PERIPHERAL NEUROPATHIES

Question 1

DEFINITION

Answer 1

A group of disorders (100+) that are caused
by damage of the nerves of the peripheral
nervous system

Mononeurpathy is damage to single nerve like carpal tunnel syndrome

nvolvement of multiple nerves called polyneuropathy is far more common. Damage typically begins in the nerves farthest from the central nervous system and progresses symmetrically
- Diabetic neuropathy

Question 2

CLASSIFICATION

Answer 2

According to type of affected nerves
 Motor, sensory, autonomic or mixed

According to number of affected nerves
 Mononeuropathy: affects one nerve
 Polyneuropathy: affecting many nerves
 Mononeuritis multiplex: damage to 2 or few separate nerves at the
same time (asymmetric)

According to pathology of the affected nerve
 Axonopathy: affecting the axons
 Myelinopathy: affecting the myelin
 Ganglionopathy: affecting the cell body
 Mixed

Question 3

EPIDEMIOLOGY

Answer 3

Prevalence
 2.5 – 3 % in general population
 ~ 2 million Canadians have experienced neuropathic pain
 8% in population older than 55 years
 ~ 50% Diabetics
 ~ 80 % with limb loss (phantom pain)
 Most common polyneuropathy  Diabetic Neuropathy
 Most common genetic polyneuropathy  Charcot-MarieTooth disease
 Most common mononeuropathy  Carpal Tunnel Syndrome

Question 4

ETIOLOGY

Answer 4

Mechanical compression, entrapment
 For mononeuropathies e.g. Carpal tunnel syndrome
Trauma
Diseases
 Diabetes, cancer, vasculitis, sarcoidosis, critical illness neuropathy
 Infections e.g. HIV, syphilis, leprosy, hepatitis C
 Nutrition deficiency e.g B12, B6

Immune-mediated neuronal destruction
 e.g. GBS, CIDP

Guillain-barre syndrome. This is a syndrome that associated with sudden demyelination of the neurons, the axons. The electrical impulses can be dissipated and the muscle will, like the neuron will be weak, the nerve transmission will be weak and result in sudden muscle weakness.

chronic inflammatory demyelinating polyneuropathy.

Genetics
 e.g. Fabry disease, Charcot-Marie-Tooth neuropathy
Drugs
 e.g. Isoniazid, cisplatin, vincristine, amiodarone, metronidazole, statins
Toxins
 e.g. Diphtheria toxin, tetanus, ethanol
Unknown

Question 5

PATHOPHYSIOLOGY

Answer 5

Wallerian degeneration: the black arrow arrow, this, this actually is the site of the injury. So actually this happens like neuron damage distal to the site of the injury. Simply like someone had a car accident and cut one of the nerves and their hands. So this results in damage to many of the nerves distal to the site of the injury over here. And if this nerve is associated with a muscle, this muscle usually gets atrophy. Smaller muscle. Also seen with mononeurpathies (liek carpal)

Segmental demyelination. This is, remember the Guillain-Barre syndrome, actually the myelination of the neurons. However, the axon will be retained, the axon function. And because the axon is still retain, its the prognosis of segmental demyelination pathology is way better than Valerian degeneration, axonal degeneration.

axonal degeneration with this is what we call a dying back phenomenon. This is, we see that e.g. in polyneuropathies and diabetic neuropathy. Neuropathy, which is the neuron slowly distally dies and keeps dying until whole neuron goes away. if the nerve dies less likely to come back. metabolic diseases and other conditions that lead to loss of nutrition

Question 6

CLINICAL PRESENTATION

sensory

Answer 6

 Sensory
 Sensory impairment/loss: touch, pain, temperature, vibration,
position (imbalance, ataxia)
 Paresthesia, pain
 Patients description: pins and needles, stabbing pain, tingling, electric
shocks, lightening pain, burning
 With or without stimulus
 Allodynia: painful sensation to non-painful stimulus
 Hyperesthesia: abnormal increased sensation to stimuli
 Hperalgesia: abnormal increased sensitivity to pain
 Causalgia: burning pain due to peripheral nerve injury

Question 7

CLINICAL PRESENTATION
motor and autonomic

Answer 7

Motor
 Muscle weakness, atrophy
 Muscle cramps, spasms and fasciculations
 Decreased or loss of tendon reflexes

Autonomic
 Due to alteration of sympathetic and/or parasympathetic nervous
system function
 Anhidrosis, heat intolerance, orthostatic hypotension, diarrhea,
constipation, incontinence, erectile dysfunction, cardiac arrhythmia,
gastroparesis, esophageal dysmotility
 Morbidity due to falls, orthostatic hypotension
 Severe dysautonomia
 Increased risk for cardiac arrhythmias and sudden cardiac death

Question 8

EVALUATION OF PERIPHERAL
NEUROPATHIEs

history

Answer 8

History
 Type of symptoms: motor, sensory, autonomic or mixed
 Distribution of weakness
 Nature of sensory involvement
 Temporal evolution
 Acute (days to 4 weeks)
 Subacute (4–8 weeks)
 Chronic (>8 weeks)
 Evidence of hereditary neuropathy
 Comorbidities e.g. DM
 Preceding events
 Drugs or toxins

Question 9

EVALUATION OF PERIPHERAL
NEUROPATHIEs

Answer 9

Labs
 CBC, SCr, BUN, electrolytes, LFTs, fasting sugar, HGb A1c, folic
acid, ESR, ANA (antinuclear antibodies), serum protein
electrophoresis, thyroid function tests

Electrophysiology
 Nerve conduction studies
 Needle EMG
Imaging
Nerve biopsies
Pain Assessment Scales

Question 10

PAIN SCALES

Answer 10

ok

Question 11

GOALS OF THERAPY

Answer 11

Treat the underlying condition
Symptom Control
Reduce the severity of symptoms e.g. pain
 Realistic goal 30-50% reduction
Balance symptom control with adverse
effects of medications

Question 12

NON-PHARMACOLOGICAL

Answer 12

 Psychological support
 Physiotherapy, exercise programs
 Rehabilitation
 Surgery in some kinds of mononeuropathies

Question 13

IMMUNE-MEDIATED NEUROPATHIES

Answer 13

Different efficacies in different conditions
Intravenous immunoglobulins (IVIG)
Therapeutic Plasma exchange (PLEX; TPE)
Immunomodulators
 Examples: corticosteroids, cyclophosphamide

neuropathy caused by an antibody against that neuron
. Immunosuppressive,plasmapheresis
take the patient blood, remove the antibodies, and put the patient blood back

those whose immune mediated neuropathies are able to immune conditions are given IVIG, they think it’s actually, it’s an immunomodulator. It’s actually accept the decoy like give the antibodies more antibodies and those antibodies a decoy like steer the attention. drug of choice for many of the neurological conditions and intravenous immunoglobulin, the work really wel
Like myasthenia gravis
response could be happened in two to three days,

Therapetuic plasma exchange is more invasive taking the blood out

Can’t do both together - immunoglobulins, they have a long half-life, like it’d be weeks. So at least you need to separate them by two weeks or four weeks actually, in order to like if you give a patient intravenous immunoglobulin, you can do TPE after the intravenous immunoglobulin.

Question 14

THERAPEUTIC PLASMA EXCHANGE

Answer 14

 An extracorporeal process where patient’s blood
components (generally plasma) are removed and the rest is
returned back to the patient with or without a replacement
fluid

TPE eemoves plasma

Plasma contains plasma proteins

Drugs in plasma (specifically those bound to plasma proteins) are removed with plasma

Drugs that are extensively distributed are hiding from TPE removal

Question 15

AUTONOMIC NEUROPATHIES

Answer 15

Treat the underlying condition
Immune-mediated  Immunomodulatory
therapies, IVIG, TPE
Diabetes  glucose control
Symptomatic therapy is essential in
untreatable autonomic neuropathies

Patient needs to drink good amount fluid. Actually patient with orthostatic hypotension, we drink like one or two cups of water and use the systolic blood pressure increases significantly.

patient wakes up, sit down on the bed and your legs makes sure the patient’s feet touch the ground slowly and then try to move slowly

Question 16

AUTONOMIC NEUROPATHIES
Symptomatic therapy:

Orthostatic hypotension
 Non-pharmacological

Answer 16

 Non-pharmacological
 Maintain fluid intake
 Slow cautious movement when changing body posture
 Sit or lie down if it happens
 Elevate head of the bed during sleep
 Compression stockings

Question 17

Symptomatic therapy (contd’):
Orthostatic hypotension
 Pharmacological

Answer 17

Pharmacological
 Fludrocortisone - mineralocorticoid
 Midodrine – beware of supine hypertension
 Sodium chloride tablets
 Other:
 Erythropoietin for those with anemia
 Desmopressin (DDAVP®) for those with nocturnal polyuria
 Beta blocqkers for tachycardia
 For postural orthostatic tachycardia syndrome (POTS
.
Midrodrine is alpha agonist which is vasoconstrictor
Usually it’s given three times a day while the patient is awake. And to try to avoid the last dose, like the evening dose, try to space it few hours before the patient sleeps
supine hypertension, and hypertension during sleep, is actually a bad thing. - long run cause of CV AE
Avoid bedtime dosing

Erythropoietin, it might help for patient with anemia, orthostatic hypotension

Desmopressin: Antidiuretic hormone , need to monitor sodium, it may go down

When the blood pressure goes down there’s reflex tachycardi

Question 18

Symptomatic therapy (contd’):
Bladder Dysfunction
 Erectile Dysfunction

Answer 18

 Bladder training, control of fluid intake
 Bladder catheterization
 Hyperactive bladder: Tolterodine and Oxybutynin
anticholinergics, make sure that they are not contraindicated with other patients co-morbidities

 Sildenafil, tadalafil, vardenafil

Question 19

Symptomatic therapy (contd’):
anhidrosis
hyperhidrosis
gI

Answer 19

Anhidrosis
 Avoid excessive heat for long period of time
 Hyperhidrosis
 Anticholinergics
Gastrointestinal
 Saliva replacement for hyposalivation
 Small frequent meals
 Decrease dietary fat
 Increase dietary fiber
 Metoclopramide, domperidone, erythromycin

Question 20

CARPAL TUNNEL SYNDROME
dfn
etiology
presentaiton

Answer 20

 Definition
 Collection of signs and symptoms due to pathology in the median
nerve of the wrist. The supply only the radial half of the ring finger, the middle finger, index finger, and the thumb
 Symptoms confined to median nerve distribution
 Etiology
 Mechanical compression of the median nerve within the carpal
tunnel
 Risk factors: obesity, repetitive motion, genetic
 Presentation
 Intermittent symptoms, associated with some activities
 Sensory: numbness, burning, tingling, pain
 Motor: weakness
 Autonomic: feeling cold/hot hands

Question 21

carpal tunnel syndrome
Management
 Non-pharmacologic

Answer 21

 Avoid/minimize exacerbating factors; activities with repeated
wrist movement
 Physical/occupational therapy e.g. splint, hand brace
 Surgical decompression for moderate to severe cases
 Greater response rate
 Considered if symptoms persist > 2-7 week with other therapies

Question 22

CARPAL TUNNEL SYNDROME
 Management
 Pharmacological

Answer 22

 Local corticosteroid injection – strong recommendation
 Methylprednisone 20-40 mg
 Evidence of long term improvement (up to 1 year)

 Short course oral corticosteroid therapy (10-30 days) – moderate
recommendation (symptom reduction at 2-8 weeks)

 No benefit compared to placebo: oral NSAIDs, vitamin B6,
diuretics, gabapentin

Question 23

POSTHERPETIC NEURALGIA

Answer 23

Following varicella zoster virus (VZV) infection, the
virus remains dormant for years in dorsal root
ganglia
 The virus can reactivate causing severe pain,
vesicular eruptions  Shingles
 Risk factors: advancing age (>50),
immunosuppression
 Pain can persist (≥1 month) after rash resolution 
postherpetic neuralgia
 Presentation:
Burning, stabbing, gnawing pain

Question 24

POSTHERPETIC NEURALGIA
pain managemnt

Answer 24

Effective
 Topical lidocaine*
 TCAs
 Gabapentin
 Combined with TCAs is more effective than monotherapy
 Pregabalin
 Opioids – Second-line

Possibly effective
 Topical capsaicin
 Epidural steroids
 Botulinum toxin A
*, first line for elderly

topical, it’s way better than, than, than oral drug because to avoid the systemic side effects. That’s why topical lidocaine by guidelines suggested the first-line agents for older adults. Otherwise, you can use the neuropathic pain medications, Gabapentin, tricyclic, antidepressant, Pregabalin

Tkaing pregab and gabapentn
No. Okay. Never do that because these are essentially the same drug, the accident, the same mechanism of action. Look at the chemical structure of those agents, pregabalin, gabapentin, I think it’s very close
they add extra side effects, as you mentioned. And, and really titrate one higher dose and don’t use both
Duplication of tx

Opioids could work but not preferred first

Question 25

SCIATICA

Answer 25

Definition
 Pain across the path of Sciatic nerve
Etiology
 Lumbar disc herniation or spinal stenosis
Clinical Features
 Unilateral leg pain, numbness and/or paresthesia
 Pain radiates to below knee to feet
 Leg pain > low back pain

Question 26

sciatica management

Answer 26

 Heat therapy
 Continue normal activity
 Exercise: best treatment for sciatica, it’s actually asking the patient to go exercise. That’s it. So continue normal activity and exercise, actually proven to chew actually reduce the sciatic pain.
 NSAIDs
 For short term pain control
 Opioids – short term for severe acute pain
 Steroids
 Epidural injection: short term pain control
 Systemic: possibly ineffective
 Gabapentin
 Muscle relaxants – weak recommendation
 Surgery
 Decompressive surgery

Question 27

TRIGEMINAL NEURALGIA

Answer 27

 Definition
 Severe, sharp, electric-like, brief unilateral pain across the path of 1
or more of the trigeminal nerves divisions
 Etiology
 Idiopathic: neurovascular compression
 Secondary: MS, compression by tumor
 Epidemiology
 Females > males
 More common ages >50

Question 28

TRIGEMINAL NEURALGIA Management

Answer 28

 First line
 Carbamazepine
 Oxcarbazepine
 Alternative or add-on to first line
 Lamotrigine
 Gabapentin/Pregabalin
 Valproic acid
 Baclofen
 Botulinum toxin A injection into painful area
 Phenytoin
 Surgical option: microvascular decompression (high success
rate)
 Avoid topical ophthalmic anesthesia (not effective)

Question 29

ALTERNATIVES

Answer 29

Gabapentin needs dose adjustment is required in renal failure and in elderly patients. Remember that for the rest of your life, please. Okay. It’s a num one of the number one causes of ER admissions for altered mental status

tricyclic antidepressants. They cause, the anti-cholinergic drugs and they’re very important to the tool to monitor the anti-cholinergic side effects.

Question 30

GENERAL PRINCIPLES

Answer 30

 Initiate low and go slow
 Monitor efficacy and tolerability
 Assess efficacy every 2-3 weeks
 Assess adverse reactions
 Target 30-50% pain relief
 Use pain assessment tool to monitor efficacy

 Allow adequate trial period of medication (~2-3
month)
 Titrate till response or adverse reactions
 If no response to certain agent
 Try different class from first line agents
 Try different agent from the same class
 Try combination from classes with synergistic efficacy
 Try to avoid combination TCA, tramadol, SNRI, SSRI