Hashimoto's encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a neurological condition characterized by encephalopathy, thyroid autoimmunity, and good clinical response to corticosteroids. It is associated with Hashimoto's thyroiditis, and was first described in 1966. It is sometimes referred to as a neuroendocrine disorder, although the condition's relationship to the endocrine system is widely disputed. It is recognized as a rare disease by the NIH Genetic and Rare Diseases Information Center.
Up to 2005, almost 200 case reports of this disease were published. Between 1990 and 2000, 43 cases were published. Since that time, research has expanded and numerous cases are being reported by scientists around the world, suggesting that this rare condition is likely to have been significantly undiagnosed in the past. Over 100 scientific articles on Hashimoto's encephalopathy were published between 2000 and 2013.
Signs and symptoms
The onset of symptoms tends to be fairly gradual and to occur over 1-12 years.
Symptoms of Hashimoto's encephalopathy may include: Personality changes Aggression Delusional behavior Concentration and memory problems Coma Disorientation Headaches Jerks in the muscles (myoclonus – 65% of cases) Lack of coordination (ataxia – 65% of cases) Partial paralysis on the right side Psychosis Seizures (60% of cases) Sleep abnormalities (55% of cases) Speech problems (transient aphasia – 80% of cases) Status epilepticus (20% of cases) Tremors (80% of cases)
Pathogenesis
The mechanism of pathogenesis is not known, but is thought to be an autoimmune disorder, similar to Hashimoto's thyroiditis, as its name suggests.
Consistent with this hypothesis, autoantibodies to alpha-enolase have been found to be associated with Hashimoto's encephalopathy. Since enolase is the penultimate step in glycolysis, if it were inhibited (for example by being bound by autoantibodies), one would expect decreased energy production by each cell, leading to resulting atrophy of the affected organ.
This would occur most likely through each cell shrinking in size in response to the energy deficit (and/or in extreme situations from some cells dying via either apoptosis or necrosis, depending on location). This may occur as a result of enough ATP not being available to maintain cellular functions - notably, failure of the Na/K ATPase, resulting in a loss of the gradient to drive the Na/Ca antiporter, which normally keeps out of cells so it does not build to toxic levels that will rupture cell lysosomes leading to apoptosis. An additional feature of a low-energy state is failure to maintain axonal transport via dynein/kinesin ATPases, which in many diseases results in neuronal injury to both the brain and/or periphery.
Pathology
Very little is known about the pathology of Hashimoto's encephalopathy. Post mortem studies of some individuals have shown lymphocytic vasculitis of venules and veins in the brain stem and a diffuse gliosis involving gray matter more than white matter.
As mentioned above, autoantibodies to alpha-enolase associated with Hashimoto's encephalopathy have thus far been the most hypothesized mechanism of injury.
Diagnosis
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% of cases) Single photon emission computed tomography shows focal and global hypoperfusion (75% of cases) Cerebral angiography is normal
Thyroid hormone abnormalities are common (>80% of cases): Subclinical hypothyroidism (35% of cases) Overt hypothyroidism (20% of cases) Hyperthyroidism (5% of cases) Euthyroid on levothyroxine (10% of cases) Euthyroid not on levothyroxine (20% of cases)
Thyroid antibodies – both antithyroid peroxidase antibodies (anti-TPO, antithyroid microsomal antibodies, anti-M) and antithyroglobulin antibodies (anti-Tg) – in the disease are elevated, but their levels do not correlate with the severity.
Electroencephalogram studies, while almost always abnormal (98% of cases), are usually not diagnostic. The most common findings are diffuse or generalized slowing or frontal intermittent rhythmic delta activity. Prominent triphasic waves, focal slowing, epileptiform abnormalities, and photoparoxysmal and photomyogenic responses may be seen.