Mononeuropathy is the damage or dysfunction of a single peripheral nerve, resulting in sensory, motor, or mixed deficits in the distribution of that nerve.

Mononeuropathy

Carpal tunnel syndrome (CTS) is the most common mononeuropathy overall, with a lifetime prevalence of ~3–5% in the general population, and up to 14% in diabetics ^[3]^[4]
Common peroneal nerve (CPN) palsy is the most common mononeuropathy in the lower limb
Ulnar neuropathy at the elbow (cubital tunnel syndrome) is the second most common upper limb entrapment neuropathy
In Hong Kong and worldwide, the prevalence of mononeuropathies is increasing due to rising rates of diabetes mellitus, obesity, and repetitive occupational strain ^[3]^[4]
Entrapment is the most common cause of mononeuropathy ^[1]^[2]

Risk Factors

Risk Factor	Mechanism / Relevance
Diabetes mellitus	Microangiopathy → nerve ischaemia; metabolic injury (sorbitol accumulation, AGEs); both entrapment and mononeuritis multiplex more common ^[3]
Obesity	Nerve entrapment — increased mechanical load on confined anatomical spaces (e.g. carpal tunnel) ^[4]
Repetitive mechanical stress	Occupational (typists, manual labourers, cyclists) → chronic compression/friction
Pregnancy	Fluid retention → swelling in confined spaces (e.g. carpal tunnel)
Hypothyroidism	Mucopolysaccharide deposition → tissue swelling → entrapment
Acromegaly	Soft tissue hypertrophy → entrapment; also nerve thickening
Rheumatoid arthritis	Synovial thickening, joint deformity → entrapment
Renal failure (on dialysis)	Amyloid deposition (β2-microglobulin) in carpal tunnel
Trauma / fractures	Direct nerve injury or compression from haematoma, callus
Prolonged immobilisation / anaesthesia	Positional nerve compression (e.g. "Saturday night palsy" for radial nerve)
Anatomical variants	Cervical rib (thoracic outlet syndrome), accessory muscles

Anatomy and Function: Key Peripheral Nerves

Understanding mononeuropathy requires knowing the anatomy — where nerves run, where they are vulnerable, and what they supply. Think of nerves as electrical cables running through tunnels: anywhere a tunnel is tight, the cable is at risk.

Upper Limb Nerves

Lower Limb Nerves

Diabetes-induced microangiopathy → mononeuritis multiplex ^[3], classically affecting:

Presentation	Nerve Involved
Ptosis and divergent squint	3rd nerve palsy (oculomotor) — classically pupil-sparing in diabetic mononeuropathy because the pupillary fibres run on the outside of CN III and are affected by compressive (e.g. aneurysm) but not ischaemic lesions ^[3]
External (lateral) rectus palsy	6th nerve palsy (abducens) ^[3]
Upper facial and eye pain	Trigeminal nerve involvement (CN V) ^[3]
Foot drop	Common peroneal nerve palsy ^[3]

Diabetic CN III Palsy: Pupil-Sparing

In a diabetic 3rd nerve palsy, the pupil is typically spared (i.e., reactive and not dilated). This is because diabetes causes microvascular ischaemia affecting the central fibres of CN III (which supply the extraocular muscles), while the parasympathetic pupillary fibres run on the periphery of the nerve and have a separate blood supply from the pial vessels. Conversely, a compressive lesion (e.g. posterior communicating artery aneurysm) affects the superficial parasympathetic fibres first → "blown pupil" (mydriasis). This distinction is a classic exam question and a critical clinical differentiation.

Aetiology (with Focus on Hong Kong)

Entrapment is the most common cause (MC) of mononeuropathy ^[1]^[2]. The aetiologies can be classified as follows:

The nerve is compressed where it passes through a tight anatomical space. Any process that reduces the space (swelling, inflammation, anatomical variant) or increases the contents (oedema, tumour, ganglion) will compress the nerve.

Syndrome	Nerve	Site	HK-Relevant Notes
Carpal tunnel syndrome	Median	Carpal tunnel (wrist)	Most common entrapment neuropathy worldwide. Very common in HK — repetitive keyboard/phone use, high prevalence of DM, hypothyroidism ^[5]
Cubital tunnel syndrome	Ulnar	Behind medial epicondyle	Associated with cubitus valgus ^[5]; common in manual workers
Guyon canal syndrome	Ulnar	Guyon canal (wrist)	Most common cause: ganglion from the triquetrohamate joint ^[5]
Thoracic outlet syndrome	Brachial plexus ± subclavian vessels	Between 1st rib & clavicle	Causes: cervical rib, fracture clavicle, Pancoast tumour ^[5]
PIN syndrome	Radial (posterior interosseous)	Arcade of Frohse	Motor weakness only ^[5]
Wartenberg's syndrome	Radial (superficial branch)	Between ECRL & BR	Sensory loss only ^[5]
Pronator teres syndrome	Median	Between 2 heads of pronator teres	Rare; mimics CTS but with forearm involvement
Common peroneal palsy	Common peroneal	Fibular neck	Leg crossing, prolonged squatting (traditional Asian sitting), casts
Tarsal tunnel syndrome	Tibial	Behind medial malleolus	Burning sole pain
Meralgia paraesthetica	Lateral cutaneous nerve of thigh	Inguinal ligament	Obesity (rising in HK), pregnancy, tight clothing

Double crush syndrome: peripheral entrapment syndromes often associated with cervical/lumbar spondylosis — proximal compression of a peripheral nerve renders it more susceptible to the effects of a second, more distal injury (e.g. cubital tunnel syndrome & Guyon's canal syndrome) ^[5]

Pathophysiology of Nerve Injury

Understanding how nerves get damaged is essential for predicting prognosis and guiding management.

Grade	Name	What Happens	Prognosis
I	Neurapraxia	Local myelin damage only; axon intact; conduction block at the site of compression	Full recovery expected (days to weeks) — the "cable" is fine, just temporarily short-circuited
II	Axonotmesis	Axon disrupted, but the surrounding connective tissue tubes (endoneurium, perineurium, epineurium) are intact → Wallerian degeneration occurs distal to injury	Good recovery — axons regrow along the intact tubes at ~1 mm/day
III–V	Neurotmesis	Complete nerve transection (including connective tissue); Wallerian degeneration	Poor recovery without surgical repair — the "tunnel" is destroyed so axons cannot find their way back

Classification of Mononeuropathy

Category	Examples
Entrapment	CTS, cubital tunnel, CPN at fibular neck, tarsal tunnel
Traumatic	Fracture-related, laceration, injection injury
Ischaemic / Vascular	Diabetic mononeuropathy, vasculitic neuropathy
Inflammatory / Granulomatous	Sarcoid, leprosy
Neoplastic	Schwannoma, tumour compression
Iatrogenic	Surgical, positional (anaesthesia)

Time Course	Typical Causes
Acute (seconds to hours)	Trauma, ischaemic (diabetic, vasculitic)
Subacute (days to weeks)	Inflammatory, infective
Chronic (weeks to months)	Entrapment (most common), neoplastic

Clinical Features

The clinical features of mononeuropathy are determined by which nerve is affected and where along its course the lesion is. All features should be explicable by the anatomy.

Specific Mononeuropathies: Symptoms and Signs with Pathophysiological Basis

A. Upper Limb

Causes: cervical rib, fracture clavicle, Pancoast tumour ^[5]. Brachial plexus and subclavian artery pass through the scalene triangle; subclavian vein passes anterior to scalenus anterior ^[5].

Three types ^[5]:

Type	Signs	Treatment
Neurological (nTOS)	Lower brachial plexus injury (e.g. paraesthesia / weakness along ulnar distribution)	Conservative initially; surgical if refractory
Arterial (aTOS)	Ischaemic signs in upper limb, Raynaud's phenomenon	Surgical
Venous (vTOS)	Paget-Schroetter syndrome — upper limb DVT, swelling, cyanosis	Anticoagulation ± surgical

B. Lower Limb

C. Cranial Nerve Mononeuropathies

Nerve	Common Site	Motor Deficit	Sensory Deficit	Key Clinical Sign	Most Common Cause
Median	Carpal tunnel	Thenar weakness (LOAF)	Lateral 3½ digits (palmar)	Thenar wasting, +ve Phalen's/Tinel's	Entrapment (CTS)
Ulnar	Cubital tunnel	Hypothenar + interossei weakness	Medial 1½ digits	Claw hand, Froment's sign	Entrapment, cubitus valgus
Radial	Spiral groove	Wrist/finger extension	Dorsal 1st web space	Wrist drop	Compression, humeral fracture
CPN	Fibular neck	Dorsiflexion + eversion	Dorsum of foot, lateral leg	Foot drop, steppage gait	Compression, DM
Femoral	Inguinal region	Knee extension	Anterior thigh, medial leg	Loss of knee jerk	Retroperitoneal haematoma, DM
LCNT	Inguinal ligament	None	Lateral thigh	Burning lateral thigh pain	Obesity, pregnancy
CN III	Cavernous sinus	EOM (except LR, SO)	—	Ptosis, "down and out", ±pupil	DM (pupil-spared), PComA aneurysm (pupil-blown)
CN VII	Facial canal	Upper + lower face	Taste anterior 2/3 tongue	LMN facial weakness	Idiopathic (Bell's palsy)

High Yield Summary

Mononeuropathy = single nerve lesion. Most common cause is entrapment (MC) ^[1]^[2]. Most common overall is carpal tunnel syndrome ^[5].
Localize the lesion by matching motor and sensory deficits to a single nerve's territory. Nerve territory ≠ dermatomal territory.
LMN signs (weakness, wasting, fasciculation, hyporeflexia) are the hallmark of peripheral nerve lesions.
Diabetic mononeuropathy: microangiopathy → mononeuritis multiplex. Classic presentations: CN III (pupil-sparing ptosis + divergent squint), CN VI (lateral rectus palsy), CN V (facial pain), CPN (foot drop) ^[3]. "Mix and match" presentations ^[3].
Diabetic CN III vs compressive CN III: Pupil-sparing = ischaemic (diabetes). Pupil-blown = compressive (aneurysm) — the parasympathetic fibres run on the surface and are vulnerable to compression but not to central ischaemia.
Double crush syndrome: proximal compression renders nerve more susceptible to distal entrapment ^[5].
Key named signs: Tinel's (tap), Phalen's (wrist flexion), Froment's (paper grip), Wartenberg's (little finger abduction), wrist drop (radial), foot drop (CPN), claw hand (ulnar).
Nerve conduction studies differentiate axonal (↓amplitude, normal velocity) from demyelinating (↓velocity, normal amplitude) pathology — only demyelinating neuropathies are usually susceptible to treatment ^[2].
Seddon classification: Neurapraxia (myelin only, full recovery) → Axonotmesis (axon cut, connective tissue intact, good recovery) → Neurotmesis (complete transection, needs surgery).
For prognosis and management: early recognition and decompression of entrapment neuropathies prevents progression from reversible demyelination to irreversible axonal degeneration.

Active Recall - Mononeuropathy

Differential Diagnosis of Mononeuropathy

The differential diagnosis of mononeuropathy operates on two levels simultaneously. First, you must confirm that the clinical picture truly represents a single peripheral nerve lesion (anatomical differential — "Where is the lesion?"). Second, once localized, you must determine the cause (pathological differential — "What is the lesion?"). This two-tiered approach is fundamental to neurological reasoning and is heavily emphasized in the GC curriculum.

Level 1: Anatomical Differential — "Where Is the Lesion?"

Before you label something a mononeuropathy, you must exclude mimics at other anatomical levels that can produce similar motor/sensory deficits. A patient presenting with, say, wrist drop or foot drop could have a lesion anywhere from cortex to muscle.

Where is the lesion (anatomical differentials)? Cerebrum, corona radiata, internal capsule, brainstem, extrapyramidal system, spinal cord, anterior horn cells, nerve root, brachial plexus, peripheral nerve, neuromuscular junction, muscle, bone and joints, metabolic, functional ^[8]

The key anatomical mimics of mononeuropathy, organized by level:

Why it can mimic: A C8-T1 radiculopathy can mimic ulnar neuropathy (both cause hand weakness + medial hand numbness); an L5 radiculopathy can mimic common peroneal nerve (CPN) palsy (both cause foot drop)
How to differentiate:
- Radiculopathy affects all muscles in that myotome regardless of which peripheral nerve they belong to, plus follows a dermatomal sensory pattern
- In CPN palsy: foot eversion is weak (superficial peroneal) + dorsiflexion weak (deep peroneal), but inversion is preserved (tibialis posterior = tibial nerve, L5 root). In L5 radiculopathy, inversion is ALSO weak (because tibialis posterior receives L5 via the tibial nerve) and hip abduction is weak (gluteus medius, L5) ^[1]
- Radiculopathy often has back/neck pain radiating in a dermatomal distribution
- Cervical spondylosis (esp. C6/7): neck pain + neck movement exacerbates ^[5]

CPN Palsy vs L5 Radiculopathy — Classic Exam Distinction

Feature	CPN Palsy	L5 Radiculopathy
Dorsiflexion	Weak	Weak
Eversion	Weak	Weak
Inversion	Preserved	Weak
Hip abduction	Preserved	Weak
Sensory loss	Dorsum of foot + lateral leg	L5 dermatome (lateral leg, dorsum foot, medial foot)
Back pain	Absent	Often present
Ankle jerk	Preserved	Preserved (S1)

This table is extremely high-yield. The key differentiator is tibialis posterior (inversion) and gluteus medius (hip abduction) — both are L5 myotome but NOT common peroneal nerve.

Differential Diagnosis by Specific Presentation

Since different mononeuropathies present with different chief complaints, here are the key differentials organized by presentation:

Diagnosis	Level	Key Distinguishing Features
Radial nerve palsy (spiral groove)	Peripheral nerve	Wrist + finger drop, sensory loss dorsal 1st web, history of arm compression/humeral fracture
C7 radiculopathy	Nerve root	Neck pain, weakness also in wrist flexors + pronators (C7 myotome crosses multiple nerves), ↓triceps jerk
Posterior cord brachial plexopathy	Plexus	Affects radial + axillary nerve territories
CNS lesion (rare)	Central	UMN signs

Diagnosis	Level	Key Distinguishing Features
CPN palsy	Peripheral nerve	Dorsiflexion + eversion weak, inversion preserved, sensory loss dorsum foot, history of leg crossing/fibular compression
L5 radiculopathy	Nerve root	Inversion also weak, hip abduction weak, back pain ± straight leg raise positive, sciatica: back pain with radiation, not relieved by resting ^[12]
Sciatic neuropathy	Peripheral nerve (proximal)	Hamstring weakness + all below-knee weakness (both peroneal AND tibial territories)
Lumbosacral plexopathy	Plexus	Multiple nerve territories affected
MND / ALS	Anterior horn cell	Mixed UMN/LMN, progressive, no sensory loss
Cauda equina	Spinal	Bilateral, saddle anaesthesia, urinary retention with overflow incontinence, faecal incontinence ^[13]

Diagnosis	Level	Key Distinguishing Features
CTS (median nerve)	Peripheral nerve	Lateral 3½ digits, nocturnal, Phalen's/Tinel's +ve, thenar wasting
Cubital tunnel (ulnar nerve)	Peripheral nerve	Medial 1½ digits, interosseous wasting, claw hand
C6/C7 radiculopathy	Nerve root	Neck pain + neck movement exacerbates, dermatomal pattern, reflex changes ^[5]
Pronator teres syndrome	Peripheral nerve	Forearm motor involvement + palmar sensation affected ^[5]
Thoracic outlet syndrome	Plexus	Lower plexus → ulnar distribution but may cross nerve boundaries ^[5]
Cervical myelopathy	Spinal cord	UMN signs in legs, myelopathic hand, Lhermitte's sign ^[13]
T1 radiculopathy	Nerve root	All hand intrinsics weak (both median and ulnar), Horner's syndrome if sympathetic chain involved

Diagnosis	Level	Key Distinguishing Features
Diabetic CN III palsy	Cranial mononeuropathy	Pupil-sparing, acute onset, painful, ptosis + divergent squint ^[3]
PComA aneurysm compressing CN III	Compressive	Pupil-blown (mydriasis), surgical emergency
Myasthenia gravis	NMJ	Fatigable ptosis, fluctuating, bilateral possible, no pupil involvement ^[9]^[10]
Horner's syndrome	Sympathetic	Partial ptosis, miotic reactive pupil, anhidrosis, enophthalmos — NO deviation of eye ^[10]
CN VI palsy (diabetic)	Cranial mononeuropathy	Lateral rectus palsy, convergent squint, horizontal diplopia ^[3]
Myopathy (e.g., mitochondrial, myotonic dystrophy, oculopharyngeal)	Muscle	Progressive, bilateral, no pupil changes, CK may be elevated ^[10]

Once you've confirmed the deficit maps to a single peripheral nerve, you must determine the aetiology. The systematic framework:

What is the lesion (pathological differentials)? Vascular, Infection, Neoplasm, Degenerative, Inflammatory, Congenital, Autoimmune, Trauma/Toxins, Endocrine ^[6]^[8]

Category	Examples in Mononeuropathy	Mechanism
Vascular	Stroke (mimic), spinal cord infarction (mimic), diabetic vasa nervorum infarction, vasculitic nerve infarction	Ischaemia of nerve or its blood supply
Infection	Leprosy, herpes zoster (Ramsay Hunt for CN VII), Lyme disease (CN VII), HIV	Direct invasion, immune-mediated damage
Neoplasm	Schwannoma, neurofibroma, Pancoast tumour (brachial plexus) ^[5], paraneoplastic	Compression, infiltration
Degenerative	Cervical myelopathy / radiculopathy, carpal tunnel syndrome ^[8], prolapsed intervertebral disc, OA	Chronic compression from degenerative structural changes
Inflammatory	Guillain-Barré syndrome (usually polyneuropathy but can rarely be focal), vasculitic neuropathy, sarcoidosis	Immune-mediated nerve damage
Congenital	Hereditary neuropathy with liability to pressure palsies (HNPP) — autosomal dominant PMP22 deletion → nerves are unusually susceptible to compression	Genetic structural nerve vulnerability
Autoimmune	Myasthenia gravis (NMJ mimic, not true mononeuropathy) ^[8], multifocal motor neuropathy with conduction block	Autoantibody-mediated
Trauma / Toxins	Fracture-associated nerve injury, subdural/epidural haematoma (cord compression mimic) ^[8], iatrogenic (surgical, positional), injection injury, neuropathy secondary to chemotherapy ^[8]	Direct mechanical damage, toxic axonal injury
Endocrine	Diabetic neuropathy (most common metabolic cause) ^[3]^[8], hypothyroidism (mucopolysaccharide deposition → CTS), acromegaly, B12 deficiency resulting in neuropathy / myelopathy ^[8]	Metabolic nerve damage, tissue swelling → entrapment

Entrapment Is the Most Common Cause — But Don't Stop There

Entrapment (MC) ^[1] accounts for the vast majority of mononeuropathies. However, in every case you should also ask: Why did this nerve get entrapped NOW? Look for underlying predisposing conditions — DM, hypothyroidism, acromegaly, RA, pregnancy, obesity, renal failure (amyloid) — because treating the underlying cause prevents recurrence.

When multiple non-contiguous nerves are affected in a stepwise, asymmetric pattern, the diagnosis shifts from simple mononeuropathy to mononeuritis multiplex. This is an important distinction because the differential is different and often points to systemic disease.

Causes of mononeuritis multiplex: Diabetes (MC), vasculitis, autoimmune, paraneoplastic ^[1]

Cause	Mechanism	Key Features
Diabetes mellitus (MC)	Microangiopathy → vasa nervorum ischaemia ^[3]	Mix and match presentations ^[3]; often cranial nerves + peripheral nerves
Vasculitis (PAN, GPA/EGPA, RA vasculitis)	Inflammation of vasa nervorum → nerve infarction	Painful, acute onset; systemic features (fever, weight loss, rash, renal involvement)
Sarcoidosis	Granulomatous inflammation of nerve	Bilateral facial palsy classic; other nerves can be involved
HIV	Direct viral invasion + immune-mediated	Risk factors for HIV; multisystem involvement
Leprosy	Mycobacterium leprae predilection for superficial nerves	Thickened palpable nerves; skin patches; endemic area exposure
Lyme disease	Borrelia burgdorferi infection	Tick bite history; erythema migrans; bilateral facial palsy
Amyloidosis	Amyloid deposition in and around nerves	Associated with myeloma, chronic dialysis
Paraneoplastic	Autoantibody-mediated (e.g., anti-Hu)	Associated malignancy (small cell lung, thymoma)
HNPP	PMP22 gene deletion → recurrent pressure palsies	Family history; recurrent, self-limiting mononeuropathies at typical entrapment sites

When to Think Beyond Simple Entrapment

If a patient presents with sequential involvement of multiple nerves, painful acute-onset neuropathy, or mononeuropathy with systemic features (fever, weight loss, rash, renal dysfunction), do NOT just diagnose "another entrapment." Think vasculitis, diabetes, or systemic disease. Check ESR/CRP, glucose/HbA1c, autoimmune screen (ANA, ANCA, RF), and urinalysis.

This is clinically important because:

A patient with CTS may ALSO have C6/7 radiculopathy — the two conditions coexist, and treating only one may leave residual symptoms
Always examine the entire nerve pathway from spine to periphery
Example: cubital tunnel syndrome & Guyon's canal syndrome can coexist ^[5]

High Yield Summary — Differential Diagnosis of Mononeuropathy

Two-tiered approach: First localize (where?), then determine aetiology (what?).
Anatomical mimics (from GC lecture slides): Cerebrum, brainstem, spinal cord, anterior horn cells, nerve root, plexus, peripheral nerve, NMJ, muscle, bone/joints, metabolic, functional ^[8].
CPN palsy vs L5 radiculopathy: The classic differentiator is inversion (tibialis posterior) and hip abduction (gluteus medius) — both preserved in CPN palsy, both weak in L5 radiculopathy.
CTS differential: Cervical spondylosis, pronator teres syndrome, thoracic outlet syndrome, peripheral neuropathy ^[5].
Diabetic CN III vs PComA aneurysm: Pupil-sparing = ischaemic (DM). Pupil-blown = compressive (aneurysm).
Ptosis differential: CN III palsy (down-and-out), Horner's (partial ptosis, miosis, NO eye deviation), MG (fatigable, no pupil changes), aponeurotic (age-related, most common acquired ptosis).
Mononeuritis multiplex: Think DM (MC), vasculitis, sarcoid, Lyme, HIV, amyloid, HNPP, paraneoplastic.
Double crush syndrome: proximal compression renders nerve susceptible to distal entrapment — always examine the whole pathway ^[5].
Pathological differential framework: VINDICATE — Vascular, Infection, Neoplasm, Degenerative, Inflammatory, Congenital, Autoimmune, Trauma/Toxins, Endocrine ^[6]^[8].

Active Recall - Differential Diagnosis of Mononeuropathy

References

^[1] Senior notes: Maksim Medicine Notes.pdf (Section 11.12 Peripheral neuropathy, p.269) ^[3] Senior notes: Block A - Deterioration of eyesight in a diabetic patient_ diabetic complications.pdf (Diabetic Mononeuropathy section, p.7) ^[5] Senior notes: Maksim Surgery Notes.pdf (Section 5.2 Compression neuropathy, p.243–246) ^[6] Lecture slides: Neurology- Two cases of lower limb weakness.pdf (p.18–20) ^[8] Lecture slides: CFB_Neuro clinical skills demonstration_01.08.22_file to students.pdf (p.7–8) ^[9] Lecture slides: GC 056. Generalized muscle weakness.pdf (p.1) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Ptosis differential, p.1089) ^[11] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (Differential diagnosis of myopathies, p.706) ^[12] Senior notes: Maksim Surgery Notes.pdf (Approach to spine diseases, p.222; Peripheral vascular disease history, p.163) ^[13] Senior notes: Maksim Surgery Notes.pdf (Cauda equina syndrome, p.222)

Diagnostic Criteria, Diagnostic Algorithm, and Investigations for Mononeuropathy

Diagnostic Criteria by Specific Mononeuropathy

While there are no universal "diagnostic criteria" for mononeuropathy as a whole, certain specific entrapment neuropathies have well-established clinical diagnostic standards:

CTS is primarily a clinical diagnosis ^[5]. The diagnostic confidence increases with the combination of:

Feature	Details
Symptoms	Paraesthesia/numbness in median nerve territory (lateral 3½ digits), nocturnal worsening, "flick sign" relief
Provocative tests	Phalen's test (wrist flexion 60s → reproduces symptoms), Tinel's sign (tapping over carpal tunnel → paraesthesia)
Motor deficit	Thenar wasting, weakness of thumb abduction (APB) and opposition
Sensory deficit	Reduced sensation in median territory; thenar eminence spared (palmar cutaneous branch arises proximal to tunnel)
NCS confirmation	Prolonged distal motor latency and/or reduced sensory nerve action potential (SNAP) amplitude across the wrist — but normal conduction does not rule out CTS ^[5]

Differential diagnosis of CTS: cervical spondylosis (esp. C6/7), pronator teres syndrome, thoracic outlet syndrome, peripheral neuropathy ^[5]

CTS is a clinical diagnosis. Nerve conduction studies (normal conduction does not r/o CTS) ^[5]

Exam Pearl: NCS and CTS

A common exam mistake is assuming that a normal NCS excludes CTS. In early or mild CTS, the nerve may have only intermittent conduction block that resolves between episodes. NCS has a sensitivity of ~85–90% — so up to 10–15% of clinically definite CTS cases will have "normal" NCS. The diagnosis remains clinical.

Investigation Modalities

1. Electrodiagnostic Studies (NCS + EMG) — The Cornerstone

These are the single most important investigations for confirming mononeuropathy, localizing the lesion, and characterizing the pathological process.

Principle: An electrical stimulus is applied to a nerve at one point, and the response is recorded at another point. This measures:

Conduction velocity (how fast the impulse travels — reflects myelin integrity)
Amplitude (how many axons are conducting — reflects axonal integrity)
Distal motor latency (time from distal stimulation to muscle response)

NCS confirms distribution of neuropathy, involvement of sensory / motor / autonomic fibers. Pattern: axonal (normal velocity, ↓amplitude) vs demyelinating (↓velocity, normal amplitude) ^[1]

Parameter	Axonal Pathology	Demyelinating Pathology
Conduction velocity	Normal or mildly reduced	↓ Velocity (often < 70% of lower limit of normal)
Amplitude	↓ Amplitude (CMAP for motor, SNAP for sensory)	Normal or mildly reduced (until secondary axonal loss)
Distal motor latency	Normal	Prolonged
Conduction block	Absent	May be present (focal block at entrapment site)
Temporal dispersion	Absent	Present (nerve impulses arrive at different times)

Important: usually only demyelinating neuropathies are susceptible to treatment ^[2] — this is why distinguishing demyelinating from axonal matters clinically. Demyelinating lesions (e.g., early entrapment) can remyelinate if the compression is relieved; axonal degeneration is much harder to reverse.

Key NCS findings in specific mononeuropathies:

Condition	NCS Finding
CTS	Prolonged distal motor latency of median nerve at wrist; reduced median SNAP across wrist; comparative studies (median vs ulnar) show selective median slowing
Cubital tunnel	Reduced conduction velocity of ulnar nerve across the elbow segment (> 10 m/s drop compared to forearm segment)
CPN palsy	Reduced conduction velocity or conduction block at fibular head; reduced CMAP amplitude in peroneal nerve
Radial nerve palsy	Conduction block at spiral groove; reduced SNAP of superficial radial nerve

NCS Limitations — High Yield

False –ve: 'Normal limits' NCV, early disease where structural changes are not obvious ^[14]. In very early mononeuropathy or in purely small-fiber neuropathy, standard NCS may be entirely normal. NCS tests large myelinated fibers only — it cannot detect small fiber dysfunction (pain/temperature).

Principle: A needle electrode is inserted into the muscle, and spontaneous and voluntary electrical activity is recorded. EMG tells you about the health of the motor unit (anterior horn cell → axon → NMJ → muscle fiber).

Key findings in mononeuropathy:

EMG Finding	What It Means	Time Course
Fibrillation potentials & positive sharp waves	Spontaneous firing of denervated muscle fibres — indicates active/ongoing axonal denervation	Appear 2–3 weeks after axonal injury
Reduced recruitment	Fewer motor units firing during voluntary contraction — consistent with nerve damage reducing the number of functioning axons	Present from onset
Large, polyphasic motor unit potentials	Surviving axons have sprouted collateral branches to reinnervate orphaned muscle fibres — indicates chronic denervation with reinnervation	Weeks to months after injury
Normal insertional activity	Needle insertion causes normal brief burst of activity — suggests no denervation or very early disease	—

EMG is most useful in distinguishing myopathic causes of weakness from neuropathic cause ^[15]

Feature	Neuropathic Pattern	Myopathic Pattern
Fibrillations	Present (if axonal loss)	May be present in inflammatory myopathy
Motor unit potentials	Large, long duration, polyphasic (reinnervation)	Small, short duration, polyphasic
Recruitment	Reduced (fewer units, fire rapidly)	Early (many units fire at low effort)
Interference pattern	Reduced	Full but low amplitude

Baseline bloods: CBC, LRFT, glucose, B12/folate, TFT, ESR/CRP, autoimmune (ANA, RF, ANCA), SPE Ig ^[1]

Test	Rationale / What You're Looking For
Glucose / HbA1c	Diabetes mellitus — most common metabolic cause of mononeuropathy and mononeuritis multiplex ^[3]
TFT	Hypothyroidism → mucopolysaccharide deposition → tissue swelling → entrapment (especially CTS)
Vitamin B12 / Folate	B12 deficiency → polyneuropathy (not typical mononeuropathy, but important to exclude; B12 deficiency resulting in neuropathy / myelopathy ^[8])
CBC	Anaemia (B12/folate deficiency), leukocytosis (infection, vasculitis), thrombocytopenia (SLE)
LRFT (Liver and Renal Function Tests)	Renal failure → uraemic neuropathy; also β2-microglobulin amyloidosis in dialysis patients → CTS
ESR / CRP	Elevated in vasculitis, infection, inflammatory conditions; unexplained raised ESR is an indication for SPE ^[16]
ANA	SLE, Sjögren's (both can cause mononeuritis multiplex or focal neuropathy)
RF	Rheumatoid arthritis → synovial entrapment, rheumatoid vasculitis
ANCA	Vasculitis (GPA, EGPA, MPA) — important cause of mononeuritis multiplex
Serum protein electrophoresis (SPE) + Immunoglobulins	Investigation of unexplained neuropathy ^[16] → paraprotein-associated neuropathy (e.g., POEMS syndrome, Waldenström macroglobulinaemia, amyloidosis). 4 patterns: normal, pan-immunoparesis, raised polyclonal Ig, paraprotein ± immunoparesis ^[16]
Anti-ganglioside antibodies	If suspecting multifocal motor neuropathy (anti-GM1) or Miller Fisher syndrome (anti-GQ1b)
HIV serology	HIV can cause various neuropathies including mononeuritis multiplex
Lyme serology	If facial palsy in endemic area or appropriate exposure history

SPE in Unexplained Neuropathy

SPE is indicated for investigation of unexplained neuropathy ^[16]. If a patient has a mononeuropathy or polyneuropathy without an obvious cause, always consider sending SPE — paraprotein-associated neuropathies (e.g., anti-MAG neuropathy in Waldenström's, POEMS syndrome) are treatable and often missed.

Modality	Indication	Key Findings
Ultrasound of nerve	CTS, cubital tunnel, other superficial entrapment sites	Increased cross-sectional area of nerve at entrapment site; swelling proximal to compression; may visualize ganglion, tenosynovitis, or other space-occupying lesion
MRI of nerve/plexus	Plexopathy, tumour compression, inflammatory neuropathy, unexplained mononeuropathy	Nerve thickening/enhancement (T2 hyperintensity = oedema/inflammation); mass lesion (schwannoma, neurofibroma); denervation changes in muscle (T2 hyperintensity = acute denervation oedema, fatty replacement = chronic)
MRI brain + MRA/CTA	CN III palsy — to exclude compressive cause (PComA aneurysm); also for CN VI, VII to exclude structural lesions	Aneurysm, tumour, cavernous sinus lesion, brainstem infarct
X-ray	Fractures (humeral shaft → radial nerve, fibular neck → CPN), cervical rib (thoracic outlet syndrome), wrist (CTS)	Fracture line, cervical rib, arthritis
CT	Bony anatomy (cervical rib, fractures), lung apex (Pancoast tumour)	Mass, bony abnormality

MRI for denervation changes — how it works:

When a muscle is acutely denervated, it develops intracellular oedema → T2 hyperintensity on MRI (within days to weeks)
Chronically denervated muscle undergoes fatty infiltration → T1 hyperintensity (weeks to months)
This allows you to estimate the chronicity of denervation and identify which muscles are affected (confirming nerve territory)

These are effectively part of the clinical examination but function as diagnostic tests:

Test	Nerve/Condition	Technique	Positive Finding
Phalen's test	Median / CTS	Sustained wrist flexion 60 seconds	Paraesthesia in median nerve territory
Tinel's sign	Any entrapment	Tap over the nerve at compression site	Electric shock/paraesthesia in nerve territory
Elbow flexion test	Ulnar / Cubital tunnel	Sustained elbow flexion 60 seconds	Paraesthesia in ulnar territory
Froment's sign	Ulnar nerve	Grip paper between thumb and index finger	FPL compensates (median nerve) → IP joint flexion of thumb
Finkelstein's test	Not a neuropathy — de Quervain's	Thumb grasped, ulnar deviation of wrist	Pain at radial styloid (tenosynovitis, not nerve)
Straight leg raise	L5/S1 radiculopathy (not mononeuropathy)	Raise straight leg passively	Radicular pain at < 60°

Suspected Cause	Investigation
HNPP (hereditary neuropathy with liability to pressure palsies)	Genetic testing for PMP22 deletion
Vasculitis	ANCA, ESR/CRP, urinalysis, nerve + muscle biopsy
Leprosy	Skin slit smear for AFB, nerve biopsy, clinical (thickened nerves + hypopigmented anaesthetic skin patches)
Sarcoidosis	ACE level, CXR (bilateral hilar lymphadenopathy), tissue biopsy (non-caseating granulomas)
Paraneoplastic	Anti-Hu, anti-CV2, CT chest/abdomen/pelvis for occult malignancy

Clinical Scenario	First-Line Investigations	Second-Line if Needed
Typical entrapment (CTS, cubital tunnel)	Clinical diagnosis ± NCS/EMG	Ultrasound of nerve, wrist X-ray; TFT, glucose to identify predisposing conditions
Acute mononeuropathy in diabetic	Glucose/HbA1c (confirm DM), MRI/MRA brain if CN III palsy (exclude aneurysm)	NCS/EMG if atypical; autoimmune screen if no clear DM cause
Trauma / fracture-related	X-ray of affected area, NCS/EMG (2–3 weeks post-injury for baseline, repeat at 3 months)	MRI if no recovery; surgical exploration if neurotmesis suspected
Mononeuritis multiplex	Glucose/HbA1c, CBC, ESR/CRP, ANA, ANCA, RF, SPE/Ig, HIV, hepatitis B/C, urinalysis, NCS/EMG	Nerve + muscle biopsy (sural nerve); CSF if infection suspected
Unexplained progressive mononeuropathy	NCS/EMG, MRI of nerve/plexus, baseline bloods, SPE	Nerve biopsy, genetic testing (HNPP), paraneoplastic screen

Investigation approach to peripheral neuropathy: Glc/A1c, CBC, L/RFT, TFT, vit B12/B9, ESR/CRP, CXR → NCS → LP → Nerve biopsy → Genetic testing ^[17]

High Yield Summary — Diagnosis and Investigations of Mononeuropathy

Mononeuropathy is primarily a clinical diagnosis based on mapping deficits to a single nerve territory. Investigations confirm and characterize.
NCS + EMG are the cornerstone investigations:
- Axonal: ↓amplitude, normal velocity. Demyelinating: ↓velocity, normal amplitude ^[1].
- Only demyelinating neuropathies are usually susceptible to treatment ^[2].
- Normal NCS does not rule out CTS ^[5].
- False –ve: 'Normal limits' NCV, early disease where structural changes are not obvious ^[14].
Baseline bloods for aetiology: Glucose/HbA1c, TFT, B12, CBC, LRFT, ESR/CRP, autoimmune screen, SPE for unexplained neuropathy ^[16].
MRI brain + MRA/CTA: mandatory for CN III palsy to exclude PComA aneurysm (compressive = pupil-blown, ischaemic/DM = pupil-spared).
Nerve biopsy: last resort for inflammatory / infective / infiltrative disorders ^[1] — usually sural nerve.
Ultrasound of nerve: increasingly used for entrapment neuropathies — shows nerve swelling at compression site, can visualize ganglions and other structural causes.
Always ask: Why did this nerve get entrapped? Screen for predisposing conditions (DM, hypothyroid, RA, pregnancy, acromegaly, renal failure).

Active Recall - Diagnosis and Investigations of Mononeuropathy

References

^[1] Senior notes: Maksim Medicine Notes.pdf (Section 11.12 Peripheral neuropathy, p.269) ^[2] Senior notes: Ryan Ho Neurology.pdf (Section 10.2 Disease of the Peripheral Nerves, p.179) ^[3] Senior notes: Block A - Deterioration of eyesight in a diabetic patient_ diabetic complications.pdf (Diabetic Mononeuropathy section, p.7) ^[5] Senior notes: Maksim Surgery Notes.pdf (Section 5.2 Compression neuropathy, p.243–246) ^[8] Lecture slides: CFB_Neuro clinical skills demonstration_01.08.22_file to students.pdf (p.7–8) ^[14] Lecture slides: GCBA_Fundamentals_Neuro_Introduction to Neurological Investigations and Emergencies_Prof KC Teo.pdf (p.9) ^[15] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (EMG in inflammatory myopathy, p.1760) ^[16] Senior notes: Block A - Introduction to Haematological investigations (CBP, Clotting).pdf (SPE indications, p.27) ^[17] Senior notes: Adrian Lui Pediatrics Notes.pdf (Approach to generalized weakness investigation table, p.134)

Management of Mononeuropathy

Management by Aetiology

A. Entrapment Neuropathies (Most Common)

The classic stepwise approach applies: Conservative → Pharmacological → Surgical ^[5].

Local steroid injection ^[5] (for CTS and cubital tunnel):
- Mechanism: Corticosteroids reduce inflammation and oedema within the confined space → reduces pressure on the nerve
- Technique: Injection into the carpal tunnel (not into the nerve itself — avoid injection-related nerve injury)
- Evidence: Provides short-to-medium term relief (weeks to months); may need to be repeated; serves as a bridge while conservative measures take effect or while awaiting surgery
- Contraindications: Infection at injection site, bleeding disorders, allergy to corticosteroids; caution in diabetics (transient hyperglycaemia)
Pyridoxine (Vitamin B6) ^[5]:
- Used adjunctively in CTS and cubital tunnel
- Mechanism is not fully established; may have a role in nerve metabolism and repair
- Evidence is mixed; considered low-risk
Diuretics ^[5] (for CTS):
- Rationale: Reduce fluid retention → reduce carpal tunnel swelling
- Especially useful in pregnancy-related CTS or CTS with systemic fluid overload
- Typically short-term use
Neuropathic pain management (applicable across all aetiologies):
- First-line: Gabapentin or pregabalin — anticonvulsants that bind α2δ subunit of voltage-gated calcium channels → reduce excitatory neurotransmitter release at hyperexcitable nerve terminals. Why does nerve damage cause pain? Damaged nerves develop ectopic sodium channels and fire spontaneously → neuropathic pain. Gabapentinoids dampen this hyperexcitability.
- Alternative: Amitriptyline (tricyclic antidepressant) — blocks norepinephrine and serotonin reuptake in descending pain inhibitory pathways + sodium channel blockade. Useful when pain has a burning/continuous quality.
- Gabapentin/pregabalin/amitriptyline for neuropathic pain ^[18]
- Second-line: Duloxetine (SNRI), topical capsaicin, tramadol
- Avoid: Opioids for chronic neuropathic pain (limited efficacy, high addiction risk)

Drug	Mechanism	Side Effects	Notes
Gabapentin	α2δ Ca²⁺ channel ligand → ↓excitatory NT release	Drowsiness, dizziness, weight gain, peripheral oedema	Dose titration needed; renal excretion — adjust in CKD
Pregabalin	Same as gabapentin but more potent and predictable pharmacokinetics	Same as gabapentin	Can be used as first-line
Amitriptyline	TCA → NE/5-HT reuptake inhibition + Na⁺ channel block	Anticholinergic effects (dry mouth, constipation, urinary retention, sedation), cardiac arrhythmia	Contraindicated in recent MI, heart block; start low dose at night
Duloxetine	SNRI → NE/5-HT reuptake inhibition	Nausea, dizziness, insomnia	Alternative to TCA with fewer anticholinergic effects

Surgery is indicated when conservative management fails or when there is evidence of significant nerve compromise.

Carpal Tunnel Syndrome — Carpal Tunnel Release:

Surgical indications ^[5]:

CTS unresponsive to conservative treatment for 6 weeks
Associated sensory / motor deficit (thenar wasting or weakness of thumb abduction — indicates axonal loss, less likely to recover spontaneously)
Axonal loss on NCS (reduced CMAP amplitude = significant axonal degeneration has occurred; delay risks permanent damage)

Procedure: Carpal tunnel release (division of flexor retinaculum): open vs endoscopic ^[5]

Open: Direct incision over the carpal tunnel, the flexor retinaculum (transverse carpal ligament) is divided under direct vision. Gold standard; excellent visualisation.
Endoscopic: Smaller incision, camera-guided division of retinaculum. Faster recovery, less scar tenderness; but slightly higher risk of incomplete release or nerve injury due to limited visualisation.

Specific complications of carpal tunnel release ^[5]:

Persistent CTS symptoms (inadequate release) — the retinaculum was not fully divided
Nerve injury: palmar cutaneous branch — this sensory branch crosses the operative field
Vascular injury: superficial palmar arch — runs deep to the retinaculum
General surgical complications: infection, wound haematoma, CRPS (complex regional pain syndrome)

When to Refer for Surgery — CTS

The key surgical indications are: (1) failure of 6 weeks conservative treatment, (2) motor deficit (thenar wasting/weakness), (3) axonal loss on NCS. Do not wait for severe atrophy — by that point, axonal damage may be irreversible even after decompression. Early referral when motor deficit is present is emphasized in surgical teaching ^[5].

Cubital Tunnel Syndrome — Surgical Options:

Surgical procedures ^[5]:

Decompression in-situ: Release the cubital tunnel retinaculum without moving the nerve. Simplest procedure; suitable when the nerve is stable and there is no subluxation.
Medial epicondylectomy: Remove the bony prominence that the nerve rides over. Reduces compression without transposing the nerve.
Anterior transposition of ulnar nerve: The nerve is moved from behind the medial epicondyle to the front of the elbow (subcutaneous, submuscular, or intramuscular). Indicated when the nerve subluxes or when in-situ decompression has failed.

Common Peroneal Nerve — Surgical Decompression:

Indicated for extrinsic compression (e.g., ganglion at fibular neck) or if no recovery after 3–6 months of conservative management
Decompression of the nerve at the fibular head / neck
If complete transection → microsurgical nerve repair or nerve grafting

Other Site-Specific Procedures:

Condition	Surgical Procedure
Guyon canal syndrome	Release of Guyon canal roof; excision of ganglion if present
Thoracic outlet syndrome	First rib resection, scalenectomy, cervical rib excision
Tarsal tunnel syndrome	Release of flexor retinaculum at medial malleolus
PIN syndrome	Release of arcade of Frohse

Management depends on the Seddon classification of nerve injury:

Grade	Pathology	Management	Expected Recovery
Neurapraxia	Focal demyelination, axon intact	Observe: splint, physiotherapy, serial NCS/EMG. Recovery in days to weeks	Full recovery
Axonotmesis	Axon disrupted, endoneurium intact	Observe: serial monitoring. Axon regenerates at ~1 mm/day (~1 inch/month) along intact tubes	Good recovery (months)
Neurotmesis	Complete nerve transection	Surgical repair (primary neurorrhaphy or nerve grafting) — ideally within days to weeks	Variable; depends on timing of repair and gap length

Key management points in trauma:

Closed injuries (compression, traction): observe first; most are neurapraxia or axonotmesis and will recover. Perform NCS/EMG at 2–3 weeks (to establish baseline) and repeat at 3 months (to assess recovery).
Sharp transection (laceration, surgical injury): immediate or early surgical repair (primary neurorrhaphy within 72 hours if wound is clean; delayed primary repair within 2–3 weeks if wound is contaminated)
Fracture-associated (e.g., radial nerve in humeral shaft fracture): Most are neurapraxia from stretching/contusion → observe. If no clinical or EMG signs of recovery by 3–4 months → surgical exploration
Splinting to prevent contractures during recovery: e.g., wrist splint in extension for radial nerve palsy (prevents flexion contracture of wrist), AFO for foot drop

When mononeuropathy (or mononeuritis multiplex) is caused by vasculitis, the treatment targets the underlying inflammatory process:

High-dose corticosteroids (e.g., prednisolone 1 mg/kg/day or IV methylprednisolone pulse for severe cases): Rapidly suppresses vasa nervorum inflammation → prevents further nerve infarction
Steroid-sparing immunosuppressants:
- Cyclophosphamide (for severe systemic vasculitis — GPA, EGPA, PAN)
- Azathioprine (for maintenance after remission induction)
- Rituximab (anti-CD20, increasingly used in ANCA-associated vasculitis)
- Mycophenolate mofetil (alternative maintenance agent)
Treat the underlying condition: e.g., treat SLE, RA, hepatitis B/C-associated vasculitis

Vasculitis	Induction	Maintenance
ANCA-associated vasculitis (GPA, MPA, EGPA)	Cyclophosphamide or rituximab + high-dose steroids	Azathioprine, rituximab, or methotrexate + steroid taper
PAN	Cyclophosphamide + steroids (if severe); steroids alone (if mild)	Azathioprine
Rheumatoid vasculitis	High-dose steroids + cyclophosphamide or rituximab	DMARDs

Cause	Treatment
Bell's palsy (idiopathic CN VII)	Prednisolone 25 mg BD for 10 days (start within 72 hours) + eye protection (lubricant drops, tape at night to prevent exposure keratopathy). Antiviral (aciclovir/valaciclovir) is controversial — current evidence suggests steroids alone are sufficient for most cases, but antivirals are added in severe palsy.
Ramsay Hunt (VZV CN VII)	Aciclovir/valaciclovir + corticosteroids. Prognosis worse than Bell's palsy.
Leprosy	Multi-drug therapy (MDT): dapsone + rifampicin ± clofazimine. Steroids for acute neuritis (nerve inflammation/pain).
Lyme disease	Doxycycline (oral for early disease) or ceftriaxone (IV for neurological Lyme)
HIV-related	Antiretroviral therapy (ART); specific neuropathic pain management

Special Considerations

Cause	Conservative	Pharmacological	Surgical	Key Points
Entrapment (CTS)	Night-time wrist splint, physiotherapy, lifestyle modification ^[5]	Local steroid injection, pyridoxine, diuretics ^[5]	Carpal tunnel release (open/endoscopic) — if fails 6 weeks conservative, motor deficit, or axonal loss on NCS ^[5]	Treat predisposing conditions
Entrapment (cubital tunnel)	Soft elbow extension splint, physiotherapy, lifestyle modification ^[5]	Local steroid injection, pyridoxine ^[5]	Decompression in-situ, medial epicondylectomy, or anterior transposition ^[5]	Check for cubitus valgus
Trauma (neurapraxia)	Splint + physiotherapy	Neuropathic pain Rx	Not needed	Full recovery expected
Trauma (neurotmesis)	Splint to prevent contracture	Neuropathic pain Rx	Urgent surgical repair (neurorrhaphy ± grafting)	Early repair = better outcome
Diabetic	Eye protection, AFO for foot drop	Gabapentin/pregabalin/amitriptyline ^[18]; glycaemic control	Generally not needed	Self-limiting; control hyperglycaemia ^[18]
Vasculitis	—	High-dose steroids + immunosuppressants (cyclophosphamide, rituximab)	—	Urgent — prevent further nerve infarction
Bell's palsy	Eye care (lubricants, taping)	Prednisolone ± antivirals within 72h	Rarely needed	~70% spontaneous recovery
Neoplastic	—	Neuropathic pain Rx	Excision (schwannoma) or treat primary tumour	Pancoast → oncological Mx

High Yield Summary — Management of Mononeuropathy

Stepwise approach for entrapment: Conservative (splint, physiotherapy, lifestyle) → Pharmacological (local steroid injection, pyridoxine) → Surgical (decompression) ^[5].
CTS surgical indications: Unresponsive to conservative Rx for 6 weeks, associated sensory/motor deficit, axonal loss on NCS ^[5].
CTS surgery: Carpal tunnel release = division of flexor retinaculum, open vs endoscopic. Complications: persistent symptoms (inadequate release), nerve injury (palmar cutaneous branch), vascular injury (superficial palmar arch) ^[5].
Cubital tunnel surgery: Decompression in-situ, medial epicondylectomy, or anterior transposition of ulnar nerve ^[5].
Diabetic mononeuropathy: Generally self-limiting; management = glycaemic control + neuropathic pain relief (gabapentin/pregabalin/amitriptyline) + supportive measures ^[18]. MRI brain to exclude stroke/aneurysm if cranial nerve involved.
Traumatic nerve injury: Neurapraxia → observe. Axonotmesis → serial monitoring (recovery ~1 mm/day). Neurotmesis → urgent surgical repair.
Vasculitic mononeuritis multiplex: Emergency immunosuppression (high-dose steroids ± cyclophosphamide/rituximab) to prevent further nerve infarction.
Bell's palsy: Prednisolone within 72 hours + eye care. ~70% complete recovery.
Neuropathic pain: First-line = gabapentin/pregabalin or amitriptyline. Gabapentinoids work by binding α2δ Ca²⁺ channel subunit → ↓excitatory neurotransmitter release at hyperexcitable nerve terminals.
Always treat the underlying condition: DM → glycaemic control; hypothyroidism → levothyroxine; RA → DMARDs; obesity → weight loss.

Active Recall - Management of Mononeuropathy

References

^[3] Senior notes: Block A - Deterioration of eyesight in a diabetic patient_ diabetic complications.pdf (Diabetic Mononeuropathy section, p.7) ^[5] Senior notes: Maksim Surgery Notes.pdf (Section 5.2 Compression neuropathy — CTS and cubital tunnel management, p.244–245) ^[18] Senior notes: Ryan Ho Endocrine.pdf (Diabetic neuropathy management, p.97)

Complications of Mononeuropathy

Complications of mononeuropathy arise from three main sources: (1) the direct consequences of nerve dysfunction (motor, sensory, autonomic deficits), (2) complications of the underlying aetiology, and (3) complications of treatment. Understanding each requires tracing the problem back to its pathophysiological origin — why does loss of a single nerve lead to these downstream consequences?

A. Complications from Motor Deficit

B. Complications from Sensory Deficit

D. Neuropathic Pain Syndromes

Previously known as: Reflex sympathetic dystrophy (Type I) or causalgia (Type II)
Mechanism: Maladaptive neuroplastic response to nerve injury → regional pain far out of proportion to the inciting event + autonomic dysfunction + trophic changes. The exact pathophysiology involves peripheral sensitization, neurogenic inflammation, sympathetic-afferent coupling, and central sensitization.
Clinical features (three stages):

Stage	Features
Acute (0–3 months)	Burning pain, oedema, warmth, erythema, increased sweating
Dystrophic (3–6 months)	Pain persists, skin becomes cool and cyanotic, nail/hair changes, stiffness
Atrophic ( > 6 months)	Skin atrophy, contractures, osteoporosis, irreversible changes

Management: Early physiotherapy (graded motor imagery, mirror therapy), neuropathic pain agents, psychological support, bisphosphonates for bone changes, sympathetic nerve blocks in refractory cases

E. Complications of Treatment

Category	Specific Complication	Mechanism	Prevention/Management
Motor	Muscle wasting, permanent weakness	Denervation atrophy, motor endplate degeneration	Early decompression; physiotherapy
Motor	Joint contractures	Unopposed antagonist pull, immobility	Splinting in functional position, ROM exercises
Motor	Falls and gait abnormality	Foot drop → steppage gait	AFO, gait training
Sensory	Neuropathic ulcers	Loss of protective sensation → unrecognized trauma	Foot care education, daily inspection, appropriate footwear
Sensory	Charcot joint	Loss of proprioception → repeated microtrauma → joint destruction	Off-loading, immobilization; avoid weight-bearing
Sensory	Burns, accidental injuries	Loss of pain/temperature sensation	Patient education
Pain	Chronic neuropathic pain	Ectopic Na⁺ channel expression, central sensitization	Gabapentin, pregabalin, amitriptyline
Pain	CRPS	Maladaptive neuroplasticity after nerve injury	Early physiotherapy, mirror therapy, pharmacotherapy
Autonomic	Dry skin, cracking, infection risk	Anhidrosis from sympathetic denervation	Moisturizers, skin care
Surgical	Persistent symptoms, nerve/vascular injury	Inadequate release, iatrogenic damage	Experienced surgeon, careful technique
Injection	Tendon rupture, hyperglycaemia	Steroid-induced collagen weakening, insulin resistance	Limit injection frequency; monitor glucose in DM
Systemic	Other diabetic complications	Shared microvascular pathology	Screen for retinopathy, nephropathy; glycaemic control
Psychosocial	Depression, occupational disability	Chronic pain, functional loss	Psychological support, occupational therapy

High Yield Summary — Complications of Mononeuropathy

Irreversible weakness occurs when axonal degeneration is prolonged ( > 12–18 months) → motor endplates degenerate → muscle replaced by fat/fibrosis. Recovery occurs unless axonal loss has occurred ^[2]. This is why early treatment matters.
Neuropathic ulcers: Loss of protective sensation + microangiopathy + autonomic dysfunction → non-healing ulcers ^[19], especially on the feet in diabetics. Can lead to osteomyelitis and amputation.
Charcot joint: Loss of proprioception/pain → repeated joint microtrauma → progressive destruction. Trophic changes are a recognized complication of peripheral neuropathy ^[2].
Contractures: Develop within weeks if paralysed joints are not splinted and mobilized. Prevention (splinting + ROM exercises) is far easier than treatment of an established contracture.
CRPS: Disproportionate pain + autonomic + trophic changes after nerve injury. Early physiotherapy is the best preventive measure.
Surgical complications of carpal tunnel release: persistent symptoms (inadequate release), nerve injury (palmar cutaneous branch), vascular injury (superficial palmar arch) ^[5].
Diabetic mononeuropathy is a marker of systemic microvascular disease → always screen for the Big 3: retinopathy, nephropathy, neuropathy ^[19]. Good glycaemic control delays all complications ^[3].
Neuropathic pain: Affects quality of life profoundly. First-line pharmacotherapy: gabapentin/pregabalin or amitriptyline.

Active Recall - Complications of Mononeuropathy

References

^[2] Senior notes: Ryan Ho Neurology.pdf (Section 10.2 Disease of the Peripheral Nerves — trophic changes, prognosis, p.179–180) ^[3] Senior notes: Block A - Deterioration of eyesight in a diabetic patient_ diabetic complications.pdf (Chronic diabetic complications, p.6–7) ^[5] Senior notes: Maksim Surgery Notes.pdf (CTS surgical complications, p.244–245) ^[18] Senior notes: Ryan Ho Endocrine.pdf (Diabetic neuropathy management, p.97) ^[19] Senior notes: Block A - Polyuria and polydipsia_ glucose metabolism; diabetes mellitus; diabetic ketoacidosis.pdf (Screening for chronic complications, p.20); Endocrine Interactive Tutorial.pdf (Non-healing diabetic foot ulcer case, p.5) ^[20] Senior notes: Handbook of Internal Medicine 2024.pdf (Painful neuromas management, p.393)

High Yield Summary

Mononeuropathy = single nerve lesion. Most common cause is entrapment (MC) ^[1]^[2]. Most common overall is carpal tunnel syndrome ^[5].
Localize the lesion by matching motor and sensory deficits to a single nerve's territory. Nerve territory ≠ dermatomal territory.
LMN signs (weakness, wasting, fasciculation, hyporeflexia) are the hallmark of peripheral nerve lesions.
Diabetic mononeuropathy: microangiopathy → mononeuritis multiplex. Classic presentations: CN III (pupil-sparing ptosis + divergent squint), CN VI (lateral rectus palsy), CN V (facial pain), CPN (foot drop) ^[3]. "Mix and match" presentations ^[3].
Diabetic CN III vs compressive CN III: Pupil-sparing = ischaemic (diabetes). Pupil-blown = compressive (aneurysm) — the parasympathetic fibres run on the surface and are vulnerable to compression but not to central ischaemia.
Double crush syndrome: proximal compression renders nerve more susceptible to distal entrapment ^[5].
Key named signs: Tinel's (tap), Phalen's (wrist flexion), Froment's (paper grip), Wartenberg's (little finger abduction), wrist drop (radial), foot drop (CPN), claw hand (ulnar).
Nerve conduction studies differentiate axonal (↓amplitude, normal velocity) from demyelinating (↓velocity, normal amplitude) pathology — only demyelinating neuropathies are usually susceptible to treatment ^[2].
Seddon classification: Neurapraxia (myelin only, full recovery) → Axonotmesis (axon cut, connective tissue intact, good recovery) → Neurotmesis (complete transection, needs surgery).
For prognosis and management: early recognition and decompression of entrapment neuropathies prevents progression from reversible demyelination to irreversible axonal degeneration.

High Yield Summary — Differential Diagnosis of Mononeuropathy

Two-tiered approach: First localize (where?), then determine aetiology (what?).
Anatomical mimics (from GC lecture slides): Cerebrum, brainstem, spinal cord, anterior horn cells, nerve root, plexus, peripheral nerve, NMJ, muscle, bone/joints, metabolic, functional ^[8].
CPN palsy vs L5 radiculopathy: The classic differentiator is inversion (tibialis posterior) and hip abduction (gluteus medius) — both preserved in CPN palsy, both weak in L5 radiculopathy.
CTS differential: Cervical spondylosis, pronator teres syndrome, thoracic outlet syndrome, peripheral neuropathy ^[5].
Diabetic CN III vs PComA aneurysm: Pupil-sparing = ischaemic (DM). Pupil-blown = compressive (aneurysm).
Ptosis differential: CN III palsy (down-and-out), Horner's (partial ptosis, miosis, NO eye deviation), MG (fatigable, no pupil changes), aponeurotic (age-related, most common acquired ptosis).
Mononeuritis multiplex: Think DM (MC), vasculitis, sarcoid, Lyme, HIV, amyloid, HNPP, paraneoplastic.
Double crush syndrome: proximal compression renders nerve susceptible to distal entrapment — always examine the whole pathway ^[5].
Pathological differential framework: VINDICATE — Vascular, Infection, Neoplasm, Degenerative, Inflammatory, Congenital, Autoimmune, Trauma/Toxins, Endocrine ^[6]^[8].

High Yield Summary — Diagnosis and Investigations of Mononeuropathy

Mononeuropathy is primarily a clinical diagnosis based on mapping deficits to a single nerve territory. Investigations confirm and characterize.
NCS + EMG are the cornerstone investigations:
- Axonal: ↓amplitude, normal velocity. Demyelinating: ↓velocity, normal amplitude ^[1].
- Only demyelinating neuropathies are usually susceptible to treatment ^[2].
- Normal NCS does not rule out CTS ^[5].
- False –ve: 'Normal limits' NCV, early disease where structural changes are not obvious ^[14].
Baseline bloods for aetiology: Glucose/HbA1c, TFT, B12, CBC, LRFT, ESR/CRP, autoimmune screen, SPE for unexplained neuropathy ^[16].
MRI brain + MRA/CTA: mandatory for CN III palsy to exclude PComA aneurysm (compressive = pupil-blown, ischaemic/DM = pupil-spared).
Nerve biopsy: last resort for inflammatory / infective / infiltrative disorders ^[1] — usually sural nerve.
Ultrasound of nerve: increasingly used for entrapment neuropathies — shows nerve swelling at compression site, can visualize ganglions and other structural causes.
Always ask: Why did this nerve get entrapped? Screen for predisposing conditions (DM, hypothyroid, RA, pregnancy, acromegaly, renal failure).

High Yield Summary — Management of Mononeuropathy

Stepwise approach for entrapment: Conservative (splint, physiotherapy, lifestyle) → Pharmacological (local steroid injection, pyridoxine) → Surgical (decompression) ^[5].
CTS surgical indications: Unresponsive to conservative Rx for 6 weeks, associated sensory/motor deficit, axonal loss on NCS ^[5].
CTS surgery: Carpal tunnel release = division of flexor retinaculum, open vs endoscopic. Complications: persistent symptoms (inadequate release), nerve injury (palmar cutaneous branch), vascular injury (superficial palmar arch) ^[5].
Cubital tunnel surgery: Decompression in-situ, medial epicondylectomy, or anterior transposition of ulnar nerve ^[5].
Diabetic mononeuropathy: Generally self-limiting; management = glycaemic control + neuropathic pain relief (gabapentin/pregabalin/amitriptyline) + supportive measures ^[18]. MRI brain to exclude stroke/aneurysm if cranial nerve involved.
Traumatic nerve injury: Neurapraxia → observe. Axonotmesis → serial monitoring (recovery ~1 mm/day). Neurotmesis → urgent surgical repair.
Vasculitic mononeuritis multiplex: Emergency immunosuppression (high-dose steroids ± cyclophosphamide/rituximab) to prevent further nerve infarction.
Bell's palsy: Prednisolone within 72 hours + eye care. ~70% complete recovery.
Neuropathic pain: First-line = gabapentin/pregabalin or amitriptyline. Gabapentinoids work by binding α2δ Ca²⁺ channel subunit → ↓excitatory neurotransmitter release at hyperexcitable nerve terminals.
Always treat the underlying condition: DM → glycaemic control; hypothyroidism → levothyroxine; RA → DMARDs; obesity → weight loss.

High Yield Summary — Complications of Mononeuropathy

Irreversible weakness occurs when axonal degeneration is prolonged ( > 12–18 months) → motor endplates degenerate → muscle replaced by fat/fibrosis. Recovery occurs unless axonal loss has occurred ^[2]. This is why early treatment matters.
Neuropathic ulcers: Loss of protective sensation + microangiopathy + autonomic dysfunction → non-healing ulcers ^[19], especially on the feet in diabetics. Can lead to osteomyelitis and amputation.
Charcot joint: Loss of proprioception/pain → repeated joint microtrauma → progressive destruction. Trophic changes are a recognized complication of peripheral neuropathy ^[2].
Contractures: Develop within weeks if paralysed joints are not splinted and mobilized. Prevention (splinting + ROM exercises) is far easier than treatment of an established contracture.
CRPS: Disproportionate pain + autonomic + trophic changes after nerve injury. Early physiotherapy is the best preventive measure.
Surgical complications of carpal tunnel release: persistent symptoms (inadequate release), nerve injury (palmar cutaneous branch), vascular injury (superficial palmar arch) ^[5].
Diabetic mononeuropathy is a marker of systemic microvascular disease → always screen for the Big 3: retinopathy, nephropathy, neuropathy ^[19]. Good glycaemic control delays all complications ^[3].
Neuropathic pain: Affects quality of life profoundly. First-line pharmacotherapy: gabapentin/pregabalin or amitriptyline.

Mononeuropathy

Definition

Epidemiology

Anatomy and Function: Key Peripheral Nerves

Upper Limb Nerves

Median Nerve (C5–T1)

Ulnar Nerve (C8–T1)

Radial Nerve (C5–T1)

Lower Limb Nerves

Common Peroneal Nerve (L4–S1) (also called Common Fibular Nerve)

Lateral Cutaneous Nerve of Thigh (L2–L3) — Meralgia Paraesthetica

Femoral Nerve (L2–L4)

Sciatic Nerve (L4–S3)

Tibial Nerve

Cranial Nerve Mononeuropathies (Relevant to Diabetes)

Aetiology (with Focus on Hong Kong)

1. Entrapment / Compression (Most Common)

2. Trauma

3. Diabetes Mellitus

4. Vascular (Non-Diabetic)

5. Inflammatory / Autoimmune

6. Neoplastic

7. Infection

8. Iatrogenic

Pathophysiology of Nerve Injury

Seddon Classification of Nerve Injury

Mechanisms of Damage

Pathophysiology in Entrapment Neuropathies

Classification of Mononeuropathy

By Mechanism

By Anatomical Level

By Time Course

Clinical Features

General Principles

Specific Mononeuropathies: Symptoms and Signs with Pathophysiological Basis

A. Upper Limb

1. Carpal Tunnel Syndrome (Median Nerve at Wrist)

2. Pronator Teres Syndrome (Median Nerve at Elbow/Proximal Forearm)

3. Anterior Interosseous Syndrome (Pure Motor Branch of Median Nerve)

4. Cubital Tunnel Syndrome (Ulnar Nerve at Elbow)

5. Guyon Canal Syndrome (Ulnar Nerve at Wrist)

6. Radial Nerve Palsy

7. Thoracic Outlet Syndrome (Brachial Plexus ± Subclavian Vessels)

B. Lower Limb

1. Common Peroneal Nerve Palsy (at Fibular Neck)

2. Femoral Neuropathy

3. Lateral Cutaneous Nerve of Thigh — Meralgia Paraesthetica

4. Sciatic Neuropathy

5. Tarsal Tunnel Syndrome (Tibial Nerve at Medial Malleolus)

C. Cranial Nerve Mononeuropathies

Diabetic Cranial Mononeuropathies

Bell's Palsy (CN VII — Facial Nerve)

Long Thoracic Nerve Palsy

Accessory Nerve Palsy (CN XI)

Approach to Clinical Localization

Summary Table: Common Mononeuropathies at a Glance

Active Recall - Mononeuropathy

References

Level 1: Anatomical Differential — "Where Is the Lesion?"

1. Upper Motor Neuron Lesion (Cortex / Internal Capsule / Brainstem / Spinal Cord)

2. Radiculopathy (Nerve Root)

3. Plexopathy (Brachial or Lumbosacral Plexus)

4. Anterior Horn Cell Disease (Motor Neuron Disease)

5. Neuromuscular Junction Disorder

6. Myopathy

7. Functional (Non-Organic) Weakness

Differential Diagnosis by Specific Presentation

A. Wrist Drop (Inability to Extend Wrist)

B. Foot Drop

C. Hand Weakness / Numbness

D. Ptosis and/or Diplopia

Level 2: Pathological Differential — "What Is the Lesion?"

Differential Diagnosis of Specific Entrapment Neuropathies

Differential Diagnosis Decision Algorithm

Special Scenario: Mononeuritis Multiplex

The "Double Crush" Phenomenon in Differential Diagnosis

Active Recall - Differential Diagnosis of Mononeuropathy

Diagnostic Principles

Diagnostic Criteria by Specific Mononeuropathy

Carpal Tunnel Syndrome (CTS)