|Year : 2021 | Volume
| Issue : 1 | Page : 31-34
Cerebral infarction in a child with congenital adrenal hyperplasia presenting as acute encephalitis syndrome
Saugata Acharyya, Kakoli Acharyya, Arnab Haldar
Department of Pediatrics, Calcutta Medical Research Institute, Kolkata, West Bengal, India
|Date of Submission||18-Jul-2020|
|Date of Decision||21-Aug-2020|
|Date of Acceptance||16-Sep-2020|
|Date of Web Publication||12-Dec-2020|
Dr. Saugata Acharyya
Department of Pediatrics, Calcutta Medical Research Institute, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
Congenital Adrenal Hyperplasia (CAH) is an inherited abnormality of steroid synthesis. It is usually diagnosed in the early neonatal period. Its association with white matter abnormalities in the developing brain has been reported. Cerebral infarction is one of the rarely associated complications of classical CAH. A 5-year-old child had presented with features of acute onset fever, refractory new-onset seizure, and altered sensorium. He was a known case of CAH, on regular exogenous steroid supplementation. Investigations revealed that he had extensive hemorrhagic cerebral infarction. No underlying infective or vascular cause could be detected to explain the etiology of cerebral infarction in this child. Hence, the effect of CAH on the developing brain and an inadequate escalation of steroid dose during stress have led to the cerebral infarction.
Keywords: Acute encephalitis syndrome, cerebral infarction, congenital adrenal hyperplasia
|How to cite this article:|
Acharyya S, Acharyya K, Haldar A. Cerebral infarction in a child with congenital adrenal hyperplasia presenting as acute encephalitis syndrome. J Pediatr Crit Care 2021;8:31-4
|How to cite this URL:|
Acharyya S, Acharyya K, Haldar A. Cerebral infarction in a child with congenital adrenal hyperplasia presenting as acute encephalitis syndrome. J Pediatr Crit Care [serial online] 2021 [cited 2021 Jan 26];8:31-4. Available from: http://www.jpcc.org.in/text.asp?2021/8/1/31/303265
| Introduction|| |
Congenital adrenal hyperplasia (CAH) is an inherited disorder of steroid synthetic pathway. It results in adrenal insufficiency. It is caused by a genetically acquired deficiency of enzymes involved in the synthesis of glucocorticoid and mineralocorticoids. CAH remains the commonest cause of primary adrenal insufficiency in the pediatric age group. It is mostly diagnosed in the early neonatal period. Its diagnosis is included in the neonatal metabolic screening panel. Classic CAH is an autosomal recessive disorder with an estimated prevalence rate of one in 15,000 live births. It is characterized by the poor synthesis of glucocorticoids and in many cases, mineralocorticoids (in the salt losing variant) and adrenal hyperandrogenism. More rare forms are caused by the deficiency of 11 β-hydroxylase, 17α-hydroxylase, 3 β-hydroxysteroid dehydrogenase, or P450 oxidoreductase. It has been postulated that even in intrauterine life, prenatal glucocorticoid deficiency has a potential impact on the fetal brain. As evidence of this, a significant decrease in the amygdala volume has been observed in CAH infants. This suggests a prenatal critical effect of hormone deficiency on the developing central nervous system (CNS). Cerebral infarction is in itself a rare condition in children. Its coexistence with CAH is more rare. However, this association might not be only coincidental. It has been suggested that CAH in itself or its treatment with glucocorticoid and/or mineralocorticoid or an inadequate treatment under stressful conditions may be the cause of cerebral infarction. The presentations of acute encephalitis syndrome in a child consist of fever of acute onset, change in sensorium, and/or recurrent new-onset seizures (excluding classical febrile seizures). We report a 5-year-old boy presenting with acute onset febrile illness, altered sensorium, and newly diagnosed refractory convulsion. He was being treated with supplementation of glucocorticoids and mineralocorticoids at home for CAH, which was diagnosed during the neonatal period. Investigations revealed that the child had underlying cerebral infarction.
| Case Report|| |
A 5-year-old boy had presented to us with acute onset fever (36 h), altered sensorium, and new-onset refractory generalized tonic-clonic seizure. He was the only child of nonconsanguineous parents. His body weight was 20 kg and most recently recorded height was 110 cm, both above the 50th centile in the age, and sex appropriate growth charts. He was born by cesarean section at term but was small for gestational age (birth weight 2.1 kg). At the age of 10 days, he was readmitted with significant weight loss and shock. Investigations revealed that he had classical CAH caused by the deficiency of 21 hydroxylases. He was put on a regular maintenance dose of glucocorticoid (15 mg/m2/day) and mineralocorticoid (0.1 mg) supplementation. His developmental milestones were normal and he was up to date with immunization. He did not have any other major illness in the past and since diagnosis, his blood pressure was normal all along.
At the time of admission, his temperature was 101°F, he was disoriented and was having a recurrent convulsion. The convulsions were controlled by two boluses of intravenous midazolam and one bolus of fosphenytoin. His capillary blood glucose was 38 mg/dl and was given a bolus of 10% dextrose. Blood pressure was 100/60 mm Hg, plantars were up going on both sides, deep-tendon jerks were brisk in the lower limbs, and the pupils were sluggishly reacting bilaterally. Routine blood investigations were sent and supportive therapy, including intravenous fluids and antimicrobials (ceftriaxone, vancomycin, and acyclovir) were started as per the unit protocol. He was also advised maintenance dose of fosphenytoin and levetiracetam as per the suggestion of pediatric neurologist. The Glasgow Coma Score was 7/15, and the child was not responding to a painful stimulus. The arterial blood gas showed predominant respiratory acidosis (pH 7.12, pCO2 68 mmHg, HCO3 18.6 mmol/L, and Base excess-5.4 mmol/L). The child was put on mechanical ventilation in the assist-control mode. The normal maintenance doses of steroids were doubled. Ophthalmological examination done before the CT scan of the brain revealed no evidence of raised intracranial pressure. An initial CT scan of the brain revealed multiple acute hematoma in the right cerebral hemisphere along with sulcal bleed and extensive infarction in the right cerebral hemisphere and left high frontal region.
Blood reports showed Hb 9.6 g/dl, total WBC count 10500/Cumm (PMN 45%, lymphocytes 42%), and platelet count 2.1 × 105/Cumm. Serum sodium was 133.6 mEq/L, potassium 4.08 mEq/L, creatinine 0.30 mg/dl, calcium 8.6 mg/dl, magnesium 1.9 mg/dl, SGPT 38 U/L, ammonia 27 mg/dl, lactate 1.8 mmol/L, and venous blood glucose was 86 mg/dl, C Reactive Protein 1.1 (normal <0.3). Malaria parasites and dual antigen, Dengue NS1 and Igm, blood and urine culture, as well as scrub typhus and Mycoplasma IgM, were all negative. The serum aldosterone level was 16 ng/dl (normal <40) and the ratio of serum aldosterone and plasma renin activity was normal (<20). The early morning serum cortisol level was 18 μg/dl (normal 3–20).
A packed red cell transfusion of 10 ml/kg was given. The prothrombin time was 11.9 s (control 11 s), APTT was 28.8 s (control 26–28 s). CSF analysis showed total cells <5 (all lymphocytes), protein 36 mg/dl, and sugar 66 mg/dl (CBG 78 mg/dl), ADA was normal, CB-NAAT negative and Japanese encephalitis, as well as the entire neurotropic microbial panel, was nonreactive. The EEG was suggestive of diffuse encephalopathy and echocardiography was normal.
The ventilation was weaned off gradually, and he was extubated on day 5. Serial blood results were normal. There was no further seizure. Phenytoin was stopped and only oral levatiracetam maintenance dose was continued. The partial parenteral nutrition was stopped and enteral feeds (started on day 1) was built up till he was fully oral fed on day 8, when he was out of supplemental oxygen. A magnetic resonance imaging (MRI) of the brain performed on day 7 revealed large subacute infarcts along with multiple hematomas [Figure 1]. The sensorium was improved gradually, but there was mild residual weakness of the left side, for which regular physiotherapy was advised. The results of investigations to delineate any underlying cause of cerebral infarction were all normal. These included normal protein C, protein S, antithrombin 3, and homocysteine levels. Serum C3 and C4 were normal, and pANCA, antinuclear, and antiphospholipid antibodies were all negative. The MR Angiogram and Doppler of the carotid vessels were normal. The child was discharged on day 14 after putting him back to his normal maintenance doses of glucocorticoids and mineralocorticoids.
| Discussion|| |
Deficiency of 21-hydroxylase, resulting from mutations or deletions of CYP21A, is the most common form of CAH, accounting for >90% of cases. CAH is a disorder of adrenal hormone synthesis. It has been suggested that among the modulator substances, adrenal hormones exert very important regulatory activities and trophic effects on cell survival, differentiation, maturation, and synaptogenesis of the CNS. Several studies based on MRI have described brain white matter abnormalities in children with CAH, with the radiological changes that can be sometimes detected from the 1st days of life in children with classic CAH. It has also been noticed that apart from the white matter changes, moderate atrophy in the right temporal cortex, small volume hippocampus, and agenesis or thinning of the corpus callosum were observed in the long-term follow-up of children with classic CAH. The pathogenesis of white matter abnormalities is still uncertain. Some authors have proposed that exposure to excess exogenous glucocorticoids during CAH treatment is the most feasible explanation for these MRI findings. This may be related to the potential inhibitory role of cortisol in the process of neuronal maturation and myelination by inhibiting the differentiation of oligodendrocyte precursors., In addition, low serum sodium, potentially leading to myelinolysis, has been suggested as a potential contributing factor to the impaired myelin formation in these patients. Many authors have also suggested that hormonal imbalance related to a deficiency in cortisol and aldosterone and overproduction of 17-OH-progesterone and androgen may further cause a destabilization of the myelin molecule leading to its degeneration.
Therefore, the characteristic neuroimaging finding in most cases of CAH is white matter degeneration or leukoencephalopathy. Extensive hemorrhagic cerebral infarction is an uncommon association. Cerebrovascular events or stroke is a more common association of syndrome of Apparent Mineralocorticoid Excess (AME) caused by the deficiency of type 2 11β-hydroxysteroid dehydrogenase (11βHSD2). In the case we have reported, the child was diagnosed to have classical CAH. There was no history of hypertension and hypokalemia. The renin and aldosterone levels were normal. Hence, AME was excluded from the study. Almost all infective or vascular etiologies and the presence of any thrombophilic state were excluded from the study. The MR Angiogram was also normal. At presentation, the child was hypoglycemic, which might be due to poor oral intake and could explain the encephalopathy. However, its role in causing an acute cerebral event of this magnitude is questionable. Significantly, the doses of supplemental corticosteroids were not escalated during the illness. Therefore, we conclude that the inadequate dose-escalation along with the possible cerebral effect of CAH itself might be responsible for the cause of cerebral infarction in this child, which had led to the acute neurologic emergency.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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