We conducted the largest PSP GWAS of the Iberian population to date (522 cases from 22 Spanish and Portuguese institutions). We independently replicated seven known PSP risk variants, and unveiled a novel locus in NFASC/CNTN2 after meta-analysing our results with a newly available Dutch cohort and publicly available summary statistics. These findings highlight the importance of neuron-oligodendrocyte interactions in PSP etiopathology. ### Competing Interest Statement Vigil Neuroscience and Prevail therapeutics are in a public-private partnerschip research program of Sven J. van der Lee. All funding is paid to his institution. ### Funding Statement This work was funded by CIBERNED (Centro Investigacion Biomedica en Red Enfermedades Neurodegenerativas) 10th internal call for cooperative projects (Register number: 2019/09). Agustin Ruiz, Pascual Sanchez-Juan, Alberto Rabano, and Maria J. Bullido received funding from this convocatory. Pablo Garcia-Gonzalez received support by CIBERNED employment plan CNV-304-PRF-866. CIBERNED is integrated into ISCIII (Instituto de Salud Carlos III). Merce Boada, Marta Marquie and Agustin Ruiz are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240. PI19/01301, PI19/00335 and PI22/011403, and CIBERNED grant 2019/08. The Genome Research @ Fundacio ACE project (GR@ACE) is supported by Grifols SA, Fundacion bancaria La Caixa, Fundacio ACE, and CIBERNED. Accion Estrategica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII - Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER - Una manera de hacer Europa). Agustin Ruiz is supported by ISCIII national grant PMP22/00022, funded by the European Union (NextGenerationEU). The genotyping service to generate GR@ACE and PSP/DEGESCO GWAS data was carried out at CEGEN-PRB3-ISCIII; it is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. Itziar de Rojas received support by a national grant from ISCIII FI20/00215. Amanda Cano acknowledges the support of the Spanish Ministry of Science, Innovation and Universities under the grant Juan de la Cierva (FJC2018-036012-I), the support of ISCIII under the grant Sara Borrell (CD22/00125), Spanish Ministry of Science and Innovation, Proyectos de Generacion de Conocimiento grant PID2021-122473OA-I00, and Fundacion ADEY under the program Proyectos de Investigacion en Salud 2023. Fondo de Investigacion en Salud (Instituto Carlos III) (PI17/00096) in the frame of the European Regional Development Fund (ERDF) and to Fundacio ́ la Marato ́ de TV3 (PI043296 and 202009-10). This work was supported by the Spanish Ministry of Science and Innovation (RTC2019-007150-1), the Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union (PI14/01823, PI16/01575, PI18/01898, PI19/01576, PI21/01875), the Consejeria de Economia, Innovacion, Ciencia y Empleo de la Junta de Andalucia (CVI-02526, CTS-7685, PY20_00896), and the Consejeria de Salud y Bienestar Social de la Junta de Andalucia (PI-0471-2013, PE-0210-2018, PI-0459-2018, PE-0186-2019). Pilar Gomez-Garre was supported by the Nicolas Monardes program (C-0048-2017) from Andalusian Regional Ministry of Health. Laura Munoz-Delgado was supported by the Rio Hortega program [CM21/00051] from the Instituto de Salud Carlos III (ISCIII-FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sven J. van der Lee was funded for this study by NWO (#733050512, PROMO-GENODE: a PROspective study of MOnoGEnic causes Of Dementia) a substantial donation by Edwin Bouw Fonds and Dioraphte. SvdL further received funding for the GeneMINDS consortium, which is powered by Health-Holland, Top Sector Life Sciences & Health. Sven J. van der Lee is a recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners participate in ABOARD. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. ABOARD also receives funding from de Hersenstichting, Edwin Bouw Fonds and Gieskes-Strijbisfonds. Array genotyping was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW projectnumber 733051061). This work has been supported by the Queen Sofia Foundation. Pascual Sanchez-Juan is supported by grants from ISCIII (PMP22/00022 and PI20/01011) and TED2021-131676B-100. Luis Miguel Real received support from The absence of seroconversion after exposition to hepatitis C virus is not related to KIR-HLA genotype combinations (GEHEP-012 study). Consejeria de Salud de la Junta de Andalucia (grant number PI-0001/2017) and CIBERINFEC -Consorcio Centro de Investigacion Biomedica en Red de Enfermedades Infecciosas- Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion y Union Europea (Spain) (NextGeneration EU) (grant number CB21/13/00118). Jose Luis Royo received support from Project 23.04.2021 from Santangela Foundation (Sevilla, Spain). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: For the Iberian cohort, this study was approved by the competent research ethical committee (MED-FACE-2020-01, Universidad Internacional de Catalunya, Sant Cugat del Valles, Spain). For the Dutch cohorts, the local Medical Ethics Committees approved the protocols for the Amsterdam Dementia Cohort (ADC) and the other studies, and all participants of the ADC provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.

BACKGROUND AND PURPOSE:Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed device-aided therapy for advanced Parkinson disease (PD) patients. The aim of this study was to report real-world evidence about the effectiveness, tolerability, and safety of LECIG in PD patients. METHODS:A multicenter observational retrospective study of the first patients who initiated LECIG in Spain was performed. All neurologists with an experience of at least two patients treated until 30 March 2024 were invited to participate. Data about effectiveness and safety from the medical records (V0, pre-LECIG; V1, initiation of LECIG; V2, post-LECIG follow-up) with a total of 246 variables were collected. RESULTS:Seventy-three PD patients (61.6% males, 70.1 ± 9.1 years old) from 21 Spanish centers with a mean disease duration of 14.4 ± 6.3 years (range = 5-31) were included. Twenty-six patients (35.6%) were switched directly from levodopa-carbidopa intestinal gel. The mean exposure to LECIG was 177.3 ± 110.5 days (range = 7-476). The mean daily OFF time decreased from 5.2 ± 3 (pre-LECIG) to 1.9 ± 1.8 (post-LECIG; n = 66, p < 0.0001). Global improvement was observed in >85% of the patients. No significant change was detected in the levodopa equivalent daily dose from V0 to V2. Only 7% received 24-h infusion, and 24.7% required more than one cartridge per day at V2. Thirty-four patients (46.6%) had at least one adverse event related to LECIG and/or the device system. Five patients (6.8%) discontinued LECIG. CONCLUSIONS:LECIG was safe and effective in advanced PD patients.

Background and objective: Staging Parkinson’s disease (PD) with a novel simple classification called MNCD, based on four axes (Motor; Non-motor; Cognition; Dependency) and five stages, correlated with disease severity, patients’ quality of life and caregivers’ strain and burden. Our aim was to apply the MNCD classification in advanced PD patients treated with device-aided therapy (DAT). Patients and Methods: A multicenter observational retrospective study of the first patients to start the levodopa-entacapone-carbidopa intestinal gel (LECIG) in Spain was performed (LECIPARK study). The MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) were collected by the neurologist at V0 (before starting LECIG) and V2 (follow-up visit). Wilcoxon’s signed rank and Marginal Homogeneity tests were applied to compare changes from V0 to V2. Results: Sixty-seven PD patients (58.2% males; 69.9 ± 9.3 years old) with a mean disease duration of 14.4 ± 6.5 years were included. The mean treatment duration (V2) was 172.9 ± 105.2 days. At V0, patients were classified as in stage 2 (35.8%), 3 (46.3%) or 4 (17.9%). The frequency of patients in stage 4 decreased to 9% at V2 (p = 0.001). The MNCD total score decreased from 6.27 ± 1.94 at V0 to 5.21 ± 2.23 (p < 0.0001). From V0 to V2, the motor (M; p < 0.0001) and non-motor symptom (N; p < 0.0001) burden decreased, and autonomy for the activities of daily living (D; p = 0.005) improved. Conclusions: The MNCD classification could be useful to classify advanced PD patients and to monitor the response to a DAT.

Idiopathic Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and postural instability. Magnetic Resonance-guided high-intensity focused ultrasound (MRgFUS) of the subthalamic nucleus (STN) is gaining recognition as a minimally invasive surgical option. This study assesses the safety and efficacy of unilateral MRgFUS subthalamotomy, aiming to create the smallest effective lesion. Between June 2021 and October 2023, twelve PD patients underwent the procedure, with primary outcomes focused on safety and motor improvements after six months. Results indicated significant motor improvements, with over 50% reduction in tremor, rigidity, and bradykinesia, while balance and gait remained stable. Quality of life also improved. Side effects were generally mild and transient, though some patients experienced involuntary movements, managed through medication adjustments. Despite limitations, this technique appears to offer a promising, less-invasive alternative for managing PD symptoms with a favorable risk-benefit profile. Further research is necessary to refine the procedure and assess long-term outcomes.

BACKGROUND:Spinocerebellar ataxia type 8 (SCA8) is a dominantly inherited expansion disorder with highly variable penetrance. ATXN8OS/ATXN8 expanded alleles have been identified in association with other types of hereditary ataxias, pointing to a possible genetic synergism. OBJECTIVES:We aimed to further investigate the molecular background of patients with SCA8 diagnosis. METHODS:Patients were selected from our cohort of 346 families. A total of 14 probands with SCA8 underwent additional investigation through exome sequencing. RESULTS:Pathogenic heterozygous STUB1 variants were found in 21.4% of SCA8 patients (3 of 14) compared to only 0.5% in the non-SCA8 group (1 of 222), indicating a statistically significant association (P < 0.05). CONCLUSIONS:The findings reported in this study might suggest a genetic synergism between STUB1 and ATXN8OS/ATXN8 expanded alleles. Further studies are needed to validate this observation and better define the clinical impact of this genetic interaction.

Subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) are the main surgical approaches for advanced Parkinson's disease. Stimulation is usually applied bilaterally in the same brain structure. However, when various motor symptoms concomitantly present in the same patient, simultaneous modulation of different brain structures may be a suitable alternative.We present a patient with advanced Parkinson's disease with a combined DBS neurosurgery. Left STN DBS optimally controlled the off right hemibody symptomatology while left side troublesome dyskinesias were successfully relieved by right GPi stimulation.Combined STN/GPi stimulation can be considered a suitable approach when challenging motor symptomatology arises in advanced Parkinson's disease patients.Estimulación cerebral profunda combinada del núcleo subtalámico y el globo pálido interno en la enfermedad de Parkinson.Introducción. La estimulación cerebral profunda (ECP) del núcleo subtalámico (NST) y el globo pálido interno (GPi) son los principales abordajes quirúrgicos en la enfermedad de Parkinson avanzada. La estimulación suele aplicarse de forma bilateral en la misma estructura cerebral. Sin embargo, cuando diferentes síntomas motores se presentan concomitantemente en el mismo paciente, la modulación simultánea de diferentes estructuras cerebrales puede ser una alternativa eficaz. Caso clínico. Presentamos un paciente con enfermedad de Parkinson avanzada en el que se realizó ECP combinada en NST y el GPi. La ECP del NST izquierdo controló de manera óptima la sintomatología del hemicuerpo derecho, mientras que las discinesias problemáticas que presentaba en el hemicuerpo izquierdo se redujeron con éxito mediante la estimulación del GPi derecho. Discusión. La estimulación combinada del NST/GPi puede considerarse un enfoque neuroquirúrgico adecuado cuando surge una sintomatología motora desafiante en pacientes con enfermedad de Parkinson avanzada.

Autosomal dominant spinocerebellar ataxia 36 (SCA36) is caused by hexanucleotide repeat expansion in the NOP56 gene.

INTRODUCTION:Subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) are the main surgical approaches for advanced Parkinson's disease. Stimulation is usually applied bilaterally in the same brain structure. However, when various motor symptoms concomitantly present in the same patient, simultaneous modulation of different brain structures may be a suitable alternative. CASE REPORT:We present a patient with advanced Parkinson's disease with a combined DBS neurosurgery. Left STN DBS optimally controlled the off right hemibody symptomatology while left side troublesome dyskinesias were successfully relieved by right GPi stimulation. DISCUSSION:Combined STN/GPi stimulation can be considered a suitable approach when challenging motor symptomatology arises in advanced Parkinson's disease patients.

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.

Continuous intestinal infusion of levodopa/carbidopa is a second-line treatment indicated in advanced stages of Parkinson's disease (PD). For its implantation, a percutaneous endoscopic gastrostomy must be performed.The main objective has been to describe the frequency and characteristics of the side effects associated with this treatment. As a secondary objective, we have analyzed the epidemiological and clinical characteristics of the PD patients who have received this treatment in our hospital.Descriptive, single-center, retrospective study for a consecutive sample of PD patients treated with Continuous intestinal infusion of Levodopa/Carbidopa from the beginning of 2006 to the end of August 2021.81 treatment planifications have been analyzed. Treatment success (duration greater than 12 months) was achieved in 78.1% (n = 50) of the patients in whom this follow-up period was available. The median duration of treatment was 35 months. 58.6% of the patients presented some type of complication. A total of 43 minor complications and 16 serious adverse events were reported.The constitution of an experienced multidisciplinary team is essential to guarantee the adequate management and follow-up of these patients.Efectos adversos y complicaciones de la infusión intestinal continua de levodopa-carbidopa en una cohorte de pacientes con enfermedad de Parkinson de un hospital terciario.Introducción. La infusión intestinal continua de levodopa/carbidopa (IICLC) es un tratamiento de segunda línea indicado en fases avanzadas de la enfermedad de Parkinson (EP). Para su implantación se debe realizar una gastrostomía endoscópica percutánea. Objetivos. El objetivo principal ha sido describir la frecuencia y las características de los efectos secundarios asociados a este tratamiento. Como objetivo secundario se han analizado las características epidemiológicas y clínicas de pacientes afectos de EP que han recibido o reciben tratamiento con IICLC. Pacientes y métodos. Estudio descriptivo, unicéntrico y retrospectivo para una muestra consecutiva de pacientes con EP tratados con IICLC desde principios de 2006 hasta finales de agosto de 2021. Resultados. Se han analizado 81 planificaciones. El éxito del tratamiento (duración mayor de 12 meses) se alcanzó en el 78,1% (n = 50) de los pacientes en los que se disponía de ese período de seguimiento. La duración media del tratamiento fue de 35 meses. El 58,6% de los pacientes presentó algún tipo de complicación. Se notificaron 43 complicaciones leves y 16 complicaciones graves. Conclusión. La constitución de un equipo multidisciplinar experimentado es fundamental para garantizar un manejo y seguimiento adecuado de estos pacientes.

Background and Objectives To determine the diagnostic efficacy of clinical exome-targeted sequencing (CES) and spinocerebellar ataxia 36 (SCA36) screening in a real-life cohort of patients with cerebellar ataxia (CA) from Eastern Spain. Methods A total of 130 unrelated patients with CA, negative for common trinucleotide repeat expansions (SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, dentatorubral pallidoluysian atrophy [DRPLA], and Friedreich ataxia), were studied with CES. Bioinformatic and genotype-phenotype analyses were performed to assess the pathogenicity of the variants encountered. Copy number variants were analyzed when appropriate. In undiagnosed dominant and sporadic cases, repeat primed PCR was used to screen for the presence of a repeat expansion in the NOP56 gene. Results CES identified pathogenic or likely pathogenic variants in 50 families (39%), including 23 novel variants. Overall, there was a high genetic heterogeneity, and the most frequent genetic diagnosis was SPG7 (n = 15), followed by SETX (n = 6), CACNA1A (n = 5), POLR3A (n = 4), and SYNE1 (n = 3). In addition, 17 families displayed likely pathogenic/pathogenic variants in 14 different genes: KCND3 (n = 2), KIF1C (n = 2), CYP27A1A (n = 2), AFG3L2 (n = 1), ANO10 (n = 1), CAPN1 (n = 1), CWF19L1 (n = 1), ITPR1 (n = 1), KCNA1 (n = 1), OPA1 (n = 1), PNPLA6 (n = 1), SPG11 (n = 1), SPTBN2 (n = 1), and TPP1 (n = 1). Twenty-two novel variants were characterized. SCA36 was diagnosed in 11 families, all with autosomal dominant (AD) presentation. SCA36 screening increased the total diagnostic rate to 47% (n = 61/130). Ultimately, undiagnosed patients showed delayed age at onset (p < 0.05) and were more frequently sporadic. Discussion Our study provides insight into the genetic landscape of CA in Eastern Spain. Although CES was an effective approach to capture genetic heterogeneity, most patients remained undiagnosed. SCA36 was found to be a relatively frequent form and, therefore, should be tested prior to CES in familial AD presentations in particular geographical regions.

INTRODUCTIONContinuous intestinal infusion of levodopa/carbidopa is a second-line treatment indicated in advanced stages of Parkinson's disease (PD). For its implantation, a percutaneous endoscopic gastrostomy must be performed.OBJECTIVESThe main objective has been to describe the frequency and characteristics of the side effects associated with this treatment. As a secondary objective, we have analyzed the epidemiological and clinical characteristics of the PD patients who have received this treatment in our hospital.PATIENTS AND METHODSDescriptive, single-center, retrospective study for a consecutive sample of PD patients treated with Continuous intestinal infusion of Levodopa/Carbidopa from the beginning of 2006 to the end of August 2021.RESULTS81 treatment planifications have been analyzed. Treatment success (duration greater than 12 months) was achieved in 78.1% (n = 50) of the patients in whom this follow-up period was available. The median duration of treatment was 35 months. 58.6% of the patients presented some type of complication. A total of 43 minor complications and 16 serious adverse events were reported.CONCLUSIONThe constitution of an experienced multidisciplinary team is essential to guarantee the adequate management and follow-up of these patients.

Spastic paraplegia type 7 (SPG7) is one of the most common hereditary spastic paraplegias. SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes. We sought to clinically and genetically characterize a Spanish cohort of SPG7 patients. Patients were recruited from our HCA and HSP cohorts. We identified twenty-one patients with biallelic pathogenic SPG7 mutations. Mean age at onset was 37.4 years (SD ± 14.3). The most frequent phenotype was spastic ataxia (57%), followed by pure spastic paraplegia (19%) and complex phenotypes (19%). Isolated patients presented with focal or multifocal dystonia, subclinical myopathy or ophthalmoplegia. p.Ala510Val was the most frequent pathogenic variant encountered. Compound heterozygous for p.Ala510Val displayed younger onset (p < 0.05) and more complex phenotypes (p < 0.05) than p.Ala510Val homozygotes. Two novel variants were found: p.Lys559Argfs*33 and p.Ala312Glu. In conclusion, spastic ataxia is the most common phenotype found in Spanish patients. Nonetheless, SPG7 analysis should also be considered in patients with less frequent clinical findings such as dystonia or ophthalmoplegia especially when these symptoms are associated with mild spastic ataxia.

Hereditary spastic paraplegias (HSP) are neurodegenerative disorders with significant clinical and genetic heterogeneity. To date, more than 80 causative loci of HSP have been identified, comprising autosomal dominant, autosomal recessive, X-linked and mitochondrial inheritance patterns.1 Spastic paraplegia type 7 (SPG7) is one of the most common autosomal recessive forms. SPG7 gene encodes paraplegin a mitochondrial metalloprotease involved in mitochondrial membrane trafficking, regulation of cell components and protein metabolism.2 SPG7 mutations have been widely referred as a frequent cause of mid-age onset hereditary cerebellar ataxia.3 Mitochondrial clinical features like optic neuropathy, progressive external ophthalmoplegia or parkinsonism are being increasingly recognized.4, 5 We report a SPG7 case presenting with multifocal dystonia with prominent cranio-cervical involvement. A 28-year-old Caucasian male with gait and speech problems was referred to our Movement Disorders clinic for further diagnostic and therapeutic assessments. He was born from healthy non-consanguineous parents. Family history was unremarkable and no relevant past medical history was reported. His neurological problems started at the age of 17 with clumsiness when playing football. One year later he suffered a quite sudden aphonia that 1 month later evolved to dysarthric speech and chewing difficulties without swallowing impairment. Cervical dystonia was especially triggered when speaking or chewing. At the age of 20, he developed clumsiness with manipulation and abnormal posturing of hands when writing. He did not recognize fluctuations throughout the day. Gait difficulties slowly worsened and at 31-years-old he was unable to run indefinitely. On initial examination oromandibular and cervical dystonia, mainly antero-caput, were prominent. He showed dystonic posturing and dystonic tremor in both hands. Dystonic postures in feet emerged when walking. Tandem gait was slightly unstable although he was able to perform it without aid. Deep-tendon reflexes were increased in lower limbs with no other pyramidal signs. Extraocular movements, smooth pursuit and saccades were normal. Levodopa trial for 4 months, tetrabenazine and trihexyphenidyl treatments reported no benefits. Botulinum toxin injections on sternocleidomastoids, digastric and genioglossus muscles achieved slight relief of speech, chewing and cervical dystonia. Acquired causes were extensively excluded. Serum copper, ceruloplasmin and 24-hour urinary copper were normal. Brain MRI demonstrated mild cerebellar atrophy and T2-weighted hyperintensities of the cerebral peduncles (Fig. 1). Corpus callosum thickness was normal. Kayser-Fleischer ring was absent and funduscopic exam was normal. A focused dystonia gene panel was negative. Neurodegeneration with brain iron accumulation disorders (PANK2 and PLA2G6) and Niemann-Pick disease were also ruled out. Informed consent was obtained before genetic analysis. Three years later, examination revealed mild abnormal extraocular movements with saccadic pursuit, hypometric saccades and horizontal gaze nystagmus. Speech was dysarthric with a mixed spastic/dystonic and cerebellar quality. Finger-nose and knee-toe maneuvers showed mild dysmetria. Generalized hyperreflexia and ankle clonus were easily elicited. Right cutaneous-plantar response was flexor and left was equivocal (Video 1 and Video 2). As pyramidal and cerebellar signs became evident, we decided to perform further genetic testing. We followed a stepwise approach and initially dynamic repeat expansion mutations (SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA12, SCA17, DRPLA, FXN) were excluded. Subsequently HSP and hereditary cerebellar ataxia genes were analyzed using a custom gene panel.6 Two previously reported4 SPG7 pathogenic variants were found: c.1529C > T(p.Ala510Val) and c.1715C > T(p.Ala572Val). Segregation analysis demonstrated that variants affected both alleles (trans configuration). Herein we describe a genetically confirmed SPG7 case presenting with multifocal dystonia with prominent bulbar and cervical involvement. Emergence of cerebellar and pyramidal signs helped us to reach diagnosis. Patient's follow up was 8 years later. At present he is 36, and ambulatory gait is still preserved. Speech and chewing impairment are the most important symptoms. Dystonia in SPG7 is uncommon. Solely cases of focal dystonia have been reported. Cervical dystonia was present in two patients from the Dutch cohort.7 Spasmodic dysphonia was described in a patient of Pakistani origin8 and recently focal limb dystonia was added to SPG7 phenotypes.9 Cerebellar atrophy is the most frequent radiological abnormality in all hereditary ataxias. It was present at initial evaluation in our patient, reflecting that clinical or radiological signs of cerebellum involvement should guide genetic testing approach in dystonia-ataxia syndromes. The finding of bilateral cerebral peduncle T2 hyperintensities should also be observed as it has never been described before. Different studies have demonstrated that dystonia is a network disorder. Lesions not only in the basal ganglia but also in the cerebellum or in sensorimotor cortex may lead to the development of dystonia. Additionally, dystonia can be the presenting symptom in inherited cerebellar diseases and cerebellar atrophy can be found both in patients with idiopathic or familial dystonia.10 Recognition of new disease phenotypes will contribute to delineate the shared genetic background of dystonia-ataxia syndromes and also improve the yield of genetic testing. This case widens SPG7 phenotype with multifocal dystonia and shows that SPG7 should be included in the differential diagnosis of combined dystonia, especially when clinical and/or radiological pyramidal and cerebellar signs are present. 1. Research Project: A Conception, B. Organization, C. Execution; 2 Statistical Analysis A. Design, B. Execution, C Review and Critique; 3. Manuscript Preparation: A. Writing the first draft, B: Review and Critique. MCR: 1A, 1B, 1C, 2A, 2B, 3A RBM: 1A, 1B, 1C, 2A, 2B, 3A ISB: 2C, 3B LB: 2C, 3B TJ: 2C, 3B IMT: 2C, 3B We thank the patient and his family for their patience and cooperation. We thank Dr Carmen Espinós and her team at the Unit of Rare Neurodegenerative Disease in Centro de Investigación Príncipe Felipe (CIPF) for performing further genetic analysis in our patient and providing comprehensive assessment of the technical methods and results. The authors confirm that the approval of an institutional review board was not required for this work. Patient provided written informed consent for clinical information and video material use for academic purposes. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The authors report no sources of funding and no conflicts of interest. The authors report no sources of funding and no conflicts of interest.

Deletions of 2p11.2-p12 are exceedingly rare with few reported cases.1,2 Most patients display a mild-to-moderate developmental delay and intellectual disability. Additional manifestations are happy disposition, tendency to obesity, and minor dysmorphic features, such as short stature, prominent forehead, hypertelorism, broad nasal bridge, or large low-set ears. Occasionally congenital malformations are present, such as chest and spine abnormalities, urogenital malformations, or atrial septal defect.1 In this study, we report a patient presenting with early-onset atypical parkinsonism carrying a heterozygous 3.9-Mb deletion on 2p11.2.