Approach to Neurologic Disease

3 primary Qs
a) First ask - IS there a neurological problem?
b) Anatomic diagnosis
a. Level of neuraxis
i. Supratentorial
ii. Posterior fossa
iii. SC / vertebral column
iv. Peripheral neuromuscular system
1. E.g. NMJ

Somatoform Disorders → Somatic symptom and related disorders

Overview
a) ALL of these diseases relate to the Q: how do we respond to stress?
b) Somatization = somatic expression of psychological distress
a. WHY do we somaticize?
i. Stigma of psychiatric symptoms VS relative acceptance of medical
problems?
1. We can brag about our soccer injuries but no one brags about
their depression 
2. Cultural component
ii. Casserole illness VS illnesses that make others uncomfortable
c) 2 golden rules – NO psych dx until
a. Other medical conditions are r/o
b. Substance use is r/o

Somatoform/somatic symptom and related disorders

a) Somatic symptom disorder
a. Features
i. Physical symptoms are NOT intentionally produced
1. Psychogenic
ii. Dx of exclusion
iii. Pts often have other co-morbidities
1. Depression
2. Anxiety
b. Treatment
i. Primary care setting
1. Develop and maintain therapeutic alliance
2. Run dx procedures and therapeutic interventions based on
OBJECTIVE findings
3. Redefine treatment as mgmt rather than cure
4. Encourage psychiatric consultation
5. Education about mind-body connection—a very delicate
discussion
 a. How we feel can inform how we feel in our gut
b. Our bodies DO respond to how we feel
i. Why can’t we have pain or numbness when we
have depression or anxiety?
c. Nervousness / blushing
d. Sexual arousement – starts in the mind
ii. Psych tx
1. Dx and treat co-morbid depressive and anxiety disorders
2. Supportive psychotherapy to improve direct expression of
emotional distress and CBT to correct dysfunctional attitudes and
encourage activities that have been avoided
b) Conversion disorder (functional neurologic disorder) = somatic symptom disorder that
involves neurologic symptoms
a. Sx are not better explained by another medical or mental disorder
b. e.g. loss of vision, seizures, speech sx, weakness,
c. Specific if:
i. Acute vs persistent
1. The FASTER it’s recognized, the better the prognosis
ii. With or without psychological stressor
d. Treatment
i. Supportive psychotherapy focusing on stress, coping, and direct
expression of emotional distress
1. Where do the symptoms come from?
2. E.g.
ii. Suggestive therapy for symptom removal
c) Somatic symptom disorder with predominant pain
a. Features
i. There IS pain, but it’s often out of proportion to etiology
ii. VS illness anxiety?
1. SYMPTOMS are most distressing
2. Thoughts/feelings follow
b. Dx considerations
i. Pain of sufficient severity to require assessment
ii. Psychological factors have a role in onset, severity, exacerbation, or
maintenance of pain
iii. NOT intentionally produced or feigned
c. Treatment – DO we treat pt’s pain?
i. Antidepressants – some are approved for pain!
1. Amitryptyline = tricyclic antidepressants
ii. Psychotherapy using CBT
d) Illness anxiety disorder (hypochondriasis) = preoccupation w/ acquiring or having a
serious illness
a. Features
i. PREOCCUPATION is the predominant feature
 ii. Somatic symptoms are not present or, if present, only mild in intensity
b. Specify whether
i. Care-seeking?
ii. Care-avoidant
c. Treatment
i. Tx as outlined for somatic symptoms disorder
ii. SSRIs – may help reduce preoccupations as there is often comorbid
anxiety and/or depression
e) Body dysmorphic disorder
a. No longer a SS&R disorder, now under obssessive-compulsive and related
disorders
b. Features
i. Preoccupation with 1+ perceived defects or flaws and physical
appearance that are NOT observable or appear slight to others
c. Specific
i. With muscle dysmorphia
1. Too small or insufficiently muscular
2.
ii. With good or fair insight
1. INSIGHT is crucial!!
iii. With absent insight / delusional beliefs
d. Treatment
i. SSRIs – effective in reducing preoccupations
ii. CBT

Factitious disorders
a) Physical symptoms are intentionally produced OR feigned in order to assume the sick
role
a. Sick role – provides security, affirmation, attention
b) Features
a. INTENTIONAL PRODUCTION OR FEIGNING of physical / psychological signs of
symptoms
b. Motivated by desire to assume sick role
c. Peregrination = changing doctors, “shopping doctors”
c) Epidemiology
a. Pts are frequently employed in health settings
d) Treatment
a. Treatment as outlined for somatization
b. Confront pt BUT we don’t want to ruin the therapeutic relationship
i. Confrontation of the factitious nature of the illness is tricky and not
always appropriate
e) Factitious disorders imposed on others
Malingering
a) Intentional production of false / grossly exaggerated physical or psychological symptoms
that is motivated by external incentives
a. e.g. pt coming to MD for specific pain reliever & making up sx
b) Features
a. Secondary gain – acquiring of prescriptions, medical leave of absence, etc
b. VS primary gain – sick role, attention
c) Mgmt
a. Confront in firm but empathic manner that leaves an opportunity for
constructive dialoguse
Dissociation and defense mechanisms
a) Dissociative disorders – response to trauma derived from an animal model of defensive
response to life-threatening stress e.g. attack by a predator
a. Freezing/tonic immobility
b. Passivity
c. Hypoarousal
d. All have analogies in human dissociative symptoms
b) DID (split personality) is a controversial dx but DISSOCIATION is NOT
c) Defense mechanism
a. Pathologic
i. Delusional projection
ii. Splitting
b. Immature defenses
i. Passive aggression
ii. Acting out
c. Neurotic defenses
i. Dissociation
ii. Reaction formation
d. Mature defenses
i. Humor
ii. Sublimation
iii. Suppression
 PNS Disorders
Motor and sensory PNS disorders
a) Affect PNS from roots out
b) GBS
a. Features
i. Ascending paralysis & areflexia
ii. Demyelinating peripheral neuropathy
iii. Acute – pt was normal weeks before, but can now scarcely walk
b. Causes of death
i. Respiratory failure
ii. PE/DVT
iii. Cardiac arrhythmias
c. Etiology
i. Weakness d/t conduction block
d. Dx
i. Spinal fluid protein is elevated, but CSF is otherwise normal
e. Tx
i. IVIG
ii. Plasmapheresis
c) Chronic sensorimotor, axonal-type peripheral neuropathy
a. Etiology
i. Most common neuropathy – 95%!
ii. e.g. diabetic neuropathy
iii. 25-50% are idiopathic
b. Features
i. Distal symmetric neuropathy
ii. Starts off as N&T of toes and feet
iii. Minimal weakness/wasting initially, but progresses over years
iv. Sx often intermittent → progress to continuous
c. Etiology
i. DM
ii. Thyroid diseases
iii. B-12 deficiency
d. Treatment
i. Treat the causes if you can find it
ii. Tx the symptoms – meds do NOT provide a high % of relief
1. Amitriptyline vs duloxetine
a. Amitriptyline = tricyclic, but lots of side effects
2. Gabapentin vs pregabalin
iii. Be VERY clear about expectations
1. Only 1 in 4 pts are satisfied with treatment
 d) Chronic inflammatory demyelinating polyneuropathy (CIDP)
a. Features
i. Progresses over weeks to months (OVER 8 weeks)
1. Similar to GBS, but progresses beyond 8 weeks
ii. Patterns can be atypical
1. Arms > legs
2. Proximal → distal
iii. Demyelinating diseases
iv. High CSF protein like GBS
b. CIDP vs GBS
i. Similarities
1. CAN have rapid onset
2. May affect proximal AND distal strength
3. Conduction block—electrical activity is indistinguishable
4. ↑ CSF protein
5. Treat with IVIG and plasmapheresis
ii. Differences
1. GBS does NOT have >1 relapse
2. CIDP does NOT cause respiratory failure
3. Prednisone is effective for CIDP\
e) Paraneoplastic pure sensory neuronopathy **review
a. Neuronopathy – affects CELL bodies
b. Features
i. Inability to control muscles
ii. Neurophysiologically, it’s a disease of sensory receptors
1. Motor manifestations are due to deficits in sensation
2. Lack of feedback
c. Pathophysiology
i. Anti-Hu antibodies attack SC and dorsal root ganglion
a) Dx
Anti-Hu antibodies
a. CT to r/o SCLC
b) Treat
a. Find and treat the disease
f) CMT disease *** review
a. CMT1 VS CMT2
i. CMT1 – slow conduction
ii. CMT2 – normal velocities
iii. PMP-22
1. Duplicated in CMT1a, which is a duplication of PMP22
Mononeuropathies – review****
a) 4 most common
a. Medial neuropathy at wrist (carpal tunnel)
b. Ulnar neuropathy near wrist
 c. Ulnar neuropathy at the elbow
d. Fibular neuropathy at the fibal nerve
e. Radial neuropathy in SC
a) Carpal tunnel
a. Most common in pts with laborious vocations—hairdressers, housekeeping
b. Dx
i. EMT / nerve conduction studies
c. Tx
i. Tx underlying conditions
ii. Work modification
iii. Carpal tunnel release
iv. Wrist splints & analgesic
b) Radiculopathies
a. Cervical roots → neck, scapular, arm pain
b. KNOW the C5, C7, L5, S1 muscles
c. Lateral radiculopathies → more red flag signs!!

Motor system diseases (NMJ diseases, ALS, myopathies)

a) Overview
a. Involve motor system
i. MN
ii. NMJ
iii. Muscle itself
b. Do NOT cause numbness, paresthesias, or incontinence
i. Pt has NO numbness or tingling or bowel control
b) Myasthenia gravis
a. 90% involves eye control and/or bulbar
i. Bulbar = swallowing
b. Ocular MG VS generalized MG
i. After 2 yrs, if restricted to MG, highly unlikely to generalize
ii. MOST MG is generalized
c. Complications
i. Respiratory failure
ii. Aspiration pneumonia
d. Pathophysiology
i. Autoimmune attack on nAChR
e. Tx
i. Pyridostigmine – cholinesterase inhibitor
ii. Thymectomy – strong evidence for good outcomes
1. Thymomas in older patients
2. Thymic hyperplasia
iii. Immunosuppression
1. Predinsone
2. PLEX = plasma exchange
 3. IVIG
iv. Ventilation if needed
c) LEMS
a. Features
i. LE weakness and fatigue
ii. Areflexia
iii. Dry mouth, constipation, and erectile dysfunction
1. Affect cholinergic symptoms
iv. A/w SCLC in 60% of cases
d) ALS
a. Features
i. Slowly progressive weakness and wasting of a limb
ii. Slowly progressive spastic dysarthria
iii. Slowly progressive diffuse spasticity
iv. NEVER CAUSES
1. Bladder / bowel incontinence
2. Diplopia / ptosis
3. Significant sensory loss
b. Dx
i. MRI most affected region
1. E.g. if limbs → appropriate spinal level
ii. EMG – widespread denervation, reinnervation
c. Tx
i. Riluzole – high cost
ii. Mobility assists
iii. Gastrostomy
iv. Hospice care
e) Myopathies
a. Dx
i. ELEVATED CK!!!
b. Types
i. Dystrophies
1. Slowly progressive
2. DMD
a. ALWAYS has an underlying cardiomyopathy
3. BMD
a. Reduced dystrophin (VS absence)
b. Can be dx much later in life
4. Myotonic dystrophy
a. Most common
b. Etiology – expanded tri-NT repeat in chromosome 19
i. Affects a glycogen kinase
ii. Genetic anticipation
c. Weakness and stiffness of distal muscles
 d. Multisystem presentation
ii. Myositis – inflammation
1. Progress over weeks to months
 Glaucoma
Anatomy - background
a) Cornea – innervated by CN V1
a. Dmg to cornea – repeated ulcers → anesthetized cornea → l/t disease
b. Activation of HSV1 → along corneal dermatomal pattern!
b) Retina
a. Brook’s membrane behind layer of RPE
c) Muscles - all muscles are covered by conjunctiva
a. Surgeries – conjunctiva must be peeled off from where it joins cornea
i. Limbus = junction of corneal and conjunctival epithelia
d) Ciliary body – makes aq humor
a. Travels thru posterior chamber → past iris → anterior chamber  trabecular
meshwork (90%)
i. Netting around eye that drains aq humor
b. 10% is drained via uveoscleral outflow—gets filtered through where it was
produced

Glaucoma – overview
a) Glaucoma = eye diseases a/w acute or chronic destruction of CN II (optic neuropathy)
a. Flow of aq humor against resistance generates IOP b/t 10-21 mmHg
b. Disruption in flow of aq humor can raise IOP leading to nerve damage and visual
impairment
c. However, IOP may or may NOT be elevated
b) Categorized based on angle of anterior chamber
a. Angle = b/t cornea and iris

b. Open angle – most common in US

c. Closed angle – can be acute or chronic; common in Asia
i. Etiology
1. Iris is stuck to cornea
2. New BV growth
3. Trauma that damages this region
 4. Cataracts push iris up
ii. Acute closed angle
1. Tx goal – lower IOP, acutely release cause of angle closure
iii. Closed angle
1. Tx goal – lower IOP
c) Diagnosis
a. Based on disc to cup ratio
i. Cup = paler region within optic disc
ii. 0.3 c/d = normal
b. Dilated fundus exam

c. VF testing
i. Superior arcuate defect – sweeping appearance that crosses midline
d. IOP
e. Central corneal thickness – thinner cornea ↑ risk of cornea or worsens
glaucoma
f. CN II imaging
i. Examine robustness of nerve fiber layer
ii. Ganglion cell density
g. Relative afferent pupillary defect (Marcus Gunn pupils!!)
i. Illuminate unaffected eye → bilateral constriction
1. Consensual pupillary reaction is intact
ii. Illuminate abnormal eye → bilateral or unilateral dilation
1. Direct response is impaired
2. Some constriction in unaffected eye?
d) Monitoring
a. IOP
b. Visual fields
i. ↑ density of arcuate defect
ii. ↓ acuity of vision due to degradation of macula
c. Retinal fiber layer
d. Macular thickness
Management of glaucoma
a) Mechanisms
a. ↓ aq humor production
b. ↑ aq humor outflow through trabecular meshwork
c. ↑ aq humor outflow through uveoscleral pathway
b) Topical prostaglandin analogs = 1L tx for OA glaucoma
a. AEs
i. iris discoloration
ii. inflammation – opening US outflow → junctions for immune cells to enter
→ macular edema
c) Beta-blockers
a. Mech – ↓ aq humor production
b. AEs – depression, bradycardia, arrhythmia
c. CI – asthma, COPD (cause bronchospasm)
d) α2 agonists (brimonidine)
a. Mech - can ↓ production AND ↑ outflow via US pathway
b. AE – redness, allergies, dry mouth, bradycardia
e) Carbonic anhydrase (dorzolamide)
a. Mech – ↓ aq humor, mildly ↑US outflow by ↑ PG synthesis
b. AE – fatigue, numbness, tingling, metallic taste, metabolic acidosis
c. CI – sulfa allergies (sulfa derived drug)
f) Cholinergics (pilocarpine)
a. Mech
i. Contraction of ciliary body muscle fibers → rounds out lens + opens
trabecular meshwork
ii. Pupillary miosis
Angle closure glaucoma
a) Acute = true ophthalmic emergency
a. Sx – extreme pain, sudden vision loss
i. EXTREMELY high IOP
ii. Mid-dilated pupil
iii. Opaque cornea
b. Dx
i. Slit lamp
1. beam comes at an oblique angle
2. shows cross sectional thickness of cornea
3. ↓ space b/t cornea and iris
 L: ↑ space b/t cornea and iris (iridocorneal angle) after repair
A: ↓ iridocorneal angle

c. Tx
i. Laser peripheral iridotomy (LPI)
1. Laser strikes iris → creates communication b/t anterior and
posterior chambers
ii. Cataract surgery – remove lens → artificial lens
iii. Manage IOP

Cataracts
a) Sx
a. Glare
b. Haloes
c. Difficulty with night driving
d. Second sight - ↑ nearsightedness → no longer need reading glasses
b) RFs – smoking, prior surgery, steroids, diabetes, trauma, infection, UV
c) Pathophysiology
a. Cloudy lens scatters light → image is out of focus and hazy

d) Tx = surgery
a. Take off anterior capsule
b. Scoop out lens
c. Leave behind capsule attached to ciliary body via zonular fibers
 d. Replace with artificial lens (thin material)
e. Capsule shrink wraps around lens
e) Secondary cataracts
a. Microscopic parts of cataract lens remain and gradually accumulate
b. Back side of lens accumulate lens → reintroduction of cataract sx
c. Tx with second cataract surgery but from posterior

Papilledema
a) Swelling of optic disc d/t ↑ IOP
b) Sx
a. Enlarged blind spot
b. Double vision from CN VI palsy
i. Stress from ↑ IOP
c. Pulsatile tinnitus – d/t spinal fluid
c) RF
a. Weight gain
b. GH, tetracyclines, vitamin A
c. Pseudotumor cerebri
d) Dx – dx of exclusion
a. r/o compressive lesions
e) Tx
a. Wt loss
b. Diuretics
c. Surgery

Macular degeneration
a) Pathophysiology
a. RPE = “garbage disposal”, metabolic products of ganglion cells, BPCs go here
 b. Dry MD
i. Degeneration of RPE → build up of
waste products (e.g. fluid,
lipofuscin) in area b/t RPE and
Bruch’s (pronounced “Brook”)
membrane → atrophy of RPE
1. Drusen = metabolite
deposits (mostly lipofuscin)
in RPE
ii. Bruch’s membrane = inner most
layer of choroid, adjacent to RPE
iii. Choroid = layer b/t sclera and retina
that contains BVs supplying eye

c. Wet MD
i. Choroidal neovascularization → leaking of IV serous fluid & blood →
sudden localized elevation of macula and/or detachment of RPE

b) Sx
a. Metamorphopsia = shape of objects appears distorted
i. Linear objects appear curvy, rounded or missing spots
ii. D/t chronic central vision distortion
iii. Can lead to acute vision loss
b. Scotomas = blind spots
c) RFs
a. Smoking, UV light, poor diet
d) Tx
a. Smoking cessation
b. AREDS-2, diet rich in leafy green vegetables
c. Anti-VEGF for wet MD
i. Direct injections
d. Genetic therapies
Diabetic retinopathy
a) Pathophysiology
a. Microaneurysms of BVs
b. Damaged capillaries
 c. Things collect in pockets of retina
b) Sx
a. Blurred vision (acute, chronic)
c) Dx
a. Exudates on fundoscopy (NOT same as drusens)
i. Fluid has dried up or digested by RPE → soap like material remains
(“bathtub ring”)
ii. Blood & hemorrhage in layers of retina
b. Fluid pockets on cross sectional scans of retina (OTCs of retina)

d) Tx
a. Blood sugar control w/ diet or medication
b. Anti-VEGF injections
c. Focal or panretinal laser
d. Surgical treatment

Central retinal arterial occlusion

a) Sx
a. Acute painless monocular vision loss
b) Dx
a. Retinal whitening + cherry-red spot
b. NEED TO R/O STROKE
i. Occlusion of artery can be from
stroke
c) DDx
a. Tay Sach’s
b. Niemann Pick
c. Branch retinal artery occlusion
i. Branch of retinal artery can be occluded
d. Commotio retinae = whiplash of eye
d) Tx
a. None proven

Horner syndrome
a) Etiology
a. Pancoast tumor of lung
b. Brown Sequard – hemi-dissection above T1
b) Pathophysiology
a. 1st order – hypothalamus → synapse in cervical SC
 b. 2nd order – from cervical SC ascends and synapses in superior cervical ganglion
c. 3rd order – travels with internal carotid artery → goes thru cavernous sinus →
joins nasociliary nerve (br of trigeminal) to enter orbit → iris dilator nerve

c) Sx: ptosis, anhidrosis, miosis

a. Ptosis – fibers innervate levator palpebrae muscle
b. Anhidrosis – supply sweat glands
c. Miosis – supply iris dilator

Cavernous sinus syndrome

a) Pathophysiology
a. Internal carotid artery
b. ↑ CSF
c. Thrombosis of venous sinus
b) Sx
a. Ipsilateral ophthalmoplegia
b. ↓corneal and maxillary sensation with normal vision

Uveitis
a) Inflammation of iris, ciliary body, and/or choroid
b) a/w systemic inflammatory disorder
a. sarcoidosis, JIA, HLA-B27
c) Dx
 a. Dilated pupil d/t increased “stickiness” of iris → stays in same shape

Retinal detachment
a) Caused by tear of retina
a. Usually by traction of vitreous humor which detaches with age