1) Cavernous sinus thrombosis is a rare but serious condition caused by infection or trauma spreading to the cavernous sinus. 2) Staphylococcus aureus and Streptococcus species are the most common infectious causes. Symptoms include fever, headache, eye signs like chemosis and proptosis. 3) Treatment involves antibiotics, surgery to drain infection sites, and controversy around the use of steroids and anticoagulants to prevent further thrombus progression while allowing antibiotic penetration.

2. DEPARTMENTOF ORAL SURGERY
nhdcri ,bilaspur
PRESENTED BY :-
DR. KAMINI DADSENA
2nd YEAR PG

3. Cavernous Sinus
Thrombosis:
Current Therapy
VALMONT DESA, DDS, MD,* AND RYAN GREEN, MD, DDS
J ORAL MAXILLOFAC SURG 70:2085-2091, 2012

4.  Cavernous sinus thrombosis represents a rare but
devastating disease process that may be associated
with significant long-term patient morbidity or
mortality. The prompt recognition and management of
this problem is critical.

5. Review of Literature :

6. Pathophysiology :
 The causes of CST are infectious or aseptic.
 Aseptic causes typically occur after surgery and after
trauma
 Infectious causes include sinusitis, otitis, odontogenic
sources, facial furuncles, and erysipelas. Childs and
Courville

7. Pathophysiology :
 Vascular flow can occur in either direction from the
emissary veins into the dural sinuses because these
structures lack valves. The emissary veins pass through
apertures in the cranial wall and establish
communication between the sinuses inside the skull and
the veins external to it. They include the condyloid
emissary vein, mastoid emissary vein, occipital emissary
vein, and parietal emissary vein. A network of veins
unites the cavernous sinus with the pterygoid plexus
through the foramen ovale. Two or 3 small veins run
through the foramen lacerum and connect the
cavernous sinus to the pterygoid plexus. A vein is
transmitted through the foramen cecum and connects
the superior sagittal sinus to the veins of the nasal cavity.

8. Pathophysiology :
 Most commonly, CST occurs secondary to the spread
of infection by veins and by direct extension. Spread
can occur by the propagation of a thrombus and/or
septic embolism. Infection spreads in anterograde
fashion through the ophthalmic veins connected to
the angular veins, which results in the classic clinical
presentation of periorbital edema. Spread can also
occur in retrograde fashion by the emissary veins
connected to the pterygoid plexus, which tends to be
a slower, more insidious progression.

9. MICROBIOLOGY :
 The microbiology of CST is well documented. The
most commonly isolated organisms are
Staphylococcus aureus (about 70%) and
Streptococcus species (about 20%). Other reported
organisms include Pneumococcus, Bacteroides,
Fusobacterium, Proteus, Haemophilus, Pseudomonas,
and Corynebacterium species. Bacteria stimulate the
formation of a thrombus by the release of a
procoagulative substance and through toxins that
cause tissue damage.3,4

10. MICROBIOLOGY :
 Sinusitis appears to be the most common cause for septic CST
based on a review of the literature and published case reports.
Sphenoid sinusitis is rare as a primary source of infection;
however, it is seen in several cases in conjunction with other
sinus infections, especially ethmoid sinusitis. Causative
organisms in sinusitis were Streptococcus species, including S
pneumoniae, and S aureus, gram-negative organisms, and
anaerobes.
 Otitis media is another source of CST, where infection spreads
through the sigmoid sinus or along the internal carotid arterial
plexus. Since the antibiotic era, otitis media as a cause of CST
has significantly decreased. Odontogenic causes are usually
mixed flora, including -hemolytic streptococci and anaerobes.
 In cases in which a facial furuncle is the cause, S aureus was the
most frequently reported organism (about 70%), followed by
Streptococcus species (20%).

11. CLINICAL COURSE :
 The typical clinical course involving pyrexia is seen
usually with a “picket fence” pattern of the temperature
chart suggestive of thrombophlebitis. Signs of sepsis,
including tachycardia, hypotension, rigors, confusion,
and eventually coma, can be seen. Headache has been
reported in 50% to 90% of cases. It is generally
unilateral, frontotemporal, or retrobulbar in location.
Nuchal rigidity has been reported in more than one third
of cases, indicating meningeal involvement.
 Eye signs are well documented. Initially, these are
secondary to venous congestion; however, as the
disease progresses, this changes to neurologic
manifestations.
 Ninety percent of cases display chemosis, periorbital
edema, and proptosis.1,2

12. CLINICAL COURSE :
 Initially, the ipsilateral eye is affected, followed by the
contralateral eye in about 48 hours. Impaired
extraocular muscle motility is seen, usually starting
with a lateral gaze.
 Cranial nerve IV is least susceptible secondary to its
anatomic location within the cavernous sinus. Visual
impairment has been reported in 7% to 22% of
caseswith blindness reported in 8% to 15% of cases.5-
9

13. CLINICAL COURSE :
 The present patient presented with chemosis and
decreased light perception on admission, which
developed into loss of vision within 12 hours.
Intracranial extension of infection may result in
meningitis, encephalitis, brain abscess, pituitary
infection, epidural and subdural empyemas, and
possible coma and death.10-12
 Cortical vein thrombosis can result in hemorrhagic
infarction and resultant hemiplegia, a complication
that was seen in the present case. Extension of the
thrombus to other sinuses, such as the petrosal,
inferior sagittal and sigmoid, can occur.

14. CLINICAL COURSE :
 A latency period occurs from the time a primary
lesion presents to the development of central nervous
signs and symptoms. Childs and Courville2 described
this as a period of 12 to 16 days; Shaw13 described
this period to be about 5 to 6 days.

15. CLINICAL COURSE :
 Hypopituitarism has been reported in 7 cases of CST, 2 of which
occurred in the acute stage.14-17 Hladky et al14 reported
acute-stage hypopituitarism with subsequent complete
recovery. Anterior hypopituitarism secondary to CST has been
reported secondary to infectious involvement of the pituitary.
The blood supply to the anterior lobe is through the
hypophyseal vessels. The mechanism is thought to be
secondary to venous thrombosis extending from the cavernous
sinus to the hypophyseal vessels. Another proposed
mechanism in the absence of an infectious source is the
proximity of the carotid artery, which makes the pituitary
susceptible to ischemia. Posterior pituitary hormones usually
are not affected because these hormones are synthesized in
the hypothalamus. Hypothalamic infarction has been reported,
with resultant panhypopituitarism secondary to inflammatory
involvement of the carotid artery.15

16.  The present patient with CST developed hyponatremia,
with a serum sodium level of 124 mEq/L and an
osmolality of 248 Osm/kg, and was placed on fluid
restriction for the possibility of a syndrome of
inappropriate antidiuretic hormone release. Laboratory
tests showed a thyroid-stimulating hormone level of
0.112 mIU/L, a free thyroxine level of 0.5 ng/dl, and a
cortisol level of 9.3 ug/dl (microgram/dl). The
endocrinology service diagnosed pituitary apoplexy
and the patient was started on thyroid replacement
and steroid supplementation.

17.  Yarington18 reported a mortality of 13% and a
morbidity of 23% for cases of CST. These rates are
improved significantly compared with a mortality of
80% and morbidity of 75% for cases treated from 1821
to 1960.19
 The improvement is attributable to improved
recognition and diagnosis, systemic antibiotics, and
supportive medical care. CST still carries a significant
mortality, commonly reported as approximately 30%,
with more than 50% cases resulting in morbidity
secondary to cranial neuropathies.20,21

18. DIAGNOSIS :
 Before the availability of computed tomography or
magnetic resonance imaging (MRI), CST was
diagnosed by clinical presentation or at autopsy
examination.
 The use of cerebral angiography or orbital
venography has been reported; however, these
techniques have the potential for serious
complications, including the dissemination of
infection.22,23

19. DIAGNOSIS :
 Direct radiographic signs include expansion of the
cavernous sinus, convexity of the normally concave
lateral wall, abnormal irregular filling defects, and
asymmetry. Indirect signs relate to venous
obstruction, dilation of the superior ophthalmic vein
(Fig 2), exophthalmos, thrombi in the veins, and sinus
tributaries to the cavernous sinus (Fig 3).22-24
 Cerebral angiography can be used for the definitive
assessment of conditions detected on computed
tomographic or MRI scans. Gallium scintigraphy also
has been reported to be useful, with increased uptake
in the cavernous sinus and affected orbits.25

20. CURRENT THERAPY :

21. Surgery :
 Surgical intervention should be directed at the
primary source of the infection and the surrounding
areas of involvement. Incision and drainage of the
involved sites should be accomplished as soon as
possible.

22. Antibiotics :
 Intravenous antibiotic therapy has significantly improved the
prognosis of CST compared with the era before antibiotics and
the early antibiotic era. Empiric antibiotic regimens should be
initiated based on the common pathogens involved,
depending on the source, such as sinusitis, dental abscesses, or
facial cellulitis. While awaiting culture results, antibiotic therapy
should consist of a third-generation cephalosporin, nafcillin,
and metronidazole. Vancomycin can be substituted for nafcillin
if the risk of methicillin resistance is high.21
 Antibiotics should be used for an extended period beyond
clinical resolution to treat the possibility of sequestration within
the thrombus. 18,19,21
 There is no consensus for the duration of antibiotic therapy. It
has been suggested that the duration of antibiotic therapy
approximates that for other intravascular infections, such as
endotheliitis or suppurative phlebitis.21

23. Steroids :
 Steroids have a controversial role in the management of CST.
The benefits of decreasing orbital inflammation, cranial nerve
edema, vasogenic edema, and intracerebral hemorrhage must
be weighed against the potential immunosuppressive effects
and possible prothrombotic properties.
 There is no liter ature to support the improved outcome using
steroids, although there are reports of improved cranial nerve
function secondary to decreased inflammation. 20,26,27
 Steroids have been reported to be useful in cases of adrenal
insufficiency secondary to pituitary dysfunction. Given the rare
occurrence of CST, randomized controlled studies will never be
realized. It would be useful to review the use of steroids in
similar pathogenic situations such as cerebral sinus thrombosis.

24. Steroids :
 Canhão et al28 reported on the use of steroids in cerebral
thrombosis. Six hundred twenty-four adult patients were
included in the International Study on Cerebral Veins and Dural
Sinus Thrombosis (ISCVT).
 One hundred fifty patients (24%) were treated with steroids.
The median duration of steroids treatment was 11 days. The use
of steroids showed a high variation across the participating
centers (from 3.3% to 72%) in cerebral sinus thrombosis.
 The study showed no evidence to support the routine use of
steroids in the acute phase of cerebral vein thrombosis, except
if indicated for the treatment of the underlying disease.
 Steroids were reported as possibly harmful and should be
avoided in patients with cerebral vein thrombosis without
computed tomographic or MRI evidence of parenchymal
lesions.

25. Anticoagulants :
 The role of anticoagulation for the treatment of CST has been
debated.20,21 The proposed benefit is the cessation of progression
of the thrombus in the septic CST. Bacteria may reside within a
thrombus for a period until canalization of the thrombus occurs,
allowing for the penetration of antibiotics. Lyons introduced
anticoagulation therapy for CST in 1941.28a Two studies have
reviewed the use of anticoagulation for CST.19,29 Southwick et al19
reviewed 86 cases of CST and reported a decrease in mortality
from 40% to 14% using heparin. The morbidity was decreased from
50% to 34% in those treated with heparin. Levine et al29 reviewed
the use of anticoagulation in cases of CST at the University of
Michigan Medical Center from 1910 through 1985 and the literature
from 1941 through 1987.
 They found no statistically significant decrease of mortality when
anticoagulation was used in combination with antibiotic therapy
(24%) compared with antibiotic therapy alone (13%). Early
anticoagulation decreased morbidity (blindness, stroke,
ophthalmoplegia, hypopituitarism, focal seizures, and vascular steal
syndrome).

26. Anticoagulants :
 The role of anticoagulation for the treatment of CST has been
debated.20,21 The proposed benefit is the cessation of progression
of the thrombus in the septic CST. Bacteria may reside within a
thrombus for a period until canalization of the thrombus occurs,
allowing for the penetration of antibiotics. Lyons introduced
anticoagulation therapy for CST in 1941.28a Two studies have
reviewed the use of anticoagulation for CST.19,29 Southwick et al19
reviewed 86 cases of CST and reported a decrease in mortality
from 40% to 14% using heparin. The morbidity was decreased from
50% to 34% in those treated with heparin. Levine et al29 reviewed
the use of anticoagulation in cases of CST at the University of
Michigan Medical Center from 1910 through 1985 and the literature
from 1941 through 1987.
 They found no statistically significant decrease of mortality when
anticoagulation was used in combination with antibiotic therapy
(24%) compared with antibiotic therapy alone (13%). Early
anticoagulation decreased morbidity (blindness, stroke,
ophthalmoplegia, hypopituitarism, focal seizures, and vascular steal
syndrome).

27. Anticoagulants :
 The neurologic outcome was more favorable in
patients who underwent early anticoagulation with
antibiotics (69%) compared with antibiotics alone
(39%) and those who underwent late anticoagulation
with antibiotics (41%).29
 Anticoagulation therapy has the risk of intracranial
and systemic hemorrhage and may result in
dissemination of septic

28.  emboli.19,29 There have been 2 cases of intracranial
hemorrhage reported in patients receiving
anticoagulation for CST. One fatal case was related to
dicumarol therapy after heparin use, where the
prothrombin time increased 3 times the normal
level.29 The other case resulted in a subarachnoid
hemorrhage with subsequent coma.
 This resolved with reversal of the anticoagulation. 30
The present patient had a watershed infarct seen on
magnetic resonance angiogram (Fig 4). Systemic
hemorrhagic complications are rare and include
gastrointestinal bleeding and hematuria

29.  Because of the difference between CST and aseptic
dural sinus thrombosis, it is not possible to extrapolate
the data. However, given the rarity of CST, it is worth
reviewing the literature for guidelines for the
management of cerebral sinus thrombosis

30.  Several recent articles have evaluated the benefits of
anticoagulation for dural sinus thrombosis.31-35 De
Bruijn and Stam31 performed a prospective, randomized,
controlled trial with low-molecular-weight heparin in the
treatment of aseptic dural sinus thrombosis. No cases of
intracranial hemorrhages were reported. There was better
overall outcome in the anticoagulant group than in the
placebo group, but this was not statistically significant.
 Different types of anticoagulation have been reported:
intravenous, subcutaneous, intramuscular, low-molecular-
weight heparin, and oral anticoagulants.

31.  A recent multicenter study evaluated unfractionated heparin
versus low-molecular-weight heparin for the treatment of
cerebral venous thrombosis.36 Unfractionated heparin has a
nonlinear dose-response effect, resulting in a less predictable
response. Unfractionated heparin does have a faster therapeutic
level and requires dose adjustments based on activated partial
thromboplastin times. In addition, it can be antagonized with
protamine sulfate in acute situations. Low-molecular-weight
heparin has a stable therapeutic effect and therefore can be
administered in a fixed weight-adjusted dose.
 There is a lower incidence of heparin-induced thrombocytopenia
with low-molecular-weight heparin. In a nonrandomized
comparison of a prospective cohort study, low-molecular-weight
heparin was associated with fewer new intracerebral
hemorrhages, especially in patients with intracerebral lesions at
baseline. There was no difference in complete recovery and
mortality.36

32.  Levine et al29 recommended a partial thromboplastin time 1.5 to 2
times the normal level and a prothrombin time at 1.3 to 1.5 times the
control level. Southwick et al19 recommended anticoagulation not to
exceed 2 times the normal level. Bhatia and Jones20 recommended a
partial thromboplastin time 1.5 to 2.5 times the normal level and an
international nor-malized ratio of 2 to 3. The duration of
anticoagulation has ranged from a few weeks to several months. It
has been suggested that anticoagulation be continued until there is
radiologic resolution of the thrombus. In a review, the European
Federation for Neurological Societies guideline on the treatment of
cerebral venous and sinus thrombosis stated that anticoagulant
therapy after the acute phase is unclear.
 Oral anticoagulation may be given for 3 months if cerebral venous
and sinus thrombosis was secondary to a transient risk factor and
longer if there was an underlying thrombophilia.37 It would be
reasonable to conclude that, in the absence of other underlying
thrombophilia, the patient with CST is considered to have a transient
risk factor, acknowledging the obvious underlying differences in
pathogenesis.

33.  Although a rare condition, clinical assessment should
guide the need for adjunctive studies in the diagnosis
of CST. The presence of constitutional symptoms and
ocular findings should be followed with an MRI scan.
Prompt incision and drainage with empiric antibiotic
therapy is necessary. The use of anticoagulation should
be determined based on the patient’s response to
initial medical management. Early anticoagulation
appears to be more effective in decreasing morbidity.
The present case reflects the potential for CST to be
progressive and cause significant morbidity, even with
aggressive surgical and medical management.

34.  Treatment guidelines are challenging to develop
because CST is rare. It would seem reasonable to
extrapolate recommendations for the managementof
cerebral venous and sinus thrombosis. Although the
pathophysiology differs, there are common features.

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