Swash M, Leigh N (1992) Criteria for the diagnosis of familial amyotrophic ... Neary D, Snowden JS, Mann DMA,. Northen B, Goulding PJ, Macdermott. N (1990) ...
Neuroradiology (1998) 40: 298±302 Ó Springer-Verlag 1998
E. Andreadou P. Sgouropoulos P. Varelas A. Gouliamos C. Papageorgiou
Accepted: 30 July 1997
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E. Andreadou ( ) × P. Sgouropoulos × P. Varelas × C. Papageorgiou Eginition Hospital, 74, Vas. Sofias Avenue, GR-11528 Athens, Greece Tel.: + 30-1-7 21 16 82; Fax: + 30-1-7 21 64 74 A. Gouliamos Department of Radiology, CT/MRI Unit, Areteion Hospital, University of Athens, Greece
D IA G N O S T I C NE UR OR A DI O LO G Y
Subcortical frontal lesions on MRI in patients with motor neurone disease
Abstract MRI was performed in 32 patients with motor neurone disease (26 men and 6 women, aged 40±77 years) and in a control group of 21 subjects. Of the patients studied, 19 had definite and 11 probable amyotrophic lateral sclerosis (ALS) and two had progressive bulbar palsy. In 10 patients there were asymmetrical bilateral foci of increased signal intensity on protondensity and T2-weighted images, confined to the white matter. Two patients had only cortical frontal atrophy and slightly increased ventricular size, whereas 20 had normal
Introduction In most cases of motor neurone disease (MND), there is progressive degeneration of the upper and lower motor neurones with relative sparing of other areas. However, in endemic and familial cases of amyotrophic lateral sclerosis (ALS) there is involvement of other systems, e. g. extrapyramidal [1]. It has generally been accepted that the degenerative process in sporadic ALS is restricted to the motor neurones. Recent studies gave some evidence of more widespread involvement. Degenerative lesions have been observed outside the pyramidal system, especially in patients on long term use of respirators [2, 3]. Extensive degeneration has been seen throughout the spinal cord, including the spinocerebellar tracts, Clarke's column and the propiospinal tracts. In addition, neuronal degeneration of the cranial motor nuclei at the level of the facial nerve nucleus has been observed. Furthermore, degenerative lesions in the substantia nigra, globus pallidus, and
MRI. The focal lesions were not confined to corticospinal tracts, but were also observed in subcortical frontal areas. While the lesions along the corticospinal tracts correspond to pyramidal tract degeneration, the subcortical foci correlate with degeneration of the frontal bundles and indicate generalised involvement of the central nervous system. Key words Magnetic resonance imaging × Motor neurone disease × Amyotrophic lateral sclerosis
Lewy bodies, without clinical extrapyramidal symptoms, have been described [3]. According to Hughes, extensive pathological lesions, including the basal ganglia, would more often be found if each ALS case was carefully assessed [4]. Underestimation of these lesions may lead to ignoring the heterogeneous character of MND. In an attempt to detect this more generalised involvement, we examined a group of patients with MND by MRI of the brain.
Material and methods We examined 32 patients (26 men and 6 women aged 40±77 years, mean 59 years) with different clinical forms of MND and 21 control subjects (17 men and 4 women aged 44±77 years, mean 60.5 years). Patients with hypertension, diabetes and cerebrovascular disease were excluded. Disease duration ranged between 2 months and 6 years. The groups were comparable for age. Control subjects had cervical myelopathy or radiculopathy and were not diabetic or hypertensive.
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Table 1 Location of high-signal foci in patients No 1 2 3 4 5 6 7 8 9 10 a b
Sex M M M M F M M F F F
Age (years) 62 66 51 62 65 57 40 75 65 53
Subcortical frontal
parietal
occipital
+a +++ ++++ +++ + +++ ++ ++++ ++
+ + + +
+b
Centrum semiovale
Corona radiata
Internal capsule
Cerebral Brain stem peduncles
+ +++ + ++ ++
+ ++ + ++ ++ ++
+ + + ++
++ +
++
1 lesion, +; 2±3, ++; 4±5, +++; 6 or more, ++++ Punctate
Table 2 Location of high-signal foci in controls No.
Sex
1 2 3 4 5 6 7 8
M M M M F M M M
a
See Table 1 Punctate
b
Age (years) 53 72 67 69 63 67 67 77
Subcortical frontal
parietal
occipital
++a ++ +b
+++ +++ ++ +b
+++ ++++ +b
The diagnosis was established on the history, physical examination and electrophysiological findings. All the patients had upper and lower motor neurone dysfunction associated with progressive weakness, atrophy and fasciculations of skeletal muscles, without sensory involvement or sphincter dysfunction. According to the criteria for ALS proposed at the workshop held in 1990 in El Escorial, Spain [5], 19 of the patients had definite and 11 probable ALS, and two had progressive bulbar palsy. Blood tests for thyroid and parathyroid function, B12 and folic acid, trace elements, immunoelectrophoresis, CEA, alphafetoprotein and b -hexosaminidase A levels and CT of the thorax and abdomen were performed to exclude other diseases. Those subjects undergoing lumbar puncture had a normal biochemical and immunoelectrophoretic spinal fluid profile, as well as normal trace elements. Brain MRI was performed in all patients, at 0.5 T using a 256 256 matrix. Pixel size was 0.9 0.9 mm with reconstruction of 5-mm-thick slices and on interslice gap of 2 mm. The technique included spin-echo and gradient-echo using repetition time (TR) 2200 ms and echo time (TE) 25±90 ms with proton-density and T2weighted axial images respectively. Sagittal T1-weighted images were also obtained with TR 300 TE 25 ms. All the high-signal lesions were counted and assessed as follows: 1 lesion, +; 2±3 lesions, ++; 4±5 lesions, +++; 6 lesions or more, ++++. Contrast enhancement was also used in selected cases.
Centrum semiovale
Corona radiata
Internal capsule
Cerebral peduncles
+ ++ +++ +b +b +b
Results There were ten patients, all with definite ALS, who had asymmetrical foci of increased signal intensity on proton-density and T2-weighted images, confined to the white matter. In two patients there was only frontal cortical atrophy and slight increase in ventricular size, while 20 patients had normal MRI (Table 1). Among the 21 control subjects, there were 8 who had white matter high-signal foci (WMF) (Table 2). Of the 10 patients with high-signal foci 9, had lesions along the pyramidal tracts (corona radiata, centrum semiovale and internal capsule). Only 2 patients had lesions in the cerebral peduncles and medulla oblongata. It is remarkable, however, that 9 of these patients also had lesions in the subcortical frontal white matter (Table 1). The number and size of these lesions were greater than in controls (Table 2). On the other hand, only one punctate lesion in the subcortical occipital area was observed in a patient, while the controls had more lesions in subcortical occipital and parietal regions (4 cases) and in the centrum semiovale (6) than in subcortical frontal areas (3 in 8 controls cases with WMF) (Table 2).
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Fig. 1 Patient 3. Axial T2-weighted image showing high-signal foci in subcortical frontal areas and centrum semiovale Fig. 2 a Patient 6. T2-weighted images showing high-signal foci in right internal capsula (a) and subcortical frontal areas and centrum semiovale (b) Fig. 3 a Patient 8. T2-weighted images showing high-signal foci in pons (a) and bilaterally in centrum semiovale (b)
1
2a
2b
3a
3b
301
Discussion Degeneration of the pyramidal tracts was first described by Kojewnikoff [6] in 1883 in a patient with ALS. Subsequently Gordon Holmes reported, in addition to degeneration of pyramidal tracts in the spinal cord, loss of Betz cells in motor cortex [7]. These lesions were confirmed by other investigators [8±10] and have been detected on MRI [11±13]. Lesions of increased signal intensity, were also reported in areas outside the pyramidal system, but not attributed to the underlying disease process. Most of our patients with abnormal brain MRI (9 out of 10) had high-signal lesions in the corona radiata and centrum semiovale; 4 had similar lesions in the internal capsule and 2 others in the cerebral peduncles as well (Table 1). The presence of such lesions confirms the previous observations. Considering that there is a dysfunction of the cortical motor neurones leading to degeneration of pyramidal tracts [11±14], it seems plausible that lesions along the pyramidal tracts are due to degeneration of the upper motor neurone. However, 9 of our 10 patients also had high-signal lesions in the frontal white matter (Table 1). This observation raises questions about the possible relationship of the lesions to the disease process. The clinical significance of high-signal areas in healthy elderly subjects has been controversial. The white matter lesions have been attributed to various risk factors. Hypertension has been considered most often, but there are also studies which have suggested cardiac disease and diabetes mellitus as potential indicators of white matter damage. In the majority of studies age has been consistently found to be the most powerful predictor of WMF; this correlation implies that WMF may represent the sequelae of age-related alterations of blood vessels, a hypothesis supported by the consistent perivascular location of WMF. No clear relationship between neuropsychological performance and WMF has been found [15]; however, their presence may suggest a subtle cognitive dysfunction in normal elderly individuals [16]. We excluded patients with hypertension, cerebrovascular disease, hydrocephalus or dementia. The mean age of the patients was 59.1 years, while those with high-signal foci had a mean of 59.6 years. The control subjects had mean age of 60.5 years. Eight of them (mean age 66.9 years) had WMF, but only three of them had subcortical frontal foci. WMF were mainly observed in the parietal and occipital regions (in seven of the eight controls). A similar location prevalence in the posterior brain regions has been reported by other investigators [15]. On the contrary, of our patients with high-signal foci, 9 of 10 had lesions in subcortical frontal areas, while only 4 had lesions in the subcortical parietal and 1 in the
occipital area. This difference may not be coincidental. The simplest interpretation is to attribute the subcortical frontal lesions to degeneration of afferent fibres to the anterior frontal cortex. Kishikava et al. [17] reported a case of ALS with atrophy of the frontal lobe and marked gliosis and myelin loss in the subfrontal white matter, and diminished cerebral metabolism of glucose has been reported on positron emission tomography in ALS. Dalakas et al. [18] found generalised hypometabolism throughout the cortex in patients with upper motor neurone signs, whereas Ludolf et al. [19] found more significant hypometabolism in the frontal cortex. Waldemar et al. [20] found reduced cerebral blood flow on single-photon emission tomography in the entire cortex, more pronounced in the frontal lobes, and Udaka et al. [21] found reduced uptake in the motor cortex. All these investigators, and others [14, 22±24], agree that in ALS there is involvement not only of the motor cortex, but of the entire cortex. These cortical changes are not usually accompanied by atrophy and may be due to loss of synapses and dendrites, as well as to functional inhibition of neurones. This dysfunction would be expected to extend to the underlying white matter, and this explanation would be compatible with our findings of subcortical frontal WMF. In addition, the reduction in the amount of subcortical frontal white matter reported by Kiernan and Hudson [25], attributed to loss of fibres afferent to the anterior frontal cortex, favours the hypothesis of a relationship of subfrontal WMF to the disease process. All available evidence supports the possibility that the subcortical frontal high-signal lesions observed in a number of patients may not be incidental and may represent an early stage of demyelination and/or gliosis related to the involvement of the frontal lobes in ALS. Other investigators believe that these findings are incidental or the result of evolving senile change. Our view can be substantiated only by a prospective, longitudinal, functional and structural imaging study to explain the widespread histological and functional disorders of the entire brain, especially the frontal lobes, in ALS.
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