Mechanism of Neurological Injury
Three independent sets of information have been used to discuss a plausible mechanism for neurological impairment observed in humans exposed to contaminated air. The first set includes clinical observations on humans exposed to water-damaged environments. The second set entails animal experiments demonstrating neurological injury from mycotoxins instilled into the olfactory mucosa. The third set of data involves clinical and pathology of brain injury to children and young adults exposed to the polluted air of Mexico City.
A. Clinical findings in patients exposed to water-damaged buildings
Both central and peripheral neuropathy have been reported in individuals chronically exposed to damp indoor environments (Gray et al, 2003; Campbell et al, 2003; 2004; Crago et al, 2003; Kilburn, 2003, 2004, 2009; Kilburn et al, 2009; Rea et al, 2003; Gordon and Cantor, 2004; Gordon et al, 2004, 2006). Briefly, exposed individuals develop peripheral neuropathy with autoantibodies directed against several neural antigens (Campbell et al, 2004).
Toxic encephalopathy involves multiple symptoms, including loss of balance, recent memory decline, headaches, lightheadedness, spaciness/disorientation, insomnia, loss of coordination (Gray et al, 2003; Rea et al, 200, 2009; Kilburn 2003, 2004). Exposed individuals had alterations in QEEG involving the frontal cortex and other regions of the brain (Crago et al, 2003) coupled with neurocognitive decline (Crago et al, 2003; Gordon and Cantor, 2004, 2006; Kilburn 2003, 2004), as well as significant changes in various neurological measurements (declines in simple reaction and choice reaction times, increased body sway with eyes open and closed, increased latency of blink reflex, and decreased grip strength, among others) (Kilburn 2003, 2004).
The probable explanation of the causative mechanism comes from both animal models and humans exposed to air pollution.
Recently, Empting (2009) published his clinical observations on mold patients suffering from chronic fungal sinusitis (CFS) with neurological complaints referred to his office by Donald (2009). Trained in Psychiatry and Neurology, he has begun defining systems of a syndrome or cluster of signs/symptoms occurring in individuals with neurological disorders following exposure to microbes (molds and bacteria) in damp indoor spaces. His goal is to delineate these mold and mycotoxin-induced signs and symptoms from classic neurologic disorders. The patients he has seen fall into categories which will be described below:
1. Local and Focal Pain Syndrome
(a) Migraine and atypical facial pain result from inflammation of the sinuses irritation to the trigeminal nerve branches as they pass through the walls of the sinuses. Alleviation of the inflammatory condition allows management of the migraines. The migraines occur in patients with or without a history of migraines and/or headaches;
(b) Pharyngitis and glossopharyngeal neuralgia. This condition results from post nasal drainage from inflamed sinuses leading to irritation of throat and are nociceptive pain generators. The inflammation irritates the innervations of the throat resulting in neuropathic pain. Once started, the condition is more easily instigated by levels of stimulation.;
(c) Local head and neck myalgias: The inflammatory, nociceptive and migraine pain in the head and throat can feed into the cranial nerve and upper cervical root pain pathways and myofascial pain loops. Secondarily, this can involve increased muscle tone, spasm and local trigger points can develop independent facial, temporal, suboccipital and cervical myofascial pain syndromes.
2. Inflammation Induction of Distant and Diffuse Pain
According to Dr. Empting, any inflammatory process in the body, including CFS, can induce myalgias and arthralgias. Inflammatory cytokines and circulating immune complexes can reach any joint, muscle or connective tissue in body via the circulatory system. Once instigated, these conditions can be self-perpetuating with continuing and/or additional exposure to the offending environment.
3. Unusual Neuropathic Focal Pain
Single or multiple peripheral nerves can occasionally become painfully involved leading to peripheral neuropathy. Dorsa root ganglia involvement (e.g., Bilateral L1, L2, L3) may rarely be involved.
4. Disorder Movements
These involve tremors, jerking movements, spastic dysphonia, tic-like motions and idiopathic paroxysmal unique involuntary movements. The movements are similar to, but not stereotypical of, well-defined neurologic signs such as chorea, hemiballismus, Parkinson’s tremor, myoclonic jerks, etc.
Other neurologic features such as strength, reflexes and sensation are almost always normal. The patient can exert some voluntary control of these movements, which is typical of an impaired, rather than a damaged, motor nervous system.
5. Balance and Ataxia
Imbalance and gait ataxia are observed more commonly than cerebellar findings. Balance relies on multiple sensory inputs (e.g., visual, proprioception, vestibular), the pyramidal motor system, and multiple extrapyramidal and cerebellar modulating systems. Having so many sites susceptible to attack makes imbalance a common symptom.
6. Diffuse Neuropsychiatric Syndromes
A common label affixed to this condition is “Brain Fog.” These individuals have varying degrees of altered mental states, usually with attention, blunted executive function and faulty short-term memory. These conditions can wax and wane (exposure vs re-exposure).
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Campbell AW, Thrasher JD, Gray MR, Vojdani A. 2004. Mold and mycotoxins: effects on neurological and immune systems in humans. Adv Appl Microbiol 55:375-406.
Crago BR, Grau MR, Nelson LA, Davis M, Arnold L, Thrasher JD. 2003. Psychological, neuropsychological, and electrocortical effects of mixed mold exposure. Arch Environ Health. 45:452-63.
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B. Instillation of mycotoxins into the olfactory mucosa of rodents
Satratoxin G, roridin A and aflatoxin B1 instilled into the olfactory area cause sensory olfactory neuron loss, nasal and brain inflammation and neurotoxicity. The mycotoxins are transported into the brain along the olfactory tract leading to inflammation and damage in the tract and the olfactory bulbs. Tritium labeled aflatoxin B1 at 0.2, 1 or 20 ug was intranasally instilled in rats and followed by autoradiography and spectrometry. The mycotoxin was bioactivated in the olfactory/nasal mucosa and transported along the olfactory tract to the bulbs. Twenty-four hours after instillation, the olfactory epithelium was disorganized and undulating with pyknotic nuclei, shrunken cytoplasm and transport of the labelled aflatoxin to the olfactory bulbs. The pathology was still present at 5 days post instillation at 20 ug (Larsson and Tjalve, 2000).
Satratoxin G was instilled into the olfactory mucosa in mice at 5 and 25 ug/kg body weight. Apoptosis of olfactory neurons occurred along with the release of proinflammatory cytokines TNF-alpha, IL-6, IL-1 and MIP-2 in the nasal airways, ethmoid turbinates and olfactory bulbs. Marked atrophy of the olfactory nerve and glomerular layers of the bulb were observed (Islam et al, 2006a, b).
Similarly, roridin A instilled into the olfactory mucosa of mice at 500 ug/kg body weight induced apoptosis of olfactory neurons, atrophy of the olfactory epithelium and olfactory bulbs. The kinetics of the reported pathology was potentiated by the simultaneous exposure to lipopolysaccharide (Islam et al, 2007).
Also, lipopolysaccharides enhance the hepatoxicity of aflatoxin B1 in rats (Barton et al, 2001; Luyendyk et al, 2002, 2003).
Finally, C-14 aromatic carboxylic acids are transferred unchanged into the brain and olfactory bulbs following intranasal instillation in mice (Eriksson et al, 1999). These observations point toward at least one probable mechanism for the encephalopathy observed in humans exposed to the biocontaminants in damp indoor spaces.
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