Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study

Salpietro, Vincenzo; Mankad, Kshitij; Kinali, Maria; Adams, Ashok; Valenzise, Mariella; Tortorella, Gaetano; Gitto, Eloisa; Polizzi, Agata; Chirico, Valeria; Nicita, Francesco; David, Emanuele; Romeo, Andrea; Squeri, Carlo A.; Savasta, Salvatore; Marseglia, Gian Luigi; Arrigo, Teresa; Johanson, Conrad E.; Ruggieri, Martino

doi:10.1515/jpem-2013-0156

Cited by 52 publications

(85 citation statements)

References 12 publications

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“…Additional pediatric cases further strengthen this link of IIH associated with hyperaldosteronism whereby children have been successfully controlled with spironolactone after failure of acetazolamide treatment. In one case the child had secondary hyperaldosteronism, and in the other case the child had metabolic syndrome, obesity, and hyperaldosteronism [12,23]. …”

Section: Ptcs Etiologymentioning

confidence: 99%

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Idiopathic Intracranial Hypertension and Obesity

Andrews

Liu

Ko³

2014

Horm Res Paediatr

100

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Idiopathic intracranial hypertension (IIH), also known as primary pseudotumor cerebri syndrome (PTCS), is a condition of unknown etiology which affects primarily overweight, reproductive-aged women and causes increased intracranial pressure (ICP). This review discusses the recently revised diagnostic criteria for PTCS for adults and children. Additionally, the role of obesity in the epidemiology, etiology, and management of IIH as well as the current knowledge of obesity profiles and markers in IIH are reviewed. We also highlight the emerging, unifying theory of the neuroendocrine effects on the mineralocorticoid receptor to explain a possible mechanism for the increased cerebrospinal fluid production and ICP in secondary PTCS.

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Section: Ptcs Etiologymentioning

confidence: 99%

“…Children with IIH but without the headache tend to have more neurological signs, and vision loss at presentation is associated with a poorer prognosis [6]. Additionally, in pediatric cases of IIH the presentation may mimic a lesion in the posterior fossa with ataxia, facial palsy, nuchal rigidity, and torticollis [12]. …”

Section: Introductionmentioning

confidence: 99%

Idiopathic Intracranial Hypertension and Obesity

Andrews

Liu

Ko³

2014

Horm Res Paediatr

100

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“…The MR(s) are abundantly expressed in the choroid plexus epithelial cells (CPEC), which are putatively crucial in the regulation of CSF production [93]. Activation of the MR or its downstream pathways can enhance and stimulate the generation of Na/K ATPase pumps, which can lead to the movement of sodium ions at the CPEC apical membrane into the cerebral ventricle and actively create an osmotic gradient to drive CSF secretion and increase CSF pressure [94, 95]. Based on this perspective, the MR signalling at the CPEC level could therefore be a key pathway in IIH pathophysiology and could explain several reported endocrine-metabolic causes of IIH (see Figure 3), including PAL and SAL, obesity, metabolic syndrome, Cushing syndrome, chronic steroid administration, hypervitaminosis A, recombinant growth hormone (r-GH) therapy, and estro-progestin supplementation [50, 89–91].…”

Section: Hyperaldosteronism and The Paediatric Brainmentioning

confidence: 99%

“…An increase in its activity in PAL and SAL disorders may potentially directly affect the ICP in IIH. Support for this perspective includes numerous recent studies demonstrating that in children and adults with PAL or SAL, those treated with spironolactone, an aldosterone receptor antagonist, had resolution of the neurological symptoms and of the ophthalmological manifestations [95, 96]. Additional paediatric cases further strengthened this association of IIH and hyperaldosteronism in which children with various conditions (e.g., metabolic syndrome, SAL due tubular dysfunction) have been successfully treated with spironolactone after a lack of clinical response to the other diuretic treatments (e.g., acetazolamide) [95–97].…”

Section: Hyperaldosteronism and The Paediatric Brainmentioning

confidence: 99%

Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

Salpietro

Polizzi

Rosa

et al. 2014

International Journal of Endocrinology

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Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal disorders and/or supraphysiological doses of corticosteroids. Physicians should be aware of potential neurological manifestations in children with adrenal dysfunction to achieve better prevention and timely diagnosis and treatment of these disorders. Further studies are needed to explore the potential neurological, cognitive, and psychiatric long-term consequences of high doses of prolonged corticosteroid administration in childhood.

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“…PTCS is a condition of unclear aetiology, characterised by increased intracranial pressure (ICP) without any radiographic evidence of brain tissue abnormalities, and with normal chemical and cytological cerebrospinal fluid (CSF) composition [31][32][33]. Multiple causes have been taken into consideration in the pathophysiology and aetiology of PTCS [32,33] including obesity, endocrine abnormalities (e.g., hyperaldosteronism, Cushing syndrome, hyperandrogenism, Addison disease), kidney disease (e.g., nephrotic syndrome), systemic disease (e.g., systemic lupus erythematous, Guillain-Barrè syndrome, antiphospholipid antibody syndrome, polycystic ovary syndrome -PCOS, Behcet disease, familial Mediterranean fever), medications (e.g., recombinant growth hormone therapy, tetracycline, steroids, mycophenolate mofetil, vitamins A and D, cytarabine, and cyclosporine A), viral infections (e.g., chickenpox, measles, reactivation of varicella infection) and changes in CSF volume and in cerebral CSF hemodynamic (increased cerebral blood volume, increased cerebrospinal fluid production, decreased cerebrospinal fluid resorption or venous flow abnormalities); PTCS has been also observed in members of the same family presenting in either an autosomal dominant or recessive manner. A recently proposed unifying (neuroendocrine) hypothesis inferred that [32] multiple neuroendocrine interactions (e.g., cortisol, aldosterone, progesteron) could influence the activation of the mineralocorticoid receptor (MR) in the choroid plexus epithelial cells, which in turn stimulates (via a nuclear pathway) the ATPase/Na + /K + pump leading to raised intracranial CSF production [25].…”

Section: Disease-modifying Therapies In Pediatric Msmentioning

confidence: 99%

The role of puberty and adolescence in the pathobiology of pediatric multiple sclerosis

Salpietro

Polizzi

Recca

et al. 2018

Mult Scler Demyelinating Disord

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Multiple sclerosis (MS) is increasingly recognized in the paediatric age. In a smaller, but well-established, proportion of paediatric MS patients [20% of total paediatric MS cases: 0.2% to 0.7% of the total MS patients] the onset of disease is before 10 years of age [pre-pubescent (childhood) MS]; in the majority [80%] of paediatric MS patients, however [1.7% to 5.6% of the total MS population], the onset of disease is between 10 and 18 years [post-pubertal (juvenile) MS]. Notably, while pre-pubertal MS occurs almost equally in both genders (female/male ratio = 0.9:1; reverting to 0.4-0.6/1 in pre-school MS children) the female/male ratio rises to 2.2/3:1 in the post-pubertal age. Interestingly, precocious puberty has been associated to: (a) a higher risk of developing MS; and (b) a more severe disease course. In addition to that, males are more susceptible to MS (and manifest more neurodegeneration) than females the latter being however more inflammatory than males; pregnancy however reduces MS relapses. All the above findings led to the suggestion of an underlying female sex hormonal involvement in the pathophysiology of MS vs. a protective role of male sex hormones. Epigenetic perspectives indicate that the interplay between genetic background, environmental triggers and neuroendocrine changes, typically occurring around the time of adolescence, could all play a combined role in initiating and/or promoting MS with onset in the paediatric age including many of the most frequent disease-associated risk factors (e.g., overweight/obesity, low vitamin D levels, reduced sunlight exposure, Epstein-Barr virus infection). According to this proposed complex multifactorial model, susceptibility to MS may be thus acquired during pre-pubertal age and children have probably to wait until the adolescence to manifest their first clinical signs/symptoms.

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Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study

Cited by 52 publications

References 12 publications

Idiopathic Intracranial Hypertension and Obesity

Idiopathic Intracranial Hypertension and Obesity

Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

The role of puberty and adolescence in the pathobiology of pediatric multiple sclerosis

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