Differentials
Common
Lumbosacral radiculopathy
History
pain, weakness, and/or numbness in distribution of involved nerve root(s); pain may originate in low back and radiate in the distribution of the involved root(s)
Exam
weakness and sensory loss usually mild; reduced deep tendon reflexes relative to asymptomatic side; provocative testing, e.g., straight leg raise, may elicit symptoms but should not be relied on in isolation
1st investigation
Other investigations
- lumbar MRI:
disk herniation, osteophytes, tumor, root avulsion, enlarged epidural veins
More - lumbar CT:
disk herniation, osteophytes, tumor, root avulsion
- lumbar x-ray:
fractures, instability, degenerative changes
Diabetic amyotrophy
History
history of diabetes mellitus, glucose-intolerant states (e.g., prediabetes), or unstable metabolic condition; severe pelvic/thigh pain, often described as "boring"; possible resolution of pain within 2 to 3 weeks, followed by weakness and muscle atrophy
Exam
hip flexion, hip adduction, and knee extension weakness; loss of patellar deep tendon reflex on the affected side; atrophy of quadriceps; possible sensory deficits in the distribution of the femoral, obturator, and saphenous nerves
1st investigation
- electromyography (EMG):
normal or denervation in an upper lumbar radicular or upper lumbar plexus distribution
- nerve conduction studies:
reduced or absent compound muscle action potentials (CMAP) in femoral nerve and sensory nerve action potentials (SNAPs) in saphenous nerve
- fasting plasma glucose:
elevated
More
Other investigations
- oral glucose tolerance test:
elevated
More
Meralgia paresthetica
History
history of obesity, wearing tight-fitting clothing, using heavy tool belts; pain, paresthesias, numbness in distribution of the lateral cutaneous nerve of the thigh
Exam
numbness and/or paresthesias over anterolateral thigh
1st investigation
Fibular neuropathy
History
potential history of nerve compression at fibular neck (surgical positioning, crossing legs, trauma); partial or complete foot drop developing over days or weeks; mostly unilateral
Exam
weakness of foot eversion and sensory disturbance over lateral calf and dorsum of foot; weakness of toe and ankle dorsiflexion; normal ankle inversion and toe flexion
1st investigation
- electromyography (EMG):
neurogenic changes involving the distal fibular-innervated muscles with sparing of the short head of the biceps femoris (unless proximal to the fibular neck) and tibial muscles
More - nerve conduction studies:
reduced deep fibular motor and superficial fibular sensory amplitudes; conduction block or decreased conduction velocity across the fibular neck
More - Neuromuscular ultrasound (NMUS):
may show increased cross-sectional area of the fibular nerve at the fibular head with or without an intraneural ganglia causing compression
Morton neuroma
History
pain usually at the base of third and fourth toes; exacerbation of symptoms with weight-bearing and repetitive use
Exam
palpable tenderness over the affected area; neurologic exam is normal; absence of weakness
1st investigation
- electromyography (EMG):
normal
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Other investigations
- MRI foot:
positive if neuroma is of sufficient size
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Uncommon
Lumbosacral plexopathy (non-neoplastic compressive)
History
asymmetric weakness, numbness, and pain that involves multiple nerve roots, trunks, or their terminal branches
Exam
weakness, atrophy, numbness, and loss of deep tendon reflexes in a pattern requiring involvement of multiple nerve roots, trunks, or their terminal branches
1st investigation
Other investigations
Obturator neuropathy
History
history of obstetric/gynecologic procedure; pain, numbness, weakness in distribution of obturator nerve
Exam
weakness of thigh adduction, preservation of other L2-L4 innervated muscles (e.g., quadriceps); numbness over proximal medial thigh
1st investigation
Sciatic neuropathy
History
weakness, numbness, pain, paresthesias in lower extremity; foot drop
Exam
weakness of knee flexion, dorsiflexion/plantar flexion of ankle and toes; sensory loss over anterior and posterior leg from the knee down, dorsum and plantar regions of foot
1st investigation
- electromyography (EMG):
denervation and/or neuropathic changes involving hamstring muscles, as well as distal fibular and tibial-innervated muscles
More - nerve conduction studies:
reduced sural and superficial fibular sensory amplitudes; reduced fibular and tibial motor amplitudes without reduced conduction velocity across the fibular head
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Tarsal tunnel syndrome
History
perimalleolar pain; ankle and sole pain described as "burning"; pain worse with weight-bearing and at night
Exam
true weakness or atrophy of intrinsic foot muscle uncommon; possible positive Tinel sign over the ankle
1st investigation
- electromyography (EMG):
neurogenic changes involving the intrinsic foot muscles
More - nerve conduction studies:
reduced mixed plantar sensory amplitudes and/or tibial motor amplitudes
More - Neuromuscular ultrasound (NMUS):
may demonstrate structural abnormalities causing compression in the tarsal tunnel, such as ganglion cysts, varices, and bone spurs
Other investigations
- MRI of foot and ankle:
positive
More
Tibial neuropathy
History
asymmetric pain, weakness, numbness involving the distal lower extremity; numbness may occur over the lateral aspect of the foot and sole
Exam
asymmetric pain, weakness, numbness involving the distal lower extremity, particularly with plantar flexion and inversion; loss of Achilles deep-tendon reflexes
1st investigation
Femoral mononeuropathy
History
pain and weakness in leg when walking; buckling of the knee resulting in falls; numbness and paresthesias may involve anterior thigh and/or medial calf; history of pelvic or hip trauma, iatrogenic injury, or diabetes mellitus
Exam
weakness of quadriceps muscle and absence of knee-jerk reflex; possible atrophy; normal hip adduction; numbness in distribution of saphenous nerve
1st investigation
Hereditary neuropathy with liability to pressure palsies (HNPP)
History
recurrent painless mononeuropathies at common compression sites (e.g., fibular neuropathy at the fibular head)
Exam
weakness and numbness in distribution of affected nerve; normal exam when asymptomatic
1st investigation
- electromyography (EMG):
decreased recruitment during episode
- nerve conduction studies:
decreased conduction velocity and/or conduction block at entrapment site
- genetic testing:
PMP 22 deletion on chromosome 17
Other investigations
- nerve biopsy:
thickening of myelin sheath
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HIV
History
often asymptomatic; fever, myalgia, diarrhea, fatigue, rashes; history of high-risk sexual activity (multiple partners, unprotected, or men who have sex with men) or IV drug use
Exam
diffuse lymphadenopathy; HIV-associated opportunistic infections and complications
1st investigation
Other investigations
- serum Western blot:
positive
Herpes zoster
History
pain followed by rash; pruritus; constitutional symptoms
Exam
pain and rash localized to affected dermatome
1st investigation
Other investigations
- PCR:
positive for varicella DNA
Herpes simplex
History
lymphadenopathy; oral or genital ulcers; fever; tingling in prodrome before lesion; dysuria in women
Exam
normal, asymptomatic genital fissures, or multiple painful ulcerations
1st investigation
Other investigations
- viral culture of lesions:
positive for HSV
- PCR:
positive for herpes simplex virus DNA
Epstein-Barr virus
History
history of infectious mononucleosis; lymphadenopathy, sore throat, malaise, fever; myalgia
Exam
splenomegaly may be found
1st investigation
Other investigations
Cytomegalovirus
History
history of transplant or immunodeficiency; fever, diarrhea, nausea and vomiting; visual floaters, blindness; pain, weakness
Exam
presence of hemorrhages on funduscopy
1st investigation
Other investigations
- PCR:
positive for CMV
Lyme disease
History
history of tick bite; rash 1 to 2 weeks after tick bite with possible central clearing; constitutional symptoms
Exam
erythema migrans
1st investigation
Other investigations
Leprosy
History
skin lesions with loss of sensation; possible muscle weakness of affected nerve
Exam
single or multiple lesions with less pigmentation than surrounding skin; loss of sensation at skin lesions to pin pricks or light touch
1st investigation
Other investigations
Peripheral nerve vasculitis
History
history of connective tissue disease, recent infections (including HIV), and autoimmune conditions; varied history due to range of underlying etiologies; weight loss, fatigue, myalgia, arthralgia
Exam
dry conjunctivae; enlarged parotid; nasopharyngeal lesions; oral ulcers; wheezing; skin lesions; splenomegaly; joint warmth/enlargement; palpably enlarged nerves
1st investigation
Sarcoidosis
History
cough, dyspnea, constitutional symptoms, lymphadenopathy
Exam
wheezing/rhonchi; cervical and submandibular lymphadenopathy; usually absence of synovial thickening; erythema nodosum, lupus pernio
1st investigation
- electromyography (EMG):
neurogenic changes in the distribution of the involved nerves or roots
More - nerve conduction studies:
variable
More - chest x-ray:
hilar and/or paratracheal adenopathy with upper lobe predominant, bilateral infiltrates; pleural effusions (rare) and egg shell calcifications (very rare) may be seen
Other investigations
- CBC:
anemia; leukopenia
More
Sjogren syndrome
History
fatigue, dry eyes, dry mouth; arthritis, arthralgia, myalgia
Exam
dental caries, oral infections, corneal ulceration, no salivary pool, enlarged salivary glands
1st investigation
Rheumatoid arthritis
History
history of active symmetric arthritis lasting >6 weeks; joint pain, swelling
Exam
rheumatoid nodules on extensor surfaces of tendons; pleuritis, pericarditis, inflammatory eye disease
1st investigation
Acquired demyelinating sensorimotor polyneuropathy
History
history of progressive or exacerbating/remitting course; history of antecedent illness such as viral infection, surgery, or diarrheal illness such as campylobacter; weakness (e.g., foot drop) usually prompts presentation to a physician
Exam
moderate to severe muscle weakness; proximal muscle groups may be as weak as distal muscle groups, globally reduced/absent reflexes; sensory impairments may be similar in the upper and lower extremities (not a clearly distal or length-dependent pattern)
1st investigation
- electromyography (EMG):
demyelination
- nerve conduction studies:
demyelination
- lumbar puncture (CSF):
acellular with increased protein
Other investigations
Lumbosacral plexopathy (inflammatory)
History
asymmetric weakness, numbness, and pain that involves multiple nerve roots, trunks, or their terminal branches
Exam
weakness, atrophy, numbness, and loss of deep tendon reflexes in a pattern requiring involvement of multiple nerve roots, trunks, or their terminal branches
1st investigation
Lumbosacral plexopathy (neoplastic compressive)
History
history of malignancy; asymmetric weakness, numbness, and pain that involves multiple nerve roots, trunks, or their terminal branches; weight loss, fatigue, back pain
Exam
weakness, atrophy, numbness, and loss of deep tendon reflexes in a pattern requiring involvement of multiple nerve roots, trunks, or their terminal branches
1st investigation
Other investigations
Radiation-induced plexopathy
History
history of malignancy with radiation therapy; asymmetric weakness, numbness, and pain that involves multiple nerve roots, trunks, or their terminal branches
Exam
weakness, atrophy, numbness, and loss of deep tendon reflexes in a pattern requiring involvement of multiple nerve roots, trunks, or their terminal branches
1st investigation
Other investigations
Lymphoma
History
night sweats; fatigue; malaise; fever
Exam
lymphadenopathy; pallor; purpura; jaundice; hepatomegaly; splenomegaly; skin nodules; abnormal neurologic exam
1st investigation
Other investigations
Amyloidosis
History
weight loss, fatigue; history of edema not responding to treatment
Exam
lower extremity edema, elevated jugular venous distention, amyloid purpura
1st investigation
- electromyography (EMG):
neurogenic changes in the distribution of the involved nerves or roots
More - nerve conduction studies:
variable
More - serum immunofixation:
presence of monoclonal protein
- urine immunofixation:
presence of monoclonal protein
- immunoglobulin free light chain assay:
abnormal kappa-to-lambda ratio
Other investigations
Paraneoplastic immune-mediated attacks
History
history of malignancy; aggressive, painful, length-dependent neuropathy
Exam
weakness, atrophy, numbness, and loss of deep tendon reflexes in a pattern requiring involvement of multiple nerve roots, trunks, or their terminal branches
1st investigation
Other investigations
- anti-Hu antibodies:
positive
- anti-CV2 antibodies:
positive
Nerve sheath tumors
History
history of type 1 neurofibromatosis; progressive dysfunction
Exam
tenderness on palpation
1st investigation
Other investigations
- MRI of tumor site:
presence of lesion
- CT of tumor site:
presence of lesion
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