Basal Ganglia Calcification Research Articles

MON-464 A Rare Case of Hypocalcemia-Induced Intractable Vomiting Requiring PEG Tube Placement

Introduction: Hypoparathyroidism is characterized by hypocalcemia and hyperphosphatemia secondary to inadequate PTH secretion. Clinical manifestations are carpopedal spasm, perioral paresthesia, and seizures. Herein, we present a case of hypoparathyroid-induced hypocalcemia requiring PEG tube placement. Case Presentation: Patient is a 41-year-old female who presents with intractable nausea, continuous vomiting, abdominal pain, and perioral paresthesia for the past 4 days. Patient has a past medical history significant for hypoparathyroidism, severe hypocalcemia, hypomagnesemia, hyperphosphatemia, and iron deficiency anemia. Patient was diagnosed with hypoparathyroidism at the age of 16 when her son was born with congenital abnormalities due to severe maternal hypocalcemia. She has 4 children, 1 son passed away in infancy from severe hypocalcemia. Out of the remaining 3 children, 2 daughters have hypoparathyroidism. Patient has had multiple recurrent admissions for severe hypocalcemia presenting as angina, syncope, and left-sided weakness. Both cardiology work up and neurology workup have been negative. MRI of the brain shows basal ganglia calcifications. Labs are significant for corrected calcium 6.72 mg/dL (n 8 to 10 mg/dL), magnesium 1.4 mg/dL (n 1.7 to 2.2 mg/dL), phosphorus 7.4 mg/dL (n 2.4 to 4.5 mg/dL), Vitamin D 14.9 ng/mL (n 30 to 100 ng/mL), and PTH level 9.8 pg/mL (n 18.5 to 88 pg/mL). Prior ACTH stimulation test was within normal limits excluding adrenal insufficiency. EGD biopsy on prior admission was positive for H. Pylori, however patient left against medical advice and did not receive triple therapy. Patient was admitted for hypocalcemic crisis and placed on a calcium gluconate drip, oral calcium, magnesium, calcitriol, and Vitamin D, in addition to H. pylori triple therapy. During the hospitalization, she was unable to tolerate oral medications for greater than 2 weeks resulting in PEG placement. The patient’s electrolytes were successfully repleted via PEG tube and she was discharged. Discussion: Spontaneous hypoparathyroidism is a rare metabolic disorder characterized by parathyroid glands that do not produce or secrete enough PTH to maintain normal levels of calcium and phosphorous in the blood. Though GI consequences such as steatorrhea may occur, to our knowledge, this is the first reported case of hypocalcemia-induced intractable vomiting requiring PEG tube. Before PEG placement, the patient had 12 admissions in 1 year. After PEG placement, the number dropped significantly to 4 admissions in 1 year. Due to the unique presentation of hypoparathyroid hypocalcemia, we would like to raise awareness regarding such a presentation which can be challenging for clinicians.

Fahr’s disease: familial idiopathic basal ganglia calcification with and without extrapyramidal disorders

Fahr’s disease (FD), also known as familial idiopathic basal ganglia calcification, is a neurodegenerative disease affecting cerebral micro vessels, mainly in the basal ganglia. It mostly presents with movement disorders, dementia and behavioral abnormalities. It is considered hereditary with an autosomal dominant transmission. Fahr’s disease is often underestimated and under diagnosed. We reported the clinical differences found in two patients with Fahr’s Disease. In particular, we described a case of Fahr’s disease with behavioral alteration with extrapyramidal movement disorders, and a rare case of Fahr’s disease with cognitive and behavioral alterations in absence of extrapyramidal movement disorders.

Cortical myoclonus and epilepsy in a family with a new SLC20A2 mutation

Idiopathic basal ganglia calcification (IBGC) or primary familial brain calcification is a rare genetic condition characterized by an autosomal dominant inheritance pattern and the presence of bilateral calcifications in the basal ganglia, thalami, cerebellum and cerebral subcortical white matter. The syndrome is genetically and phenotypically heterogeneous. Causal mutations have been identified in four genes: SLC20A2, PDGFRB, PDGFB and XPR1. A variety of progressive neurological and psychiatric symptoms have been described, including cognitive impairment, movement disorders, bipolar disorder, chronic headaches and migraine, and epilepsy. Here we describe a family with a novel SLC20A2 mutation mainly presenting with neurological symptoms including cortical myoclonus and epilepsy. While epilepsy, although rare, has been reported in patients with IBGC associated with SLC20A2 mutations, cortical myoclonus seems to be a new manifestation.

Basal ganglia infarction after mild head trauma in pediatric patients with basal ganglia calcification

ObjectivesIncidence rate of basal ganglia infarction (BGI) after mild head trauma was reported higher in children with basal ganglia calcification (BGC). We would like to review patients with BGC showed in head CT scan to see the incidence rate of stroke in these patients and the correlation of variables in these cases. Patients and methodsCT imaging data of cases with diagnosis of mild traumatic brain injury (mTBI) in a large tertiary pediatric center between Mar. 2014 and Mar. 2019 was retrospectively reviewed. Cases with findings of punctate calcification in the region of basal ganglion in CT scan were included. Correlation of variables of these cases (age, side and volume of basal ganglion calcification) with the diagnosis of BGI was the focus of this study. Results37 patients (26 males, 9 females, median age: 3.88±3.54) were included in this study. 17 cases (45.9 %) were diagnosed of BGI and were admitted into the department of neurosurgery. Altogether 63 sides of BGC were categorized into two groups based on whether BGI happened and ROC curve was drawn. ROC curve showed when the cut-off point was 6.55 mm3, the sensitivity was 88.9 % and the specificity was 87.5 %; the area under curve was 0.849 (p<0.01). All the cases were divided into two groups according to whether basal ganglia infarction occurred or not. Mann-Whitney U test showed significant difference between these two groups in age (p=0.01). ROC curve of how age affect BGI after mTBI were drawn. The cut-off point was 3.25 years, and the sensitivity was 65.0 % and the specificity was 88.2 %; the area under curve was 0.746 (p=0.01). All patients received conservative treatment and recovered. ConclusionIncidence rate is higher in children with BGC after mild head injury than that of other children. Larger BGC volume indicates higher risk of developing infarction after minor head injury. Older children with BGC are less-likely getting BGI after mTBI.

Fahr's disease: idiopathic abnormal basal ganglia calcifications in the brain

A 56-year-old diabetic man complains for isolated chronic headaches for many years. He denied any seizure, involuntary limb movements or blurring of vision. Physical examination was unremarkable for any focal neurological deficits. Cranial Computed tomography (CT) scan showed extensive symmetrical calcifications of the bilateral basal ganglia and over the lateral periventricular areas (figure). Laboratory studies including serum calcium, phosphate, parathormone, thyroid hormones and vitamins were within normal range. There was no other obvious etiology or family history of similar illness. Based on these findings, the patient was diagnosed with Fahr´s disease and was managed conservatively. Fahr´s disease (FAD), also known as “familial idiopathic basal ganglia calcification”, is a rare neurological disorder characterized by abnormal calcified deposits in the basal ganglia, cerebellum and subcortical white matter. FAD differs from Fahr´s syndrome in which there is an underlying cause for brain calcifications. Neurological and psychiatric symptoms are variable and may include deterioration of motor function, parkinsonism, seizures, headache, dysarthria, spasticity, visual disturbances, dementia, psychosis, and affective disorders. FAD could be easily confused with other more common neurological and psychiatric disorders. It is particularly important to not miss the treatable etiologies of Fahr´s syndrome. The diagnosis is based on the CT scan because it is difficult to identify calcifications by routine magnetic resonance imaging. Treatment is essentially symptomatic.

PSEUDOPSEUDOHYPOPARATHYROIDISM AS A CAUSE OF FAHR SYNDROME: HYPOPARATHYROIDISM NOT THE ONLY ONE.

Fahr's syndrome is an infrequent disorder characterized by bilateral symmetrical calcification of basal ganglia and the cerebral cortex. It can be seen genetic, idiopathic, or secondary to endocrine diseases. This disease is related to different metabolic disorders particularly with diseases of the parathyroid gland. A 63-year-old female patient applied to our clinic due to having hypoparathyroidism with bilateral basal ganglia calcification in head computed tomography(CT). She had subtotal thyroidectomy 25 years ago. In the neurological examination, mild symmetrical parkinsonism was determined. In laboratory examination Ca:8 mg/dL (8.6-10.2), P:5.1 mg/dL (2.3-4.5), PTH:9.53 pg/mL (15-65) were detected. Calcitriol 0.25 μ/day was added to her treatment. Her parkinsonism disappeared after the treatment. A 49-year-old male patient was consulted when he was admitted to the department of neurology in our hospital. The physical examination demonstrated the characteristics of Albright's hereditary osteodystrophy. The neurological examination shows bilateral symmetrical bradykinesia, dysphagia, and moderate dysarthria. In the laboratory examination PTH: 46.5 ng/L(15-65), Ca:8.6 mg/dL (8.6-10.2), P:2.7 mg/dL (2.3-4.5) were detected and were all within the normal ranges. Consequently, pseudopseudohypoparathyroidism was decided as a diagnosis. G protein alpha subunit mutation (Gsα) was not detected due to technical limitations. When a patient is diagnosed as Fahr's syndrome, we should keep in mind parathyroid disorders. Fahr's syndrome must be evaluated in patients showing intracranial calcification accompanied by parathyroid diseases.

The pathophysiology and therapeutic drug development of idiopathic basal ganglia calcification

The pathophysiology and therapeutic drug development of idiopathic basal ganglia calcification

Functional evaluation of the patient-derived iPS cells from &lt;i&gt;PDGFB&lt;/i&gt;-variants in idiopathic basal ganglia calcification

Functional evaluation of the patient-derived iPS cells from &lt;i&gt;PDGFB&lt;/i&gt;-variants in idiopathic basal ganglia calcification

Obsessive compulsive disorder with psychotic features as neuropsychiatric manifestation of fahr's disease

Fahr's disease (FD) is a rare neurological disorder characterized by idiopathic bilateral basal ganglia calcification. It manifests as psychiatric, cognitive, and neurological manifestations. FD is distinct from Fahr's syndrome, in that the latter is having the symptoms generated by preexisting disease and abnormalities evident on blood investigations. In this case report, we present a case of FD presenting as obsessive compulsive disorder with psychotic features.

Functional evaluation of the patient-derived iPS cells from &lt;i&gt;PDGFB&lt;/i&gt;-variants in idiopathic basal ganglia calcification

Functional evaluation of the patient-derived iPS cells from &lt;i&gt;PDGFB&lt;/i&gt;-variants in idiopathic basal ganglia calcification

Fahr’s disease. Literature review and clinical case observation

Calcification of basal ganglia is a radiological finding that is often secondary to a variety of conditions or physiological aging of the brain. According to the literature data, its frequency varies greatly due to the lack of modern large‑scale population studies of the prevalence of calcification, as well as significant aging of the population. Clinical manifestations of basal ganglia calcification are variable. Patterns of neuroimaging findings also differ in clinical case descriptions.Idiopathic basal ganglia calcification (Fahr’s disease) is a disease, caused by mutations of certain genes, that has specific clinical and radiological features. Since it is a rare disease, all conclusions about the disease are based on descriptions of single clinical cases and diagnostic criteria for the disease remain a debatable issue. Nowadays, there is no clear understanding of what basal ganglia calcification can be considered as Fahr’s disease. There are no clear differential diagnostic criteria for the disease, and the described spectrum of genetic mutations is constantly being updated. The most common clinical manifestations of Fahr’s disease, according to literature data, are movement disorders, which are manifested in the form of parkinsonism, chorea, tremor, dystonia, athetosis and orofacial dyskinesia. Other signs include cognitive and psychiatric disorders, cerebellar symptoms, gait disorders, speech disorders, pyramidal signs, sensitive disorders and migraine headaches. Possible approaches to the treatment of this pathology remain debatable.This article presents a review of the literature on idiopathic basal ganglia calcification, describes its genetic features, clinical manifestations, and radiological findings. Differential — diagnostic criteria of the disease according to the current literature data are offered and clinical case observation of the patient with Fahr’s disease is given.

Mechanisms of calcification in Fahr disease and exposure of potential therapeutic targets.

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. 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. Knowledge about the mutations and corresponding pathways may expose therapeutic opportunities for patients with Fahr disease and vascular calcifications in the brain in general.

Aicardi-Goutières syndrome due to a paternal mosaic IFIH1 mutation.

Progressive immune-mediated neurodegeneration is a central feature of Aicardi-Goutières syndrome (AGS), a monogenic disorder characterized by chronic activation of antiviral type I interferon (IFN).1 Typically, AGS presents as subacute infancy-onset encephalopathy with microcephaly, leukodystrophy, and basal ganglia calcification, resulting in global developmental delay. AGS is either caused by loss-of-function mutations in TREX1 , RNASEH2B , RNASEH2C , RNASEH2A , SAMHD1 , or ADAR , encoding genes involved in the metabolism of nucleic acids, or by gain-of-function mutations in IFIH1 encoding the cytosolic RNA sensor melanoma differentiation-associated protein 5 (MDA5).1 The phenotypic spectrum of IFIH1 -associated mutations includes intracerebral vasculopathy, bilateral striatal necrosis, and isolated spastic paraparesis. The authors are thankful to the family for participation in this study. The authors thank Diana Federl and Kerstin Engel for excellent technical assistance.

Hypoparathyroidism - un underestimated problem?

Hypoparathyroidism is a rare and disabilitating disorder characterized by hypocalcemia and low parathyroid hormone levels. Most of the cases occur as a result of the removal of parathyroid glands or damage to the glands during neck surgery. More rare causes include nonsurgical causes such as autoimmune or genetic diseases. In this review, a panel of experts presents the current state of diagnosis and therapy of hypoparathyroidism and explains practical aspects of caring for the affected patients. Common signs and symptoms are abnormal sensations and increased excitability in the lower limbs, paresthesia of perioral areas and nocturnal leg cramps. Renal complications frequently occur, but also basal ganglia calcification. Treatment consists of administration of vitamin D analogs in combination with 0.5-1.0 g calcium daily. An adjunctive treatment with the in April 2017 approved recombinant human parathyroid hormone (1-84) is an option for patients whose hypoparathyroidism is difficult to control by conventional treatment alone. Initially and after dose changes follow-up controls should be performed at least every 2 weeks, in well-controlled patients or in the case of chronic progression every 3-6 months.

Bilateral hypocalcemic cataract after total thyroidectomy in a young woman: case report

BackgroundHypocalcemia is a derangement in serum calcium level due to a vast spectrum of disorders, but the most common cause is surgery, usually thyroid gland surgery. Symptoms of hypocalcemia can be due to increased neuromuscular excitation resulting in tetany, paresthesia or seizure. It can also be because of deposition of calcium in soft tissues producing reduced vision /cataract or calcification of basal ganglia. Cataract is the most common ocular symptom of hypocalcemia.Case reportA twenty-six years old Ethiopian female patient presented with painless reduction of vision of both eyes. Five years prior to the reduction of vision she was diagnosed to have hypocalcemia. The serum calcium level was very low (3 mg/dl) due to damage to the parathyroid gland during total thyroidectomy for toxic goiter. She has been on supplemental calcium gluconate twice daily. She had typical bilateral symmetrical posterior sub capsular cataract with punctate iridescent opacities in the anterior and posterior cortex of the lens. Systemic examination revealed horizontal surgical scar on the anterior neck and positive Chvostek sign.

Partial reduced Pi transport function of PiT-2 might not be sufficient to induce brain calcification of idiopathic basal ganglia calcification

Idiopathic basal ganglia calcification (IBGC) is a rare intractable disease characterized by abnormal mineral deposits, including mostly calcium in the basal ganglia, thalamus, and cerebellum. SLC20A2 is encoding the phosphate transporter PiT-2 and was identified in 2012 as the causative gene of familial IBGC. In this study, we investigated functionally two novel SLC20A2 variants (c.680C > T, c.1487G > A) and two SLC20A2 variants (c.82G > A, c.358G > C) previously reported from patients with IBGC. We evaluated the function of variant PiT-2 using stable cell lines. While inorganic phosphate (Pi) transport activity was abolished in the cells with c.82G > A, c.358G > C, and c.1487G > A variants, activity was maintained at 27.8% of the reference level in cells with the c.680C > T variant. Surprisingly, the c.680C > T variant had been discovered by chance in healthy members of an IBGC family, suggesting that partial preservation of Pi transport activity may avoid the onset of IBGC. In addition, we confirmed that PiT-2 variants could be translocated into the cell membrane to the same extent as PiT-2 wild type. In conclusion, we investigated the PiT-2 dysfunction of four SLC20A2 variants and suggested that a partial reduced Pi transport function of PiT-2 might not be sufficient to induce brain calcification of IBGC.

Bilateral Calcification of Basal Ganglia in a Patient with Duplication of Both 11q13.1q22.1 and 4q35.2 with New Phenotypic Features

We report on a female patient who presented with severe intellectual disability and autistic behavior, dysmorphic features, orodental anomalies, and bilateral calcification of basal ganglia. Using a high-density oligonucleotide microarray, we have identified a de novo duplication of 11q13.1q22.1 involving the dosage sensitive genes FGF3 and FGF4, genes related to autosomal dominant disorders KMT5B, GAL, SPTBN2, and LRP5, susceptibility loci SCZD2, SLEH1, and SHANK2, mitochondrial genes NDUFV1, NDUFS8, and TMEM126B, and many loss of function genes, including PHOX2A, CLPB, MED17, B3GNT1, LIPT2, and CLPB. However, the duplication did not involve Ribonuclease H2, subunit C (RNASEH2C) which is considered to be located in the critical region for Aicardi-Goutières syndrome. In combination with the duplication at 11q13.1, a 1.849-Mb heterozygous duplication at 4q35.2 was also identified. Although this duplicated region does not contain causative genes related to brain calcification, the duplication at 4q35 was reported previously in a patient with basal ganglia calcification, coats' like retinopathy, and glomerulosclerosis. Our patient's presentation and genomic findings indicate that duplication of 4q35.2 could be a novel genetic cause of calcification of basal ganglia. Our report also underscores the clinical significance of rearrangements in 11q13.1q22.1 in the pathogenesis of basal ganglia calcification.

Kosaki overgrowth syndrome: A newly identified entity caused by pathogenic variants in platelet-derived growth factor receptor-beta.

Specific classes of de novo heterozygous gain-of-function pathogenic variants of the PDGFRB (platelet-derived growth factor receptor-beta) cause a distinctive overgrowth syndrome, named the Kosaki overgrowth syndrome (KOGS) (OMIM #616592). Until now, six patients with this condition have been reported in the literature. In addition to skeletal overgrowth, these patients exhibit hyperelastic, translucent, and fragile skin, scoliosis, progressive loss of subcutaneous adipose tissue, skull deformity, infantile myofibromas, neuropsychiatric symptoms, and arachnoid cysts in the posterior fossa and periventricular white matter signal abnormalities on neuroimaging. This constellation of phenotypes clearly distinguishes KOGS from other PDGFRB-related disorders, including idiopathic basal ganglia calcification, infantile myofibroma, and Penttinen-type premature aging syndrome. From a molecular standpoint, PDGFRB is a dimeric receptor tyrosine kinase that plays critical roles in cell growth and tumorigenesis. The two known types of pathogenic variants (p.(Pro584Arg) and p.(Trp566Arg)) of the PDGFRB that cause KOGS are exclusively located in the juxtaglomerular domain that regulates autoactivation/inhibition of PDGFRB. In-vitro evidence suggests that p.(Pro584Arg) represents a gain-of-function pathogenic variant. Inhibition of PDGFRB activity using multi-kinase inhibitors appears to be a potentially promising therapeutic approach. Investigation of the molecular mechanisms underlying the pathogenesis of this disease using induced pluripotent stem cells is under way. Presence of skeletal overgrowth, distinctive facial features, characteristic hyperelastic and fragile skin, and cerebral white matter lesions with neuropsychiatric symptoms should prompt genetic analysis of the PDGFRB.

Primary familial brain calcification: a clinical case

Primary familial brain calcification (familial idiopathic basal ganglia calcification, Fahr’s disease) is a rare neurodegenerative syndrome characterised by a symmetrical bilateral calcification in the basal ganglia, dentate nucleus, cerebral cortex, and other regions of the brain. The widespread use of multislice computed tomography and magnetic resonance imaging increased the number of diagnosed cases, yet neither causes nor efficient treatment of this disease are known to date. Due to variable symptoms, primary familial brain calcification can resemble multiple neurological, mental, and endocrine disorders. Here we describe a case of a 38-year-old woman where timely multislice computed tomography led to the proper diagnosis and successful treatment.

Fahr syndrome: A case series analysis

Fahr disease or Fahr syndrome is a rare neurological disorder characterized by abnormal calcified deposits in basal ganglia and cerebral cortex. As the disease progresses, it was found that lateral thalamus, dentate nucleus of cerebellum and the frontal cortex get affected as well. Aim of the study was to analyze 5 cases of Fahr syndrome highlighting any possible correlation between the progressive nature of the disease, clinical spectrum and neuroimaging data. Methods Five patients aged 19, 31, 43 and 53 and 56 were studied in Albania. They were hospitalized in the Neurology service, each showing a different clinical spectrum. One patient presented with seizures, another one with headache and two patients developed neuropsychiatric and cognitive disorders. Another patient was hospitalized for an acute stroke. After a thorough evaluation, brain computed tomography scans revealed calcifications in basal ganglia, with one case revealing calcifications in basal ganglia, globus pallidus, cerebellar white matter and frontal subcortical white matter. Results Although the progressive nature of the disease is estimated, different neurological manifestations account for different cases. Family history and comorbidities should always be kept in mind when analyzing the neurological signs and symptoms. Conclusion No clear cut correlation is found between the progressive nature of the disease, neurological manifestations and neuroimaging data. The concept of frontal subcortical circuits, a system of loops linking the basal ganglia and frontal brain regions, and functional neuroimaging may give additional data regarding the pathophysiology and clinical signs of the disease.