Hashimoto's encephalopathy. Case report and literature review

We present a 43-year-old man with recurrent episodes of Hashimoto's encephalopathy who was diagnosed with autoimmune thyroiditis in childhood. Encephalopathy started with subacute dementia followed by extrapyramidal and psychiatric symptoms of insidious onset. He had also status epilepticus which occurred within the first year of the disease. The patient was in euthyreosis, but increased levels of antithyroid antibodies were found. MRI of the brain was normal. Electroencephalography was initially normal and later showed diffuse slowing with generalized theta/delta activity. The cerebrospinal fluid examination revealed a high level of protein which decreased when remission of the disease was achieved. After other etiology was excluded Hashimoto's encephalopathy was diagnosed. Almost complete clinical recovery after steroid administration was observed. Attempts of prednisone withdrawal led to recurrence of neurological and psychiatric symptoms. The diagnosis of Hashimoto's encephalopathy should be considered in each case with subacute encephalopathy associated with high levels of antithyroid antibodies (despite normal thyroid function) and in the absence of other brain diseases.     

Steroid-responsive encephalopathy in autoimmune thyroiditis: Clinical spectrum and MRI observations in three cases

Hashimoto''s encephalopathy (H.E.) is probably of autoimmune etiology, and manifests with seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms, myoclonus. It is presumed to be autoimmune in origin with high serum titers of antithyroid peroxidase antibodies (anti-TPA). Thyroid function might often be normal. The diagnosis is arrived at by excluding other toxic, metabolic and infectious causes of encephalopathies, supportive clinical profile, elevated thyroid antibodies and optimum steroid response. We present the characteristic phenotypic manifestations, magnetic resonance imaging and electroechography observations and response to immunomodulation with follow-up in three cases of H.E. All the three cases manifested with subacute to chronic progressive encephalopathy, cerebellar dysfunction, seizures, behavioral abnormalities and oculomotor disturbances and had evidence of hypothyroidism, elevated titers of anti-TPA and positive thyroid anti-microsomal antibodies. Atypical and uncommon presentations are known. This report emphasizes that a high index of suspicion is often required in cases with “investigation negative encephalopathy” for early diagnosis of H.E.     

Hashimoto's encephalopathy

We describe a 59-year-old female with Hashimoto's encephalopathy whose presentation was characterized by a subacute onset of confusion, depressed level of consciousness, tremor and pyramidal signs. She was euthyroid on presentation but antithyroid antibodies were elevated. Hashimoto's thyroiditis was confirmed by thyroid biopsy. There was a spontaneous remission of the neurological disorder. Subacute encephalopathy is often investigated with thyroid function tests only. In cases of unexplained encephalopathy, thyroid antibodies and/or thyroid biopsy should be performed to exclude this condition.     

Hashimoto's encephalopathy: epidemiologic data and pathogenetic considerations

BACKGROUND: Hashimoto's encephalopathy (HE) is a condition believed to complicate Hashimoto's thyroiditis (HT). The diagnosis is suspected in the presence of high levels of serum anti-thyroid antibodies. We have recently demonstrated that in patients with HE there is an intrathecal synthesis of anti-thyroid antibodies, and concluded that the diagnosis of HE should be based on this cerebrospinal fluid (CSF) finding. OBJECTIVE: getting an estimate of the prevalence of the disease, verifying the association with HT and investigating the pathogenetic role of anti-thyroid antibodies. METHODS: 34-months prospective study in a hospital setting serving a community of 150,000 people. Patients with unexplained symptoms of acute or subacute encephalopathy or myelopathy or with a history of thyroid disorders were selected for the measurement of anti-thyroid antibodies. In the presence of high serum levels of autoantibodies, the same tests were performed in the CSF. RESULTS: Twelve patients had increased concentrations of serum autoantibodies but HE was diagnosed only in nine patients. The estimated prevalence of HE is 2.1/100,000. Only six HE patients had also HT. Four patients received corticosteroids, five patients were not treated. Five patients improved, four patients spontaneously, one patient after corticosteroids. Repeated CSF examinations showed that the titer of CSF autoantibodies did not correlate with the clinical stage of the disease nor was influenced by corticosteroids. In addition, the course of symptoms was independent of therapy. CONCLUSIONS: The association of encephalopathy and high titers of anti-thyroid antibodies is not sufficient to make a diagnosis of HE. Independent of the clinical status of the thyroid gland, the intrathecal synthesis of autoantibodies is a distinctive marker of this elusive condition.     

Hashimoto's encephalitis: a new case with spontaneous remission

Hashimoto's encephalopathy is a poor understood neurological disorder associated with thyroid disease. We describe a 12 years old woman with a relapsing clinical picture characterized by acute onset confusion, tremor, convulsive seizures and a stroke-like episode associated with autoimmune thyroid disease. High titers of antithyroid antibodies were detected in her serum. Neurologic investigation showed a marked slowing of the basic activity in EEG, diminished perfusion of left hemisphere in brain SPECT, mild CSF protein level without pleocytosis, and normal brain CT and cerebral angiogram. The clinical course was favorable without corticosteroid therapy. Antithyroid antibodies and EEG were normal after one-year follow-up. We suggest that antithyroid antibody levels should be checked in any unexplained acute or subacute encephalopathy, especially when a relapsing course, stroke-like exacerbation, seizures, tremor or elevation of the CSF protein are found.     

Subacute cognitive deterioration with high serum anti‐thyroid peroxidase antibodies: two cases and a plea for pragmatism

Autoimmune encephalopathy is a rare but potentially reversible cause of cognitive deterioration and neuropsychiatric disturbances. We describe two older female patients with subacute cognitive decline and marked neuropsychiatric disturbances in the presence of high serum anti‐thyroid peroxidase antibodies and with normal dosage of free thyroxine 4. One patient recovered almost completely after oral corticotherapy. Differential diagnosis and the role of biomarkers, in particular, are discussed. We support a pragmatic approach involving a short empirical therapeutic trial with intravenous or oral corticoids; this should be considered in all patients with subacute encephalopathy and with laboratory arguments for an underlying autoimmune aetiology.     

A case of Hashimoto's encephalopathy associated with Graves' disease]

A 23-year-old woman with Graves' disease was first admitted to a hospital because of generalized convulsion, consciousness disturbance, and tachycardia. Investigations showed biochemical hyperthyroidism and positive thyroid binding inhibitory immunoglobulin (TBII). She was treated with anticonvulsant and antithyroid therapy. One month later the patient developed the second episode of generalized convulsion, followed by cognitive deficits especially concerning short-term memory, when she was transferred to our hospital. Although thyroid function was normalized at that time, anti-thyroid peroxidase (TPO) antibodies level were elevated to 5,850 U/ml in the serum, and 4.9 IU/ml in CSF. CSF protein was elevated to 133 mg/dl. Brain SPECT showed global decrease of cerebral perfusion, and EEG demonstrated diffuse slowing of the background rhythm without any signs of epileptic activity, although brain MRI was normal. Based on a diagnosis of Hashimoto's encephalopathy associated with Graves' disease, therapy with steroids was started, which definitely improved her clinical symptoms. Anti-TPO antibodies disappeared in CSF and decreased in the serum after the treatment. Hashimoto's encephalopathy should always be kept in mind in patients with Hashimoto's disease and Graves' disease.     

Hashimoto's encephalopathy and motor neuron disease: a common autoimmune pathogenesis?

Hashimoto's encephalopathy is a rare complication of autoimmune thyroiditis not associated with thyroidal function decline. We report a 50-year-old man presenting with lower motor neuron symptoms evolving over 3 years and changes in behavior associated with attentive and cognitive impairment occurring in the last few months. Memory deficits, emotional instability, marked dysarthria, mild symmetric weakness of the lower extremities and fasciculations were the most striking clinical features. EEG was diffusely slow, cranial MRI revealed multiple subcortical white matter lesions, CSF protein was slightly elevated, electromyographic recordings showed acute and chronic denervation and extremely high TPO antibody titers were found in the serum. Hashimoto's encephalopathy and lower motor neuron disease were diagnosed. As repeated high-dose intravenous methylprednisolone administration followed by oral tapering improved both central nervous system and lower motor neuron symptoms, the question was raised whether there was a common autoimmune pathogenesis of both clinically distinct diseases.     

Reversible posterior leukoencephalopathy syndrome in Hashimoto's encephalopathy: a case report]

A 45-year-old woman with breast cancer was admitted to our hospital because of several episodes of disturbed consciousness and generalized convulsions. While these symptoms resolved quickly, dysphagia and bilateral blepharoptosis persisted. Neurological findings were improved by steroid therapy. MRI on the first hospital day showed T2/FLAIR high intensity lesions in both occipital lobes, but these lesions diminished on the 8th day, indicating reversible posterior leukoencephalopathy syndrome. A new lesion appeared in the left temporal lobe on the 8th day. A diagnosis of Hashimoto's encephalopathy (HE) was made due to the following features: 1) encephalitis not due to herpes simplex virus, 2) high titers of antithyroid antibodies in serum, 3) marked effectiveness of steroid therapy, and 4) antibodies against the amino terminal of alpha-enolase, a specific antigen for HE.     

Encephalopathy associated to autoimmune thyroid disease: a more appropriate term for an underestimated condition?

Hashimoto's encephalopathy is a severe and rather infrequent clinical condition initially described in patients suffering from chronic lymphocytic thyroiditis. Its origin is still controversial but it can be agreed to have an autoimmune etiology. In fact, its most characteristic finding is the high titre of antithyroid antibodies, especially antimicrosomal. We describe three cases of Hashimoto's encephalopathy and establish a relationship between the clinical status, the antithyroid antibody levels and its response to corticosteroid treatment. There was an excellent response to corticosteroid treatment in all three cases. Interestingly, one case was associated with Graves' disease. Given this, and after the review of the literature, we believe that the term 'encephalopathy associated to autoimmune thyroid disease' could be more appropriate to define this entity. Finally, we suggest that autoimmune thyroid encephalopathy must be suspected in the face of unaccounted acute or subacute encephalopathy with high levels of antithyroid antibodies.     

Hashimoto's encephalopathy in the elderly: relationship to cognitive impairment

Hashimoto's encephalopathy (HE) is a steroid-responsive encephalopathy associated with high titers of antithyroid antibodies. To date, 57 pediatric-, adult-, and elderly-onset cases have been described in the literature. The clinical picture is pleomorphic, and cognitive impairment is a frequently reported symptom. We report the case of a patient with slowly progressive cognitive impairment possibly caused by HE. The issue of the differential diagnosis with primary dementia is discussed. A review of cases of HE showing cognitive deterioration is also presented, and factors possibly related to characteristics of cognitive impairment and outcome after therapy are considered.     

A patient with Hashimoto's encephalopathy showing subacute global cognitive dysfunction]

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.     

Antithyroid antibodies in the CSF: their role in the pathogenesis of Hashimoto's encephalopathy

Antithyroid antibodies and circulating immune complexes (CIC) were found in the CSF of six patients with Hashimoto's encephalopathy (HE) but not in the CSF of 21 controls. The synthesis of autoantibodies and CIC was intrathecal and their titers were independent of the patients' clinical status or therapy. Their presence in the CSF of patients with acute or subacute encephalopathy may be useful in diagnosing HE.     

Infectious disease or Hashimoto's encephalopathy flares: A case report

Hashimoto's encephalopathy is an under-recognized and rare disease that presents a diagnostic conundrum since many features are suggestive of infectious etiologies and yet treatment is immunosuppressive medications. We describe a case of a male with a history of recurrent seizures who presented with a subacute onset of confusion, persistent leukocytosis and fever while on immunosuppressant therapy, whose response to high dose steroids was incomplete and who achieved a complete remission of all symptoms when plasmapheresis was initiated. A negative cerebrospinal fluid (CSF) and serum microbiological testing in a patient with an abnormal EEG, increased CSF protein, and elevated thyroid antibodies should prompt consideration of Hashimoto's encephalopathy. If after treating with high dose steroids, there is a sub-optimal clinical response, plasmapheresis should be considered.     

Non-herpetic acute limbic encephalitis-like manifestation in a case of Hashimoto's encephalopathy with positive autoantibodies against ionotropic glutamate receptor epsilon2]

A 37-year-old woman developed memory disturbance and seizures preceded by headache and high fever. Physical examination revealed persistent high fever, confusion, neck stiffness, anterograde and retrograde amnesia and disorientation. CSF showed pleocytosis and normal glucose level, and negative herpes simplex virus DNA on PCR. The fluid attenuated inversion recovery (FLAIR) MRI of the brain demonstrated nearly symmetric high signal intensity areas in the bilateral mesial temporal lobes. The tentative clinical diagnosis was non-herpetic acute limbic encephalitis (NHALE), and administration of methylprednisolone improved her conditions. Laboratory tests revealed mild hypothyroidism with high titers of serum antibodies against TPO and thyroglobulin, consistent with Hashimoto's disease. In addition, antibodies against amino terminal of alpha-enolase in the serum and those against glutamate receptor (GluR) epsilon2 in the serum and CSF were positive. A final diagnosis of Hashimoto's encephalopathy associated with GluRepsilon2 antibody was made. The present case suggests that NHALE-like clinical manifestation can be produced by autoimmune-mediated encephalopathies.     

Manifestation of Hashimoto's encephalopathy years before onset of thyroid disease

Patients with Hashimoto's encephalopathy (HE), a steroid-responsive disorder, associated with Hashimoto's disease and high levels of thyroid-related autoantibodies usually present with a subacute onset of confusion, focal or generalized seizures. Frequent EEG abnormalities include generalized, rhythmic bifrontal or temporal slowing. Elevated protein levels or an intrathecal IgG synthesis may be present in cerebrospinal fluid (CSF). A 39-year-old woman underwent a relapsing course of myocloni and generalized seizures. Initially, thyroid function, thyroid-related autoantibody screening and cerebral MRI were unrevealing. CSF showed oligoclonal bands. Short-term treatment with high doses of prednisolone resolved the myocloni. During the 5th episode of myocloni, signs of hyperthyroidism and elevation of thyroid microsomal antibody titer developed. Hashimoto's thyroiditis and HE were diagnosed. After subtotal thyroidectomy the patient remained asymptomatic.     

Hashimoto's encephalopathy: documentation of mesial temporal seizure origin by ictal EEG.

Hashimoto's encephalopathy is a chronic relapsing and remitting encephalopathy associated with antithyroid antibodies. Seizures are a frequent manifestation, but are not well characterized in the literature with respect to their onset. We describe a 48-year-old patient with recurrent encephalopathy and seizures, and elevated antithyroid antibodies. One seizure was documented with video-EEG monitoring using scalp and sphenoidal electrodes. The ictal discharge originated in the left mesial-basal temporal region. MRI showed an increased T2 signal in the white matter of the centrum semiovale, but no temporal pathology. Symptoms resolved after treatment with prednisone and azathioprine. Hashimoto's encephalopathy should be considered in patients with unexplained encephalopathy and seizures, including those originating in the temporal lobe.     

Elevated thyroid peroxidase antibodies with encephalopathy in MELAS syndrome

Both the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) and Hashimoto's encephalopathy can present with nonspecific encephalopathy. Hashimoto's encephalopathy is an association of steroid-responsive encephalopathy with elevated thyroid peroxidase antibodies. Steroid-responsive encephalopathy, however, is not characteristic of the MELAS syndrome, which typically presents with stroke-like episodes and lactic acidosis in cerebrospinal fluid and blood. Here, a patient is described with goiter, recurrent encephalopathy and elevated thyroid peroxidase antibodies who apparently responded to steroid therapy; however, magnetic resonance imaging was atypical for Hashimoto's encephalopathy, and she was diagnosed with MELAS syndrome. This syndrome can present with apparent steroid-responsive encephalopathy and elevated thyroid peroxidase antibodies, mimicking Hashimoto's encephalopathy, and should be suspected if lactic acidosis is present and typical features are detected on magnetic resonance imaging.     

Amnesic syndrome with bilateral mesial temporal lobe involvement in Hashimoto's encephalopathy

A 25-year-old woman presented with a subacute confusional state, headaches, unsteadiness, myoclonus, seizures, and an amnesic syndrome as a manifestation of Hashimoto's encephalopathy. Investigations showed biochemical hypothyroidism, raised thyroid microsomal antibodies, and weakly positive antineuronal antibodies. A T2-weighted MRI of the brain showed bilateral symmetric areas of increased signal in the mesial temporal lobes and hippocampi that had a low signal intensity on T1-weighted imaging. Despite clinical and radiologic improvement after steroid and thyroid hormone replacement therapy, a severe amnesic syndrome with associated localized MRI abnormalities persists.     

Depression, anti-thyroid antibodies and Hashimoto encephalopathy]

Psychiatric manifestations are infrequent or rarely described in Hashimoto's encephalopathy. It usually begins like a subacute diffuse encephalopathy with confusion, tremor and other neurologic symptoms. A relapsing course is characteristic. Neither biologic nor clinical symptoms are specific but high antithyroid antibodies levels are characteristic. The diagnosis can be seriously delayed by the fact that the different symptoms implicate approaches by psychiatrists, neurologists or endocrinologists. There are two clinical types. The one presented here evaluates progressively to dementia with psychotic episodes, confusion and seizures. An early steroid treatment makes the symptoms regress without aftereffects. We have analysed the clinical and biological findings of a woman who has been admitted to different neurologic and psychiatric departments before her diagnosis was made. First clinical presentation and evolution were that of a depression. Each time the antidepressive treatment was stopped, depression relapsed in spite of an appropriate steroid treatment. Literature shows that a close link exists between depression and antithyroid antibodies whatever thyroid status. This link does still exist after adjustment of psycho-social determinants of depression. The decrease of those antibodies only reflects the decrease of inflammation. So, for the psychiatrist it is important to diagnose Hashimoto's encephalopathy without delay, especially when psychiatric manifestations are in the foreground. Furthermore, a psychiatric report should systematically be added to the clinical and biological findings in order to make a better approach of the existing links between depression and other manifestations of the disease.