Thread by @AaronLBerkowitz

#MedTwitter #MedStudentTwitter #NeuroTwitter! This morning on @CPSolvers #VMR we discussed an approach to peripheral polyneuropathy so here’s a #tweetorial to add to the #EndNeurophobia series

Link to whole series here:
twitter.com/i/events/12671…
@rabihmgeha @DxRxEdu @caseyalbin

Peripheral neuropathy can be classified as:

Mononeuropathy: single nerve affected

Polyneuropathy: nerves affected throughout body symmetrically

Mononeuropathy multiplex: multiple individual nerves affected, asymmetric

Check out @DxRxEdu video!
clinicalproblemsolving.com/peripheral-neu…

MonoN and polyN are most common.

Mononeuropathy multiplex=rare

MonoN most commonly compressive or traumatic (ulnar neurop @ elbow, median neurop @ wrist, peroneal neurop @ fibular head)

Rarely: tumor (neurofibroma), infiltration (amyloid, neurolymphomatosis

Mono multiplex: rare syndrome caused by relatively rarer diseases such as...Vasculitis, Hep C w/cryoglobulinemia, leprosy, HNPP (see schema)

PolyN = LONG Ddx including

Metabolic: diabetes, B12 deficiency, uremia
Toxic: Alcohol, chemotherapy, other meds
Inflammatory: GBS, CIDP
Infectious: HIV
Malignancy: paraprotein, paraneoplastic
Genetic: Charcot-Marie-Tooth, Fabry, Tangier

Polyneuropathy should be suspected when
symmetric symptoms in extremities
- sensory–numbness, paresthesias, pain, imbalance +/-
- motor–weakness +/-
- autonomic dysfunction

Exam shows loss of sensation +/- weakness with diminished or absent reflexes

Polyneuropathy can be classified by:
- Modality/ies affected: sensory, motor, sensorimotor, autonomic
- Fiber type: large fibers vs small fibers (pain/temperature, autonomic)
- Pathophysiology: axonal vs demyelinating

So after localizing a patient’s syndrome as a polyneuropathy we can localize even further by classifying it based on modality affected, fiber type, and pathophysiology.

How? Symptoms and signs:

Small fiber N: +pain w/diminished pain sensation but preserved sensation in other modalities, motor, & reflexes (these functions are transmitted by large fibers)
DDx
Metabolic: DM
Toxic: ETOH
Inflammatory: Sjogren, sarcoid, celiac
Infection: HIV
Genetic: HSAN, Fabry, amyloid

Large fiber generally more numbness, tingling, imbalance, +/- weakness, absent reflexes

*Axonal v demyelinating distinguished by pattern/evolution of neuropathy symptoms/signs*

Axonal=LENGTH-DEPENDENT= longest fibers affected first: feet will be affected initially, hands not involved until LE symptoms/signs rise to level of mid-shin.

If dz process affects axons, longest ones affected most as most dependent on axonal function (compared to short ones)

Demyelinating=NON-Length-dependent=UE &LE proximal and distal can be affected together @ onset, signs (e.g., reflex loss) more diffuse at presentation

If dz process affects myelin, all myelin affected = both short & long neurons

*This distinction is key because helps w/DDX*

Many axonal neuropathies=toxic/metabolic

Many demyelinating=inflammatory

(Though there are many exceptions to this general principle: GBS can be either (AIDP vs AMAN/AMSAN), CMT can be either depending on mutation...)

For chronic distal symmetric neuropathy evaluation per @AANMember guidelines, test for:
-DM: fasting glucose, glucose tolerance, or A1C
-B12 deficiency: B12 level +/- MMA
-Paraprotein: SPEP/IFE (rarer but can’t-miss cause of neuropathy)

n.neurology.org/content/72/2/1…

Paraprotein-related N complicated. See table here from amazon.com/gp/product/B09…

Classic review @NEJM nejm.org/doi/10.1056/NE…

@ContinuumAAN review: @ElieNaddaf3
@mauermannmd journals.lww.com/continuum/Abst…

If no etiology identified, expanded serologic workup can include:
- Rheumatologic testing
- HIV
- Heavy metals
- Paraneoplastic
- Genetic testing

This expanded work up guided by nerve conduction which can help determine if demyelinating (decreased velocity/increased distal latency) or axonal (decreased amplitude).

If concern for inflammatory cause (e.g., CIDP), LP to look for inflammation. Why would a PERIPHERAL condition show CSF inflammation? Because CIDP affects the roots which run through the CSF space. CIDP variants in table here from amazon.com/gp/product/B09…

Still no answer? Consider nerve biopsy!

Acute peripheral neuropathy is less common, and DDx is smaller:
- GBS
- Acute heavy metal poisoning
- Porphyria
- (or perhaps it’s not neuropathy: consider botulism (NMJ d/o), acute poliomyelitis/flaccid paralysis (anterior horn cell d/o)

Big picture:

Conditions of peripheral nerve
- Mono v poly v mononeuropathy multiplex
- PolyN:
--small v large fiber?
--axonal (length-dependent) v demyelinating (non-length dependent)

Initial w/u A1c, B12, SPEP/IFE
Expanded NCS, Rheum, infxn, heavy metal, inflamm, genetic, LP

Like these tweetorials? Here's the whole list so far. What should I cover next?
twitter.com/i/events/12671…

Want to learn more #neurology in a clear and simple way? Check out my book FREE through AccessMedicine through your school digital library, or order here:
amazon.com/Clinical-Neuro…

Thoughts/additions/corrections? @caseyalbin @Tracey1milligan @CrystalYeoMDPhD @NMatch2023 @a_charidimou @MedTweetorials @CPSolvers @DxRxEdu @rabihmgeha @emeltzermd @zach_london @LyellJ @MariaMjaleman @gabifpucci

Here's our case discussion from this AM
@Rafameed @MariaMjaleman @CPSolvers @DxRxEdu @rabihmgeha