Motor Neuron Firing Dysfunction in Spastic Patients With Primary Lateral Sclerosis

Patients with corticospinal tract dysfunction have slow voluntary movements with brisk stretch reflexes and spasticity. Previous studies reported reduced firing rates of motor units during voluntary contraction. To assess whether this firing behavior occurs because motor neurons do not respond normally to excitatory inputs, we studied motor units in patients with primary lateral sclerosis, a degenerative syndrome of progressive spasticity. Firing rates were measured from motor units in the wrist extensor muscles at varying levels of voluntary contraction ≤10% maximal force. At each force level, the firing rate was measured with and without added muscle vibration, a maneuver that repetitively activates muscle spindles. In motor units from age-matched control subjects, the firing rate increased with successively stronger contractions as well as with the addition of vibration at each force level. In patients with primary lateral sclerosis, motor-unit firing rates remained stable, or in some cases declined, with progressively stronger contractions or with muscle vibration. We conclude that excitatory inputs produce a blunted response in motor neurons in patients with primary lateral sclerosis compared with age-matched controls. The potential explanations include abnormal activation of voltage-activated channels that produce stable membrane plateaus at low voltages, abnormal recruitment of the motor pool, or tonic inhibition of motor neurons.

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SMN1 Duplications Are Associated With Progressive Muscular Atrophy, but Not With Multifocal Motor Neuropathy and Primary Lateral Sclerosis

Neurology Genetics ◽

10.1212/nxg.0000000000000598 ◽

2021 ◽

Vol 7 (4) ◽

pp. e598

Author(s):

Jeroen W. Bos ◽

Ewout J.N. Groen ◽

Renske I. Wadman ◽

Chantall A.D. Curial ◽

Naomi N. Molleman ◽

...

Keyword(s):

Motor Neurons ◽

Muscular Atrophy ◽

Multifocal Motor Neuropathy ◽

Survival Motor Neuron ◽

Motor Neuropathy ◽

Disease Course ◽

Primary Lateral Sclerosis ◽

Primary Lateral ◽

Lateral Sclerosis ◽

Progressive Muscular Atrophy

ObjectiveTo assess the association between copy number (CN) variation in the survival motor neuron (SMN) locus and multifocal motor neuropathy (MMN), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS) susceptibility and to determine the association of SMN1 and SMN2 CN with MMN, PMA, and PLS disease course.MethodsIn this monocenter study, we used multiplex ligation-dependent probe amplification to determine SMN1 and SMN2 CN in Dutch patients with MMN, PMA, and PLS and controls. We stratified clinical parameters for SMN1 and SMN2 CN. We analyzed SMN1 and SMN2 exons 1–6, intron 6, and exon 8 CN to study the genetic architecture of SMN1 duplications.ResultsSMN1 and SMN2 CN were determined in 132 patients with MMN, 150 patients with PMA, 104 patients with PLS, and 956 control subjects. MMN and PLS were not associated with CN variation in SMN1 or SMN2. By contrast, patients with PMA more often than controls carried SMN1 duplications (≥3 SMN1 copies, 12.0% vs 5.0%, odds ratio 2.69 (1.43–4.91), p 0.0020). SMN1 and SMN2 CN status was not associated with MMN, PLS, or PMA disease course. In case of SMN1 exon 7 duplications, exons 1–6, exon 8, and introns 6 and 7 were also duplicated, suggesting full SMN1 duplications.ConclusionsSMN1 duplications are associated with PMA, but not with PLS and MMN. SMN1 duplications in PMA are balanced duplications. The results of this study highlight the primary effect of altered SMN CN on lower motor neurons.

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Hyperreflexia

10.1093/med/9780190661304.003.0018 ◽

2018 ◽

Author(s):

Aziz Shaibani

Keyword(s):

Motor Neurons ◽

Neuromuscular Disease ◽

Deep Tendon Reflex ◽

Primary Lateral Sclerosis ◽

Spastic Paraplegia ◽

Cortical Motor ◽

Tendon Reflex ◽

Primary Lateral ◽

Lateral Sclerosis ◽

Tendon Reflexes

Hyperactive deep tendon reflexes (DTRs) is a sign of upper motor neuron (UMN) lesions. It is also commonly seen in normal but anxious people. The proper technique of deep tendon reflex examination and experience play a major role in eliciting and categorizing DTRs. Sustained clonus is the highest degree of hyperreflexia. The most important neuromuscular disease associated with hyperreflexia is amyotrophic lateral sclerosis (ALS) due to degeneration of the cortical motor neurons. Diagnostic difficulty occurs when hyperreflexia and spasticity are the only findings. In these cases, primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and other causes of myelopathies should be entertained. Compressive myelopathies are easily excludable by neuroimaging.

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Distinguishing intrinsic from extrinsic factors underlying firing rate saturation in human motor units

Journal of Neurophysiology ◽

10.1152/jn.00777.2014 ◽

2015 ◽

Vol 113 (5) ◽

pp. 1310-1322 ◽

Cited By ~ 20

Author(s):

Andrew J. Fuglevand ◽

Rosemary A. Lester ◽

Richard K. Johns

Keyword(s):

Firing Rate ◽

Biceps Brachii ◽

Motor Units ◽

Voluntary Contraction ◽

Tendon Vibration ◽

Cellular Mechanisms ◽

Extrinsic Factors ◽

Additional Increase ◽

Firing Rates ◽

Synaptic Excitation

During voluntary contraction, firing rates of individual motor units (MUs) increase modestly over a narrow force range beyond which little additional increase in firing rate is seen. Such saturation of MU discharge may be a consequence of extrinsic factors that limit net synaptic excitation acting on motor neurons (MNs) or may be due to intrinsic properties of the MNs. Two sets of experiments involving recording of human biceps brachii MUs were carried out to evaluate saturation. In the first set, the extent of saturation was quantified for 136 low-threshold MUs during isometric ramp contractions. Firing rate-force data were best fit by a saturating function for 90% of MUs recorded with a maximum rate of 14.8 ± 2.0 impulses/s. In the second set of experiments, to distinguish extrinsic from intrinsic factors underlying saturation, we artificially augmented descending excitatory drive to biceps MNs by activation of muscle spindle afferents through tendon vibration. We examined the change in firing rate caused by tendon vibration in 96 MUs that were voluntarily activated at rates below and at saturation. Vibration had little effect on the discharge of MUs that were firing at saturation frequencies but strongly increased firing rates of the same units when active at lower frequencies. These results indicate that saturation is likely caused by intrinsic mechanisms that prevent further increases in firing rate in the presence of increasing synaptic excitation. Possible intrinsic cellular mechanisms that limit firing rates of motor units during voluntary effort are discussed.

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Rehabilitation in primary lateral sclerosis mimicking parkinsonism: A case report

Neurorehabilitation ◽

10.3233/nre-201527 ◽

2020 ◽

Vol 47 (4) ◽

pp. 381-386

Author(s):

Lucrezia Moggio ◽

Annalisa Petraroli ◽

Nicola Marotta ◽

Andrea Demeco ◽

Ilaria Pino ◽

...

Keyword(s):

Motor Neurons ◽

Balance Control ◽

Combined Treatment ◽

Gait Training ◽

Fine Motor ◽

Primary Lateral Sclerosis ◽

Rehabilitative Treatment ◽

Postural Changes ◽

Primary Lateral ◽

Lateral Sclerosis

BACKGROUND: Primary lateral sclerosis (PLS) is an upper motor neurons disease that on rare occasions may determine bradykinesia and motor fatigue. To date, no rehabilitative treatment has been described as useful for these patients. CASE PRESENTATION: A 68-year-old male developed dysarthria, spastic laugh, impairments of handwriting and fine motor, gait and dysphagia disorders for both solids and liquids over the period from 2015 to December 2018, with normal DaT scans and no clinical benefits from therapy with levodopa, pramipexole and baclofen. The patient underwent exercises for gait training and balance control with sensory treadmill and stabilometric platform and kinesiotherapy to improve fine motor skills of both hands and postural changes, five days a week for two weeks. Based on our data, the patient showed an improvement in balance and gait parameters in T2 compared to T1. CONCLUSION: Thanks to the synergistic action of a combined treatment of physical and instrumental therapy, despite the rare pathology and complex disability, the patient had important benefits in terms of performance and independence in daily activity.

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Slowly progressive dysarthria (pseudobulbar palsy) in primary lateral sclerosis

Klinische Neurophysiologie ◽

10.1055/s-0030-1250885 ◽

2010 ◽

Vol 41 (01) ◽

Author(s):

P Urban ◽

I Wellach ◽

C Pohlmann

Keyword(s):

Pseudobulbar Palsy ◽

Primary Lateral Sclerosis ◽

Primary Lateral ◽

Lateral Sclerosis

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Mills' syndrome. A clinical case of a rare degenerative pathology of the central nervous system

Spravočnik vrača obŝej praktiki (Journal of Family Medicine) ◽

10.33920/med-10-2004-07 ◽

2020 ◽

pp. 57-60

Author(s):

Konstantin Gulyabin

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neurological Diseases ◽

Cortical Atrophy ◽

Primary Lateral Sclerosis ◽

System A ◽

The Central Nervous System ◽

Primary Lateral ◽

Lateral Sclerosis ◽

Mills Syndrome

Mills' syndrome is a rare neurological disorder. Its nosological nature is currently not completely determined. Nevertheless, Mills' syndrome is considered to be a rare variant of the degenerative pathology of the central nervous system – a variant of focal cortical atrophy. The true prevalence of this pathology is unknown, since this condition is more often of a syndrome type, observed in the clinical picture of a number of neurological diseases (primary lateral sclerosis, frontotemporal dementia, etc.) and is less common in isolated form.

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