Primary Pontine Hemorrhage and Gustatory
Disturbance: Clinicoanatomic Study
NOBORU GOTO,
M.D.,
TOSHIKI YAMAMOTO,
M.D.,t
HIROSHI TOMITA,
M.D.*
MITSUO KANEKO,
M.D.,f
SUMMARY A clinicoanatomic study of 12 patients with tegmental-type primary pontine hemorrhage
proved the presence of a gustatory disturbance among other clinical symptoms on the same side of the
tongue as that of the pontine lesion, and suggested the secondary pathway of gustatory sensation from the
solitary tract nucleus ascends without decussation in the homolateral pontine tegmentum. These results
contradict textbook descriptions regarding the human secondary gustatory pathway.
Stroke, Vol 14, No 4, 1983
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IT HAD NOT BEEN SYMPTOMATOLOGICALLY
established that primary pontine hemorrhage could
produce a gustatory disturbance. But, complaints of
taste disorder by one of our tegmental-type primary
pontine hemorrhage (T-PPH) patients led us to study
the connection between the disturbance and the disease.
Anatomic knowledge of the gustatory pathway in
the peripheral nervous system (including the solitary
tract) in man has been provided by many researchers. 1-7 That of the secondary pathway in the brainstem,
however, remains at a rudimentary stage. Spontaneous
destructions of various nervous pathways by diseases
occasionally provide an opportunity to verify or even
to deny anatomic data collected in animals by the experimental method.
This paper reports the results of a clinical gustatory
examination conducted using a new method in longsurvival patients with T-PPH which is considered to be
a rather rare and mild type compared to the other,
tegmentobasilar, type,8 and the results of an anatomic
study on localization of pontine lesions in autopsy
cases with T-PPH. Moreover, a precise investigation
concerning numbers of fibers of the solitary tract and
neuronal changes of the attendant nucleus was conducted in some of the autopsy cases.
Methods
Out of 12 cases collected for this study (table 1),
three clinical long-survival patients (6y6mo; 4y8mo;
2y8mo) with T-PPH were clinically examined for the
clarification of the presence of gustatory disturbance.
For this purpose, a new gustometry9 was adopted:
namely a qualitative and semiquantitative test using
small filter-paper discs (5 mm in diameter) impregnated just before the test with diluted solutions (five gradations) of the four cardinal taste substances: sugar,
salt, tartaric acid and quinine hydrochloride (table 2).
Points of gustatory stimulation are shown in figure 1.
From the Departments of Neuroanatomy and *Otorhinolaryngology,
Nihon University School of Medicine, 30 Oyaguchi, Itabashi, Tokyo
173, Japan, and from tthe Department of Neurosurgery, Hamamatsu
Medical Center Hospital, 328 Tomizuka, Hamamatsu, Shizuoka 432,
Japan.
Address correspondence to: Dr. Noboru Goto, Department of Neuroanatomy, Nihon University School of Medicine, 30 Oyaguchi, Itabashi,
Tokyo 173, Japan.
Received September 24, 1982; revision accepted January 12, 1983.
For the morphologic study, nine autopsy cases of
tegmental type primary pontine hemorrhage were
used. The brainstems and cerebelli of the cases were
carefully examined macroscopically, and microscopically after making histologic sections at various levels
to determine the location of the hemorrhagic lesions
and ascertain which tracts or nuclei were involved. The
methods adopted for the histologic investigation are
the same as in our previous report.8 Four autopsy cases
with different survival periods after the onset were
selected for precise neuroanatomic investigations. The
numbers of nerve fibers in the solitary tract at the upper
level of the medula oblongata were counted under microscopic observation of transverse slices (30 fim
thick) stained by Kultschitzky's method of myelin
staining. The total area of each solitary tract was measured through a microscope using an optical electronic
planimeter (Digiplan, Kontron Co.) in combination
with a microscopic projecting apparatus (Olympus
Co.) and a diode flashing tracer. A desk-top computer
(type 2200, Wang Co.) was also used for calculation of
total number of nerve fibers from the data obtained
through systemic sampling of five (dorsal, ventral,
medial, lateral and central) areas of the solitary tract on
each side of the medulla oblongata. Each sampling
covered an area of 6.25 X 10" 4 mm2. Neuronal
changes of the solitary trace nucleus were also observed in sections stained by Kluver-Barrera's method
(luxol fast blue and cresyl violet staining).
Results
Gustatory Disturbance
Main clinical manifestations of all the cases are listed in table 1. In this paper, only gustatory disturbances
will be mentioned.
Clinical case Patient I had been complaining of gustatory disturbance for more than six years, after recovery from a disturbance of consciousness. She had been
noticed to prefer more strongly seasoned food than
before the disease, and was thought to have decreased
taste, but conventional test for taste could not define
her gustatory disturbance accurately probably because
of the diffusion of taste substances over the midline of
the tongue. The other two patients, however, had not
been aware of any taste disorder by the time they
underwent taste examination for this study.
Thanks to the new gustometry adopted in this study,
they were all ascertained to have gustatory disturbance
508
STROKE
VOL 14, No 4, JULY-AUGUST
1983
TABLE 1 List of 12 Cases of Tegmental Type Primary Pontine Hemorrhage
Case
Alive cases
Patient I
Age/sex
Survival
period
Laterality
CT
(pontine
tegmentum)
38/F
6y6mo
Patient II
56/M
4y8mo
LDA
(2y later)
Patient III
53/F
2y8mo
HDA
Autopsy cases
A-275
69/M
Main clinical manifestations
L-abducent palsy, R-horizontal nystagmus,
L-facial palsy, R-hypoesthesia, L-hemiparesis of the tongue, reduction of L-gag reflex, R-cerebellar signs, L-lateral gaze palsy, gustatory disturbance, etc.
oscillopia, R-hemiplegia, L-facial palsy,
PPLOD myoclonus, R-hypoesthesia, R-facial anesthesia, L-abducent palsy, etc.
coma, B-pin-point pupils, L-hemiplegia, Rhemiparesis, no horizontal eye movements,
B-cerebellar signs (R > L), L-facial palsy,
L-tongue hypoesthesia, etc.
9.5mo
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coma, miosis, insufficient respiration, L-facial palsy, R-hemiplegia, one-and-a-half
syndrome, pseudobulbar palsy, etc.
coma,
decerebrate rigidity, dyspnea, pin8.5mo
A-574
54/M
HDA
point pupils, L-ocular bobbing, L-facial
palsy, etc.
84/M
stupor, L-hemiplegia, decerebrate rigidity, inHDA
L
22d
A-686
voluntary vertical eye movements, etc.
52/F
stupor, anisocoria (L > R), no horizontal eye
none
R
21d
A-365
movements, L-hemiplegia, R-facial palsy,
etc.
stupor, L-facial palsy, R-hemiplegia, skew
HDA.4VH
L
21d
53/F
A-1013
deviation, anisocoria (L > R), etc.
R
15d
75/M
stupor, L-hemiparesis, pin-point pupils, ocuHDA,4VH
A-1098
lar bobbing, etc.
coma, apnea, irregular respiration, pin-point
HDA,4VH
L
9d
73/F
A-807
pupils, fixed eyes, status epilepticus, etc.
L
5d
65/M
stupor, irregular respiration, miosis, skew denone
A-325
viation, L-facial palsy, R-hemiplegia, etc.
L
16h
66/F
coma, no pupillary reaction to light, decerenone
A-1021
brate posture, etc.
Abbreviations 4VH: fourth ventricular hemorrhage; B: bilateral; CT:computerized tomogram; d: days; F: female; h:
hours; HDA: high density area; L: left; LDA: low density area; M: male; mo: months; PPLOD: palato-pharyngo-laryngooculo-diaphragmatic; R: right; y: years
(hemihypogeusia in two; hemiageusia in one) on the
same side as that of the primary pontine lesion (See
results in table 3).
Pontine Lesions
It is not difficult to diagnose a T-PPH with the help
of computerized tomography. Out of the seven cases in
which CT was performed, six showed a high density
area in the one-sided pontine tegmentum, with fourth
ventricular ruptures in three of those six. In two of the
autopsy cases, an upward extension of the high density
area into the mesencephalon was also observed on CT
films (A-807, A-1013). But one clinical case (Patient
II) which was examined by CT two years after the
onset, showed a low density area in the ipsilateral
pontine tegmentum.
Autopsy examinations disclosed the exact localization of one-sided pontine tegmental lesions containing
the following main structures: reticular formation,
central tegmental tract, medial lemniscus, lateral lem-
TABLE 2 Gradation of Taste Substances for Taste Examination
Grade
Taste substance
I
II
V
Taste
sensation
III
IV
10%
20%
80%
sweet
5%
10%
20%
salty
Sugar
0.3%
2.5%
Salt
0.3%
1.25%
Tartaric acid
0.02%
0.2%
2%
4%
8%
sour
Quinine hydrochloride
0.001%
0.02%
0.1%
0.5%
4%
bitter
Evaluation Grade I: hypergeusia; Grade II and III: normal range; Grade IV and V: hypogeusia; over Grade V: ageusia.
PONTINE HEMORRHAGE AND GUSTATORY DISTURBANCE/Goto et al.
509
N. petrosus major
N. glossopharyngeus
Chorda tympani
FIGURE 2. Left-sided tegmental-type primary pontine hemorrhage with a fourth ventricular rupture. A-807.
Kultschitzky's
myelin staining.
2cm
FIGURE 1.
Three points of gustatory
stimulation.
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with just a slight extension to the contralateral pontine
tegmentum (inner part of the medial lemniscus and
medial part of the reticular formation) in two (A-365,
A-1098; fig. 3).
niscus, motor trigeminal nucleus, superior sensory trigeminal nucleus (all observed in all 9 cases), superior
vestibular nucleus (in 7 out of 9 cases), superior cerebellar peduncle and nucleus loci coerulei (6/9), abducens nucleus (4/9), trapezoid body and superior central
nucleus (3/9), etc. The lesions were without a contralateral extension (fig. 2) in seven cases; with ruptures
into the fourth ventricle (figs. 2 and 3) in five (only
three were detected by CT); with upward mesencephalic extensions in two (A-807, A-1013); with homolateral involvements of middle and inferior cerebellar
peduncles in three (A-365, A-574, A-807; fig. 2); and
TABLK 3
Neuroanatomic Findings
In the morphological analysis, the numbers of nerve
fibers in the solitary tract on both sides of the medulla
oblongata were counted and neuronal changes of the
solitary tract nucleus were observed.
The results are shown in table 4, where the numbers
of fibers are listed together with the ratios to the oppo-
Results of Taste Examination
Q.H.
T.A.
Salt
Sugar
L.
R.
L.
R.
L.
R.
L.
R.
Chorda tympani
A
Ill
A
II
A
Ill
A
III
N. petrosus major
A
III
A
II
A
IV
A
IV
N. glossopharyngeus
A
III
A
II
A
111
A
III
Chorda tympani
III
11
IV
II
IV
II
V
I
N. petrosus major*
—
—
—
—
—
—
—
—
N. glossopharyngeus
[V
II
[V
II
IV
II
III
II
IV
II
III
II
III
1
V
I
III
V
II
V
II
—
—
—
—
—
Patient I
Patient 11
Patient 111
Chorda tympani
N. petrosus major
IV
III
V
N. glossopharyngcust
—
—
—
I—IV: see table 2 for explanation; A; ageusia; *test not conducted because of palatal myoclonus; itest not conducted
because of limitation of jaw opening; L; left; R; right; Q.H.: quinine hydrochloride; T.A.: tartaric acid.
TABLE 4
Morphological Analyses of Solitary Tract and Attendant Nucleus
No. of fibers in
solitary tract
Side of
Case
hemorrhage
L.
Neuronal changes of solitary
tract nucleus
R.
L.
R.
A-275
L.
1.427(67%)*
2.138
atrophic
A-574
R.
3.502
2.184(62%)*
normal
atrophic-
A-365
R.
4.406
2,563(58%)*
atrophict
atrophic
A-325
L.
1.962(78%)*
2.519
slightly atrophic
normal
*percentage to opposite side; tsee text for details; L; left; R: right.
normal
510
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1983
% •
* 4U,
-**' «
*
•"«*
FIGURE 3. Right-sided tegmental-type primary pontine hemorrhage with a fourth ventricular rupture and a slight contralateral extension. A-365, Kultschitzky's myelin staining.
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site side. As can be seen, a reduction of the numbers of
nerve fibers occurs on the same side as that of the
pontine lesions.
As far as the neurons of the solitary tract nucleus are
concerned, they appeared atrophic on the same side as
the pontine lesions in three cases (although only mildly
so in A-325). In case A-365, which showed a slight
contralateral extension into the opposite tegmentum,
the neurons of the solitary tract appeared atrophic on
both sides (fig. 4).
Discussion
Gustatory Disturbance
The reason why gustatory disturbance had so far not
been included in the clinical manifestations of primary
pontine hemorrhage can be explained by the fact that
most primary pontine hemorrhage cases become fatal
shortly after the onset, even in mild cases like tegmental type hemorrhage, with a longer survival period, a
patient is seldom conscious of taste disorder by himself, unless the gustatory disturbance extends over
both sides of the tongue.
Secondary Gustatory Pathway in Man
It had been considered for many years that relay
neurons from the solitary tract nucleus crossed the
midline and turned upward into the pontine tegmentum
to form the gustatory lemniscus,10-12~" although some
researchers preferred to say that they were not certain
of that. "~13 If this description which appeared in almost
all human neuroanatomy textbooks'2'15 is true, a onesided pontine tegmental lesion should logically cause a
gustatory disturbance on the opposite side of the
tongue. This, however, was not the case in our study:
Three patients showed gustatory disturbances on the
same side of the tongue as that of the pontine tegmental
lesions. In four autopsy cases precise morphological
analyses showed a reduction of the number of nerve
fibers in the solitary tract compared to the other side
and neuronal changes in the solitary tract nucleus, on
the same side as that of the pontine lesions. In this
study, no comparison was made with the number of
nerve fibers of normal aging controls because as far as
we know such data are not available. Our aim was only
If «
0»M*
0 . 5mm
FIGURE 4. Atrophic neurons of the left solitary tract nucleus.
A-365, Luxol fast blue and cresyl violet staining.
to compare the diseased side with the opposite side.
The next question that flashed through our minds
was where the secondary gustatory pathway was located in the human pontine tegmentum. In order to find an
answer to that question, we carefully examined A-365
in which solitary tract nuclei appeared atrophic on both
sides. In this case, the hemorrhagic lesion extended to
the medial parts of the medial lemniscus and reticular
formation on both sides at the level of the upper two
thirds of the pons. All we can say then, is that the
human secondary gustatory pathway ascends homolaterally either through the medial part of the medial
lemniscus or through the medial part of the reticular
formation. In animals, it has been found through experimental works that the secondary gustatory pathway ascends contralaterally through the medial part of
the medial lemniscus,10 which has been called the gustatory lemniscus.12
Recently, the idea of the presence of a relay nucleus,
termed pontine parabrachial nucleus or pontine taste
area (PTA), has been introduced after experimental
works by some researchers, l6~20 one of whom gives the
following description:17 (The central gustatory pathway of the albino rat has been traced using a combined
electrophysiological-neuroanatomical technique. Fibers do not cross as expected into the medial lemniscus, but instead travel rostrally to terminate ipsilaterally in a small-celled area (PTA) adjacent the superior
cerebellar peduncle as it enters the pons. Lesions of
PTA result in degeneration of a bilateral ascending
pathway travelling in the dorsomedial tegmentum to
terminate in the classical gustatory nuclei of the thalamus.)
The existence of a relay nucleus, however, could not
be proved in this study because of direct destruction
next to, or affecting, the superior cerebellar peduncle.
Acknowledgments
The authors would like to thank Mr. S. Okabe of the Nihon University School of Medicine for photography.
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Platelet Function Tests in Thrombotic
Cerebrovascular Disorders
SHINICHIRO UCHIYAMA,
ITSURO KOBAYASHI,
M.D.*,
M.D.*,
MEGUMI TAKEUCHI,
SHOICHI MARUYAMA,
M.D.*,
M.D.*,
AND KOSHICHIRO HIROSAWA,
MIKIO OSAWA,
M.D.*,
MASAHIKO AOSAKI,
M.D.t,
M.D.t
SUMMARY A variety of platelet function tests were performed in patients with four forms of obstructive
cerebrovascular disease (CVD); transient ischemic attacks (TIA), reversible ischemic neurological deficit
(RIND), cerebral infarct, and cerebral embolism of cardiac source in rheumatic valvular heart disease
(RVHD). Platelet studies included platelet aggregation induced by ADP and ristocetin, spontaneous platelet
aggregation, v<>n Willebrand factor (VIIDvWF), platelet aggregation enhancing factor (PAEF), and percentage of large platelets (megathrombocytes). Serial testing was carried out in acute stroke patients. The
effect of aspirin therapy was also evaluated. A clear difference in results was observed between patients with
cardiogenic embolism and those with other forms of CVD. In patients with TIA, RIND, and cerebral
infarct, platelet aggregation, both induced and spontaneous, was enhanced along with elevation of plasma
VIIDvWF and PAEF, and increased percentage of megathrombocytes. In patients with cardiogenic embolism, however, these studies were negative except for percent megathrombocytes. This value was increased
in the embolic patients with RVHD in comparison with non-embolic patients with RVHD. Increase in
platelet aggregation to ADP and percent megathrombocytes developed slowly over a week following stroke.
Induced and spontaneous platelet aggregation, and percent megathrombocytes could be normalized with
600 mg aspirin p.o. These studies suggest that a systemic increase of hyperaggregable platelets and of
plasma activators of platelet function exists in thrombotic CVD and may be related to its pathogenesis, while
local hemodynamic factors may be more important in the thrombogenesis of cardiogenic embolism.
Stroke Vol 14, No 4, 1983
AN EARLY ARTERIAL THROMBUS consists largely of platelets. This suggests that platelets play an
important role in arterial thrombogenesis in vivo.
Platelet aggregation is reported increased in patients
with TIA or cerebral infarct.1-7 The purpose of this
study was 1) to confirm the participation of platelets in
thrombogenesis in thrombotic CVD by performing
tests of different aspects of platelet reactions, 2) to
study the time course of platelet function in acute
stroke patients by frequent serial testing, 3) to examine
the relationship between platelet function and various
types of ischemic CVD as well as clinical severity, and
4) to estimate the efficacy of an antiplatelet agent,
aspirin in modifying various platelet function tests.
From *the Department of Neurology, Neurological Institute and tthe
Department of Cardiology, Heart Institute of Japan, Tokyo Women's
Medical College, 10 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.
Address correspondence to: Dr. Uchiyama, Department of Neurollogy, Neurological Institute, Tokyo Women's Medical College, 10
Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.
Received March 11, 1982; revision accepted January 6, 1983.
Materials and Methods
Patients and Controls Studied
Tests were performed in patients with TIA, RIND,
cerebral infarct, and cerebral embolism originated
from RVHD. All patients were evaluated by the staff
of the Neurological Institute of Tokyo Women's Medi-
Primary pontine hemorrhage and gustatory disturbance: clinicoanatomic study.
N Goto, T Yamamoto, M Kaneko and H Tomita
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Stroke. 1983;14:507-511
doi: 10.1161/01.STR.14.4.507
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