Differentiating lower motor neuron syndromes

Abstract

Lower motor neuron (LMN) syndromes typically present with muscle wasting and weakness and may arise from pathology affecting the distal motor nerve up to the level of the anterior horn cell. A variety of hereditary causes are recognised, including spinal muscular atrophy, distal hereditary motor neuropathy and LMN variants of familial motor neuron disease. Recent genetic advances have resulted in the identification of a variety of disease-causing mutations. Immune-mediated disorders, including multifocal motor neuropathy and variants of chronic inflammatory demyelinating polyneuropathy, account for a proportion of LMN presentations and are important to recognise, as effective treatments are available. The present review will outline the spectrum of LMN syndromes that may develop in adulthood and provide a framework for the clinician assessing a patient presenting with predominantly LMN features.

Keywords: GENETICS; MOTOR NEURON DISEASE; NEUROIMMUNOLOGY; NEUROPATHY; NEUROPHYSIOLOGY.

Figure 1

Spinobulbar muscular atrophy (Kennedy's disease): (A) facial asymmetry due to asymmetrical facial muscle weakness which is accentuated by pursing the lips; (B) tongue wasting resulting in scalloping of the lateral borders and midline furrowing.

Figure 2

Asymmetric wasting of thenar eminence in a 71-year-old male with an upper limb predominant motor neuropathy associated with anti-GM1 IgM antibody (A). High doses of intravenous immunoglobulin were required to achieve disease stabilisation. The CMAP was unrecordable on the right from APB. The distal APB CMAP on the left was normal, but there was marked dispersion and reduction in CMAP amplitude with stimulation at the elbow (B). A, amplitude; A, area; APB, abductor pollicis brevis; d, duration; CMAP, compound muscle action potential; CV, conduction velocity; NCS, nerve conduction studies.

Figure 3

This 46-year-old man presented with a 20-year history of progressive distal wasting and weakness of the right hand and forearm muscles. Symptoms developed in the left hand 5 years prior to presentation. Upper limb reflexes were depressed. Needle electromyography revealed chronic neurogenic changes in clinically affected muscles. There were no sensory abnormalities. (A and B) Asymmetrical wasting of the hands and forearm affecting C7-T1 musculature with striking preservation of brachioradialis in the right upper limb; (C) sagittal T2-weighted STIR image demonstrating a linear hyperintensity within the cervical cord at C6 and C7 associated with cord atrophy; (D) axial T2-weighted image with ‘snake eyes’ appearance in the anterior horns. STIR, Short TI Inversion Recovery.

Figure 4

Diagnostic algorithm for a patient presenting with a LMN syndrome. ALS, amyotrophic lateral sclerosis; CB, conduction block; dHMN, distal hereditary motor neuropathy; FHx, family history; GBS, Guillain-Barré syndrome; LL, lower limb; LMN, lower motor neuron; MMA, monomelic amyotrophy; MMN, multifocal motor neuropathy; MND, motor neuron disease; NCS, nerve conduction studies; NGS, next-generation sequencing; PMA, progressive muscular atrophy; SBMA, spinobulbar muscular atrophy; SMA, spinal muscular atrophy; UL, upper limb.

Figure 5

Proposed pathogenic mechanisms for LMN syndromes. LMN syndromes may arise from disease processes affecting the anterior horn cell or the motor axon and/or its surrounding myelin. (A) A variety of mechanisms have been implicated in the degenerative and hereditary syndromes including mitochondrial dysfunction, altered RNA processing and impaired axonal transport (see text for further details). (B) Anti-GM1 antibodies may bind to GM1 in the paranodal region leading to disruption of ion channel clusters and paranodal anatomy. Although not a purely LMN syndrome, IgG4 antibodies against NF155 and CNTN1 have recently been described and may similarly disrupt paranodal anatomy resulting in a sensorimotor neuropathy. CNTN1, contactin-1; LMN, lower motor neuron; NF155, neurofascin-155.