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Unità di Neuropatologia Sperimentale
Istituto di Neurologia Sperimentale INSPEDivisione di Neuroscienze
Ospedale San RaffaeleDr. Angelo Quattrini
Lecce 21 gennaio 2015
Unità di Neuropatologia Sperimentale
Attività clinica: • Biopsia di nervo sensitivo• Biopsia di nervo motorio• Biopsia di cute
Attività di Ricerca:• Biomateriali per la rigenerazione del sistema
nervoso• Neuropatie periferiche e malattie del
motoneurone• Validazione di modelli sperimentali (SNC – SNP)
• 15 Patients: 9 MND and 6 MN
• MN: demyelination with small onion
bulb, clusters of regeneration
• MND: loss of fibers, acute fiber
degeneration, rarity of regenerative
clusters.
Usefulness of motor nerve biopsy: diagnostic validation
Case #3
Case #4 Case #7
Validate by two-year clinical follow up the diagnostic usefulness of
the motor nerve biopsy
21 patients (between 2003-2006) - Progressive muscular weakness and wasting of unknown
origin affecting more than one limb - onset extending 1 months or more - no signs of sensory
neuropathy - EMG features of neurogenic changes
Baseline: neuropathological diagnosis:
12 patients: MND (CD<20/mm2)
1 patient: not diagnostic
8 patients: MN
1: amyloid neuropathy (CD: 24/mm2)
4 signs of demyelination/remyelination
Follow-up: neuropathological diagnosis:
12 patients: MND
1 patient: MND
8 patients: MN/SMN
1: SM amyloid neuropathy
Case 4: 58y/M
Symmetric
weaknes: LL>UL
D=P
Clinical follow-up:
ALS
MND: typical features. Axonal degeneration, no regeneration, focal/pathcy reduction of nerve fibres
Motor neuropathies: typical features
Case 16: 60y/M
Symmetric
weaknes: LL>UL
D=P
Clinical follow-up: SMN
Conclusions
• Biopsy of the motor nerve to the gracilis muscle is a simple procedure. It has an acceptably low complication rate.
• Motor nerve pathologic examination was helpful for early differential diagnosis of LMN syndromes
• Motor nerve biopsy should be considered as a potential diagnostic tool for early differential diagnosis of selected cases of LMND and MN
Exploring the peripheral nervous system path to unravel Amyotrophic Lateral sclerosis
Razionale: La degenerazione a carico dei nervi periferici è un evento precoce della malattia nonché una delle principali causa di debolezza muscolare.
Obiettivo: definire il ruolo del sistema nervoso periferico nell’evoluzione della SLA.
L’obiettivo sarà identificare nuovi marcatori diagnostici di malattia. Il desiderio è quello di individuare, inoltre, potenziali target terapeutici con lo scopo di proteggere le fibre dei nervi periferici dalla progressiva degenerazione e mantenere la forza muscolare nei pazienti affetti da SLA.
Foglio1
Pagina 1
Probe ID Gene Symbol
ILMN_1815556 PRAP1
ILMN_1792356 DPYSL4
ILMN_1705397 PDK2
ILMN_1767015 BCORL1
ILMN_2318568 HCFC1R1
ILMN_1741755 TRIM29
ILMN_1653927 SNORD83A
ILMN_1660501 LY6H
ILMN_1652147 MRPL43
ILMN_2237252 LY6H
ILMN_1661708 LGALS7
ILMN_1702009 SV2A
ILMN_2053992 HIST4H4
ILMN_1712913 UNC5A
ILMN_1701875 ZYX
ILMN_2052438 CYorf14
ILMN_1800843 SCAMP4
ILMN_2300695 IKZF3
ILMN_1674243 TFRC
ILMN_1675331 PEG3
ILMN_1695311 HLA-DMA
ILMN_1726327 AMY1B
ILMN_3310216 MIR1911
ILMN_2294762 AMY1A
ILMN_2213558 TMED10P
ILMN_1696035 C12orf8
ILMN_1739622 PPP1R12A
ILMN_2102515 PGAM4
ILMN_1777976 SLC25A26
ILMN_3243441 EEF1AL7
ILMN_1690894 TRA1P2
Up-regulated genes
Down-regulated
genes
Microarray Gene Expression
Neuropathological features of Metachromatic Leukodystrophy mice
Consiglio A. et al, Nat Med 2001;7:310-316
Correction of established neurological deficits.
The neurophysiological deficits were normalized in treated mice along with the major
histopathological abnormalities:
Consiglio A. et al, Nat Med 2001;7:310-316Biffi A. et al, J Clin Invest 2004;113:1118-1129Biffi A. et al, J Clin Invest. 2006;116:3070-3082
Animal experiments and human studies are complementary and both are necessary.
HSC gene therapy can prevent progression of MLD.