Overview

Hashimoto encephalopathy is a neurological, as well as endocrinological, disorder, whose symptoms are caused by a high count of antithyroid antibodies.¹  The disease is an encephalopathy, a term which generally refers to a disease of the brain, and should not be confused with encephalitis, which is an inflammation of the brain. The high number of antithyroid antibodies impairs the thyroid function and the thyroid itself, leading to organ damage and tissue inflammation. The result is a lower thyroid function, which generally leads to symptoms of hypothyroidism. Hashimoto encephalopathy is a controversial disorder as its symptoms are not only endocrinological, but also fall under the neurological spectrum, and include seizures, cognitive and psychiatric symptoms, movement disorders and coma. This article will overview the pathological aspects of the disorder, how these are diagnosed, and finally the repercussions of the autoimmune diseases on neurological symptoms will be discussed. 

Signs and symptoms

The symptoms of Hashimoto encephalopathy involve both the disruption of the thyroid’s normal function, as well as neurological features.¹ Most cases of the disease show symptoms of hypothyroidism, a condition in which the thyroid is underactive, leading to fatigue, lethargy, weight gain, constipation, cold intolerance or dry skin.² However, some cases of Hashimoto encephalopathy do not involve signs of hypothyroidism, and some symptoms of thyroid overactivity have been reported.¹ The defining signs of the disease involve neurological aspects, ranging from movement disorder to psychiatric conditions or seizures. The neurological symptoms that arise from a high count of antithyroid antibodies that define the condition are, in fact, very broad and subject-specific. For example, the movement impairment symptoms that can be seen in patients are transient aphasia, which impairs the capacity to produce oral speech, ataxia, which leads to poor muscle control and consequently to impaired gait patterns, and tremor. As far as the psychiatric signs of Hashimoto encephalopathy are concerned, some patients experience paranoia or visual hallucinations, as well as sleep disturbances and headaches.

The autoimmune reaction effect on the brain

To explain why an autoimmune reaction which directly attacks the thyroid gland, which is an endocrine organ responsible for regulating our hormones, leads to neurological symptoms, differential techniques have been used.³ To understand the cellular effects of the disease, post-mortem studies on Hashimoto encephalopathy patients have been useful, although in a limited number of reported cases, to explain mechanisms of the appearance of neurological symptoms. Alternatively, imaging techniques have been used to understand the disease pathology in living patients.

From a molecular point of view, the elevated number of antibodies responsible for Hashimoto encephalopathy causes infiltration of lymphocytes, which are molecules of the immune system produced by the body, in some areas of the brain. These brain areas comprise the cortex, the basal ganglia, the thalamus and the hippocampus. Other molecules produced by immune reaction by the immune system are T-cells, and these appear to infiltrate predominantly the brainstem. For both the immune system molecules, the infiltration happens and is found by analysis of the blood supply system to the brain to the aforementioned areas, which are responsible for many functions, for example, movement and memory. The impairment of these areas leads to the symptoms of Hashimoto encephalopathy.

Imaging techniques have been able to show, also supported by cellular studies, that the autoimmune reaction, characteristic of the disease, also reduces axonal integrity. Axons are parts of all neurons, and their function is to allow information flow between separate neurons: in some instances these axons are covered in a fatty layer, myelin, to allow a faster flow of information. The high number of circulating lymphocytes, caused by the elevated number of antithyroid antibodies, causes myelin destruction in part of the neurons, consequently impairing proper neuronal communication.

As we have seen, the impaired function of one organ, such as the thyroid, is not limited to the organ itself, but causes damage to other systems: Hashimoto encephalopathy is a condition which highlights the intrinsic link between our endocrine, immune and nervous system, which is of essential study for this condition, but also for other conditions with mainly only apparent neurological symptoms. 

Clinical features of encephalopathies

Hashimoto encephalopathy leads to common features for encephalopathies, for example personality, changes and altered states of consciousness.³ These clinical features can be either fluctuating or continuous. 

In more than 80% of the reported cases, some form of cognitive dysfunction is present: often these are connected with speech disorders or memory impairments. In 25 to 30% of the cases, stroke-like episodes have been reported, while in approximately 1/3 of the cases, seizure-like episodes are a common symptom, accompanied by movement and gait impairments. Another common clinical feature is disturbed sleep, both due to insomnia or hypersomnolence and disturbed rapid-eye-movement sleep.

Lastly, several reported cases of Hashimoto encephalopathy also report instances of psychosis and hallucinations. The neuropsychiatric features of Hashimoto encephalopathy can lead to psychosis with delusions, and predominantly visual hallucinations, although some auditory hallucinations have been described in the literature. As far as mood is concerned, both depressive states as well as elated states have been described, as a consequence of autoimmune reactions underlying the neurological features.

Diagnosis

The underlying cause of the broad spectrum of endocrine and neurological symptoms of the disorder stems from the common diagnosis of an elevated number of antithyroid antibodies present in the bloodstream.¹ The difficulty with reaching this diagnosis is that sometimes, as the symptoms are not related to thyroid functions, the high number of antithyroid antibodies is not promptly found.

Other than antithyroid antibodies (anti-TSH), blood tests aim to detect the presence of antithyroid peroxidase antibodies (anti-TPO), as these antibodies indirectly attack the thyroid function, and therefore are responsible for the disease pathogenesis.³ Another diagnostic measurement for encephalopathies is to measure the protein count in cerebrospinal fluid (CSF), which is higher than normal in around 80% of Hashimoto encephalopathy patients, although attention has to be posed in what type of protein is collected from the CSF.

Alternative screening methods for Hashimoto encephalopathy are not well established, as electroencephalogram findings are not specific to the disease, and other methods, such as imaging techniques, have not been studied extensively enough as of now.

Epidemiology

Hashimoto encephalopathy is found in approximately 2.1 over 100,000 people, by estimating the detectable levels of antithyroid antibodies that underlie the pathology.³ It is therefore a rare condition, that often is not detected, as the hypothyroidism symptoms, which lead to a more prompt investigation of thyroid function, are mainly present in some population groups only, for example in women over 65 years.² However, the condition has been reported in aged populations, as well as adult and paediatric populations, with a mean onset age between 45 and 55 years.³

Treatment and management

The disease is mainly treated and is responsive to, high doses of corticosteroids, such as prednisolone.³ The function of corticosteroids is to lower the autoimmune reaction that causes the initial rise in antibodies that, in the case of Hashimoto encephalopathy, causes the impaired function of the thyroid and the neurological symptoms of the disease.

As Hashimoto encephalopathy’s symptoms, both the neurological ones and the end ones, are caused by an autoimmune reaction, corticosteroid administration is effective for treatment. However, it has to be considered that long-term administration of the drugs for disease management can cause adverse effects, for example, osteoporosis, a condition which leads to more fragile bone structure. To avoid damage caused by the long-term administration of corticosteroids, these can be administered in pulses, but this technique has to be considered on a single-patient basis, as it does not always yieldthe same beneficial effect for Hashimoto encephalopathy treatment.

Summary

Hashimoto encephalopathy is an endocrine and neurological disease which leads to a broad spectrum of symptoms, both involving thyroid function and neural activity. Its neurological symptoms derive from the effects of a higher count of antithyroid antibodies, which both cause endocrine imbalances, by directly attacking the thyroid gland and also cause neurological symptoms. These neurological symptoms can include episodes of amnesia, seizures, mood disorders or visual hallucinations. The disease can be managed as it responds well to treatment through corticosteroids, whose administration aims to reduce the initial immune response that causes the increase of antithyroid antibodies, responsible for the symptoms and Hashimoto encephalopathy itself.