Havana Syndrome Among Canadian Diplomats: Brain Imaging Reveals Acquired Neurotoxicity

Abstract

BACKGROUND: In late 2016, US diplomats stationed in Havana began presenting with a variety of neurological manifestations that proved difficult to diagnose. Though previous studies suggested a likely association with brain injury, the mechanism of injury, brain regions involved, and etiology remained unknown. METHODS: We conducted a multimodal study examining 26 Canadian diplomats and their family members, the majority of whom presented with symptoms similar to their American counterparts while residing in Havana. Assessments included a medical history, self-reported symptom questionnaires, cognitive assessments, blood tests, and brain imaging assessments (magnetic resonance imaging (MRI) and magnetoencephalography (MEG)). Individuals showing signs of brain injury underwent further neurological, visual, and audio-vestibular assessments. Eight participants were tested both before and after living in Havana. RESULTS: Our assessment documents multiple functional and structural impairments, including significant spatial memory impairment, abnormal brain-stem evoked potentials, degradation of fibre tracts in the fornix and posterior corpus callosum, blood-brain barrier injury to the right basal forebrain and anterior insula, and abnormal paroxysmal slowing events of cortical activity. Subsequent mass-spectrometry and blood analyses documented reduced serum cholinesterase activity and the presence of organophosphates (Temephos) and pyrethroid metabolites (3-phenoxybenzoic acid or 3-BPA). CONCLUSIONS: Our findings confirm brain injury, specify the regions involved, and raise the hypothesis of overexposure to cholinesterase inhibitors as a plausible etiology. If correct, our hypothesis bears public health ramifications (see Discussion) and suggests a course of action for reducing exposure in the future. FUNDING: Global Affairs Canada.

Clinical and Psychological Factors Associated With Return to Work Among United States Diplomats Who Sustained a Work-Related Injury While on Assignment in Havana, Cuba

“…Given that the symptom complex with which these diplomats presented suggested potential mild traumatic brain injury, 1 a 23-item Symptom Score Questionnaire (SSQ), derived from the symptom evaluation section of the 22 item Sports Concussion Assessment Tool (SCAT), 12 was administered at each visit (Table 1 ). Five additional questions were added to the SSQ: 1) hearing difficulty in the form of tinnitus, 2) sleeping less than usual, 3) sleeping more than usual, 4) anxiety, and 5) numbness or tingling, the latter added given that a toxicologic source 13 , 14 was being considered in the differential diagnosis at the time. Four questions were removed: 1) confusion as it was evaluated elsewhere, 2) neck pain, 3) pressure in head because there was no evidence of physical head injury, and 4) “don’t feel right.”…”

Symptoms reported by Canadians posted in Havana are linked with reduced white matter fibre density

“… 3 A similar set of symptoms was later reported by the Canadian diplomats stationed in Havana and their families. 4 A multimodal assessment of clinical and psychological symptoms revealed that the symptoms were similar to those of the American diplomats. The cause for these changes remains unclear and this ambiguity necessitates an investigation into the relationship between neural effects and the symptoms.…”

“… 5 In a cohort of 26 Canadian diplomats and their family members, our group has previously reported the evidence of abnormalities in WM (examined using diffusion-weighted MRI, dMRI), blood-brain barrier integrity and brain electrical activity (studied using magnetoencephalography). 4 The studies of US diplomats have highlighted the resemblance of the observed symptoms to the sequela of traumatic brain injury (TBI). 2 , 5 However, to date there is no consensus regarding the cause of the symptoms, and the proposed aetiologies include both those of internal and external origin.…”

“… 2 , 5 However, to date there is no consensus regarding the cause of the symptoms, and the proposed aetiologies include both those of internal and external origin. 3 , 4 Hence, the identification of the potential neurological origins of the symptomatology may help the treatment of patients and prevention of future injuries.…”

Quantitative T2 MRI is predictive of neurodegeneration following organophosphate exposure in a rat model

“…Victims of the 1995 Tokyo subway sarin attack had decreased brain volume in the insular and temporal cortex, 5 to 6 years following the attack 61 . A recent report on the Havana Syndrome, which suspects OP insecticide exposure, has found BBB leakage in the insular cortex 62 . Both of these studies were conducted using MRI and detected subtle changes.…”