Pediatr Radiol (2008) 38:101–103 DOI 10.1007/s00247-007-0608-9
CASE REPORT
Intracranial calcification in central diabetes insipidus Salwa Ramadan Al-Kandari & Tarun Pandey & Mona H. Badawi
Received: 14 May 2007 / Revised: 21 July 2007 / Accepted: 23 July 2007 / Published online: 23 October 2007 # Springer-Verlag 2007
Abstract Intracranial calcification is a known but extremely rare complication of diabetes insipidus. To date, only 16 patients have been reported and all had the peripheral (nephrogenic) type of diabetes insipidus. We report a child with intracranial calcification complicating central diabetes insipidus. We also report a child with nephrogenic diabetes insipidus, and compare the patterns of intracranial calcification. Keywords Diabetes insipidus . Intracranial calcification . CT . Children
central deficiency or insufficient renal response to antidiuretic hormone (ADH) [1]. To date, intracranial calcification (ICC) has not been reported as a complication of the central type of diabetes insipidus (CDI). The few reports of this complication published in the literature have all concerned patients with the peripheral or nephrogenic form of this disease (NDI) [2–9]. Here we present a child with ICC uniquely complicating CDI. A further child is presented in whom ICC complicated NDI. The intracranial changes seen in the index patient on serial CT scans showed progressive changes that seemed to correlate well with the clinical abnormalities.
Introduction Diabetes insipidus is an uncommon disorder (prevalence 1 in 25,000) of impaired water metabolism that may be due to
Case reports Patient 1
S. R. Al-Kandari : T. Pandey Department of Clinical Radiology, Al Razi Hospital, Gamal Abdel Nasser Street, Kuwait 4234, Kuwait M. H. Badawi Department of Paediatrics, Al-Adan Hospital, Kuwait, Kuwait T. Pandey (*) 11720 Pleasant Ridge Circle, #1602 Little Rock, AR 72205, USA e-mail:
[email protected] Present address: T. Pandey Radiology Department, University of Arkansas for Medical Sciences, 4301, W. Markham #556, Little Rock, AR 72205, USA
A 4-year-old boy presented to the pediatric emergency department in a state of shock due to dehydration and was admitted to the intensive care unit. There was a 1-month history of polyuria and polydipsia and immediately prior to admission he had high fever, multiple episodes of vomiting and nonbloody diarrhea. The central nervous system examination showed increased muscle tone and exaggerated deep tendon reflexes. The rest of the organ system examination was unremarkable. He was the product of a full-term vaginal delivery with no significant perinatal problems; his birth weight was 3.25 kg. However, developmental history revealed evidence of delayed milestones. His parents were second-degree cousins and they had three other healthy children. There was no family history of a similar illness, epilepsy or neurodegenerative disease. Investigations revealed the presence of severe hypernatremia (serum sodium 170 mmol/l)
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referred to the Center for Clinical Genetics and Developmental Medicine to determine whether a metabolic or hereditary disease was present, but despite thorough investigation, none was identified. The patient was put on desmopressin nasal spray 10 μg/day and at the time of this report was on regular follow-up. Developmental assessment at the age of 7 years revealed a maturity level corresponding to that of a 4-year-old. Patient 2
and severe acidosis. Cerebrospinal fluid (CSF) analysis was normal. Blood and CSF cultures were sterile. Serum osmolality was 343 mosm/kg and the urine osmolality was 192 mosm/kg. Two days after admission, a CT scan of the brain was obtained that showed multiple, symmetrical heavily calcified deposits in the basal ganglia and subcortical white matter of the frontal and parietooccipital lobes (Fig. 1). Based on the biochemical and electrolyte changes, a diagnosis of CDI was suspected and confirmed following a positive desmopressin test (urine osmolality increased from 207 to 524 mosm/kg after 2 h). The ADH level was 0.6 ng/l (normal 0–6 ng/l) at a serum osmolality of 344 mosm/kg. Secondary causes of ICC were excluded by history, clinical assessment and appropriate tests. These included serology for the presence of any congenital infections, serum calcium, phosphate and alkaline phosphatase and parathormone levels for the presence of hypo-, pseudohypo- or pseudopseudohypoparathyroidism. All these tests were negative. In addition, the patient was also
This was the first child of healthy, first-degree related parents and was delivered at full term weighing 3.25 kg. His neonatal period was uneventful, but at 2 months of age he was admitted with fever. There was clinical suspicion of acute meningitis for which a CT scan of the brain was performed but revealed no definite abnormalities (Fig. 2). CSF analysis was also normal. Other investigations confirmed the presence of otitis media. From that time he had continuous fever, and his mother reported that he was always asking for more water. He was thoroughly investigated, but no obvious cause was identified. His developmental milestones were normal initially but started to lag after 10 months of age. He was readmitted at the age of 15 months with fever, dehydration and difficulty in breathing. Investigations revealed the presence of hypernatremia, serum osmolality of 340 mosm/kg, metabolic acidosis and renal failure. His urine output was good despite the renal failure, but the urine was persistently hypotonic (osmolality 146 mosm/kg, specific gravity 1.005) and unresponsive to vasopressin administration. He also developed convulsions that were controlled by intravenous diazepam. The diagnosis of primary NDI was made after excluding secondary causes. A CT scan of the brain obtained at this time showed symmetrical calcifications similar to those seen in patient 1 (Fig. 2). Therapy was
Fig. 2 Patient 2. Nephrogenic diabetes insipidus. a Initial axial noncontrast CT scan of the brain at 2 months of age shows no obvious parenchymal calcification. b Axial noncontrast CT scan at 15 months of age shows the pattern and distribution of ICC similar to that seen in
patient 1. Prominent CSF spaces are also noted, possibly due to brain shrinkage secondary to dehydration. c Follow-up CT scan after 1 year shows an increase in the amount and density of the calcifications. The CSF spaces now appear almost within normal limits
Fig. 1 Patient 1. Central diabetes insipidus. Axial unenhanced CT scan of the brain shows characteristic symmetrical calcifications in the basal ganglia and subcortical white matter of the frontal and temporoparietooccipital regions
Pediatr Radiol (2008) 38:101–103
initiated with hydrochlorothiazide and amiloride and the parents were counseled regarding adequate provision of water and a salt-restricted diet for their child. These measures were associated with a decrease in urine output, increase in urine osmolality and normalization of serum electrolytes and other renal parameters. After 1 year, a follow-up CT scan showed an increase in the amount and density of the cerebral calcifications (Fig. 2). At this time the child had gained weight and had normal serum electrolytes, but his developmental milestones were still delayed. Two months later the child was admitted to the intensive care unit with fever, convulsions and severe dehydration and could not be revived despite all life-saving efforts.
Discussion Diabetes insipidus generally presents with polyuria and polydipsia. However, these are uncommon in infants and presentation is usually with features of dehydration such as fever, constipation, vomiting, failure to thrive and developmental delay. The diagnosis is usually delayed until hypernatremia is noted [9]. Imaging has very little role to play in these patients, but rarely characteristic ICC develops that may help in making a diagnosis. The calcifications are seen symmetrically in the basal ganglia and the gray-white matter junctional regions of the frontal, parietal, temporal and occipital lobes [2–9]. Calcium deposition occurs within or around the brain capillaries and vessels without affecting the neurons [4]. This could explain the location and symmetry of the calcifications as well as the relative lack of neurological abnormalities seen in this disease. It has been suggested that recurrent hypernatremic dehydration may damage endothelial and other cells and this initiates dystrophic calcification within or around vessel walls [10]. However, the role of hypernatremia alone has been questioned in the absence of any report of ICC in patients with CDI. But, the findings in patient 1 (a unique case of CDI) lend more support to the theory that hypernatremia may indeed be an important causative factor. It is possible that other undefined mechanisms were also operative. The severity, duration and age of onset of hypernatremia may be important additional factors in the occurrence of calcification [6, 11]. Our two patients showed no difference in the pattern and distribution of ICC which were similar to those described in the literature.
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In patient 2, we identified a pattern of imaging findings during follow-up. The initial CT scan did not show any ICC while subsequent scans did reveal characteristic calcifications that appeared to increase in severity with time. Mild brain atrophy was also seen in later scans in this patient, but was not present initially. These observations indicate that there may be a spectrum of radiological abnormalities in this disease progressing from a morphologically normal brain to brain with calcifications and atrophy. This may correspond to a clinical spectrum from minimal or no clinical findings to severe psychomotor retardation. In summary, we observed that both CDI and NDI can give rise to essentially identical ICC and that the spectrum of imaging findings correlates well with the clinical abnormalities in these conditions. It is important to maintain a high index of suspicion for diabetes insipidus whenever ICC is seen in a child with urinary symptoms and developmental delay.
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