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MRI in amyotrophic lateral sclerosis: more than a promise
  1. Julian Grosskreutz
  1. Correspondence to Dr Julian Grosskreutz, Hans-Berger Department of Neurology, University Hospital Jena, Erlanger Allee 101, Jena 07747, Germany; julian.grosskreutz{at}

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In amyotrophic lateral sclerosis, the deadliest form of motor neuron diseases, physicians observe the spread of non-painful paralysis with intact sensory function often presenting as asymmetric muscle atrophy and brisk or maintained reflexes. Using Awaji criteria to estimate upper and lower motor neuron signs in bulbar, cervical, thoracic and lumbar regions, and the highly sensitive electromyography (EMG), they diagnose amyotrophic lateral sclerosis (ALS) in a majority of the cases. The spread of symptoms is attributed to spinal motor neuron pathology, but experienced ALS neurologists will agree that a slowing of movement, loss of fine motor control and occurrence of mass or mirror movements indicate central motor pathway dysfunction, even in the absence of definite pyramidal signs. ALS naïve physicians may misinterpret these ‘soft signs’ of upper motor neuron dysfunction as stroke sequelae and not ALS related, and contribute to unnecessary delays in diagnosis. Unfortunately, we have no tool available to quantify central motor pathway dysfunction, and neither did we know whether lower motor neuron deficits anatomically correspond to central motor pathway pathology in ALS.

In the paper by Bede et al,1 state of the art computerised MRI analysis tools explored the cortical involvement in ALS patients grouped according to the regions primarily affected by the disease. The authors elegantly reduced the analysed brain volume to the sensorimotor cortex using brain anatomy maps. Where other authors failed,2 ,3 Bede et al found a significant correlation of the ALS functional rating scale, revised version (ALSFRS-R) readout in primary arm, leg or bulbar involvement with the corresponding anatomical cortical areas. This is strong evidence for the view that the anatomical connection of cortical motor neurons with their corresponding spinal motor neurons plays a key role in ALS pathology, which has, at present, no molecular explanation. Unfortunately, these MRI techniques are not (yet) sensitive enough to detect pathology in single subjects. Wet biomarkers are just beginning to detect brain disease in ALS, and provide no anatomical information on disease distribution in the brain.4

The limitations of MRI as a diagnostic and monitoring tool in ALS or other neurodegenerative diseases may soon be overcome with international multicentre collaborations such as the Alzheimer Disease Neuroimaging Initiative and the NeuroImaging Symposia in ALS ( Bede et al have taken a major step forward in honing MRI techniques to monitor ALS brain pathology in a cohort of patients which could even today be applied in clinical trials, at least on a test basis. None of the presently planned drug trials incorporate MRI as a monitoring tool, and the funding required may have to be raised by the community. In my opinion, an effort worthwhile because without doubt ALS trials desperately need a reliable tool to quantify the extent of brain pathology. The currently used ALSFRS-R readout worsens when all physiological compensation mechanisms have failed beyond repair. We need to know earlier to stage a successful intervention in ALS.


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  • Contributors There is no contribution by other parties.

  • Funding European Union Joint Programming for Neurodegenerative Diseases (JPND) grant SOPHIA.

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.

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