Multiple Sclerosis 2005; 11: 282 /285
www.multiplesclerosisjournal.com
Trigeminal involvement in multiple sclerosis: magnetic resonance imaging
findings with clinical correlation in a series of patients
CJ da Silva*,1,2, AJ da Rocha1,2, MF Mendes3, ACM Maia Jr 1, FT Braga1,2 and CP Tilbery 3
1
Centro de Medicina Diagnóstica, Setor de Imagem, Laboratório Fleury, São Paulo-SP, Brazil; 2Section of Radiology, Santa
Casa de Misericórdia de São Paulo, CEP 01333910 São Paulo-SP, Brazil; 3Section of Neurology, Santa Casa de
Misericórdia de São Paulo, CEP 01333910 São Paulo-SP, Brazil
Trigeminal involvement detected by magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients is usually associated with
trigeminal neuralgia (TN) or painless paraesthesia in the trigeminal distribution. Our aim is to review the incidence of trigeminal
involvement on MRI in a series of patients with MS at our institution, with further clinical correlation. We reviewed MRI scans of 275 MS
patients for the presence of gadolinium enhancement on postcontrast T1-weighted images, anatomical and signal abnormalities on
different sequences at the pontine trigeminal root entry zone (REZ) and in the cisternal portion of the nerves. We observed enhancement
in the cisternal portion of the nerves and signal abnormalities (with or without enhancement) at the pontine trigeminal REZ in 8 (2.9%)
patients, and enhancement was bilateral in 6 (75%) of those. Despite the inflammatory activity, none of them had TN and 3 (37.5%) had
only painless paraesthesias in the correspondent V3 distribution. We also found a marked trigeminal hypertrophy in 2 (25%) patients, both
with a longer period of disease. Our results confirm a high and clinically silent incidence of trigeminal involvement in MS patients, and
suggest a simultaneous role of the central and peripheral type of myelin in trigeminal demyelination.
Multiple Sclerosis (2005) 11, 282 /285
Key words: gadolinium enhancement; magnetic resonance imaging (MRI); multiple sclerosis (MS); trigeminal nerve; trigeminal neuralgia; trigeminal
symptoms
Introduction
Previous studies have showed that trigeminal involvement detected by magnetic resonance imaging (MRI) in
multiple sclerosis (MS) patients is usually associated with
trigeminal neuralgia (TN) or painless paraesthesia in the
distribution of the fifth nerve.1 3 In MS, TN occurs more
frequently than in the general population, and it is more
likely to be bilateral and to affect patients at a younger
age.4,5 The prevalence of TN in MS patients based on
clinical grounds is approximately 1%.4 The role of central
and peripheral mechanisms in the aetiology of TN in MS
is not entirely clear, but the rare post-mortem studies
provide evidence for demyelination within intra- and
extrapontine trigeminal pathways, probably due to the
damage of myelin components present in both
compartments.5 7 MRI has had a major impact in the
last two decades in understanding and managing MS, and
is the method of choice to demonstrate the disease
dissemination in time and space.8 Despite this, there is
still little information about the trigeminal involvement
on MRI and its clinical correlation.7 We found eight MS
*Correspondence: Carlos Jorge da Silva, Centro de
Medicina Diagnóstica / Setor de Imagem, Laboratório
Fleury, Rua Cincinato Braga 282, Paraı́so CEP 01333910,
São Paulo-SP, Brazil.
E-mail: [email protected]
Received 19 September 2004; accepted 30 November 2004
# 2005 Edward Arnold (Publishers) Ltd
patients with simultaneous involvement of the intra- and
extrapontine trigeminal pathways on MRI scans. Our aim
is to describe the MRI characteristics and some peculiarities of the trigeminal involvement in our group of
patients, not previously mentioned, with further clinical
correlation.
Materials and methods
We reviewed MRI scans of 275 consecutive MS patients
(208 relapsing /remitting [RR] and 67 secondary progressive [SP]) at our institution, from 05/16/02 to 08/15/04 at
1.0 T, using our routine protocol for demyelinating diseases. After three localizing scans in the axial, coronal and
sagittal planes, axial slices covering the whole brain were
aligned with the bicommissural line. Imaging parameters
were identical (24 cm FOV, 6 mm thickness, 0.3 mm gap,
205 /512 matrix). Our protocol included axial fluidattenuated inversion recovery (FLAIR) sequence (TR
11 000 ms, TE 140 ms, TI 2600 ms), fast spin-echo (FSE)
acquisitions to obtain proton density (PD) and T2weighted images (TR 4500 ms, TE 15 ef-100 ef ms, echo
train length 15) and T1 SE/MTC (TR 510 ms, TE 12 ms/
magnetization transfer contrast pulse on resonance)
sequence before and after a single dose (0.1 mmol/kg)
injection of intravenous dimeglumine gadopentetate. We
also obtained an identical delayed T1 SE/MTC sequence,
approximately 15 minutes after gadolinium (Gd) injection.
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10.1191/1352458505ms1186oa
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CJ da Silva et al.
283
We detected trigeminal involvement based on Gd enhancement, anatomical and signal abnormalities at the
pontine trigeminal root entry zone (REZ) and in the
cisternal portion of the nerves. The Gd enhancement of
the involved nerves was subjectively compared to the
normal pontine parenchyma, and was considered as
‘discrete’ when we detected a slight signal increase on
postcontrast acquisitions, and ‘marked’ when the enhancement was evident. We used coronal postcontrast
T1-weighted sequences to evaluate trigeminal thickness.
All patients filled the recommended diagnostic criteria
proposed by McDonald et al . for definite MS before the
MRI scans.8 All examinations were reviewed by two
neuroradiologists (AJR, CJS). We performed clinical correlation based on revision of medical records at the time of
the MRI scans, and on an active search for trigeminal
symptoms in subsequent medical attendances. We used
Fisher’s exact test (P B/0.05) to compare the incidence of
trigeminal involvement in the RR and SP groups.
Results
Eight (2.9%) out of 275 MS patients presented extrapontine trigeminal involvement characterized by enhancement of the entire cisternal portion of the nerves on
postcontrast T1-weighted images (Figures 1 and 2) and
intrapontine involvement characterized by hyperintense
linear lesions at the correspondent pontine trigeminal REZ
on FLAIR, PD and T2-weighted (Figure 2) sequences. Two
(25%) of those patients also presented Gd enhancement of
the correspondent pontine trigeminal REZ (Figures 1 and
2). All involved nerves showed a more conspicuous
enhancement on the delayed (15 minutes) postcontrast
acquisitions and in two (25%) patients the trigeminal
enhancement was only detected by this sequence (Figure
1). The involvement was bilateral in six (75%) patients.
We observed trigeminal involvement in three (1.4%) out
of 208 RR and in five (7.5%) out of 67 SP patients
(P /0.0226). Two (25%) patients with the longest period
of disease also presented trigeminal hypertrophy, confirmed by a transverse section of the nerves on coronal
postcontrast T1-weighted images (Figure 3). The disease
Figure 1 Patient 5. (A) Axial immediate postcontrast T1weighted image do not show any abnormal enhancement.
(B) Axial delayed (15 min) postcontrast T1-weighted image shows
a marked enhancement of the entire cisternal portion of the
trigeminal nerves and at the left pontine trigeminal REZ, with
much more conspicuity when compared to (A).
Figure 2 Patient 4. (A) Axial FLAIR image shows a linear
hyperintensity at the left pontine trigeminal REZ. (B) Axial
delayed (15 min) postcontrast T1-weighted image shows a marked
enhancement of the entire cisternal portion of the left trigeminal
nerve and at the homolateral pontine trigeminal REZ.
duration median and the mean age of the 208 RR/67 SP
patients were 6/8 and 31.3/33.4 years, respectively. Seventy-five and 73% of patients were female in the RR and
SP groups, respectively. All patients presented typical and
simultaneous involvement of the periventricular white
matter, corpus callosum and brainstem. Relevant data
concerning the trigeminal involvement are summarized
in Tables 1 and 2.
Discussion
Quite similar to a previous study,7 we found active lesions
in the cisternal portion of the trigeminal nerve in 8 (2.9%)
of our 275 patients. The prevalence of TN based on
clinical grounds in MS is approximately 1% and may be
preceded by paraesthetic symptoms in the trigeminal
distribution.4 Although none of our eight patients had
TN, 3 (37.5%) had paraesthetic symptoms in the corresponding V3 distribution.
Bilateral enhancement of the trigeminal nerve was seen
in 6 (75%) patients, similar to a previous study,7 where
bilateral trigeminal enhancement was seen in 66.7%, but
in contrast to the prevalence of approximately 11% of
bilateral TN in MS patients based on clinical grounds.4
The difference between the incidence of bilateral trigeminal enhancement and the prevalence of bilateral TN in
MS is evident. CNS demyelination usually presents a great
discrepancy between clinical and MRI findings.9 Similar
to the encephalic regions, enhancement seems to be more
sensitive than either clinical examination or T2-weighted
images in detecting inflammatory activity in the cisternal
portion of the fifth nerve, as none of our patients had TN,
despite the active demyelination.
All involved nerves showed a more conspicuous enhancement on the delayed (15 min) postcontrast acquisitions. A single dose (0.1 mmol/kg) of contrast, in
combination with MTC pulses, has been reported to
increase the sensitivity to enhancing lesions in RR and
SP patients,10 as well as the delayed post-Gd acquisitions
using MTC pulses,11 corroborating with our observations.
We found a significant predominance of trigeminal
involvement in SP patients (P B/0.05). The hypothesis
that SP patients are more predisposed to trigeminal
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Multiple Sclerosis
Trigeminal involvement in MS: MRIclinical correlation
CJ da Silva et al.
284
Figure 3 Patient 2. (A) Axial T1-weighted image shows a marked bilateral trigeminal hypertrophy. (B) Axial delayed (15 min)
postcontrast T1-weighted image shows a discrete bilateral trigeminal enhancement. (C) Coronal postcontrast T1-weighted image
confirms the trigeminal hypertrophy based on a transverse section of the nerves (arrows).
involvement due to the greater duration and dissemination of the disease must be considered.
A quite relevant observation is the presence of simultaneous hyperintense linear lesions at the pontine trigeminal REZ in all involved nerves, with Gd enhancement at
this site in two patients (Figures 1 and 2). Some reports
showed similarly shaped pontine lesions on MRI in a few
MS patients, especially in those with symptoms and signs
related to the trigeminal nerve.1 3 These lesions, as well
as the enhancement of the cisternal portion of the nerves,
appear to be specific for demyelination in MS patients.
Pathological studies demonstrated that TN in MS can be
caused by a demyelination plaque at the pontine trigeminal REZ, indicating a central (oligodendroglia type of)
myelin lesion.2 The transition from the peripheral
Schwann cell investment to the central sheath of oligodendroglia in the sensory root is abrupt, occurring at a
distance of less than 10 mm from the pons.12,13 In our
study, all involved nerves showed enhancement of the
entire cisternal portion (between the pons and Meckel’s
cave), indicating also a peripheral (Schwann type of)
myelin lesion, similar to the findings of van der Meijs
et al .7 Central and peripheral myelin have several proteins
in common, including myelin basic protein, Connexin32
and myelin-associated glycoprotein, which might play an
important role in this setting.14,15
A new interesting finding is the presence of trigeminal
hypertrophy in two SP patients, both with the longest
period of disease, confirmed by transverse sections of
the nerves on coronal postcontrast T1-weighted images
(Figure 3). To the best of our knowledge, this finding was
Table 1 Clinical data of the eight MS patients with trigeminal
involvement detected by MRI
Patient
1
2
3
4
5
6
7
8
Age
(years)
Sex
40
38
27
28
30
40
28
40
M
M
F
F
M
M
M
F
Clinical
form
Disease
duration
(years)
EDSS
SP
SP
SP
SP
SP
RR
RR
RR
20.0
12.0
3.0
3.0
4.0
3.5
5.0
2.0
6.0
6.5
4.5
6.0
6.0
3.5
1.5
1.0
never mentioned on MRI in this setting, perhaps because
previous investigators did not evaluate and confirm
trigeminal thickness on coronal plane. Another relevant
observation is that trigeminal hypertrophy presented an
inverse correlation with enhancement. These two SP
patients presented a marked nerve hypertrophy with
minimal enhancement even in the delayed postcontrast
acquisition (Figure 3). For the other individuals, we
observed a marked trigeminal enhancement with no
evidence of nerve hypertrophy (Figures 1 and 2). Other
causes of trigeminal hypertrophy and vascular compressions were ruled out after an extensive search. We
presume that this is an example of demyelination and
remyelination occurring repeatedly and simultaneously in
the same plaque, with the predominance of reparative
processes mediated by Schwann cells in older lesions, as
proposed by Prineas et al .,16 and could serve as a model
in vivo to their findings, explaining at least in part, the
marked trigeminal hypertrophy observed in our two SP
patients. The marked Gd enhancement observed in the
remaining individuals could reflect the predominance of
inflammatory activity in more recent lesions. However, we
have no neuropathological studies and this hypothesis
needs histological confirmation.
Conclusion
The clinical and MRI evaluation of the trigeminal involvement in our group of MS patients lends further knowledge
Table 2 Data of the eight MS patients with trigeminal involvement detected by MRI
Side
Nerve
enhancement
Nerve
hypertrophy
Symptoms Figure
number
B
B
R
L
B
B
B
B
Discrete
Discrete
Marked
Marked
Marked
Marked
Marked
Marked
Yes
Yes
No
No
No
No
No
No
No
No
No
Yesa
Yesb
Yesb
No
No
a
Multiple Sclerosis
2
1
Homolateral painless paraesthesia in the V3 distribution.
Bilateral painless paraesthesia in the V3 distribution.
Abbreviations: B, bilateral; R, right; L, left.
b
Abbreviations: EDSS, Expanded Disability Status Scale.
3
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CJ da Silva et al.
285
in this field, confirming a high and clinically silent
incidence of this affection, as none of them had TN. MRI
represents an important tool to evaluate demyelinating
lesions in cranial nerves even in asymptomatic or oligosymptomatic patients, including T2-weighted and mainly
delayed postcontrast acquisitions that might demonstrate
trigeminal involvement and justify an active search for
specific symptoms. Relevant observations concerning the
trigeminal involvement were the significant predominance in SP patients, a simultaneous role of the central
and peripheral myelin in trigeminal demyelination, as
well as two different MRI patterns characterized by a
marked nerve hypertrophy with minimal postcontrast
enhancement observed in advanced disease and the
predominance of enhancement with no hypertrophy in
more recent lesions, which needs pathological correlation.
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Multiple Sclerosis