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Neuropsychiatric Features of Corticobasal Degeneration

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Neuropsychiatric Features of Corticobasal Degeneration J Neurol Neurosurg Psychiatry 1998;65:717–721 717 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.5.717 on 1 November 1998. Downloaded from Neuropsychiatric features of corticobasal degeneration Irene Litvan, JeVrey L Cummings, Michael Mega Abstract Corticobasal degeneration (CBD) is a neuro- Objective—To characterise the neuropsy- degenerative disorder characterised clinically chiatric symptoms of patients with corti- by steadily progressive motor (for example, cobasal degeneration (CBD). dystonia, asymmetric parkinsonism not ben- Methods—The neuropsychiatric inven- efitting from levodopa therapy, myoclonus, tory (NPI), a tool with established validity balance disturbances, and pyramidal signs) and and reliability, was administered to 15 cognitive (for example, ideomotor apraxia, patients with CBD (mean (SEM), age 67.9 alien hand syndrome, aphasia, visual and (2) years); 34 patients with progressive sensory neglect) disturbances presenting after supranuclear palsy (PSP) (66.6 (1.2) the age of 40.12Neuropathologically, it features years); and 25 controls (70 (0.8) years), circumscribed parietal or frontoparietal atro- matched for age and education. Both phy, severe cortical neuronal loss, and intense patient groups had similar duration of astrogliosis, spongiosis, swollen and achro- symptoms and mini mental state exam- matic neurons (ballooned cells), neuropil ination scores. Semantic fluency and threads, and occasionally, neurofibrillary tan- motor impairment were also assessed. gles. In addition, basophilic argyrophilic and Results—Patients with CBD exhibited tau protein positive inclusions are found in the depression (73%), apathy (40%), irritabil- neurons of the substantia nigra and basal gan- ity (20%), and agitation (20%) but less glia (subthalamic nucleus, striatum, and palli- often had anxiety, disinhibition, delusions, dum), and also may be present along the den- or aberrant motor behaviour (for exam- tatorubrothalamic tracts. Feany and Dickson3 ple, pacing). The depression and irritabil- recently described the “astrocytic plaque” as ity of patients with CBD were more copyright. frequent and severe than those of patients being pathognomonic of this disorder. Clinical with PSP. Conversely, patients with PSP and neuropathological variations have been Neuropharmacology exhibited significantly more apathy than described which overlap with progressive Unit, Defense and supranuclear palsy (PSP) and Pick’s Veteran Head Injury patients with CBD. The presence of high 1 2 4–9 Program, Jackson disease. Several studies have characterised depression and irritability and low apathy 1 10–14 Foundation and the scale scores correctly diVerentiated the the motor and cognitive features of CBD, Medical Neurology patients with CBD 88% of the time. The but the patients’ neuropsychiatric symptoms Branch have rarely been described.15 16 I Litvan irritability of patients with CBD was significantly associated with disinhibition Neuropsychiatric symptoms are important National Institutes of (r=0.85) and apathy (r=0.72). In CBD, predictors of burden of the caregiver and the Neurological Disorders potential for admitting patients to apathy was associated with disinhibition http://jnnp.bmj.com/ 17–20 and Stroke, National (r=0.67); disinhibition was associated with institutions. Thus identification and treat- Institutes of Health, aberrant motor behaviour (r=0.68) and ment of the associated behavioural abnormali- Bethesda, Maryland, ties may be relevant for improving the quality USA apathy (r=0.67); and aberrant motor be- I Litvan haviour with delusions (r=1.0). On the of life of patients with CBD and their other hand, depression was not associated caregivers. In addition, increasing insight into Department of with any other behaviour, suggesting that the neurobiological basis of neuropsychiatric Neurology it has a diVerent pathophysiological disorders facilitates understanding how behav- J L Cummings mechanism. Symptom duration was asso- iourally relevant circuits are involved in CBD. on September 30, 2021 by guest. Protected M Mega ciated with total motor scores (r=0.69). We administered the neuropsychiatric inven- Department of However, total motor score was not asso- tory (NPI), a tool with established validity and Psychiatry and ciated with any behaviour or cognitive reliability, to assess the behavioural abnormali- Biobehavioral Science, scores. ties of patients with CBD.21 The NPI evaluates UCLA School of Conclusions—The findings indicate that both the frequency and severity of 10 behav- Medicine, Los Angeles, frontosubcortical pathways mediating CA, USA iours that are commonly reported in patients J L Cummings cognition, emotion, and motor function in with cognitive disturbances: delusions, halluci- CBD are not aVected in parallel. Patients nations, agitation, depression, anxiety, eupho- Correspondence to: with CBD and PSP have overlapping neu- ria, apathy, disinhibition, irritability, and aber- Dr Irene Litvan, NINDS, ropsychiatric manifestations, but they NIH, Federal Building, rant motor behaviour (for example, pacing). To Room 714, Bethesda, MD express distinctive symptom profiles. better characterise the behavioural aspects of 20892–9130, USA. Evaluating the behavioural abnormalities patients with CBD and to search for distinctive Telephone 001 301 496 of parkinsonian patients may help clarify 1189; fax 001 301 496 2358. behavioural characteristics, we compared their the role of the basal ganglia in behaviour. performance on the NPI to that of a group of (J Neurol Neurosurg Psychiatry 1998;65:717–721) Received 2 February 1998 patients with PSP of similar age, education, and in revised form 27 April 1998 Keywords: corticobasal degeneration; progressive su- and cognitive impairment and to age matched Accepted 7 May 1998 pranuclear palsy; neurobehaviour normal controls. 718 Litvan, Cummings, Mega J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.5.717 on 1 November 1998. Downloaded from Table 1 Demographics of study group dementia rating scale and those that were not, (age, education, MMSE scores, symptom Corticobasal Progressive Healthy degeneration supranuclear controls duration, and motor scores). Verbal fluency Characteristics (n=15) palsy (n=34) (n=25) (semantic fluency: number of names of items Age (y) 67.9 (2) 66.6 (1.2) 70 (0.8) from a supermarket and phonemic fluency: Sex 8M/7F 23M/11F 14M/11F number of words starting with the letter “F”, Education (y) 14.3 (0.8) 14.4 (0.5) 13.2 (0.4) produced in one minute), and motor impair- Duration (months) 46.5 (5.7) 52 (4.5) — Mini mental state examination score 26.1 (1.2) 26 (0.8)* 28.6 (0.3) ment (modified unified Parkinson’s disease Total Mattis dementia rating scale score† 120.5 (4.2) 118.6 (2.4) — rating scale total motor score (UPDRS)25) were Total UPDRS motor scores 26.2 (2)* 21.2 (1.3) — assessed in the patients. We computed the Data are presented as mean (SEM). UPDRS=unified Parkinson’s disease rating scale score; motor function axially and in the most affected UPDRS maximum score was 54, and included only motor evaluation of axial and most aVected limb. Both patient groups had similar symptom limb (bradykinesia, rigidity, tremor, or dystonia). *Patients with progressive supranuclear palsy had a significantly lower (worse) mini mental state duration, MMSE, and Mattis dementia rating examination score than controls (ANOVA, p<0.05), patients with corticobasal degeneration had a scale scores, but the patients with CBD had a higher (worse) total motor score than those with progressive supranuclear palsy (p<0.05). The higher UPDRS total motor score (table 1). score of normal controls, not tested in this study with the Mattis dementia rating scale score, is >136. †This analysis included 12 patients with corticobasal degeneration and 28 with progressive Statistical analyses included bootstrap analy- supranuclear palsy. sis, analysis of variance (ANOVA), logistic regression, and discriminant function analyses. Subjects and methods A histogram of NPI data disclosed that Fifteen patients with CBD and 34 with PSP, composite scores do not generate a normal dis- presenting to the National Institutes of Neuro- tribution. Multiplying the frequency (1–4) by logical Disorders and Stroke (NINDS) as out- the severity (1–3) subscores will not produce a patients, participated in the study (table 1). 5, 7, or 11 composite score. The use of non- The patients with CBD were diagnosed parametric analysis (for example, the Mann- according to the modified criteria of Lang .4 et al Whitney test) partially accommodates such which included a progressive course of an U skewed data but results in a loss of power. asymmetric parkinsonism not benefiting from Because NPI data generate a non-normal levodopa therapy; the presence of either a dys- distribution, precluding traditional parametric tonic limb or focal myoclonus; the presence of analysis, a bootstrap analysis26 was employed. either ideomotor apraxia, alien limb syndrome, or cortical sensory loss; and absence of resting The program Resampling Stats® was used to tremor, autonomic disturbance, or laboratory evaluate significant diVerences among patient evidence of other disorders. The diagnosis of groups’ mean composite scores for each of the copyright. one of the 15 patients with CBD was later con- 10 NPI behaviours. Bootstrap analysis com- firmed by necropsy. The PSP study subjects bines the raw composite scores for any given met the NINDS-Society for PSP, Inc (NINDS- behaviour of the entire dataset and randomly PSP) clinical research
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