Those who have HE are all too familiar with the significance of thyroid antibody levels. This newly published article discusses the clinical relevance of thyroid antibodies in pregnancy:
Thyroid Autoantibodies in Pregnancy: Their Role, Regulation and Clinical Relevance
Full text available at:
We added the following article to the Case Studies and Research section of the site today:
Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens
Yael Hacohen, Sukhvir Wright, Patrick Waters, Shakti Agrawal, Lucinda Carr, Helen Cross, Carlos De Sousa, Catherine DeVile, Penny Fallon, Rajat Gupta, Tammy Hedderly, Elaine Hughes, Tim Kerr, Karine Lascelles, Jean-Pierre Lin, Sunny Philip, Keith Pohl, Prab Prabahkar, Martin Smith, Ruth Williams, Antonia Clarke, Cheryl Hemingway, Evangeline Wassmer, Angela Vincent, Ming J Lim
J Neurol Neurosurg Psychiatry. 2012 Nov 22.
Although this article is not specific to HE, the research on which it reports concerns autoimmune encephalopathies, of which HE is a type.
Dr. Dalmau, one of the leading international authorities on autoimmune encephalopathy, coauthored an article that appeared in Psychiatric Times in March 2010 titled “Psychiatric Presentation of Autoimmune Encephalopathies.” As readers of this site may know all too well, many HE patients are misdiagnosed with psychiatric disorders by treaters unfamiliar with autoimmune encephalopathy, Here are excerpts from the article:
“While a biological basis for numerous psychiatric illnesses has become increasingly appreciated, few mechanistic hypotheses have gripped psychiatric researchers as strongly as an autoimmune basis for behavioral abnormalities. Perhaps the most extreme example of autoimmune phenomena that result in psychiatric changes can be found in antibody-mediated limbic encephalitis. In these syndromes, autoantibodies interfere either directly or indirectly with neuronal function, the outcome of which is striking cognitive and behavioral changes often accompanied by severe neurological symptoms…
Another group of autoimmune-mediated disorders results in limbic encephalitis but is not usually associated with an underlying neoplasm….
Hashimoto encephalopathy is an autoimmune limbic encephalitis characterized by high levels of antithyroid antibodies in serum, although usually without clinically relevant thyroid dysfunction. Patients are women in their 40s to 50s who present with waxing and waning cognitive impairment, such as memory dysfunction and speech abnormalities. Psychiatric disturbances are extremely frequent as well and include disorganized behavior with poor self-care, psychosis (often with visual hallucinations), changes in mood or personality, and sleep dysfunction.
Seizures are often associated with Hashimoto encephalopathy, but unique to this syndrome are fluctuating stroke-like episodes that span multiple different vascular territories. Other neurological symptoms such as myoclonus, tremor, ataxia, and headache have been reported in one-third of cases.
Thyroid peroxidase antibodies assist in the diagnosis of Hashimoto encephalopathy. This finding is reported in nearly all cases. However, a well-defined pathogenic role for these antibodies has not been established, and the antibodies are highly prevalent in the general population, which complicates diagnosis based on antibodies alone. Results of brain MRI scans are normal 50% of the time, and changes are nonspecific, even when abnormal.
Finally, another critical feature that supports the diagnosis of this disorder is the response to treatment: Hashimoto encephalopathy is almost uniformly responsive to a prolonged course of high-dose corticosteroids. On average, treatment continues 4 to 6 weeks before clinical recovery starts and corticosteroid taper is initiated.Multiple studies have described relapse of symptoms with early cessation of therapy, which highlights the need to continue therapy beyond simply the appearance of improvement. …
An autoimmunological basis for psychiatric disturbances such as schizophrenia and depression has been theorized for decades.55,56 The characterization of multiple encephalopathies as autoimmune in nature provides a foothold for a greater under-standing of how antibody-mediated syndromes can manifest with behavioral changes. Paraneoplastic limbic encephalitis, nonparaneoplastic limbic encephalitis, and encephalitis that involves glutamate receptors represent a heterogeneous group of disorders with common pathogenic mechanisms.
The diverse cognitive and behavioral symptoms in these disorders emphasize the need for psychiatrists to consider such syndromes in their differential diagnosis for patients with atypical behavioral changes. Moreover, given the potential for a significant role in recognition of these neurologically complex disorders, psychiatrists should become familiar with diagnostic criteria and appropriate therapeutic options.”
We’ve had quite the discussions on the forum lately about Low Dose Naltrexone (LDN) and if it is a viable treatment for HE. 2 people requested the “kid’s” version so they can better understand. So here’s my attempt at an explanation. Just so you know, I did do copious amounts of research and run this by my neurologist and he believes I am correct. So here we go…
LDN has 2 primary functions in the possible benefit for those suffering from HT/HE.
1. LDN works by blocking opioid receptors, (example seen in the picture 2 where it has accepted opioids into the receptors) which in turn release a bunch of endorphins. But in diseases like HE and HT that have shown no evidence of a lack of endorphins, endorphins just make you feel good. Picture 1 just kinda gives you a better view of the brain. So LDN would kinda be like a placebo effect if it were not (possibly) for number two…
2. LDN blocks ‘toll-like receptor 4 (TLR4)’ on microglia. See picture 3. First of all, normally microglia are the first and the main form of active immune defense in the CNS. They’re like the soldiers on the front line. Glial cells form myelin, supply nutrients and oxygen to neurons and modulate neurotransmission. It has been shown that dysfunctional microglia play a big role in neurodegenerative disorders. See the right side of picture 3.
Ok, I hope this clears things up a little better for people. The primary benefit, I believe is the blockage of the TLR4 receptor so the microglia can’t become messed up and cause neurodegeneration.
Here’s a video someone posted: (skip past the middle about 42:45 for the LDN brain stuff)
Research has indicated vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. I have found a lot of data linking deficient vitamin D levels to patients with autoimmune diseases. Although I could find almost no reputable information linking it to HE, the statistics from the HELPS forum were good enough for me to make a reasonable connection.
I sent out an email to the HELPS forum requesting what vitamin deficiencies we have. Of the 8 people who responded (including myself), 7 reported vitamin D deficiency. The 8th person reported multiple deficiencies, but did not explicitly report vitamin D deficiency. There are also other vitamin deficiencies noted in the below table.
I found many case studies linking vitamin D deficiency to autoimmune diseases such as MS, Grave’s Disease, Hashimoto’s Thyroiditis, arthritis and diabetes. First, I’ll start with the case studies on vitamin D deficiency with cognitive impairment. This seems like it could be related to HE.
Vitamin D Impact on Cognitive Impairment
The 2010 case study, 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services, sought to examine the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). There were 318 participants with a mean age of 73.5, mostly women. There was a higher prevalence of dementia among patients with 25(OH)D insufficiency (<20 ng/mL). The conclusion was that a vitamin D insufficiency was associated with more than twice the odds of all-cause dementia, Alzheimer disease, stroke, and MRI indicators of CVD. “These findings suggest a potential vasculoprotective role of vitamin D.”
The 2010 case study, Association of vitamin D deficiency with cognitive impairment in older women, sought to examine the association between serum 25(OH)D (25-HydroxyvitaminD) deficiency and cognitive impairment while taking confounders (like age, body, chronic disease, physical activity, etc.) into account. The groups of women (752 subjects over age 75) were divided according to their serum 25(OH)D concentrations either being deficient (<10 ng/mL) or non-deficient (>10 ng/mL). The conclusions found that 25-Hydroxyvitamin D deficiency was associated with cognitive impairment in these subjects.
Vitamin D Impact on Multiple Sclerosis
The 2004 case study, Vitamin D intake and the incidence of multiple sclerosis, sought to indicate a protective effect of vitamin D on the risk of MS. The study compared women at relative risk for developing MS. Intake of vitamin D supplements was inversely associated with the risk of MS, compared to no supplemental intake. Although purely statistical, “these results support a protective effect of vitamin D intake on risk of developing MS.”
In the 2004 paper, Vitamin D supplementation in the Fight Against Multiple Sclerosis, indicates “In summary, vitamin D hormone has numerous effects on the immune system and acts within the CNS. All of these effects have the combined result of significantly reducing inflammatory autoimmune reactions from occurring and they readily explain the impressive correlation between MS prevalence and vitamin D supply and why vitamin D hormone is so effective in suppressing a variety of animal autoimmune diseases including EAE (animal MS).”
Other research has shown that the levels of vitamin D in the body can predict periods of low or high MS disease activity, so the higher the vitamin D, the lower the disease activity.
Vitamin D and Graves’ Disease and Hashimoto’s Thyroiditis
The 2002 study, A Polymorphism with the Vitamin d-Binding Protein Gene Is Associated with Graves’ Disease nut Not with Hashimoto’s Thyroiditis, investigated the polymorphic vitamin D-binding protein (DBP) gene, which greatly facilitates vitamin D actions, with association with thyroid autoimmunity. They found, “allelic variants of the DBP gene confer susceptibility to Graves’ disease but not to Hashimoto’s thyroiditis in our population. These findings support a role of the vitamin D endocrine system in thyroid autoimmunity.”
Their study also indicated, “There is evidence for a role of the vitamin D endocrine system in the pathogenesis of thyroid autoimmunity. 1,25(OH)2 D3 prevents autoimmune thyroiditis in animal models. In humans, serum levels of 1,25(OH)2 D3 were found to be significantly lower in autoimmune than in nonautoimmune hyperthyroidism.”
A 2006 study, Vitamin D receptor gene polymorphisms are associated with risk of Hashimoto’s thyroiditis in Chinese patients in Taiwan, investigate if single nucleotide polymorphisms (SNPs) of the Vitamin D receptor (VDR) are associated with HE patients. “The results revealed a significant difference between HT patients and normal controls in VDR SNP and a statistic correlation between VDR-FokI polymorphisms and HT formation. It could be concluded that patients who carry the C/C homozygote of the VDR-FokI gene polymorphism in exon 2 may have a higher risk of developing HT in Chinese patients in Taiwan.”
Vitamin D and Environmental Factors
The 2000 case study, Vitamin D and Autoimmunity: Is Vitamin D Status an Environmental Factor Affecting Autoimmune Disease Prevalence?, indicates “Geographical areas with low supplies of vitamin D (for example Scandinavia) correlate with regions with high incidences of multiple sclerosis, arthritis, and diabetes. The active form of vitamin D has been shown to suppress the development of autoimmunity in experimental animal models. Furthermore, vitamin D deficiency increases the severity of at least experimental autoimmune encephalomyelitis (mouse multiple sclerosis).”
Lack of Vitamin D and Aggravating Immune Response
A 2009 article, Vitamin D Deficiency Related To Increased Inflammation In Healthy Women, indicates “The findings reveal that low vitamin D levels negatively impact inflammation and immune response, even in healthy women,” said Catherine Peterson, assistant professor in the MU College of Human Environmental Sciences. “Increased inflammation normally is found in people with obesity or chronic diseases; a small decrease in vitamin D levels may aggravate symptoms in people who are sick.”
Ending thoughts on this post:
Although I couldn’t find any published information directly linking Vitamin D deficiency to HE, it is clear that it plays a role in many other autoimmune diseases. One question is what role the deficiency plays in the cause or result of the disease.
The case studies have shown from a symptomatic level that Vitamin D deficiency is linked to cognitive impairment and inflammatory responses. Increasing /supplementing Vitamin D in the patient has been shown to help reduce and alleviate symptoms, and in animals has even been shown to suppress the development of autoimmunity.
Out of the 8 people who responded in the HELPS group, 7 had confirmed Vitamin D deficiency (the 8th is unconfirmed). Although it would have been nice for more to respond, I think it is clear Vitamin D deficiency is playing a role in our disease.
Anyone who is Vitamin D deficient, should consult their doctor to be put on supplementation.