Peripheral Neuropathy - New Diagnosis/Evaluation

VERSION: 1.2
CREATED: January 14, 2026
REVISED: January 14, 2026
STATUS: Revised per physician feedback

---

DIAGNOSIS: Peripheral Neuropathy - New Diagnosis/Evaluation

ICD-10: G62.9 (Polyneuropathy, unspecified); G60.0 (Hereditary motor and sensory neuropathy); G60.9 (Hereditary and idiopathic neuropathy, unspecified); G62.0 (Drug-induced polyneuropathy); G62.1 (Alcoholic polyneuropathy); G63 (Polyneuropathy in diseases classified elsewhere)

SYNONYMS: Peripheral neuropathy, polyneuropathy, neuropathy, peripheral nerve disease, neuropathic disorder, sensorimotor neuropathy, distal symmetric polyneuropathy, DSPN, axonal neuropathy, demyelinating neuropathy, nerve damage

SCOPE: Initial diagnostic workup and symptomatic management of suspected or newly diagnosed peripheral neuropathy. Covers etiologic evaluation, electrodiagnostic testing, pain management, and lifestyle modifications. For acute inflammatory neuropathies (GBS, CIDP), use dedicated templates. For diabetic neuropathy-specific management, this template applies but see also diabetes care protocols for glycemic optimization.

---

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════

1. LABORATORY WORKUP

1A. Essential/Core Labs

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
CBC with differential (CPT 85025)	STAT	STAT	ROUTINE	STAT	Anemia (B12), infection, malignancy screen	Normal
CMP (BMP + LFTs) (CPT 80053)	STAT	STAT	ROUTINE	STAT	Renal dysfunction (uremic neuropathy), hepatic disease, electrolytes	Normal
Fasting glucose (CPT 82947)	STAT	STAT	ROUTINE	STAT	Diabetes screening	<100 mg/dL
HbA1c (CPT 83036)	URGENT	ROUTINE	ROUTINE	URGENT	Diabetes/prediabetes (most common cause)	<5.7%
Vitamin B12 (CPT 82607)	URGENT	ROUTINE	ROUTINE	URGENT	B12 deficiency neuropathy	>300 pg/mL
Methylmalonic acid (MMA) (CPT 83921)	-	ROUTINE	ROUTINE	-	If B12 borderline (200-400); more sensitive	Normal
Folate (CPT 82746)	URGENT	ROUTINE	ROUTINE	URGENT	Folate deficiency	Normal
TSH (CPT 84443)	URGENT	ROUTINE	ROUTINE	URGENT	Hypothyroidism causes neuropathy	Normal (0.4-4.0 mIU/L)
ESR (CPT 85652)	URGENT	ROUTINE	ROUTINE	URGENT	Inflammatory/vasculitic process	Normal (<20 mm/hr)
CRP (CPT 86140)	URGENT	ROUTINE	ROUTINE	URGENT	Inflammatory marker	Normal

1B. Extended Workup (Second-line)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Oral glucose tolerance test (2-hour)	-	ROUTINE	ROUTINE	-	Detects IGT missed by FBG/HbA1c; high yield in idiopathic neuropathy (34-62% have abnormal OGTT)	<140 mg/dL at 2h
Serum protein electrophoresis (SPEP) with immunofixation (CPT 86334)	-	ROUTINE	ROUTINE	-	Monoclonal gammopathy (MGUS, myeloma)	No M-spike
24-hour urine protein electrophoresis (UPEP) (CPT 86335)	-	ROUTINE	ROUTINE	-	Light chain disease	No monoclonal protein
Free light chains (kappa/lambda)	-	ROUTINE	ROUTINE	-	AL amyloidosis, light chain deposition	Normal ratio (0.26-1.65)
Vitamin B1 (thiamine) (CPT 84425)	-	ROUTINE	ROUTINE	-	Alcoholism, malnutrition, bariatric surgery	Normal
Vitamin B6 (pyridoxine)	-	ROUTINE	ROUTINE	-	Deficiency OR toxicity (>200 mg/day) causes neuropathy	Normal (5-50 ng/mL)
Vitamin E	-	ROUTINE	ROUTINE	-	Malabsorption, cholestasis	Normal
Copper (CPT 82390)	-	ROUTINE	ROUTINE	-	Copper deficiency (zinc excess, bariatric surgery)	Normal
Zinc (CPT 84630)	-	ROUTINE	ROUTINE	-	Zinc excess suppresses copper	Normal
HIV antibody (CPT 87389)	-	ROUTINE	ROUTINE	-	HIV-associated distal sensory polyneuropathy	Negative
Hepatitis B surface antigen/antibody (CPT 80074)	-	ROUTINE	ROUTINE	-	Hepatitis B-associated PAN, cryoglobulinemia	Negative
Hepatitis C antibody (CPT 80074)	-	ROUTINE	ROUTINE	-	HCV-associated cryoglobulinemia, vasculitic neuropathy	Negative
Lyme serology (endemic areas)	-	ROUTINE	ROUTINE	-	Lyme neuroborreliosis	Negative
ANA (CPT 86235)	-	ROUTINE	ROUTINE	-	Connective tissue disease screen	Negative or low titer
RPR/VDRL (CPT 86592)	-	ROUTINE	ROUTINE	-	Syphilitic neuropathy	Negative
Rheumatoid factor	-	ROUTINE	ROUTINE	-	Rheumatoid vasculitis	Negative
Anti-SSA/SSB (Ro/La)	-	ROUTINE	ROUTINE	-	Sjögren syndrome (small fiber)	Negative
ACE level	-	ROUTINE	ROUTINE	-	Sarcoidosis	Normal

1C. Rare/Specialized (Refractory or Atypical)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Anti-MAG antibody (CPT 86255)	-	EXT	EXT	-	IgM paraproteinemic neuropathy	Negative
Anti-ganglioside antibodies (GM1, GD1a, GD1b, GQ1b) (CPT 86255)	-	EXT	EXT	-	If motor-predominant or acute onset (GBS variants)	Negative
Paraneoplastic panel (CPT 86255)	-	EXT	EXT	-	Subacute sensory neuronopathy, weight loss, smoking	Negative (Anti-Hu, CV2)
Cryoglobulins	-	EXT	EXT	-	Hepatitis C, autoimmune, vasculitic neuropathy	Negative
Anti-CASPR2, Anti-LGI1	-	EXT	EXT	-	Neuromyotonia, Morvan syndrome	Negative
Fat pad or sural nerve biopsy	-	EXT	EXT	-	Amyloidosis, vasculitis, CIDP variants	No amyloid or vasculitis
Genetic testing (CMT panel, TTR gene)	-	-	EXT	-	Hereditary neuropathy, familial amyloidosis	No pathogenic variant
Skin punch biopsy for IENFD (CPT 11104)	-	-	EXT	-	Small fiber neuropathy confirmation	>8.8 fibers/mm (varies by site/age)
Heavy metal panel (lead, arsenic, thallium, mercury)	-	EXT	EXT	-	Occupational/environmental exposure	Normal

---

2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Nerve conduction studies (NCS) (CPT 95907-95913) and EMG (CPT 95886)	-	ROUTINE	ROUTINE	-	Optimal 3-4 weeks after symptom onset (allows Wallerian degeneration to manifest); can be done earlier if acute weakness suspected	Pattern determines axonal vs demyelinating, distribution, severity	Pacemaker (relative); anticoagulation for needle EMG (relative)

2B. Extended

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI spine (cervical/lumbar) with and without contrast	URGENT	ROUTINE	ROUTINE	URGENT	If radiculopathy, myelopathy, or polyradiculopathy suspected	Nerve root enhancement (radiculopathy), cord signal change	GFR <30, pacemaker, gadolinium allergy
MRI lumbar plexus with contrast	-	ROUTINE	ROUTINE	-	Lumbosacral plexopathy, asymmetric proximal weakness	Plexus enhancement, mass lesion	Same as above
MRI brachial plexus with contrast	-	ROUTINE	ROUTINE	-	Brachial plexopathy, Parsonage-Turner syndrome	Plexus enhancement, denervation changes	Same as above
Autonomic function testing (QSART, tilt table, HRV)	-	-	ROUTINE	-	Autonomic symptoms (orthostasis, anhidrosis, GI dysmotility)	Abnormal sudomotor or cardiovagal function	None significant
Quantitative sensory testing (QST)	-	-	EXT	-	Small fiber neuropathy evaluation	Abnormal thermal thresholds	None significant
Chest X-ray (CPT 71046)	URGENT	ROUTINE	ROUTINE	URGENT	Lung cancer (paraneoplastic), sarcoidosis	Normal	Pregnancy (relative)
CT chest/abdomen/pelvis	-	ROUTINE	ROUTINE	-	Occult malignancy if paraneoplastic suspected	No mass	Contrast allergy, renal impairment

2C. Rare/Specialized

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
PET-CT (CPT 78816)	-	EXT	EXT	-	Occult malignancy, amyloidosis	No FDG-avid lesions	Pregnancy, uncontrolled diabetes
Nerve ultrasound	-	EXT	ROUTINE	-	CIDP (nerve enlargement), entrapment	Normal nerve caliber	None
MR neurography	-	EXT	EXT	-	Focal nerve pathology, plexopathy	Normal nerve signal/caliber	Same as MRI
Sural nerve biopsy (CPT 64795)	-	EXT	-	-	Vasculitic neuropathy, amyloidosis, CIDP	No vasculitis or amyloid deposits	Coagulopathy

LUMBAR PUNCTURE

Indication: Suspected inflammatory/demyelinating neuropathy (GBS, CIDP), infectious etiology, leptomeningeal disease, or atypical presentation

Timing: URGENT if GBS/CIDP suspected; ROUTINE for chronic neuropathy workup

Volume Required: 10-15 mL (standard diagnostic)

Study	ED	HOSP	OPD	Rationale	Target Finding
Opening pressure	URGENT	ROUTINE	ROUTINE	Rule out elevated ICP	10-20 cm H2O
Cell count (tubes 1 and 4)	URGENT	ROUTINE	ROUTINE	Inflammation, infection	WBC <5, RBC 0
Protein (CPT 84157)	URGENT	ROUTINE	ROUTINE	Albuminocytologic dissociation in GBS/CIDP	Normal 15-45 mg/dL; elevated in GBS/CIDP
Glucose with serum glucose (CPT 82945)	URGENT	ROUTINE	ROUTINE	Infection, carcinomatous meningitis	Normal (>60% serum)
Gram stain and culture	URGENT	ROUTINE	ROUTINE	Rule out infection	No organisms
Cytology (CPT 88104)	-	ROUTINE	ROUTINE	Leptomeningeal carcinomatosis	Negative
VDRL (CSF) (CPT 86592)	-	ROUTINE	ROUTINE	Neurosyphilis	Negative
Lyme PCR/antibody index	-	ROUTINE	ROUTINE	Endemic areas	Negative

Special Handling: Cytology requires rapid transport (<1 hour).

Contraindications: Elevated ICP without imaging, coagulopathy (INR >1.5, platelets <50K), skin infection at LP site

Note: CSF protein may be normal in first 1-2 weeks of GBS. Elevated protein with normal cell count ("albuminocytologic dissociation") is classic for GBS/CIDP.

---

3. TREATMENT

3A. Acute/Emergent

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Thiamine IV (if alcoholic or malnourished)	IV	-	500 mg :: IV :: TID :: 500 mg IV TID × 3 days, then 250 mg IV daily × 3-5 days, then oral	None significant	Anaphylaxis (rare)	STAT	STAT	-	STAT
Vitamin B12 IM (if deficient)	IM	-	1000 mcg :: IM :: daily :: 1000 mcg IM daily × 7 days, then weekly × 4 weeks, then monthly	Cobalt allergy	Reticulocyte count at 1 week; B12 level at 1-2 months	URGENT	URGENT	ROUTINE	URGENT
Glucose control optimization	-	-	7% :: - :: - :: Per diabetes protocol; target HbA1c <7%	Hypoglycemia risk	Glucose monitoring	STAT	STAT	ROUTINE	STAT

3B. Symptomatic Treatments - Neuropathic Pain

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Gabapentin	PO	Neuropathic pain (first-line)	300 mg :: PO :: qHS :: Start 300 mg qHS; increase by 300 mg every 1-3 days; target 900-1800 mg TID; max 3600 mg/day	Renal impairment (adjust dose per CrCl: CrCl 30-59: max 900-1400 mg/day; CrCl 15-29: max 600 mg/day; CrCl <15: max 300 mg/day)	Sedation, dizziness, peripheral edema; taper to discontinue	-	ROUTINE	ROUTINE	ROUTINE
Pregabalin	PO	Neuropathic pain (first-line)	75 mg :: PO :: BID :: Start 75 mg BID; increase to 150 mg BID after 1 week; max 300 mg BID	Renal impairment (adjust dose per CrCl); Class V controlled substance	Sedation, weight gain, peripheral edema	-	ROUTINE	ROUTINE	ROUTINE
Duloxetine	PO	Neuropathic pain (first-line, especially diabetic)	30 mg :: PO :: daily :: Start 30 mg daily × 1 week; increase to 60 mg daily; max 120 mg/day	Hepatic impairment; CrCl <30; concurrent MAOIs; uncontrolled narrow-angle glaucoma	Nausea (usually transient), BP; discontinuation syndrome (taper over 2+ weeks)	-	ROUTINE	ROUTINE	-
Venlafaxine XR	PO	Neuropathic pain	37.5-75 mg :: PO :: daily :: Start 37.5-75 mg daily; increase by 75 mg every 4-7 days; max 225 mg daily	Uncontrolled hypertension; concurrent MAOIs	BP monitoring; discontinuation syndrome	-	ROUTINE	ROUTINE	-
Amitriptyline	-	Neuropathic pain (second-line)	10-25 mg :: PO :: qHS :: Start 10-25 mg qHS; increase by 10-25 mg weekly; max 150 mg qHS	Cardiac conduction abnormality; recent MI; urinary retention; narrow-angle glaucoma; elderly (anticholinergic burden)	ECG if dose >100 mg/day; anticholinergic effects	-	ROUTINE	ROUTINE	-
Nortriptyline	-	Neuropathic pain (second-line)	10-25 mg :: PO :: qHS :: Start 10-25 mg qHS; increase by 10-25 mg weekly; max 150 mg qHS	Same as amitriptyline	Same; fewer anticholinergic effects than amitriptyline	-	ROUTINE	ROUTINE	-
Desipramine	PO	Neuropathic pain (second-line)	25 mg :: PO :: qHS :: Start 25 mg qHS; increase by 25 mg weekly; max 150 mg daily	Same as amitriptyline	Same; least anticholinergic TCA	-	ROUTINE	ROUTINE	-
Carbamazepine	PO	Trigeminal neuralgia, lancinating pain	100 mg :: PO :: BID :: Start 100 mg BID; increase by 200 mg/day every 3-7 days; max 1200 mg/day	AV block; bone marrow suppression; concurrent MAOIs	CBC, LFTs, sodium at baseline and periodically; HLA-B*1502 screening in at-risk populations	-	ROUTINE	ROUTINE	-
Oxcarbazepine	PO	Trigeminal neuralgia, lancinating pain	300 mg :: PO :: BID :: Start 300 mg BID; increase by 300 mg every 3 days; max 1200 mg BID	Hypersensitivity to carbamazepine	Sodium (hyponatremia risk); HLA-B*1502 screening	-	ROUTINE	ROUTINE	-
Capsaicin cream 0.025-0.075%	-	Localized neuropathic pain	N/A :: - :: TID-QID :: Apply TID-QID to affected area; takes 2-4 weeks for effect	Open wounds; avoid eyes/mucous membranes	Initial burning (decreases with continued use); wash hands after application	-	-	ROUTINE	-
Capsaicin 8% patch (Qutenza)	Transdermal	Localized neuropathic pain (refractory)	N/A :: Transdermal :: q3mo :: Applied by healthcare provider for 30-60 minutes; may repeat every 3 months	Same as above	Must be applied in clinic; pretreat area with topical lidocaine	-	-	ROUTINE	-
Lidocaine 5% patch	Transdermal	Localized neuropathic pain	N/A :: Transdermal :: per protocol :: Apply 1-3 patches to painful area for 12 hours on, 12 hours off	Severe hepatic impairment; application to broken skin	Minimal systemic absorption; local irritation	-	ROUTINE	ROUTINE	ROUTINE
Tramadol	PO	Moderate neuropathic pain (adjunct)	50 mg :: PO :: q6h :: Start 50 mg q6h PRN; may use ER 100 mg daily; max 400 mg/day	Seizure disorder; concurrent MAOIs; concurrent SSRIs (serotonin syndrome)	Serotonin syndrome; seizures; dependence (Schedule IV)	-	ROUTINE	ROUTINE	-
Tapentadol ER	PO	Moderate-severe neuropathic pain	50 mg :: PO :: BID :: Start 50 mg BID; increase by 50 mg BID every 3 days; max 250 mg BID	Same as tramadol	Same; Schedule II	-	-	ROUTINE	-
Morphine ER	-	Severe refractory pain	15 mg :: - :: q12h :: Start 15 mg q12h; titrate every 1-2 days; no max (titrate to effect)	Respiratory depression; paralytic ileus; concurrent MAOIs	Sedation, constipation, respiratory status; naloxone available	-	ROUTINE	ROUTINE	ROUTINE
Oxycodone ER	PO	Severe refractory pain	10 mg :: PO :: q12h :: Start 10 mg q12h; titrate every 1-2 days	Same as morphine	Same; Schedule II	-	ROUTINE	ROUTINE	ROUTINE
Methadone	PO	Severe refractory neuropathic pain	2.5-5 mg :: PO :: TID :: Start 2.5-5 mg TID; titrate slowly (long half-life); specialist management	QT prolongation; concurrent QT-prolonging drugs	ECG at baseline and with dose changes; QTc monitoring	-	-	EXT	-

Combination Therapy Note: For refractory neuropathic pain, combining agents from different classes (e.g., gabapentinoid + SNRI, or gabapentinoid + TCA) is often more effective than maximizing monotherapy. Avoid combining TCAs with SNRIs (serotonin syndrome risk).

3C. Symptomatic Treatments - Other Symptoms

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Midodrine	-	Orthostatic hypotension	2.5 mg :: - :: TID :: Start 2.5 mg TID (upon awakening, midday, mid-afternoon); increase by 2.5 mg every 1-2 weeks; max 10 mg TID; do NOT take within 4 hours of bedtime	Severe heart disease; urinary retention; pheochromocytoma	Supine hypertension (avoid lying flat within 4 hours); urinary retention	-	ROUTINE	ROUTINE	ROUTINE
Fludrocortisone	PO	Orthostatic hypotension	0.1 mg :: PO :: daily :: Start 0.1 mg daily; increase by 0.1 mg every 1-2 weeks; max 0.3 mg daily	CHF; hypertension	Potassium, BP, edema; hypokalemia; supine hypertension	-	ROUTINE	ROUTINE	ROUTINE
Droxidopa (Northera)	PO	Neurogenic orthostatic hypotension	100 mg :: PO :: TID :: Start 100 mg TID; increase by 100 mg TID every 24-48 hours; max 600 mg TID	Concurrent ergot alkaloids; hypersensitivity	Supine hypertension (do not take within 3 hours of bedtime); use caution with MAOIs and triptans (hypertensive risk)	-	-	ROUTINE	-
Pyridostigmine	PO	Orthostatic hypotension (off-label)	30-60 mg :: PO :: TID :: 30-60 mg TID	Mechanical GI/GU obstruction; asthma (relative)	Cholinergic effects; less supine hypertension than midodrine	-	-	ROUTINE	-
Polyethylene glycol 3350	-	Constipation (autonomic)	17 g :: - :: daily :: 17 g daily; adjust to effect	Bowel obstruction	Electrolytes with prolonged use	-	ROUTINE	ROUTINE	-
Docusate sodium	PO	Constipation	100 mg :: PO :: BID :: 100 mg BID; max 500 mg/day	Intestinal obstruction	Minimal efficacy alone	-	ROUTINE	ROUTINE	-
Senna	PO	Constipation	8.6-17.2 mg :: PO :: qHS :: 8.6-17.2 mg qHS; max 34.4 mg/day	Intestinal obstruction; acute abdominal pain	Cramping	-	ROUTINE	ROUTINE	-
Metoclopramide	PO	Gastroparesis	5-10 mg :: PO :: qHS :: 5-10 mg 30 minutes before meals and qHS; max 40 mg/day; limit to 12 weeks (FDA black box: tardive dyskinesia risk)	Bowel obstruction; Parkinson disease; tardive dyskinesia history	Tardive dyskinesia (limit duration); QT prolongation	-	ROUTINE	ROUTINE	-
Domperidone	PO	Gastroparesis (if metoclopramide contraindicated)	10 mg :: PO :: TID :: 10 mg TID before meals; max 30 mg/day	QT prolongation; concurrent QT-prolonging drugs	ECG at baseline; not FDA-approved (requires special access)	-	-	EXT	-
Oxybutynin IR	PO	Bladder urgency (anticholinergic caution in neuropathy)	5 mg :: PO :: BID :: Start 5 mg BID-TID; max 5 mg QID	Urinary retention; narrow-angle glaucoma	Dry mouth, constipation, cognitive impairment	-	ROUTINE	ROUTINE	-
Mirabegron	PO	Bladder urgency	25 mg :: PO :: daily :: Start 25 mg daily; may increase to 50 mg daily	Uncontrolled hypertension	BP monitoring; fewer anticholinergic effects	-	-	ROUTINE	-
Tamsulosin	PO	Urinary retention	0.4 mg :: PO :: daily :: 0.4 mg daily 30 minutes after same meal each day	Severe sulfonamide allergy	Orthostatic hypotension (caution if already orthostatic)	-	ROUTINE	ROUTINE	-
Sildenafil	PO	Erectile dysfunction	50 mg :: PO :: - :: 50 mg 30-60 min before activity; may adjust 25-100 mg; max 100 mg/day	Concurrent nitrates; recent MI/stroke	Hypotension; priapism	-	-	ROUTINE	-
Tadalafil	PO	Erectile dysfunction	10 mg :: PO :: once daily :: 10 mg before activity (max once daily) OR 2.5-5 mg daily	Same as sildenafil	Same	-	-	ROUTINE	-
Hydroxyzine	PO	Anxiety, pruritus	25-50 mg :: PO :: TID :: 25-50 mg TID-QID PRN; max 400 mg/day	QT prolongation (high doses)	Sedation; anticholinergic effects	-	ROUTINE	ROUTINE	-
Buspirone	PO	Generalized anxiety	5 mg :: PO :: TID :: Start 5 mg TID; increase by 5 mg every 2-3 days; max 60 mg/day	Concurrent MAOIs	Takes 2-4 weeks for effect; no dependence	-	-	ROUTINE	-
Trazodone	PO	Insomnia with chronic pain	25-50 mg :: PO :: qHS :: Start 25-50 mg qHS; increase to 100-150 mg; max 200 mg qHS	Concurrent MAOIs; QT prolongation	QTc; priapism (rare); sedation	-	ROUTINE	ROUTINE	-
Melatonin	PO	Insomnia (adjunct)	3-5 mg :: PO :: qHS :: 3-5 mg qHS 30 minutes before bed	None significant	Generally well-tolerated	-	ROUTINE	ROUTINE	-

Note for ICU: Midodrine and fludrocortisone marked ROUTINE in ICU for continuation of home regimen in admitted patients; typically not initiated in ICU setting.

3D. Disease-Specific Treatments

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
IVIG	PO	CIDP, MMN, GBS	2 g/kg :: PO :: - :: 2 g/kg divided over 2-5 days (induction); maintenance 0.4-1 g/kg every 2-4 weeks	-	IgA deficiency (use IgA-depleted product); renal failure; thrombosis risk	Renal function, headache, thrombosis, infusion reactions	-	URGENT	ROUTINE	URGENT
Plasma exchange (PLEX)	-	CIDP, GBS	N/A :: - :: once :: 5-7 exchanges over 10-14 days	-	Hemodynamic instability, sepsis	BP, electrolytes, coags, fibrinogen	-	URGENT	-	URGENT
Prednisone	PO	CIDP, vasculitic neuropathy	1 mg/kg :: PO :: - :: 1 mg/kg/day (max 80 mg) × 4-6 weeks; taper over 3-6 months	-	Active untreated infection, uncontrolled diabetes, psychosis	Glucose, BP, mood, bone density with prolonged use	-	ROUTINE	ROUTINE	-
Rituximab (CPT 96365)	IV	Anti-MAG neuropathy, vasculitic neuropathy, refractory CIDP	375 mg :: IV :: - :: 375 mg/m² IV weekly × 4 weeks OR 1000 mg IV × 2 doses 14 days apart	-	Active hepatitis B; active infection	Hepatitis B serology, infusion reactions, infection monitoring	-	EXT	EXT	-
Azathioprine	PO	Steroid-sparing for CIDP, vasculitis	50 mg :: PO :: daily :: Start 50 mg daily; increase to 2-3 mg/kg/day over weeks	-	TPMT deficiency (test before starting); pregnancy	CBC weekly × 1 month, then q2-4 weeks; LFTs monthly; TPMT genotype	-	EXT	ROUTINE	-
Mycophenolate mofetil	PO	Steroid-sparing for CIDP, vasculitis	500 mg :: PO :: BID :: 500 mg BID × 2 weeks, then 1000 mg BID	-	Pregnancy (teratogenic); concurrent azathioprine	CBC q2 weeks × 3 months, then monthly; GI upset	-	EXT	ROUTINE	-
Cyclophosphamide	IV	Vasculitic neuropathy (severe)	1-2 mg/kg :: IV :: monthly :: 1-2 mg/kg/day PO OR 500-1000 mg/m² IV monthly × 6 months	-	Pregnancy; bone marrow suppression; active infection	CBC weekly; urinalysis (hemorrhagic cystitis); cumulative dose limit	-	EXT	EXT	-
Tafamidis (Vyndamax/Vyndaqel)	PO	Hereditary transthyretin (hATTR) amyloidosis with polyneuropathy	61 mg :: PO :: daily :: 61 mg (Vyndamax) or 80 mg (Vyndaqel) daily	-	None absolute	LFTs; clinical response	-	-	ROUTINE	-
Patisiran (Onpattro)	IV	hATTR amyloidosis with polyneuropathy	0.3 mg/kg :: IV :: - :: 0.3 mg/kg IV every 3 weeks	-	None absolute	Vitamin A supplementation at RDA required (patisiran reduces serum vitamin A via TTR reduction); infusion reactions	-	-	ROUTINE	-
Inotersen (Tegsedi)	SC	hATTR amyloidosis with polyneuropathy	284 mg :: SC :: once :: 284 mg SC once weekly	-	Platelet count <100,000; prior glomerulonephritis from inotersen	Platelet count weekly throughout treatment (more frequent if <75 × 10⁹/L); continue monitoring 8 weeks post-discontinuation; renal function q2 weeks; REMS program required	-	-	ROUTINE	-

---

4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation	ED	HOSP	OPD	ICU	Indication
Neuromuscular neurology referral	URGENT	URGENT	ROUTINE	URGENT	All new neuropathy diagnoses for etiology workup and management
Electrodiagnostic medicine/EMG referral	-	ROUTINE	ROUTINE	-	NCS/EMG for characterization (axonal vs demyelinating, pattern)
Physical therapy consult for balance and gait	-	ROUTINE	ROUTINE	ROUTINE	Gait instability, weakness, falls prevention
Occupational therapy consult for hand function	-	ROUTINE	ROUTINE	-	Fine motor impairment, ADL difficulty
Podiatry referral	-	ROUTINE	ROUTINE	-	Diabetic neuropathy, foot care education, orthotics, wound prevention
Endocrinology referral	-	ROUTINE	ROUTINE	-	Diabetes management optimization if HbA1c not at goal
Pain management/Anesthesia referral	-	-	ROUTINE	-	Refractory neuropathic pain, spinal cord stimulator evaluation
Rheumatology referral	-	ROUTINE	ROUTINE	-	Suspected vasculitic neuropathy, connective tissue disease
Hematology/Oncology referral	-	URGENT	ROUTINE	-	Paraproteinemic neuropathy, suspected malignancy, amyloidosis
Genetic counseling referral	-	-	ROUTINE	-	Suspected hereditary neuropathy (CMT, hATTR), family history
Psychiatry/Psychology referral	-	ROUTINE	ROUTINE	-	Chronic pain management, depression, anxiety
Social work consult	-	ROUTINE	ROUTINE	-	Disability resources, insurance navigation, DME assistance
Wound care referral	-	URGENT	ROUTINE	URGENT	Diabetic foot ulcers, non-healing wounds
Orthotics/Prosthetics	-	-	ROUTINE	-	AFOs for foot drop, custom orthotics
Nutrition/Dietitian referral	-	ROUTINE	ROUTINE	-	Alcoholic neuropathy, nutritional deficiencies, bariatric surgery patients
Addiction medicine/Psychiatry	-	ROUTINE	ROUTINE	-	Alcohol use disorder, opioid risk mitigation

4B. Patient Instructions

Recommendation	ED	HOSP	OPD
Return to ED if sudden severe weakness, difficulty breathing, or rapid symptom progression	✓	✓	✓
Inspect feet daily for cuts, blisters, or wounds (use mirror for soles)	✓	✓	✓
Wear well-fitting, protective footwear at all times (never barefoot)	✓	✓	✓
Test bath water temperature with elbow or thermometer before entering (avoid burns)	-	✓	✓
Avoid prolonged hot or cold exposure to affected extremities (impaired sensation increases injury risk)	-	✓	✓
Use night lights and handrails to prevent falls	-	✓	✓
Report new numbness, weakness, or autonomic symptoms (dizziness, bladder changes)	✓	✓	✓
Keep pain medication diary to track effectiveness and side effects	-	✓	✓
Do not stop gabapentin/pregabalin abruptly - taper under medical guidance	-	✓	✓
Neuropathic pain medications take 2-4 weeks to reach full effect	-	✓	✓
Avoid alcohol (worsens neuropathy, interacts with pain medications)	✓	✓	✓
Rise slowly from sitting/lying position if orthostatic hypotension present	-	✓	✓
Increase salt and fluid intake if orthostatic (unless contraindicated by cardiac/renal disease)	-	✓	✓
Wear compression stockings for orthostatic hypotension	-	✓	✓
Do not drive until cleared if significant sensory loss or weakness affects pedal control	✓	✓	✓
B12 injections: if self-administering, use proper technique and rotate injection sites	-	✓	✓

4C. Lifestyle & Prevention

Recommendation	ED	HOSP	OPD
Strict glycemic control (HbA1c <7% or individualized target) - most important modifiable factor	✓	✓	✓
Complete alcohol cessation (alcoholic neuropathy is reversible if early)	✓	✓	✓
Smoking cessation (microvascular disease worsens neuropathy)	✓	✓	✓
Regular exercise as tolerated (improves circulation, glycemic control, reduces pain)	-	✓	✓
Balance exercises and strength training (PT-guided) to prevent falls	-	✓	✓
Pool therapy/aquatic exercise (reduces fall risk while exercising)	-	-	✓
Vitamin B12 supplementation if vegan/vegetarian or on metformin	-	✓	✓
Review medications for neurotoxic agents (metronidazole, nitrofurantoin, chemotherapy, amiodarone, statins)	-	✓	✓
Avoid excessive vitamin B6 supplementation (>100 mg/day can cause neuropathy)	-	✓	✓
Blood pressure control (target <130/80 for diabetic patients)	-	✓	✓
Weight loss if obese (reduces pressure on nerves, improves metabolic syndrome)	-	-	✓
Fall prevention: remove throw rugs, ensure adequate lighting, use assistive devices	-	✓	✓
Annual foot exams by podiatry or primary care for diabetic patients	-	✓	✓
Regular ophthalmology exams if diabetic (concurrent retinopathy common)	-	-	✓

---

═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Diabetic polyneuropathy	Symmetric, length-dependent, sensory-predominant, feet before hands, burning/tingling	HbA1c >6.5% (or 2-hour OGTT >200); NCS shows axonal sensorimotor polyneuropathy
Alcoholic neuropathy	History of chronic alcohol use, nutritional deficiency, burning feet	History, thiamine level, liver function tests
Vitamin B12 deficiency	Subacute combined degeneration, myelopathy features (ataxia, Romberg), macrocytic anemia	B12 <200 pg/mL or MMA elevated; may have cord signal changes on MRI
Chronic inflammatory demyelinating polyneuropathy (CIDP)	Progressive or relapsing weakness >8 weeks, proximal and distal, areflexia	NCS shows demyelination; CSF protein elevated; nerve enlargement on ultrasound
Guillain-Barré syndrome (GBS)	Acute ascending weakness <4 weeks, areflexia, post-infectious	NCS early may be normal then demyelinating; CSF albuminocytologic dissociation
Hereditary neuropathy (CMT)	Family history, pes cavus, hammertoes, childhood onset, slowly progressive	Genetic testing; NCS shows uniform slowing in CMT1
Hereditary transthyretin amyloidosis (hATTR)	Autonomic dysfunction, carpal tunnel, cardiac involvement, family history	TTR gene mutation; tissue biopsy with amyloid
Monoclonal gammopathy-associated neuropathy	Distal sensory-predominant, ataxia (IgM anti-MAG), older patient	SPEP/UPEP; anti-MAG antibody; may need bone marrow biopsy
Vasculitic neuropathy	Mononeuritis multiplex pattern (asymmetric, stepwise), pain, systemic symptoms	Elevated ESR/CRP; ANCA; nerve/muscle biopsy shows necrotizing vasculitis
Paraneoplastic sensory neuronopathy	Subacute onset, asymmetric, dorsal root ganglia involvement, weight loss	Anti-Hu antibody; CT chest for small cell lung cancer
Radiculopathy	Dermatomal distribution, unilateral, neck/back pain, preserved reflexes outside affected root	MRI spine; NCS/EMG shows radicular pattern
Lumbosacral plexopathy (diabetic amyotrophy)	Acute/subacute proximal weakness, thigh pain, unilateral then contralateral	NCS/EMG; MRI lumbosacral plexus; diagnosis of exclusion
Small fiber neuropathy	Pain/autonomic symptoms with normal NCS, preserved reflexes	Skin biopsy for IENFD; autonomic testing
Charcot-Marie-Tooth disease	Childhood/adolescent onset, pes cavus, distal atrophy, family history	Genetic testing (PMP22 duplication most common)
Chemotherapy-induced peripheral neuropathy (CIPN)	Temporal relationship to neurotoxic chemotherapy (platinum, taxanes, vincristine)	History; dose-dependent; may improve after discontinuation
HIV-associated distal sensory polyneuropathy	HIV+ patient, distal symmetric painful neuropathy	HIV testing; CD4 count
Lyme disease	Endemic area, prior tick bite, radiculopathy, cranial neuropathy, polyradiculopathy	Lyme serology; may need CSF analysis
Sarcoidosis	Multifocal neuropathy, cranial neuropathy (especially VII), pulmonary symptoms	ACE level; chest imaging; biopsy (non-caseating granulomas)
Leprosy	Endemic areas, skin lesions, enlarged palpable nerves, anesthetic patches	Skin smear/biopsy for AFB; nerve biopsy

---

6. MONITORING PARAMETERS

Venue column indicates where monitoring is typically ordered/initiated. Most monitoring continues in outpatient setting.

Parameter	ED	HOSP	OPD	ICU	Frequency	Target/Threshold	Action if Abnormal
HbA1c	-	ROUTINE	ROUTINE	-	Every 3 months until stable, then every 6 months	<7% (individualize)	Intensify glycemic therapy; endocrinology referral
Vitamin B12	-	ROUTINE	ROUTINE	-	1-2 months after starting supplementation, then annually	>300 pg/mL	Continue supplementation; rule out malabsorption
Pain scores (0-10 NRS)	ROUTINE	ROUTINE	ROUTINE	ROUTINE	Each visit	Reduction ≥30-50% from baseline	Titrate medications; consider adjuncts or referral
Foot exam	-	ROUTINE	ROUTINE	-	Every visit; comprehensive annually	No wounds, calluses, deformity	Podiatry referral; wound care
Blood pressure (supine and standing)	URGENT	ROUTINE	ROUTINE	ROUTINE	Each visit if orthostatic symptoms	Orthostatic drop <20 mmHg systolic	Adjust orthostatic hypotension medications; consider compression
Gait and fall risk assessment	-	ROUTINE	ROUTINE	-	Each visit	No falls, stable gait	PT referral; assistive devices; home safety evaluation
Creatinine clearance	STAT	ROUTINE	ROUTINE	STAT	Baseline; with renal disease, elderly, or gabapentinoid use; with dose changes	CrCl >60 for full gabapentinoid dosing	Adjust gabapentin: CrCl 30-59 max 900-1400 mg/day; CrCl 15-29 max 600 mg/day; CrCl <15 max 300 mg/day
LFTs (if on high-dose gabapentinoid)	-	ROUTINE	ROUTINE	-	Baseline, then annually	Normal	Dose adjustment if hepatic impairment
Renal function	-	ROUTINE	ROUTINE	-	Every 6-12 months	Stable	Adjust renally cleared medications (gabapentin, pregabalin)
CBC (if on immunotherapy)	-	ROUTINE	ROUTINE	ROUTINE	Per medication protocol	Normal	Adjust immunosuppression dose; infection evaluation
NCS/EMG follow-up	-	ROUTINE	ROUTINE	-	6-12 months if treatment initiated; PRN for symptom change	Stable or improved	If progressive despite treatment, reconsider diagnosis or escalate therapy
ECG (if on TCAs)	URGENT	ROUTINE	ROUTINE	URGENT	Baseline; with dose increases >100 mg	QTc <500 ms; no heart block	Reduce dose or switch medication
Weight (if on gabapentinoid)	-	ROUTINE	ROUTINE	-	Each visit	Stable or controlled	Diet/exercise counseling; consider switch
Depression/anxiety screening (PHQ-9, GAD-7)	-	ROUTINE	ROUTINE	-	Annually or with symptom concern	Not clinically significant	Psychiatry referral; pharmacotherapy
Respiratory function (if GBS/CIDP suspected)	STAT	STAT	-	STAT	Q4h if concern; FVC and NIF	FVC >20 mL/kg, NIF <-30 cm H2O	ICU transfer if FVC <20 or NIF >-30; intubation if declining

---

7. DISPOSITION CRITERIA

Disposition	Criteria
Discharge home	Stable symptoms; chronic/slowly progressive course; ambulatory; reliable follow-up with neurology within 2-4 weeks; pain controlled; able to perform ADLs; no fall risk requiring inpatient therapy
Admit to floor	Acute/subacute progression concerning for GBS or CIDP; significant functional decline; falls requiring therapy evaluation; severe uncontrolled pain; new autonomic instability; workup requiring inpatient procedures (nerve biopsy, LP)
Admit to ICU	GBS with respiratory compromise (FVC <20 mL/kg, NIF >-30, or declining trajectory); autonomic instability with cardiac arrhythmia or BP lability; aspiration risk
Transfer to higher level	EMG/NCS not available urgently; neuromuscular specialist not available; PLEX/IVIG needed but not available; rehabilitation services not available

---

8. EVIDENCE & REFERENCES

Recommendation	Evidence Level	Source
Diabetes is most common cause of polyneuropathy in developed countries	Class I	Dyck PJ et al. Neurology 1993
HbA1c <7% reduces neuropathy incidence in Type 1 DM	Class I, Level A	DCCT/EDIC
Gabapentin, pregabalin, duloxetine first-line for painful diabetic neuropathy	Class I, Level A	AAN/AANEM Practice Guideline 2011, 2022 update
Tricyclic antidepressants effective for neuropathic pain	Class I, Level A	Finnerup NB et al. Lancet Neurol 2015
NCS/EMG for characterization of peripheral neuropathy	Class I, Level B	AAN Practice Parameter
SPEP indicated in idiopathic neuropathy workup	Class II, Level B	England JD et al. Neurology 2009
OGTT detects IGT in 34-62% of idiopathic neuropathy patients	Class II, Level B	Singleton et al. Diabetes Care 2001; Hoffman-Snyder et al. Arch Neurol 2006
Skin biopsy (IENFD) for small fiber neuropathy	Class II, Level B	Lauria G et al. Eur J Neurol 2010
IVIG first-line for CIDP	Class I, Level A	Cochrane Review, EFNS/PNS Guidelines
Thiamine supplementation in alcoholic neuropathy	Class II, Level B	AAN Practice Parameter
Foot care reduces amputations in diabetic neuropathy	Class I, Level A	Multiple RCTs, ADA Guidelines
Capsaicin 8% patch effective for localized neuropathic pain	Class I, Level A	Multiple RCTs
Tafamidis for hATTR polyneuropathy	Class I, Level A	ATTR-ACT Trial, Adams et al. NEJM
Patisiran/inotersen for hATTR polyneuropathy	Class I, Level A	APOLLO, NEURO-TTR Trials
Combination therapy for neuropathic pain improves outcomes	Class II, Level B	Multiple RCTs

---

CHANGE LOG

v1.2 (January 14, 2026) - Added venue columns (ED, HOSP, OPD, ICU) to Section 6 Monitoring Parameters for plan builder compatibility - Venue indicates where monitoring is typically ordered/initiated - Added respiratory function monitoring (FVC, NIF) for GBS/CIDP - critical for ICU triage - Added explanatory note about venue interpretation for monitoring parameters

v1.1 (January 14, 2026) - Moved OGTT from Section 1C to 1B (Extended Workup) based on evidence of high diagnostic yield (34-62% of idiopathic neuropathy patients have abnormal OGTT) - Added OGTT indication note referencing high yield in idiopathic neuropathy - Corrected gabapentin renal dosing: CrCl 15-29 max changed from 700 mg/day to 600 mg/day per conservative dosing references - Added specific CrCl threshold ranges to gabapentin dosing in Section 3B - Added creatinine clearance monitoring with specific dose adjustment guidance to Section 6 - Corrected inotersen monitoring: changed from "weekly × 8 weeks then q2 weeks" to "weekly throughout treatment; more frequent if platelets <75; continue 8 weeks post-discontinuation" - Clarified droxidopa interactions: ergot alkaloids as contraindication; MAOIs and triptans as cautions (not absolute contraindications) - Added patisiran vitamin A supplementation mechanism note - Clarified EMG timing guidance: "optimal 3-4 weeks after symptom onset (allows Wallerian degeneration to manifest)" - Added combination therapy note after Section 3B pain medications - Added sleep management options to Section 3C: trazodone, melatonin - Added anxiety treatment options to Section 3C: hydroxyzine, buspirone - Changed midodrine and fludrocortisone ICU column from "-" to "ROUTINE" with note about continuation of home regimen - Added temperature sensitivity patient instruction to Section 4B - Added OGTT reference to Evidence section

v1.0 (January 14, 2026) - Initial creation - Comprehensive laboratory workup including metabolic, inflammatory, infectious, and genetic etiologies - Full electrodiagnostic and imaging recommendations - Extensive neuropathic pain medication section with individual drugs and complete dosing - Autonomic symptom management (orthostatic hypotension, bladder, GI) - Disease-specific treatments (IVIG, PLEX, immunosuppression, hATTR therapies) - Comprehensive referral list including podiatry, pain management, genetic counseling - Detailed patient instructions for foot care and fall prevention - Lifestyle modifications emphasizing glycemic control and alcohol cessation