Journal of Neurology, Neurosurgery, and Psychiatry 1985;48:1165-1168

Short report

The neuroanatomy of vomiting in man: association ofprojectile vomiting with a solitary metastasis in thelateral tegmentum of the pons and the middlecerebellar pedunclePHILIP CH BAKER, JAMES L BERNAT

From Napier Hospital, Napier, New Zealand, and Dartmouth Medical School, Hanover, USA

SUMMARY Animal studies have indicated a "vomiting center" situated in the dorsal portion of thelateral reticular formation of the medulla at the level of the dorsal nucleus of the vagus. There isalso a chemoreceptor trigger zone in the floor of the fourth ventricle in the area postrema whichinfluences the vomiting center. A 63 year old man with a three year history of metastaticmalignant melanoma presented with nausea, projectile vomiting, gait ataxia and diplopia associ-ated with horizontal and vertical nystagmus. CT scan showed a solitary brainstem metastasiswithout hydrocephalus and he was treated with radiotherapy with resolution of his vomiting afterfour weeks. At post mortem three months later a metastasis was found in the right middlecerebellar peduncle and lateral tegmentum of the pons; there was no pathological change in thearea of the vomiting center or area postrema. It is postulated that this lesion caused projectilevomiting because of involvement of either afferent or efferent projections to the vomiting center.The neuroanatomy of vomiting is discussed.

Clinical studies have shown that there is a "vomitingcentre" situated in the dorso-lateral reticular forma-tion of the medulla with a chemoreceptor triggerzone for vomiting in the area postrema in the floorof the caudal part of the fourth ventricle.' The vom-iting centre was defined by Borison and Wang in19492 in a series of experiments on decerebrate cats.They showed that electrical stimulation of the lateralreticular formation in the vicinity of the fasciculussolitarius, but no other region of the brain-stem,resulted in immediate projectile vomiting whichcontinued for as long as the stimulus was applied.Hess3 found that stimulation of points in the dien-cephalon and forebrain occasionally produced vom-iting but this consisted of rhythmic retching move-ments rather than projectile vomiting and generallythere was some delay in onset. The vomiting centre

Address for reprint requests: PCH Baker, Napier, New Zealand.

Received 11 December 1984 and in revised form 26 April 1985.Accepted 10 May 1985

in the medullary reticular formation is not itself sen-sitive to centrally-acting emetic drugs such asapomorphine but rather these drugs act on a sepa-rate receptor area which, in the cat, is located in thearea postrema; this area differs from surroundingbrain tissue in that it is permeable to many particu-late substances such as tryphan blue, indicating abreakdown in the "blood-brain barrier." Ablationof the area postrema results in abolition of the eme-tic response to intravenous apomorphine whereasthe response to oral copper sulphate (which is pre-sumably mediated through afferent nerve fibresfrom the gut), is not affected unless the ablation alsoinvolves the lateral reticular formation.

Projectile vomiting in man has been associatedwith conditions of raised intracranial pressure, and,more particularly, with lesions of the posterior fossa.The pathophysiology of this response however hasnot been clearly defined. The patient who isreported in this paper is of interest in that he pre-sented with projectile vomiting and was found tohave a single lesion, which did not directly involve

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the medullary reticular formation or the caudal partof the fourth ventricle.

Case report

A 63-year old-man had a malignant melanoma removed

Afferents

Cerebellum Lateral reticularformation

Baker, Bernat

from his back three years earlier; he subsequently had asingle lung metastasis removed and later developed metas-tases in the bowel and buttock. Over the course of severaldays he developed nausea, projectile vomiting, diplopiaand ataxia. Lying down flat or leaning forwards producedvertigo and vertical diplopia, together with sudden, uncon-trollable forceful vomiting; when he sat or stood still how-ever he was reasonably comfortable. He had marked hori-zontal nystagmus on looking to either side, more on theright than the left, and vertical nystagmus on lookingupwards. There was no apparent paresis of eye movementbut looking upwards and laterally to either side producedvertical diplopia, with the abnormal image coming fromthe abducted eye. Pupils reacted normally and there werenormal corneal reflexes, facial sensation, facial movement,hearing, gag reflex, speech and tongue movement. Motorand sensory examination, deep tendon reflexes and plantarresponses were all normal. Tests of fine hand movementsshowed slight dysmetria bilaterally but his gait was mar-kedly ataxic with falling to either side. A CT scan showed asingle posterior fossa lesion extending from the lateralmargin of the pons into the right cerebellum; all four ven-tricles were normal in size. He was treated with high-dosesteroids and 2800 whole-brain irradiation; he also hadradiotherapy for recurrent metastases in the chest and but-tock. Vomiting improved after four weeks but the gait

Efferents

Dorsolateral pontinetegmentum

Vestibular sensoryepithelium /

Area Postrema

DrugsToxins

Nucleus

Respiratory centresVasomotor centreVII,IX (taste)

Gut / Spinal cord ant. horn cells

Sympathetic(b) Splanchnic nerves Respiratory Abdominal

muscles muscles

Fig (a) Dorsal view ofthe brain-stem showing malignant melanoma centred on the right middle cerebellar peduncle.Tumour also extends into the lateral tegmentum ofthe pons. (b) Major afferent and efferentpathways to the vomiting centre.? indicates that the assumed pathway has not been identified.

of X

:)Vagus'

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The neuroanatomy ofvomiting

ataxia did not change. He later developed pneumonia andsepticaemia and died about three months after his initialneurological presentation.

PathologyAt necropsy a solitary brain metastasis was found (fig, a);there was no hydrocephalus or any other pathologicalchange in the rest of the brain. The metastasis was centredon the right middle cerebellar peduncle and also involved aportion of the lateral basis pontis and the lateral tegmen-tum of the pons. Its caudal extent was marked by the facialcolliculus and rostrally it reached no further than the isth-mus; laterally it extended into the corpus medullare but didnot involve cerebellar cortex. In its caudal portion itincluded the superior and lateral vestibular nuclei andtherefore abutted the pontine lateral reticular formation;however it did not extend into the medulla at all. Thetumour was close to but did not involve the floor of therostral fourth ventricle and it did not obstruct or distort theanatomy of the ventricle.

Discusson

This patient had a single lesion which did not involveeither the classical vomiting centre in the medullarylateral reticular formation or the chemoreceptortrigger zone. We have considered two main pos-sibilities to account for his symptom of projectilevomiting. Firstly, he probably had raised intracranialpressure and movements of his head may havecaused further transient rises in pressure resulting invomiting. Against this suggestion is the fact that hedid not have hydrocephalus and the location andsize of the lesion, both on CT and post mortem,suggest that intermittent hydrocephalus would beunlikely to occur. If raised intracranial pressure isthe cause of projectile vomiting the question can stillbe asked what part of the vomiting mechanism isaffected by this factor; raised pressure in the IVthventricle could possibly exert an effect on the areapostrema, but we are not aware of any experimentalevidence to support this. Certainly any theory wouldhave to explain why projectile vomiting is muchmore common with lesions in the posterior fossathan with metabolic encephalopathies which causegeneralised cerebral oedema. Secondly, the lesionmay involve either efferent or afferent connectionsto the vomiting centre. Major efferent pathways arefound between the lateral reticular formation (LRF)and the cranial nerve motor nuclei controlling jaw,mouth and tongue movements and there are alsopathways to the motor neurons that controlrespiratory muscles and the striated abdominal mus-cles that are of prime importance in the expulsivephase of vomiting. Both efferent and afferent con-nections are made between the vomiting centre andthe various other centres in or adjacent to the LRF;these include the inspiratory and expiratory

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respiratory centres; the vasomotor centre and thesalivatory nucleus, each of which representsactivities that form part of the motor expression ofvomiting. The principal afferents to the vomitingcentre come from the area postrema and from thegut via both vagus and sympathetic splanchnicnerves, often with a relay in the adjacent nucleussolitarius. None of these pathways helps to explainthe cause of vomiting in our patient.

Since motion is a common cause of nausea andvomiting it has long been assumed that there mustbe some connection between the vestibular systemand the LRF. Labyrinthectomy, or section of theeighth cranial nerves, or removal of the cerebellarnodulus and pyramis prevents motion-induced vom-iting in animals.4 5 Removal of the cerebellum doesnot however reduce the emetic action of drugs suchas apomorphine, whereas if animals are made insen-sitive to the action of apomorphine by ablation ofthe area postrema, they are also rendered insensitiveto the emetic action of motion.6 This suggests thatthe area postrema is in the direct pathway betweenthe vestibular system and the vomiting centre. How-ever, to date this pathway has not been defined andno direct vestibular-reticular or cerebello-reticularpathways have been found, with the exception of thecerebello-reticular fibres found by Ramon y Cajal in1903,' which have only been identified in the rat andguinea-pig and not in other species.More recently it has been shown that there are

efferent fibres to the vestibular sensory epitheliumof the semi-circular cells which have their originpartly in the vestibular nuclei, but mainly in the LRFat the level of the upper medulla and lower pons;8this part of the LRF in its rostral extent is close tothe tumour found in our patient. It has been specu-lated that the vestibular efferents modulate thedynamic range of vestibular afferents to matchexpected acceleration of the head, and it is possiblethat mis-matching of vestibular impulses could con-tribute to nausea and/or vomiting. Motion sicknesshowever differs from projectile vomiting in thatnausea and retching are prominent and thereforethe same connection between the vestibular systemand the vomiting centre would not be expected tosubserve both processes.Recent studies using the technique of horse radish

peroxidase injections have shown that there aremany more connections between the LRF (now alsotermed the parvicellular reticular formation) andother brain-stem structures (fig, b). This subject hasrecently been reviewed by Mehler.9 Of particularinterest is the finding of ascending fibres from theLRF of the medulla and from the area postrema tothe dorso-lateral pontine tegmentum where theyterminate on or ventral to the parabrachial nuc-

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lei.>-"I There are also descending projections fromthe dorso-lateral tegmentum of the pons (from theKoelliker-Fuse nucleus which is ventro-lateral to theparabrachial nuclei), to the facial, ambiguus andhypoglossal nuclei and motor neurons of the spinalcord.'2 Since the lesion in our patient was located inthis same area of the tegmentum of the pons it ispossible that involvement of these pathways mayhave been the cause of his projectile vomiting.

Finally, it is interesting to turn to other casereports. Adams and Victor in their textbook Princi-ples of Neurology, state that the most persistentvomiting they have seen is in patients who have aposterior fossa lesion and they cite a case of abrain-stem glioma and a posterior fossa meningiomawithout otherwise specifying the location of thelesions. The most useful information comes fromLindstrum and Brizzee who report five patients withintractable vomiting, whom they treated by bilateralablation of the area postrema.'3 In each case spon-taneous vomiting and apomorphine-sensitive vomit-ing were abolished and this was achieved withoutproducing any other neurological sequelae. Thisreport is important in confirming that thechemoreceptor trigger zone in man is located in thearea postrema and also establishes a safe form oftreatment for intractable vomiting. It also providesfurther information about the nature of the lesionsthat can produce severe vomiting. In two of theircases there appeared to be a generalised cerebraldysfunction; the diagnosis in one was a non-specificencephalitis principally affecting brain-stem func-tion and with features of raised intracranial pres-sure; in the second, self-induced vomiting followinga possible encephalitis. The third patient wasassumed to have a brain-stem glioma; she had occi-pital pain, diplopia, ataxia, dysarthria and raisedintracranial pressure with papilloedema, as well asvomiting, but the lesion was not found at the time ofoperation for thermal ablation of the area postrema.The two final patients had clearly defined lesions inthe posterior fossa; one had a single metastaticlesion in the right cerebellum and the other hadmetastases in the midbrain, including "the posteriorhalf of the third ventricle and the left superior half ofthe fourth ventricle" (therefore including thedorso-lateral tegmentum of the pons). It is interest-ing to note that both the third and fifth patients wereexquisitely sensitive to movement; it is commentedthat they lay "motionless" in bed since even slightmovements induced vomiting'. This sensitivity tomovement, which was also seen in our patient, again

Baker, Bernat

raises the possibility of vestibular connections beinginvolved in the genesis of their vomiting.

In conclusion, while it is known that there is avomiting centre in the medulla, there is still much tobe learnt about the afferent and efferent connec-tions, and the exact pathophysiology of the varioustypes of vomiting has yet to be defined. The locationof a lesion causing projectile vomiting in man cannotbe predicted reliably but the clinico-pathologicalevidence we have presented suggests that there ismore likely to be involvement of the dorso-lateraltegmentum of the pons or the adjacent cerebellarpeduncles rather than the medulla.

References

'Borison HL, Wang SC. Physiology and pharmacology ofvomiting. Pharmacol Rev 1953;5: 193-230.

2 Borison HL, Wang SC. Functional localization of centralco-ordinating mechanism for emesis in cat. JNeurophysiol 1949; 12:305-13.

Hess WR. Vegetative Funktionen und Zwischenkirn.Helvet Physiol Acta 1947; Suppl 4.

Bard P, Woolsey CN, Snider RS, et al. Determination ofcentral nervous mechanisms involved in motion sick-ness. Fed Proc 1947;6:72.

Tyler DB, Bard P. Motion sickness. Physiol Rev1949;29:311-69.

6 Wang SC, Chinn HI. Emetic trigger zone and motionsickness in dogs. Fed Proc 1952;11:400.

Ramon y Cajal. La doble via descendente nacida delpedunculo cerebelloso superior. Trab Lab Invest BiolUniv Madrid 1903;2:23-29.

8 Ito J, Takahashi H, Matsuoka I et al. Vestibular efferentfibres to ampulla of anterior, lateral and posteriorsemi-circular canals in cats. Brain Res 1983;259:293-7.

Mehler WR. Observations on the connectivity of theparvicellular reticular formation with respect to avomiting center. Brain Behav Evol 1983;23:63-80.

'° King GW. Topology of ascending brainstem projectionsto nucleus parabrachialis in the cat. J Comp Neurol1980; 191:615-38.

Shapiro RE, Miselis RR. An efferent projection fromthe area postrema and the caudal medial nucleus ofthe solitary tract to the parabrachial nucleus in rat.Neurosci Abstr 1982; 8:269.

12 Mizuno N, Nomura S, Takeuchi Y. The parabrachialnucleus as an intermediate relay station of the visceralafferent pathways in the cat, In Ito: Integrative ControlFunction of the Brain. Vol. 3. Amsterdam, Elsevier,1981. pp 1-20.

3 Lindstrom PA, Brizzee KR. Relief of intractable vomit-ing from surgical lesions in the area postrema. JNeurosurg 1962;228-36.

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doi: 10.1136/jnnp.48.11.1165 1985 48: 1165-1168J Neurol Neurosurg Psychiatry

 P C Baker and J L Bernat peduncle.pons and the middle cerebellarin the lateral tegmentum of the vomiting with a solitary metastasisman: association of projectile The neuroanatomy of vomiting in

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