"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.
According to conventional wisdom, white women who live far from the equator and have possible or confirmed histories of vitamin D deficiency and/or prior infection with Epstein-Barr virus are the most likely candidates for a diagnosis of multiple sclerosis (MS), the chronic autoimmune demyelinating condition affecting the central nervous system.
This clinical shorthand is both convenient and well established, but a recent study suggests it may also encourage clinicians to overlook patients with MS who don't fit the paradigm. In 2023, Mitchell T. Wallin, MD, MPH, of the University of Maryland School of Medicine in Baltimore, and colleagues published a in JAMA Neurology that used health insurance claims data to calculate MS prevalence in the U.S. based on race/ethnicity, stratified by age, sex and region.
The researchers found a higher prevalence of MS in northern regions of the U.S. compared with southern regions and a higher prevalence of MS in white people, followed by Black people, "other races," and people with Hispanic/Latinx ethnicity. Out of approximately 750,000 cases of MS, 76% occurred in women.
However, the estimated prevalence of approximately 3 cases per 1,000 people in Black Americans compared with about 4 cases per 1,000 people in white Americans led the , which funded the study, to emphasize that MS can affect anyone, regardless of race or locale.
"In the United States, MS affects diverse racial and ethnic groups," Wallin and colleagues concluded. "Prevalence of MS increases significantly and nonuniformly with latitude in the United States, even when adjusted for race, ethnicity, age, and sex. These findings are important for clinicians, researchers, and policy makers."
Given that MS is the in young adults in many countries, including the U.S., providing an accurate, early diagnosis is essential in helping patients obtain the best possible outcomes.
Data from the , however, reveal that a variety of obstacles exist globally that interfere with prompt diagnosis. "Diagnostic delays persist in MS care and even within national health care systems with robust resources, comprehensive registries, and MS subspecialist referral networks," wrote Andrew J. Solomon, MD, of the University of Vermont in Burlington, and colleagues.
With responses from 107 countries that represent 82% of the global population, the Atlas of MS identifies "lack of awareness of MS symptoms among health care professionals" as the second most frequently reported barrier to diagnosis at 59%, second only to "lack of awareness of MS symptoms among the general public" at 68%. The Atlas also identifies "lack of availability of health care professionals with knowledge to diagnose MS" as a concern among 44% of respondents.
Prompt Diagnosis is Key
can vary widely based on the severity and locations of lesions within the central nervous system (CNS), so clinicians should be familiar with the full array.
In a in the American Journal of Medicine, Stephen Hauser, MD, and Bruce Cree, MD, PhD, both of the University of California San Francisco Weill Institute for Neurosciences, noted that MS is characterized by two pathological hallmarks: inflammation with demyelination, and astroglial proliferation (gliosis) and neurodegeneration. Tissue damage in MS is restricted to the CNS, sparing the peripheral nervous system.
Among the noteworthy :
- Visual: optic neuritis, blurred vision, pain with eye movements, loss of vision in one eye, poor contrast or color vision
- Motor: muscle weakness, spasticity, gait problems, hyperreflexia
- Sensory: numbness, paresthesia, dysesthesia, trigeminal neuralgia, Lhermitte's sign, allodynia
- Cerebellar: tremor, ataxia, loss of coordination
- Genitourinary: urgency/frequency/retention, incontinence, frequent urinary tract infections, constipation, sexual dysfunction
- Neuropsychiatric: depression, anxiety, irritability, "brain fog"
- Other common symptoms are vertigo, heat sensitivity, and unusual fatigue
Differential Diagnosis
With such a range of symptoms, developing an appropriate differential diagnosis is especially important in diagnosing MS quickly and accurately. The National MS Society has a " to aid clinicians in preparing a differential diagnosis:
- Autoimmune or inflammatory conditions: neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, myelin oligodendrocyte glycoprotein (MOG) antibody disease, Sjogren's syndrome, CNS lupus, sarcoidosis, Behcet's disease, CNS vasculitis
- CNS infections: neurosyphilis, Lyme disease, HIV
- Metabolic: vitamin B12 deficiency, mitochondrial disease, leukodystrophies
- Vascular: stroke, small vessel disease, Susac syndrome, antiphospholipid antibody syndrome
Similarly, for other diagnoses can speed the time to correct diagnosis. For example, a normal MRI and normal neurological exam exclude a diagnosis of MS.
Other red flags that can help steer away from a differential diagnosis of MS are the following:
- Bilateral vision loss
- Seizures
- Abrupt onset of symptoms
- Peripheral neuropathy
- Early dementia
- Cortical deficits such as aphasia and apraxia
- Onset before age 10 or after age 50
Understanding the 'McDonald Criteria'
Since 2017, the has guided clinicians in correctly diagnosing MS. Compared with previous editions, the current McDonald criteria to be more sensitive but less specific for a second attack of demyelinating CNS symptoms.
In MS, the McDonald criteria specify that the disease process must be disseminated in space and time, meaning that more than one CNS location must be affected. Additionally, the effects must change or evolve over time.
MRI and cerebrospinal fluid (CSF) following lumbar puncture are the main tests needed to make an MS diagnosis in conjunction with clinical symptoms.
To meet the dissemination in space points of the McDonald criteria, there must be:
- Objective clinical evidence of at least two lesions or objective clinical evidence of one lesion with reasonable historical evidence of a prior attack involving a different CNS site
- At least one T2 lesion in at least two of four MS-typical regions of the CNS: periventricular, (juxta)cortical, infratentorial, spinal cord
To meet the dissemination in time criteria, there must be:
- At least two attacks separated by a period of at least 1 month
- Simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time
- A new T2 and/or gadolinium-enhancing lesion on follow-up MRI, irrespective of its timing with reference to a baseline scan
- Demonstration of CSF-specific oligoclonal bands (as a substitute for demonstration of dissemination in time)
Diagnostic Considerations
In their discussion of diagnostic pathways in MS, Hauser and Cree noted that recent lesions enhance with gadolinium on MRI. "Lesions in juxtacortical (adjacent to the cerebral cortex) white matter, infratentorial white matter, and within the spinal cord are also suggestive of MS and contribute to 'dissemination in space,'" they wrote. "Although MS plaques can involve subcortical white matter, lesions in this location are considered non-diagnostic because other pathologies are associated with similar lesions."
The authors noted that lumbar puncture is especially important when there is a suspicion of primary progressive MS. "Oligoclonal bands reflect the products of a highly focused immune response by activated B cells in the CNS," Hauser and Cree said. "The abnormal intrathecal synthesis of gamma globulins, measured by an elevated IgG [immunoglobulin G] index or two or more discrete oligoclonal bands not present in a paired serum sample, is present in >90% of MS patients."
Additionally, the use of evoked potentials can detect conduction delay in visual, auditory, or sensory pathways and so may be an effective diagnostic adjunct to MRI and lumbar puncture.
A Look at Clinically Isolated Syndrome
Clinicians should be familiar with (CIS), a single episode of CNS inflammatory demyelinating symptoms that suggest MS. Most often seen in young adults, CIS is usually self-limiting and typically starts with an acute or subacute onset and peaks within 2 to 3 weeks in extreme cases.
Writing in the Archives of Neuropsychiatry, Hüsnü Efendi, MD, of Kocaeli University in Turkey, noted that CIS presentations can be monofocal or multifocal and typically involve the optic nerve, brainstem, cerebellum, spinal cord, or cerebral hemispheres. The diagnostic criteria for CIS include a duration of . There must be no fever or infection, including no clinical features of encephalopathy.
Patients with CIS face the greatest risk of developing MS -- 60% to 80% -- when their MRI shows brain lesions typical of those seen in MS. If no brain lesions are seen on MRI, the patient's risk of developing MS is much lower -- around 20%.