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:

Stroke/TIA

Epilepsy

Multiple Sclerosis

AMS / Encephalopathy

Dementia

Sports Concussions

Bell’s Palsy

Paraneoplastic Syndromes

Not addressed:

Movement D/O:

PD/ET

Neuropathy

Headache

Myasthenia Gravis

Muscular Dystrophies

Myopathies

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 tPA?

1. 2. 3. 4.

0% 0%0%0%

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: Subtypes

85% Ischemic

15% Hemorrhagic

Assessment

Stroke

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

Ischemic Stroke: Pathophysiology

Mechanisms and Workup

• The Pump

• The Pipes

• The Blood

Management

Stroke

• Large vessel Stroke:

•Atherothromboembolism

•Distal hypoperfusion –

stenotic lesion

• Cardioembolism

•Structural cardiac lesion

•Atrial Fibrillation

•Small Vessell (lacunar)

•Penetrating arteries narrow

or occluded

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

Recent events

Stroke

Myocardial

infarction

Trauma

Surgery

Bleeding

Comorbid diseases

Hypertension

Diabetes mellitus

Use of medications

Anticoagulants

Insulin

Antihypertensives

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 Mimics

411 patients initially diagnosed

as having stroke

333 – stroke

78 – other

Differential Dx:

Seizures

Conversion D/O

Systemic Infection

Toxic Metabolic Disease

• Hypoglycemia

• Hypertensive Encephalopathy

Complicated Migraine

Stroke

Toxic-

Metabolic

Seizure Systemic

Infection Brain

Tumor

Assessment

Stroke

Emergency Diagnostics

All patients:

Noncontrast CT or MRI

Blood glucose

Serum electrolytes/renal

function tests

ECG

Markers of cardiac ischemia

CBC

PT / INR*

Activated partial

thromboplastin time*

Oxygen saturation

Selected patients:

Hepatic function tests

Toxicology screen

Blood alcohol level

Pregnancy test

ABG (if hypoxia suspected)

CXR (if lung disease

suspected)

LP (if SAH is suspected and

CT scan is negative)

EEG (if seizures are

suspected)

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

Blood Pressure Management Acute Ischemic Stroke, tPA inelgible

Stroke. 2003;34:1056

Management

Stroke

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

Heparin - Exceptions

Mildly symptomatic severe carotid stenosis

Dissection, especially if symptomatic

Progressive posterior circulation ischemia

Intracardiac clot on ECHO

Cerebral venous thrombosis*

Treatment

Stroke

Recanalization:

Thrombolysis

Intravenous:

tPA, urokinase, streptokinase,

desmoplase

Intra-arterial

tPA, urokinase (pro-UK)

Treatment

Stroke

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

Symptoms rapidly improving or minor

Hemorrhage on CT scan

glucose < 50 or > 400, Hct < 25, or 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.

Higher Hemorrhage Risk

Age > 80 (unknown)

Signs of a very severe stroke

Early ischemia CT changes

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.

The ATLANTIS, ECASS, and NINDS rt-PA

Study Group Investigators. Lancet 2004; 363

(9411): 768-774.

Time is an effect modifier

Human Nature? onsetER= 113.783-.54981Doorndle

Onset-

to-d

oor

(min

) tim

e

Door-to-needle time (min)0 50 100 150 200

0

30

60

90

120

150

180

210

240

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

Stroke 1999;30:2280-2284

Hemorrhagic Infarction

HI1: Small Petechial

Infarction

HI2: more confluent

petechiae

Parenchymal Hematoma

PH1: <30% of infarct

PH2: >30% of infarct

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

Management

Stroke

Risk Factor Assessment and

Secondary Prevention

Age

Race

High blood pressure

Heart disease

Diabetes

Smoking

Previous stroke

Atrial Fibrillation

Hyperlipidemia (LDL>70)

Assessment

Stroke

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)

40% - 60% of TIA patients have ischemic

injury on DWI

(Albers et al. New Engl J Med; 2002; 347: 1713-1716)

(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

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

Half of the strokes occurred in the first 2 days

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

Ischemic Stroke – Long Term Management

and Secondary Stroke Prevention

ACE-inhibitors vs. ARB

HCTZ

Statins

Antiplatelets

PT/OT/Speech

Management

Stroke

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

CT Angiography

Carotid Duplex Ultrasound

Transcranial Doppler Ultrasound

Entrees CTA / CTP

DWI / MRP / MRA

T2*MR / GRE

Cerebral Angiography

Dessert SPECT / XeCT

Chef’s Specials

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

UPMC

STRokE DOC

CO-DOC

STARR Network

MUSC Reach

RUN-FC – France

TRUST-TPA –

France

TELESTROKE –

Finland

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

A diagnosis is not the same as a classification

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 - Myoclonic atonic - Myoclonic tonic

Clonic Tonic Atonic

Seizure types thought to

occur within and result from

rapid engagement of

bilaterally distributed systems

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

Alzheimer’s

Dementia

AD in the US (2010-2050) estimated using the 2010 census

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

1-2% per year 10-15% per year

Normal Elderly MCI

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.

Responses remain anonymous!

1. Poor

2. Fair

3. Average

4. Good

5. Excellent

1. 2. 3. 4. 5.

0% 0% 0%0%0%

10

1. Poor

2. Fair

3. Average

4. Good

5. Excellent

Poor

Fair

Aver

age

Good

Excel

lent

0% 0% 0%0%0%

10

0%

0%

0%

10

1. Yes

2. No

3. N/A

1. Poor

2. Fair

3. Average

4. Good

5. Excellent

1. 2. 3. 4. 5.

0% 0% 0%0%0%

10

0%

0%

10

1. Yes

2. No