Review
Biochemistry & Molecular Biology
Shih-Ying Chen, Chen-Jui Ho, Yan-Ting Lu, Chih-Hsiang Lin, Min-Yu Lan, Meng-Han Tsai
Summary: Primary Familial Brain Calcification (PFBC), also known as Fahr's disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia. It can also affect other brain regions such as the thalamus, cerebellum, and subcortical white matter. Common symptoms include movement disorders, cognitive deficits, and psychiatric disturbances. Genetic studies have identified seven genes associated with PFBC, and further research is needed to uncover additional genes. Understanding the underlying pathogenic mechanisms may lead to the development of new therapies for PFBC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sandrine Lenglez, Ariane Sablon, Gilles Fenelon, Anne Boland, Jean-Francois Deleuze, Claire Boutoleau-Bretonniere, Gael Nicolas, Jean-Baptiste Demoulin
Summary: This study conducted a comprehensive molecular analysis and functional studies on PDGFRB gene variants associated with primary familial brain calcification, identifying pathogenic variants and discussing the relationship between residual activity of variants, incomplete penetrance, brain calcification, and neurological symptoms.
HUMAN MOLECULAR GENETICS
(2022)
Article
Psychology, Clinical
Evan Zahniser, Thomas D. Bird, Dong-Hui Chen, Shu-Ching Hu, Wendy H. Raskind, Emily H. Trittschuh
Summary: This study presents neurogenetic, neuroimaging, neurological, and serial neuropsychological data of a father and son with FIBGC. The results show that both subjects have brain calcification mainly in the basal ganglia and cerebellum, but present different clinical symptoms. Longitudinal observation revealed relatively stable cognitive performance in various domains for both subjects.
ARCHIVES OF CLINICAL NEUROPSYCHOLOGY
(2022)
Article
Clinical Neurology
Meiying Li, Qin Fu, Liangxu Xiang, Yingwei Zheng, Wenjing Ping, Yongjun Cao
Summary: This study reports a case of familial basal ganglia calcification caused by a frameshift mutation in the SLC20A2 gene. A new mutation site was identified, which expands the range of known SLC20A2 mutations and aids in the genetic diagnosis of IBGC.
Article
Multidisciplinary Sciences
Tomiko Takeuchi, Hisami Aoyagi, Yoshimi Kuwako, Isao Hozumi
Summary: This study aims to identify the experiences of patients with PDGFB variants of primary brain calcification after diagnosis. Semi-structured interviews were conducted with five patients over the age of 21 for three years. The results revealed seven categories, 15 subcategories, and 129 codes, including shock at hearing the term 'brain calcification' for the first time, anxiety regarding the risk of heredity, anxiety along with severe headaches and various other symptoms, gratitude for family members who care, accepting the disease as a non-life-threatening illness, feeling alienated due to the rare and intractable disease, and modifying lifestyle due to the illness.
Article
Clinical Neurology
Kenji Sakai, Chiho Ishida, Koji Hayashi, Naotaka Tsuji, Takayuki Kannon, Kazuyoshi Hosomichi, Nobuyuki Takei, Akiyoshi Kakita, Atsushi Tajima, Masahito Yamada
Summary: We describe a postmortem case of familial idiopathic basal ganglia calcification (FIBGC) in a 72-year-old Japanese man. The patient showed progressive cognitive impairment with calcification of the basal ganglia, thalami, and cerebellar dentate nuclei. A novel heterozygous missense variant in SLC20A2 was identified, along with typical neuropathological findings of FIBGC. Immunohistochemistry and Western blot analysis revealed the potential role of the variant in the regulation of inorganic phosphate transport activity. Abnormal clearance of inorganic phosphate in the brain could be related to the development of vascular smooth muscle damage and subsequent brain calcification in patients with FIBGC.
Editorial Material
Clinical Neurology
Shanyu Pi, Qiuxiang Li, Jing Li, Hongyu Long, Bo Xiao
Summary: A 14-year-old girl presented with acute ascending, symmetric numbness, and flaccid paralysis 3 weeks after a suspected gastrointestinal infection. She had experienced anorexia since this gastrointestinal episode. EMG showed a sensorimotor axonal polyneuropathy. Routine CSF analysis and serum-specific antibodies were all negative. Brain MRI showed bilateral symmetric basal ganglia lesions. A more thorough and detailed history indicated exercise intolerance, and specific examinations subsequently revealed an underlying etiology.
Article
Clinical Neurology
Sofia Maldonado Slootjes, Koenraad Nieboer, Sylvie De Raedt
Summary: An right-handed elderly woman with a history of multiple medical conditions presented with sudden-onset global aphasia and right-sided hemiparesis. Initial imaging with non-contrast brain CT showed a unilateral hyperdensity in the left caudate and lentiform nuclei. Further laboratory studies were pending at the time of imaging. What is your diagnosis?
NEUROLOGICAL SCIENCES
(2023)
Article
Medicine, General & Internal
Bei-Ni Fei, Hui-Zhen Su, Xiang-Ping Yao, Jing Ding, Xin Wang
Summary: Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative disease characterized by symmetrical calcification of basal ganglia and other brain regions. Detection of MYORG mutation is crucial for better understanding and potential treatments, especially in patients without an obvious family history.
WORLD JOURNAL OF CLINICAL CASES
(2021)
Review
Clinical Neurology
Jatinder Singh Goraya
Summary: Mineralizing lenticulostriate vasculopathy is a well-known risk factor for basal ganglia stroke in infants and young children after minor head trauma. It can be diagnosed through computed tomography and cranial ultrasound. Magnetic resonance imaging fails to detect its presence. The condition is considered to be the end-stage pathology of lenticulostriate vasculopathy and is associated with a variety of etiologies. Its importance lies in its high prevalence as a risk factor for basal ganglia stroke in Indian children.
PEDIATRIC NEUROLOGY
(2023)
Article
Cell Biology
Miao Zhao, Hui-Zhen Su, Yi-Heng Zeng, Yuan Sun, Xin-Xin Guo, Yun-Lu Li, Chong Wang, Zhi-Yuan Zhao, Xue-Jing Huang, Kai-Jun Lin, Zi-Ling Ye, Bi-Wei Lin, Shunyan Hong, Jitan Zheng, Yao-Bin Liu, Xiang-Ping Yao, Dehao Yang, Ying-Qian Lu, Hai-Zhu Chen, Erwei Zuo, Guang Yang, Hong-Tao Wang, Chen-Wei Huang, Xiao-Hong Lin, Zhidong Cen, Lu-Lu Lai, Yan-Ke Zhang, Xi Li, Tianmin Lai, Jingjing Lin, Dan-Dan Zuo, Min-Ting Lin, Chia-Wei Liou, Qing-Xia Kong, Chuan-Zhu Yan, Zhi-Qi Xiong, Ning Wang, Wei Luo, Cui-Ping Zhao, Xuewen Cheng, Wan-Jin Chen
Summary: Brain calcification is a critical pathology associated with aging. This study identifies biallelic variants of the CMPK2 gene as novel genetic factors for familial brain calcification (FBC) and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, highlighting mitochondria dysregulation as a critical mechanism underlying brain calcification.
Article
Endocrinology & Metabolism
Guido Zavatta, Peter J. Tebben, Cynthia H. McCollough, Lifeng Yu, Thomas Vrieze, Bart L. Clarke
Summary: Basal ganglia calcification is more common in chronic hypoparathyroidism patients, especially in nonsurgical patients with lower serum calcium and calcium/phosphate ratio.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Clinical Neurology
Esther J. M. de Brouwer, Pim A. de Jong, Annemarieke De Jonghe, Marielle H. Emmelot-Vonk, Huiberdina L. Koek, Jan-Willem Dankbaar, Firdaus A. A. Mohamed Hoesein, Wim Van Hecke
Summary: Incidental basal ganglia calcifications are commonly seen on CT scans. A study on the histological characteristics of these calcifications found that they are mainly located in the tunica media of arterioles in the globus pallidus, suggesting a vascular origin. However, these calcifications are not likely related to atherosclerosis.
Article
Neurosciences
Jinnan Gong, Sisi Jiang, Zhiliang Li, Haonan Pei, Qifu Li, Dezhong Yao, Cheng Luo
Summary: This study utilized diffusion and functional MRI to investigate the pathoglytic changes in the basal ganglia-thalamocortical and cerebellum-thalamocortical pathways in people with idiopathic generalized epilepsy (IGE). The findings revealed connectivity changes with perception and cognition systems and identified abnormal integration of sensorimotor and visual information in IGE. Aberrant functional and structural integration of cerebellum, basal ganglia, and thalamus were linked to cognitive impairment and epileptic activities in IGE.
HUMAN BRAIN MAPPING
(2021)
Article
Psychiatry
Masanori Isobe, Matilde Vaghi, Naomi A. Fineberg, Annemieke M. Apergis-Schoute, Edward T. Bullmore, Barbara J. Sahakian, Trevor W. Robbins, Samuel R. Chamberlain
Summary: The study demonstrates a link between cognitive inflexibility and putamen morphology in OCD patients and their relatives, indicating a familial marker of OCD. The findings suggest a shared abnormality in basal ganglia structure associated with cognitive rigidity among individuals with OCD and their asymptomatic relatives.
BRITISH JOURNAL OF PSYCHIATRY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Keith A. Josephs, Nirubol Tosakulwong, Stephen D. Weigand, Marina Buciuc, Val J. Lowe, Dennis W. Dickson, Jennifer L. Whitwell
Summary: F-18-flortaucipir PET uptake is not associated with 4R tau lesion types, but may have marginal correlation with thread-like lesions in specific brain regions and astrocytic lesions in the red nucleus.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Yi Xiao Jiang, Qin Cao, Michael R. Sawaya, Romany Abskharon, Peng Ge, Michael DeTure, Dennis W. Dickson, Janine Y. Fu, Rachel R. Ogorzalek Loo, Joseph A. Loo, David S. Eisenberg
Summary: This study found that amyloid fibrils in FTLD-TDP patients are formed by TMEM106B protein rather than TDP-43 protein. In addition, abundant non-fibrillar aggregated TDP-43 protein was observed.
Article
Neurosciences
Shunsuke Koga, Mariam Ishaque, W. Jeffrey Elias, Binit B. Shah, Aya Murakami, Dennis W. Dickson
Summary: This study reports the first postmortem neuropathologic findings of FUS thalamotomy in a patient with tremor-dominant PD. The results suggest that FUS thalamotomy can improve tremor symptoms and cause thalamic lesions, with implications for understanding PD-related pathology. Further pathological assessments are needed.
NPJ PARKINSONS DISEASE
(2022)
Editorial Material
Clinical Neurology
Shunsuke Koga, Hiroaki Sekiya, Nicholas B. Martin, Dennis W. Dickson
Article
Clinical Neurology
Aya Murakami, Shunsuke Koga, Hiroaki Sekiya, Bjorn Oskarsson, Kevin Boylan, Leonard Petrucelli, Keith A. Josephs, Dennis W. Dickson
Summary: This study aimed to assess and compare the burden of transactive response DNA-binding protein of 43 kDa (TDP-43) pathology and clinical features of amyotrophic lateral sclerosis (ALS) in three age groups. The study found that the amygdala and hippocampus are vulnerable to TDP-43 pathology in older patients with ALS.
Article
Neurosciences
Diego Iacono, Shunsuke Koga, Hui Peng, Arulmani Manavalan, Jessica Daiker, Monica Castanedes-Casey, Nicholas B. Martin, Aimee R. Herdt, Michael H. Gelb, Dennis W. Dickson, Chris W. Lee
Summary: Krabbe Disease is an autosomal recessive disorder caused by mutations in the GALC gene, leading to demyelination in the central and peripheral nervous systems. Research shows that GALC protein is mainly located in oligodendrocytes in the cerebral white matter, associated with myelination. Neuropathological changes associated with KD onset and severity were observed.
NEUROBIOLOGY OF DISEASE
(2022)
Letter
Clinical Neurology
Shan Ali, Philip W. Tipton, Shunsuke Koga, Erik H. Middlebrooks, Keith A. Josephs, Audrey Strongosky, Dennis W. Dickson, Zbigniew K. Wszolek
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Clinical Neurology
Apoorva A. Kumar, Natalie Yeo, Max Whittaker, Priya Attra, Thomas R. Barrick, Leslie R. Bridges, Dennis W. Dickson, Margaret M. Esiri, Chad W. Farris, Delyth Graham, Wen Lang Lin, Daniel N. Meijles, Anthony C. Pereira, Gregory Perry, Douglas L. Rosene, Anan B. Shtaya, Tom Van Agtmael, Giovanna Zamboni, Atticus H. Hainsworth
Summary: Vascular collagen-IV in cerebral small arteries of older people is negatively associated with radiological SVD severity, but not related to history of hypertension. Reduced collagen-IV is accompanied by accumulation of fibrillar collagens. Brain collagen-IV is elevated in older normotensive primates, but not associated with hypertension. Collagen-IV in arterial tissue does not differ between genetically hypertensive and normotensive rats.
Article
Clinical Neurology
Shunsuke Koga, Shan Ali, Matthew C. Baker, Klaas J. Wierenga, Michelle Dompenciel, Dennis W. Dickson, Zbigniew K. Wszolek
Summary: Sporadic, adult-onset cerebellar ataxia is a disease with multiple etiologies. In this viewpoint article, two patients with rapidly progressive disease course and extracerebellar symptoms resembling prion disease are described. Pathological findings reveal degenerative changes in both the cerebellar cortex and thalamus. Whole genome sequencing did not identify any pathogenic variants associated with cerebellar ataxia.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Clinical Neurology
Nicholas B. B. Martin, Shunsuke Koga, Brian S. S. Appleby, Hiroaki Sekiya, Dennis W. Dickson
Summary: Two cases of patients who were misdiagnosed with multiple system atrophy (MSA) actually had Creutzfeldt-Jakob disease (CJD), as confirmed by neuropathological findings. This suggests that when the disease progresses rapidly or the clinical course is atypical, even if clinical features suggest MSA, the possibility of CJD should also be considered.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Letter
Clinical Neurology
Shunsuke Koga, Aya Murakami, Nicholas B. Martin, Dennis W. Dickson
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Hiroaki Sekiya, Shunsuke Koga, Aya Murakami, Miki Kawazoe, Minji Kim, Nicholas B. Martin, Ryan J. Uitti, William P. Cheshire, Zbigniew K. Wszolek, Dennis W. Dickson
Summary: The study compared the diagnostic accuracy of the MDS criteria and second consensus criteria for MSA, finding that the MDS criteria had higher specificity for clinically established and probable MSA, while the second consensus criteria had higher sensitivity for probable and possible MSA.
Article
Multidisciplinary Sciences
Junhao Li, Manoj K. Jaiswal, Jo-Fan Chien, Alexey Kozlenkov, Jinyoung Jung, Ping Zhou, Mahammad Gardashli, Luc J. Pregent, Erica Engelberg-Cook, Dennis W. Dickson, Veronique V. Belzil, Eran A. Mukamel, Stella Dracheva
Summary: The repeat expansion in the C9orf72 gene is a common genetic cause of ALS and FTD. The study found pervasive alterations in gene expression and chromatin accessibility in neurons and astrocytes of C9-ALS patients, as well as gene expression changes in glial cells of C9-FTD patients. These findings indicate unique molecular disruptions in different cell types, brain regions, and diseases.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Aimee R. Herdt, Hui Peng, Dennis W. Dickson, Todd E. Golde, Elizabeth A. Eckman, Chris W. Lee
Summary: Krabbe disease is a neurologic disorder characterized by the accumulation of psychosine in the CNS. In a mouse model, treatment with AAV1-GALC, a viral vector expressing GALC, significantly improved body weight gain and survival, as well as normalized psychosine levels in the brain.
Letter
Clinical Neurology
Miki Kawazoe, Shunsuke Koga, Dennis W. Dickson
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
