The chronic fatigue syndrome (CFS) has been intensively
studied over the last 40 years, but no conclusions have yet
been agreed as to its cause. Most cases nowadays are sporadic.
In the established chronic condition there are no consistently
abnormal physical signs or abnormalities on laboratory
investigation. Many physicians remain convinced that the
symptoms are psychological rather than physical in origin.
This view is reinforced by the emotional way in which many
patients present themselves. The overlap of symptoms between
CFS and depression remains a source of confusion and
difficulty. But even if all CFS patients were rediagnosed as
depressives, this would not negate the possibility of an
underlying organic cause for the condition, in view of the
growing evidence that depression itself has a physical cause
and responds best to physical treatments.
There is some evidence both for active viral infection and for an
immunological disorder in the CFS. Many observations suggest
that the syndrome could derive from residual damage to the
reticular activating system (RAS) of the upper brain stem
and/or to its cortical projections. Such damage could be
produced by a previous viral infection, leaving functional
defects unaccompanied by any gross histological changes.
In animal experiments activation of the RAS can change sleep
state and activate or stimulate cortical functions. RAS
lesions can produce somnolence and apathy. Studies by modern
imaging techniques have not been entirely consistent, but many
magnetic resonance imaging (MRI) studies already suggest that
small discrete patchy brain stem and subcortical lesions can
often be seen in CFS. Regional blood flow studies by single
photon-emission computerized tomography (SPECT) have been more
consistent. They have revealed blood flow reductions in many
regions, especially in the hind brain. Similar lesions have
been reported after poliomyelitis and in multiple
sclerosis–in both of which conditions chronic fatigue is
characteristically present. In the well-known post-polio
fatigue syndrome, lesions predominate in the RAS of the brain
If similar underlying lesions in the RAS can eventually
be identified in CFS, the therapeutic target for CFS would be
better defined than it is at present. A number of logical
approaches to treatment can already be envisaged.