Answer: The Kansas criteria is the brain psychological assessment tool for evaluating the severity of Gulf War Illness among veterans.
Gulf War Illness (GWI), sometimes also called the Persian Gulf Syndrome or Medically Unexplained Chronic Multisystem Illness, is a set of somatic and psychological symptoms that primarily affect deployed veterans of the first Persian Gulf War (1990-1991).
The cause of GWI is still unknown. Some theories suggest that it is a result of a combination of factors, ranging from combat stress to exposure to organopesticides, Sarin nerve gas, or depleted uranium. To some degree, the unique combination of environmental influences influenced brain activity among veterans that led to eventual presentation of GWI.
One of the mechanistic explanations of the pathology of the disorder is a hyper-cholinergic brain state, where excess signaling by the neurotransmitter acetylcholine in the brain leads to excess glutamate release, which can cause excitotoxicity. This theory comes about from the observation that organophosphate toxins are often cholinesterase inhibitors, which increase brain levels of acetylcholine. Additionally, stress results in dysregulated glutamate transmission as well as a disruption of the blood-brain barrier, a protective anatomical adaptation that prevents toxins from easily entering the brain.
There is debate about the diagnosis of GWI. Unfortunately, nearly 60% of veterans are told by their physician that their GWI is a psychosomatic illness, which adds to the mental health stigma that these people face. However, the Centers of Disease Control (CDC) and the National Academy of Sciences recognized that GWI is a genuine medical condition, indicating that these veterans are a unique population that requires individualized attention and treatment approaches due to the challenges they face.
One of the major difficulties with making a diagnosis of GWI is there is often a delayed onset of symptomatology, sometimes manifesting or becoming more serious decades later. This often leads to unemployment issues or impaired social interactions from the disabilities related to the Gulf War illness.
The other major challenge is that the symptoms may be comorbid with other well-characterized conditions, such as generalized anxiety disorder (GAD), chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD), and pain medication use. Because there is so much overlap between these cases, it becomes very difficult to identify which came first, akin to the chicken and the egg problem.
The Kansas criteria is a self report questionnaire that asks the patient to rate their recent experiences regarding a variety of symptoms. It is made up of 37 questions, for which the patients will report the severity of each on a scale: none (0), trivial (1), mild (2), moderate (3), and severe (4).
The Kansas criteria is made up of nine major categories of symptoms. Each of them contain a series of subquestions to provide more specific examples.
Fatigue and Sleep
“Not feeling rested after sleep”
“Fatigue”
“Problems falling or staying asleep”
“Feeling unwell after exercise or exertion”
Pain
“Body pain”
“Joint pain”
“Muscle pain”
Neurologic and Cognitive
“Memory”
“Concentration”
“Word finding”
“Numbness”
“Blurred vision”
“Tremors”
Mood
“Irritable”
“Depressed”
Sensory 1
“Light sensitivity”
“Headaches”
“Tinnitus”
“Sinus congestion”
“Hearing loss”
Sensory 2
“Temperature sensitivity”
“Dizziness”
“Response to chemicals”
“Night sweats”
Airway
“Dyspnea”
“Persistent cough”
“Sore throat”
“Swollen lymph”
“Wheezing”
Abdominal
“Abdominal pain”
“Diarrhea”
“Nausea”
Epithelial
“Problems with teeth or gums”
“Rashes”
“Mouth sores”
“Hair loss”
“Burning after sex”
One self report study of a total of 485 patients (392 male; 93 female) suggested that many Gulf War veterans reported moderate to severe fatigue and sleep deficits, unusual pain sensations, neurologic / cognitive changes, and mood changes. They also reported between trivial and moderate symptoms on the other categories.
Non human studies of GWI
While human studies are critically important for a therapeutic perspective, biomedical researchers have developed non-human models of Gulf-War Illness to try to understand the molecular and cellular level changes that happen from an experimental angle. These tools exist to mimic the various conditions in rats or mice in order to develop chemical therapies that could be eventually brought into the clinic to help veterans.
One study published in the journal Neuroscience Insights described the use of the organophosphate compound diisopropyl fluorophosphate (DFP) as a way to model the chemical exposure that Gulf War veterans experienced. DFP is a pesticide that was used during the Gulf War. When the rats were injected with a low dose of DFP over the span of 5 days, they did not experience any significant symptoms initially. However, 3 to 6 months later, they experienced psychiatric impairments, such as depression-like behaviors, anxiety, as well as cognitive deficits. Because of the delayed onset of symptom presentation, just like in veterans with GWI, this DFP exposure paradigm has been used as a model for the human illness.
These researchers were then curious to the mechanism of what kinds of cellular changes were observed in these animals. Their primary theory was that dysfunction of the mitochondria was a key part of the disorder, and that the neurotransmitter systems acetylcholine and glutamate interact with each other resulting in excessive neuronal levels of calcium. In agreement with their hypothesis, the DFP exposed rats had significantly elevated levels of intracellular calcium in the neurons of the hippocampus at the 3 and 6 month time points. Changes in the cells of the hippocampus likely leads to the cognitive behavioral deficits observed in veterans, as the cellular process of long-term potentiation is likely disrupted in these synapses.
The DFP exposure paradigm is not the only nonhuman study used to model GWI. A different research group exposed rats to a combination of chemicals including the insecticides diethyltoluamide (DEET) and permethrin as well as the anti-nerve gas agent pyridistigmine bromide with physical stressors. This group discovered that the electrophysiological properties of the hippocampus were changed as well as an increase in levels of the inflammatory signals IL-13.
One pharmacological approach that shows promise in nonhumans with treatment of GWI is a compound called LDN/OSU-215111. Through a still unknown mechanism, LDN/OSU-215111 is a small-molecule that strengthens the structure and function of the astrocytes and glutamatergic synapses. The astrocytic processes and glutamatergic synapses communicate at specific sites in the brain called the tripartite synapse. In some mouse studies, the compound was able to reverse some of the behavioral deficits seen in GWI (open field test, elevated plus maze, tail suspension test). In line with the glutamatergic excitotoxity theory, restoring glutamate function is a key aspect that mediates the deficits in GWI. This study implies that the restoration of functions between the astrocytes and glutamatergic synapses is important for fixing the deficits seen in Gulf War Syndrome.