Disorders of Nerve, Neuromuscular Junction, and Muscle

Neuro anatomy Chapter 8 (P327-335)

Disorders of Nerve, Neuromuscular Junction, and Muscle  Disorders of PNS can be distinguished from CNS dysfunction by anatomical pattern of sensory or motor deficits o Presence of lower motor neuron signs such as atrophy, fasciculations (involuntary muscle contraction), decreased tone, or hyporeflexia suggest PNS dysfunction; paresthesias in peripheral nerve distribution  Neuropathy – nerve disorder; site of pathology can be axons, myelin, or both; usually affect both sensory and motor fibers in nerve, although one or other may be preferentially involved o Mononeuropathy – focal neuropathy o Mononeuropathy multiplex – multifocal neuropathy o Polyneuropathy – generalized neuropathy o Radiculopathy – neuropathy affecting spinal nerve roots  Important causes of neuropathy include diabetes, mechanical causes, Lyme disease, HIV, CMV, varicella-zoster virus, hepatitis B, toxins, malnutrition, immune disorders (Guillain-Barré syndrome), and hereditary neuropathies (Charcot-Marie-Tooth disease)  Diabetic neuropathy – produced by compromise of microvascular blood supply of peripheral nerves, o xidative stress, autoimmunity, and neurotrophic and biochemical disturbance o Most common is distal symmetrical polyneuropathy (glove and stocking pattern of sensory loss) o Acute diabetic mononeuropathy can affect any cranial or spinal nerve; most common in CN III and femoral and sciatic nerves; often partial or complete recovery over course of weeks to months  Mechanical causes of nerve injury include extrinsic compression, traction, laceration, or entrapment by intrinsic structurs o Neurapraxia – temporary impairment of nerve conduction that usually resolves in hours to weeks o Wallerian degeneration – degeneration of axons and myelin distal to site of injury . As long as structural elements of nerve intact, axonal regeneration may occur at 1 mm/day o Complex regional pain syndrome type 1 – reflex sympathetic dystrophy; follows injury without specific nerve damage o Complex regional pain syndrome type 2 – causalgia; follows damage to specific nerve o Both types of complex regional pain syndrome characterized by intense local burning pain accompanied by edema, sweating, and changes in skin blood supply  In some situations when peripheral nerves severed or otherwise disrupted, they can be reanastomosed surgically; some entrapment syndromes amenable to surgical decompression  Painful paresthesias associated with neuropathies treated with anticonvulsants, serotonin-norepinephrine reuptake inhibitors, or tricyclic antidepressants  Guillain-Barré syndrome – acute inflammatory demyelinating polyneuropathy (AIDP); caused by immune- mediated demyelination of peripheral nerves o Onset typically occurs 1-2 weeks following viral illness, Campylobacter jejuni enteritis, HIV infection o Presents with progressive weakness, areflexia, and tingling paresthesias of hands and feet o Motor involvement typically much more severe than sensory o Symptoms at worst 1-3 weeks after onset; recovery occurs over many months o Diagnosis based on CSF demonstrating elevated protein without significantly elevated WBC o EMG/nerve conduction studies compatible with demyelination o Recovery occurs more quickly when patients treated with plasmapheresis or IV immunoglobulin therapy o In severe cases, patients require intubation and mechanical ventilation o Autonomic dysfunction can be prominent in some cases o With care and immune therapy, majority of patients get complete or near-complete recovery  Impaired neuromuscular transmission can lead to motor weakness without sensory deficits  Myasthenia gravis – immune-mediated disorder in which there are circulating antibodies against postsynaptic nicotinic acetylcholine receptors at neuromuscular junction of skeletal muscle cells o Sometimes accompanied by other autoimmune phenomena o Onset in 10s-20s more common in women; onset in 50s-60s more common in men o Clinical features include generalized symmetrical weakness, especially of proximal limb muscles, neck muscles, diaphragm, and eye muscles o Involvement of bulbar muscles can cause facial weakness, nasal-sounding voice, and dysphagia o Reflexes and sensory exam normal o Weakness becomes more severe with repeated use of muscle or during course of day o 15% of cases involve only extraocular muscles and eyelids (ocular myasthenia) o Ice pack test – placing bag of ice on closed eyelids for 2 minutes and reevaluating for improvement of ptosis (reduced cholinesterase function at lower temperatures) o Can also check clinical response to intermediate-acting acetylcholinesterase inhibitors (neostigmine) o Anti-acetylcholine receptor antibodies (AchR-Ab) positive in 85% of cases of generalized myasthenia and 50% of cases of ocular myasthenia o Half of patients with generalized myasthenia who are AchR-Ab negative have positive serology for MuSK-Ab o 12% of patients with myasthenia have thymoma, and many others have thymic hyperplasia o Treated by immune therapy (anticholinesterase medications); titrate and monitor doses because excess anticholinesterase can worsen weakness . Pyridostigmine – long-acting cholinesterase inhibitor o Many treated with thymectomy (whether thymus problems present or not); for patients under 60 . Should be performed when patients relatively clinically stable to minimize complications o Short-term immunotherapy with plasmapheresis or IVIg can be helpful, particularly when patients in myasthenic crisis requiring intubation, experiencing severe worsening symptoms, or in preparation for elective surgery o Longer-term immunosuppressive agents (steroids, azathioprine, mycophenolate, cyclosporine) help  Myopathies – muscle disorders that produce weakness typically more severe proximally than distally without loss of sensation or reflexes o Common causes include thyroid disease, malnutrition, toxins, viral infections, dermatomyositis, polymyositis, and muscular dystrophy  Dermatomyositis and polymyositis – immune-mediated inflammatory myopathies; CPK elevated o EMG (electromyography) studies compatible with myopathy o In dermatomyositis, characteristic violet-colored skin rash, typically involving extensor surface of knuckles and other joints  Duchenne muscular dystrophy – most common form of muscular dystrophy; X-linked inheritance Back Pain  Musculoskeletal causes are most common; in individuals with onset over age 50, suspect neoplasm  Back pain in younger person that worsens with exertion and improves with rest usually caused by musculoskeletal problem like disc herniation  Rule out radiculopathy  Never forget to evaluate bladder, bowel, and sexual function in patients with back pain so irreversible loss of function can be prevented

 Spondylolysis – fractures that appear in interarticular portion of vertebral bone between facet joints  Spondylolysthesis – displacement of vertebral body relative to vertebral body beneath it o Anterolisthesis is anterior displacement; retrolisthesis is posterior displacement o Anterolisthesis often coexists with spondylolysis  Osteophytes – bony spurs that form on regions of apposition between adjacent vertebrae because of chronic degeneration Radiculopathy  Radiculopathy – sensory or motor dysfunction because of nerve root pathology o Often associated with burning, tingling pain that radiates or shoots down limb in dermatome of affected nerve root o May be loss of reflexes and motor strength in radicular distribution  Chronic radiculopathy can result in atrophy and fasciculations  Sensation may be diminished fi single dermatome involved, but sensation not usually absent because of overlap of adjacent dermatomes; testing with pinprick more sensitive than touch  Mild or recent-onset radiculopathy can cause sensory changes without motor deficits  T1 radiculopathy can interrupt SNS pathway to cervical sympathetic ganglia, resulting in Horner’s syndrome  Most common cause of radiculopathy is disc herniation; common in C6, C7, L5, and S1 nerve roots  Straight-leg raise test helpful in diagnosis of mechanical nerve root compression in lumbosacral region; provides traction on nerve roots  Crossed straight-leg raising test – elevating asymptomatic leg causes typical symptoms in symptomatic leg  Radicular symptoms may be increased by Valsalva maneuver  Cervical radiculopathy – symptoms increased by flexing or turning head toward affected side  Pain on percussion of spine may indicate metastatic disease, epidural abscess, osteomyelitis, or other disorders of vertebral bones (not absolutely specific or diagnostic)  Incidental disc bulges and other degenerative changes of spine common findings in asymptomatic individuals  Lumbar stenosis – may result in neurogenic claudication (bilateral leg pains and weakness during walking)  Diabetic neuropathy can involve nerve roots, particularly at thoracic levels, producing abdominal pain  Epidural metastases most commonly occur in vertebral bodies, but can extend laterally to compress nerve roots o Spread of cancer cells within CSF can involve nerve roots  Guillain-Barré syndrome has predilection for nerve roots  Reactivation of latent varicella-zoster virus (chickenpox) in DRG produces painful blistering lesions of herpes zoster or shingles; occurs in dermatomal distribution and associated with sensory loss (less commonly motor) o Herpes zoster most common in thoracic dermatomes but can occur anywhere o Treatment with oral antiviral can shorten duration of blistering lesions o Postherpetic neuralgia – severe pain that can persist after blistering eruption; shortened by treatment with antiviral medications o When herpes zoster occurs in CN V1, it can threaten vision, so prompt treatment critical  Lyme disease – spirochete borne by ticks; can cause radiculopathies  CMV polyradiculopathy seen in patients with HIV infection, most commonly in lumbosacral roots o Milder form of radiculopathy caused by HIV itself  Dumbbell-shaped nerve sheath tumors (schwannomas and neurofibromas) can occur in neural foramen, producing radiculopathy; neurofibromatosis – presence of neurofibromas

Cauda Equina Syndrome  Cauda equina syndrome – impaired function of multiple nerve roots below L1 or L2  If deficits begin at S2 roots and below, there may be no obvious leg weakness  Involvement of S2-S4 can produce distended atonic bladder with urinary retention or overflow incontinence, constipation, decreased rectal tone, fecal incontinence, and loss of erections  Conus medullaris syndrome – similar deficits that occur as result of lesions in sacral segments of spinal cord  Causes of cauda equina syndrome include compression by central disc herniation, epidural metastases, schwannoma, meningioma, neoplastic meningitis, trauma, epidural abscess, arachnoiditis, and CMV polyradiculitis Common Surgical Approaches to the Spine  Indications for urgent surgery include rare instances where cord compression or cauda equina syndrome occurs  Semiurgent surgery indicated in patients with progressive or severe motor deficits or occasional patient with intolerable, medically intractable pain  Elective surgery contemplated when clear radiculopathy present and conservative measures have been tried for 1-3 months but were ineffective  Posterior approach with laminectomy (removal of lamina over affected levels); combined with discectomy to remove herniated disc materla o Posterior approach for foraminotomy to widen lateral recess thorugh which nerve root passes just before it exits intervertebral foramen o Preferred approach in lumbar spine  Anterior approach can be used in C-spine; provides direct access to discs without traversing spinal canal and allows mechanical fusion of adjacent vertebral bodies, usually using bone graft o Favored in cases of thoracic disc herniation