Escorial Research Articles

Does limited EMG denervation in early primary lateral sclerosis predict amyotrophic lateral sclerosis?

Objective: We assessed whether a cohort of patients with primary lateral sclerosis (PLS) and limited electromyography (EMG) motor unit denervation changes evolve into amyotrophic lateral sclerosis (ALS) with prolonged follow-up. Methods: We initially ascertained all PLS patients diagnosed at Mayo Clinic-Rochester (1990–2016). Of 64 total cases, 43 had normal EMGs (“pure” PLS) during the first 4 years after symptom onset and were the focus of a prior publication, documenting absence of evolution to ALS. The remaining 21 patients had limited motor unit changes on EMG needle examination (denervation and most with fibrillation or fasciculation potentials) but insufficient to raise a strong suspicion of ALS; these 21 patients were followed to determine whether they evolved into ALS. Results: Of these 21 patients, the median follow-up was 7 years’ disease duration (range: 4–27 years; IQR 5–8.5). They included 11 females (52%) with median onset-age of 57 years (range: 42–72 years). Two patients (10%) subsequently met revised El Escorial criteria for ALS after 7 and 13 years, respectively. The remainder had stable EMG changes with a persistent PLS phenotype. Among these remaining 19 patients, the PLS course was somewhat more aggressive than our previously reported series of 43 patients devoid of EMG denervation. The paraparetic variant was more common than the hemiparetic and bulbar variants, similar to “pure” PLS. Conclusions: Among PLS patients with definite but limited EMG denervation, 2/21 (10%) later developed ALS. The patients in this series had a more progressive clinical course compared to our previously reported pure PLS cases.

Revealing the Mutational Spectrum in Southern Africans With Amyotrophic Lateral Sclerosis.

Background and ObjectivesTo perform the first screen of 44 amyotrophic lateral sclerosis (ALS) genes in a cohort of African genetic ancestry individuals with ALS using whole-genome sequencing (WGS) data.MethodsOne hundred three consecutive cases with probable/definite ALS (using the revised El Escorial criteria), and self-categorized as African genetic ancestry, underwent WGS using various Illumina platforms. As population controls, 238 samples from various African WGS data sets were included. Our analysis was restricted to 44 ALS genes, which were curated for rare sequence variants and classified according to the American College of Medical Genetics guidelines as likely benign, uncertain significance, likely pathogenic, or pathogenic variants.ResultsThirteen percent of 103 ALS cases harbored pathogenic variants; 5 different SOD1 variants (N87S, G94D, I114T, L145S, and L145F) in 5 individuals (5%, 1 familial case), pathogenic C9orf72 repeat expansions in 7 individuals (7%, 1 familial case) and a likely pathogenic ANXA11 (G38R) variant in 1 individual. Thirty individuals (29%) harbored ≥1 variant of uncertain significance; 10 of these variants had limited pathogenic evidence, although this was insufficient to permit confident classification as pathogenic.DiscussionOur findings show that known ALS genes can be expected to identify a genetic cause of disease in >11% of sporadic ALS cases of African genetic ancestry. Similar to European cohorts, the 2 most frequent genes harboring pathogenic variants in this population group are C9orf72 and SOD1.

Los mármoles cálcicos de El Escorial (Complejo Metamórfico Cushamen, Macizo Norpatagónico): caracterización isotópica de 87Sr-86Sr y edad de sedimentación

The El Escorial marbles (Cushamen Metamorphic Complex) along with amphibolites form metamorphic septa within the permian granitoids of the Mamil Choique Formation (261-286 Ma). The metamorphism, determined in granulite facies migmatic gneisses septa cropping out 120 km southwest of El Escorial, occurs at 311 ± 27 Ma (CHIME method in monazite). The marbles are calcitic (calcite > 95%, R.I.: 0.5 to 2.5%) and show 87Sr/86Sr values between 0.70768 and 0.70825 (n = 10). The data provided in this work, added to previous contributions, allow to constraints the sedimentation age of the silicic-carbonate successions of the Cushamen Metamorphic Complex between ca. 385 and 335 Ma. This suggests the existence of a mixed carbonate-siliciclastic platform at least in the southernmost portion of southwestern Gondwana between Middle Devonian and early Carboniferous (Middle Mississippian).

Resting-state EEG reveals four subphenotypes of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a devastating disease characterized primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. Amyotrophic lateral sclerosis is both clinically and biologically heterogeneous. Subgrouping is currently undertaken using clinical parameters, such as site of symptom onset (bulbar or spinal), burden of disease (based on the modified El Escorial Research Criteria) and genomics in those with familial disease. However, with the exception of genomics, these subcategories do not take into account underlying disease pathobiology, and are not fully predictive of disease course or prognosis.Recently, we have shown that resting-state EEG can reliably and quantitatively capture abnormal patterns of motor and cognitive network disruption in amyotrophic lateral sclerosis. These network disruptions have been identified across multiple frequency bands, and using measures of neural activity (spectral power) and connectivity (comodulation of activity by amplitude envelope correlation and synchrony by imaginary coherence) on source-localized brain oscillations from high-density EEG. Using data-driven methods (similarity network fusion and spectral clustering), we have now undertaken a clustering analysis to identify disease subphenotypes and to determine whether different patterns of disruption are predictive of disease outcome.We show that amyotrophic lateral sclerosis patients (n = 95) can be subgrouped into four phenotypes with distinct neurophysiological profiles. These clusters are characterized by varying degrees of disruption in the somatomotor (α-band synchrony), frontotemporal (β-band neural activity and γl-band synchrony) and frontoparietal (γl-band comodulation) networks, which reliably correlate with distinct clinical profiles and different disease trajectories. Using an in-depth stability analysis, we show that these clusters are statistically reproducible and robust, remain stable after reassessment using a follow-up EEG session, and continue to predict the clinical trajectory and disease outcome.Our data demonstrate that novel phenotyping using neuroelectric signal analysis can distinguish disease subtypes based exclusively on different patterns of network disturbances. These patterns may reflect underlying disease neurobiology. The identification of amyotrophic lateral sclerosis subtypes based on profiles of differential impairment in neuronal networks has clear potential in future stratification for clinical trials. Advanced network profiling in amyotrophic lateral sclerosis can also underpin new therapeutic strategies that are based on principles of neurobiology and designed to modulate network disruption.

Amyotrophic lateral sclerosis mimicking radiculopathy: a case series.

ABSTRACTThe clinical findings of early stage amyotrophic lateral sclerosis (ALS) are similar to those of cervical or lumbar radiculopathy. In the current study, we describe 3 cases of ALS that were misdiagnosed as cervical or lumbar radiculopathy. Three patients (a 48-, a 52-, and an 80-year-old) visited our clinic due to motor weakness on either the upper or lower extremities. At other clinics or hospitals, they were diagnosed with radiculopathy due to herniated lumbar disc or cervical foraminal stenosis. The motor weakness in these patients was ipsilateral or bilateral but dominant on one side. Sensory deficits or bulbar symptoms were not observed. Of the 3 patients, 2 had neuropathic pain, but it was not dermatome related. We conducted an electrodiagnostic test and observed a low amplitude of compound motor action potential on the affected nerve and positive sharp waves on muscles of involved segments, including thoracic paraspinalis. All the patients were diagnosed with probable laboratory-supported ALS or possible ALS based on the established diagnostic criteria (El Escorial Criteria). In the present study, we showed three cases of ALS that were misdiagnosed as radiculopathy. Our study would be helpful for early and accurate diagnosis of patients with ALS.

Prevalence of amyotrophic lateral sclerosis in Latium region, Italy.

ObjectivePrevalence estimate of amyotrophic lateral sclerosis (ALS) ranged between 1.1/100,000 and 11.2/100,000 inhabitants with different design of the study (prospective or retrospective) and sample size. The aim of this study is to conduct for the first time an estimate of the ALS prevalence in the Latium region.Materials and methodsThe study was performed in Latium, a region located in the center of Italy, with a population, as of January 1, 2016, of 5888.472 inhabitants. In this region, a network of 15 clinical centers (of which 4 referral ALS centers are located in Rome) and 10 local health authorities involved in the diagnosis and treatment of ALS patients has been identified. Each patient was classified according to the El Escorial revised criteria.ResultsThe prevalence study in 2016 identified 353 ALS cases (200 males). By considering population aged >=20 years, the total crude prevalence rate resulted 7.33 (CI95% 6.59–8.14) × 100,000 and 8.75 and 6.05 in males and females, respectively. Age‐specific prevalence rates did not differ among males and females in the population aged less than 49 years. The difference emerged in population aged > 50 years. This type of diagnosis was recorded for 343 patients (11 missing). 68% of these patients have a definite diagnosis, 14% likely, 11% possible, and 12% defined as suspect.ConclusionsThe estimate of prevalence rates observed in this study is probably in line with the values reported in the literature for prospective prevalence studies.

Эскориал — идея, образ, стиль королевской резиденции Филиппа II

The paper explores the architecture of King Philip II royal residence. El Escorial monastery palace represents a system of art treasures of the Spanish Renaissance, manifested in the method of implementing the figurative absolutization of the Classical aesthetics, revealing the ideas of the magnificence of the “Roman spirit” of the Habsburg empire. By reinterpreting the legacy of the theory of architectural rules, El Escorial was the standard of classical construction in late 16th century Spain. The Christian ideas become the cement of the Empire governance. It is symbolic that the year of the completion of Trento Cathedral (1563) was also the year the construction of El Escorial had begun. The first executor of the project was the architect, philosopher, and mathematician Juan Bautista de Toledo, who studied in Rome and Naples under the masters of the Italian Renaissance. He was later replaced by Juan de Herrera, the acclaimed spokesman of the royal architectural style. The paper covers the most controversial issues: problems of the ensemble concept, their interpretations, the role of theoretical sources, biblical semantics, etc.

Phase 3 trial of ultra-high dose methylcobalamin in early-stage amyotrophic lateral sclerosis

In the post-hoc analyses of our previous study conducted to verify efficacy and safety of ultra-high dose methylcobalamin against patients diagnosed by the revised El Escorial criteria (rEEC), methylcobalamin may prolong survival and retard symptomatic progression without major side effects if started early (≤12 months' duration). The objective of next trial: The Japanese Early Stage Trial of High Dose Methylcobalamin for Amyotrophic Lateral Sclerosis (JETALS) is to reconfirm the efficacy and safety of ultra-high dose methylcobalamin for ALS patients in their early stages.

MOTOR NEURON DISORDERS AND NEUROPATHIES: EP.243 Young-onset SOD1-ALS caused by a novel homozygous mutation, a family report

Amyotrophic lateral sclerosis (ALS) is a fatal disease primarily affecting motor neurons. In Europe and North America, about 5 % of ALS patients report a positive family history (familial ALS, fALS). The remaining is classified as sporadic ALS (sALS). A genetic basis for ALS has been demonstrated for both fALS and sALS and variants in >40 genes have been associated with ALS. Following linkage analysis in families with Mendelian dominantly inherited fALS, mutations in the gene encoding the free radical scavenging enzyme Cu/Zn superoxide dismutase 1 (SOD1) were discovered in 1993. Since then, more than 200 mutations in SOD1 have been described. We here report a novel SOD1 homozygous mutation with an early onset, rapidly progressive phenotype in a family with two affected members from southern Egypt. The parents are cousins with three children. At age 10 years old, the youngest son initially developed a foot drop of one limb followed by a rapidly progressive disease affecting the other limbs and bulbar innervated muscles. He died from respiratory failure at the age of 12 years. At age 25 years, the eldest sister developed ALS with a similar phenotype. She is still alive at age 28 years. Both patients were diagnosed to have ALS according to the revised El Escorial criteria. SOD1 DNA analysis was performed using bi-directional Sanger sequencing of the 5 exons and adjacent 30-50 bp intronic sequences. Mutations in a number of other ALS-causing genes were excluded. Genetic screening revealed a novel exon 3 homozygous p.Ser69Pro SOD1 mutation in the affected female patient; while her parents and unaffected younger brother are heterozygous for the mutation (no sample is available from the deceased son). So, we report a novel homozygous p.Ser69Pro SOD1 mutation associated with early onset of asymmetrical weakness of lower limbs with a rapidly ascending paresis. It is likely that her deceased brother had the same genotype. The early onset and rapidity of evolution of disease suggest a strong dose-effect of the mutant SOD1 protein. Exon 3 mutations in SOD1 are frequently associated with reduced disease penetrance but we cannot exclude the possibility that the p.Ser69Pro SOD1 also predisposes heterozygous individuals for ALS later in life.

Gold Coast diagnostic criteria increase sensitivity in amyotrophic lateral sclerosis

ObjectiveThis study evaluates diagnostic accuracy of the proposed ‘Gold Coast’ (GC) diagnostic criteria for amyotrophic lateral sclerosis (ALS). MethodsFive European centres retrospectively sampled consecutive patients referred for electromyography on suspicion of ALS. Patients were classified according to the GC criteria, the revised El Escorial (rEE) criteria and the Awaji (AW) criteria without and with the ‘Possible’ category (+ Poss). Reference standard was ALS confirmed by disease progression at follow-up. ResultsOf 404 eligible patients 272 were diagnosed as ALS, 94 had mimicking disorders, 35 were lost for follow-up, and three had insufficient data. Sensitivity for the GC criteria was 88.2% (95% CI: 83.8-91.8%), which was higher than for previous criteria, of which the AW + Poss criteria reached the highest sensitivity of 77.6% (95% CI: 72.2–82.4%) (p < 0.001). Specificity was high for all criteria. The increase in sensitivity for the GC criteria was mainly due to the inclusion of 28 patients with progressive muscular atrophy (PMA). ConclusionsThe simpler GC criteria increase the sensitivity, primarily due to considering PMA as a form of ALS with high specificity preserved. SignificanceThis validation study supports that GC criteria should be used in clinical practice and may be used for inclusion in trials.

The\xa0Gold Coast criteria increases the diagnostic sensitivity for amyotrophic lateral sclerosis in a Chinese population

ObjectivesThe aim of this study was to assess and compare the diagnostic utility of a new diagnostic criteria for amyotrophic lateral sclerosis (ALS), abbreviated as the ‘Gold Coast Criteria’, with the revised El Escorial (rEEC) and Awaji criteria.MethodsClinical and electrophysiological data of 1185 patients from January 2014 to December 2019 in the Peking Union Medical College Hospital ALS database were reviewed. The sensitivity of the Gold Coast criteria was compared to that of the possible rEEC and Awaji criteria (defined by the proportion of patients categorized as definite, probable, or possible ALS).ResultsA final diagnosis of ALS was recorded in 1162 patients. The sensitivity of the Gold Coast criteria (96.6%, 95% confidence interval [CI] = 95.3%–97.5%) was greater than that of the rEEC (85.1%, 95%CI = 82.9%–87.1%) and Awaji (85.3%, 95%CI = 83.2%–87.3%). In addition, the sensitivity of the novel criteria maintained robust across subgroups, and the advantage was more prominent in limb-onset ALS patients and those who completed electromyographic tests. In those who did not achieve any of the rEEC diagnostic categories, the sensitivity of Gold Coast criteria was 84.4%.ConclusionsThe current study demonstrated that the Gold Coast criteria exhibited greater diagnostic sensitivity than the rEEC and Awaji criteria in a Chinese ALS population. The application of the Gold Coast criteria should be considered in clinical practice and future therapeutic trials.

The Evaluation of Pain with Nociceptive and Neuropathic Characteristics from Three Different Perspectives in Amyotrophic Lateral Sclerosis Patients: A Case Controlled Observational Study in Southwestern China.

Background Pain was considered a common and neglected symptom in amyotrophic lateral sclerosis (ALS) and had a substantial impact on the quality of life of ALS patients and their caregivers. However, pain in ALS was mainly evaluated from the perspective of nociceptive pain; only three studies referred to neuropathic pain in ALS, and there has been yet no study considering the neuropathic pain characteristics in ALS patients from China. Therefore, the purpose of our study was to determine characteristics of pain (nociceptive pain and neuropathic pain) by three different types of questionnaires. The correlation between pain and clinical parameters in ALS patients was also evaluated. Methods Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria. Healthy normal controls, matched to ALS patients by age and gender, were recruited. Pain was evaluated by numerical pain rating scale (NRS), Brief Pain Inventory (BPI), and Douleur Neuropathique-4 (DN4) in ALS patients and controls. Physical status of ALS patients was evaluated with ALS Functional Rating Scale-revised (ALSFRS-R). Results 65 patients with sporadic ALS and 100 healthy normal controls in Southwestern China were included. Pain in the preceding week was more frequently reported by patients with ALS (30, 46.2%) than controls (36, 36%) (p = 0.193). DN4 score⩾4 was found in three ALS patients and one control (p = 0.480). Ten ALS patients (33.3%) and twenty-eight controls (77.8%) (p < 0.001) received therapy for pain. ALS patients with a DN4 score ≥ 4 had a longer disease duration and a higher PSI and PII score than ALS cases reporting nociceptive pain (p = 0.041, 0.048, and 0.027, respectively). Pain mainly interfered with ALS patients' mood, enjoyment of life, and the Pain Interference Index (PII) score. Conclusions Our findings indicated that pain in our ALS cohorts was insufficiently treated and interfered with patients' mood and enjoyment of life. Most notably, we found that ALS patients with a DN4 score⩾4 may have a longer disease duration and a higher PSI and PII score than ALS patients reporting nociceptive pain, which has never been reported, strongly deserving further validation.

Coffee and Tea Consumption Impact on Amyotrophic Lateral Sclerosis Progression: A Multicenter Cross-Sectional Study.

Background/objectives: Amyotrophic lateral sclerosis (ALS) is a devastating and still untreatable motor neuron disease. The causes of ALS are unknown, but nutritional factors may impact the rate of disease progression. We aimed to ascertain the influence of coffee and tea consumption on ALS progression rate.Subjects/methods: In this multicenter cross-sectional study, we recruited 241 patients, 96 females, and 145 males; the mean age at onset was 59.9 ± 11.8 years. According to El Escorial criteria, 74 were definite ALS, 77 probable, 55 possible, and 35 suspected; 187 patients had spinal onset and 54 bulbar. Patients were categorized into three groups, according to their ΔFS (derived from ALS Functional Rating Scale-Revised score and disease duration from onset): slow (81), intermediate (80), and fast progressors (80).Results: Current coffee consumers were 179 (74.3%), 34 (14.1%) were non-consumers, and 22 (9.1%) were former consumers, whereas six (2.5%) consumed decaffeinated coffee only. The log-ΔFS was weakly correlated with the duration of coffee consumption (p = 0.034), but not with the number of cup-years, or the intensity of coffee consumption (cups/day). Current tea consumers were 101 (41.9%), 6 (2.5%) were former consumers, and 134 (55.6%) were non-consumers. Among current and former consumers, 27 (25.2%) consumed only green tea, 51 (47.7%) only black tea, and 29 (27.1%) both. The log-ΔFS was weakly correlated only with the consumption duration of black tea (p = 0.028) but not with the number of cup-years.Conclusions: Our study does not support the hypothesis that coffee or tea consumption is associated with the ALS progression rate.

Motor neuron disease (MND) O-MN001. Association of sympathetic skin response in amyotrophic lateral sclerosis

Introduction. Amyotrophic lateral sclerosis (ALS) is the most common type of motor neuron disease. General concept is autonomic disturbances are extremely rare in ALS. Some hypotheses have put forward to see autonomic involvement in ALS. Previous studies have found an association between sympathetic skin response (SSR) and ALS as a part of autonomic involvement. The study was aimed to explore the association of SSR in ALS. Methods. This case control study was carried out in the Department of Neurology, BSMMU, Dhaka, from April 2018 to September 2019. Total 70 subjects were enrolled as study population after fulfilling inclusion and exclusion criteria. Among them, 35 were grouped as case and rest 35 were as control. All patients with ALS were diagnosed according to The Revised El Escorial diagnostic criteria fulfilling definite, probable, probable lab-supported and possible cases of ALS with no family history of ALS. Results. The study included 35 ALS patients and 35 age- and sex-matched controls. SSR was absent in 6 (17.1%) cases in upper limbs and 20 (57.1%) cases in lower limbs. In 4 patients, SSR was absent in both upper and lower limbs. Among control group SSR response was present in all population. There was significant difference in mean latency and amplitude of SSR in case and control group (p-value < 0.001). Absent SSR in ALS with bulbar palsy showed obvious difference with ALS without bulbar palsy (p-value 0.040). There was an association of SSR with severity of disease in ALS patient (p-value 0.030) but we could not establish it with duration of disease. Conclusion. In this study we found significant relationship between SSR and ALS. We noticed an association of SSR with severity of disease in ALS.

Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case

BackgroundNeuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS.Case presentationA 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient.ConclusionsWe describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.

Randomized phase 2 study of perampanel for sporadic amyotrophic lateral sclerosis

ObjectiveTo evaluate the efficacy and safety of perampanel in patients with sporadic amyotrophic lateral sclerosis (SALS).MethodsThis randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical study was conducted at 12 sites. Patients with probable or definite ALS as defined by revised El Escorial criteria were enrolled. Sixty-six patients were randomly assigned (1:1:1) to receive placebo, 4 mg perampanel, or 8 mg perampanel daily for 48 weeks. Adverse events (AEs) were recorded throughout the trial period. The primary efficacy outcome was the change in Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R) score after 48 weeks of treatment.ResultsOne patient withdrew before starting the treatment. Of 65 patients included, 18 of 22 patients randomized to placebo (82%), 14 of 22 patients randomized to 4 mg perampanel (64%), and 7 of 21 patients randomized to 8 mg perampanel (33%) completed the trial. There was a significant difference in the change of ALSFRS-R scores [− 8.4 (95% CI − 13.9 to − 2.9); p = 0.015] between the placebo and the perampanel 8 mg group, primarily due to worsening of the bulbar subscore in the perampanel 8 mg group. Serious AEs were more frequent in the perampanel 8 mg group than in the placebo group (p = 0.0483).ConclusionsPerampanel was associated with a significant decline in ALSFRS-R score and was linked to worsening of the bulbar subscore in the 8 mg group.

The importance of heart rate variability in predicting cardiac autonomic dysfunction in patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive disease characterized by degeneration in the upper and lower motor neurons of the corticospinal tract, brain stem, and spinal cord. Recent studies have revealed that the disease does not present solely with motor neuron involvement. Accordingly, the aim of this study is to investigate the presence of cardiac autonomic impairment in patients diagnosed with ALS. A total of 61 patients, who were diagnosed with ALS according to the Revised El Escorial Criteria (R-EEC), were included in this prospective study, in addition to the 29 healthy individuals, who were included in the study as controls. In order to assess the cardiac autonomic involvement, the presence of orthostatic hypotension was investigated, and transthoracic echocardiography and 24-hour electrocardiogram (ECG) using a Holter monitor were performed. Orthostatic hypotension was detected in 14 (22.2%) patients. Holter electrocardiogram results of the patient group revealed statistically significantly lower heart rate variability (HRV) indicators in the time domain (SDNN, SDANN, SDNN index, rMSSD, and pNN50) and in the frequency domain (high frequency [HF], low frequency [LF], and very low frequency [VLF]) than those of the control group (P<.05). Contrary to the popular opinion, cardiac autonomic dysfunction in patients with ALS can occur at any stage of the disease. Therefore, it is recommended that the patients are evaluated via periodic examinations during the follow-up period for cardiac autonomic involvement.

Late-onset neuromuscular disorders in the differential diagnosis of sarcopenia

BackgroundSarcopenia is the age-related loss of muscle mass and strength. Undiagnosed late-onset neuromuscular disorders need to be considered in the differential diagnosis of sarcopenia.AimBased on emblematic case reports and current neuromuscular diagnostic guidelines for three common late-onset neuromuscular disorders, a differential diagnostic approach for geriatric patients presenting with a sarcopenic phenotype is given.MethodsPatients over 65 years of age with sarcopenia, amyotrophic lateral sclerosis, inclusion body myositis and myotonic dystrophy type 2 were recruited. All patients were assessed for sarcopenia based on the revised European consensus definition. Patients with neuromuscular diseases were diagnosed according to the revised El Escorial criteria and the European neuromuscular centre criteria. Phenotypes and diagnostic criteria for all patients were summarized including their specific histopathological findings.ResultsAll patients with neuromuscular diseases were positively screened for sarcopenia and classified as severe sarcopenic by means of assessment. The clinical phenotype, the evolution pattern of weakness and muscle atrophy combined with laboratory finding including electromyography could unquestionably distinguish the diseases.DiscussionNeuromuscular disorders can manifest beyond the age of 65 years and misdiagnosed as sarcopenia. The most common diseases are inclusion body myositis, amyotrophic lateral sclerosis and myotonic dystrophy type 2. A diagnostic work-up for neuromuscular diseases ensures their correct diagnosis by clinical-, electrophysiological, histopathological, and genetic work-up.ConclusionsIn geriatric patients with a focal or asymmetrical muscular weakness and atrophy, sarcopenia assessment should be extended with patient’s history of disease course. Furthermore, concomitant diseases, analysis of serum creatine kinase, electrophysiological examination, and in selected patients muscle biopsy and gene analysis is needed to rule out a late-onset neuromuscular disorder.

Awaji criteria for the diagnosis of amyotrophic lateral sclerosis in Hanoi, Vietnam.

The aim of the article was to evaluate the role of electromyography and the value of Awaji criteria for the diagnosis of ALS in the early stage. The study involves 48 patients (27 male and 21 females from 41 to 84 years old) who went to Bach Mai Hospital and Dong Do Clinic in Hanoi and were diagnosed with ALS according to Awaji criteria. All patients underwent clinical examination for ALS. The patients were examined for nerve conduction (motor and sensory conduction) using needle electromyography (EMG). Upper motor neuron (UMN) signs and lower motor neuron (LMN) signs were most common in the cervical region (89.58%), the lumbosacral region (70.83%), and the bulbar region (56.25%). The sensory nerve conduction was normal. The spontaneous activities (fasciculation, fibrillation, positive wave) accounted for more than 50% in all 4 regions: bulbar, cervical, thoracic, and lumbosacral regions. The abnormality of both clinical and electrodiagnosis was seen in the cervical region (87.5%) and lumbosacral one (70.83%) while the bulbar region and thoracic one usually had abnormal electrodiagnosis before clinical. There were 60.42% of patients with "definite ALS" by Awaji criteria. It allowed to make an earlier diagnosis cause the sensitivity of Awaji criteria (93.75%) was higher than the revised El Escorial criteria (85.42%) (p < 0.05). The needle EMG makes it possible to detect the early-stage symptoms of ALS in a situation where there are no clinical manifestations, especially in bulbar and thoracic regions.

Non-Motor Features of Amyotrophic Lateral Sclerosis

Introduction:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of motor neurons. Spread of pathology to other brain areas leads to development of non-motor symptoms (NMSs). These usually remain undiagnosed because of overwhelming motor problem and are responsible for significant distress to the patient. Our objective was to explore the burden of various NMSs of patients with ALS, compare between limb-onset and bulbar-onset patients, and to correlate with severity and duration of disease.Methods:Fifty patients with ALS diagnosed according to revised El Escorial Criteria and 50 healthy controls were included in this study. They were assessed with NMS Questionnaire, Beck's Depression Inventory, Center for Neurologic Study-Lability Scale, Drooling Frequency and Severity Scale, Epworth Sleepiness scale, Bengali Mental State Examination, and Frontal Assessment Battery and relevant statistical analyses were carried out.Results:The patients with ALS had significantly increased prevalence of almost all NMSs compared to controls. There was also significant increase in depression, suicidal ideation, pseudobulbar affect, and daytime sleepiness in patients with ALS. The bulbar onset subgroup had significantly increased daytime drooling, dysphagia, nausea and vomiting, whereas the limb onset subgroup reported increased frequency of leg swelling. Executive dysfunction was detected in 24% of patients with ALS and 9.8% had mild cognitive impairment. Weight loss, frequency of falling, insomnia, unpleasant nocturnal leg sensations, difficulty having sex, depression, and cognitive impairment increased significantly with an increase in severity of the disease.Conclusion:NMSs were significantly more prevalent in patients with ALS. Some NMSs worsened with advancement of the disease.