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Memon ZF, Memon SF, Memon MF, Shah HH, Hussain T. A Rare Case of Hypoparathyroidism With Basal Ganglia Calcification in a 17-year-old Epileptic Patient Presenting With Falciparum Malaria, Thrombocytopenia and Anemia. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2025; 18:11795476251332438. [PMID: 40313403 PMCID: PMC12044265 DOI: 10.1177/11795476251332438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 03/18/2025] [Indexed: 05/03/2025]
Abstract
Fahr Syndrome or Strio-Pallido Dentate Calcinosis is a rare neurological syndrome characterized by deposition of calcium in basal ganglia, which usually occurs secondary to other underlying endocrinological disorders like hypo/hyper-parathyroidism. Symptoms vary greatly and may range from psychiatric ones like confusion and hallucination to neurological like Tremors, Rigidity, with seizures being the rarest manifestation. Laboratory tests and brain imaging play a crucial role in establishing the diagnosis, while treatment primarily focuses on managing symptoms. Here, we report a case of a 17-year-old female diagnosed with Fahr's syndrome secondary to hypo-parathyroidism, onset of the disease at such young age coupled with uncommon presentation of fits makes this case rather remarkable.
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Affiliation(s)
- Zauha Fawad Memon
- Medicine, Peoples University of Medical and Health Sciences, Nawabshah, Sindh, Pakistan
| | - Sibgha Fawad Memon
- Medicine, Peoples University of Medical and Health Sciences, Nawabshah, Sindh, Pakistan
| | - Matia Fawad Memon
- Medicine, Peoples University of Medical and Health Sciences, Nawabshah, Sindh, Pakistan
| | | | - Tooba Hussain
- Medicine, Dow University of Health Sciences, Karachi, Sindh, Pakistan
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Mishra A, Dawadi B, Neupane N, Khanal SB, Neupane NP, Mishra A, Chaudhary B. Fahr's disease presenting with ischemic stroke in young adult: a case report of rare disease with unique presentation. Ann Med Surg (Lond) 2025; 87:2444-2448. [PMID: 40212149 PMCID: PMC11981330 DOI: 10.1097/ms9.0000000000003151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 02/22/2025] [Indexed: 04/13/2025] Open
Abstract
Introduction and importance Fahr's disease, or bilateral striopallidodentate calcinosis, is a rare autosomal dominant neurological disorder characterized by bilateral symmetrical calcifications in the basal ganglia, thalamus, hippocampus, dentate nucleus, cerebral cortex, and cerebellar subcortical white matter. Typically presenting with cognitive, psychiatric, and extrapyramidal symptoms in middle age, its presentation as an acute ischemic stroke is exceedingly rare. This case report presents this unusual occurrence. Case presentation A 32-year-old female presented with sudden onset weakness in her left lower limb, slurred speech, and facial deviation to the right. Over the next 2 days, the weakness extended to her left upper limb. Neurological examination revealed left-sided lower motor neuron lesion of the facial nerve, upper motor neuron signs, mild left-sided motor weakness, and cerebellar signs. Non-contrast computed tomography (CT) and magnetic resonance imaging (MRI) imaging showed extensive symmetrical calcifications in the basal ganglia, thalamus, dentate nucleus, and other deep gray matter structures, along with acute ischemic changes in the right corona radiata and internal capsule. All metabolic and endocrine evaluations were normal. Discussion Fahr's disease is associated with abnormal calcium deposition in the brain. The underlying mechanisms for the calcifications remain unclear but may involve disrupted calcium metabolism and alterations in the blood-brain barrier, contributing to a cycle of vascular injury. The coexistence of acute ischemic stroke in this context is rare and may result from microinfarcts due to calcification in small vessels. Conclusion This case illustrates that acute ischemic stroke can occur as a manifestation of Fahr's disease. CT scan plays vital role in establishing diagnosis by revealing the symmetrical calcification pattern in the basal ganglia, thalami, and cerebellar dentate nucleus. Establishing the association between Fahr's disease and cerebrovascular disease warrants further studies.
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Affiliation(s)
- Ashish Mishra
- Maharajgunj Medical Campus, Tribhuvan University Institute of Medicine, Kathmandu, Nepal
| | - Bipin Dawadi
- Maharajgunj Medical Campus, Tribhuvan University Institute of Medicine, Kathmandu, Nepal
| | - Nischal Neupane
- Maharajgunj Medical Campus, Tribhuvan University Institute of Medicine, Kathmandu, Nepal
| | - Sunil Babu Khanal
- Department of Internal Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
| | - Narayan Prasad Neupane
- Maharajgunj Medical Campus, Tribhuvan University Institute of Medicine, Kathmandu, Nepal
| | - Aryan Mishra
- Manipal Teaching Hospital, Fulbari, Pokhara, Nepal
| | - Bikash Chaudhary
- Maharajgunj Medical Campus, Tribhuvan University Institute of Medicine, Kathmandu, Nepal
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Mathijssen G, van Valen E, de Jong PA, Golüke NMS, van Maren EA, Snijders BMG, Brilstra EH, Ruigrok YM, Bakker S, Goto RW, Emmelot-Vonk MH, Koek HL. The Association between Intracranial Calcifications and Symptoms in Patients with Primary Familial Brain Calcification. J Clin Med 2024; 13:828. [PMID: 38337525 PMCID: PMC10856178 DOI: 10.3390/jcm13030828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/23/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
(1) Background: Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcifications of the basal ganglia and other intracranial areas. Many patients experience symptoms of motor dysfunction and cognitive disorders. The aim of this study was to investigate the association between the amount and location of intracranial calcifications with these symptoms. (2) Methods: Patients with suspected PFBC referred to our outpatient clinic underwent a clinical work-up. Intracranial calcifications were visualized on Computed Tomography (CT), and a Total Calcification Score (TCS) was constructed. Logistic and linear regression models were performed. (3) Results: Fifty patients with PFBC were included in this study (median age 64.0 years, 50% women). Of the forty-one symptomatic patients (82.0%), 78.8% showed motor dysfunction, and 70.7% showed cognitive disorders. In multivariate analysis, the TCS was associated with bradykinesia/hypokinesia (OR 1.07, 95%-CI 1.02-1.12, p < 0.01), gait ataxia (OR 1.06, 95%-CI 1.00-1.12, p = 0.04), increased fall risk (OR 1.04, 95%-CI 1.00-1.08, p = 0.03), and attention/processing speed disorders (OR 1.06, 95%-CI 1.01-1.12, p = 0.02). Calcifications of the lentiform nucleus and subcortical white matter were associated with motor and cognitive disorders. (4) Conclusions: cognitive and motor symptoms are common among patients with PFBC, and there is an association between intracranial calcifications and these symptoms.
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Affiliation(s)
- Gini Mathijssen
- Department of Geriatrics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Evelien van Valen
- Department of Geriatrics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Pim A de Jong
- Department of Radiology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Nienke M S Golüke
- Department of Geriatrics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
- Department of Geriatrics, Hospital Gelderse Vallei, Willy Brandtlaan 10, 6716 RP Ede, The Netherlands
| | - Emiel A van Maren
- Department of Radiology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Birgitta M G Snijders
- Department of Geriatrics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Eva H Brilstra
- Department of Genetics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Ynte M Ruigrok
- Department of Neurology and Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, Utrecht University, 3584 CX Utrecht, The Netherlands
| | - Susan Bakker
- Department of Rehabilitation, Physical Therapy Science & Sports, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Renzo W Goto
- Department of Geriatrics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Marielle H Emmelot-Vonk
- Department of Geriatrics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
| | - Huiberdina L Koek
- Department of Geriatrics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Golüke NMS, Meijer E, van Maren EA, de Jonghe A, Emmelot-Vonk MH, van Valen E, de Jong PA, Koek HL. Amount and Distribution of Intracranial Calcification in Symptomatic and Asymptomatic Primary Familial Brain Calcification. Neurol Clin Pract 2023; 13:e200163. [PMID: 37179845 PMCID: PMC10173887 DOI: 10.1212/cpj.0000000000200163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 03/03/2023] [Indexed: 05/15/2023]
Abstract
Background and Objectives In clinical practice, it can be difficult to differentiate between intracranial calcifications related to primary familial brain calcification (PFBC) or aging. Also, little is known about the consequences of the amount of intracranial calcifications in patients with PFBC. Therefore, we aimed to compare the amount and distribution of intracranial calcifications in persons with PFBC with controls and between asymptomatic and symptomatic PFBC cases. Methods This was a case-control study including patients with PFBC and controls. Controls received a CT of the brain because of a trauma and had at least some basal ganglia calcification. The Nicolas score and volume of calcification were used to quantify intracranial calcifications on the CT scans. Receiver operating characteristic curves were obtained to calculate optimal cutoff points to discriminate between cases and controls. Mann-Whitney U tests and logistic regression, adjusted for age and sex, were used to compare the amount of calcification. Results Twenty-eight cases (median age 65 years, 50.0% male) and 90 controls (median age 74 years, 46.1% male) were included. Calcification scores were higher in cases (median volume: 4.91 cm3 against 0.03 cm3, p < 0.001, median Nicolas score: 26.5 against 2.0, p < 0.001) than controls. Calcifications were also more diffusely distributed in cases. To differentiate between cases and controls, optimal cutoff points were ≥0.2 cm3 for the calcification volume and ≥6.0 for the Nicolas score. Calcification was higher for symptomatic than asymptomatic cases (calcification volume: 13.62 cm3 against 1.61 cm3, p = 0.01, Nicolas score: 39.0 against 15.5, p = 0.02). After adjustment for age and sex, the Nicolas score remained significantly higher in symptomatic patients, and the calcification volume did not. Discussion Patients with PFBC had more severe intracranial calcifications, and these calcifications were more diffusely distributed through the brain compared with controls. Symptomatic patients with PFBC might have more intracranial calcifications than asymptomatic persons.
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Affiliation(s)
- Nienke M S Golüke
- Department of Geriatrics (NMSG, EM, MHE-V, EvV, HLK), University Medical Center Utrecht, Utrecht University; Department of Geriatrics, (NMSG, AdJ), Tergooi Medical Center, Blaricum; and Department of Radiology (EAvM, PAdJ), University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Enrico Meijer
- Department of Geriatrics (NMSG, EM, MHE-V, EvV, HLK), University Medical Center Utrecht, Utrecht University; Department of Geriatrics, (NMSG, AdJ), Tergooi Medical Center, Blaricum; and Department of Radiology (EAvM, PAdJ), University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Emiel A van Maren
- Department of Geriatrics (NMSG, EM, MHE-V, EvV, HLK), University Medical Center Utrecht, Utrecht University; Department of Geriatrics, (NMSG, AdJ), Tergooi Medical Center, Blaricum; and Department of Radiology (EAvM, PAdJ), University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Annemarieke de Jonghe
- Department of Geriatrics (NMSG, EM, MHE-V, EvV, HLK), University Medical Center Utrecht, Utrecht University; Department of Geriatrics, (NMSG, AdJ), Tergooi Medical Center, Blaricum; and Department of Radiology (EAvM, PAdJ), University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Mariëlle H Emmelot-Vonk
- Department of Geriatrics (NMSG, EM, MHE-V, EvV, HLK), University Medical Center Utrecht, Utrecht University; Department of Geriatrics, (NMSG, AdJ), Tergooi Medical Center, Blaricum; and Department of Radiology (EAvM, PAdJ), University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Evelien van Valen
- Department of Geriatrics (NMSG, EM, MHE-V, EvV, HLK), University Medical Center Utrecht, Utrecht University; Department of Geriatrics, (NMSG, AdJ), Tergooi Medical Center, Blaricum; and Department of Radiology (EAvM, PAdJ), University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Pim A de Jong
- Department of Geriatrics (NMSG, EM, MHE-V, EvV, HLK), University Medical Center Utrecht, Utrecht University; Department of Geriatrics, (NMSG, AdJ), Tergooi Medical Center, Blaricum; and Department of Radiology (EAvM, PAdJ), University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Huiberdina L Koek
- Department of Geriatrics (NMSG, EM, MHE-V, EvV, HLK), University Medical Center Utrecht, Utrecht University; Department of Geriatrics, (NMSG, AdJ), Tergooi Medical Center, Blaricum; and Department of Radiology (EAvM, PAdJ), University Medical Center Utrecht, Utrecht University, the Netherlands
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Salamon A, Zádori D, Ujfalusi A, Szpisjak L, Lukács M, Bihari B, Szépfalusi N, Németh VL, Maróti Z, Horváth E, Balogh I, Bereczki C, Klivényi P, Kalmár T. Hereditary and non-hereditary etiologies associated with extensive brain calcification: case series. Metab Brain Dis 2021; 36:2131-2139. [PMID: 34287746 DOI: 10.1007/s11011-021-00790-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 07/01/2021] [Indexed: 10/20/2022]
Abstract
Cerebral calcification may be caused by several potentially treatable conditions, however, in most cases it does not receive special attention in clinical practice. From the point of view of etiology, the diseases associated with cerebral calcification can be divided into two main groups: idiopathic (mostly incurable) and secondary (potentially treatable). The first group includes mainly the hereditary diseases identified before 2021 (primary familial brain calcification subtypes, previously known as Fahr's disease or Fahr's syndrome). In contrast, the second group includes diseases with cerebral calcification that develop generally as a consequence of metabolic/endocrine/autoimmune abnormalities. The aim of our research was to present hereditary and non-hereditary etiologies associated with extensive brain calcification. We compare the detailed clinical, radiological and laboratory results of 6 patients with prominent cerebral calcification identified in our clinic in the last 3 years (idiopathic and secondary etiologies as well). Our research draws attention to the complexity of the etiologies in the context of cerebral calcification. We recommend, beside NGS-based sequence analyses, the application of array comparative genomic hybridization as well, to identify potential genetic etiologies associated with brain calcification.
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Affiliation(s)
- András Salamon
- Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | - Dénes Zádori
- Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | - Anikó Ujfalusi
- Division of Clinical Genetics, Department of Laboratory of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - László Szpisjak
- Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | - Melinda Lukács
- Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | | | - Noémi Szépfalusi
- Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | - Viola Luca Németh
- Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | - Zoltán Maróti
- Department of Pediatrics, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor 14-15, Szeged, H-6725, Hungary
| | - Emese Horváth
- Department of Medical Genetics, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | - István Balogh
- Division of Clinical Genetics, Department of Laboratory of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Csaba Bereczki
- Department of Pediatrics, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor 14-15, Szeged, H-6725, Hungary
| | - Péter Klivényi
- Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary
| | - Tibor Kalmár
- Department of Pediatrics, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor 14-15, Szeged, H-6725, Hungary.
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Fahr's syndrome due to hypoparathyroidism revisited: A case of parkinsonism and a review of all published cases. Clin Neurol Neurosurg 2021; 202:106514. [PMID: 33529967 DOI: 10.1016/j.clineuro.2021.106514] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/18/2021] [Accepted: 01/19/2021] [Indexed: 11/23/2022]
Abstract
INTRODUCTION Fahr's syndrome due to hypoparathyroidism refers to bilateral basal ganglia (BG) calcifications and manifests with movement disorders, seizures, cognitive and behavioral symptoms. CASE PRESENTATION We report a case of a 74-year-old woman, who presented with parkinsonism due to post-surgical hypoparathyroidism and normal DaT scan, despite extensive calcifications of the BG, periventricular white matter, and cerebellum. METHODS A comprehensive literature review of all reported cases of Fahr's syndrome due to hypoparathyroidism was conducted in the electronic databases PubMed and Web of science. Moreover, demographic and clinical characteristics of the patients overall were calculated and associated with radiological findings. RESULTS We reviewed a total of 223 cases with Fahr's syndrome due to hypoparathyroidism (124 female, 99 male). Mean age on presentation was 44.6 ± 17.7 years. Thirty nine percent of patients had idiopathic hypoparathyroidism, 35.4 % acquired and 25.6 % pseudohypoparathyroidism. Almost half of the patients had tetany, seizures or a movement disorder and approximately 40 % neuropsychiatric symptoms. The patients with a movement disorder had a 2.23 likelihood of having neuropsychiatric symptoms as well (OR 2.23, 95 % CI 1.29-3.87). Moreover, there was a statistically significant association between the phenotype severity (i.e. the presence of more than one symptom) and the extent of brain calcifications (χ2 = 32.383, p = 0.009). CONCLUSION Fahr's syndrome is a rare disorder, which nonetheless manifests with several neurological symptoms. A head CT should be considered for patients with hypoparathyroidism and neurological symptoms. More studies using DaT scan are needed to elucidate the effects of calcifications on the dopaminergic function of the BG.
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Kumar P, Singh R, Shah K. Psychiatric Manifestations in Fahr's Syndrome: A Case Report. Cureus 2020; 12:e10770. [PMID: 33154842 PMCID: PMC7606226 DOI: 10.7759/cureus.10770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Fahr's syndrome is a rare neurological entity, primarily impacting basal ganglia with bilateral intracranial calcium deposition. It mainly manifests motor and psychiatric symptoms in affected individuals. After the patient and her family members' consent and proper ethical clearance from the institutional ethical committee, we here report a case presented with a few motor symptoms, features of delirium, and prominent psychiatric symptoms such as disorganized behavior, auditory hallucinations, and delusions. The imaging study found bilateral basal ganglia calcification and edema in the parietal region, primarily on the right side. Laboratory studies revealed mildly low parathyroid hormone and calcium levels, but no significant findings in other investigational tests. Her past medical and psychiatric history were negative, except for her well-adjusted pre-morbid personality. Our aim through this case is to highlight the psychiatric manifestation of a rare neurological syndrome. It also showcases the importance of ruling out medical causes when a patient presents primarily with behavioral symptoms.
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Scarlini S, Cavallieri F, Fiorini M, Menozzi E, Ferrara F, Cavalleri F, Reale C, Garavaglia B, Pietrangelo A, Valzania F, Corradini E. Idiopathic brain calcification in a patient with hereditary hemochromatosis. BMC Neurol 2020; 20:113. [PMID: 32228506 PMCID: PMC7106592 DOI: 10.1186/s12883-020-01689-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 03/17/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Detection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported. CASE PRESENTATION A 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D-PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative. CONCLUSIONS This report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.
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Affiliation(s)
- Stefania Scarlini
- Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Francesco Cavallieri
- Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123 Reggio Emilia, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Massimo Fiorini
- Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Elisa Menozzi
- Department of Neuroscience, S. Agostino-Estense Hospital, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Francesca Ferrara
- Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Francesca Cavalleri
- Department of Neuroradiology, Policlinico|, Azienda Ospedaliero Universitaria di Modena, Modena, Italy
| | - Chiara Reale
- Medical Genetics and Neurogenetics Unit, Movement Disorders Diagnostic Section, Fondazione IRCCS Istituto Neurologico “C. Besta”, Milan, Italy
| | - Barbara Garavaglia
- Medical Genetics and Neurogenetics Unit, Movement Disorders Diagnostic Section, Fondazione IRCCS Istituto Neurologico “C. Besta”, Milan, Italy
| | - Antonello Pietrangelo
- Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Franco Valzania
- Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123 Reggio Emilia, Italy
| | - Elena Corradini
- Internal Medicine Unit and Centre for Hemochromatosis and Heredometabolic Liver Diseases, EuroBloodNet Referral Center for Iron Disorders, Policlinico, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
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Peters MEM, de Brouwer EJM, Bartstra JW, Mali WPTM, Koek HL, Rozemuller AJM, Baas AF, de Jong PA. Mechanisms of calcification in Fahr disease and exposure of potential therapeutic targets. Neurol Clin Pract 2019; 10:449-457. [PMID: 33299674 DOI: 10.1212/cpj.0000000000000782] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 10/10/2019] [Indexed: 11/15/2022]
Abstract
Purpose of review There is growing interest in disorders involved in ectopic mineralization. Fahr disease or idiopathic basal ganglia calcification can serve as a model for ectopic mineralization in the basal ganglia, which is fairly common in the general population. In this review, we will focus on causative gene mutations and corresponding pathophysiologic pathways in Fahr disease. Recent findings Patients with Fahr disease have a variability of symptoms, such as movement disorders, psychiatric signs, and cognitive impairment, but can also be asymptomatic. Fahr disease is mostly autosomal dominant inherited, and there are mutations found in 4 causative genes. Mutations in SLC20A2 and XPR1 lead to a disrupted phosphate metabolism involving brain-specific inorganic phosphate transporters. Mutations in PDGFB and PDGFRB are associated with disrupted blood-brain barrier integrity and dysfunctional pericyte maintenance. In addition, the MYORG gene has recently been discovered to be involved in the autosomal recessive inheritance of Fahr. Summary Knowledge about the mutations and corresponding pathways may expose therapeutic opportunities for patients with Fahr disease and vascular calcifications in the brain in general.
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Affiliation(s)
- Melissa E M Peters
- Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands
| | - Esther J M de Brouwer
- Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands
| | - Jonas W Bartstra
- Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands
| | - Willem P Th M Mali
- Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands
| | - Huiberdina L Koek
- Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands
| | - Annemieke J M Rozemuller
- Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands
| | - Annette F Baas
- Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands
| | - Pim A de Jong
- Departments of Radiology (MEMP, JWB, WPTMM, PAdJ), Geriatrics (EJMdB, HLK), Pathology (AJMR), and Genetics (AFB), University Medical Center Utrecht, The Netherlands
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10
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Kobayashi S, Utsumi K, Tateno M, Iwamoto T, Murayama T, Sohma H, Ukai W, Hashimoto E, Kawanishi C. Longitudinal observation of ten family members with idiopathic basal ganglia calcification: A case report. World J Clin Cases 2019; 7:1483-1491. [PMID: 31363477 PMCID: PMC6656673 DOI: 10.12998/wjcc.v7.i12.1483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 04/18/2019] [Accepted: 05/02/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Familial idiopathic basal ganglia calcification (FIBGC) is a rare autosomal dominant disorder that causes bilateral calcification of the basal ganglia and/or cerebellar dentate nucleus, among other locations.
CASE SUMMARY The aim of this study is to report 10 cases of FIBGC observed in a single family. Seven patients showed calcification on their computed tomography scan, and all of these patients carried the SLC20A2 mutation. However, individuals without the mutation did not show calcification. Three patients among the 7 with calcification were symptomatic, while the remaining 4 patients were asymptomatic. Additionally, we longitudinally observed 10 subjects for ten years. In this paper, we mainly focus on the clinical course and neuroradiological findings in the proband and her son.
CONCLUSION The accumulation of more case reports and further studies related to the manifestation of FIBGC are needed.
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Affiliation(s)
- Seiju Kobayashi
- Shinyukai Nakae Hospital, Sapporo 0010022, Japan
- Department of Neuropsychiatry, Sapporo Medical University Graduate School of Medicine, Sapporo 0608543, Japan
| | - Kumiko Utsumi
- Department of Psychiatry, Sunagawa City Medical Center, Sunagawa 0730196, Japan
| | - Masaru Tateno
- Tokiwa Child Development Center, Tokiwa Hospital, Sapporo, Japan, Department of Neuropsychiatry, Sapporo Medical University Graduate School of Medicine, Sapporo 0050853, Japan
| | - Tomo Iwamoto
- Department of Neuropsychiatry, Sapporo Medical University Graduate School of Medicine, Sapporo 0608543, Japan
| | - Tomonori Murayama
- Department of Neuropsychiatry, Sapporo Medical University Graduate School of Medicine, Sapporo 0608543, Japan
| | - Hitoshi Sohma
- Department of Educational Development, Sapporo Medical University Center for Medical Education, Sapporo 0608543, Japan
- Department of Biomedical Engineering, Sapporo Medical University, School of Medicine, Sapporo 0608543, Japan
| | - Wataru Ukai
- Department of Educational Development, Sapporo Medical University Center for Medical Education, Sapporo 0608543, Japan
- Department of Neuropsychiatry, Sapporo Medical University Graduate School of Medicine, Sapporo 0608543, Japan
| | - Eri Hashimoto
- Department of Neuropsychiatry, Sapporo Medical University Graduate School of Medicine, Sapporo 0608543, Japan
| | - Chiaki Kawanishi
- Department of Neuropsychiatry, Sapporo Medical University Graduate School of Medicine, Sapporo 0608543, Japan
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11
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Huang YT, Zhang LH, Li MF, Cheng L, Qu J, Cheng Y, Li X, Zou GY, Zhou HH. Clinical Features of Primary Familial Brain Calcification in 17 Families. Chin Med J (Engl) 2018; 131:2997-3000. [PMID: 30539916 PMCID: PMC6302657 DOI: 10.4103/0366-6999.247218] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Indexed: 12/17/2022] Open
Affiliation(s)
- Yuan-Tao Huang
- Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan 410008, China
| | - Li-Hua Zhang
- Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan 410008, China
| | - Mei-Fang Li
- Department of Otorhinolaryngology, The Brain Hospital of Hunan Province, Changsha, Hunan 410007, China
| | - Lin Cheng
- Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China
| | - Jian Qu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, Changsha, Hunan 410011, China
| | - Yu Cheng
- Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan 410008, China
| | - Xi Li
- Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan 410008, China
| | - Guo-Ying Zou
- Department of Clinical Laboratory, The Brain Hospital of Hunan Province, Changsha, Hunan 410007, China
| | - Hong-Hao Zhou
- Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan 410008, China
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12
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Koyama S, Sato H, Kobayashi R, Kawakatsu S, Kurimura M, Wada M, Kawanami T, Kato T. Clinical and radiological diversity in genetically confirmed primary familial brain calcification. Sci Rep 2017; 7:12046. [PMID: 28935882 PMCID: PMC5608910 DOI: 10.1038/s41598-017-11595-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 08/25/2017] [Indexed: 01/03/2023] Open
Abstract
Primary familial brain calcification (PFBC) is a rare neuropsychiatric disorder with characteristic symmetrical brain calcifications. Patients with PFBC may have a variety of symptoms, although they also may be clinically asymptomatic. Parkinsonism is one of the most common movement disorders; however, the underlying mechanism remains unclear. This condition is typically transmitted in an autosomal dominant fashion. To date, mutations in SLC20A2, PDGFRB, PDGFB, and XPR1 have been reported to cause PFBC. The aim of the study was to identify the genetic cause of brain calcification in probands from three PFBC families and in 8 sporadic patients and to perform clinical and radiological assessments focusing on parkinsonism in mutation carriers. Three familial PFBC probands and their relatives and eight sporadic patients affected with brain calcifications were enrolled in this study. Whole-exome sequencing identified three novel mutations: c.269G > T, p.(Gly90Val) and c.516+1G > A in SLC20A2 in familial cases, and c.602-1G > T in PDGFB in a sporadic patient. The c.516+1G > A mutation resulted in exon 4 skipping in SLC20A2 (p.Val144Glyfs*85). Dopamine transporter single photon emission computed tomography using 123I-ioflupane and 123I-metaiodobenzylguanidine cardiac scintigraphy revealed pre-synaptic dopaminergic deficit and cardiac sympathetic nerve dysfunction in two SLC20A2-related PFBC patients with parkinsonism.
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Affiliation(s)
- Shingo Koyama
- Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
| | - Hidenori Sato
- Genomic Information Analysis Unit, Department of Genomic Cohort Research, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan
| | - Ryota Kobayashi
- Department of Psychiatry, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan
| | - Shinobu Kawakatsu
- Department of Neuropsychiatry, Aizu Medical Center, Fukushima Medical University, 21-2 Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu, Fukushima, 969-3492, Japan
| | - Masayuki Kurimura
- Department of Neurology, Okitama Public General Hospital, 2000 Nishi-otsuka, Kawanishi-machi, Higashi-okitama-gun, Yamagata, 992-0601, Japan
| | - Manabu Wada
- Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan
| | - Toru Kawanami
- Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan
| | - Takeo Kato
- Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan
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13
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Song CY, Zhao ZX, Li W, Sun CC, Liu YM. Pseudohypoparathyroidism with basal ganglia calcification: A case report of rare cause of reversible parkinsonism. Medicine (Baltimore) 2017; 96:e6312. [PMID: 28296742 PMCID: PMC5369897 DOI: 10.1097/md.0000000000006312] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
RATIONALE Parkinsonism can be secondary to many internal diseases, in some certain conditions, it seems that the clinical manifestations of parkinsonism presenting reversible. We report a case of patient with parkinsonism secondary to pseudohypoparathyroidism, who improved markedly after the supplement of serum calcium. PATIENT CONCERNS AND DIAGNOSES A 52-year-old woman with acute parkinsonism was diagnosed as pseudohypoparathyroidism after the conducting of brain computed tomography, laboratory examinations, and gene detection. The son of the patient was also examined and was diagnosed as pseudohypoparathyroidism, who had ever complained of the history of epilepsy. The clinical manifestations of parkinsonism of the patient was reevaluated after the supplement of serum calcium according to the diagnosis. INTERVENTIONS AND OUTCOMES The brain computed tomography revealed the basal ganglia calcification of the patient, accompanying by serum hypocalcemia and hyperphosphatemia. Loss of function mutation also confirmed the diagnosis. Five days after the therapy targeting at correction of serum hypocalcemia, the patient improved greatly in dyskinesia. LESSONS This study reported a patient presenting as acute reversible parkinsonism, who was finally diagnosed as pseudohypoparathyroidism. It indicated us that secondary parkinsonism should be carefully differentiated for its dramatic treatment effect. And the family history of seizures might be an indicator for the consideration of pseudohypoparathyroidism.
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14
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SÍNDROME DE FAHR SECUNDÁRIA AO METOTREXATO EM PACIENTE COM ARTRITE IDIOPÁTICA JUVENIL. REVISTA BRASILEIRA DE REUMATOLOGIA 2017. [DOI: 10.1016/j.rbr.2017.07.462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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15
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Takeuchi T, Muraoka K, Yamada M, Nishio Y, Hozumi I. Living with idiopathic basal ganglia calcification 3: a qualitative study describing the lives and illness of people diagnosed with a rare neurological disease. SPRINGERPLUS 2016; 5:1713. [PMID: 27777849 PMCID: PMC5050183 DOI: 10.1186/s40064-016-3390-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 09/26/2016] [Indexed: 01/30/2023]
Abstract
PURPOSE Idiopathic basal ganglia calcification (IBGC) is a rare, intractable disease with unknown etiology. IBGC3 is a familial genetic disease defined by genetic mutations in the major causative gene (SLC20A2). People with IBGC3 experience distress from the uncommon nature of their illness and uncertainty about treatment and prognoses. The present study aimed to describe the lives and illness of people with IBGC3. METHODS Participants were recruited from patients aged 20 years or older enrolled in a genetic study, who were diagnosed with IBGC3 and wanted to share their experiences. In-depth semi-structured interviews were conducted with six participants. Interviews were conducted between December 2012 and February 2014, and were recorded and transcribed verbatim. Qualitative data analysis was performed to identify categories and subcategories. Efforts were made to ensure the credibility, transferability, dependability, conformability, and validity of the data. RESULTS Six thematic categories, 17 subcategories, and 143 codes emerged. The six categories were: (1) Frustration and anxiety with progression of symptoms without a diagnosis; (2) Confusion about diagnosis with an unfamiliar disease; (3) Emotional distress caused by a genetic disease; (4) Passive attitude toward life, being extra careful; (5) Taking charge of life, becoming active and engaged; and (6) Requests for healthcare. CONCLUSIONS The qualitative data analysis indicated a need for genetic counseling, access to disease information, establishment of peer and family support systems, mental health services, and improvement in early intervention and treatment for the disease.
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Affiliation(s)
- Tomiko Takeuchi
- Department of Gerontological Nursing, Toyama University, Toyama, Japan
| | - Koko Muraoka
- Department of Adult Health Nursing, Toho University, Tokyo, Japan
| | - Megumi Yamada
- Department of Neurology and Geriatrics, Gifu University, Gifu, Japan
| | - Yuri Nishio
- Laboratory of English Studies, Gifu Pharmaceutical University, Gifu, Japan
| | - Isao Hozumi
- Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan
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16
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de la Plaza Llamas R, Ramia Ángel JM, Arteaga Peralta V, Hernández Cristóbal J, López Marcano AJ. Brain calcifications and primary hyperparathyroidism. Cir Esp 2016; 94:e5-e7. [PMID: 26531147 DOI: 10.1016/j.ciresp.2015.08.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 07/22/2015] [Accepted: 08/01/2015] [Indexed: 11/21/2022]
Affiliation(s)
- Roberto de la Plaza Llamas
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Guadalajara, Guadalajara, España.
| | - José Manuel Ramia Ángel
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Guadalajara, Guadalajara, España
| | - Vladimir Arteaga Peralta
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Guadalajara, Guadalajara, España
| | | | - Aylhin Joana López Marcano
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario de Guadalajara, Guadalajara, España
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17
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Kimura T, Miura T, Aoki K, Saito S, Hondo H, Konno T, Uchiyama A, Ikeuchi T, Takahashi H, Kakita A. Familial idiopathic basal ganglia calcification: Histopathologic features of an autopsied patient with an SLC20A2 mutation. Neuropathology 2015; 36:365-71. [PMID: 26635128 DOI: 10.1111/neup.12280] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 11/10/2015] [Accepted: 11/10/2015] [Indexed: 12/17/2022]
Abstract
Idiopathic basal ganglia calcification (IBGC), or Fahr's disease, is a neurological disorder characterized by widespread calcification in the brain. Recently, several causative genes have been identified, but the histopathologic features of the brain lesions and expression of the gene products remain unclear. Here, we report the clinical and autopsy features of a 62-year-old Japanese man with familial IBGC, in whom an SLC20A2 mutation was identified. The patient developed mild cognitive impairment and parkinsonism. A brain CT scan demonstrated abnormal calcification in the bilateral basal ganglia, thalami and cerebellum. An MRI study at this point revealed glioblastoma, and the patient died 6 months later. At autopsy, symmetric calcification in the basal ganglia, thalami, cerebellar white matter and deeper layers of the cerebral cortex was evident. The calcification was observed in the tunica media of small arteries, arterioles and capillaries, but not in veins. Immunohistochemistry using an antibody against type III sodium-dependent phosphate transporter 2 (PiT-2), the SLC20A2 product, demonstrated that astrocytic processes were labeled in several regions in control brains, whereas in the patient, reactivity in astrocytes was apparently weak. Immunoblotting demonstrated a marked decrease of PiT-2 in the patient. There are few autopsy reports of IBGC patients with confirmation of the genetic background. The autopsy features seem informative for better understanding the histogenesis of IBGC lesions.
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Affiliation(s)
- Tadashi Kimura
- Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan
| | - Takeshi Miura
- Departments of Neurology, Brain Research Institute, University of Niigata, Niigata, Japan.,Departments of Neurology, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Kenju Aoki
- Departments of Neurology, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Shoji Saito
- Departments of Neurosurgery, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Hiroaki Hondo
- Departments of Neurosurgery, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Takuya Konno
- Departments of Neurology, Brain Research Institute, University of Niigata, Niigata, Japan
| | - Akio Uchiyama
- Departments of Pathology, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Takeshi Ikeuchi
- Departments of Molecular Genetics, Brain Research Institute, University of Niigata, Niigata, Japan
| | - Hitoshi Takahashi
- Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan
| | - Akiyoshi Kakita
- Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan
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18
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Vilder EYGD, Vanakker OM. From variome to phenome: Pathogenesis, diagnosis and management of ectopic mineralization disorders. World J Clin Cases 2015; 3:556-574. [PMID: 26244149 PMCID: PMC4517332 DOI: 10.12998/wjcc.v3.i7.556] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 02/27/2015] [Accepted: 05/18/2015] [Indexed: 02/05/2023] Open
Abstract
Ectopic mineralization - inappropriate biomineralization in soft tissues - is a frequent finding in physiological aging processes and several common disorders, which can be associated with significant morbidity and mortality. Further, pathologic mineralization is seen in several rare genetic disorders, which often present life-threatening phenotypes. These disorders are classified based on the mechanisms through which the mineralization occurs: metastatic or dystrophic calcification or ectopic ossification. Underlying mechanisms have been extensively studied, which resulted in several hypotheses regarding the etiology of mineralization in the extracellular matrix of soft tissue. These hypotheses include intracellular and extracellular mechanisms, such as the formation of matrix vesicles, aberrant osteogenic and chondrogenic signaling, apoptosis and oxidative stress. Though coherence between the different findings is not always clear, current insights have led to improvement of the diagnosis and management of ectopic mineralization patients, thus translating pathogenetic knowledge (variome) to the phenotype (phenome). In this review, we will focus on the clinical presentation, pathogenesis and management of primary genetic soft tissue mineralization disorders. As examples of dystrophic calcification disorders Pseudoxanthoma elasticum, Generalized arterial calcification of infancy, Keutel syndrome, Idiopathic basal ganglia calcification and Arterial calcification due to CD73 (NT5E) deficiency will be discussed. Hyperphosphatemic familial tumoral calcinosis will be reviewed as an example of mineralization disorders caused by metastatic calcification.
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19
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Fazekas F, Enzinger C, Schmidt R, Grittner U, Giese AK, Hennerici MG, Huber R, Jungehulsing GJ, Kaps M, Kessler C, Martus P, Putaala J, Ropele S, Tanislav C, Tatlisumak T, Thijs V, von Sarnowski B, Norrving B, Rolfs A. Brain Magnetic Resonance Imaging Findings Fail to Suspect Fabry Disease in Young Patients With an Acute Cerebrovascular Event. Stroke 2015; 46:1548-53. [DOI: 10.1161/strokeaha.114.008548] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 03/16/2015] [Indexed: 11/16/2022]
Abstract
Background and Purpose—
Fabry disease (FD) may cause stroke and is reportedly associated with typical brain findings on magnetic resonance imaging (MRI). In a large group of young patients with an acute cerebrovascular event, we wanted to test whether brain MRI findings can serve to suggest the presence of FD.
Methods—
The Stroke in Young Fabry Patients (SIFAP 1) study prospectively collected clinical, laboratory, and radiological data of 5023 patients (18–55 years) with an acute cerebrovascular event. Their MRI was interpreted centrally and blinded to all other information. Biochemical findings and genetic testing served to diagnose FD in 45 (0.9%) patients. We compared the imaging findings between FD and non-FD patients in patients with at least a T2-weighted MRI of good quality.
Results—
A total of 3203 (63.8%) patients had the required MRI data set. Among those were 34 patients with a diagnosis of FD (1.1%), which was definite in 21 and probable in 13 cases. The median age of patients with FD was slightly lower (45 versus 46 years) and women prevailed (70.6% versus 40.7%;
P
<0.001). Presence or extent of white matter hyperintensities, infarct localization, vertebrobasilar artery dilatation, T1-signal hyperintensity of the pulvinar thalami, or any other MRI finding did not distinguish patients with FD from non-FD cerebrovascular event patients. Pulvinar hyperintensity was not present in a single patient with FD but seen in 6 non-FD patients.
Conclusions—
Brain MRI findings cannot serve to suspect FD in young patients presenting with an acute cerebrovascular event. This deserves consideration in the search for possible causes of young patients with stroke.
Clinical Trial Registration—
URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00414583.
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Affiliation(s)
- Franz Fazekas
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Christian Enzinger
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Reinhold Schmidt
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Ulrike Grittner
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Anne-Katrin Giese
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Michael G. Hennerici
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Roman Huber
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Gerhard J. Jungehulsing
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Manfred Kaps
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Christof Kessler
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Peter Martus
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Jukka Putaala
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Stefan Ropele
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Christian Tanislav
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Turgut Tatlisumak
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Vincent Thijs
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Bettina von Sarnowski
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Bo Norrving
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
| | - Arndt Rolfs
- From the Department of Neurology (F.F., C.E., R.S., S.R.) and Division of Neuroradiology, Department of Radiology (C.E.), Medical University of Graz, Graz, Austria; Department of Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin, Berlin, Germany (U.G.); Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany (A.-K.G., A.R.); Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (M.G.H.); Department of
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Fujioka S, Strongosky AJ, Hassan A, Rademakers R, Dickson DW, Wszolek ZK. Clinical presentation of a patient with SLC20A2 and THAP1 deletions: differential diagnosis of oromandibular dystonia. Parkinsonism Relat Disord 2015; 21:329-31. [PMID: 25609077 DOI: 10.1016/j.parkreldis.2014.12.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 12/18/2014] [Accepted: 12/27/2014] [Indexed: 01/30/2023]
Affiliation(s)
- Shinsuke Fujioka
- Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA; Department of Neurology, Fukuoka University, Fukuoka, Japan
| | - Audrey J Strongosky
- Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA
| | - Anhar Hassan
- Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| | - Rosa Rademakers
- Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA
| | - Dennis W Dickson
- Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA
| | - Zbigniew K Wszolek
- Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA.
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Kim H, Choi HA, Lee K, Jeon SB. Brain Calcification Associated with Pseudohypoparathyroidism. JOURNAL OF NEUROCRITICAL CARE 2014. [DOI: 10.18700/jnc.2014.7.2.145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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22
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Heck D, Mergen M, Ganner A, Pelisek J, Mader I, Weiller C, Niesen WD. POEMS syndrome, calciphylaxis and focal segmental glomerulosclerosis - VEGF as a possible link. BMC Neurol 2014; 14:210. [PMID: 25369758 PMCID: PMC4226878 DOI: 10.1186/s12883-014-0210-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Accepted: 10/18/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Polyneuropathy organomegaly endocrinopathy M-protein skin changes (POEMS) syndrome is a rare cause of polyneuropathy. Calciphylaxis, a severe disease leading to necrotic ulcers of the skin, is associated with POEMS syndrome and also with renal disease. This case report describes a patient with POEMS syndrome plus primary focal segmental glomerulosclerosis. CASE PRESENTATION A 27-year-old Caucasian woman with chronic renal insufficiency due to focal segmental glomerulosclerosis and calciphylaxis presented to our institution with polyneuropathy and encephalopathy. An extensive diagnostic workup revealed POEMS syndrome. Serum concentrations of vascular endothelial growth factor (VEGF) were highly elevated, consistent with POEMS syndrome. CONCLUSION To our knowledge, this is the first report of a patient with POEMS syndrome and primary focal segmental glomerulosclerosis. The combination of POEMS syndrome, calciphylaxis and primary focal segmental glomerulosclerosis may be coincidental, suggesting the need for additional studies to confirm or exclude this association. VEGF may be an important pathogenetic link, suggesting that treatment with antiangiogenic agents may improve patient outcomes.
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Giordano A, Amboni M, Tessitore A. Valproate-Induced Generalized Choreoathetosis. Mov Disord Clin Pract 2014; 1:271-272. [PMID: 30713866 DOI: 10.1002/mdc3.12069] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Revised: 06/09/2014] [Accepted: 06/12/2014] [Indexed: 11/08/2022] Open
Affiliation(s)
- Alfonso Giordano
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences Second University of Naples Naples Italy.,IDC Hermitage Capodimonte Naples Italy
| | - Marianna Amboni
- IDC Hermitage Capodimonte Naples Italy.,Department of Neurological Sciences University of Naples "Federico II" Naples Italy
| | - Alessandro Tessitore
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences Second University of Naples Naples Italy
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Goswami R, Millo T, Mishra S, Das M, Kapoor M, Tomar N, Saha S, Roy TS, Sreenivas V. Expression of osteogenic molecules in the caudate nucleus and gray matter and their potential relevance for Basal Ganglia calcification in hypoparathyroidism. J Clin Endocrinol Metab 2014; 99:1741-8. [PMID: 24552219 PMCID: PMC5393477 DOI: 10.1210/jc.2013-3863] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Basal ganglia calcification (BGC) is an interesting example of ectopic calcification in patients with hypoparathyroidism. Its pathogenesis and reasons for predilection of calcification at basal ganglia are not clear. OBJECTIVE To assess the expression of osteogenesis-related molecules in the caudate nucleus and surface gray matter (an area spared from calcification) and discuss potential relevance of the results in context of BGC in idiopathic hypoparathyroidism. METHODS Caudate nucleus and gray matter were obtained from 14 autopsies performed in accidental deaths. The mRNA expression of bone transcription factors (RUNX2/osterix), bone morphogenetic proteins (BMPs) 2 and 4, osteonectin, osteopontin, osteocalcin, vitamin D receptor, calcium sensing-receptor, Na phosphate transporters (PiTs) 1 and 2, N-methyl-D-aspartate receptor 2B (NMDAR2B), carbonic anhydrase II (CA-II), PTH1 receptor (PTH1R), PTH2R, and PTHrP were assessed by RT-PCR. Western blot, spot densitometry, and immunohistochemistry were performed to assess protein expression of molecules showing differences in mRNA expression between caudate and gray tissues. RESULTS The mean mRNA expression of PiT1 (11.0 ± 10.39 vs 32.9 ± 20.98, P = .003) and PTH2R (1.6 ± 1.47 vs 13.7 ± 6.11, P = .001) were significantly lower in the caudate nucleus than the gray matter. The expression of osteonectin, osteopontin, and CA-II were significantly higher in the caudate nucleus than the gray matter (P = .01, .001, and .04, respectively). The mRNA expression of other molecules was comparable in the 2 tissues. The protein expression of both CA-II and osteonectin was 24% higher and PiT1 17% lower in caudate than the gray matter. The differences in the PTH2R and osteopontin protein expression were not appreciable. CONCLUSIONS The presence of several osteogenic molecules in caudate nucleus indicates that BGC would probably be the outcome of an active process. The differences in expression of these molecules in caudate over gray matter could favor BGC at this site in the unique biochemical milieu of hypoparathyroid state.
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Affiliation(s)
- Ravinder Goswami
- Departments of Endocrinology and Metabolism (R.G., S.M., M.D., M.K., N.T., S.S.), Forensic Medicine (T.M.), Anatomy (T.S.R.), and Biostatistics (V.S.), All India Institute of Medical Sciences, New Delhi 110029, India
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Hmami F, Chaouki S, Benmiloud S, Souilmi FZ, Abourazzak S, Idrissi M, Atmani S, Bouharrou A, Hida M. [Seizures revealing phosphocalcic metabolism abnormalities]. Rev Neurol (Paris) 2014; 170:440-4. [PMID: 24726042 DOI: 10.1016/j.neurol.2014.02.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2013] [Revised: 01/28/2014] [Accepted: 02/18/2014] [Indexed: 10/25/2022]
Abstract
Hypocalcemia due to hypoparathyroidism produces a broad spectrum of clinical manifestations, but overt symptoms may be sparse. One unusual presentation is onset or aggravation of epilepsy in adolescence revealing hypoparathyroidism. This situation can lead to delayed diagnosis, with inefficacity of the antiepileptic drugs. We report five cases of adolescence-onset epilepsy with unsuccessful antiepileptic therapy, even with gradually increasing dose. Physical examination revealed signs of hypocalcemia, confirmed biologically. Full testing disclosed the origin of the seizures: hypoparathyroidism in three patients and pseudohypoparathyroidism in the other two. In four of five patients, computed tomography showed calcification of the basal ganglia, defining Fahr's syndrome. The patients were treated with oral calcium and active vitamin D (1-alphahydroxy vitamin D3). Seizure frequency progressively decreased and serum calcium levels returned to normal. These cases illustrate the importance of the physical examination and of routine serum calcium assay in patients with new-onset epileptic seizures in order to detect hypocalcemia secondary to hypoparathyroidism.
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Affiliation(s)
- F Hmami
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc.
| | - S Chaouki
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc
| | - S Benmiloud
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc
| | - F Z Souilmi
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc
| | - S Abourazzak
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc
| | - M Idrissi
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc
| | - S Atmani
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc
| | - A Bouharrou
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc
| | - M Hida
- Service de pédiatrie, CHU Hassan II - Fès, B.P. 1835, Atlass, 30000 Fès, Maroc
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Faye AD, Gawande S, Tadke R, Kirpekar VC, Bhave SH. A case of psychosis due to Fahr's syndrome and response to behavioral disturbances with risperidone and oxcarbazepine. Indian J Psychiatry 2014; 56:188-90. [PMID: 24891710 PMCID: PMC4040070 DOI: 10.4103/0019-5545.130506] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Calcification of basal ganglia or Fahr's syndrome is a rare disease characterized by bilateral and symmetrical intracranial deposition of calcium mainly in cerebral basal ganglia. Motor and neuropsychiatric symptoms are prominent features. We report a case presented with a few motor symptoms, features of delirium and prominent psychiatric symptoms (disorganized behavior) predominantly evident after the improvement in delirium. Radiological findings were suggestive of bilateral basal ganglia calcification. Parathyroid hormone levels were low with no significant findings in other investigations and negative family history. Patient showed significant improvement in behavioral disturbances with risperidone, low dose of lorazepam, oxcarbazepine, and memantine.
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Affiliation(s)
- Abhijeet Dhawalram Faye
- Department of Psychiatry, NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur, Maharashtra, India
| | - Sushil Gawande
- Department of Psychiatry, NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur, Maharashtra, India
| | - Rahul Tadke
- Department of Psychiatry, NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur, Maharashtra, India
| | - Vivek C Kirpekar
- Department of Psychiatry, NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur, Maharashtra, India
| | - Sudhir H Bhave
- Department of Psychiatry, NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur, Maharashtra, India
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Zhu M, Zhu X, Wan H, Hong D. Familial IBGC caused by SLC20A2 mutation presenting as paroxysmal kinesigenic dyskinesia. Parkinsonism Relat Disord 2013; 20:353-4. [PMID: 24411498 DOI: 10.1016/j.parkreldis.2013.12.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Revised: 11/29/2013] [Accepted: 12/16/2013] [Indexed: 12/17/2022]
Affiliation(s)
- Min Zhu
- Department of Neurology, The First Affiliated Hospital of Nanchang University, Yong Wai Zheng Street 17#, Nanchang 330006, PR China
| | - Xuan Zhu
- Department of Neurology, The First Affiliated Hospital of Nanchang University, Yong Wai Zheng Street 17#, Nanchang 330006, PR China
| | - Hui Wan
- Department of Neurology, The First Affiliated Hospital of Nanchang University, Yong Wai Zheng Street 17#, Nanchang 330006, PR China
| | - Daojun Hong
- Department of Neurology, The First Affiliated Hospital of Nanchang University, Yong Wai Zheng Street 17#, Nanchang 330006, PR China.
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Stamelou M, Adams M, Davagnanam I, Batla A, Sheerin U, Talbot K, Bhatia KP. Progressive ataxia and palatal tremor associated with dense pontine calcification: A unique case. Mov Disord 2013; 28:1155-7. [PMID: 23436739 PMCID: PMC4235245 DOI: 10.1002/mds.25310] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
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Globus pallidus and substantia nigra hypointensities on T2*-weighted imaging in MELAS. J Neurol 2012; 259:2720-2. [DOI: 10.1007/s00415-012-6633-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2012] [Revised: 07/16/2012] [Accepted: 07/18/2012] [Indexed: 01/30/2023]
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Goswami R, Sharma R, Sreenivas V, Gupta N, Ganapathy A, Das S. Prevalence and progression of basal ganglia calcification and its pathogenic mechanism in patients with idiopathic hypoparathyroidism. Clin Endocrinol (Oxf) 2012; 77:200-6. [PMID: 22288727 DOI: 10.1111/j.1365-2265.2012.04353.x] [Citation(s) in RCA: 125] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The pathogenesis of basal ganglia calcification (BGC) in hypoparathyroidism is not clear. Its occurrence in hypocalcaemic milieu of hypoparathyroidism is believed to be due to high serum calcium-phosphorus product and poor calcium control. OBJECTIVE To report details of BGC in patients with idiopathic hypoparathyroidism (IH) and factors determining its progression during follow-up. METHOD Clinical, biochemical characteristics and a meningioma-expressed antigen-6 (MGEA6) gene polymorphism were analysed in 145 patients with IH, recruited since 1998, to determine the factors associated with BGC. The progression of BGC and its relationship with metabolic control of serum calcium, phosphorus, serum 25(OH)D and 1,25(OH)(2) D were assessed after a mean of 6·9 ± 3·5 years in 49 of them. RESULTS Basal ganglia calcification was present in 73·8% (95% CI: 66·6%-81·0%) of subjects affecting the globus pallidus (68·8%) putamen (55·9%) and caudate nucleus (54·8%). The other sites calcified were grey-white junction (39·8%), cerebellar parenchyma (31·2%), thalamus (29·0%) and dentate nuclei (24·7%). Parkinsonism and dystonic symptoms were present in three cases. The presence of BGC at presentation was associated with calcification of the choroid plexus, cataract and an increased risk of seizures but not tetany. The progression of BGC during follow-up was related to calcium/phosphorus ratio. For every 1% increase in this ratio, the odds of progression decreased by 5% (OR: 0·95, 95% CI: 0·93-0·99, P < 0·001). A MGEA6 polymorphism, serum 25(OH)D and 1,25(OH)(2)D did not affect progression of BGC. CONCLUSION Basal ganglia calcification occurs in 73·8% of patients with IH and correlates with the duration of hypocalcaemia, choroid plexus calcification, seizures and cataract. The progression of BGC is related to the calcium/phosphorus ratio during follow-up. This brings forth the importance of adequate phosphorus control in the management of hypoparathyroidism.
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