Central Vein Sign: a Diagnostic Biomarker in Multiple Sclerosis

Sponsor:

Brief Summary:

The need for improved diagnostic methods in Multiple Sclerosis (MS) is widely recognized.
Although Magnetic Resonance Imaging (MRI) is a longstanding tool for detecting MS lesions,
diagnostic inaccuracies persist. Up to 20% of people diagnosed with MS (1 in 5) are later
found not to have the disease. This is highly consequential, as more than two-thirds of
misdiagnosed patients are unnecessarily exposed to risks from disease-modifying therapies,
which in rare cases can be life-threatening.

Moreover, the current standard in MS diagnosis – the McDonald criteria, which combine
clinical symptoms and MRI findings – were developed from studies in people with typical
clinical presentations of MS. This reduces the specificity of these criteria, rendering them
uninformative for the nearly half of MS patients who present to neurologists with atypical or
nonclassical symptoms.

Timeliness of MS diagnosis is also key, as diagnostic delay is common in cases of
relapsing-remitting MS and can carry severe and lifelong consequences.

The CentrAl Vein Sign in MS (CAVS-MS) study has been designed to assess whether Central Vein
Sign (CVS) criteria can help address some of these unmet diagnostic needs. It will
specifically explore the role of presentation type by enrolling a mixed population of
patients with typical clinical presentations (n = 200) and those with atypical presentations,
including suggestive MRI findings in the absence of neurologic symptoms (n = 200) across
North America.

Criteria

Inclusion Criteria:

Inclusion criteria for participants with typical presentations will include:

1. Age 18 to 65 inclusive

2. Referral to a study academic site for a clinical suspicion of MS

3. Onset with typical symptom onset including: acute unilateral optic neuritis, double
vision due to an internuclear ophthalmoplegia or sixth nerve palsy, facial sensory
loss or trigeminal neuralgia in a young adult (<40 years of age), cerebellar ataxia and nystagmus, partial myelopathy, sensory symptoms in a CNS pattern, Lhermitte's symptom, asymmetric limb weakness, urge incontinence or erectile dysfunction, or other neurological presentation considered to be typical by the site investigator. 4. Able to provide written informed consent to participate in the study 5. For participants referred for clinical suspicion of multiple sclerosis who had workup prior to referral or who are taking disease-modifying therapies for MS, digital availability of diagnostic cranial MRI with gadolinium within 3 months of initial symptoms 6. Onset of typical neurological symptoms within 10 years of screening. Inclusion criteria for participants with atypical presentations will include: 1. Age 18 to 65 inclusive 2. Referral to a study academic site for a suspicion of MS 3. Onset with atypical onset including: bilateral optic neuritis or unilateral optic neuritis with a poor visual recovery, complete gaze palsy or fluctuating ophthalmoparesis, intractable nausea, vomiting, or hiccups, complete transverse myelopathy with bilateral motor and sensory involvement, encephalopathy, subacute cognitive decline, headache or meningismus, isolated fatigue or asthenia, constitutional symptoms, other clinical presentations considered atypical by the site investigator (examples include: vague or patchy sensory symptoms, pain, short lasting bilateral blurred vision, etc.), or absence of clinical symptoms with MRI features suggestive of MS 4. Able to provide written informed consent to participate in the study 5. For participants referred for clinical suspicion of multiple sclerosis who had workup prior to referral or who are taking disease-modifying therapies for MS, digital availability of diagnostic cranial MRI with gadolinium within 3 months of initial symptoms 6. Onset of atypical neurological symptoms within 10 years of screening. Exclusion Criteria: Exclusion criteria for both typical and atypical populations will include: 1. Contraindication to MRI studies; metal or metal implants incompatible with MRI 2. Inability to tolerate MRI due to claustrophobia or known excessive movement (e.g. tremor) 3. Contraindication to use of gadolinium containing contrast agents (allergy or renal failure) 4. Treatment with systemic corticosteroids in the 4 weeks preceding enrollment.

Locations

Cedars-Sinai Medical Center, Los Angeles, California, United States, 90048
University of Southern California, Los Angeles, California, United States, 90089
University of California San Francisco, San Francisco, California, United States, 94115