Survey of Neurology

Eric Kraus, MD

WAPA

4/22/17

NCCPA List

Diseases of nerves

» Peripheral neuropathy

» CRPS

» GBS

Movement D/Os

» Parkinson Dis

» Huntington Dis

» Essential tremor

» Tourette syndrome

Seizures

Syncope

Multiple sclerosis

Myasthenia gravis

Cerebral palsy

Altered mental status

» Dementia

» Delirium

Head injury

» Concussion

» Post-concussion syndrome

Covered elsewhere

» Stroke

» Headache

» Infections

ARS Question

This is a 22 yo woman with sensory loss in the right hand that spread

to her right trunk and leg over 2 weeks. No weakness. Last year she

had numbness in her left face for 4 weeks. Her exam reveals the

sensory loss to pinprick.

What test is likely to confirm your diagnostic suspicion?

A. Brain MRI

B. Spinal fluid evaluation

C. Lumbar MRI

D. Electrodiagnostic testing

E. Tibial evoked potentials

Multiple Sclerosis

CNS disease

Primarily demyelinating

» Axonal loss is also present

Females/white > males/non-white

Sex 2-3:1 = F:M

Prevalence 5-250/100,000 population

Associated with Vit D deficiency and EBV

exposure

MS: Types

Relapsing-remitting MS

(RRMS)

» 60-80%

» Secondary progressive

» Progressive relapsing

Primary progressive MS

(PPMS)

» 20-30%

» Older, cervical disease

MS: Clinical

Optic neuritis » Blurry, color desaturation

» Painful eye movement

Weakness, spasticity

Sensory » most common initial

presentation

Ataxia, tremor

Cognitive

Lhermitte’s sign

Fatigue

Heat and exercise

intolerance

Bladder

Sexual dysfunction

MS: Testing

MRI

CSF (Oligoclonal bands)

Evoked potentials

MRI

90-95% sensitive at

first presentation

Visual detection of

plaques

» Demyelination

» Gliosis

» Inflammation

Location

» Periventricular

» Corpus callosum

» Cerebellum

» Brain stem

Acute lesions

enhance (Gd+)

MacDonald Criteria

MRI MRI

Axial flair Coronal T1 with Gad Sagittal flair

MS: Treatment

Acute

» Glucocorticoids

Chronic (Disease modifying drugs)

» Interferon beta-1b (Betaseron, Extavia): SC qod

» Interferon beta-1a (Avonex): IM weekly

» Interferon beta-1a (Rebif): SC 3x/wk

» Glatiramir acetate (Copaxone): SC daily

» Nataluzimab (Tysabri): IV monthly

» Fingolimod (Gilenya): oral, new in 2010

» Teriflunomide (Aubagio): oral, new in 2012

» Dimethyl fumarate (Tecfidera): oral, new in 2013

» Mitoxantrone (worsening RRMS and SPMS)

ARS Question

A 48 yo man presents with 5 years of trouble eating

and writing. Your exam reveals a tremor with

outstretched hands R>L.

You make a presumptive diagnosis and suggest:

A. Medication review

B. Alcohol

C. Propranolol

D. Lab work-up

E. All of the above

Essential Tremor

Most common movement d/o

Postural and kinetic

Slowly progressive

Prevalence increases with age

» Mean age of presentation 35-45

» Adolescence onset

» 0.5-5% population

» F:M 1:1

Genetic - AD

» FH (+) 50-60%

Distribution

» Hands (symmetric)

» (30%) head, voice, jaw, face

» Legs

» Trunk

Worsened by:

» Emotion

» Hunger

» Fatigue

» Temperature

» Drugs/toxins

Action Tremor Work-up

Review medications

Ask about alcohol (response and abuse), illicit drugs

Labs » M7, LFTs, TSH, B12

» Ceruloplasmin and serum Cu

» Urine tox screen

» Rare: Vit E, heavy metals

Consider MRI for unilateral tremor and acute onset

Review psychiatric history

Drugs/Toxins

Steroids

Thyroid hormone

Lithium

Valproic acid

Cyclosporine

Tricyclics

Beta agonists

Theophyline

Neuroleptics

SSRIs

Caffeine

Nicotine

Arsenic

Lead

Cocaine/amphetamines

Alcohol withdrawal

Benzo withdrawal

Other drug withdrawal

ARS Question

A 56 yo man presents with trouble walking, small

hand writing, and a resting tremor.

You make a presumptive diagnosis and suggest:

A. Sinemet trial

B. Head MRI

C. Propranolol for essential tremor

D. Stroke work-up

Parkinson’s Disease

Loss of dopaminergic neurons in the

substantia nigra

Lewy bodies

Differentiate from broader classification

of parkinsonism

Mean age of onset 55yo

Parkinsonism

Parkinson’s Disease

Neuroleptic side effect

Post-encephalitic

Toxins (Mn, CO, MPTP)

Dementia

Wilson’s disease

Basal ganglia

calcifications

Parkinson-plus

syndromes

» Progressive supranuclear

palsy

» Corticobasoganglionic

degeneration

» Multisystem atrophy

– Autonomic

– Cerebellar

» Diffuse Lewy body

disease

PD: Clinical

Slow progressive course

4 cardinal features

» Resting tremor

» Bradykinesia

» Rigidity (cogwheel)

» Postural reflex impairment

Other: dementia, depression, autonomic

PD: Treatment

Sinemet = carbidopa/levodopa

» Levodopa converts to dopamine

» Most potent drug for PD

Dopamine agonists

» Act directly on dopamine receptors

» Synergy with levodopa

» Ex. Pramipexole, Ropinirole

COMT inhibitors

» Block COMT metabolism of levodopa to DA

» Ex. Entacapone

Other

Treatment Flow Chart

ARS Question

This 19 year-old male complains of excessive

blinking and the need to clear his throat. Onset

was at the age of 8.

You make a presumptive diagnosis and ask

questions about:

A. Sexual abuse

B. Attention deficit d/o

C. Numbness

D. Exercise program

E. Smoking

Tourette Syndrome

Clinical

» Tics: motor and vocal

» Involuntary but

suppressible

» Daily > 1 year

» Onset before age 21

(median age = 7)

» Lifelong, decline with age

» OCD

» ADHD

Prevalence 40/100k

Genetics

» 4:1 M:F

» AD with incomplete

penetrance

» MZ twins 80%

ARS Question

This 42 year-old female complains of a progressive

inability to keep her arms and legs still. She has

had depression for 10 years.

You make a presumptive diagnosis and ask

questions about:

A. Sexual abuse

B. Alcohol use

C. Family history

D. Exposure to lead

E. Smoking

Huntington Disease

Genetics

» CAG repeat

» AD

» Chrom 4

Pathology

» Loss of GABA

neurons in striatum

» Diffuse atrophy

Clinical

» Chorea

» Dementia

» Psychiatric

Treatment

» Neuroleptics

» Clonazepam

» Tetrabenazine

» Antidepressants

ARS Question

This 24 year-old man began having tingling

in his toes 3 days ago. Rapidly, it has

moved to the whole body accompanied by

weakness such that he can’t get out of bed

and is having trouble breathing and

swallowing. Reflexes are absent.

The most likely cause of this neuropathy is:

A.Vasculitis

B.Diabetes

C.B12 deficiency

D.Complex regional pain syndrome

E.Guillain-Barre syndrome

ARS Question

This 64 year-old man began having burning

pain in his toes 3 years ago. Slowly, it has

moved to the knee. The hands became

dysesthetic 1 year ago. No weakness.

Reflexes are absent at the ankles.

The most likely cause of this neuropathy is:

A. Vasculitis

B. Diabetes

C. B12 deficiency

D. Complex regional pain syndrome

E. Guillain-Barre syndrome

ARS Question

This 54 year-old has had stepwise

progression of sensory and motor

symptoms over the last 3 weeks. First in

the right hand (median), followed by the left

leg (sural), right leg (peroneal), and left

hand (ulnar).

The most likely cause of this neuropathy is:

A. Vasculitis

B. Diabetes

C. B12 deficiency

D. Complex regional pain syndrome

E. Guillain-Barre syndrome

ARS Question

This 56 year-old woman had right knee

surgery 2 weeks ago. For three days her

foot is too painful to put a sock on and there

is swelling.

The most likely cause of this condition is:

A. Vasculitis

B. Diabetes

C. B12 deficiency

D. Complex regional pain syndrome

E. Guillain-Barre syndrome

Guillain-Barre Syndrome

AIDP: Acute Inflammatory Demyelinating

Polyneuropathy (80-90%)

AMAN: Acute Motor Axonal Neuropathy

AMSAN: Acute Motor Sensory Axonal

Neuropathy

MFS: Miller Fisher Syndrome

Guillain-Barre Syndrome

Clinical (AIDP, AMSAN)

» Paresthesias

» Ascending weakness

» Face

» Mostly symmetric

» Absent DTRs

» Autonomic

Studies

» High CSF protein

» Slow nerves

Course

» Max weakness < 4wks

» Slow recovery

» 85% do very well

» 10% disabled

» 5% die

Treatment

» Avoid complications

» Plasmapheresis

» IVIG

Diabetic Neuropathy

Symmetric

» Distal sensory

» Autonomic

» Proximal lower limb

» Acute cachectic

» Treatment induced

Focal

» Cranial nerve

– Pupil sparing 3rd

» Mononeuropathy

– Limb

– Trunk

» Proximal lower limb

AAN Consensus

Conclusion: Patients with distal symmetric sensory polyneuropathy have a relatively high prevalence of diabetes or pre-diabetes (impaired glucose tolerance), which can be documented by blood glucose, or GTT (Class III).

Recommendation: When routine blood glucose testing is

not clearly abnormal, other tests for pre-diabetes (impaired

glucose tolerance) such as a GTT may be considered in

patients with distal symmetric sensory polyneuropathy,

especially if it is accompanied by pain (Level C).

Neuropathy Work-up

Diabetes

B12 + methylmalonic acid

SPEP

JD England, et.al. Practice Parameter: Evaluation of distal symmetric

polyneuropathy: Role of laboratory, genetic, and autonomic testing;

nerve biopsy; and skin biopsy (an evidence-based review).

Neurology 2009;72:185

Treatment

V Bril, et. al. Evidence-based guideline: Treatment of painful

diabetic neuropathy. Neurology. 2011; 76:1758

Recommendation

Level A 2+ class 1 studies Pregabalin

Level B 1 class 1 study or Gabapentin, Sodium valproate

2 class 2 studies Duloxetine, Venlafaxine,

Amitriptyline, Tramadol, Opiates,

Capsaicin, TENS

Level U No class 1-3 studies Topiramate, SSRI, nortriptyline,

Insufficient evidence Lidocaine, Alpha lipoic acid

Not helpful Evidence against Lamotrigine, Oxcarbazepine,

Lacosamide, Mexilitine, Laser

Complex Regional Pain Syndrome

A chronic, progressive disease often limited to one

body region (arm, leg), following a noxious event and

characterized by severe pain (allodynia), autonomic

dysregulation, swelling, skin and bony changes.

Types

» I = No demonstrable nerve injury (90%) (formally called reflex

sympathetic dystrophy)

» II = Nerve injury (formally called causalgia)

Best treatment is early and often use of the limb

ARS Question

This 38 year-old man has SOB, trouble smiling and chewing, and mild

proximal arm weakness. Both diplopia and ptosis are present. The

symptoms are better in the morning and after rest. They are worse

when reading, walking, and lifting.

Which two tests will help confirm your diagnosis?

A. CPK and brain MRI

B. Repetitive nerve stimulation and CPK

C. Repetitive nerve stimulation and brain MRI

D. Ach Rec Abs and brain MRI

E. Repetitive nerve stimulation and Ach Rec Abs

Myasthenia Gravis

Definition: autoimmune

disease of the

neuromuscular junction

characterized by fatigable

weakness

Antibodies against multiple

epitopes on the muscle side

» Acetylcholine Rec

» MuSK (Muscle Specific

Kinase)

Types

» Generalized 85%

» Ocular 15%

» Neonatal

– Abs from mother

Myasthenia Gravis

Clinical

» Fatigability

» Ptosis and diplopia

» Sensory normal

» Reflexes maintained

» Bedside maneuvers

Diagnosis

» H&P

» Repetitive stimulation

» Antibodies

» Tensilon test

» Chest imaging

Myasthenia Gravis

Treatment

» Thymectomy (not MuSK)

» Anticholinesterase agents

» Immunosuppression

» Immunomodulation (plasmapheresis, IVIG)

ARS Question

This 39 year-old woman has recurrent

episodes of staring with inability to get her

attention. Duration ~30 secs. Started one

month ago after a car accident in which she

hit her head.

How should we classify her seizures?

A. Myoclonic

B. Complex partial

C. Simple partial

D. Absence

E. Generalized

EEG

ARS Question

A 53 yo man presents with loss of consciousness

and is witnessed to have whole body shaking for

10 secs and is sweaty. He wakes up immediately

and can talk.

You make a presumptive diagnosis and suggest a

work-up for:

A. Syncope

B. Alcohol withdrawal

C. Seizure

D. Conversion d/o

E. Illicit drug use

Classification

Partial onset

» Simple partial

» Complex partial

» Secondarily

generalized tonic-

clonic

Generalized onset

» Absence

» Myoclonic

» Atonic

» �Tonic

» Clonic

» Tonic-clonic

Partial Onset Seizure

Partial = focal

Simple

» Consciousness normal

» Smell, taste, vertigo, fear,

etc.

Complex

» Consciousness altered

» Blinking, lip smacking,

vocalizations, etc.

Partial Onset Seizure

Secondarily

generalized

Tonic-clonic

Generalized Onset Seizure

Source?

» Deep structure

EEG

» Bilateral synchronous

discharges

Genetic

Onset usually before

age 20

Differential Diagnosis

Syncope

» Definition: Loss of

consciousness due to

insufficient blood flow to

the brain

Migraine

Sleep d/o and

narcolepsy

TIA

Movement disorder

Psychiatric

Cardiac arrhythmia

Blood flow obstruction

» Structural cardiac dis

» Structural

cerebrovascular dis

Orthostatic hypotension

Neurally-mediated

Syncope vs. Seizure

Syncope

» LOC

» Tonic-clonic

– 5-15 sec.

» Urinary incontinence

» Tongue bite

» Low BP

» No post-ictal period

Seizure

» LOC

» Tonic-clonic

– 10-120 sec.

» Urinary incontinence

» Tongue bite

» High BP

» Post-ictal period

ARS Question

A 25 year-old male was brought to the ER after dropping

in the hallway in front of co-workers who describe tonic-

clonic activity. Four more seizures occurred while in

transport and you witness another in the ER. He never

regains consciousness in between.

You make a presumptive diagnosis and order what

emergent intervention first:

A. Benzodiazepines

B. MRI head

C. ABG

D. Neurology consult

E. Tox screen

Status Epilepticus

ABCs

IV

Labs

» ABG

» Toxicology

» Drug levels

» CBC, M7

Head CT?

Immediate drugs

» Benzos (diazepam,

lorazepam)

» Followed by…(phenytoin,

phenobarbital)

Refractory status

» Intubate

» Paralyze

» Continuous EEG

» Other drugs

ARS Question

A 16 yo female was hit in the head playing soccer.

Brief LOC if at all. She is dizzy on the sideline and

can’t answer questions about the score.

Can she go back in the game?

A. Now

B. Next game

C. Next year

D. Never

E. Only when her symptoms have improved.

Concussion

GCS of 13-15, measured at 30 min after acceleration, deceleration or contact forces to head

Loss of consciousness (<10%)

Typically with grossly normal imaging

Symptoms » Amnesia (post-traumatic, retrograde)

» Attention deficit

» HA, dizziness, blurred vision

Management

Sports » Graded return to play.

No symptoms at rest mild activity full contact.

Medications » None specific

» Symptomatic

Acute

» ABC’s

» Spine immobilization

» Head CT rules

Subacute

» Physical and mental rest

Prognosis

Post concussive syndrome

» Variable definition: symptoms remaining (7 days, 4 weeks, 3

months) after the mild TBI

» More prevalent in pts w/ depression or anxiety prior to injury

» Uncommon in children

» Longer duration of sx when involved in litigation

Vast majority (85-90%) better by 3 months

Question?

Early in the disease process

Dementia

» Normal level of consciousness

» Decreased content of consciousness

Delirium

» Altered level of consciousness (sleepy, obtunded or hyperactive)

» Acute or subacute

» Fluctuating

» Disorientation to place and time

» Hallucinations

» Large differential

What is the level of consciousness?

Dementia Delirium

Next question

Question?

Depression

» Screen

» Medication trial

» Neuropsychological testing

Is the patient depressed?

Dementia Pseudodementia

Next question

Example Case

This is an 64 year-old male who comes to the office alone to

discuss memory loss. His wife died 2 years ago of breast cancer.

His children live on the east coast. He used to like playing golf but

rarely joins his friends for a round. Sleep is disrupted and he wants

a sleeping pill. On exam he sighs a lot and doesn’t try to answer

the “day”.

Pseudodementia (depression)

Question?

Not easy to tell the difference. Time may be needed.

Normal changes » Forgetfulness » Small pupils » Decreased upgaze » Increased muscle tone » Impaired vision, smell, hearing, taste

Dementia definition » Decline in cognitive functioning severe

enough to impair activities of daily life or independence.

» Memory loss is almost always an early feature. Plus….

» Disorder of language, apraxia (motor function), agnosia (recognition), executive function (behavior, directions).

Could it be normal aging?

Dementia Age-related

Next question

Question?

History » Alcohol

» Medications

» Gait disturbance followed by urinary

incontinence and dementia (NPH)

» Head trauma

» Headaches

» Stroke symptoms

Physical » Abnormal/focal exam

» Mental status testing

Everyone labs » B12, TSH, BUN/Cr, Calcium

Individualized labs » TPPA (or other syphilis), HIV, Lyme, ESR,

copper/ceruloplasmin, heavy metals

Imaging CT/MRI » Tumor, subdural, stroke, hydrocephalus

Consider neuropsychological testing

Is the dementia reversible/treatable?

No Yes/Maybe

Dementia syndromes

AAN Dementia Workup Recommendations

B12

Thyroid function testing

Dementia Screening

Neuroimaging

Example Case

This is a 77 year old female who is brought to the clinic by her

family. They are greatly concerned because the patient has been

talking about gremlins climbing the walls in her apartment for three

weeks. The family investigated but found nothing out of the

ordinary. On further questioning the family reports memory difficulty,

increased sleep, and walking trouble with two falls in the last 4

months. On exam she needs to push to get out of the chair, has a

slow walk, and there is mild arm cogwheel rigidity.

Diffuse Lewy-body disease

Example Case

This is a 53 year old female who is brought to the clinic by her

family because of change in personality over 1 year. She used to

be a quiet church going woman, but has recently been growing

more vulgar, and the other day began cursing in the middle of a

church service when her tic-tacs spilled out of her purse. Her family

reminds her to shower or she won’t for days. Her apartment is

always a mess. The patient is frustrated, and says there is nothing

wrong with her, and doesn’t know why her family is treating her so

poorly. She says she is sharp as a tack, spitting out the day, week,

month, season, and year without any difficulty.

Frontotemporal dementia: behavioral variant

Example Case

This is an 82 year-old male who is brought to your office by his son.

The son reports that there has been a gradual decline in his

father’s memory over the past three years. One month ago while

out on a walk he got lost, and was found by police wandering a

rough part of the neighborhood. Recently the family has taken over

financial responsibilities for him, after he wrote a check for $10,000

to his cable company. The MMSE score is 18/30, but he is

otherwise physically well.

Alzheimer disease

Alzheimer: Treatment

Neuro protection: NONE

Cholinesterase inhibitors:

» Mechanism: augment cholinergic function

» Donepezil: mild/moderate/severe dementia

» Rivastigmine, Galantamine: mild/moderate dementia

NMDA receptor antagonist

» Mechanism: antagonizes glutamate at NMDA receptor, may

improve signal transmission

» Memantine: moderate/severe dementia

Modest effects

Dementia Prevalence, US

Alzheimer’s disease 1450 (per 100K)

Frontotemporal dementia 16

Progressive supranuclear palsy 5

Prion disease < 1

Adapted from Pruisner NEJM 2001

ARS Question

A 16 month-old boy is not meeting motor milestones. He

sat late and is not yet scooting on the floor. Your exam

shows spastic legs with increased DTRs.

You make a presumptive diagnosis and ask questions

about:

A. Prematurity

B. Language delays

C. Head circumference

D. Kernicterus

E. All of the above

Cerebral Palsy: Overview

A disorder of movement and posture presenting in childhood

thought secondary to a pre-, peri-, or post-natal CNS insult

» May be associated with:

– Mental retardation

– Vision and hearing impairments

– Speech and language disorders

More common in preterm infants

» Stroke, infections, hypoxia, kernicterus

Non-progressive

Wide range of presentations

» Most common is spastic diplegia

» Quadraplegic, hemiplegic, ataxic, athetoid

END