Plasmapheresis is Viable Treatment Option for Patients with Hashimoto’s Encephalopathy Nonresponsive to Steroids

Researchers recommend having a low clinical threshold for the diagnosis of Hashimoto’s encephalopathy in patients who reveal no apparent cause for their altered mental status, given the heterogenous nature of the condition’s presentation.

Plasmapheresis may be an option for patients with Hashimoto’s encephalopathy who are unresponsive to steroids and intravenous immunoglobin (IVIG) therapy, according to a case report published in Cureus.

Hashimoto’s encephalopathy is often called steroid-responsive encephalopathy associated with autoimmune arthritis (SREAT). However, the cases presented highlight the heterogenous nature of Hashimoto’s encephalopathy, describing 2 patients who found relief using plasmapheresis (PLEX) therapy when treatment with steroids was unsuccessful.

The first case involved a 42-year-old female patient with a past medical history of type 2 diabetes mellitus, hypertension, and hypothyroidism. The patient presented with an altered mental status following total thyroid resection for papillary thyroid cancer.

She was found comatose with an initial Glasgow Coma scale of 4 only a few hours after presenting with a normal state of health. She was electively intubated and admitted to the intensive care unit.

Extensive testing did not reveal the etiology of her acute encephalopathy. Initial evaluation for acute encephalopathy showed a normal computed tomography of the head. Infectious workup blood cultures, urine cultures, and screenings were all negative.

A complete blood count and complete metabolic panel showed no leukocytosis or metabolic derangements. Her thyroid-stimulating hormone was only mildly elevated at 5.04 MIU/L (reference range: 0.27-4.2 MIU/L); however, inflammatory markers were significantly elevated.

A lumbar puncture revealed an elevated opening pressure of 40 mmHg and a mildly elevated protein CSF concentration, but no evidence of underlying infection or oligoclonal banding. The patient underwent unremarkable magnetic resonance imaging.

A continuous electroencephalogram revealed diffuse, generalized slowing, consistent with a moderate nonspecific encephalopathy. After the patient was extubated, her persistent encephalopathy prevailed.

Further workup with a systemic autoimmune screen ruled out any cause of autoimmune cerebritis. Additional biopsies revealed nothing significant.

Subsequent treatment attempts with a course of empiric high-dose corticosteroids and IVIG therapy were futile. The patient remained encephalopathic 3 months following presentation, dependent on nasogastric feeding.

When inflammatory markers remained elevated, but a CSF autoimmune panel returned negative, physicians began to consider Hashimoto’s encephalopathy. Her serum theroid antibodies revealed normal titers or thyroid peroxidase antibodies but significantly elevated anti-thyroglobulin antibody 154.1 IU/mL (reference range: 0.0-0.9 IU/mL).

After a discussion across specialties, plasmapheresis (PLEX) therapy for 10 sessions was implemented.

With each session, the patient demonstrated significant improvement. By her second session, she became alert and oriented. Repeat anti-thyroglobulin antibody testing revealed significant improvement.

She was able to tolerate an oral diet, converse, and respond to commands. She was successfully discharged, with no recurrence during 2 years of follow-up.

The second case involved an 18-year-old male patient with a history of cerebral palsy. The patient presented to the hospital with a generalized tonic-clonic seizure. His caregiver stated that the patient was able to conduct a normal conversation and perform small tasks without difficulties at baseline.

Initially, the patient was successfully managed with intravenous lorazepam and midazolam. However, the patient remained encephalopathic with catatonic postures after the termination of his seizure.

The patient was unable to follow commands or speak meaningful sentences. Initial concerns for malignant catatonia were excluded by the psychiatry team.

Examination revealed no leukocytosis, anemia, or metabolic derangements. The patient had a normal TSH and free T4.

Diffuse, generalized slowing consistent with a moderate encephalopathy was observed in this patient as well. Neuroimaging with CT head and a lumbar puncture were generally unremarkable, though a minor elevation in CSF protein was noted.

For this patient, a complete serum and CSF autoimmune panel were negative, dismissing concerns about possible autoimmune encephalitis.

Physicians collected thyroid antibodies to determine whether Hashimoto’s thyroiditis could be excluded. The patient was found to have an elevated thyroid peroxidase antibody level of 80 IU/mL (reference range: 0-26 IU/mL), and an elevated thyroglobulin antibody of 22 IU/mL (reference range 0-0.9 IU/mL).

A decision was made to treat the patient for SREAT, or Hashimoto’s thyroiditis.

A course of IV methylprednisolone and subsequent IVIG therapy caused no improvement in the patient’s clinical status. Physicians decided to proceed with 10 sessions of PLEX therapy.

By the fourth session, the patient was more alert and less catatonic. The patient improved from a state of complete inattentiveness and disorientation to being alert and oriented to time, place, and person. He also became able to converse with his mother and returned to his functional baseline.

After tolerating all 10 sessions, the patient was discharged. The patient has not reported recurrence since discharge, according to the report.

These cases highlight the varied nature of the clinical presentation of Hashimoto’s encephalopathy. In both cases, a significant increase in the patient’s thyroid antibody titer was observed, with a negative CSF autoimmune panel and significant elevation in inflammatory markers.

Hashimoto’s encephalopathy is considered a rare disease, and currently has no definitive diagnostic study. As demonstrated by the 2 reported cases, the majority of neurological studies including a lumbar puncture, cEEG, and brain MRI, reveal only nonspecific findings.

Despite a majority of cases being characterized by an elevation in thyroid antibodies and a positive response to corticosteroid therapy, the authors suggest that positive thyroid antibody titers should not be reliably used in the diagnosis of Hashimoto’s encephalopathy. They recommend that empiric therapy be considered based on high clinical suspicion, even when initial thyroid antibody testing is negative.

Though they encourage further research assessing the benefit of long-term immunosuppression and other treatments for this patient population through randomized controlled trials, they encourage the use of PLEX therapy in certain patients.

Reference

Karan A, Nuthulaganti S R, Zhang Y, Kandah F, Gutierrez M, Reddy P. Two perplexing cases of Hashimoto’s encephalopathy unresponsive to steroid and intravenous immunoglobin therapy. Cureus. 2022;14(7):e26853. https://www.cureus.com/articles/101825-two-perplexing-cases-of-hashimotos-encephalopathy-unresponsive-to-steroid-and-intravenous-immunoglobulin-therapy. Published July 14, 2022. Accessed July 20, 2022.