SOURCES OF INFORMATION
The committee’s Statement of Task requested an “assessment of treatment options.” However, as discussed above, individual-specific data on treatment and clinical outcomes were not readily available to the committee. It was privy to anecdotal information about the treatment of some individuals, but this information was not standardized or systematic. The approach to initial treatment and rehabilitation was also complicated by a number of factors including remote locations and difficult access to specialized care, diverse clinical presentations by affected personnel, and a variety of reporting schemes at different times. It is beyond the scope of this report to assess the efficacy of specific treatments of individuals. It is important to note that in most injuries to the brain or vestibular system, poorly understood recovery or compensatory mechanisms lead to functional improvement over time. Non-pharmacologic therapies targeted at the person’s deficit enhance or quicken the process of functional improvement.
The information available to the committee about the acute treatment of Department of State (DOS) personnel derived from direct testimony to it by affected personnel, summative reports in the literature, or information provided to it by the clinical investigators. In general, the personnel were treated acutely with rest and instructions to avoid the circumstances associated with the initial signs and symptoms. In the absence of recovery and out of an abundance of concern, some personnel were transferred to Miami where further evaluation was performed. Very limited information on treatment that occurred at that time was available to the committee.
The data available to the committee on chronic treatment derived from direct testimony to it by several affected personnel, reports in the literature, and a presentation by Penn clinicians involved in the care of the affected DOS employees and their families. In general, the data were presented in summary form without specific details. For example, the granularity of the detail was at the level of general cognitive, neuro-optometric, vestibular and vocational rehabilitation interventions. Some more specific information is found on page 1130 of the publication by Swanson et al. (2018). The committee lacked specific information on patient-specific treatment approaches and responses, which would have helped in generating recommendations on potential alternatives. However, information made available to the committee suggested that affected individuals did improve after referral to vestibular or cognitive therapy.
Given these limitations, the committee focused its efforts instead on a review of the current state-of-the art in neurological, vestibular, and neuropsychological rehabilitation, with the goal of offering general guidance (this section) and recommendations (see Section 6) for treatment of patients with unexplained neurological or other medical manifestations like these in the future.
ASSESSMENT AND FINDINGS
The committee distinguishes observations related to care of the acute syndrome from those for longer-term care of the chronic syndrome associated with the Embassy employees in Havana.
In the case of acute symptoms that are thought to be caused by injury to the central nervous system, it is important that expert clinicians perform an evaluation as early as possible after the onset of the illness. This can include immediate care by on-site medical personnel, but it is unlikely that such personnel will be expert in the assessment of neurological injuries. In addition, although some level of care can and should be provided by telemedicine, it is very likely that parts of the neurological examination and much of the required early testing will not be feasible on-site. Hence, both to avoid further injury and to insure the most rapid access to expert care, there should be plans in place, as needed, for each embassy to remove the affected individuals to a protected site where this evaluation can be done. The actual indicated treatment will be specific to the type of injury that has been sustained. If removing personnel is required for evaluation, this evaluation should be completed as soon as possible and then personnel should be returned to whatever is the most supportive environment. Rehabilitation will also be guided by evidence of damage to specific parts of the nervous system.
The absence of a known cause of the symptoms and signs in the affected DOS employees complicates initial treatment and early rehabilitation to some degree. However, it is not unusual for patients to develop chronic nonspecific symptoms (e.g., fatigue, dizziness) following acute medical events such as mild traumatic brain injuries, acute peripheral vestibulopathies, cardiovascular or cerebrovascular events, cancer treatments, and complex surgical procedures, which may differ among individuals (Donnell et al., 2012; Gunstad and Suhr, 2001; Julien et al., 2017; Pavawalla et al., 2013; Polusny et al., 2011; Voormolen et al., 2019) despite the same exposure and mechanism of injury (Collins et al., 2016; Gardner et al., 2019; Nelson et al., 2019; Si et al., 2018). Thus, even in the setting of an identified precipitant, it is not always clear that the acute event and the chronic symptoms are directly related. Nevertheless, the absence of a known cause or mechanism does not diminish the value or relevance of management guidelines. Accordingly, the committee offers general guidance below on the future management of patients with clinical presentations similar to those of DOS Embassy employees; for example, as commonly seen in individuals suffering from mild traumatic brain injury (Bomyea et al., 2019; Chen et al., 2019; Iverson et al., 2015; Kontos et al., 2018, 2019, 2020; Sweeney et al., 2020; Yue et al., 2019).
- Early evaluation and treatment are essential. A significant body of literature demonstrates that the earlier an evaluation is undertaken and treatment initiated, the better the outcome (Belanger et al., 2015; Lacour and Bernard-Demanze, 2014; Lacour et al., 1976, 2020; Mittenberg et al., 1996; Ponsford et al., 2002). In general, early treatment can prevent development of chronic neurological conditions (GilJardine et al., 2018; Mittenberg et al., 1996; Ponsford et al., 2002; Seabury et al., 2018; Snell et al., 2009; Twamley et al., 2015; Wade et al., 1998), which are much more difficult to treat (Hiploylee et al., 2017; Perry et al., 2016; Snell et al., 2009, 2019).
- Avoid removing personnel from supportive environments. A supportive environment contributes to treatment success in rehabilitation of chronic symptoms that develop after brain injury or other acute medical events such as those listed above (Polich et al., 2020; Vanderploeg et al., 2018). Relocation of affected personnel to a site for chronic rehabilitation without providing for social supports, such as family or close colleagues, can result in social isolation and exacerbate anxiety. The committee heard accounts of such.
- Initial treatment should emphasize early assessment, education, and return to activity. Proactive therapeutic interventions, sleep hygiene and exercise are simple but helpful measures.
- Chronic neurological syndromes require a multi-disciplinary approach. Treatment of chronic syndromes may require more intensive treatment. The length of time to recovery may be months, and some residual symptoms may persist. Experience with persistent postural-perceptual dizziness (PPPD) provides useful lessons.
The diagnosis of PPPD in some Havana cases informs prognosis (Popkirov et al., 2018; Staab, 2020). With a well-integrated, multi-disciplinary treatment plan of physical and psychological therapies and medication provided over a course of 3-6 months, most patients with PPPD are able to achieve a reduction in symptoms to a level at which they are not impaired in their performance of routine daily activities inside or outside the home. Despite improvement, they may remain vulnerable to temporary (hours to days) exacerbations of symptoms on exposure to provocative stimuli such as extensive physical activity or motion-rich environments. Approximately 10-20 percent of patients in the general population who have had PPPD for more than 4 years remain work-disabled by their symptoms even after achieving their maximal response to currently available treatments (Schaaf and Hesse, 2015; Trinidade and Goebel, 2018).
As described previously, psychological disorders may develop as secondary complications of acute illnesses, regardless of cause. Data provided by the National Institutes of Health (NIH) team suggested that a considerable number of patients with ongoing physical symptoms may be experiencing clinically significant psychological distress. The most likely causes of these symptoms are secondary depressive, anxiety, traumatic stress, or somatic symptom disorders. The committee had no individual patient-level data with which to reach any conclusions about the presence of these conditions among patients with persistent symptoms. However, all of these are treatable conditions, which means that proper diagnosis and application of scientifically validated therapies could lead to a reduction in morbidity and improvements in functioning among affected individuals, regardless of the nature or cause of the initial illness or the presence of co-existing chronic conditions.
- Understand the phenotype. Personal characteristics and situational and biological differences may all impact approach and response to treatment. In general, phenotypes that predict a more successful response to neurological rehabilitation include higher level of education, resilience in other settings, and job satisfaction. Negative prognostic features include stressful job and life situation, previous history of depression, and anxiety. Significant efforts are under way to identify genetic and other factors that may affect responsiveness to neurological rehabilitation. Further efforts to link mechanism of injury with clinical manifestations (phenotype), and
- selection of and response to different treatment modalities will be important. The committee anticipates that a telemedicine team (see Section 6) assembled to help locally available clinicians in situations like those faced by the affected DOS employees would understand this evolving literature and adapt their approaches to the latest interventions available.
- Testing and therapies without established validation should be for research purposes only. The committee was asked to comment on the use of diffusion tensor imaging to establish brain injury and on visual rehabilitation for vestibular symptoms after brain injury in DOS personnel. As noted in Section 3, the findings with diffusion tensor imaging did not convince the committee of the validity of this approach as a diagnostic method, although it may have value as a research method in future events. Visual training therapy is widely practiced for patients with vestibular symptoms, but the evidence base for this type of treatment remains controversial (Barton and Ranalli, 2020). Hence, while there is not adequate evidence to recommend such therapies for routine treatment of patients suffering from traumatic brain injury (TBI) or symptoms similar to TBI, the committee concluded that if clinicians based on their judgment wanted to offer them to individual patients, that the patients should be informed that the therapy was not supported by adequate evidence, but that there were reports of it being helpful in some patients.
- Interdisciplinary consultation. The committee observed that a potential shortcoming of the medical evaluations and treatment received by DOS patients was that they were provided by teams focused on one area of clinical medicine (e.g., otology in Miami, brain injury at Penn). When symptoms are as enigmatic as those experienced by DOS patients, early involvement of a broader group of clinical specialists, paired with experts in epidemiology and environmental exposures (e.g., toxicologists, radio frequency engineers, and others as determined by the situation) would reduce the chances that early clues about causality would be missed or that premature conclusions would be drawn about potential diagnoses. These additional experts could contribute in person or virtually.
The committee lacked information on patient-specific treatment approaches and responses, which would have helped in generating recommendations on potential alternatives. In reviewing best practices in neurological rehabilitation, the committee finds that early evaluation and treatment are essential for optimal outcomes, a supportive environment is important, and an interdisciplinary approach for rehabilitation of chronic neurological conditions is best, as are appropriate and early education and realistic expectation-setting.
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