A case report of severe hypocalcemia secondary to Fahr's syndrome

In clinical practice, it can be difficult to differentiate between intracranial calcifications related to primary familial brain calcification (PFBC) or aging. Also, little is known about the consequences of the amount of intracranial calcifications in patients with PFBC. Therefore, we aimed to compare the amount and distribution of intracranial calcifications in persons with PFBC with controls and between asymptomatic and symptomatic PFBC cases. This was a case-control study including patients with PFBC and controls. Controls received a CT of the brain because of a trauma and had at least some basal ganglia calcification. The Nicolas score and volume of calcification were used to quantify intracranial calcifications on the CT scans. Receiver operating characteristic curves were obtained to calculate optimal cutoff points to discriminate between cases and controls. Mann-Whitney U tests and logistic regression, adjusted for age and sex, were used to compare the amount of calcification. Twenty-eight cases (median age 65 years, 50.0% male) and 90 controls (median age 74 years, 46.1% male) were included. Calcification scores were higher in cases (median volume: 4.91 cm3 against 0.03 cm3, p < 0.001, median Nicolas score: 26.5 against 2.0, p < 0.001) than controls. Calcifications were also more diffusely distributed in cases. To differentiate between cases and controls, optimal cutoff points were ≥0.2 cm3 for the calcification volume and ≥6.0 for the Nicolas score. Calcification was higher for symptomatic than asymptomatic cases (calcification volume: 13.62 cm3 against 1.61 cm3, p = 0.01, Nicolas score: 39.0 against 15.5, p = 0.02). After adjustment for age and sex, the Nicolas score remained significantly higher in symptomatic patients, and the calcification volume did not. Patients with PFBC had more severe intracranial calcifications, and these calcifications were more diffusely distributed through the brain compared with controls. Symptomatic patients with PFBC might have more intracranial calcifications than asymptomatic persons.

Fahr’s disease, or primary familial brain calcification (PFBC), is a rare neurodegenerative disorder characterized by bilateral intracranial calcifications, often involving the basal ganglia, cerebellum, and subcortical white matter. Clinical manifestations may include seizures, cognitive decline, movement abnormalities, and psychiatric symptoms. Although Fahr's disease is often idiopathic with an autosomal dominant inheritance, similar imaging findings may arise from non-hereditary secondary causes such as metabolic, infectious, or toxic conditions. Identifying the underlying etiology is essential for guiding management. We present the case of a 48-year-old African-American male with a history of intellectual disability, psychiatric illness, and gait instability, who was brought to the emergency department after a witnessed generalized tonic-clonic seizure. Non-contrast computed tomography (CT) imaging of the head revealed extensive bilateral calcifications involving the basal ganglia, cerebellum, and cerebral white matter. Laboratory findings showed marked hypocalcemia, low parathyroid hormone levels, and borderline elevated phosphate. No history of prior neck surgery or known familial endocrine disorder was reported. The patient was treated with calcium and vitamin D supplementation, antiepileptic therapy, and continued psychiatric management. He was discharged to subacute rehabilitation (SAR) with plans for follow-up in neurology and endocrinology clinics. This case illustrates the diagnostic complexity of intracranial calcification syndromes. While certain clinical and imaging features raised suspicion for idiopathic Fahr’s disease, the presence of metabolic abnormalities suggested a secondary etiology related to long-standing hypoparathyroidism. The absence of a definitive family history and social support, together with the chronicity of symptoms, added further ambiguity to the diagnostic picture. Whether the calcifications resulted primarily from an idiopathic process or developed in the context of longstanding, unrecognized hypoparathyroidism remains uncertain, though the latter was the leading hypothesis. A complete workup, including metabolic investigation and genetic evaluation when feasible, is critical in such cases. In patients presenting with seizures and neuropsychiatric symptoms alongside extensive intracranial calcifications, both idiopathic and secondary causes of Fahr’s disease should be considered. This case highlights the importance of integrating clinical, biochemical, and imaging data to guide diagnosis and management. Early identification and treatment of modifiable factors, even when the etiology is unclear, may improve patient outcomes.

Introduction: Vascular calcification is an important pathophysiological factor contributing to neurodegenerative diseases such as primary familial brain calcification (PFBC) and is a potential therapeutic target. Hypothesis: Given the essential role of tissue-nonspecific alkaline phosphatase (TNAP) in biomineralization, we tested the hypothesis that upregulation of TNAP activity can lead to intracranial calcification. Methods: We previously reported that overexpression of TNAP in endothelial cells (eTNAP) leads to arterial calcification. Here we analyzed intracranial calcification in eTNAP on the original B6;129 and on the C57BL/6 (B6) genetic backgrounds. Histology was performed on formalin-fixed cryo-preserved tissues. Locomotion testing was performed at 23 weeks and analyzed in Matlab. Gene expression was analyzed by qPCR. Results: On the B6;129 background, eTNAP mice developed progressive intracranial calcification (0% were affected at 8 weeks, 71% at 13 weeks, and 100% at 23 weeks, n=7 per group). At 23 weeks, calcification was undetectable in the middle cerebral arteries but was associated with microvasculature in the basal ganglia, thalamus, hindbrain, and cerebellum. Calcified lesions were accompanied by astro- and micro-gliosis. Extravasation of IgG into the brain parenchyma was evident in eTNAP; blood-brain barrier was intact in controls (n=3 per group; 23 weeks). There were no significant differences in the locomotion or behavior (open field exploration) between the eTNAP and controls on the B6;129 background (n=6 per group). On B6 background, eTNAP mice displayed significant motor deficits - reduced ambulation (p&lt;0.01), rearing (p&lt; 0.01), speed (p&lt;0.05), and acceleration (p&lt;0.05; n=7-9 per group). There were no changes in osteogenic gene expression or phosphate transporters in eTNAP brains compared with controls. However, we detected significant regional differences between the thalamus and cortex in the levels of RumX2 , Spp1 , SLC17a7 , SLC17a6 of both control and eTNAP mice. Conclusions: Upregulation of TNAP activity can lead to intracranial vascular calcification. Given the similarities in presentation between eTNAP mice and PFBC patients, this model can advance the understanding of PFBC disease progression.

Fahr’s syndrome is a neurodegenerative disorder characterized by abnormal deposition of calcium in the brain, especially in basal ganglia. The term Fahr’s disease is used when primary familial brain calcification is present, and the term Fahr’s syndrome is used for secondary causes. Our patient is a 35-year-old male who presented to our hospital with complaints of two episodes of generalized tonic-clonic seizures. He had a history of recurrent episodes of seizures since the age of 15 and they all were generalized tonic-clonic seizures. He did not have a family his­tory of epilepsy. Lab investigations showed a normal hemogram, and liver and renal function were within normal limits. Serum electrolyte levels showed hypocalcemia, but other electrolyte levels were normal. He had low parathyroid hormone levels and normal levels of vitamin D. Brain imaging studies with non-contrast CT and a contrast-enhanced MRI showed bilaterally symmetrical dense calcifications. The etiology in our patient was the primary hypoparathyroidism and was treated accordingly. He reported symptomatic improvement with treatment and had no episodes of seizures after the commencement of the treatment. So, in cases of Fahr’s syndrome, treatable etiologies must be ruled out as they can delay the progression of the disease.

Fahr syndrome and neurological manifestations in hypoparathyroidism patients

Fahr's syndrome is a rare, progressive, neuropsychiatric disorder characterized by bilateral and symmetrical calcifications over the basal ganglia and other parts of the brain, leading to a wide range of clinical manifestations ranging from neurologic symptoms of movement disorders, seizures, and cerebellar dysfunction to neuropsychiatric symptoms such as dementia, psychosis, and mood disorders. The widespread calcific deposits within the brain tissue that characterize Fahr's syndrome develop secondary to different underlying conditions such as parathyroid disorders, brain infections, and toxic exposures. Hypoparathyroidism, a rare disorder of calcium and phosphate metabolism, is the most commonly identified etiology of Fahr's syndrome. In this case, we report a case of a 17-year-old female patient who presented with status epilepticus. Her past medical history was positive for intermittent episodes of generalized tonic-clonic seizures for the past year. Upon presentation,she had a decreased level of consciousness with a Glasgow Coma Scalescore of 9 (eye-opening = 2, verbal response = 2, motor response = 5). Chvostek's and Trousseau's signs were positive. Initial laboratory workup revealed severe hypocalcemia, hyperphosphatemia, and markedly low parathyroid hormone levels. Computed tomography of the brain showed extensive, bilateral, symmetrical calcifications over the basal ganglia, thalami, corona radiata, and dentate nuclei. She was subsequently diagnosed with Fahr's syndrome secondary to hypoparathyroidism and was managed with calcium gluconate, vitamin D, and sodium valproate, which improved her condition. A slit lamp examination of the eyes revealed a bilateral posterior subcapsular cataract more severe in the right eye, for which small incision cataract surgery was performed on her right eye. This case report underscores the importance of considering a diagnosis of Fahr's syndrome in adolescent patients with a history of seizures and unexplained intracranial calcifications on brain imaging. It also emphasizes the necessity of thorough clinical assessment and laboratory tests to identify the underlying cause, as the treatment of Fahr's syndrome primarily focuses on identifying and managing the underlying etiology.

A Rare Association of Fahr's Disease With an Autoimmune Triad.

Fahr's syndrome a rare neurological condition characterized by an abnormal basal ganglia calcification. The condition has both genetic and metabolic causes. Here, we describe a patient who had Fahr's syndrome and basal secondary to hypoparathyroidism, and her calcium level raised after the administration of steroid therapy. We presented a case of a 23-year-old female with seizures. Associated symptoms included headache, vertigo, disturbed sleep, and reduced appetite. Her laboratory workup revealed hypocalcemia and low parathyroid hormone level, computed tomographic (CT) scan of the brain showed diffuse calcification in the brain parenchyma. The patient was diagnosed as a case of Fahr's syndrome secondary to hypoparathyroidism. The patient was started on calcium and calcium supplementations along with anti-seizure therapy. Her calcium level raised after the initiation of oral prednisolone and she remained asymptomatic. Steroid could be considered as an adjunct therapy with calcium and vitamin D supplementation in patient whose Fahr's syndrome is secondary to primary hypoparathyroidism.

(1) Background: Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcifications of the basal ganglia and other intracranial areas. Many patients experience symptoms of motor dysfunction and cognitive disorders. The aim of this study was to investigate the association between the amount and location of intracranial calcifications with these symptoms. (2) Methods: Patients with suspected PFBC referred to our outpatient clinic underwent a clinical work-up. Intracranial calcifications were visualized on Computed Tomography (CT), and a Total Calcification Score (TCS) was constructed. Logistic and linear regression models were performed. (3) Results: Fifty patients with PFBC were included in this study (median age 64.0 years, 50% women). Of the forty-one symptomatic patients (82.0%), 78.8% showed motor dysfunction, and 70.7% showed cognitive disorders. In multivariate analysis, the TCS was associated with bradykinesia/hypokinesia (OR 1.07, 95%-CI 1.02–1.12, p &lt; 0.01), gait ataxia (OR 1.06, 95%-CI 1.00–1.12, p = 0.04), increased fall risk (OR 1.04, 95%-CI 1.00–1.08, p = 0.03), and attention/processing speed disorders (OR 1.06, 95%-CI 1.01–1.12, p = 0.02). Calcifications of the lentiform nucleus and subcortical white matter were associated with motor and cognitive disorders. (4) Conclusions: cognitive and motor symptoms are common among patients with PFBC, and there is an association between intracranial calcifications and these symptoms.

Fahr syndrome is a rare neurologic disorder, usually affecting young and middle-aged adults, that can present with symptoms ranging from extrapyramidal to neuropsychiatric abnormalities. Pseudohypoparathyroidism (PHP), characterized by parathyroid hormone (PTH)-resistance or PTH-unresponsiveness at target organs, is associated with Fahr syndrome and typically presents with hypocalcemia. The following case presents a 39-year-old-woman with PHP complicated by symptomatic hypocalcemia, hypokalemia, and movement disturbances, who had computed tomography imaging showing basal ganglia calcifications consistent with Fahr syndrome. She initially presented with headache and was hospitalized for hypertensive emergency and severe hypocalcemia. Examination, including the neurologic examination, was unrevealing aside from hypertension and central adiposity. Laboratory tests were consistent with PHP, showing hypocalcemia with elevated PTH, and negative for hyperaldosteronism. Management of hypocalcemia consisted of intravenous calcium infusion, oral calcium carbonate, oral vitamin D3, and oral calcitriol. Patients with severe hypocalcemia and elevated PTH who present with new neurological symptoms despite normal general neurologic examination may warrant consideration for brain imaging to evaluate for Fahr syndrome. Further investigations are necessary to determine the prevalence of Fahr syndrome and hypokalemia in patients with PHP, explore if these findings are significantly associated with PHP-1b subtype, and ultimately inform potential new screening pathways for these patients.

Fahr's syndrome is a rare condition characterized by deposition of bilateral symmetric calcium deposits in the basal ganglia and cerebellar region, leading to neurological and psychiatric sequelae. Herein we describe a case of a 62-year-old female presented with aphasia, bilateral lower limb rigidity, tremors, and gait disturbance. Her past medical history included thyroidectomy and radiation therapy 10 years back due to papillary carcinoma of the thyroid gland. On examination, she had poor speech, resting tremor, walking difficulty, and decreased power in all limbs with rigidity. Her Chvostek and Trousseau signs were positive. Serum investigations revealed hypocalcemia and low levels of parathyroid hormone and thyroid-stimulating hormone. Brain magnetic resonance imaging revealed calcified lesions in basal ganglia, thalami, and dentate nuclei. She was diagnosed with Fahr's syndrome due to hypoparathyroidism, and she was managed with calcium gluconate, vitamin D, salt-free albumin, and levodopa-carbidopa, improving her condition. The patient was then discharged on calcium gluconate, calcitriol, recombinant parathyroid hormone, and levodopa-carbidopa with follow-up.

Intracranial calcification can occur physiologically in some cases, typically without symptoms and is discovered incidentally through neuroimaging. However, pathological calcification in the basal ganglia is often caused by underlying conditions such as metabolic disorders, infections, and genetic diseases. Here we present a 50-year-old male presented with multiple episodes of generalised tonic-clonic seizures. A brain CT scan revealed extensive symmetrical basal ganglia and periventricular calcification. Further testing showed low calcium levels, high phosphorus levels, and low parathyroid hormone levels, leading to a diagnosis of primary hypoparathyroidism and thereby Fahr Syndrome. The patient was initially treated with intravenous calcium gluconate and calcitriol, which resulted in significant clinical and laboratory improvements, effectively managing the condition and its symptoms.

Patients with chronic idiopathic hypoparathyroidism may develop neurological complications, including calcification of the basal ganglia and other areas of the brain. In Fahr's syndrome, intracranial calcification is associated with an underlying disorder such as hypo or hyperparathyroidism. We report the case of a 37-year-old gentleman, with a history of bilateral cataract surgery and seizures, who presented with a new episode of seizure and was found to have severe hypocalcemia and bilateral symmetric intracranial calcification due to previously diagnosed primary hypoparathyroidism. He had symptoms and signs mimicking ankylosing spondylitis (AS), but with negative radiological and serological findings, not fitting into the diagnosis of axial spondyloarthropathies (SpA), as per standard criteria. Patients with long-standing idiopathic hypoparathyroidism can have severe calcification of soft tissues and bones, including vertebrae and paravertebral soft tissues, causing inflammatory back pain and stiffness. It is vital to report such cases as their occurrence is rare, and physicians should be aware of the possibility while evaluating patients with inflammatory back pain. Treatment in these cases is directed towards hypocalcemia and underlying primary pathology rather than spondyloarthropathy.

Fahr syndrome (FS) is a rare neurological disorder characterized by bilateral and symmetrical intracerebral calcifications, mainly affecting the basal ganglia, thalamus, and cerebellar nuclei. It is frequently associated with metabolic disturbances, particularly parathyroid dysfunctions such as pseudohypoparathyroidism (PHP). PHP is a rare inherited condition marked by resistance to parathyroid hormone, resulting in hypocalcemia and hyperphosphatemia despite normal or elevated PTH levels. This article reports the case of a 15-year-old adolescent presenting with abnormal movements and confusion, found to have severe hypocalcemia and extensive brain calcifications on imaging. The diagnosis of Fahr syndrome secondary to PHP was established. The patient was treated with intravenous then oral calcium and active vitamin D, leading to clinical and biochemical improvement. This case highlights the diagnostic and therapeutic challenges posed by the rare association of FS and PHP, underlining the importance of early recognition, multidisciplinary management, and regular follow-up to prevent irreversible neurological complications. The article also reviews the pathophysiology, clinical features, and management strategies for FS and PHP, emphasizing the need for awareness of metabolic causes in patients with unexplained neurological symptoms and intracranial calcifications.

Fahr ’ s syndrome is a rare, degenerative, and neuropsychiatric disorder characterized by seizures, extrapyramidal and neuropsychiatric symptoms as a result of symmetric and bilateral calcifications of the nucleus pallidus, the putamen, the dentate nucleus of the cerebellum, and the hemispheric white matter at the base of the skull. The female patients, who has 53-year-old, was admitted in the intensive care unit with status epilepticus for 24 hours associated to acute respiratory failure due to aspiration pneumonia. She had undergone a thyroidectomy 22 years ago, when she started involuntary lasting muscular contractions of the upper extremities, which progressed to convulsions throughout the years. There were Chvostek and Trousseau signs. Laboratory tests showed ionic calcium of 0.55 mmol / L. Computed tomography scan of the brain showed intracranial symmetrical calcifications of the basal nuclei, semioval center, occipital, and cerebellar cortex. According to the clinical presentation, examination findings, and subsequent investigation exams, our case was diagnosed as Fahr ’ s syndrome due to post-thyroidectomy hypoparathyroidism . Fahr ’ s syndrome should be considered in patients with neuropsychiatric disturbances and seizure disorder, especially following thyroidectomy. doi: http://dx.doi.org/10.4021/jmc1252e