46e56cd2dda8e7401f17d433fc07cfce 264659.pdf b30c294e98d86fe819df7880ed09f1b94fe2c218 264659.pdf bd58de1040b472eb49297b110679382d94697def170a925cfe95a57a0c607dce 264659.pdf Title: Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up Subject: Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson's Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity. Keywords: changes; motor; Parkinson’s disease; phenotype; PIGD; Tremor Author: Diego Santos García, Lucía Naya Ríos, Teresa de Deus Fonticoba, Carlos Cores Bartolomé, Lucía García Roca, Maria Feal Painceiras, Cristina Martínez Miró, Hector Canfield, Silvia Jesús, Miquel Aguilar, Pau Pastor, Marina Cosgaya, Juan García Caldentey, Nuria Caballol, Inés Legarda, Jorge Hernández Vara, Iria Cabo, Lydia López Manzanares, Isabel González Aramburu, María A. Ávila Rivera, Víctor Gómez Mayordomo, Víctor Nogueira, Víctor Puente, Julio Dotor, Carmen Borrué, Berta Solano Vila, María Álvarez Sauco, Lydia Vela, Sonia Escalante, Esther Cubo, Francisco Carrillo Padilla, Juan C. Martínez Castrillo, Pilar Sánchez Alonso, Maria G. Alonso Losada, Nuria López Ariztegui, Itziar Gastón, Jaime Kulisevsky, Marta Blázquez Estrada, Manuel Seijo, Javier Rúiz Martínez, Caridad Valero, Mónica Kurtis, Oriol de Fábregues, Jessica González Ardura, Ruben Alonso Redondo, Carlos Ordás, Luis M. López Díaz, Darrian McAfee, Pablo Martinez-Martin and Pablo Mir Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 17 11:40:40 2021 CET ModDate: Fri Dec 17 13:27:34 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2497721 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- KWUCKX+VnURWPalladioL Type 1 Custom yes yes no 10 0 KRIXTQ+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 WHKODD+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 ZWFPDR+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 WIRPUU+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 BXZUUH+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 CZMDWU+CMSY10 Type 1 Builtin yes yes no 78 0 CKBPVA+EURM10 Type 1 Builtin yes yes no 88 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 117 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:22:50 CEST RepresentationInformation: 264659.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 11:59:20 CEST Size: 2497721 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 284 FreeObjects: 5 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Diplopia Definition Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Serum Biomarkers Determination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Data Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Standard Protocol Approvals, Registrations, and Patient Consents Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Info: Title: Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up Author: Diego Santos García, Lucía Naya Ríos, Teresa de Deus Fonticoba, Carlos Cores Bartolomé, Lucía García Roca, Maria Feal Painceiras, Cristina Martínez Miró, Hector Canfield, Silvia Jesús, Miquel Aguilar, Pau Pastor, Marina Cosgaya, Juan García Caldentey, Nuria Caballol, Inés Legarda, Jorge Hernández Vara, Iria Cabo, Lydia López Manzanares, Isabel González Aramburu, María A. Ávila Rivera, Víctor Gómez Mayordomo, Víctor Nogueira, Víctor Puente, Julio Dotor, Carmen Borrué, Berta Solano Vila, María Álvarez Sauco, Lydia Vela, Sonia Escalante, Esther Cubo, Francisco Carrillo Padilla, Juan C. Martínez Castrillo, Pilar Sánchez Alonso, Maria G. Alonso Losada, Nuria López Ariztegui, Itziar Gastón, Jaime Kulisevsky, Marta Blázquez Estrada, Manuel Seijo, Javier Rúiz Martínez, Caridad Valero, Mónica Kurtis, Oriol de Fábregues, Jessica González Ardura, Ruben Alonso Redondo, Carlos Ordás, Luis M. López Díaz, Darrian McAfee, Pablo Martinez-Martin and Pablo Mir Subject: Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269 4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012 1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson's Disease Rating Scale III (OR = 1.039; 95%CI, 1.023 1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001 1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity. Keywords: changes; motor; Parkinson’s disease; phenotype; PIGD; Tremor Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 17 11:40:40 CET 2021 ModDate: Fri Dec 17 13:27:34 CET 2021 ID: 0xda00a22c0258e334e300bd831fec6ddc, 0xda00a22c0258e334e300bd831fec6ddc Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: WHKODD+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 150 FontDescriptor: FontName: WHKODD+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WBVKDJ+URWPalladioL-BoldItal FontSubset: true FirstChar: 112 LastChar: 112 FontDescriptor: FontName: WBVKDJ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ZWFPDR+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 250 FontDescriptor: FontName: ZWFPDR+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CKBPVA+EURM10 FontSubset: true FirstChar: 11 LastChar: 11 FontDescriptor: FontName: CKBPVA+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: KWUCKX+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: KWUCKX+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WIRPUU+VnURWPalladioL-Bold FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: WIRPUU+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CZMDWU+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: CZMDWU+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: KRIXTQ+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: KRIXTQ+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 168, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 141, 641, 152, 654 Annotation: Subtype: Link Rect: 483, 641, 494, 654 Annotation: Subtype: Link Rect: 350, 628, 361, 642 Annotation: Subtype: Link Rect: 145, 603, 156, 617 Annotation: Subtype: Link Rect: 211, 603, 223, 617 Annotation: Subtype: Link Rect: 495, 603, 506, 617 Annotation: Subtype: Link Rect: 282, 590, 293, 604 Annotation: Subtype: Link Rect: 295, 566, 306, 579 Annotation: Subtype: Link Rect: 147, 553, 159, 566 Annotation: Subtype: Link Rect: 407, 540, 418, 554 Annotation: Subtype: Link Rect: 540, 528, 551, 541 Annotation: Subtype: Link Rect: 117, 344, 154, 353 Annotation: Subtype: Link Rect: 35, 332, 152, 341 Annotation: Subtype: Link Rect: 35, 162, 97, 184 Annotation: Subtype: Link Rect: 153, 89, 154, 98 Annotation: Subtype: Link Rect: 35, 77, 147, 86 Annotation: Subtype: Link Rect: 127, 17, 291, 28 Annotation: Subtype: Link Rect: 394, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 480, 87, 499 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 327, 203, 333, 212 ActionDest: 137 Annotation: Subtype: Link Rect: 347, 178, 354, 186 ActionDest: 137 Annotation: Subtype: Link Rect: 526, 165, 533, 174 ActionDest: 137 Annotation: Subtype: Link Rect: 536, 165, 543, 174 ActionDest: 137 Annotation: Subtype: Link Rect: 455, 115, 462, 124 ActionDest: 137 Annotation: Subtype: Link Rect: 351, 102, 358, 111 ActionDest: 137 Annotation: Subtype: Link Rect: 349, 90, 356, 99 ActionDest: 137 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 437, 710, 444, 719 ActionDest: 137 Annotation: Subtype: Link Rect: 319, 584, 326, 593 ActionDest: 140 Annotation: Subtype: Link Rect: 349, 569, 560, 581 Annotation: Subtype: Link Rect: 166, 556, 288, 568 Annotation: Subtype: Link Rect: 440, 559, 452, 568 ActionDest: 140 Annotation: Subtype: Link Rect: 234, 521, 246, 530 ActionDest: 140 Annotation: Subtype: Link Rect: 229, 308, 241, 317 ActionDest: 140 Annotation: Subtype: Link Rect: 448, 308, 460, 317 ActionDest: 140 Annotation: Subtype: Link Rect: 246, 257, 258, 266 ActionDest: 140 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 366, 710, 373, 719 ActionDest: 137 Annotation: Subtype: Link Rect: 374, 710, 381, 719 ActionDest: 137 Annotation: Subtype: Link Rect: 495, 685, 506, 694 ActionDest: 140 Annotation: Subtype: Link Rect: 169, 506, 300, 518 Annotation: Subtype: Link Rect: 227, 141, 235, 153 ActionDest: 92 Annotation: Subtype: Link Rect: 314, 66, 322, 78 ActionDest: 92 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 484, 250, 491, 262 ActionDest: 103 Annotation: Subtype: Link Rect: 200, 212, 208, 224 ActionDest: 103 Annotation: Subtype: Link Rect: 194, 137, 201, 149 ActionDest: 114 Annotation: Subtype: Link Rect: 494, 99, 501, 111 ActionDest: 121 Page: Sequence: 6 Page: Sequence: 7 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 195, 288, 202, 300 ActionDest: 121 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 448, 631, 455, 640 ActionDest: 137 Annotation: Subtype: Link Rect: 549, 631, 556, 640 ActionDest: 137 Annotation: Subtype: Link Rect: 387, 581, 394, 590 ActionDest: 137 Annotation: Subtype: Link Rect: 388, 518, 400, 527 ActionDest: 140 Annotation: Subtype: Link Rect: 518, 493, 525, 502 ActionDest: 137 Annotation: Subtype: Link Rect: 526, 493, 533, 502 ActionDest: 137 Annotation: Subtype: Link Rect: 497, 430, 509, 440 ActionDest: 140 Annotation: Subtype: Link Rect: 288, 418, 300, 427 ActionDest: 140 Annotation: Subtype: Link Rect: 256, 406, 267, 414 ActionDest: 140 Annotation: Subtype: Link Rect: 359, 405, 371, 414 ActionDest: 140 Annotation: Subtype: Link Rect: 427, 405, 439, 414 ActionDest: 140 Annotation: Subtype: Link Rect: 525, 393, 537, 402 ActionDest: 140 Annotation: Subtype: Link Rect: 340, 343, 347, 352 ActionDest: 137 Annotation: Subtype: Link Rect: 254, 317, 266, 327 ActionDest: 140 Annotation: Subtype: Link Rect: 239, 230, 251, 239 ActionDest: 140 Annotation: Subtype: Link Rect: 230, 142, 237, 151 ActionDest: 137 Annotation: Subtype: Link Rect: 237, 142, 244, 151 ActionDest: 137 Annotation: Subtype: Link Rect: 270, 92, 277, 101 ActionDest: 137 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 543, 722, 555, 731 ActionDest: 140 Annotation: Subtype: Link Rect: 424, 622, 431, 631 ActionDest: 137 Annotation: Subtype: Link Rect: 355, 584, 362, 593 ActionDest: 137 Annotation: Subtype: Link Rect: 538, 534, 545, 543 ActionDest: 137 Annotation: Subtype: Link Rect: 443, 421, 455, 430 ActionDest: 140 Annotation: Subtype: Link Rect: 388, 358, 399, 367 ActionDest: 140 Annotation: Subtype: Link Rect: 237, 308, 249, 317 ActionDest: 140 Annotation: Subtype: Link Rect: 191, 245, 198, 254 ActionDest: 137 Annotation: Subtype: Link Rect: 198, 245, 210, 254 ActionDest: 140 Annotation: Subtype: Link Rect: 211, 245, 223, 254 ActionDest: 140 Annotation: Subtype: Link Rect: 226, 245, 238, 254 ActionDest: 140 Annotation: Subtype: Link Rect: 384, 220, 391, 229 ActionDest: 137 Annotation: Subtype: Link Rect: 531, 145, 543, 154 ActionDest: 140 Annotation: Subtype: Link Rect: 544, 145, 556, 154 ActionDest: 140 Annotation: Subtype: Link Rect: 386, 107, 393, 116 ActionDest: 137 Annotation: Subtype: Link Rect: 367, 69, 379, 79 ActionDest: 140 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 203, 697, 210, 706 ActionDest: 137 Annotation: Subtype: Link Rect: 211, 697, 217, 706 ActionDest: 137 Annotation: Subtype: Link Rect: 218, 697, 225, 706 ActionDest: 137 Annotation: Subtype: Link Rect: 419, 633, 560, 644 Annotation: Subtype: Link Rect: 166, 621, 288, 632 Annotation: Subtype: Link Rect: 339, 140, 459, 151 Page: Sequence: 12 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 401, 556, 522, 567 Annotation: Subtype: Link Rect: 339, 544, 453, 555 Annotation: Subtype: Link Rect: 390, 233, 427, 243 Annotation: Subtype: Link Rect: 455, 209, 492, 220 Annotation: Subtype: Link Rect: 498, 209, 534, 220 Annotation: Subtype: Link Rect: 519, 186, 557, 197 Annotation: Subtype: Link Rect: 59, 175, 95, 186 Annotation: Subtype: Link Rect: 95, 152, 133, 163 Annotation: Subtype: Link Rect: 139, 152, 175, 163 Annotation: Subtype: Link Rect: 462, 129, 499, 140 Annotation: Subtype: Link Rect: 505, 129, 541, 140 Annotation: Subtype: Link Rect: 437, 106, 474, 117 Annotation: Subtype: Link Rect: 376, 94, 413, 105 Annotation: Subtype: Link Rect: 224, 72, 261, 82 Annotation: Subtype: Link Rect: 267, 72, 304, 82 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 196, 699, 234, 709 Annotation: Subtype: Link Rect: 336, 629, 374, 640 Annotation: Subtype: Link Rect: 380, 629, 416, 640 Annotation: Subtype: Link Rect: 218, 594, 256, 605 Annotation: Subtype: Link Rect: 262, 594, 298, 605 Annotation: Subtype: Link Rect: 59, 549, 97, 559 Annotation: Subtype: Link Rect: 271, 514, 308, 525 Annotation: Subtype: Link Rect: 314, 514, 351, 525 Annotation: Subtype: Link Rect: 230, 480, 268, 490 Annotation: Subtype: Link Rect: 520, 456, 557, 467 Annotation: Subtype: Link Rect: 355, 422, 393, 433 Annotation: Subtype: Link Rect: 498, 399, 536, 410 Annotation: Subtype: Link Rect: 161, 354, 198, 364 Annotation: Subtype: Link Rect: 205, 354, 241, 364 Annotation: Subtype: Link Rect: 118, 331, 155, 341 Annotation: Subtype: Link Rect: 234, 308, 271, 318 Annotation: Subtype: Link Rect: 278, 308, 314, 318 Annotation: Subtype: Link Rect: 324, 284, 362, 295 Annotation: Subtype: Link Rect: 368, 284, 404, 295 Annotation: Subtype: Link Rect: 279, 261, 315, 272 Annotation: Subtype: Link Rect: 59, 238, 97, 249 Annotation: Subtype: Link Rect: 103, 238, 139, 249 Annotation: Subtype: Link Rect: 388, 215, 426, 226 Annotation: Subtype: Link Rect: 310, 180, 348, 191 Annotation: Subtype: Link Rect: 182, 146, 220, 157 Annotation: Subtype: Link Rect: 300, 111, 338, 122 Checksum: 8e287fee Type: CRC32 Checksum: 46e56cd2dda8e7401f17d433fc07cfce Type: MD5 Checksum: b30c294e98d86fe819df7880ed09f1b94fe2c218 Type: SHA-1