Neurocase The Neural Basis of Cognition ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/nncs20 Dementia and Parkinson-like syndrome with basal ganglia lesion in neuromyelitis optica spectrum disorders Akiyuki Hiraga, Masahiro Mori & Satoshi Kuwabara To cite this article: Akiyuki Hiraga, Masahiro Mori & Satoshi Kuwabara (2021) Dementia and Parkinson-like syndrome with basal ganglia lesion in neuromyelitis optica spectrum disorders, Neurocase, 27:2, 223-226, DOI: 10.1080/13554794.2021.1921222 To link to this article: https://doi.org/10.1080/13554794.2021.1921222 Published online: 02 May 2021. Submit your article to this journal Article views: 39 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=nncs20 NEUROCASE 2021, VOL. 27, NO. 2, 223–226 https://doi.org/10.1080/13554794.2021.1921222 Dementia and Parkinson-like syndrome with basal ganglia lesion in neuromyelitis optica spectrum disorders Akiyuki Hiragaa, Masahiro Morib and Satoshi Kuwabarab a Department of Neurology, Chiba Rosai Hospital, Chiba, Japan; bDepartment of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan ABSTRACT ARTICLE HISTORY Brain lesions in neuromyelitis optica spectrum disorders (NMOSD) are generally located at sites of high anti-aquaporin 4 (AQP4) expression. Clinical features of NMOSD associated with basal ganglia damage in sites not enriched with AQP4 remain unknown. Here we describe the case of an 82-year-old woman who developed dementia and bradykinesia for 5 weeks. Brain magnetic resonance imaging revealed obvious basal ganglia abnormalities. Test for serum anti-AQP4 antibody was positive, and she was diagnosed with NMOSD. Our case showed that NMOSD associated with dementia and/or Parkinson-like syndrome with basal ganglia lesions could be another clinical presentation in NMOSD. Received 20 March 2021 Accepted 19 April 2021 Introduction Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory diseases of the central nervous system (CNS) that are frequently positive for antiaquaporin 4 (AQP4) antibody (Wingerchuk et al., 2015). Brain lesions in NMOSD are commonly located at sites with high AQP4 expression (Pittock et al., 2006; Wingerchuk et al., 2015). However, little is known regarding basal ganglia lesions in NMOSD and clinical symptoms of NMOSD associated with basal ganglia damage. Here we describe the case of a patient with NMOSD who presented with dementia as the primary manifestation with atypical brain damage mainly involving the bilateral basal ganglia. Case An 82-year-old woman with a past history of hepatitis C virus (carrier), hypertension and multiple vertebral compression fractures developed appetite loss; 2 weeks later, she devel­ oped bradykinesia, incontinence and cognitive decline. On examination, loss of facial expression and small voice were noted. Orthopedics recommended that she should be assessed at the clinic for memory loss at 1 month after the onset. Five weeks after onset, she was admitted to the internal medicine department of Chiba Rosai Hospital for the appetite loss, and then transferred to the neurology department 2 weeks after admission. On examination, she was disoriented and slow to respond to questions. She showed memory loss. Her speech was small and monotonous. She had very mild lead-pipe rigidity at the bilateral elbows. Additionally, she demonstrated remarkable bradykinesia. There was no resting tremor. She could not walk. Revised Hasegawa Dementia Scale score was 5/30, which indicated severe cognitive decline. She had mild hypersomnolence. Blood examination CONTACT Akiyuki Hiraga hiragaa@yahoo.co.jp © 2021 Informa UK Limited, trading as Taylor & Francis Group KEYWORDS Neuromyelitis optica spectrum disorders; antiaquaporin 4 antibody; parkinsonism; dementia; basal ganglia demonstrated a white blood cell count of 6000/mm3 and C-reactive protein of 0.19 mg/dL. Test results for rheumatoid factors, anti-nuclear antibodies, anti-Sm antibodies, antineutrophil antibodies, anti-SS-A and SS-B antibodies were negative. Brain fluid attenuation inversion recovery (FLAIR) image showed bilateral lentiform nucleus, lateral capsule, left medial temporal lobe and left medial orbital gyrus (Figure 1). Magnetic resonance imaging (MRI) enhanced with gadolinium showed “cloud-like” enhancement of the bilateral lentiform nucleus (Figure 1). Cerebrospinal fluid (CSF) exam­ inations showed normal cell count (1/mm3) and elevated protein levels (90 mg/dL). CSF culture was negative for patho­ gens; CSF cytology showed no malignancy. CSF interleukin-6 level was normal (2.9 pg/ml). We suspected an autoimmune inflammatory CNS disorder and administered three courses of intravenous methylprednisolone pulse therapy (1 g/day for 3 days) followed by gradually tapered oral corticosteroids. Corticosteroid therapy resulted in mild improvement of MRI abnormalities of the bilateral lentiform nuclei (Figure 1). However, the patient showed minimal clinical improvement and required the use of a wheelchair. Her speed of responding to questions mildly improved, whereas no improvement was seen in parkinsonism and dementia. Her revised Hasegawa Dementia Scale’s score after corticosteroid treatment remained to be 5 (Figure 2). Because of severe osteoporosis, long-term corticosteroid therapy was contraindicated. Because brain MRI was atypical for multiple sclerosis and NMOSD, anti-AQP4 antibody was not assessed at first exam­ ination. However, after administering corticosteroid therapy, examinations of serum samples before corticosteroids treat­ ments revealed positive results for anti-AQP 4 antibody assessed using both enzyme-linked immunosorbent assay and cell-based assay. Anti-human myelin oligodendrocyte glycoprotein (MOG) antibody and anti-NMDAR antibody in Department of Neurology, Chiba Rosai Hospital,2-16 Tatsumidai-Higashi, Ichihara-shi, Chiba 290-0003, Japan 224 A. HIRAGA ET AL. Figure 1. (A, B) brain magnetic resonance imaging enhanced with gadolinium before administering corticosteroid therapy showed cloud-like enhancement in the bilateral lentiform nuclei. (C, D) brain fluid attenuation inversion recovery (FLAIR) imaging before corticosteroid therapy showed high signal intensities at the bilateral lentiforme nucleus, lateral capsule, left medial temporal lobe and left medial orbital gyrus. (E, F) serial FLAIR images showed improvement of high signal intensities in the lentiform nucleus (E, after two courses of steroid pulse therapy; F, 4 months after steroid pulse therapy). Figure 2. Clinical course of the patient from disease onset to the first three months. the x-axis shows the days after onset. HDS-R: revised hasegawa dementia scale, mPSL: methylprednisolone. pretreatment serum, assessed retrospectively, were negative. Oligoclonal bands of CSF samples at 4 months after the initial corticosteroid therapy was positive and the IgG index was 0.74. Enhanced MRI of the spinal cord at 4 months after initial therapy showed no atrophy or abnormal signal intensities, and MRI of optic nerve at the 4 months after initial therapy showed no abnormal lesions. We diagnosed her as NMOSD because of positive anti-AQP4 antibody, and acute diencepha­ lic clinical syndrome (hypersomnolence) with acute periepen­ dymal cerebral lesions, and preventive treatment with oral azatioprine (50 mg/day) was initiated; the patient was stable at 1 year follow-up. NEUROCASE Discussion Acknowledgments We identified the case of a patient with NMOSD who presented with both clinical (dementia and bradykinesia) and imaging (basal ganglia abnormalities) symptoms that are not typical for NMOSD. In our case, the putamen was found to be bilater­ ally damaged; considering its role in cognition and motor function, we believe this lesion to be responsible for the symp­ toms of dementia and parkinsonian motor disturbances. Brain MRI abnormalities associated with NMOSD were clas­ sified as follows: periependymal lesions surrounding the ven­ tricular system (third ventricles and cerebral aqueduct), dorsal brainstem lesions adjacent to the fourth ventricle, periependy­ mal lesions surrounding the lateral ventricle, hemispheric white matter lesions (often tumefactive) and lesions involving the corticospinal tract and nonspecific lesions (H.J. Kim et al., 2015). Conversely, basal ganglia lesions in NMOSD might be underdiagnosed. Previous brain MRI studies have shown that the basal ganglia are involved in 3–15% of Asian cases of NMOSD (Chan et al., 2011; J.E. Kim et al., 2011; Li et al., 2008; Liao et al., 2014). Alternatively, a recent UK study showed no basal ganglia involvement in NMO, MOG syndrome and multi­ ple sclerosis (MS) (Jurynczyk et al., 2017). In fact, putaminal involvement was less frequent in NMOSD than in acute disse­ minated encephalomyelitis (ADEM), suggesting that lesion of the putamen may be useful in differentiating ADEM from MS and NMOSD (Zhang et al., 2014). Although the typical brain abnormalities are critical for the early diagnosis of NMOSD, when patients present with only atypical brain lesions, diagno­ sis is difficult, particularly in the absence of current or past optic neuritis or myelitis (as was observed in our case). The characteristics surrounding the clinical presentation of NMOSD with basal ganglia lesion were unclear. Although no clinical characteristic is pathognomonic of NMOSD, some brain lesions are linked with the characteristic clinical syndrome in NMOSD, such as hiccup due to medullary lesions and narco­ lepsy due to hypothalamus lesion (Wingerchuk et al., 2015). However, progressive dementia or parkinsonism due to basal ganglia lesions are atypical indications in NMOSD. Recently, a case of progressive leukoencephalopathy presenting with progressive dementia was found to involve lesion of the lenti­ form nuclei (Sechi et al., 2018). Thus, both this case and ours suggest that NMOSD presenting with dementia and basal ganglia lesions could be a rare clinical presentation of NMOSD. Because the basal ganglia do not strongly express AQP4, it is unclear why this lesion occurred considering the presence of AQP4 autoimmunity. Although severe inflamma­ tion or regional variations in resistance to complementdependent cytotoxicity might be the possible explanations, our case showed normal CSF interleukin-6 levels, thereby mak­ ing the possibility of severe inflammation highly unlikely. In conclusion, although rare, dementia and Parkinsonian syndrome may be the main clinical manifestations of NMOSD when MRI findings indicate that basal ganglia lesions are involved. Recognizing this as atypical NMOSD is important to rapidly and accurately diagnose the disorder, as well as to improve the outcomes of intervention. We thank Dr. Keiko Tanaka for measuring the anti-NMDA antibody. 225 Statement of ethics This case report was approved by the ethical committee. Written informed consent for publication of medical records, including images was obtained from the daughter of the patient. Disclosure statement The authors declare that they have no competing interests. Funding This case report was supported, in part, by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology;a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. References Chan, K. H., Tse, C. T., Chung, C. P., Lee, R. L., Kwan, J. S., Ho, P. W., & Ho, J. W. (2011). Brain involvement in neuromyelitis optica spectrum disorders. 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