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Year : 2016  |  Volume : 59  |  Issue : 4  |  Page : 513-517
A child with neurological deficits, electrolyte imbalance, and arrhythmia

1 Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
2 Department of Pediatrics, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
3 Department of Pediatrics, TN Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India

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Date of Web Publication10-Oct-2016


A child presented with an acute febrile illness associated with neurological symptoms. The differential diagnoses of such a presentation with effects of prolonged hospitalization is discussed.

Keywords: Arrhythmia, child, electrolyte imbalance, neurological deficits

How to cite this article:
Vaideeswar P, Karande S, Bavdekar S, Momin S, Goel N. A child with neurological deficits, electrolyte imbalance, and arrhythmia. Indian J Pathol Microbiol 2016;59:513-7

How to cite this URL:
Vaideeswar P, Karande S, Bavdekar S, Momin S, Goel N. A child with neurological deficits, electrolyte imbalance, and arrhythmia. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Jul 4];59:513-7. Available from: https://www.ijpmonline.org/text.asp?2016/59/4/513/191807

   Clinical Protocol Top

An 11-year-old boy was admitted to our institution with drowsiness and slurred speech, following two episodes of tonic posturing of all four limbs with frothing at mouth. There had been an alleged history of fall in bathroom 2 days back and a history of low-grade fever off and on for 5 days. His birth history and developmental milestones were normal; there were no focal neurological deficits or episodes of convulsions in the past. There was a history of ear discharge at 4 years of age. There was no history of tuberculosis or tuberculous contact.

   Clinical Examination and Investigations Top

On examination, the child was afebrile with a pulse rate of 80/min, respiratory rate of 40/min, and blood pressure of 98/62 mm Hg. He weighed 26 kg (below fifth percentile as per the National Center for Health Statistics [NCHS] weight-for-age charts), with a height of 142 cm (between 25 th and 50 th percentile as per NCHS height-for-age charts). On systemic examination, the child was comatose, responding only to deep stimuli (modified Glasgow Coma Scale of E1M4V1). His pupils were constricted and sluggishly reacting to light. He had hypertonia in all four limbs, brisk reflexes, and ill-sustained ankle clonus. Signs of meningeal irritation were present. Other systemic examinations were normal. With a provisional clinical diagnosis of either cerebral concussion or meningoencephalitis, he was shifted to the Pediatric Intensive Care Unit (PICU). He was started on ceftriaxone, valproate, dexamethasone, mannitol, and intravenous fluids. In view of poor general condition and gasping respiration, he was put on ventilator support. Initial investigations revealed a normal hemogram, normal random blood glucose, and calcium and renal/liver function tests with hyponatremia (126 mEq/L) and hypokalemia (2.8 mEq/L). Ultrasonography of the abdomen was normal. Computed tomography (CT) of the brain revealed communicating hydrocephalus probably secondary to tuberculous meningitis with infarcts in the left thalamus and right basal ganglia [Figure 1]a. With appropriate intravenous fluids, an attempt was made to correct the electrolyte imbalance. A burr hole and ventricular tap were done to reduce raised intracranial tension; the aspirated fluid was normal.
Figure 1: (a) Computed tomography brain showing communicating hydrocephalus with infarcts in the left thalamus and right basal ganglia (arrows). (b) Day 7 of admission showed normal sinus rhythm and normal axis with multiple ventricular premature contractions of multiple morphologies. (c) Supraventricular tachycardia and left axis deviation

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   Course in the Hospital Top

On day 2 of admission, a right femoral central line was inserted for long-term venous access. With a provisional diagnosis of tuberculous meningoencephalitis, anti-tuberculosis treatment (isoniazid, rifampicin, ethambutol, and pyrazinamide) was started. Hyponatremia (118 mEq/L) persisted and was treated with hypertonic (3%) saline and restricted intravenous fluids. A persistent irregular pulse was noted; electrocardiogram (ECG) showed ventricular bigeminus rhythm with ventricular ectopics arising from the right ventricle [Figure 1]b. Serum calcium (1.14 mEq/L) and magnesium (2.1 mEq/L) levels were normal.

On day 3, mannitol was stopped and acetazolamide started. As per the PICU protocol, intravenous antimalarial agents (artesunate and clindamycin) for Plasmodium falciparum malaria were empirically started. Ventricular tap was repeated by neurosurgeons to release raised intracranial tension. Hyponatremia (116 mEq/L) persisted despite treatment. The sputum was negative for acid-fast bacilli (AFB); ventricular tap fluid, blood, and urine culture did not grow any organisms. He was HIV negative. The electrolyte imbalance and ECG changes persisted on days 4 and 5 with the development of supraventricular tachycardia [Figure 1]c. On day 6, the cardiologist opined that ECG rhythm changes could probably be explained by the persistent hyponatremia. Meanwhile, the child's sensorium improved, with response to oral commands and weaning from ventilator was started. The child was extubated on day 7 and kept on oxygen by mask. A workup for syndrome of inappropriate antidiuretic hormone secretion (SIADH) was planned on the next day due to continuation of hyponatremia and ECG changes. However, on day 8, he developed bradycardia with desaturation, was intubated, and cardiopulmonary resuscitation was given. After 4 h, he developed pulseless ventricular tachycardia; cardioversion and amiodarone were given along with cardiopulmonary resuscitation, but he could not be revived.

   Unit's Final Diagnosis Top

Tuberculous meningoencephalitis complicated by either "SIADH" or "cerebral salt-wasting syndrome" with "persistent hyponatremia" causing ventricular bigeminus rhythm and ventricular ectopics arising from the right ventricle.

   Discussion on Clinical Protocol by Professor, Pediatrics Top

This 11-year-old child was brought with alteration in the central nervous system (CNS) function in the form of altered sensorium, slurred speech, and two episodes of tonic posturing, soon after a fall in the bathroom. The presence of neurological dysfunction, seizures, signs of meningeal irritation, and demonstrable infarcts and hydrocephalus pointed toward the existence of a widespread CNS damage due to a subacute or chronic disorder. In this situation, it is reasonable to make a presumptive diagnosis of CNS tuberculosis even in absence of a definitive cerebrospinal fluid picture or microbiological confirmation. It may be added that childhood tuberculosis is a paucibacillary disease and even with tuberculous meningitis, mycobacteria are most often not demonstrated on smear or culture. [1] Tuberculomas as a reason for CNS manifestations are less likely as they would have been seen on neuroimaging. Other causes of subacute or chronic meningitis or meningoencephalitis (such as fungal, neurocysticeral, or eosinophilic meningitis) were ruled out on the basis of clinical manifestations and investigations.

The patient also had persistent hyponatremia from the day of admission. The cause could be related either to SIADH or cerebral salt wasting syndrome, both of which can occur in tuberculous meningoencephalitis. [2] These complications could not be confirmed since the patient succumbed to the illness before osmolality studies and analysis of urinary electrolytes could be carried out. Addison's disease could have been considered as a cause for hyponatremia had it been associated with hyperkalemia. Dyselectrolytemia is known to cause cardiac arrhythmias; [3] though hyponatremia, by itself, is unlikely to give rise to ventricular ectopic beats arising from the right ventricle with bigeminal rhythm. [4] Raised intracranial pressure (ICP) is also known to give rise to arrhythmias but it is mainly associated with sinus node dysfunction giving rise to bradycardia and bradyarrhythmias. [5],[6]

Is it possible to explain the CNS and cardiac manifestations on the basis of a single disease? There are a few disorders that can manifest with both CNS and cardiovascular manifestations [Table 1]; however, they are unlikely in view of late presentation and absence of associated features. The fact that the patient developed arrhythmias of the right ventricular origin during his PICU stay, and which persisted even after his neurological condition improved, is a pointer to the separate etiologies for the CNS and cardiac manifestations. Per se, ventricular tachyarrhythmias are uncommon arrhythmias in children. [6] Apart from electrolyte imbalances or drugs, the possible cardiac etiologies in this child could include varied conditions such as structural congenital [7] or acquired defects, [8] cardiac tumors, [9] and myocardial diseases, [8] especially arrhythmogenic right ventricular cardiomyopathy/dysplasia. [10] However, these diagnoses seem unlikely (even though echocardiography was not performed) as the child did not have any cardiac complaints in the past; clinically also, there was no evidence of any cardiac murmur, cardiomegaly, or congestive cardiac failure. Apart from the rhythm changes, the ECG did not reveal any other abnormality. Moreover, none of the drugs used in the treatment had any arrhythmogenic potential.
Table 1: Diseases associated with central nervous system dysfunction and cardiac arrhythmias in children

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   Final Clinical Diagnosis Top

Tuberculous meningoencephalitis complicated by either "SIADH" or "cerebral salt-wasting syndrome" with "persistent hyponatremia" causing ventricular bigeminus rhythm and ventricular ectopics arising from the right ventricle.

   Pathology Protocol by Professor and Associate Professor Pathology Top

A complete autopsy had been performed. Remarkable findings were present in the brain, heart, and lungs. The brain appeared edematous with patchy leptomeningeal thickening and opacification. Whitish exudates were seen over the convexities, mainly along the congested cortical vessels. Dense yellowish white granular exudates were present at the base of the brain, especially in the interpeduncular fossa, prepontine cistern, and over the pons embedding the cranial nerve roots. On histology, these areas showed widening of the subarachnoid space by necrotic material, fibrin and dense mononuclear cell inflammatory, chiefly lymphocytes, macrophages, loosely arranged epithelioid cells, and plasma cells; inflammatory cells were also seen in the Virchow-Robin spaces [Figure 2]. Some of the leptomeningeal vessels that appeared thick-walled and prominent on gross examination showed a palisade of similar cells at histology [Figure 3]a. Serial coronal slices of the cerebral hemispheres revealed 2.5 cm x 1.5 cm x 1.5 cm friable focally hemorrhagic area of infarction involving left basal ganglia. In this region, the arteries in the vicinity also showed a prominent perivascular inflammatory cuff [Figure 3]b and c. Serial sections of the brainstem showed a tuberculoma, which appeared as a well circumscribed pale yellow firm nodule in the midline of the cerebellum [Figure 4]a, not involving the fourth ventricle. It was composed of caseation necrosis surrounded by a granulomatous reaction [Figure 4]b. The leptomeninges over the pituitary showed similar inflammation and vascular changes. Much of the gland showed foci of hemorrhage; dense lymphocytic infiltrate were also present within the remnants of the gland [Figure 4]c. Zeihl-Neelsen stain for acid-fast bacilli (AFB) was negative.
Figure 2: Extremely dense lymphocytic infiltrate in the subarachnoid space over the (a) cerebral gyri and (b) extending into the sulci. (c) The capillaries within the Virchow-Robin space are also surrounded by lymphocytes (H and E, ×250)

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Figure 3: The arteries in the (a) subarachnoid space and (b) within the necrotic parenchyma are surrounded by a thick cuff of inflammatory cells (H and E, ×250). (c) The artery is surrounded by lymphocytes with radiating undifferentiated histiocytes and epithelioid cells. Note that there is no infiltration of the wall or its destruction (H and E, ×400)

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Figure 4: (a) Scanned slide of the cerebellum showing a tuberculoma T in the mid - portion. The space is artefactual. (b) The caseation C is surrounded by the characteristic granulomatous reaction (H and E, ×400). (c) Groups of pituicytes (arrow) surrounded by dense lymphocytic infiltrate

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The heart was mildly enlarged and weighed 120 g. Mound-like, friable, granular light brown to pale yellow 1.6 cm x 1.0 cm thrombus was present in the right atrial cavity at the flutter isthmus [Figure 5]a. On histology, a fresh thrombus was seen adherent to the endocardium, which showed fibrocellular thickening with prominent fibroblastic proliferation and histiocytic infiltration; granulation tissue was present at the interphase with the myocardium [Figure 5]b. No organisms were identified, even on special stains. Rest of the chambers and valves appeared normal, but focal interstitial myocarditis was present in the left ventricular sections. Both lungs had a normal size and shape with patchy pleural thickening and opacification. The lungs were rubbery to feel and had a uniform brown color. The trachea, main bronchi, and the intra-parenchymal bronchi showed the presence of shaggy exudates and mucosal ulceration due to acute inflammation [Figure 5]c. Zeihl-Neelsen stain for AFB was negative. Interestingly, many of the arteries were occluded by fresh thrombi, which were confirmed on histology [Figure 5]d. Other organs were normal.
Figure 5: (a) Below the opening of the inferior vena cava (white arrows) and behind the opening of the coronary sinus (black arrow) is a large thrombotic mass. (b) Histology reveals adherence of thrombus to a mildly thickened and inflamed endocardium (H and E, ×100). (c) Bronchiole showing acute inflammatory exudate. (d) Occlusive fresh thrombus in a large muscular pulmonary artery (H and E, ×250)

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   Final Diagnosis Top

Tuberculous meningitis with cerebellar tuberculoma, pituitary tuberculosis, and panhypopituitarism-related arrhythmias; nosocomial tracheobronchitis; and catheter-induced right atrial mural thrombosis with pulmonary thromboembolism.

   Clinicopathologic Correlation Top

Childhood tuberculous meningitis is more common than bacterial meningitis with varied clinical manifestations. [11] Prompt diagnosis using clinical and investigational parameters is essential to prevent ensuing morbidity and mortality. However, due to nonspecific manifestations coupled with low sensitivity of the diagnostic tools generally available to clinicians working in resource-poor settings, an early diagnosis is at times compromised. In this case, the diagnosis of CNS tuberculosis was done on the basis of a conglomerate of clinical clues without the benefit of any definitive pathological, radiological, or microbiological help. This ensured that appropriate management (as per the standard guidelines) was initiated soon after presentation.

Apart from the usual sequelae of hydrocephalus and raised ICP, CNS tuberculosis is often complicated by vasculitis and consequent infarction. [12] The vasculitis tends to involve the medium-sized and small-sized arteries in the middle cerebral artery territory. The ischemic necroses characteristically occur in the basal ganglia region, especially the "tubercular zone," which includes the caudate nuclei, anterior thalamus, anterior limb, and genu of the internal capsule. [13] In this case, there was no active invasion of the vessels, but there was periadventitial cuffing by the granulomatous reaction, which is a common pattern seen. [12] Furthermore, even the capillaries within the infarcted parenchyma were surrounded by mononuclear inflammatory cells. On postmortem examination, the meningitis was associated with a solitary cerebellar tuberculoma, a common location in children. This was not detected antemortem, probably because the CT scan is known to be less sensitive and inferior to magnetic resonance imaging in detecting abnormalities in the infratentorial region. [14] Thankfully, this would not have affected management as the patient was treated with antitubercular drugs, corticosteroids, and measures for control of raised ICP. However, the precise cause of persistent hyponatremia could not be confirmed as the patient succumbed before serum osmolality studies and analysis of urinary electrolytes could be carried out. Hyponatremia is commonly seen in association with tuberculous meningitis and is supposedly caused by SIADH. [2] The perplexing issue in this case was the occurrence of arrhythmias in the patient in absence of any evidence of underlying heart disease. However, this could be explained on the dysfunction of the hypothalamic-pituitary axis dysfunction, a rare manifestation of CNS tuberculosis. This occurs with or without direct involvement of the pituitary gland; surprisingly patients may not have diabetes insipidus. [15] A prompt clinical diagnosis is required as the inflammation responds to antituberculous therapy; however, long-term follow-up is required to detect pituitary hormonal deficiency.

At autopsy, a right atrial thrombus was noted, which is an uncommon, but the well-documented complication of peripherally inserted central venous catheters (PICC). [16] It has been reported that due to the constant pumping movement of the heart, the catheter tip may cause damage to the wall of atrium, resulting in mural thrombus formation at the point of contact. [17],[18] Moreover, in the pediatric population, the distance between the right atrial chamber and the tricuspid valve is small and the risk of causing arrhythmias is higher as the catheters slide up and down the chamber with normal motions. [19] In the present case, it appears that the tip of the PICC was not placed freely in the right atrium, but the PICC may have been over-inserted resulting in not only the formation of a right atrial thrombus but also gave rise to fatal pulmonary thromboembolism.

   Conclusion Top

The present case reiterates the need for all pediatric intensivists to be aware that (1) development of a cardiac arrhythmia in a child with tuberculous meningitis or tuberculoma can indicate the involvement of the hypothalamic-pituitary axis and (2) a PICC can lead to the formation of a thrombus in the right atrium, which can result in pulmonary embolism and sudden death.

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   References Top

Chiang SS, Khan FA, Milstein MB, Tolman AW, Benedetti A, Starke JR, et al. Treatment outcomes of childhood tuberculous meningitis: A systematic review and meta-analysis. Lancet Infect Dis 2014;14:947-57.  Back to cited text no. 1
van Toorn R, Solomons R. Update on the diagnosis and management of tuberculous meningitis in children. Semin Pediatr Neurol 2014;21:12-8.  Back to cited text no. 2
Egom EE, Wong KY, Clark AL. Life-threatening hyponatraemia. BMJ Case Rep 2011;2011. pii: Bcr1220103594.  Back to cited text no. 3
Diercks DB, Shumaik GM, Harrigan RA, Brady WJ, Chan TC. Electrocardiographic manifestations: Electrolyte abnormalities. J Emerg Med 2004;27:153-60.  Back to cited text no. 4
Baranchuk A, Nault MA, Morillo CA. The central nervous system and sudden cardiac death: What should we know? Cardiol J 2009;16:105-12.  Back to cited text no. 5
Bourdages M, Bigras JL, Farrell CA, Hutchison JS, Lacroix J; Canadian Critical Care Trials Group. Cardiac arrhythmias associated with severe traumatic brain injury and hypothermia therapy. Pediatr Crit Care Med 2010;11:408-14.  Back to cited text no. 6
McComb JM, Vincent R, Hilton CJ. Recurrent ventricular tachycardia associated with anomalous left coronary artery from the pulmonary artery in a child managed by revascularisation and map-guided endocardial resection. Br Heart J 1989;62:396-9.  Back to cited text no. 7
Htwe TH, Khardori NM. Cardiac emergencies: Infective endocarditis, pericarditis, and myocarditis. Med Clin North Am 2012;96:1149-69.  Back to cited text no. 8
Careddu L, Oppido G, Petridis FD, Liberi R, Ragni L, Pacini D, et al. Primary cardiac tumours in the paediatric population. Multimed Man Cardiothorac Surg 2013;2013:mmt013.  Back to cited text no. 9
Thiene G, Corrado D, Basso C. Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Orphanet J Rare Dis 2007;2:45.  Back to cited text no. 10
Wolzak NK, Cooke ML, Orth H, van Toorn R. The changing profile of pediatric meningitis at a referral centre in Cape Town, South Africa. J Trop Pediatr 2012;58:491-5.  Back to cited text no. 11
Younger DS. Vasculitis of the nervous system. Curr Opin Neurol 2004;17:317-36.  Back to cited text no. 12
Misra UK, Kalita J, Maurya PK. Stroke in tuberculous meningitis. J Neurol Sci 2011;303:22-30.  Back to cited text no. 13
Ahluwalia VV, Dayananda SG, Singh TP, Arora N, Narayan S, Singh MM. MRI spectrum of CNS tuberculosis. J Indian Acad Clin Med 2013;14:83-90.  Back to cited text no. 14
Dhanwal DK, Vyas A, Sharma A, Saxena A. Hypothalamic pituitary abnormalities in tubercular meningitis at the time of diagnosis. Pituitary 2010;13:304-10.  Back to cited text no. 15
Burns KE, McLaren A. Catheter-related right atrial thrombus and pulmonary embolism: A case report and systematic review of the literature. Can Respir J 2009;16:163-5.  Back to cited text no. 16
Fuchs S, Pollak A, Gilon D. Central venous catheter mechanical irritation of the right atrial free wall: A cause for thrombus formation. Cardiology 1999;91:169-72.  Back to cited text no. 17
Forauer AR, Theoharis C. Histologic changes in the human vein wall adjacent to indwelling central venous catheters. J Vasc Interv Radiol 2003;14(9 Pt 1):1163-8.  Back to cited text no. 18
Bhutta ST, Culp WC. Evaluation and management of central venous access complications. Tech Vasc Interv Radiol 2011;14:217-24.  Back to cited text no. 19

Correspondence Address:
Pradeep Vaideeswar
Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College and KEM Hospital, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.191807

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

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