Peripheral neuropathy

Question 1

Most common type of peripheral neuropathy

Answer 1

Axonal(75%)
Demyelinating(20%)
Neuronopathy (5%)

Question 2

Axonal neuropathy features

Common etiology for axonopathies

Answer 2

Chronic
Prediliction for large, long fibres
Sensory>motor, areflexia
Specific axonal neuropathy involve small diameter fibres

Diabetes, alcohol, uremia, toxic, paraneoplastic,nutritional

Question 3

NCS and EMG findings in axonopathy

Answer 3

Reduced or absent sensory potentials lower>upper
Low amplitude distal motor responses-mildly delayed F waves
Conduction velocities decreased

EMG -Neurogenic-distal>proximal
Fibrillation potentials, positive sharp waves
Motor units- high amplitude,long duration,polyphasic

Question 4

Demyelinating neuropathy

Answer 4

Primary destruction of myelin sheath
Secondary axonal degeneration late in disease
Weakness -proximal and distal (MAG, hereditary)
Sensory-mild, symmetric, distal
Tendon reflexes- reduced/absent -diffuse
Less wasting compared to axonal

Question 5

Etiology for demyelinating

Answer 5

Immune/inflm-GBS,CIDP,MMP,POEMS,HIV,Paraprotein
Metabolic-leukodystrophies, mitochon(NARP,MNGIE)
Drugs/toxin- Amiodarone, HCQ,Bortezomib, tacrolimus,,TNF-alpha blockers,nivolumab, diphtheria

Question 6

Neuronopathy

Answer 6

*Often one modality. Onset subacute
Motor -involvement of AHC
Sensory (common)-sensory ganglionopathy -severe deficit, poor response to Rx
Autonomic -rare
*Prox and distal
*Face and bulbar common
*Assymetric

Question 7

Sensory neuronopathies

Answer 7

Idiopathic
Immune-Sjogrens,paraneoplastic-anti-Hu,Ri,CRMP5,Ma
Acute sensory neuronopathy
Drugs -B6, cisplatin
Hereditary-Fabry’s
NCS- Normal motor/Fwave, normal EMG, absent sensory potentials

Question 8

Workup of peripheral neuropathy

Answer 8

FBC,RFT, B12,folate, B6,TFT, LFT,SPEP, ESR,Auto ab
NCS
CSF (pn,cells), heavy metals, QST, skin Bx, nerve Bx

Question 9

NCS in demyelinating neuropathy

EMG findings

Answer 9

Very slow conduction velocity
Conduction block-failure of condn along intact neuron
Dispersion of motor response
Prolonged distal latencies and F waves

Reduced motor unit recruitment(fast firing motor)
Less commonly fibrillations/PSW at rest
Motor units themselves normal

Question 10

Indication for sural nerve biopsy

Answer 10

Select cases if etiology unclear, treatable cause, functionally disabling
Useful if -assymetric ,sensory, abnormal NCS, affected nerve not degenerated
DDx-vasculitis,amyloidosis, sarcoidosis, leprosy,tumour infiltration,inherited(HNPP)

Question 11

CIDP features

Answer 11

Proximal and distal weakness
Distal sensory loss
Absent or impaired reflexes
Autonomic/resp uncommon
Onset -gradual over 2 months
Types-c/c progressive, relapsing remitting,monophasic
M>F, all ages (mean 50)
Spontaneous remission may occur

Question 12

CIDP Investigations

Answer 12

NCS-segmental demyelination
Motor slowing, conduction block/dispersion
Lond distal/F wave latencies
Absent/reduced SNAP UL>LL
CSF -protein elevated, cells<10
MRI -root hypertrophy, enhancement
Nerve Bx- inflamm+atrophy, segmental demyelination

Question 13

CIDP Mx

Answer 13

Prednisolone
IV Ig
PLEX
Pulse steroids -
IV MP/Dex+/- Aza/
                  \+/-Cyclosp,mycophenolate,Ritux
                  \+/-Cyclophosphamide

Question 14

Multifocal motor neuropathy features

Answer 14

Young adults<45yrs
M>F 2:1
Slowly progressive, assymetric distal weakness, wasting fasciculations
Upper>lower extremities
No UMN /bulbar signs
Reflexes normal or depressed
Sensory -normal
Dx - NCS
       Anti-GM1ab in 60-80% cases
Rx- IV Ig, IV cyclophosphamide, Rituximab
NO RESPONSE TO STEROIDS

Question 15

Chemotherapy induced peripheral neuropathy

Answer 15

Taxol- Sensory>motor, large and small fibre, progression dose dependent
Cis/carboplatin- dose dependent severe pan sensory neuropathy, proprioceptive loss, sensory ataxia, pseudoathetosis
Vincristine -mixed sensory+motor+auto, Can cause profound weakness,distal weakness late,legs>arms
Bortezomib-painful sensory axonal neuropathy
Immune mediated neuropathy motor>sens demyelinating, can respond to immune treatment

Question 16

Oxaliplatin associated neurotoxicity

Answer 16

A/c neurosensory Sx- begin on infusion,peak 24-48hrs
Cold induced parasthesias, pharyngolaryngeal dysaesthesia, muscle tightness, leg cramps. Resolve in 1 week
C/c neurotoxicity -Sensory axonal neuropathy+neuronopathy, accumulation of platinum based compound in DRG

Question 17

TNF alpha blocker drugs causing neuropathy

Answer 17

Infliximab, adalimumab, etanercept
Develops early (in months after Rx)
Immunomodulating Rx required even if drug discontinued

Question 18

Genes involved in CMT subtypes

Answer 18

CMT 1( demyelinating) - duplication of PMP-22 gene
HNPP -PMP22 deletion
CMT I X- XLD -GJB1 gene codes for connexin
MFN2 (mitofusin 2)
MPZ (Myelin protein zero)