Basal Ganglia Calcification Research Articles

Chronic subdural hematoma associated with fahr syndrome: A clinical association or just a simple coincidence?

The Fahr syndrome (FS) is a rare degenerative neurological disorder (its prevalence is <0.5%). FS is distinguished by the presence of abnormal bilateral intracranial calcifications with a predilection for the basal ganglia, also presented by movement disorders such as parkinsonism, paresis, and speech disorders. Chronic subdural hematoma (CSH), which is typically the result of mild head trauma, is a regularly encountered condition in elderly. A 63-year-old man has referred to our clinic from another hospital with a history of mild head trauma approximately a month ago. At the time of admission, the patient's Glasgow Coma Scale point was 15 points. In the history, there was only mild ataxia and right-sided hemiparesis. The laboratory examination revealed no electrolytes level abnormalities and normal endocrinal test examinations. Computed tomography revealed bilateral calcifications of basal ganglia, dentate nuclei which were misinterpreted as intracerebral contusion; with CSH of left temporal and parietal region. The hematoma was evacuated by burr-hole drainage. The patient was discharged 5 days after the surgery. The pathophysiology of FS is still unrevealed. There are some suggestions such as secondary to local disturbance of blood-brain barrier or a calcium neuronal metabolism disorder. However, on the other hand, local blood-brain barrier disturbance would also take part in CSH pathology. We hypostasized that patients with the history of FS, who had mild head traumas, might prone to subdural collections. On the other hand, FS and CSH coexistence is very unusual. Neurosurgeons might keep in mind FS when bilateral calcifications are seen in a patient.

Woodhouse-Sakati Syndrome With Psychosis and Basal Ganglia Calcification: A Case Report

Woodhouse Sakati syndrome is a rare autosomal recessive multisystem disorder characterized by neuropsychological, endocrinal, and ectodermal symptoms. We report a 52-year-old Saudi female with psychosis, extrapyramidal signs, sensorineural hearing loss, diabetes, hypothyroidism, amenorrhea, hypergonadotropic hypogonadism, absence of secondary sexual characters, and alopecia totalis. Her brain computed tomography (CT) showed bilateral basal ganglia calcification and her genetic testing confirmed homozygous single nucleotide deletion (C.436delC) of frameshift mutation (p.A147HfsX9) in exon 4 of the gene DCAF17 gene. Woodhouse Sakati syndrome seems to be more prevalent, and probably underdiagnosed, in the Middle East and Arab countries, and should be considered in patients with a combination of neurological and endocrinal dysfunction. To our knowledge, this is the first case reported to have psychotic symptoms. J Med Cases. 2018;9(2):73-75 doi: https://doi.org/10.14740/jmc2996w

SCL20A2 mutation presenting with acute ischemic stroke: a case report

BackgroundPrimary familial brain calcification (PFBC) is a rare disorder characterized by distinctive bilateral brain calcification and variable clinical presentations. However, cerebrovascular attack was rarely reported in PFBC patients. We here reported a SLC20A2 mutation patient presenting with acute ischemic stroke.Case presentationA 56 years old man was transferred to our hospital because of 6 days of melena and 3 days of somnolence, agitation and mood changes. Computed tomography (CT) scan showed symmetrical calcifications in bilateral basal ganglia, caudate nucleus, thalami, subcortical white matter and cerebellum, which is consistent with PFBC. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke in bilateral basal ganglia and periventricular regions. Mutational analysis identified a SLC20A2 gene mutation c.344C > T (p.Thr115Met) in exon 3. One of his daughters had also suffered from brain calcification. MR perfusion imaging revealed hypoperfusion in bilateral basal ganglia, prefrontal and temporal lobe. After treatment, he discharged with a favorable functional outcome but cognitive impairment.ConclusionsIschemic stroke can occur in PFBC patients, which may be associated with hypoperfusion and calcification of arteries. And hypoperfusion in frontotemporal lobar may be related with their cognitive impairment.

Stroke After Minor Head Trauma in Infants and Young Children With Basal Ganglia Calcification: A Lenticulostriate Vasculopathy?

The authors retrospectively reviewed charts of the children with basal ganglia stroke who either had preceding minor head injury or showed basal ganglia calcification on computed tomography (CT) scan. Twenty children, 14 boys and 6 girls were identified. Eighteen were aged between 7 months to 17 months. Presentation was with hemiparesis in 17 and seizures in 3. Preceding minor head trauma was noted in 18. Family history was positive in 1 case. Bilateral basal ganglia calcification on CT scan was noted in 18. Brain magnetic resonance imaging done in 18 infants showed acute or chronic infarcts in basal ganglia. Results of other laboratory and radiological investigations were normal. Four infants were lost to follow-up, 9 achieved complete or nearly completely recovery, and 7 had persistent neurological deficits. Basal ganglia calcification likely represents mineralized lenticulostriate arteries, a marker of lenticulostriate vasculopathy. Abnormal lenticulostriate vessels are vulnerable to injury and thrombosis after minor head trauma resulting in stroke.

Hypoparathyroidism – Review of the Literature 2018

Hypoparathyroidism is a rare endocrine disorder characterized by low calcium and high phosphate levels, in the setting of a low or inappropriately normal PTH level. Given its rarity, it has been classified as an orphan disease in the United States and by the European Commission. The first international conference on the management of hypoparathyroidism was convened in Florence Italy 2015 and resulted in the publication of detailed guidelines on the epidemiology, presentation, clinical features and management of hypoparathyroidism. Hypoparathyroidism may be associated with a spectrum of clinical manifestations, ranging from asymptomatic in the setting of mild hypocalcemia, to life threatening cardiac arrythmias, seizures or laryngospasm, in the setting of severe acute hypocalcemia. The most common cause is postsurgical hypoparathyroidism following anterior neck surgery, followed by autoimmune disorders and rarely genetic disorders. Establishing a diagnosis of hypoparathyroidism is important as it is associated with the development of kidney stones, renal insufficiency, cataracts, basal ganglia calcifications, as well as a reduced health-related quality of life. Most patients with chronic hypoparathyroidism require lifelong high dose calcium and activated vitamin D supplements. The goals of treatment are 3 fold, namely, relieve symptoms of hypocalcemia, raise calcium concentration to the low-normal range and avoid hypercalciuria. For those individuals who cannot maintain a stable serum and urine calcium with conventional calcium and activated Vitamin D regimens, the addition of recombinant PTH (1-84) is currently an option. The approval of recombinant PTH (1-84) represents a significant step forward in the management of this disorder.

A Unique Presentation Of Fahr Syndrome Secondary To Chronic Hypoparathyroidism: A Case Report

Idiopathic basal ganglia calcification, or Fahr Syndrome, often presents in middle-aged patients presenting with parkinsonian symptoms. Unique presentation of young patient presenting with a seizure, and without the presence of parkinsonian symptoms. Imaging revealed near complete calcification of bilateral basal ganglia. Most common etiology of basal ganglia calcification is idiopathic or familial, but may also be secondary to metabolic derangements.

Woodhouse-Sakati Syndrome With Psychosis and Basal Ganglia Calcification: A Case Report

Woodhouse-Sakati Syndrome With Psychosis and Basal Ganglia Calcification: A Case Report

A Rare Case of Acute Symptomatic Seizure, Tetany and Poor Sensorium Secondary to Autosomal Dominant Hypocalcemia and Hypercalciuria

Symptomatic seizures are due to varied etiologies. Genetic disorders causing seizures are well known. Described initially in 1993, Autosomal dominant hypocalcemia with hypercalciuria is a rare genetic disorder, secondary to defective calcium sensing receptor gene (CASR). Two types of mutations can occur in CASR gene which could be activating and inactivating. ADHH occurs due to the activating mutation of the gene. It results in hypocalcemia, hypercalciuria, hypomagnesemia which can manifest as tetany, seizures and worsening sensorium. Here we describe one such case where seizure was the initial presentation followed by tetanic spasms, decreased sensorium and bilateral basal ganglia calcifications in CT brain.

A boy with bird-like facies and ataxia: Cockayne syndrome

Introduction: Congenital photosensitive disorders are a group disorders presenting with photosensitivity, short stature (SS), systemic manifestations and susceptibility to malignancy. These include Bloom syndrome, Cockayne syndrome (CS), Rothmund-Thompson syndrome, etc. Early identification and differentiating the syndrome from other congenital disorder is essential as the prognosis of each disorder differs. Case Report: A 4year-old-boy presented with photosensitive rash over the butterfly area of the face. He had history of delayed developmental milestones. His height and weight for his age were below the first percentile. On examination, patient had microcephaly, bird-like facies including sunken eyes, pinched nose, cachectic physique, ataxia and flexural contractures at elbow, knee and ankle joints. Ophthalmic examination showed pigmentary retinopathy on fundoscopy. CT scan of brain revealed bilateral basal ganglia calcification and evidence of premature mild cerebral atrophic changes. On the basis of clinical and lab investigations, we diagnosed this case as CS. Discussion: CS is a rare AR disorder characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. They have SS, sexual immaturity, and/or retinal pigmentation. Diagnosis of the CS is made by characteristic clinical features specific to this, but the definitive diagnosis is achieved by laboratory investigations such as cytogenetic, biochemical and molecular methods. Although there is no specific treatment, avoidance of sun exposure and protection by sunscreens can help prevent some of the cutaneous eruptions associated with photosensitivity.

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification

Background and PurposeThe idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. MethodForty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18–32 and 33–45 years of age) and gender (male, female). ResultsWe detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18–32 years and 33–45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). ConclusionConsidering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker.

Ifngr1 and Stat1 mediated canonical Ifn-γ signaling drives nigrostriatal degeneration

Brain expression of AAV-Ifn-γ leads to reactive gliosis, nigrostriatal degeneration and midbrain calcification in wild type mice. This mouse model phenocopies idiopathic basal ganglia calcification which is associated with Parkinsonian symptoms. To understand how the nigro-striatal pathway is selectively vulnerable to Ifn-γ, we determined if the phenotype is driven by canonical signaling intermediates, Ifngr1 and Stat1. Using focused bioinformatic analysis and rotarod testing, we show that neuroinflammation and motor abnormalities precede the appearance of midbrain neuropathologies in the brains of Ifn-γ mouse model. To test whether canonical Ifn-γ signaling is a key driver of progressive nigrostriatal degeneration, we overexpressed Ifn-γ in the brains of Ifngr1−/− and Stat1−/− mice. Expression of Ifn-γ in Ifngr1−/− mice did not result in any neuroinflammation, midbrain calcinosis or nigrostriatal degenerative pathology. Interestingly, in Stat1−/− mice, Ifn-γ expression resulted in gliosis without recapitulating the neurodegenerative phenotype. Overall, our data shows that canonical Ifn-γ signaling triggers midbrain calcinosis and nigrostriatal neurodegeneration, providing mechanistic insights into cytokine-driven selective neuronal vulnerability. Our study establishes the broader relevance of inflammatory signaling in neurodegenerative diseases and can potentially identify novel immunological targets for Parkinsonian syndromes.

Estimation of minimal disease prevalence from population genomic data: Application to primary familial brain calcification.

Primary Familial Brain Calcification (PFBC) is a rare calcifying disorder of the brain with autosomal dominant inheritance, of unknown prevalence. Four causal genes have been identified so far: SLC20A2, PDGFB, PDGFRB, and XPR1, with pathogenic, probably pathogenic or missense variants of unknown significance found in 27.7% probands in the French PFBC series. Estimating PFBC prevalence from a clinical input is arduous due to a large diversity of symptoms and ages of onset and to incomplete clinical penetrance. Abnormal calcifications on CT scan can be used as a reliable diagnostic biomarker whatever the clinical status, but differential diagnoses should be ruled out including the challenging exclusion of common basal ganglia calcifications. Our primary aim was to estimate the minimal prevalence of PFBC due to a variant in one of the known genes. We extracted variants from the four known genes present in the gnomAD database gathering genomic data from 138,632 individuals. We interpreted all variants based on their predicted effect, their frequency, and previous studies on PFBC patients. Using the most conservative estimate, the minimal prevalence of PFBC related to a variant in one of the four known genes was 4.5 p. 10,000 (95%CI [3.4-5.5] p. 10,000). We then used variant detection rates in patients to extrapolate an overall minimal prevalence of PFBC to 2.1 p. 1,000 (95%CI [1.9-2.4] p. 1,000). The population-based genomic analysis indicates that PFBC is not an exceptionally rare disorder, still underestimated and underdiagnosed.

Presumed Zika virus-related congenital brain malformations: the spectrum of CT and MRI findings in fetuses and newborns.

The new epidemic of Zika virus infection raises grave concerns, especially with the increasingly-recognized link between emerging cases of microcephaly and this infectious disease. Besides small cranial dimensions, there are striking morphologic anomalies in the fetal brain. Key anomalies include cortical developmental malformations and a peculiar distribution of pathologic calcifications. These potentially indicate a new pattern of congenital central nervous system infection. Eight women underwent fetal MRI. Four infants also underwent postnatal CT. Five of the women underwent amniocentesis. All neonates were born with microcephaly. On fetal MRI, ventriculomegaly, marked reduction of white matter thickness, severe sylvian fissure simplification, abnormal sulcation, and diffuse volumetric loss of cerebellar hemispheres were consistently seen. On postnatal CT, diffuse subcortical and basal ganglia calcifications were observed. The Zika virus was detected in two amniocenteses by polymerase chain reaction assays. We hope to assist the medical community in recognizing the spectrum of encephalic changes related to congenital Zika virus infection.

Fahr’s Disease in a 26 year-old female: A case report

Background: Fahr’s disease is a rare, degenerative neurological-psychiatric disorder characterized by idiopathic symmetrical and bilateral intracranial calcification. Prevalence of <1:1,000,000, usually presents at middle age group, rarely in the young. Calcification are deposited in basal ganglia, thalamus, putamen, hippocampus, cerebral cortex, cerebellar subcortical white matter and dentate nucleus. Diagnosis requires certain clinical criteria: absence of biochemical abnormalities and somatic features; absence of infection, trauma, toxic cause; presence of progressive neuropsychiatric dysfunction with onset of symptoms at 4th – 5th decade of life, presence of bilateral basal ganglia calcification visualized on neuroimaging and family history with autosomal dominant inheritance or sporadic.

Fahr’s disease: Idiopathic basal ganglia calcification in two young Filipino women a case report

Introduction: Fahr’s Disease is a rare, autosomal dominant neurologic disorder that presents with neurologic and neuropsychiatric symptoms. It is characterized by the presence of calcium deposits in the basal ganglia documented through CT Scan.

Cerebral Manifestations of Mitochondrial Disorders.

This review aims at summarizing and discussing previous and recent findings concerning the cerebral manifestations of mitochondrial disorders (MIDs). MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) either already at onset or later in the course. After the muscle, the brain is the organ second most frequently affected in MIMODS. Cerebral manifestations of MIDs are variable and may present with or without a lesion on imaging or functional studies, but there can be imaging/functional lesions without clinical manifestations. The most well-known cerebral manifestations of MIDs include stroke-like episodes, epilepsy, headache, ataxia, movement disorders, hypopituitarism, muscle weakness, psychiatric abnormalities, nystagmus, white and gray matter lesions, atrophy, basal ganglia calcification, and hypometabolism on 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron-emission tomography. For most MIDs, only symptomatic therapy is currently available. Symptomatic treatment should be supplemented by vitamins, cofactors, and antioxidants. In conclusion, cerebral manifestations of MIDs need to be recognized and appropriately managed because they strongly determine the outcome of MID patients.

Musculoskeletal Disease in MDA5-Related Type I Interferonopathy: A Mendelian Mimic of Jaccoud's Arthropathy.

To define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet, including camptodactyly, subluxation, and tendon rupture, reminiscent of Jaccoud's arthropathy. We identified 2 families segregating an autosomal-dominant phenotype encompassing musculoskeletal disease and variable additional features, including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma, and basal ganglia calcification. We measured the expression of interferon (IFN)-stimulated genes in the peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA (dsRNA) sensor melanoma differentiation-associated protein 5 (MDA-5). We also assessed the functional consequences of IFIH1 gene variants using an in vitro IFNβ reporter assay in HEK 293T cells. We recorded an up-regulation of type I IFN-induced gene transcripts in all 5 patients tested and identified a heterozygous gain-of-function mutation in IFIH1 in each family, resulting in different substitutions of the threonine residue at position 331 of MDA-5. Both of these variants were associated with increased IFNβ expression in the absence of exogenous dsRNA ligand, consistent with constitutive activation of MDA-5. These cases highlight the significant musculoskeletal involvement that can be associated with mutations in MDA-5, and emphasize the value of testing for up-regulation of IFN signaling as a marker of the underlying molecular lesion. Our data indicate that both Singleton-Merten syndrome and neuroinflammation described in the context of MDA-5 gain-of-function constitute part of the same type I interferonopathy disease spectrum, and provide possible novel insight into the pathology of Jaccoud's arthropathy.

Comprehensive molecular screening strategy of OCLN in band-like calcification with simplified gyration and polymicrogyria.

Occludin (OCLN) is an important component of the tight junction complex, providing apical intercellular connections between adjacent cells in endothelial and epithelial tissue. In 2010 O'Driscoll et al reported mutations in OCLN to cause band-like calcification with simplified gyration and polymicrogyria (BLC-PMG). BLC-PMG is a rare autosomal recessive syndrome, characterized by early onset seizures, progressive microcephaly, severe developmental delay and deep cortical gray matter and basal ganglia calcification with symmetrical, predominantly fronto-parietal, polymicrogyria. Here we report 4 additional cases of BLC-PMG with novel OCLN mutations, and provide a summary of the published mutational spectrum. More generally, we describe a comprehensive molecular screening strategy taking into account the technical challenges associated with the genetic architecture of OCLN, which include the presence of a pseudo-gene and copy number variants.

Reversible central neural hyperexcitability: an electroencephalographic clue to hypocalcaemia

A 23-year-old male patient presented with cognitive decline and seizures. Examination revealed Chvostek's and Trousseau's signs. Investigations revealed hypocalcaemia, hyperphosphatemia and normal intact parathyroid hormone levels. Imaging showed calcifications in...

Induced pluripotent stem cells derived from a patient with familial idiopathic basal ganglia calcification (IBGC) caused by a mutation in SLC20A2 gene

Idiopathic basal ganglia calcification (IBGC), also known as Fahr disease or primary familial brain calcifications (PFBC), is a rare neurodegenerative disorder characterized by calcium deposits in basal ganglia and other brain regions, causing neuropsychiatric and motor symptoms. We established human induced pluripotent stem cells (iPSCs) from an IBGC patient. The established IBGC-iPSCs carried SLC20A2 c.1848G>A mutation (p.W616* of translated protein PiT2), and also showed typical iPSC morphology, pluripotency markers, normal karyotype, and the ability of in vitro differentiation into three-germ layers. The iPSC line will be useful for further elucidating the pathomechanism and/or drug development for IBGC.