Posterior Fossa Re-exploration

1. Repeat posterior fossa
exploration for patients with
persistent or recurrent
idiopathic trigeminal
neuralgia
Nelly Amador et al
Mayo Clinic College of
Medicine, Rochester, Minnesota

2. Trigeminal neuralgia
• most common and disabling forms of facial pain
• paroxysmal, shock-like pain in ≥ 1 divisions of the
trigeminal nerve
• incidence of 26.8 cases per 100,000 person-years
Medically refractory TN:
• MVD, glycerol rhizotomy, balloon
microcompression of the trigeminal ganglion,
radiofrequency rhizotomy, stereotactic
radiosurgery

3. MVD
• Less destructive of the nerve
• Durable pain relief
• preferred operation for patients with
medically unresponsive TN

4. Facial pain after MVD
Dilemma:
• should these patients undergo less
invasive procedures associated with a
higher risk for sensory loss
or
• should they undergo repeat PFE in the
hope of relieving their facial pain and not
having new or additional facial sensory
loss?

5. Repeat PFE
• Thirty of 186 patients (16%) had earlier undergone a
PFE for idiopathic TN
• September 2000 and November 2006
• 29 patients underwent repeat PFE for persistent TN.
• mean age 29 patients (14 men, 15 women) was 61.1
years (range 32–81yrs)
• mean duration of pain in these patients was 11.2
years (range 4–29 years).
• Single division pain 9 patients (31%)
• Multiple divisions pain 20 patients (69%).

6. Repeat PFE
• Intent of surgery was to remove any compression
from the trigeminal nerve if possible
• If no compressing lesions were noted at the time of
surgery, or if it was believed to be unsafe to perform
an MVD, then a Partial nerve section (PNS) was
performed
• mean patient follow-up after surgery was 33.7
months (range 4 days–72 months)
Facial pain outcomes were defined as
• excellent (no pain and not receiving medications),
• good (no pain, taking medications at a reduced dose
compared with before surgery)
• poor (pain despite receiving medications).

7. Results
• Average time interval between PFEs was 5.8 years
(range 4 days–29 years)
• Compression of the trigeminal nerve was noted by
– artery (13 patients, 45%),
– vein (4 patients, 14%), or
– Teflon (7 patients, 24%)
• MVD was performed in 18 patients (62%)
• Compressive lesions
– superior cerebellar artery (10 patients),
– superior and anterior inferior cerebellar arteries (2 patients),
– basilar and superior cerebellar arteries (1 patient),
– Teflon (3 patients),
– Teflon and veins (1 patient),
– veins (1 patient)

8. Results
• PNS was performed in 11 patients (38%)
• In 5 of these patients a compressive lesion was noted
(vein, 2 patients; Teflon, 3 patients), but a PNS was
performed as well because the observed
neurovascular compression was believed to be
relatively minor and an MVD alone might not relieve
the patient's facial pain.
• Excellent facial pain outcome (no pain, not receiving
medications) was achieved and maintained for
– 80% of patients at 1year
– 75% of patients at 3 years

9. Results
• Fifteen patients (52%) had new or increased facial
numbness after surgery
• New or increased trigeminal deficits were noted in
– 10 (91%) of 11 patients who underwent a PNS
– 5 (28%) of 18 patients who underwent an MVD.
• Two patients (7%) developed anesthesia dolorosa
• Other postoperative complications included
– hearing loss (2 patients),
– temporary ataxia (2 patients),
– cerebrospinal fluid leak (1 patient),
– aseptic meningitis (1 patient), and
– wound infection (1 patients).

10. Conclusions
• Repeat PFE for patients with persistent or recurrent
TN after prior PFE is a safe and effective option
• Results comparable with other destructive
procedures
• risk of hearing loss is greater with repeat operations
compared with primary procedures
• Patients with ongoing TN after prior PFE should be
considered for repeat PFE if they are medically well,
especially if less invasive surgeries have not relieved
their facial pain.

11. Pituitary apoplexy:
correlation between
magnetic resonance
imaging and
histopathological results
Patrick L. Semple et al
University of Cape Town, South
Africa

12. Objective
• To correlate the MRI findings in pituitary
apoplexy with histopathological results
• To determine whether the
histopathology influences clinical
presentation and outcome

13. Methods
• 36 patients with histologically confirmed
pituitary apoplexy
• between 1996 and 2006
• MR images were divided into 3 groups:
1) infarction alone;
2) hemorrhage with or without infarction;
3) tumor only with no evidence of
apoplexy

14. Methods
• Histological examination was divided into
– Infarction alone or
– Hemorrhagic infarction/hemorrhage
• MR imaging findings correlated with the
histopathological results to assess how
accurately the histopathology was predicted
by the MR imaging
• Clinical features and outcomes of the two
histopathological groups were also compared

15. Methods
• MR images as well as the radiologists' reports were
studied in 19 patients, and in 17 patients only the
radiologist's report was available
• Features that were noted :
– the presence of blood products indicating hemorrhage or
hemorrhagic infarction;
– the appearance of infarction alone with no blood products;
– the presence of a pituitary tumor alone with no obvious
evidence of pituitary apoplexy; and
– the presence of mucosal thickening in the sphenoid sinus

16. Results
• MR imaging findings were able to
predict the histopathology accurately in
the majority of cases
• Group of patients with infarction had
less severe clinical features and a better
outcome than those with hemorrhagic
infarction/hemorrhage.

17. Results
• Average length of time from the onset of symptoms
until presentation was 14.8 days (range of 1 to > 90
days)
• Four patients had a history of a pituitary adenoma
– 1 Nelson’s syndrome
– 1 earlier operated for pituitary adenoma
• Identifiable predisposing factors in 8 patients.
– Four patients had undergone recent surgery: 2 had coronary
artery bypass surgery immediately prior to apoplexy.
– One patient had disseminated intravascular coagulation
secondary to liver failure,
– 1 was postpartum,
– 1 was receiving anticoagulant therapy, and
– 1 had just received Gamma Knife treatment for Nelson's
syndrome on the day the apoplexy developed

18. Results: HPR
• 36: Pituitary adenoma with apoplexy
• 1 bleed into Rathke’s cleft cyst.
Histopathological findings were divided into 2
groups.
• first group: included patients in whom only
infarction could be identified after
histopathological examination (ghost cells),
with no evidence of hemorrhage.
• second group consisted of patients in whom
the histopathological sections showed
hemorrhagic infarction or hemorrhage alone.

19. Results HPR
• MR images were divided into 3 groups:
1) infarction alone;
2) hemorrhage with or without
infarction;
3) tumor only with no evidence of
apoplexy

20. MRI vs HPR
MRI:
• only infarction of the pituitary tumor: 17 patients
• hemorrhage with or without infarction:15 patients
• only pituitary tumor with no imaging evidence of
hemorrhage or infarction: 4 patients
Correlates:
• MR imaging diagnosis of infarction was accurate in
16 (94%) of 17 patients
• Hemorrhagic infarction/hemorrhage in only 2 patients
(12%) of 15 patients
• Of 4 with MRI showing tumor alone, the
histopathology results 3 demonstrated hemorrhagic
infarction or hemorrhage, and in 1 patient infarction
only

21. MRI vs HPR

22. HPR vs MRI

23. HPR vs MRI
• Of the 19 patients who showed
histopathological grouping of hemorrhagic
infarction or hemorrhage,
– hemorrhagic infarction or hemorrhage was
diagnosed in 13 patients (68%),
– pituitary tumor in 3 (16%), and
– infarction alone in 3 (16%) using MR imaging.
• Therefore, in 68% of cases the
histopathology results correlated with results
that had been demonstrated on MR imaging.

24. HPR vs MRI
• Of the 17 patients with a histopathology
diagnosis of infarction alone,
– 14 (82%) were believed to only have evidence of infarction
alone on MR imaging,
– 2 (12%) were believed to have hemorrhagic infarction or
hemorrhage, and
– 1 (6%) only a pituitary tumor.
• Therefore the histopathology results
correlated with the MR imaging findings in
82% of the patients when studied
retrospectively.

25. HPR vs Clinical presentation
severe neurological deficits—namely diminished level
of consciousness and blindness—in those patients
with hemorrhagic infarction/hemorrhage on
histopathological examination.

26. HPR vs Outcome

27. HPR vs outcome
Visual outcome at follow-up
In the infarction group: (17)
• normal in 14 patients (82%)
• improved with minor visual deficits in 3 patients
(18%).
• No patient was blind.
In the hemorrhagic infarction/hemorrhage
group: (19)
• normal in 12 patients (63%),
• improved with functional vision in 4 patients (21%),
and
• blind in 2 (11%).
• One patient was lost to follow-up early and was not

28. HPR vs outcome
Ophthalmoplegia
In the infarction group (17)
• Fourteen of the patients had no ophthalmoplegia
• 3 still had residual deficits although they were
improved
In the hemorrhagic infarction/hemorrhage
group: (19)
• 13 patients had no ophthalmoplegia,
• 5 were improved, and
• 1 patient was lost to follow-up and could not be
assessed

29. Conclusion
• Correlation between the histopathological
groups regarding clinical presentation and
outcome, with the patients in the infarction
group showing a less severe presentation
• Magnetic resonance imaging appears to be
able to predict the histopathological diagnosis
and consequently may help in further
improving the outcome in these patients.

30. Ventricular catheter
trajectories from traditional
shunt approaches: a
morphometric study in
adults with hydrocephalus
Christopher R. P. Lind et al
University of Auckland,
Auckland City, New Zealand

31. Objective
• To compare the margins of error of different
shunt catheter approaches to the lateral
ventricle
• To assess surface anatomical aiming
landmarks for free-hand ventricular catheter
insertion in adult patients with hydrocephalus.

32. Methods
• Four adults who had undergone stereotactic
brain magnetic resonance (MR) imaging and
had normal ventricles, and 7 prospectively
recruited adult patients with acute
hydrocephalus were selected for inclusion in
this study
• Reconstructed MR images obtained prior to
surgical intervention were geometrically
analyzed with regard to frontal, parietal, and
parietooccipital (occipital) approaches in both
hemispheres using image guidance software.

33. Approaches
The approaches modeled
• the frontal approach, with an entry point 11
cm caudal to the orbital rim and 3 cm lateral
to the midline;
• 2 parietal entry points, either 2.5 cm superior
to the top of the pinna and 2.5 cm posterior,
or 3 cm superior and 3 cm posterior;
• 2 occipital entry points, either 6 cm superior
to the inion and 3 cm lateral to it, or 6 cm
superior and 4 cm lateral to the inion.

34. Approaches
Frontal horn location was defined as
• anterior to the interventricular foramen of
Monro
• was the target zone of the frontal and
occipital approaches.
Atrium location was defined as
• posterior to the pulvinar of the thalamus and
anterior to the posteromedial angulation of
the occipital horn
• was the target zone of the parietal approach

35. Methods
• Lines were projected from the bur hole entry
point to the most medial and lateral (coronal
plane), and the most superior and inferior
(sagittal plane) extents of the ventricular
target zone relevant to the approach.
• Trajectories through the thalamus were
excluded. Angles between the lines in each
plane were calculated to generate the range
of successful trajectories
• The 4 lines were projected onto the forehead
or scalp of the side of the head and related
geometrically to the frontonasal angle and
external auditory meatus.

36. Results
• Frontal approach yielded the widest range of
successful trajectories to the dilated frontal
horn, the mean being 42° in the sagittal plane
and 30° in the coronal plane (p < 0.001
compared with the occipital)
• No statistically significant difference between
the frontal and parietal approaches

37. Results
• The parietal approach yielded mean
trajectory ranges of 23° in the sagittal plane
and 36° in the coronal plane in patients with
hydrocephalus.
• The occipital trajectory range was the
smallest for patients with hydrocephalus, at
8° in the sagittal plane and 11° in the coronal
plane
(p < 0.001 compared with either frontal or
parietal approaches)

38. Results

39. Results

40. Conclusions
• The frontal approach provides the greatest
range of trajectories to the successful
catheterization of the frontal horn in adults
• Parietal catheters still have a role in the
hands of neurosurgeons with an advanced
anatomical sense or extensive experience in
individualizing catheter trajectories

41. Conclusions
• Generic guides may improve this to some
degree but do not hold theoretical promise for
guaranteed accurate positioning.
• Patient-specific stereotaxy is the most likely
to enable the accuracy of first-pass
ventricular catheterization to approach 100%.

42. Phase II clinical trial of Wilm’s
tumor 1 peptide vaccination for
patients with recurrent glioblastoma
multiforme
Shuichi Izumoto et al
Osaka University Graduate School of
Medicine

43. Objective
• To investigate the safety and clinical
responses of immunotherapy targeting the
WT1 (Wilms tumor 1) gene product in
patients with recurrent glioblastoma
multiforme (GBM).

44. Methods
• The WT1 Peptide
The immunization consisted of an HLA-
A*2402–restricted, modified 9-mer WT1
peptide (amino acids 235–243
CYTWNQMNL), in which Y was
substituted for M at amino acid position 2
(the anchor position) of the natural WT1
peptide (lyophilized peptide )

45. Inclusion criteria
• Recurrent or progressive GBM resistant to
conventional chemotherapy and radiotherapy
• Patients who had refused chemotherapy but
wanted to receive WT1 vaccine therapy under the
auspices of this clinical trial
• Metabolic imaging or histologically proven true
recurrence in patients who received stereotactic
radiosurgery

46. Inclusion criteria
• age between 16 and 80 years
• expression of WT1 in the glioma cells determined
by immunohistochemical analysis
• HLA-A*2402–positivity
• estimated survival of more than 3 months
• ECOG Performance Status Grade 0–2, 6) no
severe organ function impairment
• the written informed consent of the patient

47. Vaccine Preparation and
Vaccination
• Patients received intradermal injections of 3.0 mg of HLA-
A*2402–restricted modified 9-mer WT1 peptide
emulsified with Montanide ISA51 adjuvant.
• The WT1 vaccinations were scheduled to be given weekly
for 12 consecutive weeks.
• Twelve weeks after the initial vaccination, the response
was evaluated on MR imaging.
• If an effect was observed after the 12 vaccinations, WT1
vaccination was continued at 1-week intervals (with the
patients' informed consent) until tumor progression was
again noted.

48. Immunohistochemical Analysis
• Immunohistochemical analysis was performed to confirm
WT1 protein expression in malignant glioma tissue
• Expression of WT1 seen in the sections was classified on a
scale from 0 to 4 based on the staining density and the
pattern of the glioma cells according to the following
criteria:
– 0, negative staining;
– 1, slightly increased staining in some tumor cells compared with
that in normal glial cells;
– 2, staining at intermediate intensity in some tumor cells;
– 3, strong staining in some tumor cells and intermediate staining in
almost all tumor cells; and
– 4, greatly increased staining in almost all tumor cells compared
with that in normal glial cells.

49. MRI
• Magnetic resonance imaging was performed every
4 weeks
• The tumor size, corresponding to the contrast-
enhanced area on T1-weighted MR images, was
measured and analyzed according to RECIST
(Response Evaluation Criteria in Solid Tumors)
• Results reported as complete response, partial
response, stable disease, and progressive disease.

50. Calculations
• The response rate was calculated as the percentage
of the number of cases in which there was a
complete or partial response divided by the total
number of cases.
• The effective rate was calculated as the percentage
of the number of cases in which there was a
complete or partial response or stable disease
divided by the total number of cases

51. • If an effect was observed after 12 vaccinations,
further WT1 vaccination at 1-week intervals was
given only with the patients' informed consent.
• The PFS period was calculated from the day of the
first WT1 vaccination to the day of the last image
prior to the detection of disease progression; this
was used as the principal end point.

52. Results
• 21 patients (7 women and 14 men) with
HLA-A*2402–positive type were enrolled
in the study
• 16 patients with HLA-A*2402–negative
type were excluded
• Median survival time after tumor recurrence
in the HLA-A*2402–negative patients was
21 weeks

53. Results
• Of the 21 patients, 15 had recurrent disease
and 6 had disease progression after initial
therapy.
• All patients had radiotherapy with or
without chemotherapy or interferon
treatment

54. Clinical Response to Vaccination
• Clinical responses included
– partial response in 2 patients;
– stable disease in 10 patients; and
– progressive disease in 9 patients, including 2 who
dropped out of the trial due to tumor progression and
poor general condition
• Patients who had an effective response continued
to receive vaccinations until tumor progression
was demonstrated

55. • The overall response rate was 9.5%
• The disease control rate, calculated from the
number of patients with complete response,
partial response, or stable disease in the
initial 3 months (the clinical trial period)
was 57.1%.

56. • Median PFS in the 21 patients with GBM who
were included in the study was 20.0 weeks, and
the PFS rate at 6 months (26 weeks) was 33.3%.
• Median overall survival after initial vaccination
was 36.7 weeks.
• Median overall survival after tumor recurrence in
WT1-vaccinated patients was 46 weeks.

57. Partial response
• Two patients experienced partial response.
• In both cases, immunohistochemical analysis of
the tumor specimens showed high WT1
expression levels, but neither patient survived for
a long period (PFS of 23.4 weeks and 20.0 weeks)
• Both patients had disease progression after the 12-
week trial period, with leptomeningeal
dissemination

58. Stable disease
• 4 patients
• experienced gradual tumor stabilization;
that is, they had a response during the late
period of the 3-month WT1 vaccination
course.
• These patients survived for a long time
without progression: (PFS > 96.0 weeks,
51.3 weeks, 42.4 weeks and > 43.6 weeks).

59. Relationship Between PFS and
WT1-Immunostaining Intensity
• In all 21 patients, immunostaining was
positive for WT1.
• The WT1 expression score was 4 in 7 cases,
3 in 8 cases, 2 in 4 cases, and 1 in 2 cases
• Both of the patients who had a partial
response to vaccination had Score 4
immunostaining

60. Relationship Between PFS and
WT1-Immunostaining Intensity
• The patients with Score 3 or 4 had a
statistically longer PFS time than the
patients with Score 1 or 2 (p = 0.0020)
• Patients with Score 4 had a shorter PFS
time than those with Score 3, although
partial response was achieved in 2 patients
with Score 4.

61. Relationship Between PFS and
WT1-Immunostaining Intensity
• Score 4 had high proliferation activity of the
GBM cells that was recognized by the high
MIB-1 staining index, although they also
had the highest amount of target WT1
protein recognized by the induced WT1-
specific CTLs.

62. Conclusions
• WT1 peptide vaccination had disease-
stabilizing, as well as disease progression–
inhibiting, effects that were equal or
superior to those of chemotherapy
• Systemic toxicity that was much less than
that of chemotherapy and thus allowed the
vaccinations to be given for a long time

63. Normobaric oxygen therapy
strategies in the treatment of
postcraniotomy pneumocephalus
Pankaj A. Gore et al
Barrow Neurological Institute, St. Joseph's
Hospital and Medical Center, Phoenix,
Arizona

64. Postsurgical pneumocephalus
• typically asymptomatic
• headaches, lethargy, and neurological
deficits
• can progress to life-threatening tension
pneumocephalus
– when N2O is used for anesthesia in subsequent
nonintracranial procedures
– in discharged patients who travel to a higher
altitude

65. Postsurgical pneumocephalus
• supplemental O2 treatment is a common
neurosurgical practice
• scant clinical data on the efficacy of this
therapy and on the rate of pneumocephalus
absorption
• role of supplemental O2 therapy for the
treatment of postoperative pneumocephalus
in a prospective, pseudorandomized setting

66. Clinical Materials and Methods
• Patients who had undergone a craniotomy within 24 hours
and had ≥ 30 ml of intracranial air, as estimated on routine
postoperative MRI or CT
• Exclusion criteria:
age < 18 or > 80 years, pregnancy, need for O2 due to
pulmonary status, and chronic obstructive pulmonary
disease associated with retention of CO2 ,
Patients with endotracheal tubes and those with drains
(subdural, epidural, or subgaleal) located in proximity to
the pneumocephalus

67. Methods
• Patients were alternately assigned to the treatment or
control group based on their order of enrollment
• Individuals in the treatment group received 100%
(normobaric) supplemental O2 through a nonrebreather
mask at 12 L/minute, equivalent to an FiO2 concentration
of 68% for ~ 24 hours
• Patients in the control group were maintained with room
air for the same length of time
• study protocol allowed supplemental O2 to be delivered to
any patient in the control group with hypoxemia (O2
saturation < 93%)

68. Methods
• CT scans were obtained with axial 1.25-mm
thin slices to allow optimum volumetric
analysis.
• Both groups of patients underwent a second
noncontrast CT scan of the head ~ 24 hours
after their initial enrollment.

69. Results
• Seven patients (5 males, 2 females; mean age 61 years)
were enrolled in the control group
• 6 patients (3 males, 3 females; mean age 53 years) were
enrolled in the treatment group
• In the control group, pneumocephalus resulted from
craniotomy for the treatment of 5 tumors and 2 aneurysms.
• In the treatment group, pneumocephalus resulted from
craniotomy for the treatment of 5 tumors and from
microvascular decompression in 1 case

70. Results
• None of the patients in either group were
clinically symptomatic from
pneumocephalus.
• None of the patients in the control group
required supplemental O2 administration
for any reason.
• One patient from each group excluded for
epidural hematoma and patient non-
cooperation for O2 mask.

71. Results
• The mean change in the volume of
pneumocephalus was 18 ml in the control
group compared with 35 ml in the treatment
group
• The difference in the rate of absorption of
1.3%/hour in the control group compared
with 2.7%/ hour in the treatment group was
statistically significant (p = 0.009).

72. Conclusions
• Administration of normobaric supplemental O2
significantly increases the rate at which
pneumocephalus is resolved after a craniotomy
• The mean rate at which pneumocephalus resolves
at room air (21% FiO2) is 31% per 24 hours.
• The nonrebreather mask used to deliver 68% FiO2
results in a mean rate of resolution of
pneumocephalus of 65% per 24 hours.