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mainstay of definitive treatment . Both are equally effective in reducing time to walk unaided and time on ventilator . ⁵⁷ Various clinical parameters determine the time of initiation of these therapies , and the choice is guided by availability and the patient ’ s comorbid conditions . Plasma exchange results in physical removal of immune moieties including autoantibodies , cytokines , complement and immune complexes and boosts suppressor T-cell function . IVIg is pooled IgG from blood donors that significantly boosts the recipient ’ s serum IgG . Steroids are contraindicated , as IV steroids are no better than placebo and oral steroids may worsen the outcome . ⁵⁷

Chronic acquired demyelinating polyneuropathies

These conditions ( CIDPs ) are classified based on their pattern of motor and sensory involvement ( see table 6 ). Although this assists with early clinical detection , in the absence of definitive pathophysiological mechanisms underlying these disorders , there may be significant overlap between the groups . It is important to recognise this group of disorders , as many of them respond extremely well to immunomodulation ( including with corticosteroids ).

Pioneering research by Dyck et al outlined criteria to facilitate early diagnosis . In patients presenting with symmetric motor and sensory involvement with progression beyond four weeks from onset , these are : clinical hyporeflexia , CSF albuminocytologic dissociation , neurophysiological evidence of demyelination , and neuropathological evidence of demyelination and inflammation on nerve biopsy . ⁶⁰

Clinical acumen takes precedence over rigid adherence to specific diagnostic criteria . ⁵⁷

In patients with CIDP who have exclusive distal involvement ( this is uncommon ), it is vital to exclude metabolic / toxic , vasculitic and hereditary causes . Response to therapy may vary in patients with CIDP who have purely distal involvement . ⁶¹

The is no difference in efficacy between corticosteroids , IVIg and plasmapheresis , so the choice is often guided by the individual ’ s ease of access to therapy . ⁵⁷

Pulsed steroid therapies have similar efficacy to daily oral steroids , with

Figure 5 . Cervical spinal cord MRI in a 49-year-old male presenting with subacute combined degeneration due to a deficit of B12 .

A . The midsagittal T2 weighted image shows linear hyperintensity in the posterior portion of the cervical tract of the spinal cord ( black arrows ).

B . Axial T2 weighted images reveal the selective involvement of the posterior columns .

62 , 63 significantly fewer adverse effects . More than two-thirds of patients respond to one of the three initial therapies ( steroids , IVIg , plasmapheresis ) and more than 89 % respond will respond to one of them . ⁶⁴

Alternate modes of immunomodulation , including mycophenolate mofetil , azathioprine , methotrexate cyclophosphamide , cyclosporine and rituximab , are offered to those who do not respond to initial therapy . ⁶⁴

It is important to distinguish DADS ( distal acquired demyelinating symmetric neuropathy ) from toxic / metabolic / vasculitic neuropathies , MMN ( multifocal motor neuropathy ) from MND ( motor neurone disease ) and MADSAM ( multifocal acquired demyelinating sensory and motor neuropathy ) from HNPP ( hereditary neuropathy with pressure palsies ) given the potential for treatment in these patients who present differently from the classic presentation of CIDP with symmetric proximal and distal motor and sensory involvement . Box 2 highlights the importance of differentiating between the neuropathies .

Subacute inflammatory demyelinating polyneuropathy

Patients who progress clinically beyond four weeks but not more than eight weeks and have neither acute inflammatory demyelinating polyneuropathy ( AIDP ) nor CIDP are classed as having SIDP . These patients have high rates of complete recovery , have a good chance of not experiencing relapse within two years of onset , and are more likely to have a history of infection preceding the onset ( thereby being closer to AIDP than CIDP in long-term prognosis ). ⁶⁷

Acquired immune axonal neuropathies

Immune axonopathies have a diverse clinical presentation ranging from mononeuropathy to plexopathy and can include radiculopathy , cranial neuropathies and small fibre neuropathies . ⁶⁸ They manifest on neurophysiological testing as relatively preserved motor / sensory latencies and velocity of conduction with reduced amplitude of compound muscle action potential ( CMAP ) and sensory nerve action potential ( SNAP ).

While neurological and neurophysiological features delineate the axonal

Table 5 . Carpal tunnel syndrome stratification

Severity of CTS

Clinical features Neurophysiology Treatment

Moderate

Severe

Sensory symptoms with some motor symptoms ( dropping of objects , clumsiness with fine motor skills )

Sensory symptoms with motor symptoms including weakness of APB , opponens pollicis and wasting of thenar eminence ( see figure 7 )

nature of involvement , systemic features may identify the secondary immune mechanisms , such as vasculitis , underlying acquired immune axonopathies ( see table 7 ). The pathophysiology of vascular inflammation with hyalinisation of the vasa nervorum leads to vascular occlusion and necrosis of the nerve axon .

Painful mononeuropathies at sites not prone to compression should raise suspicion of a vasculitic neuropathy .

Reduced amplitude of SNAP , prolonged sensory latency and reduced sensory nerve conduction velocity with mild prolongation of distal motor latency

Absent SNAP , reduced CMAP amplitude or absent CMAP , changes of denervation on needle EMG

Ancillary serology ( rheumatoid factor , ANA , dsDNA , c-ANCA , p-ANCA , SSA and SSB [ antinuclear antibodies ], infectious serology [ HIV , hepatitis B , hepatitis C , syphilis , CMV , Lyme disease ]) may identify a cause of secondary vasculitic neuropathy . Direct further investigation based on the type of vasculitis suspected . Nerve biopsy may be required to establish inflammation . ⁶⁸

Immunomodulation is the mainstay of treatment , and the regimen is based

Wrist splint Anti-inflammatory agents , antineuralgic agents ( pregabalin , gabapentin , duloxetine )

Local steroid injections

Decompressive surgery to transect the transverse carpal ligament

NCS = nerve conduction study , APB = abductor pollicis brevis , SNAP = sensory nerve action potential , CMAP = compound muscle action potential , EMG = electromyography

Figure 7 . Untreated carpal tunnel syndrome with wasting of the thenar eminence .

Table 6 . CIDP clinical types

Type of CIDP

Classic CIDP

Treatment

Steroids , IVIg , plasma exchange ( PE )

Figure 6 . Illustration of carpal tunnel syndrome .

Steroids , IVIg , PE

IVIg preferred Avoid steroids

Ancillary diagnostic features

Demyelination on neurophysiology and pathology , Albuminocytologic dissociation on CSF

Distal demyelination on neurophysiology

Demyelination on neurophysiology

Conduction blocks , AntiGM1 Ab

Box 2 . Importance of differentiating between neuropathies

• Differentiate between classic CIDP and AIDP since CIDP responds to steroids and AIDP is often worsened by steroids .

• Differentiate DADS neuropathy from the more prevalent metabolic axonopathies ( for example , diabetic neuropathy ) and from classic CIDP as the response to treatment varies with each entity .

• Both MMN and MND present with asymmetric pure motor involvement : — Motor involvement in the pattern of individual nerves , rather than the spinal myotome , reinforces a diagnosis of MMN in a patient with asymmetrical weakness that starts in upper limbs and resembles the presentation of motor neuron disease .

— While antiGM1 antibodies and the presence of conduction blocks help in diagnosis , their absence does not exclude the diagnosis of MMN provided other neurophysiological and clinical features of demyelination exist . ⁵⁷

— Unlike classic CIDP , plasmapheresis and / or steroids are not consistently effective in patients with MMN and may exacerbate the condition ; IVIg is the preferred option . ⁶⁵

• The clinical , neurophysiological and CSF features of MADSAM strikingly resemble those of HNPP ; genetic testing for HNPP may be required . It is also important to differentiate MADSAM from MMN given that the former ’ s responds to steroids while steroids may worsen MMN . ⁶⁶

Important differentials

AIDP

Toxic , metabolic , vasculitic neuropathies

HNPP , MMN

MND , MADSAM