Leprous neuropathy: a clinical and neurophysiological study

Leprosy is one of the most common treatable causes of neuropathy in the world. Peripheral nerves and skin are commonly affected. We reported the clinical features and electrophysiological findings in 46 patients with leprosy. The aim of our study was to evaluate the nature of damage in the nerve fibres, especially in the first phase of disease. Forty‐six patients (mean age: 44.8 ± 17.8) with diagnosed leprosy were studied by neurological examination and nerve conduction studies (NCS). Twenty‐eight patients were examined for a mean period of 34.8 months. The number of tests for patients varied from 1 to 13 controls. Amplitude of sensory and motor action potentials (SNAP and MAP), sensory‐motor conduction velocity of median, ulnar, tibialis, peroneal and sural nerves were evaluated. Abnormalities were found in 282 of 647 nerves investigated (37.56%), sensory nerve abnormalities being more frequent than motor (50.16% 29.45). Of 282 nerves with neurophysiological abnormalities, 123 were clinically asymptomatic (43.62%). A statistically significant correlation between duration of disease and number of electrophysiological abnormalities was demonstrated. In 19 nerves partial "conduction‐block"(reduction of cMAP > 50% in the proximal response) was individuated. The first electrophysiological alteration, suggesting segmental demyelination, was detected in 41 nerves of 21 patients (33.3 %). According to this view, our data support the hypothesis that leprosy induces a neuropathy of demyelinating nature in the first phase.     

A 2-year follow-up survey of 523 cases with peripheral nerve injuries caused by the earthquake in Wenchuan,China

We performed a 2-year follow-up survey of 523 patients with peripheral nerve injuries caused by the earthquake in Wenchuan, Sichuan Province, China. Nerve injuries were classified into three types: type I injuries were nerve transection injuries, type II injuries were nerve compression injuries, and type III injuries displayed no direct neurological dysfunction due to trauma. In this study, 31 patients had type I injuries involving 41 nerves, 419 had type II injuries involving 823 nerves, and 73 had type III injuries involving 150 nerves. Twenty-two patients had open transection nerve injury. The restoration of peripheral nerve function after different treatments was evaluated. Surgical decompression favorably affected nerve recovery. Physiotherapy was effective for type I and type II nerve injuries, but not substantially for type III nerve injury. Pharmacotherapy had little effect on type II or type III nerve injuries. Targeted decompression surgery and physiotherapy contributed to the effective treatment of nerve transection and compression injuries. The Louisiana State University Health Sciences Center score for nerve injury severity declined with increasing duration of being trapped. In the first year after treatment, the Louisiana State University Health Sciences Center score for grades 3 to 5 nerve injury increased by 28.2% to 81.8%. If scores were still poor(0 or 1) after a 1-year period of treatment, further treatment was not effective.     

Electrophysiological evaluation of peripheral and autonomic involvement in leprosy

OBJECTIVE: Motor and sensory nerve conductions, F responses, sympathetic skin responses and R-R interval variations (RRIV) were studied to determine the type of peripheral neuropathy among patients with leprosy. METHODS: Twenty-nine consecutive patients with leprosy (25 male, 4 female) hospitalized in the "Istanbul Leprosy Hospital" between January - December, 1999 were included in this study. Ten patients had borderline lepromatous leprosy, and 19 had lepromatous leprosy. None of the patients studied had the tuberculoid form. The mean age was 55 +/- 12 years. The control group consisted of 30 (26 male, 4 female) healthy volunteers (mean age: 58.1 +/- 7.8 years). All subjects included in the study underwent neurological examination and electrophysiological evaluation. Standard procedures were performed for evaluating sensory and motor conduction studies. Motor studies were carried out on both left and right median, ulnar, tibial and common peroneal nerves while median, ulnar, sural and superficial peroneal nerves were examined for sensory studies. Sympathetic skin response recordings on both hands and RRIV recordings on precordial region were done in order to evaluate the autonomic involvement. RESULTS: The lower extremity was found to be more severely affected than the upper, and sensory impairment predominated over motor. Of 58 upper limbs examined, no sympathetic skin responses was recorded in 46 (79.3%). Compared with the controls, the RRIVs of the leprosy patients were found to be reduced during both resting and deep forced hyperventilation. CONCLUSION: Our results indicate that leprosy causes a predominantly axonal polyneuropathy that is more severe in the lower extremities. Sensory nerve damage is accompanied by autonomic involvement.     

Peripheral neuropathy in children on long-term phenytoin therapy

Nerve conduction studies of the ulnar, median, posterior tibial, peroneal and sural nerves were performed in 21 epileptic children aged 6 to 17 years on long-term phenytoin therapy. Auditory brain stem evoked responses were obtained in 16 patients to evaluate the effect of phenytoin on central nervous system synapses. Of the 21 patients examined, 15 (71.4%) showed abnormal findings. The most frequent abnormality was slowed motor conduction velocity of the ulnar nerve (33.3%) and posterior tibial nerve (23.8%), followed by slowed sensory conduction velocity of the sural nerve (20%), lowered H/M ratio (14.3%), slowed motor conduction velocity of the peroneal nerve (14.3%) and of the median nerve (14.2%). A significant correlation was noted between the total dosage and duration of therapy with PHT and the reduction of motor conduction velocity in the posterior tibial nerve. Auditory brain stem evoked responses showed no significant differences in each peak latency between the patients and the normal control group. The study indicates that long-term phenytoin therapy can cause latent impairment of peripheral nerve function in children with no clinical evidence of peripheral neuropathy.     

Immunohistological localization of mycobacterial antigens within the peripheral nerves of treated leprosy patients and their significance to nerve damage in leprosy

The presence and distribution of Mycobacterium leprae-specific and cross-reacting antigens within the peripheral nerves of multidrug-treated patients with leprosy was investigated to gain a better understanding of the mechanism of nerve damage and the effect of multidrug therapy (MDT) on it. There was no specific qualitative difference in the type of antigens in the leprosy spectrum. However, our results indicate that there may be differential handling of antigens by the macrophages as compared to Schwann cells. This could play a key role in the pathogenesis of the disease. Multidrug treatment is effective in arresting the progression of the disease process as well as in reducing the viable bacterial load, both in borderline lepromatous and lepromatous (MB) and borderline tuberculoid and tuberculoid (PB) cases. However, the presence of M. leprae antigens in all the multidrug-treated MB nerve lesions and 87% of PB nerve lesions suggest that the antigens persist for a prolonged period. Hence, the risk of immunological reaction and antigen-associated silent nerve damage may continue even after majority of M. leprae were killed. The findings give further support to the view that most of the nerve damage is due to bacterial antigens.Supported by LEPRA     

Clinical and electrophysiological findings and follow-up in tarsal tunnel syndrome

The authors report clinical and electrophysiological findings in 59 patients with tarsal tunnel syndrome (TTS) and follow-up in 23 of them. The entrapment was prevalent in females; was bilateral in 6 patients and involved medial plantar in 7 and lateral plantar nerves in two cases. Eleven presented with other nerve entrapment syndromes or focal mononeuropathies, due to hereditary neuropathy with liability to pressure palsy or systemic diseases. The other 48 subjects had TTS without any other related entrapment syndromes: 23 were idiopathic cases, 13 had a history of local trauma, 3 had systemic diseases and the others had external or intrinsic compressions. The most frequent symptoms were paraesthesia or dysaesthesia (86% of feet) and pain (55%). Hypoaesthesia of the sole and weakness of toe flexion were evident in 74% and 22% of feet, respectively. Absence of sensory action potential or slowing of sensory conduction velocity (SCV) of the plantar nerves were present in 77% of feet; significant differences of SCV between affected and unaffected plantar nerves and/or between distal sural and plantar nerves were evident in 14%. Abnormalities of plantar SCV were therefore absent in only 9% of feet. Distal motor latency was delayed in 55% and electromyography showed neurogenic changes in 45% of sole muscles. Five cases (6 feet) underwent surgery with excellent or good results in 5, 4 of them also showing improvement in distal conduction of the plantar nerves. Nine were treated with local steroid injections, with good results shown in 6 patients. Nine other patients who did not receive any therapy showed a disappearance of symptoms or good outcome in 6 cases. The subjects with poor therapeutic results had S1 radiculopathy or systemic diseases. The authors underline that patients with connective tissue diseases should not be treated by surgical decompression because they may have subclinical neuropathy. Some subjects with idiopathic or trauma-induced TTS recover spontaneously. Surgical release should be limited to cases with space-occupying lesions and when conservative treatments fail.     

Subclinical cranial nerve involvement in hereditary motor and sensory neuropathy: a combined conduction study with electrical and magnetic stimulation.

OBJECTIVE: To evaluate the electrophysiological findings of clinically unaffected cranial nerves (facial, accessory and hypoglossal nerves) in hereditary motor and sensory neuropathy (HMSN). METHODS: The conduction times of the facial, accessory, and hypoglossal nerves in 10 patients with HMSN type I (HMSN I), 2 patients with HMSN Type II (HMSN II), and 20 normal controls were determined. The extra- and intracranial segments of the cranial nerves were stimulated electrically and magnetically, respectively. The relationships between the conduction parameters of the cranial nerves and limb nerves were analyzed. RESULTS: In patients with HMSN I, the conduction times of the distal and proximal segments were significantly prolonged in all 3 cranial nerves. A positive correlation was found between the conduction parameters of the cranial nerves and the limb nerves. CONCLUSIONS: Electrophysiological involvement of the whole segment of the facial, accessory and hypoglossal nerves is common in patients with HMSN I without clinical signs of alterations. The degree of conduction slowing of the facial, accessory, and hypoglossal nerves paralleled that of limb nerves.     

Facial nerve conduction in diabetic neuropathy

Diabetes mellitus (DM) has a severe influence on the nervous system and it is more likely to occur on the nerves of the upper and lower extremities than on the cranial nerves. According to the statistics, the incidence of cranial nerve involvement ranges anywhere from 3% to 14%. The aim of this study is to perform facial nerve conduction studies in diabetic patients with peripheral neuropathy, confirmed by electrophysiological methods, to determine the frequency of affection of a cranial nerve conduction in a neuropathy which mainly occurs in a distal, symmetric fashion. The study was conducted in a group of 20 diabetics who had electrophysiologically confirmed polyneuropathy. All of the patients had type 2 DM. Sixteen of the patients were receiving insulin therapy and 4 were treated with oral hypoglycaemic agents only. We found prolonged facial nerve distal latency at least on one tested side in 70% of patients. Distal latency and amplitudes of muscle responses to facial nerve stimulation showed a statistically significant difference from controls (p < 0.001). This study has shown that proximal nerves like cranial nerves are affected in a high proportion of cases in a neuropathy which mainly occurs in a distal symmetric fashion. The facial nerve is one of the most easily accessible nerves in the proximal part of the body (head-face) and makes it suitable for routine evaluation. We believe this conduction abnormality may give us the chance to classify these neuropathies as more severe than the ones that only have limb conduction abnormalities. Further studies should be performed in order to confirm these findings.     

The pathology of early leprous neuropathy

A qualitative and quantitative study was made of early changes in nerves from 10 patients with tuberculoid or lepromatous type of leprosy. Five nerve biopsies, taken from sites remote from skin lesions, were considered to be unaffected when examined by paraffin histology but showed abnormalities in semi-thin resin sections and by electron microscopy; 5 showed mild to moderate involvement by paraffin histology. Changes in 'unaffected' nerves in both types of leprosy included the presence of subperineurial oedema; occasional evidence of fibre regeneration, sometimes with atypical features; increased numbers of small myelinated fibres, possibly a consequence of axonal atrophy; a few thinly remyelinated fibres, probably due to secondary demyelination, and some loss of unmyelinated axons. In more affected nerves there was variable loss of axons, both myelinated and unmyelinated. Demyelination was not a conspicuous feature; there was evidence of axonal atrophy in some fibres. Similarities in some of the changes observed in tuberculoid and lepromatous types of leprosy suggest a common mechanism of nerve damage, at least in the early stages. The presence of abnormalities in nerves at a distance from skin lesions implies a more diffuse nerve involvement than might have been expected in both types of leprosy.     

Mandating nerve biopsy: A step towards personalizing therapy in pure neuritic leprosy

Pure neuritic leprosy (PNL) accounts for 5% to 10% of leprosy patients who usually present with asymmetrical neuropathy in the absence of lepra bacilli on slit‐skin smears. However, nerve biopsies in PNL lack appropriate categorization in current immunologic terms. We aimed to classify nerve biopsies according to the immune spectrum of leprosy and assess the role of histologic classification of nerve biopsies in treating PNL. Patients from two tertiary care referral centres were enrolled in this incident case study. Patients presenting with mononeuropathy and multiple mononeuropathies presumably with leprosy, without skin lesions, underwent nerve biopsy and slit‐skin smear examination. Amongst 78 patients with mononeuropathy, 38 were diagnosed with leprosy on nerve biopsy. Leprosy was classified as tuberculoid in 16, lepromatous in 5 and borderline in 17 patients. Lepra bacilli were present in 15 biopsies. On comparing histologic subtypes with number of nerves involved clinically, a significant number of cases with single nerve involvement showed multibacillary (BB, BL or LL) histology and vice versa. Nerve biopsy helps in diagnosing patients presenting with PNL and aids in classifying it to customize the treatment for best results. Current treatment recommendations for PNL from WHO and National Leprosy Eradication Program are based on clinical assessment only, which are likely to result in inconsistent treatment and possibly relapse in cases where histomorphology shows disparity. Inclusion of nerve biopsy to guide therapy in patients with PNL is suggested.     

Somatosensory evoked potentials in Charcot-Marie-Tooth disease

SEPs by median nerve stimulation have been performed in 18 adult patients (12 males and 6 females) affected by CMTD (type I, 13 patients; type II, 5 patients). All patients underwent MCV studies (median, ulnar, peroneal nerve), SCV studies (median and sural nerve), VEP, BAEP. N9 and N13 peaks were not detectable in 7/13 and 5/13 cases (HMSN type I) while cortical N19 were always recorded. Latency values of all responses were moderately or markedly delayed in all cases with HMSN type I, but proved normal or slightly delayed in HMSN type II cases. The prolonged latencies were mainly related to slowing of peripheral conduction. N9-N13 inter-peak was abnormally prolonged in 2 cases and N13-N19 in 2 other cases; both were prolonged in another case. In another 3 cases an abnormal BAEP was recorded. The few patients with abnormal CCT and BAEP probably belong to a borderline form between HMSN and hereditary ataxias.     

Electromyographic diagnosis of leprosy

Eighty untreated patients suspected to have leprosy were submitted to neurophysiological examination and later compared with the clinical diagnosis. Among the patients who had leprosy confirmed, 98% had EMG abnormalities. Motor and sensory amplitude reduction was the earliest and the most frequent abnormality. Low conduction velocity of the ulnar nerve across the elbow was present in over 55% of the patients. A "mosaic" peripheral polyneuropathy was the most characteristic finding, and seems to be helpful to the diagnosis of leprosy. All of the clinical forms showed EMG abnormalities, and even some asymptomatic contacts, however the abnormalities increase from the undetermined and tuberculous to the borderline and Virchow's forms.     

Teased fibre study of early nerve lesions in leprosy and in contacts, with electrophysiological correlates.

A teased fibre technique was used to study 19 biopsies of the index finger branch of the radial cutaneous nerve of leprosy patients and contacts. These were compared with four normal nerves. Five nerves were from patients with preclinical nerve lesions, five from leprosy patients with minimal sensory nerve impairment, and five from contacts of lepromatous leprosy. The extent of demyelination in preclinical nerve lesions in leprosy and in contacts of leprosy is recorded. The usefulness of nerve conduction velocity studies in early leprosy patients and in contacts is discussed.     

Peripheral nerve biopsies in the diagnosis of leprosy in Aboriginal patients from the Northern Territory of Australia.

In the 12 years from 1964 to 1976, 171 peripheral nerve biopsies were taken from 81 Aboriginal patients in the Northern Territory of Australia, in whom a diagnosis of leprosy was either known or strongly suspected. Sixty-eight biopsy samples were from 19 patients known to have leprosy, and who were under assessment for nerve grafting, results of which have already been published. We describe here the histopathological findings in the remaining 62 patients, in whom a diagnosis of leprosy was suspected on clinical grounds, backed in many cases by abnormalities of nerve conduction. Forty-one patients (66%) had abnormal histopathological findings in the nerve biopsy sample, 19 (31%) showing definite evidence of leprosy. Several patients with enlarged peripheral nerves, in whom the biopsy findings did not confine leprosy, remain under observation; their future investigation will include lymphocyte transformation tests and testing with refined lepromin, together with repeat nerve biopsy, where ethical and feasible. The clinical and epidemiological data suggest that a previous, and perhaps self-healing, form of leprosy may account for the neurological findings.     

Nerve conduction defects are retarded by tight metabolic control in type I diabetes

This follow-up study examines whether the development of nerve dysfunction is retarded by tight metabolic control in patients with type I diabetes mellitus. Seventy-one patients and 115 age-matched healthy control subjects underwent studies of nerve conduction in peroneal and sural nerves. The presence of diabetes was associated with a reduction in peroneal motor nerve conduction velocity (MCV) by 5.9 m/s, sural sensory nerve conduction velocity (SCV) by 3.4 m/s, and sural sensory nerve action potential (SNAP) amplitude by 22%. Dysfunction in peroneal MCV, sural SCV, and sural SNAP were related to long-term poor metabolic control. Eleven of 12 patients with HbA1c <6.5% had normal nerve conduction or abnormality in only one nerve as compared to 2 of 15 patients with HbA1c >8.0%. It is concluded that tight long-term metabolic control (HbA1c <6.5%) can retard nerve dysfunction in patients with type I diabetes mellitus and a mean disease duration of 12 years.     

Pathological,ultrasonographic, and electrophysiological characterization of clinically diagnosed cases of pure neuritic leprosy

A subset of neuritic form of leprosy, called pure neuritic leprosy (PNL), seen in a minority of leprosy patients, is characterized by peripheral neuropathy without skin lesions and an absence of acid‐fast bacilli on skin smears. Patients with PNL are often started on drug therapy without confirmation of diagnosis. We, therefore, did a prospective study of clinically diagnosed PNL patients with correlation of ultrasonographic and biopsy findings. A total of 100 consecutive patients with PNL, diagnosed according to the consensus case definition, were included in the study. All patients underwent nerve conduction study, peripheral nerve ultrasonography, and sural nerve biopsy. Multiple mononeuropathies were present in 75% of cases, mononeuropathy in 18%, and polyneuropathy in the remaining 7%. Compared to clinical examination, ultrasonographic assessment of the peripheral nerves was not only better at the detection of thickening but also helped in characterization of their fascicular architecture, echogenicity, and vascularity. A total of 32 cases were confirmed on nerve biopsy, out of which 75% had demonstrable lepra bacilli. Cranial nerve involvement, presence of trophic ulcers, and bilateral thickening of the great auricular nerve were significantly associated with the positivity of lepra bacilli. A significant improvement in the disability score happened after multidrug therapy. A comprehensive electrophysiologic, ultrasonographic, and histological evaluation may be helpful in establishing a diagnosis of PNL with greater confidence, while ruling out other non‐leprosy diagnoses.     

Perforating branches from offending arteries in hemifacial spasm: anatomical correlation with vertebrobasilar configuration

OBJECTIVE: In microvascular decompression for hemifacial spasm, the perforating branches around the facial nerve root exit zone occasionally complicate facial nerve decompression. In this context, the vertebrobasilar configuration was retrospectively correlated with the perforating branches. METHODS: Based on vertebral angiography, magnetic resonance angiography, and three dimensional computed tomographic angiography, 69 patients were divided into three groups, according to the anatomy of the vertebrobasilar system. In patients with the type I configuration, the vertebral artery on the affected side was dominant and had a sigmoidal course. The type II patients had the basilar artery curving mainly towards the affected side. The type III patients showed the basilar artery either running straight or curving toward the unaffected side. The relation of the anatomical configuration of these vessels with the perforating branches around the facial nerve exit zone was investigated. RESULTS: The posterior inferior cerebellar artery in type I patients (n=33) and the anterior inferior cerebellar artery in type II (n=5) and type III (n=31) patients were the most common offending arteries. More than half of the type I patients (n=20) showed no perforating branches around the facial nerve exit zone. However, the type II (n=3) and III patients (n=23) often showed one or more perforating branches around that region. CONCLUSIONS: The configuration of the vertebrobasilar system has a significant correlation with the presence of perforating branches near the site of microvascular decompression. These perforating vessels are often responsible for the difficulty encountered in mobilising the offending artery during the procedure.     

Cranial nerve involvement in patients with leprous neuropathy

BACKGROUND: Leprosy is one of the most common causes of peripheral neuropathy, perhaps closely matched by diabetic neuropathy. Patterns of peripheral neuropathy in leprosy can be varied, which may include mononeuropathy, mononeuritis multiplex and symmetric polyneuropathy. Cranial nerves, especially facial and trigeminal nerves, are also commonly involved in leprosy. AIMS: To find out the pattern and spectrum of cranial nerve involvement in a consecutive series of patients with leprous neuropathy. SETTINGS AND DESIGN: A retrospective review of patients admitted with leprosy to the Neurology Department of a tertiary care center. MATERIALS AND METHODS: All consecutive patients admitted during an 8-year period (1995-2003) and diagnosed to have leprosy were included. They were clinically evaluated to determine the frequency and pattern of cranial nerve involvement. RESULTS: About 18% (9/51) of the leprosy patients seen during that period had clinical evidence of cranial nerve involvement. Facial and trigeminal nerves were the most commonly affected (five and four patients respectively). CONCLUSIONS: Cranial nerve involvement is common in leprosy, which emphasizes the need to carefully examine them. Also, one should exclude leprosy in patients presenting with isolated cranial neuropathies.     

Respective importance of different nerve conduction velocities in leprosy

Motor and sensory nerve conduction studies were performed in the distal part of the ulnar, median and radial nerves of 12 tuberculoid and 12 lepromatous leprosy patients, compared with 15 normal subjects. Slowing of sensory conduction velocity (SCV) was shown in all nerves with no difference between tuberculoid and lepromatous patients. The radial SCV slowing is correlated (P < 0.001) with the clinical findings. Impairment of motor distal latencies was observed only in tuberculoid patients. It is concluded that the radial SCV is the most reliable conduction test and is proposed as an early diagnostic test for leprosy.     

神经型布氏杆菌病周围神经损害的临床与电生理研究

目的研究神经型布氏杆菌病周围神经损害的临床特征,探讨电生理对其的诊断价值。方法对32例神经型布氏杆菌病周围神经损害患者(病例组)和32名性别及年龄与病例组匹配的正常对照组进行神经电生理检查,并对所得检查结果进行统计学分析。结果病例组与对照组在运动末梢潜伏期(distal motor latency,DML)、复合肌肉动作电位(compound motor active potentials,CMAP)波幅、运动神经传导速度(motor nerve conduction velocity,MCV)、感觉神经动作电位潜伏期(sensory nerve action potential latency,SL)、感觉神经动作电位(sensory nerve action potential,SNAP)波幅及感觉神经传导速度(sensory nerve conduction velocity,SCV)方面的比较,差异均有统计学意义(P0.05)。电生理检查提示上下肢周围神经损害,感觉神经及运动神经均受累,其中感觉神经占55.47%,运动神经占16.80%,上肢以正中神经(64条)最多见,下肢以腓肠神经(16条)最多见。四肢运动神经256条中43条传导速度减慢,占16.80%,四肢感觉神经256条中142条传导速度减慢,占55.47%,SCV较MCV改变明显,上肢病变重于下肢。结论神经电生理检查为神经型布氏杆菌病周围神经损害的临床诊断提供了客观依据。