[Grisel's syndrome causing torticollis in children].

This is a case report of an eight-year-old boy with CT-confirmed changes bringing attention to Grisel's syndrome as a differential diagnosis to torticollis. The syndrome - also known as atlantoaxial subluxation - is a complication to operations or infections in the ear, nose and throat region. It usually presents as a slightly flexed and rotated neck, and characteristic radiographic findings. Complications include neurological symptoms and rarely spinal cord compression. The treatment is debated, but it takes the underlying cause and immobilisation in consideration. In severe cases, repositioning in general anaesthesia or even surgical fusion may be necessary.

[Narcolepsy in a seven-year-old girl]. / Narkolepsi hos en syvårig pige.

Narcolepsy is a life-long disease commonly diagnosed in adults. Although the first symptoms often appear during childhood, paediatric narcolepsy is often underrecognised and underdiagnosed. The presentation can be very variable, this making diagnosis difficult. We describe a paediatric case with narcolepsy. The patient had the typical symptoms with excessive daytime sleepiness, sleep attacks and cataplexy. The aim of this case report is to draw paediatricians' attention to childhood narcolepsy. An early and sufficient treatment is necessary to avoid socio-emotional disorders and poor school performance in these patients.

[Arteriovenous malformation as a cause of intracerebral haemorrhage in a 13 year-old girl]. / Arteriovenøs malformation som årsag til intracerebral hæmoragi hos en 13-årig pige.

Spontaneous intracranial haemorrhages in children are rare. The leading cause of spontaneous bleeding is a rupture of arteriovenous malformations (AVM). This case study presents a 13 year-old girl with headache and slightly altered mental status due to bleeding from an unknown cerebral AVM. Although the initial symptoms may be non-specific it is a disease, which results in a significant mortality. A physician should keep the diagnosis in mind even though the incidence in children is very low.

[Aicardi syndrome as cause of severe epilepsy and mental retardation]. / Aicardis syndrom som årsag til svær terapirefraktær epilepsi og udviklingshæmning.

Aicardi syndrome is a very rare disease. It is characterised by a triad of callosal agenesis, infantile spasms and chorioretinal lacunae. Other congenital defects of the eyes, ribs and vertebrae and other malformations also occur frequently. Mental retardation and usually intractable seizures are constant features. Treatment is only symptomatic and the outcome is very severe in most cases. This case report describes a newly diagnosed patient with Aicardi syndrome. To our knowledge it is the second case diagnosed in Denmark.

[Moyamoya]. / Moyamoya.

The disease moyamoya is rare in Europe, but it is seen more frequently in Japan and other Asian countries. Moyamoya is characterized by progressing occlusion of the cerebral arteries and secondary development of pathological collateral vessels induced by ischaemia. This case report describes a newly diagnosed patient with moyamoya, who was referred to a paediatric clinic because of headache and involuntary movements and sounds. Due to the rare occurrence of moyamoya, the purpose of this case report is to draw attention to its diagnosis with a view to achieving an early diagnosis of the disease.

Autonomic nervous system function in infants and adolescents: impact of autonomic tests on heart rate variability.

Measurement of heart rate variability (HRV) shows information on the functional state of the autonomic nervous system (ANS). In adults there are standardized autonomic tests and well-established ranges of normal values, which is not the case in children. The aim of the present study was (1) to introduce an ANS test battery, especially for children and adolescents; (2) to establish normative HRV parameters; and (3) to determine the impact of ANS tests on HRV parameters compared with baseline measurements. We investigated 100 healthy children and adolescents between 6 and 15 years old. We subdivided the investigated group into a group of children (5-11 years old) and adolescents (12-15 years old) and measured HRV by time and frequency domain parameters during baseline, rhythmic breathing, Valsalva test, active standing, tilt-table testing, and handgrip test. The normative HRV data are presented by means, SDs, medians, and percentiles. The results described refer to baseline values for each HRV parameter separately to demonstrate the influence of age on HRV parameters. The study results present not only first normative HRV data for an autonomic test battery especially adapted to children and adolescents, but they also quantify the autonomic changes induced by test procedures compared with baseline measurements.

High incidence of vaproate-induced coagulation disorders in children receiving valproic acid: a prospective study.

Reports have been published on blood coagulation disturbances by valproate therapy. In the present prospective trial, blood samples were drawn before valproate therapy, after 6 weeks of therapy, after more than 6 weeks and after longer than 6 months of valproate therapy from 23 children newly treated with valproate. Two children developed thrombocytopenia, and six children with initial normal von Willebrand factor showed acquired von Willebrand's disease. Fibrinogen levels dropped below the lower limit in 12 patients and subnormal factor XIII plasma levels were observed in 17% of patients. No patient developed signs of hemorrhage. Eight percent of patients developed valproate-induced thrombocytopenia. Reduction in platelets did not reach statistic significance. Thrombelastography showed a 47% incidence of altered platelet function. We found a statistically significant, positive correlation between clotting time of collagen extrinsic pathway inhibitor and, accordingly, adenosindiphosphate and valproate level. Plasmatic coagulation investigations showed a significant decrease of prothrombin time. Activated partial thromboplastin time measurements also showed significant prolongation with valproate. Activity of von Willebrand factor antigen and von Willebrand factor ristocetin cofactor significantly decreased. Factor XIII activity significantly decreased after valproate therapy for longer than 6 months (17% of children). Fibrinogen was significantly reduced. In the coagulatory system a decrease in the main antiprotease antithrombin III activity was observed. Blood coagulation disturbances are common in patients with valproate, but rarely become clinically symptomatic. Acquired von Willebrand's disease and hypofibrinogenemia may become relevant in patients with surgery or trauma. Particular attention should be paid to factor-XIII deficiency, which is especially seen with valproate therapy.

Vagus nerve stimulation improves severely impaired heart rate variability in a patient with Lennox-Gastaut-Syndrome.

Vagus nerve stimulation (VNS) is a new therapeutic option for refractory epilepsy. We report a patient with Lennox-Gastaut-Syndrome (LGS) and a severe impairment of heart rate variability (HRV), we could demonstrate in our patient that HRV was improved by VNS.

Internet-based knowledge management database for children and adults with epilepsy: a possible model project for evidence-based medicine in the future.

With an incidence of nearly 1%, epilepsy represents one of the most frequent diseases in the population. Nevertheless substantial information gaps exist as to the exact incidence, prevalence, therapy and particularly to associated therapeutic success. Adequate studies are not performed on many of these issues which are primarily beyond the current interests of the pharmaceutical industry. An Internet-based knowledge management database is presented to illustrate initial results of the online system with a focus on medication and side effects (http://www.ligaepilepsie.org/KnowledgeDB/index.htm). Further, it is worth noting that this database was designed as a potential model for similar projects in other medical fields.

Reversible hepatotoxicity, pancreatitis, coagulation disorder and simultaneous bone marrow suppression with valproate in a 2-year-old girl.

Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies, including special epileptic syndromes like the WEST-syndrome. The drug is usually well tolerated; rare serious complications may occur in some patients, including haemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy. We report a case of combined appearance of several severe VPA-associated side effects in a two- and a half-year-old girl with lissencephaly.

Valproic acid-induced pancreatitis: 16 new cases and a review of the literature.

BACKGROUND: Acute pancreatitis is rarely seen in children, and, in contrast to cases in adults, it is often drug induced. One possible medication is the antiepileptic drug valproic acid (VPA), which is commonly prescribed for generalized and focal epilepsy, migraine, neuropathic pain, and bipolar disorder. The common side effects associated with VPA are typically benign, but less common but more serious adverse effects may occur. These include hepatotoxicity, hyperammonemic encephalopathy, coagulation disorders, and pancreatitis. Since 1979, a few cases of pancreatitis induced by VPA have been published in the medical literature. METHODS: We mailed a questionnaire to all members of the "German Section of the International League against Epilepsy," asking about VPA-induced side effects. We also reviewed the medical literature for VPA-induced pancreatitis. RESULTS: Fifty-three publications (90 patients) published from 1979 to 2005 were found. Our survey in Germany, however, yielded 16 cases of pancreatitis from 1994 to 2003 whose original files we could study in detail. None of these patients had been published previously. CONCLUSIONS: The difference between 90 patients reported worldwide from 1979 to 2005 and the 16 new documented cases from only Germany over 10 years corroborates that the occurrence of this severe side effect is under reported.

Effects of valproate on acylcarnitines in children with epilepsy using ESI-MS/MS.

PURPOSE: To determine the influence of valproate (VPA) treatment on acylcarnitines in children with epilepsy. METHODS: Determination of acylcarnitines (including free carnitine and acylcarnitines from C2 to C18) in dried blood spot specimens using tandem-mass spectrometry. Longitudinal study of changes in acylcarnitines in children under VPA treatment without pretreatment (group 1) or with pretreatment with other antiepileptic drugs (group 2) before the start of VPA treatment at an early and a late treatment interval (12-66, 90-260 days after the beginning of treatment, respectively). Cross-sectional comparison of these two VPA groups and of a group receiving carbamazepine monotherapy (group 3) with controls. RESULTS: Acylcarnitines in epileptic patients before VPA therapy did not differ from control values. In group 1, decreases of C0 (-26%), C2 (-12%), C16 (-31%), C18 (-41%), C(total) (-10%), increases of C5OH (+31%), C8 (+33%) in the early treatment interval, and decreases of C16 (-21%), C18 (-42%), and increases of C2 (+26%), C5OH (+44%) in the late treatment interval were significant. In group 2, both in the longitudinal and the cross-sectional study, only a decrease of C18 (-41%, -43%, respectively) in the late treatment interval was found. In group 3, no significant changes have been observed. CONCLUSIONS: We could prove changes in acylcarnitine subspecies, which were associated with VPA treatment in children with epilepsy. The treatment interval with the most marked changes coincides with the interval of highest risk for VPA-induced hepatotoxicity. The observed specific acylcarnitine pattern might point to the impaired intermediary metabolism that is responsible for VPA-induced hepatotoxicity.

Oral rapid loading of valproic acid--an alternative to the usual saturation scheme?

Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies. Due to its broad field of application and its good compatibility, VPA is one of the most frequently prescribed antiepileptic drugs (AED) worldwide. Previous studies have examined the safety and tolerability of rapid intravenous-loaded VPA in the treatment of epilepsy and status epilepticus, but rapid oral loading has not been evaluated in paediatrics systematically in the past. The standard titration scheme takes 10-14 days, some physicians prefer a slower titration of up to 4 weeks. At many institutes, especially children are treated as inpatients until the desired dosage is reached. This causes high costs to the health system and is very inconvenient for the families affected. We have developed a new loading scheme to achieve a therapeutic serum level on the third day of treatment, in order to minimize the time between the beginning of the therapy and reaching the therapeutic serum level. This is the first attempt at doing this with VPA for children with epilepsy.

Capillary microscopy and hemorheology in children during antiepileptic monotherapy with carbamazepine and valproate.

The interactions of epilepsy and antiepileptic therapy an one hand and cardiovascular system on the other hand are multiple and complex. Antiepileptic drugs (AEDs) cause alterations of serum lipids and of the fatty acid composition of the membranes. Homocystein, known to induce vascular endothelial damage was found to be elevated in patients on valproate (VPA) and carbamazepine (CBZ) therapy. Marked coronary artherosclerosis and myocardial infarction may already occur in children treated with CBZ. Community based studies corroborated a higher incidence of myocardial infarction, peripheral vascular diseases hypercholesterinemia, left ventricle hypertrophy and stroke in patients with epilepsy. In this context, we wanted to elevate changes of microcirculation related to AEDs commonly prescribed such as VPA and CBZ. Capillary microscopy is a non-invasive technique for measuring the velocity of red blood cells and for determining nutritional blood flow in the capillaries of the skin. It can easily be performed in children. The aim of this study was to look for possible effects an antiepileptic monotherapy with carbamazepine or valproate has on the peripheral microcirculation in epileptic children. We were able to examine 14 children with CBZ and 24 children with VPA, recruited in our neuropediatric Unit. The results were compared to normative values, determined in former analyses of 207 healthy children. We found significant differences in capillary density, tortuous index of the capillaries, capillary diameter and flow rate of erythrocytes for both antiepileptic drugs. Additionally, there were changes in plasma viscosity and the aggregation of erythrocytes. These microcapillary effects could be of special interest in the relationship of a long-term antiepileptic therapy and the development of vascular diseases. We suggest that the influence of AEDs on microcirculation should also be considered in further studies on cardiovascular changes in patients with antiepileptic long-term medication.

Valproate-associated coagulopathies are frequent and variable in children.

PURPOSE: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. The clinical relevance of coagulopathies, known as side effects of VPA therapy, especially thrombocytopenia, von Willebrand disease, and a decrease of factor XIII, is still unclear. METHODS: In our institute, we noticed a high incidence of clinically relevant coagulation problems related to VPA in eight patients within 1 year only and a further seven children with significant coagulopathy were identified in the context of planned surgery. RESULTS: We provide an overview of these patients and all six VPA-induced coagulopathies. CONCLUSIONS: At this time, it cannot be recommended to control all hemostatic parameters in every patient. Whenever an increased bleeding tendency is observed, or before surgical procedures, a platelet count, thrombelastography, prothrombin time, activated partial thromboplastin time, TT, fibrinogen, von Willebrand factor, and factor XIII should be examined. With 385 VPA-treated patients per year and 15 cases of coagulation disorders in this period, we estimate the incidence of coagulation disorders related to VPA in children to be nearly 4%.

Maturation of the autonomic nervous system: differences in heart rate variability in premature vs. term infants.

AIMS: Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS). This study was initiated to assess the physiological- and maturational development of the ANS by comparing HRV data of healthy prematures with term infants. METHODS: Short-term recordings of HRV in 39 premature healthy infants (29-35 weeks' gestation) were performed and compared with normative data of term infants. Frequency domain HRV parameters are computed in three frequency bands. RESULTS: Gestational age of newborn infants is correlated with HRV. Prematures showed significant lower HRV parameters than term infants. The most significant differences were discerned for HRV parameters reflecting parasympathetic activity, whereas the pulse of the baro-receptor reflex was similar for prematures and term infants at 0.07 Hz (0.1 Hz adults). A respiratory peak in the HF-band according to respiratory sinus arrhythmia (RSA), as is common in adults, was not detected for prematures as it is not detected in term infants. CONCLUSIONS: Maturation of the ANS is accompanied by increasing HRV with a pronounced increase of parasympathetic activity. These changes are measurable by short-term recordings. The physiological pulses concerning baroreceptor reflex activity and respiratory modulation were similar in prematures and term infants.

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.

Heart rate variability during extracorporeal membrane oxygenation and recovery in severe neonatal disease.

BACKGROUND: Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS) in neonates. During severe illness, heart rate variability is impaired. AIM: This study was initiated to measure the changes in HRV in neonates during extracorporeal membrane oxygenation (ECMO) and recovery from severe respiratory and circulatory failure. Moreover, we compared our data with HRV data of healthy newborns and we investigated the differences in HRV parameters between ECMO-survivors and non-survivors. STUDY DESIGN: This study is of an observational character. We performed short-term recordings of heart rate variability in 14 neonates during ECMO and recovery. We computed time- and frequency-domain HRV parameters. RESULTS: ECMO significantly affects time-domain HRV parameters. Severe neonatal illness causes a significant reduction of all calculated HRV parameters; clinical recovery is accompanied by an increase of HRV. In comparison with normative data of healthy newborns, however, HRV remains impaired. The ECMO-development ratio separated the non-survivors from the survivors during ECMO therapy. CONCLUSIONS: During severe neonatal illness, HRV is impaired. It remains to be clarified whether the impairment of HRV during severe illness can predict the neurological outcome. The ability of the E/D ratio as an HRV parameter to serve as a predictive tool has to be corroborated in larger group of patients.