Nonspecific symptoms common in NMOSD before first disease attack
New study findings support idea of prodrome prior to overt disease signs
In the five years before their first disease attack, people with neuromyelitis optica spectrum disorder (NMOSD) required significantly more doctor’s office visits and hospitalizations than their peers in the general population, a new study from Canada found.
The researchers believe these findings point to the presence of an NMOSD prodrome, a period of often nonspecific symptoms that precede the first overt clinical manifestations of a disease.
“Prodromal phases are well recognized in many inflammatory and neurodegenerative diseases. … Our findings support a prodromal phase preceding clinical onset of … NMOSD,” the scientists wrote.
If these results are confirmed in further studies, they could potentially lead to new ways of managing the disease, according to the team.
“Our results raise the possibility, if validated, of underlying biologic onset of NMOSD years before the first typical … attack and suggest that NMOSD could be identified, monitored, and treated in some cases before a disabling attack occurs,” the researchers wrote.
The study, “Investigation of health care use and a possible prodrome before the first attack in NMOSD and MOGAD,” was published in the Multiple Sclerosis Journal.
Looking for a potential prodrome in NMOSD
NMOSD, myelin oligodendrocyte glycoprotein antibody disease, called MOGAD, and multiple sclerosis, or MS, are a group of related but distinct neurodegenerative conditions characterized by inflammatory attacks on the central nervous system (CNS), comprised of the brain and spinal cord.
As these abnormal attacks result in damage and loss of myelin, the protective sheath around nerve fibers, all three conditions are considered demyelinating disorders.
It has become increasingly recognized that a number of neurodegenerative diseases have a prodrome that arises in the years before diagnosis and which may signal the future onset of disease.
In MS, analyses of healthcare data show that patients use more healthcare services in the 5-10 years before their diagnosis or first disease attack, indicative of a prodrome. However, the possible existence of a prodrome in NMOSD and MOGAD has not been as well explored.
But in NMOSD, antibodies against the aquaporin-4 (AQP4) protein — the most common type of NMOSD-causing antibodies — can be detected years before the first disease attack. Moreover, individual case studies have reported symptoms emerging before the clinical onset of the disease.
Now, the team of scientists from institutions across Canada looked for further evidence of a possible NMOSD or MOGAD prodrome. To that end, they examined administrative healthcare data from a large Canadian province.
Disease activity manifesting as nonspecific symptoms may occur in NMOSD
The analysis involved records from 96 NMOSD patients with anti-AQP4 antibodies, each of whom was matched in terms of age, sex, and other factors to five people in the general population who had no demyelinating disease. Overall there were a total of 479 such controls.
In the five years before their first disease attack, the number of outpatient visits and hospitalizations was higher for NMOSD patients than their matched controls over the same timeframe.
NMOSD patients were found to be 47% more likely to need an outpatient visit and 67% more likely to be hospitalized during that period.
The higher likelihood of outpatient visits relative to the control group notably increased in the two years just prior to the first disease attack, from 1.37 times two years before to 2.24 in the last year, a twofold rise.
The relative difference in hospitalization rates were more variable year-to-year, but spiked in the year just before disease onset, reflecting a nearly three times higher likelihood in the NMOSD group relative to the general population.
It is possible that subclinical NMOSD disease activity in the CNS [central nervous system], or CNS disease activity manifesting with milder, non-specific symptoms, may be present before the first typical attack.
The team found no similar trends when comparing data from MOGAD patients and matched controls.
Overall, the researchers believe the findings are indicative of an NMOSD prodrome.
“It is possible that subclinical NMOSD disease activity in the CNS, or CNS disease activity manifesting with milder, non-specific symptoms, may be present before the first typical attack,” the researchers wrote.
More studies to look at disease biomarkers during this prodromal phase “may allow us in the future to pinpoint when CNS damage begins in prodromal NMOSD, monitor patients, and flag those in need of treatment,” the team added.
Second study looked more closely at patients’ early symptoms
A few days after their study was published, the researchers published another study in the same journal, titled “Is there a prodrome to NMOSD? An investigation of neurologic symptoms preceding the first NMOSD attack.” In that work, they more closely examined the specific prodromal neurological symptoms experienced by NMOSD patients.
The team reviewed medical records from 116 NMOSD patients seen at four Canadian demyelinating disease centers, 17 of whom (14.7%) experienced prodromal neurological symptoms at least a month before their first disease attack.
Similar to interim study data presented at a scientific meeting, these results showed that the most common symptoms experienced by patients were numbness or tingling, affecting nine individuals, nerve-related pain affecting five, and visual disturbances experienced by four.
Other disease symptoms included muscle spasms, an electric shock-like sensation down the neck and back, severe headache, a lack of coordination, weakness, psychosis, and seizure.
More than two-thirds (70.6%) underwent MRI scans at the time of prodromal symptoms, and in three of the five patients showing abnormal findings, lesions were believed to potentially explain their symptoms.
A total of 12 patients (70.6%) had complete symptom resolution before the first NMOSD attack, which occurred a median of 14 months, or a little more than a year, after prodromal symptoms.
Although many of these symptoms are nonspecific, most are consistent with NMOSD, and the researchers believe they could be relevant for flagging the presence of the condition early on, and perhaps distinguishing it from MS.
“Further systematic investigation is needed to better understand the relationship between prodromal symptoms, imaging and fluid biomarkers, and the development of NMOSD,” the team concluded.
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