Treatment of Ballism and Pseudobulbar Affect with Sertraline

OBSERVATION Treatment of Ballism and Pseudobulbar Affect With Sertraline

Michael S. Okun, MD; Alonso R. Riestra, MD; Stephen E. Nadeau, MD

Background: The pathogenesis of ballism is uncertain Results: Complete remission of symptoms within 48 and may involve more than one mechanism; treatment hours of each drug trial. is not always efficacious.

Objective: To provide evidence of a nondopaminergic Conclusion: Sertraline may offer an alternative with a mechanism and the potential for a prompt and nearly com- better adverse effect profile than dopamine receptor plete response to a serotonergic agent. blockers in the treatment of patients with ballism.

Methods: Report of 2 separate trials of sertraline hy- drochloride in a single patient. Arch Neurol. 2001;58:1682-1684

HE MECHANISM of ballism is not smoked in 25 years. He was a former uncertain, and its re- railroad worker now practicing television sponse to treatment with evangelism. neuroleptics is frequently Although the patient’s vital signs were slow, fraught with adverse normal, he had an irregularly irregular effects,T and occasionally so unsatisfac- heartbeat. He recalled none of 3 objects af- tory as to motivate surgical treatment. We ter several minutes of distraction, and he report a case that suggests that an alter- had an anomic aphasia. He had a de- native treatment, sertraline hydrochlo- pressed mood and flattened affect, and he ride, may be rapidly effective and associ- frequently exhibited pseudobulbar cry- ated with few adverse effects. This and ing. When asked, he denied that he was sad other reported cases also suggest that the on these occasions. Cranial nerve exami- mechanism of ballism may be complex and nation results were normal with the excep- susceptible to different treatments in dif- tion of an incongruous right homony- ferent patients. mous hemianopia, saccadic breakdown of ocular smooth pursuit movements, and a REPORT OF A CASE mild right supranuclear palsy of the sev- enth cranial nerve. During a motor exami- A 73-year old, previously healthy right- nation, there was facilitatory paratonia in handed man had a 10-day history of right- the right upper and lower extremities, a sided weakness, unpredictable jerking of his mild right hemiparesis (4/5 in the deltoid, right upper extremity and, to a lesser ex- distal upper extremity muscles, and hip From the Department of tent, his right lower extremity, and uncon- flexors), and pronation drift of the right up- Neurology, Emory University trollable crying spells. He also complained per extremity. At rest he exhibited fre- (Dr Okun), Atlanta, Ga; the of recent difficulty with short-term memory, quent, irregular, high-amplitude ballistic Department of Neurology, mild slurring of speech, an inability to see movements of his proximal right upper ex- University of Florida College objects on his right side, and a several- tremity. Adventitious movements of the of Medicine (Drs Riestra and month history of intermittent palpitations. right lower extremity were of much lower Nadeau), and the Geriatric He had no double vision, dysphagia, dys- amplitude. These movements were worse Research, Education and arthria, dizziness, or sensory symptoms. He during intentional activity, including finger- Clinical Center and the Brain Rehabilitation Research Center, had a history of hypertension and type 2 dia- to-chin and toe-to-target maneuvers and Malcom Randall Department betes mellitus that was diet controlled, and ambulation. He also had mild, nearly con- of Veterans Affairs Medical he had undergone coronary artery bypass tinuous choreiform movements of the right Center (Dr Nadeau), surgery. There was no history of stroke. He upper and lower extremities, both at rest Gainesville, Fla. had a 60 pack-year smoking history but had and with intentional activity, that were

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Magnetic resonance imaging study (fluid-attenuated inversion recovery sequences) obtained 15 days after the onset of symptoms.

present between the episodes of ballistic movement. There sertraline was then stopped, and within 48 hours the pa- was mild, symmetric impairment in all sensory modali- tient again became morose, exhibited uncontrollable cry- ties extending to the ankles, and there was a decrease in ing episodes, and experienced a return of the ballism. pinprick and temperature sensation in the right upper and Symptoms resolved within 48 hours of resumption of lower extremities. Cerebellar function was intact. Re- treatment. flexes were slightly more brisk on the right, and plantar responses were equivocal. COMMENT The results of a complete blood cell count, mea- sures of electrolytes, a metabolic profile, and liver func- The anterior choroidal artery supplies anterior regions tion studies were normal. An electrocardiogram re- of the medial temporal lobe (most consistently includ- vealed atrial fibrillation. An echocardiogram revealed an ing the anterior hippocampus), dorsomedial portions of ejection fraction of 25%. A 4-hour electroencephalo- the lateral geniculate nucleus and adjacent optic tract and gram did not reveal any epileptiform activity, even dur- radiations, ventral and retrolenticular portions of the pos- ing the patient’s involuntary movements and pseudobul- terior limb of the internal capsule, the medial globus pal- bar episodes. Goldmann perimetry of the left eye lidus, dorsal portions of the subthalamic nucleus, the H2 demonstrated a right hemianopia detectable only with field of Forel, the zona incerta, and in some cases, the the smallest, least intense target. Perimetry of the right middle portion of the cerebral peduncle and adjacent sub- eye revealed a dense right superior quadrantanopia ex- stantia nigra.2,3 On MRI studies of our patient, infarc- tending inferiorly as far as the 330° radian in the right tion was not visible through the entire territory of the inferior quadrant. artery, presumably because of the limited sensitivity of The lesion was mapped using axial 3-mm sections MRI in detecting ischemic damage short of complete in- from a magnetic resonance imaging (MRI) study of the farction.4 Nevertheless, it may reasonably be inferred that brain (Figure) onto plates from the Schaltenbrand and the memory deficits seen in our patient reflect involve- Bailey1 atlas with a modified camera lucida technique. ment of mesial temporal structures; the hemianopia re- The lesion involved posterior portions of the posterior flects involvement of the optic tract, lateral geniculate limb of the internal capsule, posterolateral portions of nucleus, or proximal portions of the geniculocalcarine the pulvinar, portions of the body and tail of the cau- tract; the language deficits, characteristic of thalamic apha- date, portions of the lateral geniculate nucleus, the hip- sia, reflect damage to thalamocortical pathways by the pocampus and adjacent parahippocampal gyrus, and pos- internal capsule lesion4; and the ballism reflects disrup- teroinferior portions of the amygdala and periamygdaloid tion of the subthalamopallidal pathway or damage to the cortex. There was a small region of hemorrhage in the subthalamic nucleus. The origin of the depression and area of infarction. The locus and extent of the lesion were pseudobulbar affect is uncertain. The territory of the an- entirely consistent with a left anterior choroidal artery terior choroidal artery extends sufficiently medially be- distribution infarct even though involvement of the en- low the thalamus to include the ascending noradrener- tire territory of the artery was not evident. No other le- gic and serotonergic pathways traveling in the median sions appeared on the MRI. forebrain bundle.3,5 Thus, the depression and pseudo- A dose of 50 mg/d of sertraline was initiated 10 days bulbar affect could reflect depletion of norepinephrine after the onset of symptoms. Marked improvement in de- and serotonin in the mesolimbic structures. pression, pseudobulbar symptoms, and ballism was noted The treatment of pseudobulbar affect with selec- within 24 hours, and these problems had completely re- tive serotonin reuptake inhibitors (SSRIs) such as ser- solved following 48 hours of treatment. The only re- traline is well established in the literature,6 although there sidual movement disorder was a subtle, intermittent cho- is some uncertainty about the mechanism underlying its rea of the arm at rest that increased during walking. The effects. Patients typically respond rapidly and to low doses.

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 The favorable response of pseudobulbar affect to sertra- an alternative to haloperidol by virtue of its fast onset of line in our case may reflect the effect of this SSRI on se- action and better adverse effect profile (low risk of par- rotonin levels in the limbic system, the nucleus accum- kinsonian effects or tardive dyskinesia), or it could pro- bens, or the cerebral cortex on the involved side. vide an alternative for patients in whom the mechanism Neuroleptics have been the mainstay of treatment of ballism makes the disorder susceptible to treatment that for hemiballism.7 However, approximately 16% of af- potentiates serotonergic activity. Because we did not test fected patients fail to respond to these or other antido- the merits of sertraline relative to typical or atypical D2 (do- paminergic drugs or to clonazepam, and the mean delay pamine) receptor blockers, we can draw no conclusions to response in one series was 15 days.8 In some patients, regarding these possibilities. the disorder is so severe and refractory that it motivates surgical treatment.9 Thus, there is a need for alternative Accepted for publication May 23, 2001. pharmacological approaches. The response to sertraline Corresponding author: Stephen E. Nadeau, MD, in our patient was both dramatic and prompt. It is con- GRECC-182, Malcom Randall DVA Medical Center, Gaines- ceivable that the improvement reflected a placebo ef- ville, FL 32608-1197 (e-mail: [email protected]). fect, but this seems unlikely because we told the patient that we were targeting only the emotional incontinence. REFERENCES It is unlikely that the improvement reflected spontaneous resolution because symptoms recurred following dis- 1. Schaltenbrand G, Bailey P. Introduction to Stereotaxis With an Atlas of the Hu- continuation of sertraline. man Brain. Stuttgart, Germany: Verlag; 1959. This may represent the first report of successful treat- 2. Pullicino PM. The course and territories of cerebral small arteries. In: Pullicino ment of ballism with sertraline. It is not the first report of PM, Caplan LR, Hommel M, eds. Cerebral Small Artery Disease. New York, NY: a favorable response to a drug that potentiates serotoner- Raven Press; 1993:11-39. 10 11 3. Pullicino PM. Diagrams of perforating artery territories in axial, coronal and sag- gic activity : Lenton et al described successful treat- ittal planes. In: Pullicino PM, Caplan LR, Hommel M, eds. Cerebral Small Artery ment with valproate sodium in 1981. The mechanism un- Disease. New York, NY: Raven Press; 1993:41-72. derlying the beneficial effect of sertraline is uncertain, but 4. Nadeau SE, Crosson B. Subcortical aphasia. Brain Lang. 1997;58:355-402, 436- there are several possibilities. First, serotonin is known to 458. play a role in modulating the presynaptic release of sev- 5. Felten DL, Sladek JR Jr. Monoamine distribution in primate brain V: monoamin- ergic nuclei: anatomy, pathways and local organization. Brain Res Bull. 1983; eral neurotransmitters via its action on serotonin (5- 10:171-284. HT)1B and 5-HT2 receptors, and SSRIs have been shown 6. Mukland J, Kaplan M, Senno RG, Bishop DS. Pathologic crying and laughing: to reduce dopamine release in the striatum.12,13 By this treatment with sertraline. Arch Phys Med Rehabil. 1996;77:1309-1311. mechanism, sertraline could have emulated the benefi- 7. Bressman SB, Greene PE. Treatment of hyperkinetic movement disorders. Neu- rol Clin. 1990;8:51-75. cial effects of dopamine receptor blockers in the treat- 8. Vidakovic A, Dragasevic N, Kostic VS. Hemiballism: report of 25 cases. J Neurol ment of ballism. This same effect may account for the oc- Neurosurg Psychiatry. 1994;57:945-949. casional development of extrapyramidal features in patients 9. Kraus JK, Mundinger F. Functional stereotactic surgery for hemiballism. J Neu- given SSRIs,14 including sertraline,15 and in patients given rosurg. 1996;85:278-286. sumatriptan succinate, a specific 5-HT agonist.16 These 10. Maes M, Calabrese J, Jayathilake K, Meltzer HY. Effects of subchronic treatment 1B with valproate on L-5-HTP-induced cortisol responses in mania: evidence for in- characteristics most often consist of akathisia or dystonia creased central serotonergic neurotransmission. Psychiatry Res. 1997;71:67-76. but may include more classical parkinsonian features. 11. Lenton RJ, Copti M, Smith RG. Hemiballismus treated with sodium valproate. Second, postsynaptic serotonergic effects of sertra- BMJ. 1981;283:17-18. line may have increased the firing rate of neurons within 12. Dewey SL, Smith GS, Logan J, et al. Serotonergic modulation of striatal dopa- 17 mine measured with positron emission tomography (PET) and in vivo microdi- the subthalamic nucleus that, via the globus pallidus alysis. J Neurosci. 1995;15:821-829.

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