Incontro Nazionale Neurofisiologia:

Nuove Strategie  

“Controversie sulla diagnosi e terapia del

dolore neuropatico”

Opinioni a confronto

Domenico A. RestivoU.O. di Neurologia

P.O. “Nuovo Garibaldi”, Catania

Acido lipoico e dolore neuropatico diabetico

NONO

There is insufficient evidence to support or refute the usefulness of vitamins and alpha-lipoic acid in the treatment of PDN (Level U).

AANEM GUIDELINES - 2011

BRIL ET AL., 2011

Golbidi et al., 2011

ALA AND NEUROPATHIC PAIN

•ALADIN I

•ALADIN III

•SYDNEY

•NATHAN II

•SYDNEY 2

•NATHAN I

ALA RCTs

Misure di outcome inappropriate per valutare il dolore

neuropatico

Misure di outcome inappropriate per valutare il dolore

neuropatico

TSS (Total symptoms Score: points: 0-14.64): Sensory symptoms (Ziegler et al., 2004)

Neuropathy TSS: Sensory symptoms (Bastyr et al., 2002)

TNS (Total Neuropathy Score): Sensory, motor, and autonomic symptoms;Sensory and motor signs; reflexes; QST (vibration); sensory and motor NCS. (Cornblath et al., 1999)

NSS (Neuropathy Symptoms Score): Sensory, motor, and autonomicSymptoms (Dyck et al., 1988)

NIS (Neuropathy Impairment Score): NIS LL: Sensory and motor signs; Reflexes in the lower limbs; NIS LL + 4: Sensory and motor signs; Reflexesin the lower limbs + motor NCS; NIS LL + 5: Sensory and motor signs; Reflexesin the lower limbs + motor NCS + QST (vibration); NIS LL + 7: Sensory and motorsigns; Reflexes in the lower limbs + sensory and motor NCS + QST (vibration) +AFT (Dyck et al., 1997)

OUTCOME MEASURES IN ALA RCTs

Patients: 328Outcome primario: TSSOutcome secondario: NSS,Neuropathy Disability ScoreResults: improvement in TSS

TSSTSS

Significant changes in TSS score

ALADINTSSTSS

Patienti: 509Outcome primario: TSSOutcome secondario:NIS, NIS-LLRisuatati: No miglioramento inTSS; SI NIS

Pazienti: 60 vs 60 controlliOutcome primario: TSSOutcome secondario: NIS, NSC, NCS, QST, AF testRisultati: miglioramento significativo in TTS, NIS, NCS

NO IMPROVEMENTIN QST

Patients: 181Primary Outcome: TSS Secondary Outcome :individual symptoms of TSS, NIS, NSC, Patient’sGlobal Assessment (PGA) Results: improvement in TSS, individual symptoms of TSS, NSC, PGA

Primary outcomePrimary outcome

Secondary outcomesSecondary outcomes

Patients: 460Primary outcome: NIS-LL 7Secondary outcome: NIS, NIS-LL, NCS, QST

Results: no significant improvement inthe primary endpoints

EFFECTS OF ALA ON DIFFERENT OUTCOME MEASURES

Restivo et al., unpublished data

20 DPNP PTS

0

1

2

3

4

5

6

7

8

9

10

baseline week1 week2 week3 week4

Burning

Pressing

Paroxysmal

Evoked

Par/Dysesth

NPSI: SIGNIFICANT IMPROVEMENT ONLY FORDEEP SPONTANEOUS PAIN (PRESSING) ANDPARESTHESIA/DYSESTHESIA

ALA

NPSI

QUESTO DATO POTREBBE IN QUALCHE MODO SPIEGAREL’ASSENZA DI MIGLIORAMENTO DEL QST DOPO ALA

20 DPNP PTS

Neuropatie Dolorose in corso di Diabete PoliNPT sensitiva dolorosa associata a ridotta tolleranza al Glc NPT da iperglicemia o funzionale NPT acuta dolorosa precipitata dal controllo glicemico PoliNPT prevalentemente sensitiva distale e simmetrica NPT delle fibre di piccolo calibro NPT cachettica o NPT dolorosa acuta Anoressia con neuropatia dolorosa acuta Mononeuropatie singole o multiple Radicolopatia toracica multipla dolorosa Radicolo-plessopatia lombosacrale dolorosa acuta Mononeuropatie da intrappolamento NPT oftalmoplegica

Risposta migliore nei pz con polineuropatia simmetrica sensitiva distaleScarsa risposta in pz con neuropatia prevalentemente a caricodelle piccole fibre

ALA

BPI

POTREBBE L’EFFETTO DELL’ALA DIPENDERE DAL TIPO DI NEUROPATIA ?

15 SFDN PTS; 22 DSP PTS

The absolute refractory periods (ARP) of single sensory axons issignificantly shorter in diabetic patients (Mackel and Brink 2003)

The shorter ARP in diabetic nerves may be consistent with reducednodal Na+ currents (Quasthoff, 1998), which is a consequence of reduction of Na+-K+ ATPase activity, which play an important role inthe pathophysiology of DN (Distal Simmetric Polyneuropathy)

Stimulation of distal sensory axons to study

the neural impulse generation in individual nerve fibers by-passing

the receptor organ

Stimulation of distal sensory axons to study

the neural impulse generation in individual nerve fibers by-passing

the receptor organ

The absolute refractory period is the shortest interpulse interval at whichan action potential is generated and propagated in response to a secondstimulus

ARP

ALA INCREASE ARP IN DISTAL SIMMETRIC POLYNEUROPATHY

12 PTS

No correlation between ARP increase and BPI changes in patients with diabetic distal sensory neuropathy and pain

COSTI

IN ITALIA LA TERAPIA PER UN MESE CON ACIDO LIPOICOCOSTA CIRCA 20 EURO…

HA UN SENSO SOTTOPORRE IL PAZIENTE AD UNA SPESA,NON SEMPRE DA TUTTI SOSTENIBILE, IN ASSENZA DI SICURIBENEFICI E/O SOLO SULLA BASE DEL PRESUPPOSTO CHE:

“TANTO NON FA MALE…”

???

CONCLUSIONI

NON VI SONO SUFFICIENTI EVIDENZE CHE L’ACIDO LIPOICOPOSSA MIGLIORARE IL DOLORE NEUROPATICO ASSOCIATOA DIABETE MELLITO

ULTERIORI STUDI RANDOMIZZATI-CONTROLLATI CHE UTILIZZINOMISURE DI OUTCOME PIU’ “SPECIFICHE” SONO NECESSARIPRIMA DI UN SICURO E DEFINITIVO UTILIZZO DELL’ALA SUL DPNP