MANAGEMENT OF LEPROUS
NEURITIS
Introduction
• Inflammation of the pereipheral nerves
(Dermal / Cutaneous / Nerve Trunks)
• Centripetal, Ascending in natu...
• Mediated by
– Schwann cell bacillation
– Contact Demyelination
– Immune / Inflamm reactions
– Mechanical Compression by ...
Stages of nerve involvement
• Stage of parasitization
• Host response

• Clinical involvement
• Nerve damage
• Nerve destr...
CLINICAL FEATURES
• Neuritis/neuropathy :
Acute/ subacute/
chronic, demyelinating, nonremitting event
involving cutaneous ...
NFI
early

Late

Sensory :
Altered heat & cold
sensitivity, hypoesthesia

Sensory :
Hypoesthesia, anesthesia leading to
ne...
• Silent (Quiscent) neuritis :
progressive sensory or motor impairment
without pain, paraesthesia or tenderness of
nerve &...
Grading of neuropathic pain
Grade

Degree

Description

0

None

No nerve pain

1

Mild

Complains of nerve pain even when...
Classification of Neuritis
• Acute neuritis : swelling due to nerve abscess
or recent onset rapidly progressing
neurologic...
• Recurrent neuritis : an episode of neuritis
recurring after a symptom free interval of min
03 mo
• Catastrophic paralysi...
Principles of Therapy
• MDT continuation
• Treating complicating Reactional States
• Prolonged Anti-inflammatory therapy
•...
Anti-inflammatory Therapy
• Corticosteroids
• Clofazimine
• Thalidomide
• AZA
• CsA
• NSAIDs
• Intraneural Drugs
Corticosteroids
• Anti-inflammatory + Immunosuppressive
• Genomic Action (Nuclear Receptors) – Immediate
Action (Dec Edema...
WHO regime
Initiate Prednisolone at 40 mg – taper every 02
weeks over 12 weeks (40-30-20-15-10-5-X)
Prolonged Therapy (24 ...
ADRs (TRIPOD)
• Minor (20%)
Gastric Intolerance / Fungal Inf / Acne
Major (02%)
Peptic Ulcer / Bacterial Sepsis / DM
Immun...
Clofazimine
• Phenazine derivative
• Dec Granulocyte Chemotaxis / stabilizes
Lysosomes ; binds to Mycobacterial DNA

• Ste...
REGIME
• 300 mg daily PO X 12 weeks

• 200 mg daily PO for a few months
• 100 mg daily PO continued

ADRs

Cutaneous / Muc...
Thalidomide
• Glutamic Acid derivative
• Anti TNF-A
• Immunomodulatory / Anti-inflamm /
Hypnosedative effects
• FDA-approv...
• 100-400 mg daily till pain subsides  decrease by 50mg
every 02-04 weeks
• ADRs

Paradoxical Peripheral Neuropathy
50% R...
AZA
• Immunosuppessive + Anti-inflamm + SSA
• 6-TP (Guanine) ; purine analogue inhibits cell
division , T & B cell functio...
CsA
• Immunosuppressant

• Calcineurin Inhibitor  Calcium-Calmodulin complex
 dec activity of NFAT-1  inhibit IL-2 prod...
Intraneural Therapy
• Severe Uncontrolled Neuritic Pain
• Isoxsurpine / Tolazoline (VASODILATORS) help
spread Corticostero...
Chr Neuropathic Pain
• Primary lesion / dysfunction of Nerve produces
pain – continuous, burning, Glove-and-Stocking
distt...
• NSAIDs not effective
• TCAs (NTP / Amytriptyline)
• AEDs (CBZ)

• GABA–analogues (Gabapentin / Pregablin)
• Opioids - Tr...
Surgical Correction
• Nerve Sx - improves function
Recon Sx – improves disability
• Corticosteroid coverage ?

Indications...
EXTRA-NEURAL NEUROLYSIS
Decompression Sx – removes fibrotic bands / ligaments to
open fibro-osseous channels – relives ext...
General Measures
•
•
•
•
•
•
•

Rest for Acutely inflamed Nerve
Avoidance of trauma
Immobilization with padded splints
Gra...
PREVENTION
• Early Detection of Hansen’s / Reactions
• Prompt initiation of MDT
PROPHYLAXIS
• 20mg/day Prednisolone with 1...
EXPERIMENTAL THERAPY
• Drugs and Vaccines blocking Mycobacterial
attachment to Schwann Cell-Axon Unit /
Specific Bacterial...
THANK YOU
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Leprous neuritis management by aseem

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Leprous neuritis management by aseem

  1. 1. MANAGEMENT OF LEPROUS NEURITIS
  2. 2. 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 )
  3. 3. • Mediated by – Schwann cell bacillation – Contact Demyelination – Immune / Inflamm reactions – Mechanical Compression by Intra / Perineural edema – Segmental demyelination  Wallerian / Axonal degeneration
  4. 4. Stages of nerve involvement • Stage of parasitization • Host response • Clinical involvement • Nerve damage • Nerve destruction
  5. 5. 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
  6. 6. 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
  7. 7. • 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
  8. 8. 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
  9. 9. 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
  10. 10. • 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
  11. 11. Principles of Therapy • MDT continuation • Treating complicating Reactional States • Prolonged Anti-inflammatory therapy • Surgery • Rest / Physical Therapy • Physiotherapy
  12. 12. Anti-inflammatory Therapy • Corticosteroids • Clofazimine • Thalidomide • AZA • CsA • NSAIDs • Intraneural Drugs
  13. 13. 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
  14. 14. 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)
  15. 15. 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
  16. 16. 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
  17. 17. 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
  18. 18. Thalidomide • Glutamic Acid derivative • Anti TNF-A • Immunomodulatory / Anti-inflamm / Hypnosedative effects • FDA-approved for ENL
  19. 19. • 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
  20. 20. 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
  21. 21. 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
  22. 22. 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
  23. 23. 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
  24. 24. • NSAIDs not effective • TCAs (NTP / Amytriptyline) • AEDs (CBZ) • GABA–analogues (Gabapentin / Pregablin) • Opioids - Tramadol
  25. 25. 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)
  26. 26. 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
  27. 27. 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
  28. 28. 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
  29. 29. 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
  30. 30. THANK YOU
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