Hashimoto Encephalopathy (HE)
A form of potentially reversible Autoimmune Dementia
Steroid Response Encephalopathy Associated With Autoimmune Thyroiditis (SREAT), also known as Hashimoto Encephalopathy (HE) is characterised by confusion with or without myoclonus, seizures, hyperreflexia, and psychosis.
Presentation may be an insidious development of cognitive impairment or recurrent acute episodes of focal neurological deficit with confusion (can present acutely with multiple recurrent focal neurological events or with a progressive, diffuse pattern characterized by cognitive impairment). It is under-recognized by physicians.
Source: Department of Neurology, Mercy University Hospital, Cork, Ireland
Case Reports in Medicine Volume 2012 (2012), Article ID 782127, doi:10.1155/2012/782127
Hashimoto’s Encephalopathy (HE) is a rare, still not well understood, autoimmune disease with neurological and psychiatric manifestations and elevated titers of antithyroid antibodies in serum and cerebrospinal fluid (CSF) as a hallmark of the disease. Patients are mostly women. Current diagnostic criteria include corticosteroide responsiveness, but it is the case in only 50% of patients with HE. In steroid non-responders other immunomodulatory therapies or plasmapheresis could be applied. Disease course can be acute, subacute, chronic or relapsing-remitting. Two distinct forms emerged from the reported cases: a vasculitic type characterized by multiple relapsing-remitting stroke-like episodes and mild cognitive impairment; and a diffuse progressive type characterized by dementia and psychiatric symptoms.
Source: PubMed.gov US National Library of Medicine http://www.ncbi.nlm.nih.gov/pubmed/19846119
Before we move on to discussing signs and symptoms of HE, as well as treatment protocols and tests, here are some important comments you should read if you believe you or someone you care about may have HE.
– HE is commonly referred to as being rare, however, some documents on PubMed.gov suggest that that it may not be as rare as it is underreported or underdiagnosed, due being a relatively newly discovered condition (only discovered in 1967).
– That would seem to be supported by the fact that within just a few days of initially researching HE, we had no problem finding upwards of 100 people on internet discussion boards who report being diagnosed with HE by their physicians, and responding favorably to steroid treatment.
– Be prepared for the fact that your doctor most likely will never have heard of this condition when you discuss it with him/her. Be prepared to advocate for yourself and INSIST on having your anti-thyroid antibodies tested if you are experiencing the signs and symptoms of HE. The information provided below will tell him everything he needs to know at a quick glance, but he will want to verify it with his own research which is understandable. Many patients have been misdiagnosed as having other conditions when in fact they had HE and could have received treatment instead of continuing to suffer symptoms that can shut a persons life down. Its YOUR life, you have a right to ensure you receive the proper testing and diagnoses to be well. If your doctor refuses to test your thyroid antibody levels, or refuses a trial dose of high-dose steroids if you do have any elevated thyroid antibodies, you need to find another doctor. HE can be reversed if treated promptly. Left untreated for too long it could cause permanent life-long damage. Some doctors are very resistant to patients who come in armed with research, or patients who suggest diagnoses. We understand that doctors probably deal with a lot of patients who are unreasonable and that may put them off when patients start making suggestions, but a good doctor should be open to considering the research you’ve done on your own, and the suggestions you bring to them. You know your body better than they do, and often the patient is spot-on in what they come up with on their own. Doctors need to understand that it doesn’t mean they aren’t good doctor if the patient found the cause of the problem when they (the doctor) did not. What makes a good doctor is their openness to hearing the patient, and their dedication to making sure the patient gets the help they need, no matter what. There is no place for ego when a patient’s quality of life is at stake.
(In Presence of High Levels of Antithyroid Antibodies)
Some patients may experience many of these symptoms, others may show some but not all of the symptoms listed here. Symptoms include:
- Cognitive Difficulties
- Concentration Problems
- Attention Span Problems
- Difficulty Retaining Information
- Short Term Memory Problems
- Seizure Activity
- Myoclonus – Rapid, Involuntary, Uncontrollable Muscle Jerks or Spasms
- Dementia and dementia-related symptoms
- Coordination Difficulties
- Episodes of Stroke
- Episodes of Stroke-Like Deterioration
- Right Sided Hemiparesis – Right Sided Partial Paralysis
- Left Sided Hemiparesis – Left Sided Partial Paralysis
- Aphasia – Speech Difficulties
- Articulation Difficulties
- Word Finding Difficulties
- Fine Motor Movement Problems – Coordination of Arms, Hands, Fingers
- Also read elsewhere that Hearing Loss is a symptom
- Also read elsewhere that Incontinence is a symptom
- Also read elsewhere that Sleep Disorders are a symptom
- Also read elsewhere that Impulsive Behavior are a symptom
- Also read elsewhere that Restlessness are a symptom
[The Source of this information is “Hashimoto’s Encephalopathy,” Hubert C. Chen, MD, Umesh Masharani, MD, Division of Endocrinology, University of California at San Francisco. Southern Medical Journal, 93(5):504-506, 2000. ]
Though there is no specific, diagnostic test for Hashimoto’s Encephalopathy, (H.E.,) the following Test results may well indicate an H.E. Diagnosis. However, some patients MAY, some patients MAY NOT show the following results on some of these specific Tests. That is why the Symptoms presented, in combination with Elevated Thyroid Autoimmune Antibodies are so important for diagnosis.
EEG – May show generalized diffuse slowing, slow wave activity or bilateral temporal and frontal spikes, or the test may be Normal.
CSF, SPINAL TAP – May show elevated Protein, Oligoclonal Bands, or may be Normal.
MRI – May show subcortical high signal lesions on T-2 weighted images, or mild cerebral atrophy with temporal predominance. Also may show lesions. Could show white matter abnormalities. White matter lesions can be reversible with clinical improvement involving Steroids. Or test may be Normal.
ENDOCRINOLOGY TESTS – BLOOD TESTS
TSH – Thyroid Stimulating Hormone
T- 4 – Free Thyroxine
Patient may have hypothyroidism. Or the patient may be Euythyroid – no thyroid problem indicated – BUT – the patient still can have H.E. AND Elevated Thyroid Autoimmune Antibodies.
Tests that will show Elevated Thyroid Autoimmune Antibodies:
Thyroid Microsomal Antibody Titer (TMAb) – Thyroid Autoimmune Antibody Test
Thyroglobulin Antibody Titer (TgAb) – Thyroid Autoimmune Antibody Test
The Thyroid Antibody Tests above will also confirm a Diagnosis of Hashimoto’s Thyroiditis, (H.T.) also known as Hashimoto’s Disease in which case the patient will also be Hypothyroid.
OBTAINING AN H.E. DIAGNOSIS
IMPORTANT – A patient may be Euythyroid OR Hypothyroid upon onset of H.E. Also patients that are Euythyroid or Hypothyroid will have Elevated Thyroid Autoimmune Antibodies.
That is why it is so important to have the patient, in addition to Extensive Neurological Testing, undergo thorough Thyroid Function Tests – with the Symptoms and Elevated Thyroid Antibodies a diagnosis of H.E. should be considered and Treatment for H.E. should begin.
If a person has unexplained episodes of: Dementia, Myoclonus, Seizures, Neurological Deficits, Cognitive Problems, Psychiatric Disorder Symptoms and all Extensive Neurological Tests eliminate other diagnoses, has Elevated Anti-Thyroid Autoimmune Antibodies, H.E. should be seriously considered, and Treatment for H.E. should begin.
If the patient Tests with an abnormal EEG, Elevated Anti-Thyroid Autoimmune Antibody Titer, Elevated Proteins or Oligoclonal Bands in the Cerebrospinal Fluid (CSF, Spinal Tap) and an unrevealing Cerebral MRI, the patient should be diagnosed with H.E. Treatment should begin.
A patient may test Normal on all Extensive Neurological Tests, be Hypothyroid or Euythyroid, have Elevated Thyroid Autoimmune Antibodies and importantly, show some of the Symptoms as indicated, an H.E. Diagnosis should proceed with appropriate H.E. Treatment.
If a patient responds well, then a Diagnosis and Treatment for H.E. should proceed.
IMPORTANT – Even though clinical improvement (Symptoms improve) occurs after treatment with Steroids (or IVIG Treatment for those who cannot tolerate Steroids), Thyroid Antibodies WILL remain elevated.
Source: “Hashimoto’s Encephalopathy,” Hubert C. Chen, MD, Umesh Masharani, MD, Division of Endocrinology, University of California at San Francisco. Southern Medical Journal, 93(5):504-506, 2000.
1) Check Thyroid Anitbody levels… elevated antibodies in the presence of HE symptoms may warrant a trial of high dose steroids. The only way to know for certain if the patient has HE (assuming there is an elevation of anti-thyroid antibodies) is to prescribe the steroids and see if symptoms improve or reverse.
2) Neurological symptoms
3) Test EEG brain function and response, then do a trial steriodal run for Hashimotos Encephalopathy. Retest the brain function and see if there is improvement. Once this is done and improvement is noted you can determine HE.
TYPE I and TYPE II Hashimoto’s Encephalopathy
Symptoms present as Stroke-like episodes. It can include epileptic like seizures, neurological deficits, cognitive impairment, aphasia, and ataxia. Myoclonus, tremors, confusion. Dimness or loss of vision in one eye. Dizziness, unsteadiness, balance problems, and frequent headaches.
TYPE II H.E.
Symptoms present as dementia to a progressing dementia, psychosis, coma, cognitive deficits and impairment, psychotic episodes, altered consciousness, incontinence both urine and fecal. Seizures, hallucinations, myoclonus, tremors and confusion. In addition, some Symptoms listed above can also present in Type I H.E.
Source: “Hashimoto’s Encephalopathy,” Hubert C. Chen, MD, Umesh Masharani, MD, Division of Endocrinology, University of California at San Francisco. Southern Medical Journal, 93(5):504-506, 2000
Treatment of initial or acute/subacute presentation of HE usually consists of
high dose oral prednisone (50–150 mg/day) or high dose IV methylprednisolone (1 g/day) for 3–7 days, which typically results in marked improvement of neurological symptoms (including reduction of refractory seizures) within 1 week (some report 4–6 weeks) and sometimes as early as 1 day, as seen in our two cases.
To avoid recurrences a slow taper of prednisone over weeks to months, depending on the clinical response, has been suggested. Cases with multiple recurrences or cases failing to respond to the above therapy have been placed on longterm treatment with prednisone, azathioprine, cyclophosphamide, plaquenil, methotrexate, periodic intravenous immune globulin (IVIG), plasma exchange, and various combinations of these treatments, usually
with good success. We now add cellcept to the list. Our review of the literature indicates that 4 of 5 cases were treated successfully with azathioprine and prednisone, while 1 case failed treatment with azathioprine alone. Two of 3 cases were treated successfully
with cyclophosphamide alone, while 1 of 2 cases was treated successfully with cyclophosphamide and prednisone. Two cases were treated successfully with
methotrexate, 1 with (our case) and 1 without prednisone. One of 2 cases was treated successfully with periodic IVIG alone. One case was treated successfully with plasma exchange and prednisone, while 1 casefailed treatment with plasma exchange alone. One
case was treated successfully with plaquenil and prednisone. One case (our case) was possibly treated successfully with cellcept and prednisone (a longer followup
period is needed to determine treatment success). As indicated above there is almost no information about long-term treatment of HE with monotherapy other than prednisone.
The little information available about combination therapy suggests reasonable success, most notably when azathioprine is added to prednisone. Therefore, if prednisone monotherapy fails or one wants to reduce the dose of prednisone to avoid side effects, combination therapy is recommended. However, long-term immunomodulatory treatment is not risk free—it may result in serious side effects and requires frequent monitoring of clinical and laboratory parameters.
Normalization of CSF, EEG, and quantitative neuropsychological testing serves as a good indicator of treatment efficacy, though EEG normalization often lags about 2 weeks after clinical recovery.7,12,13 A review of the literature reported improvement in 98% of cases treated with steroids, 92% treated with steroids and levothyroxine, and 67% treated with levothyroxine, while 9% of cases did not improve with any of the above combinations. 90% of cases stayed in remission even after discontinuation of treatment.7,11 Duration of disease has been reported to range between 2 and 25 years.25 Cases of the relapsing/remitting type usually did better than the progressive type, a few of which developed irreversible persistent cognitive impairment.7 One study noted that incomplete recovery might be more frequent in the elderly.9 However, HE has an overall favorable long-term prognosis with treatment.7,20 Three of 85 cases died, 2 while still being treated.2 The clinical findings of HE resemble those seen in Creutzfeldt-Jakob disease (CJD), which is a fatal and incurable disease.
The recently quoted prevalence figures for HE are higher than expected when compared to the few cases reported in the literature, which suggests that this condition is presently underdiagnosed. Therefore, it remains important to maintain a high clinical suspicion for HE since it is a readily treatable condition that carries a good prognosis, unlike many of the other diagnoses it resembles.
HIGH DOSE STEROID TREATMENT
Hashimoto’s Encephalopathy, (H.E.) responds to Steroid therapy. People respond dramatically to this Treatment. They are often asymptomatic (No Symptoms) in 1 to 3 days, but of course this depends on how long the patient has gone untreated among many other factors. While rapid improvement is common, keep in mind that some patients take 4 weeks to 3 months to show improvement to treatment . Dosage varies from High Dose Intravenous Steroid Therapy, then released on estimate of 96 milligrams orally of Steroids such as Medrol (Methylprednisolone), Prednisolone, Prednisone or any such Corticosteroid.
HIGH PULSE IV STEROID TREATMENT
1 Gram Solu-Medrol IV, (Methylprednisolone) usually given in one hour or throughout the day.
IV given every day in the Hospital for 3 days.
Discharge patient on 48 milligrams of oral Methylprednisolone (Medrol) twice a day, total milligrams a day, 96.
Slowly decrease milligrams over a period of 2 – 4 months.
Note that patient may relapse as dosage is tapered down. Upon presenting symptoms of a Relapse, milligrams should be upped to dosage before Relapse, therefore correct dosage will be realized to stabilize patient.
When/If Relapse occurs, either increase daily dosage by 2 milligrams or double daily dose of milligrams for 2 – 3 days to counteract Relapse, then back to original daily dosage. This depends on the clinical course of the Patient.”
Per the Case Studies on H.E., some patients are and some are not given the High Pulse IV Steroid Treatment, but put on 50 milligrams to 150 milligrams of oral Steroids daily. Remember that each person is different. Someone may be able to tolerate a certain drug, or dosage and another may not. All are then slowly decreased over many months, depending on their clinical course. Rapid improvement can often be observed within 1 to 3 days, though it can take 4 weeks to 3 months to observe any signs of improvement in some cases. However, overall it can take a very long time of slowly decreasing the Steroids to get optimum results.
Most patients (90%) stay in Remission even after Treatment has been discontinued. H.E. is a Relapsing condition.
Patients should have follow-ups for up to 10 years or more. Few patients with H.E. fail to respond to Steroids unless they have been left untreated for much too long OR, in some cases, a few patients may be steroid resistant.
Sources: “Hashimoto’s Encephalopathy,” Hubert C. Chen, MD, Umesh Masharani, MD, Division of Endocrinology, University of California at San Francisco. Southern Medical Journal, 93(5):504-506, 2000.
H. E. TREATMENT – IVIG – INTRAVENOUS IMMUNOGLOBULIN TREATMENT
Typically, the Treatment for H.E. that initially will be done by a Physician, will be the High Pulse IV Steroid Treatment (some physicians opt for oral high dose steroids initially rather than IV). This was and still is the preferred Treatment for H.E. However, it has been discovered that people who do not respond well to the Steroid Treatment do have an option – IVIG Treatment, formally known as: Intravenous Immunoglobulin Treatment.
To explain briefly, (a more detailed description follows the Introduction,) this therapy is rather new. Its purpose is to replace Antibodies with donated Antibodies, after careful screening for any contaminates, into someone elses body via IV. In Autoimmune Diseases, for unknown reasons, the body’s Antibodies attack the body’s own tissues and organs.
IVIG – INTRAVENOUS IMMUNOGLOBLULIN TREATMENT
Also known as IGIV, and Immune Globulin Intravenous (Human) (Systemic).
IVIG belongs to a group of medicines known as immunizing agents. It is used to prevent or treat some illnesses that can occur when your body does not produce enough of its own immunity to prevent those diseases. It is important that before this Therapy you inform your Doctor if you have any allergic reaction to intramuscular or intravenous immune globulins, or if you are allergic to any other substances such as foods, preservatives or dyes. You should inform your Doctor if you are on a special diet such as low-sodium or low-sugar diet. Make sure your Doctor is aware of any other Medical problems especially: Diabetes Mellitus, Heart Problems, Immunoglobulin A (IgA) deficiencies, Kidney Problems or Severe allergic reaction to any previous IGIV/IVIG. If you have recently received a live virus vaccine, you should wait at least 2-3 weeks before having IVIG Treatment, ask your Doctor since this depends on the vaccine you received. Also, wait 5 to 11 months after IVIG Treatment before receiving any live virus vaccines, also depending on the vaccine received.
This IV therapy replaces antibodies with infusion of donated antibodies. Antibodies – Proteins that help combat toxins and bacteria are extracted from the blood of hundreds of donors, then they are treated to remove contaminants and freeze-dried. The Antibodies are then mixed with a sterile solution and given intravenously. This Treatment usually is given on an Outpatient basis. The first Treatment may be done as an In-Patient in the Hospital to monitor for any side effects. The patient may go twice a week for the IV, and may take from 3 to 4 hours for each infusion. This Treatment continues monthly, usually from twice a week every month, to once a week every month, to once a month. It depends on the clinical response by the patient. Frequency of treatment depends on the individual. Usually the slower rate of infusion (IV Drip) the better. This could be from 4 to 6 hours. IVIG is delivered via IV and based on your weight. Remember – every one will react differently, and at different times to any procedure, any medication, and any dosage. Prognosis for IVIG is to go as long as possible between infusions and still feels well.
This Treatment is less toxic, and has fewer side effects than the High Dose IV Steroid Treatment for H.E. However, the recommended Treatment for H.E. is the High Dose IV Steroid Treatment (Immunosuppression.) IVIG is used only when someone DOES NOT respond to the Steroid Treatment. IVIG is used as a treatment for many other illnesses, such as: Guillain-Barre Syndrome, Lupus, Multiple Sclerosis, etc.
Source: National Institute of Health, Washington, D.C. Other Resources. Drug Information. Web Site: www.nih.gov/health.
A Few Case Studies For Easy Reference
An internet search for the term Hashimoto’s Encephelopathy will yield a wide range of case studies, depicting patients ranging in age from their 20s to their 80s, and displaying a wide range of symptoms. Here, briefly, are 2 such case studies, as well as a posting from an internet discussion board.
Brief Case Studies for Quick Reference:
1) [A patient with Hashimoto’s encephalopathy showing subacute global cognitive dysfunction].
Department of Neurology, Juntendo University School of Medicine.
We report a 66-year-old woman with Hashimoto’s encephalopathy who showed rapidly developing cognitive deficits, inactivity, and gait disturbance without involuntary movements or convulsions. She had had right-sided hemiparesis and dysarthria caused by a lacunar infarction and had been admitted to our hospital for 2 weeks. Although the dysarthria and hemiparesis gradually improved, difficulty in walking, disorientation, and drowsiness developed 2 months after discharge. Upon readmission, the patient was alert but apathetic and sometimes sleepy. The right upper and lower limbs showed mild weakness, which was considered to be due to the previous infarction. Cerebrospinal fluid showed mild elevation of protein without pleocytosis. An electroencephalogram was normal, and a magnetic resonance imaging of the brain showed only the old lacunar infarction. Titers of antithyroglobulin antibodies and levels of thyroid stimulating hormone in serum were elevated. We made a diagnosis of Hashimoto’s encephalopathy and treated the patient with high-dose corticosteroids. Within 1 week, her mental status improved and she was able to walk. Generalized seizure, myoclonus, and tremor, which are characteristic of Hashimoto’s encephalopathy, never developed. The findings in this patient suggest that Hashimoto’s encephalopathy, a treatable condition, should be included in the differential diagnosis of dementia.
2) Reversible dementia with psychosis: Hashimoto’s encephalopathy.
Neuropsychiatry Unit, Melbourne Neuropsychiatry Center, Royal Melbourne Hospital, Melbourne, Austrailia. Ramon.Mocellin@nh.org.au
A case of presumed Hashimoto’s encephalopathy (HE) is presented. The presentation included memory loss, delusions, functional decline and culminated in a generalized seizure. Anti-thyroid antibodies were detected and symptoms resolved with prednisolone. Patients with HE may present with prominent neuropsychiatric symptoms, attract psychiatric diagnoses and present to psychiatric services. Primarily a diagnosis of exclusion, HE should be considered in cases of encephalopathy in which standard investigations are negative.
[PubMed – indexed for MEDLINE]
3) On an Internet Discussion Board, Poster’s Mother Diagnosed & Successfully Treated for HE:
My mom’s neurological symptoms were cleared in a matter of 2 days after starting IV steroids therapy at hospital. She had 1 g of Solumedrol for 5 days and then was put on oral Prednisolone(started with 80 mg and decreased to 20 in 2 weeks). Ten days after start of steroid treatment she was back to normal mental status, she may have some forgetfulness sometimes, but she’s absolutely normal. She can walk, cook, solve crosswords puzzles, sudoku, etc. This is unbelievable that doctors still question this disease! I think this is a classic case of steroid responsive encephalopathy with high TPO levels. Mom’s doctors never heard about this disease before I gave them printed copies of health studies on HE, but were willing to try steroid IV therapy when she was hospitalized last time. It saved her life and brought her back to normal mental status!