Hashimoto's encephalopathy

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. This suggests that this rare condition is likely to have been undiagnosed in the past.

History
The first case was described by Brain et al. in 1966. The patient was a 48 year old man with hypothyroidism, 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-enolase 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
 * coma
 * disorientation
 * headaches
 * jerks in the muscles (myoclonus - 65% cases)
 * lack of coordination (ataxia - 65% cases)
 * partial paralysis on the right side
 * psychosis
 * seizures (60% cases)
 * sleep abnormalities (55% cases)
 * speech problems (transient aphasia - 80% cases)
 * status epilepticus (20% cases)
 * tremors (80% cases)

Laboratory and radiological findings

 * Increased liver enzyme levels (55% cases)
 * Increased thyroid-stimulating hormone (55% cases)
 * Increased erythrocyte sedimentation rate (25% cases)

Cerebrospinal fluid findings:
 * Raised protein (25% cases)
 * Negative for 14–3–3 protein
 * May contain antithyroid antibodies


 * Magnetic resonance imaging abnormalities consistent with encephalopathy (26% cases)
 * Single photon emission computed tomography 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 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.

Differential diagnosis

 * Alzheimer's disease
 * Cerebrovascular accidents
 * Creutzfeldt-Jakob disease
 * Viral encephalitis

Treatment
Because most patients respond to steroids or immunosuppressant 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.

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