Hans-Jürgen Christen

Epidemiology and Clinical Manifestations of Lyme Borreliosis in Childhood.: A Prospective Multicentre Study with Special Regard to Neuroborreliosis

ABSTRACT. Lyme borreliosis is a tick‐borne infection caused by the spirochete Borrelia burgdorferi, whose discovery in 1982 solved an aetiological mystery involving a variety of dcrmatological and neurological disorders and explained their association with Lyme disease. Lyme borreliosis occurs frequently and is readily treatable with antibiotics.

Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance spectroscopy in vivo

The brain morphology and chemistry of seven children with late infantile (4/7) and juvenile (3/7) forms of metachromatic leukodystrophy (MLD) were investigated by magnetic resonance imaging (MRI) and localized proton magnetic resonance spectroscopy (MRS). Patients who were examined at least 6 months after the onset of symptoms (6/7) had severe leukodystrophic changes on MRI. Proton MRS revealed a marked reduction of the neuronal markerN-acetylaspartate in white and grey matter and elevated lactate in demyelinated areas. In contrast to other leukodystrophies MLD patients showed a generalized increase of brainmyo-inositol (2- to 3-fold in white matter), indicating a specific role in the pathophysiology of demyelination in MLD.

Lyme Disease—Current State of Knowledge

BACKGROUND Lyme disease is the most frequent tick-borne infectious disease in Europe. The discovery of the causative pathogen Borrelia burgdorferi in 1982 opened the way for the firm diagnosis of diseases in several clinical disciplines and for causal antibiotic therapy. At the same time, speculation regarding links between Borrelia infection and a variety of nonspecific symptoms and disorders resulted in overdiagnosis and overtreatment of suspected Lyme disease. METHOD The authors conducted a selective review of the literature, including various national and international guidelines. RESULTS The spirochete Borrelia burgdorferi sensu lato is present in approximately 5% to 35% of sheep ticks (Ixodes ricinus) in Germany, depending on the region. In contrast to North America, different genospecies are found in Europe. The most frequent clinical manifestation of Borrelia infection is erythema migrans, followed by neuroborreliosis, arthritis, acrodermatitis chronica atrophicans, and lymphocytosis benigna cutis. Diagnosis is made on the basis of the clinical symptoms, and in stages II and III by detection of Borrelia-specific antibodies. In adults erythema migrans is treated with doxycycline, in children with amoxicillin. The standard treatment of neuroborreliosis is third-generation cephalosporins. CONCLUSIONS After appropriate antibiotic therapy, the outcome is favorable. In approximately 95% of cases neuroborreliosis is cured without long-term sequelae. When chronic borreliosis is suspected, other potential causes of the clinical syndrome must be painstakingly excluded.

Characterization of Borrelia burgdorferi strains in Lyme arthritis

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.

Primarily chronic and cerebrovascular course of Lyme neuroborreliosis: case reports and literature review

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.

Potential prognostic value of C-erbB-2 expression in medulloblastomas in very young children.

Purpose The expression of the c-erbB-2 oncogene was studied in childhood medulloblastoma to evaluate its prognostic value, which has been claimed previously. Patients and Methods 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. Results 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. Conclusion 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.

PERIPHERAL FACIAL PALSY IN CHILDHOOD - LYME BORRELIOSIS TO BE SUSPECTED UNLESS PROVEN OTHERWISE

ABSTRACT. 27 consecutive cases with acute peripheral facial palsy were studied for Lyme borreliosis. In 16 out of 27 children Lyme borreliosis could be diagnosed by detection of specific IgM antibodies in CSF. CSF findings allow a clear distinction according to etiology. All children with facial palsy due to Lyme borreliosis revealed lymphocytic CSF pleocytosis, whereas in cases of unknown etiology CSF was usually normal. Bilateral facial palsy occurred only in children with Lyme borreliosis. All cases with a positive history of tick bite and/or erythema migrans in the head‐neck region showed ipsilateral neurological affection suggesting a direct invasion via the affected nerve by Borrelia burgdorferi.

Hypoparathyroidism and deafness associated with pleioplasmic large scale rearrangements of the mitochondrial DNA : A clinical and molecular genetic study of four children with Kearns-Sayre syndrome

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 population (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.

Acute Flaccid Myelitis in German Children in 2016 - the Return of Polio?

BACKGROUND Although poliomyelitis has almost been eradicated worldwide, cases of a polio-like disease with asymmetrical flaccid paralysis of variable severity have been seen repeatedly in recent years. METHODS Data were collected on children treated in hospitals in the German federal states of Bavaria and Lower Saxony in 2016. The frequency of disease across Germany was estimated on the basis of voluntary reporting to the Robert Koch Institute. 16 cases were registered there for the entire year 2016. RESULTS 7 children with flaccid paralysis of acute onset were treated in the participating hospitals in the summer and fall of 2016. We describe two illustrative cases, one with a mild course and one with a severe course. Rapid diagnosis requires not only clinical neurological assessment but also neurophysiological studies, magnetic resonance imaging (MRI), and targeted microbiological testing. The characteristic features include damage to the anterior horn of the spinal cord that can be seen on MRI and/or electrophysiologically demonstrable abnormalities indicating motor neuron damage. A pathogen can hardly ever be identified in the cerebrospinal fluid, but the epidemiological context and the detection of viruses in the stool or respiratory secretions indicate that entero - viruses may be responsible. CONCLUSION The prognosis of this disease cannot be reliably assessed at first, and no specific treatment is currently available.

Lyme Borreliosis in Children

Lyme borreliosis is a common infectious disorder in children. The daily life and play routines in particular make them more likely than adults to be bitten by ticks and thus more likely to be infected by Borrelia burgdorferi. Lyme borreliosis as a clinical entity was first recognized in children suffering from arthritis (1). In the meantime, research in this field has mainly been focused on the disease in adults. Epidemiological data about the true incidence of Lyme borreliosis in childhood are still sparce. The whole clinical spectrum of Lyme borreliosis described in adults is also found in children, but age-specific differences in the relative frequency of certain manifestations, in the course of the disease as well as in diagnostic pecularities are evident (2–9).