Leprous neuritis management by aseem

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Information about Leprous neuritis management by aseem

Published on February 18, 2014

Author: talkoncorners2

Source: slideshare.net

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

NFI early 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 pain Grade 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 + Antileprosy 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 pigmentation Gastrointestinal Intolerance Ichthyosis

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 Neuropathy 50% 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 NEUROLYSIS Decompression Sx – removes fibrotic bands / ligaments to open fibro-osseous channels – relives external pressure INTRA-NEURAL NEUROLYSIS Longitudnal Incisons in Nerve Sheath Epineurium INTERFASCICULAR NEUROLYSIS Individual Nerve Fibres dissected and separated ; risk of damaging Vasa Nervorum , Fibrosis NERVE ABSCESS DRAINAGE Longitudnal incision  drain Caseous material NERVE TRANSPOSITION Medial 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

THANK YOU

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