|Year : 2017 | Volume
| Issue : 2 | Page : 89-91
Hashimoto's encephalopathy in a 10-year-old girl
V Shobi Anandi, Shaila Bhattacharyya, Bidisha Banerjee
Department of Pediatrics, Manipal Hospital, Bengaluru, Karnataka, India
|Date of Web Publication||26-May-2017|
V Shobi Anandi
Department of Pediatrics, Manipal Hospital, Bengaluru - 560 017, Karnataka
Source of Support: None, Conflict of Interest: None
Hashimoto's encephalopathy (HE) is a rare but probably an unrecognized and underdiagnosed condition in children. Early diagnosis is critical since these patients respond dramatically to corticosteroid therapy. The diagnosis of HE requires a strong clinical suspicion along with a triad of positive antithyroid antibodies, encephalopathy not explained by another etiology, and a response to corticosteroids. We report the case of a 10-year-old female child with HE and review the literature.
Keywords: Acute encephalopathy, children, Hashimoto's encephalopathy, thyroid autoantibodies
|How to cite this article:|
Anandi V S, Bhattacharyya S, Banerjee B. Hashimoto's encephalopathy in a 10-year-old girl. Thyroid Res Pract 2017;14:89-91
| Introduction|| |
Hashimoto's encephalopathy (HE) is a steroid-responsive acute or subacute encephalopathy associated with elevated antithyroid antibodies. It was first reported in association with Hashimoto's thyroiditis by Brain et al. in 1966.
It is still unknown whether this is a true syndrome seen in patients with autoimmune thyroiditis or coincidental finding. A review of all reported cases by Canelo-Aybar et al. showed that the combination of encephalopathy, high serum antithyroid antibodies, and favorable response to steroids was unlikely to be due to chance, giving it a status of a new syndrome. The role of thyroid antibodies in the etiopathogenesis of encephalopathy is unclear, and the severity of symptoms does not correlate with the antibody titer; however, normalization of the titers after clinical recovery has been reported by some authors., Furthermore, antithyroid antibodies occur in 10% of the normal population. The neurologic manifestations may develop up to 3 years before the onset of autoimmune thyroiditis. The thyroid status in these patients can range from euthyroidism (18%–45%), subclinical hypothyroidism (23%–35%) to hypothyroidism (17%–20%) and hyperthyroidism (7%). Therefore, “steroid-responsive encephalopathy associated with autoimmune thyroiditis” rather than HE would be the more appropriate term to describe this entity.
| Case Report|| |
A 10-year-old female child presented to us with history of fever, headache, and altered sensorium of 4 days duration. On examination, she was irritable and drowsy. Her weight was 25.4 kg (3rd–10th centile) and height was 133 cm (10th–25th centile). Neurologic examination revealed hyperreflexia and positive Babinski sign. Other systemic examination was within normal limits. Her investigations were as follows: Hemoglobin 11 g/dl, total counts 16,410/mm 3, platelets 2.87 lakh/mm 3. C-reactive protein (CRP) and procalcitonin were negative, and erythrocyte sedimentation rate (ESR) was raised (78 mm at the end of 1 h). Cerebrospinal fluid (CSF) analysis was suggestive of 10 cells (all lymphocytes), CSF glucose 54 mg/dl, and CSF protein 50 mg/dl. CSF culture and herpes simplex virus polymerase chain reaction were negative. Magnetic resonance imaging (MRI) of the brain showed T2 and T2 fluid-attenuated inversion recovery hyperintensity in the right medial temporal lobe and hippocampus [Figure 1]. Electroencephalogram (EEG) was suggestive of diffuse slowing. She was started on intravenous antibiotics and acyclovir as the etiology for the encephalopathy was not apparent at that time. The sensorium continued to deteriorate over the next 4 days with increasing agitation, inconsolable cry, and auditory hallucinations. Repeat CSF examination revealed increase in cells (190 – 96% lymphocytes), CSF glucose 60 mg/dl, and CSF protein 61 mg/dl. CSF culture was sterile. Xcyton panel for panencephalitis was negative. Autoimmune encephalitis workup (N-methyl-D-aspartate receptors, voltage-gated potassium channel, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1 and 2, gamma-aminobutyric acid receptor, and anti nuclear antibody [ANA]) was negative. Antithyroid peroxidase (anti-TPO) antibody (386.6 IU/L) and antithyroglobulin (anti-Tg) antibody (185.4 IU/L) were positive. On further probing, there was history of hypothyroidism in mother and maternal grandmother. However, she did not have goiter or any other signs of thyroid dysfunction or evidence of other autoimmune disorders. Her thyroid function tests were normal as follows: Thyroid-stimulating hormone was 1.28 mIU/ml (0.35–4.94) and free T4 was 1.15 ng/dl (0.8–2.2).
|Figure 1: Axial magnetic resonance imaging of the brain suggestive of T2 fluid-attenuated inversion recovery hyperintensities in the right medial temporal lobe and hippocampus|
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Based on above scenario, a diagnosis of HE was made. Intravenous methylprednisolone was given at 30 mg/kg/day for 5 days, followed by oral prednisolone at 1 mg/kg/day. Risperidone was used for neuropsychiatric manifestations. The sensorium and behavior dramatically improved. Gradual tapering of steroid was attempted after 6 weeks but was associated with reappearance of hallucinations and behavioral problems. Hence, she was restarted on the original dose of steroids. Currently, she continues be on oral steroids (1 mg/kg/day prednisolone) and tapering is planned over a period of 3–6 months based on clinical improvement.
| Discussion|| |
HE, mostly described in adults, with a female-to-male ratio of 4:1, is a relatively rare entity in the pediatric population and probably underrecognized as a cause of acute encephalopathy in children.,, Increasing awareness has resulted in the condition being now recognized in children and adolescents and reported to occur even in the preschool age group.,
HE is a controversial diagnosis in the absence of an underlying pathophysiologic basis. It is considered to be an autoimmune condition because of female preponderance, fluctuating course of the disease, its association with other autoimmune diseases, inflammatory findings in CSF, and dramatic response to treatment with steroids., Autoimmunity against common brain-thyroid antigens resulting in disseminated encephalomyelitis with or without autoimmune cerebral vasculitis is the most probable etiology.
The clinical presentation is variable and nonspecific. In adults, 25% present with seizures, acute deterioration of consciousness, and stroke-like episodes (vasculitic type), and 75% present with insidious cognitive function deterioration leading to dementia, confusion, agitation, restlessness, and hallucinations or inactivity, apathy, and social isolation (diffuse progressive type)., Tremors, seizures (one-third cases), stupor, and myoclonus may be seen in both the forms. The two clinical types may overlap during the disease. Children usually present with seizures - generalized tonic–clonic or complex partial seizures with or without secondary generalization, confusion, or hallucinations. Focal neurologic signs are less common in children than in adults. Progressive cognitive decline is manifested by deteriorating school performance. Our patient presented with acute encephalopathy, hallucinations, and behavioral problems in the absence of seizures.
The diagnosis of HE is likely to be missed if not suspected. However, the more common causes of encephalopathy such as infection, electrolyte disturbances, metabolic conditions, toxins, neoplasms, and vasculitic syndromes should be excluded before making a diagnosis of HE. HE should be considered as an important differential diagnosis in cases of “investigation negative encephalopathies.”
Positive titers of antithyroid antibodies (anti-TPO, anti-Tg) are essential to make the diagnosis. Thyroid function tests are usually normal, but cases associated with hypo- and hyper-thyroidism have been reported., Antithyroid antibodies and circulating immune complexes may be demonstrable in the CSF although the titer does not correlate with the clinical status., A new autoimmune antigen amino terminal of alpha-enolase along with a high level of antibodies against this antigen has been found in the brain of HE patients and may be diagnostic. EEG is suggestive of diffuse slowing of the background in 98% of the cases. CSF examination may be normal or may show lymphocytic pleocytosis or high proteins., Neuroimaging is usually normal (50%); however, MRI reveals bilateral subcortical high-signal lesions on T2-weighted images, ischemic areas, multiple tumors or granulomas, or other degenerative changes, which may be reversible with treatment., Computed tomography and angiography are typically normal. Single photon emission computed tomography shows global hypoperfusion or decreased perfusion in the cortical areas or basal ganglia., CRP, ESR, or liver enzymes may be elevated in some patients. Our patient had hyperintensity signals on MRI of the brain and elevated ESR. A combination of neurological findings, positive antithyroid autoantibodies, and responsiveness to steroids is diagnostic of HE. Our patient had all three of these criteria.
High-dose pulse intravenous methylprednisolone therapy is the preferred choice for acute encephalopathy of HE., This is followed by prednisone (1–2 mg/kg/day, max 60 mg/day) for 6–8 weeks, followed by gradual tapering. Rapid improvement may be seen in a few days and significant clinical improvement occurs over 3–6 months., In spite of adequate treatment, patients may have a relapse during the reduction of steroid therapy. Restarting the previous dose and gradual tapering over a prolonged period are proposed to achieve remission. Steroid treatment for at least 6 months has been advocated by some authors, but duration of therapy should be individualized as per the clinical response and normalization of EEG and neuropsychologic testing. Immunomodulatory treatments, such as azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, intravenous immunoglobulin, and plasmapheresis, alone or in combination, have been used in some cases with variable results. Treatment with risperidone can help in resolution of neuropsychiatric symptoms.
The prognosis of HE in adults when treated is good, and almost 90% of patients are in remission after 10 years, but children and adolescents may experience residual cognitive deficits.,
| Conclusion|| |
HE is rarely suspected at initial presentation. HE should be considered in any patient with unexplained acute encephalopathy, seizures, and acute psychosis or with progressive deteriorating cognitive behavioral functions and movement disorders. A high index of suspicion is necessary for early recognition of the condition as aggressive treatment may result in a favorable clinical outcome.
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Conflicts of interest
There are no conflicts of interest.
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