MS & ALS Flashcards
What 4 things is MS characterized by?
- Episodic Neurological Symptoms
- Pts usually under age 55 at onset
- Single lesion cannot explain the clinical findings
- Multiple inflammatory foci best visualized on MRI
MS Epidemiology
- Autoimmune with genetic susceptibility
- More common in people of Western- European descent who live in temperate zones (unheard of in the tropics)
- F>M
MS Overview (4)
- Most common autoimmune inflammatory demyelinating disease of the CNS
- Multifocal areas of demyelination with loss of oligodendrocytes and astroglial scarring
- Axonal damage is the prominent pathologic feature
- Lesions are commonly found in the white matter of the brain, spinal cord and optic nerves (MRI)
Common Initial Presentations of MS (5)
– Numbness, weakness, tingling or unsteadiness in a limb
– Spastic paraparesis (weakness rather than paralysis)
– Dysequilibrium
– Sphincter disturbance (urinary urgency or
hesitancy)
– Diplopia
Retrobulbar Optic Neuritis (5)
- One of the initial presentations of MS
- Demyelinating inflammation of the
optic nerve posterior to the globe - Typically one eye at a time
- Papilledema
- Most commonly associated with MS, but ddx can include infection, tumor, temporal arteritis, toxins, etc.
Symptoms of Retrobulbar Optic Neuritis
– blurred or dimmed vision – blind spots, particularly with central vision – pain with eye movement – headache – sudden color blindness – impaired night vision
What are the 3 types of presentation/progression of MS?
- Relapsing-remitting dz
- Secondary progressive dz
- Primary progressive dz
Relapsing Remitting Dz
– Interval of months to years between initial episode and new symptoms or recurrence
– Eventually there are relapses and incomplete remissions leading to progressive disability
– Weakness, spasticity, ataxia of limbs
– Late findings include
• Optic atrophy, nystagmus, dysarthria
• Pyramidal, sensory or cerebellar deficits in some or all of the limbs
Secondary Progressive Dz
In some MS patients, the clinical course changes from relapsing-remitting to a steady deterioration, unrelated to acute relapses
Primary Progressive Dz
– Less commonly patients will have steadily
progressive symptoms from the outset
– Disability develops at a relatively early stage
What are 3 things that precipitate a relapse in MS?
Many factors may precipitate a relapse – Infection
– Stress
– Post-partum (relapse is less common during pregnancy, however)
What are 4 things used to Diagnose MS?
– Involvement of different parts of the CNS at different times (clinical)
– MRI demonstrating multiple lesions
– Evoked potentials
– CSF analysis
What are the criteria for McDonald’s Criteria?
– Clinical diagnosis requiring dissemination in time and space.
• Two lesions
• Two separate times
Diagnosis of MS
– It must be multifocal (2 foci)
– It must relapse and remit (2 episodes)
– Diagnosis is probable in patients with one lesion and two episodes or two lesions and one episode
Evoked Potentials–MS
It may be worthwhile to check for subclinical manifestations (don’t show up on MRI right away) – use evoked potentials to detect small lesions
CSP Analysis–MS
CSF (elevated protein, elevated lymphocytes, IgG) is not specific to MS but will help exclude other causes of the symptoms
What is clinically isolated Syndrome?
Pts with a single clinical episode who do not meet radiographic criteria
– These patients are at risk for developing MS and beta-interferon is sometimes offered
– Repeat MRI should be performed 6-12 months later to assess for new lesions
What should you expect from treatment of MS?
- At least partial recovery from acute exacerbations
- Relapses
- No means of preventing progression
- Half of patients are without significant disability even 10 years after the onset of symptoms
How should you treat acute relapses in MS?
- Corticosteroids
- Prednisone
- Long term tx with corticosteroids provides no benefit
How should you treat relapsing remitting dz and secondary progressive dz?
- Long term Beta interferon
- SQ glatiramer acetate
- Both reduce frequency of exacerbations
- Natalizumab can be used but it has the risk of progressive multifocal leukoencephalopathy
Other Tx for MS
- Other immunosuppressants like cyclophosphamide, azathioprine, methotrexate, cladribine, mitoxantrone may help arrest secondary progressive MS
- Plasmapheresis sometimes helps with severe relapses that do not respond to corticosteroids
- Symptomatic therapy for spasticity, neurogenic bladder and fatigue may be required
Other Myelopathies (7)
- Acute disseminated encephalomyelitis(ADEM)
- Neuromyelitis optica (Devic disease)
- HTLV-1 Associated Myelopathy (HAM)/ (Tropical spastic paraparesis)
- HIV Myelopathy
- Subacute combined degeneration of the spinal cord
- Wernicke Encephalopathy
- Neurogenic bladder
Acute Disseminated Encephalomyelitis (ADEM)
- demyelinating disease of the CNS that usually presents with multifocal neurologic symptoms and encephalopathy
- Follows a viral or bacterial illness (lung)
ADEM Symptoms (5)
– Fever, headache, vomiting, meningismus
– Encephalopathy, altered LOC
– Maximum deficits within 4-7 days of onset
– Acute hemiparesis, cerebellar ataxia, cranial nerve palsies (optic neuritis), spinal cord dysfunction
– Aphasia, movement disorders, seizures and sensory deficits can happen but are less common
ADEM Clinical Course (4)
– Lasts 2-4 weeks
– Usually recover completely
– Survival is 100%
– Hemorrhagic variant (prognosis is worse)
How do you diagnose ADEM?
- Clinically
- MRI
Tx for ADEM
Supportive
Neuromyelitis Optica
- AKA Devic dz
- Characterized by optic neuritis and acute myelitis with MRI changes that involve at least three segments of the spinal cord (brain MRI usually does not show white matter involvement but if present it does not rule out this dx)
- Isolated myelitis or optic neuritis may occur
- Specific antibody marker (NMO-IgG)
- Treatment is long-term immunosupression
HTLV-1 Associated Myelopathy (HAM) (6)
- Myelopathy develops in some infected pts after an initial latency period of several years
- F>M
- Slowly progressive weakness and spasticity of one or both legs, hyper-reflexia, ankle clonus, lumbar pain, paresthesias (esp loss of vibration), incontinence
- Progress to wheelchair confinement over 21 years
- Treatment with oral corticosteroids may be helpful
- Prevention of transmission is key
How do you differentiate HAM from MS? (4)
- MRI, CSF, EP findings may mimic MS
- Differentiated from MS by the presence of HTLV-1 antibodies in blood and CSF
- No involvement of the arms
- Cognitive function is not impaired
HIV Myelopathy (3)
- Presents as weakness in the legs and incontinence
- Spastic paresis and sensory ataxia are seen on physical exam
- Late manifestation
Diagnosis of HIV Myelopathy
• Diagnosis of exclusion
– LP to rule out CMV polyneuropathy
– MRI to exclude epidural lymphoma
Subacute Combined Degeneration of the spinal cord
Due to vitamin B12 deficiency (pernicious anemia, megaloblastic anemia)
Presentation of Subacute Combined Degeneration of the Spinal Cord
Predominant pyramidal and posterior column deficits plus
– Polyneuropathy
– Mental changes
– Optic neuropathy
Tx of Subacute Combined Degeneration of the Spinal Cord
Treatment is with vitamin B12 100mg IM daily x 1 week, weekly for 1 month, then monthly forever
Wernicke’s Encephalopathy
- Due to Thiamine deficiency
- Confusion, ataxia, nystagmus leading to ophthalmoplegia (LR)
- +/- Peripheral neuropathy (Korsakoff’s)
- Occurs in alcoholics (AIDS, hyperemesis, bariatric surgery)
Wernicke’s Encephalopathy Tx
- If suspected, do not delay treatment waiting for confirmatory labs
- Thiamine 50mg IV, then IM daily until improvement
- IV glucose prior to supplement -> worse pt
Neurogenic Bladder
Neurogenic bladder is a problem in which a person lacks bladder control due to a brain or nerve condition
– Overactive bladder
– Underactive bladder
Neurogenic Bladder- Overactive
– Having to urinate too often in small amounts
– Problems emptying all the urine from the bladder
– Loss of bladder control
Neurogenic Bladder- Underactive
– Bladder becomes too full and you may leak urine
– Problems starting to urinate or emptying all the urine from the bladder
– Unable to tell when the bladder is full
– Urinary retention
Degenerative Motor Neuron Diseases
- Progressive Bulbar Palsy
- Pseudobulbar Palsy
- Spinal Muscular Atrophy (SMA)
- Primary Lateral Sclerosis
- Amyotrophic Lateral Sclerosis
Characteristics of Degenerative Motor Neuron Diseases
- Weakness
- No sensory loss or sphincter disturbance
- Progressive course
- No identifiable cause other than genetic in familial cases (usually sporadic)
- Onset between age 30 and 60
Progressive Bulbar Palsy
- Motor nuclei of the cranial nerves (IV-XII) are most affected (lower motor neuron)
- Patients often present with slurred speech and difficulty chewing and swallowing
- Exam: drooping of palate, depressed gag, pooling of saliva, wasted, fasciculating tongue
- All cranial nerves have bilateral innervation except: VII and XII
Pseudobulbar Palsy
- Bilateral involvement of motor cranial nerves
- Similar presentation to Progressive Bulbar Palsy in terms of symptoms EXCEPT it is an upper motor neuron dysfunction
- Exam: tongue is spastic and contracted, cannot move quickly from side to side
- “Pseudobulbar affect” – uncontrollable and inappropriate laughing or crying
Spinal Muscular Atrophy
Lower motor neuron deficit in the limbs due to degeneration of the anterior horn cells in the spinal cord
- Familial from chromosome 5
Name the 4 types of Spinal Muscular Atrophy
– Type 1 (infantile) – common and severe
– Type 2 (intermediate form)
– Type 3 (mild form)
– Type 4 (adult onset) – rare, mild
Spinal Muscular Atrophy Clinical Presentation
– Diffuse, symmetric proximal muscle weakness
– Affects lower limbs > upper limbs
– Absent or nearly absent DTRs
– Upper cranial nerves are spared but bulbar CN are not (voice changes, dysphagia, aspiration, fasciculations of the tongue)
– Respiratory difficulties
Primary Lateral Sclerosis
- Purely an upper motor neuron deficit in the limbs
- Involves the lateral corticospinal tract
Primary Lateral Sclerosis Presentation
• Slower progression than ALS
– No weight loss
– No lower motor neuron findings on exam or EMG
– If lower motor neuron symptoms develop, then the patient is re-classified as upper motor neuron- dominant ALS (intermediate course)
Amyotrophic Lateral Sclerosis
- Mixed upper and lower motor neuron deficit in the limbs
- Sometimes there is cognitive decline (fronto- temporal dementia)
- Also associated with pseudobulbar affect or parkinsonism
- Progressive – fatal within 3-5 years
- Patients with bulbar involvement have poorer prognosis
Degenerative Motor Neuron Disease Evaluation
– Muscle biopsy shows changes of denervation atrophy
– CSF is normal
– CK may be slightly elevated but not as high as in muscular dystrophies
Overall Tx of Degenerative Motor Neuron Diseases
– Physical therapy – exercise of facial muscles – Braces or walker – Portable suction • Feeding tube gastrostomy • Cricopharyngomyotomy • Tracheostomy • Palliative care
Pharmacological Tx of Degenerative Motor Neuron Diseases
– Riluzole
– Monoclonal gammopathy (increased IgG)
– Symptomatic treatment with anticholinergic drugs dries up oral secretions
– Spasticity may be helped by Baclofen or Valium
