A Stroke from the Bishops Cap

1
A Stroke from the Bishops Cap

• Thomas A. Showalter, III, DO
• Resident, Internal Medicine
• CPC
• August 10th, 2007

2
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.

3
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 SW

4
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.

5
The Case continued

• PSH
• Appendectomy as child
• Chest tube placement for Spontaneous PTx
• Meds
• none
• Allergies
• none

6
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.

7
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.

8
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

9
The Data
13.6
138 100 10
8.7
273
39.0
4.3 23 0.8

• Diff
• Neut 54
• Lymph 27
• Mono 7

LFTs Normal Coags Normal
10
The Data continued

• CXR
• normal
• EKG
• marked sinus bradycardia with sinus arrhythmia,
  early repolarization

• MRI Brain
• chronic left MCA infarct and several chronic
  tiny cerebellar infarcts
• MRA Head/Neck normal Circle of Willis and great
  vessels of head and neck

11
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
12
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.

13

• The Case
• Problem List
• DDx of Stroke in a Young Person
• DDx of a Left Atrial Mass
• Conclusions

14
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
15
Stroke in Young Adults

• Usually defined as age lt 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

16
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 lt 45 years of age
  (yoa).
• Developing countries had 20-30 of strokes lt 45
  yoa
• United States, 8-10 of strokes in patients lt 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

17
DDx of Stroke in Young Adults

• Subarachnoid Hemorrhage
• Intracerebral Hemorrhage
• Cerebral Ischemic Infarcts

18
Cerebral Ischemic Infarct

• 3 of all cerebral infarcts occur between 15-45
  years of age 3
• Etiologies
• Atherosclerotic
• Nonatherosclerotic
• Cardioembolic
• Ages 15-35, cardioembolic and nonatherosclerotic
  causes predominate
• After age 35, traditional atherosclerotic stroke
  risk factors become prime determinants of stroke

19
Atherosclerotic causes

• Traditional risk factors
• Hypertension, Smoking, Hyperlipidemia, Diabetes
  Mellitus
• Age 15-30 -gt 2
• Age 30-45 -gt 30-35
• Homocystinuria premature large vessels disease
• Carotid Atheroma formation due to local radiation
  for laryngeal tumors
• Cranial radiation produces a radiation
  vasculopathy

20
The Myriad of Nonatherosclerotic causes

• Dissection
• Illicit drug use
• Infection
• Prothrombotic States
• Migraine
• Sickle Cell Disease

• Genetic Disorders
• Inborn Errors of Metabolism
• Moyamoya
• Hyperestrogenemic States
• Vasculitis
• Arteritis due to Neoplasms

21
The Myriad of Nonatherosclerotic causes

• Dissection
• Illicit drug use
• Infection
• Prothrombotic States
• Migraine
• Sickle Cell Disease

• Genetic Disorders
• Inborn Errors of Metabolism
• Moyamoya
• Hyperestrogenemic States
• Vasculitis
• Arteritis due to Neoplasms

22
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

23
(No Transcript)
24
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

25
DDx of Left Atrial Mass

• Endocarditis
• Nonbacterial Thrombotic Endocarditis (Marantic)
• Libmann Sachs endocarditis
• Bacterial endocarditis
• Left Atrial Thrombus
• Tumor
• Metastatic
• Primary, Benign or Malignant

26
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 Trousseaus Syndrome
• Predisposed by prothrombotic states, valvular
  endothelial disruption and underlying valve
  disease

27
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

28
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

29
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, Oslers nodes, Janeways
  lesions
• Neurologic complications
• 20-40 will have neurologic complication!
• 65 of embolic phenomena involve the CNS

30
The Duke Criteria

• Introduced by group at Duke University in 1994,
  modified in 2000
• Specificity 99
• NPV gt 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
  gt 92
• Other clinical and laboratory findings
• Only 5-7 of patients have sterile blood
  cultures

31
(No Transcript)
32
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

33
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

34
Cardiac Tumors

• Metastatic
• 20-40 times more common than primary tumors
• Pericardium gt Myocardium gt 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 -gt 75
• Myxomas comprise 50 of benign
• Myxomas comprise 80-90 of left atrial primary
  tumors
• Malignant -gt 25
• Sarcomas comprise 75 of malignant

35
Frequency of Cardiac Tumors
Atlas of Heart Disease Cardiopulmonary Diseases
and Cardiac Tumors. Vol III. 1995. Philadelphia
Mosby.
36
Relative Incidence of Primary Malignant Tumors of
the Heart
Other sarcomas include liposarcomas, synovial
and neurogenic sarcomas
Adapted from Braunwalds Heart Disease 7th edition
37
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

38
Malignant Cardiac Tumors

• 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

39
Treatment of Cardiac Sarcomas

• 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

40
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

41
Angiosarcoma

• 30 of primary cardiac sarcomas
• 31 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

42
Angiosarcoma

• 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

43
Rhabdomyosarcoma

• 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

44
Fibromyosarcoma

• 5-10 of cardiac sarcomas
• Fibroblastic in differentiation, composed of
  spindle-shaped cells containing areas of
  hemorrhage and necrosis
• Extensively infiltrate the heart
• Often involving more than one chamber spreading
  to the pericardium

45
Relative Incidence of Benign Tumors of the Heart
other tumors include cystic tumors of the
atrioventricular node, endocrine tumors and
histiocytoid tumors
Adapted from Braunwalds Heart Disease 7th edition
46
Relative Incidence of Benign Tumors of the Heart
other tumors include cystic tumors of the
atrioventricular node, endocrine tumors and
histiocytoid tumors
Adapted from Braunwalds Heart Disease 7th edition
47
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

48
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

49
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

50
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

51
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

52
Comparison with NonvalvularCardiac Tumors

• Most common nonvalvular -gt Myxoma
• Most common valvular -gt Papillary fibroelastoma

Edwards et al Primary Cardiac Valve Tumors Ann
Thorac Surg 1991 321131
53
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

54
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

55
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

56
Myxomas

• 3rd and 6th decades of life
• Mean age at presentation 50 years
• Age range newborn to 95 years
• 2/3s females

57
Myxomas

• Location
• 75 Left Atria
• 15-20 Right Atria
• 3-4 Left Ventricle
• 3-4 Right Ventricle

• Attachment
• Interatrial Septum
• Limbus of Fossa Ovalis
• Posterior Atrial wall
• Anterior Atrial wall
• Atrial appendage
• Rarely endocardial

58
Myxomas

• Average size 5-6 cm in diameter
• Size Range lt 1 to gt 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

59
Myxoma Path

• Embryonic mesenchymal cells with multipotent
  capability
• Myxoid matrix of acid- mucopolysaccharide- rich
  stroma
• Immunohistochemical studies
• Vimentin
• neuroendocrine markers (S-100)
• gene product 9.5 and calretinin

60
Myxomas

• Surface of tumor is often covered with thrombi
• Embolism occurs in 30-40 of patients
• Usually systemic, majority are cerebral
• Infected myxomas have been described
• Greater danger of systemic embolism

Excised Villous Left Atrial Myxoma
61
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

62
Myxomas

• The Physical Exam
• Murmur heard gt 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

63
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

64
Treatment of Benign Cardiac Tumors

• Operative excision under direct vision using
  cardiopulmonary bypass
• Schaff and Mullany, 2000
• Orthotopic heart transplant
• Autotransplantation

65
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. Braunwalds Heart
  Disease, 7th Ed.

66
Discussion

• Multiple Strokes
• Left Atrial Mass

Tumor
Myxoma Papillary Fibroelastoma
Tumor with or without thrombus?
Tumor with or without infection?
67
Diagnosis
Myxoma
Requested Procedure
Surgical Resection
68
References

• Gandolfo, C. and M. Conti. Stroke in young
  adults epidemiology Neurological Science 2003
  24 S1-S3.
• Jacobs, B.S., et al. Stoke in the young in the
  Northern Manhattan Stroke Study Stroke 2002 33
  2789-96.
• Hart, R.G. et al., Diagnosis and management of
  ischemic stroke. II. Selected controversies
  Current Problems in Cardiology 1983 8(7)
  43-53.
• Birgitte, H. et al. Stroke in Young Adults and
  Children Current Neurology and Neuroscience
  Reports 2001 1 54-66.
• Martin, P.J., et al. Causes of ischaemic stroke
  in the young Postgraduate Medical Journal 1997
  73 8-16.
• Guillon, B. et al., Internal carotid artery
  dissection an update Journal of Neurologic
  Science 1998 153 146- 158.
• Sloan, M.A., Illicit drug-associated ischemic
  stroke in the Baltimore-Washinton Young Stroke
  Study Neurology 1998 19 1688-93.
• Biller, J. et al., Spontaneous subarachnoid
  hemorrhage in young adults Neurolosurgery 1987
  21(5) 664-7.
• Mylonakis, E. and Calderwood, S.B., Infective
  Endocarditis in Adults NEJM 2001 345(18)
  1318-1330.
• Cerebral Embolism Task Force. Cardiogenic Brain
  Embolism. The Second Report of the Cerebral
  Embolism Task Force Archives of Neurology 1989
  46 727-43
• Klein, A.L. et al., Use of transesophageal
  echocardiography to guide cardioversion in
  patients with atrial fibrillation NEJM 2001 May
  10 344(19) 1411-20.
• Srimannaraya, J. et al., Prevalence of left
  atrial thrombus is rheumatic mitral stenosis with
  atrial fibrillation and its response to
  anticoagulation a transesophageal
  echocardiographic study Indian Heart Journal
  2003 Jul-Aug 55(4) 358-61.
• Omran, H. et al., Incidence of left atrial
  thrombi in patients in sinus rhythm and with a
  recent neurologic deficit American Heart
  Journal 2000 140(4) 685-62.
• Reardon, M.J. and Smythe, W.R. Cardiac Surgery in
  the Adult. 2nd Ed. 2003. Chapter 58 Cardiac
  Neoplasms. New York McGraw-Hill.
• Sabatine, M.S. et al. Braunwalds Heart Disese A
  Textbook of Cardiovascular Medicine 7th Ed. 2005.
  Chapter 63 Primary Tumors of the Heart.
  Saunders.
• Edwards, F.H., et al. Primary Cardiac Valve
  Tumors Annals of Thoracic Surgery 1991 52
  1127-31.
• Reynen, M.D. Cardiac Myxomas NEJM 1995
  333(24) 1610-1617.
• www.uptodate.com
• The Grand Tetons

69
Special Thanks

• Dr. Chiles
• Dr. Elieson
• Dr. Sibbitt
• Dr. Mock
• Dr. Fillmore

70
Thank You