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|Year : 2015 | Volume
| Issue : 6 | Page : 970-972
Familial idiopathic basal ganglia calcification (Fahr's disease) and diabetes mellitus: A review of literature
Jinzhan Liu, Weifeng Guo
The First Clinical Medical College, Nanjing Univerity of Chinese Medicine, Nanjing, Jiangsu, China
|Date of Web Publication||20-Nov-2015|
The First Clinical Medical College, Nanjing Univerity of Chinese Medicine, Nanjing, Jiangsu
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Liu J, Guo W. Familial idiopathic basal ganglia calcification (Fahr's disease) and diabetes mellitus: A review of literature. Neurol India 2015;63:970-2
Familial idiopathic basal ganglia calcification (BGC; Fahr's disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Both familial and sporadic cases of Fahr's disease have been reported. The condition is predominantly found to be autosomal-dominant. The etiology of Fahr's disease is very complex and still remains unknown. However, calcium deposits are the major elements responsible for the radiological appearance of the disease. Moreover, the link between calcium homeostasis and a compromised blood–brain barrier has been hypothesized as an etiological factor, which is based on the findings that psychiatric conditions may be associated with calcium dysregulation, calcium signaling, and altered calcium homeostasis. To the best of our knowledge, Fahr's disease is an inherited disorder, in which intracranial calcifications are easily formed in type 2 diabetes mellitus (DM) due to calcium deposition and atherosclerosis. However, the relationship between diabetes and Fahr's disease has not been reported previously. Here, an elderly male patient with a 10-year history of diabetes presented with significant BGCs.
We report the case of a 63-year-old male patient who had a decrease in the ability to recall events that developed 3 years ago. His ability to perform activities of daily living was normal. He had a history of diabetes mellitus (DM). Progressive neurological symptoms of the extrapyramidal system (unstable gait, dysphagia and lalopathy as well as resting tremor) were also reported since 1 year, and plasma glucose level was poorly controlled. Computed tomography (CT) of the patient showed extensive bilateral calcification in the basal ganglia and the thalamus [Figure 1]. BGC were also noticed in his brother and daughter [Figure 2] and [Figure 3]. However, no clinical symptoms were observed in them, and they had no history of diabetes. He also had a mild neurocognitive impairment (Mini-Mental State Examination [MMSE]: 23 points). Laboratory results revealed hyperglycemia and normal metabolism of calcium and phosphorus.
|Figure 1: CT of the patient, with two axial sections showing bilateral massive calcifications of the cerebellar dentate nucleus and white matter, basal ganglia region, thalamus, frontal lobe, and white matter of the centrum semiovale|
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|Figure 2: CT of the patient's brother, with two axial images showing marked bilateral calcification of the cerebellar dentate nucleus and the white matter of the cerebellum, basal ganglia region, thalamus, and the white matter of the centrum semiovale|
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|Figure 3: CT of the patient's daughter showing bilateral calcification of the globus pallidus|
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Neurologic examination revealed the following abnormalities: Dysarthria, dysphagia, reduced pharyngeal reflex, weakness in lower extremity muscles, and lead-pipe rigidity in the limb muscles. Deep tendon reflexes of the lower extremities were increased, and Babinski's sign was present in the left sided limbs. Ankle clonus and the palm–chin reflexes were positive. The patient could not complete both-hand alternating movement test, Knee–heel–shin test, and finger–nose test.
Ultimately, the patient was diagnosed to be having Fahr's disease, and Parkinsonian syndrome secondary to Fahr's disease. The differential diagnosis of Fahr's disease is a diagnosis of exclusion, mainly eliminating other conditions that can cause intracranial calcifications. The differential diagnosis includes neoplastic, vascular (aneurysms, arteriovenous malformations), infectious (neurocysticercosis, congenital childhood infections), congenital (Sturge– Weber syndrome More Details, tuberous sclerosis, lipomas, neurofibromatosis), and metabolic (hypoparathyroidism, pseudohypoparathyroidism, hyperparathyroidism) disorders. Based on family history, clinical manifestations, laboratory examination, and imaging, all the aforementioned differential diagnoses were effectively ruled out in our case. Initially, levodopa was administered for the Parkinsonian syndrome, and the type 2 diabetes mellitus was treated with metformin and acarbose; an additional treatment with donepezil was also instituted to improve memory. There was no satisfactory improvement in his symptoms, and the patient's blood glucose level was not well controlled. After controlling the blood glucose with insulin, blood sugar levels reached a satisfactory level, and the neurological symptoms improved. At follow-up, 3 months after discharge, it was confirmed that these manifestations did not recur, the blood glucose level was satisfactory, and the Parkinsonian syndrome was well controlled.
In this case of Fahr's disease, the Parkinsonian syndrome was the predominant neurological complication, and our patient also presented with DM. Various experiments and clinical researches indicate that diabetes and BGCs are closely related. An animal experimental study indicated that BGCs occurs more commonly in those animals that have the longest duration of diabetes. Moreover, correlation analysis of calcium content with calculated insulin resistance index, a homeostasis model assessment of insulin resistance, shows a positive correlation of insulin resistance with vascular calcification.
Brain imaging (CT) results regarding the patient's lineal consanguinity showed that BGCs were found in his brother and daughter also. However, no clinical symptoms were noticed in them, and they did not have a history of diabetes. We conclude that Fahr's disease is not a characteristic pathological change of diabetes mellitus, and genetic factors play a key role in the development of BGCs. There was no satisfactory control of symptoms by the usual medication. However, when blood glucose was well controlled, the clinical symptoms improved. According to literature, diabetes is associated with an increased predisposition to developing Parkinson's disease (PD). It is possible that chronic inflammation and oxidative stress noted in diabetes may also lead to a higher risk of developing PD years later. Furthermore, in vivo and invitro studies show the role of insulin in the regulation of brain dopaminergic activity. Insulin dysregulation and changes in insulin action have been of concern in the pathophysiology and clinical symptomatology of PD. Therefore, we propose that for patients with Fahr's disease, genetic factors play a key role in the development of BGCs, and diabetes mellitus may aggravate the development of intracranial calcification, induce the occurrence of complications, and increase the disease progression. When blood glucose is fully controlled, it may reduce clinical symptoms of Fahr's disease and delay the progress of the disease.
In conclusion, if patients with BGCs present with diabetes mellitus, we should give importance to controlling their blood sugar levels to improve the curative effect of medications on their symptomatology and to delay or control complications.
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[Figure 1], [Figure 2], [Figure 3]