PERIPHERAL NEUROPATHIES Flashcards
DEFINITION
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
CLASSIFICATION
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
EPIDEMIOLOGY
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
ETIOLOGY
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
PATHOPHYSIOLOGY
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
CLINICAL PRESENTATION
sensory
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
CLINICAL PRESENTATION
motor and autonomic
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
EVALUATION OF PERIPHERAL
NEUROPATHIEs
history
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
EVALUATION OF PERIPHERAL
NEUROPATHIEs
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
PAIN SCALES
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GOALS OF THERAPY
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
NON-PHARMACOLOGICAL
Psychological support
Physiotherapy, exercise programs
Rehabilitation
Surgery in some kinds of mononeuropathies
IMMUNE-MEDIATED NEUROPATHIES
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.
THERAPEUTIC PLASMA EXCHANGE
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
AUTONOMIC NEUROPATHIES
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
AUTONOMIC NEUROPATHIES
Symptomatic therapy:
Orthostatic hypotension
Non-pharmacological
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
Symptomatic therapy (contd’):
Orthostatic hypotension
Pharmacological
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
Symptomatic therapy (contd’):
Bladder Dysfunction
Erectile Dysfunction
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
Symptomatic therapy (contd’):
anhidrosis
hyperhidrosis
gI
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
CARPAL TUNNEL SYNDROME
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etiology
presentaiton
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
carpal tunnel syndrome
Management
Non-pharmacologic
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
CARPAL TUNNEL SYNDROME
Management
Pharmacological
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
POSTHERPETIC NEURALGIA
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
POSTHERPETIC NEURALGIA
pain managemnt
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
SCIATICA
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
sciatica management
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
TRIGEMINAL NEURALGIA
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
TRIGEMINAL NEURALGIA Management
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)
ALTERNATIVES
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.
GENERAL PRINCIPLES
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
