Bilateral basal ganglia calcification and recurrent generalized seizures as initial presentation of idiopathic hypoparathyroidism in an infant.

Pathological calcification of basal ganglia has been encountered in children since long back and is associated with various disease entities both acute and chronic. Idiopathic hypoparathyroidism is an important cause of basal ganglia calcification and can account for up to 73.8% of cases. The pathogenesis of basal ganglia calcification in hypoparathyroidism is not clear, however, a high calcium-phosphorus product and poor calcium control are believed to be directly related to calcification. Besides, a direct correlation is seen with the duration of hypocalcemia; the critical duration being ≥4 years. In the presented patient, basal ganglia calcification was seen at a very young age of 6 months. To best of our knowledge, this is probably the youngest case of bilateral basal ganglia calcification in idiopathic hypoparathyroidism in literature. This suggests that besides duration of hypocalcemia, certain genetic factors and the intrauterine milieu may have a role in the pathogenesis of basal ganglia calcification.

Introduction

The basal ganglia comprise principally of caudate, putamen and globus pallidus nuclei, and form the core of the extrapyramidal system. Basal ganglia calcification is a common entity in children and may be the end result of various pathological processes both acute and chronic. A number of infections, various metabolic disturbances, and theraupeutic side effects of certain drugs can manifest as basal ganglia calcification.[12] Idiopathic hypoparathyroidism is an important cause of basal ganglia calcification and accounts for 73.8% of cases, and there is a direct correlation of basal ganglia calcification with duration of hypocalcemia.[3] The increased vulnerability of basal ganglia to damage in children is on account of increased metabolic rate.[4] Bilateral basal ganglia lesions frequently manifest with nonfocal clinical features ranging from increased irritability, lethargy, behavioral changes, seizures or dystonia to more serious respiratory distress, and coma.[56]

Case Report

A 6-month-old female baby, product of nonconsanguineous marriage, second in birth order, born at term by normal vaginal delivery had presented with history of two episodes of generalized tonic-clonic seizures 24 h after diphtheria, pertussis, tetanus vaccination at the age of 4 months. Patient was taken to a physician who put the patient on liquid phenytoin. Electroencephalogram and magnetic resonance imaging (MRI) brain at that time were unrevealing. In the present admission, the patient had a history of recurrent episodes of generalized tonic-clonic movements of both upper and lower limbs. There was no prior history of fever, vomiting or vaccination. On examination, the patient was actively convulsing with a pulse rate of 110 per min, blood pressure 70/50 mmHg. Neck was free and systemic examination was inconclusive. Patient was immediately started on intravenous phenytoin infusion. Biochemical evaluation of patient revealed serum sodium of 134 mEq/l, serum potassium (3.5 mEq/l), pH (7.43), bicarbonate (26 mmol/l), serum glucose (96 mg/dl), serum calcium (3.5 mg/dl), and serum phosphorus of 5.6 mg/dl. Renal function, liver functions, and other biochemical investigations were normal [Table 1]. Due to severe hypocalcemia and resistant seizures, the patient was put on intravenous calcium and midazolam infusion that resulted in control of seizures. On further evaluation, anthropometry revealed height of 66 cm (54th centile), weight of 7.5 kg (58th centile), and head circumference of 42 cm. There was no facial dysmorphism or any other skeletal anomaly [Figure 1]. Intact serum parathyroid hormone (PTH) was <1 pg/ml, 25-OH Vitamin D 36 nmol/l, 8 am serum cortisol 22.31 μg/dl, and thyroid function tests were normal. Computed tomography (CT) of brain showed bilateral basal ganglia calcification [Figures 2 and 3]. Echocardiography and abdominal ultrasonography were normal. Patient was discharged on phenytoin 25 mg twice a day, levetiracetam 200 mg/day, liquid calcitriol 37.5 μg/day, and liquid elemental calcium of 500 mg/day. Patient is presently 14-month-old seizure free, development is normal, and milestones are consistent with age.

Table 1

Laboratory parameters

Figure 1

6-month-old baby with no facial dysmorphism

Figure 2

Bilateral globus pallidus calcification

Figure 3

Bilateral globus pallidus calcification

Discussion

Hypocalcemia is an important cause of seizures in newborn. The cause of hypocalcemia in our patient was idiopathic hypoparathyroidism: A rare disorder characterized by low calcium, high phosphorus, and low serum PTH concentration in the absence of renal impairment, malabsorption, and any previous history of neck surgery or irradiation.[4] Idiopathic hypoparathyroidism is an important cause of basal ganglia calcification; the association was first noticed by Eaton et al. in 1939.[7] However, with the availability of advanced imaging techniques such as CT and MRI, the incidence of basal ganglia calcification has increased.[8] Basal ganglia calcification occurs in 73.8% patients with idiopathic hypoparathyroidism as was observed by Goswami et al. Who also found that basal ganglia calcification has direct correlation with duration of hypocalcemia, choroid plexus calcification, seizures, and cataract. It was further observed that critical duration associated with the occurrence of basal ganglia calcification was 4 years.[3] This was unlike our patient in whom the calcification was seen at a very young age of 6 months suggesting that not only duration of hypocalcemia but various other undetermined genetic and intrauterine factors may be influencing basal ganglia calcification. In another study by Illum and Dupont basal ganglia calcification in idiopathic hypoparathyroidism was seen in 69% of patients.[8] The median age of CT finding in his study was 43 years (range: 12–71 years). Though basal ganglia calcification occurs with increased frequency in hypoparathyroidism and pseudohypoparathyroidism, other clinical conditions associated with pathological basal ganglia calcification include infective and metabolic causes such as hypoxia, hypoglycemia, carbon monoxide poisoning, hemolytic uremic syndrome, toxoplasmosis, cytomegalovirus infection, congenital rubella, chicken pox, and acquired immune deficiency syndrome.[13] Physiological basal ganglia calcification is encountered in 0.3–1.5% cases.[1910]

The pathogenesis of basal ganglia calcification in idiopathic hypoparathyroidism is not well understood; however, it is believed to be due to high serum calcium-phosphorus product and poor calcium control.[3] The calcification starts in the vessel wall and the surrounding perivascular space and progressively extends to invade the neuronal tissue, which explains the varied clinical presentation.[11] Duckett et al. found that calcification occurs due to deposition of calcium and other minerals in the walls of arterioles, small veins, capillaries, and perivascular space.[12] The possible explanation for the mineral deposition was suggested by Gomez et al. who observed that abnormalities of vascular membrane was responsible for leakage of plasma-derived substances, which in turn attract inflammatory reaction and eventually result in deposition of calcium and other minerals.[13]

The basal ganglia calcification may present with a variety of symptoms ranging from tetany, seizures and mental retardation to extrapyramidal, cerebellar signs, and intracranial hemorrhage.[56] Since the basal ganglia calcification is directly related to duration and severity of hypocalcemia; treatment of hypocalcemia reduces the progression of calcification.[214] This emphasizes early treatment with calcium and Vitamin D besides regular monitoring of serum calcium and phosphate levels to ensure prevention of neurological complications in patients with hypoparathyroidism.

Conclusion

Besides duration and severity of hypocalcemia, certain undetermined genetic and intrauterine factors may be responsible for basal ganglia calcification in a subset of patients with idiopathic hypoparathyroidism.