Advances in Autism Research
compiled by Teresa Binstock for
Autism Research Institute
April 2008

Noteworthy Treatments
That Help Some Autistic Children
 

One-size-fits-all is a notion thoroughly inapplicable for evalutating and treating autistic children. According to parents and clinicians, each of the treatments listed herein helps some autistic children. Furthermore, parents, researchers, and clinicians are encouraged to study the parent ratings of treatment efficacy, data compiled by the Autism Research Institute (1).
 

1. Parent Ratings of Behavioral Effects of Biomedical Interventions
compiled by Autism Research Institute and updated periodically
http://www.autismwebsite.com/ARI/treatment/form34q.htm

Caterories include pharmaceuticals; non-drug interventions including supplements, and special diets. No single treatment helps all autistic children. Notice the ratio of improved/worsened in regard to each treatment.

2. HBOT: Hyperbaric Oxygen Therapy: Physican and autism-parent Dan Rossignol, M.D., and colleagues have published several peer-reviewed articles about HBOT in regard to autistic children.

2a. The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study

Rossignol DA et al.
BMC Pediatr. 2007 Nov 16;7:36.
http://www.biomedcentral.com/1471-2431/7/36

BACKGROUND: Recently, hyperbaric oxygen therapy (HBOT) has increased in popularity as a treatment for autism. Numerous studies document oxidative stress and inflammation in individuals with autism; both of these conditions have demonstrated improvement with HBOT, along with enhancement of neurological function and cognitive performance. In this study, children with autism were treated with HBOT at atmospheric pressures and oxygen concentrations in current use for this condition. Changes in markers of oxidative stress and inflammation were measured. The children were evaluated to determine clinical effects and safety. METHODS: Eighteen children with autism, ages 3-16 years, underwent 40 hyperbaric sessions of 45 minutes duration each at either 1.5 atmospheres (atm) and 100% oxygen, or at 1.3 atm and 24% oxygen. Measurements of C-reactive protein (CRP) and markers of oxidative stress, including plasma oxidized glutathione (GSSG), were assessed by fasting blood draws collected before and after the 40 treatments. Changes in clinical symptoms, as rated by parents, were also assessed. The children were closely monitored for potential adverse effects. RESULTS: At the endpoint of 40 hyperbaric sessions, neither group demonstrated statistically significant changes in mean plasma GSSG levels, indicating intracellular oxidative stress appears unaffected by either regimen. A trend towards improvement in mean CRP was present in both groups; the largest improvements were observed in children with initially higher elevations in CRP. When all 18 children were pooled, a significant improvement in CRP was found (p = 0.021). Pre- and post-parental observations indicated statistically significant improvements in both groups, including motivation, speech, and cognitive awareness (p < 0.05). No major adverse events were observed. CONCLUSION: In this prospective pilot study of children with autism, HBOT at a maximum pressure of 1.5 atm with up to 100% oxygen was safe and well tolerated. HBOT did not appreciably worsen oxidative stress and significantly decreased inflammation as measured by CRP levels. Parental observations support anecdotal accounts of improvement in several domains of autism. However, since this was an open-label study, definitive statements regarding the efficacy of HBOT for the treatment of individuals with autism must await results from double-blind, controlled trials. TRIAL REGISTRATION: clinicaltrials.gov NCT00324909.
    PMID: 18005455

2b. Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism

Rossignol DA.
Med Hypotheses. 2007;68(6):1208-27. Epub 2006 Dec 4.

Autism is a neurodevelopmental disorder currently affecting as many as 1 out of 166 children in the United States. Numerous studies of autistic individuals have revealed evidence of cerebral hypoperfusion, neuroinflammation and gastrointestinal inflammation, immune dysregulation, oxidative stress, relative mitochondrial dysfunction, neurotransmitter abnormalities, impaired detoxification of toxins, dysbiosis, and impaired production of porphyrins. Many of these findings have been correlated with core autistic symptoms. For example, cerebral hypoperfusion in autistic children has been correlated with repetitive, self-stimulatory and stereotypical behaviors, and impairments in communication, sensory perception, and social interaction. Hyperbaric oxygen therapy (HBOT) might be able to improve each of these problems in autistic individuals. Specifically, HBOT has been used with clinical success in several cerebral hypoperfusion conditions and can compensate for decreased blood flow by increasing the oxygen content of plasma and body tissues. HBOT has been reported to possess strong anti-inflammatory properties and has been shown to improve immune function. There is evidence that oxidative stress can be reduced with HBOT through the upregulation of antioxidant enzymes. HBOT can also increase the function and production of mitochondria and improve neurotransmitter abnormalities. In addition, HBOT upregulates enzymes that can help with detoxification problems specifically found in autistic children. Dysbiosis is common in autistic children and HBOT can improve this. Impaired production of porphyrins in autistic children might affect the production of heme, and HBOT might help overcome the effects of this problem. Finally, HBOT has been shown to mobilize stem cells from the bone marrow to the systemic circulation. Recent studies in humans have shown that stem cells can enter the brain and form new neurons, astrocytes, and microglia. It is expected that amelioration of these underlying pathophysiological problems through the use of HBOT will lead to improvements in autistic symptoms. Several studies on the use of HBOT in autistic children are currently underway and early results are promising.
    PMID: 17141962

2c. Hyperbaric oxygen therapy may improve symptoms in autistic children

Rossignol DA, Rossignol LW.
Med Hypotheses. 2006;67(2):216-28.

Autism is a neurodevelopmental disorder that currently affects as many as 1 out of 166 children in the United States. Recent research has discovered that some autistic individuals have decreased cerebral perfusion, evidence of neuroinflammation, and increased markers of oxidative stress. Multiple independent single photon emission computed tomography (SPECT) and positron emission tomography (PET) research studies have revealed hypoperfusion to several areas of the autistic brain, most notably the temporal regions and areas specifically related to language comprehension and auditory processing. Several studies show that diminished blood flow to these areas correlates with many of the clinical features associated with autism including repetitive, self-stimulatory and stereotypical behaviors, and impairments in communication, sensory perception, and social interaction. Hyperbaric oxygen therapy (HBOT) has been used with clinical success in several cerebral hypoperfusion syndromes including cerebral palsy, fetal alcohol syndrome, closed head injury, and stroke. HBOT can compensate for decreased blood flow by increasing the oxygen content of plasma and body tissues and can even normalize oxygen levels in ischemic tissue. In addition, animal studies have shown that HBOT has potent anti-inflammatory effects and reduces oxidative stress. Furthermore, recent evidence demonstrates that HBOT mobilizes stem cells from human bone marrow, which may aid recovery in neurodegenerative diseases. Based upon these findings, it is hypothesized that HBOT will improve symptoms in autistic individuals. A retrospective case series is presented that supports this hypothesis.
    PMID: 16554123

3. SCD: Specific Carbohydrate Diet: Late in her life, Elaine Gottschall made a major contribution to the Autism Research Institute and its Defeat Autism Now! Her work with the SCD and its scientific basis remain important because the SCD helps some autistic children in ways no other therapies achieve.

3a. Breaking the Vicious Cycle: Intestinal Health Through Diet
by Elaine Gottschall, B.A., M.Sc.
http://autismstore.dyndns.org/Books-Breaking_the_Vicious_Cycle.html

The sourcebook for the Specific Carbohydrate Diet (SCD). Gottschall’s work is rightly considered a breakthrough by families whose autistic children were impervious to all other treatments. Based on decades of scholarly research and personal experience... 2004, paperback, 207 pages.

3b. The Specific Carbohydrate Diet: a nutritional regimen that is promoted as treating a variety of chronic and auto-immune disorders including Crohn's...
http://en.wikipedia.org/wiki/Specific_Carbohydrate_Diet

3c. Pecanbread: Kids and the SCD
http://www.pecanbread.com/

4. LOD: Low Oxalate Diets: Susan Costen Owens is a long-time colleague of the Autism Research Institute and a very thorough researcher. She has been calling attention to a subgroup of autistic children with elevated oxalates and has founded an online discussion group wherein acendotal and scientific information is shared (4a).

4a. Trying_Low_Oxalates: A discussion/research group moderated by Susan Owens.
http://health.groups.yahoo.com/group/Trying_Low_Oxalates/

"This group is set up for those wanting to explore the low oxalate diet, and will offer information and support on how to implement this diet and other methods of lowering oxalates. Oxalates are present in much higher quantities in some foods compared to others. This becomes more of a problem when the gut is leaky, because higher quantities of oxalates will be absorbed from foods..."

4b. Estimation of the oxalate content of foods and daily oxalate intake

Holmes RP, Kennedy M.Collaborators (1)
Kidney Int. 2000 Apr;57(4):1662-7.
http://www.nature.com/ki/journal/v57/n4/full/4491506a.html

BACKGROUND: The amount of oxalate ingested may be an important risk factor in the development of idiopathic calcium oxalate nephrolithiasis. Reliable food tables listing the oxalate content of foods are currently not available. The aim of this research was to develop an accurate and reliable method to measure the food content of oxalate. METHODS: Capillary electrophoresis (CE) and ion chromatography (IC) were compared as direct techniques for the estimation of the oxalate content of foods. Foods were thoroughly homogenized in acid, heat extracted, and clarified by centrifugation and filtration before dilution in water for analysis. Five individuals consuming self-selected diets maintained food records for three days to determine their mean daily oxalate intakes. RESULTS: Both techniques were capable of adequately measuring the oxalate in foods with a significant oxalate content. With foods of very low oxalate content (<1.8 mg/100 g), IC was more reliable than CE. The mean daily intake of oxalate by the five individuals tested was 152 +/- 83 mg, ranging from 44 to 352 mg/day. CONCLUSIONS: CE appears to be the method of choice over IC for estimating the oxalate content of foods with a medium (>10 mg/100 g) to high oxalate content due to a faster analysis time and lower running costs, whereas IC may be better suited for the analysis of foods with a low oxalate content. Accurate estimates of the oxalate content of foods should permit the role of dietary oxalate in urinary oxalate excretion and stone formation to be clarified. Other factors, apart from the amount of oxalate ingested, appear to exert a major influence over the amount of oxalate excreted in the urine.
    PMID: 10760101

4c. Genetic and dietary influences on urinary oxalate excretion

Holmes RP, Assimos DG, Goodman HO.
Urol Res. 1998;26(3):195-200.

Several genes contribute to the development of calcium oxalate nephrolithiasis as it is a polygenic disease. To explore the influence of genetic factors on oxalate excretion we have examined the distribution of oxalate excretions in 101 normal individuals who consumed self-selected diets. The distribution was apparently trimodal, consistent with the existence of three classes of oxalate excretors reflecting two allelic genes determining high and low oxalate excretion occurring with frequencies of 0.32 and 0.68 respectively. The pattern of inheritance in eight families was compatible with the expression of a pair of codominant alleles. A comparison of the distribution of excretory classes among the 101 normal individuals with that of 101 calcium oxalate stone formers suggests that high oxalate excretion may be associated with a 4-fold increased risk of stone disease and intermediate excretion with a 1.6-fold increase. Control of dietary factors influencing oxalate excretion apparently improved the discrimination between excretory classes in 17 individuals but the intra-individual variability in oxalate excretion was not reduced in four of nine individuals in whom this parameter was evaluated. More stringent dietary control than that applied in this study may be required before more extensive genotyping of individuals is attempted.
    PMID: 9694602

4d. Effect of calcium intake on urinary oxalate excretion in calcium stone-forming patients

Nishiura JL et al.
Braz J Med Biol Res. 2002 Jun;35(6):669-75.
http://tinyurl.com/48dnwg

Dietary calcium lowers the risk of nephrolithiasis due to a decreased absorption of dietary oxalate that is bound by intestinal calcium. The aim of the present study was to evaluate oxaluria in normocalciuric and hypercalciuric lithiasic patients under different calcium intake. Fifty patients (26 females and 24 males, 41 +/- 10 years old), whose 4-day dietary records revealed a regular low calcium intake (<or=500 mg/day), received an oral calcium load (1 g/day) for 7 days. A 24-h urine was obtained before and after load and according to the calciuria under both diets, patients were considered as normocalciuric (NC, N = 15), diet-dependent hypercalciuric (DDHC, N = 9) or diet-independent hypercalciuric (DIHC, N = 26). On regular diet, mean oxaluria was 30 +/- 14 mg/24 h for all patients. The 7-day calcium load induced a significant decrease in mean oxaluria compared to the regular diet in NC and DIHC (20 +/- 12 vs 26 +/- 7 and 27 +/- 18 vs 32 +/- 15 mg/24 h, respectively, P<0.05) but not in DDHC patients (22 +/- 10 vs 23 +/- 5 mg/24 h). The lack of an oxalate decrease among DDHC patients after the calcium load might have been due to higher calcium absorption under higher calcium supply, with a consequent lower amount of calcium left in the intestine to bind with oxalate. These data suggest that a long-lasting regular calcium consumption <500 mg was not associated with high oxaluria and that a subpopulation of hypercalciuric patients who presented a higher intestinal calcium absorption (DDHC) tended to hyperabsorb oxalate as well, so that oxaluria did not change under different calcium intake.
    PMID: 12045831

4e. Ascorbate increases human oxaluria and kidney stone risk

Massey LK, Liebman M, Kynast-Gales SA.
J Nutr. 2005 Jul;135(7):1673-7.
http://jn.nutrition.org/cgi/content/full/135/7/1673

Currently, the recommended upper limit for ascorbic acid (AA) intake is 2000 mg/d. However, because AA is endogenously converted to oxalate and appears to increase the absorption of dietary oxalate, supplementation may increase the risk of kidney stones. The effect of AA supplementation on urinary oxalate was studied in a randomized, crossover, controlled design in which subjects consumed a controlled diet in a university metabolic unit. Stoneformers (n = 29; SF) and age- and gender-matched non-stoneformers (n = 19; NSF) consumed 1000 mg AA twice each day with each morning and evening meal for 6 d (treatment A), and no AA for 6 d (treatment N) in random order. After 5 d of adaptation to a low-oxalate diet, participants lived for 24 h in a metabolic unit, during which they were given 136 mg oxalate, including 18 mg 13C2 oxalic acid, 2 h before breakfast; they then consumed a controlled very low-oxalate diet for 24 h. Of the 48 participants, 19 (12 stoneformers, 7 non-stoneformers) were identified as responders, defined by an increase in 24-h total oxalate excretion > 10% after treatment A compared with N. Responders had a greater 24-h Tiselius Risk Index (TRI) with AA supplementation (1.10 +/- 0.66 treatment A vs. 0.76 +/- 0.42 treatment N) because of a 31% increase in the percentage of oxalate absorption (10.5 +/- 3.2% treatment A vs. 8.0 +/- 2.4% treatment N) and a 39% increase in endogenous oxalate synthesis with treatment A than during treatment N (544 +/- 131 A vs. 391 +/- 71 micromol/d N). The 1000 mg AA twice each day increased urinary oxalate and TRI for calcium oxalate kidney stones in 40% of participants, both stoneformers and non-stoneformers.
    PMID: 15987848

5. LDN: Low Dose Naltrexone: Jaquelyn McCandless, M.D., has been researching low-dose Naltrexone therapy in regard to intestinal disorders, autism subgroups, and HIV+ individuals. She has an online discussion group focused mainly on LDN efficacy in autistic children.

5a. Autism_LDN:discussion group led by Dr. McCandless
http://groups.yahoo.com/group/Autism_LDN/

"This is a group for discussing and reporting treatment results with LDN (low dose naltrexone) in autism spectrum disorder. This is a new treatment and the goal is to get as much information as possible to help parents decide if this is an appropriate and safe treatment for their autistic child."

5b. The Low Dose Naltrexone Homepage
http://www.lowdosenaltrexone.org/

5c. Low dose naltrexone
Wikipedia
http://en.wikipedia.org/wiki/Low_dose_naltrexone

5d. Low-dose naltrexone therapy improves active Crohn's disease

Smith JP et al.
Am J Gastroenterol. 2007 Apr;102(4):820-8.

Related articles via PubMed
http://tinyurl.com/42sq5v

OBJECTIVES: Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues. In an open-labeled pilot prospective trial, the safety and efficacy of low-dose naltrexone (LDN), an opioid antagonist, were tested in patients with active Crohn's disease. METHODS: Eligible subjects with histologically and endoscopically confirmed active Crohn's disease activity index (CDAI) score of 220-450 were enrolled in a study using 4.5 mg naltrexone/day. Infliximab was not allowed for a minimum of 8 wk prior to study initiation. Other therapy for Crohn's disease that was at a stable dose for 4 wk prior to enrollment was continued at the same doses. Patients completed the inflammatory bowel disease questionnaire (IBDQ) and the short-form (SF-36) quality of life surveys and CDAI scores were assessed pretreatment, every 4 wk on therapy and 4 wk after completion of the study drug. Drug was administered by mouth each evening for a 12-wk period. RESULTS: Seventeen patients with a mean CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased significantly (P= 0.01) with LDN, and remained lower than baseline 4 wk after completing therapy. Eighty-nine percent of patients exhibited a response to therapy and 67% achieved a remission (P < 0.001). Improvement was recorded in both quality of life surveys with LDN compared with baseline. No laboratory abnormalities were noted. The most common side effect was sleep disturbances, occurring in seven patients. CONCLUSIONS: LDN therapy appears effective and safe in subjects with active Crohn's disease. Further studies are needed to explore the use of this compound.
    PMID: 17222320

6. Valtrex and mB12: According to numerous parental reports and summaries from many clinicians - in the context of diet, special training, and child-specific supplement regimens - the therapeutic use of Valtrex and methylcobalamin (mB12, methyl B12) helps some autistic children in ways other therapies do not.  Valtrex is related to acyclovir and has shown efficacy against many but not all strains of some herpes viruses, including HSV1, HSV2, and VZV (chickenpox), with lesser degrees of effectiveness against EBV, HHV6, and possibly CMV. Stan Kurtz is an autism parent who has become a respected colleague of the Autism Research Institute. He has founded a discussion group wherein anecdotal, clinical, and scientific information is shared. Methylcobalin and autism are presented elsewhere in these webpages.

6a. mb12valtrex: a discussion group
Stan Kurtz, moderator
http://health.groups.yahoo.com/group/mb12valtrex/

6b. James Neubrander, M.D. and MethylCobalamin (mB12) links
 http://www.drneubrander.com/page2old.html

6c. Adult-onset temporal lobe epilepsy associated with smoldering herpes simplex 2 infection

Cornford ME, McCormick GF.
Neurology. 1997 Feb;48(2):425-30.

A 40-year-old man with chronic genital herpes simplex infection developed partial complex temporal lobe seizures of insidious onset, with EEG and MRI evidence of a unilateral temporal lobe destructive, atrophic process. Extensive workup did not reveal an infectious etiology. Three years of escalating number and severity of daily seizures with memory loss led to temporal lobectomy. Histologic study revealed active, low-level viral infection in the resected hippocampus and temporal lobe cortex, with immunohistochemical evidence for infection by herpes simplex 2, principally in neurons. In situ hybridization confirmed the presence of herpes simplex virus in neurons. Anticonvulsant-resistant seizure episodes began to recur several times daily soon after surgery, but the addition of acyclovir to the treatment regimen resulted in a substantial reduction in seizure occurrence, maintained for the subsequent 2.5 years.
    PMID: 9040733

6d. Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders

Nicolson GL et al.
J Neurosci Res. 2007 Apr;85(5):1143-8.

We examined the blood of 48 patients from central and southern California diagnosed with autistic spectrum disorders (ASD) by using forensic polymerase chain reaction and found that a large subset (28/48 or 58.3%) of patients showed evidence of Mycoplasma spp. infections compared with two of 45 (4.7%) age-matched control subjects (odds ratio = 13.8, P < 0.001). Because ASD patients have a high prevalence of one or more Mycoplasma spp. and sometimes show evidence of infections with Chlamydia pneumoniae, we examined ASD patients for other infections. Also, the presence of one or more systemic infections may predispose ASD patients to other infections, so we examined the prevalence of C. pneumoniae (4/48 or 8.3% positive, odds ratio = 5.6, P < 0.01) and human herpes virus-6 (HHV-6, 14/48 or 29.2%, odds ratio = 4.5, P < 0.01) coinfections in ASD patients. We found that Mycoplasma-positive and -negative ASD patients had similar percentages of C. pneumoniae and HHV-6 infections, suggesting that such infections occur independently in ASD patients. Control subjects also had low rates of C. pneumoniae (1/48 or 2.1%) and HHV-6 (4/48 or 8.3%) infections, and there were no coinfections in control subjects. The results indicate that a large subset of ASD patients shows evidence of bacterial and/or viral infections (odds ratio = 16.5, P < 0.001). The significance of these infections in ASD is discussed in terms of appropriate treatment. (c) 2007 Wiley-Liss, Inc.
    PMID: 17265454

6e. Acquired reversible autistic syndrome in acute encephalopathic illness in children

DeLong GR, Bean SC, Brown FR 3rd.
Arch Neurol. 1981 Mar;38(3):191-4.

In seeking the neurologic substrate of the autistic syndrome of childhood, previous studies have implicated the medial temporal lobe or the ring of mesolimbic cortex located in the mesial frontal and temporal lobes. During an acute encephalopathic illness, a clinical picture developed in three children that was consistent with infantile autism. This development was reversible. It was differentiated from acquired epileptic aphasia, and the language disorder was differentiated aphasia. One child has rises in serum herpes simplex titers, and a computerized tomographic (CT) scan revealed an extensive lesion of the temporal lobes, predominantly on the left. The other two, with similar clinical syndromes, had normal CT scans, and no etiologic agent was defined. These cases are examples of an acquired and reversible autistic syndrome in childhood, emphasizing the clinical similarities to bilateral medial temporal lobe disease as described in man, including the Klüver-Bucy syndrome seen in postencephalitic as well as postsurgical states.
    PMID: 6162440

6f. Reduction of symptoms by valacyclovir in cytomegalovirus-seropositive individuals with schizophrenia

Dickerson FB et al.
Am J Psychiatry. 2003 Dec;160(12):2234-6.
http://ajp.psychiatryonline.org/cgi/content/full/160/12/2234

OBJECTIVE: The study was an investigation of the effect of the antiviral medication valacyclovir on the symptoms of outpatients with persistent schizophrenia. METHOD: Oral valacyclovir, 1 g twice daily, was administered to 65 outpatients over 16 weeks along with their usual psychiatric medications. Changes in psychiatric symptoms were measured with the Positive and Negative Syndrome Scale and were tested for correlations with antibodies to potentially neurotropic human herpesviruses, as measured by immunoassay before the start of the therapy. RESULTS: There was a significant improvement in the psychiatric symptoms of individuals who were seropositive for cytomegalovirus. Improvement was not associated with antibodies to other herpesviruses or to a range of demographic and clinical variables. CONCLUSIONS: The replication of cytomegalovirus may contribute to the symptoms of schizophrenia in some individuals.
    PMID: 14638597

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