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Amyotrophic lateral sclerosis (ALS)

Clinical information

Motor neuron diseases (MND) are a group of neurodegenerative diseases that are characterised by degeneration of the upper and lower motor neurons. MND include amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy and pseudobulbar palsy. ALS is the most frequent MND with a worldwide incidence of around 2/100,000 people per year.

In the early stage of ALS, patients experience unspecific symptoms such as muscle weakness or cramps in the arms and legs or dysphagia and dysarthria. As the disease proceeds, the symptoms spread to the whole body and continuously increase in their intensity until the patients are unable to care for themselves and lose their ability to communicate.

ALS cannot be healed. The majority of patients succumb to the disease within 3 to 5 years after onset of the first symptoms. While mutations have been found in various genes, which explain only a small part (5 to 10% of ALS cases) of familial ALS cases, the root cause of sporadic ALS is yet unkown despite intensive research.

Diagnostics

The El Escorial criteria for the diagnosis of ALS are based on the evaluation of clinical symptoms and the description of motor neuron failures, e.g. by means of electromyography (EMG). Although these diagnostic critiera are standardised, they are only useful at the later stages of the disease, when a large number of motor neurons have already degenerated. From the first description of symptoms to the final diagnosis it often takes more than 12 months. This is particularly critical because of the short life expectancy of ALS patients. For earlier diagnosis and reliable differentiation of ALS from other diseases that show ALS-like symptoms especially in their initial stage (MND mimics: polyneuropathy, myopathy, sporadic inclusion body myositis, etc.) there is an urgent need for novel diagnostic methods.

pNf-H concentration by level of degenerationPhosphorylated neurofilament heavy chain (pNf-H), a main component of the neuronal cytoskeleton that is released when neuronal damage occurs, is a promising biomarker of ALS. The concentration of pNf-H in the cerebrospinal fluid (CSF) of ALS patients is significantly increased in the early disease stage. Moreover, the pNf-H concentration correlates with the level of degeneration of the motor neurons. Several studies suggest that the pNf-H value in CSF is a better diagnostic means in ALS than neurofilament light chain (NfL). The pNf-H level in the blood correlates with the CSF level and is increased up to 18 months before first diagnosis. The determination of the pNf-H concentration is therefore suited for diagnostics, differential diagnostics and prognosis of ALS. It is recommended that this marker be included into MND routine diagnostics.

 

Brochure: Neurofilaments in diagnostics - Biomarkers for neuroaxonal damage

Techniques

Method
Parameter
ELISA
neurofilament (pNf-H)
determination in CSF and serum
Details
ELISA
neurofilament (pNf-H)
highly sensitive determination
in serum and plasma
Details
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