Lower Motor Neuron Syndrome Research Articles

Neuromuscular ultrasound in combination with nerve conduction studies helps identify inflammatory motor neuropathies from lower motor neuron syndromes.

Identifying patients with inflammatory motor neuropathies (IMNs) is warranted since effective treatments are available and the prognosis of these patients differs from that of amyotrophic lateral sclerosis patients. Between January 2019 and May 2022, 102 consecutive treatment-naïve lower motor neuron syndrome (LMNS) patients were recruited; these patients were suspected of having multifocal motor neuropathy, pure motor chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis with initial lower motor neuron presentation. Neuromuscular ultrasound (US) and nerve conduction studies (NCSs) were conducted at baseline. Relevant diagnostic investigations were performed if clinically warranted. The proposed US evidence of IMN was as follows: (i) nerve enlargement at ≥1 of the predetermined sites or (ii) absence of high intensity fasciculations in predefined muscle groups. Final diagnoses were made by experienced physicians after a prolonged follow-up period (≥12 months). IMN patients were defined as LMNS patients who experienced convincing improvements in response to immunotherapies. IMN patients without electrodiagnostic demyelinating features were diagnosed with treatment-responsive LMNS (TR-LMNS). In total, 16 patients were classified as IMN, including nine chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy patients and seven TR-LMNS patients. Six TR-LMNS patients were identified by neuromuscular US. The sensitivity and specificity of NCSs, nerve US and muscle US were 56.3% and 100%, 43.8% and 90.7% and 68.8% and 97.7%, respectively. When these three modalities were combined, the sensitivity and specificity were 93.8% and 88.4%, respectively. Neuromuscular US studies are supplementary modalities to NCSs, and the combined use of these techniques might improve the identification of IMNs in LMNS patients.

Reversible sub-acute motor neuron syndrome after mushroom intoxication masquerading as amyotrophic lateral sclerosis

A 56-year-old man presented with rapidly evolving/sub-acute upper and lower motor neuron syndrome in 2015 with significant weakness in the four limbs and the bulbar region. Amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-r) was rated 34/48. On electromyography, there was a diffuse and active denervation in the four limbs and the tongue. A diagnosis of definite ALS according to international criteria was made. Six months later the patient stopped worsening. In the following years he progressively recovered. ALSFRS-r score improved to reach 48/48 in 2021. His neurological examination is normal and electromyography shows no denervation. Inquiry revealed that he presented a few months and, again a few days before onset, a mushroom poisoning. He was used to eating false morels either crude or undercooked and developed muscles cramps, nausea and vertigo. The relationships between this reversible sub-acute motor neuron syndrome and mushroom intoxication are discussed in the light of the recently described cluster in the Alps with a high incidence of ALS cases. Epidemiological investigations showed that all patients, but not their spouses, used to eat crude or undercooked false morels. Such a mushroom contains hydrazines, a known neurotoxic agent. We are not aware of another case of ALS reversal in that cluster area. We propose that a potential mushroom poisoning be thoroughly searched for when facing with a patient with sub-acute or rapidly worsening ALS syndrome.

Recovery after traumatic thoracic- and lumbar spinal cord injury: the neurological level of injury matters.

Multicenter prospective cohort. To discern neurological- and functional recovery in patients with a traumatic thoracic spinal cord injury (TSCI), conus medullaris syndrome (CMS), and cauda equina syndrome (CES). Specialized spinal cord injury centers in Europe. Lower extremity motor score (LEMS) and spinal cord independent measure (SCIM) scores from patients with traumatic TSCI, CMS, and CES were extracted from the EMSCI database. Scores from admittance and during rehabilitation at 1, 3, 6, and 12 months were compared. Linear mixed models were used to statistically analyse differences in outcome, which were corrected for the ASIA Impairment Scale (AIS) in the acute phase. Data from 1573 individuals were analysed. Except for the LEMS in patients with a CES AIS A, LEMS, and SCIM significantly improved over time for patients with a TSCI, CMS, and CES. Irrespectively of the AIS score, recovery in 12 months after trauma as measured by the LEMS showed a statistically significant difference between patients with a TSCI, CMS, and CES. Analysis of SCIM score showed no difference between patients with TSCI, CMS, or CES. Difference in recovery between patients with a traumatic paraplegia is based on neurological (motor) recovery. Regardless the ceiling effect in CES patients, patients with a mixed upper and lower motor neuron syndrome (CMS) showed a better recovery compared with patients with a upper motor neuron syndrome (TSCI). These findings enable stratifications of patients with paraplegia according to the level and severity of SCI.

Rate of Information Flow Across Layered Neuro-Spike Network in the Spinal Cord.

Spinal Cord Injury (SCI) is a severe condition that can result in loss of motor and sensory functions by disrupting communication among neurons, i.e., neuro-spike communication. Future information and communication technology (ICT) based treatment techniques for SCI are expected to rely on nano networks, deployed inside the body. In this respect, modeling neuro-spike communication channels in the spinal cord and revealing the relationship between channel metrics and SCI are required to realize these treatment techniques and diagnosis tools such as replacement neural implants, high-performance diagnosis tools, which are based on ICT metrics instead of large medical data. Therefore, in this study, we focus on a spinal cord network, namely the descending spinal cord pathway, which is responsible for the transmission of brain motor signals to the spinal cord. We aim to analyze the rate of motor information flow to the corresponding muscle. To this end, we model the spinal cord motor network as a layered network consisting of a cascade of two independent neuro-spike channels, which are brain-spinal cord network and spinal cord interneuron-spinal cord motoneuron network. We derive upper and lower bounds for the total rate across the brain-spinal cord network and interneuron-spinal cord network. Our evaluations demonstrate that the total rate in the case of upper motor neuron syndrome (UMNS), which manifests itself with muscle weakness, approaches zero, where the brain-spinal cord network becomes a bottleneck. In lower motor neuron syndrome (LMNS), which results in muscle atrophy, the total rate again approaches zero with the loss of spinal cord motoneurons (MN).

Methods of Detecting Lesions of Upper Motor Neuron in Amyotrophic Lateral Sclerosis using Transcranial Magnetic Stimulation

Introduction: Coexistent involvement of upper and lower motor neurons is a characteristic feature of amyotrophyc lateral syndrome (ALS) necessary for the diagnosis. Diagnosis of upper motor neuron involvement in ALS is based solely on clinical features, which may not be detected at the disease onset and in rare forms manifesting clinically as the pure lower motor neuron syndrome (LMNS). The main method of assessment of the functional state of the upper motor neuron in ALS is transcranial magnetic stimulation (TMS). It allows assessing the excitability of motor cortex, corticospinal tract function, and mapping of cortical representation of the muscles. In patients with ALS changes of various indicators demonstrating hyperexcitability as well as degenerative lesions of the motor cortex and the corticospinal tracts are recorded on TMS. Objective: to discuss changes in the TMS in patients with ALS, pathophysiological mechanisms of their formation and possible diagnostic value. Results: In 22 patients with LMNS, navigated TMS revealed disturbances of intracortical inhibition on paired stimulation and recording cortical silent period, increase of motor threshold in dominant hemisphere, decrease of the weighted area and reorganization of cortical representations of the hand muscles. Conclusion: The data obtained allow to consider navigated TMS as a promising technology for identifying upper motor neuron involvement in patients with ALS.

Chronic inflammatory demyelinating polyneuropathy with tongue fasciculation: A case report

Chronic inflammatory demyelinating polyneuropathy is one of the immune-mediated polyneuropathies responsive to immunotherapy. Its usual clinical presentation is a chronic course of symmetric sensorimotor affectation of both proximal and distal extremities with signs of demyelination on electrophysiologic studies. Cranial nerve signs in this condition is not commonly encountered, particularly involvement of the hypoglossal nerve. To date, there are only three published cases of hypoglossal involvement in this condition. This case report presents a patient with tongue fasciculation, which is an uncommon finding in chronic inflammatory demyelinating polyneuropathy. This paper highlights the importance of considering chronic inflammatory demyelinating polyneuropathy in the differential diagnoses of a patient with tongue fasciculation as it has been found to be responsive to immunotherapy in comparison to other lower motor neuron syndromes.

A mutation in the filamin c gene causes myofibrillar myopathy with lower motor neuron syndrome: a case report

BackgroundMyofibrillar myopathies (MFMs) are a genetically heterogeneous group of muscle disorders. Mutations in the filamin C gene (FLNC) have previously been identified in patients with MFM. The phenotypes of FLNC-related MFM are heterogeneous.Case presentationThe patient was a 37-year-old male who first experienced weakness in the distal muscles of his hand, which eventually spread to the lower limbs and proximal muscles. Serum creatine kinase levels were moderately elevated. Obvious neuropathic changes in the electromyographic exam and edema changes in lower distal limb magnetic resonance imaging were observed. Histopathological examination revealed the presence of abnormal protein aggregates and angular atrophy in some muscle fibers. Ultrastructural analysis showed inordinate myofibrillar structures and dissolved myofilaments. DNA sequencing analysis detected a heterozygous missense mutation (c.7123G > A, p.V2375I) in the immunoglobulin (Ig)-like domain 21 of FLNC.ConclusionsFLNC mutation c.7123G > A, p.V2375I in the immunoglobulin (Ig)-like domain 21 can be associated with distal myopathy with typical MFM features and lower motor neuron syndrome. Although electromyographic examination of our patient showed obvious neuropathic changes, MFM could not be excluded. Therefore, genetic testing is necessary to make an accurate diagnosis.

Voxel-based morphometry in amyotrophic lateral sclerosis

Objective:to investigate changes in grey matter volume in patients with classical amyotrophic lateral sclerosis (ALS) and lower motor neuron syndrome (LMNS) with voxel-based morphometry (VBM).Material and methods. 30 patients with classical ALS, 22 patients with LMNS and 23 age and gender matched healthy controls were enrolled in this study. All participants underwent a T1MPR (multiplanar reconstruction) magnetic resonance imaging with post-processing included spatial normalization, segmentation and smoothing. VBM was used to investigate changes in grey matter volume across the groups.Results. There was a significant decrease in grey matter volume of middle part of left pre- and postcentral gyri, middle part of right precentral gyrus, right and left occipital lobes in patients with classical ALS compared to healthy subjects. There was no difference in grey matter volume between patients with LMNS and healthy controls. Patients with classical ALS showed a significant decrease in grey matter volume of middle part of left preand postcentral gyri, upper part of left precentral gyrus, middle and upper parts of right precentral gyrus, right and left occipital lobes compared to patients with LMNS. There was no significant correlation between grey matter volume and clinical findings in patients with ALS and LMNS.Conclusion.VBM reveals a decrease in grey matter volume of motor and nonmotor brain regions in patients with classical ALS, but not in patients with LMNS.

Current Best Peripheral Nerve Transfers for Spinal Cord Injury.

After reviewing this article, the participant should be able to: 1. Understand the anatomy and pathophysiology of spinal cord injury and the resulting upper and lower motor neuron syndromes. 2. Recognize who may benefit from nerve transfers. 3. Understand the role of history, examination, imaging, and electrodiagnostics in the determination of time-sensitive lower motor neuron injury versus non-time-sensitive upper motor neuron injury. 4. Outline the surgical options and perioperative care for those undergoing nerve transfer and the expected outcomes in restoring shoulder, elbow, wrist, and hand function. This article outlines how to localize and differentiate upper motor neuron from combined upper and lower motor neuron injury patterns in spinal cord injury by means of detailed history, physical examination, imaging, and electrodiagnostic studies to formulate appropriate surgical plans to restore function in this complex population.

Motor neuron disease of paraneoplastic origin: a rare but treatable condition

Paraneoplastic motor neuron disorders (MND) are rare conditions; their exact clinical and electrophysiological phenotype have not been exhaustively described yet. The purpose of this study is to depict the main characteristics of paraneoplastic MND to highlight the features that may allow its diagnosis. Based on the description of eight original cases, and on the revision of 21 patients identified from a systematic review of the literature, the main features of paraneoplastic MND can be summarized as follows: (1) subacute; (2) lower motor neuron syndrome, associated or not with upper motor neuron involvement; (3) predominant asymmetric upper limb involvement; (4) presence of other non-motor neurological manifestations, including sensory neuronopathy; (5) signs of inflammation in the cerebrospinal fluid (CSF); (6) neurological improvement or stabilization after immunotherapy and tumor treatment. The diagnosis of paraneoplastic MND may be difficult because of its rarity, the absence of pathognomonic clinical features, and the frequent absence of prior tumor history. However, it is of capital importance to correctly identify patients with paraneoplastic MND, as this represents a potentially treatable condition. In the presence of subacute lower motor neuron impairment, especially when atypical clinical features for degenerative MND or other non-motor neurological manifestations are present, we recommend testing for onconeural antibodies. In the case, the search for onconeural antibodies is negative, but it exists a strong clinical suspicion for a paraneoplastic etiology; CSF analysis and total-body 18FDG-PET/CT imaging should be performed to circumstantiate diagnosis.

Prediction of sexual function following spinal cord injury: a case series.

Spinal Cord Injury (SCI) affects sexual response based on the level and degree of completeness of injury. By using the International Standards for the Neurologic Classification of SCI in conjunction with lumbo-sacral reflexes these effects can be predicted. The International Standards for the Assessment of Autonomic Function after SCI (ISAFSCI) document the impact of SCI on sexual responses including psychogenic and reflex arousal (erection or lubrication), orgasm, ejaculation, and sensation of menses. Responses are described based upon a 0 to 2 scale with 0 being absent, 1 altered, and 2 normal response. Additionally, the lesion is described as supraconal, conal or infraconal. We present 4 representative cases of the impact of SCI on sexual responses and course of treatment. Case 1 describes a complete supraconal lesion above T6 with upper motor neuron syndrome. Case 2 describes a supraconal complete lesion including the T11-L2 segment. Case 3 describes an infraconal (cauda equina) lesion with lower motor neuron syndrome. Case 4 is theoretical and describes a supraconal lesion above T6 with upper motor neuron syndrome, partial sensation in T11-L2 dermatomes, and other medical comorbidities. Neurologic examination combined with reflex testing allows prediction of sexual responses after SCI. It would be useful for version 2.0 of the ISAFSCI to assist clinicians in determining the anticipated changes, whether their patients are functioning as anticipated sexually after SCI or whether other concerns also require treatment.

Paraneoplastic subacute lower motor neuron syndrome associated with solid cancer

We retrospectively analyzed three patients with pure motor neuronopathy followed for more than four years in our center. The patients presented a rapidly progressive lower motor neuron syndrome (LMNS) over the course of a few weeks leading to a severe functional impairment. The neurological symptoms preceded the diagnosis of a breast adenocarcinoma and a thymoma in the first two patients, one of them with anti-CV2/CRMP5 antibodies. Cancer was not detected in the third patient who had circulating anti-Hu antibodies. A final diagnosis of paraneoplastic syndrome was made after investigations for alternative causes of lower motor neuron syndrome. Early diagnosis, combined treatment of the underlying cancer, and immunomodulatory treatment led to neurological improvement of the disease in two out of the three cases in which the cancer was diagnosed. Cases of subacute LMNS with rapid progression may occur as an expression of a paraneoplastic neurological syndrome. Identification of these syndromes is important, as the treatment of underlying malignancy along with immunomodulatory treatment may result in a favorable long-term outcome of these potentially fatal diseases.

A Rarely Seen Late Complication, Radiation-Induced Lower Motor Neuron Syndrome

There is a dramatic increase in the number of cancer patients nowadays. Improvement of treatment results in the field of radiotherapy provided an increase in life expectancy of cancer patients, but on the other hand, a lot of late complications, including the nervous system, have started to be encountered. In this case report, a patient with rarely seen radiationinduced lower motor neuron syndrome (LMNS) will be discussed.

Revisiting the spectrum of lower motor neuron diseases with snake eyes appearance on magnetic resonance imaging.

The 'snake eyes' sign refers to bilateral hyperintensities of the anterior horns on axial spinal cord imaging. Based on sporadic reports, it has been associated with a range of lower motor neuron (LMN) syndromes, such as spondylotic amyotrophy and Hirayama disease, as well as spinal cord infarction. The objective of our study was to comprehensively characterize the full diagnostic spectrum of LMN syndromes with this radiological clue and discuss potential aetiological factors. A large patient cohort with snake eyes sign and upper limb LMN degeneration was recruited from three French neuromuscular units. Patients underwent detailed electrophysiological, radiological, clinical and anamnestic profiling. Twenty-nine patients were ascertained and followed up for 9.5 ± 8.6 years. The majority of the patients were male (86.2%) with a mean age of 37.3 ± 14.4 years. Symptoms were bilateral in most cases (86.2%). Patients with predominantly proximal and distal deficits were equally represented (44.8% and 55.2%, respectively). A history of preceding trauma or intense physical activity was confirmed in 58.6% of the cases; 27.6% of the patients were given an initial clinical diagnosis of amyotrophic lateral sclerosis (ALS), and 51.7% were originally suspected to have multifocal motor neuropathy. None of the patients developed ALS on longitudinal follow-up. The snake eyes sign on magnetic resonance imaging is associated with a wide spectrum of neurological conditions and is more common in young men with a history of strenuous activity or antecedent trauma. The recognition of this syndrome is crucial as many of these patients are initially misdiagnosed with ALS.

Lower motor neuron syndrome associated with IgG anti-GM1 antibodies revisited

A patient, who developed an amyotrophic lateral sclerosis-like disorder subsequent to ganglioside treatment, had IgM antibodies to GM2 as well as to minor gangliosides X1 and X2 containing GM2 epitope. These gangliosides as well as GM1 were tested in 655 sera obtained from patients who were suspected of having amyotrophic lateral sclerosis or motor neuron disease to find a treatable condition. Three patients had high titers of IgG anti-GM1 antibodies, but no IgM anti-GM1 antibodies. One of the patients also had IgG anti-X2 antibodies. The patients, being diagnosed with having lower motor neuron syndrome, had neither upper motor neuron signs nor multifocal conduction block. Both IgM and IgG anti-GM1 antibodies should be tested in patients who have lower motor neuron syndrome.

Minor cognitive disturbances in X-linked spinal and bulbar muscular atrophy, Kennedy's disease

Spinal and bulbar muscular atrophy (SBMA), Kennedy's disease, is an adult-onset hereditary neurodegenerative disorder, associated predominantly with a lower motor neuron syndrome and eventually endocrine and sensory disturbances. In contrast to other motor neuron diseases such as amyotrophic lateral sclerosis (ALS), the impairment of cognition in SBMA is not well documented. We conducted a systematic cross-sectional neuropsychological study in order to investigate cognition in SBMA patients more thoroughly. We investigated 20 genetically proven SBMA patients compared to 20 age- and education-matched control subjects using a comprehensive neuropsychological test battery, measuring executive functioning, attention, memory and visuospatial abilities. The SBMA patients performed significantly worse than healthy controls in three sub-tests in the executive and attention domains. This low performance was in the working memory (digit span backward task), verbal fluency category (single letter fluency task) and memory storage capacity (digit span forward task). No disturbances were detected in other cognitive domains. The impairments were subclinical and not relevant to the patients’ everyday functioning. In addition, no correlations were found between cognitive scores and the CAG repeat length. In conclusion, we found minor cognitive disturbances in patients with SBMA, which could indicate subtle frontal lobe dysfunction. These findings extend our neurobiological understanding of SBMA.

D90A-SOD1 ALS mimicking monoclonal gammopathy-associated ALS

Several studies have suggested a pathogenetic association between monoclonal gammopathy of undetermined significance (MGUS) and motor neuron diseases, including not only lower motor neuron syndrome...

A Patient with Intravenous Immunoglobulin-Responsive Lower Motor Neuron Syndrome

We report a 50-year-old woman who developed localized proximal muscle weakness, in addition to transient elevation of antibodies to GM-1 ganglioside, without multifocal conduction block. She was treated with intravenous immunoglobulin (IVIg) and steroid pulse therapy, which were effective for over 10 years. Her clinical course and laboratory tests were consistent with lower motor neuron syndrome (LMNS) with localized proximal muscle weakness. We suggest that some patients diagnosed as LMNS may remain responsive to IVIg or steroid pulse therapy for a long time.

Chronic motor axonal neuropathy

The identification of a distinct subgroup of patients within the spectrum of lower motor neuron syndromes (LMNS) is crucial as some are potentially treatable. We describe the clinical and neuropathological characteristics of a patient presenting with a rapidly progressive LMNS associated with high titers of anti-GM1 antibodies, leading to respiratory failure within 10 months. Histopathological study of a biopsy of a obturator nerve motor branch demonstrated a predominantly axonal motor neuropathy, while electron microscopy analysis localized macrophages located within the periaxonal space. Immunohistochemistry demonstrated deposits of complement activation products (C3i) and immunoglobulins (IgM) on nerve fibers. The patient's clinical, immunological and pathological findings are consistent with a diagnosis of a chronic motor axonal neuropathy (CMAN), likely of immune-mediated origin.

Predicting a positive response to intravenous immunoglobulin in isolated lower motor neuron syndromes.

ObjectiveTo determine clinically related characteristics in patients with pure lower motor neuron (LMN) syndromes, not fulfilling accepted diagnostic criteria, who were likely to respond to intravenous immunoglobulin (IVIg) treatment.MethodsDemographic, clinical, laboratory and neurophysiological characteristics were prospectively collected from patients with undifferentiated isolated LMN syndromes who were then treated with IVIg. Patients were classified as either responders or non-responders to therapy with IVIg based on clinical data and the two groups were compared.ResultsFrom a total cohort of 42 patients (30 males, 12 females, aged 18-83 years), 31 patients responded to IVIg and 11 did not. Compared to patients that developed progressive neurological decline, responders were typically younger (45.8 compared to 56.0 years, P<0.05) and had upper limb (83.9% compared to 63.6%, NS), unilateral (80.6% compared to 45.5%, P<0.05), and isolated distal (54.1% compared to 9.1%, P<0.05) weakness. Patients with predominantly upper limb, asymmetrical, and distal weakness were more likely to respond to IVIg therapy. Of the patients who responded to treatment, only 12.9% had detectable GM1 antibodies and conduction block (not fulfilling diagnostic criteria) was only identified in 22.6%.ConclusionsMore than 70% of patients with pure LMN syndromes from the present series responded to treatment with IVIg therapy, despite a low prevalence of detectable GM1 antibodies and conduction block. Patients with isolated LMN presentations, not fulfilling accepted diagnostic criteria, may respond to IVIg therapy, irrespective of the presence of conduction block or GM1 antibodies, and should be given an empirical trial of IVIg to determine treatment responsiveness.