Current Paediatrics (1996) 6, 168-172

©1996 Pearson Professional Ltd

Mini-symposium:Neurology

Child with weak muscles: recognition, causes

and management

N. E C. C a v a n a g h

RECOGNITION AND CAUSES

Not all children with weak muscles have muscle dis-

ease. Muscle weakness may be due to an upper motor
neurone (UMN) lesion or a lower one, or to a combi-
nation of both. The anterior horn is the cut off point.
A disease, 'a lesion', affecting the anterior horn cell
or peripheral nerve, or the muscle/nerve junction, or
the muscle cells themselves, gives rise to a lower Corticospinal
UI I tract
motor neurone (LMN) weakness. By contrast a dis-
ease affecting motor pathways (cortico-spinal tracts,
motor cortex) above the level of the anterior horn,
manifests with U M N muscle weakness (Fig. 1).

H o w to tell the difference between upper and lower

Anterior
motor neurone 'lesions' at the bedside horn cell

Upper motor neurone weakness

The weakness caused by a U M N lesion has a charac-

teristic distribution best recognized by recalling
the posture adopted by a child with hemiplegia (Fig. 2
Nerve
and Box). Furthermore, this distribution of weakness
is usually associated with other U M N signs such as
brisk tendon reflexes, extensor plantar responses, LMN ~ Neuromuscular
clonus and increased tone of a spastic kind. junction
There are two kinds of increased tone, spasticity
and rigidity. They are distinguished as follows: spas-
ticity is an increased resistance to passive movement ,res

in one direction only, e.g. on forearm supination but

not pronation, on wrist dorsiflexion not extension,
ankle dorsiflexion but not plantar flexion, whereas
rigidity is a resistance to passive movement in all
directions. Furthermore, with spasticity there is often
a catch then a give during the passive movement.

N. P. C. Cavanagh, Chelsea & Westminster Healthcare N H S Trust,

Fig. 1 Lesion above the anterior horn cell - upper motor neurone
369 F u l h a m Road, L o n d o n S W l 0 9NH.
lesion (UMN). Lesion below that level - lower motor neurone
Correspondence and requests for offprints to NPC. lesion (LMN).

168

Fig 2. Hemiplegicposture.
Low er motor neurone weakness
The distribution of weakness varies with the underly-
ing cause.
It may affect predominantly the limb girdle muscu-
lature, showing itself clinically in difficulty in elevating
the arms above the head or getting up from
the floor. The latter may manifest as a positive
Gower's manoeuvre, when the child has to push up on
his own legs.
It may be predominantly distal as found, for
example, in a motor neuropathy (the wrist drop of
lead poisoning is a good example), or in distal, spinal
muscular atrophy.
The weakness may be generalized as may be found,
for example, in metabolic myopathies.
Lower motor neurone weakness is usually
associated with reduced resistance to passive
movement - hypotonia. But not all hypotonia is of
L M N origin (see below).
Child with weak muscles 169
Box The distributionof weaknessin an UMN lesionaffectingthe
motor pathways.
Shoulderabduction weaker than abduction
Elbow extension weaker than flexion
Wrist extension weakerthan flexion
Thumb abduction weakerthan adduction
Hip extension weakerthan flexion
Knee extension weakerthan flexion
Ankle dorsiflexion weaker than flexionetc
Some further points for clarification
Difficulty may arise when both U M N and L M N signs
are present simultaneously in a child with, for
example, mitochondrial myopathy. There are a number
of features that might alert one to this possibility.
• The presence of diverse neurological signs such
as cerebellar ones (which give rise to ataxia), brain
stem signs (causing disconjugate eye movements),
retinopathy (as evidenced by pigmentary changes)
and sensory-neural deafness.
• Also more systemic abnormalities such as short
stature, and renal complications and cardiac
problems, for example.
Hypotonia may be a prominent feature of cerebel-
lar dysfunction which is a U M N sign. If the cerebellar
signs are easily detected (finger/nose ataxia, heel/shin
unsteadiness, broad-based gait), then the origin of the
hypotonia is clear. However, it can happen that the
cerebellar dysfunction mainly, or only, arises from
abnormality of the vermis in which case the signs are
confined to truncal dysequilibrium. In a small child
this would show itself with undue clinginess or fear of
being separated from a supporting adult.
Although hyporeflexia is a common feature of
L M N disorder, reflexes may be exaggarated in the
presence of a significant motor neuropathy. This com-
bination may occur, for example, in some progressive
degenerative diseases of the central nervous system.
A history of progressive physical deterioration with or
without an evolving dementia should alert the doctor
to the correct explanation of this unusual association.
Joint hypermobility should not be confused with
hypotonia - it is not associated with any muscle weak-
ness or hyporeflexia, may be familial, and may be
associated with some degree of clumsiness of non-
cerebellar origin.
Other features associated with neuromuscular weakness
From the history there may be evidence of the following:
(a) Reduced foetal movements.
(b) Weak cry in infancy.
(c) Weak suck or undue breathlessness with sucking.
170 Current Paediatrics
(d) Delayed motor as distinct from delayed social
and speech milestones.
(e) Diurnal variation of muscle weakness. For
example increasing weakness at the end of the day
or following exercise suggesting myasthenia gravis.
(f) Difficulty or inability in going up stairs or a
persistance with putting two feet to a step
beyond the normal age (around 2.5 years-of-age).
(g) Variability of weakness with temperature as seen
in myotonia congenita, hypo- or hyperkalaemic
paralysis, etc.
(h) Muscle pain during, or closely following, exercise
suggesting a metabolic myopathy.
(i) History of some improvement in power with age,
as found for example in congenital muscular
dystrophy or Nemaline myopathy.
(j) Reduced sensitivity to pain or other sensory
modalities (light touch, hot and cold, vibration
sense, joint position sense) as may be found in,
for example, some of the hereditary sensory and
motor neuropathies.
(k) Failure to thrive as may be found in metabolic
myopathies.
(1) Respiratory failure, e.g. from diaphragmatic
involvement as found in myotonic dystrophy or
in metabolic myopathy.
From the neurological examination the following may
be found:
(a) Tongue fasciculation which may be found in
spinal muscular atrophy types 1 and 2.
(b) Fasciculation of the small muscles of the hand,
another feature of the spinal muscular atrophies.
(c) Calf hypertrophy or hypertrophy of other
muscles, e.g. the masseters as found in Duchenne
muscular dystrophy.
(d) Muscle contractures - at birth these may be
found in spinal muscular atrophy type 1
(Wernig- Hoffman disease) and congenital
muscular dystrophy - later on in infancy and
childhood they are found in many
neuromuscular disorders.
(e) Poor head control, a feature found in many
neuromuscular disorders, particularly prominent
in botulism poisoning.
(f) Muscle tenderness to palpation, for example in
myositis.
(g) Myotonia in the child, or in the mother, for
example in myotonic dystrophy.
(h) Muscle wasting.
(i) Waddling gait and/or positive Trendelenberg sign.
The general examination may show some of the fol-
lowing signs:
(a) Secondary orthopaedic problems - scoliosis, hip
dislocation, tight tendo-achilles.
(b) Cardiomyopathy as may be found in
mitochondrial myopathy, or in glycogen storage
disease.
(c) Hepatomegaly also found in glycogen storage
disease.
(d) Retinopathy as may be found in
fascioscapulohumeral dystrophy and in
mitochondrial myopathies.
(e) Dysmorphic features such as talipes,
diaphragmatic hernia (both of which may be
found in myotonic dystrophy).
DIAGNOSIS
Biochemical tests
A useful indicator of muscle disease is an elevation of
blood creatine phosphokinase (CPK) measurement.
However, a normal CPK level does not exclude a
myopathy, and spuriously elevated CPK levels may
result from prolonged squeezing of the upper arm in
association with venepuncture, or in a struggling
child. Blood obtained from an in-dwelling needle in
a sleeping or resting child may be needed.
Metabolic muscle disease
Much progress over the last decade has been made
in the investigation of these muscle diseases. 1,2 The
clinical clues to such diseases have been alluded to
above. The biochemical indicators/investigations are
as follows.
Carbohydrate metabolism disorders
(a) hypoglycaemia
(b) disturbed liver function tests (LFTs)
(c) hyperuricaemia
(d) myoglobinuria
(e) lack of elevation of blood lactate in the
ischaemic forearm test.
Fat metabolism disorders
(a) hypoglycaemia without ketosis
(b) blood carnitine and acyl carnitine levels
(c) measurement of carnitine palmitoyl transferases
1 and 2, and translocase, acyl CoA
dehydrogenases (in blood or in skin fibroblasts).
Mitochondrial respiratory chain disorders
(a) Lactic acid in blood, urine and CSE
(b) Blood gas analysis (metabolic acidosis).
Electrophysiology
Clinically, it is sometimes difficult to distinguish a
neurogenic from a myopathic condition. Depressed or
absent reflexes suggest the former (whether from an
anterior horn cell involvement or in a neuropathy),
but may be found in myopathic disorders. Whilst an
 Child with weak muscles 171

elevated CPK suggests a myopathy, it may also be Molecular genetic analysis

found in chronic neurogenic lesions in which sec-
In terms of neuromuscular disease there are a
ondary myopathic changes may occur.
number of single gene disorders which can now all
Electrophysiological tests should help to pinpoint
be tested for.
the lesion to one site (Fig. 1), and, by motor and
Duchenne/Becker muscular dystrophy (X-linked
sensory studies, distinguish a motor from a sensory
recesssive progressive). Approximately 65% of boys
neuropathy. 3
with these conditions have dystrophin gene deletions.
Broadly speaking, nerve conduction studies seek to
The 5' and 3' multiplex reactions will detect about
establish amplitude, latency (distal motor latency in
98% of these deletions. Carrier detection and prenatal
motor studies), nerve conduction velocities and
diagnosis by mutation detection or linkage.
whether there is any decrement with repetitive stimu-
The three types of childhood spinal muscular atro-
lation (as may be found in myasthenia).
phy have been matched to chromosome 5q13 from
Electromyography observes spontaneous activity,
where two genes have been isolated. Deletions of
insertional activity, internal stability and the interfer-
exons 7 and 8 of the survival motor neurone gene are
ence pattern.
very frequent, and a homozygous deletion has been
Large amplitude action potentials with a reduced
found in 95% of cases.
interference pattern and an increased internal instabil-
In HMSN type I, most families have a duplication
ity point to a neurogenic disorder. By contrast, small
of the peripheral myolin protein, 22 gene.
amplitude muscle action potentials with an increased
In myotonic dystrophy large numbers of copies of
interference pattern indicate a myopathic disturbance.
a triplet repeat sequence have been identified.
An increased insertional activity would point to a
Recently, the genes of some other neuromuscular
myotonic disorder.
diseases have been isolated, including mutations in
the laminin alpha II chain gene in merosin deficient
Muscle biopsy congenital muscular dystrophy, and mutations in
alpha, beta, and gamma sarcoglycan have been shown
This would be performed in most circumstances when to cause limb/girdle muscular dystrophy.
a myopathic disorder is suspected. The clinical and
electrophysiological findings should be sufficiently
strong in myotonic disorders and in myasthenia as to Mitochondrial DNA analysis
make a muscle biopsy unnecessary. It would not usu-
Mitochondria have their own DNA, and the human
ally be necessary to perform a muscle biopsy when
mitochondrial genome was fully characterized and
indications have been of a neurogenic lesion, as it is
sequenced in 1981. Since then a number of mitochon-
unlikely that further diagnostic information would be
drial myopathies have been shown to be caused by
obtained.
either deletions, duplication, or point mutations of
A muscle biopsy should be done from a site that
mtDNA. Some, for example infantile cytochrome
has not recently been needled, and preferably from a
oxidase deficiency, are diagnosed on muscle biopsy.
muscle well known to the histologist/histochemist, e.g.
Others may be detected by DNA analysis of
quadriceps femoris, etc.
peripheral blood, e.g. Kearns Sayers syndrome, the
The biopsy tissue should be placed lengthwise on a
mitochondrial myopathy with diabetes mellitus.
piece of gauze which has been lightly soaked in nor-
mal saline and put in a petri dish, kept covered and
transferred without delay to the laboratory. Once TREATMENT
there, routine histology, routine histochemistry and
preparation of mitochondrial fraction for detailed At the time of writing it is the case that there have not
biochemical analysis should be undertaken. Specific been any spectacular advances in specific treatment
histochemistry for demonstration of succinated dehy- or cures for neuromuscular diseases. Trials of treat-
drogenase, cytochrome oxidase, and other respiratory ment are ongoing; in the area of muscular dystrophy
chain complexes, also individual glycolytic enzymes, where the gene product is known, the prospects are
immunohistochemical analysis of sarcolemmal mem- potentially exciting. Treatment with Carnitine or
brane proteins (e.g. dystrophin, merosin, spectrin, Riboflavin, for example, has been tried in some mito-
adhalin, betadystroglycan, etc.) and electron micro- chondrial disorders with variable and inconsistent but
scopy, should be performed. sometimes encouraging results. In these conditions,
careful attention to diet to prevent prolonged fasting
and the provision of low fat and high carbohydrate
Genetic studies
intake is beneficial.
Advances have occurred rapidly and recently in both The mainstay of treatment is still the maintenance
molecular genetic analysis and in mitochondrial of good posture, prolonging ambulation as long as pos-
DNA analysis. 4,5 sible with judicious surgery, intervention with calipers,
172 Current Paediatrics
ankle/foot orthoses and other aids. Schemes to avoid
injury in conditions where there is sensory impairment
and ventilatory support, where needed, are also used.
If prevention is better than cure, then the rapid
advances in molecular and mitochondrial D N A
genetics will offer increasing scope for carrier detec-
tion and antenatal diagnosis.
REFERENCES
1. Jackson M J, Bindoff L A, Turnbull D M. Recent advances in
metabolic muscle disease - Carbohydrate and fat metabolism.
Hospital Update 1994; 20:11 527 11 536.
2. Jackson M J, Bindoff L A, Turnbull D M. Recent advances in
metabolic muscle disease - Mitochondrial metabolism,
molecular biology and management. Hospital Update 1994;
12: 582-585.
3. Payan J. In: Brett E, ed. Paediatric neurology. 2nd ed. 1991:
Chapter 26, 797-829.
4. Yates J R W. Recent Advances in Medical Genetics. British
Medical Journal 1996, 312:1021-1025
5. Poulton J. Annotation. Mitochondrial DNA and Genetic
Disease. Developmental Medicine and Child Neurology 1993;
35: 833-840.