One of the five most common reasons for neurologic consultation
Prevalence in the general population is 2.4% and increases with advancing age to an estimated 8% in individuals older than 55 years.
It is estimated that 15–20 million people in the United States have some form of peripheral neuropathy.
In patients with newly diagnosed diabetes is evident in 8% of cases and increases with disease duration to 30-60%, depending upon the definition by clinical or electrophysiological criteria.
Prevalence of neuropathy is about 20% in obese individuals.
Occurs in more than 6% of the population older than age 60 years.
Loss of Achilles tendon reflex and vibratory sensation are the earliest symptoms of diabetic neuropathy.
The most important neurologic finding is the loss of protective sensation.
Distal symmetric polyneuropathy in the primary care setting is the most common systemic complication of diabetes mellitus.
Patients usually present with sensory signs or symptoms before motor or autonomic symptoms prevail.
Sensory symptoms of numbness, tingling, weakness, autonomic symptoms of early satiety, impotence, orthostatic hypotension, sweating abnormalities, burning, stabbing, electrical discomfort suggest the presence of a peripheral neuropathy.
Sensory fibers include large diameter fibers mediating vibratory sensation and proprioception and small diameter fibers mediating pain and temperature sensation.
Most neuropathies affect both large and small fibers, and symptoms vary on the basis of the relative involvement of each group.
When motor deficits are equal to or greater than sensory deficits, demyelinating disorders such as chronic inflammatory demyelinating polyneuropathy and hereditary neuropathies are considered.
The sensory examination should test both large and small fibers-large fibers relate to vibratory and proprioception and small fibers pain and temperature.
Proprioception abnormalities manifest as sensory ataxia, mimicking cerebellar dysfunction.
The Romberg sign is an effective screening tool for sensory ataxia.
Deep tendon reflexes may be diminished in a links dependent pattern with unobtainable ankle reflexes.
Diffuse arreflexia should indicate the presence of chronic inflammatory demyelinating polyneuropathy or hereditary neuropathy.
Asymmetrical reflexes may suggest mononeuropathy or a radiculopathy.
Accentuated deep tendon reflexes suggest a superimposed CNS involvement, such as cervical spinal stenosis or vitamin B 12 deficiency.
Neuropathic pain occurs in 1/3 of patients with peripheral neuropathy.
Some patients experience hyperesthesia, an accentuated sensation of tactile stimulation, or allodynia, the perception of normally non-painful stimuli as painful.
Autonomic symptoms are often underrecognized, but have a great impact on quality of life.
Orthostatic intolerance, gastroparesis, constipation, diarrhea, neurogenic bladder, erectile dysfunction, pupillomotor and vasomotor symptoms, leading to dry eyes, mouth, skin was burning and flushing are relatively common.
On rare occasions autonomic symptoms may be the most prominent or only symptoms indicating neuropathy.
Most common in patients with diabetes mellitus, HIV, dysproteinic disorders and in patients receiving chemotherapy.
When symptoms of neuropathy develop acutely, differential diagnosis is narrowed significantly: Guillain-Barre syndrome, vasculitis, critical illness polyneuropathy, porphyria, and toxic exposure.
Differential diagnosis-diabetes, amyloidosis, paraproteinemia, autoimmune disorders lupus, Behcet’s disease, antiphospholipid syndrome, ating polyneuropathies, Guillain-Barre syndrome, hereditary sensory and autonomic neuropathy, Charcot-Marie Tooth disease, Friedreich’s ataxia, HIV medications, hypothyroidism, acromegaly, hepatitis B, hepatitis C, HIV, Lyme disease, leprosy, vasculitis, chronic inflammatory ating polyradiculopathy, sarcoidosis, primary biliary cirrhosis, paraneoplastic syndromes, lymphoma, Hodgkin’s disease, multiple myeloma, amiodarone, colchicines, isoniazid, metronidazole, nitrofurantoin, hydralazine, phenytoin, statins, fibrates, vitamin B12 deficiency, folic acid deficiency, vitamin B1 deficiency, deficiency of copper, supratherapeutic doses of pyridoxine, exposure to cold, exposure to hypoxia, renal insufficiency, toxic exposure to alcohol, arsenic, lead, mercury or organophosphorous agents.
Symptoms of loans such as burning feet and poor diagnostic accuracy for neuropathy.
Neurologic examination findings such as sensory loss or absent ankle jerks are more sensitive and specific.
The presence of two or three suggestive symptoms, abnormal temperature sensation, or diminished reflexes are 87% sensitive and 91% specific for neuropathy.
Neuroimaging is not routinely indicated in patients with neuropathy, but is considered when examination suggest a concurrent myelopathy or when the diagnosis of neuropathy is not firmly established and lumbosacral radiculopathy remains in differential diagnosis.
The most reliable diagnosis for neuropathy rests on the combination of symptoms, neurologic findings on examination, and confirmatory testing on nerve conduction studies and electromyography.
A study of Medicare patients demonstrated that only 20% of patients underwent electrodiagnostic examinations within six months of their initial diagnosis of neuropathy.
Annual screening for PN is recommended for diabetics.
Screening recommendations for PN include my touch perception to a 10 gm Semmes-Weinstein monofilament, vibration testing with 120 Hz tuning fork, superficial pain with pinprick for perception, or testing of ankle deep tendon reflexes.
Monofilament light touch vibration testing are more sensitive and specific than pinprick pain or ankle reflex testing.
Single testing with one modality may miss 25-50% of patients with diabetic neuropathy because peripheral neuropathirs may affect different types of nerve fibers to varying degrees.
A combination test of vibration plus monofilament testing provides the best and efficient testing for diabetic peripheral neuropathy has it is 90% sensitive and 85 to 89% specific for diabetic neuropathy and correlates with the development of diabetic foot ulcers.
Vibration sensation declines with age and almost one fourth of individuals older than 65 years and one third older than 75 years have absent vibration sensation on examination.
The most common type of clinical peripheral neuropathy is length-dependent peripheral neuropathy.
Length-dependent peripheral neuropathy is symmetrical and begins in the longest nerves at their terminals, meaning the distal foot.
Distal symmetric polyneuropathy is length dependent: there is diffuse involvement of multiple nerves with symptoms and signs that affect the most distal segment first.
Symptoms or signs in the legs usually reach the knees or just above before symptoms or signs occur in the fingers.
A non-length-dependent pattern or asymmetry may indicate a secondary process through which is the differential diagnosis is different.
The etiology of 20-25% of these neuropathies remains uncertain and the natural history of the idiopathic neuropathies progress slowly and are unlikely to cause severe physical disabilities.
Negative sensory symptoms such as lack of feeling and positive sensory symptoms such as prickling, tingling, burning usually precede motor weakness.
Symptoms in length-dependent neuropathy ascend up the leg, with symptoms often becoming evident when leg symptoms approached the knee.
Neuropathies may be sensory predominate, motor manifestations are usually more evident than in length dependent neuropathies.
Rarely patients present with multifocal clinical symptoms such as wrist drop followed by foot drop.
Polyradiculoneuropathies and multifocal neuropathies have differential diagnostic patterns than length dependent neuropathies.
Polyradiculopathies and multifocal neuropathies etiology include sarcoidosis, amyloidosis, neoplastic, vasculitic, infectious, and inflammatory immune mediated causes.
Upper limb involvement with length-dependent peripheral neuropathy may never occur, and development of symptoms in the hands and feet at the same time is atypical for diabetic length-dependent neuropathy and may indicate coexistence of carpal tunnel syndrome or some other cause such as a toxic etiology.
In length-dependent PN proprioception is spared relative to the sensory findings in mild to moderate disease and only becomes affected as the neuropathy severity progresses.
With proprioceptive deficits with gait disorder or imbalance with eyes closed, evaluation requires work up for posterior column disease or for sensory cell body dysfunction as seen in the Sjogren’s syndrome or a paraneoplastic disorder.
Majority of PNs are length-dependent, sensory predominant, mild to moderate in severity, and without major functional limitations.
Neuropathy that is sensory and motor symptomatic and is more diffuse, length-independent involving proximal and distal limbs suggest a polyradiculoneuropathy.
In length-independent neuropathy sensory abnormalities may predominate but motor manifestations are usually more evident than in length-dependent neuropathies.
The differential diagnoses differ in length-dependent neuropathies from polyradiculoneuropathies and multifocal neuropathies: etiologies of the latter include sarcoidosis, amyloidosis, neoplastic, paraneoplastic, vasculitic, infectious, and inflammatory immune mediated.
The evaluation of length-dependent neuropathy a diagnosis with a combination of history, examination, laboratory testing, and serologic evaluation can be made in approximately 74-82% of the time.
In 20-25% of cases the etiology of length-dependent peripheral neuropathy remains undiagnosed, but the natural history is that these processes progress slowly and are unlikely to cause severe physical disability.
Serologic evaluation from mild to moderate, symmetric, sensory-predominant length-dependent peripheral neuropathy includes testing for diabetes, B12 deficiency with methylmalonic acid and serum protein electrophoresis for monoclonal abnormalities.
Evaluation for chronic, length-dependent peripheral neuropathy includes: CBC, renal testing, liver function testing, sedimentation rate, hemoglobin A-1 C, thyroid stimulating hormone, serum protein electrophoresis, vitamin B12 level with methylmalonic acid, infectious evaluation for Lyme disease, HIV, and family history of peripheral neuropathy, hammertoes or pes cavus.
Mononeuropathy including carpal tunnel syndrome with median nerve neuropathy at the wrist, radiculopathy, in the cervical and lumbosacral spine with signs and symptoms are restricted to the distribution of a single nerve, myotome, or dermatome.
Multiple concurrent mononeuropathies-mononeuropathy multiplex may suggest a vasculitic etiology.
Diabetes is the most common cause of peripheral neuropathy in Western countries, with a prevalence of up to 30-66% of diabetics.
Despite the high prevalence of neuropathy, only 10-15% of patients with diabetic neuropathy are symptomatic from motor, sensory or autonomic dysfunction but 11-26% have associated neuropathic pain.
Many patients with examination evidence of diabetic neuropathy are asymptomatic but at risk for injury to insensate feet.
All patients with diabetic neuropathy should be screened for diabetes with fasting blood sugar and hemoglobin A-1 C measurements.
Risk of diabetic neuropathy can be reduced with tight glycemic control.
Impaired glucose tolerance has been noted to be more prevalent in patients with idiopathic neuropathy than in controls.
25-50% of idiopathic neuropathies may be explained by impaired glucose tolerance.
B12 is integral in the development and maintenance of myelin and its deficiency can cause subacute combined degeneration or an isolated peripheral neuropathy without CNS involvement.
Among patients with a low-normal B12 level 5 to 10% will have elevated serum methylmalonic acid concentrations indicating cellular B12 deficiency.
By adding a methylmalonic acid level to a screen of patients with length-dependent peripheral neuropathy the finding of a cellular B12 deficiency as the cause of neuropathy will occur 2 to 8% of cases.
10% of peripheral neuropathies are associated with dysproteinemia.
Dysproteinemias associated with a sixfold increase over the general population in the incidence of peripheral neuropathy.
The majority of peripheral neuropathies associated with dysproteinemias are due to monoclonal gammopathy of undetermined significance.
The finding of a monoclonal gammopathy and peripheral neuropathy requires the exclusion of the diagnoses of amyloidosis, multiple myeloma, POEMS, lymphoma, Waldenstrom’s macroglobulinemia, or cryoglobulinemia.
The peripheral neuropathy associated with POEMS syndrome is typically a mixed ating and axonal length-independent polyradiculoneuropathy.
Atrophy can be seen in chronic neuropathy distal atrophy, hammertoes and his cave pectus characteristic of long-standing neuropathy.
Preventive role of metformin on peripheral neuropathy induced by diabetes
Treatment with metformin prevents axonal atrophy and fiber degeneration.
Metformin stimulates the expression of neurotrophic and angiogenic factors in the peripheral nerve.
Metformin attenuates inflammation of nerve tissue exposed to chronic hyperglycemia.
Metformin increases the expression of anti-inflammatory markers.
One reply on “Peripheral neuropathy”
This article provides a comprehensive overview of the prevalence, risk factors, and symptoms of neuropathy. However, it fails to discuss the psychological impact of neuropathy on patients. Chronic pain and reduced quality of life can lead to depression, anxiety, and social isolation. Therefore, it is important to address not only the physical symptoms but also the emotional well-being of neuropathy patients. Healthcare providers should consider implementing a multidisciplinary approach that includes psychological support in the management of neuropathy.