Peripheral

Neuropathy
Dr Hazem Alhewag, MD
 Introduction
 Classification
 Approach to PN
 Pathology
 Mononeurpathies

 Polyneuropathies:

Hereditary
Acquired
 Plexus lesions
 Classification
 Anatomical:
Peripheral nerve lesion
Root & plexus

 Pathological:
Demyelinating
Axonal
 Etiology
Hereditary
Acquired
 Symptoms
Motor Sensory Autonomic

Weakness Paresthesia Postural

hypotension
Cramps Dysesthesia B/ B
dysf unction
Fasciculation Pain I mpotence

Loss of I mpaired
sensation sweating
 Complaint

Weakness
Pain
Burning
Thick soles
Walking on stones
Tingling
Imbalance
 Clinical History
 Time course:
Acute: GBS, diphtheria, porphyria.
Gradual: CIDP, hereditary, metabolic
 Age of onset: HPN, Cancer,
 Medical history: as DM, collagen diseases

 Drug & alcohol history: As chemotherapy ,

 FH

 Occupational history: as painters, manual

work, exposures to heavy metals.

Distribution of numbness
or weakness in peripheral
neuropathy
 Physical Examination
 Localizethe deficit:
Mononeuropathy
Mononeuropathy multiplex
Polyneuropathy
 Motor; Sensory; Autonomic:

Predominantly motor
Predominantly Sensory
Autonomic
involvement
 Causes of Neuropathy
 Inflammatory (blood vessels or
myelin)
 Hereditary (Charcot Marie Tooth)
 Metabolic (diabetes, liver, kidney)
 Toxic (alcohol, chemical exposure)
 Vitamin deficiency (B12, D,
Thiamine…)
 Drug related (chemo drugs)
 Related to tumor (paraneoplastic)
 Pathology
(1) Axonal Loss:
Most common
DM, RF, Hereditary
Distal weakness
Absent reflexes
Distal sensory loss
NCS
Partial recovery
NCS of axonal
neuropathy
Causes of axonal
neuropathy
(2) Myelin loss:
Hereditary
Immune-mediated neuropathies
(GBS) compression
Weakness
Absent reflexes
Better prognosis
NCS
Onion bulb
Causes of demyelinating
neuropathy
NCS of demyelinating
neuropathy
 Differential Diagnosis of
Neuropathies by Clinical Course
Acute Subacute Chronic course/ Relapsing/
onset onset insidious onset remitting
(within (weeks to course
days) months)
Guillain-Barré Maintained Hereditary motor Guillain-Barré
syndrome exposure to sensory neuropathies syndrome
toxic
agents/medicati
ons
Acute Persisting Dominantly inherited CIDP
intermittent nutritional sensory neuropathy
porphyria deficiency
Critical illness Abnormal CIDP HIV/AIDS
polyneuropath metabolic state
y
Diphtheric Paraneoplastic Toxic
neuropathy syndrome
Thallium CIDP Porphyria
toxicity
 Diagnostic Approach
 The differential diagnosis of peripheral
neuropathy is significantly narrowed by a
focused clinical assessment that
addresses several key issues –

 Does the patient actually have a neuropathy?

 What is the pattern of involvement?
 Is the neuropathy focal, multifocal or
symmetric?
 If the neuropathy is symmetric, is it proximal
or distal?
Does the patient actually
?have a neuropathy
 Causes of generalized weakness
include motor neuron disease,
disorders of the neuromuscular
junction and myopathy.

 Peripheral neuropathy can also be

mimicked by myelopathy,
syringomyelia or dorsal column
disorders, such as tabes dorsalis.

 Hysterical symptoms can sometimes

mimic a neuropathy.
Is the neuropathy focal,
multifocal or symmetric?
 Focal neuropathies include common
compressive neuropathies such as
carpal tunnel syndrome, ulnar
neuropathy at the elbow or peroneal
neuropathy at the fibular head

 A multifocal neuropathy suggests a

mononeuritis multiplex that may be
caused, for example, by vasculitis or
diabetes
 If the neuropathy is
symmetric, is it proximal or
?distal
 Most toxic and metabolic
neuropathies present as a distal
symmetric or dying-back process.
 Proximal sensory neuropathies are

rare and include porphyria.

 Predominantly motor neuropathies

are often proximal and include

acquired inflammatory neuropathies
such as Guillain-Barré syndrome.
 An exception is lead neuropathy, which
initially affects motor fibers in radial
and peroneal distributions.
Mononeuropathies
(1) Median Neuropathy
 Most common
 CTS: Most common
 Women 3:1, DM, rheumatoid arthritis,
hypothyroidism, pregnancy
 Nocturnal numbness or pain
 Dropping things: APB weekness
 + Tinel’s, phalen’s signs
 NCS/EMG
 Splinting vs. surgical decompression
Median Nerve lesion
(2) Ulnar Neuropathy
 Elbow

Trauma, bone deformity, leprosy,

idiopathic
 Elbow pain
 Intrinsic hand muscle weakness
 Paresthesia

 NCS/EMG
 Conservative vs. surgery
 Radial Neuropathy )3(
 Humerus fracture
 Pressure palsy

 Crutches
 Wrist drop, other extensors

 Triceps & brachialis reflexes

 Dorsal sensory loss
 NCS/EMG
 Common Peroneal )4(
Neuropathy
 Compression:
Coma, prolonged bed rest,
crossed legs
 Trauma
 Systemic disorders:
HNPP, DM, Leprosy
 Foot drop, steppage gait
 NCS/EMG
 Conservative ttt & physiotherapy
 Differential diagnosis of
wasting of small muscles of
.the hands
 Lesions of the AHCs
( A) lesions of acute onset e.g poliomyelitis,
Acute cord compression AHCs

(B) Lesions of slow onset e.g. MND:.

 Syringomyelia:
 Spinal cord tumours.
 Syphilitic meningomyelitis or in
arachnoiditis
 Lesions of spinal nerves “ Root avulsion”.
 Lesion of brachial plexus.
 Lesions of peripheral nerves (median and
ulnar)
 Muscle lesions
 Physical Examination
 The motor examination includes a
search for fasciculations or cramps,
or loss of muscle bulk.

 Tone is normal or reduced

 The pattern of weakness helps narrow

the diagnosis: symmetric or
asymmetric, distal or proximal, and
confined to a particular nerve, plexus
or root level
 Deep tendon reflexes are reduced or
absent.
 Proximal weakness results in an
inability to squat or to rise unassisted
from a chair
 The general physical examination can
provide evidence of orthostatic
hypotension without a compensatory
rise in heart rate when autonomic
fibers are involved.
 Respiratory rate and vital capacity
should be evaluated in Guillain-Barré
syndrome to assess for respiratory
compromise.

 The presence of lymphadenopathy,

hepatomegaly or splenomegaly, and
skin lesions may provide evidence of
 Hereditary Neuropathies
(1) Charcot-Maries-Tooth
Distal weakness
Wasting
Absent reflexes
Pes cavus
Demyelinating (CMT1); Axonal
(CMT2)
AD, AR, X-linked
(2) Friedreich’s Ataxia:
AR
Trinucleotide repeat (9q13-21)
Sensory loss
Absent reflexes
(3) HNPP:
AD
Simple or multiple mononeuropathies at
compression sites
 Acquired
Neuropathies
 Acute Idiopathic Inflammatory )1(
Polyneuropathy (GBS or AIDP
 Clinical Features: Acute
to subacute Preceding
febrile illness (Flue, GI, Vaccine..)
Proximal & ascending symmetrical
weakness
Respiratory involvement
Sensory complaints (subjective)
Absent reflexes
Autonomic : hypotension and arrhythmias,
sphincter intact and if affected only
transient
CN may be involved
4 w progression 4 w stationary 4 w
regression
Diagnosis and treatment
 Clinical features
 investigation
 CSF protein
Normal CSF cell count (<10)
NCS:
Slow motor velocity
treatment:
Plasmapharesis, IVIG
Symptomatic: Respiratory, DVT,
Autonomic, Nutrition....and physiotherapy
 Prognosis: good
 Chronic inflammatory )2(
Demyelinating Polyneuropathy
(CIDP)
 Chronic progressive or relapsing
course
 Similar to GBS
 Similar CSF
 Electrodiagnosis:
Demyelinating & axonal
 Steroids
 Plasma exchange, IVIG
 Immunosuppression
 Diabetic peripheral
neuropathy
 DM is one of the most common
causes of disableing polyneuropathy.

 DPN was present in 66% of IDDM and

59% NIDDM.

 However only 20% are symptomatic

 Etiology of DPN
 Hyperglycemic –polyol-myoinositol
hypothesis:
Glucose— Hexokinase Glucose 6 phosphate→ Krebs's cycle
In diabetics glucose inter to polyol pathway
with excess production of sorbitol and
increase of intracellular myoinositol

This result in defective of Na/ K ATPase

activity leading to reduction of axonal
transport
 Other theories

 Microangiopathy:
 Structural change at the node of
Ranvier: ATPase deficiency increase of Na
lead to detachment of myelin and dying
back of axon
 Vsaculitic neuropathy: lymphocytic
inflammatory vasculopathy as in painful
proximal diabetic neuropathy.
 Nerve growth factor deficiency:
Skin of foot of diabetics show marked
reduction of NGF which responsible on
small sensory fiber neuropathy.
Classification of diabetic
neuropathy
 Two classification systems for diabetic
neuropathy are the Thomas system
and the symmetrical-versus-
asymmetrical system.
 The Thomas system (modified) is as
follows:
The Thomas system
classification
 Hyperglycemic neuropathy
 Generalized symmetrical polyneuropathies
 Sensory neuropathy
 Sensorimotor neuropathy
 Autonomic neuropathy
 Focal and multifocal neuropathies
 Superimposed chronic inflammatory
demyelinating polyneuropathy
 Distal symmetrical sensorimotor
polyneuropathy
 Distal symmetrical sensorimotor polyneuropathy is
most common for of diabetic neuropathy and defined
according to the following 3 key criteria:
1. The patient must have diabetes mellitus
consistent with a widely accepted definition.
2. Severity of polyneuropathy should be correlate
with duration and severity of diabetes.
3. Other causes of sensorimotor polyneuropathy
must be excluded
Asymmetrical neuropathies
:include the following

 Median neuropathy of the wrist

(carpal tunnel syndrome)
 Other single or multiple limb
mononeuropathies
 Thoracic radiculoneuropathy
 Lumbosacral radiculoplexus
neuropathy
 Cervical radiculoplexus neuropathy
 Clinical features of diabetic
polyneuropathy
 Mainly sensory :paraesthesiae and pain
 Deep sensation affection and sensory
ataxia
 “Neuropathic Arthoropathy”
most affected joint tarsometatarsal then
metatharsophalengial joint
 Unrecognized fractures
 Ulcers
 If prominent motor features must suspect
CIDP
 Acute painful diabetic
neuropathy
 Acute or subacute burning lower limb pain
with marked cutanous hyperalgesia, with
no definite distal sensory loss, and slight
reduction of ankle jerk
 So may confusing as psychogenic
condition specially that 70% of cases
associated with depression
 Most of cases associated with rapid weight
loss
 And usually follow tight gylcemic control
 Diabetic truncal
radiculoneuropathy
 Attacks of truncal pain with no
specific sensory disturbance of
abdomen
 Occur in fifth to seventh decades
female with type2 DM
 Focal abdominal wall paralysis and
increase of abdominal protuberance
 Marked weigh loss ?????
 Diabetic proximal
neuropathy
 The disorders range from familiar extreme
of acute asymmetrical painful proximal
weakness within days to painless
symmetrical proximal weakness occur
over weeks or months
 The disorders carry many terms as:
Diabetic (myelopahty, amyotrophy,
myopathy, radiculopathy, lumber
radiculopathy, or neuropahtic cachexia).
 Clinical features
 Occur in fifth to seventh decades in type2
DM
 Anterior thigh muscle pain usually first
presenting symptoms
 Characteristic involvement of quadriceps
weakness
 Lost knee jerks
 Extensor planter
 In spite of unilateral onset 50% of cases
bilateral affection within few weeks
 Marked weight loss
 Increase of CSF protein ???
 Mononeuropathy and cranial
neuropathy
 Mononeuropathy: as CTS
 Cranial neuropathy :
Either ischemic or vasculitic ???
Most common affected nerves are
ocular nerves third, sixths and less
common fourth
Other nerves may be affected specially
facial and usually preceded by pain
around ear ????
 Autonomic neuropathy
 Is the most serious and disabling
neuropathy with DM

 Most of functional abnormalities of

organ as kidney, heart, retina ,
bladder ect…. Are due to
sympathetic denervation of these
organs .
 Sweating abnormalities
 Abnormal sweating is the first
presenting symptoms of autonomic
neuropathy which precede other
symptoms by many years as:
1. Defective sweating in foot
2. Gustatory sweating which highly
characteristic symptoms of diabetic
autonomic neuropathy.
 Orthostatic hypotension
 ↓of systolic Bp >30 mmHg or diastolic > 10
with setting position
 Features:
1. Headedness, dizziness with longstanding or
when patient awake from sleep
2. Gray mistiness of vision follow by curious pain
in back of neck and shoulders “ coat hanger”
distribution and later loss of consciousness
3. Orthostatic hypotension worse with of
insulin due to reduction of peripheral vascular
resistance with insulin