Article
Clinical Neurology
David Pellerin, Carlo Wilke, Andreas Traschuetz, Sara Nagy, Riccardo Curro, Marie-Josee Dicaire, Hector Garcia-Moreno, Mathieu Anheim, Thomas Wirth, Jennifer Faber, Dagmar Timmann, Christel Depienne, Dan Rujescu, Jose Gazulla, Mary M. Reilly, Paola Giunti, Bernard Brais, Henry Houlden, Ludger Schoels, Michael Strupp, Andrea Cortese, Matthis Synofzik
Summary: Intronic GAA repeat expansions in the FGF14 gene are a common cause of cerebellar ataxia with polyneuropathy and/or bilateral vestibulopathy. They have potential phenotypic overlap with RFC1-related CANVAS syndrome. This study found a high frequency of FGF14 GAA repeat expansions in patients with an unexplained CANVAS-like phenotype.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Review
Clinical Neurology
Martje E. van Egmond, Tjerk J. Lagrand, Gintaute Lizaitiene, Marenka Smit, Marina A. J. Tijssen
Summary: Adult-onset dystonia can be acquired, inherited or idiopathic. Recent advances in neuroimmunology and genetic diagnostics have increased our understanding of the disease. To ensure early diagnosis and prevent unnecessary investigations, a new five-step diagnostic approach has been designed. The approach focuses on early identification of treatable forms of dystonia, both acquired and genetic. This novel diagnostic method can aid clinicians in deciding when to perform additional tests, including genetic testing, and facilitate timely treatment.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Clinical Neurology
Pablo Iruzubieta, David Pellerin, Alberto Bergareche, Ines Albajar, Elisabet Mondragon, Ana Vinagre, Roberto Fernandez-Torron, Fermin Moreno, Jon Equiza, David Campo-Caballero, Juan Jose Poza, Marta Ruibal, Alessandro Formica, Marie-Josee Dicaire, Matt C. Danzi, Stephan Zuchner, Ioana Croitoru, Montserrat Ruiz, Agatha Schluter, Carlos Casasnovas, Aurora Pujol, Bernard Brais, Henry Houlden, Adolfo Lopez de Munain, Javier Ruiz-Martinez
Summary: This study aimed to investigate the frequency and phenotype of SCA27B in patients with unsolved late-onset cerebellar ataxia (LOCA). The results showed that SCA27B is the most common cause of LOCA and screening for FGF14 GAA repeat expansion is recommended as a first-tier genetic test in these patients.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
V Montano, D. Orsucci, V Carelli, C. La Morgia, M. L. Valentino, C. Lamperti, S. Marchet, O. Musumeci, A. Toscano, G. Primiano, F. M. Santorelli, C. Ticci, M. Filosto, A. Rubegni, T. Mongini, P. Tonin, S. Servidei, R. Ceravolo, G. Siciliano, Michelangelo Mancuso
Summary: The study reviewed the prevalence and clinical features of movement disorders in adults with primary mitochondrial diseases of the Italian Collaborative Network of Mitochondrial Diseases. It emphasizes the importance of considering a mitochondrial etiology in the diagnostic flowchart of a movement disorder.
JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Santiago Perez-Lloret, Bart van de Warrenburg, Malco Rossi, Carmen Rodriguez-Blazquez, Theresa Zesiewicz, Jonas A. M. Saute, Alexandra Durr, Masatoyo Nishizawa, Pablo Martinez-Martin, Glenn T. Stebbins, Anette Schrag, Matej Skorvanek
Summary: This study evaluated the clinimetric properties of various ataxia rating scales and functional tests, identifying recommended scales and tests for patients with major hereditary ataxias and other cerebellar disorders. However, the main limitations of these instruments include limited assessment of patients on the severe end of the spectrum and children. Further research is needed in these populations.
MOVEMENT DISORDERS
(2021)
Article
Neurosciences
Vittorio Riso, Salvatore Rossi, Tommaso F. Nicoletti, Alessandra Tessa, Lorena Travaglini, Ginevra Zanni, Chiara Aiello, Alessia Perna, Melissa Barghigiani, Maria Grazia Pomponi, Filippo M. Santorelli, Gabriella Silvestri
Summary: The study retrospectively evaluated the molecular diagnostic rate of Hereditary Spastic Paraplegias (HSP) and inherited cerebellar ataxias (CA) in 192 unrelated families in a third-level reference center, indicating that the diagnostic rate of HSP and CA is influenced by patient selection and suggesting the important role of experienced clinicians in diagnostic assessment and clinical research.
Review
Biochemistry & Molecular Biology
Konrad Kaminiow, Izabella Rygula, Justyna Paprocka
Summary: There are over 150 inherited metabolic disorders that can present as ataxia in children. Neuroimaging studies and genetic studies are essential for diagnosis. Prompt treatment can positively influence neurodevelopment.
Article
Clinical Neurology
Chi-Ying R. Lin, Nadia Amokrane, Serena Chen, Tiffany X. Chen, Ruo-Yah Lai, Paula Trinh, Michael J. Minyetty, Haidyn Emmerich, Ming-Kai Pan, Daniel O. Claassen, Sheng-Han Kuo
Summary: This study describes the development and validation of a new scale (CIA) to assess impulsive and compulsive behaviors (ICBs) in cerebellar ataxia patients. The findings show that patients with ICBs have three times higher total CIA scores than those without ICBs, and CIA demonstrates good internal consistency across all items.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Review
Neurosciences
Chun-Hwei Tai, Sheng-Hong Tseng
Summary: Deep brain stimulation (DBS) is an effective treatment for various movement disorders, but some disorders do not respond well to current DBS therapy. Recent studies have suggested that cerebellar DBS may be beneficial for these non-responsive movement disorders. This article reviews the clinical data of cerebellar DBS, including indications, surgical targets, programming details, and outcomes, and discusses the potential mechanism of action. The study of new DBS targets in the cerebellum is important for a comprehensive treatment of movement disorders.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Neurosciences
Mehri Salari, Masoud Etemadifar, Ronak Rashedi, Sayna Mardani
Summary: This review article examines ocular movements in cerebellar ataxias to enhance clinical knowledge of these disorders and their subtypes. English papers published from January 1990 to May 2022 were analyzed, focusing on the clinical presentation, mutations, underlying pathology, and ocular movement alterations. The study discusses 43 subtypes of spinocerebellar ataxias and several autosomal dominant and autosomal recessive ataxias, emphasizing ocular abnormalities. A flowchart and illustrated models were created to differentiate ataxia subtypes and better understand the underlying pathology of each.
Article
Clinical Neurology
Filip Milosavljevic, Irene Brusini, Andrea Atanasov, Marina Manojlovic, Marija Vucic, Zorana Orescanin-Dusic, Jelena Brkljacic, Cedo Miljevic, Aleksandra Nikolic-Kokic, Dusko Blagojevic, Chunliang Wang, Peter Damberg, Vesna Pesic, Rachel F. Tyndale, Magnus Ingelman-Sundberg, Marin M. Jukic
Summary: It was found that humanized CYP2C19 transgenic mice exhibited abnormal gait and functional motor impairments, possibly due to aberrant cerebellar development.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Review
Clinical Neurology
Poonam Bhatia, Jennifer Heim, Patricia Cornejo, Lauren Kane, Jason Santiago, Michael C. Kruer
Summary: Opsoclonus-myoclonus-ataxia syndrome is a rare neuroimmunologic disorder that typically occurs in infants and toddlers, with about half of cases associated with neuroblastoma. The syndrome is characterized by saccadic intrusions, myoclonus, and behavioral abnormalities, and historically had poor long-term outcomes. Recent immunotherapy regimens offer hope for better outcomes in these children.
JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Anthony J. Linares, Brent L. Fogel
Summary: Late-onset genetic cerebellar ataxias are clinically heterogenous and can present with variable phenotypes, including dementia. Understanding the relationship between ataxia and dementia can guide clinical genetic evaluation.
CURRENT OPINION IN NEUROLOGY
(2023)
Review
Clinical Neurology
Paulina Gonzalez-Latapi, Mario Sousa, Anthony E. Lang
Summary: Hypogonadism is associated with various movement disorders, with ataxia being the most common one. Tremor is also frequently described, especially in genetic conditions like aneuploidies. Clinicians should be aware of this association and accompanying symptoms for precise diagnosis.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2021)
Review
Clinical Neurology
Malco Rossi, Moath Hamed, Jon Rodriguez-Antiguedad, Mario Cornejo-Olivas, Marianthi Breza, Katja Lohmann, Christine Klein, Rajasumi Rajalingam, Connie Marras, Bart P. van de Warrenburg
Summary: This article systematically reviewed the genotype-phenotype relationships and reevaluated the pathological range of repeat expansions in ATX-TBP. The study proposed new cutoff values for reduced penetrance (41-45 expanded repeats) and full penetrance (46-66 expanded repeats), which have important diagnostic and counseling implications and may guide future clinical trial protocols.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Blas Couto, Susan Fox, Maria Carmela Tartaglia, Ekaterina Rogaeva, Jeffrey Antwi, Puja Bhakta, Gabor G. Kovacs, Anthony E. E. Lang
Summary: The study focuses on the development and initial experience of the Rossy PSP Centre in Canada, which aims to advance clinical and basic research in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The study collects extensive demographic and longitudinal clinical information using standardized forms, as well as biofluids for genetic analysis and neuroimaging research protocols. The preliminary results show a typical distribution of phenotypes, demographics, and response to symptomatic treatments in the cohort. Future steps include enrolling patients in earlier stages, developing biomarkers, and fast-tracking well-characterized patients into clinical trials.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Letter
Clinical Neurology
Hidetomo Tanaka, Megan A. Hird, David F. Tang-Wai, Gabor G. Kovacs
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Shojiro Ichimata, Ain Kim, Naoki Nishida, Gabor G. G. Kovacs
Summary: The aim of this study is to clarify whether there is a difference in amyloid-beta burden between gyral crests (GCs) and sulcal depths (SDs) in different neurodegenerative proteinopathies. The study found that amyloid-beta is almost evenly distributed in both GCs and SDs in the frontal and temporal lobes.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Agoston Patthy, Janos Hanics, Gergely Zachar, Gabor G. Kovacs, Tibor Harkany, Alan Alpar
Summary: The expression and function of CB1R in the developing human brain, as well as in Down syndrome foetuses, were analyzed. The study found that CB1R expression was delayed in age-matched foetuses with Down syndrome, and abnormal CB1R signaling was identified. In vitro experiments showed that CB1R excitation led to excessive microtubule stabilization and reduced neurite outgrowth.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Caterina Marchioretti, Giulia Zanetti, Marco Pirazzini, Gaia Gherardi, Leonardo Nogara, Roberta Andreotti, Paolo Martini, Lorenzo Marcucci, Marta Canato, Samir R. Nath, Emanuela Zuccaro, Mathilde Chivet, Cristina Mammucari, Marco Pacifici, Anna Raffaello, Rosario Rizzuto, Andrea Mattarei, Maria A. Desbats, Leonardo Salviati, Aram Megighian, Gianni Soraru, Elena Pegoraro, Elisa Belluzzi, Assunta Pozzuoli, Carlo Biz, Pietro Ruggieri, Chiara Romualdi, Andrew P. Lieberman, Gopal J. Babu, Marco Sandri, Bert Blaauw, Manuela Basso, Maria Pennuto
Summary: Marchioretti and colleagues demonstrate that there are reversible alterations in gene expression related to muscle contraction and mitochondrial respiration in the skeletal muscle of SBMA mice and patients. These alterations are accompanied by calcium accumulation inside the mitochondria, motor dysfunction, and late changes in muscle structure. The deregulation of expression of genes involved in excitation-contraction coupling (ECC) occurs with sexual maturity and androgen increase in the serum. Surgical castration and AR silencing alleviate the early and late pathological processes, indicating an androgen-dependent nature of these alterations.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Ramachandran Prakasam, Angela Bonadiman, Roberta Andreotti, Emanuela Zuccaro, Davide Dalfovo, Caterina Marchioretti, Debasmita Tripathy, Gianluca Petris, Eric N. Anderson, Alice Migazzi, Laura Tosatto, Anna Cereseto, Elena Battaglioli, Gianni Soraru, Wooi Fang Lim, Carlo Rinaldi, Fabio Sambataro, Naemeh Pourshafie, Christopher Grunseich, Alessandro Romanel, Udai Bhan Pandey, Andrea Contestabile, Giuseppe Ronzitti, Manuela Basso, Maria Pennuto
Summary: Prakasam and colleagues demonstrate that targeting overexpressed co-activators Lsd1 and Prmt6 with artificial miRNAs can attenuate polyQ-expanded androgen receptor toxicity, ameliorating spinal-bulbar muscular atrophy phenotypes in flies and mice. This study suggests that targeting these co-regulators could be a potential therapeutic strategy for patients with SBMA, as it helps mitigate toxic gain-of-function without exacerbating loss-of-function mechanisms.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Diana Piol, Laura Tosatto, Emanuela Zuccaro, Eric N. Anderson, Antonella Falconieri, Maria J. Polanco, Caterina Marchioretti, Federica Lia, Joseph White, Elisa Bregolin, Giovanni Minervini, Sara Parodi, Xavier Salvatella, Giorgio Arrigoni, Andrea Ballabio, Albert R. La Spada, Silvio C. E. Tosatto, Fabio Sambataro, Diego L. Medina, Udai B. Pandey, Manuela Basso, Maria Plennuto
Summary: Spinal and bulbar muscular atrophy is caused by polyglutamine expansions in androgen receptor, leading to gain-of-function toxicity. This study investigates the phosphorylation of polyglutamine-expanded receptor and its role in neurodegeneration. The researchers find that certain kinases and phosphatases can modify the function and toxicity of the receptor, and targeting these enzymes can potentially be used as a therapeutic approach.
Article
Clinical Neurology
Krisztina Danics, Naomi P. Visanji, Shojiro Ichimata, Sarika Mathur, Gabriella Sara-Klausz, Gabor G. Kovacs
Summary: This study investigates the prevalence and distribution of pathological alpha-synuclein deposition in the central and peripheral nervous systems of the homeless population. The findings suggest that alpha-synuclein pathology is prevalent in this vulnerable population, supporting the need for further research.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shojiro Ichimata, Ivan Martinez-Valbuena, Seojin Lee, Jun Li, Ali M. Karakani, Gabor G. Kovacs
Summary: Limited comparative data exist on the molecular spectrum of amyloid-beta (Aβ) and tau deposition in individuals with Down syndrome (DS) and sporadic Alzheimer's disease (sAD). We found that DS cases had more severe Aβ and tau deposition in the temporal lobe and cerebellum compared to sAD cases, as confirmed by both semi-quantitative and quantitative analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Johanna Junker, James Hall, Brian D. Berman, Marie Vidailhet, Emmanuel Roze, Tobias Baeumer, Irene A. Malaty, Aparna Wagle Shukla, Joseph Jankovic, Stephen G. Reich, Alberto J. Espay, Kevin R. Duque, Neepa Patel, Joel S. Perlmutter, H. A. Jinnah, Valerie Dystonia Coalition Study Group, Valerie Brandt, Norbert Brueggemann
Summary: This study aimed to determine longitudinal predictors of health-related quality of life in patients with isolated dystonia. The results showed that depressive symptoms, generalized anxiety disorder, and social anxiety disorder significantly impacted HR-QoL, highlighting the importance of incorporating mental health treatment into treatment regimens.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Emily J. Hill, Jennifer Sharma, Benjamin Wissel, Russell P. Sawyer, Megan Jiang, Luca Marsili, Kevin Duque, Vanesa Botsford, Christopher Wood, Kelly DeLano, Qin Sun, Brett Kissela, Alberto J. Espay
Summary: This study aimed to determine whether excluding diagnoses of peripheral parkinsonism and drug-induced parkinsonism improves the accuracy of ICD-9 and -10 codes for Parkinson's disease. The study found that although accuracy was lowest in Black patients, removing other parkinsonism codes had a significant impact on accuracy. This highlights the limitations of using current real-world electronic health record data in Parkinson's disease research and calls for further study.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Audiology & Speech-Language Pathology
Fulvio Mammarella, Antonella Loperfido, Elizabeth G. Keeling, Gianluca Bellocchi, Luca Marsili
Summary: The aim of this study was to gather data on a large community sample of Meniere's disease (MD) patients in Italy through a web-based nationwide survey. Demographic, clinical, and epidemiological information was collected from members of the Italian Association of Meniere's Disease (AMMI) using an online questionnaire. The study included 520 patients, with an average age of 51.4 years and a disease duration of 9.9 years. The findings provide valuable insights into the epidemiology and current treatment patterns of MD in Italy and highlight the potential utility of web-based surveys in improving patient management.
AUDIOLOGY RESEARCH
(2023)
Article
Clinical Neurology
Agoston Patthy, Janos Hanics, Gergely Zachar, Gabor G. Kovacs, Tibor Harkany, Alan Alpar
Summary: The study revealed significant changes in CB1R expression in different brain regions during human embryonic development, as well as delayed CB1R development in individuals with Down syndrome. This delayed development may lead to impairments in brain neuroarchitecture, affecting neuronal development and synaptogenesis.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Letter
Clinical Neurology
Luca Marsili, Marcelo A. Kauffman, Diandra Rufin Florat, Amir Zaidi, Vanesa Botsford, Jennifer Sharma, Elizabeth G. Keeling, Joseph P. Broderick, Saulius Sumanas, Alberto J. Espay
Summary: This article describes an elderly woman who meets the criteria for vascular parkinsonism/dementia associated with a likely pathogenic COL22A1 gene variant. The findings are supported by functional experiments in a zebrafish model. The authors suggest that white matter hyperintensities may not represent small-vessel ischemic disease and propose that COL22A1 may be included among the adult-onset leukoencephalopathies mislabeled as vascular parkinsonism.
PARKINSONISM & RELATED DISORDERS
(2023)