peripheral neuropathy · 2019. 5. 2. · “peripheral neuropathy” joseph s. lubeck, do poma...

“Peripheral Neuropathy”Joseph S. Lubeck, DO

POMA 111th Annual Clinical Assembly & Scientific SeminarMay 1-4, 2019

Peripheral NeuropathyJOSEPH LUBECK, DO

DisclosuresI have no relevant financial relationships or conflicts of interest to disclose.

#POMA19 #CHOOSEKNOWLEDGE

Case StudyoA 55 YO overweight man presents with numbness and burning in both feet. It began 6 months ago in his toes and has ascended to the midfoot. It is worse at night, less troublesome when weight bearing

oPMH – hypertension, hyperlipidemia

oMeds – Lisinopril, Atorvastatin, ASA

oExamo feet warm, good pulses

oMild loss of pinprick in the toes, feels a fully percussed tuning fork for 12s in each foot

o All reflexes present


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Case Study•What could it be?

•What diagnostic studies are necessary?

•What can we do for him?


Prevalence of Peripheral NeuropathyOverall prevalence = 2-4%

Increases to 8% in patients >55

In developed world, diabetes is most common cause, affecting ~ 50% of diabetics

In developing world, most common is leprosy


Axonal DegenerationPathology begins distally and spreads proximally

Most metabolic neuropathies

Usually begins as stocking glove sensory loss

Distal neuropathic pain

Loss of distal reflexes

Generally sensory > motor


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Segmental DemyelinationDemyelinating neuropathies

Focal◦ Carpal tunnel syndrome

◦ Peroneal neuropathy

Generalized◦ Guillain Barre Syndrome

◦ CIDP (chronic immune demyelinating polyneuropathy)

◦ Hereditary (Charcot Marie Tooth)


Clinical PresentationSensory

◦ Stocking > glove sensory loss

◦ Loss of vibratory sensation◦ Record perception (in seconds) in great toe of maximally percussed tuning fork

◦ Loss of proprioception ----→ imbalance without dizziness

◦ Distal loss of pinprick or temperature sensation◦ Record point of normal perceived pinprick sensation

◦ Pain◦ Burning, stinging, tightening


Motor – usually occur later than sensory symptoms◦ Distal weakness

◦ Atrophy◦ Usually seen first in intrinsic foot muscles


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Peripheral Neuropathy - EtiologiesMotor predominant

◦ Guillain-Barre

◦ CIDP

◦ Porphyria

◦ Hereditary neuropathies

◦ Toxic exposure (amiodorone, vincristine)


Peripheral Neuropathy - EtiologiesSensory Predominant

◦ Diabetes

◦ B12 deficiency

◦ HIV

◦ Amyloid

◦ Uremia

◦ Sarcoid

◦ Paraproteinemias – responsible for 10% of neuropathies originally classified as cryptogenic

◦ Toxic◦ Amiodorone, metronidazole, platinoids, phenytoin, antiretrovirals

◦ Statins – 1 additional case / 2200 patient years◦ However, diabetics treated with statins have lower incidence of neuropathy


Initial Laboratory Evaluation of Distal Sensory Neuropathy

Fasting glucose*

HbA1C

BMP

CBC

Sedimentation rate

Urinalysis

B12, Folate* (Methylmalonic Acid if B12



Lumbar Spinal Stenosis•Typically presents with ambulatory buttocks and lower extremity pain, diminished with lumbar flexion• Shopping cart or bicycle test to differentiate from vascular claudication

•Common presenting neurological findings• Numbness in feet

• Loss of Achilles reflexes


Electrodiagnostic EvaluationNerve conduction studies only measure velocity of the fastest conducting fibers

Axonal neuropathies◦ Nerve conduction velocity normal or minimally slowed, amplitudes mildly reduced

Demyelinating neuropathies◦ Nerve conduction velocities significantly slowed

◦ Conduction block

Small fiber neuropathies◦ Nerve conduction studies normal

◦ Report should indicate small fiber neuropathy not excluded if in differential


Nerve / Sites Lat. Amp.1-2 Dist. d Lat. Vel.

ms mV cm ms m/s

L MEDIAN - APB

Wrist 2.75 14.8 7

Elbow 6.55 14.1 22 3.80 57.9

Motor Conduction Studies


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Sensory Conduction StudiesNerve / Sites Lat. Peak Lat. Amp.1-2 Dist. Vel.

ms ms µV cm m/s

L MEDIAN - Dig II

Digit II 2.15 2.75 50.9 14 65.1


Role of Electodiagnostic TestingDifferentiates axonal from demyelinating neuropathies

May exclude mimics◦ Lumbar polyradiculopathy / spinal stenosis

◦ Multiple mononeuropathies

May differentiate worsening neuropathy from superimposed mononeuropathy (carpal tunnel syndrome in DM)

Little role for serial testing in established predictable neuropathies (distal sensory neuropathy in DM)


Diabetic Neuropathy


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Diabetic Neuropathy - TypesChronic sensory motor neuropathy – most common

Acute sensory neuropathy – aka insulin neuritis◦ Most commonly occurs acutely after period of glycemic instability

◦ Ketoacidosis or institution of insulin

◦ Intense burning pain

◦ Prognosis – usually resolves, up to 12 months

Mononeuropathies◦ Diseased nerves more susceptible to compression


Carpal Tunnel Syndrome in DiabetesCTS prevalence

◦ General population – 2-5%

◦ DM w/o neuropathy – 13%

◦ DM w/ neuropathy – 30%

In diabetic patient, with or without neuropathy, hand numbness is unlikely to be related to neuropathy, unless neuropathic symptoms in lower extremities have reached the knees.


Diabetic Neuropathy - TypesLumbar plexopathy – femoral neuropathy

◦ Typically presents with acute onset of pain in the thigh, rapid onset of weakness and atrophy of quadriceps

◦ Middle aged male, type 2 DM generally under reasonable control

◦ Beware of overinterpretation of mild age related MRI abnormalities

◦ Neuro eval mandatory before spine surgery in diabetics

Autonomic neuropathy◦ Unusual in isolation

◦ Orthostatic hypotension, gastroparesis, erectile dysfunction

◦ Painless MI


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Chronic Sensory Motor NeuropathyPainful Symptoms

◦ Burning

◦ Knife-like

◦ Electrical shocks

◦ Squeezing

◦ Constricting

◦ Throbbing

◦ Freezing

◦ Allodynia

Nonpainful Symptoms◦ Numbness

◦ Tingling

◦ Prickling

◦ Asleep

◦ “Dead”


Motor ManifestationsSignificant distal weakness uncommon

Atrophy of intrinsic foot muscles

Loss of Achilles reflexes


Risk Factors for DPNPOOR GLYCEMIC CONTROL

◦ Less association in type 2 DM

◦ Neuropathy may present with impaired glucose metabolism only

Male sex

Increased height

Tobacco use

Increased lipids◦ Lowering serum lipid levels with statins and fibrates reduces incidence of neuropathy in DM


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Metformin Induced B12 DeficiencyMay occur in up to 30% of patients on chronic metformin Rx

Due to malabsorption from ileum

?Screen for B12 deficiency annually in patients on metformin or administer 1000ug annually

CONSIDER B12 DEFICIENCY IN DIABETICS ON CHRONIC METFORMIN RX WHO DEVELOP NEW OR WORENING SYMPTOMS


Question #3Level I evidence exists for relief of neuropathic pain for all of the following except:

A. Lyrica

B. Cannabinoids

C. Neurontin

D. Cymbalta

E. Amitriptyline


Pharmacologic TreatmentAntiepileptics◦ Pregabalin (Lyrica)

◦ Gabapentin

◦ Valproate (Depakote)

◦ Phenytoin (Dilantin)

◦ Carbamazepine (Tegretol)

Antidepressants◦ SNRI

◦ Cymbalta, Effexor

◦ TCA◦ Amitriptyline, Nortriptyline

Anything



Tricyclic AntidepressantsAmitriptyline, Nortriptyline

Advantages ◦ Inexpensive, aid in sleep

Concerns◦ Weight gain in DM

◦ Caution in elderly, increased risk of confusion, falls

NNT for 50% pain relief 3.6

NNT is estimate of patients needed to treat for 1 positive response that CANNOT BE EXPLAINED BY PLACEBO EFFECT. Given robust placebo response in pain, probability of any positive response is likely 2X NNT.


SNRIDuloxetine (Cymbalta), venlafaxine (Effexor)

Advantages – may be effective with comorbid mood disturbance

Disadvantages – nausea, sedation, hyperhidrosis

NNT = 6


Gabapentin◦ NNT = 6

◦ Little dose response effect

Pregabalin (Lyrica)◦ NNT = 7

◦ Dose response effect, so probably lower NNT with 600mg/day.

Adverse reactions◦ Sedation

◦ Dizziness

◦ Fluid retention, weight gain


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Capsacain cream◦ NNT = 11

Tramadol◦ NNT = 5

High potency opiods◦ NNT = 4


So, what’s new?


Cannabanoids2 Cannabanoid receptors

◦ CB1 – found in CNS: responsible for “the high”

◦ CB2 – found primarily in immune system

Smoked marijuana contains over 460 distinct constituents

Dronabinol (Marinol) ◦ CB1 receptor agonist


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CannabanoidsSativex

◦ Approved in UK, Israel and EU for treatment of MS associated spasticity and central pain

◦ Oral mucosal spray◦ THC – CB1 receptor agonist

◦ Cannabadiol – CB2 receptor agonist

◦ Single study reduced allodynia


CannabanoidsCesamet

◦ Nabilone – CB1 agonist

◦ Available in Canada for chemotherapy induced nausea and vomiting

◦ 26 of 30 patients with DPN had 30% reduction in pain


Effect of delta-9-Tetrahydrocannabinol

on

Neuropathic Pain

Frederick J, Goldstein, PhD, FCP, Principal Investigator

Kathleen Galluzzi, DO

Madeleine Brown, MS

Jenayle Smith, LPN

Joseph Lubeck, DO

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Protocol

Weeks 1 & 2: Pt records Pain scores TID

Week 3: Pt records Pain scores TID

THC 5 mg po hs


THC 10 mg po hs


THC 15 mg po hs


THC 20 mg po hs

Wks1 &2ave.

End ofWk 6

PAIN SCORES

zero

Botulinum Toxin •Lancet Neurology, May 2016

•66 patients randomly assigned to Botox or placebo. Botox injected 1.5 – 2 cm apart over painful area, up to 60 sites / 300 U. Two injections 12 weeks apart

•Majority of patients in study with post-traumatic / post surgical pain or post-herpetic neuralgia

•Only 15% of treatment group with polyneuropathy

•NNT = 7.3


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Summary•50% of diabetics will eventually develop peripheral neuropathy• However, risk can be reduced with glycemic control and lipid lowering

•Hand numbness in diabetic neuropathy is uncommon unless lower extremity numbness has reached the knees• Think superimposed CTS

•In elderly diabetic or non-diabetic, consider lumbar spinal stenosis if symptoms occur with ambulation

•Therapy:• Tricyclics best but safety concerns

• Gabapentin, Lyrica, Cymbalta and Effexor probably equal, but not great

• Marijuana – if all else fails, go for it!


THANK YOU


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peripheral neuropathy · 2019. 5. 2. · “peripheral neuropathy” joseph s. lubeck, do poma...

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