Hashimoto\'s encephalopathy (HE) has been a poorly understood disease. It has been described in all age group, yet, there is no specific HE marker. Additionally, the treatment data in the available studies are frequently divergent and contradictory. Therefore, the aim of our systematic and critical review is to evaluate the diagnosis and treatment of HE in view of the latest findings. The databases browsed comprised PubMed, Scopus, and Google Scholar as well as Cochrane Library, and the search strategy included controlled vocabulary and keywords. A total of 2443 manuscripts were found, published since the beginning of HE research until February 2024. In order to determine validity of the data collected from studies, bias assessment was performed using RoB 2 tool. Ultimately, six studies were included in our study. HE should be considered in the differential diagnosis in patients with psychiatric and neurological symptoms. According to our findings, negative thyroid peroxidase antibodies (anti-TPOs) may represent a valuable parameter in ruling out HE. Nonetheless, this result cannot be used to confirm HE. Furthermore, the proposed anti NH2-terminal-α-enolase (anti-NAE) is non-specific for HE. The effectiveness of glucocorticoid therapy is 60.94%, although relapse occurs in 31.67% of patients following the treatment. Our review emphasizes the significance of conducting further large-scale research and the need to take into account the potential genetic factor.

Hashimoto encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis, has been defined by sub-acute onset encephalopathy, with elevated thyroid antibodies, and immunotherapy responsiveness, in the absence of specific neural autoantibodies. We aimed to retrospectively review 144 cases referred with suspected Hashimoto encephalopathy over a 13-year period, and to determine the clinical utility of thyroid antibodies in the course of evaluation of those patients. One hundred and forty-four patients (all thyroid antibody positive) were included; 72% were women. Median age of symptom onset was 44.5 years (range, 10-87). After evaluation of Mayo Clinic, 39 patients (27%) were diagnosed with an autoimmune CNS disorder [autoimmune encephalopathy (36), dementia (2) or epilepsy (1)]. Three of those 39 patients had neural-IgGs detected (high glutamic acid decarboxylase-65, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-receptor and neural-restricted unclassified antibody), and 36 were seronegative. Diagnoses among the remaining 105 patients (73%) were functional neurological disorder (n = 20), neurodegenerative disorder (n = 18), subjective cognitive complaints (n = 14), chronic pain syndrome (n = 12), primary psychiatric (n = 11), sleep disorder (n = 10), genetic/developmental (n = 8), non-autoimmune seizure disorders (n = 2) and other (n = 10). More patients with autoimmune CNS disorders presented with sub-acute symptom onset (P < 0.001), seizures (P = 0.008), stroke-like episodes (P = 0.007), aphasia (P = 0.04) and ataxia (P = 0.02), and had a prior autoimmune history (P = 0.04). Abnormal brain MRI (P = 0.003), abnormal EEG (P = 0.007) and CSF inflammatory findings (P = 0.002) were also more frequent in the autoimmune CNS patients. Patients with an alternative diagnosis had more depressive symptoms (P = 0.008), anxiety (P = 0.003) and chronic pain (P = 0.002). Thyoperoxidase antibody titre was not different between the groups (median, 312.7 versus 259.4 IU/ml; P = 0.44; normal range, <9 IU/ml). None of the non-autoimmune group and all but three of the CNS autoimmune group (two with insidious dementia presentation, one with seizures only) fulfilled the autoimmune encephalopathy criteria proposed by Graus et al. (A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15: 391-404.) (sensitivity, 92%; specificity, 100%). Among patients who received an immunotherapy trial at our institution and had objective post-treatment evaluations, the 16 responders with autoimmune CNS disorders more frequently had inflammatory CSF, compared to 12 non-responders, all eventually given an alternative diagnosis (P = 0.02). In total, 73% of the patients referred with suspected Hashimoto encephalopathy had an alternative non-immune-mediated diagnosis, and more than half had no evidence of a primary neurological disorder. Thyroid antibody prevalence is high in the general population, and does not support a diagnosis of autoimmune encephalopathy in the absence of objective neurological and CNS-specific immunological abnormalities. Thyroid antibody testing is of little value in the contemporary evaluation and diagnosis of autoimmune encephalopathies.

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Pure acute onset chorea without encephalopathy has rarely been reported in anti-thyroid peroxidase (anti-TPO)/anti-thyroglobulin (anti-TG) antibody-related neurologic disorders responsive to steroids (ATANDS).
We report a 16-year-old female who presented with acute chorea without encephalopathy. Anti-TPO antibodies were found to be strongly positive (>1200 IU/ml) along with anti-thyroglobulin and anti-thyroid stimulating hormone receptor antibodies. After pulse intravenous methylprednisolone therapy (1 g/day for five consecutive days), all the movements seized, and she was discharged with oral prednisolone 30 mg/day with gradual tapering over next three months. After one year of follow-up, she is stable, drug-free, and never had any other problems.
Anti-thyroid antibodies testing should be included in routine/conventional panel that is done for elucidating causes of chorea as ATANDS can be easily missed and is treatable with widely available, relatively low-cost drugs like steroids with a promising outcome.

We report a case of a 60-year-old woman with a history of intractable seizures and isolated delusional psychosis who was later diagnosed with steroid-responsive encephalopathy associated with autoimmune thyroiditis. The patient underwent right temporal lobectomy (epilepsy surgery) 15 years before coming to this clinic, but continued to have focal seizures, resulting in frequent emergency room visits thereafter. After admission for intensive inpatient video electroencephalogram monitoring and subsequent 7 months of close follow-up, both the electroencephalogram abnormalities and isolated delusional psychosis were found to be responsive to immunotherapy. This suggests that her epilepsy may be autoimmune in nature. Steroid-responsive encephalopathy associated with autoimmune thyroiditis was diagnosed after 26 years since the onset of seizures. Performing invasive epilepsy surgery in patients with autoimmune epilepsy cannot reverse the inflammatory process; therefore, it is reasonable to test for autoimmune etiologies before excision surgery on patients with medically intractable epilepsy. This case demonstrates the clinical use of quantitative electroencephalogram in assisting with the diagnosis of steroid-responsive encephalopathy associated with autoimmune thyroiditis and supports that it is a spectrum disorder with protean manifestations.

Myoclonus and tremor are common movement disorder phenomenologies in steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT). Pure ataxia without encephalopathy has rarely been reported.
We report 21- and 40-year-old females who presented with subacute pure ataxia without encephalopathy. After immunotherapies, both exhibited initial improvement of ataxia, and subsequently remained in plateau phase.
This treatable disorder should be added to the differential diagnoses of progressive cerebellar ataxia, and anti-thyroid peroxidase and anti-thyroglobulin should be considered as part of the workup. It is crucial not to misdiagnose SREAT presenting with pure cerebellar ataxia as degenerative or spinocerebellar ataxia.

OBJECTIVE: Hashimoto encephalopathy is an autoimmune encephalopathy characterized by elevated antithyroid antibodies and a favorable response to corticosteroid. This study delineated the clinical characteristics of pediatric Hashimoto encephalopathy and the significance of low antithyroid antibody titers in diagnosis and treatment.
METHODS: Clinical manifestations, antibody titers, and treatment responses were retrospectively reviewed in six consecutive children diagnosed with Hashimoto encephalopathy between August 2008 and July 2016.
RESULTS: Age at diagnosis was 10-17years. Presenting symptoms were seizures, altered consciousness, behavioral changes, psychosis, tremor, and dystonia. Thyroid function was normal in five patients, and one had hypothyroidism prior to the encephalopathy. Antithyroid antibody titer was increased at presentation in five patients and one week later in the other. Antibody levels were extremely varied (anti-thyroglobulin, 20.5-2318.0U/ml; anti-thyroid peroxidase, 12.5-2231.0U/ml; reference range, <60U/ml) and <180U/ml in two patients. Electroencephalogram was abnormal in five patients. Brain magnetic resonance imaging was unremarkable. Four patients responded to high-dose corticosteroid and one improved with additional intravenous immunoglobulin. The remaining patient did not respond to both treatments and normalized after plasmapheresis. Autoantibody titers decreased with treatment response in the acute stage. Two patients with low antibody titers showed similar clinical presentations and responses.
CONCLUSIONS: The clinical presentations and treatment responses in Hashimoto encephalopathy were similar, irrespective of antithyroid antibody titer. Because the initial antithyroid antibody titers can be normal or mildly-elevated, follow-up testing of antithyroid antibodies is required in patients who are clinically suspect for Hashimoto encephalopathy.

BACKGROUND: Schizophreniform syndromes can be divided into primary forms from polygenic causes or secondary forms due to immunological, epileptiform, monogenic, or degenerative causes. Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a secondary immunological form associated with increased thyroid antibodies, such as antithyroid peroxidase antibodies and shows a good response to corticosteroids.
METHODS: We present the case of a 41-year-old woman suffering from a schizophreniform syndrome. Starting at the age of 35, she developed psychotic exacerbations with formal thought disorder, acoustic hallucinations, cenesthopathic experiences, and loss of ego boundaries. At the same time, she began to suffer from chronic sexual delusions and olfactory hallucinations, which did not respond to neuroleptic medication. Her levels of antithyroid peroxidase antibodies were slightly increased, and the blood-brain barrier was disturbed. An electroencephalogram (EEG) showed intermittent generalized slowing, and cerebral magnetic resonance imaging (cMRI) depicted mild temporolateral atrophy. High-dose corticosteroid treatment led to convincing improvement of attentional performance and the disappearance of delusions and olfactory hallucinations.
CONCLUSIONS: SREAT can mimic typical symptoms of schizophreniform syndromes. The increased titer of antithyroid peroxidase antibodies in combination with the EEG slowing, blood-brain barrier dysfunction, and the cMRI alterations were the basis for suspecting an immunological cause in our patient. Chronic delusions, olfactory hallucinations, and cognitive deficits were successfully treated with corticosteroids. The occurrence of secondary immunological forms of schizophreniform syndromes demonstrates the need for innovative immunosuppressive treatment options.

BACKGROUND: Steroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) is characterized by encephalopathy and the presence of antithyroid antibodies. We describe the clinical presentation, outcome and treatments for SREAT by a systematic review of the literature.
METHODS: MEDLINE via PubMed, Web of Science and the Cochrane Library were searched for articles published until 2015. Inclusion criteria were unexplained encephalopathy with antithyroid antibodies.
RESULTS: We found reports of 251 patients (median age 52years [range 18-86], 73% females, 80 [32%] with preexisting thyroiditis). Patients presented encephalitis signs with convulsions (n=117; 47%), confusion (n=115, 46%), speech disorder (n=91, 37%), memory impairment (n=107, 43%), gait disturbance (n=67, 27%) and persecutory delusions (n=61, 25%). Twenty-eight patients (11%) presented progressive memory impairment and 26 (10%) isolated psychiatric disorders. In serum, 34% of patients were positive for anti-thyroid peroxidase (TPO) antibodies, 7% for anti-thyroglobulin (TG) antibodies, and 69% both. Thyroid-stimulating hormone levels were usually normal, at 2 UI/ml [0.001-205]. Cerebrospinal fluid from 10/53 patients (19%) was positive for anti-TPO antibodies, 2/53 (4%) anti-TG antibodies and 28 (53%) both. Electroencephalography findings were abnormal for 82% of patients, showing diffuse slowing consistent with encephalopathy (70%) or epileptic activity (14%). The first-line treatment was steroids in 193 patients and other immunosuppressive drugs in 10 cases. At a median follow-up of 12months [range 0.2-110], 91% of patients showed complete or partial neurological response, with anti-TPO and -TG antibody titers at 347 UI/ml [0-825,000] and 110 UI/ml [0-50,892], respectively. During follow-up, 40 patients (16%) experienced at least one relapse. Relapse was more frequent in patients with initial coma (26% vs 13%, p=0.08).
CONCLUSIONS: The diagnosis of SREAT should be suspected in case of encephalopathy without obvious cause, to quickly start corticosteroid treatment. The exact modalities of treatment must be defined.

Autoimmune dementia and encephalopathies (ADE) are complex disorders that can cause immune-mediated cognitive deficits and have confusing nomenclature. Presentation varies from acute limbic encephalitis to subacute or chronic disorders of cognition mimicking neurodegenerative dementia. It may occur as a paraneoplastic phenomenon or an idiopathic autoimmune phenomenon. The presence of a personal/family history of autoimmunity, inflammatory spinal fluid, serologic evidence of autoimmunity (neural or nonorgan-specific), or mesial temporal magnetic resonance imaging abnormalities are clues to diagnosis. Bedside cognitive assessment and/or detailed neuropsychologic testing are useful. Neural-specific autoantibodies, mostly discovered in the past two decades, may bind antigens on the cell surface (e.g., N-methyl-d-aspartate receptor autoantibodies) and are likely to be pathogenic, with treatment aimed at antibody-depleting agents often with success, while antibodies binding intracellular antigens (e.g., antineuronal nuclear autoantibody type 1 (ANNA1 or anti-Hu)) are a marker of a T-cell-mediated process and treated with T-cell-depleting immunotherapies, with variable responses. Detection and treatment of cancer (when present) are essential. High-dose corticosteroids are the initial treatment in most patients and may serve as a diagnostic test when the diagnosis is uncertain. Repeat cognitive testing after immunotherapy helps document objective improvements. Maintenance immunotherapy is recommended in those at risk for relapse. Prognosis is variable, but paraneoplastic ADE with antibodies to intracellular antigens have a worse prognosis. The field is still developing and future studies should provide guidelines for diagnosis and treatments.