Neurology for

the Internist

Nojan Valadi, MD
Chief of Neurology
Columbus Regional Healthcare System
Disclosures

 I have received honoraria for speaking

for Genentech and Boehringer
Ingelheim.
 Neurology Essentials

Review and updates: Not addressed:

 Stroke/TIA  Movement D/O:

 Epilepsy PD/ET
 Multiple Sclerosis  Neuropathy
 AMS / Encephalopathy  Headache
 Dementia  Myasthenia Gravis
 Sports Concussions  Muscular Dystrophies
 Bell’s Palsy  Myopathies
 Paraneoplastic Syndromes
 A 75 year-old man is brought to the ER by ambulance. During
breakfast. one hour ago, his right upper limb became weak, his right
lower face sagged, and he could only mumble short words or
phrases, but understood those speaking to him. He has hypertension
and diabetes.
Temp: 36.5 C, BP 170/100, pulse 76/min, RR 12, afebrile.

1. After verifying his history

and current medications,
what should be checked
first in the ER?
2. How would you manage his
nutrition or IV fluids?
3. Do you order a CT or MRI
brain scan?
4. Is he a candidate for IV 0% 0% 0% 0%
tPA?
1. 2. 3. 4. 9
 Acute Stroke

 A-B-C’s
 NPO, intubate for inadequate airway, ventilate if needed
 Correct hypotension, rule out acute MI or arrhythmia (a-
fib)
 Rule out hypo/hyperglycemia
 Minimize hyperglycemia by running an IV of 0.9%
normal saline initially at a TKO rate
 Use parenteral antihypertensive Tx only for sustained,
very high BP (>220/120; or >185/110 for IV tPA)
 Evaluate patient for use of IV tPA
 Decide on when to get a brain scan (which type?)
 Acute stroke syndrome:
IV tPA
 Within 4.5 hrs of stroke onset, Age>18, Not pregnant
 Measurable Neurological deficit (NIHSS >4)
 Not rapidly improving (TIA) or post-ictal
 BP under 185/110
 Normal PTT, INR<1.7, platelets >100,000
 No blood, or edema/infarct > 1/3 of MCA territory on CT
 No bleeding, recent surgery, MI, arterial puncture or LP
 Blood glucose is between 50 and 400 mg/dl
 Acute stroke syndrome:
Imaging
 CT without contrast
 quickly rules out hemorrhage, mass (tumor,
abscess) or early infarct edema
 shows strokes within 10-12 hrs, may miss lacunar
infarcts (deep small strokes)
 MRI without contrast
 highest resolution scan, but longer scanning time
 DWI (diffusion weighted imaging) detects impaired
movement of water in infarct immediately by 3 hrs
 non-invasively view arterial supply (MRA)
 contraindications: pacemaker
 Acute stroke syndrome:
anticoagulation
 Anticoagulation (heparin; warfarin: INR 2.5) is
indicated in select cases:
 Atrial fibrillation*
 Carotid or vertebral dissection**
 Cerebral sinus (venous) thrombosis**
 Hypercoagulable states*
 Anticoagulation is withheld 5-7 days or more in
presence of larger, or hemorrhagic, infarcts
 Goal of preventing future infarcts*, perhaps clot
extension**
Stroke
 Define stroke, TIA and epidemiology

 Acute Therapy:
 NINDS
 ECASS III
 Recent stroke 30 min

 Secondary Prevention:
 SPARCL
 ESPS2/ESPRIT
 MATCH + CHARISMA – Plavix + ASA
 PLAVIX trials
 CHANCE

 PFO Closure, Intracranial Stenting, EC/IC surgery

 Carotid Stenting / CEA
 Dilated Cardiomyopathy
Stroke

 800,000 each year.

 550,000 first/new strokes
Third leading cause of death
( >160,000 people/year)
The Stroke Belt
 Southeastern has the highest stroke mortality rates in the country
What can we do to treat stroke?

 What we can do depends on:

 The Type of Stroke
 The time from onset of symptoms
 Symptoms
 Type of stroke
 Location of the lesion
 Contra-lateral impairment:
• weakness / numbness
 Drooping of the mouth
 Loss of vision: one side of the
visual field or one eye
 Dysarthria (slurred speech)
 Vertigo
 Aphasia / Language Problems
 Incoordination
 Stroke

Assessment
Stroke: Subtypes

 85% Ischemic
 15% Hemorrhagic
Hemorrhagic Stroke
Ischemic Stroke
Acute Ischemic Stroke
Guidelines Overview
 Preventing Clot Propagation
 Recanalization
-IV -Endovascular -Combined Reperfusion
 Surgical Intervention
 Hospital Admission and General Acute Treatment
 Treatment of Acute Neurologic Complications
 Future Therapy for stroke and stroke care
 Stroke
Ischemic Stroke: Pathophysiology
Management Mechanisms and Workup
• Large vessel Stroke:
•Atherothromboembolism
•Distal hypoperfusion –
stenotic lesion

• Cardioembolism
•Structural cardiac lesion
•Atrial Fibrillation

•Small Vessell (lacunar)

•Penetrating arteries narrow
or occluded

• The Pump
• The Pipes
• The Blood
 Stroke Chain of Survival

 Detection – signs and symptoms

 Dispatch – Call 911 and priority EMS dispatch

 Delivery – Prompt transport and notification

 Door – Immediate ED triage

 Data – ED eval, labs, and CT imaging

 Decision – Dx and decision about therapy

 Drug – Administration of appropriate Rx/Tx

EMS Assessment

 Obtain focused hx and assessment

 Last seen normal and witness contact

 Stabilization and treatment

 Immediate transport to closest, most

appropriate facility
 Advance notice to ED receiving
EMS – History: critical elements

 Onset of symptoms  Comorbid diseases

 Hypertension
 Recent events  Diabetes mellitus
 Stroke
 Myocardial  Use of medications
infarction  Anticoagulants
 Trauma  Insulin
 Surgery  Antihypertensives
 Bleeding
EMS - Management
EMS Evaluation

 ABC’s
 Prehospital Stroke Screen:
 Los Angeles Prehospital Stroke Screen
 Miami Emergency Neurologic Deficit
 Cincinnati Stroke Scale (30-60 secs)
 FSBS
Air Medical Transport

 Extend range of therapeutic therapy

 Can deliver teams that administer tPA

 Assist in rapid delivery / transport of

patients with stroke and ICH
 Cost-effective
 Stroke Centers

 Associated with improved outcomes among

patients treated for strokes:
 Stroke Units
 Written Care Protocols
 Availability of physicians with neurological
expertise
• In hospital deaths ↓50% / 24%
 Neurosurgical volumes
 Stroke Chain of Survival –
Stroke Center Effect
 Detection – signs and symptoms
 Dispatch – Call 911 and priority EMS dispatch

 Delivery – Prompt transport and notification

 Door – Immediate ED triage

 Data – ED eval, labs, and CT imaging

 Decision – Dx and decision about therapy

 Drug – Administration of appropriate Rx/Tx

Emergent Evaluation and
Diagnosis
 Physician eval, diagnostic testing,
neuroimaging, and contact with a physician
with stroke expertise should occur
concurrently
 NINDS time goals
 All patients with suspected acute stroke
should be triaged with same priority as AMI
or serious trauma, regardless of severity
 Early implementation of stroke pathways
IV tPA for Acute Ischemic Stroke
Individual Patient Data Meta-analysis

Lancet 2004; 363: 768-74

NINDS Time Goals

Genetech, Activase Slide Deck

 Emergency Evaluation

 Immediate Evaluation:
 ABC’s
 Secondary Assessment of Neurological
deficits and comorbidities
 Identify possible strokes, and exclude mimics
 History – time of onset, and exclusion criteria
 Physical and Neurological Exam and NIHSS
 Stroke

Assessment
Stroke Mimics
 411 patients initially diagnosed
Seizure Systemic
as having stroke Infection Brain
Tumor
 333 – stroke Toxic-
 78 – other Metabolic

 Differential Dx:
 Seizures
 Conversion D/O
 Systemic Infection
 Toxic Metabolic Disease
Stroke
• Hypoglycemia
• Hypertensive Encephalopathy
 Complicated Migraine
 Emergency Diagnostics
 All patients:  Selected patients:
 Hepatic function tests
 Noncontrast CT or MRI
 Toxicology screen
 Blood glucose
 Blood alcohol level
 Serum electrolytes/renal
function tests  Pregnancy test
 ECG  ABG (if hypoxia suspected)
 Markers of cardiac ischemia  CXR (if lung disease
suspected)
 CBC
 LP (if SAH is suspected and
 PT / INR*
CT scan is negative)
 Activated partial
 EEG (if seizures are
thromboplastin time*
suspected)
 Oxygen saturation
 Early supportive treatment

 Provide optimum oxygenation, and if necessary intubation

 Avoid and aggressively treat hyperthermia
 Avoid and treat Hyperglycemia (<200)
 Avoid Dextrose containing fluids for first 24 hrs
 Avoid hypotonic fluids and cerebral edema
 Passive full ROM started during first 24 hours
 Frequent turning, skin surveillance, and dysphagia screening
( 3 oz water swallow test)
 DVT prophylaxis with SCDs, SQ heparin or LMWH
Management of BP

 Permissive HTN
 Goal <220/110
 Decrease BP 15% in first 24 hrs
 Ischemic Stroke –
 ↑ Mortality 17.9% for every 10mm <150 mm
Hg, and 3.8% for every 10mm >150 mm Hg
 ICH - <160/90, MAP<110
 Goal ICP < 20, CPP>70
Hypertension Management for
t-PA in Acute Ischemic Stroke
 For BP >185/110
 Labetalol 10 mg IV over 1-2 minutes
 may repeat same dose or double dose
q 10 minutes to a total dose of 150 mg
 If BP does not respond, initiate
nicardepine, then patient is not
candidate for tPA then infuse
 Nicardepine gtt
 Stroke
Blood Pressure Management
Management Acute Ischemic Stroke, tPA inelgible

Stroke. 2003;34:1056
 Preventing Clot Propagation

Antithrombotics
 May be beneficial by preventing clot extension or recurrent
embolization, but carries risk of hemorrhagic complications
 ASA beneficial when started within 48 hrs of patient arrival, but
degree of benefit is only slight, with NNT 77
 Clopidogrel load of 375mg has been used by some to achieve rapid
therapeutic effect in aspirin allergic patients.
 NOT a substitute for other intervention/treatments
 NOT to be given in first 24 hours as adjunct to tPA
 Clopidogrel alone or in combination with ASA is not
recommended for treatment of acute stroke
 IIb/IIIa inhibitors are not recommended
Anticoagulation

 Heparin / Warfarin / LMWH

 Number of recurrent ischemic strokes
prevented equals number of cerebral
hemorrhages caused

 Not recommended for routine stroke

Stroke

Treatment
Heparin - Exceptions

 Mildly symptomatic severe carotid stenosis

 Dissection, especially if symptomatic

 Progressive posterior circulation ischemia

 Intracardiac clot on ECHO

 Cerebral venous thrombosis*

Stroke
Recanalization:
Treatment Thrombolysis
 Intravenous:
 tPA, urokinase, streptokinase,
desmoplase
 Intra-arterial
 tPA, urokinase (pro-UK)
 IV tPA - Acute Ischemic Stroke
Inclusion Criteria*

 Age 18 through 79 years

 Clinical diagnosis of ischemic stroke causing a
measurable neurologic deficit.
 Reliably timed onset of symptoms of ischemic
stroke within 3 hours of the time to initiation of
treatment with intravenous tPA.

*Adapted from guidelines published by the American Heart Association and

American Academy of Neurology.
Stroke 1996;27:1711-1718. Neurology 1996;47:835-839
 IV tPA - Acute Ischemic Stroke
Exclusion Criteria
Absolute Higher Hemorrhage Risk
 Symptoms rapidly improving or minor  Age > 80 (unknown)
 Hemorrhage on CT scan  Signs of a very severe stroke
 glucose < 50 or > 400, Hct < 25, or  Early ischemia CT changes
platelets < 100,000
 On anticoagulant therapy
 IV medications needed to lower BP below
185/110
 Hx suggestive of SAH
 Presumed septic embolus
 Recent stroke, MI, trauma, pregnancy,
surgery
 Hx of any recent hemorrhage, AVM,
aneurysm, cancer, bleeding diathesis, or
other serious or terminal illness
 Active or new seizures
 Any other condition that the physician feels
would pose a significant hazard to the
patient if tPA therapy were initiated.
IV tPA - Acute Ischemic Stroke
Risks / Benefits*
IV tPA – 3 hour window

 NNT for 1 additional patient to have a

better outcome by 1 or more grades
on the mRS as a result of tPA
treatment is 3.1
 NNH for any ICH – 17.2
 NNH for 1 more patient to have a
worsened outcome by any degree (1
mRS grade) attributable to tPA-related
SICH is between 29.7 and 40.1.
tPA risk and benefits
ECASS III
IV tPA – 3-4.5 hour window

 NNT for 1 additional patient to have a

better outcome by 1 or more grades
on the mRS as a result of tPA
treatment is 6
 NNH for any ICH – 16
 NNH for 1 more patient to have a
worsened outcome by any degree (1
mRS grade) attributable to tPA-related
SICH is 38.
 0–90 min, n=311;
91–180 min, n=618;
181–270 min, n=801;
270–360 min, n=1046.

Values do not equal 100% because of rounding.

Time is an effect modifier

The ATLANTIS, ECASS, and NINDS rt-PA

Study Group Investigators. Lancet 2004; 363
(9411): 768-774.
 Human Nature?
onsetER= 113.783-.54981Doorndle

240
Onset-to-door (min) time

210
180

150
120
90
60
30
0

0 50 100 150 200

Door-to-needle time (min)

For each 10 minute delay in ER arrival,

treatment was 18 minutes faster!
 Recanalization

Other IV therapeutics are under investigation:

 urokinase, streptokinase, desmoplase

 Endovascular IA tPA or mechanical thrombectomy

 Combined Reperfusion
 Stenting
Surgical Intervention

 Decompressive Hemicraniectomy
 Suboccipital craniotomy
 EVD Placement
 ICP Monitoring
 Carotid Endarterectomy
Surgical Intervention

 Decompressive Hemicraniectomy
 Suboccipital craniotomy
 EVD Placement
 ICP Monitoring
 Carotid Stenting
 Carotid Endarterectomy
 Extracranial-Intracranial Bypass Surgery
 PFO Closure
Case Report VL

3/10/07 02:23
Case Report VL

3/10/07 20:48
Case Report VL

3/11/07 20:47
Case Report VL

3/12/07 06:32
Case Report VL

3/13/07 17:17
2:15 20:40 44:39 54:24 89:09
Malignant MCA Syndrome
Surgical Management
Why?
 Hospital Admission and General
Acute Treatment

 Up to 25% of patients may worsen in the first 24-28

hrs
 Goals:
 Observe for changes that might prompt
medical/surgical interventions
 Observe/treat to reduce bleeding complications after
use of rtPA
 Facilitate medical/surgical measures aimed at
improving stroke outcome
 Prevent subacute complications
 Plan for long-term therapies to prevent recurrent
stroke
 Start restoring neurologic function through rehab
 Hospital Admission and
General Acute Treatment
 Use stroke units incorporating rehab
 Use standardized order sets - evaluate risk factors
 Early mobilization can prevent subacute
complications
 Assess swallowing before starting eating/drinking
 Treat suspected PNA / UTI
 SQ anticoagulants recommended for immobilized
patients for DVT prophylaxis
 Treatment of comorbid diseases
Then What?
BB 06/20/2006
DWI Upper Division MCA
Lateral view of stenosis
Severe Left ICA Stenosis
Hemorrhagic Transformation

Hemorrhagic Infarction
HI1: Small Petechial
Infarction
HI2: more confluent
petechiae
Parenchymal Hematoma
PH1: <30% of infarct
PH2: >30% of infarct

Stroke 1999;30:2280-2284
 Stroke

Management
Workup
• MRI / MRA or CT / CTA when indicated
• Trans-thoracic Echocardiogram
• Carotid Dupplex Doppler studies of intracranial and extracranial vessels
• Transcranial Doppler studies if possible
• Evaluate comorbidities and risk factors
• Check: HgbA1c, PT/PTT/INR, CMP, CBC
• EKG and Telemetry

• When indicated:
• CTA
• Trans-esophageal Echocardiogram
• Cerebral Angiography
• Hypercoaguable workup: Protein C + S, Factor V Leiden, Antithrombin III,
Anticardiolipin ab/ Antiphospholipid ab, Homocystein
• Cancer workup if suspected
 Stroke
Risk Factor Assessment and
Assessment Secondary Prevention
 Age
 Race
 High blood pressure
 Heart disease
 Diabetes
 Smoking
 Previous stroke
 Atrial Fibrillation
 Hyperlipidemia (LDL>70)
What is TIA?

 TIA is a stroke in the waiting – a transient

focal neurologic deficit lasting <24 hours
 24 hour cut off not clinically useful
 Tissue based definition:
 Rapidly resolving neurologic symptoms,
typically lasting <1 hour, with no evidence of
infarction on MRI (DWI)
(Albers et al. New Engl J Med; 2002; 347: 1713-1716)

 40% - 60% of TIA patients have ischemic

injury on DWI
(Ay et al. Cerebrovasc Dis; 2002; 14: 177-186)
What is risk of stroke after
TIA?
Kaplan-Meier Survival-Free from Stroke
90-day prognosis after ER diagnosis of TIA (N=1707)

Highest Risk of Stroke in the first few days

Half of the strokes occurred in the first 2 days

Johnston et al. JAMA; 2000; 284: 2901-2906

Is it impending doom?
TIA risk

 Are all patients at risk for early stroke?

 Is it cost-effective to admit all patients
for TIA?
 Cost of TIA hospitalization

 Cost of Stroke

 Not all TIA’s carry the same risk

 Risk Stratification
How do we identify those TIA
patients at highest risk?
California Score:
 Predict 90 day stroke risk
 Identified 5 factors associated with high
stroke risk
 Age > 60
 Diabetes
 Duration > 10 min
 Weakness
 Speech impairment

Risk: 0% if none of the above factors

34% if had all 5 factors
Johnston et al. JAMA; 2000; 284: 2901-2906
 Stroke
Ischemic Stroke – Long Term Management
Management
and Secondary Stroke Prevention

 ACE-inhibitors vs. ARB

 HCTZ

 Statins

 Antiplatelets

 PT/OT/Speech
 Treatment of Acute Neurologic
Complications

 Cerebral ischemic edema and mass effect

 Hemorrhagic Transformation

 Seizures
Advances in Stroke Care

 Neuroimaging
 Neuroprotective Agents

 Newer thrombolytics

 Telemedicine

 Newer oral anticoagulants

 Stem Cells?
 New Goals for Treating
Stroke
 Extend therapeutic window
 Determine management of wake-up strokes

 Improve efficacy of treatment

 Decrease the complication rate of treatment,

especially if we are extending window of
treatment
 How are goals to be
acheived
 Newer IV thrombolytics are in development

 Intra-arterial thrombolytics – not new, but not yet

approved
 Intra-arterial mechanical thrombolytic devices have
been / are being approved
 Partially or totally remove occluding thrombus without
requiring any, or as much of the drugs associated with
hemorrhage
 These approaches require vascular imaging during
the initial assessment of the patient
Imaging Goals

 Evaluate for
 Presence of hemorrhage
 Presence of intravascular thrombus
that can be treated with thrombolysis
or thrombectomy
 Presence and size of irreversibly
infarcted tissue
 Presence of hypo-perfused tissue at
risk for subsequent infarction
Radiology Menu
Appetizers
Computerized Tomography
Magnetic Resonance Imaging Chef’s Specials
CT Angiography
Carotid Duplex Ultrasound
Transcranial Doppler Ultrasound

Entrees
CTA / CTP
DWI / MRP / MRA
T2*MR / GRE
Cerebral Angiography

Dessert
SPECT / XeCT
CTA
CTP
Additional Diagnostic Testing
and Therapies Help us:
 Identify stroke core and possibly
salvage penumbra
 Be more aggressive in stroke
management
 Or decide when prognosis is poor and
aggressive management needs to be
avoided
 Example: Wake up stroke
Wake Up Stroke
 The Future of Stroke:
Other options
 Hypothermia
 Neuroprotective Agents:
 Minocycline
 NMDA antagonists
 NXY-059 (Cerovive)
 Magnesium
 Ebselen
 Erythropoietin, IFN-β, NO-synthase inhibitors
 Telestroke
Expanding the role of EMS

 Identification of an effective
neuroprotective therapy
 Implementation of Hypothermia
Telestroke
Telestroke

 REACH MCG  RUN-FC – France

 UPMC  TRUST-TPA –
 STRokE DOC France
 CO-DOC  TELESTROKE –
 STARR Network Finland
 MUSC Reach  Telestroke GSTT –
UK/London
Telemedicine by iPhone
“Give the Juice!”
 Epilepsy

 New Classification 2010 by ILAE:

 To provide a common international terminology
and classification
 For clinical (treatment) purposes
2005-2009 Commission Report,
Epilepsia 2010;51:676-685
 Main changes, modifications
 Language and structure for organizing epilepsies
 Generalized versus Focal Seizures
 “Etiology”
 Diagnostic specificity
 New recommended terms
 Organization
 NO changes to electroclinical syndromes
 A diagnosis can be made as previously
eg Lennox-Gastaut syndrome, childhood absence
epilepsy
Focal reconceptualized

 For seizures:
 Focal epileptic seizures are
conceptualized as originating
within networks limited to one
hemisphere. These may be
discretely localized or more
widely distributed.…
 Focal seizures
Blume et al, Epilepsia 2001

 Without impairment of consciousness or awareness

 Previous term: simple partial
 With observable motor or autonomic components
• eg. focal clonic, autonomic, hemiconvulsive
 With subjective sensory or psychic phenomena
• Aura - specific types

 Where alteration of cognition is major feature

 Previous term: complex partial
 Dyscognitive
 Focal seizures
Blume et al, Epilepsia 2001

 Evolving to bilateral, convulsive seizure

 Previous terms: partial seizure secondarily
generalized;
secondarily generalized tonic-clonic seizure
 With tonic, clonic or tonic and clonic
components
Generalized - reconceptualized

 For seizures
 Generalized epileptic seizures
are conceptualized as originating
at some point within, and rapidly
engaging, bilaterally distributed
networks. …can include cortical
and subcortical structures, but
not necessarily include the entire
cortex.
 Generalized Seizures
Tonic-clonic (in any combination)
Absence
- Typical
- Atypical
- Absence with special features
Myoclonic absence
Eyelid myoclonia
Myoclonic
- Myoclonic Seizure types thought to
- Myoclonic atonic occur within and result from
- Myoclonic tonic rapid engagement of
Clonic bilaterally distributed systems
Tonic
Atonic
 Recommended terminology
for etiology
Use terms which mean what they
say:
 Genetic

 Structural-Metabolic

 Unknown

Previously used terms denoting old concepts:

Idiopathic, cryptogenic, symptomatic
Genetic

 Concept: the epilepsy is the direct result of a

known or inferred genetic defect(s). Seizures
are the core symptom of the disorder.

 Evidence: Specific molecular genetic studies

(well replicated) or evidence from appropriately
designed family studies.

 Genetic does not exclude the possibility of

environmental factors contributing
 Structural-Metabolic

 Concept: There is a distinct other

structural or metabolic condition or
disease present.
 eg. Tuberous sclerosis

 Evidence: Must have demonstrated a

substantially increased risk of developing
epilepsy in association with the condition.
Unknown

 Concept: The nature of the underlying

cause is as yet unknown.
 Epilepsy eval & management
 Neuroimaging
 CT imaging in emergencies
 Brain MRI c/s contrast

 EEG and Epilepsy Monitoring

 Try to categorize epilepsy syndromes

 Antiepileptic Therapy

 Epilepsy Surgery

 Ketogenic Diet
Multiple Sclerosis

 New Drug Therapies

Altered Mental Status

 Differential Diagnosis
 Initial Approach and Diagnostic
Workup / Algorithm
 STAGES OF CONSCIOUSNESS

 Conscious: Awareness of self and surroundings.

 Clouding of Consciousness: Reduced attention span
with irritability.
 Confusion: Mild lowering of consciousness.
 Lethargy : Drowsy but arousable.
 Obtundation: Drowsy, slow reaction, gives appropriate
answers, back asleep on leaving alone.
 Stupor: Roused by vigorous repetitive stimuli, moans
without proper answering.
 Light coma: Unarousable, disorganized primitive
motor responses.
 Deep Coma: Absence of response to most painful
stimuli.
Dementia

 Overview and Breakdown

 Workup and evaluation

 MCI and Alzheimer’s Disease

 Management and Treatment

Dementia
Dementia by Pathological Basis
 1 Neurodegenerative D/O’s:
 Alzheimer’s Dementia
 Lewy Body D/O’s:
• Dementia with Lewy Bodies (DLB)
• Parkinson Disease dementia (PDD)
 Frontotemporal Dementias – bvFTD, PPA/SD
 Progressive Supranuclear Palsy (PSP)
 Corticobasal degeneration (CBD)
 Huntington’s Disease (HD)
 Creutzfeldt-Jakob Disease (CJD)
 Vascular Dementias:
 multi-infarct, Binswanger, CADASIL
 Inflammatory:
 MS, CNS Vasculitis
 Infectious:
 Neurosyphilis, Lyme, HIV
 Neoplastic:
 tumors, carcinomatous meningits, PNS
 Other/Physical Dementias:
 NPH, brain trauma (dementia pugilistica)
Dementia by Protein Pathology
 β-Amyloidopathy – Alzheimer’s Disease
 α-Synucleinopathy – Lewy body disorders (DLB), PDD
 Tauopathy – FTD, Pick’s Disease, PSP, CBD
 TDP-43 proteinopathy – FTD-U
 Prionopathy – CJD, FFI, GSS, vCJD
 Dementia Evaluation and Workup
 Detailed hx of time course,
functional impairment
 Interview, Family Interview
 Physical exam, Orthostatics,
Neuro exam
 Dementia Evaluation
 Depression assessment
 Neuropsych evaluation
 Lab Tests:
 CBC, CMP, TSH, drug levels
(dig), B12, VDRL/RPR
 HIV, Lyme
 Genetics, Heavy Metal, Cu
 Therapeutic / Diagnostic:
 Remove possible offending
agents
 Treat depression
 MRI brain
 EEG
 SPECT / FDG-PET
 Lumbar Puncture
Diagnostic Tools

 Folstein MMSE
 Montreal Cognitive Assessment (MoCA)
 Clinical Dementia Rating (CDR)
 Blessed Information-Memory-Concentration
Test (BIMCT)
 Disability Assessment for Dementia (DAD)
 Neuropsychologic battery
 Trails B, Stroop, CVLT
Treatment - Interdisciplenary

 Patient Function –PT/OT

 Family and Caregiver Support

 Medical Care

 Psychosocial – driving, stimulation,

depression screening and treatment
 Patient Nutrition

 Advanced Directive Planning

 AD in the US (2010-
Alzheimer’s 2050) estimated using
the 2010 census
Dementia
US mortality, education,
and new US Census
Bureau estimates of
current and future
population

Projection: 13.8 million,

with 7.0 million aged 85
years or older, by 2050

Hebert et al, Neurology 2013

Earlier dx and treatment: increased attention
to the continuum from normal aging to AD and
recognition of a transitional zone
 Mild Cognitive Impairment
 Transitional state
 (1) concern regarding a change in cognition
 (2) impairment in one or more cognitive domains that is greater
than one would expect for the patient’s age or education
 (3) preservation of independence in functional activities.
 Affects ~ 15% of older adults
 Increasing prevalence with age
 Several subtypes
 “Amnestic MCI”: memory impairment with minimal to no other
cognitive loss
 Everyday function largely preserved
 Often progressive; some stabilize; some improve
 May be prodromal to AD or other specific dementias
 Presence of biomarkers meets criteria for very mild AD

 Cholinesterase Inhibitors for MCI

 2yr galantamine, 4yr rivastigmine, 3+yr donepezil trials failed
 MCI Clinical Outcome
Convert to probable AD at an increased rate

Normal Elderly MCI

1-2% per year

10-15% per year

AD

AD
Biomarker changes during
the progression of AD

Aisen et al, 2011

 Diagnosis-Independent Alzheimer Disease
Biomarker Signature in Cognitively Normal
Elderly People De Meyer et al, 2010

•Correctly classified 90% of AD

•Unexpected presence of the AD signature in more than 1/3 of NC suggests
that AD pathology is active and detectable earlier than envisioned
PET in vivo imaging of fibrillar
amyloid ß (Aß) plaques
 Most validated marker is PiB—
first labeled with 11C but current
efforts with 18F-labelled tracers
 florbetapir (AV-45) Amyvin™ just
approved by FDA
 Increased cortical PIB closely
reflects distribution of Aß fibrillar
plaques
 Less useful for progression
 +PIB in 10-30% of NC (poor
specificity or early harbinger?)
Doraiswamy et al, 2012
Pittsburgh Compound B
AD - Diagnostic Categorization
 Pharmacotherapy for AD
Cholinergic Deficit Hypothesis
 ACh precursors  Ach
 Cholinergic agonists
 AChE inhibitors
 Tacrine – qid dosing, hepatotoxic
 Donepezil – long acting: 10mg / 23mg
 Rivastigmine – 1.5 - 6mg bid, patch
 Galantamine – 8mg, 16mg bid
• AE’s: nausea, diarrhea, vomiting, anorexia, weight loss, cramping
• Caution: ↑GERD, GI Bleed, bradycardia
 Memantine – NMDA-R-antagonist –
 mod-severe AD 5mg, 10mg bid, ER?!
 AE’s: HA, dizziness, confusion, somnolence, hallucination
 Cerebrolysin, Ginko Bilboa, CoQ100, Vitamin E, Fish Oil
Concussion in Sports
Concussions in Sports
 Concussion is recognized as a clinical syndrome of
biomechanically induced alteration of brain function,
typically affecting memory and orientation, which may
involve loss of consciousness (LOC).

 Estimates of sports-related mild traumatic brain injury

(mTBI) range from 1.6–3.8 million affected individuals
annually in the United States, many of whom do not
obtain immediate medical attention.

 Variability in care provider experience and training,

coupled with an explosion of published reports related
to sports concussion and mTBI, has led to some
uncertainty and inconsistency in the management of
these injuries.
 Clinical Questions:
1. What factors ↑/↓ concussion risk?
2. Suspected concussion:
(a) How to identify those with concussion?
(b) How to identify those at increased risk for severe or
prolonged early impairments, neurologic catastrophe,
or chronic neurobehavioral impairment?
3. Concussion: What clinical factors are useful in identifying
those at increased risk for severe / prolonged early
postconcussion impairments, neurologic catastrophe,
recurrent concussions, or chronic neurobehavioral
impairment?
4. What interventions enhance recovery, reduce the risk
of recurrent concussion, or diminish long-term
sequelae?
 Recommendations:
Preparticipation Counseling
 School-based professionals should be educated to
understand the risks of experiencing a concussion
so that they may provide accurate information to
parents and athletes
 Athletes and families should be informed of
evidence concerning the concussion risk factors as
listed below. Accurate information regarding
concussion risks also should be disseminated to
school systems and sports authorities
 Recommendations: Preparticipation
Counseling, cont.
Risks for concussion
 Type of sport. Strong evidence that concussion risk is greatest in
football, rugby, hockey, and soccer.
 Gender. In soccer and basketball there is strong evidence that
concussion risk appears to be greater for female athletes.
 Prior concussion. Hx of concussion/mTBI is a risk factor for
concussions. A recurrent concussion is more likely to occur within
10 days after a prior concussion.
 Equipment. Helmet use effectively reduces, but does not eliminate,
risk of concussion and more-serious TBI in hockey and rugby
(inferred for football). No evidence to demonstrate efficacy of soft
head protectors or different helmet types. Mouth guards protect
against dental injuries but not against concussions.
 Age or competition level. Insufficient evidence to make any
recommendation as to whether age or competition level affects risk.
 Position. Insufficient data as to whether position increases
concussion risk in most major team sports.
 Recommendations:
Suspected Concussion
 LHCPs should be instructed in the proper administration of
standardized validated sideline assessment tools
 Tools should be utilized by sideline LHCPs and the results made
available to clinical LHCPs who will be evaluating the injured athlete
 Team personnel (e.g., coaching, athletic training staff, sideline
LHCPs) should immediately remove from play any athlete suspected
of having sustained a concussion, to minimize risk of further injury
 Team personnel should not permit athlete to return to play until
assessed by an experienced LHCP with training in diagnosis and
management of concussion and recognition of more-severe TBI
 Baseline concussion assessment tool scores can help better
interpret postinjury scores, especially in younger athletes, those with
prior concussions, or those with preexisting learning disabilities or
ADHD.
Neuroimaging

 CT imaging should be obtained to rule out

more serious TBI such as an intracranial
hemorrhage in athletes who have:
 Loss of consciousness
 Posttraumatic amnesia
 Persistent AMS (GCS <15)
 Focal neurologic deficit
 Evidence of skull fracture on examination
 Signs of clinical deterioration
 Diagnosed Concussion –
Return to Play
 Prohibited from return to play/practice (contact-risk activity) until an LHCP
has judged that the concussion has resolved.
 Prohibited from return to play/practice (contact-risk activity) until the athlete
is asymptomatic off medication.
 High school age or younger athletes with concussion should be managed
more conservatively regarding return to play (RTP) than older athletes.
 Neurocognitive testing or other tools may be used to assist in determining
concussion resolution. This may include but is not limited to resolution of
symptoms as determined by standardized checklists and return to age-
matched normative values or an individual’s preinjury baseline
performance on validated neurocognitive testing.
 Individualized graded plans for return to physical and cognitive activity may
be developed, guided by a carefully monitored, clinically based approach
to minimize exacerbation of early postconcussive impairments.
 LHCPs might provide “cognitive restructuring” counseling to all athletes
with concussion to shorten the duration of subjective symptoms and
diminish the likelihood of development of chronic postconcussion
syndrome
 Concussions – Retirement
from Play after multiple
 Athletes with a history of multiple concussions and subjective
persistent neurobehavioral impairments should have
neurologic and neuropsychological assessment to help guide
retirement-from-play decisions
 Athletes with a history of multiple concussions and subjective
persistent neurobehavioral impairment should be counseled
about the risk factors for developing permanent or lasting
neurobehavioral or cognitive impairments.
 Athletes who show objective evidence for chronic/persistent
neurologic/cognitive deficits (such as seen on formal
neuropsychological testing) should retire from the contact
sport to minimize risk for and severity of chronic
neurobehavioral impairments
 Bell Palsy
 An idiopathic unilateral facial nerve (CN VII)
paralysis, usually self-limiting
 Drooling
 Eye problems, such as excessive tearing or a
dry eye
 Loss of taste (anterior 2/3) – chorda tympani
 Hyperacousis – nerve to stapedius

 No involvement of other CN’s

 No other motor or sensory involvement
Bell Palsy - Etiology

 Viral: HSV, EBV, VZV

 Lyme Disease, Trauma, Tumor,
Meningitis, Stroke, Sarcoidosis,
Brucellosis, HIV
 Emotional, Environmental (cold), or
physical stressors (Pregnancy)
 Bell Palsy

 The disease is common, with an annual incidence of

20 per 100,000
 Up to 30% of patients fail to recover facial function
completely.
 Imaging indicated when not a classic presentation
 Treatment:
 Facial Exercises
 Eye Care – lubricant, patch qHS, frequent closure
 Mouth Care - frequent brushing and flossing
 Bell Palsy Treatment:
Steroids and Antivirals
 For patients with new-onset Bell palsy, steroids are highly likely
to be effective and should be offered to increase the probability
of recovery of facial nerve function (2 Class I studies, Level A)
(risk difference 12.8%–15%).
 For patients with new-onset Bell palsy, antiviral agents
(acyclovir, famciclovir, valacyclovir) in combination with steroids
do not increase the probability of facial functional recovery by
>7%. Because of the possibility of a modest increase in
recovery, patients might be offered antivirals (in addition to
steroids) (Level C).
 Patients offered antivirals should be counseled that a benefit
from antivirals has not been established, and, if there is a
benefit, it is likely that it is modest at best
Bell Palsy – Therapy and
Options
 Physiotherapy and nerve stimulation
 Accupuncture

 Smile reconstructive surgery

 Eye Lid surgery

Paraneoplastic Syndromes

Dalmau and Rosenfeld, Paraneoplastic syndromes of the CNS,

Lancet Neurol. 2008 April ; 7(4): 327–340.
Concussion References
1. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology
and impact of traumatic brain injury: a brief overview. J Head
Trauma Rehabil 2006;21:375–378.
2. American Academy of Neurology. Practice Parameter: The
management of concussion in sports (summary statement).
Report of the Quality Standards Subcommittee. Neurology
1997;48;581–585.
3. American Academy of Neurology. 2004. Clinical Practice
Guideline Process Manual, 2004 Ed. St. Paul, MN: The
American Academy of Neurology.
4. American Academy of Neurology. 2011. Clinical Practice
Guideline Process Manual, 2011 Ed. St. Paul, MN: The
American Academy of Neurology.
5. Guyatt GH, Oxman AD, Schunemann HJ, Tugwell P,
Knottnerus A. GRADE guidelines: A new series of articles in
the Journal of Clinical Epidemiology. J Clin Epidemiol
2011;64:380–382.
 References
 Bell Palsy:
 Gary S. Gronseth and Remia Paduga, Evidence-based guideline update:
Steroids and antivirals for Bell palsy: Report of the Guideline
Development Subcommittee of the American Academy of Neurology,
Neurology published online November 7, 2012.
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