Near-Infrared
Spectroscopy Monitored Cerebral Venous Thrombolysis
Timothy
F. Witham, Edwin M. Nemoto, Charles A. Jungreis and Anthony
M. Kaufmann
Abstract:
Background: Cerebral venous thrombosis is a clinical
entity which is readily diagnosed with the advent of modern
imaging techniques. Anticoagulation is now a standard therapy,
but more recent treatment strategies have included endovascular
thrombolysis. While the endpoint of this intervention both
clinically and radiographically has not been defined, noninvasive
monitoring techniques may add further objective measures of
treatment response. Clinical Presentation: We
present a patient with a four day history of worsening headache
and papilledema on exam. Superior sagittal, straight, and
bilateral transverse sinus thromboses were identified on computed
tomography and angiography. Intervention: Emergent
endovascular thrombolysis by a transvenous approach re-established
venous patency and resulted in immediate resolution of the
patient's symptoms. Cerebral oximetry by near-infrared spectroscopy
was utilized during the procedure, and changes in chromophore
concentrations correlated directly with angiographic and clinical
resolution of the thrombosis. Conclusion: Near-infrared
spectroscopy can provide continuous feedback during thrombolytic
therapy in cerebral venous thrombosis and may help define
endpoints of such intervention.
Résumé:
À propos d'un cas de thrombolyse veineuse cérébrale
effectuée sous surveillance spectroscopique de proche
infrarouge. Introduction: La thrombose veineuse
cérébrale est une entité clinique dont
le diagnostic est facile depuis l'avènement des techniques
modernes d'imagerie. L'anticoagulation est maintenant le traitement
standard, mais il existe des stratégies de traitement
plus récentes, dont la thrombolyse endovasculaire.
Bien qu'au point de vue clinique ou radiologique les critères
de succès de cette intervention n'aient pas été
définis, les techniques non invasives de suivi peuvent
fournir des mesures objectives de la réponse au traitement.
Présentation clinique: Nous présentons
le cas d'une patiente qui s'est présentée avec
une histoire de céphalée de plus en plus sévère
depuis quatre jours et un oedème papillaire. Des thromboses
du sinus longitudinal supérieur, du sinus droit et
des sinus latéraux ont été identifiées
à la tomodensitométrie et à l'angiographie.
Intervention: Une thrombolyse endovasculaire
d'urgence par voie endoveineuse a réétabli la
perméabilité veineuse et amené une résolution
immédiate des symptômes. L'oxymétrie cérébrale
par spectroscopie de proche infrarouge a été
utilisée pendant l'intervention et les changements
de concentrations chromophores étaient en corrélation
directe avec la résolution angiographique et clinique
de la thrombose. Conclusion: Dans la thrombose
veineuse cérébrale, la spectroscopie de proche
infrarouge peut fournir des informations continues pendant
la thrombolyse et peut aider à définir les critères
de succès de telles interventions.
Can.
J. Neurol. Sci. 1999; 26:48-52
Cerebral
venous thrombosis (CVT) is a clinical entity that is being
more commonly diagnosed with the advent of modern imaging
techniques.(1) The traditionally described spectrum of symptoms
resulting from CVT includes headache, papilledema, seizures,
and focal deficits, which may progress to coma and death.(2-5)
Hemorrhagic venous infarction is common. Early reports of
mortality from CVT range from 30-50%.(2,3,5) With the advent
of early diagnostic techniques and rapid initiation of therapy,
the more recent mortality rates range from 5.5-30%.(6-9) Long
term follow-up of patients with no neurologic sequelea is
now common.(10) Anticoagulation, which is controversial in
the setting of concomittant hemorrhagic infarction, is a standard
therapy.(6,11,12) The duration of anticoagulant therapy is
usually addressed on a case by case basis. More recent treatment
strategies have included systemic thrombolytics, endovascular
thrombolysis, and surgical thrombectomy.(13-19)
We
present a patient with a four day history of worsening headache
secondary to superior sagittal, straight, and bilateral transverse
sinus thrombosis, which was associated with a factor V Leiden
mutation.(20) She underwent emergent endovascular thrombolysis
which re-established venous patency and resulted in immediate
resolution of her symptoms. Cerebral oximetry by near-infrared
spectroscopy (NIRS) was utilized during the endovascular procedure.
Changes in chromophore concentrations correlated directly
with the angiographic resolution of the thrombosis and the
immediate symptomatic relief.
Case
Report
A
35-year-old white female presented with a symptom complex
consistent with superior sagittal sinus thrombosis. She had
been previously well with no history of prior venous thrombosis,
bleeding diathesis, recent infection, pregnancy, or head injury.
There was no prior history or family history of hypercoagulable
state. Her symptoms began four days prior to admission with
an insidious onset of generalized headache which progressively
worsened. There was associated photophobia, and neck stiffness,
but no nausea or emesis. Initial systemic blood pressure was
190/110 mmHg. On examination the patient was mildly somnolent,
but easily arousable and was oriented to person, place, and
time. She had no focal neurologic deficits, but fundoscopy
revealed papilledema.
A
non-contrast cranial CT scan was obtained at a community emergency
department and demonstrated no focal mass effect, and a lumbar
puncture was then performed. The opening pressure was not
recorded. There were 20 RBCs/mm in the first tube and 16 RBCs/mm
in the fourth, 3 WBCs/mm, glucose of 71 mg/dl, and protein
of 48 mg/dl. There was no xanthochromia. Routine chemistry
studies revealed a sodium of 132 meq/l but other electrolytes
were within normal limits. Hematologic studies showed a peripheral
WBC of 15,700 with 80% neutrophils, 3% bands and, HCT of 45%.
PT, PTT, and PLT studies were within normal limits.
The
patient was transferred and evaluated by the neurosurgery
service. Review of the CT scan demonstrated a hyperdensity
in the superior sagittal sinus indicating thrombosis (Figure
1). Because of the diagnostic CT scan and clinical evidence
of symptomatic intracranial hypertension, no magnetic resonnace
imaging was performed. Instead, immediate angiography was
performed, with plans for endovascular thrombolysis.
A
5 French cerebral catheter was passed into the right jugular
vein using fluoroscopic and roadmapping guidance. The jugular
bulb was identified with the use of contrast injection and
there was a filling defect which was later confirmed to be
the inferior aspect of the thrombus. A microcatheter was then
used to probe the sinus system. The microcatheter was advanced
into the right transverse sinus and venography demonstrated
contrast stasis in both transverse sinuses (Figure
2). The catheter was advanced to the torcula where a urokinase
(UK) infusion was begun (5,000 units per cc). An intravenous
heparin bolus of 5,000 units was also administered at this
point in the case followed by a 1,000 unit per hour continuous
infusion for the remaining portion of the case. After 250,000
units of UK had been infused, flow was re-established in the
left transverse sinus (Figure
3). With gentle manipulation the microcatheter was then
directed into the superior sagittal sinus. Venography again
demonstrated minimal flow with numerous filling defects that
presumably were thrombus (Figure
4). An additional 450,000 units of UK was infused and
flow through the superior sagittal sinus was then observed
despite the presence of residual thrombus (Figure
5). At this time the patient had almost complete resolution
of her headache which had been severe prior to the endovascular
procedure. The microcatheter was repositioned in the straight
sinus and venography demonstrated slow flow. An additional
600,000 units of UK re-established flow in this region. The
catheter was withdrawn to the torcula where venography was
again performed and revealed poor flow. Patency was again
established with 600,000 additional units of UK. The procedure
was terminated.
Cerebral
oximetry by NIRS was employed during the endovascular procedure
in addition to standard clinical monitoring. A 5 mm diameter
near-infrared optode and 5 mm diameter receiving optodes were
placed 4 cm apart on the right parietal cortex in the anterior-posterior
direction approximately 3 cm from midline. The pathlength
was set at the recommended 6 cm and the sampling rate at 5
seconds. The output of the NIRO 500 was collected from the
RS232 port into a 386 PC into a serial port via a Software
Wedge program (T.A.L. Enterprises, Philadelphia, PA). Continuous
cerebral oximetry recording during thrombolysis is found in
Figure 6. Concentrations
of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb),
and total hemoglobin (Thb) were high as cerebral venography
commenced, and corresponded to low cytochrome oxidase (cytox)
concentrations. These abnormal levels had developed following
initial placement of the optodes, while the patient remained
stable but drowsy. Successful thrombolysis was associated
with a steady normalization of Hb, HbO2, Thb, and
cytox relationships, reflecting reduced cerebral blood volume.
Chromophore changes correlated with improved angiographic
flow and symptom resolution. All chromophore concentrations,
however, increased again, coincident to the finding of torcular
re-occlusion. Successful thrombolysis again correlated with
a progressive decrease in all chromophore concentrations and
a reoxidation of Cytox back to normal levels. Clinical improvement
mirrored the radiographic changes and chromophore changes
observed with NIRS.
The
patient made an excellent recovery and suffered no neurological
deficits. She was continued on intravenous, and later, oral
anticoagulation. Follow-up imaging demonstrated no evidence
of hemorrhage or infarction. Hematologic evaluation revealed
a Factor V Leiden mutation, a known risk factor for venous
thromboembolism.(21-23) Follow-up MRI performed 6 months from
the time of initial presentation showed no residual or new
thrombosis. Coumadin was then discontinued.
Discussion
Direct
endovascular thrombolysis was performed in the presented case
because the patient had extensive CVT producing intracranial
hypertension manifesting with drowsiness and papilledema.
The correlation of NIRS with successful endovascular thrombolysis
and the corresponding clinical improvement were dramatic.
Resolution of the CVT in our patient was documented with three
lines of observation. First angiographic resolution of clot
was observed during urokinase infusion. Second, the patient
immediately expressed dramatic symptomatic relief at the same
time; specifically, cessation of a generalized headache. Finally,
the changes in NIRS chromophore concentrations followed in
a very close temporal sequence.
After
the first report by Jobsis(24) demonstrating the feasibility
of using near-infrared spectroscopy (NIRS) for cerebral oximetry,
the technique has undergone considerable development.(25)
Specifically, with regard to the NIRO 500 (Hamamatsu Photonics
KK) it is now possible to quantify changes in tissue oxygenation
on the basis of measurements of oxyhemoglobin (HbO2),
deoxyhemoglobin (Hb), total hemoglobin (THb), and cytochrome
oxidase (Cytox) redox state noninvasively through the cranium
of neonates(26-29) and adults.(30-34)
This
case demonstrates the potential utility of cerebral oximetry
by NIRS to provide continuous feedback during thrombolytic
therapy in cerebral venous thrombosis (CVT) and the potential
application in thrombotic stroke. An ability to monitor the
resolution of the thrombosis and perfusion continuously may
direct the endovascular interventionalist and help reduce
the risks of reperfusion injury, edema, and hemorrhage. NIRS
may allow for continuous appreciation of the extent to which
the thrombus is being resolved without the neccessity of repeated
dye injections to follow the success of thrombolytic therapy.
NIRS may also be useful to monitor for evidence of re-thrombosis.
Development of hemorrhage or infarct may also be detected
in the post procedure period.(35,36 )
The
endpoint for thrombolytic therapy in the treatment of CVT
is not clear.(18) Some reports have utilized infusions for
many days in order to have a "normal" angiogram.(19) Others
have relied on re-establishment of fluoroscopic flow even
if some thrombus remains.(1) Further experience with NIRS
during endovascular thrombolytic procedures, arterial or venous,
may provide another valuable measure of therapeutic benefit
and thereby serve as a marker to direct treatment and its
endpoint.
The
patient described was found to have activated protein C resistance
due to a factor V Leiden mutation. Inheritance of a factor
V Leiden mutation is autosomal dominant.(26,43) Activated
protein C resistance (APC-R) is a reported risk factor for
venous thromboembolism including CVT.(21-23,37-42) Those patients
with concomittant APC-R and oral contraceptive use have a
30-50 fold increase in the risk of thrombosis.(43) In our
patient a factor V Leiden mutation leading to APC-R was felt
to be the primary etiologic factor in her development of CVT.
There is no concensus regarding the appropriate duration of
anticoagulant therapy. In the absence of prior thrombotic
events, we elected to discontinue the coumadin after six months.
MRI had confirmed normal cerebral venous patency.
The
subject of this study presented with a four day history of
progressive headache with no focal neurologic deficit. Diagnostic
evaluation revealed diffuse cerebral sinus thrombosis. Successful
endovascular thrombolysis using urokinase was performed and
the patient made an excellent recovery. Near-infrared spectroscopy
was utilized at the time of thrombolysis and chromophore changes
directly correlated with symptomatic relief and re-establishment
of venous patency as angiographically defined. We feel that
CVT represents a clinical scenario in which cerebral oximetry
may have clinical application. Tissue oximetry by NIRS is
a clinical technique enabling direct, noninvasive, and continuous
monitoring of the adequacy of cerebral tissue oxygenation.
This technology is now ready for verification of efficacy
in a variety of clinical applications.
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- From
the Departments of Neurological Surgery (T.F.W.,
E.M.N.) and Division of Neuroradiology (C.A.J.),
University of Pittsburgh School of Medicine, Pittsburgh,
Pennsylvania and Department of Clinical Neurosciences
(A.M.K.), University of Calgary, Calgary.
- Received
March 9, 1998. Accepted in final form July 13, 1998.
- Reprint
requests to: Anthony M. Kaufmann, Department of
Clinical Neurosciences, Foothills Hospital, 12th
Floor, 1403 - 29th Street N.W., Calgary, Alberta,
Canada T2N 2T9
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Can.
J. Neurol. Sci. 1999; 26:48-52
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