Peripheral Neuropathy

Carine Nyampinga, MD

1
Outlines
1. Neurologic exam
• Cranial nerves function,
• Motor function
• Reflexes
• Sensory functions
• Coordination and gait

2
Outlines (Cont’…)
2. Peripheral neuropathy
• Common peripheral nerve lesions
• Various etiologies of peripheral neuropathies
Inflammatory diseases
Infections
Metabolic disorders
Toxic injuries to the nerves
Cancer-associated neuropathy

3
1. Neurologic exam
• Helps to assess the function of the nervous system
• Mostly done on a patient with highly suspected nervous system disease
• Also in routine physical exam
• Should be systematic and complete:
Cerebrum
Brainstem
Cerebellum
Spinal cord
Peripheral nerves
Neuromuscular junction
Muscle activity
4
• While doing a neurologic exam, we assess
Mental status
Cranial nerves
Motor function
Sensory function
Reflexes
Coordination
Gait

5
Cranial nerves
• 12 pairs of cranial nerves
• Examination needs a relaxed patient
• Can be done in outpatient or inpatient settings
• Systematic and comparing both sides
• Onset and clinical history important

6
Cranial nerve Function Testing
CN I (olfactory nerve) Sense of smell Patient closes the eyes and identifies
a common odor (e.g: coffee)
CN II ( optic nerve) Mediates visual acuity and pupillary Hold your fingers in front of the
constriction patient and ask how many he can see,
test one eye at a time, move fingers to
assess visual fields
CN III (oculomotor nerve) Eye movements, pupillary constriction to light Do pupil light reflex. Look for droopy
(both CN II & CN III) eyelid (ptosis), diplopia, dilated &
fixed pupil not reacting to light
(mydriasis)
CN III (oculomotor), CN IV Control eye movement via extraocular muscles Patient looks at your finger and follow
(trochlear), CN VI (SR, IR, LR, MR inferior oblique, superior it without moving the head
( abducens) nerves oblique)
CN V (trigeminal nerve) 3 branches : Controls face and head sensory Touch the cornea with a wisp of
information,corneal reflex, motor innervation cotton (only done in patients in
of mastication muscles coma), check masseter and temporal
muscle when the patient is
masticating, open the jaw against
force, touch the face at the 3
differently innervated areas

7
Cranial nerve
CN VII (facial nerve)
CN VIII (vestibulocochlear nerve)
CN IX (glossopharyngeal) and CN X
(vagus) nerves
CN XI (accessory nerve) and CN XII
(hypoglossal)
Function Testing
Innervates the muscles of facial Ask the patient to close the eyebrows,
expression and taste on the anterior part smile, show teeth, puff out both
of the tongue cheeks
-Bell’s palsy (a lower motor neuron
(peripheral) CN VII lesion vs upper
motor neuron (central) CN VII nerve
deficit (e.g: stroke).
-Cochlear division sends information -Patient with eyes closed, rapid
about hearing, rubbing of your fingers close to the
-vestibular division transmits information ear and ask if he/she hear the sound
about balance and on which side
-Test for balance and gait
Control palate elevation, swallowing, -Ask the patient to open the mouth
taste on posterior tongue, phonation, gag and say “ah”→ look at the palate for
reflex any deviation of uvula, gag reflex (CN
IX & X)
Innervation of trapezius and SCM -Ask the patient to shrug shoulders against
muscles (CN XI) and tongue movement your resistance (trapezius) or turn their
(XII) head to each side against resistance (SCM),
ask patient to stick out the tongue
8
Motor function
• Muscle strength: test power against gravity and resistance, traces of
contaction or total loss of contraction (scale of strength /5)
• Pronator drift (upper motor neurone injury)
• Muscle tone: assess rigidity (abnormal)
• Muscle fasciculations (lower motor neurone injury)

9
Reflexes
• Tested on relaxed patients
• Use a patella hummer on corresponding tendons
• Compare reflexes symetrically
• Abnormalities correlate with different spinal levels
• Reflexes should not be exagerated
• Graded 0-4: > 2 (hyperactive reflexes), < 2 (hypoactive reflexes)
Hyperreflexia: upper motor neurone injury
Absent: lower motor neurone injury
10
 Patellar reflex (L2-L4) Biceps reflex (C5-C6)
Achilles tendon reflex (S1-S2)

Brachioradialis reflex (C5-C6) Triceps reflex (C6-C8) Cremasteric reflex (L1-L2)

11
Positive Babinski sign (upper Normal plantar reflex
motor neurone injury

12
Sensory function
• Vibration: put vibrating object on bony prominence
• Fine touch and pressure: can use a wisp of cotton in brush movement on
the skin
• Proprioception (Romberg sign): stable gait while standing and eye closed
• Pain and sharp touch: touch the skin with sharp pin (is the pain the same
in all parts?)
• Temperature: touch the skin with cold and hot objects
• Check for symetry
13
2. Peripheral Neuropathy
Peripheral nerves: Axons & myelin sheaths
• Somatic motor function
• Somatic sensory function
• Autonomic nerve fibers
• Myelinated zones (internodes) alternating with unmyelinated zones (nodes of
Ranvier)
• Neuropathies can be:
Axonal neuropathies: The axone is affected
Demyelinating neuropathies: Schwann cells and myelin sheaths affected
Neuronopathies: Destruction of cell bodies and axones
14
Axonal neuropathy
• Caused by insults that directly injure the axon
• Entire distal portion of an affected axon degenerates
• Secondary myelin loss
• Reduction in signal strength
• Regeneration takes place through axonal regrowth
• Subsequent remyelination of the distal axon

15
Demyelinating neuropathies
• Damage to Schwann cells or myelin
• Relative axonal sparing
• Slow nerve conduction velocity

Neuronopathies
• Destruction of cell bodies
• Progressive desctruction of axones

16
17
Peripheral Neuropathy (Cont’…)
Anatomic distribution may suggest specific causes
• Mononeuropathies:
Single nerve injury
Deficit in a single anatomical area
Secondary to: trauma, nerve compression, infection
• Polyneuropathies:
Symmetrical injury to multiple nerves
Deficits starts at periphery (feet and hands) and progress in ascending way:
stocking and glove
Many different causes in this category (diabetes, infections, etc…)
18
• Mononeuritis multiplex:
Multiple single nerves damaged
Nonsymmetrical haphazard pattern
Common in vasculitis-related neuropathies
• Polyradiculoneuropathies:
Nerve roots + peripheral nerves affected
Diffuse symmetric pattern

19
Clinic
• Somatic sensory nerves involvement
Numbness, tingling, pain, and gait abnormalities
Allodynia (pain on non painful stimuli)
Dysesthesia (electrical feeling on light touch)
• Somatic motor nerves involvement
Muscle weakness & atrophy
Fasciculations & yporeflexia
Foot drop & gait abnormalities
20
• Autonomic nerves involvement
Poor stomach emptying (gastroparesis)
Bladder dysfunction (incontinence, poor emptying)
Erectile dysfunction
Orthostatic hypotension

21
Causes of Peripheral Neuropathy

Inflammatory causes
1. Guillain-Barré Syndrome (Not always due to infections)
• Inflammation and demyelination
• Spinal nerve roots and peripheral nerves (polyradiculoneuropathy)
• Ascending paralysis & areflexia
• Risk of respiratory paralysis (diaphragm)
• Most probable immunologic reaction as cause
• Can be preceded/associated with some types of infections:
Campylobacter jejuni, EBV, CMV and HIV
22
Labs:
• Albuminocytologic dissociation in CSF
Treatment
• Supportive:
Cardiovascular monitoring
DVT prophylaxis
Intravenous immunoglobulin
Plasmapheresis

23
2. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
• T-cell mediated inflammatory immune response
• Targeting Schwann cell&axone junctional molecules
• Both motor and sensory abnormalities are common
• Associated with SLE and HIV infection
Treatment:
• Plasmapheresis, IV Ig, steroids & Immunosuppressive agents
3. Vasculitis-related neuropathy
• Often mononeuritis multiplex
• 1/3 of patients with vasculitis have patchy axonal degeneration

24
Infectious causes
1. Leprosy
• Lepromatous leprosy
 Destruction of Schwann cells and axons by Mycobacterium leprae
 Multiple raised skin nodules
 Symmetric polyneuropathy accentuated on distal cool extremities (feet, hands, face)
 Destruction of pain fibers → loss of sensation → auto mutilation of extremities
• Tuberculoid leprosy
 Cell-mediated immune response against the pathogen
 Patches of skin that are hypopigmented with loss of sensation
 Granulomatous inflammation → destruction (by the inflammation) of axons, Schwann cells

25
2. Lyme Disease
• Caused by the bacterium Borrelia burgdorferi
• In advanced disease: polyradiculoneuropathy, facial palsies
3. HIV infection
• Pathophysiology not fully understood
• Mononeuritis multiplex and demyelinating forms in early HIV stage
• Distal painful sensory neuropathy in advanced HIV stage
4. Varicella-Zoster Virus
• Latent viral infection in sensory ganglia and nerves
• Painful, vesicular skin eruption (shingles) following sensory dermatomes
• Neuronal death, inflammation, necrosis, hemorrhage
26
Metabolic & hormonal causes
1. Diabetes mellitus
• Most common cause of peripheral neuropathy
• Ascending distal symmetric sensory-motor polyneuropathy.
Injury mechanisms
• Glycation of proteins→ accumulation of advanced glycosylation end
products (AGEs) → activation of inflammatory signaling through the
receptor for AGE → oxidative stress on neurons

27
• Glucose in Schwann cells →Sorbitol and galactitol →low quantity of sorbitol
dehydrogenase to convert them into fructose →accumulation and osmotic
damage.
NB: Reaction above consuming too much NADPH with cells unable to produce
reduced glutathione (antioxidant against ROS) →Schwann cells injury
Clinic
• Distal symmetric polyneuropathy (numbness, loss of pain sensation,
paresthesias, …)
• Can be asymmetric if associated with microvascular diabetic disease
• Autonomic nervous system affected

28
2. Hypothyroidism
• Pathophysiology is not completely known, but
• Axonal degeneration with
Possible compression mononeuropathies
Symetric polyneuropathies

29
Nutritional causes
1. Vitamin B12 deficiency
• Spinal cord demyelination (damage on myelin basic protein)
• Subacute combined degeneration of the spinal cord (axonal damage)
• ↓proprioception (patients easily falling), hyperreflexia
• Treatment: treat the underlying cause, give B12 supplement
2. Vitamin B6 deficiency
• Often observed in patients on isoniazid ( anti TB agent)
3.Vitamin B1 deficiency
• Dry beriberi (polyneuropathy)
4. Vitamin E deficiency
30
• Antioxidant: deficiency may induce ROS related injury to nerves
Toxic causes
1. Heavy metals
• Arsenic: present in pesticides and insecticides
Can cause symetrical polyneuropathy
• Lead: Inhibit heme synthesis ( symmetrical polyneuropathy associated
with signs of anemia)
2. Medication-related neuropathies
• Chemotherapy agents (cisplatin, vinca alkaloids, taxanes, etc…)
• Metronidazole, nitrofurantoin, isoniazid, RTI for HIV, etc…
31
Cancer related causes
• Nerve compression or infiltration by tumors
• Radiotherapy, poor nutrition, chemotherapy
Paraneoplastic neuropathy
• Production of antibodies against surface proteins on cancer cells that also
damage normal neurons
E.g.:
• CD8+ cytotoxic T-cell damage on dorsal root ganglion cells
• Production of monoclonal immunoglobulins (by malignant B-cells) that
causes demyelinating peripheral neuropathy
32
Genetic defects
1. Charcot-Marie-Tooth (CMT) disease
• The most common disease in this category
• Manifests at adult age
• Group of autosomal dominant disorders with different genetic alterations
• Duplication of a region on chromosome 17 that includes the peripheral
myelin protein 22 (PMP22) gene
• Slowly progressive distal demyelinating motor and sensory neuropathy with
demyelination alternating with remyelination
• Foot deformity, hands deformity
33
Extremities deformity in Charcot-Marie-Tooth: Pes cavus (high
plantar arch), hammer toes, hands deformities
34
THANK YOU!

35