PERIPHERAL NEUROPATHIES

Neuropathies may be hereditary or acquired, generalized or localized and progressive or temporary (Table 18.40). Pathologically, neuropathies may be axonal (damage to axons) or demyelinating (damage to myelin covering the axon), though the difference is largely electrophysio­logical.

Some important peripheral neuropathies are discussed in this section, including Guillain-Barre syndrome- the commonest polyneuropathy in Indian children.

Guillain-Barre syndrome (GBS) is a post-infectious polyradiculoneuropathy characterized by acquired demyelination of motor and occasionally the sensory nerves, presenting as self-limiting, symmetrical, acute ascending flaccid paralysis.

According to pathological and electrophysiological characteristics, GBS is classified into 3 main subtypes —

TABLE 18.40: Important peripheral neuropathies

CongenitalZHereditary

Motor : Spinomuscular atrophy

Mixed : HMSN, e.g. Charcot-Marie-Tooth disease

Metachromatic leukodystrophies Others: Abetalipoproteinemia, porphyria

Autonomic : Familial dysautonomia (Riley-day syndrome)

Acquired

Guillain-Barre syndrome

Infections : Diphtheria, leprosy, bell palsy Toxins : Lead and arsenic poisoning

Drugs : Isoniazid, vincristine, cisplatin

Others : Uremia, malignancies, Bell palsy,

Vitamin B₁₂ deficiency, vasculitic neuropathies

HMSN: Hereditary motor-sensory neuropathies

(a) acute inflammatory demyelinating polyneuropathy (AIDP), (b) acute motor axonal neuropathy (AMAN), and (c) acute motor and sensory axonal neuropathy (AMSAN). AIDP is commonest variant (80-90%) while AMSAN is the most severe disease.

Incidence of GBS is 0.3-1.3/100000 children lt; 18 years of age.

Etiology: GBS is considered as an autoimmune reaction against protein component of the myelin, triggered by antecedent infections or vaccinations.

• Acute flaccid paralysis, typically bilaterally symmetrical and ascending, beginning from lower limbs with gradual involvement of trunk, upper limbs and bulbar muscles over few days. Deep tendon reflexes are usually absent but may be preserved in 30% cases.

• Respiratory failure due to bulbar, intercostals or diaphragmatic involvement in 20-30% cases.

• Paresthesia and pain in lower limbs is frequently present in early stages due to nerve root inflammation.

• Autonomic involvement with urinary retention and BP fluctuations in some cases.

Spontaneous recovery begins in 2-3 weeks from the last affected muscles and proceeds downwards. Recovery is usually complete and recurrent attacks are rare (lt;7%).

Rapid progression with maximum disability in 24 hours or persistent progression beyond 4 weeks suggests possibility of alternative etiology.

An uncommon variant of GBS, Miller-Fisher syndrome is characterized by a triad of Ataxia, areflexia and ophthalmological abnormalities.

Diagnosis depends on:

• Typical symmetrical neurological involvement,

• Abnormal CSF examination after the first week of illness, showing albumino-cytological dissociation in CSF, i.e. raised proteins and normal cell count.

• Abnormal nerve conduction studies after the first week of illness in 90% cases, suggestive of decreased NCV in AIDP variant and decreased muscle amplitude in AMAN variant.

• MRI spine with contrast imaging, showing selective anterior root enhancement, may be useful in early diagnosis of GBS, when electrophysiological findings are non-specific. It also helps to exclude other causes of AFP and myelopathy.

• Antiganglioside antibodies are present in 30% cases, though testing is not required in routine cases.

D/D of GBS includes other causes of acute flaccid paralysis (Table 10.36).

Management of GBS includes:

a. Specific therapy with:

• IV immunoglobulins 400 mg/kg/day for 5 days (or

1 gm/kg/day for 2 days), given early in the course of disease, i.e. within 2 weeks of the onset of weakness.

• Plasmapheresis (200-250 mg/kg plasma on 5 alternate day sessions) to eliminate demyelinating antibodies and other mediators in severe cases, is useful only if done within 4 weeks of weakness. However, it is not more effective than IVIG therapy.

b. Supportive therapy with:

• Monitoring for progression of weakness.

• Management of respiratory insufficiency and auto­nomic complications

• General nursing care for nutrition, hygiene, etc.

• Physiotherapy during recovery phase.

Outcome: While majority of cases improve within 3-6 weeks, reported mortality rate is ~3-10% due to respiratory failure and autonomic dysfunction, while many other are left with residual weakness or chronic pains/disability.

Treatment-related fluctuation (TRF) may occur in 10%, i.e. progression of symptoms within 2 months of initial improvement/stabilization after therapy, who might benefit with repeat course of treatment. Recurrence is rare but may occur in ~2-5%. Influenza vaccination is contraindicated in children with past history of GBS.

Chronic inflammatory demyelinating polyradiculo­neuropathy (CIDP) continues to progress beyond 4 weeks with relapsing-remitting course and concomitant sensory loss. Treatment includes long-term immunomodulator therapy with IVIG, steroids or repeated plasma exchange. Other important neuropathies in children are as follows: Hereditary neuropathies, though rare by themselves, account for ~70% of chronic peripheral neuropathies. Depending on prominent nerve involvement, this heterogeneous group may be divided into: (a) hereditary motor neuropathies, e.g.

Peroneal muscular atrophy (Charcot-Marie-Tooth disease) is commonest hereditary motor and sensory neuropathy (HMSN-I), discussed here. Other HMSN are very rare and include peroneal muscular atrophy of axonal type (HMSN-II), Dejerine-Sottas disease (HMSN-III), Roussy-Levy syndrome, etc.

Charcot-Marie-Tooth disease is a predominantly autosomal dominant peripheral neuropathy, which typically present in late childhood or adolescence with gait abnormalities, but some cases may present as early as 2 years or as late as in mid-adulthood. Peroneal and tibial nerves are the earliest and most severely affected.

Clinically, it is characterized by-(a) progressive distal lower limb weakness, (b) wasting of peroneal muscles, i.e. stork-neck deformity of legs, (c) foot drop due to weakness of ankle dorsiflexors, and (d) Pes cavus with hammer toe. Sensory loss is limited to position (proprioception) and vibration sense. Ankle jerk is usually lost earlier than knee jerk. Involved peripheral nerves may be palpably enlarged.

Disease is very slowly progressive and most patients remain ambulatory till old age. In late stages, disease may also involve distal upper extremities with atrophy of forearm and hand (claw-hand). Proximal weakness is minimal and axial muscles are spared.

Diagnosis rests on-(a) characteristic distribution of weakness with peroneal atrophy, (b) typical combination of absent ankle jerk with normal knee jerk in early stages, (c) marked slowing of motor and sensory conduction on NCS, and (d) sural nerve biopsy showing reduced number of myelinated fibers with onion-bulb formation due to collagen and Schwann cell proliferation.

Treatment is supportive with physiotherapy in early stages to prevent contractures and orthotic correction for ankle stabilization with splinting/special shoes.

Metabolic neuropathies are rare in childhood, caused by-(a) inborn errors of metabolism, e.g. porphyria, abetalipoproteinemia, Refsum disease, etc. (b) nutritional deficiencies, e.g. thiamine deficiency, and (c) late metabolic disorders, e.g. diabetes and uremia; discussed in relevant chapters.

Toxic neuropathies, common in Indian children are: Post-diphtheritic peripheral neuropathy is seen after 2-3 weeks of acute disease with loss of accommodation (occulomotor palsy) and bulbar involvement as earliest manifestations. Peripheral neuropathies are usually motor, symmetrical and often ascending, indistinguishable from GBS. Diaphragmatic paralysis is not uncommon.

Fig. 18.20: Bell (Facial) Palsy.

Drug-induced neuropathy is commonly seen with isoniazid (responds to pyridoxine), nitrofurantoin and anti-malignancy drugs, e.g. vincristine, cisplatin and cytosine arabinoside.

Heavy metal neuropathy is mostly associated with chronic lead poisoning, presenting as motor neuropathy, specially involving lower limbs.

Bell palsy is an acute unilateral infranuclear facial palsy as an isolated neurological defect, probably due to postinfectious immune-mediated demyelination.

Clinically, a classic case begins after 2-3 weeks of viral illness with acute onset of facial asymmetry and other signs of infranuclear facial palsy, sometimes associated with loss of taste in anterior 2/3rd of tongue. Exposure keratitis is common in unclosed eye. Most cases recover well in few weeks.

Diagnosis is clinical though other causes of infranuclear facial palsy, e.g. trauma, middle ear disease, facial nerve tumors and cerebrovascular insults must be excluded.

Treatment: Recovery is spontaneous, though corneal protection with lubricant eye drops, frequent facial massage (from below upwards) on affected side and supports to lift angle of mouth are advised during acute phase. Facial nerve stimulation may be used in cases with slower recovery. Other interventions, e.g. steroids and decompression of facial canal are of limited value (Fig. 18.20).

18.18.3