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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
NO
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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
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Golbidi et al., 2011
ALA AND NEUROPATHIC PAIN
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•ALADIN I
•ALADIN III
•SYDNEY
•NATHAN II
•SYDNEY 2
•NATHAN I
ALA RCTs
Misure di outcome inappropriate per valutare il dolore
neuropatico
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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
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Patients: 328Outcome primario: TSSOutcome secondario: NSS,Neuropathy Disability ScoreResults: improvement in TSS
TSS
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Significant changes in TSS score
ALADINTSS
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Patienti: 509Outcome primario: TSSOutcome secondario:NIS, NIS-LLRisuatati: No miglioramento inTSS; SI NIS
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Pazienti: 60 vs 60 controlliOutcome primario: TSSOutcome secondario: NIS, NSC, NCS, QST, AF testRisultati: miglioramento significativo in TTS, NIS, NCS
NO IMPROVEMENTIN QST
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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
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Primary outcome
Secondary outcomes
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Patients: 460Primary outcome: NIS-LL 7Secondary outcome: NIS, NIS-LL, NCS, QST
Results: no significant improvement inthe primary endpoints
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EFFECTS OF ALA ON DIFFERENT OUTCOME MEASURES
Restivo et al., unpublished data
20 DPNP PTS
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01
2345
678
910
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
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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
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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
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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
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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
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COSTIIN 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…”
???
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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
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