Hashimoto's encephalopathy

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Hashimoto's encephalopathy
Other namesSteroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT)
Affective psychosis, Hashimoto's thyroiditis, and brain perfusion abnormalities.jpg
Brain SPECT transaxial images of a patient afflicted with Hashimoto's encephalopathy.
Specialty Neurology   OOjs UI icon edit-ltr-progressive.svg

Hashimoto's encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a neurological condition characterized by encephalopathy, thyroid autoimmunity, and good clinical response to corticosteroids. It is associated with Hashimoto's thyroiditis, and was first described in 1966. It is sometimes referred to as a neuroendocrine disorder, although the condition's relationship to the endocrine system is widely disputed. It is recognized as a rare disease by the NIH Genetic and Rare Diseases Information Center. [1]

Contents

Up to 2005, almost 200 case reports of this disease were published. Between 1990 and 2000, 43 cases were published. Since that time, research has expanded and numerous cases are being reported by scientists around the world, suggesting that this rare condition is likely to have been significantly undiagnosed in the past. Over 100 scientific articles on Hashimoto's encephalopathy were published between 2000 and 2013. [2]

Signs and symptoms

The onset of symptoms tends to be fairly gradual and to occur over 1-12 years. [ citation needed ]

Symptoms of Hashimoto's encephalopathy may include:[ citation needed ]

Pathogenesis

The mechanism of pathogenesis is not known, but is thought to be an autoimmune disorder, similar to Hashimoto's thyroiditis, as its name suggests.[ citation needed ]

Consistent with this hypothesis, autoantibodies to alpha-enolase have been found to be associated with Hashimoto's encephalopathy. [3] Since enolase is the penultimate step in glycolysis, if it were inhibited (for example by being bound by autoantibodies), one would expect decreased energy production by each cell, leading to resulting atrophy of the affected organ.[ citation needed ]

This would occur most likely through each cell shrinking in size in response to the energy deficit (and/or in extreme situations from some cells dying via either apoptosis or necrosis, depending on location). [4] This may occur as a result of enough ATP not being available to maintain cellular functions - notably, failure of the Na/K ATPase, resulting in a loss of the gradient to drive the Na/Ca antiporter, which normally keeps Ca+
2
out of cells so it does not build to toxic levels that will rupture cell lysosomes leading to apoptosis. An additional feature of a low-energy state is failure to maintain axonal transport via dynein/kinesin ATPases, which in many diseases results in neuronal injury to both the brain and/or periphery. [5]

Pathology

Very little is known about the pathology of Hashimoto's encephalopathy. Post mortem studies of some individuals have shown lymphocytic vasculitis of venules and veins in the brain stem and a diffuse gliosis involving gray matter more than white matter.[ citation needed ]

As mentioned above, autoantibodies to alpha-enolase associated with Hashimoto's encephalopathy have thus far been the most hypothesized mechanism of injury. [3]

Diagnosis

Laboratory and radiological findings

Cerebrospinal fluid findings:[ citation needed ]

Thyroid hormone abnormalities are common (>80% of cases): [ citation needed ]

Thyroid antibodies – both antithyroid peroxidase antibodies (anti-TPO, antithyroid microsomal antibodies, anti-M) and antithyroglobulin antibodies (anti-Tg) – in the disease are elevated, but their levels do not correlate with the severity.[ citation needed ]

Electroencephalogram studies, while almost always abnormal (98% of cases), are usually not diagnostic. The most common findings are diffuse or generalized slowing or frontal intermittent rhythmic delta activity. Prominent triphasic waves, focal slowing, epileptiform abnormalities, and photoparoxysmal and photomyogenic responses may be seen. [6]

A study from 2006 suggested the following diagnostic criteria: [7]

  1. Encephalopathy with cognitive impairment and at least one of the following features:
    • neuropsychiatric symptoms (e.g. hallucination, delusion or paranoia)
    • Myoclonus, generalised tonic-clonic or partial seizures
    • focal-neurological deficits
  2. Elevated titres of thyroid tissue antibodies (TPO-ab or microsomal)
  3. Euthyroidism (potentially achieved by treatment with L-T4 or L-T3) or mild hypothyroidism with TSH concentration below 20 mIU/L
  4. No evidence for infectious, toxic, metabolic or neoplastic processes in blood, urine or CSF analyses
  5. No serological evidence for neuronal antibodies (e.g. voltage-gated calcium channel, voltage-gated potassium channel, or other currently recognized paraneoplastic antibodies) to support another diagnosis
  6. In imaging studies no evidence for vascular, neoplastic or structural lesions that might explain the symptoms
  7. Complete or nearly complete remission after initiation of glucocorticoid therapy.

Definition

A relapsing encephalopathy occurs in association with autoimmune (Hashimoto's or Ord's thyroiditis), with high titers of antithyroid antibodies. Clinically, the condition may present one or more symptoms. Onset is often gradual and may go unnoticed by the patient and close associates to the patients. Symptoms sometimes resolve themselves within days to weeks, leaving a patient undiagnosed. For many other patients, the condition may result in ongoing problems with a variety of manifestations, often confusing clinicians due to the diffuse nature of symptoms.[ citation needed ]

Differential diagnosis

Treatment

Because most patients respond to corticosteroids or immunosuppressant treatment, this condition is now also referred to as steroid-responsive encephalopathy.[ citation needed ]

Initial treatment is usually with oral prednisone (50–150 mg/day) or high-dose intravenous methylprednisolone (1 g/day) for 3–7 days. Thyroid hormone treatment is also included if required. Failure of some patients to respond to this first-line treatment has produced a variety of alternative treatments, including azathioprine, cyclophosphamide, chloroquine, methotrexate, periodic intravenous immunoglobulin, and plasma exchange. No controlled trials have been conducted, so the optimal treatment is not known.[ citation needed ]

Seizures, if present, are controlled with typical antiepileptic agents.[ citation needed ]

Prognosis

Duration of treatment is usually between 2 and 25 years. Earlier reports suggested that 90% of cases stay in remission after discontinuation of treatment, but this is at odds with more recent studies, which suggest that relapse commonly occurs after initial high-dose steroid treatment. [7] [8] Left untreated, this condition can result in coma and death.[ citation needed ]

Epidemiology

The prevalence has been estimated to be 2.1/100,000 [9] with a male-to-female ratio of 1:4. The mean age of onset is 44 with 20% of cases presenting before the age of 18 years. Most reported cases occur during the patient's fifth decade of life.[ citation needed ]

History

The first case of HE was described by Brain et al. in 1966. [10] The patient was a 48-year-old man with hypothyroidism, multiple episodes of encephalopathy, stroke-like symptoms, and Hashimoto's thyroiditis confirmed by elevated antithyroid antibodies.

Alternative names

Related Research Articles

<span class="mw-page-title-main">Hyperthyroidism</span> Thyroid gland disease that involves an overproduction of thyroid hormone

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon but life-threatening complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature; this often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

<span class="mw-page-title-main">Graves' disease</span> Autoimmune endocrine disease

Graves' disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 30% of people with the condition develop eye problems.

<span class="mw-page-title-main">Hypothyroidism</span> Endocrine disease

Hypothyroidism is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goitre. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.

<span class="mw-page-title-main">Hashimoto's thyroiditis</span> Autoimmune disease

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarge, forming a painless goiter. Some people eventually develop hypothyroidism with accompanying weight gain, fatigue, constipation, depression, hair loss, and general pains. After many years the thyroid typically shrinks in size. Potential complications include thyroid lymphoma. Furthermore, because it is common for untreated patients of Hashimoto's to develop hypothyroidism, further complications can include, but are not limited to, high cholesterol, heart disease, heart failure, high blood pressure, myxedema, and potential pregnancy problems.

Ord's thyroiditis is a common form of thyroiditis, an autoimmune disease where the body's own antibodies fight the cells of the thyroid.

An autoantibody is an antibody produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases are associated with such antibodies.

<span class="mw-page-title-main">Thyroid disease</span> Medical condition

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

<span class="mw-page-title-main">Thyroiditis</span> Medical condition

Thyroiditis is the inflammation of the thyroid gland. The thyroid gland is located on the front of the neck below the laryngeal prominence, and makes hormones that control metabolism.

<span class="mw-page-title-main">De Quervain's thyroiditis</span> Medical condition

De Quervain's thyroiditis, also known as subacute granulomatous thyroiditis or giant cell thyroiditis, is a member of the group of thyroiditis conditions known as resolving thyroiditis. People of all ages and genders may be affected.

Subacute lymphocytic thyroiditis is a form of thyroiditis. Subacute lymphocytic thyroiditis may occur at any age and is more common in females. A variant of subacute lymphocytic thyroiditis occurs postpartum: postpartum thyroiditis. Both of these entities can be considered subtypes of Hashimoto's thyroiditis and have an autoimmune basis. Anti-thyroid antibodies are common in all three and the underlying histology is similar. This disorder should not be confused with de Quervain's thyroiditis which is another form of subacute thyroiditis.

<span class="mw-page-title-main">Graves' ophthalmopathy</span> Medical condition

Graves’ ophthalmopathy, also known as thyroid eye disease (TED), is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and bulging eyes (exophthalmos). It occurs most commonly in individuals with Graves' disease, and less commonly in individuals with Hashimoto's thyroiditis, or in those who are euthyroid.

Postpartum thyroiditis refers to thyroid dysfunction occurring in the first 12 months after pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. According to the National Institute of Health, postpartum thyroiditis affects about 8% of pregnancies. There are, however, different rates reported globally. This is likely due to the differing amounts of average postpartum follow times around the world, and due to humans' own innate differences. For example, in Bangkok, Thailand the rate is 1.1%, but in Brazil it is 13.3%. The first phase is typically hyperthyroidism. Then, the thyroid either returns to normal or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring lifelong treatment.

<span class="mw-page-title-main">Limbic encephalitis</span> Inflammation involving the limbic system in the brain

Limbic encephalitis is a form of encephalitis, a disease characterized by inflammation of the brain. Limbic encephalitis is caused by autoimmunity: an abnormal state where the body produces antibodies against itself. Some cases are associated with cancer and some are not. Although the disease is known as "limbic" encephalitis, it is seldom limited to the limbic system and post-mortem studies usually show involvement of other parts of the brain. The disease was first described by Brierley and others in 1960 as a series of three cases. The link to cancer was first noted in 1968 and confirmed by later investigators.

<span class="mw-page-title-main">Autoimmune thyroiditis</span> Medical condition

Autoimmune thyroiditis, also known as Hashimoto's disease and chronic lymphocytic thyroiditis, is a chronic disease occurring in the thyroid, the butterfly-shaped endocrine gland in the anterior neck. This disease occurs when the body interprets components of the thyroid glands as threats, therefore producing special antibodies that target the thyroid's cells or proteins, thereby destroying it. It most commonly presents as hypothyroidism with or without a goiter. It is the most common cause of hypothyroidism in iodine-sufficient areas of the world.

<span class="mw-page-title-main">Anti-NMDA receptor encephalitis</span> Rare disease which results in brain inflammation

Anti-NMDA receptor encephalitis is a type of brain inflammation caused by antibodies. Early symptoms may include fever, headache, and feeling tired. This is then typically followed by psychosis which presents with false beliefs (delusions) and seeing or hearing things that others do not see or hear (hallucinations). People are also often agitated or confused. Over time, seizures, decreased breathing, and blood pressure and heart rate variability typically occur. In some cases, patients may develop catatonia.

Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.

Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Anti-sodium/iodide (Anti–Na+/I) symporter antibodies are a more recent discovery and their clinical relevance is still unknown. Graves' disease and Hashimoto's thyroiditis are commonly associated with the presence of anti-thyroid autoantibodies. Although there is overlap, anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and activating TRAb's are most commonly associated with Graves' disease. Thyroid microsomal antibodies were a group of anti-thyroid antibodies; they were renamed after the identification of their target antigen (TPO).

<span class="mw-page-title-main">Thyroid's secretory capacity</span>

Thyroid's secretory capacity is the maximum stimulated amount of thyroxine that the thyroid can produce in a given time-unit.

Autoimmune encephalitis (AIE) is a type of encephalitis, and one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. The clinical manifestations include behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures.

Anti-VGKC-complex encephalitis are caused by antibodies against the voltage gated potassium channel-complex (VGKC-complex) and are implicated in several autoimmune conditions including limbic encephalitis, epilepsy and neuromyotonia.

References

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  2. "Scientific Research/Articles – Articles Published in 2014". hesaonline.org. Archived from the original on 2013-07-08.
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  4. Shigeomi Shimizu2, Yutaka Eguchi, Wataru Kamiike, Yuko Itoh, Jun-ichi Hasegawa, Kazuo Yamabe, Yoshinori Otsuki, Hikaru Matsuda, and Yoshihide Tsujimoto The First Department of Surgery. Department of Medical Genetics. BiomedicalResearch Center. Osaka University Medical School, 2-2 Yatnadfioka, Sunti 56.5. Japan, and Depannient of Anatomy and Biology. Osaka Medical College. Japan.| url=http://cancerres.aacrjournals.org/content/56/9/2161.full.pdf
  5. Ihejirika DF. PASS Program Course Notes: USMLE Preparation. Lulu.com; 2014.
  6. Li, Jie; Li, Fengzhen (2019-05-08). "Hashimoto's Encephalopathy and Seizure Disorders". Frontiers in Neurology. 10: 440. doi: 10.3389/fneur.2019.00440 . ISSN   1664-2295. PMC   6517482 . PMID   31133960.
  7. 1 2 Castillo P, Woodruff B, Caselli R, et al. (February 2006). "Steroid-responsive encephalopathy associated with autoimmune thyroiditis". Archives of Neurology. 63 (2): 197–202. doi: 10.1001/archneur.63.2.197 . PMID   16476807.
  8. Flanagan EP, McKeon A, Lennon VA, et al. (October 2010). "Autoimmune dementia: clinical course and predictors of immunotherapy response". Mayo Clinic Proceedings. 85 (10): 881–97. doi:10.4065/mcp.2010.0326. PMC   2947960 . PMID   20884824.
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Further reading