[Congenital hemiplegia. A disease with manifold problems]. / Kongenitale Hemiplegie. Eine Krankheit mit vielen Problemen.

Congenital hemiplegia, defined as unilateral motor disability, is the hemiplegic type of cerebral palsy. The prevalence of congenital hemiplegia is estimated to be about 0.41-0.79/1000 live births. We examined 223 children (122 boys and 101 girls) suffering from congenital hemiplegia at the age of 3 months to 12 years. Mild hemiplegia was found in 31%, a moderate form in 48%, and a severe form in 21%. The upper limb was affected in more than half of the patients, only the lower extremity in one third, and both upper and lower limbs in 20%. Electroencephalographic abnormalities were found in 75.8% of the patients. The most frequent type of epilepsy was complex partial seizures (33%). Severity of the motor handicap, grade of EEG abnormalities, and the prevalence of epilepsy showed a significant correlation. The magnitude of the lesions in neuroimaging directly correlated with these three clinical variables, particularly in children with cortical and subcortical defects (84.2%). Strabismus was the most common visual impairment (17%), while hearing impairment was found in 8% of the patients. Of them, 38.3% showed no cognitive deficits, while those with severe congenital hemiplegia were found to have a lower intelligence quotient.

[Subacute sclerosing panencephalitis (SSPE)]. / Subakute sklerosierende Panenzephalitis (SSPE).

Subacute sclerosing panencephalitis is a rare progressive neurological disorder of childhood and early adolescence caused by persistent measles virus. The diagnosis is based upon characteristic clinical manifestations, periodic EEG discharges, raised antibody titre against measles/SSPE in the plasma and cerebrospinal fluid and increase of gamma-globulins in the cerebrospinal fluid. Histopathological examination shows neuronal loss, astrogliosis, demyelination, infiltration of inflammatory cells, and intranuclear inclusions in neurons, oligodendrocytes and astrocytes. In most cases nucleocapsids are detected by electron microscopy. Although treatment is still undetermined, combination of intrathecal high-dose interferon-alpha and intravenous ribavirin administered at an early stage of SSPE seems to be effective.

Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride.

OBJECTIVES: The Symptom Management After Reducing Therapy (SMART-1) study examined the combination of the dual action 5alpha-reductase inhibitor (5ARI) dutasteride, and alpha(1)-blocker tamsulosin, followed by withdrawal of tamsulosin in men with symptomatic BPH. METHODS: 327 BPH patients were randomised to 0.5mg dutasteride and 0.4 mg tamsulosin for 36 weeks (DT36) or 0.5 mg dutasteride and 0.4 mg tamsulosin for 24 weeks followed by dutasteride and tamsulosin matched placebo for the remaining 12 weeks (DT24+D12). Patients' assessment of their symptoms, IPSS at weeks 24, 30, and drug safety were evaluated. RESULTS: 77% of DT24+D12 patients felt the same/better at week 30 compared with week 24 (changes in IPSS were consistent with this finding). Of those subjects with an IPSS <20 who changed to dutasteride monotherapy at week 24, 84% switched without a noticeable deterioration in their symptoms. In the 27% of men with severe baseline symptoms (IPSS >or=20) who had withdrawal of tamsulosin therapy at week 24, 42.5% reported a worsening of their symptoms compared with 14% in the DT36 group. The regimens were well tolerated. CONCLUSIONS: Dutasteride can be used in a 24-week combination with tamsulosin, to achieve rapid onset of symptom relief in patients at risk of underlying disease progression. This symptom relief is maintained in the majority of patients after the alpha(1)-blocker is removed from the combination. Patients with severe symptoms may benefit from longer-term combination therapy.

[Diagnosis and outcome of neurotropic enterovirus infections in childhood]. / Diagnostik und klinischer Verlauf neurotroper Enterovirusinfektionen im Kindesalter.

BACKGROUND: Enterovirus infections are among the most common causes of aseptic meningitis. Worldwide there are reports about recurring outbreaks, especially during the summer. They are favoured by conditions of bad hygiene and contaminated water, transmission is predominantly through the faeco-oral route or by droplet infection. The most common species are Coxsackie B and ECHO (Enteric Cytopathogenic Human Orphan) virus. ECHO viruses have a worldwide distribution and usually occur as "summer flu" or aseptic meningitis and meningoencephalitis in toddlers and infants. Type 30 caused an outbreak of aseptic meningitis in the Rhein-Main region in summer 1997. During five months 63 children younger than 16 years were reported. PATIENTS AND METHODS: During this outbreak 18 children with prooved enterovirus infections were treated at the Frankfurt/Main University Children's Hospital. Standardized infectiological diagnostic procedures were performed and risc factors, clinical symptoms, inflammatory marker, neurophysiological findings (electroencephalography, evoked potentials) and outcome were assessed. RESULTS: The affected children were between 3 and 11 years old. Clinical symptoms were cephalgia, nausea, vomiting, meningism and seizures with fever. Virus isolation from faecal and cerebrospinal fluid (CSF) samples and the use of polymerase chain reaction (PCR) was superior to serological methods. Erythrocyte sedimentation rates showed more significant increase than C-reactive protein (CRP) and blood leukocytes. CSF pleocytosis showed high variation. Clinical course as well as prognosis and outcome were favourable. CONCLUSION: Virusisolation in stool and CSF is most promising in the diagnostic of cerebral enterovirus infections. Usually the outcome is favourable, encephalitis can occur as serious complication.

Minor head injury as cause and co-factor in the aetiology of stroke in childhood: a report of eight cases.

BACKGROUND: Traumatic stroke usually occurs after dissection of large extracranial or intracranial vessels, leading to disseminated cerebral embolism. Stretching and distorting forces in cerebral intraparenchymal end arteries can cause intimal lesions followed by an occluding thrombus. OBJECTIVE: To investigate the importance of traumatic endothelial lesions in intraparenchymal end arteries after minor head injuries. METHODS: The cases of eight children are reported. They were aged between two and seven years (mean 6.2 years), and they developed significant neurological deficits at 15 minutes to 72 hours (mean 16.3 hours) after minor head injuries. RESULTS: The the patients all had hemiparesis combined with other signs, including central facial paralysis, dysphasia, dysphagia, and extrapyramidal signs. Computed tomography or magnetic resonance imaging showed cerebral infarctions affecting branches of the middle cerebral artery (n = 3), anterior cerebral artery (n = 1), posterior cerebral artery (n = 1), and basilar artery (n = 3). These lesions affected the basal ganglia, the internal capsule, and the brain stem. Neither heart disease nor dissections of large vessels were present. Two children had prothrombotic risk factors (an increase in lipoprotein (a) and a factor V Leiden mutation). The follow up period was between three months and 13 years (mean 3.9 years). Outcome was classified according to the Glasgow outcome scale as moderate disability (n = 4), severe disability (n = 2), non-disabling sequelae (n = 1), and total recovery (n = 1). CONCLUSIONS: Minor head injuries can be cause and co-factor in the aetiology of stroke. The frequency of this may be underestimated, and detailed medical history of the days before stroke manifestation may identify more traumatic events, especially in the group of so called "idiopathic" strokes.

Acute encephalopathy as a primary manifestation of haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) is characterized anatomically by an infiltration of multiple tissues with lymphocytes and haemophagocytic histiocytes. First symptoms are usually hepatosplenomegaly, pancytopenia, and intractable fever. Up to 73% of those with HLH develop CNS involvement during the disease course. The peculiarity of the two patients presented here, a 20-month-old Italian female and a 4-year-old Moroccan female, is that the initial presenting neurological symptoms mimicked an encephalitis, anticipating the typical systemic symptoms by 1 and 4 months. They developed progressive encephalopathy accompanied by status epilepticus, one child developed a secondary hydrocephalus. In both children it was not possible to detect an underlying infection or malignant disease and there were no other cases in the family that suggested a familial form of HLH. Diagnosis and initiation of treatment was delayed because of the initial encephalopathic clinical picture and the late onset of the typical systemic features. As early diagnosis allows better therapeutical approaches, haemophagocytic lymphohistiocytosis should be considered in children with persistent or progressive findings of encephalopathy, especially in the absence of identification of a plausible pathogen.

[Fatal outcome during physiotherapy (Vojta's method) in a 3-month old infant. Case report and comments on manual therapy in children]. / Uber einen Todesfall während der Physiotherapie nach Vojta bei einem 3 Monate alten Säugling. Fallbeschreibung und Bemerkungen zur Manualtherapie bei Kindern.

Detailed clinical and neuropathological report on a fatal incident during the first manual therapy according to Vojta conducted in a 3 months old baby: during forced active rotation and head retraction the baby suffered from a bleeding into the adventitia of both her vertebral arteries at the level of C1 prompting ischemia of the caudal brainstem with subarachnoid haemorrhage around. It has to be suggested that similar cases already have occurred but have not been reported yet. There might be a time lag between the performance of physiotherapy and the beginning of neurologic symptoms. The risks of manual therapy in children will be discussed.

Midline developmental anomalies with lipomas in the corpus callosum region.

Three children with complete or partial callosal aplasia and intracranial lipoma in the corpus callosum region were investigated. Two lipomas were tubulonodular; one replaced the entire corpus callosum structure. Accompanying anomalies affected the cingulate gyrus, septum pellucidum, and choroid plexus. In one case, diagnosis was made in utero in the 25th gestational week by ultrasonography; in the second case it was made on the first day of life, also by screening ultrasonography. Two children had mild spastic distal diparesis; one complained of chronic headache. Electroencephalography showed no abnormalities; epilepsy anamnesis was negative. Somatosensory and visual evoked potentials showed prolonged conduction in two cases. Surgery was not indicated. Because of the risk of developing epileptic seizures, regular electroencephalographic follow-up investigations are essential.

Lyme borreliosis mimicking central nervous system malignancy: the diagnostic pitfall of cerebrospinal fluid cytology.

We report two children with acute loss of neurological functions and signs of an increased intracranial pressure. Imaging techniques ruled out space occupying lesions, whereas CSF cytology indicated CNS involvement of a non-Hodgkin lymphoma in the form of abnormal lymphocytic pleocytosis with malignancy criteria fulfilling lymphoid cells. CSF protein electrophoresis and Borrelia burgdorferi serology revealed neuroborreliosis which was successfully treated with antibiotic therapy. The malignancy mimicking cytology is based on a blastoid transformation of B- and T-lymphocytes due to the antigenic stimulus of B. burgdorferi infection. Lymphoid cells in the CSF of a patient with acute or chronic neurological symptoms raise the differential diagnosis of inflammatory etiology versus CNS lymphoma. Monomorphism and higher quantity of the lymphoid cells point to CNS lymphoma. A lower quantity and polyclonal pattern of lymphoid cells associated with an elevated protein fraction caused by intrathecal immunoglobulin synthesis suggest an inflammatory etiology.

Acute necrotising encephalopathy of childhood after exanthema subitum outside Japan or Taiwan.

Acute necrotising encephalopathy of childhood (ANE) is an uncommon disease which predominantly affects infants and young children living in Japan and Taiwan. A multifocal encephalopathy with symmetrical lesions in the thalamus, tegmentum of the brain stem, cerebral periventricular white matter and cerebellar medulla is characteristic. We present the imaging features in a 4-year-old Japanese boy who had been living in Germany for 2 1/2 years before presentation.

Post-trauma coagulation and fibrinolysis in children suffering from severe cerebro-cranial trauma.

UNLABELLED: The present study was designed to evaluate the post-trauma haemostatic changes in 27 children with severe cranio-cerebral trauma defined by a modified Glasgow Coma Score (GCS) < 10. Blood samples for coagulation studies (fibrinogen, von Willebrand factor (vWf), factor VIII:C, antithrombin, protein C, plasminogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI), D-dimer) were obtained within two hours of admission, 24 h later, and on days 3-5, 7-9, 21 and 35. Data of this study indicate that alterations of coagulation in paediatric patients are similar to those in adults: On hospitalisation, activated haemostasis was found with decreased fibrinogen, antithrombin and protein C along with enhanced t-PA and PAI. Twenty-four hours later, hypercoagulability with significantly increased vWF and fibrinogen started, with a peak level within the second week. Within 24 h of admission, 17 children developed disseminated intravascular coagulation (DIC) with a clear-cut decrease of antithrombin and fibrinogen together with platelet consumption and enhanced D-dimer. The outcome of children with DIC was significantly poorer than in those without DIC. Complete recovery was seen in five patients; sequelae no handicap and moderate disability were each found in six patients. Severe disability was diagnosed in two children, and fulminant DIC with lethal outcome occurred in eight patients. The GCS (P < 0.01) and the occurrence of DIC (P < 0.005) showed the strongest association with the patients' clinical outcome. CONCLUSION: Our data underline the significance of post-trauma disturbances of the haemostatic system for the clinical course and outcome in children with severe cranio-cerebral injuries.

[Nervous system manifestations in HIV infected children]. / Affektionen des Nervensystems bei perinatal HIV-infizierten Kindern.

In 34 perinatally HIV infected children time of manifestation, type and treatability of neurologic disorders were investigated for a period of 7 years (1987-1994). Neurological investigations were done every 6 months; EEG and MRI/CT were examined initially in the asymptomatic stage and were repeated when neurologic Symptoms occurred. Zidovudine therapy was started after onset of symptoms, dosage was raised, when treatment with Zidovudine had already begun (600-720 mg/m2/day). Various neurological manifestations were seen in 4 of 12 patients in stage B (33%) and in 11 of 14 children in AIDS (80%). 7 of the 14 AIDS-patients (50%) developed a subacute progressive course or progressive plateau course and 4 of 14 (30%) a static course of encephalopathy. Pathological changes in EEG were seen in 54% of investigated patients with neurological deficits. Neuroimaging revealed pathological findings in all symptomatic subjects, 6 of 11 patients in AIDS (55%) has a severe general cerebral atrophy and multifocal white matter lesions. Zidovudine had a positive temporary effect from 6 to 12 months in 5 of 11 treated patients (45%). At present a thorough neurological examination is the most sensitive method to detect neurological impairment in HIV infected children. In most cases CT/MRI scan provides information about the course of the encephalopathy. Antiretroviral therapy has a limited benefit, if neurologic symptoms start after the second year of life.

Accumulation of nuclear p53 protein and prognosis of astrocytomas in childhood and adolescence.

The aim of the study was to investigate whether nuclear immunopositivity for p53 is a factor of prognostic significance in astrocytomas of childhood and adolescence. Paraffin-embedded tissues of astrocytomas (10 WHO grade II, 11 WHO grade III) from 21 patients under 18 years of age, when operated for the first time, were studied immunohistochemically. We used a set of 6 different antibodies against p53, suitable for paraffin section (PAb1801, PAb240, DO-1, DO-7, BP53-12, CM-1). The intensity of the nuclear staining was scored and the percentage of stained nuclei counted. A tumor was scored positive if at least 10% of nuclei showed at least medium staining intensity with at least 1 primary antibody. No single antibody detected all cases designated immunopositive. This shows the advantage of using a set of antibodies. The time of survival in the immunopositive cases was significantly shorter, but immunopositivity was correlated with grade III (WHO). Comparing the time of survival between p53-immunopositive and -immunonegative grade III (WHO) astrocytomas no significant difference was found. We conclude that p53 immunoreactivity is not an independent unfavorable prognostic factor in astrocytomas of childhood and adolescence.

[Schimmelpenning-Feuerstein-Mims syndrome and its neurologic manifestations. 6 personal cases and review of the literature]. / Das Schimmelpenning-Feuerstein-Mims-Syndrom und seine neurologische Symptomatik. 6 eigene Kasuistiken und Literaturübersicht.

The Schimmelpenning-Feuerstein-Mims-syndrome includes deformities and dysplasias of the skin, eyes, brain, skeleton, and heart. It may result from a malformation of the ectodermal and mesodermal blastoderm in the third week of gestation. We here report on 6 patients who presented between 1977 and 1993 in comparison with those cases in the literature. All children presented neurologic symptoms. The major symptom was a linear epidermal nevus. In addition we found mental retardation, convulsions, asymmetries of the cranial structures or dilated cerebral ventricles ipsilateral to the nevus. One child had a defect of the skull and scalp, a symptom not previously mentioned in the literature. Our patients exhibited a wide phenotypice spectrum ranging from mild to severe forms. Severe neurological symptoms were also found in patients despite minimal dermal involvement.

[Neurological complications in infectious endocarditis]. / Neurologische Komplikationen bei infektiöser Endocarditis.

Despite considerable progress in both diagnostic studies and therapeutic management serious complications of infectious endocarditis have become rather more common. Next to intracardiac complications arterial embolization to the central nervous system is the second most common life-threatening event, which might lead to infarction, hemorrhage, mycotic aneurysm and/or metastatic infection with a wide spectrum of neurological symptoms and an overall very poor prognosis. The most effective prevention of neurological complications is the early diagnosis of infectious endocarditis with isolation of the infecting agent and adequate antimicrobial chemotherapy in combination with well-timed cardiosurgical measures. Computed tomography and cerebral angiography is mandatory in any patient with neurological symptoms to check the need for a neurosurgical intervention as well as in patients assigned for anticoagulation for cardiac reasons.

Cytomegalovirus myelitis in perinatally acquired HIV.

A 7 year old child perinatally infected with HIV who died from progressive muscular paralysis and central nervous respiratory failure is described. Cytomegalovirus (CMV) prophylaxis with a special intravenous CMV hyper-immunoglobulin had been successfully conducted for more than four years. Macroscopic and microscopic immunohistochemical examination of the spinal cord revealed a diffuse CMV infiltration of the entire myelon. CMV infected cells were identified as astrocytes, oligodendrocytes, neurons, macrophages, ependymal, endothelial, and Schwann cells. Other organs had no signs of CMV infection. Central nervous spinal CMV infection was most probably due to insufficient penetration of the blood-brain barrier by the CMV hyper-immunoglobulin. In suspicious cases early spinal magnetic resonance imaging (1.5 tesla) combined with an examination of urine and cerebrospinal fluid for CMV is recommended.

[Post-traumatic epilepsy]. / Posttraumatische Epilepsien.

There might be 3 different forms of epilepsy following head injury: earliest seizures with occasional characteristics, early seizures prompting considerations of differential diagnosis, and, late seizures which might have a chronic course = posttraumatic epilepsy proper. The risks to have posttraumatic epilepsy for a child suffering from head injury are: penetrating cranial trauma, early seizures, intracranial hemorrhage, unconsciousness > 24 hours, depressed fracture with dural laceration and unconsciousness > 24 hours, fractures on the base of the skull, focal synchronous activity in the EEG which is related to the site of brain injury. If a or > or = 2 of b-g are given we recommend prophylactic antiepileptic therapy: in the younger (< 5 years) with a low dose of phenobarbital and in the elder (> 5 years) carbamazepine for at least 2 years of treatment.