Harnessing the power of eye-tracking science
to elevate clinical practice

Neurological disorders

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Eye movement brain network

The analysis of eye movements has fascinated scientists since 1900s, with tens of thousands of papers analyzing how the central nervous system controls eye movements and how a neurological disease affects their normal behavior.

Scientific research has shown that our eyes are a window to our brain's health with 3% first world population suffers from neurological disorders that can be detected using eye-tracking.

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Biomarkers extracted from the eye movements

Over the last 60 years, over 80 000 scientific articles have been written linking eye movements to neurological diseases

Today, this wealth of scientific knowledge can be used in consultation to help the practitioners quantify their clinical examination.

Use case of eye tracking in neurology

Neurological conditions lack accurate and non-invasive biomarkers which could support
the healthcare practitioners across the full patient pathway:

Motor disorders :

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by the gradual loss of dopamine-producing neurons in the substantia nigra region of the brain. It affects approximately 1-2% of the population over the age of 60, leading to motor symptoms like tremors, rigidity, bradykinesia, and postural instability, primarily disrupting the basal ganglia-thalamocortical circuits.

The gold standard in PD assessment and its pains: The current clinical workup for suspected Parkinson’s disease involves a comprehensive assessment of motor symptoms, medical history, and neurological examination, often utilizing the Unified Parkinson’s Disease Rating Scale (UPDRS) to quantify symptom severity. However, challenges may arise in accurately distinguishing early-stage Parkinson’s from other movement disorders due to overlapping symptoms, leading to potential misdiagnoses, and the subjective nature of UPDRS scoring, which can introduce variability in assessing symptom progression.

The impairment of eye movements in Parkinson’s Disease is primarily related to the disruption of the basal ganglia circuits involved in coordinating and controlling eye movements.

When are eye movements useful along the patient pathway?

In parkinsonian syndromes, eye movements analysis offers a high clinical utility
while being supported by the most scientific evidence.

In diagnosis, In diagnosis, the clinical diagnosis of PD relies on differentiating from atypical parkinsonian syndromes.

An earlier, more accurate diagnosis has been shown to help delay symptoms, improve quality of life, and is estimated to reduce costs for society [link]Tinelli, Michela & Kanavos, Panos & Grimaccia, Federico. The value of early diagnosis and treatment in Parkison’s disease. London School Of Economics (LES). 2016

Put in place specific rehabilitation program and anti-fall detectors.

In care,

Assess disease progression and therapeutic efficacy objectively.

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How can neuroClues help?

Our ambition is to engage in clinical trials demonstrating a high accuracy with neuroClues in early differential diagnosis of Parkinsonian Syndromes.

It is already being used on a wide cohort of PD patients within the Iceberg cohort

neuroClues does not yet have the regulatory approvals for its use on patients.

Are you willing to engage in a joint research on that topic?

Progressive supra nuclear palsy (PSP) is an extrapyramidal syndrome in which the patient often experiences imbalance, falls and dysarthria. Its oculomotor manifestations are impaired saccades speed and gain (first vertically).

The gold standard in PSP assessment and its pains: Assessing Progressive Supranuclear Palsy (PSP) typically involves a combination of clinical evaluation, medical history analysis, and neuroimaging techniques such as MRI or PET scans. Clinical features such as supranuclear gaze palsy, postural instability, and early falls are key diagnostic criteria. However, the definitive diagnosis of PSP can only be confirmed through post-mortem brain examination. The main challenges in PSP assessment include the similarity of its symptoms to other neurodegenerative disorders like Parkinson’s disease, making accurate diagnosis challenging in early stages. Additionally, the lack of specific biomarkers and the limited effectiveness of available treatments contribute to the difficulty in managing the condition effectively.

The impairment of eye movements in Progressive supra nuclear palsy results from the degeneration of brainstem and frontal cortex areas responsible for controlling eye movement due to the accumulation of abnormal tau protein aggregates.

When are eye movements useful along the patient pathway?

In parkinsonian syndromes, eye movements analysis offers a high clinical utility
while being supported by the most scientific evidence.

In diagnosis, ocular motor dysfunction is the primary official criteria to identify PSP [link]Höglinger GU et al. Movement Disorder Society-endorsed PSP Study Group. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017 Jun , ranging from vertical supranuclear gaze palsy (level 1), slow velocity of saccades (level 2) to frequent macro square wave jerks (level 3). As the guidance mentions, inadequate ocular motor examinations may partly explain the low sensitivity early in the disease course.
Early diagnosis spares patients unnecessary workups and treatment and allows patients and their families to plan logistically and psychologically [link]Lawrence I. Golbe. Early diagnosis of progressive supranuclear palsy. Neurology Nov 2008
In care, eye movements are being considered as outcome measures within the PSP rating scale to assess disease progression and clinical efficacy in therapeutic clinical trials (examples in [link]RT001 in Patients With Progressive Supranuclear Palsy (PSP) PROGRESSIVE SUPRANUCLEAR PALSY and [link]A Phase 2a Study of TPN-101 in Patients With Progressive Supranuclear Palsy (PSP) )
With 10 ongoing clinical trials focused on finding a cure for PSP, there is a need for quantified measurements.

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neuroClues does not yet have the regulatory approvals for its use on patients.

Are you willing to engage in a joint research on that topic?

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder that affects the central and autonomic nervous systems. Another atypical parkinsonian syndrome, it presents with symptoms such as movement difficulties, along with problems with balance, coordination, and autonomic functions. The disease progresses rapidly over several years, leading to increased disability and often requiring walking aids. Additional symptoms include muscle stiffness, abnormal posture, speech problems, sleep disorders, and emotional changes.

The gold standard assessment in MSA and its pains: Assessing Multiple System Atrophy (MSA) involves a combination of clinical evaluation, neuroimaging techniques such as MRI, and autonomic function testing. Clinical features including autonomic dysfunction, parkinsonism, and cerebellar ataxia aid in diagnosis. However, definitive confirmation typically requires post-mortem brain examination to identify specific pathological markers. Like for PSP, challenges in MSA assessment include its similarity to other neurodegenerative disorders, leading to misdiagnosis, and the lack of effective disease-modifying treatments. Autonomic dysfunction and motor symptoms often lead to decreased quality of life for patients.

The impairment of eye movements in Multiple system atrophy is primarily due to the degeneration of brainstem structures involved in controlling eye movement, resulting from the accumulation of alpha-synuclein protein aggregates

When are eye movements useful along the patient pathway?

In parkinsonian syndromes, eye movements analysis offers a high clinical utility
while being supported by the most scientific evidence.

In diagnosis, oculomotor dysfunction is one of the core clinical features of MSA [link]Wenning GK et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022 Jun and expected variations of oculomotor biomarkers can help differentiate MSA from other parkinsonian syndromes [link]Leigh RJ Zee DS. The Neurology of Eye Movements. 5th ed. Oxford: Oxford University Press; 2015 .

Identifying MSA patients earlier has the potential to accelerate clinical research by improving patient selection, and prevent unnecessary medical testing or surgical (urological) procedures. [link]McKay JH, Cheshire WP. First symptoms in multiple system atrophy. Clin Auton Res. 2018 Apr

In care, there is a drastic need to better identify MSA patients in clinical trials, with a current misdiagnosis rate of 20%. [link]Litvan I et al. What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study. Arch Neurol. 1997 Aug

We’ve detailed these further in a previous newsletter.
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neuroClues does not yet have the regulatory approvals for its use on patients.

Are you willing to engage in a joint research on that topic?

Cerebellar Ataxia is a neurological disorder characterized by a lack of coordination and balance due to damage or degeneration of the cerebellum, a part of the brain responsible for motor control. It impacts the central nervous system by disrupting the precise timing and coordination of movements, leading to difficulties with walking, speech, and fine motor skills.

The gold standard in Cerebellar Ataxia and its pains: Assessing cerebellar ataxia involves a thorough clinical evaluation, neurological examination, and neuroimaging (such as MRI) to identify cerebellar abnormalities. Genetic testing can also help determine specific underlying causes when applicable. challenges in cerebellar ataxia assessment include diagnosing specific subtypes due to diverse etiologies, limited disease-modifying treatments, and the impact of ataxia on motor coordination and daily life activities.

The impairment of eye movements in Cerebellar Ataxia is primarily due to dysfunction or damage to the cerebellum, which disrupts the coordination and precision of muscle movements involved in controlling eye positioning and tracking.

When are eye movements useful along the patient pathway?

In diagnosis, eye movements help differentiate accross spinocerebellar ataxias [link]Anderson TJ, MacAskill MR. Eye movements in patients with neurodegenerative disorders. Nat Rev Neurol. 2013 Feb
Identifying the specific type of cerebellar ataxia is important for accurate diagnosis, targeted treatment, genetic counseling, and for the appropriate clinical trial selection of candidates.

We’ve detailed these further in a previous newsletter.
Don’t want to miss out for the next ones?

neuroClues does not yet have the regulatory approvals for its use on patients.

Are you willing to engage in a joint research on that topic?

Cognitive disorders :

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that affects memory, cognitive function, and behavior. It is characterized by the accumulation of abnormal protein deposits in the brain, leading to the gradual decline of a person’s ability to think, remember, and carry out daily activities. An estimated 50 million people worldwide live with dementia, 60% of which suffer of its most prominent form: Alzheimer’s Disease.

The gold standard in AD and its pains: Assessing Alzheimer’s disease (AD) involves a comprehensive evaluation of medical history, cognitive testing, neuropsychological assessments, and neuroimaging (such as MRI or PET scans) to track brain changes and rule out other conditions. Definitive confirmation typically requires post-mortem examination of brain tissue for the presence of amyloid plaques and tau tangles. Challenges in AD assessment include early diagnosis due to subtle symptoms in the early stages, limited disease-modifying treatments, and the emotional and economic burden on caregivers and families.

The impairment of eye movements in Alzheimer’s Disease, is often attributed to the degeneration of brain areas involved in eye movement control, particularly the frontal and parietal lobes. This leads to deficits in smooth pursuit, saccadic movements, and visual attention, which are commonly observed in individuals with AD.

When are eye movements useful along the patient pathway?

In diagnosis, eye movements can help identify the dementia syndrome. There have been scientific evidence of oculomotor exams useful to distinguishing AD from PCA [link]Pin G, Trompette C, Ceccaldi M, Felician O, Koric L. Interest of eye movement study in early diagnosis of posterior cortical atrophy: A case-report. Rev Neurol (Paris). 2023 Mar , from bvFTD and svPPA[link]Lage C. et al. Distinctive Oculomotor Behaviors in Alzheimer’s Disease and Frontotemporal Dementia. Front Aging Neurosci. 2021 Feb, and more generally, to differentiate across various dementia syndromes Fronto-Temporal Dementia (FTD), Parkinson’s Disease Dementia (PDD), Dementia with Lewy Bodies (DLB). [link]Leigh RJ Zee DS. The Neurology of Eye Movements. 5th ed. Oxford: Oxford University Press; 2015
In care, eye movements are being used as outcome measure in a Phase 1 clinical trial on tauopathies [link]Davunetide (AL-108) in Predicted Tauopathies – Pilot Study
As treatments are getting discovered and approved, it becomes essential to administer these at the appropriate stage of the disease, with a quantified evaluation of the disease progression.

We’ve detailed these further in a previous newsletter.
Don’t want to miss out for the next ones?

neuroClues does not yet have the regulatory approvals for its use on patients.

Are you willing to engage in a joint research on that topic?

Neuro-inflammatory disorders :

Multiple Sclerosis (MS) is a chronic neurological condition characterized by the immune system mistakenly attacking the protective covering of nerve fibers in the central nervous system, leading to communication disruptions between the brain and the rest of the body. This can result in various symptoms, such as fatigue, difficulty with coordination and balance, and problems with vision and cognition.

The gold standard in MS assessment and its pains: Assessing MS involves a combination of clinical evaluation, neurological examination, MRI scans to visualize lesions in the central nervous system, and other tests to rule out other possible causes. MS diagnosis relies on the demonstration of lesions disseminated in time and space. challenges in MS assessment include the variability of symptoms and disease progression, leading to difficulty in early diagnosis, and the limitations of available treatments, particularly for progressive forms of the disease. Symptoms range from fatigue and mobility issues to cognitive impairments.

The impairment of eye movements Multiple Sclerosis, often seen as nystagmus or difficulty moving the eyes smoothly, is primarily due to demyelination and inflammation of the nerve fibers that control eye movement within the central nervous system. This disrupts the normal signaling and coordination of eye muscles.

When are eye movements useful along the patient pathway?

As oculomotor symptoms can be subtle but debilitating, their treatment can improve the patients’ quality of life. Remyelinating therapies offer the perspectives for the patients to reduce disability in the later phases of the disease.

Don’t want to miss out information about MS ?

neuroClues does not yet have the regulatory approvals for its use on patients.

Are you willing to engage in a joint research on that topic?

Are you willing to engage in a joint research on one of these topics?

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