Post on 27-Mar-2018
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.
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