PAOLA VANNI

U.O NEUROLOGIA

OSMA - USL CENTRO FIRENZE

LE NEUROPATIE PERIFERICHE

DEFINIZIONE

Peripheral neuropathy

describes

damage to the Peripheral Nervous System.

Neuropatie

• Nei paesi sviluppati il diabete e l’alcolismo sono le cause principali.

• Nei paesi sottosviluppati la lebbra è la causa prima.

• II casi dovuti a HIV sono in aumento.

• Il 13-22% di neuropatie sono senza una causa definita accertata.

• La valutazione del paziente affetto da neuropatia è un processo

che richiede molto tempo perché è necessario un approcciosistematico clinico – strumentale.

La clinica neurologica si avvale di 3 domande

#1. Dove è la lesione?

#2. Qual è l’eziologia ?

#3. Quale il trattamento?

www.ama-assn.org/ ama/pub/category/7172.html

The clinical effect of a polyneuropathy depends on1) what modalities involved 2) what fibers are effected

3) whether the injury is axonal or demyelinating.

Adapted from http://www.neuroanatomy.wisc.edu/SClinic/Weakness/Weakness.htm

The Motor Unit

From Dumitru, D. Electrodiagnostic Medicine, Hanley & Belfus. Philadelphia. 1995

Localization and

determination of etiology

key, as treatment of

peripheral neuropathy is the

treatment of the underlying

condition.

Roots, plexus, nerves.

Peripheral nerves can be

diseased singly or multiply.

The distinction important as

the pathophysiology and

etiologies different – focal,

multifocal or diffuse. This is a

determination that can be

made at the bedside…

Plan of the Nervous System

^

^

Motor

UMN

LMN

Sensory

>

^

v

v

v

<

^

^<Autonomic

PSy

Sy

^

c

o

r

d

m.

drg

v

Spth

DorC

v

T1-L2

III,VII,IX,X

S2-4

t

h

c.

r.

g.

n.

Motor nerves Control movements of all muscles under conscious control,

such as those used for walking, grasping things, or talking.

Sensory nerves Transmit information about sensory experiences, such as

the feeling of a light touch or the pain resulting from a cut.

Autonomic nerves Regulate biological activities that people do not control

consciously, such as breathing, digesting food, and heart and gland functions.

RIASSUMENDO:

QUADRI CLINICI secondo la

topografia della neuropatia periferica

www.ama-assn.org/ ama/pub/category/7172.html

• Mononeuropatie (singolo nervo come meralgia, notalgia….)

• Polineuropatie

Nervi multipli

contigue

simmetriche

tipicamente localizzate (“stocking-glove”)

Poliradiculoneuropatie estese anche alla parte prossimale dei nn

fino alle radici (GB e CIDP)

Neuronopatie

Ganglionopatie (neuroni sensitive gangliare -

disimmuni o paraneo o idiopatiche)

Motorie (SLA)

Plessopatie (brachiale e lombare)

Mononeuropatie Multiple

Asimmetric

2 o piu’ nervi

Non contigui

Polineuropatia è piuttosto frequente (2.4% )

(8% over 55 aa)

http://www.neuro.wustl.edu/neuromuscular/pathol/nervenl.htmhttp://fulton.edzone.net/cites/winkler-science/team1/chap8.html

Qualche dato

anatomico del

nervo per meglio

comprendere se

l’interessamento

riguarda l’assone

la mielina o

entrambi

Axonopathies

By far the majority of the toxic, metabolic and endocrine causes

NCVs: CMAPs ↓ 80% lower limit of normal w/o or min velocity or distal motor latency change.

Legs>> arms.

EMG: Signs of denervation (acute, chronic) and reinnervation

Myelinopathies

By far the majority of the immunomediate, inflammaoty causes

Clues: hypertrophic nerves on exam

global arreflexia

weakness without wastingmotor >> sensory deficitsNCS can discriminate inherited from acquired

NCS: Distal motor latency prolonged (>125% ULN)Conduction velocities slowed (<80% LLN)May have conduction block

EMG: Reduced recruitment w/o much denervation

Loss of function

“- symptoms”

Disturbed function

“+ symptoms”

Motor nerves Wasting

Hypotonia

Weakness

Hyporeflexia

Orthopedic deformity

Fasciculations

Cramps

The clinical response to motor nerve injury

NEGATIVE OR POSITIVE

www.neuro.wustl.edu/neuromuscular/pics/people/patients/Hands/handatrophymnd3.jpg

Loss of function

“- symptoms”

Disordered function

“+ symptoms”

Sensory

“Large Fiber” (1)

↓ Vibration

↓ Proprioception

Hyporeflexia

Sensory ataxia

Paresthesias

Sensory

“Small Fiber” (2)

↓ Pain

↓ Temperature

Dysesthesias

Allodynia

The clinical response to motor nerve injury

NEGATIVE OR POSITIVE

1)Large fibers (thickly myelinated 50-120m/s motor and proprioception)

2)Small fibers (thinly myelinated 5-15m/s and unmyelinated 0.2-2m/s) conducting pain, touch

and autonomic fibers

Loss of function

“- symptoms”

Disturbed function

“+ symptoms”

Autonomic nerves ↓ Sweating

Hypotension

Urinary retention

Impotence

Vascular color changes

↑ Sweating

Hypertension

The clinical response to motor nerve injury

NEGATIVE OR POSITIVE

People may become unable to digest food easily, maintain safe levels of blood

pressure, sweat normally, or experience normal sexual function.

In the most extreme cases, breathing may become difficult or organ failure may

occur.

http://www.neuro.wustl.edu/neuromuscular/nother/skel.html#nosteo

La clinica neurologica si avvale di 3 domande

#1. Dove è la lesione?

#2. Qual è l’eziologia ?

#3. Quale il trattamento?

www.ama-assn.org/ ama/pub/category/7172.html

CLASSIFICAZIONI DELLE NEUROPATIE

PATTERN CLINICO

• Caratteristiche

temporali Acuto, subacuto e cronico

PATOLOGIA

• Degenerazione

assonale

• Demielinizazzione

segmentale

• Piccole fibre

• Miste

EZIOLOGIA

• Ereditaria

• Metabolica

• Nutrizionale

• Tossica (farmaci

lavoro/alcool)

• Vasculitica

• Immune

• Infettiva (lime lebbra

AIDS)

• Neoplastica

• Traumatica/compressi

va

CAUSE DI POLINEUROPATIA SUBACUTA O CRONICA SIMMETRICA, MISTA MOTORIA,

SENSITIVA AUTONOMICA

• Metaboliche

• Diabete mellito

• Insufficienza renale cronica

• Ipotiroidismo

• Acromegalia

• Disturbi metabolici ereditari

• Stati carenziali

• Tiamina (B1)

• Acido Pantotenico (B2)

• Piridossina (B6)

• Cianocobalamina (B12)

• Digiuno

• Malassorbimento

• Iperemesi

• Tossiche

• Alcool

• Tallio, Arsenico, Piombo

• N-esano

• Acrilamide

• Tri-ortocresyl fosfato

• Farmaci

• Antineoplastici: vincicristina, procarbazina, nitrofurazone,

etoposside, clorambucile

• Antimicrobici: isoniazide, etionamide, itrofurantoina,

metronidazolo, clioquinolo, dapsone

• Farmaci Cardiovascolari: perexillina, amiodarone

• Antireumatici: oro, penicillamina

• Anticonvulsivanti: Fenitoina

• Farmaci vari: disulfiram

• Neuropatia associata a carcinoma

• Neuropatie associate a disordini del sistema immunitario

in associazione con collagenopatie,

• linfomi e paraproteinemie,

• Polineuropatia infettiva subacuta,

• Infezione da HIV,

• Epstein-Barr,

• Citomegalovirus e Herpes zooster

• Iniezioni di siero di cavallo – tossina antitetanica

• Neuropatie ereditarie

ESEMPI DI NEUROPATIE PERIFERICHEDifetti metabolici sconosciuti Ereditarietà Patologia del nervo

Malattia di Charcot-Marie-Tooth, 1 e 2 Dtipo 1 demielinizzante

tipo 2 assonale

Malattia di Dèjèrine-Sottas R demielinizzante

Neuropatia sensitiva ereditaria

(Thèvenard, Denny-Brown)R assonale (DRG)

«Congenite» (ad insorgenza

precoce-Ohta, Dick)R assonale (DRG)

Disautonomia familiare (Riley-Day) R assonale (DRG)

Amiloidosi D assonale

Predisposizione ereditaria a paralisi

da pressione D demielinizzante

NB – DRG = gangli delle radici dorsali

ESEMPI DI NEUROPATIE EREDITARIEDifetti metabolici sconosciuti Ereditarietà Patologia del nervo

Deficit di uroporfirinogeno 1sintetasi

Porfiria acuta intermittente

D assonale

Deficit di Arilsulfatasi A

Leucodistrofia metacromatica

R demielinizzante

Deficit di galattosil ceramide o

betagalattosidasi- leucodistrofia a cellule

globoidi

R assonale

Deficit di lipoproteina ad alta densita’

Malattia ddi TangierR assonale

A-betalipoproteinemia o M di Bassen R assonale (DRG)

Malattia da accumulo di acido fitanico – M di Refsum

R demielinizzante

Deficit di alfa-galattosidasi AX –linked R Assonale (DRG)

NB – DRG = gangli delle radici dorsali

NEUROPATIE più frequenti

• DIABETICA

• GUILLAIN-BARRE’

• CIDP

• LES

• MGUS

• HIV

Come possiamo scegliere tra le numerose cause

per fare una diagnosi eziologica?

USANDO LE 6 D

1. What is the distribution of the deficits?

2. What is the duration?

3. What are the deficits (which fibers are involved)?

4. What is the disease pathology (axonal or

demyelinating or mixed)

5. Is there an inherited developmental neuropathy?

6. Is there drug/toxin exposure?

Quali gli esami ?Esami complementari al bilancio clinico:

1.EMG/ENG

2.Esami ematochimici (routine con protigramma,

autoimmunitari, oncogeni, dosaggio vitamine e, in ambito

specialistico,ab antigangliosidi e antiMAG, celiachia porfiria,

infettivologici, tossici esogeni) Markers genetici

3.Biopsia (raramente)

NB: La positività di alcuni tests diagnostici non necessariamente

correla con l’eziologia della PNP (p es non necessariamente una

neuropatia in un diabetico è una «PNP diabetica»)

CSF is useful in evaluation of myelinopathies and

polyradiculopathies.

An elevated total protein level with < 5

wbc(albumin/cytologic dissociation) is present in

acquired inflammatory neuropathy (e.g., Guillain-

Barré syndrome, CIDP).

Esami di laboratorio: Liquor

Nerve biopsy is only helpful in very

specific cases to diagnose vasculitis,

leprosy, amyloid neuropathy,

leukodystrophies, sarcoidosis.

Esami di laboratorio: biopsia

Other studies useful in specific clinical contexts

are:

cytology (Lymphoma)

special studies

such as Lyme polymerase chain reaction

and cytomegalovirus branched chain DNA

(polyradiculopathy or mononeuritis

multiplex in AIDS).

Esami di laboratorio

Manifestazione

Disordini che

simulano PNSPNS vere

Malattia diffusaMononeuropatia

focale

Polineuropatia

assonalePolineuropatia

demielinizzante

Mononeuropatie

multiple

AcquisitaAcquisita EreditariaEreditaria

Overview of the Lecture –Mastering polyneuropathy

#1. Where is the injury?The syndrome depends on:

what modalities are injured,

what fibers are injured,

whether axon or myelin (or both) injured.

#2. What is the etiology?Tricky – hence an approach necessary at the bedside.

#3. What is the treatment?Depends on reversing the underlying cause.

ALCUNI SEMPLICI ESEMPI CLINICI

CASI CLINICI (1)

Uomo di 60 anni AD di una nota industria dolciaria

Da circa 2 anni ipo/disestesia degli alluci e taloradolore

All’obiettività ipoestesia degli alluci con ROT achillei assenti

Anamnesi negative per comorbidità o storiafamiliare o farmaci

Effettua numerose visite ed esami di laboratorio d routine che risultano nella norma

Ethanol Neuropathy

(A common axonal polyneuropathy)

Among the most common neuropathies worldwide

Chronic

Numbness, paresthesias, pain in stocking distribution

Sensory >>> Motor

Loss of ankle reflexes

History!

Ethanol toxicity and nutritional deficiency

Vitamin B1 (thiamine)

Casi clinici (2):

Uomo di 25 anni, giocatore di calcio

Anamnesi patologica remota nella norma

Importante dolore L-S e al bacino seguito da debolezza in poche ore fino ad essereincapace di deambulare

Grave debolezza agli AAII e piu’ lieve agliAASS

Assenti I ROT agli AAII e iporeagenti agli AASS

Ipoestesia dei piedi

Un episodio di diarrea 15 gg prima

Guillain-Barre Syndrome

(A common demyelinating polyneuropathy)

Rapid, severe, typically ascending paralysis

Post infectious in 60%

Paresthesias, pain, numbness

Autonomic nerves

Reflexes lost

Cytoalbuminologic dissociation in the CSF

Casi clinici (3):

Pz di 59 anni obesa

Storia familiare di diabete

Da 4-5 anni presenta nocturia e da 1-2 anni anche poliuria

Cute dei piedi molto secca

Ipoestesia a calza

Achillei assenti

Diabetic Polyneuropathy

(A common mixed axonal & demyelinating polyneuropathy)

Multiple forms of neuropathy in diabetes

Sensory >>> motor polyneuropathy

Autonomic involvement common

CSF protein frequently elevated

Glucose control!

Foot care

Take the message:

La complessità della diagnosi

eziologica delle neuropatie

periferica impone la valutazione

del paziente nel suo insieme

anamnestico clinico e strumentale

TERAPIA

The goal of treatment is to manage the underlying condition causing the

neuropathy and repair damage, as

well as provide symptom relief.

Controlling a chronic condition may

not eliminate the neuropathy, but it

can play a key role in managing it.

TERAPIA (1):

Medications : Corticosteroids or analgesics .

Immunoglobuline or Plasmaferesis

Antiepileptic drugs, including Lyrica (pregabalin), Neurontin (gabapentin), and Tegretol(carbamazepine)

Some classes of antidepressants, including tricyclics such as Anafranil (amitriptyline) and Cymbalta (duloxetine).

Local anesthetics such as lidocaine or topical patches containing lidocaine

Codeine/oxycodone

Neurotrofici e gruppo B

Surgical intervention often can provide immediate relief from mononeuropathies caused by compression or entrapment injuries.

Repair of a slipped disk can reduce pressure on nerves where they emerge from the spinal cord; the removal of benign or malignant tumors can also alleviate damaging pressure on nerves.

Nerve entrapment often can be corrected by the surgical release of ligaments or tendons.

Terapia (2)

Conclusioni: Neuropatia periferica

1. Patterns: mononeuropathy, mononeuropathy multiplex or polyneuropathy – focal, multifocal or diffuse

2. “Signature” manifestations of a polyneuropathy depend on what modalities affected (motor, sensory, autonomic) and whether it is axonal or demyelinating.

3. Examination, NCS/EMG & biopsy can discriminate axonopathy from myelinopathy

4. The multiple potential etiologies of polyneuropathy are manageable recognizing patterns of disease by the 6 Ds

GRAZIE PER L’ATTENZIONE