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Dizziness , somnolence

Topical lidocaine

Three weeks ++ Local erythema , rash is common Local irritation

# Ceiling dose = dose at which the drug reaches its maximum effect . Increasing the dose beyond the ceiling dose does not proportionately increase its effectiveness and leads to a lower therapeutic index . * Therapeutic index = the measure of relative occurrence of beneficial effects to adverse effects . The higher the therapeutic index , the safer and better tolerated the drug .

neuropathy through the involvement of complex biochemical and signalling pathways . Treating hyperlipidaemia may slow the progression of diabetic

39 , 40 neuropathies .

A Cochrane review concluded that enhanced glycaemic control can help reduce the progression of diabetic neuropathy in patients with type 1 diabetes and possibly also type 2 . ⁴¹

Although no definitive recommendation can be made , treatment with 600mg alpha-lipoic acid orally has been shown to improve neuropathic symptoms in diabetic sensory neuropathy when treated for four years . ⁴²

With the lack of definitive treatment , symptomatic therapy for neuropathic pain often becomes the mainstay of treatment , especially in advanced stages of the disease . This includes tricyclic antidepressants , SNRIs and anticonvulsants .

Pregabalin , gabapentin , duloxetine , amitriptyline and opioids are effective in the management of diabetic neuropathic pain as evidenced in multiple class I or II clinical studies . ³²

When treating patients with neuropathic pain , bear in mind that pain is a subjective experience and psychosocial factors modify its perception . ⁴³

Treatment of orthostatic hypotension , a common manifestation of diabetic autonomic neuropathy , includes maintaining adequate hydration , elevating the bed and educating patients regarding situations that predispose them to symptoms , such as hot showers and quick changes of position . Some patients may require pharmacotherapy with mineralocorticoids ( such as fludrocortisone ). ³²

METABOLIC AND TOXIC NEUROPATHIES

CHRONIC alcohol misuse is associated with axonal polyneuropathies either through direct toxicity or secondary vitamin deficiencies . Neuropathy from direct alcohol-related toxicity is more likely to present as a slowly progressive small fibre neuropathy in contrast to the predominant large fibre affliction common with vitamin deficiency related neuropathies . ⁴⁴

Box 1 . Classification of diabetic neuropathies

• Distal symmetric polyneuropathy : — The most common type of neuropathy , affecting almost half of patients with diabetes . — Slowly progressive sensory symptoms that start distally and ascend proximally as axonal degeneration progresses ( see figure 2 ).

• May manifest as discomfort or frank pain in the legs that is worse at night :

• Pain can be perceived as a burning or searing in the feet , with autonomic dysfunction from small fibre involvement manifesting as persistently cold feet .

• The pain may extend as axonal degeneration progresses and involve calves and eventually hands . Tingling and numbness accompany the involvement of large fibres .

— Clinical features in the early stages may be limited to distal loss of pain and cold perception , sudomotor changes and minimal-to-no muscle weakness and wasting .

— Features may include burning paraesthesia and autonomic disturbances followed by loss of sensation and imbalance . As the symptoms reach the level of the knee , manifestations often emerge in the hands . ³³

• Autonomic neuropathy : — Autonomic neuropathy results from small fibre involvement that often predates the development of frank diabetes and may be present in patients with glucose intolerance . — Signs of autonomic dysfunction are found in up to 75 % of patients with type 1 diabetes at the time of diagnosis . ³⁵ — Diabetic autonomic neuropathy commonly manifests with cold feet , discoloration and hypohidrosis resulting in dry skin , development of fissures and cracks ( see figure 3 ). ³²

• Diabetic amyotrophy / plexopathies ( lumbosacral and cervical ): — This is characterised by asymmetric proximal weakness that may be associated with remarkable , unintentional weight loss ( see figure 4 ). — It is usually independent of the disease duration . — A high index of suspicion enables diagnosis and treatment and avoidance of inappropriate spinal surgical intervention . — Electrophysiological testing is helpful in documenting multifocal involvement of nerve roots , plexus , and peripheral nerves . ³⁶ — MRI of the affected region may show nerve root enhancement . — Treatment has traditionally focussed on immunomodulation either with steroids or IVIg although a 2012 Cochrane review found no evidence to support the use of immunotherapy . ³⁷

• Diabetic neuropathic cachexia : — Acute painful neuropathy affecting mainly the truncal region accompanied by unintentional weight loss . — The predominantly truncal and symmetric involvement differentiates this from diabetic amyotrophy . ³²

• Neuropathy associated with hypoglycaemia and hyperinsulinemia : — Rapid glycaemic control , especially in patients with long-standing poorly controlled diabetes , may lead to severe burning paraesthesias , pain and autonomic dysfunction ; this is often resistant to treatment and resolves with continued glycaemic control . — This is seen with both oral hypoglycaemic agents and insulin and is also referred to as treatment-induced neuropathy of diabetes mellitus or insulin neuritis in the context of insulin . ³²

• Other diabetic neuropathies — Oculomotor nerve palsy ( sometimes with pupillary involvement ) and abducens palsy , possibly from microvascular involvement , may occur . — Compressive neuropathies in the upper limb , including carpal tunnel syndrome and ulnar compressive neuropathies , occur more frequently in patients with diabetes . ³²

Uraemic neuropathy is a symmetrical sensorimotor polyneuropathy found in up to 90 % of patients with a glomerular filtration rate ( GFR ) less than 6mL / min / 1.73m2 ( normal GFR is more than 90mL / min / 1.73m ² ). ⁴⁵ Electrodiagnostic features may be evident earlier , when the GFR falls below 12mL / min . ⁴⁵ Uraemic neuropathy presents as axonal polyneuropathy with predominant involvement of large sensory fibres , causing paraesthesia and distal sensory loss in the lower limbs . Motor involvement occurs with disease progression , leading to weakness and muscle atrophy , which

45 , 46 is most prominent distally . Inherited axonal neuropathies require a high index of suspicion ; consider these in children presenting with foot deformities ( such as pes cavus and hammer toes ) and lack of positive sensory symptoms despite prominent sensory involvement . ⁴⁷

No cause is found in around 20-30 % of patients with axonal polyneuropathy , despite extensive diagnostic evaluation . Chronic idiopathic axonal neuropathy is usually slowly progressive , with most patients developing mild to moderate disability . ⁴⁸

Factors thought not to be directly causative of neuropathy are likely to predispose to the development of chronic idiopathic axonal neuropathy . These include obesity , metabolic syndrome , dyslipidaemia and hypertension . ⁴⁹

Table 4 outlines commonly