Dysfunction In Amyotrophic Lateral Sclerosis Patients Research Articles

Choroid plexus enlargement in amyotrophic lateral sclerosis patients and its correlation with clinical disability and blood-CSF barrier permeability

BackgroundUsing in vivo neuroimaging techniques, growing evidence has demonstrated that the choroid plexus (CP) volume is enlarged in patients with several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. However, although animal and postmortem findings suggest that CP abnormalities are likely important pathological mechanisms underlying amyotrophic lateral sclerosis (ALS), the third most common neurodegenerative disease, no available study has been conducted to thoroughly assess CP abnormalities and their clinical relevance in vivo in ALS patients to date. Thus, we aimed to determine whether in vivo CP enlargement may occur in ALS patients. We also aimed to identify the relationships of CP volume with clinical disabilities and blood-CSF barrier (BCSFB) permeability in ALS patients.MethodsIn this retrospective study, based on structural MRI data, CP volume was assessed using a Gaussian mixture model and underwent further manual correction in 155 ALS patients and 105 age- and sex-matched HCs from October 2021 to April 2023. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess clinical disability. The CSF/serum albumin quotient (Qalb) was used to assess BCSFB permeability. Moreover, all the ALS patients completed genetic testing, and according to genetic testing, the ALS patients were further divided into genetic ALS subgroup and sporadic ALS subgroup.ResultsWe found that compared with HCs, ALS patients had a significantly higher CP volume (p < 0.001). Moreover, compared with HCs, CP volume was significantly increased in both ALS patients with and without known genetic mutations after family-wise error correction (p = 0.006 and p < 0.001, respectively), while there were no significant differences between the two ALS groups. Furthermore, the CP volume was significantly correlated with the ALSFRS-r score (r = -0.226; p = 0.005) and the Qalb (r = 0.479; p < 0.001) in ALS patients.ConclusionOur study first demonstrates CP enlargement in vivo in ALS patients, and continues to suggest an important pathogenetic role for CP abnormalities in ALS. Moreover, assessing CP volume is likely a noninvasive and easy-to-implement approach for screening BCSFB dysfunction in ALS patients.

Subclinical articulatory changes of vowel parameters in Korean amyotrophic lateral sclerosis patients with perceptually normal voices.

The available quantitative methods for evaluating bulbar dysfunction in patients with amyotrophic lateral sclerosis (ALS) are limited. We aimed to characterize vowel properties in Korean ALS patients, investigate associations between vowel parameters and clinical features of ALS, and analyze subclinical articulatory changes of vowel parameters in those with perceptually normal voices. Forty-three patients with ALS (27 with dysarthria and 16 without dysarthria) and 20 healthy controls were prospectively collected in the study. Dysarthria was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R) speech subscores, with any loss of 4 points indicating the presence of dysarthria. The structured speech samples were recorded and analyzed using Praat software. For three corner vowels (/a/, /i/, and /u/), data on the vowel duration, fundamental frequency, frequencies of the first two formants (F1 and F2), harmonics-to-noise ratio, vowel space area (VSA), and vowel articulation index (VAI) were extracted from the speech samples. Corner vowel durations were significantly longer in ALS patients with dysarthria than in healthy controls. The F1 frequency of /a/, F2 frequencies of /i/ and /u/, the VSA, and the VAI showed significant differences between ALS patients with dysarthria and healthy controls. The area under the curve (AUC) was 0.912. The F1 frequency of /a/ and the VSA were the major determinants for differentiating ALS patients who had not yet developed apparent dysarthria from healthy controls (AUC 0.887). In linear regression analyses, as the ALSFRS-R speech subscore decreased, both the VSA and VAI were reduced. In contrast, vowel durations were found to be rather prolonged. The analyses of vowel parameters provided a useful metric correlated with disease severity for detecting subclinical bulbar dysfunction in ALS patients.

Amygdala abnormalities across disease stages in patients with sporadic amyotrophic lateral sclerosis.

To examine selective atrophy patterns and resting-state functional connectivity (FC) alterations in the amygdala at different stages of amyotrophic lateral sclerosis (ALS), and to explore any correlations between amygdala abnormalities and neuropsychiatric symptoms. We used the King's clinical staging system for ALS to divide 83 consecutive patients with ALS into comparable subgroups at different disease stages. We explored the pattern of selective amygdala subnucleus atrophy and amygdala-based whole-brain FC alteration in these patients and 94 healthy controls (HCs). Cognitive and emotional functions were also evaluated using a neuropsychological test battery. There were no significant differences between ALS patients at King's stage 1 and HCs for any amygdala subnucleus volumes. Compared with HCs, ALS patients at King's stage 2 had significantly lower left accessory basal nucleus and cortico-amygdaloid transition volumes. Furthermore, ALS patients at King's stage 3 demonstrated significant reductions in most amygdala subnucleus volumes and global amygdala volumes compared with HCs. Notably, amygdala-cuneus FC was increased in ALS patients at King's stage 3. Specific subnucleus volumes were significantly associated with Mini-Mental State Examination scores and Hamilton Anxiety Rating Scale scores in ALS patients. In conclusions, our study provides a comprehensive profile of amygdala abnormalities in ALS patients. The pattern of amygdala abnormalities in ALS patients differed greatly across King's clinical disease stages, and amygdala abnormalities are an important feature of patients with ALS at relatively advanced stages. Moreover, our findings suggest that amygdala volume may play an important role in anxiety and cognitive dysfunction in ALS patients.

Autonomic dysfunction in amyotrophic lateral sclerosis: A neurophysiological and neurosonology study.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Some ALS patients exhibit concomitant nonmotor signs, and thus ALS is considered a multisystem disorder. The aim of this study is to investigate autonomous nervous system involvement in ALS. We investigated 21 ALS patients and 28 age-matched controls. ALS patients were assessed for disease severity with the Revised-ALS Functional Rating Scale (ALSFSR) and for the presence of autonomic symptoms with the Composite Autonomic Symptom Score scale. Sympathetic nervous system was evaluated by sympathetic skin response (SSR) and parasympathetic nervous system by ultrasonography of vagus nerve (VN) at the level of the thyroid gland. SSR latencies were shorter and SSR amplitudes were higher in controls compared to ALS patients. The cross-sectional area (CSA) of the VN was significantly smaller in ALS patients (mean CSA right/left: 1.73±0.62 mm2 /1.47±0.53 mm2 ) compared to controls (mean CSA right/left: 2.91±0.79 mm2 /2.30±0.80 mm2 ), right: p <. 001, left: p <. 001. There was a significant negative correlation between disease duration and CSA of left-VN (r = -0.493, p = .023). This correlation was attenuated between disease duration and CSA of right-VN (r = -0.419, p = .059). ALSFSR-R was positively correlated to CSA of right-VN (p = .006, r = 0.590). CSA of VN did not correlate with bulbar involvement. This study confirms the presence of autonomic dysfunction in ALS patients and provides evidence of VN atrophy that correlates with disease severity and duration and is independent of bulbar involvement. Degeneration of dorsal nucleus neurons of the VN is hypothesized.

Behavioural changes predict poorer survival in amyotrophic lateral sclerosis

ObjectiveThe Motor Neuron Disease Behavioural Scale (MiND-B) is a clinically validated tool that was developed to detect behavioural dysfunction in patients with amyotrophic lateral sclerosis (ALS). The current study aimed to evaluate behavioural impairment using MiND-B, as well as cognitive dysfunction in ALS patients, and to determine their prognostic implications. MethodPatients with a clinical diagnosis of ALS were prospectively recruited from a specialised multidisciplinary ALS clinic. Patients underwent behavioural assessment with the Motor Neuron Disease Behavioural Scale (MiND-B) and cognitive evaluation using the Addenbrooke’s Cognitive Examination (ACE). Primary outcome measure was selected as survival time, defined by time from assessment to time of death or censor date. Univariate assessment of survival effect was carried out using Kaplan-Meier survival analysis followed by cox regression analysis to assess the effect of MiND-B and ACE scores on survival time. ResultsA total of 134 patients were included in the study. MiND-B testing determined that 59% were classified as having behavioural dysfunction, with deficits associated with a significantly shorter survival time (HR 2.53, p = 0.003, 95% CI 1.3–4.6). Furthermore, regression analysis demonstrated that for every 1-point reduction in the MiND-B score, risk of death increased by 3%. ACE testing established that 33% of the cohort had evidence of cognitive dysfunction. Patients with cognitive dysfunction on ACE testing had a significantly shorter survival time than patients without cognitive impairment (HR 2.0, p = 0.042, 95% CI 1.04–3.3). ConclusionThe presence of behavioural and cognitive impairments in ALS patients was associated with poor survival. The MiND-B and ACE inventories are simple and efficient clinical tools that can be administered in the multidisciplinary ALS clinic, that aid in the prognostication of this patient population.

Central motor conduction time reveals upper motor neuron involvement masked by lower motor neuron impairment in a significant portion of patients with amyotrophic lateral sclerosis

ObjectiveWe retrospectively investigated the utility of the central motor conduction time (CMCT) in detecting upper motor neuron (UMN) involvements in patients with amyotrophic lateral sclerosis (ALS). MethodsFifty-two ALS patients and 12 disease control patients participated in this study. Surface electromyograms were recorded from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. We stimulated the motor cortex, brainstem, and spinal nerve using transcranial magnetic stimulation (TMS) in order to measure the cortical, brainstem, and spinal latencies. We divided the ALS patients into 2 subgroups (with UMN impairment vs. without UMN impairment) and calculated the rates of abnormal CMCT prolongation judged by their comparison with the normal ranges obtained by the measurement in the control patients. ResultsThe CMCTs in the FDI and TA were abnormally prolonged in over 40% of the ALS patients with UMN impairment and in nearly 30% of those without UMN impairment. ConclusionsCMCT shows UMN dysfunction in ALS patients without clinical UMN impairment. SignificanceTMS still has diagnostic utility in a significant portion of ALS patients.

P74-F Vestibular evoked myogenic potentials and their clinical utility in patients with amyotrophic lateral sclerosis

To evaluate the diagnostic value of vestibular evoked myogenic potentials (VEMPs) in the assessment of brainstem function integrity in patients with amyotrophic lateral sclerosis (ALS). This was a prospective case-control study including 30 definite or probable ALS patients divided into two groups (with or without brainstem involvement) and 30 healthy controls. Cervical (c-), masseter (m-) and ocular VEMP (o-VEMP) measurements were obtained for all the participants. The c-VEMP mean p13 and n23 were significantly prolonged in the ALS patients. The interside peak differences in p13 and n23 of c-VEMP and in n10 and p15 of o-VEMP were significantly prolonged. The rates of alteration in c-VEMP, m-VEMP and o-VEMP in the ALS patients were 67%, 40%, and 45%, respectively. The ALS patients with brainstem involvement had a significantly higher percentage of VEMP abnormalities than did those without brainstem involvement (p = 0.027). c-VEMP is a sensitive tool to detect lower levels of brainstem involvement. Impairments in o-VEMP and m-VEMP indicate involvement of the upper brainstem. The use of combined VEMPs may provide useful insights into the pathophysiological mechanism of ALS. VEMPs may be useful in the evaluation of brainstem dysfunction in ALS patients.

Vestibular evoked myogenic potentials and their clinical utility in patients with amyotrophic lateral sclerosis

ObjectiveTo evaluate the diagnostic value of vestibular evoked myogenic potentials (VEMPs) in the assessment of brainstem function integrity in patients with amyotrophic lateral sclerosis (ALS). MethodsThis was a prospective case-control study including 30 definite or probable ALS patients divided into two groups (with or without brainstem involvement) and 30 healthy controls. Cervical (c-), masseter (m-) and ocular VEMP (o-VEMP) measurements were obtained for all the participants. ResultsThe c-VEMP mean p13 and n23 were significantly prolonged in the ALS patients. The interside peak differences in p13 and n23 of c-VEMP and in n10 and p15 of o-VEMP were significantly prolonged. The rates of alteration in c-VEMP, m-VEMP and o-VEMP in the ALS patients were 67%, 40%, and 45%, respectively. The ALS patients with brainstem involvement had a significantly higher percentage of VEMP abnormalities than did those without brainstem involvement (p = 0.027). Conclusionsc-VEMP is a sensitive tool to detect lower levels of brainstem involvement. Impairments in o-VEMP and m-VEMP indicate involvement of the upper brainstem. The use of combined VEMPs may provide useful insights into the pathophysiological mechanism of ALS. SignificanceVEMPs may be useful in the evaluation of brainstem dysfunction in ALS patients.

Functional Biomarkers for Amyotrophic Lateral Sclerosis.

The clinical diagnosis of amyotrophic lateral sclerosis (ALS) relies on determination of progressive dysfunction of both cortical as well as spinal and bulbar motor neurons. However, the variable mix of upper and lower motor neuron signs result in the clinical heterogeneity of patients with ALS, resulting frequently in delay of diagnosis as well as difficulty in monitoring disease progression and treatment outcomes particularly in a clinical trial setting. As such, the present review provides an overview of recently developed novel non-invasive electrophysiological techniques that may serve as biomarkers to assess UMN and LMN dysfunction in ALS patients.

Dysfunction of central control of breathing in amyotrophic lateral sclerosis.

Dysfunction in central control of breathing in some amyotrophic lateral sclerosis (ALS) patients is not adequately detected with standard evaluation for respiratory dysfunction. Nocturnal oximetry reveals periodic desaturations despite normal respiratory muscle movements. Continuous diaphragmatic electromyography has provided in vivo data consistent with impaired central control of diaphragm motor units. Current understanding of central control of breathing identifies the pre-Botzinger complex as the inspiratory rhythm generator. Animal models of pre-Botzinger complex neurodegeneration demonstrate rapid eye movement-related central sleep apneas progressing to loss of rapid eye movement sleep, also apparent in some ALS patients. Evidence supports the hypothesis that dysfunction in central control of breathing in some ALS patients may be related to pre-Botzinger complex degeneration. As the impact dysfunction of central control of breathing has on ALS becomes better defined the current standard of evaluating respiratory dysfunction in ALS patients may need updating. Muscle Nerve 56: 197-201, 2017.

Needle electromyography features and values of paraspinal muscle parameters in assessment of respiratory function of patients with amyotrophic lateral sclerosis

Objective: To analyze the features of needle electromyography (EMG) in patients with amyotrophic lateral sclerosis (ALS), and explore the correlation between EMG parameters of the tenth thoracic paraspinal muscle and disease duration, rate of disease progression, forced vital capacity (FVC) and revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Methods: Standard EMG was recorded from unilateral sternocleidomastoid muscle and/or tongue muscles, upper and lower limbs muscles and the tenth thoracic paraspinal muscle in 112 patients with definite ALS between March 2012 and June 2013 in the Department of Neurology at Chinese PLA General Hospital. Parameters studies included spontaneous potentials, duration and amplitude of motor unit potentials (MUP), pattern of recruitment. Results: EMG revealed diffuse neurogenic changes in each case. Fibrillation potential or positive sharp waves were found in some muscles in all of patients, and both of them were found in most of the cases. Fasciculation potentials (FPs) were found in 8 patients and accompanied with fibrillation potential and positive sharp waves in 5 of them. Complex repetitive discharges (CRDs) were found in only 1 patient. Duration and amplitude of MUP was prolonged and increased in ALS patients, and the rate of high amplitude and decreased recruitment pattern were 35.71% and 72.32%, respectively. Logistic regression analysis revealed an association of the FVC loss with the drop of ALSFRS-R and peak amplitude of the tenth thoracic paraspinal muscle. Conclusions: The abnormal spontaneous activity with high frequency are fibrillation potentials and/or positive sharp waves. However, FPs is observed in a small number of patients and CRDs is rarely seen in ALS. The ALSFRS-R and peak amplitude of thetenth thoracic paraspinal muscle may be of certain clinical value in estimating the severity of disease especially the respiratory dysfunction in ALS patients.

Exploring Olfactory Function and Its Relation with Behavioral and Cognitive Impairment in Amyotrophic Lateral Sclerosis Patients: A Cross-Sectional Study

Background: Behavioral and cognitive impairment are common in amyotrophic lateral sclerosis (ALS) and represent a continuum with frontotemporal dementia (FTD). Olfactory dysfunction has been described in a subset of ALS patients and might be associated with frontotemporal and insular cortex dysfunction. Objective: To evaluate olfaction dysfunction in ALS patients and its relationship with either cognition or behavioral impairment. Methods: 28 consecutive ALS patients underwent an extensive cognitive and behavioral battery and were classified as patients with normal cognition (ALS-N, n = 11) or with part of the ALS-FTD spectrum (n = 17), including either cognitive or behavioral impairment or dementia. Odor verbal and visual identification and discrimination were investigated in patients and age-matched controls using a test adapted from the Sniffin' Sticks. Results: Olfactory function was significantly different between ALS-FTD spectrum patients and controls (p < 0.001) and inversely correlated with behavioral and cognitive performance. The 10-point cutoff distinguished ALS-N from ALS-FTD spectrum patients with a sensitivity and specificity of 71 and 100%, respectively. Conclusions: Hyposmia is common in a subset of ALS patients and strongly associated with behavioral and cognitive impairment. Olfactory testing may represent an early screening tool in order to identify ALS subjects with cognitive/behavioral dysfunction. Further studies in larger series are mandatory in order to better investigate clinical and pathological aspects in this group of patients.

Cartilage dysfunction in ALS patients as side effect of motion loss: 3D mechano-electrochemical computational model.

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease characterized by progressive weakness, muscle atrophy, and fasciculation. This fact results in a continuous degeneration and dysfunction of articular soft tissues. Specifically, cartilage is an avascular and nonneural connective tissue that allows smooth motion in diarthrodial joints. Due to the avascular nature of cartilage tissue, cells nutrition and by-product exchange are intermittently occurring during joint motions. Reduced mobility results in a change of proteoglycan density, osmotic pressure, and permeability of the tissue. This work aims to demonstrate the abnormal cartilage deformation in progressive immobilized articular cartilage for ALS patients. For this aim a novel 3D mechano-electrochemical model based on the triphasic theory for charged hydrated soft tissues is developed. ALS patient parameters such as tissue porosity, osmotic coefficient, and fixed anions were incorporated. Considering different mobility reduction of each phase of the disease, results predicted the degree of tissue degeneration and the reduction of its capacity for deformation. The present model can be a useful tool to predict the evolution of joints in ALS patients and the necessity of including specific cartilage protectors, drugs, or maintenance physical activities as part of the symptomatic treatment in amyotrophic lateral sclerosis.

Relationship between cervical cord 1H‐magnetic resonance spectroscopy and clinoco‐electromyographic profile in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons, leading to limb paralysis and respiratory failure. C1-C3 cord (1) H-magnetic resonance spectroscopy ((1) H-MRS) was performed in 19 patients with ALS and 20 controls. N-acetylaspartate (NAA), choline-containing compounds, creatine plus phosphocreatine (Cr), and myo-Inositol (m-Ins) were measured. ALS functional rating scale-revised (ALSFRS) and forced vital capacity (FVC) were assessed. The rates of decline were calculated at 6 months before and after (1) H-MRS. NAA/Cr and NAA/m-Ins were decreased significantly, and m-Ins/Cr was increased significantly in ALS patients compared with controls. NAA/Cr and NAA/m-Ins were correlated with ALSFRS and FVC and inversely linked to the decline rates. NAA/Cr, NAA/m-Ins, and m-Ins/Cr were altered markedly in 9 patients with denervation and neurogenic changes in both C2 paraspinal and upper limb muscles. These metabolite ratios were associated with disease progression and ongoing denervation in neck and hand muscles. C1-C3 cord (1) H-MRS might reflect anterior horn cell damage causing neck/arm weakness and respiratory dysfunction in ALS patients.

P20 Frontal white matter connections and cognitive change in amyotrophic lateral sclerosis: a DTI-tractography study

<h3>Objective</h3> Traditionally considered a motor-neuron disorder, cognitive and behavioural impairments in a subset of non-demented amyotrophic lateral sclerosis (ALS) patients are now well-acknowledged. This study aimed to define the structural basis of cognitive abnormalities in ALS, by clarifying the involvement of specific cognitive domains and the respective contribution of white matter damage to the integrity of the uncinate (UF), inferior longitudinal (ILF) and inferior-frontal occipital (IFOF) fasciculi. <h3>Method</h3> 26 ALS patients and 27 healthy controls underwent a detailed neuropsychological assessment and a whole brain diffusion tensor imaging (DTI) scan. The two groups were matched for age, IQ, years of education, and anxiety and depression scores. Individual neuropsychological test scores were converted into four composite scores, measuring executive functions, language, memory and visuospatial ability. Changes in fractional anisotropy (FA) and mean diffusivity (MD) were measured along the UF, ILF, and the IFOF using a two-region of interest approach. <h3>Results</h3> ALS patients were found to exhibit impaired performance on the executive and language composite test scores, but not on memory and visuospatial composite test scores. DT-MRI investigations of the white matter association tracts (ie, UF, ILF and IFOF) identified no significant differences in ALS-patients compared to healthy controls with respect to mean FA values, indicating that water diffusion within these tracts still followed the main axonal direction. MD values however were found to be significantly increased within the uncinate fasciculus of ALS-patients compared to healthy controls. This is associated with neurodegeneration, as an increased MD typically arises from reduced barriers of diffusion, indicating weak axonal myelination. Correlational analysis did not find significant relationships between white matter tracts and neuropsychological composite scores. <h3>Conclusion</h3> The findings confirm the presence of executive dysfunction in ALS patients and also suggest that language deficits maybe more extensive and prevalent than has been suggested by previous research. These results suggest involvement of the UF within the disease-profile of ALS, however correlations to significant deficits remain to be found. If confirmed in a larger study this frontal white matter change could represent an important biomarker for trials in ALS.

Disruption of skeletal muscle mitochondrial network genes and miRNAs in amyotrophic lateral sclerosis

Skeletal muscle mitochondrial dysfunction is believed to play a role in the progression and severity of amyotrophic lateral sclerosis (ALS). The regulation of transcriptional co-activators involved in mitochondrial biogenesis and function in ALS is not well known. When compared with healthy control subjects, patients with ALS, but not neurogenic disease (ND), had lower levels of skeletal muscle peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA and protein and estrogen-related receptor-α (ERRα) and mitofusin-2 (Mfn2) mRNA. PGC-1β, nuclear respiratory factor-1 (NRF-1) and Mfn1 mRNA as well as cytochrome C oxidase subunit IV (COXIV) mRNA and protein were lower in patients with ALS and ND. Both patient groups had reductions in citrate synthase and cytochrome c oxidase activity. Similar observations were made in skeletal muscle from transgenic ALS G93A transgenic mice. In vitro, PGC-1α and PGC-1β regulated Mfn1 and Mfn2 in an ERRα-dependent manner. Compared to healthy controls, miRNA 23a, 29b, 206 and 455 were increased in skeletal muscle of ALS patients. miR-23a repressed PGC-1α translation in a 3′ UTR dependent manner. Transgenic mice over expressing miR-23a had a reduction in PGC-1α, cytochome-b and COXIV protein levels. These results show that skeletal muscle mitochondrial dysfunction in ALS patients is associated with a reduction in PGC-1α signalling networks involved in mitochondrial biogenesis and function, as well as increases in several miRNAs potentially implicated in skeletal muscle and neuromuscular junction regeneration. As miR-23a negatively regulates PGC-1α signalling, therapeutic inhibition of miR-23a may be a strategy to rescue PGC-1α activity and ameliorate skeletal muscle mitochondrial function in ALS.

Is there a case for diaphragm pacing for amyotrophic lateral sclerosis patients?

Respiratory pacing has advanced the long-term management of respiratory failure secondary to neurological disorders. It has an established role in curtailing invasive mechanical ventilation after upper motor neuron lesions such as spinal cord injury. There is increasing interest to expand the application of intramuscular diaphragm pacing to amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disease. Although diaphragm pacing has been offered to ALS patients, evidence-based data to determine its benefits remain lacking. The limited current literature indicates progression of respiratory dysfunction in ALS patients despite diaphragm pacing. The data from clinical trials are inadequate to substantiate its survival and sleep benefits. Its advantages over non-invasive mechanical ventilation have not been directly investigated. Furthermore, there are cautions for ALS patients to consider when opting for diaphragm pacing. Progressive degeneration of the phrenic motor neurons in classic ALS will interrupt the transmission of pacer signals to sustain diaphragm contractions. Pacing protocols that are safe for other neurological conditions may be detrimental for ALS, at least as suggested by transgenic animal models. Issues inherent to the device warrant expert intervention in implanted patients. At present, clinical effectiveness and long-term safety concerns about diaphragm pacing in ALS remain to be addressed.

Frontal Assessment Battery to Evaluate Frontal Lobe Dysfunction in ALS Patients

Assessment of frontal lobe impairment in amyotrophic lateral sclerosis (ALS) is a matter of great importance, since it often causes ALS patients to decrease medication and nursing compliance, thus shortening their survival time. The frontal assessment battery (FAB) is a short and rapid method for assessing frontal executive functions. We investigated the applicability of the FAB as a screening method for assessing cognitive impairments in 61 ALS patients. Depending on the results of the FAB, we classified patients into two subgroups: FAB-normal and FAB-abnormal. We then performed additional evaluations of cognitive function using the Korean version of the mini-mental state examination (K-MMSE), a verbal fluency test (COWAT), and a neuropsychiatric inventory (NPI). Results of these tests were compared between the two groups using Mann-Whitney U-tests, and Spearman correlation analyses were used to investigate the relationships between FAB score and disease duration and severity. Of the 61 sporadic ALS patients included in this study, 14 were classified as FAB-abnormal and 47 were classified as FAB-normal. The FAB-normal and FAB-abnormal patients performed significantly differently in all domains of the COWAT. There was no difference in behavioral disturbance, as assessed by the NPI, between the two groups. The FAB scores were found to significantly correlate with both disease duration and severity. The FAB shows promise as a method of screening for frontal lobe dysfunction in ALS, as it is not only quick and easy, but also reliable. Additional studies should examine how FAB performance changes as ALS progresses.

筋萎縮性側索硬化症におけるＦｒｏｎｔａｌ Ａｓｓｅｓｓｍｅｎｔ Ｂａｔｔｅｒｙによる前頭葉機能評価

Frontal Assessment Battery (FAB) is short neuropsychological battery for the bed side screening of frontal lobe function. Several studies have indicated that frontal lobe dysfunction is the main neuropsychological feature in Amyotrophic lateral sclerosis (ALS). We examined frontal lobe function in patients with ALS and in age-matched normal subjects by using the FAB. We examined 24 patients with sporadic ALS aged 66.0 +/- 10.1 years, with a mean disease duration of 2.0 +/- 0.7 years, a Mini-Mental State Examination score of > or = 24, a normal self-rating depression score, no dyspnea, and no or only slight disturbances in speech, cutting food, and handling utensils on the ALS Functional Rating Scale. Total FAB score, similarity score, and lexical fluency score were significantly lower in ALS patients. Total FAB score did not correlate with age, disease duration, ALS Functional Rating Scale, spirometry, or blood gas analyses. These results suggest frontal lobe dysfunction in ALS patients.

Event-related brain potentials in amyotrophic lateral sclerosis: A review of the international literature

Amyotrophic lateral sclerosis (ALS), traditionally considered as a disorder limited to the motor system, is increasingly recognized to be a multisystem disease, involving associative areas in addition to the motor cortex and therefore affecting cognition. ALS patients may present with subtle behavioural and executive dysfunctions or, less frequently, with a manifest frontotemporal dementia. Event-related potentials (ERPs) are a high-temporal resolution technique, which can be used to explore the presence of cognitive dysfunction. All the primary studies reviewed here have shown ERP abnormalities in groups of non-demented patients affected by sporadic ALS compared to healthy controls. The ERP results support findings of neuropsychological and imaging studies. Prospective studies combining simultaneous neuropsychological and imaging investigations are needed to assess the possible role of ERPs in the early detection and follow-up of cognitive dysfunction in ALS patients.