Demyelinating disorders Flashcards
Multiple Sclerosis (MS)
● MS is a relatively common neurologic condition that most likely has an autoimmune pathophysiologic basis
● Patients are most often under the age of 50 at onset of symptoms.
○ Greatest incidence in young adults (18-40)
Multiple Sclerosis (MS) pathophysiology
○ MS is the most common Demyelinating
Disease of the Central Nervous System.
Multiple Sclerosis (MS)
○ Almost certainly an autoimmune disorder.
○ As the myelin are attacked by the WBCs,
gray-white translucent areas of inflammation
develop in the white matter (called Plaques).
○ As the acute inflammation of the plaque resolves with time, the plaque
becomes a “remote plaque.”
○ Most commonly, these plaques occur in the
Periventricular White Matter (around ventricles),
and in the Optic Nerves and Spinal Cord.
○ Patients with MS typically follow either a relapsing-remitting pattern of
episodes, or a primary progressive course
Multiple Sclerosis (MS) S/S
○ Symptoms usually progressively develop over hours to days, and then
may disappear after a few days or weeks.
■ However, exam may reveal residual deficit even after symptoms have
resolved (because the plaque causes permanent damage)
○ The most common initial presentation may include motor weakness,
numbness, tingling, or unsteadiness in a limb
○ Diplopia can occur with Internuclear Ophthalmoplegia (INO)
What causes diplopia with MS?
○ This is caused by injury to the Medial Longitudinal
Fasciculus (MLF), a white matter tract that connects
different motor nuclei in the brainstem that
normally allows conjugate eye movements.
○ When the affected eye attempts to adduct (medial
gaze), it adducts minimally, if at all, or lags behind.
■ The other eye abducts as it should, but there is
often nystagmus of the eye
○ This causes the patient to “see double” (diplopia).
Multiple Sclerosis (MS) Diagnosis
○ MRI is the imaging modality of choice.
○ Lesions are often found in the periventricular
white matter, brainstem, or the spinal cord.
○ Acute lesions will enhance with contrast.
○ MRI is the imaging modality of choice.
○ Lesions are often found in the periventricular
white matter, brainstem, or the spinal cord.
○ Acute lesions will enhance with contrast.
What will CSF show with MS?
○ CSF may reveal sterile lymphocytosis (mild), or
slightly increased protein concentration
(especially soon after an acute relapse).
○ Elevated CSF IgG and discrete bands of IgG
(specifically “Oligoclonal Bands”) are
characteristic findings.
○ Diagnosis cannot be based on CSF labs alone
Multiple Sclerosis (MS) Management
○ Treatment of Acute Relapses-
■ Corticosteroids- PO or IV Methylprednisolone for 3-5 days.
○ Relapse Reduction Management-
■ For a long time IV, IM, and SC medications were the only options.
● Interferon beta 1a (Avonex), Interferon beta 1b (Betaseron), Glatiramer
(Copaxone), Natalizumab (Tysabri), some others
■ Newer PO options seem to be effective, but are quite expensive.
● Teriflunomide (Aubagio), Fingolimod (Gilenya), Dimethyl Fumarate (Tecfidera)
○ Symptomatic Therapy-
■ Pregabalin (Lyrica), Gabapentin (Neurontin), Amitriptyline (Elavil), Baclofen
or Tizanidine, SSRIs or SNRIs.
Guillain-Barre Syndrome
● An uncommon but serious acute immune-mediated peripheral
polyneuropathy (AKA Acute Idiopathic Polyneuropathy).
● Often follows minor infections, immunizations, or surgical procedures, but the cause is not identified in many cases
○ May be associated with recent Campylobacter jejuni, Mycoplasma pneumoniae, or Zika virus infection
Guillain-Barre Syndrome pathophysiology
○ Inappropriate immune response
(autoimmune) that results in the
attack of Schwann Cells
(demyelination of the PNS).
○ Interrupts motor and sensory signals
Guillain-Barre Syndrome clinical presentation
○ Characteristically presents with symmetric extremity weakness that often begins distally and ascends progressively. Weakness typically progresses over hours to a few days.
○ Deep tendon reflexes are decreased or absent.
○ Sensory abnormalities are common, but less severe than motor Sxs.
○ Cranial nerves are affected in 45-75% of patients.
○ Neuropathic pain is common (more than 85%) and can be severe.
○ Significant autonomic dysfunction can occur…
■ Tachycardia, cardiac arrhythmias, labile BP, paralytic ileus, etc.
○ Can become very life-threatening if the innervation to respiratory muscles
(25-30%) or swallowing become involved
Guillain-Barre Syndrome diagnosis
○ Diagnosis of GBS is made by recognizing the pattern of rapidly evolving motor weakness, associated loss of reflexes, absence of fever or other systemic symptoms, and the presence of possible characteristic antecedent events
○ CSF analysis after lumbar puncture-
■ Typically reveals elevated protein level without an increase in cell
count (normal WBC counts, AKA lack of pleocytosis)
○ Electrophysiologic studies (NCS/EMG)
○ When and if suspected, Pulmonary
Function Tests should be performed
to assess vital capacity
Guillain-Barre Syndrome management
○ Patients should be hospitalized quickly so that they can be monitored closely for respiratory dysfunction or autonomic dysregulation.
■ Death can occur from respiratory failure, hypotension, and/or arrhythmias
○ Consider early transfer to the ICU and prophylactic intubation if there is rapid
progression of weakness with involvement of UEs or face.
○ DVT prophylaxis is important if the patient is not ambulatory.
○ Treatments of choice- IVIG and Plasma Exchange, recommended for patients
requiring intubation or have difficulty with ambulation (most patients)
Guillain-Barre Syndrome prognosis
○ 4-15% mortality rate, occurring from complications of GBS (usually pulm).
○ Most patients with GBS begin to recover at around 28 days.
■ If complete recovery occurs, takes an average of 200 days
○ Many have residual motor and/or sensory loss at 12 months after Dx
Amyotrophic Lateral Sclerosis (ALS)
● ALS is also known as Lou Gehrig’s Disease.
● It is a progressive, fatal neurodegenerative
disease involving motor neurons
Risk factors for ALS
● Formaldehyde and smoking are risks.
● ALS is slightly more common in males.
Amyotrophic Lateral Sclerosis (ALS) pathophysiology
○ About 90% of cases are sporadic.
○ The exact pathophysiology is not fully understood.
○ Upper motor neurons in the motor cortex, brainstem, and spinal cord progressively die.
○ Lower motor neurons located in the
spinal cord progressively die.
○ Results in a mixed Upper Motor Neuron and Lower Motor Neuron clinical presentation.
Amyotrophic Lateral Sclerosis (ALS) presentation
○ Symptom onset is generally insidious.
○ Symptoms start in the limbs in about 70% of patients.
■ Weakness, cramping, and fasciculations as presentation of lower motor neuron involvement in spinal cord
■ Difficulty walking due to spasticity as presentation of upper motor neuron involvement
○ Bulbar (brainstem motor) in about 25% of patients.
■ Difficulties with speech and/or swallowing
■ Limb weakness develops later
○ Dyspnea (5%), fatigue, and decreased exercise tolerance can occur.
○ Tongue fasciculations are highly specific for
ALS (may also see weakness, atrophy).
○ Mixed UMN/LMN findings on examination of
the symptomatic extremities
Amyotrophic Lateral Sclerosis (ALS) diagnosis
○ Insidious onset of Sxs may result in delay of Dx (median = 14 months).
○ Can largely be considered a clinical diagnosis as there is no specific
laboratory or imaging study to diagnose the condition
○ Diagnosis of ALS requires all features below:
■ Presence of…
● Evidence of LMN and UMN disease on exam (maybe also NCS/EMG)
● Progressive spread of signs or symptoms
■ Absence of…
● NCS/EMG evidence of other conditions that cause UMN/LMN diseases
● Neuroimaging evidence of brain or spine maybe explaining symptoms
○ Superoxide Dismutase-1 (SOD-1) mutation may be present in patients
with familial ALS
Amyotrophic Lateral Sclerosis (ALS) management
○ Treatment of ALS is mostly symptomatic therapy and Palliative Care.
○ Riluzole (Rilutek) is a medication that may slow progression of the
disease and prolong survival by about 2-3 months.
○ Patients may need nutritional support, possibly involving a PEG tube.
○ PT and OT can help with symptoms of spasticity and nerve pain.
○ Depression, anxiety, and suicidality are all increased for ALS patients.
○ Respiratory failure is the main cause of death
○ ALS is relentlessly progressive and 50% die within 30 months of the
onset of symptoms (prognosis is better for those diagnosed young)
Transverse Myelitis
● Transverse Myelitis is an inflammation of the
spinal cord with several possible causes
● In the general population, there is a bimodal
peak incidence of 10-19 years of age and
30-39 years of age
Transverse Myelitis pathophysiology
○ Autoantibodies may contribute to the
development as many patients with
transverse myelitis have recently had a
systemic infection.
○ Hallmark signs within the spinal cord:
■ Focal collections of WBCs
■ Varying degrees of demyelination
■ Axonal injury
Causes of Transverse Myelitis
○ Idiopathic in 15-30% of all cases.
○ Parainfectious - About 50% have had antecedent infections
○ Acquired CNS demyelinating diseases (such as Multiple Sclerosis).
○ Systemic inflammatory autoimmune diseases (such as Lupus, Sjogren’s
syndrome, Antiphospholipid Antibody Syndrome, etc).
○ Paraneoplastic Syndromes.
○ Drugs and Toxins (such as TNF-alpha inhibitors, some chemotherapies,
Sulfasalazine, epidural anesthesia, heroin)
Transverse Myelitis S/S
○ Sensory symptoms (paresthesias) and motor symptoms (paresis or paralysis)
below a specific spinal cord level.
○ These spinal cord symptoms are typically bilateral, but not always symmetrical
(may be worse on one side).
○ Some patients experience significant neuropathic pain below the level of spinal
cord involvement.
○ Some experience circumferential band (constricting sensation) around the trunk
at the level of disease.
○ May have a positive Lhermitte’s Sign if disease is in the cervical spine.
○ Bowel or bladder impairments are also very common.
Transverse Myelitis diagnosis
■ MRI Brain w/ and w/o Gadolinium contrast
■ MRI of the entire spinal column w/ and w/o contrast
■ LP with CSF analysis
■ Labs:
● Vitamin B12 level
● HIV antibodies
● Syphilis serologies
● CBC with dif
Transverse Myelitis management
○ The goal of acute therapy is to stop the progression of the symptoms and spinal cord swelling, and to try to diagnose the cause
○ Consider high-dose corticosteroids (such as IV Methylprednisolone) as the first-line treatment.
○ If not responding to the corticosteroids, consider IVIG/Plasma Exchange.
○ In many cases, neurological impairments may be permanent.
○ This may include physiatrists (PM&R), physical therapists, occupational therapists, vocational therapists, and mental health care professionals.
○ Strength and function may improve with rehab even years after the initial episode
