Motor neuron disorders

Published on 19/03/2015 by admin

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Last modified 19/03/2015

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Motor neuron disorders


Diseases that affect motor neurons can be classified as either primary, secondary, or multisystem (Table 27.1). The terms ‘motor neuron diseases’ and ‘motor neuron disorders’ are used to refer to any disease affecting motor neurons. The specific term ‘motor neuron disease’ is used in Europe as a synonym for amyotrophic lateral sclerosis (ALS) and related disorders.



ALS, progressive bulbar palsy (PBP), and progressive muscular atrophy (PMA) are generally considered to be variants of a single clinicopathologic syndrome. Primary lateral sclerosis (PLS) is regarded by many workers as a distinct entity because there is no involvement of lower motor neurons. These conditions (Table 27.2) are characterized as follows:

Clinical criteria for diagnosis divide cases into definite and probable ALS (Table 27.3). Since several diseases can be associated with motor neuron loss, secondary causes of motor neuron disease must be excluded.

Table 27.3

Revised World Federation of Neurology criteria for diagnosis of ALS

The diagnosis of ALS requires:

Four diagnostic categories are recognized:

1. Clinically definite ALS: on clinical grounds alone, evidence of UMN plus LMN signs in the bulbar region and in at least two spinal regions, or the presence of UMN signs in two spinal regions and LMN signs in three spinal regions

2. Clinically probable ALS: on clinical grounds alone, UMN plus LMN signs in at least 2 regions with some UMN signs rostral to LMN signs

3. Probable, laboratory supported ALS: this is defined, after proper application of neuroimaging and clinical laboratory protocols has excluded other causes, as:

4. Possible ALS is defined, once other diagnoses have been excluded, as:

The category of suspected ALS, previously included in the El Escorial criteria has been discarded

UMN, upper motor neuron; LMN, lower motor neuron; ALS, amyotrophic lateral sclerosis.

Typically, ALS progresses to death from respiratory failure or aspiration bronchopneumonia within 5 years of onset. Approximately 10–20% of patients develop disturbed frontal lobe cognition.


The most characteristic finding is loss of motor neurons and astrocytosis in the spinal cord, brain stem, and motor cortex (Fig. 27.3). The remaining motor neurons in the spinal cord and brain stem may show cytoskeletal abnormalities.



A summary of the main genetic forms of MND is presented below.

Type of MND Linkage Gene
ALS1 AD adult 21q22 Cu/Zn SOD1 10–120% AD cases
ALS2 AR Juvenile 2q33 Alsin
ALS3 AD adult 18q21 Unknown – possibly commonest form of AD ALS
ALS4 AD Juvenile 9q34 SETX Senataxin
ALS5 AR Juvenile 15q15 SPG11 Spatacsin
ALS6 AD Adult 16p11.2 FUS Fused in sarcoma
ALS7 AD Adult 20p13 Unknown
ALS8 AD Adult 20q13.33 APB VAMP-associated protein B
ALS9 AD Adult 14q11 ANG Angiogenin
ALS10 AD Adult 1q36 TARDBP TAR DNA-binding protein
ALS11 AD Adult 6q21 FIG4 PI(3,5)P(2)5-phosphatase
ALS12 AR/AD Adult 10p15-p14 OPTN Optineurin
ALS 15 p11.23-p11.1 UBQLN2 gene
FTDALS 9p21 C9orf72 (GGGGCC)n expansion

AD, autosomal dominant; AR, autosomal recessive.

Inclusion bodies (Figs 27.427.8) may be seen in sections stained with hematoxylin and eosin (H&E) (Fig. 27.4), but the distinctive inclusions are more readily visualized by immunostaining for ubiquitin or P62 (Fig. 27.5

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