A grand round case presented at AHMC internal medicine department. discusses on the differential diagnosis and approach to CVT.

1.  Cerebral Venous Thrombosis
(CVT)

2. Cerebral Venous Thrombosis:
Thrombosis of the dural sinus and/or cerebral
veins
Cerebral vein and dural sinus thrombosis
(CVT) is less common than most other types of
stroke but can be more challenging to
diagnose

4. EPIDEMIOLOGY
 The available data suggest that CVT is uncommon
The annual incidence ranges from 0.22 to 1.57 per
100,000
 more common in women than men, with a female to
male ratio of 3:1
The imbalance may be due to the increased risk of CVT
associated with pregnancy and puerperium and with
oral contraceptives

5. the mean age of patients with CVT was 39
years
8 percent of the patients were older than 65

8. RISK FACTORS AND CAUSES
The most frequent risk factors for CVT are
Prothrombotic conditions, either genetic or
acquired
Oral contraceptives
Pregnancy and the puerperium
Malignancy
Infection
Head injury and mechanical precipitants

11.  No underlying etiology or risk factor for CVT is
found in approximately 13 percent of adult
patients
In older adult CVT patients, the proportion of
cases without identified risk factors is higher
(37 percent) than it is in adults under age 65

12. Clinical presentations
 Cerebral vein and dural sinus thrombosis has a highly
variable clinical presentation
 The onset can be acute, subacute, or chronic
 CVT most often presents with new headache or as a
syndrome of isolated intracranial hypertension
 Additional manifestations include focal neurologic
deficits, seizures, and/or encephalopathy.

13.  Symptoms and signs of CVT can be grouped in three
major syndromes:
Isolated intracranial hypertension syndrome
(headache with or without vomiting, papilledema,
and visual problems)
Focal syndrome (focal deficits, seizures, or both)
Encephalopathy (multifocal signs, mental status
changes, stupor, or coma)

14. Headache
 the most frequent symptom of CVT
 it was present in 89 percent of patients
 Headaches associated with CVT are more
frequent in women and young patients than in
men or older adults
Headache is usually the first symptom of
CVT, and can be the only symptom

15. The features of CVT-related headache are quite
variable
Head pain is more often localized than diffuse
Headache onset with CVT is usually gradual,
increasing over several days
Headache due to CVT may also resemble
migraine with aura

16. Seizures
 Focal or generalized seizures, including status
epilepticus
In the ISCVT cohort of 624 patients, seizures at
presentation occurred in 39 percent, and seizures
after the diagnosis of CVT occurred in 7 percent
 Variables associated with seizures include
supratentorial parenchymal brain lesions,
sagittal sinus and cortical vein thrombosis, and
motor deficits

17. Isolated intracranial hypertension
syndrome
headache associated with papilledema
 visual problems

18. Encephalopathy
Severe cases of CVT can cause disturbances of
consciousness and
cognitive dysfunction, such as delirium,
apathy, a frontal lobe syndrome, multifocal
deficits, or seizures.

19. Focal syndrome
Weakness with monoparesis or hemiparesis
motor weakness was present in 37 percent of
patients
 Aphasia,
Sensory deficits and visual field defects are
less common.

20. Clinical presentations
Clinical manifestations of CVT may also depend
on the location of the thrombosis
Superior sagittal sinus is most commonly
involved, which may lead to headache, increased
intracranial pressure, and papilledema.
– A motor deficit, sometimes with seizures, can also
occur.
– Scalp edema and dilated scalp veins may be seen on
examination

22. Clinical presentations
• Lateral sinus thromboses, symptoms related to an
underlying condition (middle ear infection) may
be noted, including constitutional symptoms,
fever, and ear discharge.
– Pain in the ear or mastoid region and headache are
typical
– On examination, increased intracranial pressure and
distention of the scalp veins may be noted.
– Hemianopia, contralateral weakness, and aphasia
may sometimes be seen owing to cortical
involvement

23. Clinical presentations
• Deep cerebral venous system
– Occurs in approximately 16% of patients with CVT
– Include internal cerebral vein, vein of Galen, and
straight sinus
– This can lead to thalamic or basal ganglial
infarction.
– Most patients present with rapid neurological
deterioration.

24. Clinical presentations
 important clinical features distinguish CVT
from other mechanisms of cerebrovascular
disease
1. Focal or generalized seizures are frequent,
occurring in 40% of patients
2. An important clinical correlate to the anatomy of
cerebral venous drainage is that bilateral brain
involvement is not infrequent.

25. Clinical presentations
3. Finally, patients with CVT often present with
slowly progressive symptoms.
• Delays in diagnosis of CVT are common and significant.

26. Work Up:
• A complete blood count
• Chemistry
• Sedimentation rate.
• Measures of the prothrombin time and
activated partial thromboplastin time.
• Screening for potential prothrombotic
conditions that may predispose a person to
CVT

27. • Lumbar Puncture:
– Elevated opening pressure in > 80%
– Unless there is clinical suspicion of meningitis,
examination of the cerebrospinal fluid (CSF) is
typically not helpful.
– Elevated cell counts (50%) and protein (35%)
can be seen.
• There are no specific CSF abnormalities in CVT

28. • D-Dimer
– Measurement of D-dimer, a product of fibrin
degradation
– Usually increased in cvt pts

29. • A normal D-dimer level according to a sensitive
immunoassay or rapid enzyme-linked
immunosorbent assay (ELISA) may be considered to
help identify patients with low probability of CVT
• If there is a strong clinical suspicion of CVT, a normal
D-dimer level should not preclude further
evaluation.

30. DIAGNOSIS
In patients with clinically suspected CVT
 presenting with new headache
isolated intracranial hypertension syndrome,
 focal neurologic deficits,
seizures, and/or encephalopathy
urgent neuroimaging is necessary as the first step in the
diagnostic evaluation.

31. Diagnostic approach — The diagnosis of CVT should
be suspected in patients who present with one or
more of the following:
 New onset headache
 Headache with features that differ from the usual
pattern
 Symptoms or signs of intracranial hypertension
 Encephalopathy
 Focal neurologic symptoms and signs

32. Imaging

33. Imaging
• Non Invasive Imaging:
– CT, MRI, Ultrasonography
• Invasive Imaging:
– Cerebral Angiography and Direct Cerebral
Venography

34. CT
 Plain CT being abnormal only in <30% of CVT
cases
Hyperdensity of a cortical vein or dural sinus
seen.

35. CT
• Acutely thrombosis : Hyperdensity
• Thrombosis of the posterior portion of the
superior sagittal sinus may appear as a dense
triangle – Dense delta sign
• Ischemic infarction/hemorrhage may be seen.

38. Contrast-enhanced CT:
• filling defect within the vein or sinus.
– may show the classic “empty delta” sign

43. Magnetic Resonance Imaging
MRI signal intensity vary according to duration of
the thrombus
 1st week : isointense to brain tissue on T1-weighted
images and hypointense on T2- weighted images
 2nd week - hyperintensity on T1- and T2-weighted
images.

45.  Types of parenchymal hemorrhage in CVT:
 Brain parenchymal changes in frontal, parietal,
and occipital lobes usually correspond to superior
sagittal sinus thrombosis
 Temporal lobe parenchymal changes correspond
to lateral (transverse) and sigmoid sinus
thrombosis
 Thalamic hemorrhage, edema, or intraventricular
hemorrhage, correspond to thrombosis of the
vein of Galen or straight sinus.

47. MRI and CT Venography
• CT Venography
– CTV can provide a rapid and reliable modality for
detecting CVT
– CTV is much more useful in subacute or chronic
situations because of the varied density in
thrombosed sinus

48. Noninvasive Diagnostic Modalities
• CT Venography
– Because of the dense cortical bone adjacent to
dural sinus, bone artifact may interfere with the
visualization of enhanced dural sinus.
– CTV is at least equivalent to MRV in the diagnosis
of CVT.

51. • Magnetic Resonance Venography

55. Invasive Diagnostic Angiographic
Procedures
Cerebral Angiography and Direct Cerebral
Venography
Invasive cerebral angiographic procedures are less
commonly needed to establish the diagnosis of
CVT given the availability of MRV and CTV

56. Cerebral Angiography
• findings include
The failure of sinus appearance due to the occlusion;
Venous congestion with dilated cortical, scalp, or facial
veins;
Enlargement of typically diminutive veins from
collateral drainage and
Reversal of venous flow
The venous phase of cerebral angiography will show a
filling defect in the thrombosed cerebral vein/sinus

57. • Cerebral Angiography
– Because of the highly variable cerebral venous
structures and inadequate resolution, CT or MRI
may not provide adequate visualization of
selected veins, especially cortical veins and in
some situations the deep venous structures.

59. Direct Cerebral Venography
Direct cerebral venography is performed by direct
injection of contrast material into a dural sinus or
cerebral vein from microcatheter insertion via the
internal jugular vein.
Direct cerebral venography is usually performed
during endovascular therapeutic procedures

60. An early follow-up CTV or MRV is
recommended in CVT patients with persistent
or evolving symptoms despite medical
treatment or with symptoms suggestive of
propagation of thrombus

61. Recommendations
Although a plain CT or MRI is useful in the initial
evaluation of patients with suspected CVT, a
negative plain CT or MRI does not rule out CVT
A venography study (either CTV or MRV) should
be performed in suspected CVT if the plain CT or
MRI is negative or to define the extent of CVT if
the plain CT or MRI suggests CVT

62. In patients with previous CVT who present
with recurrent symptoms suggestive of CVT,
repeat CTV or MRV is recommended
A follow-up CTV or MRV at 3 to 6 months after
diagnosis is reasonable to assess for
recanalization of the occluded cortical
vein/sinuses in stable patients

63. our case

64. • Head ache
• Blurring of vision
• Female
• Age of the patient is 33yrs
• History of using OCP for 1 month

65. • Papilledema
• MRI and MRV
.

66. Management

67. Acute Management of CVT
• CVT is an uncommon but potentially serious
and life threatening cause of stroke.
• On the basis of findings for stroke unit care in
general, management of CVT in a stroke unit
is reasonable for the initial management of
CVT to optimize care and minimize
complications.

68. Initial Anticoagulation
• There are several rationales for
anticoagulation therapy in CVT
– To prevent thrombus growth,
– To facilitate recanalization, and
– To prevent DVT or PE.

69. Initial Anticoagulation:
• Acute anticoagulation: Heparin is indicated
• Presence of pre treatment ICH is not a
contraindication
• LMW heparin is preferred over UFH
• Anticoagulation appears safe and effective

70. 9% to 13% have poor outcomes despite
anticoagulation
Anticoagulation alone may not dissolve a large
and extensive thrombus
Partial or complete recanalization rates for CVT
ranged from 47% to 100% with anticoagulation
alone.

71.  CVT with cerebral hemorrhage on
presentation can occur
 In this special situation, even in the absence of
anticoagulation, hemorrhage is associated
with adverse outcomes.

72.  Two randomized trials , which were also
analysed in a recently updated Cochrane
review
 with a total of 79 adult patients showed that
anticoagulation with heparin [unfractionated
(UFH) or low molecular-weight (LMWH)
heparin] was associated with reduce the
adverse outcomes

73.  After randomization, three patients developed a
new intracerebral haemorrhage and all were
allocated to placebo
 One of these patients later died.
 Two of the intracerebral haemorrhages occurred
in patients who did not have a

74. Recommendation
 treating adult patients with acute CVT with
heparin at therapeutic dosage
 This recommendation also applies to patients
with an intracerebral haemorrhage at baseline

75. Treatments
• Invasive treatments
– Many invasive therapeutic procedures have been
reported to treat CVT.
– These include
1. Direct catheter chemical thrombolysis and
2. Direct mechanical thrombectomy with or without
thrombolysis.
– There are no randomized controlled trials to
support these interventions compared with
anticoagulation or with each other.

76. Treatments
• Surgical Considerations
– As endovascular options for management of
venous thrombosis have evolved, surgery has
played an increasingly limited role.
– Surgical thrombectomy is needed uncommonly
but may be considered if severe neurological or
visual deterioration occurs despite maximal
medical therapy

77. Management
 Aspirin
– There are no controlled trials or observational
studies that directly assess the role of aspirin in
management of CVT
 Steroids
– No role
– steroids may enhance hypercoagulability.

78. Others
• Antibiotics
– Local (eg, otitis, mastoiditis) and systemic (meningitis,
sepsis) infections can be complicated by thrombosis
of the adjacent or distant venous sinuses.
– The management of patients with a suspected
infection and CVT should include administration of the
appropriate antibiotics and
– the surgical drainage of infectious sources (ie,
subdural empyemas or purulent collections within
the paranasal sinuses).

79. Management & Prevention of Early
Complications
These are
 Hydrocephalus
 Intracranial Hypertension,
 Seizures
 Vision loss

80. • Seizures
– Seizures are present in 37% of adults,
– Because seizures increase the risk of anoxic
damage, anticonvulsant treatment after even a
single seizure is reasonable
– In the absence of seizures, the prophylactic use of
antiepileptic drugs may be harmful

81. Recommendations
 In patients with CVT and a single seizure
without parenchymal lesions, early initiation
of antiepileptic drugs for a defined duration
is probably recommended to prevent further
seizures
 In the absence of seizures, the routine use of
antiepileptic drugs in patients with CVT is not
recommended

82. • Hydrocephalus
– The superior sagittal and lateral dural sinuses are the
principal sites for CSF absorption by the arachnoid
granulations, highly vascular structures that protrude
across the walls of the sinuses into the subarachnoid
space and drain into the venous system.
– In CVT, the function of the arachnoid granulations may
be impaired, potentially resulting in failure of CSF
absorption and communicating hydrocephalus (6.6%)

83.  Treatment
– Neurosurgical evacuation of CSF with
ventriculostomy, or
– in persistent cases, ventriculoperitoneal shunt, is
necessary

84.  Intracranial Hypertension
– Up to 40% of patients with CVT present with
isolated intracranial hypertension
– Clinical features include progressive headache,
papilledema, and third or sixth nerve palsies.

85. Intracranial Hypertension treatment
 No randomized trials are available to clarify the
optimal treatment;
 however, rational management of intracranial
hypertension includes a combination of treatment
approaches
• measures to reduce the thrombotic occlusion of venous
outflow, such as anticoagulation and possibly
thrombolytic treatment, may result in resolution of
intracranial hypertension.

86.  acetazolamide is a commonly used therapeutic
alternative for the treatment of intracranial
hypertension with CVT
 It may have a limited role in the acute
management of intracranial hypertension for
patients with CVT.

87.  Serial lumbar punctures may be necessary when
hypertension is persistent.
 In refractory cases, a lumbo peritoneal shunt may
be required.

88. Intracranial Hypertension treatment
 Because prolonged pressure on the optic nerves can
result in permanent blindness
 it is of paramount importance to closely monitor
visual fields and the severity of papilledema during
the period of increased pressure.
 Ophthalmologic consultation is helpful for this.
 Although rarely required, optic nerve fenestration is a
treatment option to halt progressive visual loss.

89. Long-Term Management
 Prevention strategies focus on preventing
recurrence of CVT or other VTE in those CVT
patients at high risk of these outcomes
 Overall, there is approximately a 6.5% annual
risk of any type of recurrent thrombosis

90. Long-Term Management
 The risk of other manifestations of VTE after
CVT ranges from 3.4% to 4.3% on the basis of
the largest studies of this medical condition
 Patients with severe thrombophilia have an
increased risk of VTE.

91. Risk Stratification for Long-Term Management
 Thrombophilias may be hereditary or acquired
 Among the patients, the hereditary
thrombophilias with the highest recurrence rates
for VTE in the absence of ongoing
anticoagulation have been
Deficiencies of antithrombin,
Protein C, and
Protein S
APS

92.  Recurrence rates were 19% 2 years, 40% at 5
years, and 55% at 10 years
 Hyperhomocysteinemia, a common
hereditary or acquired risk factor for VTE, was
not significantly associated with a high risk of
recurrence.

93. Recommendations
 Testing for prothrombotic conditions,
including protein C, protein S, antithrombin
deficiency, antiphospholipid syndrome,
prothrombin G20210A mutation, and factor V
Leiden, can be beneficial for the management
of patients with CVT.

94. Recommendations
 In patients with provoked CVT (associated
with a transient risk factor), vitamin K
antagonists may be continued for 3 to 6
months, with a target INR of 2.0 to 3.0
 In patients with unprovoked CVT, vitamin K
antagonists may be continued for 6 to 12
months, with a target INR of 2.0 to 3.0

95.  For patients with recurrent CVT, VTE after
CVT, or first CVT with severe thrombophilia
indefinite anticoagulation may be considered,
with a target INR of 2.0 to 3.0

97. CVT During Pregnancy
 Pregnancy induces changes in the coagulation
system that persist into the puerperium and
result in a hypercoagulable state, which
increases the risk of CVT.
 The greatest risk periods for CVT include the
third trimester and the first 4 postpartum
weeks.

98.  For women with CVT during pregnancy,
LMWH in full anticoagulant doses should be
continued throughout pregnancy, and
 LMWH or vitamin K antagonist with should be
continued for at least 6 weeks postpartum
(for a total minimum duration of therapy of 6
months)

99.  It is reasonable to advise women with a
history of CVT that future pregnancy is not
contraindicated
 For women with a history of CVT, prophylaxis
with LMWH during future pregnancies and
the postpartum period is probably
recommended

100. Prognosis
 Central nervous system infection,
 Any malignancy,
 Thrombosis of the deep venous system,
 Intracranial hemorrhage on admission CT/MRI,
 Glasgow Coma Scale score < 9,
 Mental status disturbance,
 Age >37 years, and
 Male sex
 Seizure

101.  Early Death
Approximately 3% to 15% of patients die in the
acute phase of the disorder
Most early deaths are a consequence of CVT

102.  The main cause of acute death with CVT is
transtentorial herniation secondary to a large
hemorrhagic lesion,
 Status epilepticus, medical complications, and PE
are among other causes of early death

103. Long-Term Outcome
• Neuropsychological and Neuropsychiatric
Sequelae
– Memory deficits, behavioral problems, or
executive deficits may persist
– Aphasia, in general of the fluent type, results from
left lateral sinus thrombosis with temporal infarct
or hemorrhage.

104. • Recovery is usually favorable, but minor troubles in
spontaneous speech and naming might persist

105. Case reports

107. 1.Case Report
• A 42-year old Nepali male was admitted to the
National Institute of Neurological and
AlliedSciences, Kathmandu complaining of a week-
long history of a continuous headache
• The headache was global in nature, with no
associated vomiting. The evening preceding
admission,
• The patient had also noted photophobia, speech
disturbance and weakness of his right upper limb.

108. • There was no history of trauma, no relevant past
medical or drug history and no family history of
note.
• On examination, the patient's observations were
stable with a GCS of 15/15
• His pupils, fundi and speech appeared normal
and there was no evidence of any focal
neurological deficit or meningism

109. • A computerized tomography (CT) scan
appeared normal and lumbar puncture
showed an opening pressure of 30 cm H2O
with normal constituents.
• D-dimer and fibrinogen degradation product
(FDP) were marginally raised;

110. • Magnetic resonance venography (MRV)
confirmed the presence of a superior sagittal
sinus thrombosis with a small venous infarct
and
• the patient was subsequently anticoagulated
with enoxaparin and warfarin.

111. • Further investigations including echocardiography,
carotid artery Doppler, coagulation studies and
antiphospholipid antibody titres were all normal
• A follow-up MRV was performed 8 days after diagnosis
which showed improved perfusion throughout the
superior sagittal sinus .
• The patient made a good recovery and was
subsequently discharged home 10 days post admission

113. 2.Case Report
• A 42 year old house wife was admitted to the stroke
unit with sudden onset of left sided numbness and
weakness.
• She was otherwise healthy with no history of any
previous medical problems
• On examination her weight was 64 kg, blood pressure
was 130/79 mmHg, pulse 80 per minute and she was
afebrile.
• General examination was unremarkable. Cardiac
and respiratory examination was also normal.

114. • Neurological examination showed normal cranial
nerves except for mild flattening of the left naso-
labial fold.
• There was mild weakness on the left side which
was graded as 4. Left side also showed
decreased sensation as compared to the right
side.
• Magnetic Resonance Imaging (MRI) of the brain
showed small right parietal stroke

115. • A workup for hypercoagulable state was
performed including anti-phospholipid
antibodies, protein C & S activity, antithrombin
III, Factor V leiden deficiency and homocystein
levels were within normal range
• As no definite cause of stroke was found, the
history was re-assessed. Patient was asked
several directed questions about medications

116. • It was revealed by the husband that she had
been on oral contraceptives for several days
prior to this episode
• She took oral contraceptives to cease her
menstrual cycle temporarily as she was going
for 'Hajj‘
• This information was not disclosed by the
patient

117. • Magnetic Resonance Venogram (MRV) was
performed after this information and a
thrombus was seen in the right transverse
sinus
• Patient was started on anticoagulation and
she recovered completely

119. 3.Case Report
 A man, aged 70 years, with progressive
occipital headache and nausea was admitted
to ward.
 He had a clinical history of hypertension that
was being treated with ramipril 5 mg per day
 The rest of his past medical history was
unremarkable.

120.  On admission, he was afebrile with a blood
pressure of 140/70 mmHg.
 Physical and neurological examinations were
normal with no evidence of meningism or any
focal neurological deficit.
 A CT scan was performed showing SAH in the
right parietal lobe showed a thrombosis in
the right transverse sinus

124.  The angiography revealed no aneurysm.
 The patient underwent a complete hemocoagulative
study comprehensive of
 protein C, protein S,
 antithrombin III,homocysteine,
 antiphospholipid antibodies and lupus anticoagulant,

125.  resistance to activated protein C, factors VIII and
VII,
 mutation analysis of the prothrombin gene, and
factor V Leiden.
 All results were in the normal range except for
total homocysteine that was 26 µmol/L (normal
value < 15
µmol/L).
 The levels of folic acid and cobalamine were
normal

126. • later it was found that the patient was
heterozygous for the
methylenetetrahydrofolate reductase C667T
mutation
• He began treatment with ordinary care

127. • Low-molecular weight heparin, 60 mg once a
day, was initiated from admission.
• The third day after admission, raised the dose
to 120 mg per day for a week.
• The patient was then started oral
anticoagulation after no evidence of worsening
of SAH
• Then after the patient clinically improved

128. • Strength
• Anti coagulations started earily
• Imaging early
• Weakness
• ?? Steriod
• Screening about the inherited hemophilias

129. Take home messages
 CVT should be considered in the differential
diagnosis of patients presenting with SAH
without evidence of aneurysm
 Pregnancy or post partal woman with stroke
CVT should be considered first and image a pt
with MRI with MRV
 Advise pts with cvt not to take ocp for the
future

130. Reference
• Up to date 2018
• Brants and Helms Fundementals of Diagnostic
Radiology 5th edition (chap..neuro radiology )
• European Academy of Neurology (EAN 2017
guidelines
• American stroke Associations (ASA) 2011
guidelines
• Internet

131. Thank you