By Craig Tanio, MD
Introduction
Cognitive impairment is a major component of fatiguing illnesses and a significant driver of disability and poor outcomes in these conditions. Cognitive impairment is part of the formal criteria in the 2015 National Academy of Medicine definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A recent review of patients with ME/CFS showed self-reported issues with memory (80%), expressing thoughts (73%), attention (69%), slower thoughts (66%), and comprehension (55%). Other clinical frameworks used to define fatiguing illnesses such as chronic inflammatory response syndrome from water damaged buildings (CIRS-WDB), mast cell activation syndrome (MCAS), and multiple systemic infectious disease syndrome (MSIDS) all identify cognitive impairment as an important subset of symptoms.
Treatment of these issues should not occur outside of the context of treating the root cause and entire condition. However, specific interventions to assess and treat cognitive impairment as part of a comprehensive plan is likely to result in improved outcomes. We use the following approach to assess and support cognitive function:
- Assess current cognitive function using a three-pronged approach that incorporates subjective patient information, formal cognitive testing, and volumetric brain imaging.
- Assess and treat cognitive function with particular attention to brain perfusion, sleep/limbic system activation, pacing/glucose metabolism/nutrition, and neuroinflammation.
- Treat the overall fatiguing illness (out of scope for this article).
Assess Cognitive Function with a Three-Pronged Approach
The discerning clinician will notice signs of cognitive impairment from the moment the patient steps in the room. Common issues that may look like problems with adherence include forgetting instructions and suggestions from a prior visit, confusion with complex explanations, and trouble remembering medications. They may have delayed verbal responses to questions that worsen during the time of the visit. Patients may also report cognitive post-exertional malaise (PEM) that occurs in a similar pattern to physical PEM.
We utilize a three-pronged approach to get an objective and practical assessment. The use of all three approaches can allow a clinician to confirm the location and degree of neurologic injury.
Cognitive testing. The use of validated brain testing software such as CNS VitalsTM is a straightforward way for the clinician to get objective measures of brain function within 30 minutes. Findings often seen include slowing of information processing speed, complex attention, and executive function, as well as changes in verbal and visual memory.
Patient surveys. Detailed brain surveys such as the Brain Function Assessment FormTM are a practical way to correlate symptoms with specific neuroanatomic pathology. Survey information cannot be taken at face value but needs to be confirmed and further explored through the history.
Volumetric imaging. We utilize volumetric MRI imaging if patient survey and cognitive testing are positive. Volumetrics MRI imaging uses software such as NeuroQuant or NeuroReader to convert 2D segmented images into 3D volumes and compare the images to a control database with reports that show gray and white matter volumes reported out in percentiles. Larger volumetric sizes may reflect neuroinflammation with likely mechanisms including micro-interstitial edema related to incompletely regulated cell danger responses, failed autophagy, apoptosis, possible mast cell activation, and microglial cell activation. Smaller volumetric sizes may reflect neurodegenerative pathology resulting from chronic neuroinflammation, mitochondrial degeneration, reactive oxygen species damage, protein misfolding, and neuronal vascular injury. It is more accurate than a radiologist in assessing atrophy. Volumetric studies of patients with fatiguing illnesses have been plagued by independent small sample studies rather than a collective registry but the types of observations include the following:
- ME/CFS – The most consistent volumetric findings have been changes in the basal ganglia, including the caudate and putamen.
- CIRS-WDB – Reported volumetric findings include increases in forebrain, hippocampus, and pallidum sizes and decreases in multiple grey matter areas, including caudate, forebrain, cortical matter.
- MCAS – Mast cells can be present in the cerebellum, ventral diencephalon, caudate, putamen, and thalamus resulting in increased volumetric sizes.
The use of volumetric imaging greatly helps patients who have often been told by previous clinicians that “it’s in their head” to understand that there are clear biologic and neurologic issues. We will review patients’ symptoms and correlate them with the location of their neurologic injury. Understanding the degree of neurologic injury can be motivating to patients at a time when they can take effective action. Finally, all three of these assessment methods can help to document clear improvement over time.
Cerebral Perfusion
The proper circulation of blood and delivery of oxygen, glucose, and other nutrients are critical for good neurologic performance.
Cognition can be readily impaired by cerebral perfusion deficits due to orthostatic intolerance (OI). OI and Postural Orthostatic Tachycardia Syndrome (POTS) can be practically demonstrated through a NASA 10-minute “lean test” that assesses postural changes in blood pressure, heart rate, and symptoms. Addressing orthostatic intolerance directly through electrolytes, hydration, compression stockings, and mineralocorticoids can often improve symptoms. At times, alpha-1 receptor agonists or low dose beta blockers may be required.
