Ipoglicemia da iperinsulinemia
Upcoming SlideShare
Loading in...5
×
 

Ipoglicemia da iperinsulinemia

on

  • 979 views

 

Statistics

Views

Total Views
979
Views on SlideShare
939
Embed Views
40

Actions

Likes
0
Downloads
2
Comments
0

1 Embed 40

http://www.dottnet.it 40

Accessibility

Categories

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Ipoglicemia da iperinsulinemia Ipoglicemia da iperinsulinemia Document Transcript

  • The Clinical Problem of Hyperinsulinemic Hypoglycemia and Resultant Infantile Spasms Anitha Kumaran, Sri Kar, Ritika R. Kapoor and Khalid Hussain Pediatrics 2010;126;e1231-e1236; originally published online Oct 18, 2010; DOI: 10.1542/peds.2009-2775 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.pediatrics.org/cgi/content/full/126/5/e1231 PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from www.pediatrics.org. Provided by GlaxoSmithKline Enterprise licence on January 21, 2011
  • CASE REPORTSThe Clinical Problem of HyperinsulinemicHypoglycemia and Resultant Infantile SpasmsAUTHORS: Anitha Kumaran, MRCPCH, Sri Kar, MRCPCH,Ritika R. Kapoor, MRCPCH, and Khalid Hussain, MD abstractLondon Center for Pediatric Endocrinology and Diabetes, Great Hyperinsulinemic hypoglycemia (HH) is a cause of severe hypoglyce-Ormond Street Hospital for Children, Clinical and MolecularGenetics Unit, Institute of Child Health, University College mia in the newborn and infancy period and is associated with a highLondon, London, United Kingdom risk of neurologic handicap and epilepsy. Infantile spasms after expo-KEY WORDS sure to HH is rare and has been described in only 1 previous report. Wepersistent hyperinsulinemia hypoglycemia of infancy, infantile report the clinical, biochemical, and neurodevelopmental characteris-spasms tics of 5 patients with neonatal-onset HH who subsequently developedABBREVIATIONS infantile spasms. All 5 patients had neonatal-onset HH of varying sever-HH—hyperinsulinemic hypoglycemiaEEG—electroencephalogram ity and duration. These patients presented with the characteristic ictalAED—antiepileptic drug pattern of spasms in clusters at a mean age of 6.6 months. Character-www.pediatrics.org/cgi/doi/10.1542/peds.2009-2775 istic hypsarrhythmia was noted in only 3 of 5 patients. Structural ab-doi:10.1542/peds.2009-2775 normality was found in only 1 of 4 patients who underwent MRI of theAccepted for publication Jun 24, 2010 brain. Infantile spasms responded to medical treatment in 3 patients,Address correspondence to Khalid Hussain, MD, Developmental spasms in 1 patient were refractory to antiepileptic drugs, and treat-Endocrinology Research Group, Clinical and Molecular Genetics ment duration was insufficient for us to comment on the response in 1Unit, Institute of Child Health, University College London, 30 patient. Developmental delay was evident in all of them. In conclusionGuilford St, London WC1N 1EH, United Kingdom. E-mail: neonatal HH of varying severity is associated with later (after a latentk.hussain@ich.ucl.ac.uk period) development of infantile spasms. The latent period before thePEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). onset of the spasms can be variable; hence, long-term neurodevelop-Copyright © 2010 by the American Academy of Pediatrics mental follow-up (until 1 year of age) is necessary. Pediatrics 2010;126:FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose. e1231–e1236PEDIATRICS Volume 126, Number 5, November 2010 e1231 Downloaded from www.pediatrics.org. Provided by GlaxoSmithKline Enterprise licence on January 21, 2011
  • Hyperinsulinemic hypoglycemia (HH) Hypoglycemic brain injury is a recog- day, which was suggestive of infantileis a cause of persistent hypoglycemia nized insult that triggers infantile spasms. She had achieved normaland occurs because of dysregulated spasms. However, the mechanism of developmental milestones that re-insulin secretion.1 This unregulated se- hypoglycemic brain injury resulting in gressed after the onset of these sei-cretion of insulin suppresses glucose infantile spasms is unclear. There has zures. Results of an MRI scan of herproduction by inhibiting glycogenolysis, only been 1 previous case report of a brain were normal at 6 weeks and 1gluconeogenesis, lipolysis and ketogene- patient with infantile spasms and HH.13 year of life. An EEG showed encepha-sis, which leads to a lack of alternative In this report, we describe the cases of lopathy with a right posterior tempo-fuels available for brain function. Hence, 5 infants with neonatal-onset HH (with ral focus and no evidence of hypsar-the brain is highly susceptible to hypo- and without seizures) who, after a la- rhythmia. Her seizures were clinicallyglycemic damage with a high risk of neu- tent period, subsequently developed felt to be infantile spasms and wererologic handicap, cerebral palsy, and ep- infantile spasms. Our case series sug- difficult to manage. Her seizures wereilepsy.2– 4 Hypoglycemic brain injury is gests that brain injury caused by neo- unresponsive to sodium valproate,typically associated with generalized natal HH (diazoxide-responsive and adrenocorticotrophic hormone, andepilepsy, although focal epilepsy might -unresponsive) may lead to the devel- prednisolone, but the seizures re-also occur.5 Generalized epilepsy in as- opment of infantile spasms later in the sponded to a combination of vigaba-sociation with HH is recognized in hy- infancy period. trin and lamotrigine. A repeat EEG at 15perinsulinism/hyperammonemia syn- months showed better background or-drome, a form of HH associated with CASE REPORTS ganization and reduction in epilepti-hyperammonemia.6– 8 Patient 1 form activity but persistent slow activ-Infantile spasms are a rare form of ep- ity in the left temporal area. Patient 1 was born via normal vaginalilepsy and have a characteristic ictal delivery at 40 weeks’ gestation with a A developmental assessment at 4pattern of spasms that occur in clus- birth weight of 3.9 kg. She presented years of age showed mild generalizedters.9 The onset is typically in infancy with generalized seizures at 3 days of hypotonia and receptive language de-(peak incidence at 6 months), and as- age (Table 1). Investigations included a lay with significant speech and expres-sociated interictal electroencephalo- full septic screen, the results of which sive language delay. She continuesgrams (EEGs) show a chaotic high- were negative, and serum calcium, with lamotrigine for ongoing seizures.voltage pattern called hypsarrhythmia, magnesium, lactate, ammonia, and Her head circumference, which was atalthough this can be variable.10 Out- blood gas measurements and liver the 75th centile at birth, is currently atcome is often poor with severe neuro- function tests, the results of which the 50th centile (Table 1). Her HH is wellcognitive impairment and evolution were all normal. However, the patient controlled on minimal doses of diazox-into other types of seizures.11 Approxi- was found to be hypoglycemic and re- ide (5 mg/kg per day).mately 9% to 15% of the cases are quired 12.5 mg/kg per minute (normal:cryptogenic, and the rest are symp- 4 – 6 mg/kg per minute) of intravenous Patient 2tomatic. The symptomatic cases are glucose to maintain normoglycemia. Patient 2 was born via normal vaginaltypically associated with several pre- Further investigations revealed HH (Ta- delivery at 40 weeks’ gestation with anatal, perinatal, and postnatal fac- ble 2). The diagnostic criteria for HH birth weight of 3.2 kg. He presented ontors (including hypoglycemia), tu- are listed in Table 3.14 The HH re- day 2 when he was found to be floppyberous sclerosis, structural brain sponded to diazoxide (13 mg/kg per and in respiratory distress. The re-lesions (such as lissencephaly, hemi- day); the seizures did not respond to sults of routine hematology, microbiol-megalencephaly, focal cortical dys- phenobarbitone or phenytoin and ogy, and biochemical investigationsplasia, septal dysplasia, and callosal were eventually controlled with clonaz- were normal. However, his blood glu-agenesis), chromosomal abnormali- epam. Over the next 6 weeks the pa- cose concentration was 0.4 mmol/Lties (such as Down syndrome and tient was weaned off antiepileptic when he was floppy. He required up todel1p36), or single gene defects (mu- drugs (AEDs) and discharged from the 12 mg/kg per minute of an intravenoustations of the ARX or CDKL5 gene).12 In hospital only on diazoxide. glucose infusion to maintain normo-the vast majority of cases there is a At 9 months the patient developed clus- glycemia. Investigation results con-temporal latency between an en- ters of head nods and jerking of her firmed HH (Table 2), which respondedcephalopathic event and the onset of upper body without lower-limb involve- to diazoxide. Despite resolution of hy-infantile spasms. ment at a frequency of nearly 200 per poglycemia he continued to have gen-e1232 KUMARAN et al Downloaded from www.pediatrics.org. Provided by GlaxoSmithKline Enterprise licence on January 21, 2011 View slide
  • CASE REPORTS eralized seizures, and an EEG revealed Near-total pancreatectomy Motor and visual delay a burst-suppression pattern. Pheno- Case 5 barbitone was used to control the sei- Hypsarrhythmia zures, and the patient was gradually Vigabatrin weaned off of it at 4 weeks. Normal Normal Female 5 mo 50th At 6 weeks of age he presented with 4.5 10 9 tonic clonic seizures that lasted 2 min- Subtotal pancreatectomy utes and were not associated with hy- poglycemia. The seizures responded Adrenocorticotropic Gross motor delay hormone 2 wk partially to phenobarbitone and phe- Hypsarrhythmia Case 4 nytoin. An EEG showed bursts of sharp Awaited left-sided activity, and results of an MRI Normal Male 1.2 y 75th scan of his brain were normal. He con- 10 9 8 tinued to have right-sided partial sei- Right parieto-occipital cyst Prednisolone; currently on zures and generalized tonic clonic con- Bilateral sharp and slow Coordination difficulties, speech and language Diazoxide, chlorthiazide vulsions almost daily for 3 months carbamazepine Case 3 despite an optimal dosage of AEDs. At 3 discharges months of age, the seizure pattern changed to 8 to 10 clusters with 5 to 6 delay Normal Male 2.5 y 50th flexor spasms within each cluster. An 9 9 9 EEG showed hypsarrhythmia. After a Vigabatrin and prednisolone previously; failed trial of vigabatrin and pred- currently on valproate, topiramate, nisolone, he was commenced on val- Hypsarrhythmia; previous burst proate and topiramate, which resulted Gross motor and visual delay Diazoxide, weaned by 9 mo in some reduction of seizures. Case 2 At 9 months of age he was successfully and levetiracetam weaned off of diazoxide. At 2.5 years of suppression age, he has significant motor and vi- sual development delay with an abnor- Normal Normal Male 2.5 y 25th mal sleep pattern and feeding difficul- 10 9 3 ties that require gastrostomy. He can and vigabatrin previously; currently on Valproate, adrenocorticotropic hormone, sit with support for short periods but does not fix or follow well. Attempts to control his spasms have been difficult. Language and speech delay He still continues to have seizures (6 to Bilateral epileptic activity Case 1 Diazoxide, chlorthiazide 10 clusters of flexor spasms) and has just been commenced on levetirac- etam with gradual withdrawal of the lamotrigine topiramate for better seizure control Normal Normal Female and to facilitate a ketogenic diet. His 75th 4y seizures now are tonic seizures and 8 9 9 occur singly or in clusters every few Age at onset of infantile spasms, mo Head circumference before spasms ammonia, urate, and carnitine analysis, cutaneous slit-lamp organic acid, serum lactate, profiles, cerebrospinal fluid weeks, and he has myoclonic jerks Results of plasma amino acid, daily. His head circumference was ini- serum pyruvate, serum ophthalmology screen TABLE 1 Demographics tially at the 25th centile, but it is cur- Treatment for seizures examination, and rently at the 0.4th centile (Table 1). Brain MRI results Treatment for HH Development Apgar score Patient 3 Current age EEG results 1 min 5 min Gender Patient 3 was born at 39 weeks’ gesta- tion with a birth weight of 3.2 kg. HePEDIATRICS Volume 126, Number 5, November 2010 e1233 Downloaded from www.pediatrics.org. Provided by GlaxoSmithKline Enterprise licence on January 21, 2011 View slide
  • TABLE 2 Results of Biochemical Investigations 1.2 years of age, he remains seizure- Case 1 Case 2 Case3 Case 4 Case 5 free with moderate global develop-Glucose, mmol/L 1.4 2.7 0.7 2.1 2.3 mental delay. Results of an MRI scan ofInsulin, pmol/l 78.9 63.8 100.4 258.3 103.3 his brain are awaited. His head cir-NEFA, mmol/L 0.180 0.110 0.008 0.008 0.160BOHB, mmol/L 0.005 0.005 0.005 0.005 0.050 cumference has remained at the 75thDay of screen 7 7 10 2 3 percentile.NEFA indicates nonesterified fatty acids; BOHB, 3- -hydroxybutyrate. Patient 5TABLE 3 Diagnostic Biochemical Features of HH was introduced. A repeat MRI scan of Patient 5 was born at 40 weeks’ gesta-Glucose infusion rate 8 mg/kg per min the brain showed persistence of right tion with a birth weight of 3.7 kg. SheLaboratory blood glucose level of 3 mmol/L with presented on day 2 with poor feeding, parieto-occipital cystic damage involv- detectable serum insulin/C-peptide suppressed/low serum ketone bodies ing the cortex and white matter. At 2.5 hypotonia, and generalized seizures. suppressed/low serum fatty acids years’ follow-up, he has coordination Her blood glucose concentration was difficulties and sleep and language de- 0.6 mmol/L at the time of presentation. lay. He continues on carbamazepine She was commenced on intravenouspresented at day 2 with poor feeding, for ongoing generalized seizures that dextrose and required 24 mg/kg perirritability, and generalized seizures. tend to wax and wane and require es- minute of dextrose to maintain normo-The only biochemical abnormality de- calation of the AED dose. His head cir- glycemia. Results of investigationstected was a low blood glucose level at cumference has remained stable at confirmed HH (Table 2). At 2 weeks, shethe time of the symptoms (blood glu- the 50th percentile. developed tonic clonic and partial sei-cose: 0.7 mmol/L). The intravenous glu- zures. These seizures were predomi-cose infusion rate required to main- Patient 4 nantly focal, involved the right or lefttain normoglycemia was 14 mg/kg per Patient 4 was born via cesarean deliv- upper and lower limbs, and lasted 5minute. Results of further investiga- ery (for polyhydramnios and reversal seconds to 2 minutes, although sometions confirmed HH (Table 2), which re- of end diastolic flow) at 33 weeks’ ges- involved her whole body. The fre-sponded to diazoxide (15 mg/kg per tation with a birth weight of 3.1 kg. He quency of the seizures was 4 to 5day). He required phenobarbitone, developed mild respiratory distress at times per week and partially re-phenytoin, and midazolam infusion for birth and required continuous positive sponded to phenobarbitone. At 82 days to control the seizures, and he airway pressure for 5 hours. He was weeks concomitant myoclonic jerkswas discharged from the hospital at 6 noted to have symptomatic (lethargy developed, and an EEG revealed parox-weeks of life with no AEDs. and floppy) hypoglycemia (1.9 mmol/L) ysmal bursts of generalized epilepti- on day 1 and required 15 mg/kg per form activity that were associated withHe presented a week later with right- clinically apparent myoclonic jerks.sided partial seizures (4 –5 episodes) minute of intravenous dextrose infu-that were not associated with hypogly- sion to maintain normoglycemia. Re- The HH was refractory to medicalcemia and responded to phenobarbi- sults of investigations confirmed HH treatment with diazoxide and oct-tone. Results of an MRI scan of his (Table 2). His HH failed to respond to reotide, and she also required a near-brain at 7 weeks showed a right diazoxide and octreotide; eventually, at total pancreatectomy at 2.5 months ofparieto-occipital cyst, and EEG results 3 months of age, he required a near- age. After pancreatectomy she devel-were reported as normal. He was total pancreatectomy for diffuse con- oped diabetes mellitus and requiredweaned off AEDs by 6 months of age. genital hyperinsulinism. After the pan- subcutaneous insulin therapy. SheAt 9 months of age he developed createctomy he developed diabetes was discharged to her local hospital atextensor-type infantile spasms, 15 in a mellitus and required subcutaneous 3 months of age on phenobarbitone,span of 2 to 3 minutes, with additional insulin injections. which was gradually weaned off over aabsence seizures. An EEG revealed At 8 months of age he developed infan- period of 4 weeks.high-amplitude sharp and slow waves tile spasms (1–2 clusters per day) with At 4.5 months of age she developedon both hemispheres (left right) developmental regression. An EEG was clusters of trunk flexion suggestive ofwith a temporal and posterior empha- abnormal with poor background ac- infantile spasms. Results of an MRIsis. The seizures responded to high- tivity and hypsarrhythmia. Seizures scan of the brain at 5 months weredose prednisolone, which was gradu- ceased after a 2-week course of adre- structurally normal. Her EEG patternally weaned off, and carbamazepine nocorticotropic hormone. Currently, at revealed typical hypsarrhythmia. Shee1234 KUMARAN et al Downloaded from www.pediatrics.org. Provided by GlaxoSmithKline Enterprise licence on January 21, 2011
  • CASE REPORTSwas commenced on vigabatrin with a uted to the early neonatal seizures. Tu- spasms as a result of immaturity of theplan to wean off of phenobarbitone. She berous sclerosis was excluded by lack myelination process, and it is possiblehad attained normal development until of any signs on neuroimaging, cutane- that repeat MRI in our patients at anthe onset of spasms, at which time her ous slit-lamp examination, and oph- older age ( 2 years) might be moredevelopment regressed (poor head con- thalmologic evaluation. Despite exten- informative.22 Although neuroimagingtrol and visual fixation). Her head cir- sive biochemical investigations (see results were normal, a decrease incumference was at the 50th centile at Table 1), no other cause of the infantile head circumference percentiles afterbirth and is currently at the 2nd centile. spasms was found. the onset of spasms was noted in 3 of Infantile spasms typically begin weeks the 5 patients (Table 1), which quiteDISCUSSION to months after an initiating injury; likely reflects the extent of brain injuryThe pathophysiological mechanisms during this latent period, neural cir- and compromise in brain growth.underlying infantile spasms are not cuits become epileptogenic. The onset Rener-Primec et al23 reported an in-known, although various etiologies (in- of infantile spasms varied from 3 to 9 creased proportion of head circumfer-cluding hypoglycemic brain injury) months in our case series. The tempo- ences below the 10th percentile in thehave been proposed.15,16 Hypoglycemia ral latency between the onset of insult infantile spasm group compared withis a recognized cause of infantile and development of infantile spasms is controls, and significantly poor neuro-spasms, but the mechanism(s) of how well documented to be variable.9,19 This developmental outcome was associ-hypoglycemic brain injury triggers in- temporal latency can probably be ex- ated if the head circumference per-fantile spasms is unclear. In a recent plained by the developmental desyn- sisted below the 10th percentile in thestudy that examined the etiology of re- chronization hypothesis, whereby an fourth and fifth month after the onsetmote symptomatic epilepsy with onset insult results in desynchronization of of infantile spasms.in the first 3 years of life, it was noted development of 2 central nervous Infantile spasms may also result fromthat neonatal hypoglycemia (not spe- system processes, which causes dis- abnormalities of structure or functioncifically HH) was the most common eti- ruption of normal functional interac- of cortical and subcortical structuresology and that infantile spasms was tions. This desynchronization becomes or their communicating pathways.24 Athe most common seizure type.17 HH is significant as the brain matures and recent multiple-hit model based ona form of hypoglycemia that is associ- results in functional deficit that mani- this concept was developed by Scant-ated with a high risk of developmental fests as infantile spasms.15 Although elbury et al.25 By introducing lipopoly-delay, mental retardation, and epilepsy.3 rare, seizures before the onset of saccharide and doxorubicin intracere-The unique biochemical profile (with spasms have been reported and asso- brally at postnatal day 3 andinsulin-inhibiting glycogenolysis, glu- ciated with unfavorable outcome and p-chlorophenylalanine intraperitone-coneogenesis, lipolysis, and ketogene- resistance to steroid treatment.20 ally at postnatal day 5, they were ablesis) observed in patients with HH ren- In our series of patients, EEGs were ab- to create a rat model that replicatesders the brain more susceptible to injury normal in all 5 patients, but typical hyp- most of the features of human infantilein comparison with other hypoglycemic sarrhythmia was seen in only 3 of spasms and would be helpful in the un-states. Our clinical observations suggest them. In a recent report by Karvelas et derstanding and development of newthat significant brain insult that results al,21 hypsarrhythmia EEG on diagnosis or improved treatment modalities forin infantile spasms and poor neurodevel- was noted in only 64% of patients in the refractory infantile spasms.opmental outcome can occur despite the symptomatic group; 22% of their pa-early diagnosis of HH. tients also experienced other seizures CONCLUSIONSIn our case series, all 5 patients pre- before the onset of infantile spasms. Neonatal-onset HH with the resultingsented with neonatal-onset HH; 4 of the Arrest or regression of development brain insult may lead to the later devel-5 patients presented with generalized/ with the onset of spasms and develop- opment of infantile spasms. The latentpartial seizures, including 1 patient mental delay are hallmarks of infantile period before the onset of the spasmswith a burst-suppression pattern in spasms and were noted in all our pa- can be variable; hence, long-term neu-the neonatal period that was indicative tients (motor, speech, and language rodevelopmental follow-up (until 1of significant underlying brain injury and visual impairment). year of age) is necessary. Further stud-and associated with poor outcome.18 Results of MRI scanning of the brain ies are required to understand how HHNone of these patients had any perina- were abnormal for only 1 patient. MRI causes brain damage, which thental asphyxia that might have contrib- results can be normal at the onset of leads to infantile spasms.PEDIATRICS Volume 126, Number 5, November 2010 e1235 Downloaded from www.pediatrics.org. Provided by GlaxoSmithKline Enterprise licence on January 21, 2011
  • REFERENCES 1. Aynsley-Green A, Hussain K, Hall J, et al. function mutations. J Pediatr. 2005;146(3): atic epilepsy. Indian Pediatr. 2009;46(2): Practical management of hyperinsulinism 388 –394 127–132 in infancy. Arch Dis Child Fetal Neonatal Ed. 9. Matsumoto A, Watanabe K, Negoro T, et al. 18. Nunes ML, Giraldes MM, Pinho AP, Costa JC. 2000;82(2):F98 –F107 Infantile spasms: etiological factors, clini- Prognostic value of non-reactive burst sup- 2. Meissner T, Wendel U, Burgard P, Schaetzle cal aspects, and long term prognosis in 200 pression EEG pattern associated to early S, Mayatepek E. Long-term follow-up of 114 cases. Eur J Pediatr. 1981;135(3):239 –244 neonatal seizures. Arq Neuropsiquiatr. patients with congenital hyperinsulinism. 10. Kellaway P, Hrachovy RA, Frost JD Jr, Zion T. 2005;63(1):14 –19 Eur J Endocrinol. 2003;149(1):43–51 Precise characterization and quantification 19. Guggenheim MA, Frost JD Jr, Hrachovy RA. 3. Menni F, de LP, Sevin C, et al. Neurologic of infantile spasms. Ann Neurol. 1979;6(3): Time interval from a brain insult to the on- outcomes of 90 neonates and infants with 214 –218 set of infantile spasms. Pediatr Neurol. persistent hyperinsulinemic hypoglycemia. 2008;38(1):34 –37 11. Koo B, Hwang PA, Logan WJ. Infantile Pediatrics. 2001;107(3):476 – 479 spasms: outcome and prognostic factors of 20. Velez A, Dulac O, Plouin P. Prognosis for sei- cryptogenic and symptomatic groups. Neu- zure control in infantile spasms preceded 4. Tyrrell VJ, Ambler GR, Yeow WH, Cowell CT, rology. 1993;43(11):2322–2327 by other seizures. Brain Dev. 1990;12(3): Silink M. Ten years’ experience of persistent 306 –309 hyperinsulinaemic hypoglycaemia of in- 12. Guerrini R, Moro F, Kato M, et al. Expansion fancy. J Paediatr Child Health. 2001;37(5): of the first PolyA tract of ARX causes infan- 21. Karvelas G, Lortie A, Scantlebury MH, Duy PT, 483– 488 tile spasms and status dystonicus. Neurol- Cossette P, Carmant L. A retrospective study ogy. 2007;69(5):427– 433 on aetiology based outcome of infantile 5. Hesdorffer DC, Verity CM. Risk factors. In: spasms. Seizure. 2009;18(3):197–201 Engel JJ, Pedley TA, eds. Epilepsy: A Compre- 13. Camurdan MO, Cinaz P, Serdaroglu A, Bideci 22. Juhász C, Chugani HT, Muzik O, Chugani DC. hensive Textbook. 2nd illustrated ed. Phila- A, Demirel F. Persistent hyperinsulinemic Neuroradiological assessment of brain delphia, PA: Lippincott-Raven; 1997:59 – 67 hypoglycemia presenting with a rare structure and function and its implication 6. Bahi-Buisson N, El SS, Soufflet C, et al. Myo- complication: West syndrome. J Pediatr En- in the pathogenesis of West syndrome. clonic absence epilepsy with photosensitiv- docrinol Metab. 2004;17(10):1465–1468 Brain Dev. 2001;23(7):488 – 495 ity and a gain of function mutation in gluta- 14. Kapoor RR, James C, Hussain K. Advances in 23. Rener-Primec Z, Lozar-Krivec J, Krivec U, mate dehydrogenase. Seizure. 2008;17(7): the diagnosis and management of hyperin- Neubauer D. Head growth in infants with in- 658 – 664 sulinemic hypoglycemia. Nat Clin Pract En- fantile spasms may be temporarily re- 7. Bahi-Buisson N, Roze E, Dionisi C, et al. Neu- docrinol Metab. 2009;5(2):101–112 duced. Pediatr Neurol. 2006;35(3):197–203 rological aspects of hyperinsulinism- 15. Frost JD Jr, Hrachovy RA. Pathogenesis of 24. Lado FA, Moshé SL. Role of subcortical hyperammonaemia syndrome [published infantile spasms: a model based on devel- structures in the pathogenesis of infantile correction appears in Dev Med Child Neu- opmental desynchronization. J Clin Neuro- spasms: what are possible subcortical me- rol. 2009;51(1):77]. Dev Med Child Neurol. physiol. 2005;22(1):25–36 diators? Int Rev Neurobiol. 2002;49:115–140 2008;50(12):945–949 16. Zupanc ML. Infantile spasms. Expert Opin 25. Scantlebury MH, Galanopoulou AS, Chu- 8. Raizen DM, Brooks-Kayal A, Steinkrauss L, Pharmacother. 2003;4(11):2039 –2048 domelova L, Raffo E, Betancourth D, Moshé Tennekoon GI, Stanley CA, Kelly A. Central 17. Udani V, Munot P, Ursekar M, Gupta S. Neo- SL. A model of symptomatic infantile nervous system hyperexcitability associ- natal hypoglycemic brain: injury a common spasms syndrome. Neurobiol Dis. 2010; ated with glutamate dehydrogenase gain of cause of infantile onset remote symptom- 37(3):604 – 612e1236 KUMARAN et al Downloaded from www.pediatrics.org. Provided by GlaxoSmithKline Enterprise licence on January 21, 2011
  • The Clinical Problem of Hyperinsulinemic Hypoglycemia and Resultant Infantile Spasms Anitha Kumaran, Sri Kar, Ritika R. Kapoor and Khalid Hussain Pediatrics 2010;126;e1231-e1236; originally published online Oct 18, 2010; DOI: 10.1542/peds.2009-2775Updated Information including high-resolution figures, can be found at:& Services http://www.pediatrics.org/cgi/content/full/126/5/e1231References This article cites 24 articles, 4 of which you can access for free at: http://www.pediatrics.org/cgi/content/full/126/5/e1231#BIBLSubspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Nutrition & Metabolism http://www.pediatrics.org/cgi/collection/nutrition_and_metabolis mPermissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.pediatrics.org/misc/Permissions.shtmlReprints Information about ordering reprints can be found online: http://www.pediatrics.org/misc/reprints.shtml Downloaded from www.pediatrics.org. Provided by GlaxoSmithKline Enterprise licence on January 21, 2011