Neuroimaging in leprosy: The nerves and beyond

The American Journal of Tropical Medicine and Hygiene

Neurotropism and infiltration by Mycobacterium leprae of peripheral nerves causing neuropathy are well established, but reports of central nervous system (CNS) damage are exceptional. We report CNS magnetic resonance imaging (MRI) abnormalities of the brain and spinal cord as well as lesions in nerve roots and plexus in leprosy patients. Eight patients aged between 17 and 41 years underwent detailed clinical, histopathological, and MRI evaluation. All had prominent sensory-motor deficits with hypopigmented and hypo/anesthetic skin patches and thickened peripheral nerves. All demonstrated M. Leprae DNA in affected peripheral nerve tissue. All received multidrug therapy (MDT). Two patients had brainstem lesions with enhancing facial nuclei and nerves, and one patient had a lesion in the nucleus ambiguus. Two patients had enhancing spinal cord lesions. Follow-up MRI performed in four cases showed resolution of brainstem and cord lesions after starting on MDT. Thickened brachial and lumbosacral plexus nerves were observed in six and two patients, respectively, which partially resolved on follow-up MRI in the two cases who had reimaging. The site and side of the MRI lesions corresponded with the location and side of neurological deficits. This precise clinico-radiological correlation of proximal lesions could be explained by an immune reaction in the gray matter corresponding to the involved peripheral nerves, retrograde axonal and gray matter changes, or infection of the CNS and plexus by lepra bacilli. Further study of the CNS in patients with leprous neuropathy is needed to establish the exact nature of these CNS MRI findings.

Skeletal Radiology, 2000

Objective. To analyze peripheral nerves with ultrasonography (US) and magnetic resonance imaging (MR) in leprosy and assess the role of imaging in leprosy patients. Design and patients. Fifty-eight nerves with abnormal clinical features or electromyograms were examined in 23 leprosy patients by means of gray-scale US, Doppler US and MR imaging. Image analysis included: measurement of nerve crosssectional area; assessment of nerve structure and MR signal intensities; identification of nerve compression within osteofibrous tunnels; detection of endoneural color flow signals and Gd-DTPA enhancement. Correlations were made with clinical findings and a control group of 20 subjects. Fourteen nerves in active reversal reaction were followed up after therapy. Results. Leprosy nerves were classified into three groups based on imaging appearance: group I consisted of 17 normal-appearing nerves; group II, of 30 enlarged nerves with fascicular abnormalities; group III, of 11 nerves with absent fascicular structure. Group II nerves were from patients subjected to reversal reactions; 75% of patients with group III nerves had a history of erythema nodosum leprosum. Nerve compression in osteofibrous tunnels was identified in 33% of group II and 18% of group III nerves. Doppler US and MR imaging were 74% and 92% sensitive in identifying active reactions, based on detection of endoneural color flow signals, long T2 and Gd enhancement. In 64% of cases, follow-up studies showed decreased color flow and Gd uptake after steroids and decompressive surgery. Conclusions. US and MR imaging are able to detect nerves abnormalities in leprosy. Active reversal reactions are indicated by endoneural color flow signals as well as by an increased T2 signal and Gd enhancement. These signs would suggest rapid progression of nerve damage and a poor prognosis unless antireactional treatment is started.

2000

A total of 33 patients, 28 males and five females, from nine to 87 years of age, with suspected leprosy associated peripheral neuropathy, without detectable skin lesion or positive skin bacilloscopy, were studied during the period of 1994 to 2004. Patients were s u b m i t t e d t o d e r m a t o

Brazilian Journal of Case Reports, 2021

Although neuropathy remains one of the most problematic issues faced by leprosy patients, the evolving process of its findings continues a challenge particularly in pure neural leprosy (PNL). We evaluated neurological examination, nerve conduction studies and histhopathological data of patients with PNL and ulnar neuropathy. Patients with longer duration of symptoms had reduction in the motor conduction velocities and patients with fibrosis in the biopsy had axonal damage in the nerve conduction studies. This suggests that focal demyelination may be present in leprosy patients at the moment of the diagnosis and be related to the duration of the neuropathy.

São Paulo Medical Journal

Introduction: Leprosy household contacts (HC) have high chances to develop leprosy. Anti-PGL-I IgM seropositivity also increases the risk of illness. Objectives: Identify neural impairment in leprosy HC by analyzing differences in high-resolution ultrasonographic (US) measurements of peripheral nerves between HC and healthy volunteers (HV). Methods: Seventy nine seropositive household contacts (SPHC), 30 seronegative household contacts (SNHC) and 53 HV underwent dermato-neurological examination and laboratorial analysis, followed by high-resolution US evaluation of cross-sectional areas (CSAs) of the median, ulnar, common fibular and tibial nerves. Results: Neural thickening was clinically observed in only 2% of SPHC and none of the SNHC. None of the HC presented skin lesion, sensory symptoms or muscular weakness. The US evaluation detected neural thickening in 26.5% of the SPHC and only in 3.3% among the SNHC. Among SPHC with thickening detected by US, the mean number of nerves aff...

São Paulo Medical Journal

Introduction: Leprosy is the most common cause of peripheral neuropathy, leading to sequelae that perpetuate the stigma linked to the disease. Electroneuromyography (ENMG) is the gold standard to evaluate neural damage, as it can detect even subclinical alterations. Objectives: To describe the electroneuromyographic findings in leprosy patients. Methods: Retrospective analysis of the records from patients with leprosy in a Brazilian Reference Center, between 2014 and 2021. The sensibility conduction of the median, ulnar, radial, sural and peroneal nerves, and motor conduction of the median, ulnar, peroneal and tibial nerves were analyzed. Results: Five hundred and thirteen patients with leprosy submitted to ENMG at the diagnosis were analyzed. The mean age was 45.8 years (±16.6) with 50.1% being male, and multibacillary represented 85.8% of the cases. Of these patients, 71.9% presented neural damage compatible with leprosy. In total, 2,627 damaged nerves were found, with a mean of 7...

Brazilian Journal of Medical and Biological Research, 2006

The nerve biopsies of 11 patients with pure neuritic leprosy were submitted to routine diagnostic procedures and immunoperoxidase staining with antibodies against axonal (neurofilament, nerve growth factor receptor (NGFr), and protein gene product (PGP) 9.5) and Schwann cell (myelin basic protein, S-100 protein, and NGFr) markers. Two pairs of non-adjacent histological cross-sections of the peripheral nerve were removed for quantification. All the fascicles of the nerve were examined with a 10X-ocular and 40X-objective lens. The immunohistochemistry results were compared to the results of semithin section analysis and clinical and electroneuromyographic data. Neurofilament staining was reduced in 100% of the neuritic biopsies. NGFr positivity was also reduced in 81.8%, PGP staining in 100% of the affected nerves, S100 positivity in 90.9%, and myelin basic protein immunoreactivity in 90.9%. Hypoesthesia was associated with decreased NGFr (81.8%) and PGP staining (90.9%). Reduced potential amplitudes (electroneuromyographic data) were found to be associated with reduced PGP 9.5 (63.6%) and nerve fiber neurofilament staining (45.4%) by immunohistochemistry and with loss of myelinated fibers (100%) by semithin section analysis. On the other hand, the small fibers (immunoreactive dots) seen amid inflammatory cells continued to be present even after 40% of the larger myelinated fibers had disappeared. The present study shows an indepth view of the destructive effects of leprosy upon the expression of neural markers and the integrity of nerve fiber. The association of these structural changes with the clinical and electroneuromyographic manifestations of leprosy peripheral neuropathy was also discussed.

Memórias do Instituto Oswaldo Cruz, 2012

Nerve biopsy examination is an important auxiliary procedure for diagnosing pure neural leprosy (PNL). When acid-fast bacilli (AFB) are not detected in the nerve sample, the value of other nonspecific histological alterations should be considered along with pertinent clinical, electroneuromyographical and laboratory data (the detection of Mycobacterium leprae DNA with polymerase chain reaction and the detection of serum anti-phenolic glycolipid 1 antibodies) to support a possible or probable PNL diagnosis. Three hundred forty nerve samples [144 from PNL patients and 196 from patients with non-leprosy peripheral neuropathies (NLN)] were examined. Both AFB-negative and AFB-positive PNL samples had more frequent histopathological alterations (epithelioid granulomas, mononuclear infiltrates, fibrosis, perineurial and subperineurial oedema and decreased numbers of myelinated fibres) than the NLN group. Multivariate analysis revealed that independently, mononuclear infiltrate and perineurial fibrosis were more common in the PNL group and were able to correctly classify AFB-negative PNL samples. These results indicate that even in the absence of AFB, these histopathological nerve alterations may justify a PNL diagnosis when observed in conjunction with pertinent clinical, epidemiological and laboratory data.

São Paulo Medical Journal

Introduction: Leprosy is the most common treatable peripheral neuropathy worldwide. The detection of peripheral nerve impairment is essential for its diagnosis and treatment. Objectives: To identify neural thickening through multisegmental ultrasonography (US). Methods: US measurements of cross-sectional areas (CSAs) of ulnar, median and tibial nerves at two points (in the osteofibrous tunnel and proximal to the tunnel), and also of the common fibular nerve at the fibular head. CSA index (ΔCSA) was calculated as the absolute difference between CSAs from the contralateral side. This is a cross-sectional study composed of 53 leprosy patients (LP) and 53 healthy volunteers (HV). Results: US evaluation detected a total of 138 enlarged nerves, implying neural impairment in 71.7% (38/53) of LP (3.6 enlarged nerves/LP). We detected only mononeuropathy on patient in 23.7% (9/38), and multiple mononeuropathy in 76.3% (29/53). The ulnar and tibial were the most frequently affected nerves. The...

PLOS Neglected Tropical Diseases, 2015

Background Neurological involvement occurs throughout the leprosy clinical spectrum and is responsible for the most feared consequences of the disease. Ultrasonography (US) provides objective measurements of nerve thickening and asymmetry. We examined leprosy patients before beginning multi-drug therapy aiming to describe differences in US measurements between classification groups and between patients with and without reactions. Methodology/Principal Findings Eleven paucibacillary (PB) and 85 multibacillary (MB) patients underwent nerve US. Twentyseven patients had leprosy reactions (type 1, type 2 and/or acute neuritis) prior to US. The ulnar (at the cubital tunnel-Ut-and proximal to the tunnel-Upt), median (M) and common fibular (CF) nerves were scanned to measure cross-sectional areas (CSAs) in mm 2 and to calculate the asymmetry indexes ΔCSA (absolute difference between right and left CSAs) and ΔUtpt (absolute difference between Upt and Ut CSAs). MB patients showed greater (p<0.05) CSAs than PB at Ut (13.88±11.4/9.53±6.14) and M (10.41±5.4/6.36±0.84). ΔCSAs and ΔUtpt were similar between PB and MB. The CSAs, ΔCSAs and ΔUtpt were similar between PB patients with reactions compared to PB patients without reactions. MB patients with reactions showed significantly greater CSAs (Upt, Ut and M), ΔCSAs (Upt and Ut) and ΔUtpt compared to MB patients without reactions. PB and MB showed similar frequencies of abnormal US measurements. Patients with reactions had higher frequency of nerve thickening and similar frequency of asymmetry to those without reactions. Conclusions/Significance This is the first study to investigate differences in nerve involvement among leprosy classification groups using US before treatment. The magnitude of thickening was greater in MB