Approach to Peripheral Neuropathy

Approach to Peripheral Neuropathy.

Pattern recognition:

Example:  Diabetic sensory polyneuropathy is an acquired, chronic, slowly progressive, length-dependent, sensory-predominant, mixed large and small fiber, primarily axonal polyneuropathy with common concomitant dysautonomia associated with a history of diabetes.

Applying the same template as above with sufficient history, examination, and testing, every peripheral nerve disorder can be described within a similar framework with components of onset, pace of progression, anatomic distribution and pattern, modalities affected, affected nerve fiber type, electrodiagnostic features, and associated clinical context. 

5. Pathology: 

6. Family history of polyneuropathy.

7. Inquiry should be made about preceding or concurrent associated medical conditions:

Pearl:  "If a patient who claims to be weak, cannot tell you about a specific activity that is problematic for him or her, then the existence of true muscle weakness remains doubtful unless it is subsequently corroborated by the physical examinations."

Pearl: "The extraocular muscles are rarely affected in motor neuron disease, the majority of polyneuropathies or acquired inflammatory myopathies."

Pearl:  "If fatigue is the predominant feature, without objective signs such as weakness or elevated CK activity, it is unlikely to be a neuromuscular disease.  Chronic fatigue syndrome is not neuromuscular disease."

Pearl:  "Hickam’s dictum, or the absence of a singular parsimonious diagnosis, applies routinely in neuromuscular settings.  Separate disease processes with distinct localizations can mimic or magnify symptoms of the peripheral nerve disease of interest and lead to a layering effect, where multiple neurologic localizations can contribute to the same clinical findings. For example, a patient presenting with a foot drop may have a simultaneous contribution from a focal fibular mononeuropathy and an L5 radiculopathy."

Pearl:  "Cervical and lumbar radiculopathies can mimic focal mononeuropathies and, if bilateral, can also mimic polyneuropathies. Myopathies and neuromuscular junction disorders can mimic pure motor neuropathies. In the central nervous system, myelopathies can present with bilateral symmetric sensorimotor abnormalities, and a parafalcine brain lesion can present with bilateral lower extremity sensorimotor deficits. Many symptoms and signs of central nervous system disorders (eg, weakness, numbness, ataxia, dysautonomia) overlap with peripheral nerve disorders."

Pearl:  "Layering of multiple peripheral nerve diseases can lead to electrodiagnostic test results that are difficult to interpret definitively. For example, a patient with a sensorimotor distal polyneuropathy may have their physical examination findings and electrodiagnostic testing results clouded by an incidental presence of a lumbar radiculopathy."

Pearl:  "Patients with idiopathic sensorimotor polyneuropathy, bilateral carpal tunnel syndrome, lumbar stenosis, and dysautonomia should be considered for amyloid testing including genetic testing for hereditary transthyretin amyloidosis."

Pearl:  "Idiopathic polyneuropathies. Despite thorough workup, 11% to 31% of polyneuropathy cases have no identifiable cause.  Repeat laboratory testing generally does not yield additional information, provided genetic testing for inherited neuropathies are tested and are negative.  Some of these cases have been classified as chronic idiopathic axonal polyneuropathy, which typically occurs between the ages of 50 to 60 years, and has a generally benign course. " 

Clinical Vignette:

A 67-year-old right-handed man with a history of type 2 diabetes, hypertension, and lung cancer presented to the neurology office reporting hand weakness.  About 1 year before presentation, the patient noticed hand grip weakness in the left hand.  About 4 months later, he started to have similar symptoms in his right hand.  He had noted muscle wasting in his hands and forearms.  He denied sensory symptoms in his upper extremities.  He had more remote symptoms of numbness and tingling in his feet, which he reported began soon after he received chemotherapy with cisplatin about 5 years earlier and overall had been stable without progression. 

On examination, he had normal mental status and cranial nerve function.  Examination of the upper extremities revealed weakness in bilateral finger abduction, which was worse on the left.  He had moderate atrophy in the hypothenar eminence and first dorsal interossei bilaterally.  Fasciculations were frequent in the bilateral first dorsal interossei.  Strength examination of the lower extremities was normal.  His muscle stretch reflexes were absent throughout.  He had absent Babinski and Hoffman signs.  Sensory examination of the feet revealed severe loss of vibration sensation and pinprick sensation up to the midshin.  In the upper extremities, vibration testing of the second digit was normal, and pinprick testing revealed mild loss of sharp sensation in the right thumb and second digit.  

The patient was evaluated via electrodiagnostic testing and laboratory testing, which led to a diagnosis of multifocal motor neuropathy with associated GM1 antibodies superimposed on a more long-standing length-dependent sensorimotor peripheral neuropathy and median neuropathy at the wrist. 

COMMENT:  This case illustrates the layering of clinical elements commonly encountered in peripheral nerve disease.  Rather than classifying the onset and pace of progression of all symptoms together, the neurologist must parse the potential clinical entities and describe them accordingly.  Although the patient had sensory neuropathy symptoms for many years in the feet, possibly from diabetes or chemotherapy (sensorimotor peripheral neuropathy), the most striking part of his presentation is the progressive hand weakness findings in the past year that may suggest a superimposed disorder (multifocal motor neuropathy).  Although there is a combination of sensorimotor findings, the clinical details regarding the hand symptoms reveal a strong motor predominance with notable atrophy and muscle strength loss with only minimal associated sensory deficits.  The pinprick loss in the right first and second digits represents an incidentally discovered carpal tunnel syndrome (median neuropathy at the wrist) that overlaps with his subacute motor-predominant hand symptoms. 

Examples of neuromuscular syndrome within systemic diseases:

Neuronopathies

Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.  Examples:  Sjogren's syndrome, HIV infection, HTLV-1, Epstein-Barr virus, varicella zoster virus, measles, monoclonal gammopathies, paraneoplastic (anti-Hu syndrome), GBS variant, idiopathic sensory neurononpathy, nicotinic acid deficiency, vitamin E deficiency, riboflavin deficiency, and drugs such as carboplatin, doxorubicin, suramin, thallium, penicillin, and pyridoxine intoxication

Sensory neuronopathies: chronological and etiological classification. 


Distal Symmetric Purely Sensory or Sensory > Motor Neuropathies


Disorders of Posterior Root Ganglia

Template:

Pins and needle sensation, burning sensation,

Pain and its ChLoRIDE-PP 

Weakness, fatigue, muscle cramps, muscle twitching, muscle stiffness and trouble relaxing, gait and balance, falling or tripping, using assistive devices, chewing or swallowing difficulties, swallowing, with choking on liquids or solids, speech and voice difficulties, 

Examples of functional abilities prior to symptoms and examples of functional abilities after symptom onset.

What are the things you were able to do before your symptoms started, that you are not able to do now?

Weight stability

Bladder and bowel dysfunction 

Visual symptoms 

Any history of similar complaints or problems in past? 

Alcoholism?

Diabetes? 

HIV? 

Thyroid disease? 

Exposure to chemotherapy agents? 

Exposure to heavy metals or solvents? 

Hepatitis B or C 

Recent viral illnesses 

New medications? 

Other systemic symptoms? 

History of back or neck trauma, back or neck surgeries? 

History of travel, camping, tick-bites, food-related illness, nausea, vomiting, diarrhea, dysentery? 

Any changes in medications, doses of medication? 

Any changes in diet?

Family hx of neuropathy or other neurologic disease? 

EMG: 

Orthostatic lightheadedness 

Syncope 

Exertional intolerance? 

Fatigue 

Brain fog 

Insomnia 

Headache 

Chest pressure 

Heart palpitations 

Shortness of breath 

Abdominal pressure 

Early satiety 

Post-prandial nausea 

Constipation 

Diarrhea 

Urinary urgency 

Urinary frequency Vomiting of undigested food?

Erectile dysfunction and decreased libido in men 

Vaginal dryness, clitoral insensitivity, dyspareunia, and loss of libido in women 

Excessively sweating 

Lack of sweating 

Heat intolerance 

Cold intolerance 

Excessively dry eyes 

Excessive dry mouth

Redness of feet and hands 

Joint hypermobility 

Joint dislocation 

Hyperelastic skin 

Food allergies 

Anaphylaxis

Pruritus 

Urticaria 

Dermatographism

Onset, pace of progression, anatomic distribution and pattern, modalities affected, affected nerve fiber type, electrodiagnostic features, and associated clinical context. 


Electrodiagnostic approach towards Polyneuropathy

The first step in the evaluation of a patient with polyneuropathy is to reduce the differential diagnosis to a smaller, more manageable number of possibilities. This usually can be accomplished by acquiring several critical pieces of information from the history, physical examination, and electrophysiologic studies.

Electrophysiologic studies can be used:

In cases in which a demyelinating polyneuropathy is found, further differentiation between an acquired and genetic condition can often be made.  The information obtained from electrophysiologic testing, in conjunction with key pieces of clinical information, usually allows the differential diagnosis to be narrowed considerably so that further laboratory testing can be more appropriately applied and a final diagnosis reached.  In addition, abnormalities in muscles and nerves on ultrasound can aid in the differential diagnosis of several selected peripheral neuropathies.

What Is the Temporal Course and Progression of Polyneuropathy (Acute, Subacute, Chronic; Progressive, Stepwise, Relapsing/Remitting)?

Which Fiber Types Are Involved (Motor, Sensory,  Large or Small Sensory, Autonomic)?

What Is the Pattern of the Polyneuropathy (Distal Dying Back [Distal-to-Proximal Gradient], Short Nerves, Multiple Nerves; Symmetry, Asymmetry)?

The overall pattern of the polyneuropathy is determined largely based on the clinical examination and is supplemented and confirmed by electrophysiologic studies.  

What Is the Underlying Nerve Pathology (Axonal, Demyelinating, or Mixed)?

Is There a Family History of Polyneuropathy?

Is There a History of Medical Illness or Are There Signs Suggesting a Medical Illness Associated With Polyneuropathy?

Is There Any History of Occupational or Toxic Exposure to Agents Associated With Polyneuropathy?

Preston and Shapiro.