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The abnormalities of metallochemical reactions may contribute to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). In the present work, an investigation of the elemental composition of the gray matter, nerve cells and white matter from spinal cord tissues representing three ALS cases and five non-ALS controls was performed. This was done with the use of the synchrotron microbeam X-ray fluorescence technique (micro-SRXRF). The following elements were detected in the tissue sections: P, S, Cl, K, Ca, Fe, Cu, Zn and Br. A higher accumulation of Cl, K, Ca, Zn and Br was observed in the nerve cell bodies than in the surrounding tissue. Contrary to all other elements, Zn accumulation was lower in the white matter areas than in the gray matter ones. The results of quantitative analysis showed that there were no general abnormalities in the elemental accumulation between the ALS and the control group. However, for individual ALS cases such abnormalities were observed for the nerve cells. We also demonstrated differences in the elemental accumulation between the analyzed ALS cases. [ABSTRACT FROM AUTHOR]

Multiplex arrays designed for enzyme-linked immunosorbent assays (ELISAs) are robust and cost-effective for profiling biomarkers. Identification of relevant biomarkers in biological matrices or fluids helps in the understanding of disease pathogenesis. Here, we describe a sandwich ELISA-based multiplex assay to assess growth factor and cytokine levels in cerebrospinal fluid (CSF) samples derived from multiple sclerosis patients, amyotrophic lateral sclerosis patients, and control subjects without any neurological disorder. Results indicate that multiplex assay designed for the sandwich ELISA method is a unique, robust, and cost-effective method for profiling growth factors and cytokines present in CSF samples., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To assess cardiovascular responses to cold face test (CFT) in patients with classic-onset ALS (bulbar or limb onset, ALS-C) and in patients with flail arm and flail leg phenotypes (FA/FL)., Methods: In 18 ALS-C, eight FA/FL patients and 10 age-matched controls we continuously monitored heart rate (HR), systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) during two-minute baseline and one-minute cold stimulus application. HR and BP responses to CFT were calculated as differences between the peak responses and baseline values (dHR, dSBP, dDBP, dMBP), as percent changes from baseline (dHR%, dSBP%, dDBP%, dMBP%), and also latencies and durations of HR and BP responses were assessed (Lat HR , t HR , Lat BP , t BP )., Results: There were no differences in baseline values of HR, SBP, DBP and MBP among ALS-C, FA/FL and controls (p > 0.05). A decrease in HR and increases in SBP, DBP and MBP were observed in all subjects (p < 0.05). However, in FA/FL, the magnitude of BP responses, i.e. dSBP, dSBP%, dDBP, dMBP, and dMBP% were significantly higher than in controls. Moreover, these BP responses occurred with a significantly shorter latency in FA/FL than in controls and ALS-C. Furthermore, duration of the BP changes was significantly longer in FA/FL than in ALS-C. In contrast, ALS-C patients had a significantly longer Lat HR and shorter t HR than healthy persons. However, no significant differences were observed in dHR or dHR% among the three groups., Conclusions: Sympathetic vascular response to facial cooling is increased in flail phenotypes of ALS.

The aim of the study was to analyse the disturbances of the oro-pharyngeal swallowing phase of dysphagia in amyotrophic lateral sclerosis (ALS) patients with the use of specific manometric measurements and to evaluate their plausible association with the duration of the disease. Seventeen patients with ALS were evaluated with manometric examinations of the oral and pharyngeal part of the gastrointestinal tract. Tests were carried out by using the oesophageal balloon-based method with four balloon transducers located 5 cm away from each other. The following manometric parameters were analysed: the base of tongue contraction (BTC) and the upper oesophageal sphincter pressure (UESP), and the hypopharyngeal suction pump (HSP) as well as the oro-pharyngeal, pharyngeal and hypopharyngeal transit time and average pharyngeal bolus velocity (oropharyngeal transit time (OTT), pharyngeal transit time (PTT), hypopharyngeal transit time (HTT) and average pharyngeal bolus velocity (APBV), respectively). Manomatric examinations during swallowing in patients with ALS showed significant weakness of BTC, a decrease of HSP and a decrease of the velocity of bolus transit inside the pharynx which were particularly marked between the first and the third examination. Manometric examinations of the oro-pharyngeal part of the gastrointestinal tract are useful and supportive methods in the analysis of swallowing disturbances in ALS patients.

Objective: Voice abnormalities are among the symptoms occurring in patients with amyotrophic lateral sclerosis (ALS). They are divergent and range from hoarseness, through the excessive adduction of false folds, up to the weakness of the vocal folds. The aim of the study was to analyze the phonatory function of the larynx in ALS patients., Methods: Seventeen patients with ALS were evaluated with subjective perceptual voice assessment (including the GRBAS scale), videolaryngostroboscopy including voice range and maximum phonation time (MPT), and objective acoustic voice analysis with IRIS software (including evaluation of jitter, shimmer, mean fundamental frequency, and noise-to-harmonics ratio (NHR)). Examinations were performed three times at 6-month intervals., Results: Hoarseness, roughness, and breathiness of voice were all found more frequently in the majority of these patients. Voice range, amplitude of vibration, mucosal wave, and glottal closure showed significant abnormalities with repeated examinations. MPT was shortened especially among women with ALS. Acoustic analysis of voice among men showed increased jitter value in the first examination only, while jitter, shimmer, and NHR in women with ALS were increased in all examinations., Conclusions: Analysis of voice qualities among patients with ALS allows for the detection of various abnormalities associated with the natural progression of the disease., (© 2015 S. Karger AG, Basel.)

Background: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak., Objectives: To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel., Methods: All available medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus., Recommendations: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non-invasive positive-pressure ventilation also improves survival and quality of life. Maintaining the patient's ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end-of-life care should be discussed early with the patient and carers, respecting the patient's social and cultural background., (© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.)

Excitotoxicity is thought to play a pathogenic role in amyotrophic lateral sclerosis (ALS). Excitotoxic motor neuron death is mediated through the Ca(2+)-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type of glutamate receptors and Ca(2+) permeability is determined by the GluR2 subunit. We investigated whether polymorphisms or mutations in the GluR2 gene (GRIA2) predispose patients to ALS. Upon sequencing 24 patients and 24 controls no nonsynonymous coding variants were observed but 24 polymorphisms were identified, 9 of which were novel. In a screening set of 310 Belgian ALS cases and 794 healthy controls and a replication set of 3157 cases and 5397 controls from 6 additional populations no association with susceptibility, age at onset, or disease duration was observed. We conclude that polymorphisms in the GluR2 gene (GRIA2) are not a major contributory factor in the pathogenesis of ALS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To determine whether 5 single nucleotide polymorphisms (SNPs) associate with ALS in 3 different populations. We also assessed the contribution of genotype to angiogenin levels in plasma and CSF., Methods: Allelic association statistics were calculated for polymorphisms in the ANG gene in 859 patients and 1047 controls from Sweden, Ireland and Poland. Plasma, serum and CSF angiogenin levels were quantified and stratified according to genotypes across the ANG gene. The contribution of SNP genotypes to variance in circulating angiogenin levels was estimated in patients and controls., Results: All SNPs showed association with ALS in the Irish group. The SNP rs17114699 replicated in the Swedish cohort. No SNP associated in the Polish cohort. Age- and sex-corrected circulating angiogenin levels were significantly lower in patients than in controls (p<0.001). An allele dose-dependent regulation of angiogenin levels was observed in controls. This regulation was attenuated in the ALS cohort. A significant positive correlation between CSF plasma angiogenin levels was present in controls and abolished in ALS., Conclusions: ANG variants associate with ALS in the Irish and Swedish populations, but not in the Polish. There is evidence of dysregulation of angiogenin expression in plasma and CSF in sporadic ALS. Angiogenin expression is likely to be important in the pathogenesis of ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase disease susceptibility. In contrast, rare copy-number variants (CNVs), which have been associated with several neuropsychiatric traits, have not been studied for ALS in well-powered study populations. To examine the role of rare CNVs in ALS susceptibility, we conducted a CNV association study including over 19,000 individuals. In a genome-wide screen of 1875 cases and 8731 controls, we did not find evidence for a difference in global CNV burden between cases and controls. In our association analyses, we identified two loci that met our criteria for follow-up: the DPP6 locus (OR = 3.59, P = 6.6 × 10(-3)), which has already been implicated in ALS pathogenesis, and the 15q11.2 locus, containing NIPA1 (OR = 12.46, P = 9.3 × 10(-5)), the gene causing hereditary spastic paraparesis type 6 (HSP 6). We tested these loci in a replication cohort of 2559 cases and 5887 controls. Again, results were suggestive of association, but did not meet our criteria for independent replication: DPP6 locus: OR = 1.92, P = 0.097, pooled results: OR = 2.64, P = 1.4 × 10(-3); NIPA1: OR = 3.23, P = 0.041, pooled results: OR = 6.20, P = 2.2 × 10(-5)). Our results highlight DPP6 and NIPA1 as candidates for more in-depth studies. Unlike other complex neurological and psychiatric traits, rare CNVs with high effect size do not play a major role in ALS pathogenesis.

Background: The microtubule-associated protein tau is thought to play a pivotal role in neurodegeneration. Mutations in the tau coding gene MAPT are a cause of frontotemporal dementia, and the H1/H1 genotype of MAPT, giving rise to higher tau expression levels, is associated with progressive supranuclear palsy, corticobasal degeneration, and Parkinson disease (PD). Furthermore, tau hyperphosphorylation and aggregation is a hallmark of Alzheimer disease (AD), and reducing endogenous tau has been reported to ameliorate cognitive impairment in a mouse model for AD. Tau hyperphosphorylation and aggregation have also been described in amyotrophic lateral sclerosis (ALS), both in human patients and in the mutant SOD1 mouse model for this disease. However, the precise role of tau in motor neuron degeneration remains uncertain., Methods: The possible association between ALS and the MAPT H1/H2 polymorphism was studied in 3,540 patients with ALS and 8,753 controls. Furthermore, the role of tau in the SOD1(G93A) mouse model for ALS was studied by deleting Mapt in this model., Results: The MAPT genotype of the H1/H2 polymorphism did not influence ALS susceptibility (odds ratio = 1.08 [95% confidence interval 0.99-1.18], p = 0.08) and did not affect the clinical phenotype. Lowering tau levels in the SOD1(G93A) mouse failed to delay disease onset (p = 0.302) or to increase survival (p = 0.557)., Conclusion: These findings suggest that the H1/H2 polymorphism in MAPT is not associated with human amyotrophic lateral sclerosis, and that lowering tau levels in the mutant SOD1 mouse does not affect the motor neuron degeneration in these animals.

Background and Purpose: Sporadic amyotrophic lateral sclerosis (sALS) is a devastating neurodegenerative disease, which results from complex genetic and environmental interactions. Recent studies have reported an association between several polymorphisms of the PON1 and PON2 genes and risk of sALS. The aim of the present study was to identify an association between the -A162G polymorphism of the promoter region of the human PON1 gene and the risk of sALS in a Polish population., Material and Methods: We included 259 patients with a diagnosis of definite or probable sALS (76 bulbar onset, 183 limb onset) and 694 healthy controls matched for age and sex. The diagnosis of ALS was established according to El Escorial criteria. The polymorphism was studied by Single Nucleotide Polymorphism Real-Time Polymerase Chain Reaction analysis., Results: No overall difference in the PON1 -A162G geno-type and allele distribution was seen between cases and controls (all p > 0.05). There was, however, a difference in the A allele frequency when the bulbar onset group was compared to the controls (p = 0.03), but this significance disappeared after the Bonferroni correction., Conclusions: The results did not show that the -A162G polymorphism of the PON1 gene is a risk factor of sALS in a Polish population; it may affect, however, bulbar onset of the disease.

Amyotrophic Lateral Sclerosis (ALS) is an untreatable, neurodegenerative disease of motor neurons characterized by progressive muscle atrophy, limb paralysis, dysarthria, dysphagia, dyspnae and finally death. Large motor neurons in ventral horns of spinal cord and motor nuclei in brainstem, large pyramidal neurons of motor cortex and/or large myelinated axons of corticospinal tracts are affected. In recent synchrotron Fourier Transform Infrared microspectroscopy (sFTIR) studies of ALS CNS autopsy tissue, we discovered a small deposit of crystalline creatine, which has a crucial role in energy metabolism. We have now examined unfixed, snap frozen, post-autopsy tissue sections of motor cortex, brain stem, spinal cord, hippocampus and substantia nigra from six ALS and three non-degenerated cases with FTIR and micro-X-ray fluorescence (XRF). Heterogeneous pigmented deposits were discovered in spinal cord, brain stem and motor neuron cortex of two ALS cases. The FTIR signature of creatine has been identified in these deposits and in numerous large, non-pigmented deposits in four of the ALS cases. Comparable pigmentation and creatine deposits were not found in controls or in ALS hippocampus and substantia nigra. Ca, K, Fe, Cu and Zn, as determined by XRF, were not correlated with the pigmented deposits; however, there was a higher incidence of hot spots (Ca, Zn, Fe and Cu) in the ALS cases. The identity of the pigmented deposits remains unknown, although the absence of Fe argues against both erythrocytes and neuromelanin. We conclude that elevated creatine deposits may be indicators of dysfunctional oxidative processes in some ALS cases., (Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)

Dysarthria is a motor disorder of speech characterized by abnormalities of the articulation and intelligibility of speech. Phonation and the rate of facial movements may also be affected. Understanding the nature and course of dysarthria in amyotrophic lateral sclerosis (ALS) is important because loss of communication prevents patients from participating in many activities, may lead to social isolation, and reduces the quality of life. The goal of management of dysarthria in ALS patients is to optimize communication effectiveness for as long as possible. The information about dysarthria in ALS is dispersed in physiological, pathological, speech therapy, otorhinolaringological and neurological publications. This review summarizes the current state of knowledge on the clinical features, differential diagnosis, pathophysiology, investigations and management of dysarthria in ALS patients. There is a need to compare the different methods used to assess dysarthria and for controlled clinical trials to assess therapeutic strategies.

We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.

Background and Purpose: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of multiple and poorly understood aetiopathogenesis. Genetic factors involved in the pathogenesis of sporadic ALS still remain unknown. A candidate gene might be matrix metalloproteinase-9 gene (MMP-9) - a member of the matrix metalloproteinase family capable of degrading elements of the extracellular matrix. Recent data suggest that MMP-9 may be involved in the pathophysiology of ALS. MMP-9 levels and activity are influenced by the -1562 C/T polymorphism of the MMP-9 gene. We have studied the association between the -1562 C/T polymorphism of the MMP-9 gene and the risk of sporadic ALS., Material and Methods: We included 228 patients with a definite or probable diagnosis of sporadic ALS and 428 healthy controls matched for age and sex. The diagnosis of sporadic ALS was established according to El Escorial criteria. The polymorphism was studied by polymerase chain reaction (PCR) and restricted enzyme digestion., Results: Distribution of genotypes and alleles of the MMP-9 gene between sporadic ALS cases and controls did not differ significantly: C/C - 168 (73.7%) vs. 304 (71.0%), C/T - 53 (23.2%) vs. 118 (27.6%), T/T - 7 (3.1%) vs. 6 (1.4%), respectively and alleles: C - 389 (85.3%) vs. 726 (84.8%), T - 67 (14.7 %) vs. 130 (15.2%), respectively., Conclusion: The polymorphism -1562 C/T of the MMP-9 gene is not associated with the risk of sporadic amyotrophic lateral sclerosis in the studied population of Polish patients.

We recently reported a joint analysis of genome-wide association (GWA) data on 958 sporadic amyotrophic lateral sclerosis (ALS) cases and 932 controls from Ireland and the publicly available data sets from the United States and the Netherlands. The strongest pooled association was rs10260404 in the dipeptidyl-peptidase 6 (DPP6) gene. Here, we sought confirmation of joint analysis signals in both an expanded Irish and a Polish ALS cohort. Among 287 522 autosomal single-nucleotide polymorphisms (SNPs), 27 were commonly associated on joint analysis of the Irish, US and Dutch GWAs. These 27 SNPs were genotyped in an expanded Irish cohort (312 patients with SALS; 259 controls) and an additional Polish cohort (218 patients; 356 controls). Eleven SNPs, including rs10260404, reached a final P-value below 0.05 in the Irish cohort. In the Polish cohort, only one SNP, rs6299711, showed nominal association with ALS. Pooling of data for 1267 patients with ALS and 1336 control subjects did not identify any association reaching Bonferroni significance (P<1.74 x 10(-7)). The present strategy did not reveal any consistently associated SNP across four populations. The result for DPP6 is surprising, as it has been replicated elsewhere. We discuss the possible interpretations and implications of these findings for future ALS GWA studies both within and between populations.

Background: Dysphagia is a common symptom of amyotrophic lateral sclerosis (ALS) and leads to increased risk of aspiration, malnutrition and dehydration. Swallowing mechanism in ALS patients has not been systematically studied., Material and Methods: Based on the manometry analysis of upper investigate tract we have measured base of tongue contraction, resting pressure of the upper esophageal sphincter and average pharyngeal bolus velocity 10 ALS patients with slight dysphagia and have compared them to control group., Results: All parameters measured were significantly changed in ALS patients indicting disturbances of oro-pharyngeal phase of swallowing even in ALS patients with slight dysphagia., Conclusion: Early diagnosis of the swallowing disturbances is important for symptomatic therapy.

There is still a debate whether primary lateral sclerosis (PLS) is a distinct pathological entity or whether it represents one end of a continuous spectrum of motor neuron disease (MND). In this report we present four PLS patients who have been observed from the time of symptom onset (1990-1999) through January 2007. All of them have had only upper motor neuron (UMN) signs and slow clinical progression. Three patients have been presented with spastic paraparesis. Spasticity was the main clinical feature in demonstrated cases with hyperactive deep tendon reflexes, clonus, and Babinski signs. One patient was presented with spastic dysarthria at the disease onset. Mean disease duration, measured from symptom onset to the present, was 11.5 years in our reported series. All four PLS patients had not developed lower motor neuron (LMN) signs during this time of observation. This prospective analysis of our PLS series is in agreement with data from other studies suggesting that pure PLS cases have a prolonged course of disease with a high level of independence when compared to other MND.

Few studies have described laryngological evaluation of patients with amyotrophic lateral sclerosis. We assessed the laryngological abnormalities of 35 such patients (24 bulbar onset and 11 limb onset). In nine limb onset patients, we discovered signs of early vagal nerve dysfunction, prior to any clinical presentation of bulbar failure. However, in all bulbar onset patients studied, we noticed changes in the uni/bilateral position of the vocal folds and in the voice quality.

The article is focused on recent EFNS recommendations for the diagnosis and management of amyotrophic lateral sclerosis (ALS). In the commentary, the need for use of EFNS recommendations for ALS in clinical practice in Poland is emphasized. The importance of 1) complex respiratory and nutritional care, 2) symptomatic treatment, 3) multidisciplinary teamwork and palliative care, as well as 4) an individual rehabilitation programme and 5) communication status improvement, is stressed as a necessary step for improving the quality of life of Polish ALS patients.

The evidence base for diagnosis and management of ALS is still weak, and curative therapy is lacking. Nonetheless, early diagnosis and symptomatic therapy can profoundly influence care and quality of life of the patient and relatives, and may increase survival time. This review addresses the current optimal clinical approach to ALS. The literature search is complete to December 2006. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. We conclude that a diagnosis of ALS can be achieved by early examination by an experienced neurologist. The patient should be informed of the diagnosis by the consultant. Following diagnosis, a multi-diciplinary care team should support the patient and relatives. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with VC <50%: RIG may be a better alternative. Non-invasive positive pressure ventilation improves survival and quality of life but is underused in Europe. Maintaining the patient's ability to communicate is essential. During the course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be discussed early with the patient and relatives if they so wish.

Background: The human paraoxonase (PON) gene family consists of three members, PON1, PON2, and PON3, located adjacent to each other on chromosome 7. PON catalytic activity may be influenced by frequent amino acid variants. Chronic exposure to certain chemicals or to environmental factors causing enhanced lipid peroxidation metabolized by paraoxonases may be a risk factor for sporadic ALS (sALS)., Objective: The aim of this study was to examine the association between PON1 Q192R, PON1 L55M, and PON2 C311S functional polymorphisms and the risk of sALS in a Polish population., Methods: The authors included 185 patients with a definite or probable diagnosis of sALS (El Escorial Criteria) and 437 healthy controls of similar age and gender. The paraoxonase polymorphisms were studied by PCR and restriction enzyme digestion., Results: Using logistic regression analyses, the C allele of the C311S polymorphism was associated with sALS in dominant and additive models, whereas the R allele of the Q192R polymorphism was associated with sALS in recessive, additive, and dominant models. The authors compared the distribution of haplotypes between cases and controls. The R-C haplotype was overrepresented among cases (odds ratio 3.44, 95% CI: 1.55 to 7.62, p = 0.002)., Conclusions: Frequent amino acid variants in the paraoxonase 1 and paraoxonase 2 genes are associated with sporadic ALS in a Polish population.

We studied phenotype-genotype correlation in a group of Polish males with spinal and bulbar muscular atrophy (SBMA) and in female carriers. Eleven males with suspected SBMA phenotype and three suspected female carriers were examined. Male patients presented with the predominant signs of progressive, symmetrical distal limb weakness with amyotrophy, facial muscular weakness with orofacial fasciculations, nasal voice and slight dysphagia, gynaecomastia, decreased potency, as well as hand tremor and distal peripheral sensory disturbances in a few cases. One of the carriers presented with a 30-year history of fasciculations and minimal distal weakness and cramps in the legs, while the other two were asymptomatic. DNA analysis revealed expanded size of CAG repeats in Xq11-12 in the AR gene in 10 out of 11 men (range 45-52 CAG repeats) and in the women (range 46-48 CAG repeats). There was no correlation between CAG repeat size and the age of disease onset and duration of the disease. A rare, predominantly distal distribution of weakness and amyotrophy was found in our group of the SBMA patients (8 out of 11 cases) from three unrelated kindreds and also in the remaining two sporadic cases. The extended CAG repeats within families were stable.

The abnormalities of metallochemical reactions may contribute to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). In the present work, an investigation of the elemental composition of the gray matter, nerve cells and white matter from spinal cord tissues representing three ALS cases and five non-ALS controls was performed. This was done with the use of the synchrotron microbeam X-ray fluorescence technique (micro-SRXRF). The following elements were detected in the tissue sections: P, S, Cl, K, Ca, Fe, Cu, Zn and Br. A higher accumulation of Cl, K, Ca, Zn and Br was observed in the nerve cell bodies than in the surrounding tissue. Contrary to all other elements, Zn accumulation was lower in the white matter areas than in the gray matter ones. The results of quantitative analysis showed that there were no general abnormalities in the elemental accumulation between the ALS and the control group. However, for individual ALS cases such abnormalities were observed for the nerve cells. We also demonstrated differences in the elemental accumulation between the analyzed ALS cases.

Swallowing is a complex motor event that is difficult to investigate in man. A slowed ability to eat a meal, loss of salivary control with drooling, episodic coughing, and choking and nasal regurgitation occurred due to the dysphagia. Swallowing disorders can be divided into oropharyngeal dysphagia and oesophageal dysphagia. The most common cause of oropharyngeal dysphagia is cerebrovascular accidents; other causes may include oropharyngeal structural lesions, systematic and local muscular diseases, and diverse neurologic disorders. Oesophageal dysphagia may result from neuromuscular disorders, mobility abnormalities, and intrinsic or extrinsic obstructive lesions. Initial evaluation of patients with suspected oropharyngeal dysphagia includes patient history, laryngological and neurological examination, and careful videofluoroscopic study of pharyngeal dynamics. Initial evaluation of patients with suspected oesophageal dysphagia includes patient history and barium swallow with oesophagography. Classifying dysphagia as oropharyngeal, oesophageal and obstructive, or neuromuscular symptom complexes leads to a successful diagnosis in 80% of patients.

Background: Not many data concerning the laryngological evaluation of Amyotrophic Lateral Sclerosis (ALS) patients exist., The Aim of Study: The profile of laryngological disturbances in patients with ALS was evaluated., Material and Methods: We have studied 25 ALS patients (10 with bulbar signs and 15 with limb signs only) in the standard laryngological examination. Vocal folds motion was examined fiberoscopically., Results: In bulbar onset ALS cases we have showed different changes of the uni- or bilateral position of the vocal folds. In 9 out of 15 ALS patients with limb signs (without clinical bulbar signs) we also have discovered the slight disturbance of vocal folds movement or unilateral decrease of tension and mobility., Conclusions: The careful laryngological examination can shows the subtle, objective signs of the early dysfunction of vagus nerves in ALS patients before the clinical presentation of bulbar failure.

Background: The occurrence of the disturbances of oropharyngeal phases of swallowing in Amyotrophic Lateral Sclerosis (ALS) patients has been well documented., The Aim of Study: Assessment of the oesophageal manometry for detection of the oesophageal phase of swallowing in ALS patients., Material and Methods: The study was carried out in 12 dysphagic ALS patients and 10 sex- and age- matched healthy volunteers., Results: The mean upper oesophageal contractile: amplitude, duration and velocity during the wet and dry swallows in ALS individuals were statistically differ as compared to control subjects. The abnormalities of vocal folds function was also found in the fiberoscopy examination of larynx in all ALS patients., Conclusions: This study reveal the occurrence of disturbances of the oesophageal phase of swallowing in ALS patients with dysphagia.

Despite being one of the most devastating diseases known, there is little evidence for diagnosing and managing patients with amyotrophic lateral sclerosis (ALS). Although specific therapy is lacking, correct early diagnosis and introduction of symptomatic and specific therapy can have a profound influence on the care and quality of life of the patient and may increase survival time. This document addresses the optimal clinical approach to ALS. The final literature search was performed in the spring of 2005. Consensus recommendations are given graded according to the EFNS guidance regulations. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. People affected with possible ALS should be examined as soon as possible by an experienced neurologist. Early diagnosis should be pursued and a number of investigations should be performed with high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with vital capacity < 50%. Non-invasive positive pressure ventilation improves survival and quality of life but is underused. Maintaining the patients ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be fully discussed early with the patient and relatives respecting the patients social and cultural background.

The role that apoptosis plays in the pathogenesis of amyotrophic lateral sclerosis (ALS) is still unclear. From our autopsy samples, we have undertaken an effort to verify if apoptosis in ALS really occurs or if can at least be detected. The study was performed using TUNEL method for screening the apoptotic changes in the autopsy samples from 8 ALS cases compared with 16 control cases. No features of apoptosis (DNA cleavages) were noted in any of the investigated regions of the central nervous system in ALS cases as well as in controls. These preliminary results seem to support the reports, which deny the role of apoptosis in human ALS. The following investigations using additional methods will be performed for detection the apoptotic signals in ALS.

The bulbar symptoms of amyotrophic lateral sclerosis (ALS) include difficulty with the management of swallowing, saliva production, aspiration of secretion to the air ways and problems with spoken communication. These symptoms originate from the malfunction of the face muscles and pharynx sphincters. Patients with early symptoms of bulbar ALS are often referred to the otolaryngologist for the evaluation and management of dysphagia and dysarthria. The bulbar onset of ALS with hypernasality, articulation defects and voice harshness make the otolaryngologists the primary diagnostician for these signs. Careful examination of the speech quality and morphology as well as the function of vocal cords should be undertaken. Once the diagnosis of ALS is made, the otolaryngologist's involvement in medical treatment is necessary at different stages of the disease.

Objectives: It has been reported that the prevalance of parkinsonism might be associated with exposure to whooping cough., Methods: Examination of levels of antibodies against Bordetella pertussis in serum using enzyme-linked immunosorbent assay (ELISA) tests [presence of IgG antibodies against filamentous hemagglutinin and pertussis toxin (PT)] were performed in 81 persons (including 45 patients with controls) (age-matched groups)., Results: Positive results were found in patients with Parkinson's disease (PD), patients with other non-inflammatory diseases, and controls (about 40-45% in each group). A detailed examination of separate responses (IgG and IgA antibodies against PT, and a whole cell immune response) and of the serum level of immunoglobulins IgG, IgA and IgM was also performed., Conclusion: Our results demonstrate numerous cases of whooping cough serum antibodies among the adult population (also among PD patients). The results of our research, i.e. a common occurrence of Bordetella pertussis infection do not provide evidence of relationship between PD and the above-mentioned infection.

The investigations were done in acute and reconvalescent phase in 34 patients with bacterial meningoencephalitis. Neurologic condition, degree of the brain injury on the basis of Glasgow Coma Scale (GCS), protein level and pleocytosis in cerebrospinal fluid (CSF), and regional cerebral blood flow on dynamic computed tomography (CT) were assessed. The brain blood flow was measured in the white matter of the frontal and occipital horns of lateral ventricles, symmetrically in both hemispheres. Statistically significant reduction of the brain perfusion in acute phase of illness was improved. In reconvalescent phase normalisation of the brain blood supply was observed. 56% of patients had changes of consciousness. There was no significant correlation between these symptoms and parameters describing blood supply. The rest of patients had neurologic abnormalities: seizure, pyramidal syndrome, injury of the central nerves due to the reduction of blood flow in selected regions of the brain. Patients who aggregated low GCS score had high inflow of the blood. In patients who were in better condition, inflow was smaller. High pleocytosis in CSF was associated with small blood inflow and perfusion in investigated regions of the brain. Whereas high protein concentration correlated with higher inflow and increase in regional perfusion. We consider, that the brain blood supply correlate with intensification of inflammatory response in CSF.

The assessment of the levels of IgG antibodies against Bordetella pertussis in serum using ELISA test was performed in 59 patients (including 30 patients with Parkinson's disease--PD, 15 patients with other non-inflammatory neurological diseases, and 14 controls). The average age in the groups was 64.0, 64.4, and 58.7 years, respectively. Positive results were found in 17/30 patients with PD, 8/15 subjects with other non-inflammatory neurological diseases and in 7/14 controls. The above results are surprising and demonstrate a high incidence of subclinical whooping cough among the adult population. No statistically significant difference has been found between patients with Parkinson's disease and patients with other neurological diseases. A tendency is observed for a higher percentage of negative results among controls in comparison with patients with Parkinson's disease and other non-inflammatory neurological diseases.

Percutaneous endoscopic gastrostomy (PEG) has been proposed as symptomatic treatment of dysphagia in amyotrophic lateral sclerosis (ALS) patients. The aim of our study was to assess the safety and complications and survival after PEG implantations in 13 ALS patients. We discuss the factors related to survival in two groups: dead (6 out of 13 patients) and alive (7 out of 13) after PEG implantations. We demonstrate that the PEG procedure is quite safe and forced vital capacity (FVC) is a major factor related to survival after PEG implantation in studied patients.