Differences in Gate Apraxia Due to Reduced Regional Cerebral Blood Flow in the Supplementary Motor Area in Corticobasal Syndrome: A Report of Two Cases

Differences in Gate Apraxia Due to Reduced Regional Cerebral Blood Flow in the Supplementary Motor Area in Corticobasal Syndrome: A Report of Two Cases | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Differences in Gate Apraxia Due to Reduced Regional Cerebral Blood Flow in the Supplementary Motor Area in Corticobasal Syndrome: A Report of Two Cases Kota Igari, Motoki Fujimaki, Mera Mai, Moe Sakuma, Shinji Saiki This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5873398/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Jul, 2025 Read the published version in BMC Neurology → Version 1 posted 11 You are reading this latest preprint version Abstract Background Gait apraxia, characterized by difficulties initiating and coordinating walking despite preserved conceptual movement abilities, is a distinct entity from lower limb apraxia. Although gait apraxia has been associated with dysfunction of the frontal lobe, particularly the supplementary motor area (SMA), the specific associated somatotopic organization phenotype remains poorly understood. Corticobasal syndrome (CBS), a clinical phenotype of corticobasal degeneration, commonly presents with upper limb apraxia, while lower limb or gait apraxia has rarely been reported. Herein, we describe two rare cases of CBS presenting with gait apraxia shown to be caused by SMA dysfunction, based on regional cerebral blood flow (rCBF) reduction on single-photon emission computed tomography (SPECT). Case presentation: Case 1 was of an 82-year-old man who exhibited right-sided apraxic gait with freezing and shuffling patterns, along with SMA hypoperfusion in both the dorsal and pre-SMA regions. Neurological examination revealed mild rigidity, right-sided Babinski sign, and clumsiness in mimicking leg movements. Gait patterns were inconsistent and unresponsive to levodopa or sensory cues. Case 2 was of an 80-year-old man who demonstrated a peculiar gait characterized by exaggerated right leg movements and everted ankle positioning. Hypoperfusion was localized to the left dorsal SMA. Examination findings included rigidity and impaired hand weight perception. Sensory tricks and levodopa provided no benefit. Conclusion These cases highlight the role of SMA dysfunction in the pathogenesis of gait apraxia. Variations in rCBF reduction correlated with distinct gait patterns. For example, the freezing gait shown in Case 1 likely resulted from pre-SMA impairment, which is critical for movement initiation, while the exaggerated leg movements in Case 2 reflected dorsal SMA dysfunction, involved in motor execution. These results indicate that gait apraxia, which is often underdiagnosed, should be recognized as a potential early indicator of CBS. Further, these cases suggest that SMA dysfunction, identified through SPECT imaging, underlies the distinct gait patterns seen in CBS patients with apraxic gait. Recognizing these symptoms, even in the absence of weakness or limb apraxia, may aid in early CBS diagnosis and improve clinical management. gait apraxia corticobasal syndrome supplementary motor area regional cerebral blood flow freezing gait neurodegeneration Figures Figure 1 Figure 2 Background Gait apraxia, although not formally classified as “apraxia,” is characterized by difficulties in initiating walking, episodes of freezing, short shuffling steps, impaired balance, and challenges in postural transitions, after excluding other potential causes [1]. In addition, gait apraxia is distinguished from lower limb apraxia based on the ability of the patient to perform conceptual movements [2]. Although the symptoms and the functional localization underlying gait apraxia have been discussed extensively with some discrepancies, it is widely acknowledged that frontal impairment—particularly in the supplementary motor area (SMA) and premotor area—is a key factor in its development [1–3]. However, the discussion about the association between the functional organization of SMA and gait apraxia is insufficient in previous reports. Corticobasal degeneration (CBD) exhibits various clinical phenotypes, including frontal behavioral-spatial syndrome, nonfluent/agrammatic variant of primary progressive aphasia, progressive supranuclear palsy syndrome, and corticobasal syndrome (CBS) [4], with CBS being the most common. CBS is a progressive neurodegenerative disorder characterized by akinetic rigidity and asymmetric limb apraxia, involving cortical and basal ganglia dysfunction. Although several diagnosis criteria for CBS have been proposed, they all share the common feature of including limb apraxia as a key clinical feature. While upper limb apraxia onset is typical for CBS, lower limb apraxia onset has also been reported in several cases. In addition, gait apraxia, although not typically emphasized, is likely underdiagnosed in these patients. Herein, we present two extremely rare cases of gait apraxia attributed to SMA dysfunction in patients with CBS. By comparing the two cases with slightly different ambulation patterns, we discuss the somatotopy and functional localization of the SMA as they are related to gait [5–7]. Furthermore, we emphasize the importance of identifying gait apraxia for aiding early diagnosis. Case Presentations Case 1 Case 1 was of an 82-year-old man who presented with a 2-year history of right lower limb mobility impairment, followed by speech difficulty 1 year later. Neurological findings included diminished verbal fluency, dyscalculia, mild lower limb rigidity, and a right-sided Babinski sign. He exhibited mild clumsiness in drawing circles and mimicking kicking a ball (Video 1). Ideational and ideomotor apraxia, alien hand syndrome, cortical sensory loss, muscle weakness, sensory loss, and cerebellar or sensory ataxia were absent. During walking, he pivoted on his left foot, with impaired right foot movement, resembling a "freezing gait" or "shuffling gait" (Video 1). Moreover, he maintained eversion of the right ankle everted while walking. Unlike typical gait freezing, his apraxic gait displayed various disorganized patterns with each step and was unresponsive to sensory tricks. He was also nonresponsive to levodopa treatment. His cerebrospinal fluid (CSF) total tau (t-tau) protein and phosphorylated tau (p-tau) protein concentrations were 265 and 40.9 pg/mL, respectively. Brain magnetic resonance imaging (MRI) revealed no bilateral difference in frontal or parietal lobe atrophy (Fig. 1 A). Moreover, 123I-IMP SPECT imaging revealed reduced regional cerebral blood flow (rCBF) in the left pre-SMA and left dorsal SMA (Fig. 1 B). A dopamine transporter scan indicated no hypo-accumulation (Fig. 1 C). Therefore, the patient was diagnosed with CBS according to the Revised Cambridge Criteria [8]. Case 2 Case 2 was of an 80-year-old man who presented with a 1-year history of right lower limb mobility impairment, which worsened to hindrance in walking 5 months later. Neurological findings included a Frontal Assessment Battery score of 9/18, impaired hand weight perception, mild upper and lower limb rigidity, and a right-sided Babinski sign. He experienced slight difficulty in kicking a ball, with no issues in drawing circles and crosses (Video 2). Ideational and ideomotor apraxia, alien hand syndrome, muscle weakness, and sensory loss were absent. He exhibited a peculiar gait pattern, lifting the right leg high, swinging it outward, and maintaining the right ankle in an everted position (Video 2). Sensory tricks did not alleviate symptoms, and he was nonresponsive to levodopa. His CSF T-tau protein and p-tau protein concentrations were 220 and 34.7 pg/mL, respectively. Brain MRI indicated no bilateral differences in frontal or parietal lobe atrophy (Fig. 2 A). SPECT revealed reduced rCBF in the left dorsal SMAs (Fig. 2 B). A dopamine transporter scan demonstrated mild left-dominant hypo-accumulation (Fig. 2 C). Therefore, the patient was diagnosed with CBS according to the Revised Cambridge Criteria [8]. Discussion These two cases highlight the following points: First, the lesion responsible for gait apraxia is identified by a reduction in the rCBF on SPECT. The two cases exhibited slightly different gait patterns, corresponding to functional impairments in different areas involved in the higher-order regulation of gait. In Case 1 , reduced rCBF was observed in the dorsal SMA and pre-SMA, whereas, in Case 1 , the reduction was confined to the dorsal SMA. Moreover, diagnosing the rare symptom of gait apraxia in CBS can facilitate early diagnosis. Gait apraxia lacks a clear, universal definition and is complicated by the fact that different authors have used various terms to describe walking disturbance, including gait apraxia. It is characterized by an inability to effectively use the lower limbs and trunk, causing a slowed, imbalanced gait with shortened steps, often appearing as “magnetic” [9]. Gait apraxia is distinguished from lower limb apraxia, which is assessed by testing conceptual movements such as kicking a ball or stubbing a cigarette with the foot [2]. Della Sala et al. [1] noted that, in contrast to ideomotor apraxia, gait apraxia affects routinized actions due to impairment of the system that controls sensorimotor and spatiotemporal movements, according to the dichotomy proposed by Benke [3]. We provisionally define “gait apraxia” as a higher-level gait disorder without lower limb apraxia and not attributable to other causes. The gait patterns observed in the two cases align with this definition and are suggestive of apraxic gait. Higher-order regulation of gait is postulated to involve multiple brain regions, including the primary sensory cortex, basal ganglia, cerebellum, vestibular cortex, temporoparietal cortex, SMA, premotor cortex, and brain stem [6]. Focusing on cortical function rather than white matter connectivity, the SMA and premotor areas are particularly involved in somatosensation and motor programming. Furthermore, regarding the somatotopic organization of the SMA, the functional areas corresponding to the lower limb, upper limb, and face are distributed from dorsal to ventral regions [5]. Hence, impairment of the dorsal SMA could evoke lower limb dysfunction due to failure in higher-order regulation. Freezing of gait may result from disruption of the basal ganglia and SMA loop responsible for initiating movement [7]. In terms of the distinction between pre-SMA and SMA, which are related to gait regulation, the pre-SMA is specifically activated during the planning and initiation of an action, whereas the SMA is activated during the movement execution stage [10]. Comparative analysis of brain imaging in patients with parkinsonism revealed that the pre-SMA is more disrupted in patients with freezing of gait [11]. Therefore, dysfunction of the pre-SMA may contribute to gait apraxia, which resembles a “freezing gait.” In a case of stroke resulting from bilateral anterior cerebral artery infarction, gait apraxia with residual clumsiness after recovery from weakness is caused by damage to the first frontal gyrus, primarily affecting the SMA. Similarly, cases of central nervous system lymphoma and cerebral lobe atrophy exhibit apraxic gait, characterized by clumsiness and difficulty in initiating movement and making turns, owing to loss of function in the SMA. These findings suggest that blood flow reduction to a very limited area, specifically the SMA, predominantly induces apraxic gait rather than limb apraxia [12]. Both the cases we described exhibit gait apraxia, and the symptoms were attributed to the dysfunction of the SMA, as indicated by the reduction of rCBF on SPECT. In Case 1 , the walking pattern was characterized by consistent freezing and shuffling gait, whereas Case 2 exhibited peculiarities and clumsiness in the right foot during walking. We attributed these differences in gait patterns to discrepancies in the impaired region of the SMA. The leg clumsiness in both cases is likely due to dysfunction of dorsal the SMA, which plays a role in controlling leg function according to the somatotopy. The characteristic gait pattern in Case 1 , resembling freezing gait in the right leg, is probably due to a dysfunction in the pre-SMA, which is activated during the initiation phase of the movement. Although freezing gait can also be induced by dysfunction of the premotor area, there are no examination findings to support this in these two cases. Notably, CBS cases of truncal or lower limb apraxia onset have been reported; however, gait apraxia as an initial symptom is rare. A retrospective study revealed that 4 out of 24 patients manifest gait onset CBS, but no further details were provided [13]. Moreover, several leg-onset CBS cases diagnosed have been reported to date; however, cases of patients presenting with lower limb apraxia or gait apraxia as an initial symptom remain uncommon [14–15]. Although gait apraxia is not included in the official CBS diagnostic criteria, it may indicate cerebral cortex dysfunction. Conclusion Overall, in the present study, we reported two remarkable cases of CBS predominantly manifesting as slightly different gait apraxia caused by loss of function in the SMA, as demonstrated by SPECT. Therefore, gait disturbances, even in the absence of weakness and limb apraxia, may be an early indicator of CBS. Abbreviations CBD - corticobasal degeneration CBS - corticobasal syndrome CSF - cerebrospinal fluid p-tau - phosphorylated tau rCBF - regional cerebral blood flow SMA - supplementary motor area t-tau - total tau Declarations Ethics approval and consent to participate : The study was approved by the institutional review board of University of Tsukuba (R06-106) and was conducted in accordance with the Declaration of Helsinki. Consent for publication : Written informed consent was obtained from the patient’s family for the publication of this case report and accompanying images. Availability of data and materials : The data that support the findings of this study are available from the corresponding author upon reasonable request. To protect patient confidentiality, only de-identified data will be shared. Competing interests : The authors declare that there are no conflicts of interest relevant to this work. Funding : No specific funding was received for this work. Author contributions : All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Kota Igari, Motoki Fujimaki, and Shinji Saiki. The first draft of the manuscript was written by Kota Igari, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgments : The authors would like to thank the patients for giving consent for publication of the videos and pictures for educational purposes. References Della Sala S, Francescani A, Spinnler H. Gait apraxia after bilateral supplementary motor area lesion. J Neurol Neurosurg Psychiatry. 2002;72:77–85. Zadikoff C, Lang AE. Apraxia in movement disorders. Brain. 2005;128:1480–97. Della Sala S, Spinnler H, Venneri A. Walking Difficulties in patients with Alzheimer’s disease might originate from gait apraxia. J Neurol Neurosurg Psychiatry. 2004;75:196–201. Armstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80:496–503. Fried I, Katz A, McCarthy G, Sass KJ, Williamson P, Spencer SS, Spencer DD. Functional organization of human supplementary motor cortex studied by electrical stimulation. J Neurosci. 1991;11:3656–66. Takakusaki K. Functional neuroanatomy for posture and gait control. J Mov Disord. 2017;10:1–17. Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011;10:734–44. Mathew R, Bak TH, Hodges JR. Diagnostic criteria for corticobasal syndrome: a comparative study. J Neurol Neurosurg Psychiatry. 2012;83:405–10. Dale ML, Curtze C, Nutt JG. Apraxia of gait–or apraxia of postural transitions? Parkinsonism Relat Disord. 2018;50:19–22. Cunnington R, Windischberger C, Robinson S, Moser E. The selection of intended actions and the observation of others' actions: a time-resolved fMRI study. NeuroImage. 2006;29:1294–1302. Onder H, Oguz KK, Has AC, Elibol B. Comparative analysis of freezing of gait in distinct parkinsonism types by diffusion tensor imaging method and cognitive profiles. J Neural Transm. 2023;130:521–35. Nadeau SE. Gait apraxia: further clues to localization. Eur Neurol. 2007;58:142–5. Sakamoto Y, Shimizu T, Tobisawa S, Isozaki E. Prevalence and clinical characteristics of corticobasal syndrome with an initial symptom outside of the upper limb. Neurol Sci. 2017;38:783–7. Horvath J, Kövari E, Bouras C, Burkhard PR. Neuropathological correlates of lower limb corticobasal degeneration. Neuropathol Appl Neurobiol. 2009;35:623–7. Compston A. From the archives. Corticobasal degeneration. By WRG Gibb, PJ Luther and CD Marsden. Brain 1989: 112; 1171–1192 with Corticobasal degeneration. A clinical study of 36 cases. By JO Rinne, MS Lee, PD Thompson and CD Marsden. Brain 1994: 117; 1183–1196. Brain. 2010;133:1860–2. Additional Declarations No competing interests reported. Supplementary Files Video1image.mp4 Video1. First part: Video of the patient drawing circles and mimicking kicking a ball. The patient exhibited slight difficulties in performing the movements. Second part: Gait. The patient struggled with postural transitions, showing titubation and instability when rising from sitting. During walking, he pivoted on the left foot, with impaired movement of the right foot. Video2image.mp4 Video 2. First part: Video of the patient drawing circles and kicking a ball. The patient exhibited slight difficulties in performing the movements. Second part: Gait. During ambulation, the patient exhibited a peculiar gait pattern, lifting the right leg high, swinging it outward, and keeping the right ankle everted. He also walked with only the right foot scraping the ground, resembling a shuffling gait. Cite Share Download PDF Status: Published Journal Publication published 29 Jul, 2025 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 26 May, 2025 Reviews received at journal 20 May, 2025 Reviewers agreed at journal 17 May, 2025 Reviewers agreed at journal 05 Feb, 2025 Reviews received at journal 29 Jan, 2025 Reviewers agreed at journal 29 Jan, 2025 Reviewers invited by journal 29 Jan, 2025 Editor invited by journal 22 Jan, 2025 Editor assigned by journal 22 Jan, 2025 Submission checks completed at journal 22 Jan, 2025 First submitted to journal 21 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5873398","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":406326410,"identity":"c9130ca1-6c45-40ad-8452-91237f8c7a6d","order_by":0,"name":"Kota Igari","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Kota","middleName":"","lastName":"Igari","suffix":""},{"id":406326411,"identity":"dadf72dc-54c9-464c-8e17-23ee6402024f","order_by":1,"name":"Motoki Fujimaki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYFACxgcMEgYMDPwMDAYgrgGDBEScGacONmYDsBbJBqDqA0RrAZt+AE0LTqA7v5lNwqJgm7zxtcMbmD/8OWxscLv5AcOPGgZ2cxxazI4xs0lIGNw23HY7rYDhYNthM4M7xwwYe44xMFs24NLCfwykhXHb7RwDhoMNh20MbiQYMPA2MDADnYrXFvvNs4FaDvwBaUn/wPiXCC2JG6RBWtiADruRY8CM35ZkZgugluQZQL8cONuWbix550zBYZljErj9cvgw422JP7dt+2cnb3xQ8cfasO92+8aHb2psknGFGAgww2IC7hIgQyLZAI8Wxg/YRO3waRkFo2AUjIIRBQDOn11ZUTBtdwAAAABJRU5ErkJggg==","orcid":"","institution":"University of Tsukuba","correspondingAuthor":true,"prefix":"","firstName":"Motoki","middleName":"","lastName":"Fujimaki","suffix":""},{"id":406326412,"identity":"671d79a7-b9c4-4a3d-b9ae-351ca6e9fea1","order_by":2,"name":"Mera Mai","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Mera","middleName":"","lastName":"Mai","suffix":""},{"id":406326413,"identity":"d02171e4-7ead-4596-bc47-88943fa8bb41","order_by":3,"name":"Moe Sakuma","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Moe","middleName":"","lastName":"Sakuma","suffix":""},{"id":406326414,"identity":"905961a2-b815-4240-a863-ea0d4820a493","order_by":4,"name":"Shinji Saiki","email":"","orcid":"","institution":"University of Tsukuba","correspondingAuthor":false,"prefix":"","firstName":"Shinji","middleName":"","lastName":"Saiki","suffix":""}],"badges":[],"createdAt":"2025-01-21 12:08:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5873398/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5873398/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-025-04332-z","type":"published","date":"2025-07-29T16:13:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":74691367,"identity":"3a36dc7f-a113-4c7d-9fd0-297260b65c1d","added_by":"auto","created_at":"2025-01-24 18:38:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":760785,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMagnetic resonance images (MRI) and three-dimensional stereotactic surface projection (3D-SSP) analysis images of 123I-IMP SPECT of case 1.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAxial T1-weighted image shows no bilateral difference in atrophy of the frontal or parietal lobes (A). 3D-SSP analysis images of 123I-IMP SPECT indicate the reduction of regional cerebral blood flow in the left pre-SMA (arrowhead) and the left dorsal SMA (arrow), with no reduction in basal ganglia. Color-coding represents the statistical significance (Z-score) of the decrease in regional cerebral blood flow (B). Dopamine transporter scan shows no hypo-accumulation, with SBR bolts of 4.39 and 4.22 on the right and left sides, respectively (C).\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-5873398/v1/579381caa0a99a514f394f70.png"},{"id":74691362,"identity":"082ba45d-6e8e-4785-a056-cd5b2b9fabec","added_by":"auto","created_at":"2025-01-24 18:38:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":834920,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMagnetic resonance images (MRI) and three-dimensional stereotactic surface projection (3D-SSP) analysis images of 123I-IMP SPECT of case 2.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAxial T1-weighted image shows atrophy of the left temporal lobe due to prior cerebral infarction and no bilateral difference in the atrophy of the frontal or parietal lobes (A). 3D-SSP analysis images of 123I-IMP SPECT indicate a reduction in regional cerebral blood flow in the left dorsal SMA (arrow), without basal ganglia reduction. Color-coding represents the statistical significance (Z-score) of the decrease in regional cerebral blood flow (B). A dopamine transporter scan demonstrates mild left-dominant hypo-accumulation, with an SBR bolt of 4.17 and 3.06 on the right and left sides, respectively (C).\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-5873398/v1/a4ea6bf0953b0115d62dd9f4.png"},{"id":88268271,"identity":"757d5d18-d059-441a-9d3a-82fab8e365a2","added_by":"auto","created_at":"2025-08-04 16:50:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1994484,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5873398/v1/30254bf4-558c-4bd9-bb56-cd04f07609cd.pdf"},{"id":74691393,"identity":"dbf3ebce-d02f-422b-bafc-5629308891c1","added_by":"auto","created_at":"2025-01-24 18:38:41","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":35072689,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVideo1.\u003c/strong\u003e First part: Video of the patient drawing circles and mimicking kicking a ball. The patient exhibited slight difficulties in performing the movements. Second part: Gait. The patient struggled with postural transitions, showing titubation and instability when rising from sitting. During walking, he pivoted on the left foot, with impaired movement of the right foot.\u003c/p\u003e","description":"","filename":"Video1image.mp4","url":"https://assets-eu.researchsquare.com/files/rs-5873398/v1/1ef9c2b975905d44db0716de.mp4"},{"id":74691364,"identity":"6857765d-b5dd-4bcd-ae01-3dc5e8940ea8","added_by":"auto","created_at":"2025-01-24 18:38:36","extension":"mp4","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":19493071,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVideo 2.\u003c/strong\u003e First part: Video of the patient drawing circles and kicking a ball. The patient exhibited slight difficulties in performing the movements. Second part: Gait. During ambulation, the patient exhibited a peculiar gait pattern, lifting the right leg high, swinging it outward, and keeping the right ankle everted. He also walked with only the right foot scraping the ground, resembling a shuffling gait.\u003c/p\u003e","description":"","filename":"Video2image.mp4","url":"https://assets-eu.researchsquare.com/files/rs-5873398/v1/ca2b4a1f45b1195d7dd4dacf.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"Differences in Gate Apraxia Due to Reduced Regional Cerebral Blood Flow in the Supplementary Motor Area in Corticobasal Syndrome: A Report of Two Cases","fulltext":[{"header":"Background","content":"\u003cp\u003eGait apraxia, although not formally classified as \u0026ldquo;apraxia,\u0026rdquo; is characterized by difficulties in initiating walking, episodes of freezing, short shuffling steps, impaired balance, and challenges in postural transitions, after excluding other potential causes [1]. In addition, gait apraxia is distinguished from lower limb apraxia based on the ability of the patient to perform conceptual movements [2]. Although the symptoms and the functional localization underlying gait apraxia have been discussed extensively with some discrepancies, it is widely acknowledged that frontal impairment\u0026mdash;particularly in the supplementary motor area (SMA) and premotor area\u0026mdash;is a key factor in its development [1\u0026ndash;3]. However, the discussion about the association between the functional organization of SMA and gait apraxia is insufficient in previous reports.\u003c/p\u003e \u003cp\u003eCorticobasal degeneration (CBD) exhibits various clinical phenotypes, including frontal behavioral-spatial syndrome, nonfluent/agrammatic variant of primary progressive aphasia, progressive supranuclear palsy syndrome, and corticobasal syndrome (CBS) [4], with CBS being the most common. CBS is a progressive neurodegenerative disorder characterized by akinetic rigidity and asymmetric limb apraxia, involving cortical and basal ganglia dysfunction. Although several diagnosis criteria for CBS have been proposed, they all share the common feature of including limb apraxia as a key clinical feature. While upper limb apraxia onset is typical for CBS, lower limb apraxia onset has also been reported in several cases. In addition, gait apraxia, although not typically emphasized, is likely underdiagnosed in these patients.\u003c/p\u003e \u003cp\u003eHerein, we present two extremely rare cases of gait apraxia attributed to SMA dysfunction in patients with CBS. By comparing the two cases with slightly different ambulation patterns, we discuss the somatotopy and functional localization of the SMA as they are related to gait [5\u0026ndash;7]. Furthermore, we emphasize the importance of identifying gait apraxia for aiding early diagnosis.\u003c/p\u003e"},{"header":"Case Presentations","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCase \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/h2\u003e \u003cp\u003e Case 1\u003c/strong\u003e was of an 82-year-old man who presented with a 2-year history of right lower limb mobility impairment, followed by speech difficulty 1 year later. Neurological findings included diminished verbal fluency, dyscalculia, mild lower limb rigidity, and a right-sided Babinski sign. He exhibited mild clumsiness in drawing circles and mimicking kicking a ball (Video 1). Ideational and ideomotor apraxia, alien hand syndrome, cortical sensory loss, muscle weakness, sensory loss, and cerebellar or sensory ataxia were absent. During walking, he pivoted on his left foot, with impaired right foot movement, resembling a \"freezing gait\" or \"shuffling gait\" (Video 1). Moreover, he maintained eversion of the right ankle everted while walking. Unlike typical gait freezing, his apraxic gait displayed various disorganized patterns with each step and was unresponsive to sensory tricks. He was also nonresponsive to levodopa treatment. His cerebrospinal fluid (CSF) total tau (t-tau) protein and phosphorylated tau (p-tau) protein concentrations were 265 and 40.9 pg/mL, respectively. Brain magnetic resonance imaging (MRI) revealed no bilateral difference in frontal or parietal lobe atrophy (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Moreover, 123I-IMP SPECT imaging revealed reduced regional cerebral blood flow (rCBF) in the left pre-SMA and left dorsal SMA (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). A dopamine transporter scan indicated no hypo-accumulation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Therefore, the patient was diagnosed with CBS according to the Revised Cambridge Criteria [8].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCase 2\u003c/h3\u003e\n\u003cp\u003e Case 2 was of an 80-year-old man who presented with a 1-year history of right lower limb mobility impairment, which worsened to hindrance in walking 5 months later. Neurological findings included a Frontal Assessment Battery score of 9/18, impaired hand weight perception, mild upper and lower limb rigidity, and a right-sided Babinski sign. He experienced slight difficulty in kicking a ball, with no issues in drawing circles and crosses (Video 2). Ideational and ideomotor apraxia, alien hand syndrome, muscle weakness, and sensory loss were absent. He exhibited a peculiar gait pattern, lifting the right leg high, swinging it outward, and maintaining the right ankle in an everted position (Video 2). Sensory tricks did not alleviate symptoms, and he was nonresponsive to levodopa. His CSF T-tau protein and p-tau protein concentrations were 220 and 34.7 pg/mL, respectively. Brain MRI indicated no bilateral differences in frontal or parietal lobe atrophy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). SPECT revealed reduced rCBF in the left dorsal SMAs (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). A dopamine transporter scan demonstrated mild left-dominant hypo-accumulation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). Therefore, the patient was diagnosed with CBS according to the Revised Cambridge Criteria [8].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThese two cases highlight the following points: First, the lesion responsible for gait apraxia is identified by a reduction in the rCBF on SPECT. The two cases exhibited slightly different gait patterns, corresponding to functional impairments in different areas involved in the higher-order regulation of gait. In Case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, reduced rCBF was observed in the dorsal SMA and pre-SMA, whereas, in Case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the reduction was confined to the dorsal SMA. Moreover, diagnosing the rare symptom of gait apraxia in CBS can facilitate early diagnosis.\u003c/p\u003e \u003cp\u003eGait apraxia lacks a clear, universal definition and is complicated by the fact that different authors have used various terms to describe walking disturbance, including gait apraxia. It is characterized by an inability to effectively use the lower limbs and trunk, causing a slowed, imbalanced gait with shortened steps, often appearing as \u0026ldquo;magnetic\u0026rdquo; [9]. Gait apraxia is distinguished from lower limb apraxia, which is assessed by testing conceptual movements such as kicking a ball or stubbing a cigarette with the foot [2]. Della Sala et al. [1] noted that, in contrast to ideomotor apraxia, gait apraxia affects routinized actions due to impairment of the system that controls sensorimotor and spatiotemporal movements, according to the dichotomy proposed by Benke [3]. We provisionally define \u0026ldquo;gait apraxia\u0026rdquo; as a higher-level gait disorder without lower limb apraxia and not attributable to other causes. The gait patterns observed in the two cases align with this definition and are suggestive of apraxic gait.\u003c/p\u003e \u003cp\u003eHigher-order regulation of gait is postulated to involve multiple brain regions, including the primary sensory cortex, basal ganglia, cerebellum, vestibular cortex, temporoparietal cortex, SMA, premotor cortex, and brain stem [6]. Focusing on cortical function rather than white matter connectivity, the SMA and premotor areas are particularly involved in somatosensation and motor programming. Furthermore, regarding the somatotopic organization of the SMA, the functional areas corresponding to the lower limb, upper limb, and face are distributed from dorsal to ventral regions [5]. Hence, impairment of the dorsal SMA could evoke lower limb dysfunction due to failure in higher-order regulation.\u003c/p\u003e \u003cp\u003eFreezing of gait may result from disruption of the basal ganglia and SMA loop responsible for initiating movement [7]. In terms of the distinction between pre-SMA and SMA, which are related to gait regulation, the pre-SMA is specifically activated during the planning and initiation of an action, whereas the SMA is activated during the movement execution stage [10]. Comparative analysis of brain imaging in patients with parkinsonism revealed that the pre-SMA is more disrupted in patients with freezing of gait [11]. Therefore, dysfunction of the pre-SMA may contribute to gait apraxia, which resembles a \u0026ldquo;freezing gait.\u0026rdquo;\u003c/p\u003e \u003cp\u003eIn a case of stroke resulting from bilateral anterior cerebral artery infarction, gait apraxia with residual clumsiness after recovery from weakness is caused by damage to the first frontal gyrus, primarily affecting the SMA. Similarly, cases of central nervous system lymphoma and cerebral lobe atrophy exhibit apraxic gait, characterized by clumsiness and difficulty in initiating movement and making turns, owing to loss of function in the SMA. These findings suggest that blood flow reduction to a very limited area, specifically the SMA, predominantly induces apraxic gait rather than limb apraxia [12].\u003c/p\u003e \u003cp\u003eBoth the cases we described exhibit gait apraxia, and the symptoms were attributed to the dysfunction of the SMA, as indicated by the reduction of rCBF on SPECT. In Case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the walking pattern was characterized by consistent freezing and shuffling gait, whereas Case \u003cspan refid=\"FPar2\" class=\"InternalRef\"\u003e2\u003c/span\u003e exhibited peculiarities and clumsiness in the right foot during walking. We attributed these differences in gait patterns to discrepancies in the impaired region of the SMA. The leg clumsiness in both cases is likely due to dysfunction of dorsal the SMA, which plays a role in controlling leg function according to the somatotopy. The characteristic gait pattern in Case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, resembling freezing gait in the right leg, is probably due to a dysfunction in the pre-SMA, which is activated during the initiation phase of the movement. Although freezing gait can also be induced by dysfunction of the premotor area, there are no examination findings to support this in these two cases. Notably, CBS cases of truncal or lower limb apraxia onset have been reported; however, gait apraxia as an initial symptom is rare. A retrospective study revealed that 4 out of 24 patients manifest gait onset CBS, but no further details were provided [13]. Moreover, several leg-onset CBS cases diagnosed have been reported to date; however, cases of patients presenting with lower limb apraxia or gait apraxia as an initial symptom remain uncommon [14\u0026ndash;15]. Although gait apraxia is not included in the official CBS diagnostic criteria, it may indicate cerebral cortex dysfunction.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOverall, in the present study, we reported two remarkable cases of CBS predominantly manifesting as slightly different gait apraxia caused by loss of function in the SMA, as demonstrated by SPECT. Therefore, gait disturbances, even in the absence of weakness and limb apraxia, may be an early indicator of CBS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCBD - \u0026nbsp;corticobasal degeneration\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCBS - \u0026nbsp;corticobasal syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCSF - \u0026nbsp;cerebrospinal fluid\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ep-tau - \u0026nbsp;phosphorylated tau\u0026nbsp;\u003c/p\u003e\n\u003cp\u003erCBF - \u0026nbsp;regional cerebral blood flow\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSMA - \u0026nbsp;supplementary motor area\u0026nbsp;\u003c/p\u003e\n\u003cp\u003et-tau - \u0026nbsp;total tau\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan lang=\"EN-GB\"\u003eEthics approval and consent to participate\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan lang=\"EN-GB\"\u003e:\u003c/span\u003e\u003c/strong\u003e \u003cspan lang=\"EN-GB\"\u003eThe study was approved by the institutional review board of University of Tsukuba (R06-106) and was conducted in accordance with the Declaration of Helsinki.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan lang=\"EN-GB\"\u003eConsent for publication\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan lang=\"EN-GB\"\u003e: \u003c/span\u003e\u003c/strong\u003e\u003cspan lang=\"EN-GB\"\u003eWritten informed consent was obtained from the patient\u0026rsquo;s family for the publication of this case report and accompanying images.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan lang=\"EN-GB\"\u003eAvailability of data and materials\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan lang=\"EN-GB\"\u003e: \u003c/span\u003e\u003c/strong\u003e\u003cspan lang=\"EN-GB\"\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request. To protect patient confidentiality, only de-identified data will be shared.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan lang=\"EN-GB\"\u003eCompeting interests\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan lang=\"EN-GB\"\u003e:\u003c/span\u003e\u003c/strong\u003e \u003cspan lang=\"EN-GB\"\u003eThe authors declare that there are no conflicts of interest relevant to this work.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan lang=\"EN-GB\"\u003eFunding\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan lang=\"EN-GB\"\u003e:\u003c/span\u003e\u003c/strong\u003e \u003cspan lang=\"EN-GB\"\u003eNo specific funding was received for this work.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan lang=\"EN-GB\"\u003eAuthor contributions\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan lang=\"EN-GB\"\u003e: \u003c/span\u003e\u003c/strong\u003e\u003cspan lang=\"EN-GB\"\u003eAll authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Kota Igari, Motoki Fujimaki, and Shinji Saiki. The first draft of the manuscript was written by Kota Igari, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan lang=\"EN-GB\"\u003eAcknowledgments\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan lang=\"EN-GB\"\u003e:\u003c/span\u003e\u003c/strong\u003e\u003cspan lang=\"EN-GB\"\u003e\u0026nbsp;The authors would like to thank the patients for giving consent for publication of the videos and pictures for educational purposes.\u003c/span\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDella Sala S, Francescani A, Spinnler H. Gait apraxia after bilateral supplementary motor area lesion. J Neurol Neurosurg Psychiatry. 2002;72:77\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZadikoff C, Lang AE. Apraxia in movement disorders. Brain. 2005;128:1480\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDella Sala S, Spinnler H, Venneri A. Walking Difficulties in patients with Alzheimer\u0026rsquo;s disease might originate from gait apraxia. J Neurol Neurosurg Psychiatry. 2004;75:196\u0026ndash;201.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArmstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80:496\u0026ndash;503.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFried I, Katz A, McCarthy G, Sass KJ, Williamson P, Spencer SS, Spencer DD. Functional organization of human supplementary motor cortex studied by electrical stimulation. J Neurosci. 1991;11:3656\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakakusaki K. Functional neuroanatomy for posture and gait control. J Mov Disord. 2017;10:1\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011;10:734\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMathew R, Bak TH, Hodges JR. Diagnostic criteria for corticobasal syndrome: a comparative study. J Neurol Neurosurg Psychiatry. 2012;83:405\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDale ML, Curtze C, Nutt JG. Apraxia of gait\u0026ndash;or apraxia of postural transitions? Parkinsonism Relat Disord. 2018;50:19\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCunnington R, Windischberger C, Robinson S, Moser E. The selection of intended actions and the observation of others' actions: a time-resolved fMRI study. NeuroImage. 2006;29:1294\u0026ndash;1302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOnder H, Oguz KK, Has AC, Elibol B. Comparative analysis of freezing of gait in distinct parkinsonism types by diffusion tensor imaging method and cognitive profiles. J Neural Transm. 2023;130:521\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNadeau SE. Gait apraxia: further clues to localization. Eur Neurol. 2007;58:142\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSakamoto Y, Shimizu T, Tobisawa S, Isozaki E. Prevalence and clinical characteristics of corticobasal syndrome with an initial symptom outside of the upper limb. Neurol Sci. 2017;38:783\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorvath J, K\u0026ouml;vari E, Bouras C, Burkhard PR. Neuropathological correlates of lower limb corticobasal degeneration. Neuropathol Appl Neurobiol. 2009;35:623\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCompston A. From the archives. Corticobasal degeneration. By WRG Gibb, PJ Luther and CD Marsden. Brain 1989: 112; 1171\u0026ndash;1192 with Corticobasal degeneration. A clinical study of 36 cases. By JO Rinne, MS Lee, PD Thompson and CD Marsden. Brain 1994: 117; 1183\u0026ndash;1196. Brain. 2010;133:1860\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"gait apraxia, corticobasal syndrome, supplementary motor area, regional cerebral blood flow, freezing gait, neurodegeneration","lastPublishedDoi":"10.21203/rs.3.rs-5873398/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5873398/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eGait apraxia, characterized by difficulties initiating and coordinating walking despite preserved conceptual movement abilities, is a distinct entity from lower limb apraxia. Although gait apraxia has been associated with dysfunction of the frontal lobe, particularly the supplementary motor area (SMA), the specific associated somatotopic organization phenotype remains poorly understood. Corticobasal syndrome (CBS), a clinical phenotype of corticobasal degeneration, commonly presents with upper limb apraxia, while lower limb or gait apraxia has rarely been reported. Herein, we describe two rare cases of CBS presenting with gait apraxia shown to be caused by SMA dysfunction, based on regional cerebral blood flow (rCBF) reduction on single-photon emission computed tomography (SPECT).\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eCase 1 was of an 82-year-old man who exhibited right-sided apraxic gait with freezing and shuffling patterns, along with SMA hypoperfusion in both the dorsal and pre-SMA regions. Neurological examination revealed mild rigidity, right-sided Babinski sign, and clumsiness in mimicking leg movements. Gait patterns were inconsistent and unresponsive to levodopa or sensory cues. Case 2 was of an 80-year-old man who demonstrated a peculiar gait characterized by exaggerated right leg movements and everted ankle positioning. Hypoperfusion was localized to the left dorsal SMA. Examination findings included rigidity and impaired hand weight perception. Sensory tricks and levodopa provided no benefit.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThese cases highlight the role of SMA dysfunction in the pathogenesis of gait apraxia. Variations in rCBF reduction correlated with distinct gait patterns. For example, the freezing gait shown in Case 1 likely resulted from pre-SMA impairment, which is critical for movement initiation, while the exaggerated leg movements in Case 2 reflected dorsal SMA dysfunction, involved in motor execution. These results indicate that gait apraxia, which is often underdiagnosed, should be recognized as a potential early indicator of CBS. Further, these cases suggest that SMA dysfunction, identified through SPECT imaging, underlies the distinct gait patterns seen in CBS patients with apraxic gait. Recognizing these symptoms, even in the absence of weakness or limb apraxia, may aid in early CBS diagnosis and improve clinical management.\u003c/p\u003e","manuscriptTitle":"Differences in Gate Apraxia Due to Reduced Regional Cerebral Blood Flow in the Supplementary Motor Area in Corticobasal Syndrome: A Report of Two Cases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-24 18:38:16","doi":"10.21203/rs.3.rs-5873398/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-26T10:13:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-20T13:45:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"81492759621526096728397033520429756283","date":"2025-05-17T06:41:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"195386439884702100730644912356271223626","date":"2025-02-05T22:24:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-29T23:17:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"148713099509288495573114653939185862808","date":"2025-01-29T21:16:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-01-29T19:12:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-01-22T19:23:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-22T12:26:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-22T12:24:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-01-21T11:59:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3b554c22-3437-4546-a139-4ba97cd38888","owner":[],"postedDate":"January 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-04T16:41:46+00:00","versionOfRecord":{"articleIdentity":"rs-5873398","link":"https://doi.org/10.1186/s12883-025-04332-z","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2025-07-29 16:13:11","publishedOnDateReadable":"July 29th, 2025"},"versionCreatedAt":"2025-01-24 18:38:16","video":"","vorDoi":"10.1186/s12883-025-04332-z","vorDoiUrl":"https://doi.org/10.1186/s12883-025-04332-z","workflowStages":[]},"version":"v1","identity":"rs-5873398","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5873398","identity":"rs-5873398","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}