Muscle complications of malnutrition in children: a clinical and electromyographic study

371

Neurophysiol Clin (1993) 2 3 , 3 7 1 - 3 8 0 © Elsevier, Paris

Memoir

Muscle complications of malnutrition in children: a clinical and electromyographic study F Renault, R Quesada Laboratoire de neurophysiologie clinique de l'enfant, h@ital Armand-Trousseau, 28, av du Dr Arnold-Netter, 75571 Paris Cedex 12, France (Received 3 August 1992; accepted 22 December 1992)

S u n u n a r y - The authors report tile clinic',d and electromyograplfic (EMG) findings in a series o f 13 clfildren with a pseudomyopatlfic motor deficit in the context of malnutrition (Body Mass Index < 3rd percentile) caused by primary protein-calorie deficiency or secondary to chronic disease. Tile infants (nine cases) manifested a regression or stagnation o f motor abilities, with hypotonia and amyotrophy; older children and adolescents (four cases) presented clear amyotrophy with a deficit in muscle strength consisting primarily of proximal muscular weakness. Detection and stimulation-detection E M G demonstrated myogenic signs in at least two muscles in all patients. Myogenic signs were dominant in all proximal muscles. Latencies were normal in all patients. Motor nerve conduction velocities were slowed in three infants and in one adolescent. A temporal dispersion of motor responses was observed in 11 proximal muscles. The muscle biopsy, performed in five cases, revealed all inequality in the calibre of fibres, with atrophy dominating in type II fibres. The authors emphasize the value of EMG in disclosing the myopathic process, thereby contributing to the etiological diagnosis of motor difficulties in children suffering from malnutrition or a chronic disease.

malnutrition ] muscle ] pseudomyopathy / electromyography [ muscle fibre atrophy

R r s u m 6 - C o m p l i c a t i o n s m u s c u l a i r e s de la m a l n u t r i t i o n chez l'enfant: fitude clinique et 61ectromyog r a p h i q u e . Les auteurs prrsentent les donnres cliniques ct 61ectromyograplfiques (EMG) d ' u n e srrie de 13 enfants qui ont install6 un drficit m o t e u r pseudomyopathique dans un contexte de malnutrition (poids/~ge < - 2 D S et poids/taille: < 3 e percentile) par carenee prodidocalorique primaire ou secondaire u n e maladie chronique. Les nourrissons (neuf cas) ont une rrgression des acquisitions motrices avec hypotonie et amyotrophie; les grands enfants et adolescents (quatre cas) prrsentent une amyotrophie nette avec un drficit de force musculalre h prrdominance proximale. L ' E M G de drtection et de stimulodrtection met en 6vidence des signes myog~nes dans au moins deux muscles chez t o u s l e s sujets. Les signes myog~nes pr&lominent dans les muscles proximaux. Les latences sont normales dans t o u s l e s territoires chez t o u s l e s sujets. Les vitesses de conduction uerveuse motrices sont ralenties chez trois nourrissons et un adolescent. Line dispersion temporelle des rrponscs motrices est observre dans 11 muscles proximaux. La biopsie musculaire, 6tudire dans cinq cas, montre une inrgalit6 de calibre des fibres et une atrophic srlective des fibres de type II sans regroupement. Les auteurs discutent la valeur diagnostique et la physiopathologie des anomalies EMG observrcs el soulignent l'intrr~t des inrthodes EMG pour drpister le

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F Renault, R Quesada

processus myog~ne, contribuam ainsi au diagnostic 6tiologique des difficult6s motrices des enfants malnutris ou porteurs d'une maladie chronique. malnutrition ] muscle ] pseudomyopathie ] ~lectromyographie ] atroplfie des fibres musculaires

Introduction

I n 1954, Udani described the " M y o p a t h i c s y n d r o m e o f malnutrition" associating hypotonia, hyporeflexia and a deficit in muscle strength. Experimental reproduction o f this syndrome in monkeys confirmed muscle involvement by demonstrating electrom y o g r a p h i c ( E M G ) signs o f m y o p a t h y and histologically a u n i f o r m decrease in the calibre o f muscle fibres (Chopra et al, 1987). In clinical disorders, publications h a v e , in particular reported the effects o f malnutrition on the size o f the brain (Prensky, 1989), on p s y c h o m o t o r development (Champakan et al, 1968), and nerve c o n d u c t i o n (Engsner and W o l d e m a r i a m , 1974; G h o s h et al, 1979; C h o p r a et al, 1986; D o n l e y and Evans, 1989). Only a few studies have investigated muscle tissue involvement in undernourished children (Sachdev et al, 1971; Faridi et al, 1988), in children fed b y continuous parenteral nutrition (Kelly et al, 1988) and in adolescents with anorexia (Alloway et al, 1985). These studies report E M G signs o f m y o p a t h y and/or type II atrophy o f muscle fibres. W e had the opportunity to examine several children presenting with a s y n d r o m e o f p s e u d o m y o p a t h y related to malnutrition in the context of a chronic disease (respiratory, cardiac or gastrointestinal), anorexia nervosa, or a p r i m a r y protein-calorie deficiency. W e report the clinical and electromyographic findings in these patients with the aim o f describing a recognizable electroclinical presentation, then we discuss the physiopathology o f muscle changes.

Materials and methods

A retrospective study was carried out between 1978 and 1990, involving 13 children who had muscle weakness and myogenic EMG signs in combination with weight loss within a context of acute or chronic malnutrition. This series involved nine infants 6 1/2 months to 24 months of age who at the time of examination showed a break in weight gain which had been present for between 2-14 months and four older children or adolescents, two of whom displayed sudden and recent weight loss, and two with weight loss of longer duration (table I). Criteria for malnutrition were a weight/age ratio less than or equal to - 2 SD (Semp6 et al, 1979) and a Body Mass Index (BMI) value less than or equal to the 3rd percentile (Rolland-Cachera et al, 1991); these criteria were present together in all cases except in child no 9 where weight loss was just as high, but in a patient who was previously obese with +2 SD. In some children, the impact of malnutrition on laboratory parameters was observed: hypochromic anemia (3/13), hypoferremia (1/13), hypoproteinemia (1/13), and hypoalbuminemia (5/13). In all cases, the absence of inflammation, of metabolic disorder and of infectious disease was verified.

Malnourished nmscle

373

Table I. Malnutrition criteria in 13 children.

No

Age

W(kg)(SD)

BMI (W/I-12)

1

Etiology

Duration* of malnutrition (month)

5 m

4.4(-3)

11.4

Dietary deficiency

4

2

6 1/2 m

4(-4)

9.5

Primary anorexia

4

3

8m

5.2(-3)

12.3

Congenital heart disease Pulmonary hypertension

7

4

10 m

4.5(-4)

10.6

Dietary deficiency

5

16 m

7.5(-3)

13.2

Congenital heart disease Pulmonary hypertension

8 14

6

17 m

8.8(-3)

14

Celia disease

7

20 m

9.1(-2)

14.8

Chronic lung disease Bronchiolar obstruction

2

8

20 m

8.1(-3)

14.6

Chronic diarrhea Cow's milk allergy

2 2

9

24 m

11.5(M)

16.1

Chronic diarrhea Food intolerance

2

14

10

8y

21(-2)

13.2

Dietary deficiency

2

l1

13 y

34(-4)

14.1

Anorexia nervosa

6 1/2

12

15 y

25(-4)

11.2

Chronic lung disease Interstitial pneumonitis

13

16 y

27.5(-3)

13.8

Dietary deficiency

60 156

* Interval between break in weight curve, M: mean, W: weight, H: height, SD: standard deviation (Semp6 et al, 1979), BMI: Body Mass Index (Rolland-Cachera et al, 1991).

E M G examinations were all performed by the same examiner according to the same protocol. In each child, four or five muscles were investigated: at least two p r o x i m a l muscles (deltoid, biceps or rectus femoris) and at least two distal muscles (abductor digiti minimi, opponens pollicis, a n d extensor digitorum brevis or flexor hallucis brevis). The electrical signal was detected b y a bipolar concentric needle electrode. A n a l y s i s of detection E M G was performed manually. W e applied the traditional criteria for myogenic recruitment pattern: an immediate interference pattern, maximum amplitude decreased b y at least 30%, mean duration of m o t o r unit action potentials ( M U P ) decreased b y at least 20% and a proportion of polyphasic potentials greater than 12% (Buchthal and Simpson, 1973). W e quote as " m y o g e n i c pattern" the tracings including at least three of these criteria. T h e technique of stimulation-detection was performed using a single electrical shock (0.1 to 0.3 ms) with supra-maximal intensity (50 to 80 mA). M y o g e n i c criteria for m o t o r response were a decrease in amplitude (< 1.5 m V ) and a m o r p h o l o g y tortl up by indentation of the slopes of principal phases (Raimbault et al, 1977). In each muscle, eight successive responses were recorded. W e quote a muscle as having " m y o g e n i c characteristics" w h e n at least four

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F Renault, R Quesada

Table II. Clinical features according to age of onset of malnutrition.

Features

6--24 months (nine cases)

8-16 years (four cases)

Weight/ago < -2 SD

8

4

Body Mass Index < 3rd percentile

8

4

Amyotrophy

8

4

Regession or stagnation of motor development

7

-

Hypotonia

6

-

Hyporeflexia

1

0

not done

3

Deficit in muscle strength (testing)

m o t o r r e s p o n s e s exhibit m y o g e n i c criieria. Latency and duration o f m o t o r r e s p o n s e s and m o t o r nerve conduction velocity ( M N C V ) were measured and interpreted according to the techniques and standards established by Raimbault (1988).

Results Neurological manifestations were dominated by muscle weakness with amyotrophy and conservation of deep tendon reflexes. Muscle weakness was obvious and quantifiable in older children and adolescents and it was manifest in infants by hypotonia with regression or stagnation of acquired motor development (table II). Serum levels of creatine phosphokinase (CK) measured in eight children were always normal. Histoenzymological study of muscle biopsy (M Fardeau) was carried out in five children (case nos 1, 3, 4, 8, and 10). In each case it re~)ealed the absence of interstitial lesions, a normal architectural arrangement,'normal differentiation of muscle fibres, absence of topographical rearrangement and absence of glycogen or lipid overload. Abnormalities observed consisted of unequal size of muscle fibres with atrophy predominant in type II fibres (case nos 1, 3, 8, 10) (fig 1) or involving both types of fibres (case no 4). Detection EMG demonstrated at least two myogenic criteria in at least two muscles in ten children. Myogenic features were most commonly observed in proximal muscles (17/19) (table III). Stimulation-detection E M G demonstrated the polyphasic hooked morphology and decreased amplitude of the motor response (fig 2) in at least two muscles in all patients with a dominance of these myogenic criteria in proximal muscles (22/29) (table IV). Latencies of muscle responses to nerve stimulation were normal in all of the areas investigated in all patients. MNCV were measured in all children: ten ulnar nerves, two median nerves, eight medial popliteal and three lateral popliteal nerves. MNCV was at least 15%

375

Malnourished muscle

A

B

F i g 1. Case no 3. Serial sections of the deltoid muscle. A. Goinori trichrome stain. B. ATPase pH 9.40. Selective atrophy o f type II fibres without topograplfical rearrangement (x 500) (M Fardeau, N Romero).

A.S.

6m15d MOTOR RESPONSE

VOLUNTARY CONTRACTION

Deltoid

Biceps brachialis

200 lav i 40 ms

200 )Jv i

,

I0 ms

F i g 2. Case no 2. Left: myogenic pattern on voluntary contraction. Right: tSolyphasic and torn morphology and low amplitude of motor responses to stimulation of motor nerve by a short electrical current (0.2 ms) at supramaximal intensity (50 mA).

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F Renault, R Quesada

Table III. Frequency of myogenic signs on detection EMG in 13 malnourished children.

Muscle

Number of muscles tested

Myogenic pattern

Deltoid Biceps brachialis Rectus femoris Total proximal muscle

9 2 8 19

8 2 7 17 (89%)

Abductor digiti minimi Opponens pollici Flexor hallucis brevis Extensor digitorum brevis Total distal muscles

8 1 6 3 18

4 0 1 0 5 (27%)

L.B. 8m

O.uadriceps

lOms Fig 3. Case no 3. Rectus femoris. Polyphasic response of increased duration (22.5 ms) to cmral nerve stimulation by a short electrical shock (0.2 ms) at supramaximal intensity (60 mA).

lower than mean values in at least one nerve trunk in three infants and in one adolescent (case nos 4, 6, 7 and 12). A temporal dispersion of motor responses (increased duration) (fig 3) was striking in 11 proximal muscles in seven infants and two adolescents (table IV).

Malnourished muscle

377

Table IV. Characteristics of motor responses on stimulation-detection EMG in 13 malnourished children. Muscle

Deltoid Biceps brachialis Rectus femoris Totalproximal muscles

Abductor digiti minimi Flexor hallucis brevis Extensor digitorum brevis Total dbtal muscles

Number of muscles tested

12 4 13 29 12 7 3 22

Myogenic characteristics

9 4 9 22 (75%) 7 1 0 8 (36%)

Increased duration

5 (_>14.5 ms) 1 (> 15 ms) 5 (> 15.8) 11 (38%) 2 (> 10 ms) 0 0 2 (10%)

Discussion Amyotrophy and motor difficulties are obvious complications of severe, persistent malnutrition such as marasmus and kwashiorkor. By studying a series of 30 children, Sachdev e t al (1971) demonstrated the frequency of anayotrophy, muscle weakness, hypotonia with hyporeflexia as well as the impact on motor performance, in particular on walking. Their E M G study of 14 cases and histopathological examination of three cases showed the association of a myopathy process with a peripheral neuropathy. Chopra et al (1986), who reproduced protein-calorie malnutrition in the Rhesus monkey, demonstrated its clinical impact (anayotrophy, muscle weakness and decreased physical activity), E M G signs and histopathological evidence of myopathy were associated with a slowing of motor MNCV. In addition, their work showed that these alterations are solely due to a protein-calorie deficit, apart from any vitamin deficiency. Nerve involvement as evidenced by slowing of M N C V (Engsner and Woldemariam, 1974; Singh et al 1976) occurs in the severest types of malnutrition where segmental demyelinization (Roy et al, 1972; Chopra et al, 1986) or even neurogenic muscle atrophy (Sachdev et al, 1971) develops. Several authors described muscle changes without any nerve involvement at an early stage of malnutrition. E M G studies exhibited the presence of traditional myogenic criteria, ie interference pattern, low amplitude, short duration M U P (Sachdev et al, 1971; Chopra et al, 1987). Histopathological studies have demonstrated a uniform decrease in the calibre of muscle fibres (Vincent and Radermaker, 1959; Montgomery, 1962; Chopra et al, 1987), loss of sarcoplasm and cross-striation (Faridi et al, 1985). Similarly, muscle involvement possibly associated with a polyneuropathy has been observed in anorexia nervosa with myogenic signs on E M G and atrophy of muscle fibres dominating in type lI fibres (Alloway et al, 1985). Motor deficit with conservation of tendon reflexes, myogenic signs on E M G and atrophy of type II muscle fibres was described in a 21 month-old child on continuous enteral nutrition

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F Renault, R Quesada

during the course of celiac disease, with this muscle disorder being attributed to selenium deficiency (Kelly et al, 1988). In our study population, nutritional deficiency was sometimes primary, sometimes secondary to subacute gastrointestinal disorder or to anorexia. In four cases, it developed during the course of congenital heart disease or severe chronic lung disease, with malnutrition being partly related to a hypermetabolic condition (Lewis and Belman, 1988). It should be noted that in three cases (nos 8, 9, and 10) the pseudomyopathic syndrome developed beginning at the second month of malnutrition while a previous series of patients involved longer-standing nutritional deficiencies (Sachdev et al, 1971; Chopra et al, 1986). Clinical findings in our cases remind us that the presentation of this muscle complication is of two different types, depending on age of onset. In infants, the warning sign is stagnation or even regression of acquired motor development with amyotrophy, hypotonia and weak but conserved deep tendon reflexes on examination. In older children and in adolescents, it is amyotrophy which draws attention and the examination objectifies muscle weakness that is primarily proximal with conservation of tendon reflexes. Results of EMG testing in this series show the value of stimulation-detection techniques and make it possible to precisely describe some abnormalities in neuromuscular activity observed in malnourished children. The technique of stimulationdetection has made it possible to demonstrate myogenic characteristics in at least two muscles in all children while traditional criteria for detection were only demonstrative in ten children. It is thus important to systematically study the morphology and amplitude of the motor response to a short electrical stimulus applied to a motor nerve, a method whose value has previously been demonstrated in various myopathies in children (Raimbault et al, 1977). It is known that myogenic EMG signs are common to the different etiologies for muscular tissue damage (Buchthal and Simpson, 1973). The proximal 13redominance of myogenic signs is consistent with the clinical pre~sentation of pseudomyopathic motor deficit. This topography of EMG myogenic p~ittern is also usual in children with muscular dystrophy (Raimbault et al, '1977). The abnormalities observed in muscle biopsies were those previously reported in prior studies: decrease in calibre of muscle fibres, either uniform or predominant in type II fibres (Alloway et al, 1985; Chopra et al, 1987; Kelly et al, 1988). This muscle fibre atrophy is a non-specific finding but is consistent with EMG pattern: low amplitude, short MUP, low amplitude and polyphasic tom-up morphology of motor response. A nerve involvement can be added to the myopathic process. We observed a slowing of MNCV in four children with a long-standing malnutrition. Alteration of motor and sensory NCV attributed to myelin damage is known to occur in severe chronic types of malnutrition such as marasmus or kwashiorkor, related to protein and/or vitamin deficiency (Roy et al, 1972; Chopra et al, 1986). Slowing of MNCV is that much more pronounced when malnutrition is of a long-standing type and began during the first months of life (Ghosh et al, 1979). Alteration of MNCV in

Malnourished muscle

379

anorexia nervosa in adolescents (case no 12) has previously been reported (Alloway et al, 1985). In this series, E M G did not disclose any sign of denervation and muscle

biopsy did not reveal any evidence of neurogenic atrophy, even in patients with slowed MNCV. This puts our patients in contrast with cases o f deficiency-induced neuropathy (Prensky, 1989; Donley and Evans, 1989). The temporal dispersion of motor responses (table IV, fig 3) observed in some muscles, most of which were proximal in nine children seems to be an original feature of malnourished muscle with respect to other specific disorders. It might be due to the onset of demyelinisation: delayed myelinisation and segmental demyelinisation have been noted in 50% of the severest cases of malnutrition reported by Chopra et al (1986) and experimental studies by Roy et al (1972) revealed changes of the myelin sheath. Further data are required to discuss the diagnostic value and pathophysiological support of this E M G finding. Thus, muscle complications of malnutrition in children constitute an electroclinical entity associating amyotrophy, muscle weakness and m y o g e n i c E M G signs, sometimes with slowing of MNCV. Our series of patients shows that this pseudom y o p a t h y syndrome can occur in the course of primary or secondary nutritional deficiencies and sometimes within a time span of less than three months. We emphasize the value o f E M G for disclosure of the myopathic process by showing the results of techniques of stimulation-detection in this disorder. A better knowledge of this syndrome could contribute to the diagnosis of neuromuscular difficulties in children suffering from malnutrition or a chronic disorder.

References

Alloway R, Reynolds EH, Spargo E, Russell GFM (1985) Neuropathy and myopathy in two patients with anorexia and bulimia nervosa. J Neurol Neurosurg Psychiatry 48, 1015-1020 Buchthal F, Simpson JA (1973) Neuromuscular diseases. In: Handbook o f EEG and Clinical N e u r o p h y s i o l o g y . Elsevier, Arr~qterdam, Vol 16, part B Champakan S, Srikantia SG, Gopalan C (1968) Kwashiorkor and mental development. Am J Clin Nutr 21,844-852 Chopra JS, Dhand UK, Mehta S, Bakshi V, Rana V, Mehta J (1986) Effect of protein-calorie malnutrition on peripheral nerves. Brain 109, 307-323 Chopra JS, Mehta J, Rana SV, Dhand UK, Mehta S (1987) Muscle involvement

during postnatal protein-calorie malnutrition and recovery in rhesus monkeys. Acta Neurol Scand 75, 234-243 Donley DK, Evans BK (1989) Reversible neuromuscular syndrome in malnourished children. Dev Med Child Neurol 31,797-815 Faridi MMA, Anzari Z, Tyagi SP (1988) Skeletal muscle changes in protein energy malnutrition. J Trop Pediat 34, 238-243 Engsner G, Woldemariam T (1974) Motor nerve conduction velocity in marasmus and in kwashiorkor. Neuropediatrics 5, 34-48 Ghosh S, Vaid K, Mohan M, Maheshwari MC (1979) Effect of degree and duration of protein energy malnutrition on peripheral nerves in children. J Neurol Neurosurg P~ychiat~ 42, 760-763

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Kelly DA, Coe AW, Shenkin A, Lake BD, Walker-Smith JA (1988) Symptomatic selenium deficiency in a child on home parenteral nutrition. J Pediatr Gastroenterol Nutr 7, 783-786 Lewis MI, Behnan MJ (1988) Nutrition and the respiratory muscles. Clin Chest Med 9, 337-348 Montgomery RD (1962) Muscle morphology in infantile protein malnutrition. J Clin Pathol 15, 511-521 Prensky A (1989) Malnutrition. In: Swaiman's Pediatric Neurology. St Louis, Mosby Co, Vol 1,541-545 Raimbault J, Renault F, Laget P (1977) La place de l'61ectromyographie dans le diagnostic des myopathies de l'enfant. Ann Pediatr 24, 451-458 Raimbault J (1988) Les conductions nerveuses chez l'enfant normal. Expansion Scientifique Fran~aise, Paris Rolland-Cachera MF, Cole TJ, Sempd M, T i c h e t J, R o s s i g n o l C, C h a r r a u d A (1991) Body Mass Index variations: centiles from birth to 87 years. Eur J Clin Nutr 45, 13-21

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