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CASE REPORT
Year : 2016  |  Volume : 4  |  Issue : 2  |  Page : 157-160

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


1 Department of Endocrinology, King Fahd Armed Forces Hospital, Jeddah 21159, Saudi Arabia
2 Department of Nephrology, King Fahd Armed Forces Hospital, Jeddah 21159, Saudi Arabia

Date of Web Publication7-Apr-2016

Correspondence Address:
Patan Murthuza Khan
Department of Endocrinology, King Fahd Armed Forces Hospital, P. O. Box 9862, Jeddah 21159
Saudi Arabia
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DOI: 10.4103/1658-600X.179823

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  Abstract 

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.

Keywords: Chorioathetosis, hyperparathyroidism, idiopathic hypoparathyroidism, intracranial calcification, secondary, seizure disorder


How to cite this article:
Bokhari SA, Khan PM, Bokhari EA. Extensive intracranial calcification presenting with neurological symptoms due to primary hypoparathyroidism and secondary hyperparathyroidism: Two case reports. J Health Spec 2016;4:157-60

How to cite this URL:
Bokhari SA, Khan PM, Bokhari EA. Extensive intracranial calcification presenting with neurological symptoms due to primary hypoparathyroidism and secondary hyperparathyroidism: Two case reports. J Health Spec [serial online] 2016 [cited 2020 Dec 5];4:157-60. Available from: https://www.thejhs.org/text.asp?2016/4/2/157/179823


  Introduction Top


Metabolic disorders affecting the calcium and phosphate homeostasis are well known to cause metastatic calcification. In brain, they usually cause calcification of basal ganglion and remain silent clinically in most of the cases. Idiopathic hypoparathyroidism (IHPT) and secondary hyperparathyroidism (SHPT) in end-stage renal disease (ESRD) leading to widespread metastatic calcification in the basal ganglion, cerebellum, cerebral cortex and presenting with neurological manifestations is rarely described in literature. We present two such rare cases, one with PHPT presenting with choreoathetotic movements and the second with SHPT in ESRD presenting with a seizure disorder.


  Case Reports Top


Case 1

A 52-year-old lady presented with a history of abnormal right-sided body movements of 1-year duration. She was a known case of type 2 diabetes mellitus on treatment and IHPT. She was diagnosed to have IHPT several years ago and was prescribed calcium and a variety of Vitamin D supplements from different hospitals which she had been taking irregularly. On examination, pulse was 78/min and blood pressure (BP) was 110/70 mmHg. No subcutaneous calcifications. No oral mucocutaneous lesions. No bradydactylies. There were no abnormal findings in cardiovascular, abdominal and respiratory systems. The neurological examination revealed hyperkinetic, irregular, involuntary movements of the right side of the body. No cogwheel rigidity. On investigation, her haemoglobin was 13.4 g/L and white blood cell count was 8800 × 109 and platelets 321 × 109. Her renal function, liver function, thyroid function, serum bicarbonate and anionic gap were normal. The serum calcium was 1.8 mmol/L (normal range: 2.15 - 2.55); urine pH was 7.1. Serum albumin 40 g/l per liter (normal range: 30 - 40), serum phosphate: 1.59 mmol/L (normal range: 0.9 - 1.32), 25, hydroxycholecalceferol level: 42 nmol/L (normal range: 75 - 250), serum parathyroid hormone (PTH) level: 1.26 pmol/l (normal range: 1.6 - 6.9). Non-contrast computed tomography (CT) scan of the brain revealed extensive bilateral symmetrical calcification involving basal ganglion, cerebellum and white matter [Figure 1] and [Figure 2].
Figure 1: Cacium × phosphate product (mmol2/L2) on vertical axis and different encounters to the hospital on horizontal axis. The red line indicates threshold for solubility in the solution in mmol2/L2

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Figure 2: Non-contrast computed tomography scan of brain showing bilateral calcification of frontal lobes, basal ganglion

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She was prescribed calcitriol 0.5 µg and calcium 1200 mg thrice daily and advised to be compliant with treatment and follow-up regularly. Unfortunately, she lost for follow-up.

Case 2

A 15-year-old boy presented with a history of recurrent seizures of 6 months' duration. He had been undergoing haemodialysis for the past 5 years secondary to ESRD due to right renal agenesis and hypertension. His course of haemodialysis treatment was complicated and interrupted due to recurrent venous access failures. At present, he is undergoing dialysis via access through permacath. His seizure disorder was difficult to control with several anti-epileptic medications.

On examination: Obese, pulse 84/min and regular, BP 107/84 mmHg. No subcutaneous calcifications. No abnormal findings in abdominal, cardiovascular and respiratory system examination. Central nervous system examination showed no localizing signs.

Investigations during a recent visit: Serum creatinine: 356 µmol/L (normal range: 62 - 106). Blood urea nitrogen: 28.5 mmol/L (normal range: 1.7 - 8.3): Serum calcium: 2.18 serum albumin: 34 g/L serum phosphate: 1.98 mmol/L, calcium × phosphate product at different visits to hospital depicted in [Figure 3]. Serum PTH level: 30.93pmol/L (normal range: 1.6 - 6.9), cerebrospinal fluid protein, sugar, and cell count was normal and cultures were negative. Electroencephalogram revealed borderline abnormality. No definite evidence of epileptic activity. Non-contrast CT brain showed widespread intracranial calcification [Figure 4] and [Figure 5].
Figure 3: Non-contrast computed tomography brain showing extensive bilateral cerebellar calcification

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Figure 4: Non-contrast computed tomography brain showing bilateral calcification starting from centrum semiovale extending to paraventricular white matter

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Figure 5: Non-contrast computed tomography brain showing extensive bilateral calcification of caudate nucleus, put amen and thalami

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In the initial years, his dialysis sessions were not regular due to venous access problems. He developed SHPT during the course of dialysis. His serum calcium and serum phosphate levels fluctuated widely with calcium × phosphate levels reaching more than 4.4 mmol 2/L 2 on several occasions. He developed seizure disorder secondary to extensive intracranial calcification, which was partially controlled by antiepileptic medications. For the past 1 year, the dialysis sessions were performed with low calcium dialyzers and sevelamer was started to control hyperphosphatemia. With control of serum calcium and serum phosphate and antiepileptic medications, his seizure disorder was better controlled with decreased frequency.


  Discussion Top


The causes of intracranial calcification include physiological and as well as pathological conditions.[1] The knowledge of physiological calcification in the brain parenchyma is essential to avoid misinterpretation. The age-related physiological calcifications are seen in the pineal gland, falx, choroid plexus and basal ganglia and are never clinically significant. The pathological intracranial calcifications may be seen in several congenital disorders like tuberous sclerosis, Sturge–Weber syndrome, neurofibromatosis, Cockayne and Grolin syndromes and basal nevus syndrome. The typical distribution of calcification and absence of specific features of these syndromes ruled out these rare causes in our patients. Vascular calcification in the arterial walls of large intracranial vessels is commonly seen in atherosclerotic disease and can be diagnosed by the typical distribution of calcification along the arteries, aneurysms and arteriovenous malformation. Congenital infections such as toxoplasmosis, other agents, rubella, cytomegalovirus, herpes syndrome, cytomegalovirus, toxoplasmosis and acquired infections such as tuberculosis, HIV and Cryptococcus were excluded by the absence of the clinical features and appropriate blood tests. A rare idiopathic disorder such as Fahr syndrome was not considered as there was an obvious cause for intracranial calcification. Renal tubular acidosis was considered in our case with primary hypothyroidism, but the normal urine pH and absence of metabolic acidosis (normal serum bicarbonate) deferred further diagnostic tests. The metabolic disorders causing a disturbance in calcium and phosphate homeostasis leading to persistent hypocalcaemia and hyperphosphatemia promote metastatic soft tissue calcification. Patients with hypoparathyroidism, pseudohypoparathyroidism, ESRD on long time dialysis, and hypothyroidism developed hypocalcaemia and hyperphosphatemia and are known to develop intracranial calcification.[2] Calcinosis exceeding the common locations like basal ganglion and involving the subcortical white matter of frontal lobe and parietal lobe, and cerebellum is rarely described in IHPT [3],[4],[5] and in ESRD with SHPT.[6],[7] Patients with intracranial calcification in these disorders are usually asymptomatic and rarely present with neurological manifestations such as choreoathetosis and seizure disorder. We present two such cases of extensive intracranial calcification beyond basal ganglion, presenting with neurological symptoms, to discuss the pathogenesis and management.

The first case diagnosed to have IHPT and extensive intracranial calcification presented with choreoathetotic movements. The mechanism of extensive intracranial calcification has not been completely elucidated and understood. It may be related to the duration of hypocalcaemia and hyperphosphatemia rather than decrease in PTH itself. Hyperphosphatemia promotes ectopic calcification in the brain and superoxide production by mitochondria should be explored in reference to intracranial calcification in IHPT.[8] Other mechanisms relate to changes in calcium and phosphate ratios in the pathogenesis of metastatic calcifications.[9] Expression of osteogenesis related molecules in caudate nucleus could favour metastatic calcification in the unique biochemical milieu of HPT. The expression of these molecules not only in the caudate nucleus but also in the grey matter could favour basal ganglion and white matter in inpatients developing widespread intracranial calcification.[10] The second case belonging to a young patient undergoing dialysis presented with difficult to control seizures due to metastatic widespread intracranial calcification secondary to SHPT. Metastatic calcification of several organs and soft tissues of the body in SHPT on dialysis has been well documented and reported in the literature, but extensive, bilateral intracranial calcification presenting with seizures in a patient on dialysis and uncontrolled SHPT is a rare condition. The exact pathogenesis of the soft tissue and vascular calcification of the dialysis patients have not been understood clearly. Hyperphosphatemia due to low clearance of phosphate is a common abnormality in ESRD. The product of serum calcium and phosphate in SHPT in ESRD results in deposition of hydroxyapatite crystals in soft tissues. In 1967, Berlyne suggested calcium phosphate product as a risk factor for extraskeletal calcification,[11] with a present consensus that it should not exceed 4.4 mmol 2/L 2. Metastatic calcification occurs when the calcium × phosphate product exceeds its solubility in serum resulting in their deposition in susceptible tissues.[12] The presence of uncontrolled SHPT and disorder of calcium and phosphate homeostasis due to the common use of large doses of calcium-containing phosphate binders and calcitriol also contribute to metastatic calcification of soft tissues.


  Conclusion Top


Metabolic diseases like IPTH and SHPT in dialysis patients affect the calcium and phosphate homeostasis profoundly. Rarely, they may present with neurological manifestations like extrapyramidal symptoms and seizures due to widespread intracranial calcification. It is important to treat the abnormalities of calcium and phosphate in these disorders with the replacement of Vitamin D in the form of calcitriol and liberal supplements of calcium to maintain the serum calcium level in the low normal range while serum phosphate level in the normal range. In SHPT in dialysis patients, additional measures like using phosphate binders, low calcium dialyzers, sevelamer may be helpful to keep calcium × phosphate product <4.4 (mmol 2/L 2) and prevent metastatic calcification. Moreover, in patients presenting with neurological manifestations in IHPT and SHPT, intracranial metastatic calcification has to be ruled out. A adequate treatment to maintain the calcium and phosphate homeostasis to near normal levels may lead to remarkable improvement in neurological manifestations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Faves MJ, Volkes TJ. Pagets disease and other dysplasias of bone. In: Jameson JL, editor. Harrisons Endocrinology. 16th ed. New York: McGraw-Hill Company; 2006. p. 485-98.  Back to cited text no. 1
    
2.
Floege J. When man turns to stone: Extraosseous calcification in uremic patients. Kidney Int 2004;65:2447-62.  Back to cited text no. 2
    
3.
Mendelsohn DB, Hertzanu Y, Friedman L. Hypoparathyroidism with cerebral calcification extending beyond the extrapyramidal system. A case report. S Afr Med J 1984;65:781-2.  Back to cited text no. 3
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4.
Rizvi I, Ansari NA, Beg M, Shamim MD. Widespread intracranial calcification, seizures and extrapyramidal manifestations in a case of hypoparathyroidism. N Am J Med Sci 2012;4:369-72.  Back to cited text no. 4
    
5.
Goel A, Bhatnagar MK, Vashishta A, Verma NP. Hypoparathyroidism with extensive intracranial calcification: A case report. Postgrad Med J 1994;70:913-5.  Back to cited text no. 5
    
6.
Rao N, Crail S. Images in clinical medicine. Metastatic calcification and long-term hemodialysis. N Engl J Med 2013;368:2415.  Back to cited text no. 6
    
7.
Bilge I, Sadikoglu B, Emre S, Sirin A, Tatli B. Brain calcification due to secondary hyperparathyroidism in a child with chronic renal failure. Turk J Pediatr 2005;47:287-90.  Back to cited text no. 7
    
8.
Fujita T. Mechanism of intracerebral calcification in hypoparathyroidism. Clin Calcium 2004;14:55-7.  Back to cited text no. 8
    
9.
Goswami R, Sharma R, Sreenivas V, Gupta N, Ganapathy A, Das S. Prevalence and progression of basal ganglia calcification and its pathogenic mechanism in patients with idiopathic hypoparathyroidism. Clin Endocrinol (Oxf) 2012;77:200-6.  Back to cited text no. 9
    
10.
Goswami R, Millo T, Mishra S, Das M, Kapoor M, Tomar N, et al. Expression of osteogenic molecules in the caudate nucleus and gray matter and their potential relevance for basal ganglia calcification in hypoparathyroidism. J Clin Endocrinol Metab 2014;99:1741-8.  Back to cited text no. 10
    
11.
Berlyne GM. Microcrystalline conjunctival calcification in renal failure. A useful clinical sign. Lancet 1968;2:366-70.  Back to cited text no. 11
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12.
Slatopolsky E, Robson AM, Elkan I, Bricker NS. Control of phosphate excretion in uremic man. J Clin Invest 1968;47:1865-74.  Back to cited text no. 12
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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