Bilateral Symmetrical Calcification Research Articles

An Elderly Lady with Tetany and Brain Calcification

We present the case of a 59-year-old Bangladeshi lady who presented in Intensive Care Unit with tetany and altered level of consciousness. Tetany resolved after giving IV calcium injection. Initial laboratory investigations showed hypocalcemia. Non-contrast CT brain showed irregular bilateral symmetrical calcifications in basal ganglia, thalami, cerebellum and corona radiata. Subsequent laboratory test revealed low parathyroid hormone level. So, she was diagnosed as Fahr’s syndrome due to secondary hypoparathyroidism. This is a rare neurological disorder characterized by metabolic, biochemical, neuroradiological and neuropsychiatric abnormalities due to symmetrical and bilateral intracranial calcifications. Bangladesh Crit Care J September 2024; 12 (2): 160-162

T-cell infiltration in the central nervous system and their association with brain calcification in Slc20a2-deficient mice.

Primary familial brain calcification (PFBC) is a rare neurodegenerative and neuropsychiatric disorder characterized by bilateral symmetric intracranial calcification along the microvessels or inside neuronal cells in the basal ganglia, thalamus, and cerebellum. Slc20a2 homozygous (HO) knockout mice are the most commonly used model to simulate the brain calcification phenotype observed in human patients. However, the cellular and molecular mechanisms related to brain calcification, particularly at the early stage much prior to the emergence of brain calcification, remain largely unknown. In this study, we quantified the central nervous system (CNS)-infiltrating T-cells of different age groups of Slc20a2-HO and matched wild type mice and found CD45+CD3+ T-cells to be significantly increased in the brain parenchyma, even in the pre-calcification stage of 1-month-old -HO mice. The accumulation of the CD3+ T-cells appeared to be associated with the severity of brain calcification. Further immunophenotyping revealed that the two main subtypes that had increased in the brain were CD3+ CD4- CD8- and CD3+ CD4+ T-cells. The expression of endothelial cell (EC) adhesion molecules increased, while that of tight and adherents junction proteins decreased, providing the molecular precondition for T-cell recruitment to ECs and paracellular migration into the brain. The fusion of lymphocytes and EC membranes and transcellular migration of CD3-related gold particles were captured, suggesting enhancement of transcytosis in the brain ECs. Exogenous fluorescent tracers and endogenous IgG and albumin leakage also revealed an impairment of transcellular pathway in the ECs. FTY720 significantly alleviated brain calcification, probably by reducing T-cell infiltration, modulating neuroinflammation and ossification process, and enhancing the autophagy and phagocytosis of CNS-resident immune cells. This study clearly demonstrated CNS-infiltrating T-cells to be associated with the progression of brain calcification. Impairment of blood-brain barrier (BBB) permeability, which was closely related to T-cell invasion into the CNS, could be explained by the BBB alterations of an increase in the paracellular and transcellular pathways of brain ECs. FTY720 was found to be a potential drug to protect patients from PFBC-related lesions in the future.

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.

Síndrome de Fahr

Miss Merry, 17 years old girl hailing from Barobila., Patkelghata, Satkhira was admitted in Khulna Medical College Hospital on 27-06-2010 with the complaints of fever, convulsion and unconsciousness for 7 days. She has also some hearing impairment, behavioral abnormalities and stunted growth since her childhood. On examination she was deeply unconscious, anaemic and febrile. CT scan of brain reveals multiple bilateral symmetrical calcification seen in the brain parenchyma involving basal ganglia, thalamus, para ventricular region, and cerebellar nucleus. Multiple ill defined hypodense areas are seen in the both parieto-occipital region, suggestive of Fahr's syndrome with meningoencephalitis. Bang Med J (Khulna) 2012; 45 : 33-35 Introduction Idiopathic Basal Ganglia Calcification, also known as Fahr's disease or Fahr's Syndrome or Bilateral StriatoPallidoDentate Calcinosis (BSPDC) is a rare, genetically dominant, inherited neurological disorder characterized by abnormal deposits of calcium in areas of the brain that control movement, including the basal ganglia and the cerebral cortex. The disease was first noted by German neurologist Karl Theodor Fahr in 1930.1 According to reports in medical literature, Fahr Disease is often familial. It is believed to have autosomal dominant inheritance but a few cases have been reported to have autosomal recessive inheritance and even some sporadic cases have been reported in literature. Idiopathic calcification of the basal ganglia, also known as Fahr's disease, is a rare neurologic disorder of unknown etiology characterized by neuropsychiatric abnormalities.2 Parkinsonian or choreoathetotic-type movement disturbance, and extensive symmetrical calcification of the basal ganglia and dentate nuclei in the cerebellum. These symptoms cannot be explained by any other particular disorder of the calcium phosphorus metabolism or any other disease. Dementia is a well-recognized neuropsychiatric, manifestation of Fahr's disease. In addition, a schizophrenia-like psychosis characterized by paranoia, hallucinations, and delusions has been reported.3 There is no cure for Fahr's syndrome, which worsens over time, nor is there a standard course of treatment.

A Case of Primary Hypoparathyroidism Presenting with Acute Kidney Injury Secondary to Rhabdomyolysis.

Hypoparathyroidism is the most common cause of symmetric calcification of the basal ganglia. Herein, a case of primary hypoparathyroidism with severe tetany, rhabdomyolysis, and acute kidney injury is presented. A 26-year-old male was admitted to the emergency clinic with leg pain and cramps, nausea, vomiting, and decreased amount of urine. He had been treated for epilepsy for the last 10 years. He was admitted to the emergency department for leg pain, cramping in the hands and legs, and agitation multiple times within the last six months. He was prescribed antidepressant and antipsychotic medications. He had a blood pressure of 150/90 mmHg, diffuse abdominal tenderness, and abdominal muscle rigidity on physical examination. Pathological laboratory findings were as follows: creatinine, 7.5 mg/dL, calcium, 3.7 mg/dL, alanine transaminase, 4349 U/L, aspartate transaminase, 5237 U/L, creatine phosphokinase, 262.000 U/L, and parathyroid hormone, 0 pg/mL. There were bilateral symmetrical calcifications in basal ganglia and the cerebellum on computerized tomography. He was diagnosed as primary hypoparathyroidism and acute kidney injury secondary to severe rhabdomyolysis. Brain calcifications, although rare, should be considered in dealing with patients with neurological symptoms, symmetrical cranial calcifications, and calcium metabolism abnormalities.

Extensive intracranial calcification presenting with neurological symptoms due to primary hypoparathyroidism and secondary hyperparathyroidism: Two case reports

Metastatic calcification involving basal ganglion in idiopathic hypoparathyroidism (IHPT) and intracranial vascular calcification in secondary hyperparathtyroidism (SHPT) in end-stage renal disease (ESRD) on hemodialysis are not uncommon. Extensive bilateral symmetrical intracranial calcification involving basal ganglion, cerebellum and white matter presenting with neurological symptoms has been rarely reported in literature. We report 2 such cases. The first case belongs to a 56 year-old lady with IHPT with extensive intracranial calcification who presented with choreoathetotic movements. The second case is concerning a 14 year-old boy with SHPT with ESRD on hemodialysis with extensive intracranial calcification who presented with seizures. The possible pathogenesis of extensive metastatic calcification and treatment was discussed with review of literature.

Hip Pain and Gait Disturbance Associated with Idiopathic Hypoparathyroidism.

Idiopathic Hypoparathyroidism (IHP) is a disease characterized by diminishes in production of parathyroid hormone due to dysfunction of the parathyroid glands [1]. IHP is characterized by soft-tissue ectopic calcifications and skeletal abnormalities. Subcutaneous calcifications around the hips and shoulders may be seen in the course of this disease [2]. Muscle cramps involving the back and legs, paresthesias, and convulsions are common complaints. The clinical manifestations of this condition are varied and nonspecific. Consequently, IHP is usually diagnosed many years after its onset [3]. Back and hip pain and stiffness are is commonly overlooked in these patients [1]. We hereby report a case of a 40-year-old man who presented with bilateral hip pain that had hindered his normal walking for 6 months. He also had a 30-year history of epilepsy and cataract surgery 10 years earlier. His family history was non-contributory. He had no history of surgical excision or damage to the parathyroid glands, radiation, or neoplastic/granulomatosis infiltration. He had no muscle weakness or cranial nerve involvement and no difficulty with speech, apathy, or mental slowness. The FADIR (flexion, abduction, and internal rotation) and FABERE (flexion, abduction, external rotation, and extension) tests were positive and painful at 15° of flexion due to hip contractures. Laboratory results demonstrated the typical findings of hypoparathyroidism: parathormone value 2 (normal level = 15–65) pg/mL, serum calcium 4.6 (normal level= 8.4–10.6) mg/dL, and phosphate 7.2 (normal level = 2.3–4.7) mg/dL. Pelvis radiography revealed bilateral ossification extending along the acetabulum [Table/Fig-1]. Computed tomography of the brain showed calcifications in the pallidum and caudate nuclei bilaterally [Table/Fig-2]. The electroencephalogram was normal. [Table/Fig-1]: Pelvis radiography shows bilateral ossification around the acetabulum. Note the preservation of the joint space. [Table/Fig-2]: Head computed tomography shows bilateral symmetrical calcifications in the pallidum and caudate nuclei. No other cause of hypoparathyroidism was found. Tests for polyendocrinopathy were normal. A diagnosis of idiopathic primary hypoparathyroidism was made. Calcium, vitamin D supplementation, paracetamol 500 mg tid, diclofenac sodium 50 mg bid, and physical therapy with range of motion and strengthening exercises were started and continued until the pain limit was reached. These therapies reduced the severity of his complaints within 1 week. IHP causes hypocalcaemia by hindering calcium reabsorption in the renal tubules and bone, and to a insufficiency in the production of 1,25-dihydroxyvitamin D. The most frequent osseous findings of IHP are localized or generalized sclerosis. Extraosseous calcification is typically seen in the basal ganglia, periarticular tissue, blood vessels, and ocular lens. The development of calcification may be associated not only parathyroid hormone deficiency but also to the duration of hypocalcaemia and hyperphosphataemia [3]. The imaging findings of IHP closely resemble those of diseases such as diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis [1–5]. Our patient’s main complaint was pain and gait difficulty and the diagnosis of IHP was delayed until the age of 40 years. Delaying diagnosis and treatment resulted in cataracts, speech difficulty, pain, limited range of motion of the hip and gait disturbance. Disclosures: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

Bilateral striopallidodentate calcinosis in a patient with myasthenia gravis

Bilateral symmetric calcification involing striatum, pallidum with or without deposit in dentate nucleus is reported fromasymptomatic individuals to a variety of neurological conditions. Clinically it may present with an array of movement disorders,dementia, cerebellar impairment and speech disorder. We report a myasthenia gravis patient with dysarthria which did notrespond to pyridostigmin. Brain MRI showed bilateral striopallidodentate calcinosis (BSPDC). To our knowledge, there is noreported case having anti-acetylcholine receptor antibody and massive intracranial calcifications. This case indicates thatBSPDC may develop in diverse neurological disorders.

Fahr's syndrome

Miss Merry, 17 years old girl hailing from Barobila., Patkelghata, Satkhira was admitted in Khulna Medical College Hospital on 27-06-2010 with the complaints of fever, convulsion and unconsciousness for 7 days. She has also some hearing impairment, behavioral abnormalities and stunted growth since her childhood. On examination she was deeply unconscious, anaemic and febrile. CT scan of brain reveals multiple bilateral symmetrical calcification seen in the brain parenchyma involving basal ganglia, thalamus, para ventricular region, and cerebellar nucleus. Multiple ill defined hypodense areas are seen in the both parieto-occipital region, suggestive of Fahr's syndrome with meningoencephalitis. DOI: http://dx.doi.org/10.3329/bmjk.v45i1-2.13628 Bang Med J (Khulna) 2012; 45 : 33-35

Idiopathic hypoparathyroidism and systemic sclerosis: An association likely missed

Hypoparathyroidism in systemic sclerosis is extremely rare with only a single case reported till date. Idiopathic hypoparathyroidism with systemic sclerosis was diagnosed in a 59-year-old gentleman who had presented with recurrent seizures, instability of gait, skin thickening and tightening over both legs and forearms, and arthritis. Examination was significant for positive Trousseau sign and cerebellar ataxia. Evaluation revealed bilateral symmetrical cerebellar and basal ganglia calcification, sensorineural deafness, low serum calcium, elevated serum phosphorus, normal magnesium, normal vitamin D, low plasma parathyroid hormone, high titer of thyroid peroxidase antibody, positive centromere pattern antinuclear antibody, strongly positive anti-topoisomerase-1 (Scl-70) antibody, nonvisualization of parathyroids on neck ultrasonography and skin biopsy suggestive of hyperkeratosis, increased collagen in dermis, and perivascular lymphomononuclear cell infiltration compatible with scleroderma. Last evaluated 10 months after the diagnosis, his ataxia had improved, he remained seizure-free, Trousseau sign was negative, and he had low-normal calcium calcium with calcium carbonate and calcitriol supplementation and switch from phenytoin to valproate. Further studies are warranted to study the use of serum calcium as a screening test for hypoparathyroidism in patients with systemic sclerosis.

Intramuscular Hemangioma of the Temporalis Muscle With Incidental Finding of Bilateral Symmetric Calcification of the Basal Ganglia: A Case Report

We report an 11-year-old boy whose brain computed tomography findings incidentally revealed bilateral basal ganglia calcification. He was symptom-free and had no abnormal neurological findings. He was diagnosed with Fahr's disease based on radiological findings and after excluding other etiologies such as infection, metabolic disorders, congenital malformation and malignancies. Most of the reported cases display an autosomal dominant mode of inheritance. Although Fahr's disease is a rare cause of basal ganglia calcification in children, this disease should be considered in children with a family history of neuropsychiatric disorders.

Fahr's Disease Vs. Drug Induced Movement Disorder: Case report and Literature Review

Abstract Fahr's disease is a rare idiopathic degenerative neurological disorder, which can be present in different heterogeneous manifestations and characterized by bilateral symmetrical cerebral calcification. These presentations usually involve basal ganglia, manifested with multiple neuropsychiatric disorders. We described a patient with acute onset schizophrenia, who developed abnormal choreoathetoid movement three years later. His brain imaging studies showed extensive bilateral cerebral calcification, the patient was diagnosed with a sporadic case of Fahr's disease. Brain imaging should be considered in acute onset schizophrenia to rule out organic causes. Fahr's disease can be a differential diagnosis when extrapyramidal symptoms and abnormal movement appear and are not improved on treatment

Multiple bilateral spinal nerve root calcifications in Charcot‐Marie‐Tooth disease

We present a patient with Charcot-Marie-Tooth disease with multiple bilateral symmetrical cervical nerve root calcifications. To our knowledge, such a finding has not been described in the literature in association with this disease. We propose that multiple bilateral symmetrical spinal nerve root calcifications may be an additional imaging feature, possibly diagnostic, in this hereditary motor and spinal neuropathy.

Intracranial bilateral symmetric calcification in hypoparathyroidism

A 42-year-old woman presented to the emergency department with a complaint of tremors in both extremities, torticollis, and agitation that had lasted 10 h. When she was 24 years old,...

Polyarticular juvenile idiopathic arthritis associated with Fahr′s syndrome

Bilateral symmetric calcification involving striatum pallidum with or without deposits in the dentate nucleus, thalamus and white matter is commonly referred to as Fahr's syndrome. Symptoms of the disorder may include deterioration of motor function, spasticity, spastic paralysis, dysarthria, dementia, seizures, headache and athetosis. The clinical and imaging abnormalities are restricted to the central nervous system (CNS). We report an unusual association of Fahr's syndrome with polyarticular juvenile idiopathic arthritis in a girl.

Elevated cerebrospinal fluid lactate levels and the pathomechanism of calcification in Fahr's disease

In this study, we report the case of a 68-year-old man complaining of involuntary movement of his left shoulder and lower jaw plus dyspnea. On cranial computed tomography and magnetic resonance imaging, marked and symmetrical calcification at the basal ganglia and dentate nuclei was documented. An elevated cerebrospinal fluid (CSF) lactate level was confirmed by spinal tap examination and magnetic resonance spectroscopy. The raised CSF lactate level, clinical characteristics such as diabetes, bilateral hearing loss and symmetrical cerebral calcification strongly suggested some kinds of mitochondrial disease. However, gene analysis of peripheral blood leukocytes revealed no typical or known mutations. Under the diagnosis of Fahr's disease, we treated him with haloperidol, which completely abolished his symptoms. In Ellsworth-Howard test, he showed markedly decreased phosphaturic response to parathyroid hormone with same pattern as type 2 pseudohypoparathyroidism. This abnormal response in our patient, probably due to respiratory alkalosis reflecting chronic hyperventilation, might in part explain similar mechanism of ectopic calcification underlying these two diseases.

Rocks in the head: extensive intracranial calcification

Basal ganglia calcification is one of the features of chronic hypocalcaemia.1 However, extensive intracranial symmetrical calcifications outside the basal ganglia have been reported rarely in patients with chronic hypocalcaemia secondary to post-surgical hypoparathyroidism. A 62-year-old woman who underwent subtotal thyroidectomy 15 years ago presented with long-term paraesthesiae in the distal extremities. Progressive cognitive impairment and unstable gait were noted by her family but she had no tetany, cramps or seizures. On examination, she had disorientation to time, place and person, and her vital signs were stable. Chvostek’s and Trousseau’s signs were negative and neurological examination was normal. Plasma biochemical analysis was as follows: urea nitrogen 4.6 mmol/L, creatinine 71 μmol/ L, calcium ions 0.68 mmol/L, magnesium 0.90 mmol/L, phosphorus 1.26 mmol/L and intact parathyroid hormone less than 9.5 ng/L. Other analytes were within normal range. Noncontrast computed tomography of the brain is shown in Figure 1. After 10-day therapy with oral calcium carbonate 1.5 g and calcitriol 0.5 μg daily, her chronic paraesthesiae resolved and plasma calcium rose to 0.90 mmol/L. Although pathologic intracranial calcification occurs with tumours, aneurysms, arteriosclerosis and several infectious diseases, the finding of bilateral symmetrical calcification of the basal ganglia, dentate nuclei and corona radiata is characteristic of chronic hypocalcaemia associated with hypoparathyroidism.2 A similar pattern of intracranial calcification may also be seen in chronic renal failure with hypocalcaemia and secondary hyperparathyroidism. The pathogenesis of intracranial calcification remains unknown. Possible determinants of extra-osseous calcification include the calcium phosphate product, metabolic acidosis, local pH change, expression of osteopontin and matrix Gla protein, and inflammation or tissue injury.3 Although chronic hypocalcaemia due to hypoparathyroidism may appear to be asymptomatic or, as in our patient, to be associated with relatively mild symptoms (paraesthesiae, with cognitive and gait disturbances), replacement therapy with calcium and vitamin D supplements is warranted to prevent progression to more severe manifestations (extrapyramidal signs, muscle spasm, seizures, psychosis). The calcium level should be kept at or slightly below the normal range to avoid potential side-effects including hypercalciuria and nephrolithiasis.

Progressive idiopathic bilateral striato-pallido-dentate calcinosis (Fahr's disease) in a person with anabolic steroid abuse

A 33-year-old male black student suddenly died during a basketball game. His previous medical history, including his neurological status, was unremarkable, but he was known to take anabolic steroids for several years. At autopsy, the cause of death was due to a fresh myocardial infarction. On neuropathological examination, there was extensive bilateral symmetrical calcification involving the basal ganglia as well as the dentate nuclei and the white matter of the cerebellum (Fahr's disease). A possible correlation between anabolic steroid-induced hypercalcemia and brain calcification is discussed.

Fahr's disease associated with astrocytic proliferation and astrocytoma

This report documents the neuropathological findings of astrocytic proliferation and astrocytoma in a patient with Fahr's disease. At autopsy, there was extensive bilateral symmetrical calcification involving basal ganglia, sulcal depth of the cerebral cortex, and dentate nuclei of the cerebellum. A large low-grade astrocytoma was identified in the left parietal lobe. Astrocytic proliferation was also noted in the areas of early calcification and at the margins of large calcareous deposits, away from the tumor.

Neurologische und psychiatrische Manifestationen der Bleiintoxikation bei Erwachsenen (Fallbericht und Literaturübersicht)

A 59-year-old potter presented with lead polyneuropathy after 37 years of occupational exposure. There was a 25-year history of normochromic normocytic anaemia with moderate basophilic stippling, mild renal failure, hyperuricaemia and abnormal porphyrins. Since 1964 three short psychotic episodes were noted. Cranial computed tomography showed extensive bilateral symmetrical calcification in the cerebellar hemispheres and slight calcification in the subcortical area of the cerebral hemispheres and basal ganglia. T2-weighted magnetic resonance imaging disclosed high signal intensities in the periventricular white matter, basal ganglia, insula, posterior thalamus and pons. Differential diagnostic aspects are discussed with special regard to CT and MRI findings. A review of the literature on neurological and psychiatric manifestations of lead intoxication in adults is given.