Simon
Senior Member
- Messages
- 3,789
- Location
- Monmouth, UK
A new review by, amongst others, Brian Walitt, the lead clinical investigator of the NIH intramural mecfs study. It argues mecfs is a somatoform illness, though it's arguing it's triggered by cyotokines leading to epigenetic changes.
Some aspects of this paper concern me, and I think it deserves some close scrutiny by the sharp eyes on this forum.
Chemobrain: A critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy
Abstract [mention of mecfs comes later]
One consequence of modern cancer therapy is chemotherapy related cognitive dysfunction or “chemobrain”, the subjective experience of cognitive deficits at any point during or following chemotherapy. Chemobrain, a well-established clinical syndrome, has become an increasing concern because the number of long-term cancer survivors is growing dramatically.
There is strong evidence that correlates changes in peripheral cytokines with the development of chemobrain in commonly used chemotherapeutic drugs for different types of cancer. However, the mechanisms by which these cytokines elicit change in the central nervous system are still unclear. In this review, we hypothesize that the administration of chemotherapy agents initiates a cascade of biological changes, with short-lived alterations in the cytokine milieu inducing persistent epigenetic alterations. These epigenetic changes lead to changes in gene expression, alterations in metabolic activity and neuronal transmission that are responsible for generating the subjective experience of cognition.
This speculative but testable hypothesis should help to gain a comprehensive understanding of the mechanism underlying cognitive dysfunction in cancer patients. Such knowledge is critical to identify pharmaceutical targets with the potential to prevent and treat cancer-treatment related cognitive dysfunction and similar disorders.
A few nuggets on mecfs
I've only started looking at this, but so far am not impressed by the authors grasp of mecfs.
Some aspects of this paper concern me, and I think it deserves some close scrutiny by the sharp eyes on this forum.
Chemobrain: A critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy
Abstract [mention of mecfs comes later]
One consequence of modern cancer therapy is chemotherapy related cognitive dysfunction or “chemobrain”, the subjective experience of cognitive deficits at any point during or following chemotherapy. Chemobrain, a well-established clinical syndrome, has become an increasing concern because the number of long-term cancer survivors is growing dramatically.
There is strong evidence that correlates changes in peripheral cytokines with the development of chemobrain in commonly used chemotherapeutic drugs for different types of cancer. However, the mechanisms by which these cytokines elicit change in the central nervous system are still unclear. In this review, we hypothesize that the administration of chemotherapy agents initiates a cascade of biological changes, with short-lived alterations in the cytokine milieu inducing persistent epigenetic alterations. These epigenetic changes lead to changes in gene expression, alterations in metabolic activity and neuronal transmission that are responsible for generating the subjective experience of cognition.
This speculative but testable hypothesis should help to gain a comprehensive understanding of the mechanism underlying cognitive dysfunction in cancer patients. Such knowledge is critical to identify pharmaceutical targets with the potential to prevent and treat cancer-treatment related cognitive dysfunction and similar disorders.
A few nuggets on mecfs
True up to a point, there are arguments about whether this is the most relevant way to measure problems (as patients are often fine for a while, then crash). A recent study found:The state of the evidence for chemobrain strongly resembles that which is seen in fibromyalgia and chronic fatigue syndrome. Like chemobrain, patients with these illnesses experience subjective and clinically distressing dyscognition, with attention, concentration, forgetfulness, word-finding, multi-tasking, and organization being the most common complaints. Also like chemobrain, measurements of objective neuropsychologic function frequently fail to demonstrate impairment and what is seen in positive studies is of small clinical magnitude [40–42].
after a 3-hour session of cognitive testing of memory and attention, healthy controls took an average of 7 hours to recover, compared with 57 hours – more than two days – for CFS patients.
Obviously the authors are not familiar with the numerous prospective studies (eg Dubbo) that find mecfs develops in a subgroup of people after some infections, notably glandular fever. One large study was by Peter White.Both of these illnesses have disputed causal triggers, such as trauma in fibromyalgia and infection in chronic fatigue syndrome, whose validity is also not answered by the scientific literature to date.
I've only started looking at this, but so far am not impressed by the authors grasp of mecfs.
The clinical and scientific experience of chemobrain is remarkably similar to the dyscognition reported in fibromyalgia and chronic fatigue syndrome. However, no comparative studies between these dyscognitive states have been performed to date. The implications of this observation are that specific chemotherapeutic-related neurologic injury is not required to create the somatic experience of chemobrain.
The discordance between the severity of subjective experience and that of objective impairment is the hallmark of somatoform illnesses, such as fibromyalgia and chronic fatigue syndrome. A somatoform view of chemobrain would consider it as an atypical yet predictable subjective experience that result from the normal functioning of the brain rather than from an injury.
Chemotherapy, or the psychological ramifications of cancer treatment, may simply be one of a variety of “triggers” that ultimately lead to dyscognition.