NeuroImmune Gastrointestinal Dysfunction Syndrome: A New Descriptor for Autism and Chronic Fatigue Syndrome? A spectrum of disease.

[Guest guest]

NeuroImmune Gastrointestinal Dysfunction Syndrome: A New Descriptor for

Autism and Chronic Fatigue Syndrome? A spectrum of disease.

Robyn E Cosford MBBS(Hons)FACNEM

Director, Northern Beaches Care Centre,

1789 Pittwater Rd,

Mona Vale,

NSW 2103

Telephone : 0299799444

Fax 0299799016

In conjunction with CPRU, University of Newcastle, and Bioscreen

Chronic Fatigue Syndrome is characterised by fatigue, gastrointestinal

symptoms with irritable bowel, food intolerance, muscle pain and weakness,

recurrent illness and neurocognitive symptoms. Neurocognitive symptoms

include cognitive dysfunction, sensitivities to stimuli such as bright

lights, noise and odours, and disordered and fragmented sleep. CFS in

adolescents typically has an onset after age 12 years. Autism is similarly

characterised by neurocognitive symptoms, albeit as the most obvious

abnormality, with sleep disorder as usual, and marked sensory sensitivity.

Gastrointestinal symptoms are also the norm, with demonstrable reactions to

certain foods, particularly gluten and casein containing foods, recurrent

infections and easy fatigue. Autism is generally diagnosed between the age

of 2 and 3 years old. In both autism and CFS, epidemiological studies have

indicated the probability of an underlying genetic susceptibility, but

prominent environmental triggers.

Various metabolic abnormalities have been identified in Chronic Fatigue

Syndrome. Increased gastric emptying times, and increased gastrointestinal

permeability have been documented in CFS as markers of gastrointestinal

dysfunction, and faecal studies demonstrate gastrointestinal dysbiosis with

overgrowth of streptococcal/enterococcal species in some 60% of CFS

patients. Urinary organic acid analyses demonstrate increased markers of

fibrillar and nonfibrillar catabolism in CFS patients, and various organic

acid abnormalities in subsets of CFS sufferers. CFS patients with prominent

visual and sensory disturbances also show a characteristic pattern of

urinary organic acid disturbance. ( GL et al 1999). Plasma lipid

analysis in CFS patients reveals predominantly low elaidic acid, which has

been shown as a marker for pain.

Similarly recent research using urinary organic acids, plasma lipids,

faecal analyses and intestinal permeability studies in children with autism

(DSMIV criteria), has identified particular patterns in these children.

Urinary organic acids indicate a strongly catabolic picture, with fibrillar

and nonfibrillar catabolism, generally low urinary glycoamines, and

abnormalities in the markers for the tricarboxylic acid cycle similar to

those seen in CFS. In addition to these changes, raised urinary

hydroxyproline, a marker of increased connective tissue breakdown, and

raised ornithine, a marker for abnormalities in the urea cycle and ammonia

metabolism, are typically seen. Plasma lipid analysis reveals lowered

levels of elaidic acid, as seen in CFS adolescents, but more

signnificantly, also a block in the betaoxidation of long chain fatty

acids, with accumulation of long chain fats, deficiency in cholesterol, and

markedly reduced eicosapenatoic and docosahexanoic acids. Notably, raised

levels of nervonic acid are consistently found. Nervonic acid forms is the

fatty acid major component of sphingomyelin and may indicate a disruption

of myelination. Faecal studies show a loss of beneficial E coli,

lactobacilli and bifidobacteria, and overgrowth of potentially pathogenic

enterococci and streptococci, and increased intestinal permeability has

been documented to occur in some 50% of children with autism. Endoscopic

studies have revealed gastric mucosal inflammation, duodenal inflammation

and colonic inflammation in a significant percentage of children with

autism. Immune abnormalities are well documented in autism by various

researchers.

The results indicate that Autism children represent a metabolically more

homogenous group than CFS patients. The metabolic disruption in Autism is

more widespread and severe, as are the neurocognitive symptoms, but the

similarities with the subgroup of CFS patients with gastrointestinal

symptoms and neurocognitive symptoms suggest a possible commonality in

aetiology. It is hypothesised that the abnormal gastrointestinal flora is

producing the measurable increase in intestinal permeability, intestinal

inflammation and disturbance in gastrointestinal motility, disruption in

digestion and food intolerance. Streptococcal toxins and immune cross

reactions have a known association with neurological phenomenon (eg

Sydenham's chorea), and recent literature has noted the connection with

streptococcus and Tourette's Syndrome, ObsessiveCompulsive Disorder, and

ADHD. It has already been hypothesised that CFS is a toxinmediated

channelopathy disorder (Chaudri). It is therefore hypothesised that in a

subgroup of CFS patients and in most children with Autism, the illness is

largely toxinmediated with a significant contribution from the toxins

generated by streptococcal overgrowth in the gastrointestinal tract. The

increased severity of the metabolic disruption and neurocognitive effects

in Autism could be attributed to the different age at which the organism

was exposed to the environmental stimuli, with the insult occuring in

autism whilst the neurological system is still in the process of

myelination and maturation and the immune system still maturing.

The term Neuroimmune Gastrointestinal Dysfunction Syndrome

would adequately describe this phenomenon.