Primary Pontine Hemorrhage and Gustatory Disturbance: Clinicoanatomic Study

NOBORU GOTO, M.D., TOSHIKI YAMAMOTO, M.D.,t MITSUO KANEKO, M.D.,f

HIROSHI TOMITA, M.D.*

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

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 long-survival 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

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508 STROKE VOL 14, No 4, JULY-AUGUST 1983

TABLE 1 List of 12 Cases of Tegmental Type Primary Pontine Hemorrhage

Case Age/sex Survival period

Later­ality

CT (pontine

tegmentum) Main clinical manifestations Alive cases

Patient I

Patient II

Patient III

Autopsy cases A-275

A-574

38/F

56/M

53/F

69/M

54/M

6y6mo

4y8mo

2y8mo

9.5mo

8.5mo

LDA (2y later)

HDA

HDA

A-686

A-365

A-1013

A-1098

A-807

A-325

A-1021

84/M

52/F

53/F

75/M

73/F

65/M

66/F

22d

21d

21d

15d

9d

5d

16h

L

R

L

R

L

L

L

HDA

none

HDA.4VH

HDA,4VH

HDA,4VH

none

none

L-abducent palsy, R-horizontal nystagmus, L-facial palsy, R-hypoesthesia, L-hemipa-resis 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-fa-cial anesthesia, L-abducent palsy, etc.

coma, B-pin-point pupils, L-hemiplegia, R-hemiparesis, no horizontal eye movements, B-cerebellar signs (R > L), L-facial palsy, L-tongue hypoesthesia, etc.

coma, miosis, insufficient respiration, L-fa­cial palsy, R-hemiplegia, one-and-a-half syndrome, pseudobulbar palsy, etc.

coma, decerebrate rigidity, dyspnea, pin­point pupils, L-ocular bobbing, L-facial palsy, etc.

stupor, L-hemiplegia, decerebrate rigidity, in­voluntary vertical eye movements, etc.

stupor, anisocoria (L > R), no horizontal eye movements, L-hemiplegia, R-facial palsy, etc.

stupor, L-facial palsy, R-hemiplegia, skew deviation, anisocoria (L > R), etc.

stupor, L-hemiparesis, pin-point pupils, ocu­lar bobbing, etc.

coma, apnea, irregular respiration, pin-point pupils, fixed eyes, status epilepticus, etc.

stupor, irregular respiration, miosis, skew de­viation, L-facial palsy, R-hemiplegia, etc.

coma, no pupillary reaction to light, decere­brate posture, etc.

Abbreviations 4VH: fourth ventricular hemorrhage; B: bilateral; CT: hours; HDA: high density area; L: left; LDA: low density area; M: male; oculo-diaphragmatic; R: right; y: years

computerized tomogram; d: days; F: female; h: mo: months; PPLOD: palato-pharyngo-laryngo-

(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

Taste substance

Sugar

Salt

Tartaric acid

Quinine hydrochloride

I

0.3%

0.3%

0.02%

0.001%

II

2.5%

1.25%

0.2%

0.02%

Grade

III

10%

5%

2%

0.1%

IV

20%

10%

4%

0.5%

V

80%

20%

8%

4%

Taste sensation

sweet

salty

sour

bitter

Evaluation Grade I: hypergeusia; Grade II and III: normal range; Grade IV and V: hypogeusia; over Grade V: ageusia.

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PONTINE HEMORRHAGE AND GUSTATORY DISTURBANCE/Goto et al. 509

N. petrosus major

N. glossopharyngeus

Chorda tympani

2cm

FIGURE 1. Three points of gustatory stimulation.

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), abdu-cens 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

FIGURE 2. Left-sided tegmental-type primary pontine hemor­

rhage with a fourth ventricular rupture. A-807. Kultschitzky's

myelin staining.

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).

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-

TABLK 3 Results of Taste Examination

Patient I

Chorda tympani

N. petrosus major

N. glossopharyngeus

Patient 11

Chorda tympani

N. petrosus major*

N. glossopharyngeus

Patient 111

Chorda tympani

N. petrosus major

N. glossopharyngcust

Sugar

L.

A

A

A

III

— [V

IV

IV

—

R.

Ill

III

III

11

— II

II

III

—

Salt

L.

A

A

A

IV

— [V

III

V

—

R.

II

II

II

II

— II

II

III

—

T.A.

L.

A

A

A

IV

— IV

III

V

—

R.

Ill

IV

111

II

— II

1

II

—

Q.H.

L. R.

A III

A IV

A III

V I

— — III II

V I

V II

— — 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

Side of No. of fibers in

solitary tract Neuronal changes of solitary

tract nucleus

Case

A-275

A-574

A-365

A-325

hemorrhage

L.

R.

R.

L.

L.

1.427(67%)*

3.502

4.406

1.962(78%)*

R.

2.138

2.184(62%)*

2,563(58%)*

2.519

L.

atrophic

normal

atrophict

slightly atrophic

R.

normal

atrophic-

atrophic

normal

*percentage to opposite side; tsee text for details; L; left; R: right.

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510 STROKE VOL 14, No 4, JULY-AUGUST 1983

% •

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.

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

* 4U,

-**' « * I f «

• " « * 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 homolat-erally 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 ipsilateral-ly 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 Universi­

ty School of Medicine for photography.

References 1. Lussana P: Recherches experimentales et observations patholo-

giques sur les nerves du gout. Arch de physiol norm path 2: 20-32. 197-209, 1869; 4: 150-167, 334-350, 1872

2. Lewis D, Dandy WE: The course of the nerve fibers transmitting

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PONTINE HEMORRHAGE AND GUSTATORY DISTURBANCE/Goto et al. 511

sensation of taste. Arch Surg 21: 249-288, 1930 3. Schwarz HG, Weddell G: Observations on the pathways transmit­

ting the sensation of taste. Brain 61: 99-115, 1938 4. Torvik A: Afferent connections to the sensory trigeminal nuclei,

the nucleus of the solitary tract and adjacent structures. An experi­mental study in the rat. J Comp Neurol 106: 51-141, 1956

5. Diamant H: The sense of taste in man. Trans Amer Acad Ophthal Otolaryng 80: 362-365, 1975

6. Rollin H: Course of the peripheral gustatory nerves. Ann Otol Rhinol Laryngol 86: 251-258, 1977

7. Schwarz HG, Roulhac GE, Lam RL, O'Leary JL: Organization of the fasciculus solitarius in man. J Comp Neurol 94:221-237, 1951

8. Goto N, Kaneko M, Hosaka Y, Koga H: Primary pontine hemor­rhage: Clinicopathological correlations. Stroke 11: 84-90, 1980

9. Tomita H: Methods in taste examination. In Surjan L, Bodo G (eds) Proc Xllth ORL World Congr: 627-631, 1981

10. Allen WF: Origin and destination of the secondary visceral fibers in the guinea-pig. J Comp Neurol 35: 275-311, 1922-23

11. Ranson SW, Clark SL: The anatomy of the nervous system. Its development and function. Philadelphia, WB Saunders Co., p 252-254, 1959

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

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 Neurol-logy, Neurological Institute, Tokyo Women's Medical College, 10 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.

Received March 11, 1982; revision accepted January 6, 1983.

12. Crosby EC, Humphrey T, Lauer EW: Correlative anatomy of the nervous system. New York, The McMillan Co., p 143-146, p 290-291, 1962

13. Brodal A: Neurological anatomy. Second ed. New York, Oxford Univ. Press, pp 402-405, 1969

14. Barr ML: The human nervous system. An anatomical viewpoint. New York, Harper & Row, p 113, 1972

15. Williams PL, Warwick R: Gray's anatomy. 35th ed., Edinburgh, Churchill Livingstone, p 1029, pp 1085-1086, 1975

16. Norgren R, Leonard CM: Taste pathways in rat brainstem. Science 173: 1136-1139, 1971

17. Norgren R, Leonard CM: Ascending central gustatory pathways. J Comp Neurol ISO: 217-238, 1973

18. Norgren R, Pfaffmann C: The pontine taste area in the rat. Brain Res 91: 99-117, 1975

19. Perrotto RS, Scott TR: Gustatory neural coding in the pons. Brain Res 110: 283-300, 1976

20. Nomura S, Mizuno N, Itoh K, Matsuda K, Sugimoto T, Nakamura Y: Localization of parabrachial nucleus neurons projecting to the thalamus or the amygdala in the cat using horseradish peroxidase. Exp Neurol 64: 375-385, 1979

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.

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-

Platelet Function Tests in Thrombotic Cerebrovascular Disorders

SHINICHIRO UCHIYAMA, M.D.*, MEGUMI TAKEUCHI, M.D.*, MIKIO OSAWA, M.D.*,

ITSURO KOBAYASHI, M.D.*, SHOICHI MARUYAMA, M.D.*, MASAHIKO AOSAKI, M.D.t,

AND KOSHICHIRO HIROSAWA, 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

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N Goto, T Yamamoto, M Kaneko and H TomitaPrimary pontine hemorrhage and gustatory disturbance: clinicoanatomic study.

Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 1983 American Heart Association, Inc. All rights reserved.

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