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Common causes of calcification arising from deep gray matter structures (thalami and basal ganglia). HIV human immunodeficiency virus, IBGC-1 idiopathic basal ganglia calcification 1, MELAS mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
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This article is the first of a two-part series on intracranial calcification in childhood. Intracranial calcification can be either physiological or pathological. Physiological intracranial calcification is not an expected neuroimaging finding in the neonatal or infantile period but occurs, as children grow older, in the pineal gland, habenula, cho...
Citations
... Note the ventricular dilatation and cyst/pseudocyst with a thin septation in the right occipital horn (asterisk). c, d Axial susceptibility-weighted MR images show punctate hypointense foci in cortical and subcortical location consistent with calcifications (dotted arrows) Cerebral calcifications Gray-white matter junction [42,43] Parenchymal and periventricular [42,43] Nodular/large diffuse [42] Periventricular and subependymal [42,43] Punctate or fine [42] Microcephaly Yes Occipital bone prominence and redundant skin fold [42,43] Less frequent [42] Yes [42,43] Neuronal migration anomalies Yes [42] No [42] Yes [ Normal [44] Hepatomegaly [42] Echogenic bowel [44] Ascites [44] Hepatomegaly [43] Echogenic bowel [44] Ascites [44] Profile ...
... Note the ventricular dilatation and cyst/pseudocyst with a thin septation in the right occipital horn (asterisk). c, d Axial susceptibility-weighted MR images show punctate hypointense foci in cortical and subcortical location consistent with calcifications (dotted arrows) Cerebral calcifications Gray-white matter junction [42,43] Parenchymal and periventricular [42,43] Nodular/large diffuse [42] Periventricular and subependymal [42,43] Punctate or fine [42] Microcephaly Yes Occipital bone prominence and redundant skin fold [42,43] Less frequent [42] Yes [42,43] Neuronal migration anomalies Yes [42] No [42] Yes [ Normal [44] Hepatomegaly [42] Echogenic bowel [44] Ascites [44] Hepatomegaly [43] Echogenic bowel [44] Ascites [44] Profile ...
... Note the ventricular dilatation and cyst/pseudocyst with a thin septation in the right occipital horn (asterisk). c, d Axial susceptibility-weighted MR images show punctate hypointense foci in cortical and subcortical location consistent with calcifications (dotted arrows) Cerebral calcifications Gray-white matter junction [42,43] Parenchymal and periventricular [42,43] Nodular/large diffuse [42] Periventricular and subependymal [42,43] Punctate or fine [42] Microcephaly Yes Occipital bone prominence and redundant skin fold [42,43] Less frequent [42] Yes [42,43] Neuronal migration anomalies Yes [42] No [42] Yes [ Normal [44] Hepatomegaly [42] Echogenic bowel [44] Ascites [44] Hepatomegaly [43] Echogenic bowel [44] Ascites [44] Profile ...
Viral infections in low-income countries such as Brazil pose a significant challenge for medical authorities, with epidemics such as Zika virus infection having lasting effects. The increase in microcephaly among newborns has prompted investigations into the association between Zika virus and this congenital syndrome. The severity and prevalence of microcephaly led to the declaration of national and international emergencies. Extensive research has been conducted to understand the teratogenic effects of Zika virus, particularly its impact on neural progenitor cells in the fetal brain. Various pre- and postnatal imaging techniques, such as ultrasound, magnetic resonance imaging (MRI), and postnatal computed tomography (CT), have played crucial roles in diagnosing and monitoring malformations linked to congenital Zika virus infection in the central nervous system (CNS). These modalities can detect brain parenchymal abnormalities, calcifications, cerebral atrophy, and callosal anomalies. Additionally, three-dimensional ultrasound and fetal MRI provide detailed anatomical images, while CT can identify calcifications that are not easily detected by other methods. Despite advancements in imaging, there are still unanswered questions and ongoing challenges in comprehending the long-term effects and developmental impairments in children affected by Zika virus. Radiologists continue to play a crucial role in diagnosing and assisting in the management of these cases.
Graphical Abstract
... The assessment of structural abnormalities caused by CTx, including calcification, ventricular dilatation, and aqueduct obstruction, can be done through ultrasonography or CT scan. Some authors suggest that the use of computed tomography scans (CT) may be preferable due to a higher sensitivity in detecting intracranial calcifications [11,14]. ...
Toxoplasmagondii is a parasite that is estimated to infect one-third of the world’s population. It is acquired by ingesting contaminated water and food specially undercooked meat, contact with domestic or wild feline feces, and during pregnancy by transplacental transmission.
Immunocompetent hosts are usually asymptomatic, and infection will be self-limited, while those patients whose immune system is debilitated by HIV infection, immunosuppressive therapy, long-term steroid treatment, and fetuses infected during gestation will show evidence of systemic activity which is more severe in the central nervous system and eyes due to insufficient immune response caused by their respective blood barriers. Congenital toxoplasmosis has an estimated incidence of 8% in mothers who were seronegative at the beginning of their pregnancy. Infection in the first trimester may result in spontaneous abortion or stillbirth; however, it is estimated that the highest risk for vertical transmission is during the second and third trimesters when blood flow and placenta thickness favor parasitic transmission.
Congenital toxoplasmosis can be detected with periodic surveillance in endemic areas, and with appropriate treatment, the risk of vertical transmission can be reduced, and the severity of the disease can be reversed in infected fetuses.
While most infected newborns will show no evidence of the disease, those who suffer active intrauterine complications will present with cerebral calcifications in 8–12% of cases, hydrocephalus in 4–30%, and chorioretinitis in 12–15%. Also, seizure disorders, spasticity, and varying degrees of neurocognitive deficits can be found in 12%.
Four distinct patterns of hydrocephalus have been described: aqueductal stenosis with lateral and third ventricle dilatation, periforaminal calcifications leading to foramen of Monro stenosis with associated asymmetrical ventricle dilatation, a mix of aqueductal and foramen of Monro stenosis, and overt hydrocephalus without clear evidence of obstruction with predominant dilatation of occipital horns (colpocephaly).
While all patients diagnosed with congenital toxoplasmosis should undergo pharmacological treatment, those presenting with hydrocephalus have traditionally been managed with CSF shunting; however, there are reports of at least 50% success when selected cases are treated with endoscopic third ventriculostomy. Successful hydrocephalus management with appropriate treatment leads to better intellectual outcomes.
... 65,66 Brain parenchyma calcifications may also occur. 69 ...
Syphilis is an infectious disease caused by the spirochete Treponema pallidum, subspecies pallidum. Although its incidence has declined after the widespread availability of penicillin, it has recently re-emerged, especially in men who have sex with men and in people living with human immunodeficiency virus (HIV). The neurological manifestations of syphilis, generally known as neurosyphilis, may appear at any time during the infection, including the initial years after the primary infection. Neurosyphilis can be asymptomatic, only with cerebrospinal fluid abnormalities, or symptomatic, characterized by several different clinical syndromes, such as meningitis, gumma, meningovascular, brain parenchyma involvement, meningomyelitis, tabes dorsalis, and peripheral nervous system involvement. However, these syndromes may simulate several other diseases, making the diagnosis often a challenge. In addition, syphilis can also be vertically transmitted from mother to child during pregnancy, leading to neurological manifestations. Neuroimaging is essential to demonstrate abnormal brain or spinal cord findings in patients with neurosyphilis, aiding in the diagnosis, treatment, and follow-up of these patients. This article aims to review the imaging features of neurosyphilis, including the early and late stages of the infection.
... While the calcification of CNS structures such as the choroid plexus or pineal gland is frequently encountered in physiological ageing, basal ganglia or subcortical calcification may be found in young individuals as part of an underlying genetic disease (after exclusion of acquired CNS calcification diseases, e.g., congenital infections, hypo/hyperparathyroidism, systemic lupus, erythematosus, etc.) [1,73]. Indeed, CNS calcification is often a hallmark and diagnostic clue of several hereditary conditions including Aicardi-Goutières syndrome (AGS; OMIM #225750), Cockayne syndrome (OMIM #216400) and Leukodystrophy with Cysts and Calcification (LCC; OMIM #614561). ...
Ectopic calcification (EC) is characterized by an abnormal deposition of calcium phosphate crystals in soft tissues such as blood vessels, skin, and brain parenchyma. EC contributes to significant morbidity and mortality and is considered a major health problem for which no effective treatments currently exist. In recent years, growing emphasis has been placed on the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of EC. Impaired mitochondrial respiration and increased levels of reactive oxygen species can be directly linked to key molecular pathways involved in EC such as adenosine triphosphate homeostasis, DNA damage signaling, and apoptosis. While EC is mainly encountered in common diseases such as diabetes mellitus and chronic kidney disease, studies in rare hereditary EC disorders such as pseudoxanthoma elasticum or Hutchinson-Gilford progeria syndrome have been instrumental in identifying the precise etiopathogenetic mechanisms leading to EC. In this narrative review, we describe the current state of the art regarding the role of mitochondrial dysfunction and oxidative stress in hereditary EC diseases. In-depth knowledge of aberrant mitochondrial metabolism and its local and systemic consequences will benefit the research into novel therapies for both rare and common EC disorders.
... As a consequence, neurological involvement, such as psychomotor retardation and intracerebral calcifications, seen in some interferonopathies such as AGS are reported early on during the disease onset (100). Interestingly, a group of organisms causing congenital fetal infections (toxoplasma, rubella, CMV, and HSV), collectively termed TORCH, also cause intracranial calcifications in neonatal periods, reminiscent of the ones found in interferonopathies (103). We will discuss here the genetic background and immunopathology of interferonopathies with neurological involvement (summarized in Table 1). ...
Type I interferons (IFNs) are major mediators of innate immunity, with well-known antiviral, antiproliferative, and immunomodulatory properties. A growing body of evidence suggests the involvement of type I IFNs in the pathogenesis of central nervous system (CNS) manifestations in the setting of chronic autoimmune and autoinflammatory disorders, while IFN-β has been for years, a well-established therapeutic modality for multiple sclerosis (MS). In the present review, we summarize the current evidence on the mechanisms of type I IFN production by CNS cellular populations as well as its local effects on the CNS. Additionally, the beneficial effects of IFN-β in the pathophysiology of MS are discussed, along with the contributory role of type I IFNs in the pathogenesis of neuropsychiatric lupus erythematosus and type I interferonopathies.
... Pathologic ICCs have heterogeneous etiologies such as neoplastic, infectious, vascular, metabolic, and genetic conditions. 49 Congenital infections with pathogens of the TORCH-spectrum, and congenital cytomegalovirus (CMV) infections in particular, account for a significant amount of congenital and pediatric ICCs that are associated with brain malformations and impaired neurodevelopment. 50 However, genetic disorders such as interferonopathies represent important differential diagnoses for congenital ICCs and some conditions significantly overlap with the symptomatic spectrum of congenital TORCH-infections. ...
PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications.
... Diferentes técnicas de imagen pueden registrar las mineralizaciones intracraneales, siendo la tomografía computarizada de haz cónico (TCHC) de campo amplio, la que permite identificar estos hallazgos en los pacientes odontológicos (1,6). La evidencia científica ha demostrado que este fenómeno se puede identificar en un aproximado del 60% de los pacientes (6). ...
... Pathological calcification can be seen in damaged, neoplastic, or malformed brains in approximately half of all occurrences, with congenital infections (neonatal "TORCH" infections including toxoplasmosis, syphilis, Varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes) figuring prominently. 28 Neurological symptoms associated with various causes of ICC depend on the specific aetiology of the causative syndrome. 29 Primary familial brain calcification (PFBC, Fahr's disease) is a group of genetic disorders characterised by calcification in the basal ganglia and other brain regions due to heterozygous mutations in several genes or homozygous mutations in OCLN, JAM2, and JAM3. ...
We describe a child from a consanguineous family born with a rare autosomal recessive disorder affecting junctional adhesion molecule 3 (JAM3) causing profound neurological and ophthalmological injury known as haemorrhagic brain destruction, subependymal calcifications, and congenital cataracts (HDBSCC; MIM# 613730). She was the product of an unremarkable pregnancy and was born near to term but was noted shortly after birth to have congenital cataracts, poor vision, increased muscle tone, seizures, and developmental delay. Her older sister had an identical syndrome and had previously been documented to have homozygous mutations in JAM3. Examination in our patient, although difficult because of
bilateral central cataracts, revealed very poor vision, attenuated retinal vessels, optic atrophy, and a retinal haemorrhage in the right eye, implying that abnormal development of the retinas and/or optic nerves may at times play a significant role in the poor vision noted in
children with HDBSCC.
... Ossification of the falx cerebri is a rare occurrence; it is present in approximately 7% of radiographs [2]. Physiological calcifications of the dura mater, including the falx cerebri, increase with age and are more common in men than in women [3,4]. In most cases, this finding has no clinical significance [1,2]. ...
... CT is the most sensitive method for detecting physiological intracranial calcifications [3]. On CT scans, falx cerebri ossifications appear as areas of focal marginal cortical bone-like density with occasional central lower density areas representative of bone marrow [1,2]. ...
The images presented in this paper are part of a series which aims to highlight anatomical variants and incidental findings which
may be placed on hybrid imaging. The current images show the incidental finding of falx cerebri ossification which has been
evident on 18F-sodium fluoride positron emission tomography/computed tomography (CT) scans of a 45-year-old female with breast cancer and a 61-year-old male with known prostate cancer. The falx cerebri is a midline fold of the dura mater which may
become ossified in some patients. This finding can have varying appearances on CT scans due to location, size, extent, and pattern
of ossification. Physicians must be able to identify this as an incidental finding rather than a pathological lesion in order to avoid
misinterpretation.
... The differential diagnosis is variable based on the location of intracranial calcifications. For example, intracranial calcifications on thalamus occur in various conditions such as Down syndrome, hypo-and hyperparathyroidism, pseudohypoparathyroidism, Fahr disease, Aicardi-Goutières syndrome, Krabbe disease, MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes), Kearns-Sayre syndrome, Cockayne syndrome, molybdenum cofactor deficiency A, sulfite oxidase deficiency, and pseudo-TORCH syndrome 1 [Gonçalves et al., 2020]. On the other hand, intracranial calcifications on periventricular white matter occur in: infections (including cytomegalovirus, toxoplasmosis, rubella, Zika virus, post-ventriculitis), tuberous sclerosis, Aicardi-Goutières syndrome, COL4A1 mutation, juvenile Alexander disease, X-linked adrenoleukodystrophy, pseudo-TORCH syndrome 2, and early infantile epileptic encephalopathy-49 [Gonçalves et al., 2020]. ...
... For example, intracranial calcifications on thalamus occur in various conditions such as Down syndrome, hypo-and hyperparathyroidism, pseudohypoparathyroidism, Fahr disease, Aicardi-Goutières syndrome, Krabbe disease, MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes), Kearns-Sayre syndrome, Cockayne syndrome, molybdenum cofactor deficiency A, sulfite oxidase deficiency, and pseudo-TORCH syndrome 1 [Gonçalves et al., 2020]. On the other hand, intracranial calcifications on periventricular white matter occur in: infections (including cytomegalovirus, toxoplasmosis, rubella, Zika virus, post-ventriculitis), tuberous sclerosis, Aicardi-Goutières syndrome, COL4A1 mutation, juvenile Alexander disease, X-linked adrenoleukodystrophy, pseudo-TORCH syndrome 2, and early infantile epileptic encephalopathy-49 [Gonçalves et al., 2020]. In the present study, we investigated these possible underlying causes in both of our patients, but we determined no additional condition. ...
... Susceptibility-weighted imaging is a sensitive sequence for the description of hemorrhage or calcification. Both hemorrhages and calcifications indicate a low signal and often artifacts on the magnitude images [Halefoglu and Yousem, 2018;Gonçalves et al., 2020]. In the present study, we showed suspicious imaging findings on MRI for calcifications in both cases, then confirmed by CT. ...
3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency is the most frequent organic aciduria detected in newborn screening programs. It demonstrates a variable heterogeneous clinical phenotype, ranging from neonatal onset with severe neurological disorders to asymptomatic adult forms. Herein, we report the first 2 related cases of 3-MCC deficiency presenting with intracranial calcification in the literature. A girl and a boy aged 3 years, 9 months and 4 years were included in the study. The main clinical manifestations were acquired microcephaly, global developmental delay, intractable seizures, mild feeding difficulty, and intermittent dystonic contractions. On physical and neurological examinations, their weights, heights, and head circumferences were below the 3rd percentile, they had acquired microcephaly, truncal hypotonia, upper and lower limb spasticity, hyperreflexia, positive bilateral Babinski signs, and clonus. The detailed biochemical and metabolic tests were unremarkable, except blood 3-hydroxyisovalerylcarnitine (C5OH) was slightly increased in case 1. Cranial computed tomography demonstrated mild cerebral and cerebellar atrophy as well as bilateral periventricular and thalamic calcifications in both cases. We identified a homozygous mutation of c.1015G>A (p.V339M) in the MCCC2gene, and the mutation was confirmed by Sanger sequencing. To the best of our knowledge, our cases are the first reported describing intracranial calcification in cases with 3-MCC deficiency. This report expands on the underlying causes of intracranial calcifications and suggests that 3-MCC deficiency may have intracranial calcifications on bilateral thalamus and periventricular white matters. If clinical findings show intracranial calcification, 3-MCC deficiency should also be kept in mind.
