Miscellaneous Neurologic Disorders - Exam 4 Flashcards
What is multiple sclerosis? What are the 4 characteristic features?
An autoimmune disorder resulting in damage to the neurons of the CNS
aka the body attacks myelin sheaths
chronic inflammation
demyelination
gliosis (plaques or scarring)
neuronal loss
What is the proposed etiology behind MS?
an environmental agent or event (eg, viral or bacterial infection, exposure to chemicals, lack of sun exposure) occurs in the presence of a genetic predisposition to immune dysfunction resulting in an autoimmune attack on the CNS neurons
In the pathophys behind MS: Insult to immune system results in development of _______ (inflammatory T cells, B cells, and macrophages) that cross the BBB. An inflammatory reaction occurs ______ around the axon resulting in what is know as an _____. The body attempts to ______ leads to a build up of rubbery or hardened _______
autoreactive lymphocytes
breaking down the myelin
MS “lesion”
remyelination
plaques (sclerosis)
MS more common in males or females? what is the typical age of onset? MC ethnicity?
more common in females
between 20-40 years of age
RRMS - average age 28-31
PPMS - average age 40
white people in the northern US
What are the risk factors for MS?
genetics
low vit D
EBV exposure
smoking
How does MS present? **What is the important phrase to remember here? What are some sensory symptoms a pt might complain about?
abrupt or insidious “attacks” that range from asymptomatic to severe that are separated in time and space and s/s are increased when the body temperature increases
sensory symptoms include: paresthesias, hypethesia (decreased sensation, numbness), unpleasant sensation, pain, shock-like sensation radiating down the back of the legs
s/s rarely follow dermatomes and sometimes the patient describes them as “weird”
What is it called when the s/s worsen by increased body temp?
Uhthoff Phenomenon
What are shock-like sensation radiating down back of legs called? Where do they RARELY present?
Lhermitte’s symptoms
rarely down the arms
What are some eye conditions that are associated with MS?
optic neuritis: usually unilateral, blurred vision, pain with EOM movements and central field disturbances, decreased color perception
RAPD: unequal response to pupillary constriction with swinging light test
optic disc may be normal or atrophied
How will the motor symptoms of MS present?
weakness: worse with exercise, facial weakness that may resemble Bell’s palsy
spasticity: if due to UMN lesions
hyperreflexia
+babinski sign
intention tremor
dysarthria: slurred speech
What cranial nerve is involved? Name 2 other s/s that can also be seen on the face with MS.
Trigeminal neuralgia - CN V
same s/s as idiopathic TN but often bilateral, occurring before age 50
facial myokymia: involuntary twitching or contraction of the facial muscles
glossopharyngeal neuralgia: intense electric shock-like pain in the posterior pharynx, tongue or ear triggered by swallowing or without warning
How does the trigeminal neuralgia seen with MS differ from idiopathic TN?
MS: bilateral and before the age of 50
idiopathic TN: unilateral and after the age of 40
What is facial myokymia? What CN? What condition?
involuntary twitching or contraction of the facial muscles
CN VII
seen in MS
What is glossopharyngeal neuralgia? What condition is it associated with?
intense electric shock-like pain in the posterior pharynx, tongue or ear triggered by swallowing or without warning
MS
What are the GU complaints seen with MS?
detrusor hyperreflexia
detrusor sphincter dyssynergia: difficulty starting and stopping urine stream, hesitancy, urinary retention, overflow incontinence, recurrent infections
bowel changes: constipation or fecal urgency/incontinence
can also have sexual dysfunction in both men and women
Can also see ______, ______ , _____ and _____ with MS
mild cognitive dysfunction
depression
fatigue
vertigo
Describe the timing of MS symptoms? They are usually precipitated by _____ or _______
Neurological symptoms lasting 10-120 seconds and occuring 5-40 x/d
Precipitated by hyperventilation or movement
What do they contribute the paroxysmal symptoms of MS to? Give some MS paroxysmal symptoms
Thought to be a result of spontaneous discharges from neurons at the edge of demyelinated plaques
Lhermitte symptoms, tonic contractions, dysarthria, ataxia, sensory disturbances
these are usually self limiting after weeks to months
What are the 5 types of MS? Which 2 are associated with the very early stages? Which 3 describe the pattern of symptoms?
very early:
Clinically isolated syndrome (CIS)
Radiologically Isolated Syndrome (RIS)
types of MS patterns:
RRMS
SPMS
PPMS
What is clinically isolated syndrome? How long does it have to last?
the first MS attack
must last for at least 24 hours, is characteristic of multiple sclerosis but does not yet meet the criteria for a diagnosis of MS
What is Radiologically isolated syndrome (CIS)?
evidence of MS on brain MRI before “clinical attack” is present
What is the MC type of MS? describe the pattern of symptoms. What is happening in between attacks?
Relapsing-remitting MS (RRMS)
discrete attacks of neurological dysfunction that evolves over days-wks (relapse), followed by partial or complete recovery over wks to months (remission)
between attacks patients are neurologically stable
What is secondary progressive MS?
starts as RRMS², at some point in the course of the disease a deterioration in function occurs unassociated with the acute attacks
aka quit seeing improvement
What is primary progressive MS?
a steady decline in function from disease onset and LACKS the relapse-remission characteristics of other forms of MS
What is the diagnostic criteria for MS? What is the timing?
2 or more episodes of symptoms and 2 or more signs that reflect pathology in different areas anatomically. lesions on MRI can act as the 2nd sign if necessary
Symptoms must last > 24 hours and must be separated by at least a month in recurrence
What will the lesions on brain MRI with gadolinium contrast look like for a pt with MS?
Acute MS lesions: larger with ill-defined margins. (lasts appx 1 month)
Chronic lesions: smaller with sharper margins
When would you use evoked potentials as a dx tool in MS? If the test is +, what will it show?
indicated for asymptomatic patients and are most effective in assessment of clinically uninvolved pathways
a marked delay in latency of a specific stimulation which is diagnostic in an asymptomatic patients
When would you order a CSF analysis in an MS pt? What would you expect to find?
Indicated in patients with CIS or an atypical presentation (e.g. MRI is nondiagnostic)
Oligoclonal bands present in 90-95%
Increased levels of intrathecal synthesized IgG (70–90%)
mildly elevated WBC (< 75 cells/μL)
CSF protein is normal to elevated
What are the some red flag findings that would make you think this is NOT MS?
symptoms localized to the posterior fossa (ataxia and imbalance), craniocervical junction (neck pain, headache, balance problems, voice changes, difficulty swallowing, respiratory problems or sleep apnea, motor speech issues such as difficulty articulating, compression of the spinal cord, spasticity, twisted or rotated neck) or spinal cord (sensory and motor symptoms only)
patient is <15 or >60 years of age
clinical course is progressive from onset
patient has NEVER experienced visual, sensory, or bladder symptoms
diagnostic findings (e.g., MRI, CSF, or EPs) are atypical
What is the tx for acute exacerbations? What is the pt does not respond to the first treatment?
glucocorticoids: High-dose IV or oral methylprednisolone: reduce severity and shorten duration of attacks
Plasma exchange to get rid of the antibodies
What is the first line tx for disease modifying treatment in MS? What is their MOA?
Monoclonal antibodies
function to decrease the AI response
**What do you need to screen for before starting a pt on monoclonal antibodies? **Why?
screen for immunity to Hepatitis A,B,C and VZV
**BBW: risk of progressive multifocal leukoencephalopathy (PML) an opportunistic viral infection (John Cunningham [JC] virus) of the brain that usually leads to death or severe disability
Need to assess if a pt has ______ before starting monoclonal antibodies. Do you want to result to be positive or negative? Why?
JC antibodies
patients who are seronegative are less likely to develop PML
**Which monoclonal antibody is the only agent indicated for PPMS? What are the rest of the agents indicated for?
ocrelizumab (Ocrevus)
rest are indicated for RRMS
What is the 2nd line tx for disease modifying therapy in MS?
Fumarates and Sphingosine 1-phosphate receptor (S1PR) modulators
______ MOA not fully known - modulates proinflammatory and anti-inflammatory cytokines. Has anti-oxidative properties. what do they end in?
fumarates
fumarates
_____ MOA binds to the lymphocyte surface (within the lymph nodes/spleen) preventing the release of lymphocytes into the PNS in turn preventing migration to the CNS. What do they end in?
Sphingosine 1-phosphate receptor (S1PR) modulators - end is “mod”
What is the 3rd line tx in MS? What is the MOA?
Platform Injection Therapy:
Glatiramer Acetate
Interferon β
Works in a variety of ways to suppress the immune system
What is used in MS to treat the ataxia/tremor? What is used to treat severe spasticity and spasms?
Clonazepam, propranolol, primidone
Thalamotomy and deep-brain stimulation - mixed results when utilized
severe: Baclofen oral or intrathecal pump if severe
______ is MS specific med that is used to treat the symptomatic LE weakness when it interferes with ambulation. What is the MOA?
dalfampridine (Ampyra)
K+ channel blocker
What factors favor a BETTER prognosis in MS?
ON or sensory symptoms at onset
fewer than two relapses in the first year of illness
minimal impairment after 5 years
What factors favor a WORSE prognosis in MS?
truncal ataxia
action tremor
pyramidal symptoms
primary progressive disease
What are the 4 pt education points needed in MS?
- maintaining an optimistic outlook
- a healthy diet
- regular exercise without excessive overheating as tolerated. swimming is often well-tolerated because of the cooling effect of cold water
- correct vitamin D deficiency
A patient with RRMS presents with complaints of increased weakness and double vision that began this morning. On exam you note a temperature of 103.2. Work-up reveals the patient is positive for Influenza A. Should we start high dose steroids to treat the symptoms of her acute MS?
not recommended to tx because the pt is experiencing “pseudo-exacerbation” due to the increase in body temperature not actually a true MS acute episode. Tx the flu and MS symptoms should improve
What is the key description of cerebral palsy? What is the underlying cause?
An umbrella term used to describe a group of disorders that cause permanent, NON-PROGRESSIVE motor dysfunction affecting muscle tone, posture, and/or movement
Results from an insult to the developing brain during birth, delivery, or in the perinatal period
______ is the leading cause of childhood disability. _____ are congenital and _____ are acquired
cerebral palsy
70-90% are congenital
10-30% are acquired
What are the risk factors for cerebral palsy? which ones are modifiable?
Genetic abnormality
toxic or infectious etiology
vascular insufficiency
Modifiable risks: maternal smoking, maternal heavy alcohol use, maternal obesity
Gross motor delay in first year of life
Abnormal muscle tone - most often hypotonia followed by spasticity
Definite hand preference before 12 months of age
Asymmetric crawling or failure to crawl
Growth disturbances (weight/height)
Hyperreflexia
Some cases - persistent primitive reflexes
What am I?
cerebral palsy
What are the different ways CP is classified? Which on is the MC?
Based upon predominant impairment AND location of disability
spastic- MC 70-80%
dyskinetic
ataxic
AND (see picture)
What type of CP?
Increased tone
Hyperreflexia
Muscle contractures
how common is it?
spastic
MC- 70-80%
What type of CP?
Involuntary movements
Hyper- or hypotonia
Trouble maintaining an upright position
Variable degree of dysarthria
Intellectual disability
how common is it?
dyskinetic CP
less common :10-15%
What type of CP?
Impaired balance and coordination
Speech typically is slow, jerky, and explosive
Hypotonia
Poor motor skills
trouble writing, typing, using scissors
Difficulty with auditory and visual processing
how common is it?
ataxic CP
least common: less than 5% of cases
How do you dx cerebral palsy? at what age?
Diagnosis is clinical - based upon history and PE
confirming dx is best deferred until after age 2 due to postnatal brain development
_____ are used most often in unstable neonates who are unable to be transported for MRI/CT when looking for CP
cranial US
______ is the best imaging modality after 2-3 weeks of age for CP. What is the imaging is normal?
brain MRI
Normal neuroimaging studies do not exclude a clinical diagnosis of CP, but may indicate a genetic or metabolic etiology
Name 3 additional tests used in CP. Why would you order each?
What is the management for CP?
no specific tx for CP so manage all the presenting symptoms individually
need to consult: physical, occupational and speech therapy
______ is a procedure used in CP to decrease spasticity. What is a brief summary of the procedure?
Selective dorsal rhizotomy
surgical ablation of 70-90% of the dorsal nerve roots
Might need to consult _____ and _____ in a child with CP. Why?
ortho and ophthalmology because muscles can get so tight that they pull bones out of the socket and strabismus in the eyes. also higher rates of cataracts
What are 3 organ systems that have frequent complications due to CP?
Respiratory- risk of aspiration pneumonia, lung/bronchopulmonary dysplasia, bronchiolitis, asthma
Gastrointestinal - reflux, constipation
Skin - decubitus ulcers
What is the prognosis with CP?
related to the severity of the condition and their individual complications
25% have mild impairment that doesn’t affect ambulation, self care or other activities
50% are able to achieve complete independence
25% are unable to walk
What is complex regional pain syndrome? What is it characterized by? What does it often follow? What age range?
An inflammatory disorder affecting a region of the body (most often an extremity)
characterized by pain, swelling, limited ROM, vasomotor instability, skin changes and patchy bone demineralization
often follows trauma but does NOT reflect the severity of the trauma
30-60 years old
What are the 3 stages of complex regional pain syndrome? How long does each last?
acute, subacute and chronic
acute: lasts approx 3 months
subacute: 3months-1 year
chronic: 1+ year after disease onset
What s/s are present during the acute stage of CRPS? What makes the pain worse? ______ of the affected limb due to a lack of use
pain is so severe it prevents the use of limb
swelling, erythema and edema of the extremity
with dependance, hyperhidrosis, skin cool to touch
neuropathic: burning, cutting, searing, pressure, tearing
constant and disproportionate to the precipitant injury
pain increases with: loud noises, stress, light touch, active or passive motion
bone demineralization
What are some s/s of the subacute phase of CRPS?
persistent severe pain and fixed edema
cyanosis or pallor
dry atrophic skin
atrophy of the subcutaneous tissue
joint fibrosis - stiffness and limited use
further bony demineralization
What are some s/s of chronic phase of CRPS?
symptoms can last for years before abating or may be permanent
pain is variable
edema resolves
skin is dry, pale, cool and shiny - flexion and extension creases become absent
joint fibrosis persists leading to loss of function and stiffness
bone demineralization become osteoporosis
**What is the criteria called for dx CRPS?
Budapest Criteria
What should be included as part of your work-up for CRPS? What are you looking for?
xray: looking for signs of demineralization
bone scintigraphy (bone scan): assesses bone metabolism in patients with active bone resorption, there will be increased radiotracer uptake in areas of demineralization
a bone scintigraphy (bone scan) areas with ______ radiotracer uptake indicate _______
increased radiotracer uptake in areas of demineralization
What is the first line tx CRPS?
first line tx -> Physical and occupational therapy as soon as dx is made
Psychosocial and behavioral therapy
Why do you give pain meds in CRPS? Which ones? What can you give if evidence of bone demineralization?
Goal - to achieve better compliance with PT/OT
- start with NSAIDs
- add neuropathic meds (gabapentin (Neurontin), pregabalin (Lyrica) or TCA
- topical agents: lidocaine or capsaicin
refer to pain management!! for injections
add bisphosphonates
What is an important pt education point for CRPS?
explain the long term benefits of PT and OT to improve compliance !!!
pt will experience an increase in pain with therapy. Remind them of the long term goal of regaining use of the affected limb
What is the prognosis with CRPS? How often does it reoccur?
Uncertain and highly variable
Most patients report some degree of prolonged disability
Recurrence is common: 10-30%
Seen most frequently in younger patients
What is Amyotrophic Lateral Sclerosis (ALS)? What is it characterized by?
A fatal neurodegenerative disease of the lower AND upper motor neurons characterized by progressive loss of motor function
progressive loss of motor function
What is the “lateral sclerosis” in ALS?
changes seen in the lateral columns of the spinal cord where the UMN degenerate and are replaced by fibrous astrocytes (gliosis)
What is the pathophys behind ALS? part 1
Impaired ____ and _____ release toxins. Impaired _____ leads to _____ at the synaptic cleft. Excessive _____ leads to increased uptake of _____.
astrocytes and microglia
astrocyte
increased glutamate
glutamate
Ca+
What is the pathophys behind ALS? part 2
_____ inside the neuron inhibits the ____ removal. Excessive _____ leads to neurodegeneration via ______. _______ form intracellular aggregates worsening _______ and turn into ______ which results in neuronal death
Mitochondrial dysfunction
calcium
calcium
oxidative stress
Mutant proteins
oxidative stress
neurofilaments
What is the etiology behind ALS?
UNKNOWN!!
family component in 5-10% of cases but SPORADIC is the key thing to remember
What are the risk factors for ALS? How do you differentiate ALS from all other motor neuron diseases?
risk increased with age - peaks in mid 70’s
family hx
smoking
ALS effects both UMN and LMN
What s/s start first in ALS? What is the MC initial symptom?
symptoms start very slow and progressive and will reflect the body segment of the affected UMN lesions
extremity dysfunction: tripping, stumbling, trouble running, foot/wrist drop, reduced finger dexterity
________ is also extremely common in ALS. How will it present?
bulbar dysfunction
Slurred speech, hoarseness, decreased volume of speech, nasal dysphonia, drooling**
involuntary laughing or crying
Eventually, ALS patients will start to show signs of _____ and _____
UMN lesions: Babinski, hyperreflexia, spasticity, hypertonia, clasp-knife rigidity¹, pronator drift
LMN lesions: muscle fasciculation, hypotonia, hyporeflexia
with generalized weakness
How do you dx ALS? What will electromygraphy show?
clinical dx! all labs and imaging will be normal
electromyography: measures the electrical activity in your muscles to evaluate how well your muscles and nerves are working
will show features of acute and chronic denervation and reinnervation
______ is a disease modifying agent in ALS that has been shown to extend the life of a pt. How does it work?
Riluzole (Rilutek)
inhibits glutamate release
_______ is a disease modifying agent in ALS that slows the functional deterioration. What is the MOA? ______ to get the best result
Edaravone (Radicava IV or ORS)
a free radical scavenger that reduces oxidative stress
best results if started early in course of disease
______ is the gene silencing therapy in ALS and is only helpful in patients with the mutation in the _____ gene
Tofersen (Qalsody)
superoxide dismutase-1 (SOD1)
What is the MOA of Tofersen (Qalsody)? What is the outcome?
binds to the SOD1 mRNA, resulting in degradation and prevention of SOD1 protein synthesis - ultimately decreasing oxidative stress
reduces progression of disease
______ was the ALS drug that was taken off the market
Sodium phenylbutyrate-taurursodiol (Relyvrio)
What is the tx for drooling in ALS?
Anticholinergics (amitriptyline, scopolamine)
Sympathomimetics (pseudoephedrine)
Salivary gland irradiation
Botulinum toxin type B
_____ is needed at night for ALS pts to help with ventilation. ______ if difficulties with swallowing/appetite. may need ______ to help sustain nutrition
BiPAP at night
speech therapy and nutritionist
(PEG) tube placement
Why does an ALS pt need to see PT/OT?
maintain a low impact exercise regimen to maintain ROM and tone, prevent contractures
_____ is the median survival of an ALS pt. What is the MC cause of death?
3 years
aspiration pneumonia
_______ is an acute condition resulting in global cerebral dysfunction in the _________
Toxic-Metabolic Encephalopathy
absence of primary structural brain disease
What is the pathophys behind toxic-metabolic encephalopathy?
Dysfunction of the ascending reticular activating system and/or its projections to the cerebral cortex, leading to impairment of arousal and/or awareness
What are risk factors for Toxic-Metabolic Encephalopathy?
ICU placement
Older patients
Underlying dementia
Cognitive dysfunction ranging from confusion to delirium or coma
Seizures
Exaggerated physiologic tremor
Asterixis - flapping tremor
Myoclonus
Presence of (+) Babinski, brisk DTRs
What am I?
What is the most common etiology?
Toxic-Metabolic Encephalopathy
sepsis
What needs to be part of the work-up for Toxic-Metabolic Encephalopathy?
CT scan/MRI: rule out ddx when focal signs are present on PE or when subdural hematoma is suggested in the history
Electroencephalography (EEG): confirms global cerebral dysfunction
labs
What is the prognosis for Toxic-Metabolic Encephalopathy?
Can be reversible if recognized and treated promptly
Neurological improvement is slower than that of underlying condition
Neurofibromatosis (NF) A genetic disorder characterized by _____ on _____ that results from a _____ or ____ of _______
tumor formation
nerve tissue
mutation or deletion
tumor suppressor genes
What is the clinical presentation of neurofibromatosis type 1? When does it appear?
-greater than 6 Cafe au lait spots
- freckling of the axilla or groin: appears by age 3-5
- Lisch nodules
- neurofibromas
- diminished bone mineral density
- optic glioma
- learning disability
-larger than normal head size
-short stature
-elevated blood pressure
What are Lisch nodules? What dz are they associated with?
Gold-tan-brown dome-shaped gelatinous masses on the surface of the iris
Neurofibromatosis Type 1
Describe the neurofibromas seen in type 1.
usually SOFT and pea sized lesions, NOT TENDER OR PAINFUL
can be on or under the skin but can grow deep inside the body
What is Plexiform neurofibroma?
tumor formation on a nerve plexus, can lead to disfigurement
Describe a pt’s bones with Neurofibromatosis Type 1?
diminished bone mineral density¹, abnormal bone growth
results in scoliosis or bowing of the lower legs
What will optic gliomas present like in Neurofibromatosis Type 1?
visual disturbances, proptosis (tumor pushes the eye outward)
compression on pituitary gland
Why is it common to see elevated blood pressure in Neurofibromatosis Type 1?
often due to renal artery stenosis or pheochromocytoma
may develop during childhood
**What is the criteria to dx neurofibromatosis type 1?
Requires at least 2 of the 7 NIH criteria
What is the tx for Neurofibromatosis Type 1?
no specific tx- tx all individual manifestations as they arise
refer to NF clinic
What is the complication from Neurofibromatosis Type 1?
Malignant peripheral nerve sheath tumors (MPNSTs) (aka neurosarcomas) a rare aggressive type of (lifetime risk of 10%).
What are the 3 red flags for a malignant tumors in Neurofibromatosis Type 1?
significant and persistent pain within the lesion
transition of lesion from soft to hard
rapid growth of a nodule
What is the life expectancy of a pt with NF type 1?
Life expectancy in NF1 is approximately 8 years less than the general population usually caused by a malignant tumor
What is the clinical presentation of NF2-SWN? Is there a strong family link? When do symptoms appear?
tumors of both the CNS and PNS with LESS prominent cutaneous manifestations than NF-1
50% are new mutation- family hx is often negative!
s/s onset usually in early adult years (20-25)
What are the MC lesions in NF2-SWN? What are the clinical findings?
benign, slow-growing tumors of the vestibulocochlear nerve
gradual hearing loss, tinnitus
ataxia
headaches
Besides the ear, name 3 additional places NF2-SWN lesions will appear?
Meningiomas - often multiple
Spinal tumors - pain, radiculopathy, weakness, paresthesias
Cataracts - visual impairment
What additional tests should you order if you suspect NF2-SWN?
genetic testing
MRI of brain and spinal to assess tumor burden
refer to ophthalmology for eye exam
a pt with NF2-SWN should be referred to _____ and annual exams by what 3 specialilties?
NF clinic for chronic management
audiologist, ophthalmologist and neurologist
What is Schwannomatosis (Non NF2 Related)? What is the key difference?
A rare condition resulting in multiple painful noncutaneous schwannomas (a benign tumor of the nerve sheath) affecting the peripheral nerves, spinal roots, and cranial nerves without vestibular involvement
WITHOUT VESTIBULAR INVOLVEMENT
This one is PAINFUL!!
What are the clinical findings in non NF2 related Schwannomatosis?
focal pain - neuropathic and nociceptive features - may be disabling
neuropathic: hot, cold, cutting, crushing, burning
nociceptive: sharp, aching, or throbbing
palpable mass - usually nontender/nonpainful
focal numbness and weakness
muscle atrophy
PAINFUL!!
What do you need to do next when working a pt up for Schwannomatosis?
genetic testing
MRI w and w/o of brain and spine and may do whole body MRI to determine extent of disease
