Hypoglycemic Seizures Research Articles

Hypoglycemic seizures and epilepsy in type I diabetes mellitus

Purpose(1) To determine the characteristics of seizures and/or epilepsy among patients with adult onset type 1 diabetes mellitus (T1DM), and (2) to determine glutamic acid decarboxylase antibody (antiGADab) titres and other autoimmune characteristics of T1DM patients with seizure and/or epilepsy. MethodsPatients were recruited after reviewing the databases of one Diabetes Unit and two Epilepsy Units. Prevalence of suffering epilepsy and/or seizures was calculated in the group of adult onset T1DM patients seen consecutively in the Diabetes Unit. Serum antiGADab titres were determined in all patients. ResultsAmong the 229 T1DM patients, two had suffered hypoglycemic seizures (0.87%) and two unprovoked seizures (0.87%). We recruited 11 of these T1DM patients. Five reported only hypoglycemic seizures, and 6 temporal lobe epilepsy (TLE).Mean antiGADab titres in patients with T1DM and hypoglycemic seizures were lower (18.42IU) than in those with T1DM and TLE (29.200IU), p: 0.006. Patients with T1DM and TLE suffered more other autoimmune diseases than those with T1DM and hypoglycemic seizures, p: 0.015. ConclusionsHypoglycemic seizures are rare in T1DM patients. AntiGADab titres do not differ from the general diabetic population. Patients with high titres of antiGADab are more likely to develop TLE.

Seizures and epilepsy in hypoglycaemia caused by inborn errors of metabolism.

The aim of the study was to characterize seizures and epilepsy related to hypoglycaemia. We analyzed the files of 170 consecutive patients referred for hypoglycaemia (onset 1h to 4y) caused by inborn errors of metabolism (glycogen storage disease type I, fatty acid β-oxidation disorders, and hyperinsulinism). Ninety patients (42 males and 48 females; 38 neonates and 52 infants/children) had brief hypoglycaemic seizures (68%) or status epilepticus (32%). Status epilepticus occurred earlier (mean 1.4d) than brief neonatal seizures (4.3d, p=0.02). Recurrent status epilepticus followed initial status epilepticus and was often triggered by fever. Epilepsy developed in 21 patients. In 18 patients, epilepsy followed hypoglycaemic status epilepticus and began with shorter delay when associated with grey matter lesions (1.9mo, standard error of the mean [SEM] 1mo) than with white matter damage (3.3y [SEM 1y], p=0.003). Three patients with hyperinsulinism developed idiopathic epilepsy following brief neonatal seizures. Brief neonatal hyperinsulinaemic hypoglycaemic seizures have characteristics of idiopathic neonatal seizures. Neonatal status epilepticus should be prevented by the systematic measurement of glucose blood level. Recurrent seizures never consist of status epilepticus when following brief initial seizures. Epilepsy is symptomatic of brain damage with shorter delay in the case of grey rather than white matter lesions, except in a few idiopathic cases in which epilepsy and hyperinsulinism may share a common genetic background.

Beta-blockers as therapy for infantile hemangiomas.

Infantile hemangiomas (IH) are common benign vascular tumors seen in children. Although the majority will improve spontaneously without treatment, a small subset will require therapy due to a variety of complications. Less than a decade ago, propranolol replaced corticosteroids as first-line treatment for most IH and it has proven to be a relatively safe, effective therapy. After initiation of propranolol, most hemangiomas show evidence of significant improvement relatively rapidly, often within days. Although propranolol is generally felt to have a more limited side-effect profile than systemic corticosteroids, its use has been infrequently associated with adverse events, including sleep disturbances, acrocyanosis, hypotension, bradycardia, respiratory events, and hypoglycemia. Rarely, hypoglycemic seizures have been reported, usually occurring in the setting of prolonged fasting.

Neurological and developmental outcome of children with neonatal hypoglycemic seizures

Objective: Neonatal hypoglycemia may lead to severe acute, and chronic neurological injuries. Hypoglycemic seizure usually follows long lasting periods of hypoglycemia and worsens cerebral injury as well as the prognosis. The aim of this study is to evaluate neurological and developmental outcomes of children with a history of neonatal hypoglycemic seizures. Methods: 21 patients who had neonatal hypoglycemic seizures and followed up in Ege University Faculty of Medicine, Department of Pediatrics, Division of Child Neurology between January 1999 and May 2011 were included in this study. The electroencephalography, brain magnetic resonance imaging and visual evoke potential results of the patients were recorded. Mental and motor developmental outcomes were evaluated. Results: The development of epilepsy, abnormal visual evoked potential responses and abnormal brain magnetic resonance findings in infants with a history of neonatal hypoglycemic seizures were found to be associated with poor neurodevelopmental outcome. Conclusion: Newborns should be carefully monitored for hypoglycemia which causes severe and permanent but preventable neurological sequelae.

Glycogen Storage Disease Type 1a: Potentially Treatable and Often Missed-A Series of 3 Patients

Introduction: Glycogen storage disease type I (GSDI) is an autosomal recessive disorder characterized by accumulation of glycogen and fat in the liver and kidneys. Most commonly, untreated infants present at age three to four months with hepatomegaly, lactic acidosis, hyperuricemia, hyperlipidemia, hypertriglyceridemia and/or hypoglycemic seizures. Affected children have doll-like faces, relatively thin extremities, short stature, and protuberant abdomen. There are two subtypes (GSDIa and GSDIb) which are clinically indistinguishable.

Paraneoplastic recurrent hypoglycaemic seizures: an initial presentation of hepatoblastoma in an adolescent male-a rare entity.

Hepatoblastoma (HB) is a rare malignant tumour of the liver and usually occurs in the first three years of life. Hepatoblastoma in adolescents and young adults is extremely rare; nevertheless the prognosis is much worse than in childhood, because these kinds of tumours are usually diagnosed late. Characteristic imaging and histopathological and AFP levels help in the diagnosis of hepatoblastoma. Paraneoplastic features of hepatoblastoma are not uncommon at presentation and include erythrocytosis, thrombocytosis, hypocalcaemia, isosexual precocious puberty, and rarely hypoglycaemia. Even though hypoglycaemia is commonly seen in hepatocellular carcinoma, its association with hepatoblastoma is very rare. We present a case of 15-year-old male patient presenting with complaints of recurrent hypoglycaemic seizures ultimately leading to diagnosis of hepatoblastoma. Managed successfully with neoadjuvant chemotherapy, surgery and adjuvant chemotherapy with adriamycin and cisplatin based regimens. An extensive review of literature in the PubMed and MEDLINE did not reveal much data on paraneoplastic recurrent hypoglycaemic seizures as an initial presentation of hepatoblastomas in adolescents and young adults.

Effect of Sensor-Augmented Insulin Pump Therapy and Automated Insulin Suspension vs Standard Insulin Pump Therapy on Hypoglycemia in Patients With Type 1 Diabetes

Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events. To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with standard insulin pump therapy. A randomized clinical trial involving 95 patients with type 1 diabetes, recruited from December 2009 to January 2012 in Australia. Patients were randomized to insulin pump only or automated insulin suspension for 6 months. The primary outcome was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment). In a subgroup, counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique. Of the 95 patients randomized, 49 were assigned to the standard-pump (pump-only) therapy and 46 to the low-glucose suspension group. The mean (SD) age was 18.6 (11.8) years; duration of diabetes, 11.0 (8.9) years; and duration of pump therapy, 4.1 (3.4) years. The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group. After 6 months of treatment, the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group. The adjusted incidence rate per 100 patient-months was 34.2 (95% CI, 22.0-53.3) for the pump-only group vs 9.5 (95% CI, 5.2-17.4) for the low-glucose suspension group. The incidence rate ratio was 3.6 (95% CI, 1.7-7.5; P <.001). There was no change in glycated hemoglobin in either group: mean, 7.4 (95% CI, 7.2-7.6) to 7.4 (95% CI, 7.2-7.7) in the pump-only group vs mean, 7.6 (95%, CI, 7.4-7.9) to 7.5 (95% CI, 7.3-7.7) in the low-glucose suspension group. Counterregulatory hormone responses to hypoglycemia were not changed. There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis. Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes. anzctr.org.au Identifier: ACTRN12610000024044.

Clinical Presentation and Management of Children With Diffuse and Focal Hyperinsulinism: A Review of 223 Cases

Congenital hyperinsulinism (HI) occurs in two distinct histologic forms: diffuse and focal. Distinguishing between them is essential because a pancreatectomy is curative for focal HI and palliative for diffuse HI. The purpose of this study was to compare the presentations, treatment, and outcomes of diffuse and focal HI. A retrospective chart review of children who underwent pancreatectomy for hyperinsulinism from December 2004 through September 2012 was conducted. Based on pancreatic histology, 223 children were classified into 3 groups: diffuse (n = 97, 44%), focal (n = 114, 51%), and other (n = 12, 5%). Children with diffuse vs focal HI had significantly different mean gestational ages (38 vs 39 weeks, P < .0005) and birth weights (3963 vs 3717 g P = .012). Children with focal HI presented at an older age (0.3 vs 0 months, P < .0005) and more frequently with seizures (50 vs 25%, P < .0005). Children with diffuse HI had higher insulin levels during hypoglycemia (31.8 vs 12 μU/mL, P < .0005) and required higher glucose infusion rates (19.2 vs 16.1 mg/kg/min, P = .002). Children with diffuse HI had a median percent pancreactectomy of 98%, and postoperatively 41% required treatment for continued hypoglycemia. Children with focal HI had a median percent pancreatectomy rate of 27%, and 94% required no treatment after surgery. Focal and diffuse HI present unique challenges, but the clinical differences between the 2 are subtle. Children with focal HI are at higher risk of delayed diagnosis and hypoglycemic seizures, but most are cured with surgery. In contrast, children with diffuse disease may be identified earlier, but face ongoing blood glucose abnormalities.

Hyperinsulinemic Hypoglycemia: Experience in A Series of 17 Cases

Objective: Hyperinsulinemic hypoglycemia (HIH) is a genetically heterogeneous disorder with both familial and sporadic variants. Patients with HIH may present during the neonatal period, infancy, or childhood and may show transient, prolonged, and persistent features. In this study, we aimed to discuss our experience with HIH patients, based on a series of 17 patients.Methods: We retrospectively analyzed the clinical and laboratory characteristics at the time of diagnosis and during treatment and evaluated the neurodevelopmental outcomes during follow-up in 17 HIH patients, who presented or were referred to the Pediatric Endocrinology Clinic of Dr. Sami Ulus Training and Research Children’s Hospital between 1998 and 2011. The patients (7 male, 10 female) were aged between the first day of life and 7 years - 10 were in their first week of life, 6 in their infancy, and 1 in childhood.Results: None of the mothers had gestational diabetes. Hypoglycemic seizure (76.5%) was the most common presenting symptom. Medical treatment failed in two patients, and was stopped in eight patients. Of two diazoxide-unresponsive patients, one underwent near-total pancreatectomy, but hypoglycaemic episodes continued after surgery. The parents of other patient refused surgery, the medical treatment was continued, nevertheless, severe motor and mental retardation developed. At follow-up, 23.5% of the patients were found to have mild or moderate psychomotor retardation, and 23.5% developed epilepsy. There was no marked difference in neurological results between cases with onset in the neonatal period or in infancy.Conclusions: Clinical course and treatment response in HIH cases are very heterogeneous. Long-term careful monitoring is needed to detect and treat the complications. Conflict of interest:None declared.

Resolution of Electroconvulsive Therapy Refractory Major Depressive Disorder With Unintentional Hypoglycemic Seizure

We report a 74-year-old white woman with type 1 diabetes and major depressive disorder refractory to multiple medications who received 15 electroconvulsive therapy treatments with minimal improvement. After an accidental hypoglycemic seizure, the patient's symptoms completely resolved. In conclusion, the present case reveals an instance where electroconvulsive therapy-induced seizures appeared to be minimally effective, whereas a single accidental hypoglycemia-induced seizure was incredibly effective for the resolutions of depressive symptoms. Although this case presents a single efficacious use of accidental insulin coma therapy, the applicability is limited because of the known risks of insulin coma therapy.

Low-level hyperinsulinism with hypoglycemic spells in an infant with mosaic Turner syndrome and mild Kabuki-like phenotype: a case report and review of the literature

Impaired glucose tolerance and type 2 diabetes are well-known features in patients with Turner syndrome. To the best of our knowledge, there is only one reported case of hyperinsulinemic hypoglycemia associated with a complex mosaic Turner syndrome available in the current literature. We report on the case of a 13-month-old girl with a complex mosaic Turner genotype and mild hyperinsulinemic hypoglycemia responsive to diazoxide therapy. Cytogenetic analyses showed two or possibly three cell lines. Sixty percent of the cell lines had a 45,X genotype and the rest had 46,XX with a marker ring chromosome. Diagnosis of a mosaic Turner syndrome and mild Kabuki-like phenotype was confirmed. Despite the rareness of this case, clinicians should be aware of the possibility of hyperinsulinemic hypoglycemia in patients with Turner syndrome to prevent further brain damage caused by hypoglycemic episodes and seizures. Although the mechanism leading to hyperinsulinism in this condition is still unknown, the present report discusses this rare presentation and gives an overview on the current literature regarding this case.

Blood glucose levels in children with Type 1 diabetes attending a residential diabetes camp: a 2-year review

The objective of this retrospective analysis of blood glucose values at a week-long residential summer camp for children with Type 1 diabetes was to provide experiential data to reinforce current summer camp guidelines and to determine if specific interventions implemented between 2009 and 2010 were effective in lowering average blood glucose among our campers without increasing risk of hypoglycaemia. Blood glucose records were obtained from a random selection of children who attended six 1-week camp sessions, three each in 2009 and 2010. Five values per day: pre-meal breakfast, lunch and dinner, pre-evening snack and midnight values were analysed. A total of 13,267 blood glucose values were included. There were no severe hypoglycaemic episodes, seizures or need for full-dose glucagon or intravenous glucose in either year. Mean blood glucose was significantly lower in 2010 compared with 2009 (9.22 vs. 10.06 mmol/l, P < 0.001). Older age and camp year were associated with lower mean blood glucose, even when controlling for gender and duration of diabetes. This analysis is the largest so far conducted at a residential diabetes camp. Mean blood glucose levels were lower than other published studies. Although we cannot attribute a cause-and-effect relationship between our interventions and the improvement in blood glucose between 2009 and 2010, the use of pre-meal insulin bolus doses, low glycaemic meals and highlighting blood glucose levels in logs before being reviewed by endocrinologists are strongly encouraged. From this study we hope to establish benchmarks for comparison among camps and begin to identify best practices.

Determination of the Potency of Extracted, Purified and Formulated Insulin from the Pancreatic Organs of the Sudanese Beef Cattle

The treatment of type 1 diabetes is mainly dependent on insulin therapy and current formulated insulin formulations are used for its control all over the world. The presented study was designed to evaluate the potency of extracted, purified and formulated insulin from the pancreatic organs of the Sudanese beef cattle. Twenty healthy rabbits were used to conduct the study following subcutaneous administration of the sample insulin, to determine the hypoglycemic effect and to analyze the potency of the testing insulin by the hypoglycemic seizure method, blood sugar method and glucose enzymatic colorimetric test (GOD-PAP) respectively. The potency of the injected insulin samples was estimated by comparing the variation in blood glucose levels produced in the treated animals with that produced by a standard insulin preparation under the suitable conditions of the blood sugar method. The results revealed that the potency of the testing beef insulin samples was slightly higher (i.e., 2.2 USP units/ml, 9%) compared to the standard and assumed potency of the prepared insulin preparations (i.e., 1-2 USP units/ml) which indicated that the solvents and diluents used to prepare the assay dilution might be of higher potency and must be diluted to such an extent that the testing insulin potency must be compatible with the standard dilutions. Furthermore, to determine the choice of an assay to analyze the potency of insulin preparations, not only the accuracy of the result but also the purpose for which the test is to be used and the time limit must be taken into consideration.

Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report

IntroductionKerosene is a freely accessible hydrocarbon used in Sri Lankan (and other Asian) households for cooking and for lighting lamps. Kerosene poisoning is rarely reported among adults and its toxicological effects are not well known. Metformin is a commonly used oral hypoglycemic drug and its overdose leads primarily to lactic acidosis. Combined poisoning of metformin and kerosene and their interactions have not been reported.Case presentationAn 18-year-old, previously healthy, unmarried Sinhalese woman was referred following ingestion of 17.5 g of metformin and approximately 200 mL of kerosene oil in a suicide attempt. She had vomiting, burning epigastric pain, and a hypoglycemic seizure (capillary blood glucose of 42 mg/dL). Subsequently, she developed severe lactic acidosis followed by acute renal insufficiency, was treated with sodium bicarbonate, and underwent intermittent hemodialysis with bicarbonate. She recovered completely.ConclusionsThis report proposes possible interactions that occur between metformin and kerosene that augment toxicity when the two are ingested together. It also stresses the importance of early treatment with intermittent hemodialysis in severe lactic acidosis with maintenance of blood glucose.

Delayed Diagnosis of Glycogen Storage Disease Type III

Delayed Diagnosis of Glycogen Storage Disease Type III

Case Study: Seizures and Hypoglycemia

A.S. is a 64-year-old man admitted to the nephrology service for dizziness and hypotension after dialysis. During his hospital stay, he experienced labile blood glucose levels and had a suspected hypoglycemic seizure. The endocrine service was consulted to assist with these findings. The patient has a history of previous stroke, remote alcohol abuse, and end-stage renal disease requiring hemodialysis 3 days/week and is awaiting a kidney transplant. He has had type 2 diabetes for 25 years and has been treated with insulin for 10 years. During the past year and a half, he reports having had two seizures. His family witnessed the first seizure and reports that he was hyperglycemic at that time. Additionally, the patient reports an event during which he suddenly “passed out” and was “out of it” for the rest of the day. At home, he takes 6 units of aspart insulin with meals and 12 units of glargine insulin in the morning. He weighs 84 kg, and his last A1C result was 6.7%. During the hospitalization, he was placed on his home insulin regimen plus a hospital preprandial correction dose of insulin. The correction dose was 2 units of aspart for blood glucose readings that were 151–200 mg/dl, increasing by 2 units of aspart for every 50 mg/dl increase in blood glucose. While in the hospital, he felt nauseated and did not eat. That afternoon, he had a witnessed seizure. He was stabilized, and routine laboratory testing was performed. His blood glucose measured …

Neonatal presentation of familial glucocorticoid deficiency resulting from a novel splice mutation in the melanocortin 2 receptor accessory protein

BackgroundFamilial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by isolated glucocorticoid deficiency. Mutations in the ACTH receptor/melanocortin 2 receptor (MC2R), the MC2R accessory protein (MRAP) or the STAR protein (STAR) cause FGD types 1, 2 and 3, respectively, accounting for ∼50% of all cases.Patient and methodsWe report a neonate of Indian origin, who was diagnosed with FGD in the first few days of life. He presented with hypoglycaemic seizures and was noted to have generalised intense hyperpigmentation and normal male genitalia. Biochemical investigations revealed hypocortisolaemia (cortisol 0.223 μg/dl; NR 1–23 μg/dl) and elevated plasma ACTH (170 pg/ml). Serum electrolytes, aldosterone and plasma renin activity were normal. Peak cortisol following a standard synacthen test was 0.018 μg/dl. He responded to hydrocortisone treatment and continues on replacement. Patient DNA was analysed by direct sequencing. The effect of the novel mutation was assessed by an in vitro splicing assay using wild type and mutant heterologous minigenes.ResultsA novel homozygous mutation c.106+2_3dupTA was found in the MRAP gene. Both parents were heterozygous for the mutation. In an in vitro splicing assay, the mutation resulted in the skipping of exon 3.ConclusionWe have identified a novel MRAP mutation where disruption of the intron 3 splice-site results in a prematurely terminated translation product. This protein (if produced) would lack the transmembrane domain that is essential for MC2R interaction. We predict that this would cause complete lack of ACTH response thus explaining the early presentation in this case.

AAA syndrome--adrenal insufficiency, alacrima and achalasia

An 8-year-old girl presented with a hypoglycaemic seizure and dark cutaneous pigmentation (Figure 1A and B). Response to synacthen stimulation was inadequate and adrenocorticotropic hormone (ACTH) was elevated [basal cortisol 174 nmol/l, stimulated cortisol 173 nmol/l (reference range >500 nmol/l), ACTH 2980 ng/l (reference range <55 ng/l)]. However renin, aldosterone and electrolytes were normal. She had no postural drop in blood pressure. She was commenced on hydrocortisone resolving her pigmentation. A Schirmer's test (Figure 1C) shows no tear production, consistent with …

It can't be december already: a real life simile to Jeffery Archer's short story.

This case reflects the difficulties arising out of the patients autonomy to choose the type, timing, and extent of the medical management even though in some clinical scenarios, like the case presented, the patient was not able to communicate his physiological needs for a safe and protected shelter from the extreme weather, and was unable to follow up with the medical plan offered at the emergency room during each of his prior visits before the catastrophic event of unwitnessed hypoglycemic seizure and severe hypothermia.

Severe Hypoglycemic Seizures in a Child Receiving 6-Mercaptopurine

A 4-year-old boy with acute lymphoblastic leukemia who was receiving 6-mercaptopurine during the maintenance chemotherapy experienced prolonged generalized tonic nocturnal seizures because of severe hypoglycemia after his evening dose by a 12-hour period of fasting. Investigations ruled out all causes of these seizures other than the 6-mercaptopurine-induced severe hypoglycemia.