Pediatric Neurology xxx (2016) 1e9 Contents lists available at ScienceDirect Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu Topical Review Hashimoto Encephalopathy Presenting With Stroke-Like Episodes in an Adolescent Female: A Case Report and Literature Review Brett R. Graham MD a, *, Natalie Shiff MD b, Munier Nour MD c, Simona Hasal MD d, Richard Huntsman MD d, Salah Almubarak MD d a Department of Medicine, Division of Neurology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Department of Pediatrics, Division of Rheumatology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada c Department of Pediatrics, Division of Endocrinology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada d Department of Pediatrics, Division of Neurology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada b abstract BACKGROUND: Hashimoto encephalopathy is a rare form of encephalopathy thought to be of autoimmune eti- ology. Cognitive changes and seizures are the most commonly reported presenting manifestation. Stroke-like episodes have also been documented in these individuals. We describe a rare adolescent with Hashimoto encephalopathy who presented with stroke-like symptoms. PATIENT DESCRIPTION: A previously well 15-year-old girl was evaluated after experiencing sudden-onset language disturbance and right hemiparesis. Her symptoms resolved, but weeks later, she began experiencing refractory seizures, episodes of status epilepticus, and cognitive decline. An extensive evaluation was unremarkable, but thyroid peroxidase antibodies were elevated, and a diagnosis of Hashimoto encephalitis was made. Steroid therapy was initiated, and her symptoms resolved with return to baseline cognitive function. CONCLUSION: Hashimoto encephalopathy is a highly treatable condition that may be considered in the differential diagnosis of children and adolescents presenting with strokelike symptoms. Keywords: Hashimoto encephalopathy, stroke, steroid-responsive encephalopathy, autoimmune encephalopathy, autoimmune thyroiditis Pediatr Neurol 2016; -: 1-9 Ó 2016 Elsevier Inc. All rights reserved. Introduction Hashimoto encephalopathy is a rare form of encephalopathy with presumed autoimmune etiology that falls along the spectrum of steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT).1 The first an individual with of Hashimoto encephalopathy was described by Brain in 1966.2 He reported an adult with Hashimoto thyroiditis who experienced fluctuating cognition, refractory epilepsy, and stroke-like episodes. Since then, most of the documented patients have been adults, but there is a growing literature on Hashimoto encephalopathy in the pediatric population.3-5 We describe an adolescent with Hashimoto encephalopathy who presented with stroke-like episodes, presentation that is rare in the pediatric Hashimoto encephalopathy literature. In addition, we present a comprehensive summary of English language full-length reports of pediatric Hashimoto encephalopathy (Table 1). Patient Description Conflicts of interest: none. Article History: Received December 5, 2015; Accepted in final form February 4, 2016 * Communications should be addressed to: Dr. Graham; Department of Medicine; Division of Neruology; University of Saskatchewan; Room 3544 RUH, 103 Hospital Drive; Saskatoon, Saskatchewan, Canada. E-mail address: brett.graham@usask.ca 0887-8994/$ e see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2016.02.003 This 15-year-old previously healthy girl presented to her local hospital with the sudden-onset right hemiparesis and paresthesias accompanied by slurred speech and expressive language difficulties. Sensorimotor symptoms began in the right hand and then, within seconds, progressed to involve the entire right side. All symptoms resolved within 35 minutes. She did not have associated headaches, visual 2 B.R. Graham et al. / Pediatric Neurology xxx (2016) 1e9 TABLE 1. Clinical Summary of Hashimoto Encephalopathy in the Pediatric Population Case Study Age, Gender Clinical Onset Clinical Progression Investigation Treatment Outcome Hilberath et al.3 13 F Weakness, dizziness. Presented with generalized seizure. Improved rapidly with high-dose steroids and thyroid replacement. EEG normalized with treatment. IV steroids with oral taper Favorable Gul Mert et al.4 13 M Fatigue, headache, withdrawn. Presented with seizure. Seizure free after 15 days of steroid therapy. High-dose oral steroids and thyroid replacement Favorable 8F Generalized seizure. Headache and encephalopathy followed by seizures. IV steroids, plasmapheresis, and IVIG IV steroids with oral taper, plasmapheresis, and IVIG Favorable 17 F Back to baseline at three months with treatment. Seizure free shortly after treatment initiated. Thyroid absdelevated MRIdnormal EEGdslowed background CSFdmild increased protein Thyroid absdelevated MRIdnormal EEGdslowed background and epileptic activity in left occipital area Thyroid absdnormal EEGdbioelectric status 11 F Neuropsychiatric changes, weakness, headache. Gradual cognitive decline, acute onset tic disorder Neuropsychiatric symptoms, seizure IV steroids with oral taper Favorable Oral steroids (1 mg/kg) with subsequent taper, thyroid replacement IV steroids with oral taper, IVIG, and rituximab Favorable Saygi et al.6 12 M Olmez et al.7 8F Mamoudjy et al.8 2F Neuropsychiatric symptoms, confusion 13 F Neuropsychiatric symptoms 11 F Tremor, dystonia, seizure Headache, tremor, seizure, encephalopathy Cerebellar symptoms, behavioral changes 13 F 10 F 12 F 15 F Arya et al.9 Seizures, confusion, left motor deficit Seizure, confusion, hallucinations 9F Seizures 11 F Seizures, encephalopathy, hallucinations 11 F Myoclonus, encephalopathy, seizures Improved quickly after treatment commenced. Improved with treatment but had one relapse. Improved with treatment but had one relapse. Initially improved but had relapse requiring escalated treatment. Thyroid absdnormal MRIdnormal EEGdslowed background and epileptiform activity in right occipital region Thyroid absdnormal MRIdnormal EEGdnormal Thyroid absdelevated MRIdnormal EEGdnormal Thyroid absdelevated MRIdnonspecific white matter changes EEGdgeneralized slowing and left temporal epileptiform activity CSFdmild pleocytosis and increased protein Thyroid absdelevated MRIdnormal EEGdnormal Thyroid absdelevated MRIdFLAIR hyperintensities in hippocampi Thyroid absdelevated MRIdnormal Thyroid absdelevated MRIdnormal Thyroid absdelevated MRIdwhite matter lesions involving the brainstem and deep gray matter Thyroid absdelevated MRIdnormal Thyroid absdelevated MRIdFLAIR hyperintensities in hippocampi Thyroid absdnormal MRIdFLAIR juxtacortical white matter hyperintensities Thyroid absdelevated MRIdnormal Thyroid absdelevated MRIdmild cerebral atrophy EEGdgeneralized slowing and Steroids, IVIG, azathioprine, and rituximab Oral steroids, IV steroids, and cyclophosphamide Favorable Favorable Favorable Unfavorable Persistent learning disability IVIG IV steroids and cyclophosphamide IV steroids and cyclophosphamide IV steroids and azathioprine IV steroids IV steroids, methotrexate, rituximab, and azathioprine High-dose oral steroids with taper Unfavorable Persistent cognitive changes and tremor Unfavorable Persistent cognitive changes Unfavorable Persistent hand tremors and headaches Favorable Back to baseline (continued on next page) B.R. Graham et al. / Pediatric Neurology xxx (2016) 1e9 3 TABLE 1. (continued ) Case Study Age, Gender Clinical Onset Clinical Progression Salpietro et al.10 13 F Fever, headache, sleepiness Started having hallucinations and developed a peripheral polyneuropathy before treatment. Zimmermann and Stranzinger11 11 F Headache, sensory disturbance, and leftsided weakness Symptoms resolved 5 days after treatment. Bektas et al.12 12 M Headache, right focal seizure Continued seizure activity until plasmapherisis initiated. Erol et al.13 9F Confusion, ataxia 15 F Seizure, encephalopathy Seizure, tremor, psychosis Breath-holding spells, behavioral changes Focal seizure 14 F 12 F Shah et al.14 13 M Berger et al.15 11 M Seizures, cognitive decline Castro-Gago et al.16 2.8 F Language deterioration, ataxia Hoffmann et al.17 6F Generalized seizure, neuropsychiatric symptoms Quick response to steroid therapy. Bismilla et al.18 11 F Seizure, encephalopathy Continued to have relapses until steroids initiated. Ray et al.19 12 M Confusion, hyperkinetic behavior Started having generalized seizures before the start of treatment. Mancardi et al.20 11 F Confusion, psychomotor instability Initially improved with mannitol but relapsed thereafter Byrne et al.21 14 F Confusion, memory problems, generalized Had multiple relapses before the start of steroids Experienced relapse with initial tapering of steroids. Responded well to IVIG. Will have recurrent seizures if a dose of IVIG missed. Complete recovery after 4 weeks of steroids Investigation generalized spike and wave discharges CSFdnormal Thyroid absdelevated MRIdinitially normal but repeat showed multiple T2/FLAIR lesions in the deep gray matter EEGddiffuse background slowing CSFdoligoclonal bands positive Thyroid absdelevated MRIddiffusion restriction in right thalamus and internal capsule CSFdnormal Thyroid absdelevated MRIdnormal CSFdnormal EEGdburst suppression and focal and generalized epileptiform discharges MRIdnormal EEGdslow background MRIdnormal EEGdslow background MRIdnormal EEGdslow background MRIdnormal EEGdnormal Thyroid absdelevated MRIdnormal EEGdbackground suppression CSFdnormal Thyroid absdelevated MRIdnormal EEGdright temporal epileptiform discharges Thyroid absdelevated MRIdnormal EEGddiffuse slowing CSFdnormal Thyroid absdelevated MRIdnormal EEGdelectrographic seizures CSFdelevated protein Thyroid absdelevated MRIdFLAIR white matter hyperintensities EEGdgeneralized slowing CSFdelevated protein Thyroid absdelevated MRIdnormal EEGdslow background with bitemporal spikes CSFdnormal Thyroid absdelevated MRIdinitially normal but then showed contrast-enhancing lesion in left nucleus accumbens EEGddiffuse slowing CSFdnormal Thyroid absdelevated MRIdnormal Treatment Outcome IV steroids, IVIG Favorable IV steroids with oral taper Favorable IVIG, plasmapheresis, and oral prednisone Favorable IV steroids with oral taper High-dose oral steroids Favorable IV steroids with oral taper High-dose oral steroids Favorable Favorable Favorable IV steroids with oral taper Favorable IV steroids with oral taper, IVIG Favorable IV steroids with oral taper Favorable IV steroids with oral taper Favorable Oral steroids and risperidone Favorable Thyroid replacement and carbamazepine Favorable High-dose corticosteroids (route not mentioned) with taper Favorable Oral steroids (1 mg/kg) with taper Favorable (continued on next page) 4 B.R. Graham et al. / Pediatric Neurology xxx (2016) 1e9 TABLE 1. (continued ) Case Study Age, Gender 12 F Clinical Onset Clinical Progression Investigation seizure with subsequent hemiplegia Headaches, emotionally labile, seizure Had one relapse with steroid taper Sybesma et al.22 12 F Unconsciousness, headache, status epilepticus Clinical picture initially deteriorated on thyroid replacement therapy. Vasconcellos et al.23 16 F Generalized seizure Intractable seizures and hallucinations prior to treatment. Balestri et al.24 8F Attention deficit, hyperactivity, cognitive decline Symptoms progressively worsened before the treatment 14 M Fever, confusion, seizure, alternating hemiplegia Symptoms slowly improved with treatment. EEGddiffuse slowing CSFdelevated protein Thyroid absdelevated MRIdnormal EEGddiffuse slowing but more prominent in left hemisphere CSFdnormal Thyroid absdelevated MRIdnormal EEGdgeneralized slowing CSFdmild elevation of protein Thyroid absdelevated MRIdnormal EEGdroutine normal but telemetry showed bitemporal seizures CSFdnormal Thyroid absdelevated Thyroid absdelevated MRIdnormal EEGdgeneralized slowing CSFdnormal Treatment Outcome Oral steroids with taper Unfavorable Persistent cognitive difficulties and right hemiparesis Thyroid replacement Favorable IV steroids with oral taper Carbamazepine Favorable Oral steroids with subsequent taper Unfavorable Symptoms have improved but not back at cognitive baseline Favorable Flunarizine (for query alternating hemiplegic migraine) and levothyroxine Abbreviations: CSF ¼ Cerebrospinal fluid EEG ¼ Electroencephalography IVIG ¼ Intravenous immunoglobulin MRI ¼ Magnetic resonance imaging changes, nausea, or vomiting. She denied any stimulus sensitivity. There was no history of preceding head or neck trauma, associated head or neck pain, or preceding infections. Past medical history was unremarkable. Specifically, she denied previous episodes of migraine headache, stroke, seizure, or venous thrombosis. She was taking no medications, and immunizations were up-to-date. Family history was not significant for neurological disease or thrombophilias. There were no developmental concerns, and she had excellent school performance before the onset of symptoms. She was transferred to a tertiary care pediatric center, where she was normothermic and her vital signs were stable. Neurological examination, including fundoscopy, was normal. Cardiac and general examinations were normal. A noncontrast cranial computed tomography (CT) performed shortly after arrival did not show any intracranial pathology. The result of computed tomography angiography was normal. Brain magnetic resonance imaging (MRI), including diffusion-weighted and gradient echo sequences, was normal the following day. Heart rhythm was sinus, and heart structure and function were normal as assessed by transthoracic echocardiography. Thrombophilia workup was negative. A diagnosis of transient ischemic attack was given, and the patient was discharged on antithrombotic medication. Two weeks later the patient experienced headache, nausea, vomiting, and bilateral lower extremity weakness while at school. The episode was short lived but was followed by a generalized toniceclonic seizure. She did not have focal or lateralizing findings on neurological examination. Treatment included intravenous benzodiazepines, phenytoin, and eventual intubation and sedation for refractory generalized seizures. The results of another noncontrast cranial CT and brain MRI and MRV were normal. Routine blood work including coagulation factors was normal. Repeat transthoracic echocardiogram with agitated saline bubble test showed no right-to-left shunt. Thyroid-stimulating hormone was elevated at 5.29 mIU/L (N 0.44 to 3.98 mIU/L) with a normal free T4 of 15.4 pmol/L (N 10.0 to 17.1 pmol/L), consistent with subclinical hypothyroidism. Lipid profile was normal. Vasculitic workup was negative including testing for antinuclear antibodies, antidouble- stranded DNA, extractable nuclear antigens, antineutrophil cytoplasmic antibodies, rheumatoid factor, complements (C3 and C4), and lupus anticoagulant. Erythrocyte sedimentation rate and c-reactive protein were normal. Cerebrospinal fluid (CSF) analysis revealed a slightly elevated protein at 0.77 g/L with only one lymphocyte. Oligoclonal bands were negative. CSF evaluation for infections yielded no positive results. A paraneoplastic panel including PNMA, CV2.1, Ri, Recoverin, SOX1, Titan, Yo, and Hu was negative. An autoimmune limbic encephalitis panel including NMDA, VGKC, GAD65, and AMPA was negative. Routine electroencephalography (EEG) did not show epileptiform activity, and EEG telemetry did not show seizures or epileptiform activity. The patient was discharged home on levetiracetam with a normal neurologic examination. Repeat thyroid function tests as an outpatient demonstrated worsening thyroid function (thyroid-stimulating hormone, 11.85 mIU/L; free T4, 9.6 pmol/L), and the patient was initiated on levothyroxine replacement. A subsequent outpatient brain and body positron emission tomography scan showed decreased fludeoxyglucose uptake in the visual cortices bilaterally (Fig 1), which was deemed nonspecific by nuclear medicine. There was no evidence to suggest a body teratoma. A thyroid ultrasound was also performed that showed a heterogeneously enlarged gland with diffuse hyperemia but no focal hypoechoic nodules, consistent with a diagnosis of Hashimoto thyroiditis. Over the next few months she continued to have generalized toniceclonic seizures despite the addition of valproic acid and clobazam to her antiepileptic medication regimen. She was again admitted after an episode of prolonged seizure activity that required intubation and sedation. Serum thyroid peroxidase antibody was found to be elevated (>1000 IU/mL; N < 34 IU/mL) with thyroglobulin antibody normal at 37.5 IU/mL (N < 40 IU/mL). Paraneoplastic and autoimmune limbic encephalitis panels were repeated and again were negative. A neuropsychologic assessment at this time showed mild-to-moderate impairment in virtually all domains of functioning including general intellectual ability, language, attention and concentration, visualespatial B.R. Graham et al. / Pediatric Neurology xxx (2016) 1e9 5 Discussion FIGURE 1. PET computed tomography (CT) head showing decreased fludeoxyglucose (FDG) uptake in both occipital lobes. PET ¼ positron emission tomography. (The color version of this figure is available in the online edition.) ability, learning and memory, visualespatial integration and processing speed, and executive functioning. A repeat EEG showed mild slowing of background activity and several brief nocturnal episodes of generalized rhythmic activity thought to be suspicious for electrographic seizure (see Fig 2A-E for a chronological summary of EEGs). She was given a working diagnosis of Hashimoto encephalopathy and methylprednisolone 1 g IV daily was given for five days followed by oral prednisone at 1 mg/kg with subsequent taper. There was no further overt seizure activity, and she was eventually discharged home on valproic acid, clobazam, phenytoin (eventually discontinued), and levothyroxine. After the initiation of steroids the patient has had no further strokelike episodes or seizures. She continues on valproic acid and clobazam with hopes of eventual discontinuation. An informal report from her school roughly 2 months after discharge indicated that her school performance was improving. Repeat neuropsychologic testing performed approximately four months after starting steroids showed normal functioning in all domains. She returned to school and community activities and reports no limitations in her abilities when compared with her functioning before the onset of her illness. Literature review MEDLINE and PubMed were searched for full case English language Hashimoto encephalopathy reports using the terms “Hashimoto or autoimmune thyroiditis,” “encephalopathy,” and “child/children.” We did not include cases only described in abstracts or with limited clinical information. In addition, cases with unclear diagnoses were excluded. Twenty articles describing 36 patients were found, and clinical summaries of these cases are provided in Table 1. Hashimoto encephalopathy is a rare form of acquired autoimmune encephalopathy. The overall incidence of the disease is reported at 2.2/100,000.25 A female preponderance is found in both the adult and pediatric literature, with recorded cases occurring up to five times more commonly in females than that in males.26 The average age of onset is 45 to 55 years,27 but the youngest reported patient was age two years and ten months.28 Clinically, Hashimoto encephalopathy can present with a myriad of symptoms, the most frequent being cognitive changes and seizures.26 This is true in both the adult and pediatric populations.5,27 Stroke-like episodes are present in 25% of adult cases29 but are less frequent in the pediatric population21 and as evident by the clinical summaries in Table 1 very rarely as a presenting feature. Seizures tend to be refractory to treatment and episodes of status epilepticus have been reported in a minority of cases.30 Two distinct clinical presentations have been described: a “vasculitic” subtype and an indolent progressive subtype.31 The vasculitic subtype is characterized by intermittent acute to subacute onset of symptoms, including stroke-like episodes, seizures, and confusion, usually with some degree of improvement between episodes. The indolent progressive subtype is characterized by gradually worsening cognitive and neuropsychiatric performance and without any definite relapses. Zimmerman and Stranzinger11 described an 11-year-old girl with sudden-onset headache and left-sided sensorimotor symptoms who also exhibited a diffusely enlarged thyroid gland and elevated thyroid peroxidase antibodies. MRI brain with diffusion-weighted imaging showed a hyperintense lesion in the right thalamus. The patient was treated with an antiplatelet agent and high-dose steroid regimen with resolution of all symptoms in five days after treatment initiation. The authors attribute the ischemic stroke to SREAT and resolution of symptoms due to steroid therapy. However, the enlarged thyroid and antibodies were found incidentally, and no note is made of clinical encephalopathy. Furthermore, an extensive workup to rule out any other underlying etiology of the stroke was not reported; therefore, a diagnosis of SREAT in this case was not conclusive. The pathogenesis of Hashimoto encephalopathy remains poorly understood. In spite of being associated with antithyroid antibodies, there is no relationship between thyroid function and disease course in this condition.4,5,26 Indirect evidence supports autoimmunity as a possible mechanism of Hashimoto encephalopathy. First, autoantibodies to thyroid antigens are present and may have some degree of cross-reactivity in the central nervous system32; however, these antibodies are found without associated neurological manifestations in approximately 10% of the general population.3 Second, response to immunosuppressive medications, such as steroids and IVIG,33 is common. Third, antithyroid antibodies have been found in the CSF34 of Hashimoto encephalopathy patients as have oligoclonal bands,35 suggesting intrathecal immunoglobulin production. Fourth, females are more frequently affected, an observation consistent with other autoimmune diseases.3 Finally, Hashimoto encephalopathy is commonly associated with other autoimmune conditions such as Behcet’s disease.36 6 B.R. Graham et al. / Pediatric Neurology xxx (2016) 1e9 FIGURE 2. (A) The first electroencephalography (EEG) performed during wakefulness when the patient was not encephalopathic. Notice the normal background and lack of epileptiform activity. (B) The second EEG performed during wakefulness showing diffuse slowing of background but no epileptiform activity. The patient was becoming intermittently encephalopathic at this stage. (C) EEG performed during an acute confusional state. Notice the diffusely slow background and burst of high amplitude rhythmic delta. (D) EEG performed during sleep. Predominantly frontal, rhythmic activity can be observed in the second half of the epoch that is suspicious for an electrographic seizure. (E) Repeat EEG during wakefulness performed 6 months after the initiation of steroids. Notice the normal background and lack of epileptiform activity. (The color version of this figure is available in the online edition.) B.R. Graham et al. / Pediatric Neurology xxx (2016) 1e9 7 FIGURE 2. (CONTINUED). A vasculitic etiology has also been proposed as lymphocytic infiltration has been found in brainstem veins37 and arterial walls38 on autopsy and brain biopsy, respectively. Interestingly, the autoantigen alpha-enolase has been found in the serum of patients with Hashimoto encephalopathy and may represent a possible pathogenic mechanism.5 Alpha-enolase cross-reacts with both thyroid and brain tissue and is expressed by endothelial cell walls, which potentially could lead to damage or disruption of cerebral vasculature.3,5 However, alpha-enolase has been found in patients with other types of encephalitis and autoimmune disorders and therefore may not be specific to Hashimoto encephalopathy.39 The diagnosis of Hashimoto encephalopathy is one of exclusion. The differential diagnosis of fluctuating encephalopathy is broad,27 as is the case for stroke-like episodes and seizures. Owing to the heterogeneity of presentation, Hashimoto encephalopathy is thought to be underdiagnosed in the pediatric population.3 However, in the right clinical setting with exclusion of other potential etiologies, a diagnosis can be suspected. Diagnostic criteria have been purposed by Chong et al.26 and Mocellin et al.27 and include the presence of neuropsychiatric disturbances, abnormally elevated serum thyroid antibodies (the presence of these antibodies in the CSF can also be helpful), exclusion of other possible etiologies, and good response to steroid therapy. Interestingly, serum antibody levels do not coincide with disease activity or severity.5,33 Aside from abnormally elevated thyroid antibodies, laboratory, neuroimaging, and neurophysiologic investigations are usually nonspecific. Elevated protein can be found in the CSF in a majority of patients,5,26 and mild lymphocytic pleocytoses have been reported.5,40 Thyroid antibodies have also been found in the CSF.34 EEG is almost always abnormal, with generalized slowing being the rule in the pediatric population.3-5,26,27 The degree of background slowing appears to correlate with the severity of encephalopathy clinically.27 Focal slowing and periodic lateralized epileptiform discharges have rarely been described in pediatric cases.5 Neuroimaging is normal in approximately two thirds of pediatric cases and when abnormal is nonspecific.3,5 SPECT can show different degrees of hypoperfusion but in no consistent pattern.3,5 8 B.R. Graham et al. / Pediatric Neurology xxx (2016) 1e9 Immunosuppressive therapy with corticosteroids is the mainstay of the treatment of Hashimoto encephalopathy. Indeed, responsiveness to steroids has been included in the diagnostic criteria.3,5 High-dose steroid regimens are usually implemented followed by tapering of the medication.31 No randomized control trials have been performed, though, so the best steroid dosage and duration are not known.3 Improvement is usually seen between four and six weeks,3,27 and steroids are continued for one to two years.5 Other immunosuppressive agents have been used in addition to or instead of corticosteroids and include azathioprine, cyclophosphamide, and methotrexate.3,27 Intravenous immunoglobulin and plasmapheresis have also been used in both the adult and pediatric populations with clinical benefit.12,15,27 Relapses occur in approximately one third of pediatric patients and may prompt medication dosage escalation or change.3 Thyroid hormone replacement may be indicated.4,5 Interestingly, we noticed that our patient was exquisitely sensitive to the adverse effects of IV benzodiazepines, leading to intubation and intensive care monitoring. In light of this, we suggest that further observation and precaution is indicated in similar patients before administering parenteral benzodiazepines. Conclusion We describe an unusual child with Hashimoto encephalopathy who presented with stroke-like symptoms and later developed fluctuating encephalopathy, refractory seizures, and multiple episodes of status epilepticus. Serum thyroid antibodies were elevated, and a myriad of other potential structural, infectious, autoimmune, metabolic, and neoplastic causes were ruled out. Other tests, including CSF analysis, brain imaging, and positron emission tomography scan, were nonspecific. Treatment with antiepileptic medications was only temporarily successful in abating seizure activity. It was only with the addition of corticosteroids that we saw the cessation of stroke-like episodes and seizures and complete resolution of cognitive issues as evident by repeat neuropsychologic testing. 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