Fahr's disease in a patient with recurrent pneumonias, parkinsonism and dementia.

Fahr's disease is a rare condition characterised by the presence of idiopathic familial bilateral basal ganglia calcifications, transmitted in an autosomal-dominant fashion. Diagnosis is based on clinical features of neuropsychiatric and somatic symptoms in conjunction with radiological findings. Our patient, a man in his early 50s, presented with pneumonia. History was significant for five admissions in the last 2 years for pneumonia and falls, with gradual cognitive and motor decline since his late 30s. Hypophonia, bradykinesia and dementia were noted on examination. CT of the brain revealed bilateral thalamic calcinosis, consistent with Fahr's syndrome. Further investigations and retrospective history taking, and similar radiological findings within first-degree and second-degree relatives with early deaths, transitioned the diagnosis from Fahr's syndrome to Fahr's disease. We present this case of Fahr's disease to emphasise the value of collaboration among multidisciplinary professionals to improve quality of care for such patients.

Fahr's syndrome associated with hypoparathyroidism: A case report.

Fahr's syndrome affects fewer than 1 in 100,000 people. It is an inherited neurological disorder, which is distinguished by atypical calcium deposition in the movement-controlling areas of brain, that is thalamus, dentate nucleus, basal ganglia, cerebellum, cerebral cortex, hippocampus and subcortical white matter. The majority of patients often experience extrapyramidal symptoms, cerebellar signs, speech difficulty, dementia and neuropsychiatric manifestations. This disease's molecular genetics have not been thoroughly investigated. Typically, young to middle-aged adults are affected though basal ganglia calcification in hypoparathyroidism is quite uncommon. Laboratory results and radiographic brain imaging helps in reaching the diagnosis. The treatment is mainly symptomatic. We present a case of Fahr's syndrome associated with hypoparathyroidism.

Basal ganglia calcifications: No association with cognitive function.

BACKGROUND AND PURPOSE: Basal ganglia calcifications (BGC), a form of vascular calcification, are a common brain computed tomography (CT) finding. We investigated whether BGC are associated with cognitive function and examined the association between vascular risk factors and BGC. MATERIAL AND METHODS: Patients who visited a memory clinic of a Dutch general hospital between April 2009 and April 2015 were included. The patients underwent a standard diagnostic work up including cognitive tests (Cambridge Cognitive Examination, including the Mini Mental State Examination) and brain CT. Vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia and smoking were assessed. CTs were analyzed for presence and severity (absent, mild, moderate or severe) of BGC. Multivariable logistic regression was used to identify risk factors for BGC and linear regression for the association between BGC and cognitive function. RESULTS: Of the 1992 patients, 40.3% was male. The median age was 80 years and 866 patients (43.5%) had BGC. BGC was associated with female gender (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06-1.53, p 0.011), and inversely associated with hypertension (OR 0.74, 95% CI 0.60-0.89, p 0.002) and use of antihypertensive drugs (OR 0.79, 95% CI 0.64-0.98, p 0.031). No association was found between presence and severity of BGC and cognitive function or other vascular risk factors. CONCLUSIONS: No association with cognitive function was found. Risk factors for BGC were female gender, while hypertension and antihypertensive drug use were associated with a lower risk of BGC.

SLC20A2-Associated Idiopathic basal ganglia calcification (Fahr disease): a case family report.

BACKGROUND: Idiopathic basal ganglia calcification (IBGC) is a genetic disorder of the nervous system commonly known as Fahr disease. IBGC patients with a genetic background are considered to have primary familial brain calcification (PFBC), also known as familial basal ganglia calcification (FBGC), or familial Fahr disease. It is a rare degenerative neurological disorder characterized by extensive bilateral basal ganglia calcification that can lead to a range of extrapyramidal symptoms and neuropsychiatric manifestations. Studies have suggested that more than 50 variants of SLC20A2 gene mutations account for approximately 50% of IBGC cases. There is a wide spectrum of mutation types, including frameshift, nonsense, and splice site mutations in addition to deletion and missense mutations. Here we report a case of familial basal ganglia calcification caused by a frameshift mutation in the SLC20A2 gene. We identified a heterozygous mutation in the SLC20A2 gene, c.1097delG (p.G366fs*89). To our knowledge, this mutation site has not been reported before. CASE PRESENTATION: A 57-year-old male patient was admitted to the hospital with "unstable walking and involuntary movements between the eyes and eyebrows for 6 months". Based on the patient's family history, symmetrical calcification foci in the bilateral caudate nucleus head, thalamus, cerebellum and parietal lobe indicated by head CT, and gene test results, the diagnosis of familial Fahr disease caused by mutations in the SLC20A2 gene, c.1097delG p.G366fs*89) was confirmed. CONCLUSION: For the first time, we identified c.1097delG (p.G366fs*89) as a frameshift mutation in the IBGC family. This frameshift mutation caused the condition in this family of patients. This mutation not only broadens the range of known SLC20A2 mutations but also aids in the genetic diagnosis of IBGC.

Ischemic stroke in a patient with Fahr's disease carrying biallelic mutations in the MYORG gene.

Fahr's disease (FD) is a neurodegenerative disorder characterized by symmetric calcifications in the bilateral basal ganglia and dentate nuclei. Mutations in six genes are known to cause FD. In the present case, a 44-year-old woman was admitted because of bradykinesia that had started developing 3 years ago. Brain CT and MRI revealed severe calcification in the bilateral basal ganglia, thalamus, dentate nuclei, and subcortical white matter. Whole-exome sequencing revealed two previously described compound heterozygous mutations within the MYORG gene. About one year later, the patient developed sudden-onset left-sided hemiparesis. The MRI revealed a small infarction in the right internal capsule. Therefore, the present case findings expand the clinical spectrum of FD. Importantly, the association between ischemic stroke and FD needs to be further studied.

SLC20A2-related primary familial brain calcification with purely acute psychiatric symptoms: a case report.

BACKGROUND: Primary familial brain calcification (PFBC) is a rare inherited neurological disorder characterized by bilateral basal ganglia calcification with a series of motor and nonmotor symptoms. Mutations in the SLC20A2 gene, encoding the PiT2 protein, are the major cause of the disease. Here, we report a Chinese PFBC family carrying a SLC20A2 gene mutation, and the proband presented with purely acute psychiatric symptoms, which has been rarely reported in this disease. CASE PRESENTATION: A 38-year-old woman was hospitalized due to disorganized speech; disordered thought contents; disorganized behaviour; emotional instability and lability; and grandiose words, actions and facial expressions. Brain computerized tomography (CT) revealed calcification in the basal ganglia; cerebellar dentate nuclei; and subcortical, periventricular, and deep white matter regions in she and her family members. Through mutation analysis, a heterozygous truncating mutation, c.1723G > T, p.(Glu575*), was identified in the SLC20A2 gene in this family. Thus, this patient was diagnosed with genetically confirmed PFBC, and she responded well to a low dose of antipsychotic drugs. The penetrance of the disease in this family was only 33%, which was significantly lower than that in most families carrying SLC20A2 gene mutations. CONCLUSIONS: Patients with SLC20A2-related PFBC might present with psychiatric symptoms alone, and the penetrance of the disease may be quite low, which adds to the clinical heterogeneity of the disease.

Fahr's Disease and Hypoparathyroidism - A Missing Link.

Fahr's disease is an idiopathic basal ganglia calcification with autosomal dominant inheritance. Prior to diagnosing Fahr's disease based on computed tomography (CT) and/or magnetic resonance imaging (MRI) of the brain, one should rule out hypoparathyroidism (HP), and pseudohypoparathyroidism (PHP). Treatments of these conditions are entirely different. HP- and PHP-related hypocalcemia requires calcium, calcitriol, and vitamin D therapy in a long run to avoid recurrent seizures whereas Fahr's disease is treated with an antiepileptic alone.

Fahr's disease: A rare neuropsychiatric disorder.

Fahr's disease is a rare clinical neurodegenerative entity, occurring mainly in 4th or 5th decade, showing gradually progressive bilateral symmetric calcifications in basal ganglia, subcortical white matter, thalami or cerebellum, which can lead to movement disorder and/or neuropsychiatric manifestations. We present two cases in the same family; a 68-year-old brother had involuntary jerky movements of hand and dysarthria for 10 years while the 44-year-old sister had right lower limb spasticity and decreased vision for 2 years. The serial MRI scans showed slow progression in the bilateral subcortical white matter and cerebellar dentate nuclei calcifications along with surrounding reactive gliosis.

COVID-19 Unveiling Brain Calcifications.

Neurological symptoms in COVID-19 patients have attracted the interest of the scientific community, yet their mechanisms remain unknown. In some circumstances, the presence of neurological manifestations may result in an incidental diagnosis after a detailed investigation. In the present letter, we discuss a case published by Demir et al., in which the diagnosis of COVID-19 enabled the diagnosis of a rare neurological disorder, characterized by bilateral brain calcifications, commonly known by the eponym Fahr's syndrome. In addition, we report a case of primary brain calcifications unveiled by a suspected coronavirus infection.

Gray matter structural plasticity in patients with basal ganglia germ cell tumors: A voxel-based morphometry study.

BACKGROUND: Basal ganglia germ cell tumors (BGGCTs) are rare intracranial germ cell tumors (iGCTs) that often presents with cognitive impairment. OBJECTIVE: To assess structural brain plasticity in the presence of unilateral basal ganglia germ cell tumors (BGGCTs), and the correlation between gray matter volume (GMV) changes and cognitive tests. MATERIALS AND METHODS: We applied voxel-based morphometry (VBM) to structural magnetic resonance imaging (MRI) scans to compare a sample of 41 patients with BGGCTs in the left (n = 22) or right (n = 19) and a sample of 16 patients as control group using a two-sample t-test, correcting for family-wise-errors. A battery of cognitive tests was administered to all BGGCTs patients prior to MRI. We used Pearson correlation analysis to assess the correlation between cognitive test scores and GMV changes. RESULTS: In patients with left BGGCTs, whole-brain VBM analysis revealed a large cluster of voxels reflecting an increase in GMV in the left parahippocampal region (k = 529 voxels, T = 4.18, p < 0.01), right middle cingulate cortex (k = 172 voxels, T = 3.96, p < 0.01), and a decrease in volume in the left thalamus (k = 527 voxels, T = -4.88, p < 0.01), right inferior frontal gyrus (k = 495 voxels, T = -4.29, p < 0.01). Pearson correlation analysis showed that the GMV were significantly correlated with the Integrated Visual and Auditory continuous performance test (IVA-CPT) scale (r = 0.637, P = 0.002), abstract reasoning (r = 0.597, P = 0.011), Self-rating Depression Scale (SAS) scale (r = -0.623, P = 0.004) and memory recall (r = 0.648, P = 0.003). CONCLUSION: These results demonstrate that slow growing but destructive BGGCTs markedly and asymmetrically effect the GMV in left parahippocampal, left thalamus, right middle cingulate cortex, right inferior frontal gyrus and GMV changes were significantly associated with cognitive test.

Histology and computed tomography of incidental calcifications in the human basal ganglia.

Incidental basal ganglia calcifications are a common finding on computed tomography (CT). We investigated the histological characteristics of these calcifications and their association with CT findings, using post-mortem basal ganglia tissue from 22 patients. Eight patients had basal ganglia calcifications on histology, and six patients had calcifications on CT, varying from mild to severe. Four patients had calcifications identified by both histology and CT, and two patients had calcifications detected by CT but not by histology, possibly because of insufficient tissue available. Calcifications were found mainly in the tunica media of arterioles located in the globus pallidus, which suggests that incidental CT calcifications are vascular in nature. However, tunica media calcifications, and thereby incidental basal ganglia calcifications, are probably not related to atherosclerosis.

Basal Ganglia Calcification Is Associated With Local and Systemic Metabolic Mechanisms in Adult Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone, which may be associated with soft tissue calcification in the basal ganglia of the brain. OBJECTIVE: To assess the prevalence and factors involved in the pathophysiology of basal ganglia calcification (BGC) in the brain in chronic hypoparathyroidism and to evaluate proposed pathophysiologic mechanisms. DESIGN: Case-control study with retrospective review of medical records over 20 years. SETTING: Single academic medical center. PATIENTS: 142 patients with chronic hypoparathyroidism and computed tomography (CT) head scans followed between January 1, 2000 and July 9, 2020, and 426 age- and sex-matched controls with CT head scans over the same interval. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Demographic, biochemical, and CT head imaging findings, with semiquantitative assessment of volumetric BGC. RESULTS: The study found that 25.4% of 142 patients followed for a median of 17 years after diagnosis of chronic hypoparathyroidism had BGC, which developed at a younger age than in controls. BGC was 5.1-fold more common in nonsurgical patients and less common in postsurgical patients. Low serum calcium and low calcium/phosphate ratio correlated with BGC. Neither serum phosphorus nor calcium × phosphate product predicted BGC. Lower serum calcium was associated with greater volume of BGC. The extent of BGC varied widely, with nonsurgical patients generally having a greater volume and distribution of calcification. CONCLUSIONS: BGC is associated with low serum calcium and low serum calcium/phosphate ratio, which may be related to severity of the disease, its etiology, or duration of treatment.

Fahr's syndrome due to hypoparathyroidism revisited: A case of parkinsonism and a review of all published cases.

INTRODUCTION: Fahr's syndrome due to hypoparathyroidism refers to bilateral basal ganglia (BG) calcifications and manifests with movement disorders, seizures, cognitive and behavioral symptoms. CASE PRESENTATION: We report a case of a 74-year-old woman, who presented with parkinsonism due to post-surgical hypoparathyroidism and normal DaT scan, despite extensive calcifications of the BG, periventricular white matter, and cerebellum. METHODS: A comprehensive literature review of all reported cases of Fahr's syndrome due to hypoparathyroidism was conducted in the electronic databases PubMed and Web of science. Moreover, demographic and clinical characteristics of the patients overall were calculated and associated with radiological findings. RESULTS: We reviewed a total of 223 cases with Fahr's syndrome due to hypoparathyroidism (124 female, 99 male). Mean age on presentation was 44.6 ± 17.7 years. Thirty nine percent of patients had idiopathic hypoparathyroidism, 35.4 % acquired and 25.6 % pseudohypoparathyroidism. Almost half of the patients had tetany, seizures or a movement disorder and approximately 40 % neuropsychiatric symptoms. The patients with a movement disorder had a 2.23 likelihood of having neuropsychiatric symptoms as well (OR 2.23, 95 % CI 1.29-3.87). Moreover, there was a statistically significant association between the phenotype severity (i.e. the presence of more than one symptom) and the extent of brain calcifications (χ2 = 32.383, p = 0.009). CONCLUSION: Fahr's syndrome is a rare disorder, which nonetheless manifests with several neurological symptoms. A head CT should be considered for patients with hypoparathyroidism and neurological symptoms. More studies using DaT scan are needed to elucidate the effects of calcifications on the dopaminergic function of the BG.