eye field hypometabolism on FDG-PET. Findings also differed by scale or instrument used. For example, prediction of ocular motor abnormalities using the PSP Saccadic Impairment Scale was stronger than with the Movement Disorders Society Diagnostic criteria for PSP oculomotor impairment designation. Combination of MRI and FDG-PET demonstrated enhanced detection of parkinsonism and frontal syndrome presence and apraxia, cognitive impairment and bradykinesia severity. Both MRI and FDG-PET patterns were able to predict some measures in the test set; however, prediction of global cognition measured by Montreal Cognitive Assessment was the strongest. MRI predictions generalized more robustly to the test set. PSP leads to neurodegeneration in motor, cognitive and ocular motor networks at cortical and subcortical foci, leading to diverse yet overlapping clinical syndromes. To advance understanding of phenotypic heterogeneity in PSP, it is essential to consider data-driven approaches to clinical neuroimaging analyses.

Artery of Percheron infarct – An ophthalmologist’s perspective

Thalamus is an important relay station in diencephalon which receives its blood supply mostly from the posterior cerebral artery. The Artery of Percheron (AOP) arises from the posterior cerebral artery and bifurcates to supply paramedian thalami. AOP infarction, though rare, presents with a triad of clinical features including altered mental status, memory impairment, and supranuclear vertical gaze palsy. Our patient had concurrent manifestation of vertical gaze palsy (both upward and downward) and third cranial nerve palsy in the left eye, which is an interesting clinical amalgamation. Our case report elucidates the quick recognition of the abnormalities in ocular motility through a simple, yet effective nine gaze ocular motility evaluation and thereby enhancing clinical recognition of this entity among the practicing general Ophthalmologists.

Progressive supranuclear palsy: Neuropathology, clinical presentation, diagnostic challenges, management, and emerging therapies

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by the accumulation of 4R-tau protein aggregates in various brain regions. PSP leads to neuronal loss, gliosis, and tau-positive inclusions, such as neurofibrillary tangles, tufted astrocytes, and coiled bodies. These pathological changes mainly affect the brainstem and the basal ganglia, resulting in distinctive MRI features, such as the hummingbird and morning glory signs. PSP shows clinical heterogeneity and presents as different phenotypes, the most classical of which is Richardson's syndrome (PSP-RS). The region of involvement and the mode of atrophy spread can further distinguish subtypes of PSP. PSP patients can experience various signs and symptoms, such as postural instability, supranuclear ophthalmoplegia, low amplitude fast finger tapping, and irregular sleep patterns. The most common symptoms of PSP are postural instability, falls, vertical gaze palsy, bradykinesia, and cognitive impairment. These features often overlap with those of Parkinson's disease (PD) and other Parkinsonian syndromes, making the diagnosis challenging. PSP is an essential clinical topic to research because it is a devastating and incurable disease. However, there are still many gaps in knowledge about its pathophysiology, diagnosis, and treatment. Several clinical trials are underway to test noveltherapies that target tau in various ways, such as modulating its post-translational modifications, stabilizing its interaction with microtubules, or enhancing its clearance by immunotherapy. These approaches may offer new hope for slowing down the progression of PSP. In this review, we aim to provide an overview of the current knowledge on PSP, from its pathogenesis to its management. We also discuss the latest advances and future directions in PSP research.

Noradrenergic current responses of neurons in rat oculomotor neural integrators.

The prepositus hypoglossi nucleus (PHN) and the interstitial nucleus of Cajal (INC) are involved in the control of horizontal and vertical gaze, respectively. A previous study showed that PHN neurons exhibit depolarized or hyperpolarized responses to noradrenaline (NA). However, the adrenoceptor types that participate in NA-induced responses and the effects of NA on INC neurons have not yet been investigated. Furthermore, the relationship between NA-induced responses and neuron types defined by neurotransmitter phenotypes has not been determined. In this study, we investigated NA-induced current responses in PHN and INC neurons and the relationships between these responses and neuron types using whole cell recordings in wild-type and transgenic rat brainstem slices. Local application of NA to the cell soma induced slow inward (SI) and slow outward (SO) currents that were mainly mediated by α1 and α2 adrenoceptors, respectively. These current responses were observed in both PHN and INC neurons, although the proportion of INC neurons that responded to NA was low. Analyses of the distributions of the current responses revealed that in the PHN, all fluorescently identified inhibitory neurons exhibited SI currents, whereas glutamatergic and cholinergic neurons exhibited both SI and SO currents. In the INC, glutamatergic and inhibitory neurons preferentially exhibited SI and SO currents, respectively. When the PHN and INC neurons were characterized by their firing pattern, we found that the proportions of the currents depended on their firing pattern. These results suggest that various modes of noradrenergic modulation in horizontal and vertical neural integrators are dependent on neuron type.NEW & NOTEWORTHY Noradrenergic modulation of oculomotor neural integrators involved in gaze control has not been elucidated. Here, we report that noradrenaline (NA)-induced slow inward (SI) and outward (SO) currents are mediated mainly by α1 and α2 adrenoceptors in neurons that participate in horizontal and vertical gaze control. The NA-induced current responses differed depending on the neurotransmitter phenotype and firing pattern. These results suggest various modes of noradrenergic modulation in horizontal and vertical integrator neurons.

Comparing classic-onset corticobasal syndrome to speech/language-onset corticobasal syndrome

IntroductionPatients with classic-onset corticobasal syndrome (CBS) present with asymmetric limb apraxia and parkinsonism. We have, however, observed patients who initially present with speech and/or language (SL) problems and several years later develop CBS (i.e., SL-onset CBS). We aimed to compare clinical, neuroimaging and pathological characteristics of classic-onset CBS with SL-onset CBS. MethodsWe conducted a retrospective cohort study of 62 patients who met criteria for CBS (17 presented with classic-onset CBS and 45 had SL-onset CBS). We compared demographics, clinical characteristics, and grey and white matter volume loss with SPM12 between groups and assessed pathology and corticobasal degeneration (CBD) pathological lesion counts in patients who had died and undergone autopsy. ResultsMedian age at CBS diagnosis was 66.4 years in classic-onset CBS and 73.6 years in SL-onset CBS. Classic-onset CBS had higher frequencies of dystonia, myoclonus, and alien limb phenomenon, while SL-onset CBS had a higher frequency of vertical supranuclear gaze palsy. Both groups showed smaller frontoparietal volumes than controls, with SL-onset CBS having greater volume loss in the left supplementary motor area than classic-onset CBS. All three classic-onset CBS cases with autopsy (100 %) had CBD pathology while 8/21 of SL-onset CBS cases (38 %) had CBD. Pathological lesion burden (including astrocytic plaques) did not differ between classic-onset and SL-onset CBS. ConclusionClassic-onset and SL-onset CBS appear to be different syndromes, with the former being a more profuse motor syndrome. The more widespread volume loss in SL-onset CBS likely reflects longer disease course.

Vertical Gaze Paralysis with Collier’s Sign and Contralesional Pseudo-abducens Paresis from Unilateral Dorsomedial Thalamic Stroke (P8-5.020)

Vertical Gaze Paralysis with Collier’s Sign and Contralesional Pseudo-abducens Paresis from Unilateral Dorsomedial Thalamic Stroke (P8-5.020)

Loss of Mickey Mouse Ears' Sign in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is the most prevalent form of degenerative atypical parkinsonism. Clinical manifestations of PSP commonly encompass deficits in vertical gaze, postural stability, akinesia, and cognitive impairment. The characteristic metabolic pattern observed in PSP through FDG PET displays hypometabolism in the midbrain, striatum, thalamus, and frontal lobe. However, visual interpretation of midbrain hypometabolism poses challenges. In this report, we aim to elucidate a novel observation termed the "loss of Mickey Mouse ears' sign," which signifies midbrain hypometabolism as detected through visual assessment of FDG PET images.

Artery Of Percheron Infarction: A Great Mimicker

The thalamus is a deep structure located in the diencephalon, whose arterial blood supply is mainly from four branches of posterior cerebral artery. The artery of percheron (AOP) is an infrequent variation of thalamic perfusion, occlusion of which presents with a heterogenous, atypical list of symptoms without focal signs. This is in contrast to the typical, easily recognizable focal neurology of other ischemic infarcts. Therefore, AOP infarctions may be misdiagnosed, delayed in diagnosis or missed altogether. It is a rare, but vital area of neurology that needs to be studied by clinicians to facilitate an overall care for patients.We report the case of a 59-year-old lady who presented to us with bilateral complete ptosis with bilateral vertical gaze palsy and nystagmus, whose initial NCCT brain was normal. Subsequent MRI showed bilateral thalamic and midbrain ischemic infarctions in the artery of Percheron distribution. Our case highlights the importance of high degree of suspicion, early diagnosis and role of MRI in the diagnosis when initial CT is normal.

Detecting Abnormal Eye Movements in Patients with Neurodegenerative Diseases - Current Insights.

This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD), Parkinson's Disease (PD), atypical parkinsonism, and others, leveraging advancements in eye-tracking technology for enhanced diagnostic precision. We delve into the different classes of eye movements, their clinical assessment, and specific abnormalities manifesting in these diseases, highlighting the nuanced differences and shared patterns. For instance, AD and ADRD are characterized by increased saccadic latencies and instability in fixation, while PD features saccadic hypometria and mild smooth pursuit impairments. Atypical parkinsonism, notably Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), presents with distinct ocular motor signatures such as vertical supranuclear gaze palsy and saccadic apraxia, respectively. Our review underscores the diagnostic value of eye movement analysis in differentiating between these disorders and also posits the existence of underlying common pathological mechanisms. We discuss how eye movements have potential as biomarkers for neurodegenerative diseases but also some of the existing limitations.

Chiari I Malformation Presenting Vertical Gaze-Evoked Nystagmus : A Case Report

Abstract
 Introduction : Chiari malformation is characterized by herniation of posterior cerebellar vermis in which type 1 malformation has coexisting syringomyelia of cervicothoracic spinal cord. This malformation can be congenital or acquired, in which gaze-evoked nystagmus is the typical movement deficit. This case aimed to report a case of vertical gaze-evoked nystagmus as a primary symptom to detect Type I Chiari Malformation.
 Case Illustration : A 44-year-old woman presented with involuntary movements of both eyes in the last 5 months with vision problems in which objects appear to jump or vibrate. Visual acuity was 20/50 in both eyes with 12 prism diopters BI exotropia. We recognized vertical and torsional nystagmus in upgaze without any movement in primary gaze. While performing supraduction, the oscillation was detected and increased. Brain MRI revealed Type I Chiari Malformation.
 Discussion : Nystagmus was seen in many diseases of the central nervous system, in particular those affecting the brainstem and cerebellum. Vertical gaze evoked nystagmus was a disorder of the gaze holding function, purely vertical gaze-evoked nystagmus is observed in midbrain lesions involving the interstitial nucleus of Cajal (INC) as the neural integrator for vertical gaze-holding function. Based on this pathophysiology, the Brain MRI of this patient revealed some degrees of compression in midbrain, and cervico medullary junction due to her brain malformation.
 Conclusion : A sustained gaze-evoked nystagmus is an important ocular finding that may indicate serious neurologic pathology. It is important for an eye care provider to thoroughly examine additional tests to determine the underlying cause of the nystagmus.