Background: The aim of this study was to evaluate the changes in regional cerebral blood flow (rCBF) in multiple cases of Hashimoto's encephalopathy (HE). Methods: Seven untreated patients with HE and 10 age-matched healthy controls underwent brain single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine. All patients had anti-NH2-terminal of α-enolase autoantibodies (Abs), which served as a useful diagnostic marker for HE, in addition to anti-thyroid Abs in their sera and responded to corticosteroid therapy. The obtained SPECT images were compared between the patients and the controls using 3D-SSP analysis. Results: The rCBF of all patients with HE was significantly decreased in the bilateral anterior cingulate areas and left prefrontal cortex compared with the controls (p < 0.05). Focusing on the HE patients with acute neuropsychiatric symptoms (n = 5) such as consciousness disturbance and/or psychosis, the decreased rCBF in these areas was more significant, and the rCBF in the right frontal cortex was also decreased. Conclusion: Statistical analysis of these multiple-case SPECT images revealed the regions of decreased CBF associated with clinical symptoms, especially acute neuropsychiatric symptoms, in HE patients. This study shed light on the pathophysiological decrease in rCBF observed in HE.

1.
Brain L, Jellinek EH, Ball K: Hashimoto's disease and encephalopathy. Lancet 1966;2:512-514.
2.
Shaw PJ, Walls TJ, Newman PK, Cleland PG, Cartlidge NE: Hashimoto's encephalopathy: a steroid-responsive disorder associated with high anti-thyroid antibody titers - report of 5 cases. Neurology 1991;41:228-233.
3.
Peschen-Rosin R, Schabet M, Dichgans J: Manifestation of Hashimoto's encephalopathy years before onset of thyroid disease. Eur Neurol 1999;41:79-84.
4.
Forchetti CM, Katsamakis G, Garron DC: Autoimmune thyroiditis and a rapidly progressive dementia: global hypoperfusion on SPECT scanning suggests a possible mechanism. Neurology 1997;49:623-626.
5.
Yoneda M, Fujii A, Ito A, Yokoyama H, Nakagawa H, Kuriyama M: High prevalence of serum autoantibodies against the amino terminal of α-enolase in Hashimoto's encephalopathy. J Neuroimmunol 2007;185:195-200.
6.
Nakagawa H, Yoneda M, Fujii A, Kinomoto K, Kuriyama M: Hashimoto's encephalopathy presenting with progressive cerebellar ataxia. J Neurol Neurosurg Psychiatry 2007;78:196-197.
7.
Matsunaga A, Ikawa M, Fujii A, Nakamoto Y, Kuriyama M, Yoneda M: Hashimoto's encephalopathy as a treatable adult-onset cerebellar ataxia mimicking spinocerebellar degeneration. Eur Neurol 2012;69:14-20.
8.
Ghika-Schmid F, Ghika J, Regli F, Dworak N, Bogousslavsky J, Städler C, Portmann L, Despland PA: Hashimoto's myoclonic encephalopathy: an underdiagnosed treatable condition? Mov Disord 1996;11:555-562.
9.
Fujii A, Yoneda M, Ito T, Yamamura O, Satomi S, Higa H, Kimura A, Suzuki M, Yamashita M, Yuasa T, Suzuki H, Kuriyama M: Autoantibodies against the amino terminal of α-enolase are a useful diagnostic marker of Hashimoto's encephalopathy. J Neuroimmunol 2005;162:130-136.
10.
Shibata N, Yamamoto Y, Sunami N, Suga M, Yamashita Y: Isolated angiitis of the CNS associated with Hashimoto's disease (in Japanese). Rinsho Shinkeigaku 1992;32:191-198.
11.
Nolte KW, Unbehaun A, Sieker H, Kloss TM, Paulus W: Hashimoto encephalopathy: a brainstem vasculitis? Neurology 2000;54:769-770.
12.
Duffey P, Yee S, Reid IN, Bridges LR: Hashimoto's encephalopathy: postmortem findings after fatal status epilepticus. Neurology 2003;61:1124-1126.
13.
Kothbauer-Margreiter I, Sturzenegger M, Komor J, Baumgartner R, Hess CW: Encephalopathy associated with Hashimoto thyroiditis: diagnosis and treatment. J Neurol 1996;243:585-593.
14.
Bertoni M, Falcini M, Sestini S, Niccoli L, Nannini C, Cantini F: Encephalopathy associated with Hashimoto's thyroiditis: an additional case. Eur J Intern Med 2003;14:434-437.
15.
Kalita J, Misra UK, Rathore C, Pradhan PK, Das BK: Hashimoto's encephalopathy: clinical, SPECT and neurophysiological data. QJM 2003;96:455-457.
16.
Chen PL, Wang PY, Hsu HY: Reversible electroencephalographic and single photon emission computed tomography abnormalities in Hashimoto's encephalopathy. J Chin Med Assoc 2005;68:77-81.
17.
Fuertes J, García-Burillo A, Castell-Conesa J, Roca I: Functional neuroimaging in Hashimoto's encephalitis: a physiopathological imaging? Eur J Nucl Med Mol Imaging 2009;36:726.
18.
Hsu CS, Wu YC, Lu MK, Hsu YT, Chiou TS, Tsai CH, Chen JC: 99mTc ECD and 99mTc TRODAT-1 SPECT in Hashimoto encephalopathy. Clin Nucl Med 2012;37:e86-e88.
19.
Minoshima S, Koeppe RA, Frey KA, Kuhl DE: Anatomic standardization: linear scaling and nonlinear warping of functional brain imagings. J Nucl Med 1994;35:1528-1537.
20.
Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE: A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995;36:1238-1248.
21.
Ishitobi M, Yoneda M, Ikawa M, Matsunaga A, Ueno K, Kimura H, Wada Y: Hashimoto's encephalopathy with hippocampus involvement detected by continuous arterial spin labeling: a case report. Psychiatry Clin Neurosci 2013;67:128-129.
22.
Pandya DN, Dye P, Butters N: Efferent cortico-cortical projections of the prefrontal cortex in the rhesus monkey. Brain Res 1971;31:35-46.
23.
Pandya DN, Van Hoesen GW, Mesulam MM: Efferent connections of the cingulate gyrus in the rhesus monkey. Exp Brain Res 1981;42:319-330.
24.
Vogt BA, Pandya DN: Cingulate cortex of the rhesus monkey. II. Cortical afferents. J Comp Neurol 1987;262:271-289.
25.
Devinsky O, Morrell MJ, Vogt BA: Contributions of anterior cingulate cortex to behaviour. Brain 1995;118:279-306.
26.
Milham MP, Banich MT, Barad V: Competition for priority in processing increases prefrontal cortex's involvement in top-down control: an event-related fMRI study of the stroop task. Brain Res Cogn Brain Res 2003;17:212-222.
27.
Seghier ML: The angular gyrus: multiple functions and multiple subdivisions. Neuroscientist 2013;19:43-61.
28.
Nagaratnam N, Phan TA, Barnett C, Ibrahim N: Angular gyrus syndrome mimicking depressive pseudodementia. J Psychiatry Neurosci 2002;27:364-368.
29.
Rubbert A, Marienhagen J, Pirner K, Manger B, Grebmeier J, Engelhardt A, Wolf F, Kalden JR: Single-photon-emission computed tomography analysis of cerebral blood flow in the evaluation of central nervous system involvement in patients with systemic lupus erythematosus. Arthritis Rheum 1993;36:1253-1262.
30.
Chen JJ, Yen RF, Kao A, Lin CC, Lee CC: Abnormal regional cerebral blood flow found by technetium-99m ethyl cysteinate dimer brain single photon emission computed tomography in systemic lupus erythematosus patients with normal brain MRI findings. Clin Rheumatol 2002;21:516-519.
31.
Huang WS, Chiu PY, Tsai CH, Kao A, Lee CC: Objective evidence of abnormal regional cerebral blood flow in patients with systemic lupus erythematosus on Tc-99m ECD brain SPECT. Rheumatol Int 2002;22:178-181.
32.
Kao CH, Ho YJ, Lan JL, ChangLai SP, Chieng PU: Regional cerebral blood flow and glucose metabolism in Sjögren's syndrome. Nucl Med 1998;39:1354-1356.
33.
Chang CP, Shiau YC, Wang JJ, Ho ST, Kao A: Abnormal regional cerebral blood flow on 99mTc ECD brain SPECT in patients with primary Sjögren's syndrome and normal findings on brain magnetic resonance imaging. Ann Rheum Dis 2002;61:774-778.
34.
Pupi A, Sestini S, De Cristofaro MT, Emmi L, Marchione T, Salvati G, Gobbi FL, Massacesi L, Meldolesi U: Use of technetium-99m hexamethylpropylene amine oxime SPET for the study of cerebral blood flow reactivity after acetazolamide infusion in patients with Behçet's disease. Eur J Nucl Med 2000;27:700-706.
35.
Watanabe N, Seto H, Sato S, Simizu M, Wu YW, Kageyama M, Nomura K, Kakishita M: Brain SPECT with neuro-Behçet disease. Clin Nucl Med 1995;20:61-64.
36.
Kao CH, Lan JL, Hsieh JF, Ho YJ, ChangLai SP, Lee JK, Ding HJ: Evaluation of regional cerebral blood flow with 99mTc-HMPAO in primary antiphospholipid antibody syndrome. J Nucl Med 1999;40:1446-1450.
37.
Pancholi V, Fischetti VA: α-Enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci. J Biol Chem 1998;273:14503-14515.
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