Review

Authors: Shafaq Saleem, Hafiz Muhammad Aslam, Maheen Anwar...

Fahr's disease or Fahr's syndrome is a rare, neurological disorder characterized by abnormal calcified deposits in basal ganglia and cerebral cortex. Calcified deposits are made up of calcium carbonate and calcium phosphate, and are commonly located in the Basal Ganglia, Thalamus, Hippocampus, Cerebral cortex, Cerebellar Subcortical white matter and Dentate Nucleus. Molecular genetics of this disease haven't been studied extensively; hence evidence at the molecular and genetic level is limited. Fahr's disease commonly affects young to middle aged adults. Etiology of this syndrome does not identify a specific agent but associations with a number of conditions have been noted; most common of which are endocrine disorders, mitochondrial myopathies, dermatological abnormalities and infectious diseases. Clinical manifestations of this disease incorporate a wide variety of symptoms, ranging from neurological symptoms of extrapyramidal system to neuropsychiatric abnormalities of memory and concentration to movement disorders including Parkinsonism, chorea and tremors amongst others. Diagnostic criteria for this disease has been formulated after modifications from previous evidence and can be stated briefly, it consist of bilateral calcification of basal ganglia, progressive neurologic dysfunction, absence of biochemical abnormalities, absence of an infectious, traumatic or toxic cause and a significant family history. Imaging modalities for the diagnosis include CT, MRI, and plain radiography of skull. Other investigations include blood and urine testing for hematologic and biochemical indices. Disease is as yet incurable but management and treatment strategies mainly focus on symptomatic relief and eradication of causative factors; however certain evidence is present to suggest that early diagnosis and treatment can reverse the calcification process leading to complete recovery of mental functions. Families with a known history of Fahr's disease should be counseled prior to conception so that the birth of affected babies can be prevented. This review was written with the aim to remark on the current substantial evidence surrounding this disease.

Topics: Basal Ganglia Diseases; Calcinosis; Female; Humans; Male

PubMed: 24098952
DOI: 10.1186/1750-1172-8-156

Review

Authors: Dun Xian Tan, Bing Xu, Xinjia Zhou...

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin's synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.

Topics: Aging; Animals; Calcinosis; Humans; Melatonin; Pineal Gland; Rejuvenation

PubMed: 29385085
DOI: 10.3390/molecules23020301

Review

Authors: Giulia Donzuso, Giovanni Mostile, Alessandra Nicoletti...

Basal ganglia calcifications could be incidental findings up to 20% of asymptomatic patients undergoing CT or MRI scan. The presence of neuropsychiatric symptoms associated with bilateral basal ganglia calcifications (which could occur in other peculiar brain structures, such as dentate nuclei) identifies a clinical picture defined as Fahr's Disease. This denomination mainly refers to idiopathic forms in which no metabolic or other underlying causes are identified. Recently, mutations in four different genes (SLC20A2, PDGFRB, PDGFB, and XPR1) were identified, together with novel mutations in the Myogenic Regulating Glycosylase gene, causing the occurrence of movement disorders, cognitive decline, and psychiatric symptoms. On the other hand, secondary forms, also identified as Fahr's syndrome, have been associated with different conditions: endocrine abnormalities of PTH, such as hypoparathyroidism, other genetically determined conditions, brain infections, or toxic exposure. The underlying pathophysiology seems to be related to an abnormal calcium/phosphorus homeostasis and transportation and alteration of the blood-brain barrier.

Topics: Autoimmune Diseases of the Nervous System; Basal Ganglia Diseases; Calcinosis; Cockayne Syndrome; Humans; Hypoparathyroidism; Lupus Vasculitis, Central Nervous System; Mitochondrial Diseases; Nervous System Malformations; Neurodegenerative Diseases; Neurotoxicity Syndromes; Pseudohypoparathyroidism; Xenotropic and Polytropic Retrovirus Receptor

PubMed: 31267306
DOI: 10.1007/s10072-019-03998-x

Review

Authors: Marion Smits

Oligodendroglioma are glial tumours, predominantly occurring in adults. Their hallmark molecular feature is codeletion of the 1p and 19q chromosome arms, which is not only of diagnostic but also of prognostic and predictive relevance. On imaging, these tumours characteristically show calcification, and they have a cortical-subcortical location, most commonly in the frontal lobe. Owing to their superficial location, there may be focal thinning or remodelling of the overlying skull. In contrast to other low-grade gliomas, minimal to moderate enhancement is commonly seen and perfusion may be moderately increased. This complicates differentiation from high-grade, anaplastic oligodendroglioma, in which enhancement and increased perfusion are also common. New enhancement in a previously non-enhancing, untreated tumour, however, is suggestive of malignant transformation, as is high growth rate. MR spectroscopy may further aid in the differentiation between low- and high-grade oligodendroglioma. A relatively common feature of recurrent disease is leptomeningeal dissemination, but extraneural spread is rare. Tumours with the 1p/19q codeletion more commonly show heterogeneous signal intensity, particularly on T2 weighted imaging; calcifications; an indistinct margin; and mildly increased perfusion and metabolism than 1p/19q intact tumours. For the initial diagnosis of oligodendroglioma, MRI and CT are complementary; MRI is superior to CT in assessing tumour extent and cortical involvement, whereas CT is most sensitive to calcification. Advanced and functional imaging techniques may aid in grading and assessing the molecular genotype as well as in differentiating between tumour recurrence and radiation necrosis, but so far no unequivocal method or combination of methods is available.

Topics: Adult; Brain Neoplasms; Calcinosis; Diagnosis, Differential; Frontal Lobe; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Middle Aged; Neoplasm Metastasis; Oligodendroglioma; Positron-Emission Tomography; Tomography, X-Ray Computed

PubMed: 26849038
DOI: 10.1259/bjr.20150857

Review

Authors: Miao Wang, Meichen Zhang, Lei Wu...

BACKGROUND

Leukoencephalopathy with calcifications and cysts (LCC) is a rare disease in which parenchymal cysts and calcifications within a widespread leukoencephalopathy can cause a broad spectrum of neurological symptoms. We present cases with adult LCC and discuss previously described entities in relevant literature.

CASE PRESENTATION

Two cases of adult-onset LCC confirmed by clinical presentations, typical neuroimaging and neuropathological findings are reported.

LITERATURE REVIEW

A detailed search of all relevant reports published in the English language between 1996 and 2015 via PubMed (http://www.ncbi.nlm.nih.gov/pubmed) was performed, with "Leukoencephalopathy", "cerebral calcifications" and "cysts" as keywords. Including the current cases, we summarized the clinical presentations, neuroimaging features, biopsy features, and genetic features of 38 LCC patients.

CONCLUSION

Our findings suggested that LCC could be diagnosed by clinical presentations, neuroimaging and gene detection, and biopsy might not be necessary. Therefore, we propose a diagnostic flow chart for neuroimaging in leukoencephalopathy, cerebral calcifications and cysts.

Topics: Adult; Brain; Calcinosis; Central Nervous System Cysts; Diagnosis, Differential; Female; Humans; Leukoencephalopathies; Young Adult

PubMed: 27772754
DOI: 10.1016/j.jns.2016.09.048

Authors: Beom Joon Kim, Seung-Hoon Lee, Chi Kyung Kim...

BACKGROUND

Coronary artery calcification (CAC) scores are widely accepted to predict risk of coronary heart diseases and are associated with atherosclerosis in other vasculatures. Cerebral small vessel diseases (SVDs), including white matter lesions (WML), silent lacunar infarction (SLI) and cerebral microbleeds (CMB), are considered to develop in conjunction with pro-atherogenic conditions, measured by CAC scores.

METHODS AND RESULTS

Of 672 individuals aged ≥65 years that underwent health screening, 312 subjects with brain magnetic resonance imagings (MRIs) were enrolled in this study. The distribution of baseline characteristics among individuals with or without MRIs was not different. Clinical and laboratory information was collected and CAC scores were measured using multi-detector computed tomography. Cerebral SVD were independently assessed by 2 raters who were unaware of the CAC scores. The prevalence of CAC (CAC>0) was 71.7% in men and 50.0% in women. The associations between moderate-to-extensive CAC (CAC score ≥100) and WML (adjusted odds ratio and 95% confidence interval, 4.99 and 1.33-18.73), SLI (5.04 and 1.86-13.63) and CMB (6.07 and 1.54-23.94) remained significant after adjusting for relevant confounders.

CONCLUSIONS

This study documents significant associations between CAC and cerebral SVDs. The findings suggest that SVDs in the brain and CAC in the heart may develop under similar systemic pathogenic processes.

Topics: Aged; Aged, 80 and over; Aging; Atherosclerosis; Calcinosis; Cell Transdifferentiation; Cerebrovascular Disorders; Cognition Disorders; Comorbidity; Coronary Artery Disease; Humans; Hyperphosphatemia; Middle Aged; Models, Cardiovascular; Muscle, Smooth, Vascular; Risk Factors; Tomography, Spiral Computed; Tomography, X-Ray Computed; Tunica Intima; Tunica Media; Vascular Resistance

PubMed: 21157110
DOI: 10.1253/circj.cj-10-0762

Review

Authors: Edoardo Monfrini, Federica Arienti, Paola Rinchetti...

Many conditions can present with accumulation of calcium in the brain and manifest with a variety of neurological symptoms. Brain calcifications can be primary (idiopathic or genetic) or secondary to various pathological conditions (e.g., calcium-phosphate metabolism derangement, autoimmune disorders and infections, among others). A set of causative genes associated with primary familial brain calcification (PFBC) has now been identified, and include genes such as , , , , , and . However, many more genes are known to be linked with complex syndromes characterized by brain calcifications and additional neurologic and systemic manifestations. Of note, many of these genes encode for proteins involved in cerebrovascular and blood-brain barrier functions, which both represent key anatomical structures related to these pathological phenomena. As a growing number of genes associated with brain calcifications is identified, pathways involved in these conditions are beginning to be understood. Our comprehensive review of the genetic, molecular, and clinical aspects of brain calcifications offers a framework for clinicians and researchers in the field.

Topics: Humans; Brain Diseases; Xenotropic and Polytropic Retrovirus Receptor; Calcium; Brain; Calcinosis; Molecular Biology; Mutation; Sodium-Phosphate Cotransporter Proteins, Type III

PubMed: 37240341
DOI: 10.3390/ijms24108995

Authors: Elena Tsolaki, Lajos Csincsik, Jing Xue...

Brain calcification (calcium phosphate mineral formation) has been reported in the past 100 years in the brains of Alzheimer's disease (AD) patients. However, the association between calcification and AD, the triggers for calcification, and its role within the disease are not clear. On the other hand, hyperphosphorylated Tau protein (pTau) tangles have been widely studied and recognized as an essential factor in developing AD. In this work, calcification in the brains of AD patients is characterized by advanced electron microscopy and fluorescence microscopy. Results are then compared to samples from cognitively healthy, age-matched donors, and the colocalization of calcification and pTau is investigated. Here, we show that AD patients' brains present microcalcification associated with the neural cell nuclei and cell projections, and that these are strongly related to the presence of pTau. The link between microcalcification and pTau suggests a potential mechanism of brain cell damage. Together with the formation of amyloid plaques and neurofibrillary tangles, microcalcification in neuronal cells adds to a better understanding of the pathology of AD. Finally, the presence of microcalcification in the neuronal cells of AD patients may assist in AD diagnosis, and may open avenues for developing intervention strategies based on inhibition of calcification. STATEMENT OF SIGNIFICANCE: Brain calcification has been reported in the past 100 years in the brains of Alzheimer's disease (AD) patients. However, the association between calcification and AD is not clear. Hyperphosphorylated Tau protein (pTau) has been studied and recognized as a key factor in developing AD. We show here that AD patients' brains present microcalcification associated with the neuronal cell nuclei and cell projections, and that these are related to the presence of pTau. The study of calcification in brain cells can contribute to a better understanding of the biochemical mechanisms associated with AD and might also reveal that calcification is part of the full disease mechanism. Moreover, this work opens the possibility for using calcification as a biomarker to identify AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Brain; Calcinosis; Cell Nucleus; Humans; Neurofibrillary Tangles; Phosphorylation; tau Proteins

PubMed: 35259518
DOI: 10.1016/j.actbio.2022.03.003

Authors: Maarten J Kamphuis, Laura T van der Kamp, Edwin Lette...

OBJECTIVES

Arterial calcification is thought to protect against rupture of intracranial aneurysms, but studies in a representative population of intracranial aneurysm patients have not yet been performed. The aim was to compare the prevalence of aneurysm wall calcification and intracranial carotid artery calcification (ICAC) between patients with an unruptured intracranial aneurysm (UIA) and a ruptured intracranial aneurysm (RIA).

MATERIALS AND METHODS

We matched 150 consecutive UIA patients to 150 RIA patients on age and sex. Aneurysm wall calcification and ICAC were quantified on non-contrast enhanced computed tomography images with the modified Agatston score. We compared the prevalence of aneurysm wall calcification, ICAC, and severe ICAC (defined as a modified Agatston score in the fourth quartile) between UIA and RIA patients using univariate and multivariate conditional logistic regression models adjusted for aneurysm characteristics and cardiovascular risk factors.

RESULTS

Aneurysm wall calcification was more prevalent in UIA compared to RIA patients (OR 5.2, 95% CI: 2.0-13.8), which persisted after adjustment (OR 5.9, 95% CI: 1.7-20.2). ICAC prevalence did not differ between the two groups (crude OR 0.9, 95% CI: 0.5-1.8). Severe ICAC was more prevalent in UIA patients (OR 2.0, 95% CI: 1.1-3.6), but not after adjustment (OR 1.0, 95% CI: 0.5-2.3).

CONCLUSIONS

Aneurysm wall calcification but not ICAC was more prevalent in UIAs than in RIAs, which corresponds to the hypothesis that calcification may protect against aneurysmal rupture. Aneurysm wall calcification should be further assessed as a predictor of aneurysm stability in prospective cohort studies.

CLINICAL RELEVANCE STATEMENT

Calcification of the intracranial aneurysm wall was more prevalent in unruptured than ruptured intracranial aneurysms after adjustment for cardiovascular risk factors. Calcification may therefore protect the aneurysm against rupture, and aneurysm wall calcification is a candidate predictor of aneurysm stability.

KEY POINTS

Aneurysm wall calcification was more prevalent in patients with unruptured than ruptured aneurysms, while internal carotid artery calcification was similar. Aneurysm wall calcification but not internal carotid artery calcification is a candidate predictor of aneurysm stability. Cohort studies are needed to assess the predictive value of aneurysm wall calcification for aneurysm stability.

Topics: Humans; Intracranial Aneurysm; Male; Female; Aneurysm, Ruptured; Middle Aged; Prevalence; Vascular Calcification; Aged; Tomography, X-Ray Computed; Risk Factors; Carotid Artery Diseases; Calcinosis

PubMed: 38806803
DOI: 10.1007/s00330-024-10789-2

Review

Authors: Neeraj Shah, Vinod Chainani, Patrice Delafontaine...

Breast arterial calcification (BAC), observed as an incidental finding on screening mammograms, represents degenerative calcific changes occurring in the mammary arteries, with increasing age. The aim of this review is to discuss relevant literature examining relation between BAC and atherosclerosis. After a thorough literature search, in OVID and PubMed, 199 studies were identified, of which 25 were relevant to our review. Data were abstracted from each study and statistical analysis was done, including calculation of odds ratios and construction of forest plots. A total of 35,542 patients were enrolled across 25 studies looking at an association between BAC and coronary artery disease, cardiovascular disease, stroke, cerebral artery disease, carotid and peripheral artery diseases, and coronary artery calcification. A majority of the studies showed a statistically significant relation between BAC and presence of coronary artery disease cardiovascular disease and associated mortality. Sensitivity of BAC in predicting cardiovascular events was low, but specificity was high. BAC was predictive of incident and prevalent stroke but not mortality of stroke. Similarly, BAC was predictive of cerebral, carotid, and peripheral artery diseases. The role of BAC as a surrogate marker of coronary and systemic atherosclerosis is currently uncertain. Its role may be further elucidated by more large-scale prospective studies and clinical experience.

Topics: Atherosclerosis; Breast; Calcinosis; Cardiovascular Diseases; Cerebral Arterial Diseases; Coronary Artery Disease; Female; Humans; Mammary Arteries; Mammography; Odds Ratio; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Stroke

PubMed: 23584424
DOI: 10.1097/CRD.0b013e318295e029