{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T01:56:36Z","timestamp":1773712596834,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The article processing charge was funded by the German Research Foundation (DFG) and the University of Freiburg in the funding program Open Access Publishing.","award":["na"],"award-info":[{"award-number":["na"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Atypical Parkinsonian syndromes with prominent frontal lobe involvement can occur in the 4R-taupathies progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Secondary forms of movement disorders may occur in the context of autoimmune encephalitis with antineuronal antibodies, such as anti-glycine receptor (anti-GlyR) antibodies, which are typically associated with Stiff-Person spectrum syndrome, or progressive encephalomyelitis with rigidity and myoclonus. Overlaps between neurodegenerative and immunological mechanisms have been recently suggested in anti-IgLON5 disease. In this case study, the authors describe a patient with a Parkinsonian syndrome with frontal lobe involvement and anti-GlyR antibodies. Case presentation: The patient presented was a 63-year-old female. Her symptoms had begun with insomnia at the age of 60, after which, since the age of 61, increasing personality changes developed, leading to a diagnosis of depression with delusional symptoms. Severe cognitive deficits emerged, along with a left-side accentuated Parkinsonian syndrome with postural instability. The personality changes involved frontal systems. Magnetic resonance imaging (MRI) showed low-grade mesencephalon atrophy. [18F]fluorodeoxyglucose positron emission tomography (FDG PET) depicted a moderate hypometabolism bilateral frontal and of the midbrain, while [123I]FPCIT single-photon emission computed tomography (SPECT) revealed severely reduced dopamine transporter availability in both striata, indicating pronounced nigrostriatal degeneration. In addition, anti-GlyR antibodies were repeatedly found in the serum of the patient (max. titer of 1:640, reference: &lt;1:20). Therefore, an anti-inflammatory treatment with steroids and azathioprine was administered; this resulted in a decrease of antibody titers (to 1:80) but no detectable clinical improvement. The cerebrospinal fluid (CSF) and electroencephalography diagnostics showed inconspicuous findings, and negative CSF anti-GlyR antibody results. Conclusion: The patient presented here was suffering from a complex Parkinsonian syndrome with frontal lobe involvement. Because of the high anti-GlyR antibody titers, the presence of an autoimmune cause of the disorder was discussed. However, since no typical signs of autoimmune anti-GlyR antibody syndrome (e.g., hyperexcitability, anti-GlyR antibodies in CSF, or other inflammatory CSF changes) were detected, the possibility that the anti-GlyR antibodies might have been an unrelated bystander should be considered. Alternatively, the anti-GlyR antibodies might have developed secondarily to neurodegeneration (most likely a 4-repeat tauopathy, PSP or CBD) without exerting overt clinical effects, as in cases of anti-IgLON5 encephalopathy. In this case, such antibodies might also potentially modify the clinical course of classical movement disorders. Further research on the role of antineuronal antibodies in Parkinsonian syndromes is needed.<\/jats:p>","DOI":"10.3390\/brainsci10060399","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T09:05:33Z","timestamp":1592903133000},"page":"399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Parkinsonian Syndrome with Frontal Lobe Involvement and Anti-Glycine Receptor Antibodies"],"prefix":"10.3390","volume":"10","author":[{"given":"Dominique","family":"Endres","sequence":"first","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Pr\u00fcss","sequence":"additional","affiliation":[{"name":"Department of Neurology and Experimental Neurology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Rijntjes","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Werden","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Nickel","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Meixensberger","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0263-4360","authenticated-orcid":false,"given":"Kimon","family":"Runge","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"Urbach","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Domschke","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Center for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp T.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludger","family":"Tebartz van Elst","sequence":"additional","affiliation":[{"name":"Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Grayson, M. (2016). Parkinson\u2019s disease. Nature, 538.","DOI":"10.1038\/538S1a"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S1474-4422(17)30157-6","article-title":"Advances in progressive supranuclear palsy: New diagnostic criteria, biomarkers, and therapeutic approaches","volume":"16","author":"Boxer","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hufschmidt, A., L\u00fccking, C., Rauer, S., and Glocker, F.X. (2017). Neurologie Compact, Thieme. Hrsg. 7. Auflage.","DOI":"10.1055\/b-005-143671"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1093\/brain\/awr179","article-title":"Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia","volume":"134","author":"Rascovsky","year":"2011","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria","volume":"32","author":"Respondek","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1097\/WCO.0000000000000106","article-title":"Update on SPECT and PET in parkinsonism\u2014Part 1","volume":"27","author":"Meyer","year":"2014","journal-title":"Curr. Opin. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1212\/WNL.0b013e31827f0fd1","article-title":"Criteria for the diagnosis of corticobasal degeneration","volume":"80","author":"Armstrong","year":"2013","journal-title":"Neurology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1590\/s1980-5764-2016dn1004003","article-title":"Corticobasal syndrome: A diagnostic conundrum","volume":"10","author":"Parmera","year":"2016","journal-title":"Dement. Neuropsychol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/neup.12590","article-title":"Chameleons and mimics: Progressive supranuclear palsy and corticobasal degeneration","volume":"40","author":"Mimuro","year":"2019","journal-title":"Neuropathology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1093\/brain\/awu256","article-title":"A disease-specific metabolic brain network associated with corticobasal degeneration","volume":"137","author":"Niethammer","year":"2014","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.2967\/jnumed.116.186403","article-title":"18F-FDG PET in Parkinsonism: Differential Diagnosis and Evaluation of Cognitive Impairment","volume":"58","author":"Meyer","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jns.2016.01.006","article-title":"Autoimmune atypical parkinsonism\u2014A group of treatable parkinsonism","volume":"362","author":"Kannoth","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/brain\/awx189","article-title":"Movement disorders with neuronal antibodies: Syndromic approach, genetic parallels and pathophysiology","volume":"141","author":"Balint","year":"2017","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00115-019-0700-z","article-title":"Autoantik\u00f6rper-assoziierte schizophreniforme Psychosen: Klinische Symptomatik","volume":"90","author":"Endres","year":"2019","journal-title":"Der Nervenarzt"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Endres, D., Leypoldt, F., Bechter, K., Hasan, A., Steiner, J., Domschke, K., Wandinger, K.-P., Falkai, P., Arolt, V., and Stich, O. (2020). Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: Clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations. Eur. Arch. Psychiatry Clin. Neurosci., 1\u201316.","DOI":"10.1007\/s00406-020-01113-2"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1152\/physrev.00010.2016","article-title":"Autoantibodies to Synaptic Receptors and Neuronal Cell Surface Proteins in Autoimmune Diseases of the Central Nervous System","volume":"97","author":"Dalmau","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1093\/brain\/awu142","article-title":"Glycine receptor antibodies in PERM and related syndromes: Characteristics, clinical features and outcomes","volume":"137","author":"Leite","year":"2014","journal-title":"Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e592","DOI":"10.1212\/NXI.0000000000000592","article-title":"Novel clinical features of glycine receptor antibody syndrome","volume":"6","author":"Piquet","year":"2019","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"804","DOI":"10.3389\/fneur.2019.00804","article-title":"Cerebrospinal Fluid Findings in Patients with Autoimmune Encephalitis-A Systematic Analysis","volume":"10","author":"Blinder","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1001\/jamaneurol.2013.574","article-title":"Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype","volume":"70","author":"McKeon","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1111\/ene.13721","article-title":"Antiglycine receptor antibody related disease: A case series and literature review","volume":"25","author":"Swayne","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S1474-4422(14)70051-1","article-title":"A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: A case series, characterisation of the antigen, and post-mortem study","volume":"13","author":"Sabater","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00401-016-1591-8","article-title":"Neuropathological criteria of anti-IgLON5-related tauopathy","volume":"132","author":"Gelpi","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_24","first-page":"1238","article-title":"A diagnostic approach in Alzheimer\u2019s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET","volume":"36","author":"Minoshima","year":"1995","journal-title":"J. Nucl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1212\/WNL.0b013e3181feb2e8","article-title":"Imaging correlates of pathology in corticobasal syndrome","volume":"75","author":"Whitwell","year":"2010","journal-title":"Neurology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1212\/WNL.0b013e318292a2d2","article-title":"The midbrain to pons ratio: A simple and specific MRI sign of progressive supranuclear palsy","volume":"80","author":"Massey","year":"2013","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrneurol.2011.43","article-title":"Corticobasal degeneration: A pathologically distinct 4R tauopathy","volume":"7","author":"Kouri","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e438","DOI":"10.1212\/NXI.0000000000000438","article-title":"Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders","volume":"5","author":"Hinson","year":"2018","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1093\/brain\/awz297","article-title":"Glycine receptor autoantibodies disrupt inhibitory neurotransmission","volume":"142","author":"Crisp","year":"2019","journal-title":"Brain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/ana.24189","article-title":"Seroprevalence of autoantibodies against brain antigens in health and disease","volume":"76","author":"Dahm","year":"2014","journal-title":"Ann. Neurol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/6\/399\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:41:46Z","timestamp":1760175706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/6\/399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,23]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["brainsci10060399"],"URL":"https:\/\/doi.org\/10.3390\/brainsci10060399","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,23]]}}}