Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Most patients die within 2–5 years of symptom onset due to the lack of effective therapy options. A diagnostic delay is encountered quite often, since disease progression as well as site and speed of onset may vary significantly. Some diseases can mimic features of ALS, especially in early stages. It is very important to differentiate those mimics from ALS as potentially treatable conditions might be missed otherwise. ALS typically affects the upper as well as the lower motor neuron, which implies that diseases sharing at least one of these clinical features have to be considered in the differential diagnosis. The following conditions should be taken into account as a differential diagnosis for ALS with predominant affection of the lower motor neuron: Immune mediated neuropathies such as multifocal motor neuropathy (MMN) with pronounced distal paresis without striking atrophy signs and conduction blocks in electroneurography, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with common signs of sensibility disturbances, areflexia and cytoalbuminologic dissociation in the cerebrospinal fluid (CSF). Sporadic inclusion body myositis (sIBM) with typical biopsy findings and clinically predominant affection of the finger flexors. Spinal and bulbar muscular atrophy (SBMA), in which androgen receptor (AR-)gene testing and clinical signs of androgen insensitivity will help to differentiate the disease from ALS. Hirayama disease shows cold paresis; a cervical MRI scan and a normal neurography will help to confirm the diagnosis. In benign fasciculation syndrome, there is no muscle paresis or atrophy, and acute denervation cannot be detected in the EMG. In spinal muscular atrophy (SMA), testing for the SMN gene will help to differentiate the condition from ALS; furthermore, SMA is a very rare disease in adults. As a differential diagnosis for ALS with both clinical affection of the upper and lower motor neuron e. g. metabolic diseases such as adrenoleukodystrophy, metachromatic leukodystrophy and Tay-Sachs disease should be taken into account. Here, laboratory tests are the most important steps for a correct diagnosis. Cervical myelopathy is also capable of affecting the upper and lower motor neuron, but can easily be differentiated by a cervical MRI scan. As a differential diagnosis of ALS with predominant affection of the upper motor neuron, we discuss hereditary spastic paraparesis (HSP) which presents with a symmetric spasticity of the legs. The MRI often shows atrophy of the spinal cord, and SPG gene testing is done to differentiate HSP from ALS.
Key words
amyotrophic lateral sclerosis - differential diagnosis - mimics - motor neuron disease
