• Acid-fast bacilli (AFB)
• High-resolution ultrasonography (HRUS)
• Multiplex polymerase chain reaction (M-PCR)
• Nerve biopsy
• Nerve conduction studies (NCS)
• Non-invasive techniques
• Pure neuritic leprosy (PNL)

• Humans
• Mycobacterium leprae/isolation & purification
• Mycobacterium leprae/genetics
• Mycobacterium leprae/immunology
• Leprosy/diagnosis
• Molecular Diagnostic Techniques/methods
• Neuritis/diagnosis
• Neuritis/microbiology
• Sensitivity and Specificity
• Multiplex Polymerase Chain Reaction/methods

• QoL
• activity limitation
• disability
• leprosy
• nerve conduction study
• nerve function impairment
• sympathetic skin response

• Humans
• Quality of Life
• Male
• Prospective Studies
• Female
• Middle Aged
• Adult
• Neural Conduction/physiology
• Leprostatic Agents/therapeutic use
• Young Adult
• Leprosy/complications
• Leprosy/physiopathology
• Peripheral Nervous System Diseases/physiopathology
• Peripheral Nervous System Diseases/diagnosis
• Aged
• Neurologic Examination
• Adolescent
• Galvanic Skin Response/physiology

• Humans
• Male
• Female
• Adult
• Leprosy/drug therapy
• Leprosy/diagnostic imaging
• Leprosy/complications
• Prospective Studies
• Middle Aged
• Peripheral Nerves/diagnostic imaging
• Ultrasonography, Doppler, Color
• Leprostatic Agents/therapeutic use
• Young Adult
• Aged
• Adolescent

• Adductor
• Compression
• Hunter’s canal
• MRI
• Saphenous nerve
• Ultrasound

• Inflammatory neuropathy
• Peripheral Neuropathy
• Sonography
• Superb microvascular imaging
• Ultrasound

• Humans
• Male
• Female
• Middle Aged
• Aged
• Microvessels/diagnostic imaging
• Microvessels/physiopathology
• Peripheral Nervous System Diseases/physiopathology
• Peripheral Nervous System Diseases/diagnostic imaging
• Adult
• Ultrasonography/methods
• Ultrasonography, Doppler, Color/methods
• Median Nerve/diagnostic imaging
• Median Nerve/physiopathology
• Ulnar Nerve/diagnostic imaging
• Ulnar Nerve/physiopathology
• Aged, 80 and over

• Humans
• Leprosy/diagnostic imaging
• Leprosy/diagnosis
• Male
• Female
• Ultrasonography/methods
• Adult
• Middle Aged
• Peripheral Nervous System Diseases/diagnostic imaging
• Peripheral Nervous System Diseases/diagnosis
• Aged
• Tibial Nerve/diagnostic imaging
• Young Adult
• Ulnar Nerve/diagnostic imaging
• Ulnar Nerve/pathology
• Case-Control Studies
• Median Nerve/diagnostic imaging

• hereditary
• immune mediated
• leprosy
• metabolic
• motor neuron disease
• polyneuropathy
• toxic
• ultrasound

• Humans
• Ultrasonography/methods
• Polyneuropathies/diagnostic imaging

• diseases
• medical research
• neurology
• signs and symptoms

• Humans
• Male
• Female
• Retrospective Studies
• Adult
• Middle Aged
• Leprosy/pathology
• Leprosy/diagnosis
• Leprosy/complications
• Peripheral Nervous System Diseases/diagnosis
• Peripheral Nervous System Diseases/pathology
• Aged
• Young Adult

• Carpal tunnel syndrome
• Diagnostic value
• Focal neuropathy
• Imaging
• Magnetic resonance neurography
• Nerve trauma
• Nerve tumors
• Nerve ultrasound
• Peripheral nerve disease
• Ulnar neuropathy

• Humans
• Electrodiagnosis/methods
• Magnetic Resonance Imaging
• Peripheral Nervous System Diseases/diagnostic imaging
• Ultrasonography

• high-resolution ultrasonography
• leprosy neuropathy
• light chains
• nerve area
• neurofilament

• Humans
• Neural Conduction/physiology
• Intermediate Filaments
• Peripheral Nerves/diagnostic imaging
• Peripheral Nervous System Diseases/diagnostic imaging
• Ultrasonography/methods
• Leprosy/complications
• Leprosy/diagnostic imaging

• demyelinating
• leprosy
• mononeuropathy
• neuropathy
• ultrasound

• Humans
• Leprosy/diagnostic imaging
• Ultrasonography/methods

• meta-analysis
• reference values
• sonography
• systematic review
• tibial nerve
• ultrasound

• SY66003 Khon Kaen University

• case report
• corticosteroid
• leprosy
• neuritis
• ultrasound

• Acro-osteolysis
• Osteolysis
• Phalanges
• Resorption

Hansen's disease (HD) is the most common cause of treatable peripheral neuropathy in the world that may or may not involve skin manifestations, and physical examination based on simplified neurologic evaluation is a subjective and inaccurate procedure. High-resolution ultrasound (HRUS) can be used to evaluate peripheral nerves and is a validated technique of good reproducibility, permitting a detailed and precise examination.

We proposed to establish objective criteria for absolute values of the measurement of the CSA of peripheral nerves and their indices of the ΔCSA and ΔTpT in the diagnosis of Hansen's disease neuropathy as compared with healthy voluntaries.

In municipalities from different regions of Brazil, we randomly selected 234 volunteer Brazilian patients diagnosed with leprosy to be submitted to peripheral nerve echography and compared with 49 healthy Brazilian volunteers.

Hansen Disease assessed by high resolution ultrasound is a primarily neural disease that leads to multiple hypertrophic mononeuropathy characterized by CSA values exceeding normal limits (Med CT = 10.2 mm²; UT = 9.8 mm²; UPT = 9.3 mm²; CFFH = 18.3 mm²; T = 9.6 mm²), and the pattern of asymmetry (ΔCSA>2.5 mm² with RR 13) and focality (ΔTPT > 2.5 mm² with RR 6.4) of this thickening has higher sensitivity (76,1%) and specificity (87,8 %) for its early diagnosis that laboratory tests. Analyzing each subject, the percentage of thickened nerves detected among the total number of nerves assessed was higher among patients with HD than among healthy individuals (p < 0.0001). Individuals with two or more thickened nerves were at 24.1 times higher relative risk (95% CI: 6.74–88.98) of HD.

• Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Ministério da Saúde
• Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
• Fundação Oswaldo Cruz

Mycobacterium leprae infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for M. leprae-induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos (Dasypus novemcinctus), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves. In this study, state-of-the-art technology was used to compare nerve function between uninfected and M. leprae-infected armadillos. Motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP), which measure changes in the rate of impulse conduction velocity and amplitude, revealed a progression of impairment that was directly correlated with the duration of M. leprae infection and enabled development of an objective nerve impairment scoring system. Ultrasonography accompanied by color Doppler imaging detected enlargement of the M. leprae-infected nerves and increased vascularity, possibly due to inflammation. Assessment of epidermal nerve fiber density (ENFD), which shows a length-dependent innervation in armadillos that is similar to humans, identified small fiber degeneration early after M. leprae infection. Staining for neuromuscular junction (NMJ) integrity, which is an indicator of signal transduction efficiency into skeletal muscle, discerned a markedly lower number and structural integrity of NMJ in M. leprae-infected armadillo footpads. These tools for assessing nerve injury were used to monitor the effects of intervention therapy. Two potential neuro-protective drugs, ethoxyquin (EQ) and 4-aminopyridine (4-AP), were tested for their ability to ameliorate peripheral nerve injury in M. leprae-infected armadillos. 4-AP treatment improved MNCV, cMAP, and EFND compared to untreated animals, while EQ had less effect. These results support the armadillo as a model for M. leprae-induced peripheral nerve injury that can provide insights toward the understanding of NFI progression and contribute to the preclinical investigation of the safety and efficacy of neuro-preventive and neuro-therapeutic interventions for leprosy.

• Division of Intramural Research, National Institute of Allergy and Infectious Diseases

Leprosy is still a prevalent disease in Brazil, representing 93% of all occurrences in the Americas. Leprosy neuropathy is one of the most worrying manifestations of the disease. Acute neuropathy usually occurs during reaction episodes and is called neuritis. Twenty-two leprosy patients were included in this study. These patients had neural pain associated with ulnar sensory neuropathy, with or without adjunct motor involvement. The neurological picture began within thirty days of the clinical evaluation. The patients underwent a nerve conduction study and the demyelinating findings confirmed the diagnosis of neuritis. Ultrasonographic study (US) of the ulnar nerve was performed in all patients by a radiologist who was blinded to the clinical or neurophysiological results. Morphological characteristics of the ulnar nerve were analyzed, such as echogenicity, fascicular pattern, transverse cross-sectional area (CSA), aspect of the epineurium, as well as their anatomical relationships. The volume of selected muscles referring to the ulnar nerve, as well as their echogenicity, was also examined. Based on this analysis, patients with increased ulnar nerve CSA associated with loss of fascicular pattern, epineurium hyperechogenicity and presence of power Doppler flow were classified as neuritis. Therefore, patients initially classified by the clinical-electrophysiological criteria were reclassified by the imaging criteria pre-established in this study as with and without neuritis. Loss of fascicular pattern and flow detection on power Doppler showed to be significant morphological features in the detection of neuritis. In 38.5% of patients without clinical or neurophysiological findings of neuritis, US identified power Doppler flow and loss of fascicular pattern. The US is a method of high resolution and portability, and its low cost means that it could be used as an auxiliary tool in the diagnosis of neuritis and its treatment, especially in basic health units.

Leprosy remains a public health problem, despite being an ancient disease. In most cases, it is associated with neuropathy that can be acute or chronic and this neural involvement can occur before, during, or after multidrug therapy (MDT). Acute neuropathy usually occurs during reaction episodes and is called neuritis. It causes compromised nerve function associated with nociceptive pain [1]. The inflammatory process can also develop neuroplasticity of the peripheral and central nervous systems, which perpetuates this sensation; this phenomenon is known as neuropathic pain, a chronic sensation in leprosy. Differential diagnosis between nociceptive and neuropathic pain is not always easy and in some patients there may be an overlap between nociceptive and neuropathic pain. Currently, clinical and electrophysiological criteria are used for the differential diagnosis of neural pain [2], but especially in the case of recurrent neuritis, these criteria are insufficient. Recent knowledge about pain mechanisms does not define the limit as to where nociceptive ends and neuropathic begins, suggesting that this process is continuous, in addition to being associated. Ultrasonography (US) has been used as an auxiliary tool in the early diagnosis of peripheral nervous system diseases. The method can be implemented in addition to clinical and neurophysiological studies for the diagnosis of neuritis, which allows for the early identification and treatment of the disease [3,4].

• Humans
• Leprosy/complications
• Leprosy/diagnostic imaging
• Neural Conduction
• Neuralgia
• Neuritis/diagnostic imaging
• Neuritis/etiology
• Ulnar Nerve/diagnostic imaging
• Ulnar Neuropathies/diagnostic imaging
• Ultrasonography

• Computed tomography
• Great auricular nerve
• Leprosy
• Ultrasound

• Armadillos
• Leprosy
• M. leprae
• Neuritis
• Rifampin
• Schwann cell

• Animals
• Armadillos
• Leprosy/complications
• Leprosy/diagnosis
• Leprosy/therapy
• Mycobacterium leprae
• Neuritis/complications
• Peripheral Nervous System Diseases/diagnosis
• Peripheral Nervous System Diseases/etiology
• Peripheral Nervous System Diseases/therapy

Assessment of peripheral nerves in leprosy by clinical methods is subject to considerable inter-observer variability. High resolution ultrasonography (HRUS) can assess peripheral nerves more objectively.

To compare the findings of peripheral nerve involvement in newly diagnosed cases of leprosy by clinical and sonological methods.

Cross sectional study in a tertiary care teaching hospital.

Four pairs of peripheral nerves of 40 newly diagnosed patients with leprosy were examined clinically and by HRUS.

Agreement between clinical examination and HRUS using kappa statistic; sensitivity; specificity; and predictive values.

Of the 320 nerves examined, 71 (22.18%) were abnormal clinically and 63 (19.7%) sonologically. Sonological abnormalities were increased cross sectional area (n = 63; 100%), hypoechogenicity with loss of fascicular architecture (n = 46; 73%) and increased vascularity (n = 35; 55.6%). There was moderate agreement (Cohen's Ḳ = 0.59) between clinical and sonological findings. HRUS findings were abnormal in 18 (7.2%) nerves that were clinically normal. HRUS was normal in 26 (36.6%) nerves which were clinically abnormal. Sensitivity of HRUS compared to clinical examination was 63%; specificity 92.7%; positive predictive value 71.4%; and negative predictive value 89.9%. Increased cross sectional area agreed with clinical findings the most.

HRUS has low sensitivity (63%) and high specificity (92.7%) to identify abnormal peripheral nerves in leprosy, compared to clinical examination. It could detect abnormality of some (n = 18, 7.2%) clinically normal nerves, but showed normal findings of some nerves (n = 26, 36.6%), which were considered clinically abnormal.

• High resolution ultrasonography
• leprosy
• ultrasonography

• CIDP
• amyotrophic lateral sclerosis
• entrapment neuropathy
• hereditary neuropathy
• neuromuscular ultrasound
• peripheral neuropathy

• Hansen's disease
• carpal tunnel syndrome
• cross-sectional area
• inching
• median nerve
• nerve ultrasound

• chronic inflammatory demyelinating polyneuropathy
• multifocal motor neuropathy
• nerve ultrasonography
• prognostic value

• Elastography
• Leprosy
• Nerve stiffness
• Neuropathy
• Shear wave
• Ulnar nerve

• High-resolution ultrasound
• leprosy
• peripheral nerve

• High-resolution ultrasonography and Color Doppler
• Leprosy neuropathy
• Leprosy reactions
• Nerve conduction studies

• Ganglionitis
• Lepra reactions
• Leprosy
• Peripheral neuropathy
• Prevention of leprosy
• Therapy

• Age
• Cervical nerve root
• Cross-sectional area
• Ultrasound

• Aged
• Body Mass Index
• Cervical Vertebrae/diagnostic imaging
• Healthy Volunteers
• Humans
• Reference Values
• Spinal Nerve Roots/diagnostic imaging
• Ultrasonography

Neuromuscular ultrasound (NMUS) is a rapidly evolving technique used in neuromuscular medicine to provide complimentary information to standard electrodiagnostic studies. NMUS provides a dynamic, real time assessment of anatomy which can alter both diagnostic and management pathways in peripheral nerve disorders. This review describes the current and future techniques used in NMUS and details the applications and developments in the diagnosis and monitoring of compressive, hereditary, immune-mediated and axonal peripheral nerve disorders, and motor neuron diseases. Technological advances have allowed the increased utilisation of ultrasound for management of peripheral nerve disorders; however, several practical considerations need to be taken into account to facilitate the widespread uptake of this technique.

• Neuromuscular ultrasound
• Peripheral neuropathy
• Polyneuropathy
• Entrapment neuropathy
• Immune-mediated neuropathy
• Hereditary neuropathy

• Mycobacterium leprae
• leprosy
• nerve thickening
• peripheral nerves
• polyneuropathy
• pure neuritic leprosy

• neuromuscular disease
• tropical medicine
• ultrasonography

• Adult
• Biopsy
• Diagnosis, Differential
• Humans
• Leprosy/complications
• Leprosy/diagnosis
• Leprosy/pathology
• Leprosy/physiopathology
• Male
• Mycobacterium leprae/isolation & purification
• Peroneal Nerve/diagnostic imaging
• Peroneal Neuropathies/diagnostic imaging
• Peroneal Neuropathies/etiology
• Skin/pathology
• Ultrasonography/instrumentation
• Ultrasonography/methods

The purpose of this study was to evaluate peripheral neural impairment in leprosy patients by ultrasonography (US). The cross-sectional areas (CSAs) of the median (M), ulnar (U) and common fibular (CF) nerves were compared in 71 leprosy patients and 29 healthy controls, and the data were analyzed between the leprosy, multibacillary (MB)/paucibacillary (PB), reaction (R)/no reaction (NR), disability (D)/no disability (ND), and longer/shorter duration groups after treatment. We found that for the nerves located in upper limbs, the CSAs were significantly increased in the leprosy patients vs the controls; the PB group vs the MB group; the R group vs the NR group; the ND group vs the D group; and the longer duration group vs the shorter duration group at some positions of the M nerve and U nerve. In contrast, for the nerves located in lower limbs, the CSAs were significantly reduced in the leprosy patients vs the controls and in the longer duration group vs the shorter duration group at some positions of the CF nerve. This result indicated that nerve enlargement and neuratrophy coexist in leprosy patients.

• color Doppler
• intraneural blood flow
• neovascularization
• nerve regeneration
• penetrating nerve injury
• ultrasonography

• neuroimaging
• neuropathy
• neurophysiology
• sonography
• ultrasound

• Dermatology
• Orthopaedics
• Peripheral nerve disease
• Radiology
• Tropical medicine (infectious disease)

• ankle surgery
• neuropathy
• open reduction internal fixation
• sural nerve
• ultrasound

Earlier studies have shown sonographic enlargement of the ulnar nerve in patients with Hansen’s neuropathy. The present study was performed to determine whether sonography or electrophysiological studies can detect the specific site of ulnar nerve pathology in leprosy.

Eighteen patients (thirty arms) with Hansen’s disease and an ulnar neuropathy of whom 66% had borderline tuberculoid (BT), 27% lepromatous leprosy (LL) and 7% mid-borderline (BB) leprosy were included in the study. Cross-sectional area (CSA) of ulnar nerve was measured every two centimeters from wrist to medial epicondyle and from there to axilla. All patients underwent standard motor and sensory nerve conduction studies of the ulnar nerve. Thirty age and sex matched controls underwent similar ulnar nerve CSA measurements and conduction studies.

Ulnar nerve was clinically palpable in 19 of the 30 arms of patients. Motor and sensory nerve conduction studies of the ulnar nerve showed a reduced compound motor action potential and sensory nerve action potential amplitude in all patients. Motor Conduction Velocity (MCV) in patients were slower in comparison to controls, especially at the elbow and upper arm, but unable to exactly locate the site of the lesion. In comparison to controls the ulnar nerveCSA was larger in the whole arm in patients and quite specific the maximum enlargement was seen between nulnar sulcus and axilla, peaking at four centimeters above the sulcus.

A unique sonographic pattern of nerve enlargement is noted in patients with ulnar neuropathy due to Hansen’s disease, while this was not the case for the technique used until now, the electrodiagnostic testing. The enlargement starts at ulnar sulcus and is maximum four centimeters above the medial epicondyle and starts reducing further along the tract. This characteristic finding can help especially in diagnosing pure neuritic type of Hansen’s disease, in which skin lesions are absent, and alsoto differentiate leprosy from other neuropathies in which nerve enlargement can occur.

Hansen’s neuropathy is caused by Mycobacterium leprae. The diagnosis of Hansen disease is based on typical skin lesions, nerve enlargement and presence of bacilli in the skin smear. One of the types of leprosy is a pure neuritic type which manifests without skin lesions. High resolution ultrasound is new modality by which the morphology of the peripheral nerves can be studied. Earlier studies have shown that peripheral nerves are thickened in Hansen’s disease and ultrasound is superior in identifying nerve enlargement when compared with clinical palpation. Good correlation exits between nerve enlargement and electrophysiological studies. The current research was to look for a specific pattern of nerve enlargement and we studied patients with Hansen’s ulnar neuropathy. We found an unique pattern of nerve enlargement in which the ulnar nerve enlargement starts at the sulcus and the enlargement is maximum four centimetres above the sulcus and then it tapers. This pattern of unique nerve enlargement can help especially in diagnosing pure neuritic type of Hansen’s disease, in which skin lesions are absent, and is also useful to differentiate leprosy from other neuropathies in which nerve enlargement can occur.

• Adult
• Aged
• Case-Control Studies
• Elbow/diagnostic imaging
• Electrophysiology
• Female
• Humans
• Leprosy/complications
• Leprosy/diagnostic imaging
• Linear Models
• Male
• Middle Aged
• Netherlands
• Neural Conduction
• Neurologic Examination
• Ulnar Nerve/diagnostic imaging
• Ulnar Nerve/physiopathology
• Ulnar Neuropathies/diagnostic imaging
• Ultrasonography
• Young Adult

• NEUROPATHY
• ULTRASOUND