J Neurol (1990) 237 : 471-474
Journal of
Neurology
© Springer-Verlag 1990
Magnetic resonance imaging in motor neuron disease M. L. Sales Luls 1'2, A. Hormigo 2, C. Maurlcio 3, M.M. Alves 2, and R. Serräo 2 1Department of Neurology, Hospital de Santa Maria, ŒCentro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa, and ~Laboratório de Ressonän¢ia Magnética, Lisboa, Portugal Received April 4, 1990 / Accepted September 3, 1990
Summary. Magnetic resonance imaging (MRI) of the brain was evaluated in 20 patients with m o t o r neuron disease ( M N D ) and in a control group of 11 healthy people. Bilateral increased signal areas of various sizes in the centrum semiovale, corona radiata, intern al capsule, pedunculi of midbrain, pons, medulla and even in the frontal lobe, topographically related with the corticospinal tract, were found in 8 out of 20 patients. T h r e e out of 4 patients with progressive bulbar paralisis and 5 out of 11 cases of amyotrophic lateral sclerosis had abnormal M R I . Such M R I abnormalities have neither been found in patients with progressive muscular atrophy nor in controls, suggesting that they m ä y be the hallmark of pyramidal tract degeneration in m o t o r neuron disease.
and sensory conduction velocities, high-fibre density and jitter values on single-fibre EMG. All had normal blood lead and hexosaminidase A levels; those undergoing lumbar puncture had a normal biochemical and immunoelectrophoretic spinal-fluid profile, None of the patients had symptoms or risk factors for cardiac and cerebrovascular disease. Patients with associated disorders were excluded. Eleven normal volunteers constituted the control group, 7 men and 4 women, aged from 45 to 74 years (mean 60.1). MRI was performed with a Signa-GE superconducting magnet operating a 1.5 tesla. The data acquisition matrices were 256 × 256; pixel size was 0.9 x0.9mm, with reconstruction of 5-mm-thick slices. The technique included spin-echo and gradient-echo using a repetition time (TR) of 2000-2600 ms and an echo time (TE) of 20-30 ms to 100 ms with proton density and T2-weighted images.
Results Key words: A m y o t r o p h i c lateral sclerosis - Progressive muscular atrophy - Bulbar palsy - Magnetic resonance imaging
Introduction The inability to study in vivo the anatomical localization and the pathophysiological mechanism of degeneration of the central nervous system (CNS) in m o t o r neuron disease ( M N D ) led us to asses M R I in 20 patients with this disorder.
Patients and methods Twenty patients were studied: 11 men and 9 women, aged from 38 to 78 years (mean 57.6) with different clinical forms of MND. These included progressive muscular atrophy (PMA: 5), progressive bulbar paralysis (PBP: 4) and amytrophic lateral sclerosis (ALS: 11 patients). Symptoms had been present for 1 to 10 years, the shorter evolution of PBP being 1 to 2 years. The diagnosis of MND was established from the history, physical examinafion and electromyography (EMG). All the patients had diffuse electromyographic neurogenic patterns, normal motor Offprint requests to: M. L. Sales Luis, Servi9o de Neurologia, Hospital de Santa Maria, Av. Prof. Egas Moniz, P 1600 Lisboa, Portugal
Patients MRI abnormalities along the pyramidal tract. In eight out of the 20 patients, M R I abnormalities were found. A m o n g the 15 patients with clinical pyramidal signs (ALS and PBP), 3 out of 4 with P B P and 5 out of 11 with A L S had abnormal M R I . The clinical features and description of M R I of the positive cases are presented in Tables 1 and 2, respectively. Other MRI abnorrnalities. One patient with PBP had only cortical atrophy. In 6 patients with ALS, two had slight cortical atrophy, one had a single oval increased signal area in the right anterior periventricular white matter and another had multiple, small subcortical foci. Patients with P M A had normal M R I with m o d e r a t e cortical atrophy in two. Controls A m o n g the 11 healthy volunteers, 4 had completely normal M R I . Seven had small bright spots, located in the periventricular region, basal ganglia and subcortical white matter. All these foci were few in number, smaU and discrete, with a completely distinct localization comparable with the characteristic images found in the patient group.
472
Table 1. Clinical features of patients Patients no., sex, age (ycars)
Agc of onset (years)
Duration (years)
Initial s y m p t o m s
UMN signs
LMN signs
Bulbar signs
Clinical form of M N D
ALS
I, F, 38
36
2
LL paralysis
+
+
+
2, F, 53
50
3
LLL paralysis
+
+
+
ALS
3, F, 49
47
2
R H paralysis
+
+
+
ALS ALS
4, F, 65
63
2
R L L paralysis
+
+
+
5, M, 49
41
8
LL paralysis
+
+
+
ALS
6, M, 68
65
3
Dysarthria, dysphagia
+
+
+
PBP
7, M, 46
44
1,5
D y s a r t h r i m dysphagia
+
+
+
PBP
8, F, 75
73
1,5
Dysarthria, dysphagia
+
+
+
PBP
U M N , U p p e r m o t o r n e u r o n : LMN, lower m o t o r n e u r o n ; LL, lower limbs: LLL, left lower limb; R H , right hand: RLL, right lower limb
Table 2. Locatization of hyperintense lesions Patient
Subcortical frontal region
Centrum semiovale
Corona radiata
÷
+
+
+
+
+
2 (Fig. 3)
+
+
+
+
+
-
-
3
-
+
+
+
+
.
4
-
-
-
+
+
-
5
-
+
+
+
+
-
-
-
6 (Figs. 4 and 5)
-
+
+
+
+
+
+
-
1 (Figs. 1 and 2)
Internal capsule
Basis pedunculi
Medulla oblongata
.
Spinal cord
.
Others
. -
7
-
+
+
+
+
-
-
+
8
-
+
+
+
+
-
-
+ (Subcortical and periventricular)
Fig. 1. Patient i. M R I coronal scan with T R - 2600 T E = 80 ms, s h o w i n g n e b u l a r h y p e r i n t e n s e lesions in the c e n t r u m semiovale, c o r o n a radiata (upper arrow). H y p e r i n t e n s e b a n d s in the imernal capsules and midbrain (lower arrows) Fig. 2. Patient 1. M R I coronal scan, T R = 2600 T E = 30 ms, showing a h y p e r i n t e n s e b a n d in the medulla oblongata and spinal cord
(Periventricular)
Fig.3, Patient 2. M R I coronal scan, T R = 2000 T E - 100 ms. Nebula hyperintensity is s h o w n in the subcortical regions of the m o t o r cortex, centrum semiovale and corona radiata (upper arrow), with a hyperintense b a n d in the internal capsules and p e d u n c u l a r pyramidal tract
473
Fig. 4. Patient 6. MRI coronal scan (TR = 2000 TE = 80 ms) showing nebular hyperintensity in the centrum semiovale and corona radiata (upper arrow) and hyperintense bands in the internal capsule and cerebral peduncular pyramidal tract Fig. 5. Patient 6. MRI coronal scan (TR = 2000 TE = 30 ms) showing hyperintense bands in the pyramidal tract through the pons, medulla oblongata and spinal cord (arrow)
Discussion While we were conducting our study, abnormal M R I was reported in 2 patients with A L S [6]. According to these authors, this m a y indicate lesions of the corticospinal tract. The M R I s of 8 of our patients with M N D , showing increased signal lesions along the corticospinal tract, f r o m the cortex to the spinal cord, seem to support this suggestion. These findings are in accordance with pathological studies that show pyramidal tract degeneration and loss of the Betz cells in M N D . Some of them point even to a wider distribution of lesions [1, 3, 4, 12-15]. Two patients with PBP and one with ALS had hyperintense lesions outside the corticospinal pathways. It seems only speculative that those lesions outside the pyramidal tract might correspond to axonal degeneration and secondary demyelination in other pathways in the CNS, as they also occurred in 7 individuals of the control group. Periventricular bright spots in T2-weighted M R I of the brain have been reported in different diseases, such as multiple sclerosis, vascular disorders, obstructive and normal-pressure hydrocephalus, dementia, and elderly patients without dementia [5, 7, 9-11]. Also, 78.5% of patients older than 50 years with cerebrovascular risk factors and symptoms had similar lesions, and even asymptomatic individuals in the same age group have identical M R I abnormalities [5]. Thus, it seems to us legitimate to consider two patterns of images in this study: the periventricular and subcortical small bright spots and the hyperintense lesions along the corticospinal pathways. The f o r m e r appear to be non-specific and were present in both patients and controls; the latter appear to be specific, as M R I did not reveal those abnormalities in the control group. A technical point is important. While in the previous study [6] the reconstruction images were obtained in the axial plane and m a y cause confusion with multiple sclerosis, ours included the coronal plane, which is the best orientation to study the corticospinal tract at all levels f r o m the cortex to the brainstem and cord.
Why some patients have M R I abnormalities and others do not remains unknown. We did not find any relationship between M R I abnormalities and the duration of illness similar to the findings in pathological studies [3]; nevertheless, they m a y be related to the severity of the pyramidal tract degeneration. Although u p p e r m o t o r neuron degeneration is present at autopsy of some patients with P M A [16], ours had no M R I abnormality in accordance with the predominant involvement of the lower m o t o r neuron. We think that the hyperintense images along the pyramidal tract in M N D m a y correspond to the degenerative process of the upper m o t o r neuron, since M R I can demonstrate Wallerian degeneration of the peripheral [8] and central nervous system [2]. F u r t h e r m o r e , M R I seems to have sensitivity and pathoanatomical specificity in diagnosing such lesions, and we suppose that in the future it m a y have a potential role in evaluating patients with primary lateral sclerosis or PBP in w h o m the diagnosis is uncertain. It m a y also allow the visualization of m o t o r and perhaps n o n - m o t o r localizations of other "degenerative" processes, such as multiple system atrophies.
References 1. Brownell B, Oppenheimer DR, Hughes JT (1970) The central nervous system in motor neuron disease. J Neurol Neurosurg Psychiatry 33 : 338-357 2. Cobb SR, Mehringer CM (1987) Wallerian degeneration in a patient with Schilder disease: magnetic resonance imaging demonstration. Radiology 162 : 521-522 3. Davison C (1941) Amyotrophic lateral sclerosis: origin and extent of the upper motor neuron lesion. Arch Neurol Psychiatry 46: 1039-1056 4. Dyck PJ, Stevens JC, Mulder DW, Espinosa R (1975) Frequency of nerve fiber degeneration of peripheral motor and sensory neurons in amyotrophic lateral sclerosis. Neurology 25 : 781-785 5. Gerard G, Weisberg LA (1986) MRI periventricular lesions in adults. Neurology 36:998-1001
474 6. Goodin DS, Rowley HA, Olney RK (1988) Magnetic resonance imaging in amyotrophic lateral sclerosis. Ann Neurol 23 : 418-420 7. Johnson KA, Doris KR, Buonanno F, Brady T J, Rosen J. Grawdon JH (1987) Comparison of magnetic resonance and Roentgen ray computed tomography in dementia. Arch Neurol 44:1075-t080 8. Jolesz FA, Polak JF, Ruenzel PW, Adams DF (1984) Wallerian degeneration demonstrated by magnetic resonance: spectroscopic measurement of peripheral nerves. Radiology 152 : 85-87 9. Kertesz A, Black SE, Nicholson I_, Carr T (1987) The sensitivity and specificity of MRI in stroke. Neurology 37:1580-1585 10. Kertesz A, Black SE, Tokar G, Benke T, Carr T, Nicholson L (1988) Periventricular and subcortical hyperintensities on magnetic resonance imaging. Arch Neurol 45 : 404-408 ! 1. Lukes SA, Crooks LE, Aminoff M J, Kaufman L, Panitch HS, Mills C, Norman D (1983) Nuclear magnetic resonance imaging in multiple sclerosis. Ann Neurol 13 : 592-601
12. Rowland EP (1988) Research progress in motor neuron diseases. Rev Neurol (Paris) 144:623-629 13. Smith MC (1960) Nerve fibre degeneration in the brain in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 23 : 269-282 14. Tandan R, Bradley WG (1985) Amyotrophic lateral sclerosis. I. Clinical features, pathology and ethical issues in management. Ann Neurol 18:271-280 15. Tohgi H, Tsukagoshi H, Toyokura Y (1977) Quantitative changes of sural nerves in various neurological diseases. Acta Neuropathol (Berl) 38 : 95-101 16. Udaka F, Kameyama M, Tomonaga M (1986) Degeneration of Betz cells in motor neuron disease. A Golgi study. Acta Neuropathol (Berl) 70 : 289-295
Journal of
Neurology
© Springer-Verlag 1990
Magnetic resonance imaging in motor neuron disease M. L. Sales Luls 1'2, A. Hormigo 2, C. Maurlcio 3, M.M. Alves 2, and R. Serräo 2 1Department of Neurology, Hospital de Santa Maria, ŒCentro de Estudos Egas Moniz, Faculdade de Medicina de Lisboa, and ~Laboratório de Ressonän¢ia Magnética, Lisboa, Portugal Received April 4, 1990 / Accepted September 3, 1990
Summary. Magnetic resonance imaging (MRI) of the brain was evaluated in 20 patients with m o t o r neuron disease ( M N D ) and in a control group of 11 healthy people. Bilateral increased signal areas of various sizes in the centrum semiovale, corona radiata, intern al capsule, pedunculi of midbrain, pons, medulla and even in the frontal lobe, topographically related with the corticospinal tract, were found in 8 out of 20 patients. T h r e e out of 4 patients with progressive bulbar paralisis and 5 out of 11 cases of amyotrophic lateral sclerosis had abnormal M R I . Such M R I abnormalities have neither been found in patients with progressive muscular atrophy nor in controls, suggesting that they m ä y be the hallmark of pyramidal tract degeneration in m o t o r neuron disease.
and sensory conduction velocities, high-fibre density and jitter values on single-fibre EMG. All had normal blood lead and hexosaminidase A levels; those undergoing lumbar puncture had a normal biochemical and immunoelectrophoretic spinal-fluid profile, None of the patients had symptoms or risk factors for cardiac and cerebrovascular disease. Patients with associated disorders were excluded. Eleven normal volunteers constituted the control group, 7 men and 4 women, aged from 45 to 74 years (mean 60.1). MRI was performed with a Signa-GE superconducting magnet operating a 1.5 tesla. The data acquisition matrices were 256 × 256; pixel size was 0.9 x0.9mm, with reconstruction of 5-mm-thick slices. The technique included spin-echo and gradient-echo using a repetition time (TR) of 2000-2600 ms and an echo time (TE) of 20-30 ms to 100 ms with proton density and T2-weighted images.
Results Key words: A m y o t r o p h i c lateral sclerosis - Progressive muscular atrophy - Bulbar palsy - Magnetic resonance imaging
Introduction The inability to study in vivo the anatomical localization and the pathophysiological mechanism of degeneration of the central nervous system (CNS) in m o t o r neuron disease ( M N D ) led us to asses M R I in 20 patients with this disorder.
Patients and methods Twenty patients were studied: 11 men and 9 women, aged from 38 to 78 years (mean 57.6) with different clinical forms of MND. These included progressive muscular atrophy (PMA: 5), progressive bulbar paralysis (PBP: 4) and amytrophic lateral sclerosis (ALS: 11 patients). Symptoms had been present for 1 to 10 years, the shorter evolution of PBP being 1 to 2 years. The diagnosis of MND was established from the history, physical examinafion and electromyography (EMG). All the patients had diffuse electromyographic neurogenic patterns, normal motor Offprint requests to: M. L. Sales Luis, Servi9o de Neurologia, Hospital de Santa Maria, Av. Prof. Egas Moniz, P 1600 Lisboa, Portugal
Patients MRI abnormalities along the pyramidal tract. In eight out of the 20 patients, M R I abnormalities were found. A m o n g the 15 patients with clinical pyramidal signs (ALS and PBP), 3 out of 4 with P B P and 5 out of 11 with A L S had abnormal M R I . The clinical features and description of M R I of the positive cases are presented in Tables 1 and 2, respectively. Other MRI abnorrnalities. One patient with PBP had only cortical atrophy. In 6 patients with ALS, two had slight cortical atrophy, one had a single oval increased signal area in the right anterior periventricular white matter and another had multiple, small subcortical foci. Patients with P M A had normal M R I with m o d e r a t e cortical atrophy in two. Controls A m o n g the 11 healthy volunteers, 4 had completely normal M R I . Seven had small bright spots, located in the periventricular region, basal ganglia and subcortical white matter. All these foci were few in number, smaU and discrete, with a completely distinct localization comparable with the characteristic images found in the patient group.
472
Table 1. Clinical features of patients Patients no., sex, age (ycars)
Agc of onset (years)
Duration (years)
Initial s y m p t o m s
UMN signs
LMN signs
Bulbar signs
Clinical form of M N D
ALS
I, F, 38
36
2
LL paralysis
+
+
+
2, F, 53
50
3
LLL paralysis
+
+
+
ALS
3, F, 49
47
2
R H paralysis
+
+
+
ALS ALS
4, F, 65
63
2
R L L paralysis
+
+
+
5, M, 49
41
8
LL paralysis
+
+
+
ALS
6, M, 68
65
3
Dysarthria, dysphagia
+
+
+
PBP
7, M, 46
44
1,5
D y s a r t h r i m dysphagia
+
+
+
PBP
8, F, 75
73
1,5
Dysarthria, dysphagia
+
+
+
PBP
U M N , U p p e r m o t o r n e u r o n : LMN, lower m o t o r n e u r o n ; LL, lower limbs: LLL, left lower limb; R H , right hand: RLL, right lower limb
Table 2. Locatization of hyperintense lesions Patient
Subcortical frontal region
Centrum semiovale
Corona radiata
÷
+
+
+
+
+
2 (Fig. 3)
+
+
+
+
+
-
-
3
-
+
+
+
+
.
4
-
-
-
+
+
-
5
-
+
+
+
+
-
-
-
6 (Figs. 4 and 5)
-
+
+
+
+
+
+
-
1 (Figs. 1 and 2)
Internal capsule
Basis pedunculi
Medulla oblongata
.
Spinal cord
.
Others
. -
7
-
+
+
+
+
-
-
+
8
-
+
+
+
+
-
-
+ (Subcortical and periventricular)
Fig. 1. Patient i. M R I coronal scan with T R - 2600 T E = 80 ms, s h o w i n g n e b u l a r h y p e r i n t e n s e lesions in the c e n t r u m semiovale, c o r o n a radiata (upper arrow). H y p e r i n t e n s e b a n d s in the imernal capsules and midbrain (lower arrows) Fig. 2. Patient 1. M R I coronal scan, T R = 2600 T E = 30 ms, showing a h y p e r i n t e n s e b a n d in the medulla oblongata and spinal cord
(Periventricular)
Fig.3, Patient 2. M R I coronal scan, T R = 2000 T E - 100 ms. Nebula hyperintensity is s h o w n in the subcortical regions of the m o t o r cortex, centrum semiovale and corona radiata (upper arrow), with a hyperintense b a n d in the internal capsules and p e d u n c u l a r pyramidal tract
473
Fig. 4. Patient 6. MRI coronal scan (TR = 2000 TE = 80 ms) showing nebular hyperintensity in the centrum semiovale and corona radiata (upper arrow) and hyperintense bands in the internal capsule and cerebral peduncular pyramidal tract Fig. 5. Patient 6. MRI coronal scan (TR = 2000 TE = 30 ms) showing hyperintense bands in the pyramidal tract through the pons, medulla oblongata and spinal cord (arrow)
Discussion While we were conducting our study, abnormal M R I was reported in 2 patients with A L S [6]. According to these authors, this m a y indicate lesions of the corticospinal tract. The M R I s of 8 of our patients with M N D , showing increased signal lesions along the corticospinal tract, f r o m the cortex to the spinal cord, seem to support this suggestion. These findings are in accordance with pathological studies that show pyramidal tract degeneration and loss of the Betz cells in M N D . Some of them point even to a wider distribution of lesions [1, 3, 4, 12-15]. Two patients with PBP and one with ALS had hyperintense lesions outside the corticospinal pathways. It seems only speculative that those lesions outside the pyramidal tract might correspond to axonal degeneration and secondary demyelination in other pathways in the CNS, as they also occurred in 7 individuals of the control group. Periventricular bright spots in T2-weighted M R I of the brain have been reported in different diseases, such as multiple sclerosis, vascular disorders, obstructive and normal-pressure hydrocephalus, dementia, and elderly patients without dementia [5, 7, 9-11]. Also, 78.5% of patients older than 50 years with cerebrovascular risk factors and symptoms had similar lesions, and even asymptomatic individuals in the same age group have identical M R I abnormalities [5]. Thus, it seems to us legitimate to consider two patterns of images in this study: the periventricular and subcortical small bright spots and the hyperintense lesions along the corticospinal pathways. The f o r m e r appear to be non-specific and were present in both patients and controls; the latter appear to be specific, as M R I did not reveal those abnormalities in the control group. A technical point is important. While in the previous study [6] the reconstruction images were obtained in the axial plane and m a y cause confusion with multiple sclerosis, ours included the coronal plane, which is the best orientation to study the corticospinal tract at all levels f r o m the cortex to the brainstem and cord.
Why some patients have M R I abnormalities and others do not remains unknown. We did not find any relationship between M R I abnormalities and the duration of illness similar to the findings in pathological studies [3]; nevertheless, they m a y be related to the severity of the pyramidal tract degeneration. Although u p p e r m o t o r neuron degeneration is present at autopsy of some patients with P M A [16], ours had no M R I abnormality in accordance with the predominant involvement of the lower m o t o r neuron. We think that the hyperintense images along the pyramidal tract in M N D m a y correspond to the degenerative process of the upper m o t o r neuron, since M R I can demonstrate Wallerian degeneration of the peripheral [8] and central nervous system [2]. F u r t h e r m o r e , M R I seems to have sensitivity and pathoanatomical specificity in diagnosing such lesions, and we suppose that in the future it m a y have a potential role in evaluating patients with primary lateral sclerosis or PBP in w h o m the diagnosis is uncertain. It m a y also allow the visualization of m o t o r and perhaps n o n - m o t o r localizations of other "degenerative" processes, such as multiple system atrophies.
References 1. Brownell B, Oppenheimer DR, Hughes JT (1970) The central nervous system in motor neuron disease. J Neurol Neurosurg Psychiatry 33 : 338-357 2. Cobb SR, Mehringer CM (1987) Wallerian degeneration in a patient with Schilder disease: magnetic resonance imaging demonstration. Radiology 162 : 521-522 3. Davison C (1941) Amyotrophic lateral sclerosis: origin and extent of the upper motor neuron lesion. Arch Neurol Psychiatry 46: 1039-1056 4. Dyck PJ, Stevens JC, Mulder DW, Espinosa R (1975) Frequency of nerve fiber degeneration of peripheral motor and sensory neurons in amyotrophic lateral sclerosis. Neurology 25 : 781-785 5. Gerard G, Weisberg LA (1986) MRI periventricular lesions in adults. Neurology 36:998-1001
474 6. Goodin DS, Rowley HA, Olney RK (1988) Magnetic resonance imaging in amyotrophic lateral sclerosis. Ann Neurol 23 : 418-420 7. Johnson KA, Doris KR, Buonanno F, Brady T J, Rosen J. Grawdon JH (1987) Comparison of magnetic resonance and Roentgen ray computed tomography in dementia. Arch Neurol 44:1075-t080 8. Jolesz FA, Polak JF, Ruenzel PW, Adams DF (1984) Wallerian degeneration demonstrated by magnetic resonance: spectroscopic measurement of peripheral nerves. Radiology 152 : 85-87 9. Kertesz A, Black SE, Nicholson I_, Carr T (1987) The sensitivity and specificity of MRI in stroke. Neurology 37:1580-1585 10. Kertesz A, Black SE, Tokar G, Benke T, Carr T, Nicholson L (1988) Periventricular and subcortical hyperintensities on magnetic resonance imaging. Arch Neurol 45 : 404-408 ! 1. Lukes SA, Crooks LE, Aminoff M J, Kaufman L, Panitch HS, Mills C, Norman D (1983) Nuclear magnetic resonance imaging in multiple sclerosis. Ann Neurol 13 : 592-601
12. Rowland EP (1988) Research progress in motor neuron diseases. Rev Neurol (Paris) 144:623-629 13. Smith MC (1960) Nerve fibre degeneration in the brain in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 23 : 269-282 14. Tandan R, Bradley WG (1985) Amyotrophic lateral sclerosis. I. Clinical features, pathology and ethical issues in management. Ann Neurol 18:271-280 15. Tohgi H, Tsukagoshi H, Toyokura Y (1977) Quantitative changes of sural nerves in various neurological diseases. Acta Neuropathol (Berl) 38 : 95-101 16. Udaka F, Kameyama M, Tomonaga M (1986) Degeneration of Betz cells in motor neuron disease. A Golgi study. Acta Neuropathol (Berl) 70 : 289-295
