The Balloon-Based Manometry Evaluation of Swallowing in Patients with Amyotrophic Lateral Sclerosis.

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.

The Evaluation of Abnormal Voice Qualities in Patients with Amyotrophic Lateral Sclerosis.

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.

A Unique Multiplex ELISA to Profile Growth Factors and Cytokines in Cerebrospinal Fluid.

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.

A large genome scan for rare CNVs in amyotrophic lateral sclerosis.

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.

EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force.

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.

Dysarthria in amyotrophic lateral sclerosis: A review.

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.

The -A162G polymorphism of the PON1 gene and the risk of sporadic amyotrophic lateral sclerosis.

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.

The C(-1562)T polymorphism of the MMP-9 gene and the risk of sporadic amyotrophic lateral sclerosis.

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.

[Analysis of oropharyngeal phase of swallowing in patients with amyotrophic lateral sclerosis]. / Analiza fazy ustno-gardlowej polykania u chorych na stwardnienie boczne zanikowe.

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.

Pure primary lateral sclerosis--Case reports.

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.

Sympathetic vascular response to facial cooling is increased in flail phenotypes of amyotrophic lateral sclerosis.

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 (LatHR, tHR, LatBP, tBP). 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 LatHR and shorter tHR 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.

[Diagnosis and treatment of amyotrophic lateral sclerosis according to EFNS recommendations (2005)]. / Rozpoznawanie i leczenie stwardnienia bocznego zanikowego zgodnie z zaleceniami Europejskiej Federacji Towarzystw Neurologicznych (EFNS) z 2005 r.

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 laryngological and neurological aspects of dysphagia]. / Laryngologiczne i neurologiczne aspekty zaburzen polykania.

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.

[Laryngological presentation of patients with amyotrophic lateral sclerosis (ALS)]. / Laryngologiczna prezentacja chorych na stwardnienie boczne zanikowe (SLA).

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.

[Analysis of disturbances of oesophageal phase of swallowing in patients with amyotrophic lateral sclerosis (ALS)]. / Analiza zaburzen fazy przelykowej polykania u chorych na stwardnienie boczne zanikowe (SLA).

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.

Does apoptosis occur in amyotrophic lateral sclerosis? TUNEL experience from human amyotrophic lateral sclerosis (ALS) tissues.

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 heterogeneity of neuropathological changes in amyotrophic lateral sclerosis. A review of own autopsy material.

As an approach to the validation of different pathological findings in ALS, we have reviewed the histopathological slides of 24 cases (12 men, 12 women) of autopsy-confirmed ALS which had been treated in our centre (18 definite, 3 probable and 3 possible ALS). The mean age and survival was 57.1 years and 23.5 months respectively. The slides (from motor cortex, basal ganglia, brain stem and spinal cord) were reviewed with special attention paid to the severity of motor cortex and corticospinal tract degeneration, infiltrations of macrophages, atrophy of lower motor neurones, accumulation of lipofuscin, chromatolysis and gliosis. We also searched for the occurrence of axonal spheroids and various kinds of inclusions, like Bunina bodies, large hyaline, Lewy-body-like inclusions and even larger "hyaline balls", and ubiquitinated inclusions. The histological examination revealed considerable differences between particular cases. Different kinds of inclusions were found in 19 out of 24 cases. A shorter duration of the disease was found in the cases with numerous macrophages. The apparent histological degeneration of the motor cortex was found in cases with longer duration of the disease. However, the differences were not significant and no correlation between the occurrence of any type of inclusion or any other pathological finding and the duration of the disease was found. Whether apparent pathomorphological "heterogeneity" reflects some true differences in the pathogenesis of ALS is disputable.

[The importance of laryngological and phoniatric evaluation at the early stage of amyotrophic lateral sclerosis]. / Znaczenie badan laryngologiczno-foniatrycznych w poczatkowym stadium stwardnienia bocznego zanikowego.

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.

[Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis patients with dysphagia. A preliminary report]. / Przezskórna gastrostomia endoskopowa u chorych ze stwardnieniem bocznym zanikowym i dysfagia. Doniesienie wstepne.

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.

[Disturbances of cerebral perfusion in patients with bacterial meningoencephalitis]. / Zaburzenia ukrwienia mózgu u chorych z ropnym zapaleniem opon mózgowo-rdzeniowych i mózgu.

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.