Hashimoto's Encephalopathy: How Doctors Diagnose And Treat This Rare Disorder

Hashimoto encephalopathy (HE) is a rare inflammatory condition first identified in a patient diagnosed with Hashimoto's thyroiditis. Although researchers estimate fewer than 1,000 people in the US are diagnosed with this often perplexing neurological disorder, many experts suspect the condition is often overlooked or misdiagnosed.¹

Why? Because the signs and symptoms of Hashimoto's encephalopathy mimic several other potentially serious health complications.

Diagnosing Hashimoto's encephalopathy requires a detailed patient history, a thorough clinical evaluation, and detectable levels of a specific antibody produced in the body. Although its exact cause is not entirely understood, most people diagnosed with this autoimmune disorder respond favorably to conventional treatments.

What is Hashimoto's disease?

Hashimoto's disease is a relatively common autoimmune disorder affecting the thyroid, the butterfly-shaped gland located just beneath your Adam's apple. Although the cause of Hashimoto's is not entirely clear, researchers believe a combination of environmental and genetic factors trigger the production of antibodies that attack healthy tissues.²

Having lupus, Sjögren syndrome, rheumatoid arthritis, or any other autoimmune disorder increases your risk of developing thyroid-damaging antibodies.

In its earliest stages, Hashimoto's disease does not cause symptoms. But as the condition progresses and thyroid function declines, a person living with Hashimoto's disease might experience any number of troubling symptoms, including weight gain, difficulty concentrating, thinning hair, menstrual irregularities, and fatigue.

Once the disease causes a significant decrease in hormone production (hypothyroidism), doctors typically prescribe a synthetic replacement. Although Hashimoto's disease is linked to Hashimoto's encephalopathy, they are not the same.

What is encephalopathy?

Encephalopathy is a term used by the medical community to refer to a group of disorders that alter brain structure or interfere with normal brain function. Many potential causes include chemical exposure, alcohol abuse, liver failure, and inadequate nutrition. Some types of encephalopathy are reversible — others are not.

For example, the symptoms of encephalopathy caused by a traumatic head injury or lack of oxygen to the brain are often permanent. But when encephalopathy is caused by metabolic dysfunction, infection, exposure to toxins, or Hashimoto's disease, its symptoms generally improve with an accurate diagnosis and the appropriate treatment.

What causes Hashimoto's encephalopathy?

When the disorder was first identified in the mid-1960s, researchers believed the elevated antithyroid antibodies produced by the immune systems of people diagnosed with Hashimoto's disease could also target the brain. But upon further investigation, there's little, if any, evidence to support that initial hypothesis.³

The research also shows that most people diagnosed with Hashimoto's encephalopathy have no symptoms of Hashimoto's thyroiditis.

With so many researchers believing the initial correlation between Hashimoto's disease and Hashimoto's encephalopathy is coincidental, some feel the "Hashimoto's" should be dropped in favor of a label that might better represent the disorder's primary cause. 

Many medical professionals believe a differential diagnosis of steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) or encephalopathy associated with autoimmune thyroid disease (EAATD) is a more accurate representation of its autoimmune pathology.

Who is most at risk of developing this disorder?

For now, "steroid-responsive encephalopathy associated with autoimmune thyroid thyroiditis" and "Hashimoto's encephalopathy" are used interchangeably. But elevated antithyroid antibodies are considered a marker of the condition rather than the cause of its progression.

Researchers estimate this rare condition affects approximately two out of every 100,000 people at some point in their lives.⁴

Based on what we know about the disorder so far, 75% of people diagnosed with Hashimoto’s encephalopathy are women, and the condition can strike at any age. However, children are rarely affected, and most cases occur between the ages of 40 and 55.⁵ ⁶

Although thyroid disease is often considered a contributing factor, up to 60% of people diagnosed with Hashimoto's encephalopathy have no history of thyroid issues before the onset of their initial symptoms.⁷

What are the signs and symptoms of Hashimoto's encephalopathy?

Hashimoto's encephalopathy can cause brain inflammation and blood vessel damage (autoimmune cerebral vasculitis). For some, the condition strikes suddenly and produces stroke-like symptoms. For others, Hashimoto's encephalopathy causes progressive cognitive decline or episodes of neuropsychiatric symptoms that resolve on their own but return. 

Based on a review of the clinical findings, antithyroid antibody levels have no bearing on disease severity, and those affected can experience any combination of the following symptoms:

• Lack of muscle control, difficulty walking, or tremors

• Sleep disturbances, stupor, or coma

• Hallucinations, psychosis, or delusions

• Personality changes or emotional instability

• Depression, anxiety, malaise, or fatigue

• Difficulty with memory, concentration, or signs of dementia

• Uncharacteristically jerky movements (myoclonus)

• Seizures, speech problems, or cerebral ischemia (lack of blood to the brain)

How is Hashimoto's encephalopathy diagnosed?

The many misconceptions about Hashimoto's encephalopathy and the limited number of case studies can make diagnosing the disorder particularly challenging for doctors. By definition, a diagnosis of Hashimoto's encephalopathy requires detectable levels of antithyroid antibodies. 

But with antithyroid antibodies relatively common in the general population and no distinct correlation between antithyroid antibody levels and symptom severity, medical professionals don't have the luxury of ordering a single test to reach a rapid conclusion. 

The condition cannot be accurately diagnosed without ruling out several other possible explanations with the following tests.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) uses a strong magnetic field and radio waves to obtain a detailed image of tissues and organs. An intravenous contrast fluid is often used to enhance visibility. Patients are placed inside a tube-like scanner, and a technician remains in contact during the test through an intercom system. 

This imaging helps rule out the possibility of structural issues, abnormal growths, fluid leaks, and other potential causes of symptoms affecting the brain. In most (but not all) cases, the detailed brain scans of people ultimately diagnosed with Hashimoto's encephalopathy are normal.

Electroencephalography

An electroencephalogram (EEG) is a non-invasive test used to record the electrical activity of the brain through a series of electrodes attached to the scalp. Electroencephalography is typically used to detect seizure activity and diagnose epilepsy. It's also commonly used to monitor brain activity during sleep studies and some types of surgery. 

Current research suggests the EEGs of 90–98% of Hashimoto's encephalopathy patients show moderate to severe abnormalities, which can include non-specific diffuse slowing of background activity (delta or theta frequency waves) or transient epileptic activity.⁸

Cerebrospinal fluid analysis

Cerebrospinal fluid analysis requires a commonly used procedure called a lumbar puncture (LP) or spinal tap. To perform this test, a needle is inserted between the bones of the lumbar spine (lower back) to collect a sample of the protective fluid surrounding the brain and spinal cord. 

This minimally invasive test is typically used to diagnose potentially life-threatening infections and other inflammatory conditions involving the central nervous system that could explain any number of neurological symptoms. For most Hashimoto's encephalopathy patients, cerebral fluid analysis reveals high concentrations of a specific protein.  

Thyroid and antibody tests

Encephalopathy has many potential causes. To determine if thyroid function is a contributing factor, a blood test can evaluate thyroid hormone production and detect the presence of two specific thyroid antibodies — thyroid peroxidase (TPO) antibodies and antithyroid globulin (TG). 

Although only a relatively small number of people eventually diagnosed with Hashimoto's encephalopathy are also diagnosed with hypothyroidism, a significant number are found to have subclinical hypothyroidism, with hormone levels not quite low enough to meet diagnostic criteria.

How is Hashimoto's encephalopathy treated?

The first line of defense against Hashimoto's encephalopathy typically involves relatively high doses of corticosteroids (prednisone) prescribed to reduce inflammation and bring the condition under control. 

Once treatment begins, symptoms tend to improve within days. Although many people find their symptoms improve (or completely resolve) with corticosteroids, some require ongoing treatment. Depending on how the brain is impacted, long-term care could include anti-seizure medication, antipsychotic medications, or any combination of the following treatment options.   

Immunosuppressive medications

Although first-line treatment with corticosteroids may be the only medical intervention necessary for many patients, some require daily medication. Since corticosteroids are not ideal for long-term use, doctors often prescribe one of several immunosuppressant medications to minimize immune system responses, protect healthy tissues, and reduce the risk of relapse.  

Intravenous immunoglobulin treatment

During intravenous immunoglobulin (IVIG) therapy, antibodies from healthy donors are delivered into the veins of Hashimoto's encephalopathy patients to help remove or inhibit the harmful effects of antithyroid antibodies.

High-dose IVIG treatment delivers a multitude of anti-inflammatory benefits and can also help regulate immune system responses and improve cognitive function. IVIG treatments can be used on their own or in combination with immunosuppressant medication or corticosteroids.

Alternative treatments

While standard therapies seem to work well for most patients, a small number of people diagnosed with autoimmune encephalopathy have persistent symptoms that don’t respond to corticosteroids or immunosuppressive medications. 

Current evidence suggests monoclonal antibodies and infusions of biological immune system mediators could be effective alternatives. In a recent review of 13 cases involving patients treated with the monoclonal antibody medication rituximab, seven experienced complete (or nearly complete) symptom resolution, including patients with incomplete responses to other treatments.  

Investigational therapies and clinical trials

The medical community relies on investigative research and numerous clinical trials to help streamline diagnosis and identify the best treatments. Patient participation typically involves donating blood and tissue samples or volunteering to help evaluate the effects of a specific treatment.⁹

Since there's no way for participants to know if they're getting a potentially effective medication or a placebo, patients are encouraged to consult a trusted medical provider before committing to a clinical trial.

Does Hashimoto's encephalopathy respond to natural treatment?

If left untreated, Hashimoto's encephalopathy can cause permanent brain damage and lasting harm. Although some medical conditions appear to respond to plant-based supplements or alternative therapies like acupuncture or biofeedback, there are currently no reports of patients minimizing symptoms or preventing relapse using "natural" alternatives. Patients should not discontinue treatment without consulting their physicians.

However, nutritional deficiencies, too little sleep, emotional stress, overexertion, and even hormonal fluctuations can trigger symptoms in many people living with autoimmune disorders.

Current evidence suggests that many people diagnosed with thyroid disease and endocrine system disorders are deficient in several essential vitamins and minerals, including vitamin D and selenium. For questions or concerns about nutrition, trouble sleeping, stress management, or the possibility of a vitamin deficiency, consult your healthcare provider.

Is Hashimoto's encephalopathy fatal? What's the prognosis for long-term patients?

Hashimoto’s encephalopathy is rare, not all that well-understood, and can be fatal if it’s not diagnosed in time. Although most people treated for HE experience significant symptom improvement within weeks of starting corticosteroids, the disease is not curable. However, many patients find the condition lapses into remission after their initial treatment.

But relapses are possible, and most patients can expect regular follow-up appointments to monitor for signs of recurrence or progression. Of those who require daily medication, many are eventually able to discontinue treatment under the guidance and supervision of their healthcare providers.

What type of doctor diagnoses and treats Hashimoto's encephalopathy?

Since Hashimoto’s encephalopathy can cause a wide range of symptoms involving the central nervous system, neurologists are typically well-equipped to diagnose the disorder and oversee treatment. But waiting for an appointment with a neurologist isn't your only option. Many physicians work in collaboration with several doctors dedicated to other specialties. 

Other specialists who could have experience diagnosing or treating this rare condition include rheumatologists, immunologists, neuropsychiatrists, family physicians, and pediatricians.

The lowdown

Hashimoto's encephalopathy is a rare inflammatory condition that attacks the brain in a way that impairs its function. Its symptoms include personality changes, loss of motor control, seizures, speech problems, hallucinations, and more. Although the condition was first identified in a patient with a history of Hashimoto's disease, there's little evidence confirming the antithyroid antibodies associated with the disorder contribute to brain damage.

Some physicians prefer the differential diagnosis of steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT).

This rare condition affects approximately two out of every 100,000 people, and women are significantly more likely to develop symptoms than men. Most people are between the ages of 40 and 55 when symptoms occur, and having an autoimmune disorder is a contributing factor.

Although there's no cure for Hashimoto's encephalopathy, most patients respond favorably to corticosteroid treatment and immunosuppressant medication. The long-term prognosis is generally good, even for people living with undiagnosed or misdiagnosed symptoms for years.