Treatment of Pathological Affect

Sudden, uncontrollable episodes of emotional display or pathological laughing and crying (PLC) occur with diverse neurologic conditions^1,2 and can be a source of significant morbidity. Although three recent placebo-controlled trials have established that effective treatments exist,^3–5 many aspects of the syndrome remain uncertain. It is not known, for example, why some patients cry while others laugh or show a mixture of the two. PLC has historically been considered a disturbance of the motor components of affective behavior, rather than a primary emotional disorder.⁶ Thus Poeck⁷ emphasized three primary features: 1) sudden loss of voluntary emotional control; 2) occurrence in response to “nonspecific,” often inconsequential stimuli; and 3) lack of clear association with prevailing mood state. Although patients may vary in the extent to which each of these aspects is found,⁸ these criteria have received wide acceptance.^3–5,9

In our work with patients who have amyotrophic lateral sclerosis (ALS), we encountered a feature not previously described: three cases of PLC in which affect changed from a predominance of crying to laughter.

CASE REPORTS

DISCUSSION

To our knowledge, these are the only reported cases of a relatively rapid transformation of crying into laughter. In Case 1, PC was directly exchanged for PL, while in the other two, mixed syndromes with a predominance of PC were replaced by PL alone, of milder intensity. The patients met criteria for pathological affect⁷ throughout. A number of possibilities could account for these observations.

First, our cases may simply demonstrate a partially treated, mixed PLC syndrome, since each patient declined an offer to adjust medications. The notion that patients may vary in their dosage requirements for full resolution of symptoms makes intuitive sense and is consistent with our clinical experience. However, none of the reported treatment studies have examined dose-response relationships.^3–5,11 Furthermore, limited detail is available regarding the nature of a “partial response” when one has occurred.^5,11 It is possible that such a response may manifest not only as a lessening in the severity of PLC symptoms (frequency, intensity, or degree of perceived control) but also as a change from a predominance of one type of affect to the other. This may be analogous to what has anecdotally been described as the natural course in some cases of PLC,^7,12,13 where a slow transition from PC to PL occurred prior to eventual symptom resolution. In our cases, a similar change may have occurred, yet at a much hastened pace due to pharmacologic intervention. Whether the direction of this change is typically from predominant crying to laughter is unknown. The possibility of a change in the opposite direction is suggested in a single case report.¹⁴

Another explanation is that PL requires a different, perhaps higher dose of medication than PC, thus leaving residual PL when a mixed syndrome is only partially treated. This possibility cannot be refuted based on the controlled treatment studies to date, which have focused largely on patients with PC.^3–5 The paucity of patients with PL in the cohorts does not permit direct comparisons of the two affective states and may, in part, reflect the fact that PC is more common than PL.^1,6–8 Although Udaka et al.¹¹ did include a significant number of patients with PL in their open trial of levodopa, they did not report drug dosages needed to obtain a response, again limiting comparisons between the two states.

A final consideration, at least in Case 1, is that the presence of an ongoing depression may affect the nature of PLC symptoms. Ross and Stewart¹⁵ have suggested that depression causes a “state change” in limbic structures, with a “lowered threshold” for displaying extreme affective responses. When depression is then combined with a cortical lesion that reduces control of limbic-associated motor behaviors, PLC may result.¹⁵ Perhaps comorbid depression can also contribute to the intensity or even the “color” that the predominant symptoms of PLC may take. Thus in Case 1, when major depression was present, the patient expressed predominantly “negative” affective displays in the form of PC. When the mood disorder resolved, residual PLC took the form of laughing. In both instances the affect was described as out of keeping with inner mood. Furthermore, the idea that depression may affect PLC symptoms is supported by a case report in which a stroke patient with PC, initially responsive to fluoxetine, relapsed with the onset of a superimposed depression.¹⁴ In addition, Robinson et al.⁴ found a trend for a cohort of PLC patients with depression to show a lesser response to treatment than a cohort without depression. Although findings on this point have not been previously described, it is possible that depression can alter the thresholds for the expression of one type of affect over another in PLC, perhaps because the two syndromes have similar limbic-associated motor networks for their expression.

In summary, we have described three patients with an unusual change in predominant pathological affect following pharmacologic intervention and have suggested possible explanations to account for the phenomenon. The cases raise intriguing questions regarding the nature and course of pathological affect, effects of pharmacologic treatment, and relationship to other neuropsychiatric syndromes, such as depression. Prospective study of the syndrome across neurological illnesses, using careful definitions for pathological laughing and crying, will further elucidate the clinical changes observed in our cases.

ACKNOWLEDGMENTS

The authors thank Marek Gawel, M.D., F.R.C.P.C., and Myrna Moore, B.Sc., R.N., of the Sunnybrook Hospital Neuromuscular Disorders Clinic for referring these patients to us.