Post-exertional malaise (PEM) is an incapacitating feature of ME that appears to be associated with impaired energy metabolism . Signs that include a marked inability to tolerate even trivial amounts of physical and/or cognitive activity, accompanied by worsening symptoms such as muscle or joint pain, memory & learning issues, and consciousness problems. The energy depletion aspects of PEM, often lasting 24 hours or more , greatly interfere with disease management (e.g. pacing daily activities). Thus, people with ME often have difficulty performing routine tasks such as getting dressed, going from sitting to standing position, climbing a flight of stairs, taking a shower, cooking meals, doing housework, driving a vehicle, and standing in line. Cognitive/behavioral impairments and PEM are considered core aspects of ME with central context underlying the manifestation of multi-systemic symptoms .
The NCRI uses powerful new techniques that offer prospect of accelerating new discoveries for improving lives of people with neurological diseases including ME.
There is an urgent need for research aimed at identifying biological indicators of ME for making accurate diagnosis. Without an accurate diagnosis, a larger percentage of patients go undiagnosed for years and are unable to gain access to services they need. The cause of ME is unknown. However, in nearly 50% of cases with viral encephalitis, the cause is not identified . To that end, the NCRI uses powerful new techniques that offer prospect of accelerating new discoveries and facilitate translation of scientific findings from the lab to real-world applications. For example, state-of-the-art electrical neuroimaging techniques such as swLORETA (standardized weighted low-resolution electromagnetic tomography) which allow for accurate mapping of neuronal activities of the brain in 3 dimensions . Electrical neuroimaging operates at the millisecond timescale which allows for a reliable linkage of brain states and brain regions linked to patient’s symptoms. Furthermore, it is far more practical in terms of cost and portability. These advantages allow researchers and clinicians to objectively measure brain function happening in real time and analyze waveform patterns for assessing the effects of disease on cognitive and behavioral functions .
Promising findings from previous studies we’ve conducted offer much support for alterations in the central nervous system in patients with ME. In our recent Stanford study  using exact LORETA (eLORETA) methods , widespread delta (slow-wave) abnormalities were found in prefrontal and limbic cortical locations and they were associated associated with clinical fatigue severity ratings. Pathological delta waves may result from damage to nuclei in the brainstem, localized damage to white matter tracts, and brain inflammatory conditions (e.g. encephalitis). At the same time, decreased beta (fast-wave activity) was also found in the primary motor cortex, indicating reduced CNS drive for voluntary movement, disturbances in pain sensations and hypersensitivity. These findings were consistent with a separate study conducted at DePaul University  which showed diminished functional brain network connectivity across three major networks thought to underlie cognitive deficits and goal-directed behavior . Likewise, another study conducted at DePaul found that the disruption of timings within the brain corresponded with neurocognitive symptom severity, serving as evidence for the role of brain network inefficiency associated with deficits found in patients . Together, the data for these studies reveal that functional alterations in the brain are contributing to the energy deficits, hypersensitivity, and neurocognitive symptoms in patients with ME.
*ME is also known as chronic fatigue syndrome (CFS) and, more recently, systemic exertion intolerance disease (SEID). Most disease states are syndromes in that they typically involve multiple signs and symptoms, specifying which ones are necessary for a diagnosis, and which ones may or may not present. The idea of a syndrome is to help define what is, and what is not, a particular disease.
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