Term
|
Definition
• Weakness
• Atrophy vs. hypertrophy
• Fasciculations, cramps, myotonia
• Pattern-symmetry, proximal vs. prox/distal |
|
|
Term
|
Definition
• Numbness, reduced sensation, postural instability
• Pain, burning, tight, electrical
• Allodynia
• Hypesthesia
• Paresthesias
• Pattern-Dermatomal, sensory level, distal symmetric |
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Term
|
Definition
• Bowel/bladder function • Orthostatic hypotension • Arrhythmias
• Sweating
• Heat intolerance
• Sexual function |
|
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Term
|
Definition
| • Weakness, MRC 1-5 • Orthopedic signs |
|
|
Term
|
Definition
• Vibration assessed with 128Hz tuning fork
• Sharp-pinprick or broken end of cotton swab
• Temperature
• Position |
|
|
Term
• ChiefComplaint:
• 59 year old man presents with progressive weakness of the arms and legs
• History:
• Symptoms began approximately 4 months ago with increasing difficulty combing his hair, arms fatigue with brushing his teeth and difficulty climbing stairs. Aching pain in the muscles of the upper arms. ROS is notable for generalized fatigue and mild difficulty swallowing.
• CranialNerves-IIthroughXIIintact
• Motor/Strength-4/5 weakness in arm abductors, biceps, hip abductors, otherwise 5/5, Mild weakness of neck flexors, tone/bulk are normal. Difficulty arising from a chair
• Sensation-intacttopp,lighttouch,vibration
• Reflexes-1+andsymmetric,toesdown
• Gait-waddling,noataxia |
|
Definition
| motor signs/symptoms, Myositos |
|
|
Term
|
Definition
| Subacute Proximal muscle weakness w Rash, inc CK, Perivascular, perimysial, perifascicular inflammation Necrotic fibers, perifasc atrophy, ANTi-MDA-5 Anti-Mi-2 Anti-TIF-1 Anti-NXP-2 |
|
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Term
|
Definition
| Subacute Proximal muscle weakness, inc CK, CD8+ cells invading healthy fibers incr expression of MHC class I antigen, Antisynthetase abs Anti-Jo-1 |
|
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Term
| Necrotizing Autoimmune Myositis |
|
Definition
| Acute/Subacute Severe Proximal muscle weawkness, most inc CK, Necrotic fibers, macrophages, No CD8+, complement depositis on capillaries, Anti-SRP Anti-HMGCR |
|
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Term
|
Definition
| Slow Proximal + distal Quads + forearms muscle weakness, slightly inc CK, CD8+, MHC expression, autophagic vacuoles, amyloid deposits, Anti-cN1A |
|
|
Term
|
Definition
| I won't go through this slide in detail, but it's just there for your reference to look at some mechanisms and understand some mechanisms of myositis and the development of activation of peripheral inflammatory cells, which then invade the muscle and go on to cause destruction. |
|
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Term
|
Definition
| Many muscle diseases, certainly the inflammatory muscle diseases in particular, are diagnosed by their pathology. And here you see a slide that demonstrates muscle pathology. So in the first picture on a, there is a norm there's muscle. And there's an abundance of inflammatory cells, which is indicative of this being an inflammatory muscle disease in myositis. You can see in the middle slide in the upper portion there's destruction of muscle. And the third slide on the right demonstrates staining for inflammatory cells, some markers of inflammatory cells. This is clearly an inflammatory muscle disease. |
|
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Term
|
Definition
• Clinical symptoms
• Myalgias in 50%
• Dysphagias 30%
• Muscle tenderness
• Extramuscular manifestation
• Heart-myocarditis, CHF, conduction defects
• Renal-mild disease, myoglobinuria
• Lungs-hypoventilation, interstitial lung disease |
|
|
Term
|
Definition
I want you to be familiar with this, which seems like a fairly rare inflammatory muscle disease, which is called inclusion body myositis. It's seen mostly in men over the age of 55. We had talked about common patterns of muscles previously. This muscle disease has a very particular clinical pattern. As you see in the slide here, the top slide demonstrates the thigh muscles and the forearm muscles. So this has a predilection of affecting those muscle groups in particular and often affecting those early.
We had said that common patterns of muscle disease are symmetric. This muscle condition tends to be asymmetric. So involvement of the quadriceps, involvement of the forearm flexors, are very commonly seen in inclusion body myositis. I've also included an MRI of the thigh, which shows scarring in the thigh muscles, as well as the pathology in inclusion body myositis, which is named for these vacuolar inclusions within the muscle. |
|
|
Term
|
Definition
New-onset: Prednisone
When weakness at onset is severe or rapidly worsening: IV glucocorticoids
For glucocorticoid sparing when pts condition responds to glucocorticoids: Azathioprine, methotrexate, mycophenolate, cyclosporine
If response to glucocorticoids in insufficient: IV immune globulin
If response to glucocorticoids and IV immune globulin is insufficient: reevaluate and reconsider diagnosis, initiate treatment w rituximab if diagnosis is reconfirmed and recommend participation in research trial if not responsive to rituximab |
|
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Term
|
Definition
Muscular dystrophies represent a large category of various inherited muscle diseases. In the upper left hand corner of the slide is a Gower's maneuver. This is a classic finding in kids with some muscular dystrophies where they have significant proximal weakness and there they need to form this three point stand to get up from a floor and climb up on themselves.
On the right you see these shaded areas of a variety of muscular dystrophies and their particular pattern of muscle involvement. The shaded areas represent the muscles that are involved in some of these various muscular dystrophies. Of course, it's difficult to just diagnose these muscular dystrophies on their clinical patterns. And in the lower left hand corner, you see these proteins that are involved in a number of the muscular dystrophies and a number of abnormalities that have been described through molecular biology findings of these deficits in these proteins. |
|
|
Term
| Duchenne Muscular Dystrophy: Treatment |
|
Definition
| I did want to point out one major breakthrough in muscular dystrophy. And this slide just demonstrates one of the treatments that is now available for Duchenne's muscular dystrophy in this extremely large protein with this mutation. There are now therapies that can skip these mutated axons and produce a protein, which isn't the full protein, a partial protein, which can be functional. This is a really exciting time in muscular dystrophy. There are a number of other therapies that are coming out and will be coming out. So it's really quite an exciting field right now. |
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Term
|
Definition
An additional muscle disease that I wanted to mention is statin myopathies. This shows you the statin enzymatic pathways. Statins are one of the most common medications that are prescribed. In a small group of people, there is this side effect of muscle disease.
It has a broad range clinical spectrum of just elevation of the CK, which is the creatine kinase, which is a marker of muscle which is spilled out of the muscles. It can be muscle pains, aches and pains, myalgias, with or without an elevation in the CK. It can be persistent muscle symptoms. Even after stopping the statins, these sometimes persist in people.
[image] |
|
|
Term
Statin Myopathy
• Clinical Spectrum |
|
Definition
• Asymptomatic elevation CK
• Myalgia + CK
• Persistent muscle sxs and high CK after statin
• Necrotizing autoimmune myositis
• Rhabdomyolysis |
|
|
Term
• Chief Complaint:
• 65 year old man presents with two month history of intermittent double vision
• History:
• Diplopia occurs mostly at the end of the day and wife observes his right eyelid is drooping. He finds it difficult to read at the end of the day due to double vision. After giving a speech his words become slurred but recover after a brief rest. He reports difficulty walking upstairs.
• CN-diplopiaafter15secondsofupgazewith drooping of the right eyelid, speech is slurred by the end of the interview, mild weakness of neck flexion
• Motor-4+/5ofarmabductorswhichworsenswith repeated testing, Neck flexors-4+/5,
• DTRs-1+symmetric,toesaredown
• Gait-normal,difficultyarisingfromfloorafter three squats |
|
Definition
|
|
Term
|
Definition
- Symptoms
• Fluctuating weakness, exacerbated by exertion, fatigue and improved by rest
• No atrophy, reflex abnormality, sensory loss
• Droopy Eyelids
• Double Vision
• Slurred Speech
• Difficulty Swallowing • Dyspnea
• Facial Weakness
• Head Drop
• Arm/Leg weakness
- Clinical forms
• Ocular: ptosis, double vision
• Bulbar: dysphagia, dysarthria, weakness of chewing
• Generalized: weakness of limbs, with proximal emphasis |
|
|
Term
|
Definition
This slide demonstrates function at the normal neuromuscular junction and then the changes in the pathophysiology you see in myasthenia gravis. So as you can see on the slide, this is the presynaptic terminal, and this is the postsynaptic membrane. Acetylcholine is packaged in these vesicles and released in the presynaptic terminal into the neuromuscular junction. It then travels across and binds the acetylcholine receptors to represent it with the short dark lines on the postsynaptic side.
Binds. When there is an adequate endplate potential, it results in contraction of the muscle. The acetylcholine is processed by acetylcholinesterase. The choline is taken up again on the presynaptic side and the process continues. Some of the changes that you see in myasthenia gravis are as a result of antibody mediated destruction of the postsynaptic membrane. You lose the membrane. There are fewer acetylcholine receptors available, and with destruction of the membrane, the distance that the acetylcholine neurotransmitter has to travel becomes further. And all of this adds up to neuromuscular junction transmission failure, which results in weakness. |
|
|
Term
|
Definition
• Incidence 3-30/1,000,000
• Bimodal distribution: Young women / Old men
• 10-20% of patients have thymoma |
|
|
Term
|
Definition
• Ocular MG (OMG)
• Generalized MG (GMG) • Early Onset MG (EOMG) • Late Onset MG (LOMG)
• Antibody Positive
- AChR, MuSK
- Others (LRP4, Agrin, etc.)
• Seronegative
• Thymoma-associated MG |
|
|
Term
|
Definition
Bed Side Tests
• Ice Pack Test
• Edrophonium test
• 70% sensitive
• Rest Test
EMG and Lab tests
• AChR Ab (acetylcholine receptor)
• MuSK Ab (Muscle Specific Kinase)
• EMG / NCS
- RNS 60% sensitive
- SFEMG 90% sensitive |
|
|
Term
|
Definition
This is one of the techniques used in nerve conduction studies, which is called repetitive nerve stimulation.
A train of stimuli are given, and in myasthenia gravis, as demonstrated here in the slide, there is a decreasing response seen which then starts to recover slowly. So sort of a U-shaped response here, which is typical of neuromuscular transmission failure and consistent with myasthenia gravis. |
|
|
Term
|
Definition
- Non-immune/Symptomatic
• Pyridostigmine 30-60mg /4-6 hours
- Immunomodulatory
• IVIG 2g/kg
• Plasma Exchange 250ml/kg
- Immunotherapy
• Prednisone
• Azathioprine
• Mycophenolate mofetil
• (Cyclosporine,Cyclophosphamide,Tacrolimus) • Rituximab |
|
|
Term
| MG: Current Clinical Trials |
|
Definition
• A Phase 2 Trial of Rituximab in Myasthenia Gravis
• A Phase 3 Trial of Eculizumab in Refractory MG |
|
|
Term
|
Definition
- Absolutely Contraindicated
• Curare and related drugs
• D-Penicillamine
• Botulinum toxin
• Interferon alfa
- Relatively Contraindicated—Likely to Adversely Affect Neuromuscular Transmission
• Aminoglycosides (gentamicin, kanamycin, neomycin, streptomycin, tobramycin)
• Macrolides (erythromycin, azithromycin, telithromycin)
• Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin)
• Quinine, quinidine, procainamide
• Magnesium salts
- Caution — May Exacerbate Weakness in Some Patients With Myasthenia Gravis
• Calcium channel blockers
• Beta-blockers
• Lithium
• Iodinated contrast agents
• Statin drugs |
|
|
Term
• Chief Complaint
• 40 year old woman with 10 year history of diabetes presents with several months of numbness and pain in the feet
• History
• Feels like her feet are “wrapped with tape”. The pain is worse in the evening. Sheets rubbing against feet hurt. Also describes pins and needles, burning/shooting pains. The pain is unpredictable and interferes with walking, sleeping.
• CNII-XII:intact
• Motor:normalwiththeexceptionofmild weakness of toe extension
• Sensory:absentvibrationsensationattoesand moderately decreased at ankles. Pinprick decreased to just below knees and wrists. Temperature sensation is reduced in legs as compared to arms
• DTRs:absentatankles,1+atknees,bicepsand triceps
• Gait:+Rhomberg,noataxia |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Diabetic Neuropathy: Clinical Classifications |
|
Definition
- Symmetrical
• Diabetic Polyneuropathy
• Autonomic neuropathy
• Painful distal with weight loss
• Insulin Neuritis
• CIDP
• Impaired glucose tolerance
- Asymmetrical/Focal and Multifocal
• Mononeuropathies
• Compressive
• Cranial neuropathies
• Thoracic Radiculopathy
• Lumbosacral Plexopathy |
|
|
Term
| Almost one half of patients with Diabetes- IDDM or NIDDM |
|
Definition
will develop neuropathy
• Most common cause of PN in Western world
• 8% neuropathy at diagnosis and 50% after 25 years |
|
|
Term
| Diabetic Neuropathy: Pathophysiology |
|
Definition
• Hyperglycemia
• Abnormalitiesoflipid or amino acid metab
• Othermetabolic causes
• Secondaryvascular insult |
|
|
Term
|
Definition
| HTN, smoking, HbA1c, diabetes duration, BMI, triglycerides, total cholesterol |
|
|
Term
| Diabetic Neuropathy: Complications |
|
Definition
Of course, this is a complication we don't want to see is these are severe diabetic foot ulcers that come from insensate feet and these lesions that progressively get worse and can develop into skin infections, bone infections, and horrible complications, and diabetes being one of the more common causes of non-traumatic amputations.
Diabetes can also cause a painful neuropathy. This is an old slide, but it shows you the frequency of painful neuropathy in people with diabetes. So of all the diabetic neuropathies, some studies have suggested that 15% experience pain with their diabetic neuropathy. And I suspect that number is even higher. So again, a very common problem. |
|
|
Term
|
Definition
|
|
Term
|
Definition
| I won't go through this slide in any detail but it does list a number of the common medications used for neuropathic pain and their target within the nervous system, if they're acting directly on the peripheral nerve, on the C-fibers, or some of the supporting cells. So I'll just leave this here for your reference. |
|
|
Term
| Distal Symmetric Polyneuropathy: Symptoms |
|
Definition
• Numbness, tingling, pain, and weakness starting in the toes
- Sensoryexamination
• Decreased pinprick and vibration sensation in a stocking-glove
- Motorexamination
• Weakness of toe extension or trouble walking on heels
- Reflexes
• Decreased reflexes starting at the ankles |
|
|
Term
|
Definition
So when you see this pattern, there have been some algorithms. So this is an algorithm for distal symmetric polyneuropathy out of the Journal of the American Medical Association. So of course this is a difficult to read slide. I've just blown up one portion of it, which just reminds you that if there are some atypical features to this distal symmetric pattern that it certainly warrants neurological consultation and probably a more extensive work up. Those atypical features include asymmetry, non-length-dependent, so it's not just a distal pattern, very prominent motor deficit, acuity, it comes on fairly fast, and significant autonomic involvement.
Otherwise, if those atypical features are not there, look for the common causes of neuropathy. We had discussed diabetes. Other common causes are alcoholism, chemotherapy, maybe some other medications. If that's clear that that's the cause, the algorithm would suggest that no other testing is needed.
And if the cause is not clear that there is some initial evaluation and laboratory tests that are outlined here. So this is just a good framework for how to think about distal symmetric polyneuropathy and how to initiate a work up for distal symmetric polyneuropathy. |
|
|
Term
|
Definition
- Symptoms
• Numbness, tingling, pain, and weakness in the distribution of 1 nerve
- Examination
• Sensory examination • Decreased pin prick and vibration sensation in the distribution of 1 nerve (ie, decreased pinprick in digits 1-3 and the lateral half of digit 4 in median neuropathy)
• Motor examination • Weakness in the distribution of 1nerve (ie, finger abduction weakness in ulnar neuropathy)
- Diagnostic testing
• Electromyography and nerve conduction studies when diagnostic uncertainty exists or surgery is contemplated |
|
|
Term
|
Definition
- Symptoms
• Numbness, tingling, pain radiating from the neck or back into the extremities in a dermatomal pattern
• Weakness in a myotomal pattern
- Examination
• Sensory examination • Results usually normal given the overlapping innervation of dermatomes
• Motor examination • Weakness in myotomal pattern (ie, dorsiflexion, ankle eversion and inversion weakness in L5 radiculopathy)
• Reflexes • Decreased reflexes in dermatomal pattern (ie, absent ankle jerk in S1 radiculopathy)
- Diagnostic testing
• Electromyography and nerve conduction studies when diagnostic uncertainty exists (of note, test is not sensitive for the detection of a sensory predominant radiculopathy)
• Magnetic resonance imaging (cervical or lumbar) for patients with progressive neurologic dysfunction or when surgery is contemplated; lack of high-quality evidence to define precise clinical scenarios in which magnetic resonance imaging should be ordered |
|
|
Term
|
Definition
Pes Cavus and Hammer Toes
I did want to briefly mention inherited neuropathies. So when you see this foot pattern, pes cavus and hammerer toes, neurologists often think of inherited nerve problems. There are other reasons to have pes cavus and these high arch feet, or flat feet for that matter. There are orthopedic reasons. But certainly the neurologic reason that it's most commonly seen in is inherited nerve disorders. |
|
|
Term
|
Definition
• Chronic, slow progression
• Minimal sensory symptoms
• Difficulty with running, sports, military
• Family history
• Foot deformities and troubles
• Examine family members |
|
|
Term
• Chief complaint
• 42 year old woman develops weakness,numbness and paresthesias over 3 days
• History
• Two weeks ago onset of viral illness. Three days ago tingling and numbness in feet. Over the next few days creeped up her legs and was followed by difficulty walking. Arms developed similar symptoms over the past 24 hours.
• Cranial Nerves: mild facial weakness involving the upper and lower face
• Motor: Moderate weakness of proximal and distal muscles in arms and legs
• Sensory: decreased sensation to vibration and pinprick
• DTRs: absent throughout
• Gait: mild ataxia, +Rhomberg |
|
Definition
|
|
Term
|
Definition
• Acute Inflammatory Demyelinating Polyneuropathy
• Ubiquitous in location age and gender
• Worldwide incidence is 1.5/100,000
• Viral prodrome 60-70% of cases |
|
|
Term
| Guillain Barre Syndrome Diagnosis |
|
Definition
• ClinicalHistoryExam-progressivediffuse weakness and hyporeflexia, primarily motor with sensory symptoms. Areflexia/Hyporeflexia. Progression up to 4 weeks
• LumbarPuncture-Cytoalbuminologic dissociation
• EMG/NCS-demyelinatingpolyradiculopathy
• Lab-Lyme,HIV,ANA/ENA,Hepatitis,CPK, Diptheria |
|
|
Term
|
Definition
| The slide here shows the typical time course of the Guillan-Barré. So this curve represents the preceding infection. And then the blue curve represents weakness, which strength is normal here, and then the weakness progresses approximately two weeks after the initial infection, and then hits maximum certainly within four weeks, and then, hopefully, there is recovery. This slide has an additional graph demonstrating the development of nerve antibodies. |
|
|
Term
|
Definition
This slide shows the typical nerve conduction findings that you see in Guillan-Barré. Over here is a fairly normal nerve conduction study. This is a single motor nerve stimulated at multiple sites. I'll point to this median nerve conduction here, which is normal when conducted at the wrist.
And when conducted at more proximal sites in the upper arm, there is this reduced response. It should look the same. There's a reduced response that's sort of spread out. And this is very typical of what you see in demyelinating neuropathies with conduction block. Again, very typical of Guillan-Barré. |
|
|
Term
|
Definition
| I won't go through this side in tremendous detail, but I did just want to point out that some of the pathophysiology of Guillan-Barré is demonstrated here in which there is a preceding infection, in this case campylobacter jejuni, a GI infection, which stimulates the immune system and then produces antibodies against the infection. But those antibodies also find similar epitopes within the nerve. And this results in a form of friendly fire where the immune system attacks your own peripheral nerves. |
|
|
Term
| guillain barre syndrome treatment |
|
Definition
• Admit to ICU
• IVIG(0.4g/kg/day x 5d) vs. Plasmapheresis • <2 weeks from onset • Severely affected
• Respiratory monitoring
• Autonomic dysfunction
• Pain management
• Venous thrombosis
• Physical therapy |
|
|
Term
• Chief complaint
• 35 year old PA complains of numbness in the hands that wakes her at night.
• History
• Tingling, paresthesias, numbness and some weakness of hand grip over the past several months, possibly longer. Symptoms are particularly worse with driving, typing and awakening.
• CN-intact
• Motor-5/5 all muscle groups
• Sensation-decreased sensation in the right hand as compared to left
• DTRs-2+ and symmetric
• Gait-Normal |
|
Definition
| Median Neuropathy/carpel tunnel |
|
|
Term
|
Definition
| So this is typical of median nerve involvement or carpal tunnel syndrome. So this is the anatomy of the median nerve. This shows you the distribution on the hand-- the typical distribution of sensory abnormalities in the median nerve, which involve the first three fingers and half of the fourth finger. That's also demonstrated here on the left as well as the anatomy of the median nerve. |
|
|
Term
|
Definition
• Mostcommonentrapmentneuropathy • Lifetimeriskof10%
• F:M,3:1
• Oftenbilateral,dominanthandfirst
• Predispositionassociatedwith
- Occupations with repetitive movement
- Age
- Obesity
- Pregnancy, thyroid disease, systemic illness, diabetes, rheumatoid arthritis |
|
|
Term
| Carpal Tunnel Syndrome: Symptoms |
|
Definition
• Pain and Paresthesias • nocturnal acroparesthesias
• Relief with shaking
• Pain at wrist, radiating to arm
• Numbness of fingers
• Weakness and Atrophy |
|
|
Term
| Median Neuropathy: Examination |
|
Definition
• Loss of sensation
• Two point discrimination
• Weakness of thumb abduction
• Atrophy of thenar eminence
• Tinels sign
• Phalen sign
• Sympathetic changes |
|
|
Term
| Median Neuropathy: Management |
|
Definition
• Remove offending agent • Ergonomic changes
• Wrist splinting
• AntiInflammatory
• ?Riboflavin
• Corticosteroid Injection
• Surgical decompression |
|
|
Term
| Amyotrophic Lateral Sclerosis From Charcot.... |
|
Definition
• A-without
• Myo-muscle
• Trophic-nourishment
• Lateral-lateral corticospinal tracts
• Sclerosis-gliosison pathology |
|
|
Term
| Amyotrophic Lateral Sclerosis aka |
|
Definition
| lou gehrig's based on yankee player |
|
|
Term
|
Definition
• Incidence2per100,000 • Prevalence5-7/100K
• 60%men
• Averageage55y
• 90%sporadic
• 10%genetic
• 50%diein30months
• 20%between5-10y |
|
|
Term
|
Definition
- Upper Motor Neuron
• Spasticity
• Hyperreflexia
• Pathological reflexes
- LowerMotorNeuron
• Weakness
• Atrophy
• Hyporeflexia
• Fasciculations |
|
|
Term
|
Definition
• Weakness
• Spasticity
• Lossofmuscle
• Dysarthria
• Dyspnea
• Dysphagia
• Cramps
• Pseudobulbar affect • Emotional lability
• Pain
• Sialorrhea
• Depression
• Cognitive and Personality changes |
|
|
Term
|
Definition
• Classic“Charcot”
• Bulbar
• Flailarm
• Flailleg
• Pyramidal
• Respiratory
• Pure lower motor neuron
• Pure upper motor neuron |
|
|
Term
|
Definition
I just want to emphasize the spectrum of disease, which is ALS, which I mentioned on the previous slide. In the upper bar is the spectrum of disease of lower motor neuron predominant or pure low motor neuron involvement and upper motor neuron involvement on the right-hand side. ALS is a combination of upper and lower motor neuron involvement. There are diseases and conditions on the extremes. PMA is progressive muscular atrophy, which is purely lower motor neuron. And PLS is primary lateral sclerosis, which is purely upper modern neuron.
It has also been well-recognized that there is cognitive dysfunction that can occur, specifically frontotemporal dementia and frontotemporal dysfunction, which can occur in association with ALS and other motor neuron diseases. And the second bar represents that spectrum in which ALS is on one in and frontotemporal dementia on the other end and some combination of the two in between. Lastly, the third bar represents what we see as classic ALS, as I described it, and other neurodegenerative conditions which have features of ALS and maybe involvement of other parts of the nervous system. |
|
|
Term
| ALS: Diagnostic Criteria El Escorial /Awaji |
|
Definition
| The clinical criteria for ALS for clinical trials, which is defined in this El Escorial/Awaji criteria divides the body into four regions-- the head, the cervical region, including the arms, the thoracic region, and the lumbar region, which includes the lower back and the legs. Involvement in three of these regions-- lower motor neuron and upper motor neuron involvement-- in three of these regions is typical of ALS. |
|
|
Term
|
Definition
| This slide demonstrates ALS pathology. We had discussed what Charcot had seen, this gliosis in the lateral corticospinal tracts in this slide of the spinal cord. Over here, you see the motor neurons within the anterior horn portion of the spinal cord. And there are these inclusions that have been seen in ALS. And on this coronal MRI, you see signal changes in the corticospinal tract that represent degeneration of the upper motor neuron. |
|
|
Term
|
Definition
C9orf72 = chromosome 9 open reading frame;
SOD1 = superoxide dismutase 1, soluble;
TARDBP = transactive response DNA binding protein
FUS = fused in sarcoma RNA binding protein.
ALS genetics is a complicated field. And there are increasing number of genes that have been associated with ALS that are being described. The most recent discovery or the most common gene, I should say, discovered in the past few years is C9orf72 or chromosome 9 open reading frame. This gene that has these repeat segments has been associated with ALS and frontotemporal dementia. And as I said, there are increasing number of genes being described in ALS. |
|
|
Term
|
Definition
| I won't go through this very busy slide with you, but it lets you know that it lays out for you a number of the theories and ideas and mechanisms that are being explored that can cause ALS, which involve the motor neuron, the postsynaptic membrane, or the supporting cells. |
|
|
Term
|
Definition
Riluzole
• Approved by FDA in 1995
• Inhibits glutamate release
• 50mg BID
• Benefit is modest
• Cohort studies suggest longer benefit
• SE-Fatigue and nausea
• Monitor LFTS
Edaravone
• Approved 2017
• Free Radical Scavenger
• Daily Infusion for 2 weeks every month
• Improvement in milder pts with short duration disease
• SE-allergic rxn |
|
|
Term
|
Definition
|
|
Term
|
Definition
• Weakness: Proximal, Symmetric, Persistent
• Weakness > Wasting
• Sensory: Normal
• Reflexes: Normal or decreased only in areas of prominent weakness
• Myositis, Muscular Dystrophy |
|
|
Term
| Neuromuscular Junction Disease |
|
Definition
• Weakness - Proximal and Distal, Extraocular muscles and face often involved
• Temporal changes: Variable, Fatigue
• Sensory: Normal
• Tendon reflexes: Normal
• Myasthenia Gravis, Botulism |
|
|
Term
|
Definition
• Motor, Sensory or Autonomic symptoms
• Distal predominant
• Decreased reflexes
• NCS-axonal and/or demyelinating features
• Diabetic neuropathy, CTS, GBS |
|
|
Term
|
Definition
• Neuromuscular diseases are common disorders
• Disease pattern recognition is key to diagnosis
• Treatment options are available for many of these diseases |
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|
