Peripheral Neuropathy

Dr. Hossam Sherif, MD

Associate Professor of Internal Medicine
The patterns of peripheral neuropathy…

1 – Mono-neuropathy:
Affects a single nerve

3 - Mononeuritis multiplex (multiple mono-neuropathies):

involvement of individual non-contiguous nerve trunk.

2 – Poly-neuropathy (the most common):

More serious and affecting more areas of the body, typically
(stocking-glove)
Causes of Peripheral Neuropathy
The Motor Unit
 Types of nerve fibers
Diameter Conduction Function
microns Velocity m/s
A alpha 1-20 70-110 Motor, Proprioception
beta 5-10 30-60 Rude touch
gama 3-6 20-30 Motor
delta 2-5 20-30 Sharp pain
B <3 5-15 Autonomic, pregangl.
C <1.3 0.5-2 Fine touch
Non myelinated
The two types of peripheral neuropathies:
axonopathies and myelinopathies
Clues to diagnosis (History)
• Viral illnesses
• lifestyle, and work and occupational exposure
• Alcohol abuse, vitamin deficiencies, and dietary habits
• Use of over-the-counter drugs, Vitamin B6 and zinc consumption
• Gastric bypass surgery (Copper Deficiency)
• Medications prescribed in the past
• HIV infection
• Diabetes
• Previous Diseases- amyloidosis, a history of thyroid disease, chronic renal and
liver disease,
• Malignancy, previous treatment with chemotherapeutic agents
• Connective tissue disorders
• recreational use of substances, and exposure to heavy metals, industrial agents,
herbicides, and pesticides
• Foreign travel (leprosy)
• A detailed family history for presence of hammer toes, high arches, weak
ankles, gait abnormalities or “muscular dystrophy,” suggesting a longstanding or
hereditary neuropathy.
• possibility of a tick bite (Lyme disease)
• it is not uncommon to find more than one in the same patient, such as diabetes,
alcohol abuse, and vitamin b 12 deficiency
 Temporal evolution?

Onset, Duration Acute (days to 4 weeks) GBS, Vasculitis, Radiclupathies,Toxic

and Evolution of neuropathies, Acute intermittent
Porphyria
symptoms Subacute (4-8 weeks)

Chronic (>8 weeks) Most Neuropathies (Diabetes, CRF,

Paraneoplastic, Hereditary motor
sensory neuropathies)
Motor Symptoms
Irritative Muscle Cramps, Fasciculation or Tremors

Destructive Weakness, Atrophy, Walking Difficulty

Difficulty in turning keys in locks, unfasten button and opening
bottles and jars

Sensory Symptoms
Irritative Paresthesia, Band-like sensation on feet or trunk,Stumbling, Tingling
Pain- Prickling, Searing, Burning,Pins and Needles
Neuropathic Pain
Allodynia, Hyperalgesia
Destructive Numbness,
Lack of feeling/Loss of sensation,
Walking on cotton wool
Autonomic Symptoms
• Anhidrosis
• Orthostatic Hypotension
• Intolerance to light
• Lack of tear and saliva
• Sexual impotence
• Bladder and Bowel dysfunction
• Gastroparesis
• Heat Intolerance
Examination
• Abnormal Sensation especially Distal vs. level.
• Weakness (typically Distal, but may be proximal/both)
• Normal Muscle Tone - No Spasticity
• Absent Tendon Reflexes (areflexia)
• Abnormal Gait
• Is there a evidence of UMN involvement- Consider combined system
degeneration with neuropathy (Vitamin B 12 deficiency, copper
deficiency, HIV, Severe Hepatic Disease)
 Signs
Early Signs
Distal sensory loss to cold, pinprick, and/or vibration
Reduced or lost ankle reflex
Romberg’s sign
Impaired tandem walking
Toe extensor weakness

Latter features
Distal loss of cold, pinprick, vibration, and joint position sense
Areflexia at ankles and knees
Foot-drop
Inability to toe-and-heel walk
Cranial Nerve Involvement
(ONLY)
Cranial Nerve Involvement

• External ophthalmoplegia: Miller-Fisher syndrome

• Trigeminal sensory loss: Sjogren's syndrome
• Lower cranial nerve palsy with gynecomastia: Kennedy's syndrome
• Facial nerve palsy: GBS, Leprosy, Lyme’s Disease, Sarcoidosis, HIV
Distribution-Focal or multifocal
• Mononeuropathy, the neurological deficit follows the distribution of a
single nerve; foot drop due to a common fibular (peroneal) nerve
lesion(sensory loss is restricted to the lower two-thirds of the lateral
leg and dorsum of the foot).
Causes-Leprosy, trauma

• Multiple mononeuropathies (mononeuropathy multiplex), the

neurological findings should point to simultaneous or sequential
damage to two or more non-contiguous peripheral Nerves.
Eg-Diabetes, Vasculitis
Causes of Multiple Mononeuropathies
Axonal injury Demyelination

Vasculitis (systemic, nonsystemic) - Multifocal motor neuropathy
Diabetes mellitus Multifocal acquired demyelinating 
Sarcoidosis sensory and motor neuropathy
Hansen disease (leprosy) (Lewis-Sumner syndrome)
HIV - Multiple compression neuropathies 
(hypothyroidism, diabetes)
- Hereditary neuropathy with liability to 
pressure palsies
 Motor or Sensory
Symmetric or Asymmetric
Proximal or Distal
Distribution of Motor and Sensory Involvement

• Predominant Motor
Guillain-Barré syndrome
Chronic inflammatory demyelinating polyradiculoneuropathy
Neuropathy with osteosclerotic myeloma
Diabetic lumbar radiculoplexopathy (Amyotrophy)
Hereditary motor sensory neuropathies (Charcot-Marie-Tooth
disease)
Porphyria
Lead intoxication
Multifocal motor neuropathy
Paraneoplastic
Acute motor axonal neuropathy
Predominant Sensory Loss
• Leprosy
• Drugs (Vincristine, INH)
• Diabetes Mellitus
• Amyloidosis
• Alcohol
• Vitamin B12
• Sjogrens Syndrome
Chronic Length Dependent Neuropathy

• Begins in toes or feet

• Stocking distribution
• Progresses centrally
• Tops and bottoms of feet
• Weakness begins in ankles when
sensation reaches calves

Sometimes diagnosable, Never treatable?

Multifocal Motor Neuropathy
• Almost always in hands and wrists
• Pattern of weakness is in the
distribution of individual
peripheral nerves
• i.e. severe involvement in ulnar distribution
sparing median
• Lack of atrophy in weak muscles
• No pathological reflexes
Uncertainty
• Many cases are not easily definable because of multiplicity of patterns
• Cases that are not clearly untreatable are possibly treatable
Type of Fiber Involved
Axonal Neuropathy Demyelinating Neuropathy
Usually Gradual and insidious Onset Usually Acute or subacute
Large and long axons are affected early, hence Diffuse process. Starts in lower limbs, but not
initially lower extremeties are affected always distal
Stocking-glove sensory motor loss results in Generalized Weakness and mild sensory loss.
symmetrical distal clinical signs in legs and arms
Distal involvement Proximal and distal involvement
Ankle jerk lost early and proximal tendon reflexes All reflexes are lost early
preserved
Muscle wasting Common Relatively absent
CSF Proteins normal CSF Proteins elevated (since nerve roots are
involved
Slow Recovery Rapid Recovery
Residual deformity Common Residual deformity less common

Normal Conduction normal or slightly lowered Nerve Conduction is slowed

Autonomic Involvement
Neuropathies with Autonomic Nervous System Involvement

Acute Guillain-Barré syndrome
Porphyria
Toxic: vincristine, Vacor (rodenticide)
Acute Pandysautonomic neuropathy(idiopathic,paraneoplastic)
Chronic Diabetes mellitus
Amyloid neuropathy (familial and primary)
HIV virus–related autonomic neuropathy
Paraneoplastic sensory neuropathy
Hereditary sensory and autonomic neuropathy
Specific Causes
Diabetic Neuropathy (Predominant Sensory
Loss)
• Distal symmetric sensory or sensori-motor polyneuropathy,
• Autonomic neuropathy,
• Mononeuropathies.
• Diabetic polyradiculopathy is a syndrome characterized by severe
disabling pain in the distribution of one or more nerve roots. It may be
accompanied by motor weakness.
• Involvement of the lumbar plexus or femoral nerve may cause severe
pain in the thigh or hip and may be associated with muscle weakness in
the hip flexors or extensors (diabetic amyotrophy). Usually self-limited
and resolve over 6–12 months
Neuropathic arthropathy (Charcot’s joint):

Can be defined as bone and joint changes that

occur secondary to loss of sensation.

A progressive, degenerative condition that affects

one or more joints especially of the foot or ankle,
is marked by bone fragmentation, swelling,
redness, pain, and joint deformity, and typically
occurs following loss of nerve sensation
associated with various diseases (such as
diabetes, syphilis, and spina bifida)..
Guillain-Barré syndrome (mainly motor)
• The body's immune system attacks part of the peripheral nervous system.
• The first symptoms of this disorder include varying degrees of weakness or
tingling sensations in the legs. In many instances, the weakness and abnormal
sensations spread to the arms and upper body. Reflexes such as knee jerks are
usually lost.
• Guillain-Barré is called a syndrome rather than a disease because it is not clear
that a specific disease-causing agent is involved.
• The cerebrospinal fluid that bathes the spinal cord and brain contains more
protein than usual, so a physician may decide to perform a LP sample.
Clinical picture:

Sensory symptoms frequently appear before or at the onset of weakness and many
patients complain of a tingling or pricking sensation (paresthesia) in their hands and feet.
Characteristically this is very symmetrical and generally progressive.

Weakness in your legs or thighs that spreads to your upper body “Trunk”. Unsteady
walking or inability to walk or climb stairs. The majority of patients with GBS
develop ascending paralysis, which starts in the legs and typically spreads to the arms.
Cranial nerve involvement is also common and 25% of patients develop respiratory
depression and require mechanical ventilation.

These symptoms can increase in intensity until the muscles cannot be used at all and the
person is almost totally paralyzed. In these cases, the disorder is life-threatening and is
considered a medical emergency.
Clinical picture:

There are 4 clinical forms of GBS:

1) Acute inflammatory demyelinating polyradiculoneuropathy,
2) Acute motor axonal neuropathy,
3) Acute sensory and motor axonal neuropathy, and
4) Miller-Fisher variant, which is characterized by ophthalmoplegia, ataxia and areflexia,
with little muscle weakness.

The three phases of GBS are the progressive phase (lasting from days to 4 weeks), a
plateau phase with little clinical change (lasting from days to months), and a recovery
phase. By 7 days, about three quarters of patients will achieve their nadir in neurologic
function, and 98% will do so by 4 weeks.
Management:

There's no cure for Guillain-Barre syndrome.

The most commonly used treatment for Guillain-Barré syndrome is intravenous

immunoglobulin (IVIG). 

The speed recovery and reducing the severity of the illness: Plasma exchange
(plasmapheresis). The liquid portion of part of your blood (plasma) is removed and
separated from your blood cells.

Corticosteroids given alone do NOT significantly hasten recovery from GBS or affect the
long‐term outcome. 

Antibiotic according to the need.

Bulbar symptoms need mechanical ventilation.

Alcoholic Neuropathy (Predominant Sensory
Loss)
• Alcoholic neuropathy is defined to be neuropathy following regular
intake of more than 100 grams of ethanol daily for at least 10 years,
with normal thiamine levels.
• Insidious and slowly progressive.
• Muscle weakness begins distally and spreads to more proximal muscles.
• Gait difficulty, weakness, and muscle cramps are common.
• Sensory loss and burning paresthesias starts distally.
• Distal muscle wasting, loss of tendon reflexes, and sensory loss of all
modalities in a stocking-glove distribution
• In advanced cases, sensory ataxia caused by loss of joint position
sense may coexist with alcoholic cerebellar ataxia.
• Autonomic dysfunction due to vagal nerve or sympathetic nerve
involvement may be present.
• EPS studies show an axonal sensorimotor polyneuropathy. Needle
EMG shows active denervation with chronic re-innervation in distal
muscles
Entrapment Neuropathies (surgical requirement)
Mechanical distortion of the nerve fibers leads to focal demyelination or, in severe
cases, to wallerian degeneration.
EPS is diagnostic -short-segment conduction delay (i.e., focal slowing) or conduction
block across the site of entrapment
Common Sites
• Median Nerve in Carpal tunnel - Paresthesia, pain, thenar atrophy
• Ulnar nerve at the elbow - Clawing and sensory loss of 4th and 5th fingers
• Lateral cutaneous nerve of thigh at the inguinal ligament - Sensory loss in lateral
thigh
• Radial in the spiral groove - Wrist drop, sensory loss
• Peroneal Neuropathy - Foot drop, weak ankle eversion,sensory loss in dorsum of
foot
Hereditary Neuropathies
The inherited neuropathies can broadly be classified into two groups:
• Those in which the neuropathy is the sole or primary part of the
disease (e.g., Charcot-Marie-Tooth disease)
• Those in which the neuropathy is part of a more generalized
neurological or multisystem disorder.
• Charcot-Marie-Tooth Disease is the most common type.
HIV
1. Distal symmetric polyneuropathy
2. Inflammatory demyelinating polyneuropathy (including both GBS
and chronic inflammatory demyelinating polyneuropathy),
3. Multiple mononeuropathies (e.g., vasculitis, CMV-related),
4. Polyradiculopathy (usually CMV-related),
5. Autonomic neuropathy,
6. Sensory ganglionitis.
Cryptogenic (idiopathic) Sensory and Sensi-motor
Polyneuropathy
• Diagnosis of exclusion
• Onset is predominantly in the sixth and seventh decades
• Both large- and small-fiber loss
• Distal numbness, tingling, and often burning pain that begins in the
feet and may eventually involve the fingers and hands.
• Patients exhibit a distal sensory loss to pinprick, touch, and vibration
in the toes and feet, and occasionally in the fingers.
Investigations
Electrodiagnosis (EPS: Nerve conduction)
Confirms diagnosis of neuropathy
Helps in differentiating
• Neuropathy vs. myopathy
• Root/Plexus vs. Distal Nerve trunk involvement
• UMN vs. LMN weakness
• Axonal vs. Demyelinating
Nature, activity and prognosis
Anatomy ( which nerves are involved)
Characterization of disorder of neuromuscular junction
Identification of chronic partial denervation, fasciculations and myotonia especially
in muscles of normal bulk and strength
Evaluation of peripheral neuropathy, following
electrodiagnosis tests are performed

• Nerve conduction study of sensory and motor nerves

• Late responses (F-response and H-reflex)
• Needle electro-myography (EMG)
Using nerve conduction studies in polyneuropathy

= Low!

= Slow!

= Slow!
Laboratory Investigations

Blood-
• CBC,DBC,ESR,Urea,Electrolytes,LFT
• Blood Sugar
• Thyroid Function Tests
• Serum Protein electrophoresis
• Autoantibodies-ANA, Rhematoid Factor, Antigangliosisde antibodies,
Antineuronal Antibodies
• Vitamin B12 level and Folate Levels
• DNA analysis-Chromosome 17 duplication (HMSN1 and HMS1A)
CSF Analysis:

• GBS and CIDP (Chronic inflammatory demyelinating polyneuropathy),-

elevated cerebral spinal fluid (CSF) protein with no pleocytosis

• If cells are present, consider HIV infection, Lyme disease, sarcoidosis,

or lymphomatous or leukemic infiltration of nerve roots
• Urine: Bence-Jones Protein, Porphyrins
• Immunoelectrophoresis, or immunofixation -a monoclonal
gammopathy in amyloidosis.
• Antineutrophil cytoplasmic antibodies (ANCA), cryoglobulins, hepatitis
serology,
• Western blot for Lyme disease,
• HIV
• Imaging-Xr ay chest for sarcoidosis and malignancy
• Skeletal survey for multiple myeloma
• Screening for malignancy
• Autonomic Function tests
Nerve Biopsy

Primary indication - suspicion for amyloid neuropathy or vasculitis,

Leprosy, Sarcoidosis and leukodystrophies
The sural nerve is most commonly biopsied because it is a pure sensory
nerve.
Drugs causing Neuropathies
Axonal Demyelinating

Vincristine Lithium Amiodarone

Nitrous oxide Alfa interferon Chloroquine and
Colchicine (Probenecid, Col- Dapsone Hydroxychloroquine
Probenecid) Phenytoin
Isoniazid Cimetidine
Hydralazine Disulfiram
Metronidazole Chloroquine
Pyridoxine Ethambutol
Didanosine Amitriptyline
Good Luck