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Patients with acute stroke were more likely than those with other conditions to have antibodies in their cerebrospinal fluid, researchers found.
Of patients who received a lumbar puncture, nearly a quarter (24.8%) of those with acute stroke had intrathecal antibodies, compared with just 2.5% of patients with other conditions (P<0.001), according to Harald Prüss, MD, of the Charité University of Medicine Berlin, and colleagues.
"The strong association between cerebrospinal fluid-specific immunoglobulin synthesis and stroke suggests a role in the development of cerebral ischemia and might constitute an immunologically defined stroke subgroup," the researchers wrote online in Archives of Neurology.
The finding "demands a systematic prospective analysis of cerebrospinal fluid and serum samples to determine the time kinetics and pathogenicity of antibodies," they wrote.
Immune mechanisms have been considered to explain some ischemic strokes, but the role of intrathecal antibodies remains unclear because diagnostic tests are not routinely performed on cerebrospinal fluid in patients after cerebral ischemia.
In the current study, Prüss and colleagues examined data from 3,050 consecutive patients with ischemic stroke who were hospitalized at their center from 2005 to 2009.
Only 318 (10.4%) underwent a lumbar puncture within 96 hours after symptom onset. Indications included seizures, suspected central nervous system infection or vasculitis, pronounced agitation or disorientation, suspected leptomeningeal carcinomatosis, mitochondriopathy, vasculopathy, or diagnostic uncertainty.
The researchers matched those 318 patients with 79 control patients who did not have a stroke but received a lumbar puncture during a diagnostic workup for headache, diabetic oculomotor or abducens nerve palsy, idiopathic facial nerve palsy, or dizziness.
The patients with stroke were more likely to have cerebrospinal fluid-specific immunoglobulin synthesis than the controls, as measured by the presence of oligoclonal immunoglobulin bands.
The high, nearly 25% prevalence of antibodies in the cerebrospinal fluid of patients with stroke "may point to a direct association between cerebrospinal fluid-specific immunoglobulin synthesis and focal cerebral ischemia," the authors wrote.
Among the patients with stroke, one-third had blood-brain barrier dysfunction and 18.1% had pleocytosis, with no differences in the rates based on the presence or absence of the antibodies.
There were also no differences in the frequency of oligoclonal bands, pleocytosis, increased protein in the fluid, age, and sex based on whether the patients had had a prior stroke.
Of the patients with stroke who did not have intrathecal antibodies after the first lumbar puncture, 12 underwent a second puncture. Half had antibodies after the second puncture, which suggests that "the percentage of patients with oligoclonal band-positive stroke might increase further with longer follow-up," according to Prüss and colleagues.
They noted that stroke-associated intrathecal immunoglobulin synthesis could result from one of three options:
- Unidentified inflammatory disease
- Undetected previous ischemic degeneration of neuronal tissue with repeated presentation of central nervous system antigen to the immune system
- Polyclonal nonspecific B-cell activation secondary to brain damage
"The second explanation might be relevant to the high proportion of patients with oligoclonal bands already present at the time of their first clinically detected stroke," the authors wrote. "The finding of oligoclonal bands in patients with transient ischemic attacks supports this notion and implies relevance for predisease stages."
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