Clinical Analysis

• 60-year-old male
• Left foot drop × 9 years (chronic, longstanding)
• Right foot drop × 1 year (sequential asymmetric involvement)
• Slippage of slippers with awareness × 1 year (steppage gait, not proprioceptive loss)
• Bilateral distal upper limb weakness — ulnar-innervated muscles + intrinsic hand muscles

Differential Diagnoses

1. Charcot-Marie-Tooth Disease (HMSN) — Most Likely

• Autosomal dominant (usually CMT1A — PMP22 duplication) or CMT2
• Onset asymmetric, slowly progressive over decades — fits left foot drop for 9 years
• Distal lower limb > upper limb involvement; intrinsic hand wasting is characteristic
• Pes cavus, absent ankle jerks, "inverted champagne bottle" legs
• Slippage of slippers = steppage gait (not sensory ataxia — patients trip, don't feel imbalanced)
• Key: the asymmetric onset (left before right, 8-year gap) is consistent with CMT

2. Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)

• Asymmetric, episodic mononeuropathies at compression sites (peroneal at fibular head → foot drop; ulnar at elbow → intrinsic hand weakness)
• Fits perfectly with sequential nerve palsies at typical entrapment sites
• PMP22 deletion; allelic to CMT1A
• EMG shows focal conduction slowing at compression sites + diffuse mild neuropathy
• Often misdiagnosed as recurrent carpal tunnel / peroneal palsies

3. Multifocal Motor Neuropathy (MMN)

• Pure motor neuropathy with asymmetric, progressive weakness in individual nerve distributions
• Ulnar (intrinsic hand wasting) and peroneal (foot drop) nerves are commonly affected
• Anti-GM1 antibodies positive in ~50%
• EMG: conduction block in motor fibers, normal sensory conduction
• Differentiated from CMT by asymmetry, later onset, and response to IVIg
• Age 60 + progressive asymmetric involvement makes this a key differential

4. Amyotrophic Lateral Sclerosis (ALS) — Lower Motor Neuron Predominant

• Can present with foot drop + intrinsic hand wasting (both peroneal and ulnar-territory muscles affected)
• Bradley & Daroff describes "severe intrinsic hand muscle atrophy with claw hand and atrophy of muscles innervated by both ulnar and median nerves" in ALS
• ALS typically begins unilaterally in a limb — the 9-year left foot drop then right foot drop fits a slow, spreading LMN pattern
• However, absence of UMN signs, bulbar symptoms, or rapid progression would weigh against
• Distinguish by: absence of sensory involvement + EMG showing active denervation in multiple myotomes + UMN signs

5. Progressive Spinal Muscular Atrophy (pSMA) / Distal SMA (Kennedy's Disease)

• Lower motor neuron degeneration without sensory involvement
• Distal SMA (DSMA) can selectively affect peroneal muscles causing foot drop + hand intrinsics
• Kennedy's disease (SBMA) in males — X-linked; progressive bulbospinal muscular atrophy + gynecomastia + sensory neuropathy; can mimic this presentation
• Progressive spinal muscular atrophy was specifically listed by Adams & Victor in the differential for steppage gait/foot drop

6. Distal Myopathy (Myopathic Causes)

• Adams & Victor notes: "certain types of muscular dystrophy in which the distal musculature is involved" can cause steppage gait
• Myotonic dystrophy type 1 (DM1): distal leg weakness + hand/forearm weakness; presents in adults; also: myotonia, ptosis, cataracts, cardiac arrhythmia
• GNE myopathy (Nonaka): bilateral foot drop from anterior tibialis involvement, later involving hand/upper limb; rimmed vacuoles on biopsy
• Welander distal myopathy: late-onset weakness of finger extensors → intrinsic hand → distal LL
• Clinical clue against myopathy: preserved intrinsic hand bulk despite weakness is more typical of neuropathy; myopathy usually has proportional wasting

7. Paraproteinemic / Inflammatory Polyneuropathy (CIDP / POEMS)

• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) can present with distal-predominant motor weakness
• POEMS syndrome (paraprotein + organomegaly + endocrinopathy + M protein + skin changes) causes progressive motor-predominant neuropathy
• Paraproteinemic neuropathies specifically mentioned in Adams & Victor as presenting "in the same way" as CMT with bilateral foot drop and hand weakness
• Check: serum protein electrophoresis, immunofixation

8. Mononeuritis Multiplex (Vasculitic Neuropathy)

• Sequential involvement of individual named nerves (left peroneal → right peroneal → bilateral ulnar)
• Causes: PAN, rheumatoid vasculitis, cryoglobulinemia, diabetes, sarcoidosis
• The asymmetric onset and slow progression fits; however, vasculitic mononeuritis typically has pain and is subacute to acute in each nerve
• 9-year course would be unusually indolent for vasculitis

Summary Table

Recommended Work-Up

1. Nerve conduction studies + EMG — most important first step: distinguishes neuropathy vs. myopathy vs. motor neuron disease; identifies conduction block (MMN), demyelination (CMT/CIDP), or axonal loss
2. Genetic panel — PMP22 duplication/deletion (CMT1A/HNPP), AR/GJB1/MPZ genes; CAG repeat for Kennedy's
3. Anti-GM1 antibodies — for MMN
4. Serum SPEP + immunofixation — POEMS, CIDP
5. CK level — mildly elevated in distal myopathies
6. Family history — essential for CMT/HNPP
7. MRI spine (cervical + lumbosacral) — rule out structural cord/root pathology
8. Muscle biopsy — if myopathy suspected despite EMG (rimmed vacuoles = GNE/IBM)