Transcript A Stoke from the Bishop`s Cap

A Stroke from
the
Bishop’s Cap
Thomas A. Showalter, III, DO
Resident, Internal Medicine
CPC
August 10th, 2007
The Case
CC: ‘my right arm and leg are weak’
HPI:
22 year old male
5 weeks prior
Right arm and leg numbness and weakness
Mild dysarthria
Night prior - 10-12 beers, smoked pot, taken 2 vicodin
Presented to outside ER
Treated with IVF for dehydration and sent home.
The Case continued…
Same day after ER discharge
Developed twitching of right side of face and arm
Returned to ER
CT head negative
All symptoms resolved with 4-5 hours
Except for mild residual right facial numbness
2 days later
Reported mild dysarthria
Right facial droop and right facial numbness
Referred to Neurology at S&W
The Case continued…
HPI:
Seen 4 weeks later
Denied paresthesias, paresis, involuntary
movements or dysarthria.
Complained of mild headache and sonophobia.
PMHx:
Substance abuse
Spontaneous Pneumothorax at age 19
One episode, 1 year ago with right sided numbness,
but no paresis.
The Case continued…
PSH:
Appendectomy as child
Chest tube placement for Spontaneous PTx
Meds:
none
Allergies:
none
The Case continued…
Social Hx:
Construction worker
+Tobacco. +THC weekly
EtoH daily with binges on weekend
Methamphetamine once monthly
No IV drug abuse
Family Hx:
Parents healthy. Sister unknown stomach disorder.
No early stroke, hypercoagulable disorders, seizures
or malignancy.
The Case continued…
Review of Systems:
No fevers, weight loss, night sweats.
No arthralgias or myalgias. No rashes.
No abdominal pain. No chest pain.
No dyspnea. No palpitations.
No dysphagia. No melena/hematochezia.
No hematuria/dysuria.
No syncope. No easy bruising or bleeding.
Physical Exam
VS: T 95.7 P 70 R 12 BP 105/62
Gen: thin male, NAD, healthy appearing.
HEENT: normal
Neck: normal
Heart: normal
Chest: normal
Extr: normal
Neuro: normal
Skin: normal
The Data
13.6
8.7
Diff:
 Neut
 Lymph
 Mono
39.0
54%
27%
7%
273
138
100
10
4.3
23
0.8
LFTs Normal
Coags Normal
The Data continued…
CXR:
normal
MRI Brain:
chronic left MCA
infarct and several
chronic tiny cerebellar
infarcts
EKG:
MRA Head/Neck:
marked sinus
normal Circle of Willis
bradycardia with sinus
and great vessels of
arrhythmia, early
head and neck
repolarization
The Data continued…
Additional lab obtained…
ESR 10
Total Cholesterol 138
Anticardiolipin IgG and IgM – negative
Lupus anticoagulant – negative
Echocardiography:
normal LV function, 1.7 cm x 1.2 cm mass on
the atrial side of the anterior leaflet of mitral
valve possibly attached by a stalk
Hospital Course


BC for bacterial and fungal organisms done.
Cardiac MRI:
– mass on atrial surface of mitral valve
– with no clear stalk
– Impression: mass consistent with either tumor or
vegetation from infective endocarditis, but more likely
endocarditis based on the location and that no stalk was
seen on the MRI.

A diagnostic procedure was performed.
I.
The Case
II. Problem List
III. DDx of Stroke in a Young Person
IV. DDx of a Left Atrial Mass
V.
Conclusions
The Problem List
Multiple chronic strokes
– Left MCA distribution infarct
– Multiple tiny cerebellar infarcts
Left Atrial Mass (with or without a stalk)
Substance abuse
Headache with sonophobia
History of…
Right arm and leg numbness and weakness
Dysarthria and facial numbness and weakness
Muscle spasm of right face and right arm
Stroke in Young Adults
Usually defined as age < 45 years
 Worldwide incidence 9-11 per 100,000 [4]
 Northern Manhattan Stroke Study, Stroke 2002

– Multiethnic population of 210,000 residents
– In a 4-yr period, 74 cases of young stroke out of 924
incident first ever strokes (8%)
– Higher incidence rates in Blacks and Hispanics
compared to Whites
Stroke in Young Adults

Italian epidemiological review by Gandolfo and
Conti Neurological Science 2003
– Western European Countries, less than 5% of all
strokes occurred in patients < 45 years of age (yoa).
– Developing countries had 20-30% of strokes < 45 yoa
– United States, 8-10% of strokes in patients < 45 yoa

Estimated lifetime cost of stroke $103,576 for US
patients. 2-4 times that is young adult due to
longer period of lost productivity [4]
DDx of Stroke in Young Adults
1.
Subarachnoid Hemorrhage
2.
Intracerebral Hemorrhage
3.
Cerebral Ischemic Infarcts
Cerebral Ischemic Infarct


3% of all cerebral infarcts occur between 1545 years of age [3]
Etiologies
1. Atherosclerotic
2. Nonatherosclerotic
3. Cardioembolic


Ages 15-35, cardioembolic and
nonatherosclerotic causes predominate
After age 35, traditional atherosclerotic stroke
risk factors become prime determinants of
stroke
Atherosclerotic causes

Traditional risk factors:
– Hypertension, Smoking, Hyperlipidemia, Diabetes Mellitus
– Age 15-30 -> 2%
– Age 30-45 -> 30-35%

Homocystinuria – premature large vessels
disease

Carotid Atheroma formation due to local
radiation for laryngeal tumors

Cranial radiation produces a radiation
vasculopathy
The Myriad of
Nonatherosclerotic causes

Dissection

Genetic Disorders

Illicit drug use

Inborn Errors of Metabolism

Infection

Moyamoya

Prothrombotic States

Hyperestrogenemic States

Migraine

Vasculitis

Sickle Cell Disease

Arteritis due to Neoplasms
The Myriad of
Nonatherosclerotic causes

Dissection

Genetic Disorders

Illicit drug use

Inborn Errors of Metabolism

Infection

Moyamoya

Prothrombotic States

Hyperestrogenemic States

Migraine

Vasculitis

Sickle Cell Disease

Arteritis due to Neoplasms
Cardioembolic causes









20-30% of young adult
Valvular heart disease
Mitral valve prolapse
Prosthetic heart valves
Rheumatic heart disease
Acute Myocardial
Infarction
Left ventricular dyskinesia
Spontaneous echo
contrast
Left ventricular aneurysm









Left atrial aneurysm
Dilated Cardiomyopathy
Atrial Septal defect
Patent Foreman Ovale
Atrial Fibrillation
(Left Atrial Thrombus)
Bacterial endocarditis
Libmann Sachs
endocarditis
Marantic endocarditis
Tumor
The Problem List
Multiple chronic strokes
– Left MCA distribution infarct
– Multiple tiny cerebellar infarcts
Left Atrial Mass (with or without a stalk)
Substance abuse
Headache with sonophobia
History of…
Right arm and leg numbness and weakness
Dysarthria and facial numbness and weakness
Muscle spasm of right face and right arm
DDx of Left Atrial Mass

Endocarditis
– Nonbacterial Thrombotic Endocarditis
(Marantic)
– Libmann Sachs endocarditis
– Bacterial endocarditis
Left Atrial Thrombus
 Tumor

– Metastatic
– Primary, Benign or Malignant
Marantic Endocardits
Nonbacterial Thrombotic Endocarditis
“Sterile” Vegetations
 Microscopic to large aggregates of platelets and fibrin on
heart valves (usually aortic or mitral)
 27% of ischemic stroke in patients with cancer [9]
 Complicates many nonmalignant wasting illnesses, i.e.
AIDS
 Continuum with Trousseau’s Syndrome
 Predisposed by prothrombotic states, valvular endothelial
disruption and underlying valve disease

Libmann Sachs Endocarditis
Verrucous Endocarditis





Accumulation of immune complexes, mononuclear cells, hematoxylin
bodies, fibrin and platelet thrombi
Occurs in minority of Systemic Lupus Erythematosis
Fewer seen in Antiphospholipid Antibody Syndrome
Most commonly the Aortic or Mitral valve, although the Tricuspid
may be affected
Typically asymptomatic, but if large enough may embolize
Infective Endocarditis





Microbial infection of the endocardial surface
Vegetation – platelets, fibrin, microorganisms
and inflammatory cells
In the U.S., incidence of community-acquired
native-valve endocarditis = 1.7 to 6.2 cases per
100,000 person-years
Median age = 47-69 years
Injection drug users
– Higher incidence in younger persons
– Incidence 150 to 2000 per 100,000 person-years
Clinical Manifestations of Infective Endocarditis
Fever – most common sign and symptom
 Subacute – anorexia, weight loss, malaise and night
sweats
 Heart murmur – new or changing, but usually
preexisting
 Petechiae on skin, conjunctivae or oral mucosa
 Splenomegaly
 Congestive heart failure
 Splinter hemorrhages, Osler’s nodes, Janeway’s lesions
 Neurologic complications:

– 20-40% will have neurologic complication!
– 65% of embolic phenomena involve the CNS
The Duke Criteria




Introduced by group at Duke University in 1994,
modified in 2000
Specificity 99%
NPV > 92%
Criteria integrated
– Factors predisposing patients to the development of endocarditis
– Blood culture isolate and persistence of bacteremia
– Echocardiographic findings
 TTE – Specificity 98%, Sensitivity 60-70%
 TEE – Specificity 85-98%, Sensitivity 75-95%, NPV > 92%
– Other clinical and laboratory findings

Only 5-7% of patients have sterile blood cultures*
Left Atrial Thrombus
45% of cardiogenic thromboemboli
13% patients with atrial fibrillation
33% patients with rheumatic mitral stenosis
May complicate primary or metastatic tumors
Regional or global wall motion abnormalities
increase risk
 Associated with the left atrial appendage
 Generally, attached to posterior left atrial wall by
a broad base, therefore immobile
 Can be pedunculated and mobile





Left Atrial Thrombus

Omran in 2000
– Sinus Rhythm
– 1% incidence of left atrial thrombus in patients with recent
neurologic deficit
– 6/583 patients (1%) had left atrial appendage
thrombus
– 3 mitral stenosis, 1 aortic stenosis, 1 dilated
cardiomyopathy, 1 coronary artery disease
Left atrial thrombi are an infrequent cause of
thromboembolism in patients in sinus rhythm and are
associated with valvular disease and atrial dysfunction.
*Left atrial thrombus is associated with left atrial tumors…
Cardiac Tumors
Metastatic

–
–
–
20-40 times more common than primary tumors
Pericardium > Myocardium > Endocardium
10-20% patients with disseminated cancer will have
involvement of heart or pericardium
Primary

–
–
–
0.17-0.19% incidence in unselected autopsy series
1 in 500 cardiac surgical cases, with exception of myxoma
Benign -> 75%


–
Myxomas comprise 50% of benign
Myxomas comprise 80-90% of left atrial primary tumors
Malignant -> 25%

Sarcomas comprise 75% of malignant
Frequency of Cardiac Tumors
Atlas of Heart Disease: Cardiopulmonary Diseases and Cardiac Tumors. Vol III. 1995. Philadelphia: Mosby.
Relative Incidence of Primary Malignant Tumors of the Heart
Malignant Tumors
Adults (%)
Children (%)
Angiosarcoma
28
6
Rhabdomyosarcoma
11
41
Fibrosarcoma
8
18
Malignant fibrous histiocytoma
6
6
Osteosarcoma
7
0
Leimyosarcoma
5
0
Myxosarcoma
3
6
Other sarcomas*
14
12
Undifferentiated sarcoma
12
12
Lymphoma
6
0
*Other sarcomas include liposarcomas, synovial and neurogenic sarcomas
Adapted from Braunwald’s Heart Disease 7th edition
Malignant Cardiac Tumors
25% of all cardiac tumors are invasive or metastatic
 95% of these are Sarcomas
(2nd to myxoma in overall frequency)
 5% are Lymphomas
 Sarcomas derive from mesenchyme, therefore have a
wide variety of morphological types
 Mutations in K-ras were seen in most cardiac sarcomas
 Any age, but most common third and fifth decades
 Except for rhabdomyosarcomas and fibrosarcomas,
distinctly unusual in infants and children

Malignant Cardiac Tumors
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

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
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25-50% patients will have metastatic disease at time of
diagnosis
Most frequent: lungs, thoracic lymph nodes,
mediastinum and vertebral column
Less frequent: liver, kidneys, adrenals, pancreas, bone,
spleen and bowel
Transesophageal Echocardiography recommended for
diagnosis
CT and MRI show degree of tumor infiltration
Often endomyocardial or open biopsy needed
Treatment of Cardiac Sarcomas



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Sarcomas proliferate rapidly
Death due to widespread infiltration of the myocardium,
obstruction of flow within the heart or distant metastasis
with a few weeks to 2 years after onset of symptoms
Median survival 6-12 months
Surgical excision considered to achieve local control and
relieve symptoms
Complete excision - median survival 12-24 months
– Possible in less than 50% of patients

Incomplete excision – median survival 3-10 months
Treatment of Cardiac Sarcomas

Autotransplantation
– Cardiac explantation, ex vivo tumor resection, cardiac
reconstruction and reimplantation

Chemotherapeutic benefits are unclear
– Data support anthracycline-based regimens is soft tissue
sarcomas
– Adjuvant chemotherapy and/or radiation therapy usually
recommended

Orthotopic heart transplantation in patients with locally
unresectable disease without evidence of metastasis
– 66% still die within 1 year either of locally recurrent or
metastatic disease
Angiosarcoma
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




30% of primary cardiac sarcomas
3:1 male-to-female ratio
Predilection for right atrium, may be either
intracavitary and polypoid or diffuse and
infiltrative
Later forms have sheet-like covering of
pericardium
Usually present with right-sided heart failure or
tamponade
Systemic signs such as fever and weight loss
Angiosarcoma




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“Cauliflower” appearance on MRI due to areas of
hemorrhage and necrosis
Tend to be discovered ‘late’, often already
metastasized
Often not amenable to complete resection
Very poor prognosis
Kaposi Sarcoma (HSV 8)
Less than 5% of pts with AIDS or solid organ
transplant
Rhabdomyosarcoma
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Most common cardiac malignancy in infants and
children
10% of all primary cardiac sarcomas
Diffusely infiltrate the ventricular myocardium
May on occasion form polypoid extension into
chamber
Usually multiple foci with occasional nodular
involvement of pericardium
Rhabdomyoblast – histological hallmark
Fibromyosarcoma




5-10% of cardiac sarcomas
Fibroblastic in differentiation, composed of spindleshaped cells containing areas of hemorrhage and
necrosis
Extensively infiltrate the heart
Often involving more than one chamber spreading
to the pericardium
Relative Incidence of Benign Tumors of the Heart
Benign Tumors
Adults (%)
Myxoma
52
Papillary fibroelastoma
16
Lipoma
16
Rhabdomyoma
1
Fibroma
3
Teratoma
1
Hemangioma
6
Other tumors*
5
*other tumors include cystic tumors of the atrioventricular node,
endocrine tumors and histiocytoid tumors
Adapted from Braunwald’s Heart Disease 7th edition
Relative Incidence of Benign Tumors of the Heart
Benign Tumors
Adult (%)
Children (%)
Myxoma
52
17
Papillary fibroelastoma
16
0
Lipoma
16
0
Rhabdomyoma
1
42
Fibroma
3
18
Teratoma
1
12
Hemangioma
6
5
Other tumors*
5
4
*other tumors include cystic tumors of the atrioventricular node,
endocrine tumors and histiocytoid tumors
Adapted from Braunwald’s Heart Disease 7th edition
Rhabdomyoma
Most common cardiac tumors
in infants and children
 ¾ occur in patients younger
than 1 year
 Left and right ventricular and
septal myocardium
 1/3 involve either or one atria
 Nearly all are multiple
 Small, lobulated
 Diameter range 2 mm to 2 cm

Rhabdomyoma
Most common presentation
is heart block or other
arrhythmias
 Echo: multiple small,
lobulated, homogenous,
hyperechoic intramural
tumors
 Association with Tuberous
Sclerosis (80%)
– Hamartomas
– Epilepsy
– Mental deficiency
– Adenoma sebaceum

Lipoma






Rare
Occur at any age with equal
male/female ratio
Diameter 1-15 cm
Sessile or polypoid
Occur in the subendocardium
or subpericardium,
¼ are completely
intramuscular
Most common chambers
affected are the left ventricle,
right atrium and interatrial
septum
Primary Cardiac Valve Tumors







Retrospective study by Edwards et al 1991
from 1932 to 1990
Walter Reed and Brooke Army Medical Centers
53 patients had 56 primary cardiac valve tumors
Age range 2 to 88 years
Average 52 years of age – 79% male
Aortic valve most commonly affected
Tumor size ranged 3 mm to 7 cm
Average size = 1.15 cm
Primary Cardiac Valve Tumors

52/56 (93%) tumors were benign
–
–
–
–
–
41 papillary fibroelastomas
5 myxomas
4 fibromas
1 hamartoma
1 hemangioma
Mitral valve most commonly symptomatic
 8/53 (15%) patients had neurologic symptoms
 6 had mitral valve tumors

– 3 myxomas and 3 malignancies
Comparison with Nonvalvular
Cardiac Tumors


Most common nonvalvular -> Myxoma
Most common valvular -> Papillary fibroelastoma
Edwards et al “Primary Cardiac Valve Tumors” Ann Thorac Surg 1991; 32:1131
Papillary Fibroelastoma





Most common tumor of the cardiac valves
Average age 60 at detection (range neonates to
92 yoa)
Men = Women
Most have concomitant valvular disease
suggesting this may predispose to papillary
fibroelastoma
90% solitary
Papillary Fibroelastoma
Median diameter = 8 mm,
largest reported 4 cm
 Any valve, aortic and mitral
most commonly

– arterial side of semilunar
valves
– atrial side of AV valves

Short pedicle 50% of time
Papillary Fibroelastoma Path


Grossly, a frond-like
appearance resembling a
sea anemone
Histological, numerous
papillary fronds consisting
of a collagen core
surrounded by elastic
fibers and loose
connective tissue, all
covered by endocardial
endothelium
Myxomas
 3rd
and 6th decades of life
 Mean age at presentation = 50 years
 Age range = newborn to 95 years
 2/3’s females
Myxomas
Location
Attachment
 75% Left Atria
1. Interatrial Septum
 15-20% Right Atria
– Limbus of Fossa
Ovalis
 3-4% Left Ventricle
 3-4% Right Ventricle 2. Posterior Atrial wall
3. Anterior Atrial wall
4. Atrial appendage
5. Rarely endocardial
Myxomas

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Average size 5-6 cm in
diameter
Size Range < 1 to > 15 cm
Echo shows a mobile,
distensible tumor connected
to the interatrial septum by
a narrow stalk
Polypoid
Usually pedunculated
Round or oval with smooth
or lobulated surface
Myxoma Path



Embryonic mesenchymal
cells with multipotent
capability
Myxoid matrix of acidmucopolysaccharide- rich
stroma
Immunohistochemical
studies
– Vimentin
– neuroendocrine markers
(S-100)
– gene product 9.5 and
calretinin
Myxomas

Surface of tumor is often
covered with thrombi
– Embolism occurs in 3040% of patients
– Usually systemic,
majority are cerebral

Infected myxomas have
been described
– Greater danger of
systemic embolism
Excised Villous Left Atrial Myxoma
Myxomas

Intracardiac obstruction
– 70% have heart failure or syncope
– Dyspnea, pulmonary edema, sudden death

Systemic embolization
– 30% of patients with myxoma with 2/3
cerebral
– 25% with emboli have evidence of multiple
embolic events

Constitutional symptoms
– Unique to myxoma, 30-40% of patients
– Synthesis of interleukin – 6
– Fatigue, fever, erythematous rash,
arthralgia, myalgia and weight loss
Myxomas

The Physical Exam
– Murmur heard > 50%
– Diastolic due to obstructed filling of the ventricle
– Systolic due to interference with closure of the AV valve
– S1 often loud and widely split
– Delay in closure of the AV valve
– “Tumor Plop” in 33% of patients
– A diastolic murmur heard 80 to 150 msec after the second
heart sound
– Pericardial friction rub
– Right atrial tumors

The “Wrecking Ball Effect”
– Recurrent collision with the pedunculated myxoma
and the mitral valve may cause permanent damage
Myxomas

Familial Myxomas
–
–
–
–

10% or less of all myxomas
Autosomal dominant
Median age 20 years
Atypical locations, often multiple and recurrent
tumors
Carney Complex
– Myxomas, Spotty skin pigmentation and endocrine
overactivity
Treatment of Benign Cardiac Tumors

Operative excision under direct vision using
cardiopulmonary bypass
– Schaff and Mullany, 2000

Orthotopic heart transplant

Autotransplantation
Discussion

Myxomas are source of most tumor emboli
because of their friable consistency and
intracavitary location, but other types may
embolize.
“An embolic stroke in a young person without
evidence of cerebrovascular disease, particularly
in the presence of sinus rhythm, should raise the
suspicion of intracardiac myxoma, as well as
infective endocarditis.” – Braunwald’s Heart
Disease, 7th Ed.
Discussion
Multiple Strokes
Left Atrial Mass
Tumor
Myxoma
Papillary Fibroelastoma
Tumor with or without thrombus?
Tumor with or without infection?
Diagnosis:
Myxoma
Requested Procedure:
Surgical Resection
References
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Reardon, M.J. and Smythe, W.R. Cardiac Surgery in the Adult. 2nd Ed. 2003. Chapter 58 Cardiac Neoplasms.
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The Showalter Family
Special Thanks
Dr.
Dr.
Dr.
Dr.
Dr.
Chiles
Elieson
Sibbitt
Mock
Fillmore
Thank You