J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.64.2.184 on 1 February 1998. Downloaded from 184 J Neurol Neurosurg Psychiatry 1998;64:184–189 Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination G K Wenning, I Litvan, J Jankovic, R Granata, C A Mangone, A McKee, W Poewe, K Jellinger, K Ray Chaudhuri, L D’Olhaberriague, RKBPearce Abstract Keywords: corticobasal degeneration; atypical parkin- Objective—To analyse the natural history sonism; survival; natural history; clinicopathological and survival of corticobasal degeneration study by investigating the clinical features of 14 cases confirmed by postmortem examin- Department of Corticobasal degeneration is increasingly rec- Neurology, University ation. ognised as a distinctive neuronal multisystem Hospital, Innsbruck, Methods—Patients with definite cortico- degeneration presenting as an atypical parkin- Austria basal degeneration were selected from the 12 G K Wenning sonian syndrome. Although several charac- research and clinical files of seven tertiary teristic clinical features have been proposed, R Granata medical centres in Austria, the United W Poewe such as unilateral levodopa unreponsive aki- Kingdom, and the United States. Clinical nesia and rigidity, dystonia, or myoclonus, as Neuroepidemiology features were analysed in detail. well as cortical signs such as ideomotor apraxia Branch, National Results—The sample consisted of eight and cortical sensory loss,13 many patients are Institute of female and six male patients; mean age at misdiagnosed during life as having Parkinson’s Neurological Disorders symptom onset was 63 (SD 7.7) years, and and Stroke, National disease, progressive supranuclear palsy, multi- Institute of Health, mean disease duration was 7.9 (SD 2.6) ple system atrophy, or some other neurodegen- Bethesda, Maryland, years. The most commonly reported erative disorder. In a recent study on clinical USA symptom at onset included asymmetric diagnostic accuracy in cases with pathologi- I Litvan limb clumsiness with or without rigidity cally confirmed corticobasal degeneration, C A Mangone (50%) or tremor (21%). At the first L D’Olhaberriague sensitivity for the diagnosis was low at the first neurological visit, on average 3.0 (SD 1.9) visit (35%), but specificity was near perfect 4 Department of years after symptom onset, the most often (99.6%). Moreover, there was only a modest Neurology, Baylor encountered extrapyramidal features in- increase in sensitivity at the last visit. Further- College of Medicine, cluded unilateral limb rigidity (79%) or more, a recent clinicopathological study dis- Houston, Texas, USA bradykinesia (71%), postural imbalance closed a striking clinical heterogeneity when J Jankovic (45%), and unilateral limb dystonia (43%). analysing definite corticobasal degeneration Department of Ideomotor apraxia (64%), and to a lesser cases with associated neuropathological 5 Neuropathology, extent cortical dementia (36%), were the disorders. Massachusetts General most common cortical signs present at the To precisely delineate the range of clinical http://jnnp.bmj.com/ Hospital, first visit. During the course of the features in this disorder, we characterised 14 Boston,Massachusetts, disease, virtually all patients developed cases of corticobasal degeneration confirmed at USA A McKee asymmetric or unilateral akinetic rigid postmortem examination. In addition, we ana- parkinsonism and a gait disorder. No lysed the natural history and clinical predictors Ludwig Boltzmann patient had a dramatic response to levo- of survival in these patients with definite corti- Institute of Clinical dopa therapy. Median survival time after cobasal degeneration acquired from seven Neurobiology, Vienna, onset of symptoms was 7.9 (SD 0.7) (range, brain banks specialising in the study of parkin- Austria sonian syndromes. on September 28, 2021 by guest. Protected copyright. K Jellinger 2.5–12.5) years, and, after the first clinic visit, 4.9 (SD 0.7) (range, 0.8–10) years. Department of Early bilateral bradykinesia, frontal syn- Methods Neurology, Institute of drome, or two out of tremor, rigidity, and Patients were selected from the research and Psychiatry, London, bradykinesia, predicted a shorter survival. clinical neuropathological files of seven medi- UK K Ray Chaudhuri Conclusion—The results confirm that uni- cal centres in three countries (Austria, the lateral parkinsonism unresponsive to levo- United Kingdom, and the United States). Ten Parkinson’s Disease dopa and limb ideomotor apraxia are the patients were previously included in a study on Society Brain Bank clinical hallmarks of corticobasal degen- the accuracy of the clinical diagnosis of Research Centre, eration, and only a minority of patients corticobasal degeneration4; the other four were London, UK with corticobasal degeneration present RKBPearce added subsequently. Three patients were pro- with dementia. The study also suggests spectively followed up until death by one of the Correspondence to: that a focal cognitive and extrapyramidal coauthors (JJ). Most patients were assessed in Dr Irene Litvan, Federal motor syndrome is indicative of corticoba- movement disorders clinics; however, several Building, Room 714, sal degeneration. Survival in corticobasal National Institutes of Health, general neurologists performed some of the Bethesda, Maryland 20892, degeneration was shortened by the early first visits. All cases met the recently published USA. presence of (more) widespread parkinso- National Institute of Neurological Disorders nian features or frontal lobe syndrome. and Stroke (NINDS) preliminary neuropatho- Received 30 May 1997 and 6 in revised form 28 July 1997 logical criteria for corticobasal degeneration. Accepted 5 August 1997 (J Neurol Neurosurg Psychiatry 1998;64:184–189) The hallmarks of corticobasal degeneration J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.64.2.184 on 1 February 1998. Downloaded from Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination 185 Table 1 Demographic characteristics of patients with corticobasal degeneration confirmed nerves or roots in some of them. Cognitive at postmortem examination (memory deficits) or behavioural changes (frontal lobe type symptomatology such as Characteristics Number (n=14) apathy, irritability, disinhibition) occurred ini- Sex 8F/6M tially in 21% of the patients, and speech prob- Age at onset (y) (mean (SD) (range)) 63 (7.7) (45-75) Disease duration (y) (mean (SD) (range)) 7.9 (2.6) (2.5-12.5) lems in 14%. Time to first visit (months, mean (SD)) 35.5 (23.2) Time between visits (months, mean (SD)) 37.4 (25.0) History of encephalitis or familial disease 0 SYMPTOMS AT FIRST VISIT The first clinic visit (table 3) occurred on aver- age 3.0 (1.9) years after onset of symptoms. At pathology, according to the NINDS criteria, the first visit, eight (57%) of the patients had include frontoparietal atrophy with severe cor- some degree of unilateral or grossly asymmet- tical neuronal loss and intense astrogliosis as ric akinesia and rigidity and two other (14%) well as swollen and achromatic neurons (with- patients had bilateral (mildly or moderately out Pick bodies) in the aVected cortex. Several asymmetric) parkinsonism. Irregular tremor, cytoskeletal abnormalities were also present in present at rest, was documented in three (21%) various combinations including neuropil patients; transient pill rolling tremor was threads, neurofibrillary tangles, and basophilic reported by a general neurologist in one (7%) inclusions (the last in the substantia nigra and patient. Three (25%) patients had focal other basal ganglia areas). Tau positive astro- myoclonus (one had an irregular resting cytic inclusions forming cortical astrocytic tremor). Unilateral limb dystonia was present plaques were also found. At present such astro- in six (43%) patients. Laterocollis to the left cytic plaques are considered highly characteris- was present in one patient. Gait disorders were tic of corticobasal degeneration. Other disor- almost always associated with postural instabil- ders mimicking some of the features associated ity and present on first neurological examin- with corticobasal degeneration such as multi- ation in six (43%) patients (small stepped ple infarcts, profound diVuse atrophy, Lewy (n=2), bradykinetic (n=4), broad based bodies, changes diagnostic of Alzheimer’s (n=3)); two patients required assistance when disease, oligodendroglial argyrophilic inclu- walking, and one was wheelchair bound. sions, Pick bodies, and prion P positive amyloid Speech was slow in five (36%) patients, slurred plaques must be excluded. in four (29%), dysphonic in two (14%), and Patients’ records were abstracted on stand- unintelligible in one (7%). Voluntary vertical ardised forms by seven of us (AM, KJ, KRC, gaze was impaired in five (36%) patients, two RKBP, LD, IL, CAM) who followed strict of whom (14%) also exhibited an abnormal instructions. Because the data were retrospec- horizontal gaze. Ideomotor apraxia (impaired tively collected in 11 of the 14 patients, a mimicking gestures and hand postures) was feature that was not specifically recorded was present in seven (64%) patients. Four (29%) coded as absent if the neurological examination patients developed an early alien hand phe- was stated to be within normal limits. If the nomenon (complex unintentional movements examination disclosed abnormalities without of one limb interfering with normal motor