Incontro Nazionale Neurofisiologia: Nuove Strategie

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Controversie sulla diagnosi e terapia del dolore neuropatico

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Opinioni a confronto

NO

Acido lipoico e dolore neuropatico diabetico

Domenico A. Restivo U.O. di Neurologia P.O. “Nuovo Garibaldi”, Catania

AANEM GUIDELINES - 2011

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

BRIL ET AL., 2011

ALA AND NEUROPATHIC PAIN

Golbidi et al., 2011

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ALADIN I

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ALADIN III

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SYDNEY

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NATHAN II

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SYDNEY 2

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NATHAN I

ALA RCTs

Misure di outcome inappropriate per valutare il dolore neuropatico

OUTCOME MEASURES IN ALA RCTs



TSS (Total symptoms Score: points: 0-14.64):

Sensory symptoms

(Ziegler et al., 2004)

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Neuropathy TSS:

Sensory symptoms

(Bastyr et al., 2002)

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TNS (Total Neuropathy Score):

Sensory, motor, and autonomic symptoms; Sensory and motor signs; reflexes; QST (vibration); sensory and motor NCS.

(Cornblath et al., 1999)

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NSS (Neuropathy Symptoms Score):

Sensory, motor, and autonomic Symptoms

(Dyck et al., 1988)

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NIS (Neuropathy Impairment Score): NIS LL:

Sensory and motor signs; Reflexes in the lower limbs;

NIS LL + 4:

Sensory and motor signs; Reflexes in the lower limbs + motor NCS;

NIS LL + 5

: Sensory and motor signs; Reflexes in the lower limbs + motor NCS + QST (vibration);

NIS LL + 7:

Sensory and motor signs; Reflexes in the lower limbs + sensory and motor NCS + QST (vibration) + AFT

(Dyck et al., 1997)



Patients: 328



Outcome primario: TSS

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Outcome secondario: NSS, Neuropathy Disability Score

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Results: improvement in TSS TSS

TSS

ALADIN

Significant changes in TSS score

Patienti: 509 Outcome primario: TSS Outcome secondario:NIS, NIS-LL Risuatati: No miglioramento in TSS; SI NIS

NO IMPROVEMENT

Pazienti: 60 vs 60 controlli Outcome primario: TSS

IN QST

Outcome secondario: NIS, NSC, NCS, QST, AF test Risultati: miglioramento significativo in TTS, NIS, NCS

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Patients: 181

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Primary Outcome: TSS

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Secondary Outcome :individual symptoms of TSS, NIS, NSC, Patient’s Global Assessment (PGA)

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Results: improvement in TSS, individual symptoms of TSS, NSC, PGA

Primary outcome Secondary outcomes

Results: no significant improvement in the primary endpoints

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

EFFECTS OF ALA ON DIFFERENT OUTCOME MEASURES

9 6 5 8 7 2 1 4 3 0 baseline week1 20 DPNP PTS TSS BPI week2 week3

Restivo et al., unpublished data

ALA

10 9 8 4 3 2 7 6 5 1 0 bas eline week1

NPSI

week2 week3 20 DPNP PTS week4 Burning Pres s ing Paroxys m al Evoked Par/Dys es th

NPSI: SIGNIFICANT IMPROVEMENT ONLY FOR DEEP SPONTANEOUS PAIN (PRESSING) AND PARESTHESIA/DYSESTHESIA QUESTO DATO POTREBBE IN QUALCHE MODO SPIEGARE L’ASSENZA DI MIGLIORAMENTO DEL QST DOPO ALA

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

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

BPI ALA

4 1 0 3 2 8 7 6 5

15 SFDN PTS; 22 DSP PTS

SF DSP baseline week1 week2 week3

Risposta migliore nei pz con polineuropatia simmetrica sensitiva distale Scarsa risposta in pz con neuropatia prevalentemente a carico delle piccole fibre

Stimulation of distal sensory axons to study the neural impulse generation in individual nerve fibers by-passing the receptor organ The absolute refractory periods (ARP) of single sensory axons is significantly shorter in diabetic patients

(Mackel and Brink 2003)

The shorter ARP in diabetic nerves may be consistent with reduced nodal Na+ currents

(Quasthoff, 1998)

, which is a consequence of reduction of Na+-K+ ATPase activity, which play an important role in the pathophysiology of DN (Distal Simmetric Polyneuropathy)

The absolute refractory period is the shortest interpulse interval at which an action potential is generated and propagated in response to a second stimulus

4 3,5 3 2,5 2 1,5 1 0,5 0 ALA INCREASE ARP IN DISTAL SIMMETRIC POLYNEUROPATHY ARP

Effects of ALA on ARP

4 3,5 3 Normals

in patients with diabetic distal sensory neuropathy and pain

1,5 DN DN 1 0,5 0

12 PTS

baseline week1 week2 week3 week4

COSTI

IN ITALIA LA TERAPIA PER UN MESE CON ACIDO LIPOICO COSTA CIRCA 20 EURO… HA UN SENSO SOTTOPORRE IL PAZIENTE AD UNA SPESA, NON SEMPRE DA TUTTI SOSTENIBILE, IN ASSENZA DI SICURI BENEFICI E/O SOLO SULLA BASE DEL PRESUPPOSTO CHE:

“TANTO NON FA MALE…”

???

CONCLUSIONI

NON VI SONO SUFFICIENTI EVIDENZE CHE L’ACIDO LIPOICO POSSA MIGLIORARE IL DOLORE NEUROPATICO ASSOCIATO A DIABETE MELLITO ULTERIORI STUDI RANDOMIZZATI-CONTROLLATI CHE UTILIZZINO MISURE DI OUTCOME PIU’ “SPECIFICHE” SONO NECESSARI PRIMA DI UN SICURO E DEFINITIVO UTILIZZO DELL’ALA SUL DPNP