Clinical and electrophysiological characteristics of neuropathic pain in leprosy patients: A prospective cross-sectional study

Introduction

Leprosy is a common, treatable cause of peripheral neuropathy in many tropical and subtropical countries.^1,2 Mycobacterium leprae has a distinct predilection for areas of low body temperature and a unique tropism for nerves. It frequently afflicts the ulnar nerve possibly due to its superficial location. The frequent delays in the diagnosis of leprosy allows the progression of nerve damage, often resulting in deformity.^1,3-5

Neuropathic pain is a common symptom afflicting over 60% of patients with leprosy and may present before, during, or after treatment. It is frequently reported during leprosy reactions.⁶ The International Association for the Study of Pain defines neuropathic pain as “pain initiated or caused by a primary lesion or dysfunction in the nervous system.”^6-9 Neuropathic pain originating in the peripheral nervous system as occurs in leprosy is characterized by injury to thin and nonmyelinated fibers. This type of injury is difficult to assess by conventional neurophysiological techniques such as electroneuromyography, although late latency evaluations such as the F-wave and sympathetic skin response are useful in their detection.¹ Even in the absence of distal alterations, the A-wave tends to appear during the F-wave study in patients complaining of neuropathic pain.^1,10,11

The previous studies have suggested that neuronal dysfunction occurs long before the clinical deterioration and the involvement of the nerve trunks.^12-15 We conducted a systematic electrophysiological evaluation of leprosy patients with neuropathic pain, to correlate the clinical and electrophysiological findings.

Methods

Results

Mononeuropathy or multiple mononeuropathy patterns were most frequently seen [Table 1]. The A-wave was infrequent (5/21) in the nerve conduction studies (19%). There was significant difference between between those with mononeuropathy/ multiple mononeuropathy and the others (Chi-square, P = 0.0088). The sympathetic skin response was absent in 16 patients – on the soles in ten patients, on the palm in one patient and on both palms and soles in five patients [Figure 1]. The superficial fibular nerve was the most affected, followed by the sural nerve. In our study, some patients with thickened nerves had normal nerve conduction studies.

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Figure 1a:

Relationship between disease duration and sympathetic skin response of the 21 patients in the study

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Figure 1b:

Pearson correlation coefficient of affected nerves according to electroneuromyography and disease duration of the studied sample. Tropical Medicine Center, HCSM-UEPA—Belém-PA, 2014

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Of the 21 enrolled patients, 13 were men and eight were women. The average age of the patients was 41.3 ± 12.4 years [Figure 1]. The majority of enrolled patients had multibacillary disease (19/21 patients). Seventeen of the patients had dimorphic leprosy and 11 patients had type I reaction [Table 2]. The duration of disease at presentation ranged from 13 to 72 months in 12 patients and the duration of multidrug therapy ranged from 7 to 12 months in 13 patients [Figure 1]. Seventeen of the 21 patients were on corticosteroid therapy [Tables 3 and 4]. The ulnar nerve was most frequently affected and 18 patients exhibited some degree of disability [Table 2].

Discussion

Neuropathic pain is a frequently overlooked symptom in the management of leprosy. Patients during or after multidrug therapy have a high prevalence of neuropathic pain.^10,19-22 Although the frequency and nature of the neuropathic pain in leprosy is unclear, it seems that late diagnosis of leprosy and the evolution of nerve damage contributes to the onset of pain [Table 3] Neuropathic pain is most commonly seen in borderline and MB cases.^10,23-26

Multifocal mononeuropathies are the most prevalent neurophysiological pattern and the ulnar nerve is most often affected.^27,28 Electromyography is an excellent tool for early detection and monitoring nerve damage.^2,29-31 In our study, some patients with thickened nerves had normal nerve conduction studies. This clinicoelectrophysiological dissociation may be due to the involvement of few fascicles initially sparing of the faster conducting fibers.^32-34 Contrary to the findings of Garbino et al., we found a low prevalence of A-waves which may be due the fact that most patients had been treated or were under treatment with corticosteroids [Table 4].^35-36

Conclusion

In this study, mononeuropathy and multiple mononeuropathy were the most common patterns and the ulnar nerve was the most affected nerve trunk. The neurophysiological assessment did not reveal the predominance of any specific electromyographic pattern and some patients in this study showed normal nerve conduction studies. The DN4 questionnaire scale revealed more intense pain in female patients and in patients on corticosteroids.