NEUROPATI

DEFINITION
Neuropathy is defined as a disease or
injury of the peripheral sensory, motor, or
autonomic nerves.
Can be : - pure motor
- pure sensory
- mixed sensorimotor
- autonomic

Category
Usually categorized separately :
Neuronopathy : selective injury to
the cell body of the axon
Radiculopathy : selective injury to
the nerve roots distal to their origin
Plexopathy : injury to the brachial or
lumbosacral plexus

EPIDEMIOLOGY & ETIOLOGY

Mononeuropathy :
Median nerve entrapment the most
common mononeuropathy
Causes :
- repetitive motion injury during manual tasks
such as keyborad operation (entrapment)
- multifocl demyelination
- ischemic injury
- trauma

EPIDEMIOLOGY & ETIOLOGY

Polyneuropathy :
hundreds of potential etilogies
DM is the most common cause in the US,
affecting at least 1-2% of the population
Leprosy remains the most common cause of
neuropathy worldwide.

CLASSIFICATION
1. BASED ON THE ONSET OF NEUROPATHY:
ACUTE NEUROPATHY
eg. : ACUTE IDIOPATHIC POLYNEUROPATHY
CHRONIC NEUROPTHY

eg.

: BERI BERI
DIABETES MELLITUS
LEPROSY

2. BASED ON SEVERITY
1. MILD NEUROPATHY :
SENSORY ONLY
2. MODERATE NEUROPATHY :
SENSORY, MOTOR, AND DECREASE
OF
TENDON REFLEXES
3. SEVERE NEUROPATHY :
SENSORY, MOTOR, DECREASE
OF TENDON REFLEXES, MUSCLE ATROPHY

3. BASED ON THE NUMBER OF

NERVES INVOLVED
1. MONONEUROPATHY SIMPLEX :
ONLY ONE PHERIPHERAL NERVE INVOLVED.
2. MONONEUROPATHY MULTIPLEX (MULTIFOCAL
NEURPATHY) :
MULTIPE, SCATTERED NERVES IN AN
IRREGULAR DISTRIBUTION
3. POLYNEUROPATHY :
SEVERAL NERVES INVOLVED, SYMMETRICAL,
SAME ONSET AND DISTAL PREDOMINANT.

4. BASED ON LESION SITE

1 DISTAL AXONOPATHY :
AXONAL LESION
2. MYELINOPATHY :
DISORDER OF MYELIN SHEATH.
3. NEUROPATHY :
DISORDER OF CELL BODY AT ANTERIOR
HORN CELLS, SPINAL CORD
OR DORSAL
ROOT GANGLION.

ETIOLOGY
1. IDIOPATHIC INFLAMMATORY NEUROPATHIES
-

ACUTE IDIOPATHIC POLYNEUROPATHY

(GUILLAIN BARRE SYNDROME)
- CHRONIC INFLAMMATORY DEMYELINATING
POLYNEUROPATHY
2. METABOLIC AND NUTRITIONAL NEUROPATHIES
- DIABETES, HYPOTHYROIDI, ACROMEGALY
- UREMIA
- LIVER DISEASES
- VIT B1, OR VIT B12 DEFICIENCY

ETIOLOGY
3. INFECTIVE AND GRANULOMATOUS
NEUROPATHIES:
AIDS, LEPROSY. DIPHTHERY, SARCOIDOSIS
4. VASCULITIS NEUROPATHIES:
- POLYARTERITIS NODOSA
- RHEUMATOID ARTHRITIS
- SYSTEMIC LUPUS ERYTHEMATOSUS

ETIOLOGY
5. NEOPLASTIC AND PARAPROTEINEMIC
NEUROPATHIES:
- COMPRESSION AND IRITATION BY TUMOR
- PARANEOPLASTIC SYNDROME
- PARAPROTEINEMIAS
- AMYLOIDOSIS

ETIOLOGY
6. DRUGS INDUCED AND TOXIC NEUROPATHIES
- DAPSONE, ISONIAZIDE, PHENYTOIN,
PIRIDOXYNE, VINCRISTIN, HIDRALAZINE.
- ALCOHOL
- TOXINS : ORGANOPHOSPHAT
ARSENIC
LEAD
THALIUM
GOLD

ETIOLOGY (cont.d)
7. HEREDITARY NEUROPATHIES
- IDIOPATHIC
HEREDITARY MOTOR AND SENSORY NEUROPATHIES
HEREDITARY SENSORY NEUROPATHIES
FAMILIAL AMYLOIDOSIS

- METABOLIC
PORPHYRIA
METACHROMATIC LEUCODYSTROPHY
ABETALIPOPROTEINEMIA

ETIOLOGY
8. ENTRAPMENT NEUROPATHIES
- UPPER LIMBS
MEDIAN NERVE (CARPAL TUNNEL SYNDROME)
ULNAR NERVE
RADIAL NERVE

- LOWER LIMBS
PERONEAL NERVE
FEMORAL NERVE
OBTURATOR NERVE

PATHOGENESIS
Axonal integrity is critical to action
potential propagation injury to the
axon may block transmission
Myelin is also critical to impule
transmission and increases conduction
velocity through saltatory conduction
demyelination disrupt saltatory
conduction, slowing NCV.
Focal demyelination leakage of axonal current
to halt AP propagation causing conduction block.

PATHOGENESIS
Can be divided into 4 major categories :
1. Neuronal degeneration : results from damage to the
motor or sensory nerve cell bodies, with subsequent
degeneration
2. Wallerian degeneration : results from damage to the axon
at a specific point below the cell body, with degeneration
distal to the injury.
3. Axonal degeneration : results from diffuse axonal
damage. The distal portion undergoes the earliest and
most severe change followed by gradual proximal ascent
with continued injury (dying back phenomenon)
4. Segmental demyelination : results from injury to the
myelin sheath without injury to the axon

PATHOPHYSIOLOGY
1. NEUROPRAXIS :
- the mildest form
- conduction disruption only
- intact nerve continuity
- recovery in minutes or weeks

PATHOPHYSIOLOGY
2. AXONOTMESIS:
- AXONAL DAMAGE FOLLOWED BY
DEGENERATION
- ENDONEURAL SHEATH REMAINS
INTACT
- POSSIBLE REGENERATION

PATHOPHYSIOLOGY
3. NEUROTMESIS:
- PARTIAL OR TOTAL NERVE DAMAGE
- SURGICAL INTERVENTION IS NEEDED
- 50% RECOVER

CLINICAL SYMPTOMS
1. SENSORY SYMPTOMS :
Involvement of sensory axons produces
impairment of sensation with dysesthesias or
paresthesias.

CLINICAL SYMPTOMS
2. MOTOR SYMPTOMS :
Involvement of motor axons produces muscle
wasting and weakness followed by atrophy and
fasciculations
- LMN TYPE MUSCLE WEAKNESS
- FOOT DROP
- WRIST DROP

CLINICAL SYMPTOMS
3. CHANGE OF TENDON REFLEXES
The tendon reflexes supplied by the
affected

nerve are depressed or absent.

decreased or absent of tendon reflexes

CLINICAL SYMPTOMS
4. AUTONOMIC :
Involvement of axons supplying autonomic
function produces loss of sweating, alteration
in bladder fuction, constipation, and impotence
in male

DIAGNOSIS
1.
2.
3.
4.
5.
6.

CLINICAL SYMPTOMS AND SIGNS

LABORATORY STUDIES
CHEST X-RAY
LP
ECG
BIOPSY : sural nerve or radial cutaneus nerve

7. ELECTROPHYSIOLOGY: EMG
NCV

ELECTRO MYOGRAPHY
INDICATIONS :
LOWER MOTOR NEURON LESIONS :
1. ANTERIOR HORN
2. NERVE ROOTS
3. NERVE PLEXUS
4. PHERIPHERAL NERVES
5. NEUROMUSCULAR JUNCTION
6. MUSCLES

DIABETIC NEUROPATHY
Neuropati diabetik :
adanya gejala dan atau tanda disfungsi saraf perifer pd
orang dgn diabetes setelah dieksklusikan penyebab lain.
Prevalence : 10 - 20 % (symptomatic)

Diabetic Neuropathy :
50% of diabetic patients
type 1 than type 2
the most common : chronic sensorimotor
50% asymptomatic
10-20% needs specific treatment

PATHOGENESIS
The etiology is uncertain.
4 hypothesis (not necessarily exclusive) :
1. Hyperglycemia-polyol-myoinositol hypothesis.
2. Microvascular hypothesis
3. Structural changes at the node of Ranvier.
4. Vasculitic neuropathy.

1. Hyperglycemia-polyol-myoinositol hypothesis

Normal : glucose hexokinase

glucose-6-phosphate Krebs cycle.
Hyperglycemia saturates hexokinase
activity glucose shunted to polyol
pathway production of sorbitol assoc w/ a
decrease in intracelluler myoinositol
defective Na/K ATPase activity defect
axon transport slowing NCV

2. Microvascular hypothesis
DM : ** thickening of capillary
basement
membrane
** increase in the size and number
of capillary endothelial cells
Microangiopathy increase number of
closed capillaries in peripheral nerves
progressive hypoxia secondary
changes in axons and Schwann cells

3. Structural changes at the node of

Ranvier
Na/K ATPase defiency increase intraaxonal Na and nodal axonal swelling
detachment of myelin myelin retraction
from the nodal area slowing of axonal
conduction.
Exposure of paranodal K channels leakage
of K impairment of axonal conduction.
Impairment of axonal transport gradual
dying back of axons starting at the distal
axons and progressing proximally.

4. Vasculitic neuropathy
Some cases of NIDDM and
proximal diabetic have a
inflammatory vasculopathy with
perivascular collections of
lymphocytes and axonal
neuropathy

DIABETIC NEUROPATHIC SYNDROMES

DISTAL SYMMETRIC NEUROPATHY :
- large fiber sensory neuropathy
numbness, paresthesias,
dysesthesias,
hyperesthesias,
ataxia.
- sensorimotor neuropathy
any of the above plus distal
weakness

DIABETIC NEUROPATHIC SYNDROMES

Small Fiber Neuropathy :
- pure small fiber neuropathy
numbness, paresthesias, painful
dysesthesias,
hyperesthesias.
- Diabetic neuropathy cachexia
subacute, severe neuropathic pain, rapid
weight loss
- Autonomic neuropathy
erectile dysfunction, orthostasis, cardiac
dysrhythmia, diarrhea, constipation

DIABETIC NEUROPATHIC SYNDROMES

Ischemic Mononeuropathy.
- cranial (eg. CNs III, VI,VII)
diplopia, pupil-sparing third nerve palsy,
hemifacial weakness
- Radicular (thoracic, lumbosacral)
pain, followed by numbness or weakness in a
radicular distribution
- Peripheral (eg. Femoral)
pain, followed by numbness, weakness or
both in territory of a single nerve

DIABETIC NEUROPATHIC SYNDROMES

Regional Neuropathic Syndromes.
- Diabetic amyotrophy
subacute weakness and atrophy of
proximal leg muscles
- Diabetic thoracoabdominal neuropathy.
subacute weakness, numbness, and
atrophy in thorax and abdomen

DIAGNOSIS

THERAPY
Intensive diabetic therapy
Maintain ideal body weight
Adjuvant analgetics :
TCA antidepressants
carbamazepine
gabapentin
intravenous lidocaine, etc

Adjuvant Analgetics

CARPAL TUNNEL SYNDROME

80% in WOMEN, A COMMON TEMPORARY
PHENOMENON DURING PREGNANCY
PRESSURE TO THE NERVE WHEN
PASSING BENEATH THE FLEXOR
RETINACULUM OBSTRUCTION OF
VENOUS CIRCULATION AND EDEMA
ISCHEMIA INCREASING PRESSURE ON
THE NERVE ISCHEMIC ATROPHY OF
NERVE FIBERS

Etiology
1. Hereditary
: HMSN type III
2. Traumatic : dislocation, fracture, hematoma, wrist
sprain
3. Infection : tenosynovitis, tbc, sarcoidosis
4. Metabolic : amyloidosis, gout
5. Endocrine : acromegaly, DM, hypothyroidism,
pregnancy
6. Neoplastic
: ganglion cysts, lipoma , myeloma
7. Collagen vascular diseases : RA, polymyalgia
rheumatica,
SLE
8. Degenerative disease
: OA
9. Iatrogenic: radial artery puncture, shunt for
dialysis,
anticoagulant therapy

Clinical Symptoms
The earliest symptoms : numbness
and paresthesias in the sensory
distribution of the median nerve in
the hand (thumb, index, middle
and lateral half of the ring finger)
Later on : pain, worst at night
Late : inability to screw bottle caps
or grip properly

SIMPLE CLINICAL TESTS FOR CTS

PHALENS SIGN (PHALENS MANEUVRE):
is present when tingling (paresthesia) is
experienced in the distribution of the median
nerve when the wrist is held in forced flexion (90 o
for 30-60 seconds)
TINELS SIGN (HOFFMANN-TINELS SIGN) :
is present when tingling (paresthesia)is
experienced when tapping lightly with a finger or
a tendon hammer over a compressed or
regenerating peripheral nerve. The tingling is
present in the distribution of the damaged nerve.

Therapy
Identified causes should be treated
Corticosteroid injection around the
median nerve in the carpal tunnel.
Surgical division of the transverse
ligament (flexor retinaculum)
Endoscopic carpal tunnel release

GUILLAIN - BARRE SYNDROME

(GBS)
ESSENTIALS of DIAGNOSIS :

Rapidly progressive paralysis, often

ascending
Areflexia
Increased CSF protein without increased cell
count (albuminocytologic dissociation)
Evidence of demyelination on nerve
conduction studies (may be delayed)
A neurologic emergency that may rapidly
progress to respiratory compromise

GBS : GENERAL CONSIDERATIONS

GB refers to a group of immune-mediated
disorders targeting the peripheral nerves.
Annual incidence : 1-2 cases per 100.000 people
The most common form : AIDP (85-90% cases)
Characterize by progressive weakness of the
extremities (more than one limb) and
attenuation or loss of reflexes
The suspected target are located on the myelin,
but the precise epitope has yet to be identified
Demyelination begins in the proximal nerves,
then extends distally as the disease progress.

GBS : GENERAL CONSIDERATIONS

URI, GI infection, nonspecific febrile
illness precedes neurologic symptoms in
about 60% cases.
The most common : URI
The most frquently identified organism :
Campylobacter jejuni.
Less common variants of GBS : AMAN
and AMSAN (10% of GBS)
Miller Fisher Syndrome (3-5%)

GBS : Subtypes and Clinical Findings

Acute inflammatory demyelinating
polyneuropathy (AIDP) :
- ascending paralysis
- minor sensory symptoms
- nonspecific antibody (Ab)
- EMG/NCV : demyelination on NCS,
absent
F waves

GBS : Subtypes and Clinical Findings

Acute motor axonal neuropathy
(AMAN) :
- flaccid paralysis
- often with Campylobacter jejuni
infection
- IgG anti-GM1, IgG anti-GD1a
- EMG/NCV : reduced motor amplitudes
normal sensory studies

GBS : Subtypes and Clinical Findings

Acute motor sensory axonal neuropathy
(AMSAN) :
- acute (< 1 week)
- profound quadriparesis
- ventilation often required
- IgG anti-GM1
-EMG/NCV : reduced or absent motor amplitudes
reduced or absent sensory amplitudes
axonal injury by EMG

GBS : Subtypes and Clinical Findings

Miller Fisher syndrome :
- ataxia
- areflexia
- opthalmoplegia
- IgG anti-GQ1b
- EMG/NCV : decreased sensory nerve AP
motor conductions often
normal

GBS : SYMPTOMS AND SIGNS

AIDP often begins 1-3 weeks after an infection
or inciting event such as surgery
70% cases initially have paresthesias or
vague numbness in their hands and feet.
Symmetric weakness appears a few days later
and progress over days to a few weeks.
Paralysis is maximal by about 2 weeks in>
50% cases, and by 1 month in > 90% cases.
Ascending weakness beginning in the distal
legs is typical, although descending paralysis
with predominant proximal muscles weakness
rarely appears.

GBS : SYMPTOMS AND SIGNS

Facial weakness occurs in half of patients with AIDP
and ophthalmoparesis and lower cranial nerves
neuropathies can cause dysarthriaand dysphagia.
AIDP require mechanical ventilation
Weakness is symmetric, and ranges from mild to
severe flaccid quadriparesis.
Sensation is usually normal, despite sensory
symptoms, although mild distal vibratory loss may
be found
Reflexes are diminished or absent
Sphincter tone is normal

GBS : DIAGNOSTIC STUDIES

Imaging studies of the spinal cord
to rule out myelopathic disease.
LP (after spinal cord disease excluded)
Evaluation for infection
ECG
Chest radiographs
EMG/NCV

GBS : DIFFERENTIAL DIAGNOSIS

Acute spinal cord disease (acute
myelopathy, transverse myelitis)
Brainstem ischemia
Acute disorders of neuromuscular junction
(myasthenia gravis, botulinum
intoxication)
Acute neuropathies (porphiric neuropathy,
diphtheritic neuropathy, mononeuropathy
multiplex, toxic neuropathy)

PREDICTORS OF SEVERE DISEASE AND

POORER OUTCOME
Old age
Rapid onset of severe tetraparesis
Need for early artificial ventilation
Severely decreased compound
muscle action potential (<20%
normal)
Acute motor-sensory axonal form of
the disease

THERAPY
PLASMAPHARESIS (5-6 exchanges over 1- 2
weeks) or
IMMUNOGLOBULIN IV (0,4 g/kg/day for 5
days)
Equally effective when given within the first 2 weeks after onset
Combination of both no additional benefit
RCTs on oral or IV corticosteroid failed to show
benefit