Occasion

: Case Report II

Title

: Patophysiology, Management and Cause of Death of

Hemorrhagic Transformation in Acute Ischemic Stroke

Date

: June 9th 2014

Presentant

: dr. Marfri Andy

Supervisor

: dr. Hj. Yuliarni Syafrita, Sp.S

Opponent

: dr. Yuri Haiga

dr. Rini Sunarti

CASE REPORT
A 47 years old female was admitted to neurology department of M. Djamil
Hospital Padang, on April 19th 2014 (6.25 PM) with :
CHIEF COMPLAINT
Weakness of the left limbs
PRESENT ILNESS HISTORY
Weakness of the left limb since 4 hours before admission. The weakness
occurred suddenly while she was in the bathroom (taking wudhu). The
patient cannot move her left arm or left limb. The weakness followed by
asymmetrical lips and difficulity in speech.
Moments later, the patient suffered for headache that she felt in all parts of
the head, the patient also vomited four times, but remain alert.
No seizure
PAST MEDICAL HISTORY
History of hypertension since 3 moths ago, the highest blood pressure 200/11
mmHg, no specific drugs was taken.
No history of diabetes, cardiac disease or previous stroke.

FAMILY HISTORY:
Her older sister suffered for hypertension.
No history of diabetes, cardiac disease or previous stroke.
SOCIAL HISTORY
Patient is a housewife, moderate daily physical activity, no history of hormonal
contraception.
General Examination :
General Appearance

: Moderately ill

Level of consciousness

: Alert

Blood Pressure

: 170/100 mmHg

Heart rate

: 80x/min

Pulse rate

: 78x/min

Respiratory Rate

: 24x/min

Temperature

: 37,0o c

Eye

: No anemic conjunctiva, no icteric sclera

Lymph nodes

: No enlargement of lymph nodes

Neck

: JVP 5-2 cm H2O, no carotid bruit

Lungs

: Symmetrical chest wall, normal fremitus, normal

percussion, vesicular sound, no ronchi, no wheezing

Heart

: No visible apex beat, palpable apex beat at the left of 5th

Inter Costal Space (ICS) medial to the mid calvicular line,
Sinus rhythm, no gallop, no murmur, HR = 88 X/minutes

Abdomen

: No sign of abdominal distentsion, liver and spleen within

normal, percussion timpani, normal bowel sounds

Neurological Examination :
Glasgow Coma Scale

: E4M6V5 (15)

Meningeal sign

Nuchal rigidity ( - )
Brudzinski I ( - )
Brudzinsky II ( - )
Kernigs sign ( - )

Signs of increasing intracranial pressure : ( - )

Cranial Nerves
Nerve I

: Olfactory sensation is normal

Nerve II

: Within normal ( + )

Nerve III,IV,VI : Pupils are equal, round, and react to light (PERRL)
3mm/3mm, ortho position, extraocular movement to the superior, medial,
lateral, and inferior within normal
Fundsucopy : Fundus Hypertension - Keith Weigner II
NV

Corneal reflex ( + )

N VII

Facial asymmetry ( + )

N VIII

Within normal

N IX, N X

Motor system

Within normal

N XI

: Within normal

N XII

: Tounge deviation while protrude (+) to the left

Extremities
Superior
Inferior
Involunter movement
Sensoric system

Dextra
555
Eutonus, Eutrofi
555
Eutonus, Eutrofi
-

Sinistra
000
Eutonus, Eutrofi
000
Eutonus, Eutrofi
-

: Exteroceptive and proprioceptive within normal

Autonomic system : Neurogenic bladder ( - )

Physiological Reflexes :
Reflexes

Right
3

Left

Biceps
Triceps
KPR
APR

++
++
++
++

+++
+++
+++
+++

Dextra
-

Sinistra
+
-

Pathological Reflexes :
Reflex
Hoffman tromner
Babinski
Oppenheim
Gordon
Chaddock
Schaefer
Laboratory findings :
Hb

: 11 g/dL

Ht

: 33 %

WBC

: 23.500/ mm3

Platelets

: 268.000/mm3

RBG

: 152 mg/dL

Natrium

: 137 mmol/L

Kalium

: 3.4 mmol/L

Clorida

: 103 mmol/L

Ureum

: 8 mg/dL

Kreatinin

: 0.6 mg/dL

Osmolarities : 286 (275-300)

ECG : sinus rhythm, HR 70 x/min, no ST depression, no ST elevation, no
inverted T, SV1+RV5 <35mm. Conclusion: within normal
Gajah Mada Score Algorhytm :

Headache ( + )
Uncosciousness ( - )
Babinksy reflexes ( + )

Assesment : Hemorrhagic Stroke

Siriraj Stroke Score : (2.5 x 0 ) + ( 2 x 1 ) + ( 2 x 1 ) + (0,1 x 100) - (3 x 0) 12

= + 2. Assesment : Hemorrhagic Stroke
NIHSS Score : 11 moderate stroke
Barthel Index : 20
Diagnosis (before Brain CT)
Clinical diagnosis

: Left hemiparesis + Paresis of N VII, N XII left central

Topical diagnosis

: Subcortical of Left Hemisphere

Etiology of diagnosis : Intra Cerebral Hemorrage

Differential diagnosis : Ischemic Stroke
Secondary diagnosis : Hypertension Stage II
Radiology Exminations :
Brain CT without contrast : large infarction on the right frontotemporal lobes with
small petechie, no midline shift.
Interpretation : Hemorragic transformation of Ischemic Stroke
Diagnosis (after Brain CT)
Clinical diagnosis

: Left hemiparesis + Paresis of N VII, N XII left central

Topical diagnosis

: Right Frontotemporal

Etiology of diagnosis : Hemorragic Transformation of Ischemic Stroke

Secondary diagnosis : Hypertension Stage II

MANAGEMENT:
Head eleveation 30
O2 3L/min
IVFD Asering every 12 hours
Liquid low salt diet
Medication given :
5

o Citicoline 2 x 500 mg (IV)

o Ranitidin 2 x 50 mg (IV)
o Mannitol 20 %
NEXT INVESTIGATION :
1. Laboratory : PT, APTT, INR, LED, Diff count, PT, APTT, INR, Total
Cholesterol, HDL, LDL, Trygliserida, GDP, GD2PP
2. Radiology : Brain CT-Scan (expertise)

FOLLOW UP
2nd day of hospitalization (April 20th 2014)
06.00 am

SUBJECTIVE : Weakness of the lower limbs, headache

OBJECTIVE :
Level of consciousness

: alert
6

Blood pressure

: 170 / 100 mmHg

Heart rate

: 88 x/min

Respiratory rate

: 23 x/minute

Temperature

: 36,8C

Neurological examination :

Glasgow Coma Scale

: E4M6V5 (15)
Meningeal sign
:(-)
Signs of increasing intracranial pressure : ( - )

Cranial nerves : Pupils are equal, round, and react to light (PERRL)
3mm/3mm, paresis of the N VII, N XII left central, swallow test (+)

Motor system

Extremity
Superior
Inferior
Involunter movement

Dextra
555
Eutonus, Eutrofi
000
Eutonus, Atrofi
-

Sinistra
555
Eutonus, Eutrofi
000
Eutonus, Atrofi
-

Sensoric and autonomic system : within normal

Physiological Reflexes :
Reflexes
Biceps
Triceps
KPR
APR

Right
++
++
++
++

Left
++
++
++
++

Dextra
-

Sinistra
+
-

Pathological Reflexes :
Reflex
Hoffman tromner
Babinski
Oppenheim
Gordon
Chaddock
Schaefer
10.00 AM :

SUBJECTIVE : Massive vomiting and unconscious

OBJECTIVE :
7

Level of consciousness

: somnolen (E3M5V3)

Blood pressure

: 160 / 100 mmHg

Heart rate

: 92 x/min

Respiratory rate

: 24 x/minute

Temperature

: 37 C

Cranial nerves : Pupils are equal, round, and react to light (PERRL)
3mm/3mm, paresis of the N VII, N XII left central, swallow test (+)

PLAN : NGT and folley cath insertion with intensive follow up

10.45 AM

SUBJECTIVE : cyanosis, not breathing (apneu), the blood pressure cannot

be measured, pulse are not palpable

OBJECTIVE :
Exmination (after 1 hour of cardiopumonal resuscitation) :
o No spontan breathing
o Blood pressure cannot be measured
o Pulse are not palpable
o Cranial nerves : midriatic pupil (6 mm / 6 mm,) no light reflexs, no
corneal reflexs, dolls eye manouvre ( - )
o ECG : asystole
The patient was confirmed passed away at 11.45 AM

DISCUSSION
On this patient, from anamnesis we found weakness of the left limb (hemiplegia),
associated with asymmetrical lips and difficulity in speech. These complaints
followed by progressive headache and vomiting during hospitality. ER
examinations revealed high blood pressure (170/100 mmHg) on this patient.
Cranial nerves examination revealed paresis of seventh and twelveth cranial
nerves, left babinsky reflex. Both Gajah Mada and Siriraj Stroke Score suggested
for hemorrhagic stroke. Laboratory examinations revealed increase of

WBC

(23.000/mm3), and Computed Tomography (CT) of the brain revealed large

infarction on the right frontotemporal with petechials inside the infarction area.
Intravenous Citicholine ( 2 x 1000 mg ), Ranitidin ( 2 x 50 mg ) and Mannitol 20
% was given. The management in this patient was facing challenge as the use of
anti aggregant or anti fibrinolytic could make the transforming stroke even worse.
9

The need to initiate to install NGT was hold as the patient remain alert and the
blood pressure that was likely to remain high.
Later on, the patient lost the spontaneous breathe with the skin turned bluish
(cyanosis), likely to be an aspiration and after 1 hour of cardiopumonal
resuscitation hour, the patient passed away due respiration failure.
Consequently, there is an urgent need to understand clinical consequences of
hemorrhagic transformation of ishemic stroke and judgement for clinician to give
appropriate treatment. The progressive and worsening of the patients, generally,
the symptoms, are indications for clinicians to transfer the patient to intensive care
unit (ICU), with a follow up of Brain CT (serial).
Hemorrhagic transformation (HT) is defined as multifocal secondary bleeding
into the ischemic tissue of a brain infarction, with the extent ranging from small
petechiae and confluent purpura to parenchymal hematoma. Early HT occurs in
about 9 % patient with parenchymal hematoma seen in about 3 % of patient.

Clinicians are often concerned when a patient with acute ischemic stroke develops
an HT, even when the lesion is asymptomatic and only detected with a computed
tomographic (CT) image. The consequences of HT vary from progressive
worsening of the patients condition and death in the acute phase to no effect at
all.
Historically,

hemorrhagic

infarction,

has

long

been

recognized

by

neuropathologists to occur as a natural consequence of ischemic brain injury.

Several early theories were advanced to explain the pathogenesis of secondary
bleeding into a bland (pale, anemic) infarction.
Cohnheim (1872) : hemorrhagic infarction resulted from the embolic
occlusion of end arteries followed by venous reflux into damaged vascular
beds
Fisher and Adamas (1951) : The concept of migratory embolism ; the
hemorrhagic portion of an infarction often lay proximal to identified emboli,
10

whereas pale zones of infarction were distal to persisting occlusions.

Proposed that the molding and fragmentation of emboli due to
hemodynamic forces results in distal clot migration, thereby exposing an
ischemically damaged vascular bed to reperfusion and subsequent bleeding.
Hain (1952) : a sufficient volume of blood that flow through the vessels
distal to the site of occlusion and sufficient alteration in the permeability of
the vessel wall to permit the escape of blood into the tissue are the
prerequisites for the production of a hemorrhagic infarction
Hemorrhagic transformation can be defined both clinically and radiographically.
Clinically, a second approach to classification describes hemorrhagic
transformation as either symptomatic or asymptomatic. The National Institute of
Neurological Disorders and Stroke (NINDS) tPA Stroke Study Group
recognized that small hemorrhages in critical areas of the brain could also be
devastating, leaving clinicians as the most qualified judges of significant
hemorrhagic transformation. If a decline in the patient's condition was
temporally associated with hemorrhage on the CT scan, the hemorrhagic
transformation was classified as symptomatic (NINDS tPA Stroke Study Group
1997). The NINDS group found that the variables independently associated with
an increased risk of symptomatic intracerebral hemorrhage were the severity of
neurologic deficit as measured by the National Institutes of Health Stroke Scale
and brain edema (acute hypodensity) or mass effect by CT before treatment.
Radiographically, the European Cooperative Acute Stroke Study (ECASS)
investigators classified hemorrhagic transformation into hemorrhagic infarction
(petechial infarction without space occupying effect) and parenchymal
hematoma (hemorrhage with mass effect). Hemorrhagic infarctions were further
subdivided into hemorrhagic infarction 1 (small petechiae) and hemorrhagic
infarction 2 (more confluent petechiae). Similarly, parenchymal hematomas
were further subdivided into parenchymal hematoma 1 (less than 33% of the
infracted area with some mild space-occupying effect) and parenchymal
hematoma 2 (greater than 33% of the infracted area with significant spaceoccupying effect or clot remote from the infracted area). In the ECASS I
analysis, hemorrhagic infarction 1, hemorrhagic infarction 2, and parenchymal
11

hematoma 1 did not modify risk of early neurologic deterioration, death, and
disability, whereas parenchymal hematoma 2 had a devastating impact on early
neurologic course and on 3-month death (Fiorelli et al 1999). A significant
hemorrhage can be defined by volume and size; a study discovered that a
hemorrhage greater than 25 mL will produce a more clinically significant
outcome in terms of a worsening NIH stroke scale at the time of a hospital
discharge than those hemorrhages less than 25 mL (Christoforidis et al 2007).

REFERENCES
1. Bayramog M, Karatas M, Leblebici B, et al. Hemorrhagic transformation
in stroke patients. Am J Phys Med Reha- bil 2003 82 : 4852
2. Park JH, Ko Y, Kim WJ, Jang MS, Yang MH, et al. Is asymptomatic
hemorrhagic transformation really innocuous? Neurology 2012 78 : 421
426.
3. Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, et al. Guidelines
for the prevention of stroke in patients with stroke or transient ischemic
attack: a guideline for healthcare professionals from the american heart
association/american stroke association. Stroke 2011 42 : 227276
4. Berger C, Fiorelli M, Steiner T, Schabitz WR, Bozzao L, et al.
Hemorrhagic transformation of ischemic brain tissue: asymptomatic or
symptomatic?. Stroke 2001 32: 13301335
5. Kablau M, Kreisel SH, Sauer T, Binder J, Szabo K, et al. Predictors and
early outcome of hemorrhagic transformation after acute ischemic stroke.
12

Cerebrovascular Disease 2011 32: 334341.

6. G R de Freitas, A Carruzzo, A Tsiskaridze, et al. Massive haemorrhagic
transformation in cardioembolic stroke: the role of arterial wall trauma and
dissection. J Neurol Neurosurg Psychiatry 2001 70 : 672674
7. Kim EY, Na DG, Kim SS, Lee KH, Ryoo RJ. Prediction of Hemorrhagic
Transformation in Acute Ischemic Stroke: Role of Diffusion- Weighted
Imaging and Early Parenchymal Enhancement. American Journal of
Neuroradiology 2005 26: 1050-1055.

13