Neurological II Module PDF

1/20/2018 Neurological II Module Patti Parker, PhD, RN Topics Covered Neck and Back Pain Disorders of Peripheral Nerves Subdural Hematoma Multiple Sclerosis Myasthenia Gravis Guillian-Barré Syndrome 1 ...

1/20/2018 Neurological II Module Patti Parker, PhD, RN Topics Covered Neck and Back Pain Disorders of Peripheral Nerves Subdural Hematoma Multiple Sclerosis Myasthenia Gravis Guillian-Barré Syndrome 1  1/20/2018 Neck and Back Pain OBJECTIVES Know and understand: What questions to ask to determine the potential cause of musculoskeletal pain Components of a thorough physical examination for investigating musculoskeletal issues  Most common causes of neck and back pain  Evidence-based management of musculoskeletal problems 2  1/20/2018 TOPICS COVERED  General Principles for Diagnosis  Evaluation and Management of Regional Complaints  Neck pain  Back pain GENERAL PRINCIPLES FOR DIAGNOSIS A musculoskeletal problem is treated most effectively if the specific cause can be identified The gold standard for determining the cause of musculoskeletal pain is the physical examination, complemented by a good history If an adult reports pain in more than one joint, a systemic process may be considered; however, the older adult often have multiple mechanical problems in different sites of the body 3  1/20/2018 GENERAL PRINCIPLES FOR DIAGNOSIS: THE HISTORY  What symptoms accompany the pain?  What brings on the pain? Is it exacerbated when going from lying to sitting, ascending or descending stairs, standing, or walking?  Is the pain worse in the morning, midday, or night?  Does the pain radiate?  Does the pain cause the patient to cease the activity associated with the pain?  Was the pain acute at onset? Or has it worsened over time? GENERAL PRINCIPLES FOR DIAGNOSIS: THE EXAM  Carefully observe the patient’s mobility  Manually examine joints and muscle groups, focusing on:  Patterns of weakness  Malalignment and swelling of joints (whether the swelling is soft tissue or bony enlargement)  Decreased range of motion (ROM)  Patterns of joint involvement consistent with specific conditions  Order imaging and laboratory tests only after formulating a list of potential diagnoses 4  1/20/2018 NECK PAIN (1 of 5)  Four general causes: systemic disease, cervical myelopathy, cervical radiculopathy, mechanical neck disease  Systemic disease  Often associated with polymyalgia rheumatica, rheumatoid arthritis, and other inflammatory conditions  Systemic symptoms and signs, other joint complaints, and prolonged morning stiffness are often present  Typical: symmetric loss of ROM of the cervical spine  Lab markers of inflammation, such as C-reactive protein and erythrocyte sedimentation rate, are often increased NECK PAIN (2 of 5)  Myelopathy produced by cervical stenosis  Does not always cause neck pain  Often characterized by spastic gait disturbance and weakness in the lower extremities with upper motor neuron signs (eg, hyperreflexia, increased muscle tone, positive Babinski signs)  Can also produce lower motor neuron findings in the upper extremities  Bladder symptoms include urgency, frequency, or retention 5  1/20/2018 NECK PAIN (3 of 5)  Cervical radiculopathy  Characterized by pain in the neck and arm, sensory loss, loss of motor function, and reflex changes in the affected nerve-root distribution  Usually due to encroachment of the neuroforamina of the cervical spine; the C7 nerve root is most frequently affected  Suggested by pain that is reproduced by rotating the head or bending it toward the symptomatic side  Most patients improve with symptomatic treatment, and only a relatively small number require surgery NECK PAIN (4 of 5)  Nonspecific mechanical disease of cervical spine: diagnosis  Cervical disc displacement appears to be a frequent cause of neck pain in older adults  Cervical spine disease can also produce local muscle spasm and tenderness, often mistaken for the “trigger points” of fibromyalgia  Typical: asymmetric loss of ROM of the cervical spine and weakness of the muscles innervated by cervical nerve roots, such as elbow extension and finger abduction in patients with C7, C8, and T1 disease 6  1/20/2018 NECK PAIN (5 of 5)  Nonspecific mechanical disease of cervical spine: treatment  Little hard data on the effectiveness of one therapy versus another  Bone and Joint Decade 2000–2010 Task Force on Neck Pain: Manual therapy and exercise are more effective than alternative strategies  Virtually all studies involved patients ≤65 years old  Surgery should be considered only for significant, persistent, and worsening neurologic signs CONDITIONS CAUSING BACK PAIN (1 of 3) Condition History Examination Lab Tests, Imaging Tumor Persistent, No focal Anemia, increased progressive abnormalities ESR, abnormal pain at rest; bone scan or MRI systemic symptoms Infection Persistent pain, Tender spine Increased ESR, WBC fever; at-risk count; positive patient (eg, bone scan or MRI indwelling catheter) Unstable Recurring Pain going MRI or CT showing lumbar episodes of from flexed to one disc space spine pain on extended narrowed and change of position sclerotic position spondylolisthesis 7  1/20/2018 CONDITIONS CAUSING BACK PAIN (2 of 3) Condition History Examination Lab Tests, Imaging Lumbar Pain on Immobile MRI or CT scan spinal standing and spine; L4, L5, showing stenosis stenosis walking S1 weakness relieved by sitting and lying Sciatica Pain in posterior Often positive Variable findings aspect of leg; straight leg may be raise; L4, L5, S1 incomplete weakness Vertebral Sudden onset Pain on any Vertebral end-plate compression of severe pain; movement of collapse; fracture resolves in 4–6 spine; no compression weeks neurologic fracture seen on deficits plain film CONDITIONS CAUSING BACK PAIN (3 of 3) Condition History Examination Lab Tests, Imaging Osteoporotic Sudden lower Sacral H-shaped uptake on sacral back, buttock, tenderness bone scan fracture or hip pain Note that systemic causes of back pain have histories quite distinct from those of mechanical pain 8  1/20/2018 Assessment of LBP in the Older Adult Symptom Condition Acute pain Vertebral compression fracture Disc displacement Osteoporotic sacral fracture Visceral origin (eg, aortic aneurysm) Positional pain Increased with standing and walking and relieved with sitting Lumbar spinal stenosis Brought on by bending, lifting, or unguarded movements Unstable lumbar spine Persistent pain (gradually increasing, Tumor non-positional) Infection BACK PAIN: THE EXAM  Evaluate the back, hips, legs, and gait  With patient upright, move the back through the 4 planes of movement of the lumbar spine (flexion to the right, flexion to the left, forward flexion, extension)  Straight leg raise tests can be helpful if positive  The most helpful physical finding in patients with possible back disease is subtle weakness of the L4L5 and L5S1 muscles 9  1/20/2018 PHYSICAL EXAM OF OLDER ADULTS WITH LOWER BACK PAIN Sign Condition Paravertebral muscle spasm Mechanical disc disease* Asymmetric ROM of the lumbar Mechanical disc disease spine Unstable lumbar spine Spinal tenderness Vertebral compression fracture Infection Weakness of L4L5 and L5S1 Mechanical disc disease muscles Lumbar spinal stenosis Normal examination of lumbar Osteoporotic sacral fracture spine Hip disease Tumor Referred visceral pain *Not caused by tumor, infection, spinal stenosis, or fracture INNERVATION OF LOWER EXTREMITIES Nerve Function Muscle Peripheral Nerve Root Great toe dorsiflexion Extensor hallucis Deep peroneal L5 longus Ankle dorsiflexion Tibialis anterior Deep peroneal L4, L5 Ankle eversion Peroneus longus, Superficial L5, S1 brevis peroneal Ankle plantar flexion Gastrocnemius, Tibial S1, S2 soleus Knee extension Quadriceps Femoral L3, L4 Hip flexion Iliopsoas Femoral L2, L3 Hip adduction Adductor magnus, Obturator L3, L4 brevis, longus Hip abduction Gluteus medius Superior gluteal L4, L5 Hip extension Gluteus maximus Inferior gluteal L5, S1 10  1/20/2018 BACK PAIN: IMAGING Red flags that warrant imaging without delay:  If the discovery of a vertebral compression fracture will change management, obtain a plain radiograph of the lumbar spine in older women, and in older men who have risk factors for osteoporosis  Acute neurologic deficit  Bowel or bladder dysfunction  Fever  History of cancer CAUSES OF BACK PAIN: SYSTEMIC  Pain due to tumor, infection, etc usually has insidious onset and becomes more persistent and severe  The pain is usually non-positional, can occur at night, and may be linked to systemic symptoms or signs  Risk of cancer as a cause of back pain increases in adults >50 years old, those with a previous history of cancer, and those with pain that persists >1 month  Fever, discrete local vertebral tenderness, pain in the upper lumbar or thoracic area, and non-positional pain may indicate vertebral infection  Evaluate infection as a source of back pain in patients at risk of endovascular infections 11  1/20/2018 CAUSES OF BACK PAIN: LUMBAR SPINAL STENOSIS (1 of 2)  Common cause of back pain in people in their late 80s and 90s, but frequently seen on spine imaging in patients without symptoms  Characteristic symptom: back pain radiating into the buttocks or legs that is worse on standing and walking (particularly downhill), relieved with sitting  A similar clinical syndrome can be seen in patients with osteoarthritis of the hips  Other common symptoms:  Sciatic pain with standing and walking  Pain in the calf when walking, relieved only by sitting down (pseudoclaudication) CAUSES OF BACK PAIN: LUMBAR SPINAL STENOSIS (2 of 2)  Conservative therapy has limited benefit  No clear evidence that physical therapy, exercise, or medications alter the natural history  A study of epidural steroid injections for spinal stenosis demonstrated minimal or no short-term benefit compared with epidural injections of lidocaine alone  Surgery was more effective than conservative therapy in a randomized multicenter study  For patients ineligible for spinal surgery, a rolling walker with an attached seat can be very helpful 12  1/20/2018 CAUSES OF BACK PAIN: SCIATICA  Older adults can develop a typical sciatica syndrome similar to that seen in younger individuals  Acute sciatica usually occurs spontaneously, with no obvious causal event  This pain can be felt in any position, is usually not relieved with sitting, and often causes a good deal of night discomfort  The clinical course in younger people is quite variable  No studies have specifically evaluated sciatica in older adults CAUSES OF BACK PAIN: VERTEBRAL COMPRESSION FRACTURES  Only 1/3 of patients have symptoms  Pain is typically abrupt, is felt deep in the site of the fracture, can be severe  Pain is usually worse on standing and walking, is relieved with lying down, may radiate to flank or legs  Diagnosis is usually made on a plain radiograph of the lumbar or thoracic spine  General consensus: Analgesics are successful in about 2/3 of patients with these fractures; reserve vertebroplasty and kyphoplasty for nonresponders  Most important intervention: treatment of osteoporosis 13  1/20/2018 CAUSES OF BACK PAIN: SACRAL FRACTURES  Osteoporotic sacral fractures in older women can cause spontaneous buttock, pelvic, and low back pain  Sacral tenderness is usually present on physical exam  Associated additional osteoporotic fractures are likely  Imaging:  Plain radiographs are usually negative  Technetium bone scans: characteristic H-shaped uptake over the sacrum  CT: displacement of the interior border of the sacrum  The pain usually resolves over 4-8 weeks CAUSES OF BACK PAIN: NONSPECIFIC LOW BACK PAIN  Very little is known about nonspecific mechanical low back pain, except that it is quite common and relatively short-lived  History and physical exam are best ways to determine probable cause of pain  Usually has a relatively sudden onset and is exacerbated by positions that stress the lumbar spine  If there is weakness of the L4L5 and L5S1 innervated muscles, pain is probably due to a displacement of disc material 14  1/20/2018 SUMMARY  Musculoskeletal issues are the most common causes of pain in older adults  The gold standard for determining the cause of musculoskeletal pain is the physical examination, complemented by a good history  Order imaging and laboratory tests only after formulating a list of potential diagnoses  Back problems are the third most common reason for clinician visits by older adults  Nonspecific mechanical low back pain is typically relatively short-lived: pain of relatively sudden onset, exacerbated by positions that stress the lumbar spine CHOOSING WISELY Recommendations based on the ABIM Foundation’s Choosing Wisely® Campaign:  Avoid NSAIDs in individuals with hypertension, heart failure, or chronic kidney disease of all causes, including diabetes mellitus.  Do not perform imaging for lower back pain within the first 6 weeks unless red flags are present (severe or progressive neurologic deficits or when serious underlying conditions are present). If there is a concern for a vertebral compression fracture, a plain lumbar spine x-ray should be done immediately after the patient is evaluated. 15  1/20/2018 CASE 1 (1 of 3)  A 79-year-old woman comes to the office because she has pain predominantly in the right buttock.  The pain is worse when she stands or walks. She has a pronounced limp, because she is unable to bear weight on her right leg without significant pain.  MRI of the lumbar spine 6 months ago showed diffuse degenerative changes throughout the lumbar area, with significant stenosis at L4-L5 and L5-S1.  The patient has been treated by a pain specialist with a series of facet joint injections, without significant relief. CASE 1 (2 of 3) Which one of the following is the most appropriate next step? A. Bone scan to exclude tumor of the spine B. Referral for decompression laminectomy of the lumbar spine C. Passive examination of the right hip D. Trial of tramadol 25 mg titrated to 4 times daily as needed E. Referral for intensive program of physical therapy 16  1/20/2018 CASE 1 (3 of 3) Which one of the following is the most appropriate next step? A. Bone scan to exclude tumor of the spine B. Referral for decompression laminectomy of the lumbar spine C. Passive examination of the right hip D. Trial of tramadol 25 mg titrated to 4 times daily as needed E. Referral for intensive program of physical therapy CASE 2 (1 of 4)  A 78-year-old man comes to the office because he has pain radiating from his buttock to his right heel.  The pain began suddenly 10 days ago.  It bothers him in all positions, particularly at night.  It limits his walking and his ability to climb stairs.  He does not recall similar pain in the past, although he has had intermittent low back pain. 17  1/20/2018 CASE 2 (2 of 4)  Physical examination  Raising the right leg to 40º reproduces the leg pain.  Mild weakness of right great toe extensor, right hip abductor, and right hip extensor  Full ROM of both hips, with no pain  MRI findings: stenosis at L4-L5 and L5-S1 and moderate disc displacement into right L4-L5 interspace CASE 2 (3 of 4) Which one of the following statements is true? A. The pattern of pain is typical for sciatica due to lumbar spinal stenosis. B. Between 50% and 75% of patients report improvement of this pattern of pain within 4 weeks. C. The patient’s age is associated with poor prognosis for sciatica. D. The disc herniation indicates a need for surgical intervention. 18  1/20/2018 CASE 2 (4 of 4) Which one of the following statements is true? A. The pattern of pain is typical for sciatica due to lumbar spinal stenosis. B. Between 50% and 75% of patients report improvement of this pattern of pain within 4 weeks. C. The patient’s age is associated with poor prognosis for sciatica. D. The disc herniation indicates a need for surgical intervention. Disorders of the Peripheral Nerves 19  1/20/2018 OBJECTIVES Know and understand: The presentation of disorders of the peripheral nerves Myelopathy Radiculopathy Peripheral Neuropathy Myopathy Amyotrophic Lateral Sclerosis TOPICS COVERED Neuromuscular Disorders, Peripheral Neuropathy, and Myelopathy 20  1/20/2018 PERIPHERAL NEUROPATHY  Can be particularly devastating in older adults because it may cause gait impairment from sensory and motor deficits, with resulting propensity to fall  Prevalence up to 10% in older adults; 30%60% in patients >60 years who have diabetes mellitus  Other common causes:  Medications, alcohol abuse, and nutritional deficiencies  Renal disease (ie, uremia)  Monoclonal gammopathy (eg, multiple myeloma)  Hereditary forms  Neoplasia DIAGNOSIS OF PERIPHERAL NEUROPATHY  History geared toward identifying possible causes and risk factors  Neurologic examination to establish evidence of a length-dependent loss of sensory and/or motor function that is maximal distally in the limbs, associated with decreased reflexes and atrophy in affected regions  Electromyography and nerve conduction studies to help classify the neuropathy  Refer acute, atypical, rapidly progressive, or severe forms of neuropathy to a neurologist with expertise in neuromuscular medicine 21  1/20/2018 TREATMENT OF PERIPHERAL NEUROPATHY  Depends on underlying cause  Optimizing glucose control can lessen the severity of diabetic neuropathy  Treating neuropathic pain (combination often needed):  Tricyclic antidepressants (off-label)  Gabapentin or pregabalin (FDA-approved for post- herpetic neuralgia; pregabalin also approved for diabetic neuropathy)  Duloxetine (FDA-approved)  Tapentadol (FDA-approved)  Tramadol and opioids (all off-label) (SOE=B)  Topical agents (eg, capsaicin cream, lidocaine patch) (SOE=B) RADICULOPATHY (1 of 2)  Cause: compression of spinal root as it exits spinal cord  In older adults may result from:  Herniated discs  Osteophyte formation  Pain may radiate down neck, back, arm, or leg  Neurologic examination may reveal:  Motor and sensory defects  Diminution of reflexes in distribution of spinal root(s) MRI with contrast and lumbar puncture with cytology may help make the diagnosis 22  1/20/2018 RADICULOPATHY (2 of 2)  Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), also termed Guillain-Barré syndrome, is an acute, immune-mediated form of polyradiculopathy  Treat acutely with plasma exchange or IV immunoglobulin  Chronic inflammatory demyelinating polyneuropathy is a chronic form of AIDP and requires long-term immunotherapy  Patients with diabetes may present with diabetic amyotrophy, a lumbosacral polyradiculitis and plexopathy  Starts with subacute onset of severe neuropathic pain in the thighs, often asymmetric, followed by proximal muscle weakness in the legs and eventual atrophy  Refer atypical and severe cases of radiculopathy to a neuromuscular specialist MYOPATHY (1 of 2)  Characterized by proximal muscle weakness, wasting, and diminished or absent reflexes  Can be accompanied by increases in muscle enzymes, myopathic pattern on electromyogram, and abnormal muscle biopsy  Polymyositis: disorder of skeletal muscle  Muscle biopsy shows signs of lymphocytic infiltration, and usually also myocyte degeneration and regeneration  Prednisone is the treatment of choice but should be used with caution in older adults 23  1/20/2018 MYOPATHY (2 of 2)  Thyroid-related myopathies  Weakness and wasting are greatest in the pelvic girdle muscles and, to some extent, the muscles of the shoulder region  Reflexes can be normal, and diagnosis is based on the distribution of muscle weakness  Improves with successful treatment of the underlying endocrine disorder, such as hypothyroidism  Drug-induced myopathy  For example, with corticosteroids, lipid-lowering agents, colchicine, procainamide MOTOR NEURON DISEASE (AMYOTROPHIC LATERAL SCLEROSIS) (1 of 2)  Progressive, fatal neurodegenerative condition involving both upper and lower motor neuron cell bodies  Progressive weakness and wasting of skeletal muscles, often in combination with bulbar palsy and respiratory failure  Common symptoms: gait disturbance, falls, foot drop, weakness in grip, dysphagia, dysarthria  Electromyography demonstrates findings consistent with diffuse denervation and poor recruitment of motor units 24  1/20/2018 MOTOR NEURON DISEASE (AMYOTROPHIC LATERAL SCLEROSIS) (2 of 2)  Differential diagnosis  Lesions at the level of the foramen magnum  Combination of cervical myelopathy associated with cervical and lumbar polyradiculopathies  Motor-predominant peripheral polyneuropathy  Average survival 2 to 3 years—presence of bulbar weakness carries a poorer prognosis  Treatment is mostly supportive—riluzole has modest effects on survival, time to tracheostomy (SOE=A) MYELOPATHY (SPINAL CORD DYSFUNCTION)  Intrinsic lesions can result from spinal cord tumors, vascular events (infarcts or hemorrhages), or trauma  Extrinsic lesions are more prevalent, such as:  Cervical spondylosis  Disc prolapse or herniation  Vertebral body subluxation due to rheumatoid arthritis  Meningioma or spinal metastases  MRI can be helpful for diagnosis, but abnormal findings are common in older adults  Decompressive surgery is recommended for persistent pain or progressive neurologic deficit 25  1/20/2018 SUMMARY Peripheral neuropathy is common in older adults  Diabetes is the most common cause in the US  Several medications are approved by the FDA for the treatment of painful diabetic neuropathy CASE 1 (1 of 4) A 63-year-old woman comes to the office because she has difficulty walking. She says her gait has changed over the last 6 months, and she now uses a walker. She fell 1 month ago while walking on uneven pavement. She states that her legs “just feel weak and lousy.” She has no pain in her lower extremities. History: diabetes mellitus, osteoarthritis, CAD Review of systems Increased urinary urgency Constipation Difficulty opening jars and buttoning blouses 26  1/20/2018 CASE 1 (2 of 4) Physical examination Impairment of fine motor skills of the hands Bilateral hyperreflexia in ankles and patella Positive Romberg test CASE 1 (3 of 4) Which of the following is the most appropriate next evaluation? A. Measure creatine kinase level. B. Measure serum vitamin B12 level. C. Obtain electromyography and nerve conduction studies of lower limbs. D. Obtain MRI of cervical spine. E. Obtain MRI of lumbar spine. 27  1/20/2018 CASE 1 (4 of 4) Which of the following is the most appropriate next evaluation? A. Measure creatine kinase level. B. Measure serum vitamin B12 level. C. Obtain electromyography and nerve conduction studies of lower limbs. D. Obtain MRI of cervical spine. E. Obtain MRI of lumbar spine. Subdural Hematoma 28  1/20/2018 Subdural Hematoma Defined as collection of blood between the dura and the arachnoid Usually due to head trauma, although the trauma may be mild, particularly in older adults Bilateral in approximately 15% of cases In older patients, chronic subdural hematoma is most relevant Incidence of Chronic Subdural Hematoma Increases with Age 29  1/20/2018 Symptoms of Chronic SDH  Headache  Slight to severe cognitive impairment  Hemiparesis  Seizures in some patients  Focal neurologic signs in some patients  Neuroimaging shows extra-axial blood collection Treatment of Chronic SDH Symptomatic and the patient’s condition is worsening—removal of the clot may be attempted Incidental finding on neuroimaging or the patient’s condition is improving— clinical monitoring is appropriate, as the hematoma may shrink and disappear without surgery 30  1/20/2018 Other Neurological Maladies— MS, GBS, Myasthenia Multiple Sclerosis 31  1/20/2018 Objectives Upon completion of this module and the assigned readings, the AGNP student will: Recognize the features of MS Understand and be able to apply diagnostic criteria Understand symptom management and disease management pharmacologic modalities for MS What Will be Covered… Prevalence Incidence Diagnostic Criteria Subtypes Management 32  1/20/2018 Prevalence  2.5 million worldwide  400,000 in US  $41,000 per pt./year [2014 costs]  2/3 more cases in women than men  2nd or 3rd decade (16-40 years old)  Before 10 or after 60 rare  More common in whites (Scandinavian or N. Europeans) Multiple Sclerosis  Most common cause of disability in young adults  Recurrent, occasionally progressive, inflammatory demyelination of white matter of brain and spinal cord  Multiple varied neuro symptoms and signs  Autoimmune attack on myelin: brain and spinal cord 33  1/20/2018 Multiple Sclerosis Cause unknown HLA antigens Genetic susceptibility Human herpes virus 6 Latent infection in CNS ? Vitamin D Deficiency Multiple Sclerosis  Typical symptoms Unilateral vision loss Diplopia (days to weeks) Hemiparesis (slow insidious) Fatigue, mobility, cognitive dysfunction, bowel and bladder, depression and mood disorders  Dx may be delayed secondary to not seeking medical attention 34  1/20/2018 Common MS Symptoms Ataxia  Numbness/paresthesias Cognitive  Bladder/bowel control dysfunction  Slow/slurred speech Diplopia  Spasticity Fatigue  Tremor Gait disorders  Weakness Optic neuritis Diagnosis History MRI [supports the diagnosis] Cerebral spinal fluid 35  1/20/2018 Differential Diagnoses  Acute disseminated  Syringomyelopathy encephalomyelitis  HIV associated  Foramen magnum lesion myelopathy  Progressive multifocal  Amyotrophic lateral leukoencephalopathy sclerosis  Pernicious anemia  Behçet's disease  Spinal cord tumor  Brain stem tumors  Vasculitis  CNS infections  Neuro syphilis  Lyme disease  Hereditary ataxia Diagnostic Criteria Two attacks, two areas of CNS involved Neuro signs at least two separate areas of involvement Best fit 36  1/20/2018 MS Subtypes Relapsing Remitting (RR) Secondary progressive (SP) Progressive relapsing (PR) Primary progressive (PP) RR and SP comprise 85% of cases Relapsing Remitting MS  Relapsing and remitting  Attacks followed by partial or complete recovery  Average untreated attack 1-2 per year  Most common  Best prognosis  Usually last 6-10 years, 30-40% transition to slow progression (SP)—clear period of remission  May have functional decline  Spastic paraparesis—use of wheelchair  Bowel and bladder dysfunction 37  1/20/2018 Primary Progressive MS 5-10% Absence of relapses, steady decline of neurologic function Marburg syndrome Rare Explosive course—rapid decline and death Management Disabling symptoms Acute attacks—therapies to reduce inflammation and shorten duration Long term treatment Five therapies approved Reduce attacks Prevent new lesions in brain Slow disability 38  1/20/2018 Nonpharmacologic Treatment Aggressive rehab after acute events 80% of patients use complementary or alternative medicine Yoga ?cannabis extracts Pharmacology  Symptomatic treatments  Sometimes overused, probably because patients may feel better, but do not change disease course  Usually relatively inexpensive  Disease modifying agents  Have the potential to change the long term sequelae of disease progression  Very expensive, long-term medications  Many side effects  Poor adherence very common  Interferon type medications  Other immune modulators 39  1/20/2018 Pharmacology / Therapy for Symptom Management…  Fatigue  Amantadine / Modafinil  Urinary symptoms  Flomax  Urodynamics / Intermittent self-catheterization  Muscle spasticity  Exercise / PT  Muscle relaxants/benzodiazepines  Depression  50% lifetime  SSRIs Relapses  Not all need to be treated  Gait and vision  Distinguish between new attack and “pseudo- attack”  Tend to have sx when ill, fatigued or overheated  Shorten duration and severity of attack  Corticosteroids (60-80 mg qd one week then slow taper)  Gold standard  Methylprednisolone: 1 gm qd IV 3-5 days  Not as much evidence for plasmapheresis, immunosuppression 40  1/20/2018 Long Term Therapies  No approved therapies for PPMS  Two recombinant interferon beta RRMS IFN-beta-1a (Avonex) Glatiramer acetate (Copaxone) myelin-like polypeptide SPMS and RRMS IFN-beta-1a (Betaseron) RRMS, SPMS, PRMS Mitoxantrone (Novantrone) anthracenedione with both anti-inflammatory and immunomodulating properties Most drugs require premedication/titration regimen Summary  Course is variable and unpredictable  Some patients live fairly normal lives with little disability  Others may live many years dependent on caregivers, formal and informal  Those without adequate resources at home, often end up in nursing facilities, sometimes at very young ages – 30-40yo 41  1/20/2018 Guillain-Barre Syndrome Guillain-Barre Syndrome (GBS)  Guillain-Barre Syndrome (GBS) is an autoimmune disorder in which the body’s immune system attacks the peripheral nervous system  The patient develops symmetrical muscle weakness and tingling sensation  Starts in the legs and spreads to arms and upper body  Symptoms increase and sometimes the patient can be paralyzed  Symptoms develop within hours to weeks  Can be life threatening requiring ventilator support 42  1/20/2018 History and Incidence of GBS  First diagnosed in 1916 by George Guillain along with Jean Barre  They described two cases of paralysis with CSF changes  Rare, affects 1 in 100,000  Can affect any age and gender  Cause is unknown, not contagious  Usually occurs after a patient has had a viral infection  Sometimes after surgery  Symptoms progress from hours to weeks  Patient is weakest by third week Pathophysiology of GBS  Myelin sheath surrounding the axons is responsible for transmission of nerve signals in the body  In GBS the immune system attacks the myelin sheath surrounding the axons of peripheral nerves  When the myelin sheath is destroyed the nerves cannot transmit signals efficiently and the brain receives less sensory signals  This causes the inability to feel pain or other sensations  Sometimes the brain receives inappropriate signals causing the tingling sensation in GBS 43  1/20/2018 Symptoms and Differentials Symptoms Differentials  Weakness  Bilateral Strokes  Facial droop  Acute Myelopathy  Dysarthria  Multiple Sclerosis  Dysphagia  Nutritional  Ophthalmoplegia Neuropathy  Muscle paralysis  Poliomyelitis  Absent reflexes Diagnostics for GBS  CBC, CMP, B12, folic acid, ESR, HgbA1c  Nerve Conduction Studies- results consistent with demyelination  Pulmonary Function Tests- to monitor respiratory status  Lumbar Puncture- elevated CSF protein with normal CSF count  Serial lumbar punctures with rising protein levels and 10 or less mononuclear cell/mm3 supports the diagnosis  MRI- may show selective anterior root enhancement but is not specific  Muscle Biopsy may be done in some cases 44  1/20/2018 Treatment for GBS  Admit to hospital for close observation  ⅓ require ICU admission due to respiratory failure  Plasmapheresis- may help by removing autoantibodies and immune complexes  Immunoglobulin therapy—lessens immune attack on the CNS  Steroids are not helpful and not used  Lovenox, heparin in hospital  Graded compression stockings (30-40 mm Hg or higher) to prevent DVTs  Patient will require PT,OT,ST depending on the symptoms and after recovery.  15 % of patients have residual weakness after 3 years Research in GBS  International Guillain- Barre Syndrome Outcome study (IGOS)  Internationally collaborated prospective trial  The aim—examine outcomes of the disease based on clinical and biological determinants and predictors in patients with GBS  Clinical course is variable and this data will help provide better treatment https://clinicaltrials.gov/ct2/show/NCT01582763 45  1/20/2018 Myasthenia Gravis Some of the data on Myasthenia is courtesy of Dr. Shirley Wray from Harvard http://www.library.med.utah.edu/N OVEL 46  1/20/2018 Myasthenia Gravis  Normally impulses travel along the nerve to the ending and release the neurotransmitter substance acetylcholine  Acetylcholine travels through the neuromuscular junction and binds to acetylcholine receptors, which are activated, and generate a muscle contraction  In myasthenia gravis, person’s own antibodies block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction, preventing muscle contraction Myasthenia Gravis Myasthenia gravis is a disease of skeletal muscle acetylcholine receptors The chemical transmitter, acetylcholine (ACh) is unable to bind to the receptors (AChR) on the postsynaptic membrane to transmit the nerve impulse to muscle fibers to produce a muscle contraction 47  1/20/2018 Myasthenia Gravis  Thymus believed to be the site of antibody production  80% of MG people have thymus hyperplasia or thymus tumor  80 – 90% of MG people have auto- antibodies directed at acetylcholine receptor sites Start with a Detailed History…. Any unrecognized myasthenia features—such as: Intermittent diplopia Focusing purchases of new glasses to correct blurry vision, difficulty focusing and/or a need for a prism correction Use of dark glasses to reduce diplopia or hide drooping eyelids 48  1/20/2018 History [con’t]  Avoidance of certain foods that become difficult to chew and swallow  Cessation of activities that require prolonged use of muscle activity Myasthenia Gravis Clinical Classification  Ocular alone  Mild generalized  Moderately severe generalized + usually some bulbar involvement  Acute severe over weeks-months with severe bulbar involvement  Late severe with marked bulbar involvement 49  1/20/2018 Ocular Myasthenia Gravis  Because the majority of patients with myasthenia gravis present with ocular manifestations—the ophthalmologist plays an essential role in the diagnosis of MG—and a high index of suspicion facilitates the diagnosis Muscle Groups Involved at Onset Analysis of 295 cases Ocular alone 34% Bulbar alone 08% Extremities alone 15% Ocular and bulbar 07% Ocular and extremities 07% Bulbar and extremities 06% Ocular, bulbar and extremities 21% 50  1/20/2018 Eyelids Findings May Simulate… Congenital ptosis Senile ptosis Horner’s syndrome Mitochondrial myopathy Ptosis  Unilateral (partial or complete), alternating with or without paradoxical lid retraction, or see-saw ptosis  Bilateral and asymmetric, variable in severity  Lid twitch—Cogan sign  Increased ptosis with repetitive eye closure  Recovery of ptosis with gentle eye closure 51  1/20/2018 Ptosis Myopathy Myasthenia Symmetric Appearance Asymmetric No Ptosis on fatigue Yes No Lid twitch Yes No Recovery w/ eye closure Yes Constant Range lev. function Varies Yes Weak orb. oculi Yes Negative Tensilon test Positive 50% Family history Rare Slowly Progressive Course Fluctuates Presentation  MG occurs at any age, involves both genders and begins insidiously  Second and third decades most common age of onset in women  Seventh and eighth decades in men  Patients c/o specific muscle weakness, not generalized fatigue  Ptosis or diplopia—initial symptoms in 65% of patients 52  1/20/2018 Presentation [con’t]  Oropharyngeal muscle weakness—difficulty in swallowing and talking is the initial symptom in 17% of patients  Limb weakness presenting symptom in only 10% of cases  Severity of weakness fluctuates during the day, less in AM, worsening as the day progresses, especially after prolonged use of affected muscles  Before steroids, near 1/3 of patients improved spontaneously, 1/3 became worse and 1/3 died Presentation [con’t]  Ocular myasthenia – if progressing to generalized MG usually does so within the first two years after onset  After 15 to 20 years—weakness becomes fixed—the “Burnt-Out-Stage” + muscle atrophy Within first year ~75% develop head/neck +/- limb weakness ~67% reach maximum MG severity ~20% experience severe exacerbation/MG crisis 53  1/20/2018 Poster Child for this Disease….. Presentation  In most cases, the first noticeable symptom is weakness of the eye muscles  Diplopia (blurred or double vision)  Ptosis (drooping of one or both eyelids) 54  1/20/2018 Presentation  Majority also have weakness of face and throat muscles  Dysphagia (difficulty in swallowing)  Dysarthria (slurred speech)  Dysphonia (voice impairment )  Risk of choking + aspiration is increased MG Weakness Farouk D, 2000 55  1/20/2018 Tensilon Test Before After The Defect in Myasthenia Gravis  The muscle end-plate membrane is distorted  Acetylcholine receptors are lost from the tips of the folds, and antibodies attach to the postsynaptic membrane  Ach is released normally but absence of receptors prevents the transmitter binding to the muscle membrane 56  1/20/2018 AChR Antibody Test Positive in 85% of MG patients Antibody level does NOT correlate with disease severity between patients In an individual patient, changes in antibody levels do correlate Acetylcholine Receptor Antibodies  75% of cases generalized MG have serum antibodies (Ab) that bind to human AChR  54% with ocular MG have antibodies  10% MG cases with no binding antibodies have other antibodies  The AChR Ab titer varies widely among those with similar degrees of weakness—amount of Ab in the serum does not predict severity of the disease in individual patients  The Ab level may be low at onset on MG and gradually become elevated in late stage  Worthwhile to repeat test when initial values normal 57  1/20/2018 AChR Antibody is Not Diagnostic for Myasthenia Gravis:  It is also present in:  Systemic lupus erythematosus  Inflammatory neuropathy  Amyotrophic lateral sclerosis  RA patients taking D-penicillamine  In cases of thymoma without MG Differential Diagnosis  Graves ophthalmopathy  Progressive External Ophthalmoplegia (PEO)  Oculo-pharyngeal Dystrophy  Myotonic Dystrophy  Lambert-Eaton Myasthenic Syndrome (LEMS)  Guillian Barre Syndrome – Miller Fisher variant 58  1/20/2018 Association of MG with other Diseases  Hyperthyroidism 6%  Rheumatoid arthritis, less than 2%  Systemic lupus erythematosus 2%  Diabetes mellitus 7%  Non thymus neoplasm 3% Factors that Aggravate MG Emotional stress Systemic illness e.g. viral URI Thyroid disease, hyper or hypo Pregnancy Menstrual Cycle Increased in body temperature Drugs 59  1/20/2018 Diagnostics  EMG (nerve conduction) tests—for specific muscle "fatigue" by repetitive nerve stimulation  They may demonstrate decrements of the muscle action potential due to impaired nerve-to-muscle transmission Diagnosis  ANA—blood test for presence of immune molecules or acetylcholine receptor antibodies  Tensilon IV—Edrophonium chloride—blocks the degradation of acetylcholine and temporarily increases the levels of acetylcholine at the neuromuscular junction ***Significant but temporary**** increased muscle strength within minutes 60  1/20/2018 Collaborative Treatment Goals  Control symptoms  Maintain functional ability (PT, OT, Speech)  Prevent complications: - Cholinergic crisis - Myasthenic crisis - Respiratory distress - Aspiration pneumonia - Malnutrition Treatment  PT and OT—help maintain daily activities during almost all phases of the disease by reducing and improving muscle weakness  Thymectomy—surgical removal of thymus gland (reduces symptoms in more than 70 % of clients without thymoma, and may cure some individuals, possibly by re-balancing the immune system)  Plasmapheresis—abnormal antibodies are removed from the blood  High-dose IV Immune Globulin—temporarily modifies immune system and provides body with normal antibodies from donated blood * (Last 2 therapies may be used to help individuals during especially difficult periods of weakness) 61  1/20/2018 Treatment The response to any form of treatment is difficult difficult to access because the severity of symptoms fluctuates Spontaneous improvement, even remissions, occur without specific therapy, especially during the early stages of the disease CHE Inhibitors  Mestinon (Pyridostigmine bromide) DOC—30 to 60 mg. q 6-8° daily  Prostigmine (Neostigmine bromide) 7.5 to 15 mg. q 6-8° daily  No fixed dosage schedule suits all patients  The need for ChE inhibitors varies from day to day and during the same day  Different muscles respond differently with any dose, certain muscles get stronger, others do not change and still others become weaker  The drug schedule should be titrated according to the patients work load and muscle activity 62  1/20/2018 ChE Inhibitors [con’t]  Many patients assume responsibility for their own drug dose  The goal is to keep the dose low enough to provide definite improvement 30 to 40 minutes later and allow the effect to wear off before the next dose  Advise patients re: adverse effects of ChE inhibitors Prednisone  Marked improvement or complete relief of symptoms occurs in 75% of cases—this improvement is in 1st 6 to 8 weeks, but strength may increase to total remission over months  Best responses in patients with recent onset MG, but chronic disease may also respond—the severity of the disease does not predict the ultimate improvement  Patients with thymoma have an excellent response to prednisone before or after thymectomy  Prednisone 60-80 mg/day until sustained improvement (usually 2 weeks)—then alternate days beginning with 120 mg tapered over months to lowest dose necessary (usually less than 20 mg alternate days) 63 1/20/2018 64  1/20/2018 GRS9 Slides Editor: Tia Kostas, MD GRS9 Chapter Author: Daniel L. Murman, MD, MS, FAAN GRS9 Question Writer: Matthew Barrett, MD Medical Writers: Beverly A. Caley Faith Reidenbach Managing Editor: Andrea N. Sherman, MS Copyright © 2016 American Geriatrics Society GRS9 Slides Editor: Mandi Sehgal, MD GRS9 Chapter Author: Leo M. Cooney, Jr., MD GRS9 Question Writers: Leo M. Cooney, Jr., MD Raymond Yung, MD Medical Writers: Beverly A. Caley Faith Reidenbach Managing Editor: Andrea N. Sherman, MS Copyright © 2016 American Geriatrics Society 65