Peripheral Neuropathies.pptx
- 1. Peripheral Neuropathies TSAMO NDOMO V. MD,MPH
- 2. Plan • Introduction • Classification • Pathophysiology • Diagnosis • History • Physical exam • Paraclinical investigations • Treatment • Conclusion
- 3. Introduction • Peripheral neuropathy describes disorders of peripheral nerves. • This include: • The dorsal or ventral nerve roots; • Dorsal root ganglia; • Brachial or lumbosacral plexus; • Cranial nerves (except I and II); • Other sensory, motor, autonomic, or mixed nerves; • The term peripheral indicates that the disorder is outside the central nervous system (brain and spinal cord).
- 4. Introduction • Peripheral neuropathy affects 2–8% of adults; • The incidence increases with age after 55 years. • Given the numerous causes of polyneuropathy, determining the etiology can be challenging. • In the developed world, diabetes mellitus is the most common cause of this disease. • Peripheral neuropathies must be addressed before they result in complications.
- 5. Classification of peripheral neuropathies • Peripheral neuropathies can be subdivided into two major categories: • primary axonopathies and primary myelinopathies. • Neuropathies can be further subdivided on the basis of the diameter of the impaired axon. • Large myelinated axons include motor axons and sensory axons responsible for proprioception, vibration, and light touch. • Thinly myelinated axons include sensory fibers responsible for light touch, pain, temperature, and preganglionic autonomic functions. • Small unmyelinated fibers convey pain, temperature, and postganglionic autonomic functions.
- 6. Classification of Neuropathy by location. Harrison’s principles of internal Medicine, 17th edition
- 7. Classification of muscle atrophy by histology, Harrison’s principles of internal Medicine, 17th edition
- 8. Etiologies • Diabete • It’s the leading cause of peripheral neuropathies in the world. • Present in up to 50% of patients, therofore warrants a systematic screening • Toxic causes • Alcohol • Chemotherapy • Metabolic or deficiencies • Vitamin B12 deficiency • Renal failure • Up to 90% of patients with kidney failure develop a uremic polyneuropathy.
- 9. Etiologies • Immunes causes • Paraproteinemia: monoclonal immunoglobulin are presents in about 3 to 4℅ of population of more than 50 years and can be the cause of a slow and progressive either under the context of multiple myeloma or monoclonal gammapathy of undetermined significance. • Vasculitis • Caracterised by an acute or subacute mononevritis. • Can present with peripheral polyneuropathy.
- 10. Etiologies • Infectious causes • HIV infection: can present as a Guillain Barre syndrome, during a primary infection, and present with a distal polyneuropathy, in up to 30 percents of patients. • Leprosy: Frequent in theses patients mostly to those with a skin biopsy
- 11. Pathophysiology • The exact pathophysiology of peripheral neuropathy is contingent on the underlying disease. • Although a wide assortment of distinct diseases can ultimately lead to peripheral neuropathies. • The mechanisms in which peripheral nerves suffer injury exhibit similar patterns. • These reactions include segmental demyelination, along with Wallerian and axonal degeneration.
- 12. Pathophysiology • Segmental Demyelination • This process refers to the process of degeneration of the myelin sheath, with sparing of the nerve axon. • This type of reaction can present in mononeuropathies, sensorimotor, or, principally, motor neuropathies. • These are often inflammatory and sometimes immune-mediated. • About 20% of symmetrical peripheral neuropathies result from damage to the myelin. • Examples include Charcot-Marie-Tooth and neuropathy associated with monoclonal gammopathy of undetermined significance.
- 13. Pathophysiology • Axonal Degeneration, also known as the dying-back phenomenon • This type of degeneration usually manifests as symmetrical polyneuropathy (around 80%) and tends to cause weakness, most notably weakness in dorsiflexion of the ankles and foot, with accompanied trophic changes to muscle. • The axon degenerates in a pattern that starts distal and progresses proximally; this is thought to be because the most distal portion of the axon is particularly vulnerable due to its distance from the cell body, which provides metabolic support. • A proposed mechanism is that insult to the nerve causes impaired delivery of local axonal survival factors, resulting in an increased level of calcium intra-axonal, leading to a calcium-dependent cytoskeletal breakdown. • Examples of diseases causing axonal degeneration include diabetes, HIV, HCV, and Guillain-Barre syndrome.
- 14. Pathophysiology • Wallerian Degeneration: This occurs after a nerve axon degenerates due to a lesion or physical compression; • the portion distal to the axon passively wastes away, likely due to a lack of nutrients from the cell body. • This reaction results in focal mononeuropathy that is secondary to trauma or infarction of the nerve. • Wallerian degeneration is immunohistochemically distinct by the localization of neuropeptide Y-Y1 receptor markers.
- 15. Main etiologies of peripheral neuropathies. Valnet et Al, 2019
- 16. Diagnostic approach: History • Sensory symptoms are often underestimated by the patient, unless they are severe. • Symptoms may be classified as either negative or positive. • Positive symptoms reflect inappropriate spontaneous nerve activity, whereas negative symptoms reflect reduced nerve activity. • Negative motor symptoms include: • weakness, • fatigue, • wasting,
- 17. Diagnostic approach: History • positive symptoms include • paresthesias: tingling • Dysesthesias: any form of abnormal sensation with or without stimulus) and pain (burns, electric shocks). • The involvement, predominantly in the lower limbs, is usually described as socks, with proximal progression. • cramps, • Twitching, • Myokymia. • Weakness may not be appreciated until 50% to 80% of nerve fibers are lost;
- 18. Diagnostic approach: History • Negative sensory symptoms include • Hypesthesia and gait abnormalities such as ataxia. • Difficulty differentiating hot from cold • Worsening balance, especially in the dark when visual input is less able to compensate for proprioceptive loss. • Positive sensory symptoms include • burning or lancinating pain, • buzzing, and tingling/paresthesia. • Discomfort to sensory stimuli that are normally not painful (allodynia) • Increased sensitivity to painful stimuli (hyperalgesia)
- 19. Diagnostic approach: History • Patients with hyperalgesia may describe a sensation of walking on hot coals. • Symptoms suggesting autonomic nerve involvement include early satiety, bloating, constipation, diarrhea, impotence, urinary incontinence, abnormalities of sweating (hyperhidrosis, anhidrosis), and light headedness. • Patients with vasomotor instability may report cold extremities associated with skin color and trophic changes.
- 20. Diagnostic approach: History • It is helpful to ask about impairment in activities of daily living, such as a change in handwriting, problems fastening jewelry or buttons or inserting and turning keys… • Details regarding disease onset, duration, asymmetry and progression are quite important for further characterization. • Social history can include questions regarding occupation (possibility of toxic exposures to solvents, glues, fertilizers, oils, and lubricants), sexual history (HIV, hepatitis C), recreational drug use (vasculitis secondary to cocaine), excessive alcohol intake, dietary habits (eg, strict vegan diet), and smoking (paraneoplastic disease).
- 21. Diagnostic approach: Physical Exam • Assessing the degree of involvement of different fiber modalities (motor, sensorimotor, sensory, autonomic nerve fibers), and the distribution of symptoms may further help to assign the patient to a particular clinical pattern. • Type of nerve fiber involvement Most peripheral neuropathies are sensory or sensorimotor neuropathies. • Pure or predominant motor signs occur in certain hereditary neuropathies or multifocal motor neuropathy, an immune-mediated neuropathy responsive to intravenous immunoglobulin treatment.
- 22. Diagnostic approach: Physical Exam • Non-neuropathic conditions mimicking neuropathies (e.g., distal myopathies, amyotrophic lateral sclerosis, or spinal muscular atrophy) should be considered in patients with a lack of sensory involvement. • A particular, though rare symptom complex constitutes early-onset ataxia and predominant loss of proprioception, which is a characteristic hallmark of sensory ganglionopathy / neuronopathy. • Autonomic dysfunction can occur throughout all clinical patterns and may indicate diabetic neuropathy, amyloidosis, vincristine-induced neuropathy.
- 23. Diagnostic approach: Physical Exam • The patient may fail to report (and sometimes even to recognize) symptoms of autonomic dysfunction. • Accordingly, history taking should include symptoms of autonomic dysfunction, e.g., orthostatic intolerance, anhidrosis, dry eyes, dry mouth, constipation or diarrhea, impotence, tachycardia following sitting or standing, and hair loss in the distal legs. • Distribution of symptoms Most neuropathies are length-dependent with a distal symmetric distribution of sensorimotor and/or autonomous neurological deficits.
- 24. Diagnostic approach: Physical Exam • This becomes obvious when tendon reflexes are examined: ankle reflexes are usually absent, while more proximal reflexes can still be elicited. • Weakness and atrophy are most prominent in foot extensor muscles resulting in foot drop, or even only in toe flexors, It may indicate long- lasting neuropathy. • Cranial nerve involvement is only occasionally seen in polyneuropathy and may, therefore, be of diagnostic value. • Neuropathies with cranial nerve involvement include diabetes mellitus (often monofocal), GBS, Lyme disease, sarcoidosis, diphtheria, or botulism.
- 25. Paraclinical investigations: functional tests • Electrodiagnostic studies • Nerve conduction studies (NCS) and needle electromyography (EMG) are carried out to confirm the clinical diagnosis of peripheral neuropathy. • Exclude neuropathy mimics (i.e., radiculopathy, distal myopathy) • To reveal subclinical involvement of clinically unaffected nerves and fiber modalities. • To assess the primary mechanism of damage (axonal vs. demyelinating), and determine disease severity.
- 26. Paraclinical investigations: functional tests • Most neuropathies are axonal, recognizable by: • Reduced compound muscle action potentials (CMAP) in motor nerves, • Reduced sensory nerve action potentials (SNAP), • Normal or slightly reduced nerve conduction velocities. • The less frequently occuring demyelinating neuropathies are characterized by: • increased distal motor latencies, • A significant slowing of nerve conduction velocities, • Conduction blocks, • Temporally dispersed potentials, and absent or delayed late responses
- 27. Paraclinical investigations: Morphological tests • Morphological tests are indicated when there’s • X-Rays can give a clue on the location of the lesion. • The aims of morphological tests is to help in localizing atypical neuropathies. • Indications of imagery (ideally MRI) include: • Polyradiculopathy, • Plexopathy, • Radiculoplexus neuropathy.
- 28. Paraclinical investigations: Biological tests • Complete blood count: Macrocytic anemia may clue the clinician to vitamin B12 or folate deficiency, or even alcohol abuse. • Complete metabolic pannel to Look for electrolyte imbalances that can contribute to neuropathy along with renal failure as uremia can also lead to neuropathy. • HbA1c • Renal function, • Liver function, • Thyroid function tests, • vitamin B12, • Serum protein immunofixation.
- 29. Peripheral neuropathy diagnosis Algorithm . Lehmannet al.Neurol.2020.
- 30. Treatment • Aims, the main goals are: • Controlling the underlying disease process • Treating troublesome symptoms • Means • Depending of the aetiology can be surgical, pharmacological or non pharmacological.
- 31. Treatment • Non pharmacologic means • Eliminating offending agents, such as toxins or medications; • Correcting a nutritional deficiency. • foot care, • weight reduction • shoe selection • Pharmacological means • Several pharmacologic options exist to treat neuropathic pain including antiseizures and antidepressants.
- 32. Drugs used in the management of peripheral neuropathies. Valnet R et Al, 2019
- 33. In Fine • Peripheral neuropathies are present in a large spectrum of diseases, with diabetes mellitus being the leading cause in the world. • Peripheral neuropathies can be classified as Axonopathies and myelinipathies. • Detailed history and physical exams are important in order to have an appropriate diagnosis. • Many drugs can be use in the management of peripheral neuropathies, but the etiologic diagnosis remain the ideal. • A multidisciplinary approach is mandatory in oder to better handle these patients.
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Editor's Notes
- #10: Paraprotéinémies La production d’une immunoglobuline monoclonale s’observe chez 3 à 4% de la population de plus de 50 ans et peut être à l’origine d’une polyneuropathie lentement progressive, soit dans le contexte d’un myélome multiple ou d’une gammapathie monoclonale de signification indéterminée (MGUS)