Thyroid Eye Disease in Hashimoto Ataxia

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Thyroid Eye Disease in Hashimoto Ataxia Amritha D. Kanakamedala, BA, Bayan A. Al Othman, MD, Ashwini T. Kini, MD, Andrew G. Lee, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 05/04/2022 H ashimoto thyroiditis is an autoimmune disease associated with antibodies against the thyroid gland (thyroid peroxidase [TPO] enzyme and thyroid-stimulating immunoglobulin) (1,2). Molecular mimicry and crossreactivity between these thyroid antibodies and orbital antigens produce thyroid eye disease (TED). TED can occur in autoimmune hyperthyroid, hypothyroid, or euthyroid states. In addition to TED, autoimmune thyroid disease can produce encephalopathy that may manifest as ataxia (Hashimoto encephalopathy [HE]).” (1) HE is very rare, and the exact pathogenesis is not well-understood. It is hypothesized that autoimmune vasculitis directed against thyroid antigens found in the brain could be a potential etiology (1). The most common symptoms and signs of HE are seizures, headaches, confusion, stroke-like episodes, cognitive impairment, focal neurologic deficits, and ataxia (1). Interestingly, cases of HE can present with ataxia as the predominant symptom and cerebellar atrophy on MRI (3). HE is associated with positive serum antibodies not only against TPO but also against the amino (NH2) terminal region of alpha enolase (NAE) (4). Steroids are the mainstay of treatment for HE (1). Below, we describe a case of Hashimoto ataxia and TED. A 48-year-old Hispanic woman presented with progressive onset loss of balance for 2 years. The patient experienced wide-based gait and falling toward the left side while walking. She developed dysarthria, difficulty writing, and slurred speech. She also noted numbness and tingling in hands and feet, worsening dizziness, blurry vision, and loss of fine motor control. Family history was negative for ataxia and neurodegenerative disorders. Thyroid hormone levels were normal, but TPO antibody was elevated to 798 IU/mL (ref range , School of Medicine (ADK), Baylor College of Medicine, Houston, Texas; Department of Ophthalmology (BAAO, ATK, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (AGL), University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Ophthalmology (AGL), Texas A and M College of Medicine, Bryan, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, Suite 450, Houston, TX 77030; E-mail: [e-mail] Kanakamedala et al: J Neuro-Ophthalmol 2021; 41: e83-e84 5) and thyroglobulin was elevated 72.7 (reference range , 4). MRI of the brain was notable for cerebellar atrophy. A lumbar puncture (LP) was normal. She was diagnosed with HE and started on IV methylprednisolone 1,000 mg for 5 days with a maintenance oral prednisolone. On neuro-ophthalmology evaluation, her bestcorrected visual acuity was 20/30 and 20/25 in the right and left eyes, respectively. Pupils were reactive in both eyes with no relative afferent pupillary defects or anisocoria. Humphrey visual field was normal in both eyes. External examination showed mild bilateral upper lid retraction. Anterior segment examination and dilated fundus examination were normal in both eyes. In primary position, the eyes were straight. Motility examination was significant for saccadic pursuits and saccadic dysmetria with hypometric saccades for horizontal greater than vertical movements. Fixation was stable in primary position with gaze-evoked nystagmus on gaze to either side. Hertel exophthalmometer measurement at a base of 107 was 20 and 21 (upper limit of normal is 20.1 mm) (5). The MRI only showed slightly larger left medial rectus enlargement (Fig. 1) but orbital ultrasound revealed more compelling enlargement of all extraocular muscles in both eyes. HE was first described in 1966 in a patient with “Hashimoto disease and encephalopathy.” (6) Since 1966, a number of patients have been noted in the literature to have different clinical presentations of HE but similar responsiveness to glucocorticoid treatment (7). Typical workup for HE includes laboratory and imaging studies, including antithyroid antibody levels, amino (NH2) terminal region of alpha enolase levels, serum thyroid stimulating hormone, T4, T3, LP with cerebrospinal fluid analysis, MRI of the brain, electroencephalogram, and neuropsychiatric evaluations (8). The diagnosis can be made based on high serum antithyroid antibodies. Treatment typically involves glucocorticoids, and intravenous immunoglobulin can serve as second-line treatment (2,9). Improvement with glucocorticoid therapy can take over 1 year (7). Despite cases being reported in the literature of HE, the etiology, pathogenesis, and clinical features of the disease are not well understood (1,7). Although Hashimoto-associated ataxia is well recognized as a nonfamilial, progressive, e83 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Coronal (A) and axial (B) MRI of the brain and orbits showing enlargement of the extraocular muscles mainly of the medial rectus muscles in both eyes. adult-onset cerebellar degeneration associated with autoimmune thyroiditis in the absence of hypothyroidism, the exact pathogenesis remains controversial. Differential diagnosis for patients with cerebellar ataxia include vitamin deficiencies, alcohol, drugs, viral infections, mitochondrial diseases, and autoimmune conditions. Hypothyroidism has also been noted as a cause of gait ataxia (10). Even fewer cases have reported ataxia as the predominant symptom in HE (3,10). Furthermore, TED in the setting of Hashimoto thyroiditis is uncommon (1,2). One study analyzing 700 patients with Hashimoto thyroiditis found that only 6% of patients had TED (11). Although other case reports have described ophthalmic manifestations of HE, such as ophthalmoparesis, saccadic eye movements, and opsoclonus, to the best of our knowledge, our case is the first to report TED in a patient with Hashimotoassociated ataxia in the English language ophthalmic literature (8,12). Ophthalmologists should be aware of the potential association of ataxia and TED and that autoimmune antibodies may be a single unifying mechanism for both findings. We recommend that neurologists test for these autoimmune antibodies in their workup of patients with cerebellar disease. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: B. A. Al Othman; b. Acquisition of data: A. D. Kanakamedala; c. Analysis and interpretation of data: B. A. Al Othman. Category 2: a. Drafting the manuscript: A. T. Kini; b. Revising it for intellectual content: B. A. Al Othman. Category 3: a. Final approval of the completed manuscript: A. G. Lee. e84 REFERENCES 1. 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Opsoclonus as a manifestation of hashimoto’s encephalopathy (P01.115). Neurology. 2012;78:1465–1466. Kanakamedala et al: J Neuro-Ophthalmol 2021; 41: e83-e84 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.