Day 5 - Multiple Sclerosis Flashcards
Definition & Pathology of MS
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS) due to immune-mediated inflammation & formation of hallmark white matter plaques → demyelination, relative axonal sparing, and brain atrophy.
Acute lesions: remyelination may occur, which results in a “remission.”
Chronic lesions: older plaques become sclerosed
Four main types of disease course in MS 🔑
Relapsing-remitting (RR MS)
The most common pattern: 85% to 90% begin with RR MS
Return to baseline or mild disability
Secondary progressive (SP MS)
50% of RRMS convert to SPMS after 10 years; 90% after 25 years
Primary progressive (PP MS)
10% of cases at disease onset & worst prognosis
Progressive Relapsing (RP MS)
Clinically Isolated Syndrome
- A first attack compatible with MS, with evidence of inflammation and demyelination
- Typically lasts a minimum of 24 hours
- Does not yet meet criteria for MS
MS commonly seen in
- Females > males 2:1
- Mean onset age 30
- Low vitamin D
Good vs Poor Prognostic Indicators 🔑
Ibn Sina “Good”: Female, ambulatory, young, optic, good recovery, RR..
- Female sex, Younger age at onset (less than 35 years of age)
- Monosymptomatic
- Sensory optic neuritis
- Sudden, good recovery with long remission (RR type)
- Low disability
- Ambulatory
Poor
- Male sex, Older at onset (age more than 35 years)
- Polysymptomatic
- Motor (first sign) ataxia and tremor
- Rapidly progressive
- High disability
- Non-ambulatory
List 6 Diagnostic Workup (Non-Blood) 🔑🔑
- MRI of the brain and spinal cord (Test of choice)
- CSF analysis (Lumbar puncture) → oligoclonal banding
- Visual evoked potentials (VEPs)
- Somatosensory evoked potentials (SSEPs)
- Brainstem auditory evoked potentials (BAEPs)
- NCS & EMG
Ref: Cucurollo
List 5 Hallmark location of demyelination 🔑
Dissemination in space, lesion in two out of five areas:
- Cortical
- Juxtacortical
- Periventricular
- Infratentorial (Cerebellar)
- Spinal Cord
Extra
- Brain stem
- Optic nerve
List 6 Differential Diagnosis of MS 🔑
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Vasculitis
- Vitamin B 12 deficiency
- Transverse myelitis
3 Most Prevalent Symptoms of MS
3 Problems Affecting ADLs Reported by Patients
Most Prevalent Symptoms of MS
- Fatigue (central in nature)
- Pain: Dysesthetic; painful spasms most common
- Bladder and bowel dysfunction
Problems Affecting ADLs Reported by Patients
- Fatigue (central in nature)
- Weakness
- Balance
Five Domains of Motor Symptoms in MS, What to examine?
- Fatigue
- Spasticity
- Weakness
- Balance
- Cerebellum: DANISHP
- Dorsal columns: impairment of deep sensation, and proprioception
- Bulbar
- Dysarthira
- Dysphagia
Five Domains of Non-motor Symptoms in MS, What to ask?
Cognition: memory, attention, processing speed, learning
Cranial Nerves
- Optic n. Optic neuritis
- CN 3,4,6 : diplopia, internuclear ophthalmoplegia
- CN 5: Facial numbness
- CN 8: Deafness, tinnitus, vertigo, vomiting
- CN 9,10,11: Dysphagia
Sensory
- Pain: Dysesthetic; painful spasms
- Heat sensitivity (Uhthoff phenomenon)
Bladder, bowel dysfunction
Bed Questions
Sleep disorders, obstructive sleep apnea (OSA), restless legs syndrome
Mood: impaired emotional responses, depression
Sexual dysfunction
List 4 Common Signs in MS🔑
- Lhermitte’s sign
Passive neck flexion causing an electric, shock-like sensation radiating to the spine and
shoulders → Increased sensitivity of the myelin to stretch or traction.
- Uhtoff’s phenomenon
Exacerbation of fatigue, weakness and other symptoms when exposed to high temperatures or increased body temperature
- Tic douloureux
Painful trigeminal neuralgia
- Upper motor neuron signs
Spasticity, Hyperreflexia, Positive Hoffman and Babinski responses
Acute Attacks Tx for MS
Methylprednisolone (1g for 3-7 days)
Decrease length of exacerbation and return to pre-morbid function
Does not prevent further attacks or alter disease progression
Acute and chronic S/E of corticosteroid
Acute
- Gastrointestinal (GI) disturbance
- Fluid retention
- Electrolyte imbalance
- Mood swings
- Insomnia
- Acne
- Hyperglycemia
- Hypertension
Chronic
- Hypertension
- Osteoporosis
- Diabetes
- Weight gain
- Cataracts
List 4 disease modifying agents for MS
Oral
- FINGOLIMOD (GILENYA)
- DIMETHYL FUMARATE (TECFIDERA)
- TERIFLUNOMIDE (AUBAGIO)
IV for okra beef
- NATALIZUMAB (TYSABRI)
- OCRELIZUMAB (OCREVUS)
- ALEMTUZUMAB (LEMTRADA)
S/C for Seron
- INTERFERON BETA-1B (BETASERON)
List 3 common side effects for MS disease modifying agents? 🔑
Reduction of immune system:
- Flu-like symptoms
- Post-injection fatigue.
- Skin reactions
Medication for improving gait & cognition in MS 🔑🔑
Dalfampridine (Ampyra) 10 mg orally twice a day
Acetylcholinesterase inhibitors e.g., donepezil (Aricept) 5mg bedtime
Expanded Disability Status Scale (EDSS)
The EDSS is a number that rates a patient’s degree of disability from MS on a scale of 0 to 10.
0 = Normal
4 = Ambulatory without aid
6 = Cane
7 = Wheelchair
8 = Bedbound
10 = Death
How do you assess and manage fatigue in MS?
Fatigue Types
- Central fatigue
- Feeling of constant exhaustion, laziness, tiredness → Not alleviated with rest.
- Peripheral fatigue
- Sense of exhaustion after a few minutes of physical activity → Alleviated with rest.
- Primary
- Disease process (MS), Heat intolerance & vigorous exercise
- Secondary
- Medical: Anemia, Hypothyroid
- Psych: Anxiety, Sleep disorder, Depression, Stress
- Spasticity
- Disease-modifying therapies
Pharma
- Dopamin Agonists
- Amantadine 100mg Twice Daily
- Modafinil
- Methylphenidate
- SSRI Fluoxetine (Prozac)
Non-Pharma “Avoid triggers”
- Resting days
- Energy conservation
- Work simplification
- Pacing work
- Avoid heat and stress
Tx Spasticity in MS.
1- Prevention: Remove noxious stimuli, optimize bowel, bladder, and skin management.
2- Modalities: Cryotherapy.
3- Orthosis: Positioning, casting and splinting,
4- PT & OT: range of motion (ROM),
5- Pharma:
Baclofen (PO or ITB pump) 1st line of treatment for central spasticity.
Diazepam and clonazepam (GABA A agonist)
Tizanidine and clonidine (central alpha-2-adrenergic receptor agonist)
Dantrolene (Ca+ channel blocker)
6- Surgical
Botox Injection
Rhizotomies, tenotomies
Exercise prescription in MS.
In mild to moderate disability from MS, exercise improves aerobic capacity, strength, mobility, fatigue, quality of life, spasticity, cognition, depression, walking ability, and memory/hippocampal volume.
Strength
- Light progressive resistive exercises prevent disuse atrophy
- Major muscle group, 10-15 Reps, 2 Sets, 2min Rest, Twice a week
- Do not exercise to the point of fatigue (submaximal exercise)
Conditioning “Aerobic”
- Aerobic training increases endurance
- 30 minutes of moderate intensity aerobic activity twice a week
- Swimming in cool temperature or cycling
Strength
- Light progressive resistive exercises prevent disuse atrophy
- Major muscle group, 10-15 Reps, 2 Sets, 2min Rest, Twice a week
Conditioning “Aerobic”
- Aerobic training increases endurance
- 30 minutes of moderate intensity aerobic activity twice a week
- Swimming in cool temperature or cycling
Contraindications
- Acute exacerbation of MS – start at beginning if present.
- Hot environment – maintain cool body temperature.
- Exercise not to point of exhaustion.
List 4 ways to manage osteoporosis in general.
Prevention
- Encourage weight-bearing
- Ensure appropriate dietary calcium and vitamin D
Treatment
- Bisphosphonates (fosamax) 5-10mg daily
- Denosumab injection (Prolia) six-monthly injection.
Causes & Tx Ataxia in MS.
Cause:
Lesion in spinocerebellar, cerebrum, and dorsal columns
Tx:
- Balance training
- Frenkel’s exercises
- Weighted ankle cuffs and utensils
- Gait aids/mobility aids
List 4 Causes of decreased communication in MS.
- Fatigue
- Depression
- Dysarthria
- Decreased voice intensity
- Cognitive impairments
List 2 Eye complications in MS and Tx.
Optic Neuritis:
Blurred vision - Residual decreased acuity - Central scotoma - Complete or partial loss of vision - Photophobia - Painful eye movement.
Tx: IV methylprednisolone, No treatment for the residual visual loss after ON.
Internuclear ophthalmoplegia (INO):
Demyelinating lesion of the medial longitudinal fasciculus (MLF)
Paresis of the medial rectus muscle → Inability to adduct the eye
- Nystagmus & Diplopia
- Blurred vision
List 3 causes of pain in MS & Tx.
- Neuropathic Pain
- allodynia and hyperalgesia
- MS hug
- Headache & Trigeminal neuralgia (TN)
- Spasticity → Musculoskeletal Pain
- Disease modifying treatment (Injection site or side effect)
Neuropathic Pain
Nonpharma
- PT/OT, therapeutic modalities (e.g., TENS)
Pharma
1- Tricyclic antidepressants (TCAs), amitriptyline
2- Anticonvulsant, Gabapentin (Neurontin), carbamazepine (Tegretol)
S/E Edema, sedation, weight gain, constipation
3- Local: Capsaicin, Lidocaine Patch (Versatis)
Managment of Bladder Dysfunction in MS.
INVESTIGATIONS
- Urinalysis
- Urine culture
- Renal ultrasound
- Post-voiding residual (PVR) volume measurement
- Urodynamic testing
FAILURE TO STORE (MOST COMMON)
- Hyperactive bladder with a small capacity
- Hx Urinary frequency, urgency, Incontinence
- Tx Detrusor muscle relaxant (Ditropan) or Vesicare
FAILURE TO EMPTY
- Hypoactive bladder: Big boggy bladder with Closed sphincter
- Hx Failure to void, overflow incontinence, incomplete emptying, slow or intermittent stream
- Tx Self-intermittent Catheterization, Alpha antagonist (Minipres)
COMBINATION BLADDER (2ND MOST COMMON)
- Bladder Sphincter Dyssynergia (DSD)
- Bladder contracts → Sphincter closes → Backflow of urine to the kidney
- Tx Pharma: Intermittent catheterization, Anticholinergics, Alpha-antagonists
- Surgical: BT injections in the sphincter, Urethral stent/Sphincterotomy
Causes and Tx of Bowel Dysfunction in MS (or any other disease)
Risk Factors
- Immobility
- Abnormal colonic contractility (autonomic dysfunction)
- Inadequate diet and fluid intake (avoid of nocturia and incontinence)
- Side effects of medications.
Non-Pharmacological Tx
- High fluid and high fiber diet
- Maximization of gastro-colic, colo-colic and recto-colic reflexes
- Bowel program
Pharmacological Tx
- Stool softeners (Docusate sodium) PO
- Laxative (Bisacodyl) PO or Suppository
- Bulk/Laxative (e.g., psyllium or Normacol)
- Fiber supplements (e.g., Metamucil)
- Fleet Enema or Bowel Irrigation
Sexual Dysfunction in MS. Risk factors, presentation, management.
Risk Factors
- Fatigue
- Decreased sensation
- Spasticity
- Depression
- Poor self-esteem
Male
- Fatigue
- Decreased libido
- Impaired genital sensation, paresthesias
- Erectile dysfunction (ED)
- Ejaculatory dysfunction, Anorgasmia
Female
- Fatigue
- Decreased vaginal sensation, paresthesias
- Anorgasmia
- Decreased libido
- Loss of lubrication
Managment
- Education and counseling
- Fatigue and spasticity management
- Erection: Viagra, Vacuum Pump, PGE1 injections, Implanted penile prostheses
- Ejaculation: Vibratory stimulation
- Adequate sexual positioning
- Hormone replacement therapy if indicated
List 4 causes of sleep disturbances in MS and Management.
1- Poor sleep hygiene
Lifestyle, Exercise, Melatonin, Antihistamin
2- Pain
Exercise, TENS, Anticonvulsant, TCA
3- Spasticity
4- Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD).
Iron supp, dopaminergic agents, benzodiazepine (clonazepam), and anticonvulsants.
5- Mood disorder (depression, anxiety)
Exercise, CBT, SSRI Prozac or SNRI Cymbalta (duloxetine)
6- Neurogenic bladder leading to nocturia
Avoiding eating, drinking before bed
7- Sleep-disordered breathing, obstructive sleep apnea, and central sleep apnea.
CPAP, Weight loss
8- Disease modifying treatment side effects
TCA in MS
Tricyclic antidepressants, should rather be avoided, due to issues with fatigue, orthostatic hypotension, balance, cognitive disturbances, and bladder problems.
What is the role of electrodiagnostics in diagnosing MS?
Typical NCS/EMG: Generally none - PNS usually spared in MS.
Evoked potentials: SSEP somatosensory, VEP visual & BEAP brainstem auditory
What are possible etiologies for pain in MS?
NEUROPATHIC:
- Trigeminal neuralgia (tic douloureux).
- Optic neuritis
- Chronic dysesthesia pain
- Lhermitte’s phenomenon
- Radicular pain
- Transverse myelitis
CENTRAL PAIN
Fibromyalgia (33% of MS Patients)
SPASTICITY
MSK (any msk problem can affect pts with MS):
- Facet syndrome
- Disc disease
- Osteoporosis
- Contractures
VISCERAL
List types of Dysarthias in MS.
Spastic (UMN), Ataxic (Cerebellar) & Mixed
