Sudden, uncontrollable episodes of emotional display or pathological laughing and crying (PLC) occur with diverse neurologic conditions1,2 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 1. A 73-year-old man presented with a 4½-year history of ALS. He had developed major depression 18 months later, following formal diagnosis with ALS. Depressive features included pervasive dysphoric mood, anhedonia, depressive cognitions, and characteristic neurovegetative changes. Prolonged episodes of uncontrollable weeping began shortly thereafter. They were reported as inappropriate, in marked excess of subjective feelings, and without precipitants. On examination corticobulbar tract signs were present: exaggerated facial reflexes bilaterally, positive snout response, spastic dysarthria, and a mildly exaggerated jaw reflex. Mini-Mental State Examination (MMSE) score10 was 28/29. The depressive symptoms, along with his pathological crying (PC), remitted on 20 mg of fluoxetine within 2 weeks, only to be replaced by pathological laughter (PL). The patient, however, wished no adjustment in medication, describing the laughter as preferable to weeping. When seen 1 year later he remained on 20 mg of fluoxetine, which continued to suppress his crying but not the subsequent laughter.
Case 2. A 64-year-old man with slowly progressive ALS for 17 years had developed mild dysarthria 8 years later, accompanied by PLC. Crying predominated over laughter. Both were described as disturbing, in marked excess of inner feelings, prolonged, and triggered by very minor stimuli. When evaluated at our clinic he did not have depression or past history of mood disorder. His wife did note mild irritability. Examination revealed exaggerated facial reflexes, positive snout response, and mild spastic dysarthria. Jaw reflex was normal. MMSE score was 28/30. Treatment with 50 mg of sertraline was started. When he was seen 1 month later his PC had resolved, although low-grade PL persisted. He found this tolerable. Irritability had stopped. At 4 months there had been no change in his symptoms, with the laughter persisting. He continued on 50 mg of sertraline and expressed no desire to alter the dose.
Case 3. A 71-year-old woman presented with a 10-year history of ALS and PLC of approximately 7 years' duration. Crying was more prominent than laughing, although both were described as frequent, uncontrollable, and in excess of inner feelings. There was no history of depression. Previous treatment by her neurologist with fluoxetine and nortriptyline had been limited by medication side effects. When seen, she showed no evidence of major depression. Examination was significant for exaggerated facial and jaw reflexes, positive snout response, and marked dysarthria. MMSE score was 28/28. She agreed to a trial of sertraline at 50 mg. One month later, her PC had resolved, but PL remained with diminished intensity. As with Case 2, she found the symptoms tolerable and preferable to an alteration in medication. She declined further follow-up.
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.
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.