MS and Encephalopathies Flashcards
True or false? MS is directly inherited
False; there is a genetic component, but having a parent with MS does not mean that the child will have MS
Complex inheritance pattern. Not direct inheritance.
What does MS affect?
- White matter (brain and spinal cord)
- New research suggests it affects gray matter also (to some degree)
3 key pathologies of MS?
- Autoimmune
- Inflammatory
- De-myelinating
Describe your “typical” MS patient
- Age: 15-45 years
- Gender: 70% women
- Red High risk=further away from equator (northern US and Canada).
Theory: maybe vitamin D disease
Sources of symptoms: Cerebellum involvement for MS. What are the symptoms?
- Tremor
- Ataxia
Sources of symptoms: Brain stem involvement for MS. What are the symptoms?
- Diplopia
- Vertigo
- Dysarthria
- Internuclear ophthalmoplegia (INO)
- Bladder dysfunction
- Sensory symptoms
- Lhermitte’s: condition where flexion of neck causes electric shock like feeling
- Pain
- Proprioception
Sources of symptoms: white matter in frontal lobe involvement for MS. What are the symptoms?
- Cognitive loss
- Emotional disinhibition
Sources of symptoms: CN II involvement for MS. What are the symptoms?
- If CNII involved, Optic neuritis
condition where flexion of neck causes electric shock like feeling
Lhermitte’s
What are the top 6 most common presenting symptoms for MS?
Symptoms vary widely in incidence and severity
- Paresthesias in arms/legs (33%)
- Monocular blindness (16%)
- Multiple symptoms at onset (14%)
- Slowly progressive motor deficit (9%)
- Diplopia (7%)
- Acute motor deficit (5%)
- Others–remainder
Patient presents with MS and has the below symptoms. Where in the brain are the symptoms from?
- Tremor
- Ataxia
Cerebellum
Patient presents with MS and has the below symptoms. Where in the brain are the symptoms from?
- Diplopia
- Vertigo
- Dysarthria
- Internuclear ophthalmoplegia (INO)
- Bladder dysfunction
- Sensory symptoms
- Lhermitte’s: electric shock like condition
- Pain
- Proprioception
Brain stem
Patient presents with MS and has the below symptoms. Where in the brain are the symptoms from?
- Cognitive loss
- Emotional disinhibition
white matter in frontal lobe
Patient presents with MS and has the below symptoms. Where in the brain are the symptoms from?
- Optic neuritis
CNII involved
The worsening of neurologic symptoms in MS when the body gets overheated from exposure to heat, fever, hot water, exercise, menstruation, or saunas and hot tubs.
Uhthoff’s phenomenon
What factor may worsen the neurologic symptoms of MS for a patient?
HEAT: think fever, hot water, exercise, menstruation, saunas, hot tubs
Which other symptoms are included as “other common MS symptoms”?
- Fatigue
- Depression
- Focal muscle weakness bowel/bladder/sexual dysfunction
- Gait problems/spaticity
- Lhermitte sign: condition where flexion of neck causes electric shock like feeling
What can patients with MS expect with regard to relapses?
Average of 1 relapse per year, fewer over time
Should a patient with MS expect to lose their ability to perform activities of daily living? Or expect to be severely disabled within a short time?
- ADLs: 25% never lose ability to perform ADLs. Thus, 75% unable to perform ADLs.
- Severly disabled: 15% become severely disabled within a short time. 85% do not.
Is MS likely to be the primary cause of mortality?
No
Disability scoring EDSS (expanded disability status score):
- Approximately how long to reach 6 (need assistance to walk)?
- To reach 8 (restricted to wheelchair at 7, helpless bed patient at 9)?
EDSS: score 0 (normal)-10 (death)
- 15 years
- 46 years
Define Relapse per MS
- Appearance of new/worsening of old symptom
- Symptoms last at least 24 hours, but usually weeks or months
- Could be attributed to MS activity
- Preceded by stability or improvement for at least 30 days
What does this qualify as with regard to MS?
- Appearance of new/worsening of old symptom
- Symptoms last at least 24 hours, but usually weeks or months
- Could be attributed to MS activity
- Preceded by stability or improvement for at least 30 days
Relapse of MS
What does this qualify as with regard to MS?
- Worsening by 1.0 point on EDSS (or by 0.5 points if EDSS greater than/equal to 5.5)
- Confirmed at 2 consecutive visits spaced 3 months apart
Progression
Define characteristics of progression per MS
- Worsening by 1.0 point on EDSS (or by 0.5 points if EDSS greater than/equal to 5.5)
- Confirmed at 2 consecutive visits spaced 3 months apart
Identify the clinical subtype of MS
- Most common
- Feel normal at baseline
- Have symptoms for 24-few months
- Return to baseline, then will relapse again
- Over time, fewer and fewer relapses
Relapsing-remitting
Identify the clinical subtype of MS
- What happens to relapsing-remitting throughout time
- Baseline, have symptom, have relapses
- Instead of relapses, have disease progression instead
Secondary progressive
Identify the clinical subtype of MS
- Have neurological dysfunction
- continue to have symptoms
- Never return to baseline; keep accumulating disability and symptoms
Primary Progressive
Identify the clinical subtype of MS
IGNORE IGNORE IGNORE; this one is controversial
Progressive-relapsing
IGNORE IGNORE IGNORE; this one is controversial
What are the 3 clinical subtypes of MS?
IGNORE IGNORE IGNORE PROGRESSIVE-RELAPSING: controversial
What is the most common subtype of MS?
Relapsing - remitting (82%)
The other remainder: primary progressive
What is likely to happen to a patient with relapsing-remitting MS over time?
Will likely develop the MS subtype secondary progressive (58% of patients)
Which is the most aggressive subtype form of MS?
Primary progressive
Describe the natural progression of MS
What determines a FAVORABLE prognosis for MS?
- Younger age at onset
- Female
- Low MRI lesion load
- Complete recovery from 1st relapse
- Low relapse rate
- No disability at 5 years
What determines UNFAVORABLE prognosis in MS?
- Older age
- Male
- High MRI lesion load
- Lack of complete recovery from 1st relapse
- High relapse rate
- Early development of disability
- Insidious motor onset
- African Americans
What causes MS?
- We don’t know
- In MS, T-cells recognize myelin as antigen
- Then, they launch attacks on myelin and nerve fibers (including axons)
- Result: obstructs nerve signals
What pathology results in permanent neurological dysfunction in MS patients?
Axonal injury and destruction
What is the result of the demyelination pathology of MS?
- Slower nerve conduction
- Body does try to heal and will remyelinate, but unable to fully heal and have as much myelin as before. Only heals a little bit
Where do MS lesions occur?
- Optic nerves
- Periventricular white matter
- Cerebral cortex
- Brain stem
- Cerebellum
- Spinal cord
How do we diagnose MS? What is key for the diagnosis of MS?
- Clinical diganosis: no definitive laboratory test
- **Requires evidence of dissemination of lesions in space and time**
What are you able to see in the CSF from a lumbar puncture in MS?
What findings are very SENSITIVE for MS in CSF? (Not specific)
- Oligoclonal bands that are not present in the serum
- (95% positive in people with MS)
- Normal glucose, normal cells, Protein <100 mg/dl
- (98% in MS)
What’s a test that analyzes the electric conduction of the optic pathway?
Visual Evoked Pathways
Will show delayed conduction for MS patients
For the sake of seeing these, which conditions can mimic MS?
Longitudinally extensive transverse myelitis:
>3 spinal segments
What does this indicate?
• RED FLAG that you are not dealing with MS
Disease: Neuromyelitis optica (Devic’s Disease)
How do you test for Neuromyelitis Optica (Devic’s Disease)?
blood test
An autoimmune disease that affects spinal cord (transverse myelitis) and optic nerves (optic neuritis). What is the antibody that is primarily responsible for this disease?
Neuromyelitis Optica
(Devic’s disease)
Antibody: NMO-IgG
How do you differentiate between a patient with Neuromyelitis Optica (Devic’s Disease) and MS?
- OCB=Oligoclonal Bands
- NMO-IgG antibody in serum (blood test) and CSF
Patient presents with the below. More likely to be Neuromyelitis Optica (Devic’s Disease) or MS?
- Bilateral optic neuritis
Neuromyelitis Optica (Devic’s Disease)
Patient presents with the below. More likely to be Neuromyelitis Optica (Devic’s Disease) or MS?
- White matter brain lesions
BOTH Neuromyelitis Optica (Devic’s Disease) and MS
Patient presents with the below. More likely to be Neuromyelitis Optica (Devic’s Disease) or MS?
- Transverse myelitis on presentation
Neuromyelitis Optica (Devic’s Disease)
Patient presents with the below. More likely to be Neuromyelitis Optica (Devic’s Disease) or MS?
- NMO-IgG antibody in serum (blood) and CSF
Neuromyelitis Optica (Devic’s Disease)
Patient presents with the below. More likely to be Neuromyelitis Optica (Devic’s Disease) or MS?
- Oligoclonal bands (OCG) in CSF
MS
What is used to improve confidence in a clinical diagnosis of MS or to make a diagnosis of MS in clinically isolated syndromes?What requirements must this show to suspect MS?
MRI
- Requirement: Dissemination of lesions in space and time
What is the hallmark of MS diagnosis?
Dissemination of lesions in space and time
If you have active demyelination, what do you get on an MRI?
Contrast enhancement; this means there was active demyelination within last 8 weeks
What is a classic MRI finding that is a trigger word for MS?
Dawson’s Fingers
MS plaques oriented at right angles to corpus callosum along veins
How do you treat an Acute MS relapse?
- High-dose steroids
- methylprednisolone IV for 3 to 5 days
- followed up tapering dose of oral prednisone
_____
Definition of Relapses:
- Focal disturbances of function >24 hours
- Occur about once a year in untreated patients
- In absence of environmental, metabolic, or infectious processes
A great MS medication that does a great job reducing acute MS relapsing
BUT had death of patients from progressive multifocal leukoencephalopathy (virus that affects white matter)
Reintroduced with black box warnings
Tysabri
What is the major reason why patients relapse with MS?
They are not taking/receiving their medication
Diffuse brain disorder (3 terms used interchangably)
- Delirium
- Acute confusional state
- Acute encephalopathy
Progressive failure of cognition, language, memory, and other intellecutal functions
Dementia
Isolated memory loss and inability to form new memories despite normal attention and alertness
amnesia
Congenital cognitive delay
Developmental cognitive delay
DSM-5 Diagnostic criteria for Delirium/Acute confusional state/acute encephalopathy
- Disturbance in attention and awareness
- Change in cognition that is not better accounted for by pre-existing, established, or evolving dementia
- The disturbance develops over a short period (hours to days)
- Fluctuates during the course of the day
- There is evidence from history, physical examination, or lab findings that the disturbance is caused by a direct physiologic consequence of a general medical condition, intoxicating substance, medication use, or more than one cause
What is rare as a presenting symptom of psychiatric disease?
Visual hallucinations
Differential diagnosis for acute encephalopathy?
- Aphasia
- Mania
- Psychosis
- Depression
- Transient global amnesia (TGA)
What patients does acute encephalopathy primarily affect?
The elderly;
10-40% hospitalized elderly
60% nursing home patients >75 y/o
True or false: Acute encephalopathy (delirium) can be progressive and fatal depending on the cause; as such, delirium requires prompt evaluation.
True
What is delirium caused by? What neurotransmitters are involved?
All delirium is caused by widespread dysfunction of both cortical and subcortical neurons
Neurotransmitters:
- Acetylcholine
- Dopamine
Which patient population is at special risk for developing delirium?
Patients with:
- dementia,
- the elderly,
- critically ill, and
- immunocompromised
are at special risk for developing delirium!!
Which of the following electrolytes, if abnormal, would not lead to acute encephalopathy?
A) Potassium
B) Magnesium
C) Sodium
D) Glucose
E) Calcium
Answer: A) Potassium
Will cause arrythmias and heart problems before delirium
If a patient is confused, which electrolytes are you going to check?
- Magnesium Mg
- Calcium Ca
- Glucose
- Sodium Na
Rapid correction of hyponatremia causing demyelination in brain (often in pons)
Central pontine myelinosis (CPM)
For familiarity: which infections cause delirium?
For familiarity: which metabolic abnormalities cause delirium?
For familiarity: which end organ failures cause delirium?
For familiarity: which endocrinopathies cause delirium?
For familiarity: which nutritional deficiencies cause delirium?
For familiarity: which toxicities cause delirium?
For familiarity: which trauma, vascular, and neoplastic cause delirium?
For familiarity: which other misc cause delirium?
Which organ in end-organ failure has its own encephalopathy named after it?
Hepatic encephalopathy
Which endocrine disease is susceptible to delirium?
Cushing’s syndrome
Patient is presenting with:
- Diarrhea
- Dermatitis
- Dementia
Vitamin B3 (niacin) deficiency
Pellagra
Encephalopathy cause
Patient is presenting with the classic triad:
- encephalopathy
- ataxia
- opthalmoparesis
Vitamin B1 (thiamine deficiency)
Werknicke’s encephalopathy
Encephalopathy cause
What is the most important component of the patient evaluation with regard to delirium?
Patieht history
- Use family members, friends, other observers for collateral information
- Should be performed in a quiet room
- Avoid interruptions/distractions
- Avoid frequent topic changes
3 major items to ask about regarding history in a patient with delirium?
________
3 Additional items to cover regarding history
- Headache
- Acute: red flag for SAH (subarachnoid hemorrhage) or ICH (intracranial hemorrhage)
- Progressive: CNS tumor, infection, hydrocephalus
- Previous brain damage
- Predisposes patient to delirium
- Try to get patient’s baseline
- Preexisting medical condition
- Cardiac/lung disease are risk factors for life-threatening conditions which cause delirium
________
- Drug History
- Exposure history (meningitis, HIV, carbon monoxide, occupational hazards)
- Medications (new meds/dose changes)
What abnormal vital signs might help you find a cause for encephalopathy?
- Hypotension
- Tachycardia
- Hypoventilation
- Increased body temperature
- Hypothermia
What other clues on general exam might you look for with encephalopathy?
- Nuchal rigidity
- Evidence of head trauma
- Purulent drainage from nares
- Gray/immobile tympanic membrane
- Icteric sclera
- Erosions in nasal septum
- Skin exam (cyanosis, hirsutism, hyperpigmentation, dermatitis, track or “pop” marks)
- Hear exam (murmurs, irregular rhythms)
- Pulmonary exam (decreased breath sounds/crackles)
- Abdominal exam (tenderness)
- Signs of hepatic failure (ascities, splenomegaly, spider telangiectasia, caput medusae, icteric sclera, jaundice)
What is a hallmark finding on the neuro exam for delirium?
Attention is poor
Neuro exam findings with delirum
nocturnal exacerbation of confusion
Sundowning
Name the 5 physical findings that are clues on neurologic exam for encephalopathy
- Papilledema
- Pupillary changes
- Changes in ocular motility
- Abnormal Movements
- Weakness
Which are the first aspects of orientation that are first to go with a patient with encephalopathy
NOT oriented to time/place
YES oriented to person
Why might memories be affected for a patient with encephalopathy?
- Memory registration depends on ability to focus attention
- Thus, patient may only be able to form new memories during a lucid interval
If there is papilledema, what does that indicate?
Increased/raised intracranial pressure
Pinpoint pupils with delirium indicates what?
opiod overdose
You are looking at your patient’s eyes and your patient presents with this symptom. You immediately think NEUROLOGICAL EMERGENCY. What is the symptom? What is it a sign of?
Blown pupil
Unilaterally dilated pupil with or without the other components of a 3rd nerve palsy
Sign of brainstem dysfunction
You are analyzing a patient’s ocular motility changes. The patient presents with:
- Unilateral impaired eye adduction
- Pupillary dilation in the unilateral eye
- Diminished consciousness
What do you think?
NEUROLOGIC EMERGENCY
Sign of increased pressure
Raised intracranial pressure can result in unilateral ____ nerve palsy
6th
If the patient is presenting with delirium plus quadriparesis, what 3 diagnoses should you consider?
- Central pontine myelinolysis (CPM)
- Progressive multifocal leukoencephalopathy (PML)
- Acute disseminated encephalomyelitis (ADEM)
Initial Lab Tests for encephalopathy
- CBC w/ diff
- Complete metabolic panel
- serum ammonia level
- thyroid studies
- arterial blood gas
- cardiac enzymes
- urine drug screen
- blood alcohol level
True or false: brain biopsy is a common test for encephalopathy
False; RARELY indicated for encephalopathy
Describe EEG with regard to encephalopathy
EEG:Normal brain background is alpha frequency (8-12 Hz). What happens in encephalopathy?
lower frequncy and disorganized background
total diagnostic approach for encephalopathy
What specialty will most likely see encephalopathies that you wouldn’t expect?
long bone surgery in elderly patients
Orthopaedics
