1. Neurology Review
MKSAP

2. Dementia
Acquired chronic impairment of memory and other aspects of cognition that impair daily function.
MCI = Mild Cognitive Impairment
MCI does not impair daily function
Degenerative or vascular disease that causes widespread or multifocal brain abnormalities.

3. Dementia Alzheimer’s Disease most prevalent Non-AD ~1/3+ of Dementias
Different clinical presentations and different Rx
FTD – presents with executive function impairment and personality change vs Memory problems of AD
Cholinergic Rx does not help FTD
Relieve FTD patients of responsibilies

4. DSM-IV criteria for Dementia
A. Development of multiple cognitive deficits with both:
1. Memory impairment
2. One or more of the following
a. Aphasia
b. Apraxia
c. Agnosia
d. Impair executive functions (planning, organizing, sequencing, abstracting)
B. A1 and A2 cause significant impairment in social or occupational functioning and represents a decline from prior functions
C. Deficits do not occur exclusively as part of a delerium

5. Pathology of Alzheimer’s Diseasse
Deposition of insoluble beta-amyloid protein in extracellular parenchymal plaques
Amyloid Plaques surrounded by dystrophic tau-positive neurites and activated microglia
Neurofibrillary tangles are microtubule-associated tau-protein; hyperphosphorylated and abnormally conformed.
Number of tangles correlates with severity of dementia
Beta-Amyloid neurotoxicity is most likely key feature.
Early degeneration of Basal Forebrain (Nucleus basalis of Meynert) results in Cholinergic deficit.
Mesial Temporal lobe degeneration results in memory impairment
Association area involvment in inferior temporal lobes, prefrontal, and parietal areas are other features
Relative sparing of subcortical and primary motor and sensory cortex.

6. Beta-Amyloid
1 – 42 fragment is cleaved by abnormal cleavage of larger Amyloid Precursor Protein.
Alpha-secretase cleavage produces soluble product.
Cleavage by beta or gamma-secretase produces toxic, insoluble 1-42 fragment.
Cascade or inflammatory and toxic events initiated.

7. APP cleaving

8. APP processing

9. Epidemiology of AD
Risk factors: advanced age, genetic predisposition, cardiovascular conditions, post-menopausal state.
Prevalence* 1.5% for age
Doubles every 5yrs to 85
Increases 10% every 5 yrs age 85 to 100
45% at age 100

10. Genetics etc of AD ~5% of cases are Mendelian
Dementia <65 some caused by Autosomal Dominant mutations in presenilin 1, presenilin 2, or APP
~25% of genetic cases are presenilin 1 mutations. Most common familial AD.
Genetic test available
Good genetic counseling required.
For late onset, no known one gene mutations known, but FH is risk factor.
RR ~2.5 if affected relative
High risk of AD in Trisomy 21. APP is on #21
Apolipoprotein e4 is risk factor; onset about 10yrs earlier
Hypertension is risk factor
Estrogen replacement controversy
? Benefit of Statin Rx
?NSAIDs

11. Mild Cognitive Impairment (MCI)
MCI is conceptually the intermediate stage between presymptomatic disease and Dementia
MCI – memory impairment without other cognitive problems and without impairment in functional independence
Progression from MCI to AD is about % per year. In one study ~80% had AD at 6 yr follow-up.

12. Progression of AD Steadily progressive deterioration over 8 – 10 yrs.
MMSE 20 – 26 = mild dementia with mild functional dependency needing some assistance (ex. Financial)
MMSE 10 – 20 = moderate dementia. More impairment and help needed. Unable to drive.
MMSE <10 = severe dementia with total dependency and constant supervision.

13. Diagnosis of Alzheimer’s Disease
Clinical diagnosis supported by imaging and tests.
Typically normal neuro exam except for cognition
No pathognomonic features or reliable biomarkers.
Diagnostic Crieteria – next slide
Not very specific. ~70% accuracy
Think other Dementias or dx when early symptoms are: impaired social behavior, gait disturbance, aphasia, hallucinations, delusions; or not insidious or chronic

14. NINCDS-ADRDA criteria
1. Dementia established by clinical examination and standardized brief mental status test and confirmed by neuropsychologic tests
2. Deficits in two or more areas of cognition
3. Progressive worsening of memory and other cognitive functions
4. No disturbance of consciousness
5. Onset between 40 – 90 years old
6. Absence of other systemic or neurologic disorder sufficient to account for the progressive cognitive defects

15. R/O secondary causes of Dementia
5 – 15% of dementias are at least partially reversible
Depression, medication induced encephalopathy and metabolic disorders most likely.
D/C unnecessary Rx, especially sedatives and anticholinergic agents.
Screen for depression, B12, hypothyroidism.
Syphilis screening if risk factors
CT or MRI to exclude structural pathology and eval for strokes or hydrocephalus
Formal Neuropsych testing may be needed if atypical, ?depression, medico-legal decisions such as competency.

16. Additional evaluation options
EEG and/or LP if fluctuating ecephalopathy or subacute progressive dementia
Functional imaging may help distinguish between FTD and AD.
Biomarkers in CSF not yet ready for primetime
Genetic testing not routinely needed.

17. AD

18. Tangles and Plaques

19. Treatment of AD
Cholinergic augmentation recommended for all mild to moderate AD.
Improves cognition and global functions
Effect lasts for about a year
Does not altered overall progression
Not shown to delay nursing home placement or death.

20. Anticholinesterase agents
Donepezil (Aricept).
Start at 5mg qd. Increase to 10mg qd in 4 – 6 weeks. Side effects: Nausea, diarrhea, Abdo pain, sleep disturbances
Rivastigmine(Exelon).
Start 1.5mg bid, titrate up to 3 – 6mg bid over 6 weeks. SE: N/V, anorexia, dizzines
Galantamine (Reminyl).
Start at 4mg/d, titrate up to 12mg bid over months. SE: N/V, anorexia, weight loss, diarrhea
Tacrine (Cognex)
not used anymore
These agents may be helpful in Lewy Body dementia and vascular dementia, but not in Fronto-temporal dementia

21. NMDA glutamate antagonist Rx
Memantine (Nemenda) – shown to be helpful for moderate to severe Alzheimer’s Disease.
Start at 5mg/d, increase up 10mg bid with weekly changes.
SE: hallucinations, confusion, restlessness, anxiety, dizziness, h/a, fatigue, constipation.
Can be combined with Anticholinesterase inhibitor.

22. Other Rx’s ?Ginkgo biloba
Not proved. ?dose. ?standardization. ?effects on other medications
?Vit E IU twice daily was shown to benefit. But other studies with increased mortality. So ?

23. Treatment of Psychiatric Symptoms
More likely to lead to institutionalization
Behavioral approaches: predictable routines, repetition, patient redirection.
AChE inhibitors help:
apathy, hallucinations, psychosis, depression,anxiety.
Trazadone or atypical neuroleptics* may help delusional or agitated behaviors.
Resperidone, olanazapine, quetiapine
* increased risk of death shown in meta-analysis. Risk vs benefit.
Remember the care givers may need care.
Elder abuse or neglect

24. Preventive Strategies
Nothing as of yet.
Goal: slow amyloid deposition in brain
Amyloid vaccines
Encephalitis
Bad-Secretase inhibitors
Good –Secretase enhancers

25. AD – Keypoint and recent advancs
Normal Neuro exam except for memory and other cognitive domain impairments
MCI is likely a predemential stage
Cholinergic augmentation is standard therapy
AChE inhibitors modesty improve cognition, global function, and psychiatric symptoms
Memantine in moderate to severe AD improves function better than AChE inhibitors
?Vit E
Antipsychotic therapy has Black Box warning.

26. Non-Alzheimer’s Dementias
Vascular dementia, Dementia with Lewy Bodies, Fronto-temporal Dementia – most common of the non-AD Dementias.
Often superimposed on AD
Prion Disease and other degenerative diseases (CBD) much less likely.

27. Vascular Dementia
Multiple or strategically placed large-vessel occlusions
Multiple small vessel occlusions***
Primary hemorrhagic process
*** likely most common

28. Vascular dementia
~25% of stroke patients meet criteria for dementia at 3 months
~1/3 of dementias a/w proximate stroke
RR for dementia is % per year in 4 years post stroke vs 1.3% per year
Vascular disease and AD synergism.
Why?

29. Vascular dementia

30. Dx of vascular dementia
H/o Stroke or risk factors
Neuro-imaging
Abrupt onset or step-wise progression
Poor sensitivity – most have insidious onset and gradual decline.
Many have no signs of stroke or h/o stroke
Often mixed
MMSE not sensitivity. Typically cognitive slowing, apathy, poor problem solving. “Subcortical dementia”.
Formal neuropsych testing may help

31. RX Vascular Dementia
Treat systolic hypertension – primary prevention. Secondary prevention – evidence of benefit not proved.
ASA
Acetyl Cholinesterase inhibitors

33. Fronto-temporal dementia (FTD)
Early, insidiously progressive impairment of personality and executive functions – decision making, prioritizing, planning.
Consensus Criteria for FTD:
Insidious onset and gradual decline
Early decline in social interpersonal conduct
Early impairment in regulation of personal conduct
Early emotional blunting
Early loss of insight
Apathy
Usually noticed by family not by patient
Memory impairment may be relatively mild

34. FTD
Disproportionate atrophy of frontal lobes and anterior temporal lobes
Pick’s Disease
Many have tau-positive inclusions in affected neurons. Cause not known
RF: age and family history
~40% familial. Tau gene mutation in many.

35. Pick’s Disease

36. Dx of FTD History from family Poor 1 minute fluency test
List words from category in 1 minute.
10,14,18
Visuo-spatial functions preserved (cf AD)
Formal neuropsych testing
Neuro-imaging

37. Rx of FTD
Medicationss can help irritability, agitation, depressive symptoms, eating disorders
Trazadone, SSRIs, Modafinil etc
Not helpful for cognitition
AChE inhibitors don’t help.
Remove from responsibilites
No driving
Decision making: financial, medical etc
Neuropsych testing have help here.

38. Dementia with Lewy Bodies (DLB)
Dementia with intraneuronal inclusions in cortex
Visual hallucinations, fluctuating cognition, parkinsonism
Can co-occur with AD

39. Criteria for probable DLB
1. Persistent memory impairment may not occur early but is usually evident with progression. Deficits of attention, frontal-subcortical skills, and visuospatial ability may be particularly prominent
2. Two of the following core features
a. Fluctuating cognition with pronounced variation in attention and alertness
b. Recurrent visual hallucinations that are typically well formed and detailed.
c. Spontaneous motor features of parkinsonism
3. Supportive features include repeated falls, syncope, neuroleptic sensitivity, delusions, hallucinations in other modalities, REM behavior disorder.
% specificity but only % sensitivity
“Fluctuating cognition”
Daytime drowsiness and lethargy despite normal sleep
Falling asleep for > hours during the day
Staring into space for long periods
Episodes of disorganized speech marked by real words linked in a disjointed manner.

40. Treatment of DLB AChE inhibitors first
Can help behavior symptoms, hallucinations and delusions
“standard neuroleptics” can be associated with neuroleptic malignant syndrome.
“Black box” warning of atypical neuroleptics
Sinemet etc

41. Creutzfeldt-Jakob Disease (CJD)
CJD is most common Prior disease
~1 per million.
Degenerative disease that may be transmissible
Transformation of prion protein into insoluble conformation
Spongioform changes in brain
~85% are sporadic
Familial forms with mutation of prion protein
Prion protein is normal constituent of CNS
New variant CJD (vCJD) in younger patients a/w consumption of meat affected with bovine spongiform encephalopathy

42. Dx of CJD Rapidly progressive disease a/w myoclonus
Death usually in 3 – 6 months
DDX includes: primary angiitis of CNS and Hashimoto’s encephalitis
Hashimoto’s: antithyroglobulin antibodies
Seizures, dementia, myoclonus, ataxia
Brain Bx may be needed

43. Clinical criteria for probable CJD
1. Rapidly progressive dementia
2. Electroencephalogram with periodic sharp waves or elevated levels of protein on CSF analysis
is non-specific neuronal marker.
limitations
Two of the following
Myoclonus
Visual or cerebellar signs
Pyramidal or extrapyramidal motor signs
Akinetic mutism
65% sensitivity, 95% specificity
EEG normal in vCJD

44. EEG in sCJD

45. CJD

46. CJD pathology

47. Key Points for non-AD dementias
Most common are Vascular dementia, DLB, FTD
Clinical Dx of VD: h/o or risk factors for stroke, a stroke-like course, and/or findings on imaging
DLB characterized by parkinsonism reponsive to dopaminergic Rx, visual hallucinations, and fluctuating cognition
Cholinergic augmentation may help psychiatric symptoms of DLB
FTD presents with early executive and personality changes, and pronounced or asymmetric atrophy of frontal lobes on imaging
CJD suspected if dementia with myoclonus that progressives of weeks to months

48. Headache and Facial Pain
Significant advances in the past 20 years
Migraine alone: 10% of people
18% of women and 6% of men
75% have moderate to severe headaches
Distinguish Primary from Secondary Headache
Primary: Migraine, Tension-type, Chronic Daily/rebound/medication overuse, Cluster.
Secondary: SAH, meningitis, PTC, Cerebral mass lesions, GCA

49. Migraine
Nausea, photophobia, phonophobia, throbbing pain. May worsen with movement and limit daily activities
Pathophysiology: begins in the brainstem and higher brain structures; distention and inflammation of meningeal vessels is FINAL manifestation.
Trigeminal vascular system: triggered to release of inflammatory peptides on blood vessels.
Autonomic and chemoreceptor systems triggered: nausea, pallor, flushing, tearing, rhinorhea, sinus congestion.
Sinus headache: fever, discolored nasal discharge and air-fluid level on CT.

50. Migraine cont’d
Prodrome in many, up to 24 hrs prior to attack: euphoria, depression, food cravings, fatigue, hypomania, cognitive slowing, dizziness, asthenia.
Auras in 15% - 20% - with hour of or during headache: visual loss or changes (ex. scintillating scotoma), hallucinations, numbness, tingling, weakness, confusion. Spreads. Caused by Spreading Cortical Depression = wave of neuronal depolarization. Auras last few minutes to up to an hour. ( Acephalgic migraine – aura without the headache.)
Complicated migraine. Rare. Aura persists over 24 hours. May result in infarction – from profound metabolic disturbance. Risk increased by OCPs and smoking.
Late life migraine accompaniments: patients over 50yrs. 20 – 60 minutes typically. (c/w TIA which usually lasts minutes.) May be repetative and not worsen in severity. (c/w TIA). ~50% a/w mild headache.

51. Migraine treatment
Acute Rx with triptans or ergots: bind directly to trigeminal nerve endings and blood vessel. Decreased release of inflammatory substances – stabilized nerve endings and blood vessel swelling. Best for patients with moderate to severe headaches.
Milder, infrequent migraines can be treated with NSAIDs or Acetominophen.
Triptan orally, intranasally, injection.
Faster but more SEs with shot: chest discomfort, nausea, dizziness, numbness, flushing
Longer half-life triptans have less side effects, but slower action and ?less effective. Idiosyncratic responses of pateints. Long half-life triptans may be useful for prophylaxis of menstrual migraine.
Low risk of cardiac side effects, but contraindicated in patients with significant coronary risk factors. Chest pain may be side effect >>> diagnostic confusion.
IV dihydroergotamine ofr status migrainosus. SEs: nausea and akasthisia. Given with anti-nausea rx. Intranasal DHE = triptans
Earlier use = better response. Rx not perfect
Central sensitization – brain hypersensitive to all stimuli – light, sound, smell, touch. Treatment less effective once Central sensitization has occurred.
No class effect for triptans. Therefore try many to find the best.
Recurrence of headache – repeat dose.

52. Acute Migraine Rx 1 mg IV DHE 1mg DHE nasal spray. (Pregnancy X)
With antiemetic. Pregnancy X
1mg DHE nasal spray. (Pregnancy X)
Triptans
Sumatriptan (Imitrex)
Rizatriptan (Maxalt)
Zolmitriptan (Zomig)
Frovatriptan (Frova) – longest half life

53. Migraine rescue Rx
For those who are resistent to triptan Rx or Rx ineffective.
Beware using opioids more than a few times per year. Beware medication over use and rebound.
Releive headache and cause sedation: cautions.
Home vs clinic/ED
IV medicaions: Haldol and Ativan together; lidocaine, MgSO4, Valproate, Solumedrol, hydroxyzine, Promethazine, Prochlorperazine, Metachopramide
Oral: Olanzapine, Quetiapine, Tizanidine, Hydroxyzine

54. Migraine Prophylaxis
Consider in patients with 2 or more migraines per week. If less, consider the severity and level of disability.
Antidepressants (tricyclics mostly), anticonvulsants, beta-blockers (Inderal FDA approved).
AEDs: decrease neuronal irritability.
Depakote and Topamax FDA approved for migraine prophylaxis
Start low, go slow. Titrate up over months. Asses effect for couple months. If controlled for 3 -6 months, can consider tapering off
Botox: may be useful. May prevent release of inflammatory peptides peripherally

55. Prophylactic Medications
Inderal LA – up to 160mg
Verapamil – may need big doses
Depakote ER – 1000mg qhs.
Pregnancy D. Take Folate supplement
Check LFTs after 1 and 3 months
Weight gain
Topamax – start at 25mg qhs up to 200mg
Weight loss, carbonic anhydrase effect, cognitive SEs
Neurontin – up to 4800mg in 3 divided doses
Keppra – start 500mg bid
Other AEDs
Elavil or Pamelor – start at 10mg or 25mg qhs.
SNRIs – Duloxetine etc
Methysergide – now not available in the US
Cyproheptadine
CoEnzyme Q10
Riboflavin
Magnesium Oxide

56. Non-pharmacologic Rx
Behavioral modications, meditation, counseling, hypnosis, acupuncture, PT, biofeedback, diet modification, sleep hygiene.
Coping strategies, reducing effect of environmental stressors and triggers
Dietary triggers (~20%): tyramines, nitrates, dairy products,xanthines
Sleep: 7 – 8 hours for adults > hours for <25. Restful sleep decreases brain irritability.

57. Menstrual Migraine 60% of women with migraine
Triggered by decrease in estrogen. Can also happen around ovulation.
Prophylaxis: estrogen rx instead of empty pill during menses, oral magnesium.
Beware estrogen in smokers or h/o hypercoagulability – increased stroke risk.
Preemptive therapy: NSAIDs or longer acting triptans – Frova or Amerge.

58. Key Points: Migraine
Migraine originates in the brainstam and higher brain structures that cause pain coming from inflamed cerebral blood vessels.
Acute migraine Rx includes specific therapy with triptans or ergot derivatives
Triptans are contraindicated in patients with significant coronary risk factors or a history of coronary disease.
Treatment should be administered as early as possible in the attack to ensure the greatest efficacy using the lowest dose of therapy.
Prophylactic therapy is indicated in patients who experience more than two days with h/a per week.
Proper sleep hygiene may be the most effective migraine prophylaxis.
Consumption of foods containing tyramine, nitrates, dairy products, and xanthines may trigger migraine in some patients.
Menstrual migraine prophylaxis includes administration of low-dose estrogen therapy during menstruation, continuous estrogen therapy during menses, or oral magnesium.

59. Tension-type Headache
Most prevalent
Mild migraine vs unique disorder?
Squeezing/pressure, bilaterally
May have light or sound sensitivity – not both
Minutes to days, constant, no nausea
Alone or with migraine
Low level of disability
If interfere with activities, Rx as migraine
Mild headaches: rx with NSAIDs or muscle relaxants

60. Medication overuse Headaches
4 - 5% of Americans have >15 headache days per month!
~75% due to medication overuse
Acute Rx more than 2 days per week >>> risk for rebound headache
Pain on or soon after waking. Pain like migraine or tension-type
Medication response poor – vicious cycle
~25% have secondary headache – r/o mass lesions, infection, inflammatory disorders, sleep disorders, cervical pathology
Rx: complete withdrawal of offending agent(s), migraine prophylactic Rx, breakthrough rx with NSAIDs, IV DHE, or steroids
2 -12 weeks of therapy
Caffeine withdrawal

61. Cluster Headache One of the most painful H/A syndromes
Pain + autonomic features
Episode lasts 15 minutes to 3 hours. (Migraine 4 hours to 3 days)
Unilateral and periorbital/temporal
Associated with at least one on same side as Headache: conjuctival irritation, lacrimation, rhinorrhea, nasal congestion, eyelid edema, facial sweating, miosis/ptosis.
Patient aggitated, can’t stay still. May touch head to help alleviate pain (c/w migraine).
May recur several times per day at the same time. No pain between episodes.
Clusters typically last 3 – 6 weeks.

62. Cluster Pathophysiology
Probably similar to migraine except trigger may be in the hypothalamus
Periodicity
Autonomic symptms
PET scan evidence
Increase levels of histamine
Sensitivity to histominogenic triggers

63. Rx of Cluster
Oral Steroid Rx for 2 – 4 weeks with taper over weeks
Anticonvulsants
Calcium Channel Blockers
(Lithium – not mentioned in MKSAP)
Fast acting triptan (injection), IV DHE, high flow Oxygen
Exclude primary sleep disorder

64. “Jabs and Jolts” H/As with Autonomic manifestations
Paroxysmal hemicrania
Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)
Shorter duration, more frequent pains that Cluster. Many per day. Seconds to minutes.
Indomethacin

65. Other primary headaches
Benign thunderclap headache
Headache upon awakening
Headache a/w sexual activity
Exercise induced headache
Benign cough headache
?pathophysiology
R/O secondary causes
Rx triptans or NSAIDs (Indomethacin)

67. Secondary Headaches Low threshold for imaging (and Neuro consult)
“CT of head is like CXR of the CNS”
DDX: AVM, TIA/Stroke, dissection, vasculitis, Venous thrombosis, tumor, seizure, acute HTN, pituitary apoplexy, acute HC, infection.
CT less sensitive for posterior fossa lesions and may miss up to 10% of SAH.
+/- MRI is less emergent situations
MRI for significant change in pattern and for focal neurologic sx/sx.
If SAH suspected and CT negative >>> LP
R/o mass lesion or obstructive HC prior to LP
Get Opening pressure along with labs
LP if fever, seizures, meningeal signs with headache.

68. Exam!

69. Giant Cell Arteritis (temporal arteritis)
Patients >50
Progressive worsening of headaches often with swollen tender scalp vasculature
Jaw claudication
Polymyalgia rheumatica
Visual blurring
Amaurosis fugax
Systemic disease affecting medium and large arteries. Predilection for cranial arteries
ESR elevated in >95% (above 50, usually )
CRP
Rx with 60mg/d prednisone to prevent visual loss from AAION (inflamation of short posterior ciliary arteries) AAION = Arteritic Anterior Ischemic Optic Neuropathy.
Ophthalmology eval for Temporal Artery Bx
May need to Bx both sides
High-dose Steroids indicated for Dx
Long term (1 -2+ years) steroid Rx may be needed if Dx proved by Bx
Monitor response to Rx by Sx and ESR
Blindness possible if not treated

70. GCA

71. Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)
Increased intracranial pressure without evidence of intracranial disease.
R/o mass lesions, hydrocephalus, Venous sinus thrombosis.
Pathophysiology: ?decreased CSF reabsorption. (narrowed cerebral venous drainage pathways.
Mostly in obese women of childbearing age.
Also a/w Tetracycline Rx, OCPs, and hypervitaminosis A
Daily non-throbbing headache worsens with cough/sneeze or lying down. +/- diplopia, TVOs, pulsative tinnitus
Papilledema, enlarge blind spot or VF changes, +/- sixth nerve palsy. Maybe get Optic nerve damage with visual loss.
Eval: MRI with MRV, LP with OP and labs.
Rx: weight loss. Diamox (carbonic anhydrase inhibitor) reduces CSF production
Optic nerve sheath fenestration. Consider CSF shunting (second choice).
Ophthalmology follow-up to monitor vision.

72. PTC

73. MRV

74. Normal CSF flow

75. Chiari Malformation

76. Chiari

77. Syringomyelia

78. Trigeminal Neuralgia
Paroxysms of pain in one or more divisions of CN V
Sharp, stabbing pains lasting seconds to a few minutes
Touching face can trigger pain
Exam typically normal. If sensory loss, this suggests secondary cause
Get MRI to exclude secondary cause in everyone
Etiology sometimes compression by vascular loop.
RX: AEDs +/- Baclofen
Tegretol
Neurontin
Trileptal
Others
Microvascular decompression in some patients,
or Gamma-knife radiotherapy – directed at the trigeminal ganglion >>> sensory loss, dry eye, anesthesia dolorosa

79. Trigeminal Neuralgia

80. Carotid Dissection
May follow head or neck trauma, but may be spontaneous
Ipsilateral head, neck, or eye pain
Sudden or gradual onset
Possible Horner’s syndrome
+/- contralateral weakness or numbness
+/- ipsilateral visual symptoms
MRA, carotid duplex

81. Guess what’s next?

82. Movement Disorders Hypokinetic (too little movement)
Ex) Parkinson’s Disease, Parkinsonian Syndromes
Hyperkinetic (too much movement)
Ex) Chorea, Dystonia, Essential Tremor

83. Parkinsonism Syndromes
Primary Parkinsism
Idiopathic Parkinson’s Disease
Juvenile parkinsonism
Secondary Parkinsonism
Medication induced
Hydrocephalus
Infectious
Metabolic – Calcium, parathyroid, Copper
Neoplastic
Toxin induced
Traumatic
Vascular
Psychogenic

84. Medication induced Parkinsonism
Antipsychotics
Antiemetics
Tetrabenazine
Reserpins
Allpha-methydopa
Calcium Channel Blockers
Lithium

85. Infectious causes of Parkinsonism
Lethargic encephalitis
AIDS
Fungal
Syphilis
SSPE
Spongiform Encephalopathy

86. Toxin induced Parkinsonism
MPTP
1-methyl-4-phenyl-1,2,3,6-tetrapyridine CO
Manganese CN
Carbon disulfide
Mercury
MeOH
EtOH

87. Basic idea of PD Rx

88. Parkinsonism-Plus Syndromes
Corticobasal Ganglionic Degeneration
Dementia Syndromes AD
Dementia with Lewy Bodies
Frontotemporal Degeneration
Multisystem Atrophy
Olivopontocerebellar Degeneration (OPCA)
Shy-Drager Syndrome
Progressive Supranuclear Palsy (PSP)

89. Hereditary and Degenerative Parkinsonism
Familial basal ganglionic degeneration
FTD with parkinsonism
Linked to chormosome 17
Huntington’s Disease
Wilson’s Disease
Fragile X premutation carriers
Other rare disorders

90. Patho-physiology of PD

91. Loss of cells in Substantia Nigra

92. Lewy Bodies

93. Parkinson’s Disease
James Parkinson, 1817 essay on the “shaking palsy”. Charcot coined the term “Parkinson’s Disease”.

94. Multiple Sclerosis

95. Multiple Sclerosis
Most common cause of non-traumatic neurologic disability in young adults
Signs/Symptoms
Diagnosis
Course
DDX
Cervical spondylosis, myelopathies, DM, neurosarcoid, SLE, Sjogren’s, Vit B12 deficiency
NMO

96. MS cont’d Rx exacerbations Disease modifying Therapies Symptomatic Rx
Interferons
Glatiramer
Natalizumab (blocks migration of inflammatory cells, a/w PML
Mitoxantrone
Other immunosuppressants
Symptomatic Rx

97. MS keypoints
On MRI, the presence of ovoid lesions perpendicular to the lateral ventricles and corpus callosum are characteristic of MS
Management of leg spaciticity a/w MS should involve PT for stretching and pharmacologic Rx
The decision to treat an exacerbation of neurologic deficit with corticosteroids is determined by whether the patient’s function is affected
Plasma exchange may benefit patients with severe exacerbations of MS that are refractory to steroids
PT, OT, ST may be appropriate after severe MS exacerbations
There is no therapy that convincingly slows degenerative processes in MS or definitively provides neuroprotection.
Treatment of primary progressive MS is limited to symptomatic Rx

98. Peripheral Neuropathies

99. Peripheral Neuropathies
Recent advance: Muscle-specific Kinase antibodies in Myasthenia Gravis
Axonal vs Demyelinating
Acquired vs hereditary
Charcot-Marie-Tooth disease is most common hereditary neuropathy
Toxins

100. Neuropathies a/w pain Cryptogenic Sensorimotor neuropathy
Diabetic Neuropathy
Vasculitis
GBS
Radiculopathy/plexopathy
Alcoholic neuropathy
HIV sensorimotor Neuropathy
Syphilis
Heavy Metal toxicity
Amyloidosis
Fabry’s disease
Hereditary sensory/autonomic neuropathy

101. Peripheral Neuropathy eval
Standard:
CBC, Chemistries, SPEP/IFE, B12, glucose assessment, RPR, TFTs
Optional:
HIV, ESR, ANA, RF, SS-A, SS-B
Anti-Hu
Genetic studies
Lyme titre
Heavy metals – 24 hour urine
Phytanic acid
LP if suspecting CIDP or AIDP
NCVs
Sensory nerve Bx
If vasculitis suspected

102. Symptomatic Rx of Neuropathic pain
TCAs
AEDs
Lidocaine Patch
Capsaicin cream
Acupuncture
Transcutaneous nerve Stim
Tramadol

103. Guillain-Barre
Rapidily progressive, immune-mediated demyelinating polyneuropathy
Up to 75% a/w preceding infection, immunization, or surgical procedure
EBV, CMV, Campylobacter, Lyme, Hepatitis, HIV
Weakness, pain, paresthesias, autonomic symptoms, facial weakness, ophthalmoparesis, respiratory failure (25%)
2 – 4 weeks
Respiratory monitoring – FVCs etc
EMG
Rx: IVIG or Plasmapheresis

104. Polyneuropathy keypoints
Asymmetric involvement should raise suspicion for MND, radiculopathies, plexopathies, compressive neuropathies, or mononeuritis multiplex
Viral illness, immunization, or surgery may precede GBS
DDX of neuropathy with Mental Status change should include B12, thiamine, or niacin deficiency
Immunosuppresive Rx indicated for CIDP
NCV may be helpful to determine Axonoal vs demyelinating process
Treatment of idiopathic polyneuropathy generally limited to pain Rx
Hospitalize and do frequent respiratory monitoring for suspected GBS
Rx with IVIG or plasmapheresis GBS patients who are unable to ambulate independently and have impaired respiratory functions or rapidly progressive weakness
Oral immunosuppressive rx for CIDP; IVIG or plasmapheresis indicated for severe or refractory CIDP

105. Amyotrophic Lateral Sclerosis
ALS – both UMN and LMN
Primary Lateral Sclerosis – UMN
Primary Bulbar palsy – Brain stem
Progressive muscular Atrophy – LMN
~2/100,000 incidence.
Slight male predominance
95% sporadic
Mean survival 2 – 5yrs

106. Rx of ALS Riluzole is approved for ALS (very modest effect) PEG
Noninvasive PP ventilation with Bilevel positive airway pressure may prolong survival and improve quality of life
Symtomatic Rx for spasticity, emotional lability, muscle cramping, and drooling may maintain dignity and quality of life

107. Myasthenia Gravis Antibodies against the AChR
Characterized by fatigable weakness
Ocular with diplopis, ptosis
Bulbar with dysarthria, dysphagia
Proximal extremity
Neck with head drop
Respiratory with dyspnea
Dx: repetitive Nerve Stim, Tensilon (not availbable) or SF-EMG may help
Rx: Mestinon, immune Rx
May initially get worse on Prednisone

108. Medications to avoid in MG
Calcium channel blockers
Beta-blockers
Quinine
Quinidine
Procainamide
Lidocaine
Aminoglycosides
Polymyxin
Morphine
Barbiturates
Neuromuscular blocking agents
Magnesium

109. MG keypoints
There is an increased incidence of thymic abnormalities and thyroid disease in patients with MG
85% of patients with generalized MG are AChR antibody positive
Mild cases may be treated with acetylcholinesterase therapy (pyridostigmine 60mg tid or qid), whereas worse presentations may benefit from immunosuppresive Rx
IVIG or Plasmapheresis may help severe weakness

110. Muscle Diseases

111. Neuro-oncology

112. Epilepsy

113. Epilepsy
Seizure or Syncope?

114. Pre-ictal features Seizure Syncope Warning: may be preceded by aura
Aura is actually part of seizure (Simple Partial)
Provocation: Alcohol or medication withdrawal, CNS infections, Trauma
Appearance: no change; may be staring
Posture: Any
Onset: Sudden
Syncope
Warning: lightheadness, feeling of faintness or “doom”.
Provocation: Change of posture, pain, dehydration, anxiety, cough, micturition, etc
Appearance: Pale, ashen, sweating
Posture: Usually upright, may be sitting
Onset: Gradual

115. Ictal features Seizure Syncope Duration: Seconds to minutes
Incontinence: May be present
Injuries: More Common
Tonic/clonic movements: Generalized or focal
Autonomic features: Tachycardia, increased blood pressure
Syncope
Duration: Seconds
Incontinence: None
Injuries: Infrequent
Tonic/clonic movements: Rare, usually bilateral
Autonomic features: Bradycardia, Low BP, Dilated pupils

116. Post-ictal Features Seizure Syncope
Confusion/Disorientation: Present for several minutes
Speech: May be garbled
Pain/muscle soreness: Present after a generalized tonic-clonic seizure
Focal transient neurologic deficits: May be present
Syncope
Confusion/Disorientation: Usually rapid return to baseline
Speech: Normal
Pain/muscle soreness: Absent
Focal transient neurologic deficits: None

118. Stroke
Sudden focal neurologic deficit caused by ischemia (80% - 85%) or Hemorrhage (15% -20%).
TIA = sudden ischemic focal neurologic deficit that resolves completely. 24 hours is current definition. (Good cause for 1 hour as cutoff.)
Hemorrhagic Stokes: SAH (5% total) or intraparenchymal (10% - 15%)
Leading cause of disability in US
Third leading cause of death in US
Incidence: 700,000+ per year. 20% recurrent
Risk increases exponentially with age.
Racial differences: higher in AA
Cost >$50,000,000,000 per year. About 50% hospital costs. Rehab and long term care account for most of the rest.
Costs of lost productivity not accounted for.

119. Pathophysiology Large vessel occlusions
MCA: contralateral hemiparesis or hemisensory loss, visual field loss
Left: aphasia
Right: hemineglect
Deep penetrating vessel occlusions
Lacunar syndromes
Pure motor hemiparesis
Internal Capsule, Corona radiata, or basis pontis
Pure sensory syndrome
VPL nucleus of Thalamus
Clumsy hand – dysarthria syndrome
basis pontis
Ataxic hemiparesis
Posterior limb of the internal capsule, basis pontis
Spinal cord strokes can occur but rare
Ischemia and Hemorrhage may be indentical clinically
Clues for Hemorrhage: headache, n/v, Severe HTN

120. Artherosclerotic lesions

121. Cerebro-vascular Territories and Syndromes
Anterior Cerebral Artery
Contralateral leg weakness
Middle Cerebral Artery
Contralateral face/arm >leg weakness
Hemisensory Loss
Visual Field cut
Aphasia/Neglect
Posterior Cerebral Artery
Contralateral Visual Field Cut
Deep or “Lacunar”
Contralateral Motor or sensory loss with “cortical signs”
Basilar Artery
Occulomotor deficits +/- ataxia with crossed motor/sensory deficits
Vertebral Artery
Lower CN deficits +/- ataxia with Crossed sensory signs
Ex) Wallenberg Syndrome

122. Blood supply to base of brain

123. Emergency Stroke Evaluation
Stroke is time-critical medical emergency
Area of infarct – minutes to hours of ischemia leads to irreversible infarct
Ischemic penumbra – area that could infarct if perfusion not restored quickly.
Most damage in first 3 – 6 hours
Penumbra is Target of Rx

124. Stroke Mimics Seizure with Todd’s Paresis Intracranial mass Migraine
Meningitis/encephalitis
Drug OD
Hyper or hypoglycemia
Unmasking of prior deficits due to acute illness
Cervical or head trauma
Post cardiac arrest ischemia
Hypertensive encephalopathy
Psychogenic

125. Emergent Eval and Rx
Sudden neurologic dysfunction over minutes to hours probably = stroke
Stroke mimics
Quick eval – NIH stroke scale
GCS not very useful for stroke
Full Neuro exam later
With TIA, risk for stroke increased with
TIA >10 minutes, limb weakness, speech disturbance, >60 yo, DM
Hospitalize TIAs – risk highest in first few days after TIA for major vascular event
Neuro-immaging: ischemic vs Hemorrhage vs ?

126. Emergent CT scan

127. NIH Stroke Scale LOC: (alert to coma) LOC questions: month and age
LOC commands: close eyes, make fist
Best Gaze
Visual Fields
Facial palsy
Left Arm
Right Arm
Left Leg
Right Leg
Limb ataxia
Sensation to Pin
Best Language
Dysarthria
Extinction

128. Neuroimaging in acute Stroke
Noncon CT first study – r/o hemorrhage
Relatively insensitive to acute stroke in first few hours
Subtle findings: Hyperdense vessels, loss of grey-white boundaries, effacement of sulci. These findings are highly specific
Noncon CT: ~100% sensitive for intraparenchymal hemorrhage; ~90% for SAH.
Xenon inhalation - map of cerebral blood flow – not widely available.
MRI: More expensive, time consuming, less available; therefore not the standard of care.
DWI: sensitive to early cytotoxic edema. May slightly overestimate area of infarction. Apparent Diffusion Coefficient (ADC) may be more accurate.
PWI: area of decreased perfusion
PWI – DWI = ischemic penumbra area
Spectroscopy: biochemical marker identification.
Vessel imaging: Conventional angiogram, CTA, MRA, Transcranial Doppler. (This info usually not critical for initial treatment decisions.

129. Neuro-imaging

130. Cerebral Angiogram

131. Acute Stroke Therapy
IV t-PA (recombinant tissue plasminogen activator) is effective for acute ischemic stroke if given within 3 hours of onset, better if given earlier.
Rigorous selection of right patients necessary to maximize efficacy and minimize risk.
Knowing time of onset is crucial.
Awaken with stroke – time last seen normal = onset
Aphasic with no witness – onset time not known; therefore contraindicated.

132. BP management in Acute Stroke
BP may be up to maintain perfusion
Elevated BP increases risk of hemorrhage after t-PA.
BP should be under 185/110 for t-PA
Use Nitro paste or Labetalol acutely to get BP down if necessary
Maintain BP below 185/105 after Rx with nicardipine, labetalol, or nitroprusside.
t-PA dose is 0.9mg/kg to max of 90mg. 10% as one minute bolus, other 90% infused over an hour.
No antiplatelet Rx for 24 hours.

133. rt-PA

134. t-PA eligibility criteria
Inclusion Criteria
Age >18
Clinical Dx of ischemic Stroke
Onset within 3 hours of Treatment
CT without hemorrhage
Exclusion Criteria – Historical
Stroke or head trauma within 3 months
History of intracranial Hemorrhage
GI or GU bleeding in previous 21 days
Major surgery or trauma within previous 14 days
Arterial puncture at noncompressible site or LP in previous 21 days
Pregnant or lactating
Exclusion Criteria – Clinical
Rapidly improving stroke symptoms
Seizure at onset
Symptoms suggestive of SAH
Persistent BP > 185/110 or aggressive rx needed to control BP
Acute/subacute MI or pericarditis
Exclusion Criteria – Radiographic
CT evidence of hemorrhage
CT sings of major early infarct *controversial
Exclusion Criteria – Laboratory
Glucose <50 or >400 mg/dl
Platelet count <100,000
If on warfarin and PT >15secs
If on Heparin with 48 hours and PTT elevated

135. If worsening while on t-PA
Stop infusion
Stat CT
Platelet count – treat if low
PT/PTT/fibrogen – Rx with cryoprecipitate if necessary
Neurosurgery consult

136. Effectiveness of t-PA
Nearly doubles the odds of recovery to independent function at 3 months: 47% vs 27%.
Symptomatic intracranial Hemorrhage risk is 6.4%
No impact on mortality after stroke.

137. Antiplatelet therapy