Dystonia-parkinsonism as the Presenting Feature of Hypothalamic Germinoma

Dystonia-parkinsonism as the Presenting Feature of Hypothalamic Germinoma | 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 Dystonia-parkinsonism as the Presenting Feature of Hypothalamic Germinoma Lívio Leite Barros, Walisson Grangeiro Bringel Silva, Pedro Lucas Grangeiro de Sá Barreto Lima, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3842746/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Parkinsonism is more often caused by lesions affecting the basal ganglia but may also occur in lesions outside of this region. Case report: We report a case of a 17-year-old boy that presented with imbalance, slowing of movements, and abnormal posturing of the right arm. Neuroimaging revealed a lesion involving the right hypothalamus, with mild volume loss of the left thalamus and putamen. Discussion: Parkinsonism caused by brain tumors is very rare. To our knowledge there is no previous report of germinomas causing parkinsonism or dystonia. Most previously reported cases of parkinsonism secondary to tumors had a favorable outcome after tumor excision, but dopaminergic treatment was ineffective. This challenging case highlights the possibility of secondary causes for dystonia-parkinsonism and the possibility of lesions outside the main basal ganglia circuit presenting with parkinsonism. Parkinsonism Hypothalamus Germinoma Dystonia Levodopa Figures Figure 1 Figure 2 Background Parkinsonism refers to a group of neurological disorders characterized by motor symptoms such as tremor, bradykinesia (slowness of movement), rigidity, and postural instability ( 1 ). While the primary cause of Parkinsonism is often associated with degenerative conditions like Parkinson's disease, it's essential to consider other potential etiologies, including neoplasias of the central nervous system (CNS) ( 2 , 3 ). Tumors within the CNS can disrupt the normal functioning of neural circuits, leading to a range of motor and non-motor symptoms, including parkinsonism ( 1 , 3 , 4 ). Germinomas are tumors derived from primordial germ cells ( 5 , 6 ), most commonly found in the pineal and suprasellar regions of the brain ( 6 ). While the majority of germinomas present with symptoms related to increased intracranial pressure or endocrine dysfunction, emerging evidence suggests a potential association with tremors ( 7 ). Our aim with this article is to present and discuss an atypical presentation of dystonia-parkinsonism associated with a hypothalamic germinoma. Case report A 17-year-old male presented with a 3-year history of abnormal posturing (extension and adduction) of the right arm followed by progressive slowing of movements. One year after disease onset he started having imbalance with frequent falls. He referred polydipsia and polyuria for the last 3 years. His parents were non-consanguineous, and his psychomotor development was normal up to the age of 14. There was no family history of neurologic disorders. On neurologic examination, we observed dystonia of the right upper limb, with shoulder extension and adduction, mild dystonia of the left arm, as well as rigidity and bradykinesia predominantly on the right side. His gait was characterized by small steps and dystonic posturing of both arms (Video 1) , with feet and fingers pointed outward. Tendon jerks were brisk, and plantar responses were flexor. Muscle strength and coordination were normal. Brain MRI revealed a T2-hyperintense lesion involving the right hypothalamus associated with atrophy of the left thalamus and putamen. There was no direct involvement of the basal ganglia (Fig. 1 -A,B,C). These MRI findings were not believed to represent the cause of the movement disorder at this point, so a next-generation sequencing (NGS) panel for dystonia and parkinsonism genes was performed and excluded the most common causes of genetic movement disorders. Antineuronal antibodies including anti-Hu, anti-Yo, anti-Ri, anti-CV2 and anti-Ma2 antibodies were negative. Levodopa was started and titrated up to 600 mg/day. After 2 weeks there was improvement in gait, rigidity and bradykinesia. Sixteen months after starting levodopa the patient showed improvement in parkinsonism but persisted with dystonia and pyramidal signs. His score on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III went from 33.5 before levodopa to 14 after treatment. Video 1 shows neurological examination before and 30 minutes after 300mg of levodopa. Follow-up MRI after 12 months revealed an increased volume of the hypothalamic lesion with intense post-contrast enhancement as well as dissemination to the left lateral ventricle (Fig. 1 -D,E,F). A stereotactic biopsy of the right hypothalamus revealed a neoplasm composed of large, irregular cells with eosinophilic cytoplasm. Immunohistochemistry showed positivity for anti-PLAP, anti-OCT3/4 and anti-CD117 antibodies (Fig. 2 ). Chemotherapy with four cycles of etoposide and cisplatin was initiated with a significant reduction in periventricular and hypothalamus lesions after 2 months. There was slight improvement in parkinsonism after chemotherapy. Discussion We report a case of hypothalamic germinoma with contralateral atrophy of the basal ganglia presenting with dystonia-parkinsonism. Parkinsonism caused by brain tumors is very rare ( 3 ), being reported in only one out of 225 patients with BG astrocytomas ( 2 , 4 ). Parkinsonism in tumors not affecting the basal ganglia circuit is even rarer. In a series of 907 patients with supratentorial tumors not infiltrating the basal ganglia, only 8 patients had parkinsonism ( 4 ). A study on lesion-induced parkinsonism found that over 90% of lesion locations were connected to the midbrain, basal ganglia, anterior cingulate cortex and cerebellum. These spots are part of an intrinsically connected brain network, with connectivity to the claustrum being the most sensitive and specific marker of lesion-induced parkinsonism ( 1 ). Animal studies have demonstrated connections of supramammillary nucleus (SuM), which is an area right below the hypothalamus, to the claustrum. Interestingly, SuM stimulation has been shown to potently drive locomotion ( 1 , 11 ). Dystonia has been reported with lesions involving the basal ganglia, thalamus, cerebellum, and cortex, especially the sensorimotor and premotor regions ( 8 ). Our patient developed bilateral dystonia and parkinsonism that was more intense ipsilateral to the hypothalamic lesion but contralateral to the basal ganglia atrophy. In cases of secondary parkinsonism, lesions in studies with functional neuroimagining showed greater involvement of the midbrain, basal ganglia and cerebral cortex. Despite their heterogeneous location, they were functionally connected to a common set of brain regions ( 1 ). The recognition of the potential of a lesion in the hypothalamus to cause Wallerian degeneration in the contralateral basal ganglia and lead to the development of parkinsonism-dystonia may lead practitioners to an earlier diagnosis and more focused treatments. Dysfunction of the lenticulothalamic neuronal circuit appears to be related to the development of dystonia, being well associated, for example, with cases of traumatic brain injury ( 9 , 10 ). Early diagnosis in these cases is important due to possible therapeutic options. Most previously reported cases of parkinsonism secondary to tumors had a favorable outcome after tumor excision ( 2 ). Dopaminergic treatment was ineffective in a few studies. Unfortunately, we were not able to perform functional studies with evaluation of dopaminergic pathways, such as TRODAT-1 SPECT. Primary germinomas of the brain are very rare. This case highlights the possibility of parkinsonism-dystonia with hypothalamic germ tumors and the potential treatment of this condition. Declarations Ethics approval and consent to participate Written informed consent to participate was obtained from the legal guardians of the subject, as the participant is less than 18 years old. The study was approved by the local ethical committee at Universidade Federal do Ceará under the number 5.952.628. Consent for publication Written informed consent to publish was obtained from the legal guardians of the subject, as the participant is less than 18 years old. Availability of data and materials All data available is contained in the manuscript and additional information. Competing interests The authors declare no competing interests Funding No external funding was provided for this research Contributors LLB, PLGBSL and PRN were responsible for the conceptualization of this report. LLB, WGBS, DABSA, DRRF, GG and DAD were the main responsible for data collection. All authors were engaged in literature review and early manuscript draft. PLGSBL, TGG, ARBP, PBN, and PRN were responsible for manuscript revision and final draft of the article. References Joutsa J, Horn A, Hsu J, Fox MD. Localizing parkinsonism based on focal brain lesions. Brain. 2018;141(8):2445-56. Polyzoidis K, McQueen J, Rajput A, MacFadyen D. Parkinsonism as a manifestation of brain tumor. Surgical neurology. 1985;23(1):59-63. Höllerhage M. Secondary parkinsonism due to drugs, vascular lesions, tumors, trauma, and other insults. International review of neurobiology. 2019;149:377-418. Krauss JK, Nobbe F, Wakhloo AK, Mohadjer M, Vach W, Mundinger F. Movement disorders in astrocytomas of the basal ganglia and the thalamus. Journal of Neurology, Neurosurgery & Psychiatry. 1992;55(12):1162-7. Horowitz MB, Hall WA. Central nervous system germinomas: a review. Archives of neurology. 1991;48(6):652-7. Simson LR, Lampe I, Abell MR. Suprasellar germinomas. Cancer. 1968;22(3):533-44. Strowd R, Burger P, Holdhoff M, Kleinberg L, Olivi A, Pardo-Villamizar C, et al. Intracranial Germinoma Associated Rubral Tremor Mimicking Neuro-Behcet Disease: Importance of a tissue diagnosis (P3. 012). AAN Enterprises; 2015. Lehéricy S, Tijssen MA, Vidailhet M, Kaji R, Meunier S. The anatomical basis of dystonia: current view using neuroimaging. Mov Disord. 2013 Jun 15;28(7):944-57. Herrero M-T, Barcia C, Navarro J. Functional anatomy of thalamus and basal ganglia. Child’s Nervous System. 2002;18:386-404. Lee M, Rinne J, Ceballos-Baumann A, Thompson P, Marsden C. Dystonia after head trauma. Neurology. 1994;44(8):1374-. Farrell JS, Lovett-Barron M, Klein PM, Sparks FT, Gschwind T, Ortiz AL, et al. Supramammillary regulation of locomotion and hippocampal activity. Science. 2021;374(6574):1492-6. Additional Declarations No competing interests reported. Supplementary Files Video1.mp4 Video 1 Intense bradykinesia is observed initially in both upper limbs with slow gait with dystonic posture more evident in the left upper limb. 30 minutes after 300 mg of levodopa, we observed an improvement in the amplitude and speed of movements, as well as greater speed during gait. Pyramidal signs and dystonia persist after levodopa. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. 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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-3842746","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":266415320,"identity":"bb76aaae-9588-4286-8716-e74b73062948","order_by":0,"name":"Lívio Leite Barros","email":"","orcid":"","institution":"Federal University of Ceará","correspondingAuthor":false,"prefix":"","firstName":"Lívio","middleName":"Leite","lastName":"Barros","suffix":""},{"id":266415321,"identity":"18aff87c-b7fb-4e53-b8aa-b34ba646a806","order_by":1,"name":"Walisson Grangeiro Bringel Silva","email":"","orcid":"","institution":"Federal University of 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Nóbrega","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYHACxgNQhuEDBgYYG8HACmCyxgYkazGTIEqLOfsZgwMfGO4x6LY3b6vmqbkjx8/A/PDRDYY7+bi0WPbkGBycwVDMYHbmWNltnmPPjCUb2IyNcxieWTbg0GJwIMfgMA9DAoPZjRyz2zxshxM3HOBhk85hOGyAyxaD82+gWu6/MSvm+UeMlhtwW3jMmHnbiNBiOeNZAdAvQC1n0ool5/YdNpZsBvnF4BlOLeb8yRsffABpOX5444c33w7L8bM3P3ycU3EHt8NABOM/hvoGIM3EA+Ixw8XxaIEBxh+4FY6CUTAKRsEIBgDdsFkgLJJ0JQAAAABJRU5ErkJggg==","orcid":"","institution":"Federal University of Ceará","correspondingAuthor":true,"prefix":"","firstName":"Paulo","middleName":"Ribeiro","lastName":"Nóbrega","suffix":""}],"badges":[],"createdAt":"2024-01-07 14:29:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3842746/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3842746/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49485322,"identity":"0fcd1bb0-501a-4b6b-bda6-ed004f9eb4a5","added_by":"auto","created_at":"2024-01-11 16:11:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":154528,"visible":true,"origin":"","legend":"\u003cp\u003eAxial and Coronal brain MRI showing a T2-hyperintense lesion involving the right anterior perforated substance and hypothalamus (A,B), associated with atrophy of the left thalamus and putamen in T1 imaging (C). MRI after 12 months revealed an increased volume of the hypothalamic lesion (D) with intense post-contrast enhancement (F) as well as dissemination to the left lateral ventricle, observed in the temporal horn with T2/Flair hyperintensity (E).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3842746/v1/9213aec255b3b18ea83ffdf4.png"},{"id":49485323,"identity":"42a018b7-9919-4bbe-9419-e10b97cf07f2","added_by":"auto","created_at":"2024-01-11 16:11:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":407626,"visible":true,"origin":"","legend":"\u003cp\u003eA – Hematoxylin-eosin stains, 200x magnification, showing a neoplasm composed of large, irregular, epithelioid, polygonal cells, with nests of small lymphocytes (A), pleomorphic neoplastic cells with evident nucleoli (B), and diffuse immunoexpression for anti-PLAP antibody (C), Anti-OCT3/4 – antibody (D), anti-CD117 antibody (E).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3842746/v1/835b79935fb86c8871c22a2f.png"},{"id":52015088,"identity":"69eb6b8e-5e0f-4786-bb77-81836083e28b","added_by":"auto","created_at":"2024-03-05 11:55:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":803683,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3842746/v1/78932793-0769-4582-af38-920b96f299a0.pdf"},{"id":49485324,"identity":"773a7874-4f9a-49f8-b9a6-aae7345f2030","added_by":"auto","created_at":"2024-01-11 16:11:22","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":9578638,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVideo 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntense bradykinesia is observed initially in both upper limbs with slow gait with dystonic posture more evident in the left upper limb. 30 minutes after 300 mg of levodopa, we observed an improvement in the amplitude and speed of movements, as well as greater speed during gait. Pyramidal signs and dystonia persist after levodopa.\u003c/p\u003e","description":"","filename":"Video1.mp4","url":"https://assets-eu.researchsquare.com/files/rs-3842746/v1/33bc06c5e3f8c250f1e1233b.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eDystonia-parkinsonism as the Presenting Feature of Hypothalamic Germinoma\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eParkinsonism refers to a group of neurological disorders characterized by motor symptoms such as tremor, bradykinesia (slowness of movement), rigidity, and postural instability (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). While the primary cause of Parkinsonism is often associated with degenerative conditions like Parkinson's disease, it's essential to consider other potential etiologies, including neoplasias of the central nervous system (CNS) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTumors within the CNS can disrupt the normal functioning of neural circuits, leading to a range of motor and non-motor symptoms, including parkinsonism (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGerminomas are tumors derived from primordial germ cells (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), most commonly found in the pineal and suprasellar regions of the brain (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). While the majority of germinomas present with symptoms related to increased intracranial pressure or endocrine dysfunction, emerging evidence suggests a potential association with tremors (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur aim with this article is to present and discuss an atypical presentation of dystonia-parkinsonism associated with a hypothalamic germinoma.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 17-year-old male presented with a 3-year history of abnormal posturing (extension and adduction) of the right arm followed by progressive slowing of movements. One year after disease onset he started having imbalance with frequent falls. He referred polydipsia and polyuria for the last 3 years. His parents were non-consanguineous, and his psychomotor development was normal up to the age of 14. There was no family history of neurologic disorders.\u003c/p\u003e \u003cp\u003eOn neurologic examination, we observed dystonia of the right upper limb, with shoulder extension and adduction, mild dystonia of the left arm, as well as rigidity and bradykinesia predominantly on the right side. His gait was characterized by small steps and dystonic posturing of both arms \u003cb\u003e(Video 1)\u003c/b\u003e, with feet and fingers pointed outward. Tendon jerks were brisk, and plantar responses were flexor. Muscle strength and coordination were normal.\u003c/p\u003e \u003cp\u003eBrain MRI revealed a T2-hyperintense lesion involving the right hypothalamus associated with atrophy of the left thalamus and putamen. There was no direct involvement of the basal ganglia (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e-A,B,C).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThese MRI findings were not believed to represent the cause of the movement disorder at this point, so a next-generation sequencing (NGS) panel for dystonia and parkinsonism genes was performed and excluded the most common causes of genetic movement disorders. Antineuronal antibodies including anti-Hu, anti-Yo, anti-Ri, anti-CV2 and anti-Ma2 antibodies were negative. Levodopa was started and titrated up to 600 mg/day. After 2 weeks there was improvement in gait, rigidity and bradykinesia.\u003c/p\u003e \u003cp\u003eSixteen months after starting levodopa the patient showed improvement in parkinsonism but persisted with dystonia and pyramidal signs. His score on the Unified Parkinson\u0026rsquo;s Disease Rating Scale (UPDRS) part III went from 33.5 before levodopa to 14 after treatment. \u003cb\u003eVideo 1\u003c/b\u003e shows neurological examination before and 30 minutes after 300mg of levodopa.\u003c/p\u003e \u003cp\u003eFollow-up MRI after 12 months revealed an increased volume of the hypothalamic lesion with intense post-contrast enhancement as well as dissemination to the left lateral ventricle (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e-D,E,F).\u003c/p\u003e \u003cp\u003eA stereotactic biopsy of the right hypothalamus revealed a neoplasm composed of large, irregular cells with eosinophilic cytoplasm. Immunohistochemistry showed positivity for anti-PLAP, anti-OCT3/4 and anti-CD117 antibodies (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eChemotherapy with four cycles of etoposide and cisplatin was initiated with a significant reduction in periventricular and hypothalamus lesions after 2 months. There was slight improvement in parkinsonism after chemotherapy.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe report a case of hypothalamic germinoma with contralateral atrophy of the basal ganglia presenting with dystonia-parkinsonism.\u003c/p\u003e \u003cp\u003eParkinsonism caused by brain tumors is very rare (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), being reported in only one out of 225 patients with BG astrocytomas (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Parkinsonism in tumors not affecting the basal ganglia circuit is even rarer. In a series of 907 patients with supratentorial tumors not infiltrating the basal ganglia, only 8 patients had parkinsonism (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA study on lesion-induced parkinsonism found that over 90% of lesion locations were connected to the midbrain, basal ganglia, anterior cingulate cortex and cerebellum. These spots are part of an intrinsically connected brain network, with connectivity to the claustrum being the most sensitive and specific marker of lesion-induced parkinsonism (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Animal studies have demonstrated connections of supramammillary nucleus (SuM), which is an area right below the hypothalamus, to the claustrum. Interestingly, SuM stimulation has been shown to potently drive locomotion (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDystonia has been reported with lesions involving the basal ganglia, thalamus, cerebellum, and cortex, especially the sensorimotor and premotor regions (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur patient developed bilateral dystonia and parkinsonism that was more intense ipsilateral to the hypothalamic lesion but contralateral to the basal ganglia atrophy. In cases of secondary parkinsonism, lesions in studies with functional neuroimagining showed greater involvement of the midbrain, basal ganglia and cerebral cortex. Despite their heterogeneous location, they were functionally connected to a common set of brain regions (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe recognition of the potential of a lesion in the hypothalamus to cause Wallerian degeneration in the contralateral basal ganglia and lead to the development of parkinsonism-dystonia may lead practitioners to an earlier diagnosis and more focused treatments. Dysfunction of the lenticulothalamic neuronal circuit appears to be related to the development of dystonia, being well associated, for example, with cases of traumatic brain injury (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEarly diagnosis in these cases is important due to possible therapeutic options. Most previously reported cases of parkinsonism secondary to tumors had a favorable outcome after tumor excision (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Dopaminergic treatment was ineffective in a few studies. Unfortunately, we were not able to perform functional studies with evaluation of dopaminergic pathways, such as TRODAT-1 SPECT.\u003c/p\u003e \u003cp\u003ePrimary germinomas of the brain are very rare. This case highlights the possibility of parkinsonism-dystonia with hypothalamic germ tumors and the potential treatment of this condition.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent to participate was obtained from the legal guardians of the subject, as the participant is less than 18 years old. The study was approved by the local ethical committee at Universidade Federal do Ceará under the number 5.952.628.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent to publish was obtained from the legal guardians of the subject, as the participant is less than 18 years old.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data available is contained in the manuscript and additional information.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo external funding was provided for this research\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLLB, PLGBSL and PRN were responsible for the conceptualization of this report. LLB, WGBS, DABSA, DRRF, GG and DAD were the main responsible for data collection. All authors were engaged in literature review and early manuscript draft. PLGSBL, TGG, ARBP, PBN, and PRN were responsible for manuscript revision and final draft of the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJoutsa J, Horn A, Hsu J, Fox MD. Localizing parkinsonism based on focal brain lesions. Brain. 2018;141(8):2445-56.\u003c/li\u003e\n\u003cli\u003ePolyzoidis K, McQueen J, Rajput A, MacFadyen D. Parkinsonism as a manifestation of brain tumor. Surgical neurology. 1985;23(1):59-63.\u003c/li\u003e\n\u003cli\u003eH\u0026ouml;llerhage M. Secondary parkinsonism due to drugs, vascular lesions, tumors, trauma, and other insults. International review of neurobiology. 2019;149:377-418.\u003c/li\u003e\n\u003cli\u003eKrauss JK, Nobbe F, Wakhloo AK, Mohadjer M, Vach W, Mundinger F. Movement disorders in astrocytomas of the basal ganglia and the thalamus. Journal of Neurology, Neurosurgery \u0026amp; Psychiatry. 1992;55(12):1162-7.\u003c/li\u003e\n\u003cli\u003eHorowitz MB, Hall WA. Central nervous system germinomas: a review. Archives of neurology. 1991;48(6):652-7.\u003c/li\u003e\n\u003cli\u003eSimson LR, Lampe I, Abell MR. Suprasellar germinomas. Cancer. 1968;22(3):533-44.\u003c/li\u003e\n\u003cli\u003eStrowd R, Burger P, Holdhoff M, Kleinberg L, Olivi A, Pardo-Villamizar C, et al. Intracranial Germinoma Associated Rubral Tremor Mimicking Neuro-Behcet Disease: Importance of a tissue diagnosis (P3. 012). AAN Enterprises; 2015.\u003c/li\u003e\n\u003cli\u003eLeh\u0026eacute;ricy S, Tijssen MA, Vidailhet M, Kaji R, Meunier S. The anatomical basis of dystonia: current view using neuroimaging. Mov Disord. 2013 Jun 15;28(7):944-57.\u003c/li\u003e\n\u003cli\u003eHerrero M-T, Barcia C, Navarro J. Functional anatomy of thalamus and basal ganglia. Child\u0026rsquo;s Nervous System. 2002;18:386-404.\u003c/li\u003e\n\u003cli\u003eLee M, Rinne J, Ceballos-Baumann A, Thompson P, Marsden C. Dystonia after head trauma. Neurology. 1994;44(8):1374-.\u003c/li\u003e\n\u003cli\u003eFarrell JS, Lovett-Barron M, Klein PM, Sparks FT, Gschwind T, Ortiz AL, et al. Supramammillary regulation of locomotion and hippocampal activity. Science. 2021;374(6574):1492-6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Parkinsonism, Hypothalamus, Germinoma, Dystonia, Levodopa","lastPublishedDoi":"10.21203/rs.3.rs-3842746/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3842746/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Parkinsonism is more often caused by lesions affecting the basal ganglia but may also occur in lesions outside of this region.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase report:\u003c/strong\u003e We report a case of a 17-year-old boy that presented with imbalance, slowing of movements, and abnormal posturing of the right arm. Neuroimaging revealed a lesion involving the right hypothalamus, with mild volume loss of the left thalamus and putamen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion:\u003c/strong\u003e Parkinsonism caused by brain tumors is very rare. To our knowledge there is no previous report of germinomas causing parkinsonism or dystonia. Most previously reported cases of parkinsonism secondary to tumors had a favorable outcome after tumor excision, but dopaminergic treatment was ineffective. This challenging case highlights the possibility of secondary causes for dystonia-parkinsonism and the possibility of lesions outside the main basal ganglia circuit presenting with parkinsonism.\u003c/p\u003e","manuscriptTitle":"Dystonia-parkinsonism as the Presenting Feature of Hypothalamic Germinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-11 16:11:17","doi":"10.21203/rs.3.rs-3842746/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"09b39600-034e-4d94-aa5e-70027f43c3ae","owner":[],"postedDate":"January 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-05T11:47:20+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-11 16:11:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3842746","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3842746","identity":"rs-3842746","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}