Hashimoto's encephalopathy
Encyclopedia
Hashimoto's Encephalopathy is a very rare condition associated with Hashimoto's thyroiditis
. It was first described in 1966. It is classified as a neuroendocrine disorder.
Up to and including 2005 there have been almost 200 case reports of this disease. Up to 1990 only 8 cases reports (including the original case) had been published. Between 1990 and 2000 43 cases were published.
More cases are being reported now, this suggests that this rare condition is likely to have been undiagnosed in the past. MRI's in combination with CSF test are utilized for the diagnosis.
, multiple episodes of encephalopathy, stroke-like symptoms and Hashimoto’s thyroiditis confirmed by elevated anti-thyroid antibodies.
Onset is gradual and may go unnoticed by the patient and close associates to the patients.
Symptoms can resolve themselves within days to weeks, leaving a patient undiagnosed.
has been identified as an autoantigen in the disease.
Some of the more common symptoms of Hashimoto's encephalopathy include:
Cerebrospinal fluid
findings:
Thyroid hormone abnormalities are common (>80% cases):
Thyroid antibodies - both anti-thyroid peroxidase
antibodies (anti-TPO, anti-thyroid microsomal antibodies, anti-M) and antithyroglobulin
antibodies (anti-Tg) - in the disease are increased but their levels do not correlate with the severity.
Electroencephalogram studies while almost always abnormal (98% cases) are usually non diagnostic. The most common findings are diffuse or generalized slowing or frontal intermittent rhythmic delta activity. Prominent triphasic waves, focal slowing, epileptiform abnormalities, photoparoxysmal and photomyogenic responses may be seen. Its use in this disease is that it usually reverts to normal after treatment.
treatment, this condition is now also referred to as steroid
-responsive encephalopathy.
Initial treatment is usually with oral prednisone (50–150 mg/day) or high dose IV methylprednisolone (1 g/day) for 3–7 days. Thyroid hormone treatment is also included if required.
Failure to respond to this first line treatment has produced a variety of alternative treatments including azathioprine
, cyclophosphamide
, chloroquine
, methotrexate
, periodic intravenous immune globulin and plasma exchange. There have been no controlled trials so the optimal treatment is not known.
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
. It was first described in 1966. It is classified as a neuroendocrine disorder.
Up to and including 2005 there have been almost 200 case reports of this disease. Up to 1990 only 8 cases reports (including the original case) had been published. Between 1990 and 2000 43 cases were published.
More cases are being reported now, this suggests that this rare condition is likely to have been undiagnosed in the past. MRI's in combination with CSF test are utilized for the diagnosis.
History
The first case was described by Brain et al. in 1966. The patient was a 48 year old man with hypothyroidismHypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, multiple episodes of encephalopathy, stroke-like symptoms and Hashimoto’s thyroiditis confirmed by elevated anti-thyroid antibodies.
Definition
A relapsing encephalopathy occurring in association with Hashimoto's thyroiditis, with high titers of anti-thyroid antibodies. Clinically, the condition may present one or more symptoms.Onset is gradual and may go unnoticed by the patient and close associates to the patients.
Symptoms can resolve themselves within days to weeks, leaving a patient undiagnosed.
Epidemiology
The prevalence has been estimated to be 2.1/100,000 with a male:female ratio of 1:4. The mean age of onset is 44 with 20% of cases presenting before the age of 18 years.Aetiology
The mechanism of pathogenesis is not known but it has been assumed to be an autoimmune disorder. Consistent with this hypothesis alpha-enolaseAlpha-enolase
Enolase 1, more commonly known as alpha-enolase, is a glycolytic enzyme expressed in most tissues, one of the isozymes of enolase. It is a homodimer composed of 2 alpha subunits.-Relationship to Myc-binding protein-1:...
has been identified as an autoantigen in the disease.
Pathology
Very little is known about the pathology of this disease. Post-mortem studies have shown lymphocytic vasculitis of venules and veins in the brain-stem and a diffuse gliosis involving gray matter more than white matter.Clinical features
The onset of symptoms tends to be fairly gradual and to occur over 1–7 days.Some of the more common symptoms of Hashimoto's encephalopathy include:
- personality changes
- aggression
- delusional behavior
- concentration and memory problems
- comaComaIn medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
- disorientation
- headaches
- jerks in the muscles (myoclonusMyoclonusMyoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...
- 65% cases) - lack of coordination (ataxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
- 65% cases) - partial paralysisParalysisParalysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
on the right side - psychosisPsychosisPsychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
- seizures (60% cases)
- sleep abnormalities (55% cases)
- speech problems (transient aphasiaAphasiaAphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....
- 80% cases) - status epilepticusStatus epilepticusStatus epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...
(20% cases) - tremors (80% cases)
Laboratory and radiological findings
- Increased liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
enzyme levels (55% cases) - Increased thyroid-stimulating hormone (55% cases)
- Increased erythrocyte sedimentation rate (25% cases)
Cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
findings:
- Raised protein (25% cases)
- Negative for 14–3–3 protein
- May contain antithyroid antibodies
- Magnetic resonance imagingMagnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
abnormalities consistent with encephalopathy (26% cases) - Single photon emission computed tomographySingle photon emission computed tomographySingle-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...
shows focal and global hypoperfusion (75% cases) - Cerebral angiography is normal
Thyroid hormone abnormalities are common (>80% cases):
- subclinical hypothyroidism (35% cases)
- overt hypothyroidism (20% cases)
- hyperthyroidism (5% cases)
- euthyroid on levothyroxine (10% cases)
- euthyroid not on levothyroxine (20% cases)
Thyroid antibodies - both anti-thyroid peroxidase
Peroxidase
Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...
antibodies (anti-TPO, anti-thyroid microsomal antibodies, anti-M) and antithyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....
antibodies (anti-Tg) - in the disease are increased but their levels do not correlate with the severity.
Electroencephalogram studies while almost always abnormal (98% cases) are usually non diagnostic. The most common findings are diffuse or generalized slowing or frontal intermittent rhythmic delta activity. Prominent triphasic waves, focal slowing, epileptiform abnormalities, photoparoxysmal and photomyogenic responses may be seen. Its use in this disease is that it usually reverts to normal after treatment.
Differential diagnosis
- Alzheimer's diseaseAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
- Cerebrovascular accidents
- Creutzfeldt-Jakob disease
- Viral encephalitis
Treatment
Because most patients respond to steroids or immunosuppressantImmunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
treatment, this condition is now also referred to as steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
-responsive encephalopathy.
Initial treatment is usually with oral prednisone (50–150 mg/day) or high dose IV methylprednisolone (1 g/day) for 3–7 days. Thyroid hormone treatment is also included if required.
Failure to respond to this first line treatment has produced a variety of alternative treatments including azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
, methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, periodic intravenous immune globulin and plasma exchange. There have been no controlled trials so the optimal treatment is not known.
Prognosis
Duration of treatment is usually between 2 and 25 years. 90% of cases stay in remission after discontinuation of treatment.Alternative names
- Steroid-responsive encephalopathy associated with autoimmune thyroiditis, SREAT
- Sometimes also mentioned as nonvasculitic autoimmune meningoencephalitis, NAIM