Robyn E Cosford MBBS(Hons)FACNEM
Director, Northern Beaches Care Centre,
1789 Pittwater Rd,
Neuro-Immune Gastrointestinal Dysfunction Syndrome: A New Descriptor for Autism and Chronic Fatigue Syndrome? A spectrum of disease.
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. (Robinson 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 (DSM-IV criteria), has identified particular patterns in these children. Urinary organic acids indicate a strongly catabolic picture, with fibrillar and nonfibrillar catabolism, generally low urinary glyco-amines, 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 beta-oxidation 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, Obsessive-Compulsive Disorder, and ADHD. It has already been hypothesised that CFS is a toxin-mediated channelopathy disorder (Chaudri). It is therefore hypothesised that in a subgroup of CFS patients and in most children with Autism, the illness is largely toxin-mediated 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 Neuro-immune Gastrointestinal Dysfunction Syndrome would adequately describe this phenomenon.
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