H J Christen

Georg-August-Universität Göttingen, Göttingen, Lower Saxony, Germany

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Publications (55)183.21 Total impact

  • Aktuelle Neurologie 01/2004; 31(S 1). · 0.32 Impact Factor
  • H.-J. Christen, H. Eiffert
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    ABSTRACT: Die Lyme-Borreliose ist die hufigste durch Zecken bertragene Infektionskrankheit. Ihre Entdeckung vor 25Jahren bildete einen Meilenstein in der modernen Infektiologie. Kinder sind hufiger als Erwachsene von Zeckenstichen betroffen und tragen damit ein hheres Infektionsrisiko. Als Multisystemerkrankung manifestiert sich die Lyme-Borreliose bei 75% der Flle mit Hautsymptomen, das Zentralnervensystem und die Gelenke sind deutlich seltener betroffen. Die akute periphere Fazialisparese und die serse Meningitis prgen das klinische Bild der Neuroborreliose im Kindesalter. Lyme-Borreliose ist eine klinische Diagnose, bei der Anamnese, klinischer Befund und Antikrperbefunde gleichberechtigt gewrdigt werden. Die spezifische Antikrperdiagnostik ist mit Sensitivitts- und Spezifittsproblemen behaftet, was das Risiko der berdiagnose und -therapie beinhaltet. Speziell bei der Neuroborreliose ist der Liquorbefund wichtig: Eine Liquorpleozytose gilt als Conditio sine qua non fr die Diagnose. Die Prognose der Lyme-Borreliose ist umso gnstiger, je frhzeitiger antibiotisch behandelt wird. Gesicherte Langzeitfolgen einer Neuroborreliose sind bei Kindern nicht bekannt, knnen aber noch nicht gnzlich ausgeschlossen werden.Lyme borreliosis is the most frequent tick-borne disorder. Its discovery 25years ago was a milestone in the field of infectious diseases. Children are especially prone to tick bites and therefore at special risk for Lyme borreliosis. Lyme borreliosis is a multisystem disorder which affects the skin in three-fourths of the cases (mainly erythema migrans) and the central nervous system and the joints clearly less frequently. In childhood acute peripheral facial nerve palsy and aseptic meningitis dominate the clinical spectrum of neuroborreliosis. Lyme borreliosis is a clinical diagnosis which is established on the basis of the history, the clinical findings, and the antibody results. Specific antibody diagnosis is complicated by the problem of insufficient sensitivity and specificity. The consequence is the risk of overdiagnosis and overtreatment. In neuroborreliosis the CSF findings are especially helpful. CSF pleocytosis is mandatory for the diagnosis of neuroborreliosis. Early and effective antibiotic treatment guarantees a good prognosis of Lyme borreliosis with quick resolvement of symptoms. Long-term sequelae of neuroborreliosis have not been proved in children, but cannot yet be excluded.
    Monatsschrift Kinderheilkunde 01/2003; 151(11):1146-1155. · 0.19 Impact Factor
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    ABSTRACT: To determine whether primary or secondary growth hormone (GH) deficiency has a causative role in linear growth retardation, a key feature in Rett syndrome (RTT). In 38 patients with Rett syndrome a variable set of investigations was performed including assays of growth and thyroid hormones, gonadotropins, gonadal and adrenal steroids and determination of bone age. Not all measurements were attainable from all patients. In three patients the 24-h growth hormone secretion profile was evaluated using the pulsar method. The bone age determined in 24 patients was found to be normal in 8, retarded in 9 and accelerated in 7 patients. Insulin-like growth factor (IGF)-1 was low in 8 out of 23 patients. IGF-binding protein (IGFBP)-3 and insulin and arginine-stimulated growth hormone secretion were both normal, indicating normal GH secretion in the majority of patients. The 24-h GH secretion profile in the first patient showed a normal day/night rhythm and a normal increase in nocturnal GH secretion. The second patient's overall GH secretion was normal but there was no day/night rhythm. The third patient showed borderline low GH secretion. Normal age-appropriate plasma values were found for the thyroid hormones (T4, TSH), TSH-night rhythm, oestradiol, prolactin and cortisol (08.00, 18.00). Our study provides no evidence that growth retardation in RTT is caused by growth hormone deficiency. A disturbed hypothalamic control cannot be excluded but it is unlikely that this is the major cause of growth retardation in RTT.
    Acta Paediatrica 12/2001; 90(11):1257-61. · 1.97 Impact Factor
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    M Wilke, H Eiffert, H J Christen, F Hanefeld
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    ABSTRACT: As part of an ongoing study aiming to define the clinical spectrum of neuroborreliosis in childhood, we have identified four patients with unusual clinical manifestations. Two patients suffered from a primarily chronic form of neuroborreliosis and displayed only non-specific symptoms. An 11 year old boy presented with long standing symptoms of severe weight loss and chronic headache, while the other patient had pre-existing mental and motor retardation and developed seizures and failure to thrive. Two further children who presented with acute hemiparesis as a result of cerebral ischaemic infarction had a cerebrovascular course of neuroborreliosis. One was a 15 year old girl; the other, a 5 year old boy, is to our knowledge the youngest patient described with this course of illness. Following adequate antibiotic treatment, all patients showed substantial improvement of their respective symptoms. Laboratory and magnetic resonance imaging findings as well as clinical course are discussed and the relevant literature is reviewed.
    Archives of Disease in Childhood 08/2000; 83(1):67-71. · 3.05 Impact Factor
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    ABSTRACT: Rhabdoid tumors of the central nervous system are rare malignancies with a still almost uniformly fatal outcome. There is still no proven curative therapy available. We report our experience with nine patients with central nervous system rhabdoid tumors. Gross complete surgical removal of the tumor was achieved in six patients. Seven patients received intensive chemotherapy. Four of these were treated in addition with both neuroaxis radiotherapy and a local boost directed to the tumor region, while two patients received local radiotherapy only. The therapy was reasonably well tolerated in most cases. Despite the aggressive therapy, eight of the nine patients died from progressive tumor disease, and one patient died from hemorrhagic brain stem lesions of unknown etiology. The mean survival time was 10 months after diagnosis. Conventional treatment, although aggressive, cannot change the fatal prognosis of central nervous system rhabdoid tumors. As these neoplasms are so rare, a coordinated register would probably be a good idea, offering a means of learning more about the tumor's biology and possible strategies of treatment.
    Child s Nervous System 05/2000; 16(4):228-34. · 1.24 Impact Factor
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    ABSTRACT: Foix-Chavany-Marie syndrome (FCMS) is a distinct clinical picture of suprabulbar (pseudobulbar) palsy due to bilateral anterior opercular lesions. Symptoms include anarthria/severe dysarthria and loss of voluntary muscular functions of the face and tongue, and problems with mastication and swallowing with preservation of reflex and autonomic functions. FCMS may be congenital or acquired as well as persistent or intermittent. The aetiology is heterogeneous; vascular events in adulthood, nearly exclusively affecting adults who experience multiple subsequent strokes; CNS infections; bilateral dysgenesis of the perisylvian region; and epileptic disorders. Of the six cases reported here, three children had FCMS as the result of meningoencephalitis, two children had FCMS due to a congenital bilateral perisylvian syndrome, and one child had intermittent FCMS due to an atypical benign partial epilepsy with partial status epilepticus. The congenital dysgenetic type of FCMS and its functional epileptogenic variant share clinical and EEG features suggesting a common pathogenesis. Consequently, an increased vulnerability of the perisylvian region to adverse events in utero is discussed. In honour of Worster-Drought, who described the clinical entity in children 40 years ago, the term Worster-Drought syndrome is proposed for this unique disorder in children.
    Developmental Medicine & Child Neurology 03/2000; 42(2):122-32. · 2.68 Impact Factor
  • P Huppke, H J Christen, B Sattler, F Hanefeld
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    ABSTRACT: We report two brothers with mental retardation, lymphoedema of the limbs and facial anomalies. Hennekam et al. (Am J Med Genet 34:593-600; 1989) described four patients with identical signs and intestinal lymphangiectasia. To confirm the diagnosis of Hennekam syndrome we undertook a duodenal biopsy from the older brother which revealed intestinal lymphangiectasia. So far only one patient with Hennekam syndrome and cerebral abnormalities has been described. This patient presented with pachygyria in the parietal area. Cerebral MRI in our two cases revealed small subcortical hyperintensities in both patients and a large cystic lesion in the younger patient probably representing an old media infarction.
    Clinical Dysmorphology 02/2000; 9(1):21-4. · 0.38 Impact Factor
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    ABSTRACT: To evaluate intracranial venous haemodynamics in craniosynostosis noninvasively, we measured the blood flow velocities and pulsatility indices in the superior sagittal sinus (SSS) and the middle and the anterior cerebral artery during the perioperative course in 21 children undergoing repair of craniosynostosis involving the midline sutures, using transcranial colour-coded duplex sonography (TCCS). An age-matched group of 12 healthy children was examined in like manner for comparison. In the healthy group, the mean pulsatility index (PI) in the SSS was 0.22 and the mean resistance index (RI) 0.20. The mean preoperative PI and RI in the synostosis group were significantly higher [0.41 and 0.34, respectively (P<0.01)], but fell to 0.19 and 0.17 (P<0.01) in the postoperative course. Our results indicate that in craniosynostosis there is an altered venous haemodynamics in the SSS, which can be observed noninvasively by TCCS.
    Child s Nervous System 03/1999; 15(2-3):110-6; discussion 117-8. · 1.24 Impact Factor
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    ABSTRACT: We report on 3 sporadic cases of in utero onset megalencephaly. Children were born to healthy nonconsanguineous parents after uneventful pregnancies. Head circumferences were just above the 97th centile at birth in 2 patients, 2 cm above the 97th centile in 1 patient, and subsequently increased to 4.5-6.5 cm above the 97th centile at age 5 years. All patients completely lacked motor and speech development and showed very little intellectual progress. There was a distinctive facial aspect with frontal bossing, low nose bridge, and large eyes, but no cutaneous abnormalities and no signs of other organ involvement. Magnetic resonance imaging showed bilateral megalencephaly with a broad corpus callosum, enlarged white matter, and focally thick gray matter, resulting in pachygyric appearance of the cortex. Opercularization was incomplete, and the Sylvian fissures were wide. Somatosensory evoked potentials in 1 patient showed normal latencies of cervical and contracortical potentials but bilaterally increased cortical amplitudes. To the best of our knowledge, no similar case observations have been recorded previously.
    American Journal of Medical Genetics 10/1998; 79(3):161-7.
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    ABSTRACT: Primary malignant rhabdoid tumor (MRT) of the central nervous system is an extremely aggressive tumor predominantly related to early childhood, with characteristic histopathological findings but unclear histogenesis. Owing to its low incidence, little knowledge exists concerning the best therapeutic strategy. Three children of our hospital with MRT of the brain underwent a maximum tumor resection followed by multidrug chemotherapy and radiation therapy to the craniospinal axis. Relapse was disseminated along the spinal subarachnoid spaces in one child and occurred at the primary tumor site in the other two patients. Maximum survival was 15 months from diagnosis. A review of patients reported in the literature and a comparison to our patients reveals a high propensity to early local relapse and meningeal dissemination. In the absence of more effective therapeutic options, we recommend multidisciplinary treatment of patients in good general condition and with resectable disease. In particular, following radiation therapy, tumor remissions and delay of tumor regrowth have been observed.
    International Journal of Radiation OncologyBiologyPhysics 08/1998; 41(5):1013-9. · 4.52 Impact Factor
  • H Eiffert, A Karsten, R Thomssen, H J Christen
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    ABSTRACT: In the study presented, we investigated whether Lyme arthritis is associated with a particular Borrelia burgdorferi genospecies. Using the PCR technique, in 7/11 samples of synovial fluid of patients with Lyme arthritis a part of the ospA-gene was identified and the strains characterized by sequencing of the amplified DNA. Borrelia burgdorferi sensu stricto was found in 3 patients, B. garinii in 3, and B. afzelii in 1 patient. In conclusion, Lyme arthritis is caused by all 3 human pathogenetic genospecies which are actually known. For clinical practice PCR proved to be a rather insensitive diagnostic method, but may confirm the diagnosis of Lyme arthritis in doubtful cases.
    Scandinavian Journal of Infectious Diseases 02/1998; 30(3):265-8. · 1.71 Impact Factor
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    ABSTRACT: Cerebral metabolites of a patient with linear nevus sebaceus syndrome and hemimegalencephaly were determined at 18 and 30 months of age by localized proton magnetic resonance spectroscopy. Clinically, the patient suffered from hemiparesis and epileptic seizures. At 18 months of age, spectroscopy of the enlarged hemisphere revealed decreased N-acetylaspartate mainly in parietal white matter relative to the unaffected hemisphere. One year later, white matter studies indicated both reduced N-acetylaspartate and elevated myoinositol. In insular gray matter the previously normal concentrations of creatine, choline-containing compounds, myoinositol, and glutamine were increased. The findings are consistent with mild neuroaxonal loss or damage (white matter) and glial proliferation (cortical gray and white matter) of the affected hemisphere. The metabolic disturbances indicate disease progression but are less pronounced than in older patients with hemimegalencephaly.
    Pediatric Neurology 02/1998; 18(2):176-80. · 1.42 Impact Factor
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    ABSTRACT: Intrakraniale Keimzelltumoren sind seltene Tumoren. Sie verursachen abhänging von ihrer Lokalisation unterschiedliche klinische Symptome. Zusätzlich können sie durch Sekretion von Choriongonadotropin (β-HCG) selbst endokrin aktiv sein und bei Jungen mit einer sexuellen Frühreife einhergehen. Wir berichten über 5 Patienten mit intrakranialen Keimzelltumoren. Zwei der 5 Patienten hatten einen suprasellären Tumor, der sich in beiden Fällen durch einen Diabetes insipidus manifestierte. Bei einem der 2 Patienten entwickelten sich weitere hypothalamisch-hypophysäre Funktionseinbußen, der andere Patient bot zusätzlich eine Pubertas praecox. Bei 2 Kindern ging der Tumor von der Pinealisregion aus. In diesen beiden Fällen stand die Hirndrucksymptomatik im Vordergrund. Einer dieser 2 Patienten hatte vor der Diagnosestellung bei exzessiver β-HCG-induzierter Testosteronproduktion einen Priapismus entwickelt. Der 5. Patient hatte einen von der Basalganglien ausgehenden Tumor, der sich durch eine Hemiparese manifestierte. Diskussion: Erworbene Defekte des hypothalamo-hypophysären Systems, insbesondere der Diabetes insipidus, aber auch die Pubertas praecox bei Jungen müssen an einen intrakranialen Keimzelltumor denken lassen, auch wenn Hirndruckzeichen und neurologische Symptome lange fehlen. Intracranial germ cell tumors are a rare finding. They can cause a variety of different clinical symptoms due to the location of the tumor. Additionaly they can secret β-HCG so that boys develop precocious puberty. We present the case history of five patients with intracranial germ cell tumors. Two of these patients had germ cell tumors of the suprasellar region; both developed diabetes insipidus. One of the two presented hypothalamic-pituitary deficits as well, the other patient showed signs of precocious puberty. The tumor of two further patients originated in the pineal region, at the time of diagnosis causing symptoms due to high intracranial pressure. One of these two patients developed priapism due to extremely elevated testosteron levels induced by his β-HCG secreting tumor. A fifth patient with a tumor of the basal ganglia developed hemiparesis. Discussion: Acquired deficits of the hypothalmic-pituitary system or precocious puberty can be symptoms of intracranial germ cell tumors even if neurological signs are missing.
    Monatsschrift Kinderheilkunde 01/1998; 146(6):585-589. · 0.19 Impact Factor
  • J Behnke, H J Christen, K Mursch, E Markakis
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    ABSTRACT: Between July 1987 and June 1994 we operated upon 30 consecutive children suffering from endophytic intra-axial tumors located in the pons and/or medulla oblongata. The 25 children operated on between July 1987 and October 1993 whose postoperative course could be assessed for a minimum of 2 years after operation were included in this study. Operability of a brain stem tumor was shown to be independent of its size. A gross tumor resection between 80% and 100% could be performed in half these cases, and subtotal or partial resection in the other half. The radicality of resection was not influenced by tumor histopathology, but was dependent on intraoperative findings relating to its consistency, infiltration, and visibility. On follow up, 15 of the 25 children were found to have died within the period of 2 years. Two children died in the immediate postoperative period (at 2 days and 2 weeks after surgery), of acute brain stem swelling and an unsuspected bleeding disorder, respectively. The other 13 of these 15 children died of tumor progression between 1 and 19 months after operation, with a median survival time of 9 months. In the group of the surviving 10 children the histopathology was grade I astrocystoma in 6 cases, angioma in 2 cases, and grade II oligodendroglioma and grade II ependymoma in 1 case each. Postoperatively, most of the children showed some increase in their preoperative deficits, but recovered after 2-3 months. After 2 years, 10 of the 25 children who were followed up are alive and 9 of them attend regular school or kindergarten.
    Child s Nervous System 04/1997; 13(3):135-46. · 1.24 Impact Factor
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    ABSTRACT: The cerebral phenotype of X-linked adrenoleukodystrophy (ALD) is a rapidly progressive neurodegenerative disorder characterized by a cerebral inflammatory response and elevated very long-chain fatty acids (VLCFA). Interferon-beta (INFB) is known to suppress the synthesis of tumour necrosis factor alpha and interferon-gamma, which have been reported to be elevated in the margin of the areas of demyelination in ALD brains. We report on treatment with interferon-beta in 8 patients with cerebral ALD, who additionally received glycerol trioleate/glycerol trierucate. INFB-1 a (Rebif, Serono, Switzerland) was given subcutaneously once a week, 3 million units for the first 3 months and 6 million units for the next 9 months. All patients showed an unimpeded progression of neurological symptoms during INFB therapy. Therapy was stopped within 6 months in 4 patients because of the fast neurological deterioration with loss of walking. In all patients the MRI demonstrated a progression of demyelination with a qualitatively unchanged gadolinium enhancement. Further studies are needed to elucidate the pathomechanism of demyelination in ALD in order to find an effective therapy for cerebral ALD patients.
    Journal of Inherited Metabolic Disease 04/1997; 20(1):59-66. · 4.07 Impact Factor
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    ABSTRACT: In four children with hypoparathyroidism and deafness as initial major manifestations of Kearns-Sayre syndrome, a unique pattern of mitochondrial DNA rearrangements was observed. Hypocalcemic tetany caused by PTH deficiency started between age of 6-13 y and was well controlled by small amounts of 1.25-(OH)2-cholecalciferol. Rearranged mitochondrial genomes were present in blood cells of all patients and consisted of partially duplicated and deleted molecules, created by the loss of 7813, 8348, 8587, and 9485 bp, respectively. The deletions were localized between the origins of replication of heavy and light strands and encompassed at least eight polypeptide-encoding genes and six tRNA genes. Sequence analysis revealed imperfect direct repeats present in all rearrangements flanking the break-points. The duplicated population accounted for 25-53% of the mitochondrial genome and was predominant to the deleted DNA (5-30%) in all cases. The proportions of the mutant populations (30-75%) correlated with the age at onset of the disease. We conclude that, unlike heteroplasmic deletions, pleioplasmic rearrangements may escape selection in rapid-dividing cells, distribute widely over many tissues, and thus cause multisystem involvement. Hypoparathyroidism and deafness might be the result of altered signaling pathway caused by selective ATP deficiency.
    Pediatric Research 03/1997; 41(2):193-200. · 2.67 Impact Factor
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    ABSTRACT: Apneusis is a disturbance of respiratory rhythm characterized by severely prolonged inspiratory effort. It may occur after damage to the respiratory network within the lower brain stem and pons from an overdose of central nervous system depressants, blockade of glutamate receptors, asphyxia, hypoxia, or ischemia. Experimental studies conducted on laboratory mammals, such as anesthetized cats and rats, suggest that apneusis results mostly from depression of glutamatergic synaptic processes that are necessary for activation of inhibitory mechanisms that terminate inspiration. The impairment of synaptic transmission leads to prolonged inspiratory efforts and apneustic discharges of brainstem respiratory neurons. Apneustic patterns can be consistently converted to normal by administration of serotonin type 1A (5-HT1A) receptor agonists. This observation encouraged a treatment of severe apneusis with buspirone, an agonist for 5-HT1A receptors, in a child after neurosurgery for an astrocytoma in the pons and medulla oblongata. Oral administration of buspirone produced a prompt and highly effective remission of apneusis without side effects. Treatment with 5-HT1A agonists, therefore, might offer a novel and effective pharmacotherapy against apneustic disturbances of breathing.
    Journal of Pediatrics 02/1997; 130(1):89-94. · 4.04 Impact Factor
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    ABSTRACT: Aromatic L-amino acid decarboxylase (AADC) deficiency results in an impaired synthesis of catecholamines and serotonin, and has been reported only in two middle eastern families. We report on a European family with an affected child. The child showed the characteristic clinical picture of an extrapyramidal movement disorder, oculogyric crises and vegetative symptoms seen in the three patients described previously. Treatment with a combination of the AADC cofactor pyridoxine, the monoamine oxidase B inhibitor selegiline and bromocriptine was started during the fifth year of life and showed only a moderate clinical improvement in contrast to patients who have been treated since the first year of life.
    European Journal of Paediatric Neurology 02/1997; 1(2-3):67-71. · 1.98 Impact Factor
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    ABSTRACT: The cerebral phenotype of X-linked adrenoleukodystrophy (ALD) is a rapidly progressive neurodegenerative disorder characterized by a cerebral inflammatory response and elevated very long-chain fatty acids (VLCFA). Interferon-ß (INFB) is known to suppress the synthesis of tumour necrosis factor a and interferon-?, which have been reported to be elevated in the margin of the areas of demyelination in ALD brains. We report on treatment with interferon-ß in 8 patients with cerebral ALD, who additionally received glycerol trioleate/glycerol trierucate. INFB-1a (Rebif, Serono, Switzerland) was given subcutaneously once a week, 3 million units for the first 3 months and 6 million units for the next 9 months. All patients showed an unimpeded progression of neurological symptoms during INFB therapy. Therapy was stopped within 6 months in 4 patients because of the fast neurological deterioration with loss of walking. In all patients the MRI demonstrated a progression of demyelination with a qualitatively unchanged gadolinium enhancement. Further studies are needed to elucidate the pathomechanism of demyelination in ALD in order to find an effective therapy for cerebral ALD patients.
    Journal of Inherited Metabolic Disease 01/1997; 20(1):59-66. · 4.07 Impact Factor
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    ABSTRACT: The expression of the c-erbB-2 oncogene was studied in childhood medulloblastoma to evaluate its prognostic value, which has been claimed previously. Tumor material from 45 patients < 15 years old at diagnosis was studied using 3 monoclonal antibodies against the internal and external domains of the c-erbB-2 oncogene product. Six of the 45 (13%) tumor specimens were found to be positive. C-erbB-2 expression was found more often in patients < 3 years old at diagnosis (4 of 15 patients, 27%) than in older patients (2 of 30, 6.6%). During the follow-up period (5.8 +/- 2.8 years) all patients with c-erbB-2 expression died of disease (after 1.2 +/- 0.7 years). Kaplan-Meier estimation revealed a highly significant correlation of c-erbB-2 expression and survival (p = 0.002). A further study of the expression of synaptophysin and the glial fibrillary acidic protein (GFAP) in the 45 tumors revealed a negative correlation of the expression of c-erbB-2 and these proteins. C-erbB-2, which may be predominantly expressed by less differentiated tumors, was found to delineate a poorer prognostic subgroup, especially when diagnosed in patients < 3 years old.
    Journal of Pediatric Hematology/Oncology 01/1997; 19(6):510-5. · 0.97 Impact Factor

Publication Stats

995 Citations
183.21 Total Impact Points

Institutions

  • 1992–2001
    • Georg-August-Universität Göttingen
      • Faculty of Medicine
      Göttingen, Lower Saxony, Germany
  • 1989–2000
    • Universitätsmedizin Göttingen
      • • Department of Ophthalmology
      • • Department of Medical Microbiology
      • • Division of Neuropediatrics
      Göttingen, Lower Saxony, Germany