MANAGEMENT OF LEPROUS NEURITIS

Introduction

• Inflammation of the pereipheral nerves (Dermal / Cutaneous / Nerve Trunks)

• Centripetal, Ascending in nature (KGK Dehio) akin to ‘fish swimming upstream’ (Khanolkar)

• Lepra Bacilli invades Peripheral Nerves Inflammation NFI ( S / M / A )

• Mediated by – Schwann cell bacillation– Contact Demyelination – Immune / Inflamm reactions– Mechanical Compression by Intra / Perineural

edema– Segmental demyelination Wallerian / Axonal

degeneration

Stages of nerve involvement

• Stage of parasitization

• Host response

• Clinical involvement

• Nerve damage

• Nerve destruction

CLINICAL FEATURES• Neuritis/neuropathy : Acute/ subacute/ chronic, demyelinating,

nonremitting event involving cutaneous nerves and larger trunks

• NFI : sensory, motor & autonomic nerve deficits

due to pathological processes from infection of nerve

NFIearly Late

Sensory :Altered heat & cold sensitivity, hypoesthesia

Sensory :Hypoesthesia, anesthesia leading to neuropathic ulcers

Motor :Mild motor weakness

Motor :Severe motor weakness progressing to paralysis

Autonomic :Decreased sweating

Autonomic :Severe dryness with fissuring of skin

• Silent (Quiscent) neuritis : progressive sensory or motor impairment

without pain, paraesthesia or tenderness of nerve & no signs of reaction

• Neuropathic pain : Pain initiated or caused by a primary lesion or

dysfunction in peripheral or central nervous system

Grading of neuropathic painGrade Degree Description

0 None No nerve pain

1 Mild Complains of nerve pain even when not asked

2 Moderate Complains severe nerve pain, sleep not disturbed, it is aggravated by repeated use of the limb

3 Severe Pain is severe & it interferes with sleep; patient keeps the limb in rest position & avoids movement

Classification of Neuritis

• Acute neuritis : swelling due to nerve abscess or recent onset rapidly progressing neurological deficit < 06 mo

• Chronic neuritis : long standing > 06 mo of gradually progressive neurological deficit with nerve tenderness or pain

• Recurrent neuritis : an episode of neuritis recurring after a symptom free interval of min 03 mo

• Catastrophic paralysis : sudden paralysis

• Completely destroyed nerves : no residual nerve function and electrophysiological studies show no conduction

Principles of Therapy

• MDT continuation

• Treating complicating Reactional States

• Prolonged Anti-inflammatory therapy

• Surgery

• Rest / Physical Therapy

• Physiotherapy

Anti-inflammatory Therapy

• Corticosteroids

• Clofazimine

• Thalidomide

• AZA

• CsA

• NSAIDs

• Intraneural Drugs

Corticosteroids

• Anti-inflammatory + Immunosuppressive

• Genomic Action (Nuclear Receptors) – Immediate Action (Dec Edema / Pro-inflamm CKs)

• Non-Genomic Action (Cystoplamic Receptors) - Immunosuppressive Action

• Indicated in ACUTE NEURITIS ; as early as detected

WHO regime

Initiate Prednisolone at 40 mg – taper every 02 weeks over 12 weeks (40-30-20-15-10-5-X)

Prolonged Therapy (24 weeks) OR High-dose Therapy (02 mg/kg)

Favourable Response :Sensory > Motor NFI (BANDS)Acute > Chronic > Recurrent Neuritis

(AMFES)

ADRs (TRIPOD)

• Minor (20%) Gastric Intolerance / Fungal Inf / Acne

Major (02%) Peptic Ulcer / Bacterial Sepsis / DM

Immunosuppression may interfere with killing of Bacilli and reduction in Antigenic Load ; Concomitant CLOFAZIMINE

Clofazimine

• Phenazine derivative

• Dec Granulocyte Chemotaxis / stabilizes Lysosomes ; binds to Mycobacterial DNA

• Steroid-sparing agent = Anti-inflamm + Anti-leprosy agent

• ENL / Reduces incidence of T1R

• Slower onset of action

REGIME

• 300 mg daily PO X 12 weeks

• 200 mg daily PO for a few months

• 100 mg daily PO continued

ADRs

Cutaneous / Mucosal pigmentationGastrointestinal IntoleranceIchthyosis

Thalidomide

• Glutamic Acid derivative

• Anti TNF-A

• Immunomodulatory / Anti-inflamm / Hypnosedative effects

• FDA-approved for ENL

• 100-400 mg daily till pain subsides decrease by 50mg every 02-04 weeks

• ADRs

Paradoxical Peripheral Neuropathy50% Reduction in SNAP-a with Normal NCV

Teratogenicity

Proximal Muscle Weakness

Somnolence

Leukopenia

AZA

• Immunosuppessive + Anti-inflamm + SSA

• 6-TP (Guanine) ; purine analogue inhibits cell division , T & B cell function

• 2nd Line Treatment for T1R (ILEP)

• 03 mg/kg/day x 12 weeks with Prednisolone 40mg tapered over 08 weeks

• Pancytopenia / Hepatotoxicity / GI Intolerance

CsA

• Immunosuppressant

• Calcineurin Inhibitor Calcium-Calmodulin complex dec activity of NFAT-1 inhibit IL-2 production Dec activity of CD4+ T-cells ; Reduction of Anti-Nerve Growth Factor (NGF) ABs

• Chronic ENL / T1R / Chronic Neuritis

• 5 mg/kg (upto 7.5 mg/kg) tapered over 12 months

• Nephrotoxicity / Hypertension / Dyselectrolemia / Hypertriglycidemia / Gum Hyperplasia

Intraneural Therapy

• Severe Uncontrolled Neuritic Pain

• Isoxsurpine / Tolazoline (VASODILATORS) help spread Corticosteroids under LA

• Treatment of Claw Hand in 60 yr old over 06 months by Nashed et al

• Intense pain, Nerve fibre damage potential

Chr Neuropathic Pain

• Primary lesion / dysfunction of Nerve produces pain – continuous, burning, Glove-and-Stocking distt

• Late complication of Hansen’s

• Small fibre neuropathy / Persistent Intraneural Inflamm

• MDT-completion + Not in Reaction + No NFI

• NSAIDs not effective

• TCAs (NTP / Amytriptyline)

• AEDs (CBZ)

• GABA–analogues (Gabapentin / Pregablin)

• Opioids - Tramadol

Surgical Correction

• Nerve Sx - improves function Recon Sx – improves disability

• Corticosteroid coverage ?

Indications

• Corticosteroid failure (No improvement / Contraindicated / ADRs)

• Intractable pain despite Medical Management• Nerve Abscess• Sudden paralysis (Catastrophic / Hyperacute Neuritis)

EXTRA-NEURAL NEUROLYSISDecompression Sx – removes fibrotic bands / ligaments to open fibro-osseous channels – relives external pressure

INTRA-NEURAL NEUROLYSISLongitudnal Incisons in Nerve Sheath Epineurium

INTERFASCICULAR NEUROLYSISIndividual Nerve Fibres dissected and separated ; risk of damaging Vasa Nervorum , Fibrosis

NERVE ABSCESS DRAINAGELongitudnal incision drain Caseous material

NERVE TRANSPOSITIONMedial Epicondylectomy for Ulnar Nerve

General Measures

• Rest for Acutely inflamed Nerve• Avoidance of trauma• Immobilization with padded splints• Graduated Exercises in Recovery phase• SWD / UST / TENS for added pain control• Hand / Foot Care• Counselling and MDT

PREVENTION

• Early Detection of Hansen’s / Reactions

• Prompt initiation of MDT

PROPHYLAXIS

• 20mg/day Prednisolone with 1st 04 months of MDT lowered risk of T1R

• 300mg/day Clofazimine for 1st 03 months of MDT lowered incidence of Neuritis

EXPERIMENTAL THERAPY

• Drugs and Vaccines blocking Mycobacterial attachment to Schwann Cell-Axon Unit / Specific Bacterial Unit causing Nerve tropism

• Neutrotropic Factors (NTFs)

Regulate Schwann Cells to regenerate Axons in PNS by increasing Impulse Transmission across Axons blocked by Mycobacterial AGs

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