Case 28 – Young Woman Feeling Sick and Confused

Abstract

A 32-year-old right-handed woman developed persistent fever with malaise and nausea. The symptoms persisted for 2 weeks, after which she was admitted because of delirium, amnesia, and repetitive generalized convulsions with loss of consciousness. She had no remarkable past and family medical history, which included a history of abortions and thyroiditis. However, she had gained a body weight of 20 kg in the 1 year preceding this episode. She was not on medication and did not smoke or consume alcohol.

Case 28 Young Woman Feeling Sick and Confused

Masamichi Ikawa , Akiko Matsunaga , and Makoto Yoneda

28.1 Clinical History

28.2 Examination

At admission, the patient had a body temperature of 37.2°C, blood pressure of 120/80 mmHg, pulse rate 70 beats per minute, regular respiratory rate of 12 breaths per minute, and oxygen saturation of 97% (room air). The patient’s height was 167 cm, while the weight was 70 kg (body mass index: 25.1). The physical examination findings were unremarkable; we did not find edema in the extremities or enlargement of the thyroid gland. The patient was drowsy and in a state of confusion, along with amnesia. The function of the cranial nerves was intact. Muscular weakness, sensory disturbance, cerebellar ataxia, and involuntary movements were not observed. Tendon reflexes in the extremities were diminished without pathological reflex.

All routine laboratory data, including the white blood cell count (2,800/mL), serum sodium level (141 mEq/L), and CRP level (0.2 mg/dL) were normal. Although the patient was clinically euthyroid (TSH: 0.9 IU/mL, free T4: 1.2 ng/mL), both the antithyroid peroxidase (TPO) and anti-thyroglobulin (TG) antibodies were detected (57.5 IU/mL and 0.6 IU/mL, respectively; normal < 0.3 for both). Antibodies to nuclear (ANA), ds-DNA, Sm, and U1-RNP as well as C-ANCA and P-ANCA were not detected. Tumor marker test results for CA19–9 and CA125 were also negative. Cerebrospinal fluid (CSF) examination showed normal protein concentration (31 mg/dL) and no pleocytosis (1 cell/mL). DNA of herpes simplex virus 1 (HSV-1) and bacterial cultures were not detected. Lactate and pyruvate levels were normal in both the serum and CSF samples. Electroencephalogram (EEG) revealed generalized slow waves with sporadic sharp waves. Brain MRI showed swelling with hyperintensities on fluid-attenuated inversion recovery (FLAIR) images in the bilateral medial temporal lobes and the insular cortices (Figure 28.1), suggesting limbic encephalitis. No obvious contrast-enhanced lesions were observed on the MRI. No tumors were identified on chest and abdominal CT images.

Figure 28.1 Brain MRI findings of the patient. FLAIR images show swelling with abnormal hyperintense signals in the bilateral medial temporal lobes (arrows), suggesting limbic encephalitis. Transverse (a) and sagittal images (b). R, right.

28.3 Special Studies

The symptoms and findings indicating encephalitis, such as persistent fever, psychosis, and dementia with seizures and abnormalities in the limbic areas on MR images, along with no evidence of infection suggested that the patient had a form of autoimmune limbic encephalitis (LE), particularly Hashimoto’s encephalopathy (HE), because of the presence of antithyroid (TPO and TG) antibodies. Myxedema was excluded because the patient was euthyroid. Thus, we examined the serum for autoantibodies against the amino (NH₂)-terminal of α-enolase (NAE), a specific diagnostic marker of HE.¹ Immunoblotting of a recombinant NAE protein with the patient’s serum sample showed a positive result for anti-NAE antibodies (titer, ×320) (Figure 28.2). In order to exclude other types of autoimmune limbic encephalitis, the serum sample was also tested for autoantibodies against the N-methyl-D-aspartate receptors (NMDAR), leucine-rich glioma inactivated 1 (LGI1), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABA_BR), and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor 1 and 2 (AMPAR1/2), none of which were detected in the serum. Paraneoplastic antibodies to Hu, Yo, and Ri were also not detected.