Lecture 13: Miscellaneous Neuro Disorders Flashcards
1
Q
What are the 4 characteristics of Multiple Sclerosis? (MS)
A
- Chronic inflammation
- Demyelination
- Gliosis (plaques/scarring)
- Neuronal loss
2
Q
What is the hypothetical etiology of MS?
A
Environmental agent/event occurs in a patient with genetic predisposition to immune dysfunction, resulting in autoimmune attack on CNS
3
Q
What exactly happens in MS?
A
- Breakdown of myelin
- Unsuccessful attempt at remyelination resulting in plaques/sclerosis
4
Q
What are the autoreactive lymphocytes that break down myelin?
A
- Inflammatory T cells
- B cells
- Macrophages
5
Q
Who is MS MC in?
A
- Females
- Caucasians and Northern US
For men, MS occurs later in life as well.
6
Q
What MS version occurs earlier?
A
Relapsing Remitting MS (RRMS)
7
Q
What are the primary RFs for MS?
A
- First-degree relative 7x risk
- Hypovitaminosis D
- EBV
- Smoking
Identical twin adds the most risk
8
Q
How does MS present?
A
- Abrupt or insidious
- Asymptomatic to severe
- Episodes can be very far apart in time and location
- Uhthoff phenomenon: Symptoms worsen by body temp increases
9
Q
What are the sensory symptoms associated with MS?
A
- Paresthesias
- Hypesthesia
- Unpleasant sensations
- Pain (neuropathic and MSK)
- Lhermitte’s symptoms (shock-like sensation down legs)
10
Q
What happens to the eyes in MS?
A
- Optic neuritis (usually unilateral)
- Blurred vision
- EOM pain
- Central field visual changes
- RAPD (swinging light test)
- Optic disc changes like atrophy post optic neuritis.
11
Q
What are the motor symptoms associated with MS
A
- Weakness worsened by exercise
- Bell’s palsy-like weakness
- Diplopia with EOM
- Spasticity
- Hyperreflexia
- Babinski
- Intention tremor
- Dysarthria
Suggestive of UMN changes
12
Q
What CNs are involved in MS?
A
- TN (CN V), but presents bilaterally and before age 50
- Facial Myokymia (CN VII): Involuntary twitching of facial muscles
- Glossopharyngeal neuralgia (CN IX): Shock-like pain in posterior pharynx/tongue/ear when swallowing or without warning
5, 7, 9
13
Q
What happens to the bladder in MS?
A
- Detrusor hyperreflexia
- Detrusor sphincter dyssynergia
14
Q
What GU symptoms are present in MS?
A
- Loss of detrusor control
- Bowel changes (constipation)
- Sexual dysfunction
15
Q
What mental changes occur in MS patients?
A
- Mild cognitive dysfunction
- Depression
- Fatigue (90% of pts)
- Vertigo
16
Q
How do neurological symptoms occur in terms of timing in MS?
A
- 10-120s at a time
- 5-40x a day
Thought to be due to spontaneous discharges from neurons at the end.
Usually self-limiting.
17
Q
What neurological symptoms occur in MS?
A
- Lhermitte’s
- Tonic contractions
- Dysarthria
- Ataxia
- Sensory disturbances
18
Q
What is clinically isolated syndrome for MS?
A
- First MS attack
- Must last 24 hrs and characteristic of MS but doesn’t meet full criteria
19
Q
What is the MC type of MS?
A
Relapsing-remitting MS (RRMS)
20
Q
How does RRMS tend to present?
A
- Disecrete relapses/attacks that evolve over time. (Relapse: days to weeks)
- Periods of partial/complete recovery in between (Remission: weeks to months)
- In between attacks, patients are neurologically stable
21
Q
How does secondary progressive MS tend to present?
A
RRMS that involves deterioration in function separate from attacks
22
Q
How does primary progressive MS tend to present?
A
Steady decline from the onset.
No remission or relapse.
23
Q
How is MS diagnosed?
A
- 2+ episodes of both signs and symptoms that relfect different areas anatomically, via MRI lesions or visualized
- Symptoms >24h and separated by 1 month in recurrence
- MRI Brain with gadolinium showing either acute MS lesions (large with ill-defined margins) or chronic lesions (small with well-defined margins)
24
Q
When is evoked potential testing indicated for MS?
A
- Asymptomatic patients
- Should show a marked delay in latency, which is diagnostic even in an asymptomatic patient
25
When is CSF analysis used to diagnose MS and what is a positive finding?
* **Anyone with CIS or atypical presentation**, aka MRI non-diagnostic.
* **Oligoclonal bands** (OGB) should be seen, representing the **disease-causing antibodies**
* Increased **intrathecal synthesized IgG**
* Mild WBC elevation
* Normal-mild elevated proteins
26
What are considered red flags/atypical presentations of MS?
* Posterior fossa/craniocervical junction/spinal cord symptom localization
* Younger than 15 or older than 60
* **Progressive from onset**
* **None of the other symptoms besides neurological**
* Atypical diagnostics
## Footnote
Posterior fossa = ataxia, imbalance
CC junction = neck pain, HA, balance, voice, dysphagia, respiratory/OSA, dysarthria
27
How do labs present in MS initially? What are the labs normally used in workup of MS?
* Normal.
* ESR
* B12
* ANA
* Treponemal antibody (Syphilis)
* Lyme titer
28
What are the 3 management categories for MS?
* Acute attack
* Disease-modifying
* Symptomatic
29
When is **acute therapy** used for MS and what are the treatments?
* Indications: **CIS/acute exacerbations.**
* **Mainstay: Glucocorticoids: methylprednisolone**
* Plasma exchange (**For pts unresponsive to glucocorticoids**)
30
What is the goal of disease-modifying therapy (DMT) in MS?
Reducing frequency of relapses and evolution of new lesions
31
What should be done prior to DMT for MS?
Screening for Hep ABC and VZV and JC antibodies
32
What is the BBW of DMT for MS?
Risk of progressive multifocal leukoencephalopathy due to JC virus
33
What are the 3 treatment modalities that fall under DMT for MS?
1. Monoclonal antibodies
2. Oral therapy
3. Platform injection therapy
34
What is the MOA of monoclonal antibodies in DMT for MS?
Decreasing immune response
| Theyre all either monthly, q6monthly, or annually.
## Footnote
Annual: alemtuzumab **starts with a for annually** :)
35
What drug classes are part of the oral therapies in DMT for MS?
1. Fumarates (antioxidants, **BID dosing**)
2. Spingosine 1-phosphate receptor modulators/S1PRs (preventing lymphocyte release to PNS, **QD dosing**)
## Footnote
Fumarates end in fumarate
S1PRs end in -imod
36
What are the 2 drugs for platform injection in DMT for MS?
1. Galtiramer acetate (SQ 3x/week or QD)
2. Interferon beta (SQ or IM ranging from QOD to biweekly)
37
How is ataxia/tremor managed in MS?
* Clonazepam
* **Propranolol**
* Primidone
* Thalatomy/DBS
38
How are spasticity and spasms managed in MS?
* Avoiding triggers: **infection, fecal impaction, bed sores**
* PT/exercise
* **Baclofen/intrathecal for severe**
* **Muscle relaxants**
39
When do we treat weakness in MS and with what?
* K+ channel blocker: **dalfampridine**
* Indication: **LE weakness interfering with ambulation**
40
How is pain managed in MS?
* Anticonvulsants
* TCAs
* Pain management if all else fails
41
How is bladder dysfunction managed in MS?
* Hyperreflexia: Frequent voiding and less intake at night + oxybutynin
* Dyssynergia: Terazosin
* Treat UTIs (**esp if pts have post void residuals of > 200mL**)
* **Self-catheterization**
42
What are the treatments for fatigue in MS?
**ALL OFF-LABEL**
## Footnote
stimulants and amantadine
43
What factors suggest a **better prognosis** for MS?
* **Optic neuritis or sensory at onset.**
* **Less than 2 relapses in the first year**
* Minimal impairment **after 5 years.**
44
What factors suggest a **worse prognosis** for MS?
* Truncal ataxia
* Action **tremor**
* Pyramidal symptoms
* **Progressive disease**
45
What are the best patient education tidbits for MS?
* Eat healthy
* Be positive
* Swimming is good
* Go stand in the sun and correct your Vit D deficiency
46
Define cerebral palsy.
1. Group of disorders causing **permanent, non-progressive motor dysfunction that affects tone, posture/and or movement**
2. Often accompanied by **sensation, cognition, communication, perception, behavior, or seizure disorders/disturbances**
47
What is the primary cause of cerebral palsy?
Congenital insult to the developing brain **within the perinatal/delivery period**
48
What are the modifiable RFs for cerebral palsy?
* Maternal smoking
* Maternal alcohol use
* Maternal obesity
49
What is the **leading cause of childhood disability?**
Cerebral Palsy (CP)
50
What are the protective factors for CP?
* Mg Sulfate
* ABX
* Corticosteroids
| **Obstetrical care**
51
How does CP present?
* Gross motor delay in **year 1**
* Hypotonia => spasticity
* **Hand preference before 12 mo**
* **Asymmetric crawling**
* **Growth disturbances**
* **Hyperreflexia**
* **Potentially persistent primitive reflexes**
| Hand preference early on = **red flag for hemiplegia**
52
What is the **MC type of CP** and how does it present?
* **Spastic CP**
* Increased tone **(Hypertonia)**
* Hyperreflexia
* Muscle contractures
53
What characterizes **Dyskinetic CP**?
* Involuntary movements
* **Hyper/hypotonia**
* **Trouble maintaing upright position**
* Dysarthria
* **Intellectual disability**
54
What is the **rarest type of CP** and what characterizes it?
* **Ataxic CP**
* **Impaired balance/coordination**
* Slow, jerky, explosive speech
* **Hypotonia**
* Poor Motor skills
* Difficulty with auditory/visual processing
55
When is CP typically diagnosed and how?
Clinically **after age 2 due to postnatal brain development**
56
What labs are generally ordered in workup of CP DDx r/o?
* Thyroid
* Ammonia
* Lactate/pyruvate
* Organic/amino acids
* Chromosome analysis
* CSF total protein (elevated in neonatal asphyxia)
57
What imaging is used for CP evaluation?
1. **Cranial US for unstable neonates unable to do MRI/CT**, but requires MRI f/u.
2. CT
3. MRI brain (**after 2-3 weeks of age**)
| **Normal imaging does not exclude CP!!!**
58
What is the main goal of managing CP?
Maximizing function
59
How do we manage spasticity in CP?
* Muscle relaxants
* BZDs
* Botox
* Intrathecal baclofen pumps
* Dorsal rhizotomy
60
How do we manage dystonia, choria, and athetosis in CP?
* Anticholinergics
* Dopaminergics
* BZDs
* DBS
61
What are the main complications associated with CP?
* Respiratory issues
* GERD/constipation
* Decubitus ulcers
62
Define Complex Regional Pain Syndrome (CRPS)
* Inflammatory disorder of a region (usually ext), characterized by **pain, swelling, limited ROM, vasomotor instability, skin changes, and patchy bone demineralization**
* Often **follows trauma**
* **MC seen in 30-60y**
63
How does the acute stage of CRPS present?
* 3 months
* Neuropathic pain that is **constant and disproportionate** and **exacerbated by ambient factors**
* Limb use is prevented by pain
* **Swelling, erythema, and edema**
* **Bone demineralization occurs**
64
How does the subacute stage of CRPS present?
* 9 months
* Persistent pain and **fixed edema**
* **Cyanosis or pallor**
* Dry, atrophic skin
* **Atrophy of SQ tissue**
* **Joint stiffness**
* More bony demineralization
65
How does the chronic stage of CRPS present?
* 1 year beyond onset
* Permanent or lasts for years
* **Edema resolves**
* **Dry, pale, cool , shiny**
* **Joint stiffness progresses**
* **Osteoporosis**
66
What is the Budapest criteria for CRPS?
1. Continuing pain **disproportionate to inciting event**
2. **1 symptoms in 3/4 cats**
3. **1 sign in 2+ cats**
4. No other better diagnosis.
67
What are the symptoms for CRPS diagnosis?
1. Sensory: hyperesthesia/allodynia
2. Vasomotor: Temp asymmetry/skin color/color asymmetry
3. Sudomotor/edema: Edema/sweating/sweating asymmetry
4. Motor/trophic: Decreased ROM/dysfunction/trophic changes
| **1 from at least 3 cats!**
68
What are the signs for CRPS diagnosis?
* Sensory: Hyperalgesia to pinprick, allodynia to light touch/deep somatic pressure/joint movement
* Vasomotor: Evidence of temp asymmetry/color changes/asymmetry
* Sudomotor/edema: Evidence of edema/ssweating changes/sweating asymmetry
* Motor/trophic: Evidence of decreased ROM/dysfunction/trophic changes
| **1 from at least 2 cats!**
69
Where does demineralization typically begin?
Ends of bones **progressing medially**
70
What does a positive bone scintigraphy look like and what is it for?
* ** Assessing bone metabolism** in pt with **active resorption**
* **Increased radiotracer uptake** in areas of demineralization
71
What is the **first-line tx** for CRPS?
OT and PT
72
What is the secondary therapy tx for CRPS?
Psychosocial and behavioral therapy
73
How is pain managed in CRPS?
* NSAIDs **First**
* Neuropathic pain drugs (gabapentin, pregabalin, TCAs)
* Lidocaine/Capsaicin topical
* Bisphosphonates for abnormal bone scans
74
When is pain management referral warranted in CRPS?
* **Progressive symptoms and signs of CRPS**
* **Unsatisfactory response to initial tx**
75
What are the more interventional pain management options for CRPS?
* Trigger point injection
* Sympathetic nerve blocks
* Spinal cord stimulation
* Dorsal root ganglia stimulation
76
What is the mainstay of patient education for CRPS?
1. **Explaining the long-term benefits of PT and OT**
2. Some degree of **prolonged disability is common**
3. Recurrence is somewhat common, esp in **younger pts**
77
Define Amyotrophic Lateral Sclerosis/ALS/Lou Gehrig's Disease
1. **Fatal** neurodegenetaive disease of **both upper and lower motor neurons** characterized by **progressive loss of motor function**
2. Amyotrophic = atrophy of muscle fibers
3. Lateral sclerosis = lateral columns of UMN get replaced by **fibrous astrocytes/gliosis**
78
Describe the pathophysiology of ALS.
1. Impaired astrocyte/microglia release toxins
2. Impaired astrocytes **increase glutamate => increased Ca2+ uptake**
3. **Too much calcium = oxidative stress in mitochondria**
4. **Mutant proteins worsen stress and turn into neurofilaments and cause neuronal death**
79
What is the MC form of ALS?
**Sporadic**
80
What are the RFs for ALS?
* Age, **peaking at mid 70s**
* FMHx
* **Smoking**
81
What is the MC **initial symptom of ALS**?
Extremity dysfunction, like tripping, foot/wrist drops, or reduced dexterity.
82
How does bulbar dysfunction look like in ALS?
* Slurred speech, hoarseness, quiet speech, **Drooling**
* Aspiration/choking while eating
* **Emotional lability**
* Pseudobulbar affect syndrome: **Involuntary laughing/crying**
83
How does ALS tend to progress symptom-wise?
Very slow and progressive, reflecting the UMN lesion area.
| Will eventually cause LMN dysfunction as well.
84
Where does generalized weakness begin in ALS?
Extremities, presenting as gait abnormalities.
85
How is ALS diagnosed and worked up?
* **Need both UMN and LMN dysfunction present.**
* **EMG** will show both **acute and chronic denervation and reinnervation**
* Everything else normal
86
Describe Riluzole.
* MOA: **inhibition of glutamate release**
* **Only proven med that extends life in ALS patients**
* BID dosing
| ALS is characterized by excess glutamate.
87
Describe Edaravone.
* Free radical scavenger (aka antioxidant)
* **Slows functional deterioration, esp if used early on**
* IV and oral
| ALS drug
88
Describe sodium phenylbutyrate-taururusodiol.
* MOA: Reduce stress response and ups the threshold for apoptosis **(reduce neuronal cell death)**
* **Slows rate of functional deterioriation**
* BID dosing
| ALS drug
89
Define Tofersen.
* **Only used for pts with a SOD1 gene mutation**
* MOA: Binds to SOD1 mRNA to prevent it from working.
* **Reduces disease progression**
90
What is the only ALS drug proven to extend patient life?
Riluzole
91
What ALS drug is used for SOD1 gene mutation carriers?
Tofersen
92
What are the drugs to manage spasticity in ALS?
* Baclofen
* Tizanidine
93
What are the drugs/tx to manage **Drooling** in ALS?
| I feel like she would ask a Q on this
* Amitriptyline, scopolamine
* Pseudoephedrine
* Salivary gland irradiation
* **Botox B (risky)**
94
What do ALS patients generally require in terms of home support?
* BiPAP
* Invasive vent + tracheostomy
* Speech therapy
* Nutritionist
* PEG tube
* PT/OT with **low impact exercise regimen**
95
What is the MCC of death in ALS?
Aspiration PNA
| Median survival is only **3 years** once weakness is seen. :(
96
What should all ALS patients NOT DO?
**SMOKE**
97
What is Toxic-Metabolic Encephalopathy?
1. Acute condition resulting in **global cerebral dysfunction without primary structural brain disease**
2. **Dysfunction of ascending RAS, leading to impairment of arousal/awareness**
98
Who is toxic-metabolic encephalopathy MC seen in/RFs?
* ICU pts
* Older pts
* Demented pts
99
How does toxic-metabolic encephalopathy present?
* Cognitive dysfunction (confusion to coma)
* Seizures
* Exaggerated physiologic tremors
* **Asterixis**
* **Myoclonus**
* **Babinski, brisk DTRs**
100
What is the MCC underlying etiology for toxic-metabolic encephalopathy?
Sepsis
101
Why would we use MRI/CT in working up toxic-metabolic encephalopathy?
If focal deficits are present, we need to rule out **SDH**
102
What diagnostic will confirm global cerebral dysfunction and differentiate toxic-metabolic encephalopathy from seizure?
EEG
103
How is toxic-metabolic encephalopathy managed?
* Treating the underlying cause (i.e. sepsis)
* Removing any delirium drugs
104
What does the prognosis look like for toxic-metabolic encephalopathy?
* **Reversible if treated promptly**
* **Neurological improvement is slower**
105
What is neurofibromatosis? (NF)
* **Genetic** disorder characterized by **tumor formation on nerve tissue due to mutation/deletion of tumor suppressor genes**
106
How does NF Type 1 present?
* Early on in childhood, **usually by age 10**
* **Strong family history**
* **Cafe au lait spots anywhere** (age 1-2)
* **Freckling of axilla/groin** (age 3-5)
* **Lisch nodules on iris**
107
How many cafe au lait spots suggest NF type 1?
More than **6**
108
What do neurofibromas look like?
* **Soft, peasized lesions**
* **Nonpainful or tender usually**
* On/under skin
* Increases the older you get
109
What does a plexiform neurofibroma look like?
Tumor growth on nerve plexus itself.
110
What happens to bones in NF type 1?
* Scoliosis
* Bowing of lower legs
111
What ophthalmic changes occur in NF type 1?
* Optic gliomas
* Visual disturbances/proptosis
* **Compression of pituitary**
| Many hormonal issues can occur, often all occurring by age 3
112
What learning disability is pretty common in NF type 1?
ADHD
113
What happens to BP, height, and head size in NF Type 1?
* BP: Very high due to RAS or pheo
* Short
* Big head due to big brain
114
How is NF Type 1 diagnosed?
1. 6+ cafe au lait spots > 5mm prepubertal and >15mm postpubertal
2. 2+ neurofibromas or 1 plexiform
3. Axillary/inguinal freckling
4. 2+ Lisch nodules
5. Optic glioma
6. Bone lesion with sphenoid dysplasia
7. 1st degree relative meeting NIH criteria
| **2 of 7 NIH criteria**
115
How is an optic glioma identified?
MRI Brain
116
How is NF Type 1 managed?
1. Treat individual manifestations
2. Annually assess all the stuff
3. Genetic counseling
117
When is surgery indicated for neurofibromas/plexiforms?
* Neurofibromas: Pain, bleeding, functional interference, disfigurement
* Plexiform: Debulking/partial resections, but residual functional deficits persist even w/ full resection.
118
What are the dangerous tumors in NF Type 1 and their red flags?
* **Malignant peripheral nerve sheath tumors (MPNSTs) and neurosarcomas**
* Large plexiforms/externa peripheral lesions are the origins usually.
* **Significant/persistent pain within lesion**
* **Soft to hard transition**
* **Rapid growth**
119
What is the MCC of death in NF1?
Malignant tumor
120
What is unique about NF2 from NF1 etiology/demographics?
* **Not genetic predisposed usually**
* **Less cutaneous manifestations**
* **Occurs later, more into teen/adult**
121
What is the MC lesion in NF2?
**Benign, slow-growing** tumor of the **vestibulocochlear nerve**
| CN 8
## Footnote
AKA vestibular schwannomas or acoustic neuromas
122
How does NF2 typically present?
* Gradual hearing loss
* Tinnitus
* Ataxia
* HA
123
What are the other possible lesions in NF2 and the clinical findings?
* Lesions: Meningiomas, schwannomas, gliomas, neurofibromas, cataracts
* Numbness/weakess in extremities
* Pain
* Balance
* Vision
124
How is NF2 diagnosed?
* **Bilateral vestibular schwannomas**
* 1st degree relative + unilateral vestibular schwannoma or 2+ of the others.
*** 1 Unilateral vestibular schwannoma** + 2 of the others
* Multiple Meningiomas + **1 unilateral vestibular schwannomas** or 2 of the others.
125
What scan is good for screening acoustic neuromas? Spinal cord lesions?
* MRI brain for acoustic neuroma screening
* MRI spine for motor/sensory changes
126
What 3 evaluations should be performed annually in NF2?
1. Auditory
2. Ophthalmic
3. Neurologic
127
What is schwannomatosis?
* Multiple, non-cutaneous schwannomas **without vestibular involvement**
* MC seen after 20
* Usually acquired genetic defect postbirth
128
How does schwannomatosis present?
* Focal pain of neuropathic and nocipceptive nature
* Focal numberness and weakness
* **Muscle atrophy**
129
What confirms a diagnosis of schwannomatosis?
1. 2+ non-intradermal schwannomas, with 1 histiologically confirmed.
2. No present of vestibular tumor via MRI
3. 1 pathologically confirmed **non-vestibular** schwannoma + 1st degree relative with above criteria.
130
What scans are used in schwannomatosis workup?
* MRI brain to r/o CN 8 (vestibulocochlear nerve)
* MRI spine to r/o spinal cord lesion
* Focused peripheral nerve test
* Whole body MRI to determine extent
131
How is schwannomatosis typically treated?
* Neuropathic pain management
* NSAIDs/short-acting opiates
* Add-on: amitriptyline, duloxetine, antiepileptics
* **Resection is last resort**
