Clinical and genetic characterization of a consanguineous family with cerebellar ataxia and tremors associated with a novel pathogenic variant in the KIF1C gene. We studied two generations of a family with cerebellar ataxia and tremor associated with a previously unreported variant in the KIF1C gene. We performed a clinical evaluation of all the available members and proceeded with genetic studies in patients with a positive clinical phenotype. A genetic analysis was also conducted, including KIF1C variant segregation analysis, runs of homozygosity analysis and haplotype analysis. Eleven individuals were identified, all exhibiting cerebellar tremors and ataxia with symptoms of onset around 45 years. Neuroimaging studies were unremarkable. Genetic testing revealed a homozygous KIF1C missense variant (NM_006612.6:c.941G > T, p.(Gly314Val)) in eight patients, and haplotype analysis confirmed a shared homozygous region surrounding KIF1C, consistent with a founder mutation. This represents the first report of this specific KIF1C variant, which is associated with late-onset symmetric tremor progressing to a pancerebellar syndrome. Unlike previously reported KIF1C-related cases (typically early-onset with prominent pyramidal signs), this cohort exhibits a later onset, rare pyramidal involvement, and no consistent neuroimaging abnormalities, thereby expanding the known clinical spectrum of KIF1C-associated disease.

Background The Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) serves as a comprehensive clinical assessment tool for non-motor symptoms in Parkinson’s disease (PD) Objectives This study aims to validate the Portuguese version of the MDS-NMS, addressing the critical need for culturally adapted rating scales in Portuguese-speaking populations. Methods This multicenter, cross-sectional study engaged native Portuguese-speaking PD patients from 16 Movement Disorders Centers across Portugal and Brazil. We conducted a meticulous translation process into Portuguese, including forward-backward translation and cognitive pretesting. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted to evaluate the psychometric properties and structural validity of the Portuguese version in comparison to the original English version. Tertiary analyses assessed the acceptability and reliability of domain scores within the cohort. Results The scale was administered to 386 PD Portuguese-speaking patients. CFA, conducted with a final sample of 303 participants, confirmed that the Portuguese version maintained a factor structure consistent with the English original, with Comparative Fit Index (CFI) values meeting or exceeding the 0.90 threshold across all subscales. High CFI values in domains such as Depression, Psychosis, and Cognition underscored the robustness of the translation. EFA revealed generally strong item-factor relationships, although domains like Gastrointestinal and Non-Motor Fluctuations exhibited more complex structures. Reliability analyses demonstrated strong internal consistency, with Cronbach's α ranging from 0.50 to 0.86 across domains, further corroborated by McDonald's ω and Greatest Lower Bound values. Conclusions The Portuguese version of the MDS-NMS demonstrates psychometric properties and structural validity that closely aligns with the original version.

Background: Deep brain stimulation of the internal globus pallidus effectively alleviates dystonia motor symptoms. However, delayed symptom control and a lack of therapeutic biomarkers and a single pallidal sweetspot region complicates optimal programming. Postoperative management is complex, typically requiring multiple, lengthy follow-ups with an experienced physician - an important barrier to widespread adoption in medicationrefractory dystonia patients. Objective: Here we prospectively tested the best machine-predicted programming settings in a dystonia cohort treated with GPi-DBS against the settings derived from clinical long-term care in a specialised DBS centre. Methods: Previously, we reconstructed an anatomical map of motor improvement probability across the pallidal region using individual stimulation volumes and clinical outcomes in dystonia patients. We used this to develop an algorithm that tests in silico thousands of putative stimulation settings in de novo patients after reconstructing an individual, image-based anatomical model of electrode positions, and suggests stimulation parameters with the highest likelihood of optimal symptom control. To test real-life application, our prospective study compared results in 10 patients against programming settings derived from long-term care. Results: In this cohort, dystonia symptom reduction was observed at 74.9 & PLUSMN; 15.3% with C-SURF programming as compared to 66.3 & PLUSMN; 16.3% with clinical programming (p < 0.012). The average total electrical energy delivered (TEED) was similar for both the clinical and C-SURF programming (262.0 & mu;J/s vs. 306.1 & mu;J/s respectively). Conclusion: Our findings highlight the clinical potential of machine-based programming in dystonia, which could markedly reduce the programming burden in postoperative management.

Movement Disorders Clinical PracticeEarly View CASE REPORT A Complex Pattern of Involuntary Movements Following Infection by Tick-Borne Encephalitis Virus of Western/European Variant, Single Case Report Mariana Vargas MD, Corresponding Author Mariana Vargas MD [email protected] orcid.org/0009-0003-8424-7309 Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal Correspondence to: Dr. Mariana Vargas, Rua Major António Fernandes Varão, lote 11 b, 2° esquerdo, 5000-055, Vila Real, Portugal; 00351913137253; E-mail: [email protected]Search for more papers by this authorAndré Costa MD, André Costa MD Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorRita Raimundo MD, Rita Raimundo MD orcid.org/0000-0002-4659-425X Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorMichel Mendes MD, Michel Mendes MD Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorAna Graça Velon MD, Ana Graça Velon MD Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this author Mariana Vargas MD, Corresponding Author Mariana Vargas MD [email protected] orcid.org/0009-0003-8424-7309 Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal Correspondence to: Dr. Mariana Vargas, Rua Major António Fernandes Varão, lote 11 b, 2° esquerdo, 5000-055, Vila Real, Portugal; 00351913137253; E-mail: [email protected]Search for more papers by this authorAndré Costa MD, André Costa MD Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorRita Raimundo MD, Rita Raimundo MD orcid.org/0000-0002-4659-425X Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorMichel Mendes MD, Michel Mendes MD Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorAna Graça Velon MD, Ana Graça Velon MD Neurology Department, Hospital de Vila Real, Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this author First published: 13 October 2023 https://doi.org/10.1002/mdc3.13899Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1Taba P, Schmutzhard E, Forsberg P, et al. EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis. Eur J Neurol 2017; 24(10): e1214–e1261. 2Schmutzhard E, Poewe W. Movement disorders in encephalitis. In: W Poewe, J Jankovic, eds. Movement Disorders in Neurologic and Systemic Disease. Cambridge, England: Cambridge University Press; 2014: 293–313. 3Pichler A, Sellner J, Harutyunyan G, et al. Magnetic resonance imaging and clinical findings in adults with tick-borne encephalitis. J Neurol Sci 2017; 15(375): 266–269. 4Gupta N, Pandey S. Post-thalamic stroke movement disorders: a systematic review. Eur Neurol 2018; 79(5–6): 303–314. 5Grygorczuk S, Parczewski M, Moniuszko A, et al. Increased concentration of interferon lambda-3, interferon beta and interleukin-10 in the cerebrospinal fluid of patients with tick-borne encephalitis. Cytokine 2015; 71(2): 125–131. 6Kaiser R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994-98: a prospective study of 656 patients. Brain 1999; 122(Pt 11): 2067–2078. 7Radzišauskienė D, Žagminas K, Ašoklienė L, et al. Epidemiological patterns of tick-borne encephalitis in Lithuania and clinical features in adults in the light of the high incidence in recent years: a retrospective study. Eur J Neurol 2018; 25(2): 268–274. 8Czupryna P, Moniuszko A, Pancewicz SA, Pancewicz SA, Grygorczuk S, Kondrusik M, Zajkowska J. Tick-borne encephalitis in Poland in years 1993–2008-epidemiology and clinical presentation. A retrospective study of 687 patients. Eur J Neurol 2011 May; 18(5): 673–679. 9Karelis G, Bormane A, Logina I, Lucenko I, Suna N, Krumina A, Donaghy M. Tick-borne encephalitis in Latvia 1973-2009: epidemiology, clinical features and sequelae. Eur J Neurol 2012; 19(1): 62–68. 10Barp N, Trentini A, Di Nuzzo M, et al. Clinical and laboratory findings in tick-borne encephalitis virus infection. Parasite Epidemiol Control 2020; 19(10):e00160. 11Kaiser R. Epidemiology and progress of early summer meningoencephalitis in Baden-Württemberg between 1994 and 1999. A prospective study of 731 patients. Dtsch Med Wochenschr 2000; 125(39): 1147–1153. 12Kaiser R. Long-term prognosis of patients with primary myelitic manifestation of tick-borne encephalitis: a trend analysis covering 10 years. Nervenarzt 2011; 82(8): 1020–1025. 13Günther G, Haglund M, Lindquist L. Tick-bone encephalitis in Sweden in relation to aseptic meningo-encephalitis of other etiology: a prospective study of clinical course and outcome. J Neurol 1997; 244(4): 230–238. 14Lenhard T, Ott D, Jakob NJ, et al. Predictors, neuroimaging characteristics and long-term outcome of severe European tick-borne encephalitis: a prospective cohort study. PloS One 2016; 11(4):e0154143. 15Kohlmaier B, Schweintzger NA, Sagmeister MG. Clinical characteristics of patients with tick-borne encephalitis (TBE): a European multicentre study from 2010 to 2017. Microorganisms 2021; 9(7): 1420. 16Radzišauskienė D, Urbonienė J, Kaubrys G. The epidemiology, clinical presentation, and predictors of severe tick-borne encephalitis in Lithuania, a highly endemic country: a retrospective study of 1040 patients. PloS One 2020; 15(11):e0241587. 17Anić K, Soldo I, Perić L, Karner I, Barac B. Tick-borne encephalitis in eastern Croatia. Scand J Infect Dis 1998; 30(5): 509–512. 18Logar M, Arnez M, Kolbl J, Avsic-Zupanc T, Strle F. Comparison of the epidemiological and clinical features of tick-borne encephalitis in children and adults. Infection 2000; 28(2): 74–77. 19Mickiene A, Laiskonis A, Günther G. Tickborne encephalitis in an area of high endemicity in Lithuania: disease severity and long-term prognosis. Clin Infect Dis 2002; 35(6): 650–658. 20Krech T. TBE foci in Switzerland. Int J Med Microbiol 2002; 291(Suppl 33): 30–33. 21Radšel-Medvešček A, Marolt-Gomišček M, Povše-Trojar M, et al. Late sequels after tick-borne meningoencephalitis in patients treated at the Hospital for Infectious Diseases University Medical Centre of Ljubljana during the period 1974-1975. In: J Vesenjak-Hirjan, ed. Arbnoviruses in the Mediterranean Countries. Vol 1980. Stuttgart: Zbl Bakt; 1982: 281–284. 22Haglund M, Forsgren M, Lindh G, et al. A 10-year follow-up study of tick-borne encephalitis in the Stockholm area and a review of the literature: need for a vaccination strategy. Scand J Infect Dis 1996; 28(3): 217–224. 23Czupryna P, Grygorczuk S, Krawczuk K, et al. Sequelae of tick-borne encephalitis in retrospective analysis of 1072 patients. Epidemiol Infect 2018; 146(13): 1663–1670. 24Grygorczuk S, Osada J, Sulik A, et al. Associations of the cerebrospinal fluid lymphocyte population with a clinical presentation of tick-borne encephalitis. Ticks Tick Borne Dis. 2023; 14(5):102204. 25Veje M, Nolskog P, Petzold M, Bergström T, Lindén T, Peker Y, Studahl M. Tick-borne encephalitis sequelae at long-term follow-up: a self-reported case-control study. Acta Neurol Scand 2016; 134(6): 434–441. 26Velay A, Solis M, Kack-Kack W, et al. A new hot spot for tick-borne encephalitis (TBE): a marked increase of TBE cases in France in 2016. Ticks Tick Borne Dis 2018; 9(1): 120–125. 27Lämmli B, Müller A, Ballmer PE. Late sequelae of early summer meningoencephalitis. Schweiz Med Wochenschr 2000; 130(24): 909–915. 28Zajkowska J, Moniuszko A, Czupryna P, et al. Chorea and tick-borne encephalitis. Poland Emerg Infect Dis 2013; 19(9): 1544–1545. 29Pogorzelski R, Drozdowski W, Rogowski M. Symptomatic palatal myoclonus with ear click after tick-borne meningoencephalitis. Eur Arch Otorhinolaryngol 2006; 263(8): 711–713. Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Epilepsy with myoclonic absences (EMA) is a very rare childhood generalized epilepsy syndrome (<1% of all generalized epilepsies) associated with frequent myoclonic absence seizures that was described in 1969 by Tassinari et al. [ [1] Tassinari C.A. Lyagoubi S. Santos V. et al. Study on spike and wave discharges in man. II. Clinical and electroencephalographic aspects of myoclonic absences. Rev Neurol. 1969; 121: 379-383 PubMed Google Scholar ]. Seizures are characterized by bilateral rhythmic jerks of the upper limbs, superimposed on tonic abduction of the arms [ [2] Bureau M. Tassinari C.A. Epilepsy with myoclonic absences. Brain Dev. 2005; 27: 178-184 Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar ]. Ictal EEG consists of 3-Hz generalized spike-and-wave complexes that are time-locked with the upper limb myoclonus, while the EMG generally shows myoclonic jerks followed by tonic contraction of both deltoids. These seizures differ from typical absences of childhood absence epilepsy, since myoclonic jerks are generally not seen in typical absences and, if present, are subtle and spare the arms. The lack of an atonic component also distinguishes these seizures from myoclonic-atonic seizures [ [3] Specchio N. Wirrell E.C. Scheffer I.E. et al. International league against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022; 63: 1398-1442 Crossref PubMed Scopus (46) Google Scholar ]. A recent position paper by the International League Against Epilepsy for the classification of epilepsy syndromes with onset in childhood retained EMA as an independent epilepsy syndrome and defined its diagnostic criteria [ [3] Specchio N. Wirrell E.C. Scheffer I.E. et al. International league against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022; 63: 1398-1442 Crossref PubMed Scopus (46) Google Scholar ]. The mandatory requirements are myoclonic absences as the predominant type of seizures, and regular 3 Hz generalized spike-and-wave complexes synchronous with myoclonus.

Movement Disorders Clinical PracticeEarly View LETTERS: PUBLISHED ARTICLES Apomorphine at the End-of-Life—A Role to Play Carolina Azoia MD, Corresponding Author Carolina Azoia MD [email protected] orcid.org/0000-0003-0737-8359 Neurology Department of the Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal Correspondence to: Dr. Carolina Azoia, Centro Hospitalar de Trás-os-Montes e Alto Douro, Serviço de Neurologia, Avenida da Noruega, 5000-508, Vila Real, Portugal; E-mail: [email protected]Search for more papers by this authorCatarina Borges MD, Catarina Borges MD orcid.org/0009-0003-5581-1441 Neurology Department of the Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorAna Graça Velon MD, Ana Graça Velon MD Neurology Department of the Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorRita Raimundo MD, Rita Raimundo MD orcid.org/0000-0002-4659-425X Neurology Department of the Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this author Carolina Azoia MD, Corresponding Author Carolina Azoia MD [email protected] orcid.org/0000-0003-0737-8359 Neurology Department of the Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal Correspondence to: Dr. Carolina Azoia, Centro Hospitalar de Trás-os-Montes e Alto Douro, Serviço de Neurologia, Avenida da Noruega, 5000-508, Vila Real, Portugal; E-mail: [email protected]Search for more papers by this authorCatarina Borges MD, Catarina Borges MD orcid.org/0009-0003-5581-1441 Neurology Department of the Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorAna Graça Velon MD, Ana Graça Velon MD Neurology Department of the Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this authorRita Raimundo MD, Rita Raimundo MD orcid.org/0000-0002-4659-425X Neurology Department of the Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, PortugalSearch for more papers by this author First published: 20 October 2023 https://doi.org/10.1002/mdc3.13907Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Castillo-Torres SA, Lees AJ, Merello M. Intermittent apomorphine use for off period Rescue in Parkinson's disease: a pragmatic review of over three decades of clinical experience. Mov Disord Clin Pract 2023; 10(2): 190–208. https://doi.org/10.1002/mdc3.13593. 2Dewhurst F, Lee M, Wood B. The pragmatic use of apomorphine at the end of life. Palliat Med 2015; 23(8): 777–779. https://doi.org/10.1177/0269216309106979. 3Oliver D, Veronese S. Specialist palliative care for Parkinson's disease. Ann Palliat Med 2020; 9(1): S52–S62. https://doi.org/10.21037/apm.2019.12.01. 4Lokk J, Delbari A. Clinical aspects of palliative care in advanced Parkinson's disease. BMC Palliat Care 2012; 11: 20–28. https://doi.org/10.1186/1472-684X-11-20. 5Hvisdak V, Huang AP, Kluger BM. Palliative Care of end Stage Parkinsonism: an overview including the five pillars framework. Mov Disord Clin Pract. 2022; 10: 1–5. https://doi.org/10.1002/mdc3.13620. Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Familial Alzheimer’s disease (AD) accounts for less than 1% of the total cases of AD and is characterized by a cognitive decline typically initiated before the age of 65 with a positive familial history, usually with a dominant inherence pattern. A 35-year-old man, whose mother died at the age of 36 with an undetermined rapidly progressive dementia, developed memory impairment and depression at the age of 33 followed by spatial disorientation, behavioral changes, and hallucinations at the age of 35. His neurological examination revealed bradyphrenia with a poor perseverative speech, executive dysfunction, dyscalculia, and bilateral frontal release signs. Blood analysis and brain MRI were normal; however, cerebrospinal fluid showed an elevated phosphorylated tau/beta-amyloid ratio, and SPECT revealed a global hypoperfusion. Therefore, a genetic testing for autosomal dominant variants of AD was performed, disclosing a presenilin 1 ( PSEN1 ) mutation, Pro117Leu, which confirms the diagnosis of familial Alzheimer’s disease. One year later, he had developed severe cognitive impairment with pyramidal and extrapyramidal signs, regardless of donepezil therapeutic regimen. PSEN1 mutation is the most common cause of familial AD and, compared to the other mutations, is associated with the youngest age of onset and with the presence of atypical neurological signs. To our knowledge, this is one of the cases with younger age of onset described in the literature.