Psychiatric aspects of progressive supranuclear palsy

EL.SEVlEK

CriticaX Review and Update From time to time, the Editors of the Journal receive articles providing a critical review and update of the work in a particular field over the last decade. Such submissions are circulated in the customary manner for prepublication review.

Psyc~i~~ic Aspects of Progressive S~u~~~~clear Palsv I-I. F. K. Chiu, M.R.C.Psych. Abstrack ~r~~i~ su~run~cZ~r palsy PSPI is c~ruc~~ized by suprunuclear ophthalmoplegia mainly ujfecting vertical gaze, nuchal dystonia in extension, pseudobulbur palsy, and ~~a1 ~nge5. The li~~~~ure on PSP has been neuroiogi~lly oriented wks the psychiatric aspects have beenrelu#ively neglected.A review of the li~~fure showsthat psychotic disturbancein PSP is commonbut with no churacferisficpaftern. Cognitive impairment,nonspecificafiectiveand behaviorald~~~~s arecommoniyfo~ffd, wafts hank psychos sisor bipolardisorderare rare. M&diagnoseswifh psychiatric disordersare commonand a heightenedawareness of the condifion is necessury for early diagnosis,

Progressive supranuclear palsy (PSP) was first described by Steele et al. [l] as a syndrome characterized by progressive supranuclear ophthalmoplegia mainly affecting vertical gaze, nuchal dystonia in extension, pseudobulbar palsy, and mild dementia. Major pathological findings included neurofibrillary degeneration, nerve cell loss, and gliosis of specific diencephalic, brainstem, and cerebellar nuclei with relative sparing of the cerebral cortex. Since its recognition 30 years ago, much literature has contributed to further knowledge and understanding of the condition. The exact prevalence is still unclear, but the incidence had been estimated as 4 per million in Western Australia ]2] and the prevalence as 1.39/1~,~ in two New Jersey counties [3]. The average age of Department of Psychiatry, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Address reptint requests to: Helen JTKChiu, MRCPsych, Department of Psychiatry, Chinese University of Hong Kong, Prince of Wales Hospit& Shatin, Hong Kong. General Hospital Psychiatry 17,135-143,1995 6 1995 EIsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010

onset is 59.6 years ]4] and the p&a& sex ratio is three males to two females [S]. The etiology remains unknown, but postulation of a toxin or a slow virus appears to be the meet p~s~g option to pursue. JDrug treatment has di~ppo~~g, probably because o ment of multiple neurotransmitter systems due to the extensive pathoiogy. Most patients are resistant to dopaminergic medications, and there are only anecdoctal reports of improvmt by tricyclic antidepressants [6,7] and me~by~~de f8]. The clinical course is that of ~~~~s and steady progression, and median survival from time af onset is about ii years [3]. The &r&al features, epidemiology, pathology, and treatment of the syndrome have been extensively reviewed recently [3-5,9,10]. Nowever, despite d&a&& description of physical aspects of the disease, psyd&ric aspects have been largely ~~ tese features were regarded as common .This review focuses on the psychiitric aspects of PSP.

Review of the LiteWme Steele et al. [l] described nine cases of PSP in their seminal article. Of these, seven patients had istellectual impairment and six had personality changes in the form of irritability, suspiciousness, and untidiness. Reactive depressio one patient and two had emotional sequent reviews have focused &I the ~e~~~ aspects, and mental changes were cursorily mentioned despite being regarded as coznmon manifestations. Brusa et al. [9] wr&e that phone changes and poor mentation were confirmed as

H. F. K. Chiu

hallmarks of PSI’ from onset. Kristensen [4] reported mental changes as early symptoms, with 14% presenting with memory defects, 26% personality changes, and 6% with depression, apathy, or euphoria. According to Lees [5], neurobehavioral disturbances were seen early in at least half the patients, and many were misdiagnosed as having dementia or a psychotic illness. Two relatively large series have attempted to delineate the natural history of PSI’. Maher and Lees [ll] carried out a retrospective case-note study of 52 cases and found that 31 (59.6%) presented with neurobehavioral changes such as poor memory, personality change, and depression. In New Jersey, changes in mentation were the initial symptoms in 22% of subjects (31. Table 1 summarizes a number of recent studies on PSP. These studies range from case reports to large series, totaling three hundred sixteen cases. They tend to include little psychiatric information and at times use unclear and overlapping terminology without stating the diagnostic criteria. This is understandable as most authors are nonpsychiatrist physicians; hence, only limited attention has been given to describe the psychopathology.

Symptomology Four symptom clusters are identified in the above publications: cognitive impairment, affective and behavioral changes, psychotic symptoms, and sleep disturbance.

Cognitive lmpairment In the original report by Steele et al. [l], dementia was present in 7 of 9 patients. A remarkable feature is the slowness of mentation. The term “bradyphrenia” has been used to denote the slowness of thought processes [12]. Subsequent reports have shown that presence and severity of dementia are variable. A plethora of terms were used in the cases described, including dementia, pseudodementia, subcortical dementia, intellectual impairment, mental impairment, mental deterioration, and poor mentation. These terms, however, might have different meanings when the diagnostic criteria were not stated. As shown in Table 1, this is the most common psychiatric symptom, being found in 217 of 316 patients (68.7%). Studies examining the nature of cognitive decline in PSI’ are limited by the small number of patients and the difficulties in carrying out neuro-

136

psychological assessment owing to the severe visual disturbance, axial dystonia, and dysarthria. Maher et al. [13] reported the presence of intellectual impairment in 18 of 27 (66.7%) patients, 9 being mild and 9 severe. In contrast, Fisk et al. [14] studied 4 patients and found no evidence of intellectual impairment except in those subtests requiring visual scanning. This was supported by Kimura et al. [15] who found that neuropsychological impairments in 7 patients were restricted to nonverbal tasks requiring visual scanning ability. In the study of Jackson et al. [16], of 16 patients, the mean IQ was only slightly below normal. Thus, the presence of dementia is an inconstant feature, and it is uncertain if the degree of cognitive impairment correlates with the severity or prognosis of the disease. Albert et al. [17] used the term “subcortical dementia” to describe the characteristic pattern of dementia in PSI’. This included forgetfulness, slowing of thought processes, emotional or personality changes (particularly apathy and depression, with occasional irritability), and impaired ability to manipulate acquired knowledge. On the basis of the available literature on 42 patients and 5 of their own cases, they detected a consistent pattern of dementia different from the “cortical dementia” seen in Alzheimer’s disease (AD). They noted that this pattern was similar to that in frontal lobe disease, and none of their patients had higher cortical defects such as aphasia, agnosia, and apraxia. Albert et al. postulated that the underlying pathophysiological mechanisms were related to impaired timing, alerting, and activating mechanisms due to damage to frontolimbic connections. Recent work has tried to delineate the specific cognitive deficits in PSI’. In one study comparing patients with PSI’, Parkinson’s disease (I’D), and AD to controls [18], all three groups had similar results on verbal, visuospatial, and global memory tests. However, PSP patients were particularly impaired on tests of attention and frontal lobe dysfunction (lexical fluency, imitation behavior, and behavioral scale). In a subsequent study, the same group of authors showed that specific features of cognitive impairment distinguished patients with AD, PSP, I’D, and Huntington’s disease (HD) 1191. These included impairment in remote memory and linguistic disorders in AD, frontal lobe-like abnormalities in PSI’, concentration and acquisition disorders in HD, and an undifferentiated profile in PD. In another study, 9 patients with PSP were compared with 16 patients with AD [20]. Patients

Progressive Supranuclear Palsy with AD were more impaired in verbal and nonverbal memory in the Boston Naming Test, whereas PSP patients were more impaired in verbal fluency. Uther studies have largely confirmed the presence of frontal lobe dysfunction [13,17, 21,223. Furthermore, frontal lobe signs including forced grasping, utilization behavior, and marked motor persevervation were manifested by some patients [13], In addition, recent positron emission tomography (PET) and SPECT studies [23-263 have demonstrated frontal hypometabolism, giving further support to the presence of frontal lobe dysfunction. Sum~ng up the literature, it appears that cognitive impairment is common and is characterized by frontal lobe dysfunction in PSP, which is different from the patterns of cognitive deficits found in AD, PD, and HD.

321. A label of organic mood disorder, depressed type, might be more appropriate. A small number of patients, however, improved with amitriptyline ]33,34]. iteratively, some patients may show a reactive depression in response to the physica disability [l]. Interestingly, suicidal ideas or attempts have not been reported.

Paranoid symptoms have been described in the literature [l], but are usually nonbizarre and more fragmented than those of functional psychiatric disorders and may spontaneously improve ]27]. Hallucinations are occasionally present f30,35], and frank psychoses are uncommon. Schizophrenia-like psychosis has been reported 1361, but this is certainly rare.

Affective and Behavioral Changes

Sleep Disturbance

Affective and behavioral changes are common in PSP. Most of the changes are personality changes with the presentation of irritability, impulsivity, untidiness, suspiciousness, emotional lability, apathy, or euphoria. Emotional lability, in particular, inappropriate laughter or uncontrolled crying spells, is usually assumed to be pseudobulbar in origin. Behavioral problems can lead to conflicts with family members, and the outbursts of anger are potentially dangerous, For example, a patient attempted to pour boiling water over his wife and ordered her to jump from the window [27]. Some patients present with depression, but the occurrence of a bipolar manic-depressive disorder is rare. Whether the depressive features are part of a depressive illness or subcortical dementia is still unclear. Prodromal changes in personality and mood, slowness, and apathy of PSP may mimic depression, and it may be difficult to distinguish between the two conditions. Study of the cases reported to be depressed shows that many patients might not really have a full-blown depressive illness according to modern diagnostic criteria. For instance, some patients were thought to have depression because of the “mental slowing and inability to concentrate” [28] or “slowing of movements and impatience” [29] which might be features of PSP per se. In the few cases where psychiatric features were described in detail, the affect is flattened, the depression usually ran a prolonged course, and it did not respond to antidepressants or electroconvulsive therapy (ECT) [30-

The most common sleep disturbance is insomnia. Sleep studies have revealed a decreas in total sleep time, increased awakening and abnormal sleep architecture, with decrease in slow wave sleep (SWS) and REM sleep [27,37,38]. Perret and Jouvet [39] showed that changes in sleep pattern and architecture were correlated with severity of the clinical picture and the stage of evolution of the disease. In severe cases, REM sleep tight be absent and EEG patterns of w~~~e~ persisted into behavioral sleep [37f. Never&e&s, hypersomnia [22,35,40-41] and inappropriate sleep attacks [42] have also been documented.

Discussion Cognitive impairment and nonspecific affective and behavioral disturbances are cicrmmortly found, whereas frank psychosis is rare in PSP. The most common psychiatric sequela is cognitive impairment, but its extent varies across studies. Inconsistency in diagnostic criteria for dementia, the use of different batteries of neuropsychological tests, and variation across the study ~p~~~~ may account for some of the observed dimparxies [43]. Furthermore, the combination of bradykinesia, bradyphrenia, dysarthria, visual disturbance, and behavioral problems makes it difficult to assess these patients. Affective disturbances most commonly present as irritability, emotional lability, apathy, or euphoria. Depressive syndrome, when present, is some-

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H. F. K. Chiu Table 1. Psychiatric

features of PSP as desscribed in the literature

Author, year

Total no. of patients

Cognitive

Steele, 1964 [l]

9

7

Barbeau, 1965 [56]

1

1

Jequier, 1965 [57] Messert, 1966 [58] Anastasopoulos, 1967 [59] Chateau, 1967 [4O] David, 1968 [60] Behrman, 1969 [61] De Renzi, 1969 [62] Blumenthal, 1969 [63] Jenkins, 1969 [64] Anzil, 1969 [65] Wagshul, 1969 [33]

3 3 7 1 6 4 2 1 1 1 2

Newman, 1970 [6] Steele, 1970 [66] Scott, 1970 [67] Constantinidis, 1970 [68] Dix, 1971 (691 Jellinger, 1971 [41] Steele, 1972 [70] Corm, 1972 [71] Mastalgia, 1973 [2]

3 1 1 1 9 2 2 7 11

2 1 1 1 6 1 1 6 11

Morax, Singh, Albert, Probst,

7 4 5 14

6

1974 [72] 1974 [73] 1974 [17] 1975 [74]

Velmurugendran, 1975 [75] Trevisan, 1975 [76] Singh, 1976 [77] Kase, 1976 [78] Leygonie, 1976 [42] Dalziel, 1977 [28]

Psychotic

Sleep

1

1 1 1 t :, 1 1 2 1 1 4 A 5 5

2

3 2 1 2 3

Schainker, 1978 [79] Perkin, 1978 [30]

1 5

Bugiani, 1979 [80] Rafal, 1981 [8] Haldeman, 1981 [81] Nuwer, 1981 [82] Kvale, 1982 [34]

5 12 3 1 1

4

Nitrini, 1983 [83] Jackson, 1983 [16] Janati, 1984 [31]

3 16 4

1 8 2

138

Affective & behavioral

3

3

Progressive

Supranuclear

Palsy

Table 1. (Continued)

Author, D’Antona,

Total no. of patients

year

Cognitive

1985 [23]

6

6

Cambier, 1985 [22] Trezepacz, 1985 [36] Izzo, 1986 [53] Maher, 1986 [ll]

10 1 1 52

10 1 1 42

Schneider,

1986 1321

Affective & behavioral

Psychotic

Sleep

1

Rea, 1987 [44] Saitoh, 1987 [34] Breuer, 1987 [85] Ishino, 1987 [86]

1 6 3

Schneider, 1989 [47] Wang, 1989 [87] Lan, 1990 [88] Frasca, 1991 [89] Lee, 1991 [27] Suresch, 1991 [31] Podoll, 1991 [90] Takeuchi, 1991 [29]

2

(:I

1

1 5 3 + 1

9 7 26 1 14 6 1

2 1

(1) Sosner,

1993 [55]

1

2

Total

1

217

316

X31

7

14

(23)

( ) = number of patients with depression. + = features

mentioned

in paper

but exact

number

of patients

times marked by a flat affect with a lack of depressive cog&ions or melancholic features typical of a functional depressive illness. Careful longitudinal examination may throw light on the nature of affective disturbance in PSP and whether there exists a pattern of organic mood disorder phenomenologically different from that in major depression. Looking at the literature, psychiatric disturbance in PSP is common, but with no characteristic pattern. The absence of a characteristic pattern may be due to a combination of factors, including a lack of recognition of psychiatric disturbance by the predominantly neurologists who report the cases, the brief, cross-sectional descriptions, and a publication bias whereby only unusual cases are published. Thus, the true prevalence of psychiatric symptoms is still unknown, and further prospective studies using stringent diagnostic criteria are required. Early diagnosis of PSP is difficult because the

unclear.

early complaints are usually vague, nonspecific and often misleading [S]. Many pat&&s are misdiagnosed as having PD, AD, psychotic illness, or depression [4,31,32,36,44]. In the ce of any specific diagnostic test, a supranuclear down-gaze palsy is essential for diagnosis Steele et al. [l] described “constant, striking, and appear late in the course [3] and, in a few cases, typical pathology of PSP has been out the patient having any oph [45]. Furthermore, lack of awareness of the condi-

AD. A detailed history, mental s&&e ~mination, and careful neurological evaluation are important in differentiating PSP from functional psychiatric illnesses. PSP is frequently misdiagnosed as PD. Indeed,

139

H. F. K. Chiu PSI’ has been identified in various clinical series in about 4% of cases with parkinsonism 116,461. The major differentiating feature is the ophthalmoplegia with vertical gaze palsy in PSI’. Typically, movements to command are more deranged than those to pursuit, with preserved doll’s eye movements. In contrast, clinically identifiable supranuclear ophthalmoplegia is not a feature of PD. Secondly, the posture in PSP is upright with upturned face and eyes, as opposed to the stooping posture in PD. In PSI’, resting tremor is unusual, and rigidity of the limbs and bradykinesia are less prominent [4]. Postural instability with frequent falls is an early feature of PSI’ but usually occurs at a later stage in PD. A tendency towards retropulsion is seen in PSP, whereas propulsion and retropulsion are both common in I’D [4]. However, it is unclear whether retropulsion per se is more common in PSI’ than in PD. Finally, the masked face in PSP is caused by spasticity and rigidity which leads to deep furrows, resulting in a characteristic “astonished” and “worried” look different from the masked face in PD due to poverty of facial expression. Thus, careful clinical examination, in particular, proper examination for gaze palsies, are important in distinguishing PSI’ from the more common and overlapping disorder of PD. The neurological basis for the mental deterioration and psychiatric symptoms is unclear. As the cerebral cortex is usually spared, mental changes may be partly related to involvement of the cholinergic nucleus basalis of Meynert, the noradrenergic nucleus locus coeruleus, or the serotonergic brainstem raphe nuclei, as axons from these nuclei project throughout the cerebral cortex [47]. Involvement of these structures can also account for the sleep disturbance, as REM sleep and NREM sleep are believed to be regulated by the raphe nuclei and the locus coeruleus, respectively. Management of the psychiatric symptoms is sometimes difficult. Behavioral problems are frequently distressing to relatives and caregivers. Temper outbursts or aggressive behavior can be a major problem. There have been anecdoctal reports of efficacy of propranolol [48], tricyclic antidepressants [34], trazodone [47], and fluoxetine [49]. The use of trazodone for behavioral disturbance in organic brain syndromes has been attributed to its serotonergic effect [50-521 and is worth exploring in future studies. Psychotic symptoms may respond to antipsychotic drugs, but caution should be exercised as these patients are prone to the extrapyramidal side effects [36]. Unfortu-

140

nately, there is no literature on the use of atypical antipsychotics such as clozapine and the substituted benzamides, which may have less propensity to produce extrapyramidal side effects. Benzodiazepines may be useful in treating insomnia. However, since they can worsen sleep apnea, this finding in patients with PSP [27] warrants further investigation. For depression, apart from the difficulty in differentiating it from subcortical dementia, its response to antidepressants is variable [32,33]. Nevertheless, there are encouraging reports about the use of tricyclic antidepressants in the control of emotional incontinence and psychomotor retardation [6,34]. Although intellectual impairment is refractory to medications, nonpharmacological therapy can provide modest benefit and improve the quality of life. A multidisciplinary approach involving occupational therapist, physiotherapist, speech therapist, psychiatrist, and neurologist is essential to any rehabilitative program for PSP [53]. Physical rehabilitation devices such as walking aids should be considered as falls are common. Retropulsion can be improved by elevating the heels of shoes, or by adding a sandbag to the front of a walker [54]. Sosner et al. [55] described a rehabilitation program consisting of cognitive and speech evaluation and training, exercises to improve strength and coordination, as well as static and dynamic balance training. A heavy shopping cart or wheelchair was provided for patients to grab so as to improve safety during ambulation. Finally, education and support of family members, provision of day care, and respite or household services may help to relieve the burden on caregivers and should form an integral part of management. PSP, though rare, is of interest to psychiatry because of the common occurrence of psychiatric symptoms and the frequent m&diagnoses with psychiatric illness. A heightened awareness of the condition and early diagnosis may prevent futile treatment with medications and lead to appropriate interventions.

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