Since 2020, updates in the diagnostic criteria for various neuromuscular diseases have emerged by advancements in electrophysiological studies, biomarker research, and imaging modalities. These developments reflect an effort to improve diagnostic accuracy and allow for earlier intervention. This review summarizes the most recent revisions in the diagnostic criteria for amyotrophic lateral sclerosis, primary lateral sclerosis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, and myasthenia gravis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of upper motor neurons in the brainstem and spinal cord and lower motor neurons. ALS was first described by Jean-Martin Charcot in 1874 based on clinical features and postmortem examinations. In 1990, the first diagnostic criteria for ALS were developed based on clinical features. Subsequently, three additional diagnostic criteria were published. In this article, we introduce the clinical features, diagnostic criteria, and diseases that need to be differentiated in ALS.

Respiratory muscle weakness caused by neuromuscular disease can lead to both acute and chronic respiratory failure. Respiratory failure caused by Guillain-Barré syndrome and myasthenia gravis can potentially improve with disease-specific therapy. However, respiratory failure in amyotrophic lateral sclerosis is irreversible, and it may be necessary to provide full-time ventilation support along with additional assistance. Noninvasive ventilation is recommended for managing acute or acute-on-chronic hypercapnic respiratory failure caused by neuromuscular disease. It has also been effective in weaning patients off invasive mechanical ventilation. Although noninvasive ventilation offers numerous benefits over invasive mechanical ventilation, it is crucial to consider the specific contraindications and limitations of noninvasive ventilation and ensure its appropriate usage based on the patient's condition and needs. The timely recognition of neuromuscular respiratory failure is critical, as early intervention can be life-saving. This review focused on the clinical assessment and management of acute respiratory failure in neuromuscular diseases.

Background
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron degeneration with phenotypic heterogeneity, including age at onset. Juvenile ALS (JALS) includes ALS patients aged less than 25 years who typically show slow progression. This study aimed to identify the characteristics of juvenile ALS from Korean ALS cohorts.
Methods
We retrospectively investigated the clinical characteristics of JALS patients, who met the revised El Escorial-Airlie House criteria, in the Korean motor neuron disease cohort om January 2002 to November 2018. To evaluate the genetic background ofin JALS, we screened the SOD1 mutation in all JALS patients using PCR.
Results
Among the seven JALS patients, the mean age was 22.1 years (± 2.19 years) and 4 patients were male. Most patients were diagnosed within less than 12 months, but in one patient, it took 96 months to make the initial diagnosis. On assessing the cognitive function, none of the patients had dementia. The progression rate of JALS during follow-up was usually low (median [IQR], 0.31 [0.11-0.52]), except in patients with SOD1 mutation (3.40) and CLEC4C mutation (1.12). One patient revealed a family history of ALS with SOD1 mutation, but we also detected the SOD1 mutation among sporadic JALS patients.
Conclusions
Although JALS patients with genetic mutations (SOD1-p.Asn87Ser and CLEC4C-p.Lys210*) showed faster progression than other JALS patients, one patient with SOD1 mutation (p.Gly17Ala) showed slow progression. Familial ALS was rare; however, it might be caused by low or incomplete penetrance of the genes or by small number of JALS patients. To investigate the other genetic causes of JALS without the SOD1 mutation, a further study including detailed genetic analysis is needed.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with numerous causes that include genetic factors. Efforts to reveal the genetics of ALS have identified several candidate genes that are associated with familial and sporadic ALS. Here we report a Korean ALS patient who showed prominent upper motor-neuron-related symptoms with marked brain atrophy and neuropsychological deficits. The findings were highly suggestive of ALS in a patient with a likely pathogenic FIG4 variant.

Citations

• Nanoparticles encapsulating phosphatidylinositol derivatives promote neuroprotection and functional improvement in preclinical models of ALS via a long-lasting activation of TRPML1 lysosomal channel
  Valentina Tedeschi, Valeria Nele, Valeria Valsecchi, Serenella Anzilotti, Antonio Vinciguerra, Laura Zucaro, Maria Josè Sisalli, Chiara Cassiano, Nunzia De Iesu, Giuseppe Pignataro, Lorella Maria Teresa Canzoniero, Anna Pannaccione, Giuseppe De Rosa, Agne
  Pharmacological Research.2024; 210: 107491.     CrossRef

Myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS) are distinct disorders. ALS affects motor neurons that control muscle movement, while MG controls communication between neurons and muscles, which occurs at neuromuscular junctions. However, on rare occasions, ALS develops after MG and vice versa. The coexistence of the two diseases represents a diagnostic challenge and requires thoughtful interpretation of clinical features. We present the case of a 53-year-old Korean male who developed ALS after MG, confirmed by clinical and electrophysiological follow-up.

Citations

• Two Cases of Sporadic Amyotrophic Lateral Sclerosis With Contrasting Clinical Phenotypes: Genetic Insights
  Andrey Frolov, Miguel A Guzman, Ghazala Hayat, John R Martin
  Cureus.2024;[Epub]     CrossRef

Detection of underling proteinopathies is becoming increasingly important across neurodegenerative conditions due to upcoming disease intervention trials. In this review, we explored how temporal lobe changes in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) can potentially predict underlying TDP-43 pathology subtypes in FTD. To date, emphasis has been given to frontal lobe changes in the study of the cognitive and behavioural impairments in both syndromes but an increasing number of pathological, imaging and neuropsychological studies suggest how temporal lobe changes could critically affect the cognition and behaviour of these conditions. In this current article, we reviewed pathological, imaging as well as clinical/neuropsychological findings of temporal involvement in the ALS-FTD continuum, how they relate to temporal lobe changes and the underlying TDP-43 pathology in FTD. Findings across studies show that TDP-43 pathology occurs and coincides in many structures in ALS and FTD, but especially in the temporal lobes. In particular, anterior and medial temporal lobes atrophy is consistently found in ALS and FTD. In addition, memory and language impairment as well as emotional and Theory of Mind processing deficits that are characteristics of the two diseases are highly correlated to temporal lobe dysfunction. We conclude by showing that temporal lobe changes due to TDP-43 type B might be particular predictive of TDP-43 type B pathology in behavioural variant FTD, which clearly needs to be investigated further in the future.

Citations

• A comparative study of cognitive and behavioral profiles between sporadic and type 8 amyotrophic lateral sclerosis
  Cássia de Alcântara, Marcelo Maroco Cruzeiro, Marcondes Cavalcante França, Mariana Asmar Alencar, Antônio Jaeger, Caroline Martins de Araújo, Natália Araújo Sundfeld da Gama, Sarah Teixeira Camargos, Leonardo Cruz de Souza
  Muscle & Nerve.2023; 68(3): 316.     CrossRef
• In vivo exploration of synaptic projections in frontotemporal dementia
  Eric Salmon, Mohamed Ali Bahri, Alain Plenevaux, Guillaume Becker, Alain Seret, Emma Delhaye, Christian Degueldre, Evelyne Balteau, Christian Lemaire, André Luxen, Christine Bastin
  Scientific Reports.2021;[Epub]     CrossRef
• Structural and functional papez circuit integrity in amyotrophic lateral sclerosis
  Ana Paula Arantes Bueno, Walter Hugo L. Pinaya, Luciana M. Moura, Maxime Bertoux, Ratko Radakovic, Matthew C. Kiernan, Antonio Lucio Teixeira, Leonardo Cruz de Souza, Michael Hornberger, João Ricardo Sato
  Brain Imaging and Behavior.2018; 12(6): 1622.     CrossRef

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that clinically manifests both upper and lower motor neuron signs. However, it is unknown where and how the motor neuron degeneration begins, and conflicting hypotheses have been suggested. Recent advanced radiological techniques enable us to look into ALS neuropathology in vivo. Herein, we report a case with upper motor neuron-predominant ALS in whom the results of brain magnetic resonance imaging (MRI) and myelin water fraction MRI suggest axonal degeneration.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by progressive death of motor neurons in the cortex, brainstem, and spinal cord. Until now, many treatment strategies have been tested in ALS, but so far only Riluzole has shown efficacy of slightly slowing disease progression. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. Other motor neuron disease such as spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA) are also progressive neurodegenerative disease with loss of motor neuron as ALS. This common thread of motor neuron loss has provided a target for the development of therapies for these motor neuron diseases. A better understanding of these pathogenic mechanisms and the potential pathological relationship between the various cellular processes have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.

Background: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). Methods: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. Results: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. Conclusions: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.

Citations

• Mechanism of motoneuronal and pyramidal cell death in amyotrophic lateral sclerosis and its potential therapeutic modulation
  Bernát Nógrádi, Dóra Nógrádi-Halmi, Barbara Erdélyi-Furka, Zalán Kádár, Tamás Csont, Renáta Gáspár
  Cell Death Discovery.2024;[Epub]     CrossRef

Background
Testosterone is reported to have neuroprotective effect in various neurological diseases. Recently, the mechanism involved in nitric oxide (NO)-mediated motor neuron death is under extensive investigation. The Cu/Znsuperoxide dismutase (SOD1) mutations has been implicated in selective motor neuron death of amyotrophic lateral sclerosis (ALS) and it is said to play an important role in NO-mediated motor neuron death. However, neuroprotective effect of testosterone on motor neuron exposed to NO has rarely been studied.
Methods
Motor neuron-neuroblastoma hybrid cells expressing wild-type or mutant (G93A or A4V) SOD gene were treated with 200 μΜ S-nitrosoglutathione. After 24 hr, cell viability was measured by MTT assay. To see the neuroprotective effect of testosterone, pretreatment with 1 nM testosterone was done 1 hr before S-nitroglutathione treatment. To study the mechanism of protective effect, 20 μΜ flutamide (androgen receptor antagonist) was also pretreated with testosterone 1 hr before S-nitroglutathione treatment.
Results
S-nitrosoglutathione showed significant neurotoxic effect in all three cell lines. Percentage of cell death was somewhat different in each cell line. 1 nM testosterone showed neuroprotective effect in G93A and wild-type cell line. In A4V cell line, testosterone did not showed neuroprotective effect. The neuroprotective effect of testosterone was reversed by 20 μΜ flutamide.
Conclusions
These results indicate that testosterone induces neuroprotection in NOmediated motor neuron death directly through the androgen receptor. This neuroprotective effect of testosterone varies according to the types of SOD1 gene mutation. These data suggest that testosterone may be of therapeutic value against ALS.

Background
& Objectives : Motor evoked potentials(MEPs) to magnetic trans cranial stimulation were performed to evaluate upper moror neuron involvement and relationship to lower motor neuron involvement in motor neuron disease patients. Method : MEPs were obtained in the 17 consecutive patients with motor neuron disease. These patients were divided into three group based on clinical evidence of upper and lower motor neuron involvement, bulbar symptom; amyotrophic lateral sclerosis(ALS), progressive muscular atrophy(PMA), Progressive bulbar palsy(PBP), MEPs were recorded from abductor pollicis brevis and abductor hallucis. Abnormal MEPs were defined by delayed central motor conduction time or absent MEP. Results : MEPs were abnormal in 64%(11/17) of patients; 100%(7/7) in ALS, 64%(4/7) in PMA, 0%(0/3) in PBP respectively. In 68 total recording muscles, 34 muscles had evidence of motor weakness and showed abnormal responses in 59%(20/34). Whereas 34 muscles with normal strength, only 3%(1/34) of muscles showed abnormal responses. Conclusion : MEPs are well correlated with upper motor neuron signs in ALS and may detect masking upper motor neuron signs I PMA. The muscles with lower motor neuron sign(weakness) usually relate with abnormal MEPs reponses.

Although the etiology and pathogenesis of amyotrophic lateral sclerosis(ALS) in unknown, increasing evidence support a role autoimmune machanisms in motor neuron degeneration. The coexistence of immune disease in ALS supports that an altered immune system may contribute to disease pathogenesis. A 55-year-old woman was admitted to our department due to dysarthria and gait disturbance. On physical and neurologic examination, she showed thyroid enlargement, tongue atrophy, muscle weakness, fasciculation, and increased deep tendon reflex. The electrophysiological studies are compatible with motor neuron disease. Cytological findings of thyroid were compatible with hashimoto's thyroiditis. Thus, we report a case of ALS combined with Hashimoto's thyroiditis. And the simultaneous presentation with ALS and Hashimoto's thyroiditis led us to consider whether this was simply a chance association or not.

Backgroun & Objectives : Hyperexciability of motor system is a well-established characteristic pathophysiologic finding of mayotrophic lateral sclerosis (ALS). Whereas little is known about the source of excitability according to the progression of the disease. We evaluated the excitability and its source in advanced ALS patients using transcranial magnetic stimulation(TMS). Material & Methods : Motor evoked potentials (MEP) by TMS were recorded for abductor pollicis brevis muscles in 20 patients, 11men and 9 women, with ALS. Mean age was 54.2?2.1 years, and mean disease duration was 13.9?3.4 years. Serial magnetic stimulations were applied to get the parameters; excitability threshold (ET), amplitude and latency of MEP. We also had a facilitated MEP (fMEP). Results : The parameters were analyzed according to the clinical setting. ET was higher in ALS(mean 63.5?8.1) than normal control (mean 46.0?.4 , p<0.01). Amplitudes of MEP were reduced I ALS (2.6?.6 mV ; control 6.5?.1mV, p<0.01). Duration of the disease and ET showed significant inverse correlation (Spearson correlation coefficient = -0.57, p<0.01). Duration of the disease and fMEP/MEP ratio showed less but also significant inverse correlation(Spearson correlation coefficient, r=-0,52, p<0.05). Conclusions : Lower ET in advanced ALS patients, in spite of decreased fMEP/MEP ratio, may indicate the hyperexcitability of lower motor neuron in these patients. This study suggests that lower motor neurons is hyperexciable due to upper motor neuron dysfunction at advanced stage.

Background
Motor unit number estimation (MUNE) can directly assess motor neuron populations in muscle and quantify the degree of physiologic and/or pathologic motor neuron degeneration. A high degree of reproducibility and reliability is required from a good quantitative tool. MUNE, in various ways, in being increasingly applied clinically and statistical MUNE has several advantages over alternative techniques. Nevertheless, the optimal method of applying statistical MUNE to improve reproducibility has not been established. Methods: We performed statistical MUNE by selecting the most compensated compound muscle action potential (CMAP) area as a test area and modified the results obtained by weighted mean surface-recorded motor unit potential (SMUP). Results: MUNE measures in amyotrophic lateral sclerosis (ALS) patients showed better reproducibility with size-weighted modification. Conclusions: We suggest size-weighted MUNE testing of "neurogenically compensated" CMAP areas present an optimal method for statistical MUNE in ALS patients.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects motor neurons.The characteristic features of this devastating disorder are the simultaneous presence of upper and lower motor neuron(LMN) signs with progression from one region of the neuraxis to the next and eventual death, typically from respiratorycompromise.Electrophysiological studies are an indispensible part of the ALS evaluation, especially serving as an extension of theclinical examination, and most useful in identifying LMN dysfunction. Not only may electrodiagnostic studies revealcharacteristic changes in those regions clinically manifesting signs, but it also serves to disclose asymptomatic areas ofinvolvement.

Background
Needle electromyography (EMG) and motor evoked potential (MEP) of the genioglossus (tongue) aredifficult to perform in evaluations of the craniobulbar region in amyotrophic lateral sclerosis (ALS). Therefore, weinvestigated the yields of needle EMG and MEP recorded from the upper trapezius, since it receives innervation fromthe lower medulla and upper cervical cord.Methods: Needle EMG and MEP of the upper trapezius were obtained in 17 consecutive ALS patients. The needleEMG parameters recorded included abnormal spontaneous activity and motor unit action potential (MUAP) morphology.An upper motor neuron (UMN) lesion was presumed when either response to cortical stimulation was absent, or thecentral conduction time was delayed (>mean+2SD).Results: Of the five patients with bulbar-onset ALS, four had abnormalities in the upper trapezius and four in thetongue by needle EMG. In contrast, of the 12 patients with limb-onset ALS, 11 had abnormalities in the upper trapezius,and only five in the tongue. When MEP was performed, it was found that three of the five patients with bulbar symptomsand three of the six patients with isolated limb involvement had abnormal MEP findings.Conclusions: Electrophysiological studies of the upper trapezius are more sensitive those of the tongue in patientswithout bulbar symptoms. Thus, needle EMG and MEP of the upper trapezius are alternative tools for assessing bulbarand rostral neuraxial involvement in the diagnosis of ALS.

Underlying neuropathies combined with amyotrophic lateral sclerosis (ALS) cast doubt on the diagnosis of ALS when present.Abnormal sural nerve conductions were found in 3 patients with clinically definite ALS. Pathologically demyelinating, axonal, or vasculitic neuropathy was suggested respectively. High dose oral corticosteroid had no effect and clinical courses were deteriorating in all the patients.The causes of combined neuropathies were unclear. Possibility of direct consequence of ALS, concomitant neuropathies, or rare variants of ALS should be considered in these cases.

We report a patient with amyotrophic lateral sclerosis (ALS) who developed a pneumothorax after needle electromyography (EMG), probably of the intercostal muscles. Needle EMG on intercostal muscles has a high risk of pneumothorax, not only because electromyographers are unfamiliar to its technique, but also due to its close anatomical location to the pleural cavity. In our patient, advanced intercostal muscle atrophy due to disease process would have increased the risk further.

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Geographical differences in the incidence of amyotrophic lateral sclerosis (ALS) have been reported, and there are stillmany unresolved problems. The incidence as well as epidemiologic data of ALS is not known in Korea. Web-based multicenterregistry of ALS, the Korean ALS registry, was established at January, 2011. The aim of