Classification based on motor neuron involvement
The brain sends messages to the muscles in a two-stage process involving upper motor neurons in the brain or spinal cord connecting with lower motor neurons located where nerves that go out to the muscles connect with the long arms or axons of neurons in the spinal cord (see diagram). Where the two different types of motor neurons connect is a junction called a synapse.
With HSP, the most common process is where only the upper motor neurons are affected with a progressive dying back of the long arm or axon of the upper motor neuron, thus impairing the connection with the lower motor neuron at the synapse and therefore, the nerve signals that go through the synapse.
This impaired signalling leads to muscle spasticity, muscle weakness and increased muscle tone. Where lower motor neurons are also affected in some types of HSP, wasting or muscle atrophy and decreased muscle tone occur.
Abstract
Hereditary spastic paraplegias (HSPs) are a group of rare inherited neurological diseases characterized by extreme heterogeneity in both their clinical manifestations and genetic backgrounds. Based on symptoms, HSPs can be divided into pure forms, presenting with pyramidal signs leading to lower-limb spasticity, and complex forms, when additional neurological or extraneurological symptoms are detected.
The clinical diversity of HSPs partially reflects their underlying genetic backgrounds. To date, 76 loci and 58 corresponding genes [spastic paraplegia genes (SPGs)] have been linked to HSPs. The genetic diagnosis is further complicated by the fact that causative mutations of HSP can be inherited through all possible modes of transmission (autosomal-dominant and -recessive, X-linked, maternal), with some genes showing multiple inheritance patterns.
The pathogenic mutations of SPGs primarily lead to progressive degeneration of the upper motor neurons (UMNs) comprising corticospinal tracts. However, it is possible to observe lower-limb muscle atrophy and fasciculations on clinical examination that are clear signs of lower motor neuron (LMN) involvement.
The purpose of this review is to classify HSPs based on their degree of motor neuron involvement, distinguishing forms in which only UMNs are affected from those involving both UMN and LMN degeneration, and to describe their differential diagnosis from diseases such as amyotrophic lateral sclerosis.
SOURCE: Rev Neurol (Paris). 2017 May;173(5):352-360. doi: 10.1016/j.neurol.2017.03.034. Epub 2017 Apr 24. Copyright © 2017 Elsevier Masson SAS. All rights reserved. PMID: 28449883
Hereditary spastic paraplegia: More than an upper motor neuron disease.
Parodi L1, Fenu S2, Stevanin G3, Durr A4.
1 Institut du Cerveau et de la Moelle épinière, ICM, Sorbonne Université, UPMC Univ Paris 06, UMRS_1127, INSERM, U 1127, CNRS, UMR 7225, Pitié-Salpêtrière University Hospital, 75013 Paris, France.
2 Institut du Cerveau et de la Moelle épinière, ICM, Sorbonne Université, UPMC Univ Paris 06, UMRS_1127, INSERM, U 1127, CNRS, UMR 7225, Pitié-Salpêtrière University Hospital, 75013 Paris, France; APHP, Genetics Departement, Pitié-Salpêtrière University Hospital, 75013 Paris, France.
3 Institut du Cerveau et de la Moelle épinière, ICM, Sorbonne Université, UPMC Univ Paris 06, UMRS_1127, INSERM, U 1127, CNRS, UMR 7225, Pitié-Salpêtrière University Hospital, 75013 Paris, France; APHP, Genetics Departement, Pitié-Salpêtrière University Hospital, 75013 Paris, France; PSL Research University, EPHE, 75014 Paris, France.
4 Institut du Cerveau et de la Moelle épinière, ICM, Sorbonne Université, UPMC Univ Paris 06, UMRS_1127, INSERM, U 1127, CNRS, UMR 7225, Pitié-Salpêtrière University Hospital, 75013 Paris, France; APHP, Genetics Departement, Pitié-Salpêtrière University Hospital, 75013 Paris, France. Electronic address: [email protected].