Multiple sclerosis (MS) is the most common immune-mediated demyelinating disease of the central nervous system (CNS). It is also characterized by inflammation and axonal degeneration in the CNS and is vastly heterogeneous in its presentation.1 Diagnosis of MS has improved over time; however, there is still room for improvement: the mean time from first medical visit to diagnosis is nearly 15 months and the mean time from onset of symptoms to diagnosis is approximately 18 months.2
Benefits of Early Treatment
Early treatment of MS is associated with decreased disease progression. Prospective trials have demonstrated that patients who do not meet diagnostic criteria for MS are at high risk for developing a clinical relapse or new brain lesion and eventually meeting that criteria.
The practice guidelines for adults with multiple sclerosis recommend treatment as early as the first clinical sign of MS because the use of disease modifying drugs (DMDs) significantly delays progression.
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In patients who have already been diagnosed, DMDs slow disease progression and delay future disability and economic burden.2,3
Barriers to Treatment Initiation
Understanding and Awareness
Classically, symptoms of MS are described as disseminated in space and time and possibly having a relapsing and remitting course. In my career as an academic physician, I’ve noticed that the former is a description that students and young physicians have trouble understanding. Indeed, even students of an advanced field such as medicine at first have difficulty suspecting MS based on initial presentation.
Clinically and in simple terms, disseminated in space means that patients experience symptoms based on what region of the central nervous system is involved. Disseminated in time means that symptoms come and go.
Evidently, in practice, the identification of MS symptoms can be challenging. The sheer number of possible sites involved and the fact that some symptoms generally improve at first means not all patients will seek medical attention. Conversely, some primary care physicians may have a low index of suspicion for MS. This is the first barrier to early diagnosis.
The “Time Matters in MS” initiative by MS Research Australia recognizes that campaigns to raise awareness about MS amongst the public and primary care physicians (PCPs) are urgently needed.4 More initiatives that raise awareness of the disease and education of PCPs and medical educators in all settings, including medical university instructors and attending physicians at teaching hospitals, may facilitate earlier detection.
Sociocultural and Socioeconomic Factors
Risk factors for later diagnosis include low education levels, living in a rural area, low access to health care, primary progressive MS, age of onset, and first clinical symptoms (for example, optic neuritis as a presenting sign is more likely to be evaluated for MS than an isolated paresthesia).2
Males make up the patient demographic least likely to seek medical attention for any condition, including the presenting symptoms of MS.5,6 Some authors argue that the gender associations of MS make it more likely to be diagnosed in women and less likely to be suspected when identical signs and symptoms are presenting in males.6
I recall the case of a patient that exemplifies many of these barriers. A church group in my country urged me to see a young man who was not interested in seeking medical attention for painful vision loss in his right eye. He consulted online after being pressured to see me for what I suspect may have been optic neuritis. I struggled to communicate, fighting poor connectivity and the low-resolution camera on his mobile. The young man seemed completely indifferent and seemingly only sought medical attention online because he was not interested in going to a hospital. The patient even endorsed a history of limb weakness “a while back.” This was concerning and MS was in the top 3 on the list of differential diagnoses. I informed the patient that his symptoms merit further investigation, but he was ultimately lost to follow-up, leaving me wondering every month or so how he is doing.
This is not an isolated event. In fact, one study in Egypt reports that pressure from family members and headlines in the media was the most common source of referral to a neurologist.7 The authors also underlined that when the initial presentation involves sensory findings, diagnosis is more likely to be delayed.
Comorbidities
The longest time to diagnosis of MS disproportionately affects 1 group of patients: those with comorbidities upon presentation. The average time to MS diagnosis is 4 years in patients who have 2 or more comorbidities. If those comorbidities are cardiac, pulmonary, cerebrovascular, diabetes, or cancer, diagnostic delay is amplified to ≥10 years. This may be attributed to physicians’ willingness to write off neurological symptoms as consequences of preexisting conditions.8
What Can Be Done?
Updated diagnostic criteria have facilitated early diagnosis and treatment for MS. Also, medical imaging techniques and advanced ancillary studies have allowed us to greatly improve our diagnostic certainty. Time to diagnosis, however, remains unsatisfactory in many situations.
The underutilization of healthcare services by men has been a challenge that many institutions face. In colleges, males are more likely to commit suicide and it’s postulated that underutilization of available mental health resources explains this.9 We observe similar behavior in MS, where the lower help-seeking behavior of men contributes to longer times to diagnosis. Improving this parameter requires generating awareness and education campaigns to normalize getting help. Complex, evidence-based models have been developed that aim to improve the utilization of mental health services by males and may inspire similar interventions to improve male help-seeking behavior across all domains of medicine.9
It is not ideal that in some circumstances the media represents one of the main reasons for referral to a neurologist. However, it does highlight the power of education and awareness campaigns. Equally, PCPs may benefit from targeted educational content which may increase their overall index of suspicion for MS and increase referrals of suspected MS patients to neurology.
One study reported that one-quarter of patients visited their PCP more than 4 times before being referred to a neurologist. Common misdiagnoses included “trapped nerve,” stroke, depression, anxiety, or stress.10 We PCPs need to better our understanding of MS and lower our threshold for referral to a neurologist if MS is suspected. This, and improving access to health care, are significant first steps towards bridging the diagnostic gap for MS.
References
1. Gloss D, Moxley RT, Ashwal S, Oskoui M. Practice guideline update summary: corticosteroid treatment of Duchenne muscular dystrophy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;86(5):465-472. doi:10.1212/WNL.0000000000002337
2. Ghiasian M, Faryadras M, Mansour M, Khanlarzadeh E, Mazaheri S. Assessment of delayed diagnosis and treatment in multiple sclerosis patients during 1990–2016. Acta Neurol Belg. 2021;121(1):199-204. doi:10.1007/s13760-020-01528-7
3. Cerqueira JJ, Compston DAS, Geraldes R, et al. Time matters in multiple sclerosis: can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis? J Neurol Neurosurg Psychiatry. 2018;89(8):844-850. doi:10.1136/jnnp-2017-317509
4. The importance of early treatment in MS. MS Research Australia. Accessed August 1, 2021.
5. Yousaf O, Grunfeld EA, Hunter MS. A systematic review of the factors associated with delays in medical and psychological help-seeking among men. Health Psychol Rev. 2015;9(2):264-276. doi:10.1080/17437199.2013.840954
6. Eccles A. Delayed diagnosis of multiple sclerosis in males: may account for and dispel common understandings of different MS ‘types’. Br J Gen Pract. 2019;69(680):148-149. doi:10.3399/bjgp19X701729
7. Tohamy AA, Swelam MS, Abdelgawad DM, Aref HA. Causes of delayed diagnosis of multiple sclerosis in Egypt. QJM Int J Med. 2020;113(Supplement_1). doi:10.1093/qjmed/hcaa054.011
8. Comorbidities delay multiple sclerosis diagnosis and increase mortality. October 6, 2017. Accessed August 1, 2021.
9. Sagar-Ouriaghli I, Godfrey E, Graham S, Brown JSL. Improving mental health help-seeking behaviours for male students: a framework for developing a complex intervention. Int J Environ Res Public Health. 2020;17(14):4965. doi:10.3390/ijerph17144965
10. MS mistaken for other conditions, survey reveals. NHS Networks. Published May 28, 2015. Accessed September 23, 2021.
