Diffusion Tensor MRI in the Diagnosis of ALS

Abstracts & Commentary

Sources: Toosy AT, et al. Diffusion tensor imaging detects corticospinal tract involvement at multiple levels in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2003; 74:1250-1257; Jacob S, et al. Diffusion tensor imaging for long-term follow-up of corticospinal tract degeneration in amyotrophic lateral sclerosis. Neuroradiology. 2003;45:598-600; Sach M, et al. Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis. Brain. 2003. In press; Ulug AM, et al. Diffusion tensor imaging in the diagnosis of primary lateral sclerosis. J Magn Reson Imaging. 2004. In press.

The diagnosis of amyotrophic lateral sclerosis (ALS) at an early stage can be difficult. It is desirable to have an accurate diagnostic test due to the prognosis of the illness, as well as the potential ability to treat patients earlier. As reviewed recently in Neurology Alert, none of the current diagnostic entities have shown high sensitivity or specificity in the diagnosis of ALS. A possible exception to this, however, is diffusion tensor imaging. This was initially shown to have some usefulness in the diagnosis of ALS in 1999. As yet, however, there have been few comprehensive studies that have followed patients or examined its overall sensitivity or specificity.

Several recent reports, however, have verified its efficacy. In Toosy and associates’ report, diffusion tensor imaging was used to examine 21 patients with ALS compared to 14 controls. Toosy et al found that the fractional anisotropy and mean diffusivity along the pyramidal tracts from the internal capsules down to the pyramids were significantly different in the ALS group compared to the controls. They did not examine whether any of these measures overlapped between the 2 groups, so one could not assess whether there was any specificity or sensitivity to the measurements. In another study by Jacob and colleagues, tensor diffusion imaging was examined in 3 patients. In the patient who had predominant involvement of upper motor neurons, there was remarkable progressive loss of diffusion anisotropy in the pyramidal tract. This was demonstrated over 9 months. This suggested that it might be a useful measure for studying disease progression. Two patients who had mainly lower motor neuron and bulbar disease did not show any temporal change in their diffusion tensor imaging over the 9-month interval. However, they were not compared to controls.

The most interesting recent study is that of Sach and associates. They studied diffusion tensor MRI in 15 ALS patients. That included patients without clinical signs of upper motor neuron lesions compared to healthy controls. They found that there was a negative correlation between the fractional anisotropy and central motor conduction time obtained by transcranial magnetic stimulation. Six of the patients had no clinical signs of upper motor neuron involvement at the time of MRI investigation but developed pyramidal tract symptoms later in the course of the disease. Sach et al found a decrease in fractional anisotropy in the cortico-spinal tract, corpus callosum, and thalamus of all 15 ALS patients. It, therefore, had 100% sensitivity in these patients.

Ulug and colleagues (including myself) have been conducting studies using diffusion tensor imaging in patients with a diagnosis of primary lateral sclerosis. We have a paper in press on 7 of these patients who met diagnostic criteria for primary lateral sclerosis. We subsequently examined an additional 2 patients. We detected abnormalities in all 9 patients. This test has had 100% sensitivity thus far in diagnosing the primary lateral sclerosis. Using quantitative diffusion anisotropy, there was 100% separation of the primary lateral sclerosis patients from the normal controls. The average diffusion constants also showed a significant separation, but there was slight overlap with the control measurements.


Diffusion tensor MRI provides an estimate of the orientation of the white matter integrity on the basis of diffusion characteristics of water. It depends on the orientation of the fiber bundles. Diffusivity is greater in directions along the fiber tract than perpendicular to them. This degree of directionality of diffusion can be measured as fractional anisotropy. This can be very valuable in assessing white matter damage. A feature of ALS as well as primary lateral sclerosis is degeneration in the posterior limb of the internal capsule. It is possible to detect this damage with great sensitivity and reliability using diffusion tensor MRI. In our hands, as well as those in the recent reports in the literature, this has been an extremely valuable test in helping to make the diagnosis in early ALS or primary lateral sclerosis. The clinical picture of some of these patients can be confusing and difficult. In primary lateral sclerosis, the differential diagnosis includes hereditary spastic paraplegia, syphilis, syringomyelia, and spinal multiple sclerosis. In addition, it can be mimicked by patients who have a partial Chiari formation or evidence of cervical spondylosis. These patients can mimic primary lateral sclerosis, and it may lead to unnecessary surgical intervention. A diagnostic test to support the diagnosis of primary lateral sclerosis is, therefore, extremely useful. Similarly, in ALS if one could make the diagnosis reliably and have perhaps a marker of disease progression, this would be extraordinarily useful in diagnosis, as well as a potential surrogate disease marker to be followed with therapeutic interventions. As such, the recent studies using diffusion tensor imaging suggest that this may be an extraordinarily valuable diagnostic tool in patients with both ALS and primary lateral sclerosis. — M. Flint Beal, Department of Neurology; Cornell University Medical College New York, NY; Editor, Neurology Alert.