Peripheral neuropathy in burn patients

0 1997 Elsevier ELSEVIER

Bmms Vol. 23, No. 7/8, pp. 579-583, 1997 Science Ltd for ISBI. All rights reserved Printed in Great Britain 0305-4179/97 $17.00 + 0.00

PII: s0305-4179(97)00068-5

Peripheral Eman M. Khedr’,

neuropathy Tayseer Khedr’,

in burn patients

Mahmoud

A. El-Oteify3

and Hosni A. Hassan4

IDepartment of Neurology, Faculty of Medicine, Assiut University, Assiut, Egypt, ‘Department of Physical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt, 3Department of Plastic Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt and 4Department of Biochemistry, Faculty of Med.icine, Assiut University, Assiut, Egypt

Neuropatky in burn patients is frequently overlooked. This study aimed at looking for neuropatkies among burn patients. It included 55 burn patients, whether symptomatic or asymptomatic, with variable depths of burn at diffrent stages. Tkeir ages ranged from 8 to 55 years with a mean age of 23.6kll.l years. All patients rc;ese submitted to clinical examination, electromyographic and motor conduction velocities of burned and unburned limbs. Sevttm electrolyte, blood urea and creafinine zuere measured for all patients. Sixteen patients (29 per cent) had Teripheral neuropatky. Only six had symptoms and signs of peripheral neuropatky. The most frequently diagnosed neuropalky in this study u)as mononeuritis multiplex in nine patients (56 per cent), then ger!eralized distal axonal neuropathy in five patients (31 per cent) a.‘Zd entrapment neuropatky in two patients (13 per cent). In patients with mononeuritis, 29 nerves were affected, 24 nerves related to the site of the burn and five nerves were away from the site of the burn. All the entrapment neuropatky developed afler wound healing. Age above 20 years, electric bunzs, burns involving full tkickness of the skin and a surface area of more than 20 per cent were associated with a significantly kigkeu prevalence of neuropathy. Other parameters were not found to be significant in ihe development of neuropatky. 0 1997 Elsevier Science Ltd foou ISBI. AlI vigkfs reserved Keywords:

Peripheral

neuropathy,

Burns, Vol. 23, No. 7/8, 579-583,

electromyography,

burn. -

1997

Introduction Feripheral neuropathy which occurs in burn patients is not well recognized, and hence is probably frequently missed. Very little has been reported in the literature concerning this problem’. Henderson et a1.2 have previously reported on the peripheral polyneuropathy found in acute burn patients. In their series, 36 cases (15 per cent) were found to have slowed motor nerve conduction velocity in at least two peripheral nerves, with a higher prevalence among patients with a total body surface area burn greater than 20 per cent. Helm and associate@ reported a 29 per cent prevalence of peripheral

neuropathy in 66 burn patients, whereas Marquez et a1.l found in a retrospective study that 16 patients (2 per cent) had peripheral neuropathy. Isolated peripheral neuropathy and multiply affected nerves not directly related to the site of burn have been reported as a complication of burn. The nature and the pathogenesis of the peripheral neuropathy in burns are not well known3. The purpose of this study was to determine the prevalence and types of ;Teripheral neurological complica-tions that can occur in burn patients, and to delineate the nature and pathophysiology of peripheral neurological abnormalities that occur with burns.

Patients and methods Seventy-five electromyography (EMG) examinations were performed in 55 burn pntients at different s’tages(acute and chronic stages) of variable degrees of depth following the accident. In 20 patients, EMG was performed more than once in the acute stage a.nd after healing. All patients were referred from the Plastic Surgery Burns Unit to the Clinical Neurophysiology Unit, Assiut University Hospital, for evaluation during the period from January 1995 to September 1996. The mean age of the 55 patients investigated was 23.6+ 11.1 years with a range of 8-55 years, 34 were females and 21 were males. Each patient was submitted to the following: l

l

l

I Careful history and physical examination including type, duration, degree, surface area and site of burn. Full neurological examination. Patients with a known history of any predisposing cause of peripheral neuropathy (diabetes mellitus, collagen disease, uraemia, alcohol abuse, etc.) were excluded from this study. Electrodiagnostic examination included electromyography and motor nerve conduction velocities (MNCV) of burn and non-burn Limbs. This was performed using the “Nihonkohden model MEB

580

Burns: Vol. 23, No. 7/B, 1997

7102” EMG machine. Motor nerve conduction velocities were assessedusing standard procedures with concentric needle electrodes. A pulse of 0.2 ms duration, at the rate of 1 per second at supramaximal intensity was used for conduction studies of median, ulnar and common peroneal nerves. The MNCV of radial, musculocutaneous and posterior tibia1 nerves were also measured if possible. The shape, amplitude and duration of the compound muscle action potential (CMAP) were measured, and the presence of abnormal temporal dispersion (abnormal shape of CMAP with multiple phases and prolonged duration) was noted. The amplitude is measured from peak-to-peak and the duration from the beginning to the end of the CMAP. MNCV can be calculated accurately by stimulating two different points along the nerve and measuring the latency for each response. MNCV (m/s) = q

Distance between two stimulation sites (mm) Conduction time (ms) between two stimulation sites The following criteria were used for the diagnosis of axonal neuropathy: Reduction of the amplitude of CMAP below the mean by 2 or more standard deviations control group with normal shape and duration, normal nerve conduction velocities (NCV), and distal latency or minimal disturbance. In addition the presence of: Fibs or positive denervation potentials, increased amplitude and duration of motor unit potentials and a reduction of recruitment in the muscle innervated by the affected nerve were noted4. The criteria used for the diagnosis of demyelination neuropat hy were: A marked prolongation of terminal latency by more than 50 per cent of normal control values, slow NCV by more than 40per cent below the normal control means with normal amplitude of CMAP, with abnormal shape of CMAP (multiple phases and prolonged time) and the same neuropathic feature of the innervated muscles previously described for the measu.rement of axonal degeneratior?. Entrapment neuropathy was diagnosed by focal slowing in a nerve across the site of entrapment by 20 per cent below the lower limit of control motor conduction value with a reduction of CMAP amplitude by -2 SD of the control value’. Although the diagnosis of mononeuropathy or mononeuritis multiplex was based on the presence of one or more affected nerves in different limbs. The results of electrophysiology were compared with an age and sex matched control group of 90 normal volunteers. Serum Ca, K, Mg, I’, Cu and Zn were measured for each patient. Blood urea and creatinine, serum albumin and protein were also measured to evaluate the metabolic and electrolyte status of the patient. All patients were receiving

various kinds of drugs, anaesthetic agents, and surgical treatment. Statistical analysis Descriptive statistics, (e.g. mean, standard deviation, frequencies, percentages) were calculated and comparison was performed using the unpaired Student’s t-test and x2 test.

Results Fifty-five burn patients with a post-burn interval ranging from 8 days to 1 year with a mean of 60 $-79 days were studied. The surface area of burn ranged from 2 to 48 per cent with a mean of 23 + 11 per cent. Forty-nine patients suffered flame burns (89 per cent), five patients suffered electric burns (9 per cent) and only one was scalded. Sixteen patients (29 per cent) were diagnosed with peripheral neuropathy by electromyography. Out of these, six patients had symptoms and signs of peripheral neuropathy. Mononeuritis multiplex was recorded in nine patients (56 per cent), diffuse distal axonal neuropathy in five patients (31 per cent) and entrapment neuropathy in two patients (13 per cent) of the total number of neuropathy patients. One patient had bilateral common peroneal nerve entrapment at the neck of the fibulae, and another had right median nerve entrapment at the wrist. Both patients had burns at the site of entrapment (Table i). Mononeuritis multiplex affected 29 nerves in the four extremities. The upper extremity was involved more frequently (23 nerves) than the lower extremity (six nerves). Twenty-four nerves were involved in burned limbs and five nerves were involved in unburned limbs. TableII shows the relative frequency of involvement of different nerves. There was a significant reduction in motor conduction velocities and amplitude of CMAPs in burn patients compared with the control group (TableIII). Table IV shows the relation of neuropathy to age, sex, and type of burn involved in burns. A higher prevalence of neuropathy was detected among patients aged over 20 years, electric burns. The study sh.owed a significantly higher percentage of neuro-

Table I. Neuropathy -

in 55 burn patients

Item Total number Patients without neuropathy Patients with neuropathy Type of neuropathy: 1. Generalized distal axonal in four limbs 2. Entrapment neuropathy 3. Mononeuritis multiplex 0 Axonal type l Demyelinated type Numbers in parentheses in mononeuritis multiplex

NQ. 55 39 16

Per cent 100.0 70.9 29.1

neuropathy 5 2 9 5 4 indicate the number and in entrapment

(3) (29) (191 (IQ)

of nerves neuropathy.

9.1 3.6 16.4 9.1 7.3 affected

Khedr

et al.: Peripheral

neuropathy

Table II. Mononeuritis unburned limbs

Nerve

multiplex

Vledian Ulnar Common peroneal Posterior tibia Radial Musculocutaneous Total

in relation

581

to burned

and -

No. of nerves affected

affected

in burn patients

11 IO 4 2 1 1 29

Neuropathy in unburned limbs

Neuropathy in burned limbs

(39.7%) (34.5%) (13.8%) (6.9%) (3.5%) (3.5%) (100.0%)

9 8 3 2 1 1 24

2 2 1 0 0 0 5

Table III. Motor nerve conduction study median, ulnar and common peroneal nerves in 55 burn patients and 90 normal control subjects (mean + SD) Distal Nerves

-

Median: e Control 6 Burn Ulnar: e Control @ Burn Common 0 Control 0 Burn

latency (m/s)

(m/s)

Amplitude lmvl

3.18kO.72

58.90 k5.70 54.00 k 7.60*

11.45*3.39 4.41+2.21*

2.10+0.44 3.18kO.72

61.06k4.90 57.05k6.70”

12.02k4.20 4.90* 2.70*

3.66 kO.58 4.40 * 0.93”

51.29*4.00 47.61 t3.70*

2.99+0.5E3

MNCV

peroneal: 8.10*1.50 4.28 k 2.30*

"P<0.001.

Table IV. Age, sex and type of burn in relation

to percentage

pathy (47.4 per cent) among patients with third degree burns, compared with ‘19.4per cent neuropathy among patients with first and second degree burns. A significantly higher percentage of neuropathy (39.3 per cent) among patients with surface area of burn more than 20 per cent, compared with 18.5 per cent neuropathy in patients with a surface area of less than 20 per cent. At the time of examination, 31 and 24 patients had unhealed and healed wounds, respectively. Neuropathy was reported in seven (22.5 per cent) and nine (37.5 per cent) patients in both groups, respectively, with no statistically significant difference. Among 20 patients followed up for 3-12 months, the prevalence of neuropathy was 25 per cent in acute phase (before healing) and became 50 per cent after healing. One patient with distal axonal neuropathy improved after healing, three patients developed entrapment neuropathy of the ulnar nerve at the elbow and common peroneal nerve at the neck of the fibula, and three patients developed mononeuritis multiplex, as shown in Table V. Renal impairment was recorded in seven patients (12per cent). Three of them had neuropathy of ;generalized axonal type. Serum albumin and protein concentration were low in 14 patients (25 per cent) (normal range 35-50 gl). Six of them had peripheral neuropathy, three had distal axonal neuropathy and another three had mononeuritis multiplex. A study of serum electrol.ytes in burn patients showed that 11 patients (20 per cent) had low serum of neuropathies

Patients without neuropathy

Ail patients No.

No.

28 27

23 16

21 34 49 5 1

Patients with neuropathy

Per cent

Type of neuropathy

No.

Per cent

82.1 59.3

5 11

17.9 40.7*

16 27

26.2 70.6

5 10

23.8 29.4

37 2 1

75.5 40.0 100.0

12 3 0

24.5 60.0” 0.0

DAN

IVIM

EN

2 3

2 7

1 1

1 4

4 4

0 2

5 1 0

5 2 0

2 0 0

Age 0 ~20 years e 220 years Sex o Males @ Females Type of burn @ Flame * Electric o Scalding “P
axonal

neuropathy;

Table V. Percentage

MN,

of neuropathy

mononeuritis

of wound

Before healing After healing P > 0.05. DAN, Distal

axonal

neuropathy;

EN, entrapment

before and after wound

neuropathy.

closure (healing)

Patients without neuropath y

All patients Stage

multiplex;

in 20 patients

Patients with neuropathy

No.

No.

Per cent

No.

Per cent

20 20

15 IO

75.0 50.0

5 10

25.0 50.0

MM,

mononeuritis

multiplex;

EN, entrapment

neuropathy.

Type of neuropathy DAN

MM

EN

2 1

3 6

0 3

582

sodium and two (3.6 per cent) patients had high serum sodium levels with a higher prevalence of neuropathy among hyponatraemic patients (54.5 per cent) than patients with normal serum sodium (21 per cent). Hypocalcaemia was recorded in 14 patients, four ,of them had neuropathy. Serum levels of potassium, magnesium and phosphorus were normal in the majority of patients. Serum levels of trace elements (zinc and copper) were within the normal. limit (124.6124.3 and 95.4 f 25.8 pg/dl, respectively).

iscu.ssion The occurrence of peripheral neuropathy in burn patients has not been extensively studied, although some researchers have addressed this not uncommon health problem. Henderson et al.” reported. peripheral pol.yneuropathy in 15 per cent of a series of 249 acute burn patients. Helm et al3 reported a prevalence of 29 per cent in 66 patients. Helm et al.” reported 74 patients (84 per cent) who had diagnosable neuromuscular problems, of which generalized peripheral neuropathy was the most common (52 per cent). Marquez et al1 recorded 16 patients with peripheral neuropathy with a prevalence of 2 per cent. This wide variation in the prevalence of eripheral neuropathy among burn patients can be explained by the fact that some studie@ selected the symptomatic patients who had weakness and/or sensory loss. Some studies? were retrospective and did not include acute burn, and the other6 recorded the prevalence in acute burn only. In the present study, 55 patients were prospectively selected (either symptomatic or asymptomatic) with variable burn depths and at different stages. All of them were submitted to clinical and electromyographic studies. Sixteen patients (29 per cent) had neuropathy, as evidenced by electrophysiology, six of whom were symptomatic. This is similar to that recorded by Helm et al.3, but much higher than that reported by Marquez et al.‘. This discrepancy can be attributed to the retrospective nature of their study, and the fact that examination included only symptomatic patients referred to their laboratory (19 patients out of 800). Neuropathies have probably been unrecognized in other patients with severe burn and contracture’. However, Helm et al5 recorded a higher prevalence (52 per cent) by selecting symptomatic patients only. In the present study, mononeuritis multiplex represented the highest prevalence (56 per cent) of neuropathy. Twenty-nine nerves were affected in affected nerves were nine patients. Twenty-four related to the site of the burn and five nerves were away from the site of the burn. This finding was in agreement with Marquez et al.l, who reported two patients (15 per cent) with neuropathy in burned and unburned areas. The possibility of a circulating burn neurotoxin being produced by muscle has been proposed’. Four patients (10 nerves) had moderate to severe reduction in motor conduction velocity consistent with demyelination along the course of

Burns: Vol. 23, No. 718, 1997

the nerves. Three of the patients had severe electric burns and one had a severe flame burn at the site of the affected nerve. So, in those four cases, the mechanisms of injury were probably due to the direct effect of electric current on the nerve, as well as the thermal effect. Mononeuritis multiplex may occur in diseases of the vasa nervosum, such as periarteritis nodosa and lupus erythematosus. It is possible that occlusion of the nutrient arteries of nerves is an important factor in burn patients. It is well known that burn trauma causes cellular necrosis, denaturation of connective tissue and vascular occlusion in the skirP. Several mechanisms have been hypothesized to explain mononeuritis multiplex associated with burn, for example protein denaturation and clumping within the vessel lumina, increased platelet aggregation, accelerated fibrin deposition and clot formation7. Also, increased thromboxane AZ a.nd prostaglandin PC& in the serum in burn patients8 may promote ischaemic nerve injury resulting in. focal or generalized neuropathies. Compressive nerve entrapments were found to occur in 13 per cent of the total number of neuropathies, all being related to the site of burn. Of interest was that all the entrapment neuropathies developed after the closure of the ,wound (healing), which could be explained by scarring and contracture, or it may be due to poor position of the limbs. This result is supported by the follow-up of 20 patients who had no entrapment at the acute stage to find that three patients developed entrapment after healing. However, further follow-up may be needed to ascertain whether entrapment neuropathy is a reversible complication of burn. This result is in agreement with that of Marquez et all, who reported that two out of 14 mononeuritis paltients appeared to have compressive neuropathy. However, Helm et a1.5recorded a higher number of compressions, perhaps due to the nature of the inclusion criteria in their study. In the present study, generalized distal axonal neuropathy was recorded in five patients (31 per cent) out of 16 neuropathies. This; finding is higher than that reported by Marquez et all, who recorded that one patient out of 16 (6 pe:r cent) had distal axonal neuropathy, in their retrospective study. This variation could be related to the difference in surface areas and degrees of burn, in addition to a difference in patient selection criteria. Looking for risk factors for developing neuropathy in burn patients, we found a significantly higher prevalence of neuropathy in patients aged over 20 years, probably because children can not withstand a burn with the same surface area as an adult. This finding was previously reported by Helm et a1.5, who stated that a greater percentage of peripheral neuropathy occurs in adults than in children who have had flame burns. Furthermore, electric burns, burns involving full thickness of skin, and surface area more than 20 per cent were associated with a significantly higher percentage of neuro-

Khedr

et al.: Peripheral

neuropathy

in burn patients

pathy of -various types. These findings are in agreement with Henderson et al.’ and Helm et aL3r5. Other factors, such as sex, electrolyte imbalance and serum levels of trace elements, were not found to be important for developing neuropathy. In the Fresent study, generalized distal axonal neuropathy as well as mononeuritis multiplex occurred more frequently (but not at statistical significance) in patients with hypoproteinaemia and hypoalbuminaemia, elevated blood urea and creatinine and hyponatraemia. These findings are in agreement with Marquez et a1.l and can be explained on the basis that extensive burns are usually associated with severe protein loss and haemoconcentration. In addition, circulating toxins may have direct or indirect effects on peripheral nerves. Conclusions Based on results of the present study, the following can be concluded: o Neuropathy frequently occurs as a complication of burn and may affect healing and recovery. The early identification of this problem may have an important influence on healing and outcome of the patie:nt. Therefore, burn patients should be submitted to electrophysiological examination on admission and at regular intervals in a subsequent follow-up. @ Age above 20 years, electric burn, third degree and surface area of burn more than 20 per cent are im.portant risk factors for neuropathies associated with burns. e Early closure of the wound and early physiotherapy may minimize late entrapment neuropathy. 8 Antiplatelet aggregation could be tried as prophylaxis against mononeuritis multiplex.

583

@ Further studies for longer periods after healing to follow the neuropathy, either progressive or regressive are highly recommended.

References 1 Marquez S., Truley J. J., Peters W. Jo Neuropathy in burn patients. Bruin 1993; 116: 471-483. 2 Henderson B., Koepke G. H., Feller I. Peripheral polyneuropathy among patients with burns. Archives of Physical Medicine and Rehabilitution 1971; 52: 149-151. 3 Helm I’. A., Johnson E. R., Carlton A. M. Peripheral neurological problems in the acute burn patient. Bum 1977; 3: 123-125. 4 Brown W. E. Negative symptoms and signs of peripheral nerve disease, In Clinical Electromyogiaphy, eds W. F. Brown, C. F. Bolton. Butterworth-Heinemann, Reed Publishing USA, Inc., 1993, pp. 93-117. 5 Helm I?. A., Pandian G., Heck E. Neuromuscular problems in the burn patient: cause and prevention. Archives of Physical Medicine and Rehabilitation 1985; 66: 451-453. 6 Jackson D. M. The diagnosis of the depth of burning. British Journal of Surgery 1953; 40: 588-596. Branemark I’. I., Breine U., Joshi M., Urbaschek 8. Part I. Pathophysiology of thermal burns. Microvascular pathophysiology of burned tissue. Annals of Ihe Nezo York Academy of Sciences 1968; 150: 474-494. Ehrlich H. P., Needle A. L., Rajartnam J., White M. E., White B. S. The role of prostacyclin and thromboxane in rat burn and freeze injuries. Experimental and Molerulur Pathology 1983; 38: 357-367.

Paper accepted 19 June 1997. Correspondence should be addressed to: M. A. El-Oteify, Department of Plastic Surgery, Faculty of Medicine, Assiut IJniversity, Assiut, Egypt.