Lower Motor Neuron Disease Research Articles

4-Phenylbutyric acid mitigates ER stress-induced neurodegeneration in the spinal cords of a GM2 gangliosidosis mouse model.

Sandhoff disease (SD), a fatal and rare lysosomal storage disorder (LSD), is caused by a deficiency of the enzyme β-hexosaminidase B and leads to severe accumulation of GM2 gangliosides in lysosomes, primarily within the central nervous system (CNS). This accumulation results in severe neurological impairment, lower motor neuron disease, and death. Currently, there are no effective therapies available for SD. Here, we explored the role of endoplasmic reticulum (ER) stress in the spinal cord during disease progression in an established mouse model of SD and revealed the beneficial outcome of off-label treatment with the FDA-approved drug, 4-phenylbutyric acid (4-PBA). We analyzed the expression and localization of ER stress and cellular apoptosis markers, which revealed significant upregulation of these factors within motor neurons. Additionally, we observed a > 50% reduction in neuronal numbers throughout all spinal cord regions. Our studies also tested the impact of the chemical chaperone 4-PBA on ER stress in mice, and following administration, we observed significant improvements in motor neuromuscular function and life span throughout disease progression. 4-PBA treatment significantly reduced apoptosis in spinal cord neurons and increased the number of choline acetyltransferase (ChAT)-positive neurons, with little effect on astrogliosis or sensory interneurons. Overall, this study provides strong evidence for the role of chronic ER stress in the pathophysiology of SD and highlights 4-PBA as a promising therapeutic treatment for SD and potentially other related LSDs.

SMN2 gene copy number affects the incidence and prognosis of motor neuron diseases in Japan

BackgroundThe copy number status (CNS) of the survival motor neuron (SMN) gene may influence the risk and prognosis of amyotrophic lateral sclerosis (ALS) and lower motor neuron diseases (LMND) other than spinal muscular atrophy (SMA). However, previous studies of this association, mainly from Europe, have yielded controversial results, suggesting possible regional differences. Here, we investigated the effect of the SMN gene in Japanese patients with ALS and LMND.MethodsWe examined the SMN copy numbers and clinical histories of 487 Japanese patients with sporadic ALS (281 men; mean age at onset 61.5 years), 50 with adult LMND (50 men; mean age at onset 58.4 years) and 399 Japanese controls (171 men; mean age 62.2 years). Patients with pathogenic mutations in ALS-causing genes were excluded. SMN1 and SMN2 copy numbers were determined using the droplet digital polymerase chain reaction.ResultsThe frequency of a copy number of one for the SMN2 gene was higher in patients with ALS (38.0%) than in healthy controls (30.8%) (odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.04–1.82, p < 0.05). The SMN2 copy number affected the survival time of patients with ALS (median time: 0 copies, 34 months; 1 copy, 39 months; 2 copies, 44 months; 3 copies, 54 months; log-rank test, p < 0.05). Cox regression analysis revealed that the SMN2 copy number was associated with increased mortality (hazard ratio = 0.84, 95% CI = 0.72–0.98, p < 0.05). Also, null SMN2 cases were significantly more frequent in the LMND group (12.0%) than in the control group (4.8%) (OR = 2.73, 95% CI = 1.06–6.98, p < 0.05).ConclusionsOur findings suggest that SMN2 copy number reduction may adversely affect the onset and prognosis of MND, including ALS and LMND, in Japanese.

124P Hidden in plain sight: genome reanalysis to identify an intragenic novel variant in the SMN locus in a patient with an undiagnosed lower motor neuron disease

124P Hidden in plain sight: genome reanalysis to identify an intragenic novel variant in the SMN locus in a patient with an undiagnosed lower motor neuron disease

98P Biallelic pathogenic PLEKHG5 variants in a girl with childhood-onset lower motor neuron disease

98P Biallelic pathogenic PLEKHG5 variants in a girl with childhood-onset lower motor neuron disease

Brachialis to Anterior Interosseous Nerve Transfer: Comprehensive Anatomic Rationale.

Distal nerve transfers for muscle reinnervation and restoration of function after upper and lower motor neuron lesions are a well-established surgical approach. The brachialis to anterior interosseous nerve (BrAIN) transfer is performed for prehension reanimation in lower brachial plexus and traumatic cervical spinal cord injuries. The aim of the study is to shed light on the inconsistent results observed in patients who undergo the BrAIN transfer. An anatomic dissection was conducted on 30 fresh upper limb specimens to examine the intraneural topography of the median nerve (MN) in the upper arm at the level of the BrAIN transfer and the presence of intraneural fascicular interconnections distally. Fascicular interconnections between the AIN and other MN branches were consistently found in the distal third of the upper arm. The first interconnection was at 3.85 ± 1.82 cm proximal to the interepicondylar line, and the second one, after further proximal neurolysis, was at 9.45 ± 1.16 cm from the interepicondylar line. Intraneural topography of the AIN at the transfer level varied, with dorsomedial, dorsolateral, and purely dorsal locations observed. Consistent fascicular interconnections between the AIN and MN branches and intraneural topography variability of the MN may lead to aberrant reinnervation.

The Spectrum of Childhood-Onset Lower Motor Neuron Disease of Spinal Muscular Atrophy Phenotype Associated with Survival Motor Neuron-2 Gene Deletion

AbstractPediatric lower motor neuron disease is clinically and genetically heterogeneous. We characterized disease progression among children with the spinal muscular atrophy (SMA) phenotype having 2:0 (group A) and 2:1 (group B) of the survival motor neuron 1/2 (SMN1:SMN2) genotype over 1 year. We included children aged 0 to 12 with the SMA phenotype between January 2018 and December 2021. Their demographic, clinical (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP-INTEND] scores), electrophysiological, radiological, and genetic data were collected from past medical records. The sequential CHOP-INTEND scores and the compound muscle action potential (CMAP) amplitudes were compared using an analysis of covariance test, controlling for age and sex. A linear regression was run to determine the association between the ages of the patients and the CHOP-INTEND scores. Among nine children in group A and six in group B, the decline of the mean (standard deviation) CHOP-INTEND score from the initial value to the 12th-month follow-up value was significant only in group A. CHOP-INTEND scores did not significantly differ between the two groups at the first admission but were significantly lower in group A at the subsequent visits. Group A patients had significantly lower CMAP amplitudes than patients in group B. There was a moderate, negative association between the age of patients and the CHOP-INTEND scores in group A. Group A patients had a significantly higher age-dependent decline in CHOP-INTEND scores and CMAP values than group B, although their age and the severity of weakness did not significantly differ at presentation.

Effects of electroacupuncture on chronic urinary retention after pelvic or lumbosacral tumor resection surgeries: a retrospective cohort study.

Chronic urinary retention (CUR) resulting from lower motor neuron lesions (LMNL) is a medical condition secondary to pelvic or lumbosacral tumor resection surgeries. Electroacupuncture (EA) is proved to be effective and safe in treating certain lower urinary tract disorders. However, the clinical benefit and optimal duration of EA treatment for CUR following LMNL remain unknown. Using a retrospective cohort design, 20 eligible patients diagnosed with CUR resulting from LMNL secondary to pelvic or lumbosacral tumor resection surgeries were included from March 1, 2017, to June 30, 2020. The patients were treated by EA three times a week for 2 to 12 weeks and followed up for 24 weeks after treatment. The electric stimulators with a 5-Hz continuous wave (5-10 mA intensity) were separately connected to bilateral Ciliao (BL32), bilateral Zhongliao (BL33), and bilateral Huiyang (BL35), and stimulators with a 10-Hz continuous wave (1-2 mA intensity) were connected to bilateral Sanyinjiao (SP6). Current intensity was adjusted according to the patients' individual tolerance. The median follow-up was 32 weeks (range, 26-36 weeks). Responders were defined as patients whose post-void residuals (PVR) reduced by 50% or more from baseline. Adverse event was recorded. Totally 20 patients [mean (standard deviation) age, 48.1 (15.5) years; 9 men (45.0%); 11 women (55.0%)] were included. Of the 20 patients, 14 (70.0%) had responded to EA treatment and stopped catheterization for achieving satisfactory spontaneous urination (PVR <100 mL without complications), 7 (35.0%) had complete resolution (90-100% reduction in PVR from baseline), and 13 (65.0%) scored 1 (much better) or 2 (moderately better) in the Patient Global Impression of Improvement (PGI-I) assessment. Moreover, 6 (30.0%) patients had responded within 4 weeks of EA treatment. According to Kaplan-Meier survival curve, we found that more than 50% patients could respond to EA treatment within 8 weeks or longer. None of the responders had ever experienced relapse in 24 weeks after EA treatment ended. None of the patients manifested urinary tract infection (UTI), newly diagnosed hydroureter or hydronephrosis. One patient diagnosed with hydronephrosis at baseline recovered after 12-week EA treatment. Two patients with UTI at baseline were prescribed antibiotics and did not present UTI again during the follow-up. EA could be a promising treatment option for CUR caused by LMNL following pelvic or lumbosacral tumor resection surgeries, with long-term effects and a good safety profile. The optimal duration of EA should be of 8 weeks at least. But this was a retrospective cohort study of a small sample size, so future studies are needed to investigate EA in larger populations in randomized controlled trials.

Role of circulating biomarkers in spinal muscular atrophy: insights from a new treatment era.

Spinal muscular atrophy (SMA) is a lower motor neuron disease due to biallelic mutations in the SMN1 gene on chromosome 5. It is characterized by progressive muscle weakness of limbs, bulbar and respiratory muscles. The disease is usually classified in four different phenotypes (1-4) according to age at symptoms onset and maximal motor milestones achieved. Recently, three disease modifying treatments have received approval from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), while several other innovative drugs are under study. New therapies have been game changing, improving survival and life quality for SMA patients. However, they have also intensified the need for accurate biomarkers to monitor disease progression and treatment efficacy. While clinical and neurophysiological biomarkers are well established and helpful in describing disease progression, there is a great need to develop more robust and sensitive circulating biomarkers, such as proteins, nucleic acids, and other small molecules. Used alone or in combination with clinical biomarkers, they will play a critical role in enhancing patients' stratification for clinical trials and access to approved treatments, as well as in tracking response to therapy, paving the way to the development of individualized therapeutic approaches. In this comprehensive review, we describe the foremost circulating biomarkers of current significance, analyzing existing literature on non-treated and treated patients with a special focus on neurofilaments and circulating miRNA, aiming to identify and examine their role in the follow-up of patients treated with innovative treatments, including gene therapy.

Rabies: Diagnostic, Treatment, and Prevention

Rabies is a neurological disease with fatal impacts because it has a high mortality rate. Animals, primarily dogs, mediate the spread of rabies. Clinical findings of rabies are divided into two categories: classic rabies (furious type) and paralytic type. Furious rabies has many cardinal features, such as fluctuating consciousness, aerophobia or hydrophobia, inspiratory spasm, and autonomic dysfunction. Ascending paralysis with a lower motor neuron lesion is the initial sign of paralytic rabies. The rabies virus invades and lives in neurons. It is virulent. Besides clinical findings, the diagnostic approach can involve radiology, microbiology, and histopathology. There are not only symptomatic treatments for rabies patients but also vaccines, immunoglobulin, and antivirals to decrease the progressivity of the disease. Vaccination programs and animal control have become essential in reducing rabies cases in Indonesia.

Spinal Muscular Atrophy: The Past, Present, and Future of Diagnosis and Treatment.

Spinal muscular atrophy (SMA) is a lower motor neuron disease with autosomal recessive inheritance. The first cases of SMA were reported by Werdnig in 1891. Although the phenotypic variation of SMA led to controversy regarding the clinical entity of the disease, the genetic homogeneity of SMA was proved in 1990. Five years later, in 1995, the gene responsible for SMA, SMN1, was identified. Genetic testing of SMN1 has enabled precise epidemiological studies, revealing that SMA occurs in 1 of 10,000 to 20,000 live births and that more than 95% of affected patients are homozygous for SMN1 deletion. In 2016, nusinersen was the first drug approved for treatment of SMA in the United States. Two other drugs were subsequently approved: onasemnogene abeparvovec and risdiplam. Clinical trials with these drugs targeting patients with pre-symptomatic SMA (those who were diagnosed by genetic testing but showed no symptoms) revealed that such patients could achieve the milestones of independent sitting and/or walking. Following the great success of these trials, population-based newborn screening programs for SMA (more precisely, SMN1-deleted SMA) have been increasingly implemented worldwide. Early detection by newborn screening and early treatment with new drugs are expected to soon become the standards in the field of SMA.

Amyotrophic lateral sclerosis with respiratory failure and dysautonomia: a case report.

A 58-year-old male presented with left lower limb limping, difficulty climbing stairs, and left foot weakness, followed by right upper limb weakness and was diagnosed with ALS and received edaravone and riluzole treatment. He presented again with right lower limb weakness, shortness of breath, and wide fluctuations in blood pressure, leading to ICU admission with new diagnosis of ALS with dysautonomia with respiratory failure and was managed with non-invasive ventilation, physiotherapy, and gait training exercises. ALS is a progressive neurodegenerative disease affecting motor neurons but non-motor symptoms can also occur, including dysautonomia, which can result in blood pressure fluctuations. Dysautonomia in ALS is caused by several mechanisms such as severe muscle atrophy, prolonged ventilatory support, and upper and lower motor neuron lesions. Management of ALS involves giving a definitive diagnosis, providing nutritional support, using disease-modifying drugs such as riluzole and non-invasive ventilation to improve survival and quality of life. Early diagnosis is essential for effective management of the disease. Early diagnosis, use of disease-modifying drugs, non-invasive ventilation, and maintaining the patient's nutritional status are crucial for managing ALS which can have non-motor symptoms as well.

Neuroimmunology: PIK3R1 Ile571TyrfsTer31 plays an important role in neuronal function and survival

Neurological complications are important causes of morbidity and mortality in patients with inborn errors of immunity (IEIs). However, the role of immune gene defects in the nervous system has not been well studied.A 42 yo M presented with recurrent infections and hypogammaglobulinemia in childhood and was found to have Ile571TyrfsTer31 in the PIK3R1. He developed spastic paraparesis at age 30 but extensive neuroinfectious and neuroinflammatory work up was unrevealing. Significant weakness in all limbs and bulbar symptoms progressed despite treatment with IVIg, cyclophosphamide and rituximab to target potential neuroinflammation. Further neurological evaluation showed both upper and lower motor neuron disease clinically consistent with ALS. We used our newly developed pipeline to evaluate the potential contribution of his PIK3R1 mutation to CNS disease.The patient’s CSF cells showed active antigen presentation and T cell activation in the CNS compartment, suggesting the possibility of immune activation due to neuronal destruction. We generated an iPSC line from patient CD34+ cells and repaired the mutation with CRISPR-Cas9 technology to investigate the role of PIK3R1 in neurons. We then differentiated patient-derived and gene-edited cells into Motor Neurons (MNs), as well as iPSC from a healthy donor. Morphologically, cells from all three lines differentiated normally to neuroepithelial cells, motor neuron precursors and terminally differentiated MNs. Electrophysiology showed significantly lower activity in patient-derived neurons compared to healthy or edited MNs, indicating that PI3KR1 plays an important role in neuronal function. NMDA treatment increased firing in MNs in healthy and edited lines but not in patient-derived neurons, indicating an abnormal response to stimulation. We also found higher levels of phosphorylated AKT in patient MNs compared to edited and healthy cells, indicating upregulation of the PI3K pathway in patient-derived cells. Patient-derived neurons were also more prone to apoptosis as shown by higher expression of Caspase 3 compared to healthy control.These findings strongly suggest that PIK3R1 plays an essential role in neuronal function and survival. iPSC-derived neuronal cells provide powerful new platforms to better investigate manifestations of IEIs in the CNS.

Paraneoplastic pure motor neuropathy in a 48-year-old male with recently diagnosed DLBCL (P3-8.014)

<h3>Objective:</h3> To report a case of paraneoplastic pure motor neuropathy associated with DLBCL <h3>Background:</h3> Paraneoplastic lower motor neuron disease is a rare clinical entity. Patient’s present with a slow progressive painless asymmetric weakness in the limbs and without upper motor neuron features. Neoplasms that are associated with this syndrome include: lymphoma, ovarian, breast, renal, and lung cancers. Usually, no paraneoplastic antibodies are identified. We report a case of a 48-year-old male with newly diagnosed DLBCL, a non-Hodgkin lymphoma (NHL), who presented with subacute painless asymmetric upper extremity weakness without clear sensory loss prior to initiation of any chemo or radiation therapy. Imaging of the bilateral plexus and cervical spine did not reveal enhancement or infiltration and cerebrospinal fluid studies were unrevealing. Electromyography provided evidence of a primarily demyelinating greater than axonal purely motor polyradiculoneuropathy limited to the arms. Neurological improvement was seen with intravenous immunoglobulin and treatment of malignancy. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> Upon literature review, a case of paraneoplastic purely motor neuron syndrome associated with an NHL such as DLBCL has not been described before. There have been reports of paraneoplastic neurological syndromes associated with NHL none of which were purely motor neuron disease. <i>Flanagan et al</i> reported a similar case of paraneoplastic motor neuron disease associated with a type of Hodgkin’s Lymphoma. Similarly, to their findings, we observed neurological improvement with concurrent IVIG and treatment of the underlying malignancy. This case highlights the continued role for documentation of peripheral neuropathies secondary paraneoplastic etiologies with goals to further characterize novel onconeural antibodies. <b>Disclosure:</b> Dr. Kolli has nothing to disclose. Dr. Ata has nothing to disclose. Dr. Hurst has nothing to disclose.

18F-FDG PET/CT as a molecular biomarker in the diagnosis of amyotrophic lateral sclerosis associated with prostate cancer and progressive supranuclear palsy: A case report

Introduction Amyotrophic lateral sclerosis (ALS) is a neurodegenerative, multisystem disorder. Its clinical presentation typically consists of progressive focal muscle atrophy and weakness. In addition to motor disorders, the association between ALS and cancer has been researched, such as frontotemporal dementia and progressive supranuclear palsy. The diagnosis is based primarily on the clinical history, physical examination, electrodiagnostic tests (with an EMG needle), and neuroimaging, such as MRI and 18 F-FDG PET/CT. Presentation of the case A 67-year-old male patient was diagnosed with prostate adenocarcinoma with a clinical picture of muscle weakness in the lower limbs that caused falls and was associated with fasciculations in the thighs and arms, alterations in the tone of voice, poor memory, and difficulty articulating words. In the neurological assessment, he described walking supported by a walker with decreased strength in both lower limbs and sensitivity without alterations. The diagnoses of upper and lower motor neuron disease and probable ALS were integrated. Furthermore, the probable coexistence of frontotemporal dementia/disorder (FDD) with ALS was considered. The main findings in the 18 F-FDG PET/CT study was hypometabolism in the cortex of the bilateral motor and premotor areas, the anterior cingulate, both caudate and putamen, a metabolic pattern compatible with ALS, and progressive supranuclear palsy. Conclusion Through the PET/CT studies, we demonstrated a case in which ALS, prostate cancer and progressive supranuclear palsy coexisted molecularly; it was clinically difficult to diagnose. Molecular imaging has potential in the diagnostic and prognostic evaluation of ALS. It is crucial to identify the disease early and reliably through metabolic patterns that allow us to confirm the disease or differentiate it from other pathologies.

A lower motor neuron disease in takahē (Porphyrio hochstetteri) is an endoplasmic reticulum storage disease

Aims: To investigate the pathogenesis of a disease in takahē with intracytoplasmic inclusion bodies in lower motor neurons. Methods: Four cases aged between 5 and 12 years, from three different wildlife sanctuaries in New Zealand were examined. Of these, only one had signs of spinal dysfunction in the form of paresis. Stained paraffin sections of tissues were examined by light microscopy and immunostained sections of the ventral horn of the spinal cord by confocal microscopy. Epoxy resin sections of the bird with spinal dysfunction were examined by electron microscopy. Results: Two types of inclusion bodies were noted, but only in motor neurons of the ventral spinal cord and brain stem. These were large globoid eosinophilic bodies up to 5 µm in diameter, and yellow/brown granular inclusions mostly at the pole of the cell. The globoid bodies stained with Luxol fast blue but not with periodic acid Schiff (PAS), or Sudan black. The granular inclusions stained with Luxol fast blue, PAS and Sudan black. Both bodies were slightly autofluorescent. On electron microscopy the globoid bodies had an even electron-dense texture and were bound by a membrane. Beneath the membrane were large numbers of small intraluminal vesicles. The smaller granular bodies were more heterogeneous, irregularly rounded and membrane-bound accumulations of granular electron-dense material, often with electron-lucent vacuoles. Others were more vesicular but contained varying amounts of electron-dense material. The large globoid bodies did not immunostain for lysosomal markers lysosomal associated protein 1 (LAMP1) or cathepsin D so they were not lysosomal. The small granular bodies stained for cathepsin D by a chromogenic method. A kindred matrix analysis showed two cases to be as closely related as first cousins, and another case was almost as closely related to one of them, but the fourth bird was unrelated to any other. Conclusions: It was concluded that this was an endoplasmic reticulum storage disease due to a specific protein misfolding within endoplasmic reticulum. It was rationalised that the two types of inclusions reflected the same aetiology, but that misfolded protein in the smaller granular bodies had entered the lysosomal system via endoplasmic reticulum autophagy. Although the cause was unclear, it most likely had a genetic aetiology or predisposition and, as such, has clinical relevance.

Abstract Number ‐ 226: Pontine Stroke Presenting as 1.5 Syndrome Evolving to 9 Syndrome over 72 Hours.

Introduction A 75 year old woman with a past medical history of hypertension developed sudden‐onset vertigo, nausea and vomiting. She did not immediately seek medical care, thinking she was suffering from food poisoning. The following day her symptoms improved however she developed new right sided weakness and gait imbalance, prompting her presentation to the ED. Her neurologic exam noted complete loss of adduction of the right eye and loss of horizontal extraocular movements of the left eye. She also displayed right upper extremity paresis, right upper extremity dysmetria and mild dysarthria. MRI of the brain disclosed acute pontine infarcts in the ventral and dorsal left paramedian regions. Over the next three days, her horizontal gaze palsy improved with some return of adduction of the right eye and horizontal movements of the left eye. However right sided paresis worsened, and in addition, progressed to include complete left facial palsy (lower motor neuron lesion). She was able to be discharged to rehab, placed on Aspirin 81 mg daily and Ezetimibe (due to elevated liver function enzymes) and 30 day Cardiac Event Monitor follow up. Methods Case report and review of literature. Results Due to the combination of multiple cranial nuclei and white matter tracts in the brainstem, ischemia can lead to several clinical manifestations. There are various presenting clinical syndromes, named numerically by structures involved and/or the clinical deficit. One‐and‐a‐half (1.5) syndrome, first reported by Fischer in 1967, is an uncommon entity caused by a lesion (most commonly infarction) in the pontine tegmentum [1]. It consists of complete ipsilateral horizontal gaze palsy (due to involvement of ipsilateral Paramedian Pontine Reticular Formation/Abducens Nucleus and Medial Longitudinal Fasciculus) and loss of adduction of the contralateral eye (due to involvement of the contralateral Medial Longitudinal Fasciculus). Extension of the lesion to the facial nucleus can produce ipsilateral lower motor neuron type facial palsy, leading to an even more uncommon 8.5 syndrome (7 + 1.5), described by Eggenberger in 1998 [2]. When the lesion involves the corticospinal tracts and/or the medial lemniscus, it can lead to contralateral hemiparesis and/or hemisensory deficits; the so called “9 syndrome” first proposed by Rosini et al in 2013 [3]. This rare entity has been reported in only a handful of cases. Conclusions The awareness of complex brainstem neuroanatomy enables precise localization of the clinical deficits. The noted slow progression of the clinical syndrome from 1.5 to 8.5 and finally 9 syndrome over 72 hours in this case highlights the complexity of small vessel brainstem ischemia.

Sporadic Spinal-Onset Amyotrophic Lateral Sclerosis Associated with Myopathy in Three Unrelated Portuguese Patients

Amyotrophic lateral sclerosis (ALS) and myopathy have been already described as part of a common genetic syndrome called multisystem proteinopathy. They may occur together or not, and can be associated with other clinical features such as frontotemporal dementia and Paget's bone disease. In addition, primary skeletal muscle involvement has been also reported in inherited forms of lower motor neuron disease, in spinal-bulbar muscular atrophy and in spinal muscular atrophy. We aim to characterize three sporadic, spinal-onset ALS patients, one with a concurrent non-specific myopathy, and two with a previous diagnosis of myopathy before upper and lower motor neuron signs emerged. Perhaps our sporadic ALS cases associated with myopathy share a common, but still unknown, pathogenic background. These cases raise the paradigm of a possible interplay between skeletal muscle degeneration and motor neuron damage.

Вопросы ранней диагностики и своевременной коррекции дыхательных нарушений при боковом амиотрофическом склерозе (обзор литературы)

Amyotrophic lateral sclerosis (ALS) is a rare severe progressive neurodegenerative disease with upper and lower motor neuron lesions, manifested by weakness of somatic muscle tissue with disorder of vital functions and leading to early disability and fatal outcome of patients. Regardless of the disease form, patients with ALS experience breathing and swallowing disorders. Hypercapnic respiratory failure (HRF) most commonly develop in patients as a consequence of respiratory muscle weakness. Instrumental diagnostic methods are currently used along with the assessment of the HRF clinical picture in ALS. Pulse oximetry and spirometry are the basic means of assessing the respiratory system function. Cardio-respiratory monitoring and arterial blood gas test play an auxiliary role in the diagnosis. To correct respiratory disorders, respiratory support is used with the help of artificial ventilation devices connected through various masks (non-invasive) or through a tracheostomy (invasive). In recent years, it has been proven that early diagnosis and correction of respiratory disorders contribute to prolonging the life of patients with ALS and improving its quality. The review presents the main development mechanisms of respiratory disorders in ALS, clinical and instrumental methods of their diagnosis, methods of correction, as well as criteria for the start of respiratory support. KEYWORDS: amyotrophic lateral sclerosis, respiratory disorders, lung ventilation, pulmonary support, neurodegeneration, NIV, ALV. FOR CITATION: Ermilov E.A., Isaeva N.V. Issues concerning early diagnosis and timely correction of respiratory disorders in amyotrophic lateral sclerosis (literature review). Russian Medical Inquiry. 2023;7(8). (in Russ.). DOI: 10.32364/2587-6821-2023-7-8-4.

Chapter 2 - Upper and lower motor neuron neurophysiology and motor control

This chapter considers the principles that underlie neurophysiological studies of upper motor neuron or lower motor neuron lesions, based on an understanding of the normal structure and function of the motor system. Human motor neurophysiology consists of an evaluation of the active components of the motor system that are relevant to volitional movements. Relatively primitive motor skills include locomotion, much dependent on the spinal cord central pattern generator, reaching, involving proximal and distal muscles activation, and grasping. Humans are well prepared to perform complex movements like writing. The role of motor cortex is critical for the motor activity, very dependent on the continuous sensory feedback, and this is essential for adapting the force and speed control, which contributes to motor learning. Most corticospinal neurons in the brain project to brainstem and spinal cord, many with polysynaptic inhibitory rather than excitatory connections. The monosynaptic connections observed in humans and primates constitute a specialized pathway implicated in fractional finger movements. Spinal cord has a complex physiology, and local reflexes and sensory feedback are essential to control adapted muscular contraction during movement. The cerebellum has a major role in motor coordination, but also consistent roles in sensory activities, speech, and language, in motor and spatial memory, and in psychological activity. The motor unit is the final effector of the motor drive. The complex interplay between the lower motor neuron, its axon, motor end-plates, and muscle fibers allows a relevant plasticity in the movement output.

Ulnar fascicle to brachialis branch of musculocutaneous nerve for restoration of elbow flexion associated with spinal cord tumor and radiation-induced lower motor neuron disease

Transfer of the ulnar fascicle to the biceps branch of the musculocutaneous nerve, or Oberlin transfer, has been widely used for the treatment of elbow flexion weakness in the setting of upper trunk brachial plexus palsy. The authors present a modified application of this technique for restoration of functional elbow flexion in a 30-year-old woman with a history of recurrent upper cervical spinal cord pilocytic astrocytoma, complex spinal deformity, and radiation-induced lower motor neuron disease. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID2299.