Article In Brief
The presentation of spontaneous intracranial hypotension varies, a new meta-analysis of the literature suggests. The findings call for new diagnostic criteria and treatment algorithms that account for the various ways that patients may present and the different settings in which they are treated, experts say.
The presentation of spontaneous intracranial hypotension (SIH) varies more widely than is commonly assumed, including patients without orthostatic headache, abnormal imaging findings, apparent spinal leaks, or abnormal cerebrospinal fluid (CSF) pressure.
That's the finding from a meta-analysis of 144 studies of SIH diagnosis and treatment published online on January 4 in JAMA Neurology.
Experts who reviewed the study for Neurology Today said the findings call for new diagnostic criteria and treatment algorithms that account for the various ways that patients may present and the different settings in which they are treated.
The lead study author, Manjit Matharu, MD, and colleagues at the National Hospital for Neurology and Neurosurgery in London, emphasized that patients suspected of having SIH should receive brain and spinal MRI with contrast. Treatment with an epidural blood patch when conservative treatment fails appears to have the highest rate of a successful outcome, they wrote.
“Our study highlights the variability in the presentation of this disorder, the limitations of the investigations available, and the efficacy of the available treatments,” said Dr. Matharu, who is an associate professor and honorary consultant neurologist.
“SIH is highly disabling, yet often underdiagnosed and undertreated. While the majority have the classical presentation of an orthostatic headache, a small minority either have a non-orthostatic headache or no headache at all. The limitations of standard investigations for SIH are often not fully appreciated by clinicians.”
“The management pathways are currently poorly defined with considerable variation in practice,” Dr. Matharu said. “We hope that our study will be a catalyst towards developing management pathways that are evidence based and thereby improve the care of this highly disabled patient group.”
Study Design, Findings
To conduct the meta-analysis, the researchers did a literature search of PubMed, MEDLINE, and other databases for English language studies on SIH or spontaneous CSF leaks reporting at least 10 patients. They excluded articles reporting intracranial hypotension or CSF leaks secondary to other causes (traumatic or iatrogenic).
They analyzed data from a total of 144 studies reporting on an average of 53 patients (cohort numbers ranged between 10 and 568). Of the 144 studies, none were controlled interventional trials; 90 (62.5 percent) were retrospective, 21 (14.6 percent) were prospective, and the remaining articles 33 (22.9 percent) did not clearly specify the type of data collection.
The researchers applied versions of the International Classification of Headache Disorders (ICHD) diagnostic criteria (to diagnose SIH in 98 articles (68 percent). According to ICHD-III, SIH is diagnosed when headache has developed spontaneously and in temporal relation to a CSF leak evident on imaging and/or CSF hypotension indicated by lumbar puncture opening pressure of less than 60 mm CSF.
While most patients in the studies did present with these symptoms, a substantial number did not. Among the principal findings:
- Headache was the most common symptom, presenting in 98.6 percent of patients, most commonly as orthostatic headache (97.7 percent), but 39 patients presented with non-orthostatic headache and 23 with no headache at all.
- Patients presented with a range of other symptoms, including dementia-like symptoms, disorders of consciousness, and movement disorders. The five most common symptoms other than headache were nausea/vomiting (775), neck pain/stiffness (507), tinnitus (295), dizziness (216), and hearing disturbances (163).
- MRI imaging showed abnormalities indicative of SIH in 71 percent of patients but was normal in 19 percent.
- Nearly a third of patients had normal lumbar opening pressures.
- Spinal neuroimaging identified leaks in only 48-67 percent of patients; moreover,
- when a leak is identified with these techniques, its exact location can often remain unknown.
- Epidural blood patches were the treatment most commonly offered to patients with the first patch reported to be successful in 64 percent of patients.
Three experts who reviewed the report for Neurology Today agreed the findings will not be surprising to clinicians who specialize in the treatment of headache and SIH but may be to many general neurologists. They also concurred that SIH is underdiagnosed or frequently missed altogether, and that the wider variability of the presentation shown in the meta-analysis is not generally understood.
“It's a review of the literature that is already out there, but it's an important undertaking,” said Wouter Schievink, MD, professor of neurosurgery and director of the cerebrospinal fluid leak program at Cedars Sinai Medical Center in Los Angeles. “Now, physicians talking to patients with SIH can give them true figures on how common it is and what its common characteristics are. There are a lot of misconceptions about this condition and hopefully, this study will disseminate information about SIH to a wider audience.”
“The vast majority of patients do present with headaches, at least early in their disease,” Dr. Schievink said. “But as time goes on other symptoms can develop or become overwhelming, in some cases causing coma or dementia.”
“The typical presentation is an acute ‘thunderclap’ headache,” he told Neurology Today. “But the headache can linger for a long time and some patients report a very insidious onset.”
Dr. Schievink noted that as many as one in four patients may have a type of CSF leak—a CSF venous fistula—that was not even known or recognized until he and colleagues reported the finding in 2014 in Neurology. “And there is still a group of patients—as many as 25 percent—for whom there is no apparent leak,” he said.
Deborah Friedman, MD, MPH, FAAN, professor of neurology and ophthalmology at the University of Texas Southwestern Medical Center, agreed that the study provides important confirmation of the wide variation in presentation.
So, too, is the quality of the literature on SIH variable. “Most of the studies are retrospective, few are prospective, and the diagnostic criteria differ across studies,” Dr. Friedman said. “Many of the studies included in the analysis didn't use any criteria at all.”
She added that patients in the studies included in the analysis likely do not represent anything like the true universe of patients with SIH. “There is an inherent bias in which patients get reported and who does the reporting, depending on where the patients present. We all see different types of patients, so the people who come to a neurologist or headache specialist are not the same ones who end up in the emergency department or in neurosurgery or neuroradiology.”
Peter Kranz, MD, division chief of neuroradiology at Duke University, emphasized that the condition is significantly underdiagnosed and a new diagnostic approach is needed. “There is no single test or symptom that absolutely rules in SIH or rules it out,” Dr. Kranz said. “We need to create a rational diagnostic approach that incorporates the many clinical forms the condition can take.”
Dr. Kranz noted that there are a variety of spinal imaging techniques—not all of them available at all centers—and some patients may need more than one test. “We need a more streamlined treatment algorithm to make this diagnosis more accessible across practice types,” he said.
“We can't lapse into diagnostic nihilism, because although any single symptom or test is not perfect, a combination of symptoms tests is much more powerful for diagnosis,” he continued. “The challenge is to craft a diagnostic workup that balances sensitivity, specificity and the availability of imaging technology at different sites.”
Echoing the study findings, Dr. Friedman recommended that all patients with suspected SIH receive an MRI with contrast; spinal imaging will depend on what centers have available.
“Don't do a lumbar puncture because it will likely be normal, may make the patient worse, and it likely won't help you,” she said.
“You really have to be a detective because the manifestations are so variable,” Dr. Friedman said. “What is prominent in one person isn't in another. Diagnosis and treatment is a process and is usually not a quick fix. A lot of patients may leak intermittently, and we won't find it. If there is a clinical suspicion of SIH, you may have to do multiple procedures and you have to be patient.”
Dr D'Antona is supported by a National Institute for Health Research Academic Clinical Fellowship and was the recipient of a research fellowship sponsored by B. Braun. Dr. Friedman serves on the advisory boards of Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Revance Therapeutics, Satsuma Pharmaceuticals,Teva Pharmaceuticals, Theranica, and.Zosano Pharma. Dr. Friedman has received grant support from Eli Lilly and Merck, and Zosano Pharma, and also serves on the medical advisory board of the CSF Leak Foundation and HealthyWomen. Drs. Kranz and Schievink had no disclosures.