Non-convulsive status epilepticus of frontal origin as the first manifestation of Hashimoto's encephalopathy

Hashimoto's encephalopathy is an often misdiagnosed, life threatening, condition which improves promptly with steroid therapy. Since clinical manifestations are heterogeneous and non-specific, the diagnosis is often difficult. Several case reports of Hashimoto's encephalopathy presenting with partial or generalised seizures are described, but only a few have focused on status epilepticus as the first clinical manifestation. We report two patients presenting with repetitive and prolonged seizures characterised by progressive reduction in contact and reactivity associated with frontal/diffuse polyspike-and-wave activities. This condition, which can be interpreted as a form of non-convulsive status epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but responded promptly to high doses of intravenous steroid treatment. In cases of unexplained encephalopathy with EEG documentation of NCSE, the early recognition and treatment of Hashimoto's encephalopathy may lead to a favourable prognosis. [Published with video sequences].     

Autoimmune thyroid encephalopathy presenting with epilepsia partialis continua.

We report the first case of an autoimmune thyroid encephalopathy presenting with multifocal motor status epilepticus. A 37-year-old female patient was admitted with multifocal motor seizures intractable to intravenous status epilepticus treatments, asymmetrical quadriparesis, truncal ataxia and continuous semi-rhythmical jerks. Pathological signal alterations were detected in both precentral cortices in MRI examination. Autoimmune thyroiditis was diagnosed after radiological examinations of the thyroid gland and thyroid function tests. Seizures promptly ceased following intravenous steroid treatment. Immunohistochemistry studies showed mild to moderate neuronal staining with the plasma and CSF samples. Remarkably, autoimmune thyroiditis may present with migrating focal motor status epilepticus. We recommend anti-thyroid antibody screening for multifocal motor status epilepticus cases of unspecified cause.     

Palatal tremor, focal seizures, repeated miscarriages and elevated anti-thyroid antibodies

Neurological manifestations of thyroid autoimmunity are heterogeneous and nonspecific. The most frequently adopted name for this entity is Hashimoto's encephalopathy although this eponym has been recently contested. In the absence of specific clinical features, diagnosis is suggested by the presence of elevated levels of anti-thyroid antibodies in the appropriate clinical context. We describe a patient with recurrent focal seizures, palatal tremor and elevated anti-thyroid antibodies but no encephalopathy. Her past medical history was marked by recurrent miscarriages. The markedly elevated thyroid antibodies, the temporal relationship between neurological symptoms and hypothyroidism, and the absence of another explanation to her symptoms suggest a causal role of thyroid autoimmunity. In the clinical setting of recurrent spontaneous miscarriages, elevated levels of anti-thyroid antibodies and neurological deficits not attributed to another disease entity, Hashimoto's encephalopathy should be suspected.     

A methodology for assessing treatment response in Hashimoto's encephalopathy: a case study demonstrating repeated computerized neuropsychological testing

Hashimoto's encephalopathy, a steroid-responsive encephalopathy, presents with cognitive deterioration, psychiatric symptoms, and seizures and is often associated with elevation of anti-thyroid peroxidase antibodies or thyroid dysfunction. Because of the absence of a gold-standard diagnostic test and serological marker of disease, improvement in cognitive impairment is an important sign when assessing response to corticosteroid treatment. The purpose of this case study is to present a methodology for tracking neurocognitive functioning using computerized testing (CNS Vital Signs) in a 14-year-old girl with Hashimoto's encephalopathy. Computerized neuropsychological testing was done prior to commencing corticosteroid treatment, as well as at 7 follow-up assessments over 1 year. Improvement in cognitive, psychological, and behavioral functioning heralded a response to treatment, which was sustained during tapering of medication. Computerized neuropsychological testing seems to be a viable tool for tracking cognitive functioning (when rapid assessments are desired) and assessing response to corticosteroid treatment in Hashimoto's encephalopathy.     

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.     

Hashimoto's encephalopathy in children and adolescents

Hashimoto's encephalopathy is an underdiagnosed, steroid-responsive, progressive or relapsing encephalopathy associated with high titers of serum antithyroid antibodies. Although Hashimoto's encephalopathy is well documented in adults, it is rarely observed or studied in children and adolescents. We describe the clinical and laboratory findings of four children (aged 9-15 years) with Hashimoto's encephalopathy. The clinical features of two patients at presentation included epileptic seizures and confusion. The other presenting signs included breath-holding spells, behavioral problems, psychosis, and ataxia (one patient each). During their presentation, three patients were euthyroid, and one was hyperthyroid. All patients manifested increased antithyroid antibodies, and all improved with steroid treatment. Hashimoto's encephalopathy is rarely suspected at presentation. Therefore, greater awareness of its signs by clinicians is necessary for proper diagnoses.     

Recurrent partial seizures with ictal yawning as atypical presentation of Hashimoto's encephalopathy (steroid-responsive encephalopathy associated with autoimmune thyroiditis)

Hashimoto's encephalopathy (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a rare condition whose pathogenesis is unknown, though autoimmune-mediated mechanisms are thought to be involved. The prevalent neurological manifestations of this disorder are epileptic seizures and psychocognitive disorders associated with EEG alterations. High anti-thyroid antibody titers (particularly in cerebrospinal fluid) and the effectiveness of steroid therapy are usually considered to be crucial elements in the diagnostic process. We describe a 19-year-old female patient who had been referred to the psychiatric unit because of behavioral disorders characterized predominantly by delirium with sexual content. She developed recurrent focal seizures characterized by atypical ictal semiology (repetitive forceful yawning) and a rare EEG pattern (recurrent seizures arising from the left temporal region without evident “encephalopathic” activity). The presence of anti-thyroperoxidase antibodies in her cerebrospinal fluid and a good response to steroids confirmed the diagnosis of HE. The atypical presentation in the case we describe appears to widen the electroclinical spectrum of HE and highlights its importance for differential diagnosis purposes in the neuropsychiatric setting.     

Auditory seizures in autoimmune epilepsy: a case with anti‐thyroid antibodies

In its classic presentation, Hashimoto's encephalopathy is an acute‐subacute complex neuropsychiatric syndrome with cognitive impairment, hallucinations, myoclonus, tremor or ataxia, associated with elevated anti‐thyroid antibodies. Corticoids and immunotherapy are dramatically effective. However, in some cases, not all the associated features are presented and this delays diagnosis and appropriate treatment. We describe a man with abrupt onset of recurrent auditory seizures resulting in refractory non‐convulsive status epilepticus. The patient was diagnosed with an autoimmune encephalopathy with elevated serum and CSF anti‐thyroid antibodies. None of the antiepileptic drugs were successful, however, following immune‐modulating therapy, the refractory non‐convulsive status epilepticus dramatically improved, as did the patient overall. We suggest that Hashimoto's encephalopathy should be suspected in otherwise healthy patients with unexplained new‐onset focal recurrent auditory seizures which do not respond to antiepileptic drugs. The presence of anti‐thyroid antibodies in the CSF supports this diagnosis.     

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.     

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.     

Hashimoto-Enzephalopathie Steroid-sensitive Enzephalopathie bei Hashimoto-Thyreoiditis

Hashimoto's encephalopathy is a steroid-responsive, relapsing or progressive encephalopathy associated with Hashimoto's thyroiditis. Characteristic clinical features are confusion, seizures, alteration in conscious level, stroke-like episodes, myoclonus, and tremulousness. High CSF protein levels without pleocytosis and a diffusely abnormal EEG are typical findings. Brain CT and MRI and cerebral angiogram are usually normal. We present two case reports of Hashimoto's encephalopathy in 55- and 77-year-old patients who both responded well to steroid therapy, and review the literature.     

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.     

Case of Hashimoto's encephalopathy with diffuse white matter lesions on diffusion-weighted MRI]

A 65-year-old woman was admitted to our hospital because of subacute deterioration of cognitive function. On admission, she presented with marked disorientation of time and place and inability to carry out commands. Mini-Mental State Examination score was 5/30. Although routine laboratory examinations including thyroid function, vitamin B1 and B12, serum syphilitic reaction, sIL-2 receptor level, titers of herpes simplex and zoster viruses, and HIV antibody were normal, titers of anti-thyroglobulin (TG) antibodies and thyroid peroxidase (TPO) antibodies were elevated. Cerebrospinal fluid showed normal findings. Brain MRI revealed diffuse high intensity in the white matter on diffusion- and T2-weighted images, mimicking leukoencephalopathy. We made a diagnosis of Hashimoto's encephalopathy, based on clinical features and high titers of anti-thyroid antibodies. Following administration of steroid hormone, her cognitive impairment gradually improved, associated with decrease of the white matter abnormality on MRI. Hashimoto's encephalopathy should be kept in mind in the differential diagnosis of subacute leukoencephalopathy with cognitive decline.     

Recurrent status epilepticus as the main feature of Hashimoto's encephalopathy

Hashimoto's encephalopathy (HE) is a severe but treatable condition that rarely complicates Hashimoto's thyroiditis. Clinically it is characterized by progressive or relapsing symptoms, including tremor, myoclonus, stroke-like episodes, seizures, impairment of consciousness, and dementia. We describe a patient presenting with recurrent generalized convulsive status epilepticus (GCSE), despite antiepileptic medications, who was successfully treated with methylprednisolone. Our observation confirms that the clinical spectrum of HE at presentation is heterogeneous and diagnosis is often difficult. This case highlights the crucial importance of antithyroid antibody measurement in patients presenting with otherwise unexplained episodes of GCSE with or without adjunctive signs of encephalopathy or thyroiditis.     

Hashimoto encephalopathy causing drug-resistant status epilepticus treated with plasmapheresis

Hashimoto encephalopathy is a rare, clinically heterogenous condition. Its treatment is based on corticosteroids. A previously normal 12-year-old boy was admitted to our pediatric emergency department with status epilepticus. He experienced a recurrence of status epilepticus after pentobarbital withdrawal, and required repeated resumptions of drug-induced coma. He manifested acute personality changes. His limbic encephalitis markers were normal, but his level of anti-thyroid peroxidase antibody was high. A diagnosis of Hashimoto encephalopathy was considered. Our patient responded to plasmapheresis instead of corticosteroid treatment. This case report is the first, to the best of our knowledge, of plasmapheresis because of Hashimoto encephalopathy in a child.     

Limbic encephalitis with severe sleep disorder associated with voltage-gated potassium channels (VGKCs) antibodies

INTRODUCTION: Voltage-gated potassium channels (VGKCs) antibodies are associated with neuromyotonia, limbic encephalitis and Morvan syndrome. CASE REPORT: We report the case of a patient who, after three weeks of fever, presented an anamnestic syndrome, associated with confusion and partial seizures. MRI showed left hyperintensity of mesial temporal structures on Flair images and right hippocampal atrophy on T1 weighted sequences. Laboratory tests only showed high level of anti-TPO antibodies. Thus, the patient was considered as having Hashimoto's encephalopathy. She was treated with intravenous methylprednisolone with no improvement of symptoms. On the contrary, the patient suffered from insomnia, deep diurnal drowsiness and complete disappearance of REM sleep. Episodes of hypothermia and severe hyponatremia were recorded. Serum VGKC antibodies were found at high level. After intravenous immunoglobulin treatment followed by methylprednisolone, we noted remarkable improvement of clinical status. Polysomnography showed reappearence of REM sleep. CONCLUSION: This case report broadens the spectrum of clinical manifestations associated with VGKC antibodies and suggests that VGKC are implicated in regulation of sleep. The potential pathophysiological mechanisms linking sleep disturbances and VGKC antibodies are discussed.     

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.     

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.     

Thyrotoxic autoimmune encephalopathy in a female patient: only partial response to typical immunosuppressant treatment and remission after thyroidectomy

Hashimoto's encephalopathy (HE) is a rare immune-mediated encephalopathy developing in patients with high serum concentrations of anti-thyroid antibodies usually in an euthyroid or hypothyroid state. We report a 31-year-old female patient with thyrotoxic HE whose daughter has been followed up with the same diagnosis. Suboptimal response was observed with intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIG) and plasmapheresis. Reduction of the anti-thyroid auto-antibody concentrations marked the patient's improvement in each episode. She relapsed under oral immunosuppressive therapy. After removing the thyroid tissue, full recovery has been achieved for the last 18 months. These data may contribute to clarification of the pathogenetic role of anti-thyroid antibodies in HE. Thyroidectomy can be considered as one of the treatment options especially in thyrotoxic HE patients with uncontrolled relapses. Our patient is the first reported HE case with a family history. Genetic background can underlie the etiopathogenesis of HE as is the case in other autoimmune disorders.