ARTICLE IN BRIEF
ALL NON-ESSENTIAL STAFF were withdrawn from the US embassy in Havana after reports of neurological symptoms among employees.
The US diplomats in Havana who reported headaches and dizziness among other symptoms had cognitive, vestibular, and oculomotor effects that were objective in nature, a new study reported. But independent experts questioned whether the symptoms were indicative of functional disorders.
What began as a political dispute over mysterious neurological symptoms reported by two dozen US diplomats stationed in Cuba has turned into a scientific dispute between neurologists and others seeking to understand the symptoms' cause.
Now, a study of 21 of the employees, published online in the Journal of the American Medical Association on February 15, concluded that the individuals “appeared to have sustained injury to widespread brain networks without an associated history of head trauma.”
The paper asserts that the cognitive, vestibular, and oculomotor effects the researchers measured are objective in nature, comparing them to the effects seen following concussion — even though the subjects had experienced no head injury.
Those findings, which the authors described as preliminary, were based on a multidisciplinary evaluation of the subjects at the Center for Brain Injury and Repair at the University of Pennsylvania's Perelman School of Medicine.
But an accompanying editorial emphasized that a psychogenic (functional) explanation for the symptoms cannot be excluded, a view supported by neurologists and others who spoke with Neurology Today.
Some of those interviewed said that the symptoms most likely represent the sort of functional disorder routinely seen by neurologists who treat post-concussive syndrome, persistent postural-perceptual dizziness (PPPD), or other ailments in which objective findings are equivocal.
What no one disputes is that, beginning in late 2016 and continuing until August 2017, a total of 24 US diplomatic personnel stationed in Havana, Cuba, experienced audible or sensory phenomena emanating from a distinct direction. When they moved, the sensation disappeared or lessened. Some described pressure-like or vibratory stimuli akin to air “baffling” inside a moving car when a single window is partially rolled down. The stimuli lasted for as little as 20 seconds to as long as 30 minutes.
The diplomats experienced the stimuli in their homes or hotel rooms, although family members and other hotel guests remained unaffected. Immediately or in the days and weeks after, the subjects reported an array of neurological impairments, including disorders of balance, sleep, vision, hearing or cognition. Headaches were also frequently reported.
In October, Secretary of State Rex W. Tillerson said that the diplomatic personnel had been the victims of “health attacks,” but that it was unclear who was to blame. In response, the Trump administration expelled a number of Cuban diplomats from their embassy in Washington, DC, and withdrew all nonessential personnel from the US embassy in Havana.
DR. DOUGLAS H. SMITH: “Other than hearing loss in a few cases, we do not believe that the sounds themselves caused most of the symptoms, since sound in the audible range does not injure the brain. Rather, the sounds may have been a coincidental side effect of another type of exposure.”
The US State Department selected the University of Pennsylvania group to coordinate clinical evaluations, treatment, and rehabilitation of the 24 subjects, out of 80 embassy personnel, who reported signs and symptoms consistent with mild traumatic brain injury.
STUDY DETAILS
After obtaining and reviewing medical records of 21 personnel who consented to the study, the researchers conducted clinical tests of vestibular (dynamic and static balance, vestibulo-ocular reflex testing, caloric testing), oculomotor (measurement of convergence, saccadic, and smooth pursuit eye movements), cognitive (comprehensive neuropsychological battery), and audiometric (pure tone and speech audiometry) functioning. Conventional magnetic resonance imaging (MRI) of the head was also obtained, with and without gadolinium contrast.
The multidisciplinary evaluations were performed an average of 203 days after personnel reported their exposures. Symptoms persisting longer than three months after exposure included cognitive (n = 17, 81 percent), balance (n = 15, 71 percent), visual (n = 18, 86 percent), and auditory (n = 15, 68 percent) dysfunction, sleep impairment (n = 18, 86 percent), and headaches (n = 16, 76 percent).
The paper deemed as “objective” findings that included cognitive (n = 16, 76 percent), vestibular (n = 17, 81percent), and oculomotor abnormalities (n = 15, 71 percent). They also identified moderate to severe sensorineural hearing loss in three individuals.
Medication was prescribed for persistent sleep dysfunction (n = 15, 71 percent) and headache (n = 12, 57 percent). At the time of the evaluation, 14 of the individuals (67 percent) were held from work, but seven of those subsequently returned to work with restrictions in place, home exercise programs, and higher-level work-focused cognitive rehabilitation.
Although the symptoms and their cause were described as objective in nature, the paper made clear that the sounds or vibrations experienced by the diplomats may have been an epiphenomenon of the true underlying cause. The researchers did not find evidence that perhaps a virus or chemical agent had been involved. Indeed, speaking against these possibilities, in some cases, symptoms from the exposures would disappear if the individual moved behind a barrier or into another room,
“Other than hearing loss in a few cases, we do not believe that the sounds themselves caused most of the symptoms, since sound in the audible range does not injure the brain,” said the senior author of the paper, Douglas H. Smith, MD, professor of neurosurgery and director of the university's Center for Brain Injury and Repair. “Rather, the sounds may have been a coincidental side effect of another type of exposure. For example, a machine could have caused both the sound and the neurological damage.”
DR. YURI AGRAWAL: “It is pretty compelling that these individuals had symptoms consistent with central nervous system damage. There is biological plausibility for sound or sudden changes in air pressure, such as those caused by blasts, leading to changes in peripheral and central nerve function.”
In an interview with Neurology Today, Dr. Smith defended his group's judgment against a functional cause of the symptoms they observed.
“Our multidisciplinary team uniformly felt we were seeing symptoms very similar to those following concussion but remarkably without a history of head impact,” he said. “Several of these individuals had no contact with others, but still had the same constellation of symptoms. Mass hysteria is not a well-defined syndrome, but what is known is that it wouldn't last for months and months.”
Furthermore, Dr. Smith said, “Some of the balance and visual tests performed, and some of the symptoms detected, cannot be faked. A deficit is not something you can practice. But regardless of these arguments, I know that some skepticism will remain until we show more tangible evidence. Therefore, we plan to use advanced neuroimaging analyses to evaluate potential damage to the brain network in this unique cohort, as is seen in persisting concussion. Stay tuned.”
A FUNCTIONAL CAUSE?
The lack of a control group, baseline evaluations, and blinding by clinical examiners complicate the interpretation of the paper, according to the accompanying editorial by Christopher C. Muth, MD, assistant professor in the department of neurological sciences at Rush University Medical Center and associate editor of JAMA, and by Steven L. Lewis, MD, FAAN, chief of neurology at the Lehigh Valley Health Network in Allentown, PA.
At least some of the abnormalities reported in the paper, they wrote, “were based on patient self-reports or involved at least some degree of subjective interpretation by the clinician performing the examination.”
Rather than compare the subjects' symptoms to concussion, the editorial said that the constellation of symptoms may be more akin to those seen in persistent PPPD, “a syndrome characterized primarily by chronic symptoms of dizziness and perceived unsteadiness, often triggered by acute or chronic vestibular disease, neurological or medical illness, or psychological distress.”
Terry Fife, MD, FAAN, director of the Balance Disorders and Vestibular Neurology Program at Barrow Neurological Institute at Dignity Health St. Joseph's Hospital and Medical Center in Phoenix, said he agreed that the symptoms described have substantial overlap with the symptoms reported with PPPD.
DR. TERRY FIFE agreed that the symptoms described have substantial overlap with the symptoms reported with persistent postural-perceptual dizziness.
“That doesn't mean that people who have dizziness or these other symptoms where you cannot find a specific cause are making it up,” Dr. Fife said. “They're severely disabled by it. But it can respond to medication, usually either tricyclic or SNRI [selective serotonin-norepinephrine reuptake inhibitor] antidepressants.”
Regarded as a chronic, functional disorder of the vestibular system, PPPD nevertheless typically begins after a person experiences some kind of minor, usually self-limiting physical injury.
“Patients who develop PPPD, by definition, have a vestibular or other physiological trigger,” said Jon Stone, PhD, a consultant neurologist and neuroscientist at the Center for Clinical Brain Sciences at the University of Edinburgh in the United Kingdom. “Normally there's an episode of acute migraine or dizziness, but then instead of recovering and getting well, the person gets stuck with the same symptoms persisting over time.”
Criticizing the paper for having what he called an “outmoded” understanding of functional disorders, Dr. Stone pointed out that symptoms routinely persist for months, and that patients are often eager to return to work. He compared PPPD to another condition, “acoustic shock,” an ailment previously described in some telephone operators who had been startled by an unexpected loud noise.
POTENTIAL CAUSAL MECHANISM
Yuri Agrawal, MD, associate professor in the division of otology, neurotology, and skull base surgery at Johns Hopkins Medicine, agreed that it is “hard to entirely discount” the possibility of the symptoms being functional.
But, she emphasized, “It is pretty compelling that these individuals had symptoms consistent with central nervous system (CNS) damage. There is biological plausibility for sound or sudden changes in air pressure, such as those caused by blasts, leading to changes in peripheral and central nerve function.”
Her own research as a neurotologist, she said, “suggests that there are CNS implications of having peripheral losses due to noise or blasts.”
She cited a study recently presented by researchers in the department of otolaryngology at the University of Mississippi showing that rats exposed to a single blast overpressure at 50 PSI stopped breathing immediately and ultimately died. Rats exposed to a single blast of 40 PSI showed progressive loss of stereocilia bundles of the balance sensors, decreased vestibular nerve activity, and loss of the function to maintain clear vision during head movements.
Yet no equivalently intense blast was experienced by any of the US diplomats, and there is no known mechanism by which such stimuli could be targeted to selected individuals in homes or hotel rooms while leaving others unaffected, the editorial noted.
Still, the clustering of symptoms experienced by the diplomats does not appear to be explained entirely by PPPD, the editorial noted. And both Dr. Stone and Dr. Fife agreed that while the symptoms most likely represent a functional disorder, other causes cannot be excluded.
“I would assume that they did hear something,” Dr. Stone said. “But the question is, in what way those sounds were causally related to subsequent illness.”
As Dr. Fife put it: “Just because an MRI is normal doesn't mean everything else is normal. Many conditions in the past that we thought were subjective turned out to be quite real.”
