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Biomedical subjects

H Siemes

Publications and source records attributed to H Siemes.

At least 19 recordsLinked to original sources
PubMed1998

[Recommendations for blood studies and clinical monitoring in early detection of valproate-associated liver failure. Results of a consensus conferences 9 May - 11 May 1997 in Berlin].

Valproate is a frequently used antiepileptic drug. It is associated with rare but serious adverse effects like liver failure. The first symptom is impairment of the patient's well being. Isolated changes of standard laboratory liver parameters are not reliable early indicators. Thus, according to the knowledge of today, prophylactic blood screening cannot predict complications. On the contrary, clinical symptoms are the most relevant indicators of impending complications, eventually supported by laboratory findings. An abrupt withdrawal of valproate and administering carnitin in parallel can interrupt the otherwise fatal course of the complication and induce a subsequent recovery. At a Consensus Conference the current knowledge about early detection and therapy of the valproate-induced serious hepatotoxicity was discussed. The results regarding recommended laboratory screening, as well as diagnostic and therapeutic strategies are reported.

Adolescent↗
PubMed1998

Long-term follow-up study of vigabatrin in pretreated children with West syndrome.

A multicentre, long-term, open-label, add-on study of vigabatrin was undertaken in 23 pretreated children with infantile spasms. After 3 months of vigabatrin therapy 11 of the 23 patients had become seizure-free. At this time two-thirds of these 11 children still received other antiepileptic drugs (AEDs) in addition to vigabatrin (mostly valproic acid and/or dexamethasone). After a mean follow-up time of 5 1/4 years (range: 4 1/4-6 1/2) 72% of 18 evaluable patients (two children died, three were lost to follow-up) revealed seizure freedom for at least 1 year. The mean duration of vigabatrin therapy had been 2 1/2 years (range: 2 weeks to 4 3/4 years). Two-thirds of the 18 children continued to take AEDs, three of them undergoing vigabatrin monotherapy. Relapses of infantile spasms had occurred in 14% of the children. The rate of vigabatrin side effects (10%) was low. At follow-up, the EEG of 13 and the 18 patients demonstrated focal or multifocal epileptic discharges. Fifty-five percent had developed another epilepsy (focal epilepsy, secondary generalized epilepsy or myoclonic-astatic epilepsy). With respect to mental functions, three children were normal or slightly retarded, four showed moderate retardation and 11 revealed severe or very severe retardation. This long-term result is comparable to that in ACTH studies with unselected patients. The conclusions are: (1) vigabatrin is an effective drug for the short-term and long-term treatment of refractory infantile spasms; (2) the relapse rate is low; (3) vigabatrin is well tolerated; (4) with respect to secondary epilepsies and mental functions the long-term outcome in these pretreated children is similar to that in earlier studies with ACTH or corticosteroids.

Adrenocorticotropic Hormone↗
PubMed1998

Quantification of cerebrospinal fluid proteins in children by high-resolution agarose gel electrophoresis.

Physiologic alterations in cerebrospinal fluid proteins occur inter alia with aging. Agarose gel electrophoresis discriminates many cerebrospinal fluid proteins and in addition quantifies concentration alterations. This study aimed to investigate the time course of these alterations in children and to establish normative values for cerebrospinal fluid protein properties. In 202 children without diseases known to alter cerebrospinal fluid, normative protein properties were quantified using nephelometry, ultrafiltration, high-resolution electrophoresis, and Gaussian curve fit densitometry. Total protein and protein concentrations (albumin and gamma-globulins) decreased from birth until 7 months age, and, from then on, increased slightly (transthyretin, albumin, and alpha2-proteins) or strongly (gamma-globulins). Protein proportions (transthyretin and transferrin) increased until about 3 years of age and decreased from then on. These normative values for children as quantified by high-resolution agarose gel electrophoresis are presented in a significance-structured percentile table. The time courses of these cerebrospinal fluid properties reflect physiologic alterations of the blood-brain barrier function during childhood.

Adolescent↗
PubMed1995

Otorhinolaryngological complications of progressive facial hemiatrophy (Romberg's disease).

Progressive facial hemiatrophy (PFH) is characterized by slowly progressive atrophy of subcutaneous tissue. Bone, muscles, nerves, the eye, and the brain may be affected by atrophy. Four patients suffering from various otorhinolaryngological complications of PFH or Romberg's disease are reported. Unilateral hearing loss could be located in the inner ear of one patient by audiologic examination. Localized bone destruction and disintegration of a portion of the anterior wall of the frontal sinus were observed in a patient after more than three decades. Marked shrinking of the homolateral parotid gland and homolateral masticatory spasm are reported as further otorhinolaryngological manifestations. The various complications of PFH call for close interdisciplinary cooperation.

Child↗
PubMed1993

Single-photon emission computed tomography investigations of alternating hemiplegia of childhood.

Alterations in regional cerebral blood-flow, as determined by single-photon emission computed tomography (SPECT) using technetium [99mTc] hexamethyl propylenamine oxime, were studied in two children presenting with alternating hemiplegia of childhood. Both experienced hemiplegic episodes several times per month, despite marked improvement on flunarizine therapy. SPECT images of both patients revealed focal areas of decreased uptake of the radiotracer, representing impaired regional cerebral blood-flow during, as well as between, seizures. The interictal finding of localized areas of reduced tracer uptake suggest that long-lasting hypoperfusion could be the pathophysiological mechanism by which the slowly resolving hemiplegia, and ultimately the permanent multifocal neurological deficits, are produced.

Brain↗
PubMed1992

Differentiation between valproate-induced anticonvulsant effect, teratogenicity and hepatotoxicity. Aspects of species variation, pharmacokinetics, metabolism and implications of structural specificity for the development of alternative antiepileptic agents such as delta 2-valproate.

Valproate is metabolized into a large number of compounds via various metabolic routes. Metabolic profiles depend on species and age. Hepatotoxicity may be correlated with abnormal metabolism, especially in young age. Teratogenicity is associated with specific structural requirements: a free carboxyl atom connected to a carbon atom which also carries a hydrogen, and two carbon chains. This provides a clue for the development of alternative antiepileptic agents.

Abnormalities, Drug-Induced↗
PubMed1992

Detection by HPLC-ICP of metallothionein in serum of an epileptic child with valproate-associated hepatotoxicity.

A patient who developed valproate-associated hepatotoxicity had significantly lower serum levels of total protein, albumin and selenium than the controls. This study shows that with the beginning of the hepatic coma metallothionein (MT) appeared in the serum mainly in the form of Zn-thionein, which altered the Zn distribution pattern of the serum in a characteristic manner. HPLC-ICP3 was successfully applied to the simultaneous speciation of elements and characterization of MT by the use of one gel permeation column.

Blood Proteins↗
PubMed1992

[Irreversible valproate-associated liver failure].

A very severely retarded infant with a Dandy-Walker malformation was treated with valproate since the age of 6 months on account of infantile spasms. Three weeks after start of therapy dexamethasone was applied additionally because valproate was ineffective. Seventy-six days after initiation of valproate therapy the infant died with the clinical signs of fulminant valproate-associated hepatotoxicity despite the discontinuation of valproate. In combination with a febrile otitis media the child had been periodically restless and lethargic during the last week prior to liver coma. Activity of liver enzymes remained within normal limits up to two days before coma occurred. Analysis of valproate metabolites by gas chromatography/mass spectrometry yielded unusually high concentrations of the di-unsaturated metabolite E,E-2,3'-dien-valproate before and during liver failure. The concentrations of the main metabolites E-2-en-valproate und 3-keto-valproate remained within the usual range found during valproate therapy at steady state. The oxydation products 4-en-valproate and E-2,4-dien-valproate which are formed by alternative pathways and are considered to be hepatotoxic were detected in very low concentrations only. The application of carnitine, of antioxidants thought to improve the capacity of the free radical scavenger system (selen, vitamin E), and of N-acetylcysteine which can detoxify reactive drug metabolites could not prevent the fatal outcome.

Dandy-Walker Syndrome↗
PubMed1990

[Benign familial neonatal seizures].

Benign familial neonatal seizures are a rare cause of newborn seizures which can be easily detected by the family history because of their autosomal dominant inheritance. Based on 20 patients documented in the literature and one patient admitted to our clinic, the clinical picture can be characterized as follows: Only newborns at term are affected. Seizure types include multifocal-clonic, focal-clonic and subtle, beginning mostly on the 3rd day after birth (range: 1-8 day), the frequency can reach 40 per day. Interictally the patients are neurologically normal. As a rule, clinical, laboratory and neuroradiological investigations show no relevant deviations. The seizures usually disappear within 8 months. Nearly all children were treated with phenobarbital. After discontinuation of therapy, the seizures relapsed transiently in a few patients. Referring to about 140 patients described in the literature, the following conclusions can be drawn with regard to prognosis: Generally, mental development is normal, however, 4% of the patients later showed mental retardation. About 10% of the children developed epilepsy during childhood or adulthood. Two children died in the neonatal period. The fifth day fits must be separated from benign familial neonatal seizures, these are not genetically determined.

Central Nervous System Diseases↗
PubMed1988

[Alternating hemiplegia in childhood. Clinical report and single photon emission computed tomography study].

From 6 months of age on this girl experienced frequent episodes of hemiplegia involving both sides of the body and lasting up to 8 days. The attacks were often precipitated by tonic deviation of the head and/or the eyes to one side and nystagmus. At this stage the girl used to cry. Squinting, tonic stiffening of body and extremities, and dystonic posturing also occurred. Autonomic dysfunctions such as paleness of the skin, sweating, respiratory embarrassment, tachycardia, and mydriasis were associated features of the attacks. Motor and mental development of the girl is delayed. Improvement concerning severity, duration and frequency of the attacks has been achieved by permanent treatment with flunarizine in combination with acetazolamide and acetylsalicylic acid. If the child falls asleep immediately after rectal application of chloral hydrate at the onset of an attack there is no hemiplegia after awakening.

Acetazolamide↗
PubMed1987

[Leigh's subacute necrotizing encephalomyelopathy due to decreased activity of the pyruvate dehydrogenase complex].

A new patient with Leigh's syndrome (subacute necrotizing encephalomyelopathy due to pyruvate dehydrogenase complex deficiency) is presented. A Turkish boy of consanguinously married healthy parents developed progressive muscle weakness since infancy. At the age of 3 years he was unable to sit, stand or walk. Clinical examination showed general muscle weakness, hypotonia, muscle hypotrophy, bilateral ptosis, partial bilateral external ophthalmoplegia, nystagmus, intention tremor and hypoactive tendon reflexes. The EEG showed diffuse slowing, the cerebral CT scan disclosed mild hydrocephalus e vacuo. Motor nerve conduction velocity was slightly decreased, the EMG revealed signs of neuropathy. In the biopsied muscle only a mild hypotrophy of type 2 fibres was found, no abnormal mitochondria could be detected. The sural nerve was slightly abnormal: loss of large myelinated axons, loss of unmyelinated nerves. CSF protein was elevated to 80 mg/dl, protein electrophoresis revealed the pattern of markedly impaired blood-CSF barrier. Serum lactate and pyruvate were permanently elevated. In the urine the excretion of alanine was raised. The clinical state deteriorated during intercurrent infections; somnolence, vomiting and Cheyne-Stoke's respiration occurred. At the age of 3 1/2 years the child died of pneumonia. In the liver tissue a decreased activity of the pyruvate dehydrogenase complex was found. Neuropathological examination of the brain demonstrated wide-spread changes of Leigh's spongiform encephalopathy. Several enzyme deficiencies have hitherto been associated with Leigh's syndrome: This patients confirms earlier findings that a subgroup of Leigh's syndrome is caused by pyruvate dehydrogenase complex deficiency.

Biopsy↗
PubMed1986

Sural nerve biopsy studies in Leigh's subacute necrotizing encephalomyelopathy.

Peripheral neuropathy marked by reduced nerve conduction velocities was found in four unrelated children, between the ages of 15 months and 9 years, whose autopsies revealed Leigh's subacute necrotizing encephalomyelopathy. Sural nerve biopsies disclosed primary demyelination and remyelination, as well as loss of myelinated and unmyelinated axons. The use of morphometric and electron microscopic studies shows that these techniques may reveal peripheral neuropathy in Leigh's disease more often than light microscopic methods alone.

Biopsy↗
PubMed1985

[Transient unilateral oculomotor paralysis].

A three-year-old girl was admitted to the hospital one day after the acute onset of drooping of the left eyelid, associated with oculomotor external ophthalmoplegia. General neurological and physical examination was unremarkable. Results of serological tests as well as the clinical course of the disease (spontaneous recovery) show that the unilateral oculomotor neuropathy was most likely due to a self-limited enteroviral infection. The virus could not be cultured in the CSF. Echovirus type 11 as well as Coxsackie B4 virus might have caused the disease. During treatment with prednisone for 3 weeks in decreasing doses the girl recovered, by the seventh day she was able to raise her eyelid. 3 1/2 months later she had no evidence of residual ptosis and full range of ocular movements.

Acute Disease↗
PubMed1984

CSF protein profile in infantile spasms. Influence of etiology and ACTH or dexamethasone treatment.

CSF proteins in 107 children ranging from 3 to 24 months of age were analyzed by means of quantitative zone electrophoresis on agarose gel. Subjects included 50 children with infantile spasms, 41 children without CNS disease serving as controls, and 16 infants with acute aseptic meningitis who demonstrated the protein pattern of blood-CSF barrier disturbance. Children with infantile spasms were subdivided into several groups according to etiological categories: symptomatic (pre-, peri-, and postnatal), doubtful, and cryptogenetic. Before any treatment was started, these children showed the protein profile of increased permeability of the blood-CSF barrier, especially for albumin. There was an association between the severity of the changes and the etiological category. Changes were most marked in the symptomatic group, intermediate in the doubtful group, and slight in the cryptogenetic group. No child with infantile spasms of doubtful or unknown etiology revealed changes of the immunoglobulin-containing gamma fractions. Ten children who had received adrenocorticotropic hormone (ACTH) or dexamethasone for 2-11 weeks no longer showed any protein leakage into the CSF. The period of ACTH or dexamethasone treatment was characterized by the following findings: the disappearance or reduction of hypsarrhythmia; the reappearance of normal cerebrovascular permeability for protein; and the occurrence of reversible dilatation of the subarachnoid and intraventricular spaces.

Acute Disease↗