Topiramate enhances the risk of valproate-associated side effects in three children.

PURPOSE: We present three children with severe therapy-refractory epilepsy who tolerated valproate (VPA) well in various combinations with other antiepileptic drugs (AEDs) but developed typical VPA side effects in combination with topiramate (TPM). METHODS: The clinical symptoms began with apathy in all three children; two of them also had hypothermia. Furthermore all children had elevated blood ammonia levels, one child in combination with increased liver transaminases and one with thrombocytopenia. RESULTS: All children recovered completely after discontinuation of VPA or TPM. CONCLUSIONS: TPM seems likely to enhance the risk of side effects usually attributed to VPA and not described in TPM monotherapy. Our case reports suggest that possible adverse effects of VPA should be given particular attention when VPA is combined with TPM.

[Long-term follow-up MRI in children with craniocerebral trauma]. / Kernspintomographische Verlaufskontrolle bei Kindern nach Schädel-Hirn-Trauma.

PURPOSE: A prospective study was initiated for the correlation of the findings in the initial cranial CT with the long-term follow-up MRI in children with severe head injury. Another aim was the evaluation of frequency and location of lesions, found only in MRI. METHODS: 70 children with severe head injury and initially performed pathological CCT were followed up (mean time 3 years) by MRI. RESULTS: 71% of the children had a pathological MRI. In 43% of the children with subdural bleeding could be found parenchymal lesions in the underlying cortex. All 15 children with epidural bleeding had unsuspicious findings at the former hematoma. All of the contusions were found as parenchymal residual lesions. 44% of the children had evidence of parenchymal lesions in the follow-up MRI initially and retrospectively not revealable. 16 lesions in the corpus callosum were only revealed by MRI. CONCLUSION: This study shows the higher sensitivity of magnetic resonance imaging in non-hemorrhagic parenchymal lesions and in "diffuse axonal injury". A MRI-examination is recommended in children with severe head injury, especially in patients with normal CCT and posttraumatic neurological deficits.

Long-term follow up of children with head injuries-classified as "good recovery" using the Glasgow Outcome Scale: neurological, neuropsychological and magnetic resonance imaging results.

UNLABELLED: The primary issues addressed in this study were: (1) determination of the significance of the classification "good outcome" utilizing the Glasgow Outcome Scale (GOS) in children at least 1 year after brain injury; (2) detection of residual lesions of brain parenchyma in these children upon follow up MRI scans; and (3) detection of relationships between neuropsychological test performance and MRI results. Selection criteria included children 6-15 years of age at the time of testing who received an initial CT scan at the time of their head injury and who had been injured at least 12 months prior to the follow up test. Only children who did not demonstrate neurological disability at the time of follow up examination were selected. The children showed a status of "good outcome" as defined by the GOS. Neurological examination, neuropsychological tests and an MRI were done. The test results of 59 patients were compared to those of a matched control group. Children, after receiving head injuries, showed significantly poorer results with respect to cognitive, motor and fine motor skills. Of all MRI-scans 66% revealed pathological findings. Cortical lesions were detected on MRI in 14% of cases; subcortical injuries were detected in 12% and, deep white matter lesions in 31%. Furthermore, corpus callosum damage was observed in 26% of cases. Pathological MRI findings were also observed in children with mild head injuries. All of the children with normal MRI findings showed abilities comparable to those of children in the control group. Patients with cortical lesions exhibited only motor deficits, whereas motor and cognitive deficits were seen in patients with deep white matter lesions. Children with multiple lesions demonstrated test results in all variables 1 to 2 standard deviations below those of the control group. CONCLUSION: Children suffering a brain injury who 1 year later are classified within the "good outcome" group according to the Glasgow Outcome Scale often have significant morphological and functional brain deficits.

How reliable is the predictive value of SEP (somatosensory evoked potentials) patterns in severe brain damage with special regard to the bilateral loss of cortical responses?

OBJECTIVE: In patients sustaining severe brain damage (SBD), prediction of later outcome is often very difficult, in particular under conditions of therapeutic management like relaxation and intravenous phenobarbital. Somatosensory evoked potentials (SEP) correlated best with later prognosis and expected neurological deficit. In detail, the primary bilateral loss of cortical responses (BLCR) is regarded to be a reliable marker for poor prognosis. The goal of the following prospective study was to reassess the prognostic value of early serial median nerve SEP recording in severe brain damage in comparison to other neurophysiological, clinical, and neuroradiological parameters and, additionally, to test the hypothesis, that the BLCR-pattern is always associated with a poor prognosis and is never reversible. DESIGN: Prospective study. SETTING: Anaesthesiological hospital intensive care unit. PATIENTS AND PARTICIPANTS: 42 comatose patients with severe brain damage (29 males/13 females), mean age 39.6 +/- 19.3 years, mean initial Glasgow Coma Score (GCS) 6.6 +/- 3.1, investigated by means of median somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) with serial recordings on day 1, 3 to 4, and 8 to 1, and repeated cranial computerized tomography. MEASUREMENTS AND RESULTS: We classified the outcome according to the Glasgow Outcome Scale (GOS). Our data showed a high correlation of initial SEP scores (Spearman correlation coefficient = -0.70) with outcome for both a favorable and an unfavorable prognosis (p = 0.0001). The reliability increased with serial recordings. The SEPs showed superiority to parallel brainstem auditory evoked potentials (Spearman correlation coefficient = -0.50, p = 0.0007), GCS, and standardized neuroradiological criteria. Primary (BLCR) occurred in 16 patients (38%) and implied a fatal prognosis in all adult patients (n = 15, specificity = 93.3%, sensitivity = 59.3%). In contrast, a young child with predominant brainstem hemorrhagic contusions regained consciousness and developed mild to moderate neurological deficit (GOS 3-4) during long-term follow-up of 4 years. This clinical improvement paralleled bilateral asymmetric recovery of cortical SEP responses. CONCLUSIONS: SEP allow an early reliable assessment of both poor and good prognosis in SBD, in particular when applied serially. BLCR does not always imply a fatal diagnosis, as a circumscribed contusional lesion rarely may lead to selective reversible blockage of ascending somatosensory pathways in the brainstem. In contradiction to this lesional etiology, a hypoxia-induced BLCR pattern seems to correlate strictly with a poor prognosis, reflecting a different pathogenesis with diffuse destruction of cortex and thalamocortical pathways.

MRI of encephalitis in children: comparison of CT and MRI in the acute stage with long-term follow-up.

We examined 14 children aged 28 days to 12.7 years with encephalitis by CT or MRI. Of the patients examined by CT 58% had a normal first scan, whereas all MRI investigations demonstrated abnormalities. The clinical features correlated with several MRI investigations. On MRI herpes (HSV) encephalitis started in the medial temporal lobe and encephalomalacia developed within a few weeks. All patients had a follow-up examination 0.5 to 6.5 years after the acute phase. MRI revealed abnormalities in 13 of the 14 children; one boy, with lesions in only the white matter, had a normal follow-up MRI. Even with immediate, optimal therapy the children demonstrated severe parenchymal abnormalities. Signal abnormalities seen in the acute phase of the disease were likely to persist. In children with HSV encephalitis atypical lesions in different areas were seen.

ARDS infolge schwerer RSV-Infektion Therapeutische Optionen: Therapeutische Optionen.

We report on a strikingly frequent referral of former preterm babies with respiratory syncytial virus (RSV) infection and subsequent ARDS in our hospital during the winter 1994/95 with regard to the clinical course under application of alternative treatment modalities. Treatment modalities like inhalational ribavirin, use of bronchodilators and instillation of surfactant had been tried without success. All children (age: 1-43 months) were ventilated for 6.6 (1-17) days with FiO2 = 1.0 and a mean airway pressure of 16.4 (10-24) cm H2O. Mean arterial blood gases were 49 (paO2) and 41 (pCO2) mm Hg, the OI was 33.4. By inhalational NO in combination with IPPV or HFOV 4 patients could be stabilized, in the other 6 ECMO became necessary. Two of them died in spite of several weeks on ECMO; 8 children survived and could be discharged home after a mean hospital stay of 3 months. Even in very severe cases of RSV infection treatment modalities like NO, HFOV and ECMO can be used successfully. The use of these treatment modalities must be considered before the lung damage is irreversible; in those cases a pre-existing BPD is no contraindication even for extracorporeal lung support.

Prognosis and outcome of neonates treated either with veno-arterial (VA) or veno-venous (VV) ECMO.

A comparison was done between neonates requiring veno-arterial (VA) ECMO (too small jugular vein, inability to insert a 12 Fr double lumen catheter or cardio-circulatory instability) and neonates treated with veno-venous (VV) ECMO in the same period of time. From 1991-1995 ECMO was done in 48 neonates after failure of maximum conventional treatments, NO-inhalation and HFOV. 30/48 babies were treated with VV-ECMO, with a switch to VA-ECMO later on in 3 of them. In 18 infants VA-ECMO was installed primarily. Differences between the VA- and VV-ECMO group were: the OI was higher in the VV-treated babies (62 +/- 20 vs. 48 +/- 13, p < 0.03), as were birth weight (3385 +/- 570 vs. 2963 +/- 653 g, p < 0.04), gestational age (39.7 +/- 1.6 vs. 37.9 +/- 2.7 weeks, p < 0.01) and MAP (18.7 +/- 2.2 vs. 17.1 +/- 2.4 cm H2O, p < 0.05). Severe ICH's occurred more frequently in the VA-treated babies (29 vs. 7%, p < 0.05), the rate of other complications was equal. The mortality rates were 43% (VA) and 15% (VV), p < 0.05. About one third of neonatal ECMO candidates will be treated with VA-ECMO, even if the VV-ECMO technique is available. Need for VA-ECMO implies--due to a higher number of preterm babies and a greater severity of illness before ECMO--a higher incidence of ICH's and a higher mortality rate.

Neonatal stroke involving the middle cerebral artery in term infants: clinical presentation, EEG and imaging studies, and outcome.

Six children with neonatal cerebral infarction of the middle cerebral artery are reported. Seizures or respiratory distress were the initial symptoms. In some cases abnormal findings appeared earlier on EEG than on ultrasound. The EEG changes were concordant with the localization of the lesion. Ultrasound examinations revealed an echodense structure within the vascular territory, after a phase of appearing to be normal, highly suggestive of cerebral infarction. The diagnosis was confirmed by CT scan. Findings on EEG, cranial ultrasound and CT suggested that the stroke represented a late intra-uterine event. At long-term follow-up, six children had failed to develop normally for age and had become obviously hemiplegic as gross motor development proceeded. Four of the patients had developed epilepsy. These data indicate that the outcome of neonatal stroke may not be as positive as previously reported.

Magnetic resonance angiography in 140 neuropediatric patients.

Three-dimensional magnetic resonance angiography (MRA) is a noninvasive technique that images the intracranial arterial vasculature without contrast agents. The suitability of MRA was evaluated for routine use and all children were prospectively studied with conventional MR imaging and time off flight MRA (FISP3D). All MR studies were performed on a 1.5 T-MRA system using a circularly polarized head coil. The study comprised 140 children, ages 3 weeks to 18 years, with different neuropediatric diseases. Major cervical and intracranial arteries were visualized in all age groups. Smaller branches of the supratentorial arteries were identified inconstantly and the number of arteries visualized increased up to the age of 6 years. Sixty-seven children (47%) had normal intracranial vasculature. MRA demonstrated anatomic variations in 21 patients (15%). Twenty-two of 32 children with congenital malformations demonstrated abnormalities of the intracranial vasculature. The diagnostic value of MRA was confirmed in 11 of 12 patients after neonatal stroke and in 3 of 10 children after stroke at older ages. Seven of 18 children with acute hemorrhage demonstrated arteriovenous malformations or an aneurysm on MRA. The correlation with digital subtraction angiographic findings was established in 13 patients. In 9 of 13 children with brain tumor, MRA proved to be diagnostically valuable. MRA proved to be of particular value in the evaluation of the carotid artery following extracorporeal membrane oxygenation therapy. MRA can be used in children of all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities.

Since our last report on valproate (VPA)-related hepatotoxicity in 1988, 8 other children have died of VPA-associated liver failure in Germany and Switzerland. We compared the clinical course of these children with that of 6 children with a reversible outcome of severe hepatotoxicity related to VPA. Thirty-five percent of patients with fatal liver failure were normally developed, 23.5% were receiving VPA monotherapy, and 35.3% were aged < or = 2 years. The initial clinical symptoms of VPA-related hepatotoxicity were nausea, vomiting, apathy or coma, and increasing seizures in more than 50% of patients, in combination with febrile infections at onset of symptoms. As compared with the series of German patients reported in 1988, one third of the fatalities occurred after the first 6 months of therapy as compared with 6% in the 1988 series. Clinical symptoms and laboratory findings were the same in patients with reversible and with fatal outcome. Early or immediate withdrawal of VPA after the first signs of VPA-associated hepatotoxicity may be responsible for the increased number of children who recovered after VPA-related severe liver failure. The pathogenesis of liver failure during VPA treatment remains unknown; metabolic defects and cofactors such as polypharmacy or infections have become increasingly likely to contribute by depleting intracellular CoA. Worldwide, 132 patients have died of VPA-associated liver failure and/or pancreatitis. Because a group at risk for fatalities with VPA cannot be defined precisely, patients treated with VPA and their families must be made well aware of the clinical symptoms of hepatotoxicity such as apathy, vomiting, or increased seizure frequency, especially in the presence of febrile infections. Laboratory tests and clinical controls during the first 6 months of therapy should not be neglected.

Childhood progressive spinal muscular atrophy with facioscapulo-humeral predominance, sensory and autonomic involvement and optic atrophy.

A female child of healthy parents developed rotary nystagmus at the age of 15 months. Ophthalmoscopy disclosed incomplete optic atrophy. Blood tests, EEG and CT scans were normal. At 20 months progressive muscular weakness and wasting with limb-girdle distribution commenced, followed later by disturbance of gait. From muscle and nerve biopsy the diagnosis of a peripheral neuropathy with neurogenic muscular atrophy was made. No mental change occurred. At 23 months she sustained cardiac arrest and was resuscitated; thereafter, she remained in a vegetative state and expired 9 months later. Her brain was markedly atrophic and firm. Diffuse old ischemic necroses and neuronal loss with gliosis were found in the cortex, the neostriatum, the thalamus, parts of the lower brainstem, and the cerebellum. Her optic nerves and tracts showed complete atrophy. The spinal cord exhibited degeneration and loss of motor neurons with cervical accentuation. The intermediolateral nuclei, the dorsal nuclei and the spinal ganglia were also involved. There was demyelination of the posterior funiculi, the pyramidal tracts, and the sciatic, peroneal, sural, and superior frontal nerve. The voluntary muscles exhibited large group atrophy with liposclerotic change and limb-girdle predominance. The neck, tongue and ocular muscles were also involved, as were, to a less extent, the lower limbs. Although the loss of motor neurons in the spinal cord and at the bulbar level with the typical pattern of neurogenic muscular atrophy, as well as its distribution, resemble the facioscapulo-humoral type of heredity motor neuropathy (HMN), early onset, rapid course, sensory and autonomic involvement, and atrophy of the optic nerve do not fit this or any one type of HMN.

[High frequency oscillatory ventilation of infants with severe respiratory disorders: possibilities, risks and limits]. / Hochfrequenzoszillationsbeatmung bei Säuglingen mit schwersten Atemstörungen: Möglichkeiten, Risiken und Grenzen.

By pediatricians the high frequency oscillatory ventilation (HFOV) is used almost only in the neonatal period. We report on the administration of HFOV in infants with pulmonary insufficiency after failure of conventional ventilatory support. 6 infants (aged 2-7 months, all former preterm babies) were referred to our hospital due to severe pneumonia after unsuccessful conservative management. Indications for HFOV were hypoxia (mean paO2 41.8 mm Hg with FiO2 = 0.95 and mean airway pressure = 16.6 cm H2O) and/or air leak syndrome. In all cases a sufficient oxygenation could be achieved by HFOV, followed then by stepwise reduction of FiO2 and MAP. The air leaks receded. After 12-178 h on HFOV a successful switchback to conventional ventilatory support (at FiO2 = 0.48 and MAP < 12 cm H2O) was possible, all infants were extubated 6-15 days later. Possible risks of HFOV are air leaks, a necrotizing tracheobronchitis and hemodynamic changes due to compression of the heart and great vessels. With the at the moment in Germany available oscillatory ventilators HFOV as a rescue therapy must be limited for infants with a body weight below 5-6 kg.

GM-2 gangliosidosis (Sandhoff's disease): two year follow-up by MRI.

Two children with GM-2 gangliosidosis type 0 (Sandhoff's disease) followed up by MRI at 1.5 Tesla for 1.8 years are reported. One was presymptomatic at the first MRI examination. As her neurological status deteriorated, MRI showed low signal in bilaterally, on T2-weighted images the white matter with involvement of the optic radiations. In the second, MRI correlated well with the clinical progression of the disease, showing in the different stages involvement of thalamus and basal ganglia. There was no contrast enhancement and the grey matter remained normal.

Results of parenchymal and angiographic magnetic resonance imaging and neuropsychological testing of children after stroke as neonates.

We describe the long-term follow up of infants after neonatal stroke of the middle cerebral artery (MCA). Stroke was diagnosed by CT scan in eight full-term neonates. Three dimensional (volume) magnetic resonance angiography (MRA) is a noninvasive technique that images the arterial vessels without contrast agents. All patients, aged from 1.5 to 8.4 years, were investigated by MRI and MRA and by neuropsychological tests. Cognitive development was investigated by intelligence tests, tests of visual perception, motor and language development. Out of the eight patients, seven had a retarded mental and motor development, and 50% of the children were treated for epilepsy. Seven patients had a spastic hemiparesis. Seven out of eight children showed major cognitive deficits. In all patients, MRI revealed clear parenchymal defects with variable distribution patterns. MRA studies showed abnormalities corresponding to the expected vascular distribution. Children with complications at delivery, with seizures, and an interruption of the main stem of MCA as demonstrated on MRA had the least favourable long-term follow up prognosis with severe cognitive delays.

[Hemimegalencephaly. Therapy with hemispherectomy]. / Hemimegalenzephalie. Therapie mit Hemisphärektomie.

Hemimegalencephaly is associated with a poor clinical course characterized by intractable seizures and severe encephalopathy. We present a case report of a girl with hemimegalencephaly. At the age of 9 month hemispherectomy was undertaken to preserve function of the other hemisphere. MRI and histologic examinations showed characteristic dysplastic malformations. Follow-up and the complications are described.

Neurological findings in newborn infants after extracorporeal membrane oxygenation, with special reference to the EEG.

Seventeen newborn infants were treated with extracorporeal membrane oxygenation (ECMO). Two died shortly after the start of ECMO due to the underlying disease, two died later in the course due to a lack of recovery of lung function and two others died weeks after ECMO from renal damage and a cardiac defect. Of the survivors, nine are developing normally (aged between one and four years) and two are severely disabled because of infarctions of the left hemisphere, acquired before and after ECMO. Intermittent-discontinuous EEGs did not indicate a poor prognosis if normalization of the EEG occurred within seven days. However, infarcted areas on ultrasonography, persistent EEG changes or deteriorating findings indicated disability or early death.

[Unusual symptoms in brain tumors in childhood]. / Ungewöhnliche Symptome bei Hirntumoren im Kindesalter.

Headache, nausea, ataxia and diplopia are leading symptoms of brain tumors in children. We report of 3 children with unusual symptoms and findings. Patient 1 complained of occasional headaches. Clinical examination showed neurological deficits and uveitis. Lumbar puncture revealed a pleocytosis and the oligoclonal banding study was positive. Cranial MRI demonstrated an enlarged pons. Under treatment with cortisone a clinical improvement was seen, but no change of the abnormalities in MRI. Several weeks later a biopsy was performed, which verified an astrozytoma. The second child developed a torticollis, following an accident, and later a refractory constipation was noted. A clinical evaluation was within normal limits. Several weeks later the patient complained of bladder disturbances. Patient 3 had a lateralized tic disorder without any neurologic deficits. CT showed an infratentorial tumor above the 4th ventricle. The tic disorder vanished only after the tumor was completely resected in the second operation. The reported cases demonstrate the fact that in an individual patient a brain tumor can cause unusual symptoms and findings which do not make the diagnosis obvious.

Psychiatric disturbances in children with hamartomas: a neglected somatopsychic issue. A case report.

To date, in publications on hamartomas, precocious puberty and laughing seizures have been discussed, but behavioural and cognitive abnormalities have been neglected. Therefore, we report a 14-year-old girl with a proven hamartoma, in which abnormalities of behaviour and cognition played an important role within the somatopsychic complex. In our patient, urinary incontinence during the seizures and psychiatric symptoms, such as eating disorder with obesity, school phobia, antisocial behaviour, withdrawal and cognitive problems (e.g. general slowness, deficiency of cognitive flexibility) came to the fore. The girl had not attended school regularly for almost 2 years, had stayed at home and was overtaxed psychosocially. The seizures and the urinary incontinence improved with drug treatment, but psychiatric difficulties increased and remained untreated until the girl came to a child psychiatric inpatient clinic where drug treatment and behavioural therapy were combined. During well-coordinated neurological and psychiatric treatment the laughing seizures (spontaneous, event-related, psychogenic) decreased and a considerable improvement in psychiatric and psychosocial problems was attained. Consequently, we recommend a close and timely integration of the psychiatric aspects in the treatment of children with hamartomas.

[Risk of recurrent seizures after the first afebrile grand mal seizure in childhood]. / Das Risiko wiederholter Anfälle nach dem ersten afebrilen Grand mal-Anfall im Kindesalter.

A cohort of 74 children three months to 16 years-old who presented with a first unprovoked seizure were followed for five years to assess the risk of recurrence. Children with febrile convulsions, immediate posttraumatic seizures, meningitis and encephalitis were not included. The risk of recurrence was 68% for a second seizure. 47% of the patients developed an epilepsy. 85% of recurrences occurred within the first 6 months and 100% within 2 1/2 years. A history of epilepsy in a first degree relative, age at first seizure, duration of seizure, initial EEG or neurologic status were not associated with significantly higher risk of recurrence.