[Acute encephalopathy in salmonella infection]. / Akute Enzephalopathie bei Salmonellenenteritis.

While infections with salmonella typhi may frequently result in encephalopathy, this complication is rare in infections with salmonella enteritidis and has been rarely reported. We report about a 21 months old girl which developed encephalopathy with convulsion, ataxia and cortical blindness following salmonella infection. Moreover, we show a summary of ten previous case reports.

[Asymptomatic carnitine depletion on ketogenic diet in patients with pharmacoresistant epilepsies]. / Asymptomatischer Carnitinmangel unter ketogener Diät bei Patienten mit pharmakoresistenten Epilepsien.

BACKGROUND: The ketogenic diet (KD) is a nutritional therapy for the treatment of epilepsies and certain metabolic disorders like the glucose-transporter-deficiency or the pyruvate-dehydrogenase-deficiency. The basis of the ketogenic diet is the change of energy metabolism to utilisation of fatty acids and their metabolites, ketonic bodies. Carnitines, which play an important role in transport and elimination of fatty acids, are essential for effective ketogenesis. Carnitine deficiency is described on ketogenic diet. The aim of this study is to evaluate when to expect a carnitine-deficiency during KD. PATIENTS: The carnitine levels of 19 patients aged 1.4 to 8.5 years (median 4.0 years), who were treated with ketogenic diet because of pharmacoresistent epilepsy, were evaluated retrospectively. RESULTS: Carnitine deficiency during KD was detected in 26 % of the patients and in 57 % of the patients without carnitine substitution. Decreased carnitine level occurred also with carnitine substitution independent from additional valproat therapy. The time of appearance of carnitine deficiency on KD was between 3 days and 248 weeks (median 32 weeks). CONCLUSION: Regular controls of carnitine levels should be performed during the treatment with ketogenic diet, both at the beginning and during longterm-therapy.

Glucose-monitoring with continuous subcutaneous microdialysis in neonatal diabetes mellitus.

BACKGROUND: Neonatal diabetes mellitus can be extremely brittle. In this situation close glucose monitoring is essential for adequate insulin treatment. Continuous subcutaneous microdialysis is a promising approach for the babies to reduce the painful stress caused by diagnostic blood sampling. The goal of this study was to evaluate the feasibility of continuous subcutaneous microdialysis for glucose monitoring in a baby with neonatal diabetes and to assess the correlation between the blood and the subcutaneous glucose profile. PATIENT AND METHOD: During a period of seven days glucose monitoring was performed on a six month old infant with neonatal diabetes mellitus. In addition to frequent capillary blood glucose determinations, a continuous subcutaneous microdialysis device was used for the detection of the subcutaneous interstitial glucose concentration. RESULTS: Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to 23.8 mM. Variations in the adipose tissue glucose concentration closely paralleled changes in the capillary blood glucose. Based on 104 reference pairs there was a high overall correlation (r = 0.89) between the subcutaneous interstitial tissue (X) and the blood (Y) glucose concentration (Y = 1.1 X + 0.29). However the glucose profiles demonstrated a considerable variation of the time lag, up to one hour, between blood and subcutaneous interstitial glucose concentration. CONCLUSIONS: Continuous subcutaneous microdialysis helps the glucose monitoring of infants with diabetes mellitus by providing additional informations about the rise and fall of the glucose concentration. Further studies should focus on how to get a tighter link between blood glucose and the subcutaneous interstitial glucose concentration in the area around the microdialysis probe. Thus monitoring the subcutaneous interstitial glucose concentration will become a reliable procedure for real-time glucose monitoring.

Subcutaneous microdialysis for children - safe biochemical tissue monitoring based on a minimal traumatizing no touch insertion technique.

BACKGROUND: Microdialysis (MD) enables analysis of extracellular metabolites without performing blood tests. Changes in the concentration of various metabolites can be monitored frequently on almost every type of human tissue. Microdialysis of subcutaneous tissue (sc MD) is of particular significance in the case of pediatric patients because diurnal profiles can be generated without repeated blood sampling. There are only a few scientific articles that describe the application of sc MD on neonates, infants, or children. So far, side effects have not been investigated comprehensively. This prospective study scrutinizes side effects of sc MD in pediatric patients, focusing on a Minimal Traumatizing Insertion Technique of the MD catheter. PATIENTS AND METHODS: 42 pediatric patients within four age categories participated in the study which involved bedside monitoring using sc MD, including 5 extremely low birth weight (ELBW) infants with a body weight <1000g. A total of 48 sc MD catheters were inserted. Selection criteria were risk of hypoglycaemia (n = 29), elevated lactate levels (n = 16), or aminoacidopathies (n = 3). Duration of sc MD ranged from 1 to 16 days. We used a Minimal Traumatizing Insertion Technique to safely insert the MD catheter into the subcutaneous tissue, characterized by blunt dissection of the tissue and by the use of a plastic cannula guidance to avoid desterilisation of the catheter. Complications and side effects related to sc MD were documented in standardized forms. RESULTS: The MD probe was easily placed even in the scanty adipose tissue of ELBW infants. During insertion of sc MD catheters accidental venous puncture occurred to 8%, and minor bleeding to 27%. Even with local anaesthesia insertion was painful for 40%. During the course of sc MD complications were rare: disturbance of perfusion flow 4%, catheter dislocation 4%, local bleeding 4%. No signs of systemic or local infection were observed, there were no cases of local incompatibility. All catheters were withdrawn completely without leaving a scar. Repeated measurements allowed the generation of diurnal metabolic profiles. In some cases (respiratory chain complex I deficiency, PDH-deficiency) significant therapeutical effects on the patients' metabolism were demonstrated. CONCLUSIONS: The present study proves long-term sc MD to be suitable and safe for biochemical tissue monitoring. Using our insertion technique, it can be applied to children of all ages without causing discomfort or severe side effects. As it permits frequent sampling it allows evaluating and optimizing therapy and means a substantial progress for pediatric observation.

Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy.

Pyridoxine-dependent epilepsy, although described some decades ago, may still be an underdiagnosed disorder. We have recently described isolated pipecolic acid elevations in the plasma and/or CSF of three patients with pyridoxine-dependent epilepsy with an intriguing inverse correlation to the oral intake of pyridoxine. We have now confirmed these findings in a further 6 unrelated patients with pyridoxine-dependent epilepsy. Pipecolic acid in plasma was 4.3- to 15.3 fold elevated compared to the upper normal range before pyridoxine and remained in the mildly elevated range while on pyridoxine. Pipecolic acid was even more markedly elevated in CSF. The extent of pipecolic acid elevation in CSF exceeded that of plasma by a factor of 2.2 to 4.8. This clearly discriminates pyridoxine-dependent epilepsy from other possible defects with elevated pipecolic acid. Determination of pipecolic acid in plasma and/or CSF should be included in the diagnostic work-up of patients with therapy-resistant seizures. It will in addition prevent patients with pyridoxine-dependent epilepsy from experiencing potentially dangerous pyridoxine-withdrawal, which until now has been necessary to prove the diagnosis.

The eye-of-the-tiger sign is not a reliable disease marker for Hallervorden-Spatz syndrome.

Pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden-Spatz syndrome, is a rare autosomal recessive disorder characterized by extrapyramidal dysfunction as demonstrated by dystonia, rigidity, and choreoathetosis. Iron deposition in conjunction with destruction of the globus pallidus gives rise to the characteristic eye-of-the-tiger sign in MRI. It has been postulated that pantothenate kinase 2 mutations underlying all cases of classic Hallervorden-Spatz syndrome are always associated with the eye-of-the-tiger sign. Here, we report a patient with classic Hallervorden-Spatz syndrome and a homozygous pantothenate kinase 2 mutation in whom the initially present eye-of-the-tiger sign vanished during the course of the disease. Thus, the alleged one-to-one correlation between the eye-of-the-tiger sign and the presence of pantothenate kinase 2 mutation does not hold true over the course of the disease in PKAN.

Pancreatic agenesis as cause for neonatal diabetes mellitus.

BACKGROUND: Pancreatic agenesis is a rare cause of neonatal diabetes mellitus and the knowledge about the clinical features is sparse. A patient with pancreatic agenesis and double outlet right ventricle is reported. This association has not previously been reported. In addition a synopsis of the patients (n = 14) with pancreatic agenesis who have hitherto been described is given. METHOD: We studied one patient and obtained information on 13 additional patients with pancreatic agenesis by reviewing literature. LITERATURE REVIEW: In one patient the pregnancy was terminated at 19 weeks. 31 % (4/13) of the infants died in the first week and 69 % (9/13) in the first six weeks of live, 17 % (2/12) were born preterm and 83 % (10/12) at term, 93 % (13/14) had severe intrauterine growth restriction, onset of diabetes was in 6 out of 10 infants during the first two days of live, ketonuria is rare and has been reported only once. 64 % (9/14) of the infants with pancreatic agenesis had additional malformations mainly of the biliary system (50 %) and/or the heart (36 %). 31 % (4/13) of the infants survived the neonatal period and developed normally. Failure to thrive was compensated by catch-up growth after replacement of pancreatic enzymes and surgical correction of the cardiac malformation. CONCLUSIONS: Pancreatic agenesis is a clinical entity characterized by severe intrauterine growth retardation, early onset of permanent neonatal diabetes mellitus without ketoacidosis, failure to thrive due to pancreatic exocrine dysfunction and associated malformations mainly of the biliary system or of the heart. Because of the high neonatal mortality, awareness of pancreatic agenesis as a possible cause of severe intrauterine growth restriction is important for the optimal treatment of diabetes mellitus, exocrine pancreatic insufficiency and the associated malformations.

[The ketogenic diet in German-speaking countries: update 2003]. / Die ketogene Diät in den deutschsprachigen Ländern im Jahr 2003: eine Standortbestimmung.

BACKGROUND: The ketogenic diet has been used for decades to treat intractable childhood epilepsies. It is also the treatment of choice for GLUT1 deficiency syndrome and pyruvate-dehydrogenase-complex-deficiency. Recent studies have once again confirmed the efficiacy of the diet, but the diet is hardly known in Europe and has never been quite accepted as an effective treatment of childhood epilepsy. PATIENTS: We report retrospective data on 146 children treated with the ketogenic diet in Austria, Switzerland, and Germany. METHOD: In 2000 and 2002, standardized questionaires were sent to 13 neuropediatric departments to evaluate indications, effects and side effects. RESULTS: In children with refractory epilepsy (n = 111), 8 % became seizure-free on the diet. Seizure reduction of > 90 % was achieved in additional 9 % of patients, a seizure reduction of 50-90 % in additional 14 % of patients. There was a great variability between epilepsy departments. All patients with GLUT1 deficiency syndrome (n = 18) and pyruvate-dehydrogenase-complex-deficiency (n = 15) showed clinical improvement. In GLUT1 deficiency syndrome, complete seizure control was achieved in 94 % of patients. Compliance was good in 82 % of all patients regardless of the indication for the diet. CONCLUSION: In contrast to the general restraint towards the ketogenic diet in Europe, our data supports its effectiveness as the treatment of choice for GLUT1-deficiency syndrome und pyruvate-dehydrogenase-complex-deficiency. In children with refractory epilepsy, the ketogenic diet matched the effect of most anticonvulsants and was well tolerated. These data and two workshops resulted in recommendations for the use of the ketogenic diet in children as a basis for a general diagnostic and therapeutic standards to compare and improve the use of the ketogenic diet in Europe.

Fatal propofol infusion syndrome in association with ketogenic diet.

Propofol is used for the treatment of refractory status epilepticus. When given as a long-term infusion propofol may cause a rare but frequently fatal complication, the propofol infusion syndrome. The hallmarks are metabolic acidosis, lipemia, rhabdomyolysis and myocardial failure. Propofol infusion syndrome is caused by impaired fatty acid oxidation. Beside anticonvulsants the ketogenic diet, a high-fat, low-carbohydrate, adequate-protein diet, is an effective treatment for difficult-to-control seizures. We report a 10-year-old boy with catastrophic epilepsy, who developed fatal propofol infusion syndrome when a ketogenic diet was initiated. Substances like propofol which impair fatty acid oxidation may pose an increased risk if combined with ketogenic diet.

Cloning of the breakpoints of a de novo inversion of chromosome 8, inv (8)(p11.2q23.1) in a patient with Ambras syndrome.

Ambras syndrome (AMS) is a unique form of universal congenital hypertrichosis. In patients with this syndrome, the whole body is covered with fine long hair, except for areas where normally no hair grows. There is accompanying facial dysmorphism and teeth abnormalities, including retarded first and second dentition and absence of teeth. In 1993, Baumeister et al. reported an isolated case of Ambras syndrome in association with a pericentric inversion of chromosome 8. Subsequently, another patient with congenital hypertrichosis and rearrangement of chromosome 8 was reported by Balducci et al. (1998). Both of these patients have a breakpoint in 8q22 in common suggesting that this region of chromosome 8 contains a gene involved in regulation of hair growth. In order to precisely determine the nature of the rearrangement in the case of Ambras syndrome, we have used fluorescent in situ hybridization (FISH) analysis. We have cloned the inversion breakpoints in this patient and generated a detailed physical map of the inversion breakpoint interval. Analysis of the transcripts that map in the vicinity of the breakpoints revealed that the inversion does not disrupt a gene, and suggests that the phenotype is caused by a position effect.

[Alström-syndrome: a missed diagnosis with consequences]. / Alström-Syndrom: Eine verkannte Diagnose mit Konsequenzen.

BACKGROUND: Alström-syndrome (OMIM: 203 800) is a rare disease with autosomal recessive inheritance. Characteristic features are retinal degeneration, truncal obesity, diabetes mellitus and sensorineural hearing loss. Further variable symptoms include chronic hepatitis and asthma. CASE REPORT: A patient with asthma associated with retinal degeneration is presented. The investigations demonstrated truncated obesity, sensorineural deafness and impaired glucose tolerance and Alstrom-syndrome was diagnosed. She received hearing aids, diabetes training and is regularly reinvestigated for further manifestations of Alström-syndrome.

Butane abuse associated Encephalopathy.

Butane contained in household products is easily available for abuse and is not subject to legal prosecution in Germany. The toxicological properties of butane mainly affect the heart and the CNS. A serious pathophysiological mechanism is asphyxia due to the replacement of oxygen by butane. We report an abusive butane inhalation in a 15-year old girl, resulting in cardiopulmonary resuscitation and subsequent development of severe brain damage. After reviewing the medical literature and questioning German toxicological information centres it became obvious, that abuse of butane is an increasing problem. We give an survey about the complications associated with butane intoxication.

[Infratentorial pathology a pitfall for neonatal cerebral sonography: Additional sonographic imaging through the posterolateral fontanelle, a prospective study]. / Infratentorielle Läsionen, eine diagnostische Lücke in der zerebralen Sonographie: Die hintere Seitenfontanelle als zusätzliches Schallfenster.

BACKGROUND: Routine assessment of the neonatal brain is performed by ultrasound through the anterior fontanelle. The infratentorial structures can be visualised more detailed by sonography through the posterolateral fontanelle. This prospective study was performed to evaluate anterior fontanelle and posterolateral fontanelle for the detection of infratentorial lesions. PATIENTS: Cerebral sonography was performed in 100 preterm infants at the median (range) age of 9 days (0 - 91 days). Median gestational age at birth was 33 weeks (23 - 36 weeks). METHOD: Scanning through the posterolateral fontanelle was performed after sonography through the anterior fontanelle. RESULTS: Neuropathology could be detected in 22 of the 100 preterms. In six patients infratentorial lesions were present in association with supratentorial pathology. The infratentorial abnormalities were clots in the IV. ventricle (n=3), clots in the cisterna magna (n=2), dilation of the IV. ventricle (n=3), dilation of the aqueduct (n=1), and a intraparenchymatous echodensity in the cerebellum (n=1) which receded. When clots were present in the lateral ventricles only the sonography through the posterolateral fontanelle allowed the detection of the infratentorial abnormalities. CONCLUSION: Sonography through the posterolateral fontanelle allows the detection of infratentorial pathology missed by sonography through the anterior fontanelle. Additional scanning through the posterolateral fontanelle should be part of the standard neonatal cerebral sonography.

Glucose monitoring with long-term subcutaneous microdialysis in neonates.

BACKGROUND: Microdialysis is a new approach for continuous monitoring of small molecules in the extracellular space, and hypoglycemia is a common problem in neonatal intensive care. The objective of this study was to evaluate subcutaneous microdialysis for long-term glucose monitoring in neonatal intensive care. We determined the relative recovery of the microdialysis system in vitro and in vivo, the stability of the relative recovery in vivo during long-term microdialysis, and the correlation between blood and dialysate concentrations of glucose and urea. Furthermore, we evaluated the sensitivity and specificy of subcutaneous microdialysis for the diagnosis of hypoglycemia. PATIENT AND METHODS: Thirteen infants (10 neonates) with gestational ages of 30.2 to 45.6 weeks were investigated by microdialysis of subcutaneous adipose tissue and blood sampling. Subcutaneous microdialysis was performed for a median (range) duration of 9 (4-16) days. RESULTS: The application was safe, even in extremely low birth weight infants (<1000 g) with scanty subcutaneous adipose tissue. The mean +/- standard deviation of the relative recovery in vitro was 101 +/- 3% for glucose and 100 +/- 2% for urea. Using urea as the internal standard, the mean relative recovery in vivo was 96.4 +/- 12.7% at the beginning and remained constant up to 16 days. The correlation between microdialysate and blood was significant for glucose (r = 0.88) and urea (r = 0.98). Subcutaneous microdialysis allowed the detection of asymptomatic hypoglycemias. The diagnostic sensitivity of a dialysate glucose

Determination of amino acid tissue concentrations by microdialysis: method evaluation and relation to plasma values.

Microdialysis is an in vivo technique to monitor tissue concentrations of low molecular weight substances by means of a continuously perfused artificial capillary with a semipermeable membrane placed into the region of interest. The suitability of microdialysis to determine tissue concentrations of amino acids was evaluated in vitro by placing the catheter into Ringer buffer or into a plasma protein (50g/l) solution containing 32 different amino acids (150 micromol/l each). All amino acids tested crossed freely the microdialysis membrane with recoveries close to 100%. Microdialysis fluid was sampled from subcutaneous tissue of five newborns and amino acid content analysed. Total and non protein bound amino acids were determined in the patients plasma by acid precipitation or ultrafiltration, respectively. Mean subcutaneous tissue concentrations were lower as compared to plasma for taurine, serine, alanine, aspartate, glutamate and ornithine and higher for valine, isoleucine, leucine, methionine, phenylalanine, tyrosine and arginine, indicating net uptake or release of amino acids from subcutaneous tissue. Thus, microdialysis offers a convenient and minimal invasive way to study tissue amino acid composition and appears to be a promising analytical tool for the study of amino acid metabolism in vivo.

Griscelli syndrome: report of the first peripheral blood stem cell transplant and the role of mutations in the RAB27A gene as an indication for BMT.

Griscelli syndrome is characterized by partial albinism with variable immunodeficiency. Two different gene loci are responsible for this rare, autosomal recessive disease: the myosin Va gene and the RAB27A gene. As recently reported, only patients with mutations of the RAB27A gene suffer from immunodeficiency and hemophagocytic lymphohistiocytosis. Thus, only patients who suffer from the Griscelli syndrome with mutations of the RAB27A gene should receive BMT/PBSCT, which is the only curative therapy. Due to the risk of early relapse or severe infections, BMT/PBSCT should be carried out as soon as possible; if patients do not have HLA-identical family members, valuable time may be lost by searching for an HLA-identical unrelated donor. We report the first peripheral blood stem cell transplant (PBSCT) with T cell depletion in a 6-month-old girl with Griscelli syndrome, and a deletion of the RAB27A gene. The donor was her phenotypically HLA-identical mother. Conditioning included busulfan, VP16 and cyclophosphamide. The patient was transfused with 15.4 x 10(6)CD34-positive cells/kg and 17.6 x 10(3) CD3-positive cells/kg recipient weight. Three months after the transplant, a curable lymphoproliferative syndrome occurred. 26 months after the transplant, the patient is doing well with stable mixed chimerism (52% donor cells).