{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:06:40Z","timestamp":1788962800162,"version":"build-2803163510"},"update-to":[{"DOI":"10.12688\/f1000research.133838.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000}}],"reference-count":44,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Alien hand syndrome (AHS) is a rare neurological phenomenon first described by Van Vleuten over a century ago. The most widely recognized variants in literature are frontal, callosal, and posterior AHS. AHS due to the corpus callosum lesion can occur alone or as part of callosal disconnection syndrome (CDS). This report presents a unique CDS case manifesting clinical features from all three AHS variants, resulting from an extensive corpus callosum infarct. Our patient exhibited various clinical features from the three AHS variants, which include grasping, groping, and difficulty releasing objects from the hand (anterior); intermanual conflict (callosal); arm levitation, mild hemiparesis, and hemisensory loss (posterior). Additionally, the extensive disruption of the corpus callosal fibers produced neurological manifestations of CDS, such as cognitive impairment, ideomotor and constructional apraxia, behavioral disorder, and transcortical motor aphasia. We employed a range of rehabilitation interventions, such as mirror box therapy, limb restraint strategy, verbal cue training, cognitive behavioral therapy, bimanual hand training, speech and language therapy, and pharmacological treatment with clonazepam. The patient showed almost complete resolution of CDS and AHS features by nine months post-stroke Our case report highlights distinctive clinical variations of AHS and the challenging correlation between clinical manifestations and neuroanatomical substrates. Future studies are necessary to explore the intricate neural connections and the precise function of the corpus callosum. This can be achieved by combining comprehensive neuropsychological testing with diffusion tensor tractography studies. It is also essential to develop a validated tool to standardize AHS assessment. Finally, the scarcity of evidence in rehabilitation interventions necessitates further studies to address the wide knowledge gap in AHS and CDS management.<\/ns4:p>","DOI":"10.12688\/f1000research.133838.2","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T14:05:48Z","timestamp":1718633148000},"page":"529","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case Report: Callosal disconnection syndrome manifesting as mixed frontal-callosal-posterior alien hand syndrome following extensive corpus callosum infarct"],"prefix":"10.12688","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6498-7736","authenticated-orcid":false,"given":"Muhamad Faizal","family":"Zainudin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kar Chuan","family":"Soo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3933-0050","authenticated-orcid":false,"given":"Khin","family":"Nyein Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"77-94","DOI":"10.1006\/nimg.2002.1136","article-title":"Virtual in vivo interactive dissection of white matter fasciculi in the human brain.","volume":"17","author":"M Catani","year":"2002","journal-title":"NeuroImage."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e240-e244","DOI":"10.1016\/j.jstrokecerebrovasdis.2012.10.015","article-title":"Callosal disconnection syndrome after corpus callosum infarct: a diffusion tensor tractography study.","volume":"22","author":"S Jang","year":"2013","journal-title":"J. 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Adult."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/12-529\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/12-529\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/12-529\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T14:05:54Z","timestamp":1718633154000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/12-529\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,17]]},"references-count":44,"URL":"https:\/\/doi.org\/10.12688\/f1000research.133838.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.133838.1","asserted-by":"subject"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,17]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/12-529\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.146853.r266220, Stefano L Sensi, Matteo Alessandro De Rosa, University G. d'Annunzio of Chieti-Pescara, Chieti, 03 May 2024, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/12-529\/v1#referee-response-266220","order":0,"name":"referee-response-266220","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Khin Nyein Yin<\/b>; \n<i>Posted: 11 Jun 2024<\/i>; Thank you for your positive review. We appreciate the comments and have provided responses to your inquiries below:  1.&nbsp;&nbsp; &nbsp;It would be important to understand the timing of the second CT scan and why an MRI was not performed. An MRI would certainly have given further information about the features and anatomical sites involved.  Response:  The second CT was done on the day the patient had a drop in her GCS. We have added this information to the text:  \u201cA repeat CT scan was done urgently on the same day and displayed\u2026.\u201d (Page 4, line 50)  An MRI was not performed due to service limitations. We expanded the study limitations in a separate paragraph:  \u201cIn our setting, a tertiary government hospital with heavy patient loads and limited resources, there is no in-house clinical psychologist. Additionally, MRI availability is restricted and reserved for a limited number of cases. Given that an MRI would not alter the management of the stroke itself, the request for an MRI in this case was not granted. The patient was advised to consider obtaining an MRI and neuropsychological evaluation at a private center; however, these investigations were not performed due to financial constraints.\u201d (Page 10, lines 233-239)   2.&nbsp;&nbsp; &nbsp;Has a neuropsychological evaluation been performed to assess the cognitive domains involved? It could have been very useful for an assessment at baseline and to evaluate improvements  Response  A neuropsychological evaluation would have been invaluable to the case. Unfortunately, we do not have an in-house clinical psychologist. This is explained in the study limitations paragraph:  \u201cIn our setting, a tertiary government hospital with heavy patient loads and limited resources, there is no in-house clinical psychologist. Additionally, MRI availability is restricted and reserved for a limited number of cases. Given that an MRI would not alter the management of the stroke itself, the request for an MRI in this case was not granted. The patient was advised to consider obtaining an MRI and neuropsychological evaluation at a private center; however, these investigations were not performed due to financial constraints.\u201d (Page 10, lines 233-239)   3.&nbsp;&nbsp; &nbsp;Finally, how do you explain the occurrence of AL so far from the acute event? Please explain these aspects in more details.  Response  The patient was treated in a different hospital during the acute event. The nearly three-week stay was complicated by medical issues such as upper gastrointestinal bleeding and anemia requiring blood transfusions, and poorly-controlled diabetes. During medical stabilization, there was no dedicated caregiver accompanying her in the ward. She was reported to be sleeping in bed most of the time, and there was no documentation of abnormal movement from the referring hospital. Without eyewitness or documented evidence, it is difficult to ascertain the onset of AHS itself.","URL":"https:\/\/f1000research.com\/articles\/12-529\/v2#referee-comment-11756","order":1,"name":"referee-comment-11756","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.146853.r258091, Victor W Mark, University of Alabama at Birmingham, Birmingham, 06 May 2024, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/12-529\/v1#referee-response-258091","order":2,"name":"referee-response-258091","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Khin Nyein Yin<\/b>; \n<i>Posted: 11 Jun 2024<\/i>; We thank you and appreciate your review. The feedback you provided has helped improve the quality and clarity of this manuscript. Below are our responses to your inquiries.  1.&nbsp;&nbsp; &nbsp;The Abstract and Introduction attribute the first report of alien hand to Goldstein 1908. Most review papers point to this paper. However, in my own literature review, I find alien hand in yet an earlier report, from 1907 (Van Vleuten CF). This report has only rarely been mentioned in neuroscience literature, and not with attention to alien hand except in a superficial manner (cf Graff-Radford NR).  Response  Thank you for this valuable information that we missed. Information on the Van Vleuten paper is scarce, and most papers only briefly reference the article, including the reference you suggested. We have amended the information on the earliest reported cases of AHS by referencing Van Vleuten\u2019s study. The report by Van Vleuten can be found in the following sentences:  \u201c\u2026..first described by Van Vleuten\u2026\u2026\u201d (Abstract)  \u201cIt was first described by Van Vleuten in 1907 in a patient with a left-hemisphere brain tumor that had invaded the corpus callosum and exhibited right-hand grasping.\u201d (Page 3, lines 18-20)  \u201cAHS has been a subject of intrigue in the neurological community since its initial description by Van Vleuten &nbsp;more than a century ago.\u201d (Page 6, lines 138-139)   2.&nbsp;&nbsp; &nbsp;Under Patient Rehabilitation, the passage that the patient had a \u201cleft-sided hemisensory loss,\u201d but without details. Unclear whether this reflected light touch, pin, or otherwise.  Response  We have added the information to the revised manuscript:  \u201cAdditionally, there was left-sided hemisensory loss in both pin-prick and light touch sensation but intact proprioception,\u2026..\u201d (Page 5, lines 76-78)   3.&nbsp;&nbsp; &nbsp;Under Outpatient rehabilitation, the top paragraph indicates that the patient\u2019s left hand would rise (levitation) that occurred specifically during walking. While this does indeed suggest the posterior form of alien hand, this also suggests a form of paroxysmal kinesigenic dyskinesia. These may not be mutually exclusive diagnoses; I suggest review this possible alternate diagnosis.  Response  Thank you for the suggestion. We have expanded the discussion on the arm levitation and the consideration of PKD as a differential diagnosis:  \u201cThe arm levitation presentation in our patient could also indicate paroxysmal kinesigenic dyskinesia (PKD), a rare disorder characterized by involuntary movements such as dystonia and choreoathetosis, precipitated by sudden movement or startle (new reference no. 2). However, several characteristics suggest that PKD is less likely than posterior AHS. Firstly, PKD attacks are typically triggered by abrupt movement, an increase in speed, amplitude, or strength, the sudden addition of new actions during ongoing steady movements, or a change in direction (new reference no. 3). In our case, the arm levitation was triggered only by walking\u2014a step-wise, voluntary movement that did not involve sudden movement. The speed and direction of walking did not affect the manifestation of arm levitation. Secondly, the duration of PKD attacks is typically brief, mainly lasting less than a minute (new reference no. 3). In contrast, the arm levitation in our patient persisted throughout her ambulation. Thirdly, most cases of PKD are preceded by a premonition or aura (new reference no. 2), which was absent in our patient. Lastly, new PKD attacks cannot be induced for a refractory period of approximately 20 minutes (new reference no. 3). However, arm levitation could easily manifest upon walking without any such refractory period in our patient. Therefore, the arm levitation in this patient aligns more with the posterior AHS presentation than with PKD.\u201d (Page 8-9, lines 161-177)","URL":"https:\/\/f1000research.com\/articles\/12-529\/v2#referee-comment-11757","order":3,"name":"referee-comment-11757","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}