Magnetic Resonance Imaging 24 (2006) 173 – 179

Amyotrophic lateral sclerosis with predominant pyramidal

signs—early diagnosis by magnetic resonance imaging
Sunil Pradhana,4, Ramakant Yadava, Vijay Nath Mishraa,
Kaustubh Aurangabadkara, Vijay Sawlanib
a
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India
b
Department of Radiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India
Received 20 September 2005; revised 16 October 2005; accepted 16 October 2005

Abstract
Objective: To evaluate the role of magnetic resonance imaging (MRI) in the early diagnosis of amyotrophic lateral sclerosis (ALS) with
predominant upper motor neuron (UMN) signs in the initial stage of the disease.
Patients and Method: Two patients with ALS were found to have spastic quadriparesis with no wasting or fasciculation in the limbs in the
early stage of the disease. Both were subjected to MRI of the head and cervical spine to look for any specific diagnostic feature. Both of them
were followed with clinical evaluation and electroneuromyography (ENMG) for the definitive diagnosis of ALS.
Results: Magnetic resonance imaging showed selective degeneration of the pyramidal tracts in the contiguous axial cuts from subcortical
white matter to cerebral peduncles. The finding was more visible in the coronal section. In addition, there was T1 hyperintensity visible along
the anterior aspect of the spinal cord in the cervical region. These findings were suggestive of ALS, the diagnosis that was subsequently
confirmed by serial clinical follow-up and ENMG.
Conclusion: It is difficult to diagnose ALS in the early stage of the disease especially if the pyramidal signs predominate over the lower
motor neuron (LMN) signs; MRI might be useful in such cases.
D 2006 Elsevier Inc. All rights reserved.
Keywords: Amyotrophic lateral sclerosis; Motor neuron disease; Magnetic resonance imaging; Primary lateral sclerosis; Pyramidal tracts

1. Introduction slow and late in PMA. In the PLS form of MND, UMN
signs continue to predominate for a long period before the
Motor neuron disease (MND) is a degenerative disease of
appearance of LMN signs (fasciculation and wasting of
the motor neurons in which the upper as well as the lower
muscles), and the diagnosis of MND is difficult during the
motor neurons (LMNs) are involved almost exclusively.
stage of pure UMN signs. This is more so because of the
Motor neuron disease may manifest with pure upper motor
fact that there is no diagnostic test available for MND, and a
neuron (UMN) degeneration as seen in primary lateral
lot depends on electroneuromyography (ENMG), which
sclerosis (PLS), pure spinal LMN degeneration as seen in
helps in the diagnosis only when LMN signs are present.
progressive muscular atrophy (PMA), pure bulbar LMN
Observing muscle wasting and fasciculation in the limbs
degeneration as seen in progressive bulbar palsy (PBP) or a
that are spastic and hyperreflexic but with no sensory loss
combination of all the three as seen in the most common
suggests the diagnosis of ALS [1]. Clinical diagnosis of
form, amyotrophic lateral sclerosis (ALS) [1,2]. The clinical
ALS is easy when LMN signs are seen in combination with
presentation is highly variable. While the PBP of all patients
UMN signs but becomes extremely difficult in some rare
rapidly progresses to ALS, development of UMN signs is
cases with almost exclusive UMN signs in the beginning
[3]. We report two cases of ALS who had no wasting or
4 Corresponding author. Tel.: +91 522 2668700x2171; fax: +91 522
fasciculation in the initial stage of the disease and in whom
2668017. pyramidal signs continued to predominate the clinical
E-mail address: spradhan@sgpgi.ac.in (S. Pradhan). picture in the form of PLS for a long period. The diagnosis
0730-725X/$ – see front matter D 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.mri.2005.10.003
174 S. Pradhan et al. / Magnetic Resonance Imaging 24 (2006) 173 – 179

was suspected on the basis of MRI features suggestive of
corticospinal tract degeneration and further confirmed on
serial clinical examination and ENMG.
2. Patients and methods
During the routine clinical screening of patients with
MND, two patients were found in previous one year to have
spastic dysarthria and UMN type quadriparesis as initial
presenting features. At this stage of the disease, there was no
other clue to suspect MND as there was no LMN sign in the
extremities, and ENMG showed no fibrillation or fascicu-
lation potential. Both patients were subjected to craniospinal
MRI to know the cause of spastic bulbar and spinal
symptoms and signs.
Conventional spin echo proton density, T2- (TR/TE 1,2/
n =2200/12,80/1) and T1-weighted MRI (1000/15/2) were
performed in axial plane using 192256 matrix, 0.5 inter-
slice gap and 5 mm slice thickness. T1-weighted magneti-
zation transfer spin echo MRI was also performed with
exactly the same parameters as for T1 except for the off-
resonance pulse. Any abnormal signal seen on MRI was

Fig. 1. T2-weighted serial axial MR images of the brain of patient 1 at the level of the internal capsule (A, B) showing oval hyperintense signals in the posterior
part of the posterior limb of the internal capsule, suggesting degeneration of the corticospinal tracts also traceable in axial sections through cerebral peduncles in
the upper mid brain (C) and in the lower pons (D).
 S. Pradhan et al. / Magnetic Resonance Imaging 24 (2006) 173 – 179
noted down for correlation with existing knowledge about
such change.
Both patients were managed conservatively after find-
ing no organic cause of the disease. They were followed
up at two monthly intervals for any change in the clinical
profile of the disease or appearance of any diagnostic
ENMG feature.
3. Results and case reports
One of the patients was followed for 14 months and the
other for 4 years. On initial examination, both showed only
Fig. 2. T2-weighted (A) and PD-weighted (B) coronal MR images of
patient 1 showing linear hyperintense signals along the corticospinal tracts,
suggesting degeneration of these tracts in the internal capsule.
175
Fig. 3. T1-weighted axial MR image of patient 1 through the upper cervical
cord showing hyperintensity in the anterolateral columns.
the UMN signs involving bulbar and spinal regions.
Magnetic resonance imaging performed at this stage showed
evidence of pyramidal tract degeneration that could be
traced from corona radiata to cerebral peduncles. There was
also evidence of disease in the anterolateral columns in the
cervical spinal cord. In the follow-up, both patients
continued to have pure UMN features for 8 and 6 months.
Following that, the LMN signs started appearing in the
form of wasting of the small muscles of the hand and
fasciculations in all the extremities. Electroneuromyography
done at this stage showed evidence of widespread fibrilla-
tion and fasciculation in most of the limb muscles. There
were no sensory sign and symptoms, and sensory nerve
conduction studies were normal. This strongly suggested
MND. Further follow-up showed relentlessly downhill
course with further deterioration of the condition. Details
of the two cases are given below.
3.1. Case 1
A 56-year-old woman from Uttar Pradesh province of
India presented with 6 months’ history of gradually progres-
sive stiffness and weakness of all the four limbs without
sensory dysfunction. The problem started with difficulty in
walking. Initially, there was inability to clear the toes off the
ground, and, later on, there was bilateral circumduction
during walking. Paresthesia or numbness was never experi-
enced. Bladder and bowel habits remained normal. Her
speech had spastic slurring. She could walk with support with
spastic gait. Memory, intelligence and other cognitive
functions were normal. Gag reflex and jaw jerk were brisk.
Muscle power was grade 2 –3 in the lower limbs and grade 4
in the upper limbs on 0 –5 MRC scale. Weakness was uniform
in the upper limbs, but in the lower limbs, distal muscles were
weaker than the proximal. There was no wasting of muscles,
and fasciculations were not visible. All the limbs were
moderately spastic. Deep tendon reflexes were generally
176 S. Pradhan et al. / Magnetic Resonance Imaging 24 (2006) 173 – 179

brisk, and the plantar response was bilaterally extensor.
Abdominal reflex was absent. Further examination did not
reveal any sensory or autonomic abnormality.
Her hemogram and routine biochemical investigations
were normal. Electroneuromyography done at this stage
showed normal sensory and motor conduction studies,
including normal amplitudes of compound muscle action
potentials. There was no electromyographic evidence of
spontaneous activity in the muscles at rest and on effort;
motor unit potentials were normal. Cranial MRI showed
normal cerebral and cerebellar cortex but round hyperin-
tense lesions bilaterally in the posterior limbs of the internal
capsules on T2-weighted image. These hyperintense lesions
could be traced to the same spot in all the contiguous sec-
tions of the brain at the level of the internal capsule (Fig. 1A
and B) and then down to the lateral parts of cerebral
peduncles (Fig. 1C) and pons (Fig. 1D). These findings
were suggestive of corticospinal tract degeneration as seen
in ALS. In coronal section, corticospinal tracts were visible
as hyperintense on T2-weighted (Fig. 2A) and PD (Fig. 2B)

Fig. 4. T2-weighted serial axial MR images of the brain of patient 2 at the level of the lower part of corona radiata close to the internal capsule (A); upper and
lower segments of the posterior limb of the internal capsule (B and C) showing oval hyperintense signals on T2-weighted image. This degeneration of the
corticospinal tracts was also traceable in axial section through the lateral part of cerebral peduncles (D).
 S. Pradhan et al. / Magnetic Resonance Imaging 24 (2006) 173 – 179
images in sections through the posterior limb of the internal
capsule. Magnetic resonance imaging of the cervical spine
showed normal findings on T2-weighted and proton-density
(PD) images, but there were hyperintensities in the antero-
lateral columns of the spinal cord in axial section on T1-
weighted image (Fig. 3).
Subsequently, routine examinations were carried out at
about two monthly intervals. After 8 months, wasting was
Fig. 5. T2-weighted (A) and PD-weighted (B) coronal MR images of
patient 2, showing hour glass-type linear hyperintense signals along
the corticospinal tracts, suggesting degeneration of these tracts in the in-
ternal capsule.
177
Fig. 6. T1-weighted axial MR image of patient 2 through the upper cervical
cord showing hyperintensity in the anterolateral columns.
noticed in the distal muscles that were more marked in the
upper limbs. Fasciculations gradually appeared in all the
limb muscles as well as truncal muscles. The weakness
increased further in the next 6 months to the extent that she
could barely walk with support. Nerve conduction study and
electromyography of the upper and lower limb muscles
were performed again. Sensory nerve conduction study
showed normal findings. Motor conduction studies showed
decreased amplitudes of compound motor action potentials
with borderline normal conduction velocities. Electromy-
ography showed spontaneous activity in the form of posi-
tive sharp waves and fibrillation potentials. Fasciculations
were visible in different muscles but were infrequent.
Pseudomyotonic discharges could be observed in some
of the muscles. On mild effort, there was increased pro-
portion of large amplitude and long duration motor unit
potentials, suggesting denervation with chronic reinnerva-
tion. Recruitment was incomplete. These findings were
consistent with LMN degeneration at the anterior horn
cell level.
The patient was treated conservatively and showed no
improvement and rather a slight deterioration during the
further 6 months of follow-up.
3.2. Case 2
A 43-year-old housewife from Uttar Pradesh province
of India presented with progressive dysarthria and difficulty
in walking for 10 months. Illness started with insidious
onset spastic weakness of the right side, which progressed to
the left side over a period of 4 months. She also noticed
slurring of speech at that time. Fatigue and generalized
weakness progressed for 2 years with no problem in
swallowing semisolid and liquid items. There was no nasal
regurgitation. Bladder and bowel movements were normal.
178 S. Pradhan et al. / Magnetic Resonance Imaging 24 (2006) 173 – 179
Examination revealed normal higher mental functions.
Cranial nerves were normal with no atrophy or fascicula-
tions in the tongue. Gag reflex and jaw jerk were increased.
There was spastic quadriparesis with power grade 3+ to 4 on
0–5 MRC scale. All deep tendon reflexes were brisk, and
both plantars were extensor. Frontal lobe release signs and
cerebellar signs were absent. However, she had mild
pseudobulbar affect. At this stage of the disease, there was
no wasting of proximal or distal group of muscles. Nerve
conduction study showed no abnormality, and electromy-
ography showed no denervation potential or fasciculation.
Some large amplitude (5– 8 mV) and long duration (8 –12
ms) polyphasic motor unit potentials were observed in small
muscles of the hand, but their proportion was less than 20%
and these were passed on as normal variation. Magnetic
resonance imaging of the brain showed hyperintensities
along the pyramidal tracts on T2- and PD-weighted images
similar to Case 1. The hyperintense signal could be seen in
the lower part of corona radiata (Fig. 4A), posterior limb of
the internal capsule (Fig. 4B and C) and lateral parts of the
cerebral peduncles (Fig. 4D). The pyramidal tract degener-
ation was more visible in the coronal section on T2 (Fig. 5A)
and PD (Fig. 5B) sequences. Brain stem appeared normal.
In the upper cervical cord, axial section showed hyper-
intensities in the anterolateral columns on T1 (Fig. 6). The
patient was prescribed conservative treatment, but the
symptoms gradually increased in severity. For the next
6 months, she continued to have only pyramidal signs
consistent with the diagnosis of PLS. Thereafter, she had
great difficulty in walking, getting up from squatting
position and eating with her hands. Examination done at
this stage showed wasting in small muscles of the hand,
fasciculation in all limb muscles, slight wasting and
fasciculation in the tongue and increase in the severity of
the pyramidal signs. Electromyography done at this stage of
the disease showed evidence of acute denervation and
reinnervation along with fasciculation potentials. These
findings suggested ALS. There was slow progression of
the disease in the next 1.5 years of follow-up.
4. Discussion
These two cases highlight the importance of MRI in the
diagnosis of those rare patients with ALS in whom wasting
and fasciculation are absent in the early stage of the
disease, and the clinical presentation is predominantly with
pseudobulbar palsy and spastic quadriparesis (PLS). This
is in contrast to the current practice of neuroimaging in
ALS in which the MRI is done essentially to exclude other
differential pathological conditions.
In the previous few years, several novel MRI features have
been described in ALS. The most important and consistent
finding is the degeneration of corticospinal tracts visible as
hyperintense signal on T2- and PD-weighted images [4 –7].
Clinical correlation of this MR finding is necessary because
22% of the normal controls in one study and 78% of the
normal controls in another study also had similar findings
when age-matched elderly controls were studied [8,9].
Large, round, hyperintense signals with high T2 values on
grading, visible bilaterally in several slices along the
pyramidal tracts, as were seen in our case, are more typical
of ALS [6,9]. However, other authors have contradicted this
observation and found no difference on T2 quantitation
between ALS patients and controls of different ages [10]. It
has also been observed that hyperintensity in the cortico-
spinal tracts on proton density images, as was visible in our
cases, is more specific for ALS as compared to controls
[6,10]. This hyperintensity on T2 and PD sequences suggests
axon lysis and myelin degradation into proteins and lipids
with local release of water contents. From these studies,
one can infer that this MRI finding should not be read in
isolation, and a good clinical correlation is needed to
interpret it as suggestive of ALS. In this regard, our
patients with mainly UMN syndrome correlate well with
the MRI findings. Apart from high signal changes in the
corticospinal tracts, T2 hypointense lesions have also been
described in the pre-central motor cortex of ALS patients
[6]. This finding was absent in our cases, and various
authors have doubted the utility of this finding due to its
presence in several normal controls and its absence in
several ALS patients [8,11]. Some authors have also
described atrophy of the superior parietal gyrus [9], but
this was not observed by other authors and was not seen in
our cases as well. Another abnormality described in ALS
is the high signal in the fibres of the corpus callosum on
PD- and T2-weighted spin echo images [12]. We looked
for this finding in our cases in coronal sections but it was
absent. In addition, both of our cases had hyperintense
signals in the anterolateral columns of the cervical spinal
cord on T1-weighted image. This finding possibly indi-
cates early stage of degeneration of pyramidal fibres lying
in these columns, but the possibility of glial proliferation
in the degenerating anterior horn cell region cannot be
ruled out. At the biochemical level, these hyperintensities
would indicate T1-shortening effect due to cellular
oxidative stress with or without the local release of
paramagnetic substances. Other authors have also reported
similar spinal cord findings [13].
The MR findings reported in this paper are some-
what similar to what has been reported in Wallerian
degeneration following insult to cerebral cortex as happens
in strokes and head injuries [14]. In these conditions, the
primary insult is to the ganglionic cells of the gray matter
and there is secondary degeneration of the tracts (axons).
This Wallerian degeneration can be distinguished from
ALS by way of asymmetrical distribution limited to the side
of insult.
In conclusion, MRI may be useful in detecting
degenerative changes in the pyramidal tracts from their
origin in the cerebral cortex to their termination in the
anterolateral columns of the spinal cord. Changes are most
 S. Pradhan et al. / Magnetic Resonance Imaging 24 (2006) 173 – 179
visible at the level of the internal capsule. Proper corre-
lation of these observations with clinical and electromyo-
graphic findings would help in the early diagnosis of these
difficult cases of ALS.
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