incontro nazionale neurofisiologia: nuove strategie
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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
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
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
TSS
Significant changes in TSS score
ALADINTSS
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 outcome
Secondary 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Restivo et al., unpublished data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
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
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
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
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…”
???
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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