10.4. Differential Diagnosis of Symmetric Sensory Polyneuropathies
- Inherited Sensory Neuropathies:
- Hereditary sensory autonomic neuropathy I, II, IV, V:
- foot ulcers
- self-mutilation
- profound associated anhidrosis, pupillary abnormalities and autonomic dysregulation
- Type II (AR large fiber greater than small fiber loss)
- Bassen Kornsweig Disease:
- absence of apolipoprotein b; very low density and low density lipoproteins
- ataxia, poor proprioception, dysarthria, areflexia
- pes cavus and scoliosis
- Fabry's Disease:
- burning acroparesthesias
- angiokeratoma in bathing suit distribution
- anhidrosis
- stroke, renal failure, X-linked recessive
- SANDO:
- sensory ataxia
- dysarthria
- ophthalmoplegia
- Perrault syndrome:
- ovarian dysgenesis
- VIIIth nerve dysfunction
- kinesthetic and vibratory loss
- Amyloidosis (FAP):
- decreased pain and thermal sensitivity
- primary uveal veil (Andrade Type I)
- congestive heart failure
- small fiber characteristics (burning/lancinating pain)
- Hereditary spinocerebellar degeneration:
- Friedreich's ataxia
- SCA-5
- primarily proprioceptive and vibratory loss
- dysarthria
- scoliosis, pes cavus, other dysmorphisms
General Features of Inherited Neuropathies with Primary Sensory Symptoms
- Dysmorphisms:
- Pes cavus or "rocker bottom" feet
- scoliosis; high insertion of gastrocnemius muscles; intrinsic foot and hand muscle wasting
- No paresthesias; positive paresthesias are characteristic of acquired neuropathies
- Insidious course
- Inherited neuropathies demonstrate selective fiber size involvement (large diameter α A or AB or C and A-delta small fiber); acquired neuropathies tend to affect all fiber sizes
- Specific associated features:
- Orange tonsils (Tangier)
- Angiokeratoma (Fabry's)
- Ulcerated foot (HSAN)
- Genetic history
Sensory Symptoms as the Presenting Feature of a Generalized Neuropathy Metabolic Sensorimotor Neuropathy
- Sensory symptoms may precede motor and autonomic signs in characteristic sensorimotor neuropathies. This pattern is common in:
- Diabetes (CTS, numb or burning feet)
- Hypothyroidism (CTS, Vth nerve involvement)
- Uremia-(numb or burning feet)
- Acromegaly (CTS and tarsal tunnel syndromes)
- Primary biliary cirrhosis (itch, numb feet)
- Hepatic failure (encephalopathy and myelopathy)
- Hypoglycemia (most often a motor neuropathy; occasionally distal lower extremity numbness)
- Toxic neuropathies with primary sensory symptoms:
- Arsenic (nausea, keratosis of palms)
- Ethylene oxide (confusion; memory loss; rash)
- Thalidomide (allodynia and hyperalgesia; severe constipation)
- Hydralazine (numbness and paresthesias)
- Isoniazid (seizures, hyperpyrexia)
- Metronidazole/misonidazole (paresthesias, burning)
- Nitrofurantoin (rapid development of sensory loss)
- Nitrous oxide (distal arm paresthesias; myelopathy)
- Perhexiline maleate (facial diplegia; perioral numbness)
- Propafenone (arrhythmia; blurred vision; dizziness)
- Colchicine (associated myopathy; increased CK)
- Disulfiram (optic neuropathy, gait unsteadiness)
- Amiodarone (corneal deposits; dermatitis)
- Gold (rapid development; myokymia)
- Trichloroethylene (II, V, VII cranial nerve)
- Chloramphenicol (calf pain; concomitant optic atrophy)
- Hexacarbons (sensory loss, hands and feet; rarely to knees)
- Thallium (behavioral changes; hair loss)
- Phenytoin (loss of deep tendon reflexes)
- Amylamine (hallucination; memory loss; tremor)
- Organophosphorus esters (delayed neurotoxicity)
- Carbon disulfide (retinopathy; extrapyramidal, psychiatric)
- L-tryptophan (myopathy, hallucination; rash)
- Vincristine (bowel; bladder dysfunction)
- Metal toxic syndromes (Meoes lines)
- Eosinophilia–myalgia syndrome (brown skin induration)
- Paclitaxel (predominate sensory; weakness rare)
- DMAPN-(small fiber; bladder and sexual dysfunction)
- Alkyl mercury (distal paresthesias)
- Nutritional deficiency states:
- B12 (cranial nerve I dysfunction dorsal column loss; ataxia; paresthesias; spasticity)
- B6 (burning paresthesias)
- Pantothenic acid (associated with chronic alcoholism; burning feet)
- Thiamine (ophthalmoplegia; encephalopathy; ataxia)
- Vitamin E deficiency (nutritional and tocopherol transporter genetic defect)
- Chronic alcoholic neuropathy (associated with multiple vitamin deficiencies)
- Infections:
- Lyme (encephalopathy; bilateral VIIth nerve)
- Leprosy (enlarged nerves; cold areas of the body are anesthetic; leonine facies)
- Brucellosis (remitting fever; L5 radiculopathy)
- HIV (burning feet; wasting)
- Syphilis (stamping gait; Argyle–Robertson pupils)
- CMV (lumbosacral radiculopathy; bladder dysfunction)
- HZ-(dermatomal sensory loss with hyperalgesia and allodynia)
- Herpes simplex (regional hyperalgesia)
- Large fiber neuropathies (ataxia; kinesthetic loss):
- Sjögren's (NISP)
- Paraneoplastic (MISP)
- SICCA complex
- Hypothyroidism
- Uremia (may be predominately small fiber)
- Vitamin B12
- Tabes dorsalis
- IgM paraproteinemia
- Cisplatinum
- Nitrous oxide
- Pyridoxine
- Doxorubicin
- Metastasis to DRG
- CIDP (associated IgM, anti sulfatide, GD lb antibodies )
- Processes that may primarily affect the posterior roots:
- Lymphoreticular or plasma proliferative disease
- Meningeal carcinomatosis
- GBS (sensory variant)
- CIDP (sensory variant)
- Differential diagnosis of MISP from NISP
NISP (non-malignant inflammatory sensory polyneuropathy)
- Autoimmune (Sjögren's)
- Female
- Less common
MISP (malignant inflammatory sensory polyneuropathy)
- Malignancy
- Male = female
- Ataxia (hyperalgesic associated)
- Ataxia gastrointestinal (dysmotility)
Differential diagnosis of MISP from NISP
- NISP (non-malignant inflammatory sensory polyneuropathy)
- Autoimmune (Sjögren's)
- Female
- Less common
- MISP (malignant inflammatory sensory polyneuropathy)
- Malignancy
- Male = female
- Ataxia (hyperalgesic associated)
- Ataxia gastrointestinal (dysmotility)
Differential diagnosis of dorsal root ganglion
- NISP (autoimmune)
- MISP (paraneoplastic)
- Pyridoxine excess
- Doxorubicin
- Cisplatin
- Tabes dorsalis
- Herpes zoster
- GBS (sensory variant)
- CIDP (sensory variant)
- Carcinomatosis of the meninges
- Lymphoproliferative disorders
- Central sensory syndrome (compression of dorsal column nuclei; thalamic or cortical SI caesius
Differential diagnosis of axonal sensory neuropathy (acute)
- cisplatinum
- paclitaxel
- CM Fisher variant of GBS (may be demyelinating)
- Paraneoplastic (hyperalgesic – ataxic form)
- Acute pyridoxine overdose
- Idiopathic sensory neuropathy
Subacute/chronic axonal sensory neuropathy
- HSMN-I (large nerves)
- Paraneoplastic (ataxia; hyperalgesia; GI dysmotility)
- Dysproteinemia (IgM; osteoclastic multiple myeloma)
- Sjögren's (cranial nerve V; mucous membrane involvement)
- SCCA complex (mucous membrane dryness; an hidrosis)
- Mitochondrial cytopathies (VIIIth nerve, fatigue, heart involvement)
- Thalidomide (constipation; allodynia, hyperalgesia)
- Dideoxycytidine (burning feet)
- Didanosine (burning feet)
- Pyridoxine (ataxia, numbness, paresthesias of extremities)
- CIDP (length dependent sensory loss; perioral numbness)
- Primary biliary cirrhosis (severe itching)
- Vitamin E deficiency (dorsal column dysfunction is the predominate feature)
- Friedreich's ataxia (dementia, cerebellar signs, heart failure)
Sensory neuropathy with antibodies to specific epitopes
- MAG (myeline associated glycoprotein)
- SGPG (small fiber)
- Anti-Hu (ANNA-1) small fiber predominant
- Anti-sulfatide (small fiber)
- CM Fisher variant ( GT1a; GQ1b)
- GTA-D- (large fiber)
- GD3
Demyelinating sensory neuropathy with antibodies to specific epitopes
- MAG
- SGPG
- CM Fisher variant of GBS ( GT1a)
- CIDP
Ataxic sensory polyneuropathy
- Carcinomatous sensory neuropathy
- Sjögren's syndrome
- Noncancerous inflammatory sensory polyneuropathy
- Malignant inflammatory sensory polyneuropathy
- CM Fisher variant of GBS
- MAG
- Sensory CIDP
- Immunoglobulin associated paraproteinemia
- Pyridoxine excess
- Cisplatinum
- Doxorubicin
- idiopathic (acute; chronic; monomelic)
Sensory neuropathy associated with systemic disease
- Diabetes (burning feet syndrome)
- Uremia (burning feet)
- Paraneoplastic (sensory ataxia; small fiber)
- Sjögren's (Vth nerve; SICCA complex)
- Hypothyroidism (CTS, TTS, upper extremity; Vth nerve)
- Sensory perineuritis (primarily around the ankle)
- Ischemic neuropathy (lower extremities; all modalities)
- Malabsorption (B12, Vit E-primary large fibers)
- Hypertriglyceridemia (predominately small fiber)
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