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One day, you’re feeling fine, and within a few short days, you’re feeling profoundly exhausted, finding it difficult to speak, and having minor seizures. Your doctor suspects that you may have had a stroke! Or, despite being far too young to develop dementia, you’re slowly noticing that you’re having significant memory problems and even occasional hallucinations and delusions! These symptoms are understandably quite terrifying and would send most people running to the nearest psychiatrist or neurologist!
Most people – and even some doctors – don’t know, however, that these can be symptoms of a little-known – but treatable – autoimmune disease called Hashimoto’s Encephalopathy. Ahead, a look at this rare condition, its symptoms and causes, how it’s diagnosed, and the treatment options.
Hashimoto’s encephalopathy (HE) is a rare neurological disorder that develops when the immune system targets the thyroid gland and produces antibodies that then mistakenly attack and damage brain tissue and cells.
Hashimoto’s is part of the name because HE patients typically have elevated antibodies against the thyroid that are also seen in Hashimoto’s thyroiditis. HE is considered a neurological and not thyroid disorder because the majority of HE patients have no change in thyroid function. As a result, some experts now prefer to use an alternate name: steroid-responsive encephalopathy associated with autoimmune thyroiditis, or SREAT.
According to the National Organization for Rare Disorders, the prevalence of HE is estimated at 2.1 per 100,000 people. Still, because the condition is very misunderstood and has confusing symptoms, the likelihood is that there is a significant level of undiagnosed HE. The condition is more common in women than men, and the mean age of onset is 44, but HE can affect both genders at any age.
According to researchers, the main feature of HE is encephalopathy, the medical term for brain inflammation and swelling. The inflammation can cause various neurological, physical, and psychiatric symptoms outlined here. Symptoms can develop rapidly or slowly and typically follow one of two usual courses:
- Relapsing and remitting HE is characterized by acute stroke-like episodes and varying cognitive dysfunction, followed by periods of remission.
- Progressive HE, the more common form, often shows up as a gradual neurological and cognitive decline that worsens over time.
The following are the most common symptoms of both types of HE.
Cognitive impairment symptoms in HE include memory loss, difficulty concentrating, inattentiveness, confusion, or disorientation. Some people may also experience difficulty with language, including reading, writing, and speaking.
HE can cause emotional instability, including anxiety, depression, mood swings, and personality changes.
Other Mental Health Symptoms
Other mental health symptoms associated with acute HE episodes include hallucinations, psychosis, paranoia, and delusional behavior.
Seizures are another common symptom of HE. They can range from mild seizures that affect only one part of the body to more severe seizures that involve convulsions, loss of consciousness, and even coma.
Tremors and Movement Disorders
Some people with HE may experience over-responsive reflexes and movement disorders such as tremors, muscle stiffness, or sudden spasms and jerking movements known as myoclonus. A condition called ataxia may be diagnosed, which involves difficulties with balance, speaking, and using the fingers and hands, as well as difficulty walking. You may also see experience involuntary muscle jerks, more frequent hiccups, and hypnic jerks (also known as “sleep starts.”)
Headaches are another common symptom of HE. They can be mild or severe and have migraine-like characteristics such as nausea, vomiting, or sensitivity to light or sound.
In some cases, HE can cause vision problems such as blurry vision, double vision, or even blindness in one or both eyes.
HE is also associated with significant fatigue and poor appetite.
Researchers are working to understand what causes HE, but currently, the exact cause remains unknown. However, certain factors are thought to contribute to the development of this condition.
HE is considered an autoimmune disorder, which means that the body’s immune system mistakenly attacks healthy cells and tissues. In this case, the immune system is attacking the brain.
Hashimoto’s thyroiditis, a condition in which the immune system attacks the thyroid gland, is associated with Hashimoto’s encephalopathy. In some cases, autoimmune thyroid disease – even when asymptomatic -- appears to trigger the immune system to attack the brain.
Some researchers believe that viral infections – including Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) – may trigger HE, as they have been found in many patients with this condition.
Certain environmental factors may also contribute to the development of HE. Exposure to toxins and chemicals, such as pesticides and heavy metals, may trigger the immune system to attack the brain.
There may be a genetic component to HE. Some studies have shown that specific genes may increase the risk of developing the condition.
Only 3 in 10 people with HE has subclinical hypothyroidism, a mild form of an underactive thyroid usually presented as normal TSH levels and elevated T4 levels.
HE is associated with elevated levels of thyroid antibodies, including Thyroid Peroxidase (TPOAb) antibodies, Thyroglobulin antibodies (TgAb), and Thyrotropin Receptor antibodies (TRAb). While the antibodies don’t appear to play a role in the development of HE, they are a marker for HE.
About 35% of HE patients have evidence of some degree of subclinical or overt hypothyroidism. But the majority of HE patients are “euthyroid” – they have normal thyroid function – despite elevated thyroid antibodies.
There’s no definitive or conclusive test for HE, and because the symptoms often mimic those of other neurological disorders, a differential diagnosis is required.
When encephalopathy is suspected, the diagnostic process must first exclude any other potential causes, such as traumatic brain injury, exposure to heavy metals, drug use, Creutzfeldt-Jakob Disease (“Mad Cow”), and other conditions.
The next step is blood tests for TPOAb and TgAb. Antibody testing is essential, as the presence of antithyroid antibodies is necessary for an HE diagnosis, and ultimately, the diagnosis of HE is made after excluding other potential causes, along with the presence of elevated TPOAb or TgAg.
A thyroid panel – evaluating thyroid stimulating hormone (TSH), free thyroxine (Free T4), and free triiodothyronine (Free T3) – is also done to determine if thyroid function is affected. Research shows that less than 30% of HE patients have thyroid dysfunction.
Magnetic Resonance Imaging (MRI)
Magnetic resonance imaging (MRI) scans use a powerful magnetic field and radio waves to create detailed images of the brain. MRI scans are advantageous because they can detect brain structure and function changes that may indicate HE. Specific patterns on an MRI scan can help confirm the diagnosis of the condition, such as showing an increase in white matter lesions, which is a common feature in Hashimoto’s encephalopathy. Additionally, MRI scans can help monitor the disease’s progression and treatment effectiveness over time.
Computed Tomography (CT) scans
Computed tomography (CT) scans are another imaging technique to diagnose Hashimoto’s encephalopathy. CT scans use X-rays to create cross-sectional images of the brain. CT scans can detect abnormalities in the brain structure and can, in some cases, show a pattern of Hashimoto’s encephalopathy. However, CT scans are limited because they cannot offer the same level of detail as MRI scans, and they may not show early changes in the brain that MRI scans can detect.
Combined MRI/CT scanning
Combined MRI/CT scanning can improve the accuracy of diagnosis in Hashimoto’s encephalopathy. By combining the strengths of both imaging techniques, physicians can get a complete picture of the brain and identify early changes in the structure and function. This comprehensive picture can help guide treatment decisions and can help monitor the effectiveness of treatment over time.
EEG (Electro-Encephalogram) is a non-invasive diagnostic technique that measures the brain’s electrical activity. It involves placing electrodes on the scalp and recording the brain’s electrical signals. EEG can detect abnormalities in brain wave patterns and help diagnose neurological disorders. In the case of Hashimoto’s encephalopathy, EEG can play a vital role in identifying specific abnormalities associated with this condition.
One of the typical EEG findings in an autoimmune encephalopathy like HE is diffuse slow-wave activity. This reduction in the frequency of brain waves indicates that the brain is not functioning optimally. Another typical EEG finding in this condition is epileptiform activity, which refers to abnormal spikes in brain waves that can lead to seizures. These findings can help doctors confirm a diagnosis of Hashimoto’s encephalopathy.
Moreover, EEG also plays a key role in monitoring the progression of Hashimoto’s encephalopathy. In cases where patients have abnormal EEGs, regular monitoring through EEG can track any changes in brain wave activity and help doctors evaluate the effectiveness of treatment.
A lumbar puncture can help identify whether an underlying inflammatory process is occurring in the brain. In a lumbar puncture, a small amount of cerebrospinal fluid (CSF) is extracted from the lower back and tested for the presence of lymphocytes and other markers of inflammation.
In patients with HE, CSF is often found to show elevated levels of lymphocytes and other markers of immune activation. In this way, a lumbar puncture can help confirm the diagnosis of HE and rule out other potential causes of symptoms.
There are several treatments for HE, but the first line of treatment is corticosteroid drugs to reduce inflammation in the brain.
Corticosteroids are a group of hormones produced by the adrenal gland that have anti-inflammatory and immunosuppressive properties. In the case of HE, corticosteroids are used to suppress the autoimmune response causing brain inflammation. Several studies have shown that corticosteroid treatment can significantly reduce symptoms of HE, including seizures, memory loss, and confusion.
The recommended dose of corticosteroid treatment varies depending on the severity of the patient’s symptoms, age, and other health factors. Treatment typically starts with a high dose of intravenous corticosteroids, followed by a tapering period of oral corticosteroids over several months. Frequent monitoring is necessary to ensure the patient responds well to the treatment and to avoid any potential side effects associated with corticosteroid use.
Although corticosteroid treatment can effectively manage HE symptoms, it has risks. Prolonged use of corticosteroids can lead to various side effects, including weight gain, mood changes, increased blood sugar levels, and high blood pressure. Patients should be closely monitored by their healthcare provider during treatment, and any potential side effects should be promptly addressed.
It’s important to note that research reports that most HE cases respond to corticosteroid drug treatment. (Steroid responsiveness is even considered a possible diagnostic criterion for HE.)
Intravenous Immunoglobulin (IVIG)
Intravenous Immunoglobulin (IVIG) is a treatment that involves the infusion of antibodies into the bloodstream. These antibodies come from blood donors and are purified into a solution for infusion. The antibodies bind to cells in the immune system, which can block the harmful antibodies attacking healthy cells in the body. IVIG can also regulate the immune system’s response and decrease inflammation.
Research has shown that IVIG can effectively treat the symptoms of HE. Studies have found that IVIG can improve cognitive function, reduce seizures, and stabilize mood and behavior in people with HE. IVIG can also help alleviate symptoms related to inflammation, including headaches and joint pain.
IVIG is administered intravenously, usually through a drip infusion. The treatment can take several hours to complete, and the duration and frequency of the treatment depend on the severity of the symptoms and the individual’s response to the treatment. In some cases, more frequent infusions may be necessary to relieve symptoms.
IVIG treatment is generally safe and well-tolerated but can cause side effects in some individuals. These side effects can include headaches, fever, chills, and fatigue. More severe side effects, such as blood clots, can occur in rare cases. If you experience any side effects during or after treatment, it’s important to discuss them with your doctor.
Azathioprine is an immunosuppressant drug that suppresses the immune system to prevent the body from attacking its own tissues. In the case of HE, azathioprine is used to reduce inflammation in the brain and improve cognitive function.
According to research, azathioprine is effective in treating HE. In a study published in the Journal of Neuropsychiatry and Clinical Neurosciences, patients with HE were treated with azathioprine and showed significant improvement in cognitive function and neurological symptoms.
However, azathioprine is not suitable for everyone. Patients with a history of liver disease or blood disorders are not recommended for azathioprine treatment. Additionally, certain medications, including allopurinol and ACE inhibitors, can interact with azathioprine and cause adverse reactions.
Cyclophosphamide is a chemotherapy drug that works by suppressing the immune system. It is often prescribed to patients with various autoimmune disorders because it targets and destroys the white blood cells that mistakenly attack healthy tissues. In HE, the drug is prescribed to reduce the inflammation that damages the brain cells and causes neurological symptoms.
Studies have shown that cyclophosphamide can effectively reduce the severity and frequency of seizures, improve cognitive function, and stabilize mood in HE patients. It is often combined with other immunosuppressive drugs or steroids to achieve the best results. Cyclophosphamide may benefit HE patients who don’t respond well to other treatments or have especially severe symptoms.
Like any chemotherapy drug, cyclophosphamide has potential side effects ranging from mild to severe. Common side effects include nausea, vomiting, hair loss, diarrhea, and fatigue. More severe side effects include infections, anemia, and damage to the liver and kidneys. It is crucial to work closely with your doctor and report any side effects promptly. HE patients who take cyclophosphamide must also undergo regular blood tests to monitor white blood cell levels and liver and kidney function.
Mycophenolate mofetil (CellCept)
Mycophenolate mofetil, also known as CellCept, is an immunosuppressant drug commonly used to prevent organ rejection in transplant patients. It works by suppressing the activity of T cells responsible for attacking healthy cells in the body. Researchers have also found that mycophenolate mofetil can effectively treat autoimmune disorders like HE.
In a study published in the Journal of Neurology, Neurosurgery, and Psychiatry, researchers found that mycophenolate mofetil effectively treated patients with HE. The researchers found that after six months of treatment, 75% of the patients treated with mycophenolate mofetil showed significant improvement in their symptoms.
Another study published in the Journal of Clinical Neurology found similar results. The study evaluated HE patients treated with mycophenolate mofetil. The researchers found that after a median follow-up of 18 months, 83% of the patients showed significant improvement in their symptoms.
Mycophenolate mofetil is typically prescribed with other treatments, such as corticosteroids or intravenous immunoglobulin. It is important to note that mycophenolate mofetil can have side effects, including gastrointestinal symptoms, fatigue, and increased susceptibility to infections. Patients should be closely monitored by their healthcare provider while taking this medication.
Thyroid hormone replacement
There’s no evidence that thyroid hormone replacement medication has a specific role in treating Hashimoto’s encephalopathy. However, when thyroid function tests show subclinical or overt hypothyroidism, patients with HE will often be treated with thyroid hormone replacement medications.
In addition to immunotherapy and thyroid treatment, other treatments may be used to manage the symptoms of Hashimoto’s encephalopathy. These include:
- antiepileptic medications for seizures
- antidepressants or mood stabilizers for mood disorders, and
- physical or occupational therapy for movement disorders or difficulties with everyday activities.
Individuals with Hashimoto’s encephalopathy need to work closely with their healthcare providers to manage their symptoms effectively. Regular monitoring of thyroid hormone levels, EEG, and MRI may be required to evaluate the effectiveness of treatment and adjust as necessary.
The good news is that more than 90% of people with HE respond quickly to drug treatment, and symptoms improve – or even go into complete remission – with their symptoms improving or even resolving within a few months. The majority of HE patients remain in remission after drug treatment.
While HE is highly treatable and has a favorable prognosis, like most autoimmune diseases, it’s not considered curable. However, a long remission is likely in most HE cases.
Recognizing and diagnosing Hashimoto’s encephalopathy can be confusing, and HE is frequently misdiagnosed as stroke, dementia, or Alzheimer’s disease, among other conditions. A correct diagnosis of HE starts with excluding other causes of encephalopathy and then evaluating other factors consistent with HE.
If you or someone close to you develops neurocognitive symptoms or has a diagnosis of unexplained encephalopathy, be sure to mention any personal or family history of Hashimoto’s disease, autoimmune disease, or other thyroid conditions so your healthcare provider practitioner can look into HE as a possible cause.