Current Journal Clinical Note of Neurology Curr J Neurol 2021; 20(2): 115-7

Can multiple system atrophy clinically

Received: 10 Dec. 2020 be misdiagnosed as corticobasal Accepted: 07 Feb. 2021 syndrome in the early stages?

Yasaman Saeedi1, Maziar Emamikhah1, Ali Shoeibi2, Mohammad Rohani1

1 Department of Neurology, Hazrat Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran 2 Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Keywords is challenging, especially at early stages when the Multiple System Atrophy; Corticobasal Degeneration; manifestations overlap. We report three probable Corticobasal Syndrome; Atypical Parkinsonism; MSA cases, with unusual presentation (asymmetric Asymmetric Parkinsonism; Hand Dystonia parkinsonism, severe limb dystonia, and prominent myoclonus) initially diagnosed as CBS. Case 1: This was a 57-year-old woman; her problems started 10 years ago with jerky tremor Multiple system atrophy (MSA), an atypical of left hand. Her movements gradually got slower parkinsonian syndrome (APS) and without response to levodopa. During the last synucleinopathy, usually presents with early 2 years, she had not been able to walk autonomic dysfunction, symmetrical levodopa- independently and been suffering from a fixed unresponsive parkinsonism, and cerebellar posture in the left hand, making it immobile and symptoms. Myoclonus, speech disturbance, useless. She had a history of RBD and nocturnal rapid-eye-movement sleep behavior disorder stridor for years and urinary incontinence since (RBD), stridor and dystonia are other features. the last year. Her family history was negative. Cognition is not impaired in majority.1 Examination revealed normal cognition, Corticobasal degeneration (CBD), another APS, anarthria, slow saccadic eye movements, severe is characterized by cognitive and asymmetrical jaw-closing dystonia, dystonic posture of hands motor symptoms. Prominent unilateral akinetic- (fixed-posture in left), hypokinesia, and rigidity, rigid parkinsonism, limb dystonia, myoclonus, more severe in the left side (video 1). corticospinal tract involvement, and cortical sensory loss are the cardinal manifestations.2 CBD How to cite this article: Saeedi Y, Emamikhah M, is a pathologic diagnosis (tauopathy) while the Shoeibi A, Rohani M. Can multiple system atrophy term corticobasal syndrome (CBS) describes the clinically be misdiagnosed as corticobasal clinical syndrome without pathologic confirmation. syndrome in the early stages? Curr J Neurol 2021; Diagnosis of APSs (including MSA and CBD) 20(2): 115-7.

Copyright © 2021 Iranian Neurological Association, and Tehran University of Medical Sciences Corresponding Author: Maziar Emamikhah Published by Tehran University of Medical Sciences Email: [email protected]

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 international license (http://creativecommons.org/licenses/by- nc/4.0/). Non-commercial purposes uses of the work are permitted, provided the original work is properly cited.

http://cjn.tums.ac.ir 04 April MSA presenting very similar to CBS

She was not able to walk without aid. With the fingers (video 2). There was no cognitive bilateral support the gait was not wide based. As dysfunction, apraxia, or cortical sensory loss. Brain far as it was possible to examine there was no MRI betrayed a typical hot-cross-bun sign in the apraxia or ataxia in the limbs. Brain magnetic pons, atrophic putaminal slit sign (Figure 1, c-e). resonance imaging (MRI) revealed pallidal Case 3: A 61-year-old woman visited our clinic hypointensity on fluid-attenuated inversion with a history of gait disturbance, imbalance, and recovery (FLAIR) with putaminal slit/rim sign recurrent falls beginning four years earlier. She (Figure 1, a-b). mentioned RBD but no urinary disorder or Case 2: This 62-year-old man came with orthostatic dizziness. Her family history was slowness of movements, progressive clumsiness, negative. Increasing the dose of levodopa (up to and slowing of left hand, which began 9 years 600 mg per day) did not improve parkinsonism, earlier. He had been wheelchair-bound since the gait, or dystonia. Urinary incontinence developed last year. He had a history of RBD and urinary after three years of disease onset. She had incontinence for a couple of years. Progressive hypophonic speech with slow saccades. There parkinsonism, gait disturbance, and limb was severe dystonic posture with finger posturing along with urinary incontinence had poly-mini-myoclonus in the left hand and severe been the major clinical picture in the last several rigidity and hypokinesia in the left limbs. There years. Levodopa therapy (up to 600 mg levodopa was no cortical dysfunction. She had severely per day) had no significant benefit neither on asymmetric parkinsonian gait with postural parkinsonism nor dystonia. His family history instability two year after symptom onset and was was negative. Examination revealed hypophonic not able to walk independently after four years speech, slow saccades, rigidity and hypokinesia of (video 3). Brain MRI showed hot-cross-bun sign in limbs more severe on the left side, severe dystonic the pons and bilateral atrophic putamina with slit posture in the left hand, and myoclonic jerks of sign (Figure 1, f-i).

Figure 1. a, b, e, f, g, and h) T2 and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) of patients showing bilateral putaminal atrophy and putaminal slit sign; c, d, and i) FLAIR and T2 MRI showing hot-cross-bun sign; planes a and b related to case 1, c-e to case 2, and f-i to case 3

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Autonomic dysfunctions, symmetrical similar asymmetric parkinsonism had many parkinsonism, and cerebellar and corticospinal common features with our patients. Similar to our involvements are the main clinical manifestations cases, they were dominated by asymmetric of MSA. In contrast, significant motor asymmetry parkinsonism with limb dystonia without associated with higher-cortical malfunctions is the prominent ataxia or apraxia and with normal main feature of CBS. Although dystonia is more cognition.10 This may highlight the notion for this typical of CBS, different types of dystonia such as phenotype of MSA when cortical signs are absent camptocormia, blepharospasm, oromandibular or minimal and the advantage of using additional and cervical dystonia (retrocollis and antecollis) diagnostic tests such as brain MRI which can be may be observed in MSA. However, limb revealing in APS. Hot-cross-bun in the pons, dystonia particularly restricted to one side is more pontine and/or cerebellar atrophy, and putaminal characteristic for CBD.3,4 Antecollis is the most rim sign are suggestive of MSA, whereas brain common form of dystonia in MSA.5 Prominent MRI in CBS typically shows asymmetrical and myoclonic jerks of fingers, combined with focal cortical atrophy.9 dystonic hand in the second and third cases made In conclusion, despite the usual symmetric CBS even more probable. Mini-myoclonus of findings, MSA can present with asymmetrical fingers is observed in MSA, but it is common in dystonia, myoclonus, and parkinsonism leading CBS too. Nevertheless, in CBS, myoclonus is to CBS misdiagnosis. Normal cognition, RBD, asymmetric and limited to the dystonic limb.1-5 stridor, and autonomic dysfunction are clues for

Autonomic dysfunction, an essential feature of the correct diagnosis of MSA, as are typical brain

MSA, can present as orthostatic hypotension, MRI findings. sphincter dysfunction, or impotency. However, it Conflict of Interests is rare in CBD.1-5 All three patients had incontinence in the course of their illness, even The authors declare no conflict of interest in this though, orthostatic hypotension was not detected. study. Cognition remained normal even in the advanced stages, which is in accordance with the diagnosis Acknowledgments of MSA.1 In contrast, multiple cognitive domains This study was approved by the ethics committee are usually impaired in CBD and it can be the first of Iran University of Medical Sciences, Tehran, presentation.5-10 Our patients had prominent RBD, Iran and performed in accordance with the ethical a characteristic finding in synucleinopathies standards of the institutional and/or national including MSA, but it is rare in CBD.4 In addition, research committee and with the 1964 Declaration stridor in the first case is highly suggestive for of Helsinki (DoH) and its later amendments or MSA. The previously reported five patients with comparable ethical standards.

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