Hashimoto’s encephalopathy (HE) is an infrequent form of encephalopathy characterized by diverse neurological symptoms linked with elevated levels of antithyroid antibodies (ATA), including antithyroglobulin antibody (anti-TG) or antithyroid peroxidase antibody (anti-TPO) [1]. Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome characterized by typical neurological manifestations such as severe headache, altered mental status, visual impairment, and seizures, commonly associated with vasogenic edema (VE), and affecting predominantly the posterior occipital and parietal lobes of the brain [2].

We encountered a patient with HE demonstrating clinical features similar to PRES, who exhibited marked amelioration in neurological manifestations following administration of anti-seizure medication and corticosteroids. Herein, we explore potential pathomechanisms underlying this observed clinical response.

A 52-year-old female patient presented to the emergency department with a seizure and altered mental status. The patient had a history of hypertension and had been receiving treatment with an antihypertensive medication (amlodipine 5 mg daily) for the past seven years, with effective control of blood pressure. The patient denied prodromal symptoms or auras preceding the seizure. Both the patient and her family members denied any prior history of seizures. Her blood pressure was elevated at 180/96 mmHg, but she did not report headache or visual disturbance. After admission, her blood pressure decreased to 154/86 mmHg without administration of antihypertensive medication. Nonetheless, the patient subsequently manifested a second seizure episode, lasting approximately 3 minutes, during which tongue biting and involuntary voiding occurred. Immediate intervention was initiated with intravenous administration of lorazepam (4 mg), followed by a loading dose of valproic acid (30 mg/kg). Despite the administered treatment, the patient remained in a state of stupor for 12 hours. Electroencephalography (EEG) conducted post-seizure revealed intermittent bi-frontal slowing (Figure 1A). Subsequently, corticosteroid treatment commenced with intravenous methylprednisolone administered at a dosage of 500 mg per day, alongside concurrent blood tests to assess thyroid function and ATA levels. Prior to corticosteroid treatment, cerebrospinal fluid (CSF) analysis was conducted to exclude viral, paraneoplastic, or autoimmune limbic encephalitis (ALE). The day following treatment initiation, the patient returned to alertness with restored orientation.

Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI), performed on the second day of admission, demonstrated multifocal high signal intensity in the bilateral parietal, occipital, and temporal cortices and subcortical white matter on fluid-attenuated inversion recovery (FLAIR) images. No diffusion restriction was evident; however, high signal intensity was observed in the same regions on the apparent diffusion coefficient (ADC) image (Figure 2A, B, and C). Thyroid function test revealed no abnormality; however, anti-TPO level was elevated to 4,676.2 IU/mL (normal range, 0–60 IU/mL). Anti-TG level was not elevated (2.7 IU/mL; normal range, 0–4.5 IU/mL). The CSF test revealed no pleocytosis, but there was a mild elevation in protein level (78.2 mg/dL; normal range, 8.0–32.0 mg/dL). No paraneoplastic antibodies or antibodies associated with ALE were evident on CSF analysis. Polymerase chain reaction test for herpes simplex virus yielded negative results. Anti-nuclear antibody and anti-neutrophil cytoplasmic antibody were also negative.

Methylprednisolone was administered intravenously for 5 days, followed by a transition to oral prednisolone at a dosage of 30 mg. The patient was admitted for 10 days and was subsequently discharged without any neurological sequelae. However, after discharge, the patient complained of menstrual irregularities and weight gain. Oral prednisolone was gradually tapered and discontinued one month after discharge, subsequently replaced with azathioprine (100 mg twice daily). Follow-up EEG (Figure 1B) and brain MRI with DWI and ADC map image (Figure 2D, E, and F), conducted 3 months after discharge, were normal. Valproate was administered at a dosage of 500 mg twice daily for one month, gradually tapered, and ultimately discontinued at 3 months following discharge. During the 3-month follow-up period, there was no recurrence of symptoms.

This study was approved by the Institutional Review Board of Nowon Eulji Medical Center (IRB no. 2025-04-006). Written informed consent by the patients was waived due to a retrospective nature of our study.

HE represents a rare neurological disorder that poses diagnostic challenges. Furthermore, the status of HE as a distinct neurological entity remains in debate [1]. Since the recognition of ALE in the mid-2000s, such as anti-N-methyl-ᴅ-aspartate receptor and leucine-rich glioma-inactivated 1 encephalitis [3], the validity of HE has been increasingly questioned. Nonetheless, HE demonstrates distinct clinical features compared to typical ALEs, including early responsiveness to steroid therapy [1]. While ALEs might exhibit some degree of response to steroids alone, such a response tends to be inadequate [4]. Our patient displayed an elevation in anti-TPO level without evidence of paraneoplastic encephalitis, ALE, or other autoimmune diseases. This suggests that HE might represent a distinct disease entity.

PRES is commonly associated with hypertension, eclampsia, renal disease, immunosuppressive therapy, and cytotoxic drugs. The hallmark radiological feature of PRES is VE, predominantly affecting the posterior regions of the brain, particularly the parieto-occipital lobes, although other areas can also be involved. The exact pathophysiology of PRES is not fully understood, but it is thought to involve endothelial dysfunction, impaired cerebral autoregulation, and disruption of the blood-brain barrier leading to fluid extravasation and subsequent edema formation [2].

HE and PRES are neurological disorders that can present with overlapping clinical features, leading to potential diagnostic confusion. Both conditions involve endothelial dysfunction, though different mechanisms [1,2]. In HE, autoimmune-mediated inflammation can lead to endothelial damage; in PRES, hypertension-induced endothelial dysfunction is thought to play a central role. It is possible that the autoimmune process that leads to HE also might contribute to VE, also a distinctive feature in PRES, through mechanisms such as blood-brain barrier disruption and endothelial dysfunction [2,5].

Initially, the patient showed elevated blood pressure measuring 180/96 mmHg, raising suspicion for hypertensive PRES. However, subsequent monitoring revealed a reduction in blood pressure to a mild hypertensive state in the absence of antihypertensive medication. Furthermore, the absence of associated symptoms such as headache and visual disturbance decreased the likelihood of hypertensive PRES. The initial elevation in blood pressure could potentially be linked to post-ictal sympathetic hyperstimulation.

HE can be diagnosed based on three criteria: (1) neurological clinical manifestations after excluding other causes of encephalopathy, (2) elevated levels of ATA, and (3) significant clinical improvement following immunomodulatory treatment [6]. The clinical features of our patient conform well to these criteria. For an accurate diagnosis of HE, clinical suspicion and appropriate testing for ATA are essential.

Long-term steroid treatment may cause severe adverse effects and hormonal disturbances. Azathioprine can be used as an effective steroid sparing agent, useful especially in avoiding the morbidities associated with long-term steroid use [7].

To the best of our knowledge, this is the first case report of HE presenting with PRES with a focus on differential diagnosis from ALE. HE and PRES represent distinct disease entities characterized by differing pathophysiological mechanisms. Nonetheless, both conditions can induce VE through varying mechanisms, potentially leading to diagnostic ambiguity. Differential diagnosis of PRES and HE is challenging, especially when lesions are located in the posterior cerebral region. Neuroimaging often reveals similar findings, such as VE. In our cases, the absence of common associated factors—such as drug use or severe hypertension—combined with elevated levels of ATA was a critical point for differentiation. Treatment strategies also diverge between the two diseases. Timely recognition and precise diagnosis are imperative for facilitating recovery.