Biomedical subjects

L H van den Berg

Publications and source records attributed to L H van den Berg.

At least 19 recordsLinked to original sources

PubMed2006

Increased glutamine synthetase but normal EAAT2 expression in platelets of ALS patients.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and glutamate excitotoxicity has been implicated in its pathogenesis. Platelets contain a glutamate uptake system and express components of the glutamate-glutamine cycle, such as the predominant glial excitatory amino acid transporter 2 (EAAT2). In several neurological diseases platelets have proven to be systemic markers for the disease. We compared properties of key components of the glutamate-glutamine cycle in blood platelets of ALS patients and healthy controls. Platelets were analyzed for (3)H-glutamate uptake in the presence or absence of thrombin and for EAAT2 and glutamine synthetase protein expression by Western blotting. Platelets of ALS patients showed a 37% increase in expression of glutamine synthetase, but normal expression of glutamate transporter EAAT2. Glutamate uptake in resting or thrombin-stimulated platelets did not differ significantly between platelets from ALS patients and controls. Thrombin-stimulation resulted in about a seven-fold increase in glutamate uptake. Our data suggest that glutamine synthetase may be a peripheral marker of ALS and encourage further investigation into the role of this enzyme in ALS.

Adult↗

PubMed2005

Ultrasonography shows extensive nerve enlargements in multifocal motor neuropathy.

Using ultrasonography we found multiple sites with nerve enlargement along the course of the brachial plexus, median, ulnar, and radial nerves in the majority of 21 patients with multifocal motor neuropathy. Sonography and electrophysiologic studies showed more abnormalities than expected on purely clinical grounds. Moreover, sonography revealed nerve enlargement without clinical or electrophysiologic abnormalities.

Adult↗

PubMed2005

Intravenous immunoglobulin for multifocal motor neuropathy.

BACKGROUND: Multifocal motor neuropathy is a rare, probably immune mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. The treatment options for multifocal motor neuropathy are sparse. Patients with multifocal motor neuropathy do not usually respond to steroids or plasma exchange, and may even worsen with these treatments. Many uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin. OBJECTIVES: To review systematically the evidence from randomised controlled trials concerning the efficacy and safety of intravenous immunoglobulin in multifocal motor neuropathy. SEARCH STRATEGY: We used the search strategy of the Cochrane Neuromuscular Disease Review Group to search the Disease Group register (searched September 2003), MEDLINE (January 1990 to September 2003), EMBASE (January 1990 to September 2003) and ISI (January 1990 to September 2003) databases for randomised controlled trials. SELECTION CRITERIA: Randomised controlled studies examining the effects of any dose of intravenous immunoglobulin versus placebo in patients with definite or probable multifocal motor neuropathy. Outcome measures had to include one of the following: disability, strength, or conduction block. Studies which reported the frequency of adverse effects were used to assess safety. DATA COLLECTION AND ANALYSIS: Two authors reviewed literature searches to identify potentially relevant trials, scored their quality and extracted data independently. For dichotomous data, we calculated relative risks, and for continuous data, effect sizes and weighted pooled effect sizes. Statistical uncertainty was expressed with 95% confidence intervals. MAIN RESULTS: Four randomised controlled trials including a total of 34 patients were suitable for this systematic review. Strength improved in 78% of patients treated with intravenous immunoglobulin and only 4% of placebo-treated patients. Disability improved in 39% of patients after intravenous immunoglobulin treatment and in 11% after placebo (statistically not significantly different). Mild, transient side effects were reported in 71% of intravenous immunoglobulin treated patients. Serious side effects were not encountered. AUTHORS' CONCLUSIONS: Limited evidence from randomised controlled trials shows that intravenous immunoglobulin has a beneficial effect on strength. There was a non-significant trend towards improvement in disability. More research is needed to discover whether intravenous immunoglobulin improves disability and is cost-effective.

Demyelinating Diseases↗

PubMed2005

Physical activity and the association with sporadic ALS.

OBJECTIVE: To assess whether lifetime physical activity during work and leisure time is associated with an increased risk of developing ALS and to determine the association between physical activity and duration or age at onset of disease. METHODS: Patients referred to our clinic during the 1-year period 2001 to 2002 who had definite, probable, or possible ALS according to El Escorial criteria, without a familial history of ALS, were asked to participate in the study. A case-control study was performed taking into account all occupational and leisure time activities of patients (n = 219) and controls (n = 254). Multivariate analysis included confounding factors (sex, age, level of education, body mass index, alcohol use, and smoking). Three quantitative measures of cumulative physical activity were calculated: until 1 year before the onset of disease (total physical activity), the last 10 years before the onset of disease (late physical activity), and until the age of 25 (early physical activity). In addition, a systematic review of all published data is presented. RESULTS: Smoking and alcohol use were independently associated with ALS (current smoking increased risk, OR = 1.8, 95% CI = 1.0 to 3.0, p = 0.03, ever/current alcohol use decreased risk, OR = 0.6, 95% CI = 0.3 to 0.9, p = 0.04). No significant association with occupational or leisure time physical activity was found (all ORs < or = 1.7), which was in agreement with most studies with the highest level of evidence in the systematic review. Higher leisure time activities were associated with an earlier age at onset: activity levels before age of 25 (p < 0.001, 7 years earlier), and activity during the last 10 years (p < 0.001, 3 years earlier). CONCLUSIONS: There is no association between physical activity and the risk of developing ALS.

Adult↗

PubMed2005

Few adverse effects of long-term creatine supplementation in a placebo-controlled trial.

Although oral creatine supplementation is very popular among athletes, no prospective placebo-controlled studies on the adverse effects of long-term supplementation have yet been conducted. We performed a double-blind, placebo-controlled trial of creatine monohydrate in patients with the neurodegenerative disease amyotrophic lateral sclerosis, because of the neuroprotective effects it was shown to have in animal experiments. The purpose of this paper is to compare the adverse effects, and to describe the effects on indirect markers of renal function of long-term creatine supplementation. 175 subjects (age = 57.7 +/- 11.1 y) were randomly assigned to receive creatine monohydrate 10 g daily or placebo during an average period of 310 days. After one month, two months and from then on every fourth month, adverse effects were scored using dichotomous questionnaires, plasma urea concentrations were measured, and urinary creatine and albumin concentrations were determined. No significant differences in the occurrence at any time of adverse effects due to creatine supplementation were found (23 % nausea in the creatine group, vs. 24 % in the placebo group, 19 % gastro-intestinal discomfort in the creatine group, vs. 18 % in the placebo group, 35 % diarrhoea in the creatine group, vs. 24 % in the placebo group). After two months of treatment, oedematous limbs were seen more often in subjects using creatine, probably due to water retention. Severe diarrhoea (n = 2) and severe nausea (n = 1) caused 3 subjects in the creatine group to stop intake of creatine, after which these adverse effects subsided. Long-term supplementation of creatine did not lead to an increase of plasma urea levels (5.69 +/- 1.47 before treatment vs. 5.26 +/- 1.44 at the end of treatment) or to a higher prevalence of micro-albuminuria (5.4 % before treatment vs. 1.8 % at the end of treatment).

Administration, Oral↗

PubMed2005

Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis.

AIMS: Riluzole is used in a fixed dosing schedule of 50 mg twice daily to treat patients with amyotropic lateral sclerosis (ALS), one form of motor neurone disease. The large variability in the pharmacokinetics of riluzole may be a factor contributing to its limited therapeutic benefit. Riluzole is assumed to be mainly metabolized by the cytochrome P450 enzyme 1A2 (CYP1A2). The aim of the study was to investigate the relationship between CYP1A2 activity and riluzole clearance with a view to optimize drug treatment. METHODS: A group of 30 ALS patients participated in the study. In each patient the CYP1A2 activity was determined using caffeine as a metabolic probe. Riluzole clearance was estimated from serum drug concentration measurements followed by Bayesian fitting. RESULTS: Riluzole clearance and the serum paraxanthine : caffeine (P/C) ratio showed a positive correlation (r = 0.693; P = 0.0002). Linear regression analysis identified the P/C ratio (beta: 1.16) and height (beta: 0.027) as independent predictors of riluzole clearance (adjusted r2 = 0.369). CONCLUSIONS: The P/C ratio, used as measure of CYP1A2 activity, significantly correlated with the riluzole clearance, although only 37% of the observed variability could be explained.

Administration, Oral↗

PubMed2004

[From gene to disease: amyotrophic lateral sclerosis].

Amyotrophic lateral sclerosis is a progressive neurological disorder. It is characterised by selective motor-neuron degeneration in the cortex, brainstem, and spinal cord. Consequently, patients suffer from muscle weakness and usually die within 3-5 years after diagnosis from respiratory insufficiency. About 5-10% of the patients have a family history of ALS, the remaining are classified as sporadic ALS. There is only limited information about genetic susceptibility factors in sporadic ALS. Some patients with familial ALS have mutations in the gene encoding for copper/zinc superoxide dismutase, a protein involved in scavenging superoxide radicals. This results in a toxic gain of function. Mutations in the gene coding for alsin, ALS2, have been shown to be responsible for an autosomal recessive form of juvenile ALS.

Amyotrophic Lateral Sclerosis↗

PubMed2004

[Amyotrophic lateral sclerosis: mechanical ventilation--or not right?].

In two patients (men aged 64 and 62 years, respectively) with amyotrophic lateral sclerosis (ALS) tracheostomy ventilation was initiated following (imminent) acute respiratory failure; in one patient this was done because advance directives were lacking, while in the other non-invasive ventilation (NIPPV) was no longer an option. A third ALS patient, a woman aged 36 years, already had chronic respiratory failure when she presented at the local centre for home mechanical ventilation. As a result, the placement of a percutaneous endoscopic gastrostomy (PEG) was impossible. Instead, she had to use a nasopharyngeal feeding tube, which diminished the effectiveness of her NIPPV. The fourth patient, a man aged 60 years, was referred in good time and hence had sufficient time to consider domiciliary ventilation. Following the placement of a PEG he started NIPPV electively. In patients with ALS, domiciliary ventilation should be discussed early in the course of the disease. Advance directives with regard to domiciliary ventilation are important, not only to avoid undesired (invasive) ventilation, but also with respect to the placement of a PEG and the appropriate use of oxygen and morphine.

Adult↗

PubMed2004

[The symptomatic treatment of amyotrophic lateral sclerosis].

Patients with amyotrophic lateral sclerosis (ALS) have symptoms of progressive muscle weakness, of disturbed speech and swallowing, and in the terminal phase those of respiratory weakness. Treatment options, in particular those for excessive weight loss and respiratory weakness, should be introduced to the patients and their families when the patient is emotionally capable and before dysarthria severely hampers communication. Special equipment for keeping the patient as mobile as possible should be made available much earlier than in the case of other diseases of the muscles as in ALS progression is much faster. Cramps, pathological crying or laughter, spasms, and spasticity can all be treated by medication. When speech can no longer be understood, adaptive strategies such as sign language, mime, posture and communication apparatus varying from a note pad to advanced computer systems can be used. Sialorrhoea, caused by difficulty swallowing with its accompanying danger of aspiration can be halted by the use of medication, by radiotherapy and by the injection into the salivary glands of botulin A toxin. Weight loss, also a result of dysphagia, can be avoided by eating frequent small meals or if necessary performing a percutaneous endoscopic or radiological gastroscopy. Excess mucus in the respiratory tract can be treated with anticholinergics. Difficulty in coughing up thick and sticky mucus cannot always be adequately helped. Respiratory weakness is treatable by external respiratory supportive therapy using a nasal mask, as well as invasive respiratory support via a trachcostoma and by treating the symptoms of respiratory weakness. The latter form of treatment is palliative and forms part of terminal care. During the terminal phase restlessness, anxiety, pain, and dyspnoea require the most attention. Treatment requires careful multidisciplinary cooperation.

Amyotrophic Lateral Sclerosis↗

PubMed2004

A validated HPLC assay to monitor riluzole plasma or serum concentrations in patients with amyotrophic lateral sclerosis.

A specific, accurate and precise high-performance liquid chromatographic assay was developed for the determination of riluzole, a drug used to treat patients with amyotrophic lateral sclerosis. Samples were treated by extraction with dichloromethane followed by reversed-phase chromatography with ultraviolet detection at 260 nm. Preset validation criteria were met from 20 to 2000 ng/mL with a linear response curve. Extraction recovery of riluzole was 65-76%. The accuracy of the method was 102-103%. Intra- and inter-day coefficients of variation were in the ranges 2.8-4.9% and 1.8-9.7%. A detection limit of 5 ng/mL was found. Determination of concentrations in serum and plasma resulted in similar results below 500 ng/mL. At higher values a matrix effect cannot be excluded. This presented method can be used to monitor plasma or serum levels in ALS patients treated with riluzole.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Pathogenicity of anti-ganglioside antibodies in the Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a postinfectious inflammatory polyradiculo-neuropathy characterized by flaccid paralysis. Antibodies directed against glycolipid structures (gangliosides), which are highly expressed in the peripheral nervous system, are frequently detected in sera from GBS patients. These antibodies interfere with nerve conduction and have been shown to activate phagocytes via IgG receptors (FcgammaR). These findings support an important role of glycolipid-specific antibodies in the pathogenesis of GBS.

Antibodies↗

PubMed2003

Zinc amplifies mSOD1-mediated toxicity in a transgenic mouse model of amyotrophic lateral sclerosis.

Transgenic mice overexpressing the human mutated form (G93A) of Cu,Zn-superoxide dismutase (mSOD1) develop motor neuron degeneration resembling amyotrophic lateral sclerosis. In vitro studies have shown that mSOD1-induced, reactive oxygen species-mediated apoptosis of motor neurons depends on the presence of copper and the relative absence of zinc. Oral intake of zinc sulphate induces the expression of metallothioneins, enzymes that decrease oxidative stress, and leads to higher serum zinc, and lower copper levels. We therefore tested the effect of chronic oral administration of zinc sulfate (0.075 and 0.375 g/kg) on disease onset and survival of mSOD1 transgenic mice. We observed that zinc sulfate, rather than prolonging survival, decreased survival. We conclude that zinc sulfate amplifies the mSOD1 transgenic mouse phenotype. This finding may shed more light on the role of zinc in mSOD1-mediated toxicity.

Amyotrophic Lateral Sclerosis↗

PubMed2003

Increase of sural nerve T cells in progressive axonal polyneuropathy and monoclonal gammopathy.

The authors investigated whether T cells have a role in the pathogenesis of axonal polyneuropathy and monoclonal gammopathy by comparing the presence of T cells in sural nerves of 23 patients with axonal polyneuropathy and monoclonal gammopathy (12 IgM, 11 IgG), of 15 patients with chronic idiopathic axonal polyneuropathy, and of 10 autopsy cases. Seven patients with an increased T-cell density had a progressive disease course, and four of these patients were treated with prednisone with a good response, suggesting that vasculitis plays a role in the pathogenesis.

Axons↗

PubMed2003

[From gene to disease; Wilson disease: copper storage due to mutations in ATP7B].

Wilson disease is an autosomal recessive disorder of copper metabolism. The gene defective in Wilson disease encodes a copper transporting P-type ATPase expressed in the liver. The disturbed export of copper into bile results in accumulation of copper in liver and secondarily in other organs such as the brain. These patients generally present with either hepatic or neurological symptoms.

Adenosine Triphosphatases↗

PubMed2003

Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients.

Myasthenia gravis (MG) susceptibility is partially determined by allelic heterogeneity of immune-modulatory genes. IgG receptors (FcgammaR) link the humoral and cellular branches of the immune system, and regulate immune responses and inflammation. Three FcgammaR subclasses (FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb) exhibit functional polymorphisms, which affect efficiency of FcgammaR-mediated functions. FcgammaRIIa genotypes, but not FcgammaRIIIa and FcgammaRIIIb genotypes, were differentially distributed among 107 MG patients as compared to 239 healthy controls (Pz.Lt;0.01), with a relative increase of the FcgammaRIIa-R/R131 genotype (Odds ratio 2.4, 95% confidence interval 1.4-3.9). These data suggest that the FcgammaRIIa-R/R131 genotype is a marker for susceptibility to MG.

Adolescent↗

PubMed2003

Sexual differences in onset of disease and response to exercise in a transgenic model of ALS.

Transgenic mice that overexpress the mutant human SOD1 gene (hSOD1) serve as an animal model for amyotrophic lateral sclerosis (ALS). Age and sex are recognized as risk factors for ALS, but physical activity remains controversial. Therefore, we investigated the effect of exercise on the phenotype of male and female hSOD1 mice. Onset of disease, progression of disease and survival were measured in low-copy and high-copy hSOD1 mice that were randomized to an exercise or sedentary group. We found that onset of disease was different for the two sexes: significantly earlier in male than in female hSOD1 mice. Exercise delayed the onset of disease in female but not in male hSOD1 mice. Also, exercise delayed the total survival time in female high-copy hSOD1 mice. Muscle morphometry and motor neuron counts were similar in all experimental groups at the end of training. Sedentary female hSOD1 mice showed more frequently irregular estrous cycles suggesting a higher estrogen exposure in exercising female mice. These results suggest a possible neuroprotective effect of female sex hormones and support the view that ALS patients should not avoid regular exercise.

Age Factors↗

PubMed2003

Comparison of maximal voluntary isometric contraction and hand-held dynamometry in measuring muscle strength of patients with progressive lower motor neuron syndrome.

Context. Maximal voluntary isometric contraction, a method quantitatively assessing muscle strength, has proven to be reliable, accurate and sensitive in amyotrophic lateral sclerosis. Hand-held dynamometry is less expensive and more quickly applicable than maximal voluntary isometric contraction. Objective. To investigate if hand-held dynamometry is as reliable and valid as maximal voluntary isometric contraction in measuring muscle strength in patients with an adult-onset, non-hereditary progressive lower motor neuron syndrome. Design. Two testers performed maximal voluntary isometric contraction and hand-held dynamometry measurements in six muscle groups bilaterally in patients with progressive lower motor neuron syndrome to assess reliability and validity of both the methods. Setting. Outpatient units of an academic medical center. Patients. A consecutive sample of 19 patients with non-hereditary progressive lower motor neuron syndrome (median disease duration 32.5 months, range 10-84) was tested. Outcome measures. Comparison between maximal voluntary strength contractions as measured by hand-held dynamometry and maximal voluntary isometric contraction. Results. Low intra- and interrater variation in all muscle groups were found, intraclass correlation coefficients vary between 0.86 and 0.99 for both methods. Both methods correlated well in all muscle groups with Pearson's correlation coefficients ranged between 0.78 and 0.98. Scatter plots indicated a trend to under-estimate muscle strength above 250 N by hand-held dynamometry as compared with maximal voluntary isometric contraction. Conclusions. For longitudinal evaluation of muscle strength in patients with progressive lower motor neuron syndrome (i.e. between 0 and 250 N), muscle strength can be accurate quantified with both hand-held dynamometry and maximal voluntary isometric contraction. Hand-held dynamometry has the advantage of being cheap and quickly applicable. However, our results indicate that hand-held dynamometry is less sensitive than maximal voluntary isometric contraction in detecting subnormal muscle strength in strong muscle groups (i.e. >250 N), due to limited strength of the tester.

Adult↗

PubMed2003

Sporadic lower motor neuron disease with adult onset: classification of subtypes.

The discovery of the genetic basis of hereditary lower motor neuron disease (LMND) and the recognition of multifocal motor neuropathy as a distinct clinical entity necessitate a new classification of LMND. To this end, we studied the clinical and electrophysiological features of 49 patients with sporadic adult-onset LMND in a cross-sectional study. Disease duration was more than 4 years to exclude the majority of patients with amyotrophic lateral sclerosis. Based on the pattern of weakness, we identified three groups: 13 patients with generalized weakness (group 1); eight patients with symmetrical, distal muscle weakness (group 2); and 28 patients with non-generalized asymmetrical weakness of the arms in most patients (group 3). Group 3 could be subdivided into patients with weakness in predominantly the distal (group 3a) or the proximal (group 3b) muscle groups, both with disease progression to adjacent spinal cord segments. Distinctive features of group 1 were an older age at onset, more severe weakness and muscle atrophy, lower reflexes, greater functional impairment, more widespread abnormalities on concentric needle EMG, respiratory insufficiency and serum M-protein. In groups 2 and 3, concentric needle EMG findings also suggested a more widespread disease process. Retrospectively, the prognosis of sporadic adult-onset LMND appears to be favourable, because clinical abnormalities were still confined to one limb in most patients after a median disease duration of 12 years. We propose to classify the patients in the different subgroups as slowly progressive spinal muscular atrophy (group 1), distal spinal muscular atrophy (group 2), segmental distal spinal muscular atrophy (group 3a) and segmental proximal spinal muscular atrophy (group 3b). The described clinical phenotypes may help to distinguish between different LMND forms.

Adult↗