Hashimoto’s encephalopathy (HE), a rare autoimmune disorder associated with thyroiditis, is a condition with no definitive cause. Symptoms include altered mental status, seizures, and cognitive impairment. When diagnostic criteria are met, steroids are the cornerstone of treatment with a reported good response. This report presents a 26-year-old female with HE who presented with persistent status epilepticus and altered mental status, complicated by aspiration pneumonia and laryngeal edema, and had been managed successfully. After exclusion of the common causes of acute altered mental status and seizures, early workup for treatable rare causes such as HE can help rapid recovery and avoid complications. However, proper management of complications such as lower respiratory tract infection, if happened, is necessary for good outcome.
Steroid-responsive encephalopathy associated with thyroiditis (SREAT), or Hashimoto’s encephalopathy (HE), is a rare autoimmune disorder associated with thyroiditis. In addition to affecting the nervous system, it also affects the endocrine system. It is characterized by anti-thyroid antibodies and a steroid response . The symptoms include myoclonus, seizures, confusion, and fluctuating levels of consciousness. Paranoid delusions and hallucinations may also be associated with the condition. Yet, the cause has not been determined .
In most cases, immunoglobulin G indices are within normal limits, though occasionally oligoclonal bands may be seen. The most consistent cerebrospinal fluid (CSF) finding is an elevated protein level without pleocytosis. Brain imaging with magnetic resonance imaging (MRI) and computed tomography (CT) reveals a wide range of findings, ranging from entirely normal to various abnormalities, including cerebral atrophy, white matter abnormalities, cortical irregularities, and vasculitic changes [3, 4]. The literature suggests that the disease evolves through a pathological inflammatory response. The association between encephalopathy and Hashimoto’s thyroiditis (HT) is still unclear. The association of SREAT with anti-thyroid antibodies and its responsiveness to steroids and other therapies, such as plasmapheresis, support the hypothesis that it is an immunopathogenic disorder. However, the role of anti-thyroid antibodies in encephalopathic processes is still debated [3, 4].
There are several forms of SREAT, including acute, subacute, and chronic. It has a wide range of severity from mild cognitive impairment or psychological abnormalities to severe life-threatening seizures, disturbed levels of consciousness, and coma. Our case hereby is an example of the severe life-threatening presentation as the patient lost consciousness, developed status epilepticus, and needed intubation and mechanical ventilation.
A 26-year-old female presented initially to the emergency room with high-grade fever, recurrent dizziness, and vomiting over 2 days and was managed with intravenous (IV) antipyretic and antiemetic medications and discharged home on analgesic, antiemetic, and prokinetic tablets. She experienced sudden onset loss of consciousness, seizures, and marked oral secretions at home and was brought to emergency room again by ambulance. On examination, she was in generalized tonic-clonic (GTC) fits that were resistant to initial benzodiazepine, so she was intubated to secure the airway, started on midazolam and propofol IV infusions, and admitted to the intensive care unit (ICU).
After 10 days of ICU stay in the previous hospital, the patient was referred to our hospital, on mechanical ventilation, sedated with propofol 50 mg/h and fentanyl 150 mic/h, tachycardic (140 beat/min) with high-grade fever (40°C) and high blood pressure (150/95 mm Hg). Her medical report stated that the workup included two brain CT scans, both of which showed no abnormalities. Additionally, CSF analysis was performed and was within normal limits, as was a basic metabolic profile. They suspected meningoencephalitis and started antimicrobials including antibacterial and antiviral drugs as well as anticonvulsants including phenytoin, levetiracetam, and valproate, but there was no adequate response in terms of fever and seizure control. They concluded that the patient is still undiagnosed for further investigations.
On admission to our ICU, we did brain magnetic resonance images, magnetic resonance venography, and magnetic resonance arteriography with contrast; however, all were reported normal (Fig. 1-5). Chest X-ray showed bilaterally increased broncho-vascular markings and nodular infiltrations (Fig. 6, 7). Electroencephalogram was done and reported non-specific slow waves in the left fronto-parieto-temporal areas. We repeated the CSF analysis and sent a thorough laboratory workup including cultures for sputum, urine, blood, throat swab, and CSF; basic metabolic profile; antineutrophil cytoplasmic antibodies (ANCA)-C, ANCA-P; antinuclear antibodies; antibody to double-stranded deoxyribonucleic acid; and thyroid function tests. In addition, the CSF sample was also sent for acid fast bacilli stain, tuberculosis polymerase chain reaction, and brucella antibodies.
The inflammatory markers were elevated (total leucocytic count 12.5, C-reactive protein 71.8 mg/L, erythrocyte sedimentation rate 60 mm/h), while most of the basic metabolic profile was within normal (venous blood gases: pH 7.45 pCO2 39 HCO3 23, serum sodium 140 mEq/L, serum potassium 3.9 mEq/L, blood urea 23 mg/dL, serum creatinine 0.84 mg/dL, total calcium 7.8 mg/dL, magnesium 0.8 mmol/L, activated partial thromboplastin time 32.2 s, international normalization ration 1.1). The exceptions were a mild elevation of serum lactate (2.9 mmol/L), liver transaminases (alanine aminotransferase 58 U/L, aspartate aminotransferase 52 U/L), and a mild hypoalbuminemia (albumin 3.24 g/dL).
We started broad-spectrum antimicrobials including meropenem 1 g every 8 h, vancomycin 1 g every 12 h, and acyclovir 800 mg every 8 h, waiting for culture results. A sedation vacation followed by a spontaneous breathing trial then extubation were done on day 11 and day 13; however, both trials failed due to stridor and restlessness despite Glasgow Coma Scale (GCS) of 10 (Eye 4 Motor 5 Verbal 1) and good motor power. So, the patient was re-intubated within 12 h, and video laryngoscopy was done, which revealed marked vocal cords’ edema. As a result, dexamethasone 4 mg twice daily for 2 days was started, and the patient was planned for tracheostomy to avoid complications of prolonged intubation.
On day 15, throat swab culture and sensitivity reported Acinetobacter species multidrug-resistant (MDR) sensitive only to colomycin and aminoglycosides, and urine culture reported candida species with persistent fever, so colomycin and micafungin were started, and all other antimicrobials were discontinued. CSF acid fast bacilli and tuberculosis polymerase chain reaction were negative. All vasculitis markers were reported normal, so anti-thyroglobulin and anti-thyroid microsomal antibodies were sent.
On day 17, a tracheostomy tube insertion was done, and the sputum culture and sensitivity reported Acinetobacter species (MDR) with the same sensitivity as throat swab culture result. The fever subsided despite stationary total leucocytic count and a rising C-reactive protein level (Fig. 8). Both anti-thyroid microsomal and anti-thyroglobulin antibodies reported high: 403 IU/mL (reference: less than 9) and 644 IU/mL (Reference: less than 18), respectively. Therefore, the diagnosis of steroid-responsive encephalopathy associated with thyroiditis (SREAT) was established according to the modified diagnostic criteria by Graus et al. . A pulse steroid therapy started with 1 g of methyl-prednisolone IV daily for 3 days, followed by oral prednisolone 50 mg daily for 7 days. We observed a decrease in thyroid-stimulating hormone (TSH) from the first to the seventh days of admission to our ICU from 5.8 µIU/mL to 1.5 µIU/mL (reference: 0.45–4.68) without any significant abnormalities in free T3 and free T4.
Daily sedation vacation showed a gradual improvement of consciousness on day 19 (2 days after starting pulse steroid treatment) until she regained full consciousness on day 21 and was successfully disconnected from the ventilator. Over the next 4 days in ICU, a rehabilitation program involving physiotherapy and social support was implemented, the patient regained her normal physical activity, and the tracheostomy was downsized and then closed.
Eventually, after a total of 25 days in ICU, the patient was discharged to the ward on maintenance prednisolone 45 mg daily dose and dual anti-epileptic (levetiracetam 500 mg twice daily and valproate 500 mg twice daily) planned for slow-down titration in follow-up Outpatient Department visits over 6 months.
The estimated prevalence of HE, a rare neurological disorder, is about 2 cases per 100,000 of the general population . The first description of HE was in 1966, and it was thought that it was related to HT . Yet, it is still a very rare presentation; about 20 cases worldwide were reported with Graves’ disease . The case presented here was finally diagnosed as HE based on the presence of both anti-thyroid microsomal and anti-thyroglobulin antibodies with a high titer ; however, the patient was not known to have a thyroid disease. There are no specific guidelines for diagnosing SREAT. The diagnosis is based on clinical and laboratory findings and the exclusion of other causes of encephalopathy .
The presentation of HE did not require the prior existence of obvious hyperthyroidism, as it can occur in patients with hyperthyroidism, euthyroidism, and even subclinical thyroid impairment . Our patient was not known to have hyperthyroidism or even subclinical thyroid impairment before the onset of this illness, making the diagnosis more challenging. However, the thyroid profile – free T3, free T4, and TSH – was in the normal range during the illness period except for a non-significant decrease in TSH from the first to the seventh days of admission without any abnormalities in free T3 and T4. This change can occur in any critically ill patient, even non-thyroid dysfunction patients . The HE patients either had stroke-like episodes or relapsing seizure patterns, including status epilepticus and myoclonus, as well as transient neurological abnormalities, including dementia, tremor, and consciousness disruption, as well as a range of mental symptoms like schizophrenia and depression . The presentation of our patient was persistent high-grade fever, loss of consciousness, and status epilepticus, which resisted the usual management of seizure attacks and required intubation and mechanical ventilation under propofol and midazolam as dual sedatives. The fever was also reported in patients with HE [1, 13]. Our patient had a high-grade persistent fever at her first presentation. Therefore, a central nervous system infection was suspected initially after exclusion of vascular causes (e.g., ischemic or hemorrhagic stroke or venous sinus thrombosis) by 2 CT brain scans, one upon admission and another 48 h after. However, CSF analysis did not show any cell or protein derangements even after repeating 2 times.
Corticosteroids and other immunosuppressive therapies (e.g., IV immunoglobulin, plasmapheresis) improve or completely resolve symptoms in many patients [1, 6]. However, despite treatment, it can follow a relapsing-remitting course, resolve with treatment, or self-limit without treatment . Our patient responded dramatically to the pulse steroid therapy and was continued on a maintenance dose of prednisone and anti-epileptic medications, which were planned for slow titration over 6 months. In selection of anticonvulsants, neurologists preferred levetiracetam, avoided phenytoin, and planned for gradual tapering of valproate to avoid their teratogenic side effects as the patient was in childbearing period.
Many complications have been reported with HE; one of them was an infection, which was the cause of death in 2 of the 9 died patients in a systematic review . Our patient had MDR aspiration pneumonia. Hospital-acquired infections have been reported in patients with HE. So, it is crucial to prevent and treat infections, especially relapsing symptoms after improvement [14, 15]. The patient also had post-extubation laryngeal edema which is reported to occur in 30% of extubated patients, of whom 4% need reintubation . However, the patient was managed successfully for both complications.
In this report, we presented a case of Hashimoto encephalopathy in a young female who presented with persistent status epilepticus and altered mental status, complicated by aspiration pneumonia and laryngeal edema. The patient was challenging to diagnose due to the absence of prior thyroid dysfunction and normal thyroid function during the hospital course. So, thyroid antibodies should be checked in patients suspected of having HE, even with normal thyroid function. The steroids are the cornerstone in managing HE, and our patient was steroid responsive. Infection is not a rare complication in HE patients, and it is crucial to prevent and treat, especially relapsing symptoms after improvement.
The author would like to thank S.C. (Alexandria, Egypt) for drafting the initial version of the manuscript and providing language editing for the authors’ final version.
Statement of Ethics
This case study presents only one case and thus does not need approval according to the Research Ethics Committee (REC). A written informed consent was obtained from the patient for publication of the details of her medical case and any accompanying images.
Conflict of Interest Statement
The author has no conflicts of interest to declare.
No funding was received.
The corresponding author contributed entirely to the work.
Data Availability Statement
All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.