The researchers recommend having a low clinical threshold for the diagnosis of Hashimoto encephalopathy in patients who reveal no apparent cause for their altered mental status, given the heterogeneous nature of disease presentation.
According to a case report published in Cureus.
Hashimoto’s encephalopathy is often referred to as steroid-responsive encephalopathy associated with autoimmune arthritis (SREAT). However, the cases presented highlight the heterogeneous nature of Hashimoto’s encephalopathy, describing 2 patients who found relief with plasmapheresis therapy (PLEX) when steroid treatment failed.
The first case involved a 42-year-old female patient with a 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 in a coma with an initial Glasgow Coma Scale of 4 just hours after presenting as normal. She was electively intubated and admitted to the intensive care unit.
Extensive tests did not reveal the etiology of his acute encephalopathy. Initial evaluation for acute encephalopathy showed a normal CT scan of the head. Blood cultures for infection, urine cultures and screens were all negative.
A complete blood count and a complete metabolic panel showed no leukocytosis or metabolic dysregulation. His thyroid-stimulating hormone was only slightly elevated at 5.04 MIU/L (reference range: 0.27-4.2 MIU/L); however, inflammatory markers were significantly elevated.
A lumbar puncture revealed a high burst pressure of 40 mmHg and a slightly elevated CSF protein concentration, but no evidence of underlying infection or oligoclonal bands. The patient underwent unremarkable magnetic resonance imaging.
A continuous electroencephalogram revealed diffuse and generalized slowing consistent with mild nonspecific encephalopathy. After the patient was extubated, her persistent encephalopathy prevailed.
A complementary assessment with systemic autoimmune screening ruled out any cause of autoimmune cerebritis. Additional biopsies revealed nothing significant.
Subsequent attempts at treatment with a course of high-dose empiric corticosteroids and IVIG therapy were unsuccessful. The patient remained encephalopathic 3 months after presentation, dependent on nasogastric feeding.
When inflammatory markers remained elevated, but an autoimmune CSF panel came back negative, doctors began to consider Hashimoto’s encephalopathy. Her serum anti-thyroid antibodies showed normal titers or thyroid peroxidase antibodies but significantly elevated anti-thyroglobulin antibodies at 154.1 IU/mL (reference range: 0.0-0.9 IU/mL) .
After a discussion between the specialties, plasmapheresis therapy (PLEX) for 10 sessions was set up.
At each session, the patient demonstrated significant improvement. By her second session, she became alert and oriented. Repeated anti-thyroglobulin antibody testing revealed significant improvement.
She was able to tolerate an oral diet, converse and respond to commands. She was successfully released with no recurrence during the 2-year follow-up.
The second case involved an 18-year-old male patient with a history of cerebral palsy. The patient presented to hospital with a generalized tonic-clonic seizure. His carer said the patient was able to hold a normal conversation and perform small tasks without difficulty initially.
Initially, the patient was successfully managed with intravenous lorazepam and midazolam. However, the patient remained encephalopathic with catatonic postures after his seizure ended.
The patient was unable to follow commands or speak meaningful sentences. Initial concerns about malignant catatonia were ruled out by the psychiatry team.
Examination revealed no leukocytosis, anemia or metabolic disorders. The patient had normal TSH and free T4.
A diffuse and generalized slowing consistent with moderate encephalopathy was also observed in this patient. Neuroimaging with head CT and a lumbar puncture were generally unremarkable, although minor elevation of CSF proteins was noted.
For this patient, a complete autoimmune panel of serum and CSF was negative, ruling out concerns of possible autoimmune encephalitis.
Doctors took thyroid antibodies to determine if Hashimoto’s thyroiditis could be ruled out. The patient had an elevated thyroid peroxidase antibody level of 80 IU/mL (reference range: 0-26 IU/mL) and an elevated anti-thyroglobulin antibody level 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 followed by IVIG therapy did not result in any improvement in the patient’s clinical condition. The doctors decided to proceed with 10 sessions of PLEX therapy.
By the fourth session, the patient was more alert and less catatonic. The patient went from a state of complete inattention 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 base.
After having tolerated the 10 sessions, the patient was discharged. The patient has not reported a 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 LCR autoimmune panel and a significant elevation of inflammatory markers.
Hashimoto’s encephalopathy is considered a rare disease and currently has no definitive diagnostic studies. As demonstrated by the 2 reported cases, the majority of neurological studies, including lumbar puncture, cEEG, and brain MRI, reveal only nonspecific findings.
Although the majority of cases are characterized by elevated 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 considering empirical treatment based on strong clinical suspicion, even when the initial thyroid antibody test is negative.
Although they encourage further research evaluating the benefits of long-term immunosuppression and other treatments for this patient population through randomized controlled trials, they encourage the use of PLEX therapy in some patients. .
Karan A, Nuthulaganti SR, Zhang Y, Kandah F, Gutierrez M, Reddy P. Two troubling cases of Hashimoto encephalopathy unresponsive to steroids 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.