Copyright
Blackwell Munksgaard 2003

Acta Neurol Scand 2003: 107: 215220

Printed in UK. All rights reserved

ACTA NEUROLOGICA
SCANDINAVICA
ISSN 0001-6314

Long-term follow-up of 44 patients with

brachial monomelic amyotrophy
Gourie-Devi M, Nalini A. Long-term follow-up of 44 patients with
brachial monomelic amyotrophy.
Acta Neurol Scand 2003: 107: 215220.
Blackwell Munksgaard 2003.
Objectives Monomelic amyotrophy of a single upper limb termed
brachial monomelic amyotrophy (BMMA) is a benign lower motor
neuron disorder in the young, with male preponderance, insidious onset
of atrophy and weakness, electromyographic evidence of neurogenic
pattern without conduction block, slow progression for 24 years
followed by a stationary course. The aim of the study was to determine
whether (i) atrophy and weakness in the aected limb progresses
beyond 5 years; (ii) the illness spreads to the other limbs; and (iii) the
disease progresses to amyotrophic lateral sclerosis. Material and
methods Forty-four patients who had a duration of illness of 5 years
or more at the last follow-up examination were included in the study.
Assessment of symptom prole, neurologic decit and disability was
performed at variable intervals during the follow-up period.
Results Progression of the disease was seen in 37 (84.1%) patients, up
to 5 years in 35 (79.5%), 6 years in one and 8 years in another patient.
In seven patients (15.9%) the atrophy was accidentally noticed and no
further change in the neurologic decit was observed thereafter.
Subsequent to attaining a stationary course, none of the 44 subjects
developed fresh symptoms or signs during a mean follow-up period of
9.7 years (range 2.523). The mean duration of illness at last follow-up
was 12.8 years (range 526.5) and in 22 (50%) subjects the disease
duration was more than 10 years. Seven patients (15.9%) at
presentation had minimal involvement of contralateral upper limb with
gross asymmetry and later one more patient developed similar features.
Thus, in only a small proportion (18.2%) of patients the neurologic
decit had extended beyond the connes of one upper limb. None of the
patients developed involvement of cranial nerves, lower limbs or
pyramidal signs. Conclusions Progression of the neurologic decit in
the aected limb was seen up to 5 years in the majority followed by a
stationary phase with no evidence of fresh neurologic decit during the
follow-up period. Spread to the contralateral upper limb with minimal
neurologic decit was seen in less than a fth of the patients, but
involvement of lower limbs was not observed. BMMA did not evolve to
amyotrophic lateral sclerosis. These observations underscore the benign
and self limiting course of BMMA.

Monomelic amyotrophy (MMA) has been reported chiey from Asia, including Japan (14), India
(59), Sri Lanka (10), Korea (11), Hong Kong (12),
Taiwan (13) and Malaysia (14). Very few cases
have been reported from the western countries
(1518). At the National Institute of Mental
Health and Neurosciences, Bangalore, India,
during a 10-year period from 1973 to 1982, 211
cases of motor neuron disease were seen, with

M. Gourie-Devi, A. Nalini
Department of Neurology, National Institute of Mental
Health and Neurosciences, Bangalore, India

Key words: monomelic amyotrophy; brachial; follow-up

M. Gourie-Devi, Director, Vice Chancellor and Professor
of Neurology, National Institute of Mental Health and
Neurosciences, Bangalore 560029, India
Tel.: 91-80-6564140
Fax: 91-80-6564830
e-mail: mgd@nimhans.kar.nic.in
Accepted for publication August 13, 2002

MMA accounting for 12.8% (19). The characteristic clinical features of this interesting benign
variant of motor neuron disease are young age at
onset, sporadic occurrence, male preponderance,
wasting and weakness conned to a single upper
or lower limb without involvement of cranial
nerves, pyramidal tracts, sensory, cerebellar or
extrapyramidal systems and cortical functions.
Less common features are coldness of hands,
215

Gourie-Devi & Nalini

hyperhidrosis, aggravation of motor symptoms on
exposure to cold and abnormalities of sympathetic
skin response (1, 5, 20). Neurogenic pattern on
electromyography (EMG) and histologic evidence
of neurogenic atrophy suggest anterior horn cell
lesion. The nomenclature of brachial monomelic
amyotrophy (BMMA) is adopted in the present
study to differentiate it from MMA of lower limb.
In the etiopathogenesis of this disorder, viral
infections (21), vascular insufciency of the spinal
cord (22), heavy physical activity (23) and focal
cord atrophy (24, 25) as a result of stretching of the
cord during exion of the neck (26) have been
considered, but as yet there is no convincing
evidence to explain the unique geographic distribution and the predilection to Asians.
In the vast majority, the onset is insidious with a
slow progression over 24 years followed by a
stationary phase. This impression is based on the
analysis of various cross-sectional studies (114).
However, there are no long-term follow-up studies
except for a brief comment by Peires et al. (10) and
a recent report on three patients by Barontini et al.
(27). The concerns in BMMA are, the period of
progression and whether the disease evolves to
amyotrophic lateral sclerosis (ALS).
In the present longitudinal study, we report the
clinical course of 44 patients who had a duration of
illness of 5 years or more. The 5-year limit of
duration was arbitrarily chosen based on the
published reports (2, 7) and our earlier observations (5, 19) that the disease usually remains
stationary beyond 4 years after the onset of symptoms. The objectives of this study are to address
the following aspects: (i) Does wasting and weakness in the affected limb progress beyond 5 years?;
(ii) Does the illness spread to the other limbs? and
(iii) Does the disease progress to involve cranial
nerves, pyramidal tracts and evolve to ALS?

Patients and methods

Inclusion criteria

(i) Insidious onset and slow progression of atrophy weakness of unilateral upper limb in a young
subject; (ii) wasting and weakness of (a) distal
muscles including small muscles of the hand,
forearm exors and extensors or (b) proximal
muscles including triceps, biceps, deltoid, pectoralis, scapular and spinati or (c) both distal and
proximal muscles; (iii) normal or sluggish tendon
reexes; (iv) absence of Homann and Babinski
signs; (v) absence of involvement of cranial nerves,
pyramidal tracts, sensory, cerebellar and extrapyramidal systems; (vi) electroneuromyographic
216

ndings suggestive of neurogenic pattern with no

evidence of conduction block; (vii) absence of a
compressive lesion of the spinal cord, roots, plexus
or intramedullary lesion on radiologic investigations; and (viii) absence of history of residual
decit shortening of the limb following poliomyelitis in childhood.
Electromyography of the aected and unaected
muscles of the involved limb was performed. The
distal and proximal muscles of the other limbs were
also sampled. Motor and sensory conduction studies were performed in all the four limbs with special
care to look for conduction block. Hemogram,
creatine kinase level, liver and renal function tests
were performed. Detailed radiologic investigations
including plain X-ray, myelogram computed
tomography myelogram magnetic resonance imaging were performed to exclude compressive lesions.
The disability consequent to the wasting and
weakness assessed by the activities involving the
atrophied limb including writing, buttoning, mixing
food, breaking chapattis (Indian bread), threading
a needle and stitching, gripping objects and lifting
weights, was graded as none, mild, moderate and
severe. Transfer of activities from the atrophied to
the healthy limb, if present, was recorded.
Follow-up assessment

The 44 patients were assessed at variable intervals.

They either attended the clinic for follow-up or
came in response to letters. The assessment included (i) symptom prole; (ii) the pattern of atrophy
of the muscles; (iii) measurement of the girth of
atrophic and healthy limb for comparison; (iv)
grading of muscle weakness using Medical Research
1 Council (MRC) scoring system; (v) disability; (vi)
detailed examination of other limbs, cranial nerves,
pyramidal, sensory, cerebellar and extra pyramidal
systems.
Progression of the disease was determined by (i)
involvement of new muscle groups; (ii) worsening
of muscle weakness by at least one MRC score; (iii)
decrease in the girth of the limb; and (iv) worsening
of disability or change of limb in carrying out the
activities of daily living. Evidence of spread to other
limbs or involvement of cranial nerves, pyramidal
tracts, sensory, cerebellar or extrapyramidal system
was recorded. Based on these observations the (i)
period of progression and (ii) time taken to attain a
stationary course were determined.
Results

The mean age at onset of 44 patients was

19.8 years with a range of 1332 years. The age

Brachial monomelic amyotrophy long-term follow-up

at onset in 26 (59.1%) patients was between 16 and
20 years and in 10 (22.7%) it was 2125 years;
thus, 82.0% had onset of illness between 16 and
25 years. There were three (6.8%) patients in the
age group of 1115 years and ve (11.4%) between
26 and 32 years. There was a marked preponderance in the males, with a M : F ratio of 10:1. There
was no signicant dierence in the frequency of
right or left upper limb involvement (R)21; L)23).
All were sporadic with no family history of similar
illness. Based on the nature of work, occupation
was categorized as manual or sedentary and it was
observed that 43% were involved in manual work
and 57% were in sedentary jobs.
The duration of illness at presentation ranged
from 3 to 264 months with a mean of 4.1 years.
Further analysis showed that in 11 patients (25%)
the duration of illness was less than 12 months and
in 21 patients (47.7%) it was between 13 and
60 months; thus, 72.7% sought the advice of the
neurologist within 5 years after the onset of symptoms. The remaining 12 patients (27.3%) had
symptoms ranging between 5 and 22 years. In
this group, the limb atrophy was accidentally noted
either by a family member, friend or doctor.
The wasting and weakness involved predominantly the small muscles of the hand and forearm in
the distribution of C8T1 segments in 19 patients
(43.2%). In 24 patients (54.5%) there was evidence
of involvement of distal and proximal muscles and
in 20 of them the distal muscles were more severely
affected than the proximal group; while, in four
patients the proximal muscles were affected to a
greater degree. Only in one (2.3%) patient there
was isolated atrophy and weakness of proximal
muscles. Other features were, irregular coarse
tremors suggestive of minipolymyoclonus (28) in
36 (81.8%), muscle cramps in seven (15.9%),
fasciculations in 21 (47.7%), coldness of hand in
eight (18.2%) and worsening of motor symptoms
on exposure to cold weather or immersion of hands
in cold water in 12 (27.3%) patients. Tendon
reexes were sluggish absent in 16 (36.4%),
normal in 24 (54.5%) and brisk in four (9.1%)
patients.
Clinical examination of the contralateral upper
limb showed that in ve patients (11.4%) there
were minimal neurologic signs of minipolymyoclonus and subtle wasting of small muscles of the
hand in all and minimal weakness in only one
patient. The tendon jerks in the contralateral upper
limbs were normal in 42 (95.5%) and brisk in two
(4.5%). These latter two patients had brisk reexes
in the atrophied upper limb also.
None of the 44 patients had weakness or wasting
of the lower limbs and the tendon reexes were

normal in 41 (93.2%) and brisk in three (6.8%).

These three patients also had brisk reexes in the
atrophied limb. There were no other neurologic
decits.
Electromyography and nerve conduction

Concentric needle EMG of the atrophied limb

showed chronic denervation with motor unit loss
and giant potentials suggesting reinnervation in all.
Acute denervation as seen by presence of brillations and positive sharp waves was observed in 20
(45.5%) patients. Motor and sensory nerve conduction studies did not show evidence of conduction block or any other abnormality. EMG of the
contralateral upper limb showed neurogenic pattern in seven patients (15.9%), acute denervation in
ve and chronic denervation of the small muscles
of the hand in all seven patients. Five of these seven
patients had clinical features. EMG of the lower
limbs in all 44 patients was normal, as also nerve
conduction studies in the contralateral upper limb
and both the lower limbs.
Course of illness

The atrophy and weakness had slowly progressed

in 37 (84.1%) and in the remaining seven patients
(15.9%) there was no change after the decit was
accidentally noticed. Of the 37 patients the progression was observed for 2 years in 26 (70.3%),
5 years in nine patients (24.3%) and only in two
the progression continued for 6 and 8 years. Thus
in 35 patients (94.6%) the illness attained a
stationary phase by the end of 5 years.
Disability

The disability was mild in 30 (68.2%), moderate in

10 (22.7%) and severe in two (4.5%) patients,
while in the remaining two patients there was no
disability. Because of disability, three patients (two
with severe and one with moderate degree) were
compelled to use the unaected limb for the
activities earlier performed by the atrophied limb.
Follow-up assessment

The mean period of follow-up was 9.7 years with a

range of 2.523 years. Thirty patients (68.2%) had
a follow-up of more than 10 years and seven of
these for more than 20 years. Eight patients
(18.2%) had a follow-up of 510 years and six
patients (13.6%) 25 years. During the follow-up
period there was no evidence of fresh neurologic
decit or worsening of disability of the aected
217

Gourie-Devi & Nalini

limb after having attained a stationary course. The
mean period of stationary phase was 10.8 years
(range 125.5). In 39 patients (88.6%) the stationary phase was more than 5 years and in 18
(40.9%) of them it was more than 10 years. The
mean duration of the disease as on last follow-up
was 12.8 years (range 526.5). In 22 (50.0%)
patients it was between 5 and 10 years, in 14
(31.8%) from 10 to 20, and in eight (18.2%) more
than 20 years.
In addition to the ve patients who had minimal
clinical involvement of contralateral upper limb
and EMG evidence of neurogenic pattern, three
others developed fresh evidence of minimal atrophy and minipolymyoclonus. Interestingly, two of
these latter three patients had EMG evidence of
neurogenic pattern at the initial assessment. One
of the ve patients who had contralateral limb
involvement at presentation showed slight progression of the symptoms while in the other four the
disease was stationary. Thus, as on the last followup assessment, in eight (18.2%) of 44 patients there
was evidence of minimal involvement of the
contralateral upper limb. It needs to be emphasized
that there was gross asymmetry in all these
patients. However, there was no evidence of
spread to involve the lower limbs or other parts
of the nervous system.
A special mention needs to be made of the four
patients with brisk reexes in the aected upper
limb, two of whom also had brisk reexes in the
contralateral upper limb and three in both lower
limbs. The mean follow-up period was 12.9 years
(range 8.620) and the mean duration was
14.9 years (range 622). There was no progression
of neurologic decit nor was there appearance of
fresh neurologic signs. These four patients with
brisk tendon reexes did not develop ALS, thus the
outcome was similar to the patients with sluggish
or normal reexes.
Discussion

The benign nature of MMA, the lack of spread to

the other limbs in the majority of patients and the
restriction of the disease process to the lower
motor neurons has been emphasized. These aforesaid observations are essentially based on crosssectional studies reported chiey from Japan and
India (19). Recognizing the need for a follow-up
study for validation, we analyzed the data of 44
patients of BMMA, who had a duration of illness
of 5 or more years. As it is reported from the
literature that the disease slowly progresses over
24 years followed by a stationary course, the
5-year period was arbitrarily chosen as a cut-off
218

limit (2, 5, 10). Of the 44 patients, the progression

of atrophy, weakness and disability was observed
in 37 patients and in 35 of them the disease ceased
to progress beyond 5 years. Even in the two
patients who continued to progress after 5 years,
stationary phase was attained by the end of 6 and
8 years. It is noteworthy that in seven patients
there was no change after the neurologic decit was
accidentally observed.
After attaining a stationary course none developed fresh symptoms or signs during the mean
follow-up period of 9.7 years. It is noteworthy that
even the 30 patients who had a long period of
follow-up of 1030 years did not develop any late
progression of the decit. In our study, only 4.5%
(two patients) progressed beyond 5 years which is
comparable with the gure of 5% (one of 20)
reported by Hirayama et al. (2). Singh et al. (7)
did not observe progression beyond 5 years in all
their 24 patients. However, in the series reported
by Sobue et al. (4) (nine of 71, 12.7%) and Peires
et al. (10) (26 of 102, 25%), a larger number had
disease progression beyond 5 years. In these two
reports, patients with bilateral involvement, either
symmetrical or asymmetrical, formed a signicant
proportion of the series and therefore do not
strictly conform to the clinical description of
MMA. The variation in the clinical course may
be attributed to the selection of patients. The lack
of progression, even after a duration of illness of
1020 years in 14 patients (31.8%) and more than
20 years in eight (18.2%), re-emphasizes that
MMA is a self-limiting disease with a spontaneous
arrest, with no evidence of late progression, unlike
as in progressive muscular weakness in postpoliomyelitis (6, 2931).
Clinical features of coarse tremors, minipolymyoclonus and minimal wasting of distal
muscles with gross asymmetry and neurogenic
pattern on EMG of the contralateral upper limb
was seen in ve patients. In two additional patients
EMG evidence of chronic denervation was seen,
thus seven patients (15.9%) had bilateral involvement. In the reported series bilateral involvement
ranged from 33.8 to 61.8%, but asymmetrical
involvement was a consistent feature in all these
studies (4, 7, 10, 13). It is interesting to note that
Hirayama et al. (1, 2) did not observe bilateral
involvement. In the present study, during the
follow-up, only one additional patient developed
minimal involvement of the contralateral limb and
thus a total of eight patients (18.2%) had involvement of the contralateral limb, but asymmetry
continued to persist.
There was no evidence to suggest involvement of
pyramidal tracts or cranial nerves during the

Brachial monomelic amyotrophy long-term follow-up

follow-up assessment. Therefore, our follow-up
study demonstrates that MMA does not progress
and evolve to ALS. The observations of Barontini
et al. (27), in a longitudinal study of 1315 years in
three cases, are similar to our present series. An
isolated report from Italy (32) describes a young
man from South India with MMA who, after
11 years, developed features suggestive of Madras
pattern of motor neuron disease (33, 34).
Observations from our follow-up study of
BMMA rearm the benign nature of the illness
justifying the earlier suggestion to refer to this
entity as benign monomelic amyotrophy subsequently reiterated by others (35, 36). The fear that
MMA may become generalized and progress to
ALS may be allayed and the patients reassured
about the self-limiting course of the disease.
Acknowledgements
The authors thank D.K. Subbakrishna (Department of
Biostatistics) and Vijendra Kargudri (Department of Epidemiology), National Institute of Mental Health and Neurosciences, for their help in data analysis.

13.

14.
15.
16.
17.

18.

19.

20.
21.

22.

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