Accrued somatic mutations (nucleic acid changes) trigger ALS: 2005–2015 update

Amyotrophic lateral sclerosis (ALS) is a multilevel disease of the motor neuron system. The mechanisms triggering disease onset should be considered separately from those facilitating its spread and motor neuron death. In 2005, I brought together clinical and epidemiological evidence to support the hypothesis that acquired nucleic acid changes may trigger sporadic ALS. Since 2005, the conceptual foundations for this hypothesis have been strengthened. The journal Amyotrophic Lateral Sclerosis was renamed Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration. The focal onset, with simultaneous initial maximal upper and lower motor neuron involvement in the region of onset, and patterns of spread, were characterized further. Clues from the epidemiology of sporadic ALS were affirmed by quantitative analysis, including the increase in disease incidence with age, suggesting accrual of time‐dependent changes, and the confirmation of smoking as an established risk factor. Additional observations support the conclusion that accrued somatic mutations trigger onset of ALS. Muscle Nerve 53 : 842–849, 2016     

Distal Predominance of Electrodiagnostic Abnormalities in Early‐Stage Amyotrophic Lateral Sclerosis

Introduction: In this study we compared the electrodiagnostic (EDX) yield of limb muscles in revealing lower motor neuron (LMN) dysfunction by electromyography (EMG) in early‐stage amyotrophic lateral sclerosis (ALS). Methods: This investigation was undertaken as a retrospective review at a single center. Results: Our study included 122 consecutive patients with possible ALS, as defined by revised El Escorial criteria. Distal limb muscles showed more frequent EMG abnormalities than proximal muscles. EDX yield was found to be higher in the limb where weakness began and when clinical signs of LMN dysfunction were evident. Adoption of the Awaji criteria significantly increased the yield of EMG‐positive segments in the cervical (P < 0.0005) and lumbosacral (P < 0.0001) regions, and upgraded 19 patients into the probable category and 1 patient into the definite category. Discussion: EMG abnormalities are predominant in the distal limb in early‐stage ALS. A redefinition of an EDX‐positive cervical or lumbosacral segment, with an emphasis on distal limb muscles, may result in an earlier ALS diagnosis. Muscle Nerve 58 : 389–395, 2018     

Pattern difference of dissociated hand muscle atrophy in amyotrophic lateral sclerosis and variants

Introduction: Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). Methods: We evaluated the pattern difference of intrinsic hand muscles of upper limb‐onset ALS (UL‐ALS), upper limb‐onset progressive muscular atrophy (UL‐PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. Results: The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL‐ALS than other variants, but a considerable proportion of UL‐ALS cases had an amplitude ratio in the range of other variants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (≥4) occurred only with UL‐ALS. Conversely, an absent ADM CMAP was identified only in UL‐PMA and BAD. Conclusions: The absolute ADM/APB CMAP amplitude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help predict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS. Muscle Nerve 51: 333–337, 2015     

Motor unit number index and neurophysiological index as candidate biomarkers of presymptomatic motor neuron loss in amyotrophic lateral sclerosis

Introduction: Our objective was to determine the utility of motor unit number index (MUNIX) and neurophysiological index (NI) as surrogate biomarkers of disease progression in limbs without clinical signs of lower motor neuron (LMN) involvement from patients with slowly progressive amyotrophic lateral sclerosis (ALS). Methods: Patients with slowly progressive ALS and at least 1 clinically unaffected limb were prospectively enrolled. Clinical signs of LMN loss and results from hand‐held dynamometer (HHD), revised ALS Functional Rating Scale (ALSFRS‐R), mean‐MUNIX (from 3 different muscles), and NI were longitudinally recorded. Results: Eighteen patients with 43 presymptomatic muscles were evaluated. Twenty‐seven muscles remained clinically unaffected during study, with stable ALSFRS‐R subscores and HHD measures. However, a significant decline in mean‐MUNIX and NI was detected. Discussion: Mean‐MUNIX and NI were more sensitive than clinical measures at detecting LMN loss in presymptomatic limbs from patients with slowly progressive ALS. Therefore, these electrophysiological biomarkers should be included in early study phases as meaningful outcome measures. Muscle Nerve 58 : 204–212, 2018     

Amyotrophic lateral sclerosis regional progression intervals change according to time of involvement of different body regions

Background and purpose

The prediction of disease course is one of the main targets of amyotrophic lateral sclerosis (ALS) research, particularly considering its wide phenotypic heterogeneity. Despite many attempts to classify patients into prognostic categories according to the different spreading patterns at diagnosis, a precise regional progression rate and the time of involvement of each region has yet to be clarified. The aim of our study was to evaluate the functional decline in different body regions according to their time of involvement during disease course.

Methods

In a population-based dataset of ALS patients, we analysed the functional decline in different body regions according to time and order of regional involvement. We calculated the regional progression intervals (RPIs) between initial involvement and severe functional impairment using the ALS Functional Rating Scale revised (ALSFRS-r) subscores for the bulbar, upper limb, lower limb and respiratory/thoracic regions. Time-to-event analyses, adjusted for age, sex, ALSFRS-r pre-slope (ΔALSFRS-R), cognitive status, and mutational status were performed.

Results

The duration of RPI differed significantly among ALS phenotypes, with the RPI of the first region involved being significantly longer than the RPIs of regions involved later. Cox proportional hazard models showed that in fact a longer time between disease onset and initial regional involvement was related to a reduced duration of the RPI duration in each different body region (bulbar region: hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.06–1.16, p < 0.001; upper limb region: HR 1.16, 95% CI 1.06–1.28, p = 0.002; lower limb region: HR 1.11, 95% CI 1.03–1.19, p = 0.009; respiratory/thoracic region: HR 1.10, 95% CI 1.06–1.14, p = 0.005).

Conclusions

We found that the progression of functional decline accelerates in regions involved later during disease course. Our findings can be useful in patient management and prognosis prediction.     

Fibromyalgia‐like symptoms associated with irritable bowel syndrome: A challenging diagnosis of late‐onset Pompe disease

Introduction: Late‐onset Pompe disease (LOPD) is a rare autosomal recessive disorder which usually presents as a limb‐girdle myopathy with early respiratory involvement. Methods: We report 2 sisters with an uncommon presentation of LOPD characterized by fibromyalgia‐like pain associated with irritable bowel syndrome. Results: In both sisters, clinical examination was normal and had remained stable for 10 years. The serum creatine kinase level was mildly elevated. Several muscle biopsies showed slight nonspecific myopathic abnormalities. A dried blood spot test indicated acid maltase deficiency. The diagnosis of LOPD was confirmed genetically. Both sisters subsequently developed proximal muscle weakness after pregnancy and started enzyme replacement therapy. Under treatment, gastrointestinal symptoms improved, but pain persisted. Conclusions: Clinicians should be aware of this atypical presentation of LOPD to enable earlier diagnosis and treatment. Muscle Nerve 52 : 300–304, 2015     

Pseudopolyneuritic form of ALS revisited: Clinical and pathological heterogeneity

Pseudopolyneuritic form of ALS is a subtype of ALS characterized by distal weakness of the unilateral lower limb and absence of Achilles tendon reflex (ATR) at disease onset. Recognition of this form of ALS is important for clinicians because the combination of distal weakness of the lower limb and absence of ATR usually suggests peripheral neuropathy. We reviewed the clinical records of 42 autopsy‐proven sporadic ALS cases and found three cases that showed onset of weakness of the unilateral lower limb with distal dominance and absence of ATR. The disease duration in the three cases was 2, 3 and 19 years, respectively. The clinical features of the patient with a course of 19 years had been restricted to lower motor neuron signs. Histopathologically, consistent findings in the three cases were severe motor neuron loss throughout the whole spinal cord, with relative preservation of the hypoglossal nucleus. Reflecting this finding, TDP‐43‐positive neuronal cytoplasmic inclusions in the spinal cord were sparse in two cases, and absent in a third. In the patient showing a clinical course of 19 years, mild corticospinal tract degeneration appeared to correspond to the absence of upper motor neuron signs and prolonged disease duration. In this case only, Bunina bodies were not demonstrated. In this study, we clarified the clinical and pathological heterogeneity of this form of ALS.     

Signs and symptoms at diagnosis of amyotrophic lateral sclerosis: a population-based study in southern Italy

Amyotrophic lateral sclerosis (ALS) diagnostic criteria are used to select patients for clinical trials based on different levels of diagnostic certainty, according to the spread of upper (UMN) and lower motoneuron (LMN) signs in different anatomic regions. However, the clinical presentation of ALS patients is extremely variable and this can delay the time to diagnosis and decrease the likelihood for trial entry. The aims of the study were to describe the signs and symptoms of diagnosis in a population‐based incident cohort of ALS cases, using the El Escorial (EEC) and the Revised Airlie Diagnostic Criteria (AHC). The source of the study was a prospective population‐based registry established in Puglia, southern Italy, in 1997. The diagnosis and the classification of the cases were based on EEC and AHC. All incident ALS cases during the period 1998–1999 were enrolled and followed up. During the surveillance period, we identified 130 ALS incident cases, and bulbar‐ALS represented 20% of our cohort. The highest risk for bulbar onset was among subjects aged >75 years [RR: 20.1, 95% confidence interval (CI) 3.4–118.0] compared with subjects aged <55 years and among females compared with males (Relative risk (RR): 2.75, 95% CI: 1–7.3). The vast majority of patients (72%) referred progressive muscle weakness in the limbs as the presenting symptom. Eighty percent of cases presented contemporary bulbar or spinal involvement; UMN signs in the bulbar region were present in 24% of cases and any motoneuronal sign in thoracic region in only 15% of the cases. In this population‐based series, progressive muscle weakness was the most common presenting sign; bulbar onset was associated with advanced age and female sex. UMN signs in the bulbar region and any motoneuronal sign in the thoracic region were observed in 20% of our case series. This may represent the main limitation to show the spread of signs during diagnostic assessment for inclusion in epidemiological studies and clinical trials.     

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

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons, leading to limb paralysis and respiratory failure. Methods: C1–C3 cord ¹H‐magnetic resonance spectroscopy (¹H‐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 ¹H‐MRS. Results: 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. Conclusions: These metabolite ratios were associated with disease progression and ongoing denervation in neck and hand muscles. C1–C3 cord ¹H‐MRS might reflect anterior horn cell damage causing neck/arm weakness and respiratory dysfunction in ALS patients. Muscle Nerve, 2013     

Natural history of muscle cramps in amyotrophic lateral sclerosis

Introduction: Muscle cramping is a common symptom in amyotrophic lateral sclerosis (ALS) that lacks efficacious treatment. The natural history of this symptom is unknown, which hampers efforts to design optimal clinical trials. Methods: We surveyed early stage ALS patients about their experience with cramps each month by phone for up to 21 months. Results: Cramps developed in 95% of patients over the course of their disease. The number of cramps experienced by an individual varied widely from month‐to‐month and trended lower after the first year of illness (P = 0.26). Those with limb‐onset and age >60 years had more cramps than bulbar‐onset (P < 0.0001) and younger patients (P < 0.0001). Conclusions: The high variability of the number of cramps experienced suggests that clinical trials will need to use crossover designs or large numbers of participants, even when the treatment effect is substantial. Muscle Nerve 53 : 513–517, 2016     

APOE ε4 allele is associated with an increased risk of bulbar‐onset amyotrophic lateral sclerosis in men

Objective: Several association studies have identified possible susceptibility factors for sporadic amyotrophic lateral sclerosis (SALS). Studies on the APOE gene provided conflicting results, especially about the effect on bulbar onset. We assessed the possible role of APOE gene in a large cohort of patients with ALS and matched controls. Methods: The APOE alleles were determined in 1482 patients with SALS and 955 controls and analysed by univariate and multivariate statistics, taking into account gender, site‐of‐onset and age‐at‐onset. Results: Patients with bulbar onset were more likely to be women [odds ratio (OR) = 2.17; 95% CI: 1.74–2.72] and to be older (OR = 3.47; 95% CI: 2.58–4.67). The ε4‐carriers were more frequent in the bulbar‐onset group than in the limb‐onset group (OR = 1.39 bulbar onset versus limb onset; 95% CI: 1.08–1.80) but this association was observed amongst men (OR = 1.78; 95% CI: 1.25–2.53) and not women (OR = 1.09; 95% CI: 0.75–1.59). Conclusion: Our study provides evidence for a contribution of the ε4 allele in the occurrence of bulbar‐onset ALS amongst men. We propose that men are normally protected by androgens against bulbar onset and that the ε4 allele inhibits this protection, perhaps by interfering with the androgen pathway.     

Chorea‐ballism associated with familial amyotrophic lateral sclerosis. A clinical,genetic, and neuropathological study

Hyperkinetic movements in amyotrophic lateral sclerosis (ALS) are extremely rare. We present clinical, neuropathological, and genetic data for a 53‐year‐old woman with spinal onset ALS presenting chorea affecting the face, mouth, neck, and hands, and ballism in both arms 31 months after leg weakness onset. Her father and older sister had ALS, but had no movement disorders. As well as the typical neuropathological findings of ALS (marked upper and lower motor neuron loss), post‐mortem examination showed prominent neuronal loss and gliosis in the subthalamus, and in the internal globus pallidus, substantia nigra pars compacta, and red nucleus. No abnormalities were found in the caudate, putamen, and thalamus. No defects were found in the SOD1, HD, and DRPLA genes. These data support the idea that choreo‐ballism in ALS Plus may be the result of pallido‐luyso‐rubro‐nigral atrophy, despite not being the result of concomitant DRPLA based on neuropathological and genetic criteria. © 2007 Movement Disorder Society     

肌萎缩侧索硬化三例误诊分析

目的掌握肌萎缩侧索硬化(ALS)的诊断标准,以便早期准确诊断,避免误诊。方法分析3例ALS患者早期被误诊的临床资料。结果 3例患者均以下肢无力发病,逐渐波及上肢或对侧肢体,脊柱MR I示颈部或腰部椎间盘突出压迫硬膜囊,手术治疗后,症状无缓解,病情仍进行性加重,经肌电图检查证实为ALS。结论临床医师应熟知ALS的诊断标准,对患者详细询问病史、认真查体和电生理检查是减少ALS误诊的关键。     

Riluzole and amyotrophic lateral sclerosis survival: a population-based study in southern Italy

Riluzole is to date the only treatment that prolongs amyotrophic lateral sclerosis (ALS) survival. However, results on the efficacy of riluzole in observational population‐based studies with a longer follow‐up are conflicting and it is still unclear if the effect of the drug is limited to an early stage of the disease and to some specific subgroups of patients. The objective is: (i) to evaluate the effect of riluzole on ALS survival in a cohort of incident cases; (ii) to examine whether bulbar‐ALS benefits from the medication to a greater extent and (iii) to assess the efficacy of the drug in elderly patients. Source of the study was a prospective population‐based registry of ALS established in Puglia, Southern Italy. We examined survival of 126/130 incident ALS cases diagnosed during the period 1998–1999. Seventy‐three patients were prescribed riluzole and the remaining 53 were not. Riluzole therapy increased survival rates at 12 months by approximately 10% and prolonged survival by 6 months (18.2 months vs. 12.4; peto‐test: 2.78; P = 0.09). This beneficial effect was present amongst bulbar‐onset ALS (peto‐test: 4.11; P = 0.042), but not in subjects with limb‐onset (peto‐test: 0.48; P = 0.4). In patients aged >70 years riluzole treatment was associated with an 8 months longer median survival time [15.4 months vs. 7.1] and a reduction in mortality rate at 12 months by 27%, regardless of site of symptoms onset. In multivariate analysis, riluzole use was an independent predictor of survival at 12 months from the diagnosis with borderline significance (P = 0.06). Riluzole was effective amongst cases with bulbar‐onset ALS (P = 0.04), whereas in subjects with limb‐onset there was no effect on survival at 12 months (P = 0.5). In each model riluzole did not influence survival at 24 months. Conversely, riluzole use was associated with an improvement in survival amongst elderly patients both at 12 (P = 0.07), at 24 months (P = 0.03) and in the entire follow‐up period (P < 0.04). In this population‐based series, we found that riluzole therapy improves ALS survival. The efficacy of the drug was present amongst bulbar‐onset ALS and older patients, but not in subjects with limb‐onset. The favourable effect of the drug was transient, as it was lost in prolonged follow‐up. Our observations support the use of riluzole at an early stage of ALS in bulbar and elderly patients. However, the appropriate duration of riluzole treatment remains to be established.     

Diagnostic criteria for late‐onset (childhood and adult) pompe disease

The diagnosis of late‐onset (childhood and adult) Pompe disease can often be challenging, as it is a rare disease and the heterogeneous clinical presentation can mimic the presentation of other neuromuscular disorders. The objective was to develop a consensus‐based algorithm for the diagnosis of late‐onset Pompe disease. A systematic literature search was conducted, and an expert panel composed of neuromuscular specialists and individuals with expertise in Pompe disease reviewed the literature and convened for consensus development. An algorithm for the diagnosis of late‐onset Pompe disease was created. Patients presenting with either a limb‐girdle syndrome or dyspnea secondary to diaphragm weakness should undergo further testing, including evaluations of muscle strength, motor function, and pulmonary function. A blood‐based acid α‐glucosidase (GAA) enzyme activity assay is the recommended tool to screen for GAA enzyme deficiency. The diagnosis should be confirmed by a second test: either a second GAA enzyme activity assay in another tissue or GAA gene sequencing. Muscle Nerve 40:149–160, 2009     

Hereditary pure lower motor neuron disease with adult onset and rapid progression

We describe three members each of two families presenting with a hereditary form of lower motor neuron disease with adult onset and rapid progression and compare their pathological and clinical features with hereditary lower motor neuron disease with adult onset, as described in the literature. No involvement of upper motor neurons was found either clinically or pathologically. Disease progression was rapid, and the majority of patients died from respiratory failure within 1–5 years after onset of disease. On pathological examination of the spinal cord we found ballooned neurons, neuronophagia and gliosis in family A, which have been regarded as characteristic pathological features of infantile-onset spinal muscular atrophy (SMA). In family B specific neuronal changes were observed that also occur in patients with amyotrophic lateral sclerosis (ALS). An autosomal dominant mode of inheritance would seem likely in both families. In family A the pathological findings and the clinical presentation with symmetrical proximal limb weakness show similarities with autosomal dominant SMA. Based on the finding of pathological features in family B that also occur in ALS, together with the distal asymmetrical muscle weakness and bulbar signs and a high age at onset we hypothesize that the members of family B suffered from familial ALS. The disease forms in both families in our opinion further broaden the spectrum of motor neuron disease Received: 2 June 2000, Received in revised form: 1 September 2000, Accepted: 23 October 2000     

The role of cranial and thoracic electromyography within diagnostic criteria for amyotrophic lateral sclerosis

Introduction: The contribution of cranial and thoracic region electromyography (EMG) to diagnostic criteria for amyotrophic lateral sclerosis (ALS) has not been evaluated. Methods: Clinical and EMG data from each craniospinal region were retrospectively assessed in 470 patients; 214 had ALS. Changes to diagnostic classification in Awaji‐Shima and revised El Escorial criteria after withdrawal of cranial/thoracic EMG data were ascertained. Results: Sensitivity for lower motor neuron involvement in ALS was highest in the cervical/lumbar regions; specificity was highest in cranial/thoracic regions. Cranial EMG contributed to definite/probable Awaji‐Shima categorization in 1.4% of patients. Thoracic EMG made no contribution. For revised El Escorial criteria, cranial and thoracic data reclassified 1% and 5% of patients, respectively. Conclusion: Cranial EMG data make small contributions to both criteria, whereas thoracic data contribute only to the revised El Escorial criteria. However, cranial and thoracic region abnormalities are specific in ALS. Consideration should be given to allowing greater diagnostic contribution from thoracic EMG. Muscle Nerve 54 : 378–385, 2016     

Amyotrophic lateral sclerosis: a clinical review

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting primarily the motor system, but in which extra‐motor manifestations are increasingly recognized. The loss of upper and lower motor neurons in the motor cortex, the brain stem nuclei and the anterior horn of the spinal cord gives rise to progressive muscle weakness and wasting. ALS often has a focal onset but subsequently spreads to different body regions, where failure of respiratory muscles typically limits survival to 2–5 years after disease onset. In up to 50% of cases, there are extra‐motor manifestations such as changes in behaviour, executive dysfunction and language problems. In 10%–15% of patients, these problems are severe enough to meet the clinical criteria of frontotemporal dementia (FTD). In 10% of ALS patients, the family history suggests an autosomal dominant inheritance pattern. The remaining 90% have no affected family members and are classified as sporadic ALS. The causes of ALS appear to be heterogeneous and are only partially understood. To date, more than 20 genes have been associated with ALS. The most common genetic cause is a hexanucleotide repeat expansion in the C9orf72 gene, responsible for 30%–50% of familial ALS and 7% of sporadic ALS. These expansions are also a frequent cause of frontotemporal dementia, emphasizing the molecular overlap between ALS and FTD. To this day there is no cure or effective treatment for ALS and the cornerstone of treatment remains multidisciplinary care, including nutritional and respiratory support and symptom management. In this review, different aspects of ALS are discussed, including epidemiology, aetiology, pathogenesis, clinical features, differential diagnosis, investigations, treatment and future prospects.     

Quantitative assessment of lingual strength in late‐onset Pompe disease

Introduction: Skeletal muscle is common in late‐onset Pompe disease (LOPD). Recent data implicate common bulbar muscle involvement (i.e., the tongue). Methods: We used quantitative assessment of lingual strength to retrospectively determine the frequency and severity of lingual weakness in LOPD. We additionally examined associations between lingual strength and the presence or absence of dysarthria, and dysarthria severity. Results: Quantitative assessment revealed lingual weakness to be present in 80% of the sample. In the 24 affected patients, severity was mild in 29%, moderate in 29%, and severe in 42%. Patients with clinical dysarthria had greater lingual weakness than those without. As dysarthria severity increased, lingual strength decreased by an average of 6.82 kPa. Conclusions: These quantitative data provide additional evidence for presence of bulbar muscle disease in patients with LOPD. Further study is necessary to determine functional effects, temporal progression, and effects of treatment. Muscle Nerve 51 :731–735, 2015     

Interleukin‐17 and interleukin‐23 are elevated in serum and cerebrospinal fluid of patients with ALS: a reflection of Th17 cells activation?

Rentzos M, Rombos A, Nikolaou C, Zoga M, Zouvelou V, Dimitrakopoulos A, Alexakis T, Tsoutsou A, Samakovli A, Michalopoulou M, Evdokimidis J. Interleukin‐17 and interleukin‐23 are elevated in serum and cerebrospinal fluid of patients with ALS: a reflection of Th17 cells activation?
Acta Neurol Scand: 2010: 122: 425–429.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Background – There is evidence that immunological factors may involved in pathogenetic mechanisms of amyotrophic lateral sclerosis (ALS). Th17 cells are characterized by predominant production of IL‐17 and are suggested to be crucial in destructive autoimmunity. Interleukin‐23 (IL‐23) appears to play a supporting role in the continued stimulation and survival of Th17. Patients and methods – We measured by enzyme‐like immunosorbent assay (ELISA) serum and cerebrospinal fluid (CSF) levels of IL‐17 and IL‐23 in 22 patients with ALS and 19 patients with other non‐inflammatory neurological disorders (NIND) studied as a control group. IL‐17 and IL‐23 serum and CSF levels were also correlated with duration of the disease, the disability level and the clinical subtype of the disease onset in patients with ALS. Results – IL‐17 and IL‐23 serum levels were higher in patients with ALS as compared with patients with NIND (P = 0.015 and P = 0.002 respectively). IL‐17 and IL‐23 CSF levels were also increased in patients with ALS (P = 0.0006 and P = 0.000001 respectively). IL‐17 and IL‐23 levels were not correlated with disease duration, disability scale or clinical subtype of the disease onset in ALS patients. Conclusions – Our findings suggest that these molecules may be involved in the pathogenetic mechanisms acting as potential markers of Th17 cells activation in ALS.