References

1. Ross ED: The aprosodias: Functional ana-tomic organization of the affective componentsof language in the right hemisphere. Arch Neurol1981;38:561-569.

2. Ross ED, Mesulam M-M: Dominant lan-guage functions of the right hemisphere?: Proso-dy and emotional gesturing. Arch Neurol 1979;36:144-148.

3. Heilman KM, Scholes R, Watson RT: Audi-tory affective agnosia: Disturbed comprehensionof affective speech. J Neurol Neurosurg Psychia-try 1975;38:69-72.

4. Tucker DM, Watson RT, Heilman KM: Dis-crimination and evocation of affectively intonedspeech in patients with right parietal disease.Neurology 1977;27:947-950.

5. Larsen B, Skinh\l=o/\jE, Lassen NA: Variationsin regional cortical blood flow in the right andleft hemispheres during automatic speech. Brain1978;101:193-209.

6. Ross ED: Modulation of affect and nonver-bal communication by the right hemisphere, inMesulam M-M (ed): Principles of BehavioralNeurology. Philadelphia, FA Davis Co Publish-ers, 1985, chap 6.

7. Hughes CP, Chan JL, Su MS: Aprosodia inChinese patients with right cerebral hemispherelesions. Arch Neurol 1983;40:732-736.

8. Gorelick PB, Ross ED: The aprosodias: Fur-ther functional-anatomic evidence for the orga-nization of affective language in the right hemi-sphere. J Neurol Neurosurg Psychiatry, inpress.

9. Fisher CM: The pathologic and clinicalaspects of thalamic hemorrhage. Trans Am Neu-rol Assoc 1959;84:56-59.

10. Bugiani O, Conforto C, Sacco G: Aphasia inthalamic hemorrhage. Lancet 1969;1:1052.

11. Samarel A, Wright TL, Sergay S, et al:Thalamic hemorrhage with speech disorder.Trans Am Neurol Assoc 1976;101:283-285.

12. Reynolds AF, Harris AB, Ojemann GA, etal: Aphasia and left thalamic hemorrhage.J Neurosurg 1978;48:570-574.

13. Reynolds AF, Turner PT, Harris AB, et al:Left thalamic hemorrhage with dysphasia: Areport of five cases. Brain Lang 1979;7:62-73.

14. Cappa SF, Vignolo LA: 'Transcortical' fea-tures of aphasia following left thalamic hemor-rhage. Cortex 1979;15:121-130.

15. Alexander MP, LoVerme SR: Aphasia afterleft hemispheric intracerebral hemorrhage. Neu-rology 1980;30:1193-1202.

16. Demeurisse G, Derouck M, Coekaerts MJ,et al: Study of two cases of aphasia by infarctionof the left thalamus without cortical lesion. ActaNeurol Belg 1979;79:450-459.

17. Cohen JA, Gelfer CE, Sweet RE: Thalamicinfarction producing aphasia. Mt Sinai J Med1980;47:398-404.

18. Gorelick PB, Hier DB, Benevento L, et al:Aphasia after left thalamic infarction. ArchNeurol 1984;41:1296-1298.

19. McFarling D, Rothi LJ, Heilman KM:Transcortical aphasia from ischemic infarcts ofthe thalamus: A report of two cases. J NeurolNeurosurg Psychiatry 1982;45:107-112.

20. Smyth GE, Stern K: Tumors of the thala-mus: A clinico-pathological study. Brain 1938;61:339-374.

21. Damasio AR, Damasio H, Rizzo M, et al:Aphasia with nonhemorrhagic lesions in thebasal ganglia and internal capsule. Arch Neurol1982;39:15-20.

22. Naeser MA, Alexander MP, Helm-Esta-

brooks N, et al: Aphasia with predominantlysubcortical lesion sites: Description of three cap-sular/putaminal aphasia syndromes. Arch Neu-rol 1982;39:2-14.

23. Cappa SF, Cavalotti G, Guidotti M, et al:Subcortical aphasia: Two clinical CT scan corre-lation studies. Cortex 1983;19:227-241.

24. Wallesch C-W: Two syndromes of aphasiaoccurring with ischemic lesions involving the leftbasal ganglia. Brain Lang 1985;25:357-361.

25. Tanridag 0, Kirshner HS: Aphasia andagraphia in lesions of the posterior internalcapsule and putamen. Neurology 1985;35:1797\x=req-\1801.

26. Ross ED, Harvey JH, deLacoste-UtamsingC, et al: How the brain integrates affective andpropositional language into a unified behavioralfunction. Arch Neurol 1981;38:745-748.

27. Benson DF: Aphasia, Alexia and Agraphia.New York, Churchill Livingstone Inc, 1979.

28. Ross ED, Edmondson JA, Seibert GB, et al:Acoustic analysis of affective prosody duringright-sided Wada Test: A within-subjects verifi-cation of the right hemisphere's role in language.Brain Lang, in press.

29. Ross ED, Holzapfel D, Freeman F: Assess-ment of affective behavior in brain-damagedpatients using quantitative acoustical-phoneticand gestural measurements. Neurology 1983;33(suppl 2):219-220.

30. Geschwind N: Discussion of cerebral con-nectionism and brain function, in Millikan CH,Darly FL (eds): Brain Mechanisms UnderlyingSpeech and Language. New York, Grune & Strat-ton, 1967, pp 71-72.

31. McKissock W, Paine KWE: Primarytumors of the thalamus. Brain 1958;81:41-63.

Behavioral Manifestations ofCentral Pontine MyelinolysisBruce H. Price, MD, M.-Marsel Mesulam, MD

\s=b\A young woman with a clinical histo-ry and magnetic resonance imaging scanconsistent with central pontine myelinoly-sis came to medical attention because ofprominent behavioral symptoms. Markedclinical recovery occurred despite persis-tent radiologic abnormalities. Rapid cor-rection of hyponatremia was probablyrelated to the development of the centralpontine myelinolysis. A normal computedtomographic scan and the absence ofbrain-stem signs delayed accurate diag-nosis.

(Arch Neurol 1987;44:671-673)

(""'entrai pontine myelinolysis (CPM)was first described by Adams et

al1 in 1959. Early descriptions empha-

sized its grave prognosis.2 More recentreports have documented survival andrecovery.3 Ventral pontine involve¬ment with subacute onset of cerebel¬lar, cranial nerve, and pyramidal tractdysfunction is the typical presenta¬tion.4

We describe a patient in whomreversible behavioral abnormalitiesconstituted the major manifestationof CPM. One purpose of this article isto alert physicians to the possiblebehavioral presentation of CPM.Another is to reemphasize the rela¬tionship between rapid correction ofhyponatremia and CPM. We also for¬ward some thoughts on the patho¬physiology of these behavioralchanges.

REPORT OF A CASE

A 29-year-old right-handed professionalwoman was in excellent health until herreturn from Mexico. She developed intract¬able nausea, anorexia, and diarrhea for oneweek, leading to a 2.2-kg (5-lb) weightloss.

Results of a clinical examination at thattime were normal, except for orthostatichypotension. Laboratory test results dis¬closed the following values: serum sodium,114 mEq/L (114 mmol/L); potassium, 1.9mEq/L (1.9 mmol/L); arterial blood gasesdemonstrated respiratory alkalosis; heralanine aminotransferase level was ele¬vated to 128 U/L; and aspartate amino¬transferase, to 115 IU/L. Campylobacterwas grown from her stools. There was nohistory of major psychiatric disease in thepatient or her family.

She received 2 L of normal saline withpotassium supplementation. Seventeenhours later, her sodium level was 133 mEq/L (133 mmol/L), and her potassium levelwas 4.2 mEq/L (4.2 mmol/L). She recov-

Accepted for publication Dec 15, 1987.From the Division of Neuroscience and Behav-

ioral Neurology, Charles A. Dana Research Insti-tute, Beth Israel Hospital, Boston.

Reprint requests to Division of Neuroscienceand Behavioral Neurology, Charles A. DanaResearch Institute, Beth Israel Hospital, 330Brookline Ave, Boston, MA 02215 (Dr Price).

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Magnetic resonance sagittal image demonstrating triangular area of increased signal intensity inupper, midportion of pons without associated mass effect.

ered uneventfully and was dischargedafter two days.

Six days after discharge, while on duty,her colleagues noted inappropriate, con¬fused, and restless behavior. Neurologicexamination disclosed an inattentive, agi¬tated woman with pressured, tangentialspeech, mild dysarthria, word-finding dif¬ficulties, and right-hand clumsiness. Judg¬ment and insight were markedly impaired.She kept circulating throughout the hospi¬tal despite admonishment to remain in herroom, denied the importance of her illness,groomed herself publicly in the hallways,spoke of her difficulties to strangers, andinappropriately attempted to resume herprofessional activities. Other than occa¬sional paraphasic errors, no cognitive defi¬cits were apparent.

Results of laboratory tests, including acomplete blood cell count, electrolytes, thy¬roid functions, vitamin B12 and folate lev¬els, toxic screens, antinuclear antibody,hepatitis surface antigen (HBsAg), andechocardiogram were unremarkable, aswas a contrasted computed tomographic(CT) scan of the head. Her erythrocytesedimentation rate was elevated to 37 mm/h. Cerebrospinal fluid analysis, includingIgG and oligoclonal bands, was normal.Bilateral carotid angiogram and visual,auditory, median, and tibial somatosenso¬ry evoked potentials were normal. Electro-encephalography (EEG) showed left ante¬rior sylvian to midtemporal delta slowingand occasional biposterior generalizedsharp waves. Magnetic resonance imaging(MRI) scanning using steady-state freeprocession and spin-echo sequences with

sagittal and axial images demonstrated atriangular area of increased signal intensi¬ty in the midportion of the pons withoutmass effect (Fig 1).

The patient's behavior, speech, and dex¬terity returned to normal over a period oftwo weeks. In four weeks, she returned toher occupation full-time without difficulty.An EEG performed three months afterdischarge demonstrated high-voltage al¬pha bursts over the left anterior and mid-temporal region, with brief paroxysmalgeneralized bifrontal theta. Her erythro¬cyte sedimentation rate returned to nor¬mal, electrolytes remained stable, and arepeat MRI scan performed 2xk monthsafter onset showed no change in theappearance of the brain-stem lesion.Twelve months after onset, she continuesto do well.

COMMENT

Patients who subsequently developCPM characteristically arrive at thehospital in a debilitated state with alow serum sodium level.5 There aremany reports of intractable nausea,vomiting, and diarrhea prior toadmission. Though frequently associ¬ated with Wernicke's encephalopathyand chronic alcoholism,2 CPM mayoccur in the context of other condi¬tions such as pneumonia, neoplasms,malnutrition, ataxia, weight loss, gas¬trointestinal bleeding, Wilson's dis¬ease, and renal transplantation.6·7 Thepeak age of incidence is the fourth

through seventh decades; however,CPM has been documented in childrenas well.2·8 A low sodium level withrapid correction (or overcorrection) isa common feature, and may constitutean important factor in the cause ofthe myelinolysis.5 A positive correla¬tion between the severity of the sodi¬um deficits, the rate of its correction,and the size of the lesion has beensuggested.' The rapid correction ofelectrolytes and especially serumsodium in these patients is thought tolead first to improvement, and then,in three to ten days, to the pontinemyelinolysis with associated cerebel¬lar ataxia, cranial nerve dysfunction,and quadriparesis with respiratorydifficulties.5

Emotional lability, especially cry¬ing, has been reported in CPM andthought to be secondary to corticobul-bar lesions.10 Confusion and disorien¬tation have been noted in somepatients, and may precede other signsor symptoms. However, the cause ofthese symptoms is unclear, given theassociated diseases that can indepen¬dently lead to a metabolic encephalop¬athy.6 The behavioral changes de¬scribed in CPM are almost alwaysovershadowed by more prominentbrain-stem signs. The maximal neuro¬logic deficit usually emerges one tothree weeks later, and, in severe cases,intercurrent illness causes death twoto four weeks after onset.' In otherinstances, improvement and completerecovery have been reported.3

Cerebrospinal fluid analysis inCPM is usually normal. Brain-stemauditory evoked potentials may ormay not demonstrate prolongation ofwave I through V latencies.1113 The CTscan may demonstrate a nonenhanc-ing, hypodense ventral-pontine lesion,but normal CT scans have also beenreported.13·14 The CT abnormality maylast longer than clinical symptoms.16In one patient who completely recov¬ered after six months, only partial CTresolution was apparent after 12months, with complete CT resolutionshown 22 months after onset.17 TheEEG is usually normal or nonspe¬cific.6 Magnetic resonance imagingscans have been reported to show anabnormal density signal in the ventralpons without mass effect.13 RepeatedMRI scans performed 15 weeks toeight months later may or may notdemonstrate interval changes, despiteclinical improvement.18 A specificantemortem test for the diagnosis ofCPM is currently unavailable.

In our patient, the diagnosis of CPMis suggested mostly by the MRI scanabnormality and the rapid correction

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of hyponatremia eight days prior tothe onset of symptoms. Albeit mild,the right-handed clumsiness, thedysarthria, and the rate of clinicalresolution are consistent with thisdiagnosis. The marked behavioralabnormalities in the absence of prom¬inent brain-stem signs and the settingof a young person in good underlyinghealth are the unusual features. TheEEG focality and language impair¬ments are atypical in that they indi¬cate a lesion in the left hemisphere,but they could be associated withextra pontine myelinolysis that hasbeen reported in CPM.9

PATHOANATOMIC STUDIES

Central pontine myelinolysis is aunique clinical pathologic entity,which involves median pontine struc¬tures and usually spreads in a centrif¬ugal, symmetric fashion.1 It mayinvolve the corticospinal, corticobul-bar, and pontocerebellar tracts, crani¬al nerves, and other ventral pontinestructures.1·6 Extensive involvement ofthe midbrain, pontine tegmentum,paramedian reticular area, sympa¬thetic fibers, and sensory pathwaysmay occur.1·'1' Approximately 10% ofcases have associated extra pontinelesions in the spinal cord, medulla,mesencephalic tectum, basal ganglia,cerebellum, internal capsules andthalami, cerebral peduncles, opticradiations, lateral geniculate bodies,hemispheric white matter, and cere¬bral cortex.9·20

Incomplete demyelination and ede¬ma is seen with preservation of nervecells, axis cylinders, and blood vessels.There are no signs of inflammation.1Central pontine myelinolysis as veri¬fied by postmortem examination maynot be clinically obvious. Of the fourcases originally reported by Adams etal,1 two manifested no clinical symp¬toms. The small size of their lesionswas the suggested explanation. Nor-enberg et al5 and Wright et al' alsoreported CPM at postmortem exami¬nation, which may not have been clin¬ically apparent.9·5

The exact pathophysiology of ourpatient's altered behavior remainsobscure. Since the onset occurredeight days after correction of her elec¬trolyte abnormalities, a metabolicderangement is unlikely. Instead, it ismore plausible that these behavioralalterations were caused by the CPM.The location of the MRI abnormalitysuggests that the lesion may haveinterfered with the ascending projec¬tions of the raphe nuclei, pontomesen-cephalic reticular formation, and per¬haps even those of the nucleus locus

coeruleus. This would interfere withthe cortical and thalamic supply ofserotonin, acetylcholine, and norepi¬nephrine, respectively. Considerableevidence indicates that alterations inthese neurotransmitter pathwaysplay a role in the modulation of moodand arousal.21

Behavioral abnormalities with oth¬er pontine lesions have been reported.In pediatrie pontine tumors, profoundmental status changes may precedeother signs and symptoms.22·24 Thesebehavioral changes may range fromrestlessness, irritability, aggression,and rage, to apathy, lethargy, disori¬entation, and confusion.

Animal experiments suggest thathyponatremia rapidly corrected byhypertonic saline can induce demye¬lination, whereas hyponatremia aloneor its slow correction does not.25 Cur¬rent indications are to reverse hypo¬natremia to prevent seizures andencephalopathy, but to do so slowly. Ifthe serum sodium level is below 105mEq/L (105 mmol/L), initial correc¬tion at 2 mEq/L/h (2 mmol/L/h) isrecommended for the first 20 mEq/L(20 mmol/L). The serum sodium levelshould then be allowed to drift tonormal range. If the serum sodiumlevel is 105 mEq/L (105 mmol/L) orgreater, it can be corrected at thesame rate to a level of 125 to 130mEq/L (125 to 130 mmol/L). Serumsodium levels above 120 mEq/L (120mmol/L) usually do not requireimmediate correction.26 Adherence tothese guidelines could reduce the inci¬dence of CPM.

This patient indicates that CPMshould be included in the differentialdiagnosis of acute behavioral changes,especially if rapid correction ofhyponatremia has occurred in therecent past. In fact, CPM may occurmore frequently than clinically sus¬pected, and MRI scanning may beessential for accurate diagnosis.

The preparation of this manuscript was sup¬ported in part by the Javits Neuroscience Inves¬tigator Award, National Institutes of Health,Washington, DC.

We wish to thank Mark Aronson, MD, forreferring the patient, Donald Schomer, MD, forinterpreting the electroencephalograms, FerencJolesz, MD, for interpreting the magnetic reso¬nance imaging scans, Nan Rubin, MS, for admin¬istering language examinations, and LoraineKarol for her secretarial assistance.

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