Interview with Dr - Dr. Neubrander

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D.A. Rossignol and T. Small/Medical Veritas 3 (2006) 944–951 947 mencement of HBOT at 1.5 ATA. All three patients had improvement in the oxygenation of these areas as seen on post- HBOT SPECT scans, which was correlated with clinical improvement. So did this correlate with clinical improvement and post- HBOT SPECT scan images -- both Right -- that’s exactly right. He was able to show that not only did they get better clinically, but they had increased oxygenation and perfusion to their brain on SPECT scans. What kinds of disorders involving cerebral hypoperfusion other than autism have benefited from HBOT HBOT has been used with clinical effectiveness in other cerebral hypoperfusion disorders including lupus and traumatic midbrain syndrome, and may be beneficial in acute ischemic stroke, and acute myocardial infarction (or heart attack). In addition, HBOT has been used in several studies on children with cerebral palsy (CP). Some children with CP due to perinatal asphyxia have focal areas of cerebral hypoperfusion on SPECT scans. Significant clinical improvements were found in one study of children with CP after 20 sessions of HBOT at 95% oxygen and 1.75 ATA. Some other studies using HBOT in cerebral hypoperfusion disorders have been performed at lower pressures (1.5 ATA or less). Stoller recently reported on one pediatric case of fetal alcohol syndrome, which is considered “irreversible and incurable” and is characterized by cerebral hypoperfusion on SPECT studies. Using HBOT at 1.5 ATA, the child had statistically significant improvements in verbal, memory, reaction time, impulse control, and visual motor scores. Now what about autism Interestingly, a case report appeared in a journal called Hyperbaric Oxygen Report in 1994 about a child name Michael who had autism and received HBOT. The title of the report was: “Little Michael’s development had stopped—it was called childhood autism—until hyperbaric oxygen therapy.” This is typical of some things in medicine—someone may notice an improvement with a new therapy, but this may go unnoticed by others for many years. In this case we are 12 years out from this case report. In another case, Heuser treated a four-year old autistic child using lower pressure HBOT at 1.3 ATA (and 24% oxygen) and reported “striking improvement in behavior including memory and cognitive functions” after only ten sessions. Furthermore, the child had improvement of cerebral hypoperfusion as measured by pre-HBOT and post-HBOT SPECT scans. So some “irreversible” and permanent neurological conditions can have clinical improvements with HBOT Studies have shown improvements in: Cerebral Palsy, Fetal Alcohol Syndrome, Amyotrophic Lateral Sclerosis also called Lou Gehrig’s disease, multiple sclerosis, Complex Regional Pain Syndrome, Ischemic Brain Injury, Traumatic Midbrain Syndrome and stroke. These conditions, in most cases, are considered “irreversible” and permanent. Is it possible that the increased oxygen delivered by hyperbaric could overcome any hypoxia caused by hypoperfusion and improve symptoms for children with autism In one study of cerebral blood flow in autistic children compared to non-autistic children, the amount of perfusion to the brain in autistic children was approximately 5-8% less than typical children when measured by PET Scan. It is unknown if this hypoperfusion leads to hypoxia in autistic children although SPECT scans performed on autistic children (including the case report by Heuser) do show evidence of relative hypoxia. Follow-up SPECT scans in autistic children after HBOT also show evidence of increased oxygenation to the brain. It is certainly plausible that the increased oxygen delivery by HBOT could overcome any hypoxia caused by hypoperfusion and thus lead to improvements in the symptoms of autistic children. What evidence of neuroinflammation is there in autism, especially in the brain Recent studies reveal that autism is characterized by neuroinflammation. The study by Vargas on autopsy brain samples from autistic patients demonstrated an active neuroinflammatory process in the middle frontal gyrus, anterior cingulate gyrus, and cerebellar hemispheres including increased microglial and astroglial activation and increased proinflammatory cytokines. Furthermore, cerebrospinal fluid obtained from living autistic patients also “showed a prominent proinflammatory profile.” Previous studies of autistic children have shown circulating serum autoantibodies to brain elements including neuronaxon filament protein and glial fibrillary acidic protein, the caudate nucleus, cerebral cortex and cerebellum, and neuronspecific antigens including myelin basic protein. But inflammation in autistic children is not limited to the brain. When compared to typical children, autistic children make significantly more serum antibodies against gliadin and casein peptides—which is the basis of the gluten and casein free diet, produce more pro-inflammatory cytokines, and have an imbalance of CD4+ and CD8+ cells. Furthermore, some patients with autism have mucosal inflammation of the stomach, small intestine and colon characterized by ileo-colonic lymphoid nodular hyperplasia. In these children, the gastrointestinal mucosa has evidence of proinflammatory cytokines, increased lymphocytic density, and epithelial IgG deposits mimicking an autoimmune lesion. Does HBOT have anti-inflammatory tissue effects Several animal studies have revealed that HBOT has potent anti-inflammatory tissue effects with equivalence to diclofenac 20 mg/kg noted in one study using HBOT at 2.4 ATA and 100% oxygen. HBOT has also been shown to decrease the symptoms of advanced arthritis in rats and attenuates the inflammatory response in the peritoneal cavity caused by injected meconium. In addition, one animal study using HBOT at 2.5 ATA showed increased survival and decreased proteinuria, antidoi: 10.1588/medver.2006.03.00110
948 D.A. Rossignol and T. Small/Medical Veritas 3 (2006) 944–951 dsDNA antibody titers, and immune-complex deposition in lupus-prone autoimmune mice. HBOT has also been shown to decrease markers of inflammation including IL-1, IL-6 and TNF-α in humans. Does HBOT help gut issues such as colitis and yeast HBOT has been used in animal studies to improve colitis. Interestingly, thirty sessions of HBOT at 2.0 ATA has been used in humans to achieve remission of ulcerative colitis not responding to conventional therapies. HBOT has also been used extensively and successfully in patients with Crohn’s disease not responding to medical therapy. I think there is more evidence that HBOT works for Crohn’s disease than for many other so-called “approved” conditions. This may be relevant in autistic children given the higher prevalence of gastrointestinal mucosal inflammation described above. HBOT may help with yeast but this is something that needs further study to clarify. What is oxidative stress, and what evidence of this is there in autism Oxidative stress is mainly due to what are called free radicals. Free radicals are highly reactive, unstable molecules that have an unpaired electron in their outer shell. They react with various cellular components including DNA, proteins, lipids and fatty acids and cause DNA damage, mitochondrial malfunction, cell membrane damage and eventually cell death. Free radicals are formed during a variety of biochemical reactions and cellular functions (such as mitochondria metabolism). The steady-state formation of free radicals (which are also called pro-oxidants) is normally balanced by a similar rate of consumption by antioxidants. Oxidative stress results from an imbalance between formation and neutralization of pro-oxidants. Various pathologic processes disrupt this balance by increasing the formation of free radicals in proportion to the available antioxidants (thus, oxidative stress). Examples of increased free radical formation are immune cell activation, inflammation, ischemia, infection, cancer and so on. Free radical formation and the effect of these toxic molecules on cell function (which can result in cell death) are collectively called “oxidative stress.” Antioxidants are molecules or compounds that act as free radical scavengers. Most antioxidants are electron donors and react with the free radicals to form innocuous end products such as water. These antioxidants bind and inactivate the free radicals. Thus, antioxidants protect against oxidative stress and prevent damage to cells. By definition, oxidative stress results when free radical formation is unbalanced in proportion to the protective antioxidants. There are many examples of antioxidants: Intracellular enzymes: superoxide dismutase (SOD), glutathione peroxidase Endogenous molecules or molecules normally found in the body: glutathione (GSH), sulfhydryl groups, alpha-lipoic acid, Coenzyme Q10 Essential nutrients: vitamin C, vitamin E, selenium, N-acetyl cysteine (NAC) Dietary compounds: such as bioflavonoids All cells have intracellular antioxidants (such as superoxide dismutase and glutathione) which are very important in protecting all cells from oxidative stress at all times. Glutathione is very important as an intracellular antioxidant. GSH has been found to be low in many disease states indicating oxidative stress and inadequate antioxidant activity to “keep up” with the free radicals. Recent studies have shown that autistic children have evidence of increased oxidative stress including lower serum glutathione levels. One study demonstrated that autistic children had increased red blood cell nitric oxide, which is a known reactive free radical and is toxic to the brain. Jill James recently showed that total serum glutathione levels were 46% lower and oxidized (or the bad form of) glutathione was 72% higher in autistic children when compared to neurotypical controls. This led to decreased antioxidant ability in these autistic children. Lower serum antioxidant enzyme, antioxidant nutrient, and glutathione levels, as well as higher pro-oxidants have been found in multiple studies of autistic children. Furthermore, treatment with anti-oxidants has been shown to raise the levels of reduced glutathione in the serum of autistic children and appears to improve symptoms. Does HBOT have any effect on this Multiple studies have shown neutral effects on oxidative stress with HBOT use. In one study on horse platelets, measures of oxidative stress were not increased after HBOT; in fact, a rise in the antioxidant enzyme superoxide dismutase (SOD) was found 24 hours after HBOT without a fall in glutathione levels. In another study on dogs, following 18 minutes of complete cerebral ischemia, HBOT at 2.0 ATA reduced brain damage without increasing oxidative stress. Furthermore, in a rat model of reperfusion, HBOT extended skin flap life without evidence of oxidative stress. In addition, numerous studies have shown improvements in oxidative stress with HBOT including increased production of antioxidants and antioxidant enzymes and decreased markers of oxidative stress such as malondialdehyde. An improvement in the survival rate of skin flaps and an increase in SOD levels were found in one study when rats were exposed to hyperbaric oxygen at 2.0 ATA. In another study, HBOT at 2.5 ATA induced the production of antioxidants and decreased malondialdehyde levels in rats. Furthermore, in a study of rats with pancreatitis, HBOT at 2.5 ATA decreased oxidative stress markers including malondialdehyde, and increased the levels of the antioxidant enzymes glutathione peroxidase and SOD. HBOT has also been shown to acutely raise the levels of reduced glutathione in the plasma and lymphocytes of some humans after just one treatment session at 2.5 ATA. Finally, ischemiareperfusion injuries usually cause oxidative stress through decreases in glutathione levels and activities of catalase and SOD. However, in one rat study of ischemia, pretreatment with 1-3 doses of HBOT caused an increase in liver glutathione and SOD levels and protected against liver injury; control animals not receiving HBOT actually had drops in glutathione and antioxidant enzyme levels and had liver damage associated with this. doi: 10.1588/medver.2006.03.00110
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