Peripheral Neuropathy — Viva Defence

Long case viva — diabetic neuropathy with superimposed vasculitis

Candidate's opening statement (SASPOP)

"Doctor, my patient is a 62-year-old man with a 15-year history of type 2 diabetes. His problems are: a chronic distal symmetric polyneuropathy from poorly controlled diabetes (3 years of burning foot numbness, stocking sensory loss, absent ankle reflexes, and a painless foot ulcer); a superimposed subacute mononeuritis multiplex affecting the right peroneal and ulnar nerves over 6 weeks — painful, asymmetric, and stepwise — which is the signature of vasculitic neuropathy and is a neurological emergency; systemic symptoms of weight loss and night sweats, suggesting an underlying systemic vasculitis or paraproteinaemic process; a small IgM kappa paraprotein that requires characterisation, including exclusion of cryoglobulinaemic vasculitis and hepatitis C; poor glycaemic control with an HbA1c of 78 mmol per mol; and a 20 pack-year smoking history contributing to his peripheral arterial disease and foot ulcer risk. My priorities are to confirm the vasculitic neuropathy with a sural nerve biopsy, initiate urgent immunosuppression to prevent further irreversible nerve infarction, manage the foot ulcer aggressively to prevent amputation, optimise his glycaemic and cardiovascular risk factor control, and characterise the paraprotein." [1]

Problem list

1. Chronic diabetic distal symmetric polyneuropathy with a painless foot ulcer (the triad of neuropathy, ischaemia, and deformity).
2. Subacute vasculitic mononeuritis multiplex (right peroneal and ulnar) — a neurological emergency.
3. Small IgM kappa paraprotein — possible cryoglobulinaemic vasculitis, anti-MAG, or incidental MGUS.
4. Systemic symptoms (weight loss, night sweats) — possible systemic vasculitis or malignancy.
5. Poor glycaemic control (HbA1c 78 mmol per mol).
6. Peripheral arterial disease and smoking — foot amputation risk. [1]

Integrated management plan

Confirm the diagnosis. The key investigation is a sural nerve biopsy to confirm vasculitic neuropathy, combined with a vasculitic and paraproteinaemic blood panel (ANA, ANCA, rheumatoid factor, cryoglobulins, complements, hepatitis B and C, HIV, anti-MAG antibody), and nerve conduction studies to document the background axonal DSPN and the superimposed axonal mononeuropathies. [1]

Treat the vasculitic neuropathy urgently. Once the biopsy is obtained, commence intravenous methylprednisolone 1 g daily for 3 to 5 days followed by oral prednisolone 1 mg per kg per day, with intravenous cyclophosphamide pulses for severe disease [4]. Add pneumocystis prophylaxis, gastric and bone protection, and monitor for cyclophosphamide toxicity (haemorrhagic cystitis, cytopenias, infection). Maintenance with azathioprine or methotrexate follows induction.

Manage the foot ulcer. Urgent podiatric and vascular assessment: debridement, offloading with a total contact cast, ankle-brachial index and vascular imaging for peripheral arterial disease, wound culture, and antibiotics for infection. The ulcer precedes 85 per cent of diabetes-related amputations and is preventable with early aggressive management [1].

Optimise glycaemic and cardiovascular risk. Intensify diabetes therapy, add a statin and antihypertensive, and counsel on smoking cessation. Glycaemic control is the only disease-modifying therapy for the DSPN, with the strongest effect in type 1 diabetes and a more modest effect in type 2. [1]

Control neuropathic pain. First-line pregabalin or duloxetine for the burning pain; short-term opioid analgesia for the acute vasculitic pain, which will improve with immunosuppression. [1]

Characterise the paraprotein. Anti-MAG antibody, cryoglobulins (sent and transported warm), hepatitis C serology, serum free light chains, and a bone marrow biopsy if the paraprotein is significant or haematology parameters are abnormal. [1]

Examiner probing questions

Examiner: "Why do you think this is two separate neuropathic processes rather than one?" [1]

Because the patterns are distinct and the time courses are different. The chronic (3-year), symmetric, length-dependent, painless neuropathy with absent ankle reflexes and a foot ulcer is the classic pattern of diabetic DSPN. The subacute (6-week), painful, asymmetric, stepwise involvement of two individual named nerves (peroneal and ulnar) is the classic pattern of mononeuritis multiplex, which is vasculitic until proven otherwise. The systemic symptoms and the paraprotein further support an independent vasculitic or paraproteinaemic process. A single process would not typically produce both patterns simultaneously. [1]

Examiner: "What would the nerve conduction studies show?" [1]

A background distal symmetric axonal sensorimotor neuropathy — reduced sural and peroneal amplitudes with relatively preserved conduction velocity — consistent with diabetic DSPN. Superimposed axonal mononeuropathies of the right peroneal and ulnar nerves — reduced amplitudes in those nerves with evidence of active denervation (fibrillation potentials) and chronic reinnervation (large polyphasic motor units) on needle EMG. The axonal pattern in the mononeuropathies, combined with the asymmetric stepwise evolution, is consistent with vasculitic nerve infarction rather than demyelination or entrapment [2].

Examiner: "How do you justify the nerve biopsy?" [1]

The sural nerve biopsy carries a risk of permanent sensory loss in the biopsied distribution and wound complications, so it is reserved for when the result will change management [2]. In this patient, the biopsy is justified because the suspected vasculitic neuropathy requires confirmation before committing to potentially toxic immunosuppression, and less invasive tests (bloods, NCS) may not be definitive. A combined nerve and muscle biopsy (sural and peroneus brevis) increases the yield for vasculitis.

Branching scenario — Guillain-Barre syndrome

Examiner: "Now consider a 45-year-old man who presents with progressive ascending weakness over 5 days, from the legs to the arms, with areflexia and mild facial weakness. He had a diarrhoeal illness 2 weeks ago. What is the diagnosis, the key investigations, and the management?" [1]

This is Guillain-Barre syndrome (GBS) — an acute, monophasic, immune-mediated demyelinating polyradiculoneuropathy, classically preceded by a Campylobacter jejuni gastrointestinal infection 1 to 3 weeks earlier [3]. The diagnostic triad is progressive symmetrical ascending weakness with areflexia reaching nadir within 4 weeks, CSF cytoalbuminologic dissociation (high protein, normal cell count — though the protein may be normal in the first week), and demyelination on nerve conduction studies (prolonged distal latencies, F-wave abnormalities, conduction block).

Management has three pillars. First, admit and monitor respiratory function — forced vital capacity, maximum inspiratory and expiratory pressures, and single breath count, with a low threshold for intensive care and mechanical ventilation (approximately 20 to 30 per cent require it). Second, immunotherapy — intravenous immunoglobulin 0.4 g per kg per day for 5 days, or plasma exchange (5 exchanges over 1 to 2 weeks), both equally effective and both should be given within 2 to 4 weeks of onset. Corticosteroids are not effective in GBS. Third, supportive care — prophylactic low-molecular-weight heparin for venous thromboembolism prophylaxis, autonomic monitoring (heart rate variability, blood pressure), pain management, nutrition, and early physiotherapy. The Miller Fisher variant (ophthalmoplegia, ataxia, areflexia) is associated with anti-GQ1b antibodies. Most patients recover fully or with minor residual deficits over months to 1 to 2 years. [1]

Branching scenario — CIDP

Examiner: "What if the weakness had progressed over 4 months rather than 4 days, with proximal and distal involvement and a relapsing course?" [1]

This is chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) — the chronic counterpart of GBS [1]. The distinction is the time course: GBS reaches nadir within 4 weeks, while CIDP progresses or relapses over more than 8 weeks. CIDP presents with symmetrical proximal and distal weakness, sensory loss, and diffuse areflexia, often with large fibre sensory involvement and a relapsing or progressive course. The 2021 EAN/PNS guideline classifies it as CIDP or possible CIDP, based on the clinical phenotype (typical versus atypical variants) and electrophysiological evidence of demyelination. CSF shows cytoalbuminologic dissociation.

Unlike GBS, corticosteroids are effective in CIDP. First-line treatment is intravenous immunoglobulin, corticosteroids, or plasma exchange (all effective); many patients need maintenance IV immunoglobulin infusions (0.4 to 1 g per kg every 2 to 6 weeks), and steroid-sparing agents (azathioprine, mycophenolate, rituximab) are used for refractory or steroid-dependent disease. The distinction from GBS matters because CIDP requires long-term immunotherapy while GBS is treated once acutely. [1]

Branching scenario — Charcot-Marie-Tooth disease

Examiner: "What if this were a 25-year-old woman with lifelong foot problems, pes cavus, hammer toes, and difficulty running, whose father has similar feet?" [1]

This is Charcot-Marie-Tooth disease (CMT) — the most common inherited neuropathy [5]. The clinical hallmark is a slowly progressive distal motor and sensory neuropathy beginning in childhood or adolescence, with the inverted champagne-bottle leg (wasted below the knee), foot deformity (pes cavus, hammer toes), stepping gait from foot drop, loss of ankle reflexes, and distal sensory loss that is often asymptomatic. The hands become involved later. The family history (autosomal dominant in CMT1 and CMT2) and the lifelong, slowly progressive course are the key discriminators from acquired neuropathies.

NCS partitions the subtypes: CMT type 1 (demyelinating, uniformly slowed conduction velocities) from PMP22 duplication on chromosome 17 (the most common cause), and CMT type 2 (axonal). Genetic testing — PMP22 duplication or deletion first, then a hereditary neuropathy gene panel — confirms the diagnosis. Management is supportive: podiatry, orthotics (ankle-foot orthoses for foot drop), physiotherapy, and avoidance of neurotoxic drugs (vincristine can cause severe worsening in CMT1). Life expectancy is normal. HNPP (PMP22 deletion) presents with recurrent painless pressure palsies. [1]

Branching scenario — critical illness polyneuropathy

Examiner: "A 55-year-old man has been in ICU for 3 weeks with severe sepsis and acute respiratory distress syndrome. He is now difficult to wean from the ventilator and has flaccid weakness in all four limbs. What is the diagnosis and how do you manage it?" [1]

This is critical illness polyneuropathy and myopathy (CIP and CIM) — the major causes of ICU-acquired weakness [4]. The presentation is flaccid quadriparesis and failure to wean from mechanical ventilation in a patient who has survived the acute critical illness. The pathophysiology involves microvascular dysfunction, hyperglycaemia, catabolism, and an acquired sodium channelopathy, with axonal degeneration (CIP) and muscle necrosis with myosin loss (CIM). Diagnosis is by electrophysiology (low amplitudes on motor and sensory NCS, myopathic changes on needle EMG) and clinical assessment; biopsy is rarely needed.

Management is primarily preventive: intensive insulin glycaemic control (modest effect), minimising sedation and neuromuscular blocking agents, early mobilisation, and nutrition. Recovery is slow and often incomplete — persistent weakness and disability at 1 to 2 years are common in survivors. The condition is an important cause of prolonged rehabilitation and reduced quality of life after critical illness. [1]

Short-case discussion — neurological examination of the lower limbs

Examiner: "Examine this patient's lower limbs. He has a peripheral neuropathy." [1]

My routine: general inspection for muscle wasting (especially the inverted champagne-bottle appearance of CMT, or distal wasting in any axonal neuropathy), foot deformity (pes cavus, hammer toes, claw toes), scars and ulcers, and fasciculations; tone (usually normal or reduced in a neuropathy); power in proximal (hip flexion, knee extension, knee flexion) and distal (ankle dorsiflexion, plantarflexion, toe flexion and extension, eversion and inversion) muscle groups, with attention to foot drop (L5, peroneal nerve); reflexes — knee jerks and ankle jerks, using the Jendrassik reinforcement manoeuvre if they appear absent; coordination (heel-shin testing); sensation to pinprick, light touch, vibration (128 Hz tuning fork at the great toe, moving proximally to find the sensory level), and joint position sense at the great toe; and gait including heel-toe walking and the Romberg test. [1]

Presentation: "Doctor, on lower limb examination there is distal muscle wasting, with weakness of ankle dorsiflexion bilaterally (MRC grade 4) and absent ankle reflexes with reinforcement. There is a stocking-distribution sensory loss to pinprick and vibration to the mid-shin bilaterally. Joint position sense is impaired at the great toes. Gait demonstrates a high stepping component, and Romberg is positive. These findings are consistent with a distal symmetric sensorimotor polyneuropathy, with sensory ataxia. I would proceed to nerve conduction studies to determine whether the process is axonal or demyelinating, and to a blood panel to identify the cause." [1]

Examiner: "How do you use the Jendrassik manoeuvre?" [1]

I ask the patient to hook their flexed fingers together and pull them apart hard while I strike the tendon. The manoeuvre reinforces the reflex arc by increasing gamma motor neuron activity, and it can reveal a reflex that appeared absent on standard testing. A reflex that is absent even with reinforcement is truly absent and indicates lower motor neuron, root, or plexus pathology. [1]

Examiner: "How do you distinguish sensory ataxia from cerebellar ataxia?" [1]

Sensory ataxia is due to loss of proprioceptive input (large fibre neuropathy, dorsal column disease). It worsens with eye closure — a positive Romberg sign — and is associated with loss of vibration and joint position sense. Cerebellar ataxia is present with the eyes open (because the cerebellum cannot coordinate movement regardless of visual input), and is associated with dysmetria on finger-nose and heel-shin testing, dysdiadochokinesia, nystagmus, and scanning dysarthria. The Romberg test is the key discriminator: a positive Romberg indicates sensory (proprioceptive) ataxia, not cerebellar ataxia. [1]