ARTICLE IN BRIEF:
Using a large series of cases of spontaneous spinal cord injury, a research team has proposed diagnostic criteria for the rare, disabling form of stroke, based on clinical, laboratory, and MRI clues.
Spontaneous spinal cord infarction (SCI), a rare and disabling condition which usually results from ischemia within the spinal cord or an extravertebral artery, is often misdiagnosed, exposing patients to potentially deleterious treatments.
Sudden loss of strength, particularly in both legs and resulting in paraplegia, are the classic symptoms, one expert told Neurology Today. Patients often experience sudden and severe back pain, followed immediately by rapidly progressive bilateral flaccid limb weakness and loss of temperature sensation. They become so weak that they are unable to walk and may have trouble with bowel and bladder function.
But a new report, published January 1 in JAMA Neurology, aims to improve diagnosis and care of these patients by describing the clinical characteristics of spontaneous SCI and proposing diagnostic criteria for the condition.
The comprehensive review of a large series of patients with spontaneous SCI provides clinical, laboratory, and MRI clues to enhance understanding of the spectrum of its presentation.
Spontaneous SCI diagnosis can be challenging without an instigating event such as a surgical procedure, the team of investigators from Mayo Clinic wrote.
“Onset is more protracted and radiologic distinction from competing diagnoses is more difficult than with cerebral infarction,” the study authors noted in the report. For these reasons, patients with a spontaneous SCI are often misdiagnosed, most commonly with transverse myelitis.
Recent studies suggest that spontaneous SCI is underdiagnosed. The authors cited two large studies published in 2018 in Neurology, for example, that reported that 14-16 percent of patients referred for the evaluation of transverse myelitis ultimately received a diagnosis of spontaneous SCI.
Recognition of SCI's characteristics is the first step toward making advances for a condition accounting for less than 1 percent of strokes, the study's first author, Nicholas L. Zalewski, MD, assistant professor of neurology at Mayo Clinic in Rochester, MN, told Neurology Today.
“It is unclear from the data we have what the optimal way is to treat these patients, which largely comes from not recognizing the diagnosis early,” Dr. Zalewski said, citing the absence of a clear biomarker for identifying SCI. Patients typically develop this severe acute spinal cord disorder within 12 hours or less, and rapid MRI with diffusion-weighted imaging (DWI) is recommended to support the diagnosis and to exclude other treatable acute spinal cord disease.
“If they present with rapid severe spinal cord deficits in this time frame and MRI does not show compression, then a spinal cord infarction is very likely,” he said. “These cases are fairly distinct and do look very different the vast majority of the time” from other conditions affecting the spinal cord.
Interpretation of spinal cord imaging is a complex undertaking at times but is easier to interpret when the clinical suspicion for stroke is high, Dr. Zalewski added. “Stroke findings aren't nearly as distinct” on a spinal cord MRI as on a brain MRI, especially when DWI is not requested or has artifact,” he said. “Rarely is there a diagnostic dilemma when questioning stroke of the brain like there is in the spinal cord.”
Finding effective therapies for spontaneous SCI has been difficult, the study authors noted. Although lumbar drainage and blood pressure augmentation are utilized for SCI in the context of aortic surgery, there is no evidence to promote the use of these approaches in spontaneous SCI.
In prior cases and in two of these patients, intravenous tissue plasminogen activator was not harmful, but there are no data to support its efficacy in SCI. When concern persists for a possible inflammatory myelopathy, a brief course of empirical intravenous methylprednisolone treatment would be a reasonable measure, Dr. Zalewski.
He and his colleagues advised against the administration of plasma exchange, which can decrease cord perfusion, and intravenous immunoglobulin, which is prothrombotic. They recommended intensive rehabilitation, which resulted in many patients attaining a good outcome (47 percent without a gait aid).
Using an institution-based search tool, investigators identified 133 patients, 18 years and older, who had a diagnosis of spontaneous SCI evaluated at Mayo Clinic in Rochester, MN, from January 1, 1997, to December 1, 2017; 280 Controls were chosen from a database of alternative myelopathy etiologies for validation of the proposed diagnostic criteria.
None of the 133 patients with a spontaneous SCI had spinal cord trauma, compression, or a recent procedure within one month. Fifty-three percent (71) of the patients were women and 93 percent (124) were white. The high proportion of white patients likely reflected the predominantly white population of the upper Midwest, affecting the study's generalizability to other racial and ethnic groups, Dr. Zalewski noted.
At presentation, the median age was 60 years; 76 percent (101) had vascular risk factors. Seventy-seven percent (102) had rapid onset of severe deficits reaching nadir within 12 hours; 23 percent (31) had a stuttering decline, and sensory loss occurred in 95 percent (126) of the patients, affecting pain/temperature in 39 percent (49) of them.
Initial MRI spine results were normal in 24 percent (30) of the patients. Sixty-five percent (82) had characteristic MRI T2-hyperintense patterns, such as owl eyes, and 40 percent had pencil-like hyperintensity. Gadolinium enhancement in more than a third was frequently linear and observed in the anterior gray matter. Confirmatory MRI findings included DWI/apparent diffusion coefficient restriction, adjacent dissection/occlusion, and vertebral body infarction.
Cerebrospinal fluid revealed mild inflammation in 8 percent (seven) of 89 patients. Diagnostic criteria were proposed for definite, probable, and possible SCI of periprocedural and spontaneous onset. In the validation cohort, 3 percent (nine patients) met criteria for possible SCI, and none met criteria for probable SCI.
Several neurologists interviewed by Neurology Today welcomed the study's in-depth review of spontaneous spinal cord infarction, which has received limited attention in scientific research and literature.
Despite the study's design as a retrospective analysis, it consists of a thorough evaluation, robust sample size of patients with a rare disorder, and detailed criteria that “help define this population better,” said Shazam Hussain, MD, director of the Cerebrovascular Center at Cleveland Clinic and associate professor of medicine (neurology) at the Cleveland Clinic Lerner College of Medicine.
“It is a very devastating type of stroke when it does happen,” Dr. Hussain said, explaining that the spinal cord does not recover well, and most patients become severely disabled and dependent on a wheelchair. “The problem is the location. The spinal cord is very sensitive to the lack of blood flow.”
Greater awareness of the SCI criteria set forth in the study may lead to a swifter diagnosis for some patients. If the symptoms are caught early enough, it may be possible to reverse a stroke or help prevent further damage, Dr. Hussain said.
Until this study, limited guidance was available to clinicians in the literature on SCI. Investigating such a rare disease is encumbered by the dearth of patients to follow at most institutions, said Fernando D. Goldenberg, MD, associate professor of neurology and surgery (neurosurgery), director of neuroscience critical care, and co-director of the Comprehensive Stroke Center at University of Chicago Medicine.
“This study was possible because Mayo Clinic has maintained a large and organized database with a very impressive number of patients,” Dr. Goldenberg said. “Not every medical center has those capabilities, and therefore, it represents only one institution.”
But, he added, the analysis of 133 patients with spontaneous SCI “makes this study of significant value.”
Dr. Goldenberg added that collecting data from different sources is important to validate the condition, but that is unlikely to occur due to the rarity of SCI.
In the neurointensive care unit at University of Chicago, neurologists encounter only a few SCI cases per year, he said. Around the world, the majority of patients with SCI seek medical attention in smaller hospitals where the intensive care unit is generally overseen by a general intensivist who may come across only a few of these cases throughout an entire career. The newly proposed diagnostic criteria would be useful for these practitioners in making a prompt diagnosis and optimizing treatment, Dr. Goldenberg said.
The clinical grouping of the study's findings is also helpful. It offers insight into certain vascular patterns commonly indicative of spontaneous SCI, but more supplemental tables would have added clarity to the report's presentation, said Jennifer A. Frontera, MD, FNCS, professor of neurology in the division of neurocritical care at NYU Langone Hospital-Brooklyn.
Without a gold standard for imaging SCI, spontaneous cases may elude diagnosis, Dr. Frontera said. As a result, it is not surprising that an estimated 15 percent of patients diagnosed with transverse myelitis actually had SCI, she said.
“Although neurologists tend to be more on alert for potential SCI after cardiothoracic surgery, any time there is rapid onset of severe deficits, it should be on your radar,” she said.
Too often, patients undergo dangerous treatments with immunosuppressants instead of the secondary stroke prevention that they desperately need. The study “suggests a paradigm for evaluating these patients,” Dr. Frontera said.
Drs. Zalewski, Hussain, Frontera, and Goldenberg had no relevant disclosures.
“If they present with rapid severe spinal cord deficits in this time frame and MRI does not show compression, then a spinal cord infarction is very likely.”
—DR. NICHOLAS L. ZALEWSKI