Original article
Progressive supra-nuclear palsy: frequency of cardinal extrapyramidal features at first presentation Sunil Pradhan, Ruchika Tandon Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India Correspondence to Dr Sunil Pradhan, Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India; [email protected] Received 23 March 2014 Revised 26 February 2015 Accepted 17 March 2015
ABSTRACT Objectives Cardinal extrapyramidal features of progressive supranuclear palsy (PSP) help in clinically differentiating this condition from Parkinson’s disease and other Parkinsonian syndromes. However, not all extrapyramidal features may be initially present, thus posing a difficulty in early diagnosis. We studied their frequency at the time of first presentation. Methods Patients diagnosed clinically with PSP using the National Institute for Neurological Disorders and Society for PSP (NINDS/SPSP) criteria and seen between August 2010 and April 2013 were examined for the presence, ‘presence with deviation’ or absence of six extrapyramidal features: axial rigidity, symmetry, extended posture, backward falls, absence of tremors and lack of levodopa response. Results Twenty-eight patients (mean (SD) age 64.86 (9.72) years; 16 (57%) men) met the inclusion criteria. Of these, 14% had all six extrapyramidal features associated with PSP, 39% had five, 29% had four, 14% had three and 4% had two. The most frequent extrapyramidal sign was axial rigidity (68%). Axial plus peripheral rigidity was found in 18% of patients and peripheral rigidity alone in 14%. Extrapyramidal features were symmetrical in 29% and asymmetrical beyond 1 year in 29%. Body posture was extended in 46% and flexed in 21%. Backward falls were found in 50% and forward falls in 11%. Pill-rolling tremors were observed in 29%. Response to levodopa therapy was poor in 21% and good beyond 6 months in 39%. Conclusions Only 14% of PSP patients present with all six cardinal extrapyramidal features. Also, deviations from standard descriptions are common in the initial stages of disease.
INTRODUCTION
To cite: Pradhan S, Tandon R. Postgrad Med J 2015;91:274–277. 274
Progressive supranuclear palsy (PSP) is a degenerative disorder characterised by the presence of supranuclear ophthalmoplegia, postural instability and a Parkinsonian syndrome.1–3 PSP is a rare progressive disease with average survival ranging from 6 to 8.6 years.4–6 The prevalence of PSP ranges from 5 to 6.4/100 000.7 8 PSP mimics Parkinson’s disease (PD) in its initial stages. However, six clinical features differentiate PSP from PD: axial rigidity, symmetry, extended posture, backward falls, absence of postural tremors in the upper limbs and lack of response to levodopa.9–11 PSP is classically associated with these six extrapyramidal features/signs.9–11 Although not studied systematically, exceptions to these so-called cardinal features are asymmetry,12–14 peripheral rigidity,15 16 flexed posture,17 18 forward falls, tremors and levodopa responsiveness. However, these exceptions are uncommon and rarely reported in the literature.
Since the prognosis of patients of PSP is poor compared to patients with PD, it is important to differentiate PSP from PD in its early stages.19 The objective of this study was to describe extrapyramidal signs, particularly the prevalence of specific cardinal features, in patients with PSP.
METHODS Patients Consecutive patients diagnosed with PSP in the Neurology Unit of Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India, between August 2010 and April 2013 were recruited for this study. Each year around 30 000– 40 000 neurology patients are seen in SGPGIMS, a tertiary care super-speciality hospital which serves as a referral centre for patients from northern and north-eastern India. PSP inpatients and outpatients were included and all were under the care of the authors. When these patients first presented to the hospital, they were clinically examined by the authors and a history (including details on stepwise progression of the disease) was taken.
Inclusion and exclusion criteria Inclusion criteria were adapted from possible and probable National Institute for Neurological Disorders and Society for PSP (NINDS/SPSP) criteria.20 These included gradually progressive disorder with onset above 40 years of age with either vertical supranuclear palsy or slowing of vertical saccades and postural instability with falls within a year of disease onset. Supportive features included akinesia or rigidity, abnormal neck posture, early dysphagia and dysarthria, early onset of cognitive impairment including two or more of the following: apathy, impairment in abstract thought, decreased verbal fluency, utilisation or imitation behaviour, or frontal release signs. Supportive MRI features such as mid-brain tegmental atrophy leading to ‘morning glory’ and ‘humming bird’ signs, were also considered inclusion criteria. Exclusion criteria included recent history of encephalitis, alien limb syndrome, cortical sensory deficits, focal frontal or temporo-parietal atrophy, hallucinations or delusions unrelated to dopaminergic therapy, cortical dementia of Alzheimer type, prominent early cerebellar symptoms, unexplained dysautonomia, neuroradiological evidence of relevant structural abnormality and denial of consent for the study.
Clinical details History and examination A history of present and past illness was taken and a physical examination was performed by both
Pradhan S, et al. Postgrad Med J 2015;91:274–277. doi:10.1136/postgradmedj-2014-132696
Original article authors. Six cardinal extrapyramidal features of PSP were studied in detail. It was determined whether rigidity was predominantly axial (cardinal feature), equally axial and peripheral ( partial deviation) or predominantly peripheral (complete deviation). Similarly, it was evaluated whether there was symmetrical onset of rigidity (cardinal feature), initial asymmetrical rigidity becoming symmetrical within 1 year of onset of disease ( partial deviation), or asymmetrical rigidity persisting beyond 1 year (complete deviation). It was observed whether the posture was extended (cardinal feature), erect ( partial deviation) or flexed (complete deviation). It was also recorded if falls were backwards only (cardinal feature), both forwards and backwards ( partial deviation) or forwards only (complete deviation). Absence of tremors was considered a cardinal feature of the disease, the presence of tremors not amounting to pill-rolling was considered a partial deviation, and the presence of typical pill-rolling tremors either during walking or at rest was considered a non-cardinal feature of the disease. Unified Parkinson’s disease rating scale (UPDRS) scores were determined prior to treatment and then during follow-up after the administration of a levodopa-carbidopa combination to evaluate the response to levodopa. If there was a poor levodopa response or if there was a visible response for less than 3 months, it was classified as a cardinal feature. If there was a response for 3–6 months only, it was classified as a partial deviation, and if there was a good response even after 6 months, then it was classified as a complete deviation. Further analysis was carried out to determine how many of the six cardinal extrapyramidal features were present at the time of first diagnosis. For this purpose, cardinal features and features showing partial deviation were combined together and considered cardinal features of the disease, while complete deviations from normal were considered non-cardinal features. Data were collected from the history of present and past illness, physical examination and investigations.
Data analysis Simple data descriptors for continuous variables and counts and proportions for categorical variables were used to describe the clinical characteristics of the patients. SPSS V.20 was used.
Patient consent Although the study did not involve any alteration in patient evaluation or treatment, informed consent was taken from each patient or his/her close relative for the possible reporting of anonymised clinical findings in future for scientific purposes, according to the guidelines of the institutional ethical committee.
RESULTS Patient demographics A total of 28 cases satisfied the inclusion criteria for PSP. There were 16 (57%) males and 12 (43%) females. The mean (SD) age of patients was 64.9 (9.7) years with a median of 64 years.
Extrapyramidal features All PSP patients had rigidity: 19 (68%) had predominantly axial rigidity, five (18%) had almost equal axial and peripheral rigidity, and four (14%) had predominantly peripheral rigidity. The frequency of cardinal features, partial deviation from cardinal features and complete deviation from cardinal features among patients is given in table 1. The mean (SD) UPDRS score for all 28 patients was 106.11 (18.148) before levodopa treatment and 64.18 (16.984) after treatment, and the difference was 41.929 (11.835). Other clinical features of PSP such as blepharospasm were present in two (7%) patients, dystonia in eight (29%), dysphagia in nine (32%), masking in 13 (46%), dysarthria in 12 (43%) and cognitive impairment in 22 (79%). Analysis revealed that at the time of first diagnosis, four (14%) patients had all six cardinal extrapyramidal features, 11 (39%) had five features, eight (29%) had four features, four (14%) had three features and one (4%) had two features.
Laboratory findings
DISCUSSION
Patient MRI scans were performed using 3T-MRI. Blood samples were taken for blood tests (blood counts, liver, renal and thyroid function tests, and vitamin B12 and folic acid levels).
In this study of 28 PSP patients, we found that only 14% had all six of the extrapyramidal features classically associated with PSP. The mean age of patients was similar to that found in other
Table 1
Cardinal features and deviation from cardinal features in patients with progressive supranuclear palsy
Clinical feature
Cardinal/deviation from cardinal
Clinical feature
Frequency (percentage)
Rigidity
Cardinal feature Partial deviation from cardinal Complete deviation from cardinal Cardinal feature Partial deviation from cardinal Complete deviation from cardinal Cardinal feature Partial deviation from cardinal Complete deviation from cardinal Cardinal feature Partial deviation from cardinal Complete deviation from normal Cardinal feature Partial deviation from cardinal Complete deviation from cardinal Cardinal feature Partial deviation from cardinal Complete deviation from cardinal
Predominantly axial rigidity Equal axial and peripheral rigidity Predominantly peripheral rigidity Symmetrical onset of rigidity Asymmetrical onset of rigidity but symmetrical within 1 year Asymmetrical rigidity beyond 1 year Extended posture Erect posture Flexed posture Backward falls Forward as well as backward falls Forward falls Absence of tremors Tremors not amounting to pill-rolling Typical pill-rolling tremors Poor response or visible response for less than 3 months Response for 3–6 months only Good response even after 6 months
19 (68) 5 (18) 4 (14) 8 (29) 12 (43) 8 (29) 13 (46) 9 (32) 6 (21) 14 (50) 11 (39) 3 (11) 8 (29) 12 (43) 8 (29) 6 (21) 11 (39) 11 (39)
Symmetry or asymmetry
Posture
Direction of falls
Tremors
Response to levodopa
Pradhan S, et al. Postgrad Med J 2015;91:274–277. doi:10.1136/postgradmedj-2014-132696
275
Original article studies.5 6 21 Previous reports have shown that axial rigidity is more common in patients with PSP and is considered a cardinal feature. However, according to this study, PSP patients may also present with peripheral rigidity, which can be considered a deviation from the cardinal feature. A few studies have shown the presence of prominently peripheral rigidity in PSP.22 In this study, a significant number of patients presented with asymmetric onset of rigidity that became symmetrical within 1 year, while in some the asymmetric rigidity lasted for more than 1 year. Symmetric rigidity in PSP patients is more common than asymmetric rigidity. Asymmetrical involvement can be found in some PSP patients and is a deviation from the cardinal feature.12 14 Limb rigidity may occur in PSP.23 In this study, we found that predominantly lower limb rigidity is more common than predominantly upper limb rigidity in PSP patients. Several patients in this study had a flexed posture. Although considered a feature of Parkinson disease, some reports have mentioned flexed posture in PSP patients.17 18 At presentation, several patients had forward as well as backward falls and many patients had forward falls only, suggesting that a history of forward falls should not be negative for PSP. Half of the patients (50%) presented with falls/postural instability, while 50% presented with slowness of movement/ stiffness. In the former group, several patients had instant falls at presentation, without first having propulsion or retropulsion. Thus, there can be two different presentations of PSP. Although a previous report found tremors in only 12–16% of PSP cases,24 limb tremors (mainly postural tremors) were found in 71% of PSP patients in this study, while typical pill-rolling tremors were seen in 28.6%. This finding implies that the presence of tremors cannot be used to exclude a PSP diagnosis. In the present study, a large number of patients have shown good response to levodopa, some for more than 3 months. Very few other studies have shown good levodopa responsiveness in PSP.25 The six extrapyramidal features are important in the diagnosis of PSP. However, our findings suggest that deviations are quite common and therefore the cardinal features should not be taken as essential criteria for early diagnosis. Instead, these features should be followed in subsequent visits as some deviations are corrected over time. This study investigated only a few patients, so a longer follow-up period and further studies are needed to determine how patients with non-cardinal extrapyramidal features fare in the long term.
Current research questions ▸ Is the prognosis of progressive supranuclear palsy patients presenting with non-cardinal extrapyramidal features different from those presenting with cardinal extrapyramidal features? ▸ Can patients presenting with non-cardinal features be classified as a separate group? ▸ How do patients with non-cardinal extrapyramidal features fare regarding response to levodopa and other antiparkinsonian drugs?
Key references ▸ Tsuboi Y, Josephs KA, Boeve BF, et al. Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome. Mov Disord 2005;20:982–8. ▸ Bhidayasiri R, Tarsy D. Anterocollis in parkinsonism. Curr Clin Neurol 2012:134–5. ▸ Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (SteeleRichardson-Olszewski syndrome): report of the NINDS-SPSP International Workshop. Neurology 1996;47:1–9. ▸ Brooks DJ. Diagnosis and management of atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry 2002;72(Suppl I):i10–16. ▸ Constantinescu R, Richard I, Kurlan R. Levodopa responsiveness in disorders with parkinsonism: a review of the literature. Mov Disord 2007;22:2141–8; quiz 2295.
Contributors SP and RT certify that we are responsible for significantly contributing to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; and drafting the work or revising it critically for important intellectual content; and final approval of the version to be published; and that we have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Competing interests None declared. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
Main messages
2
▸ At presentation only 14% of patients with progressive supranuclear palsy (PSP) had all six cardinal features. ▸ At first diagnosis 47% patients had less than five of the cardinal features. ▸ Tremor, usually associated with Parkinson’s disease, was present in 71%, and pill-rolling tremor was infrequent. ▸ Almost 40% of patients with PSP remained responsive to levodopa after 6 months of therapy, suggesting the need for a review of advice about the use of levodopa in patients with PSP.
276
3 4 5 6
7 8
Alvarez-González E, Maragoto-Rizo C, Arteche-Prior M, et al. A clinical and epidemiological description of a series of patients diagnosed as suffering from progressive supranuclear palsy. Rev Neurol 2004;39:1006–10. Armstrong RA. Visual signs and symptoms of progressive supranuclear palsy. Clin Exp Optom 2011;94:150–60. Carrilho PE, Barbosa ER. Progressive supranuclear palsy in a sample of Brazilian population: clinical features of 16 patients. Arq Neuropsiquiatr 2002;60:917–22. Chiu WZ, Kaat LD, Seelaar H, et al. Survival in progressive supranuclear palsy and frontotemporal dementia. J Neurol Neurosurg Psychiatry 2010;81:441–5. Aiba I, Saito Y, Tamakoshi A, et al. Prognosis of patients with progressive supranuclear palsy. Rinsho Shinkeigaku 2005;45:565–70. Birdi S, Rajput AH, Fenton M, et al. Progressive supranuclear palsy diagnosis and confounding features: report on 16 autopsied cases. Mov Disord 2002;17:1255–64. Schrag A, Ben-Shlomo Y, Quinn NP. Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study. Lancet 1999;354:1771–5. Nath U, Ben-Shlomo Y, Thomson RG, et al. The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK. Brain 2001;124(Pt 7):1438–49.
Pradhan S, et al. Postgrad Med J 2015;91:274–277. doi:10.1136/postgradmedj-2014-132696
Original article 9
10
11 12
13
14
15 16
Litvan I, Mangone CA, McKee A, et al. Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. J Neurol Neurosurg Psychiatry 1996;60:615–20. Maher ER, Lees AJ. The clinical features and natural history of the Steele-Richardson-Olszewski syndrome ( progressive supranuclear palsy). Neurology 1986;36:1005–8. Macia F, Ballan G, Yekhlef F, et al. [Progressive supranuclear palsy: a clinical, natural history and disability study]. Rev Neurol (Paris) 2003;159:31–42. Oide T, Ohara S, Yazawa M, et al. Progressive supranuclear palsy with asymmetric tau pathology presenting with unilateral limb dystonia. Acta Neuropathol 2002;104:209–14. Takia M, Ishiia K, Fukuda T, et al. Evaluation of cortical atrophy between progressive supranuclear palsy and corticobasal degeneration by hemispheric surface display of MR images. AJNR 2004;25:1709–14. Tsuboi Y, Josephs KA, Boeve BF, et al. Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome. Mov Disord 2005;20:982–8. Deering R. Progressive Supranuclear Palsy: A Neurophysiological Report. 27 February, 2002. http://serendip.brynmawr.edu/bb/neuro/neuro02/web1/rdeering.html (1 June 2013). Kleinschmidt-DeMasters BK. Early progressive supranuclear palsy: pathology and clinical presentation. Clin Neuropathol 1989;8:79–84.
17
18 19 20
21 22 23 24 25
Pradhan S, et al. Postgrad Med J 2015;91:274–277. doi:10.1136/postgradmedj-2014-132696
Brigo F, Bovi T, Ferigo L, et al. Head drop in progressive supranuclear palsy: An unusual association with amyotrophic lateral sclerosis. Parkinsonism Relat Disord 2013;19:467–8. Bhidayasiri R, Tarsy D. Anterocollis in parkinsonism. Curr Clin Neurol 2012:134–5. Macleod AD, Taylor KS, Counsell CE. Mortality in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 2014;29:1615–22. Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP International Workshop. Neurology 1996;47:1–9. Baba Y, Putzke JD, Whaley NR, et al. Progressive supranuclear palsy: phenotypic sex differences in a clinical cohort. Mov Disord 2006;21:689–92. Rojo A, Pernaute RS, Fontán A, et al. Clinical genetics of familial progressive supranuclear palsy. Brain 1999;122:1233–45. Brooks DJ. Diagnosis and management of atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry 2002;72(Suppl I):i10–16. Masucci EF, Kurtzke JF. Tremor in progressive supranuclear palsy. Acta Neurol Scand 1989;80:296–300. Constantinescu R, Richard I, Kurlan R. Levodopa responsiveness in disorders with parkinsonism: a review of the literature. Mov Disord 2007;22:2141–8; quiz 2295.
277
Copyright of Postgraduate Medical Journal is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Progressive supra-nuclear palsy: frequency of cardinal extrapyramidal features at first presentation Sunil Pradhan, Ruchika Tandon Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India Correspondence to Dr Sunil Pradhan, Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India; [email protected] Received 23 March 2014 Revised 26 February 2015 Accepted 17 March 2015
ABSTRACT Objectives Cardinal extrapyramidal features of progressive supranuclear palsy (PSP) help in clinically differentiating this condition from Parkinson’s disease and other Parkinsonian syndromes. However, not all extrapyramidal features may be initially present, thus posing a difficulty in early diagnosis. We studied their frequency at the time of first presentation. Methods Patients diagnosed clinically with PSP using the National Institute for Neurological Disorders and Society for PSP (NINDS/SPSP) criteria and seen between August 2010 and April 2013 were examined for the presence, ‘presence with deviation’ or absence of six extrapyramidal features: axial rigidity, symmetry, extended posture, backward falls, absence of tremors and lack of levodopa response. Results Twenty-eight patients (mean (SD) age 64.86 (9.72) years; 16 (57%) men) met the inclusion criteria. Of these, 14% had all six extrapyramidal features associated with PSP, 39% had five, 29% had four, 14% had three and 4% had two. The most frequent extrapyramidal sign was axial rigidity (68%). Axial plus peripheral rigidity was found in 18% of patients and peripheral rigidity alone in 14%. Extrapyramidal features were symmetrical in 29% and asymmetrical beyond 1 year in 29%. Body posture was extended in 46% and flexed in 21%. Backward falls were found in 50% and forward falls in 11%. Pill-rolling tremors were observed in 29%. Response to levodopa therapy was poor in 21% and good beyond 6 months in 39%. Conclusions Only 14% of PSP patients present with all six cardinal extrapyramidal features. Also, deviations from standard descriptions are common in the initial stages of disease.
INTRODUCTION
To cite: Pradhan S, Tandon R. Postgrad Med J 2015;91:274–277. 274
Progressive supranuclear palsy (PSP) is a degenerative disorder characterised by the presence of supranuclear ophthalmoplegia, postural instability and a Parkinsonian syndrome.1–3 PSP is a rare progressive disease with average survival ranging from 6 to 8.6 years.4–6 The prevalence of PSP ranges from 5 to 6.4/100 000.7 8 PSP mimics Parkinson’s disease (PD) in its initial stages. However, six clinical features differentiate PSP from PD: axial rigidity, symmetry, extended posture, backward falls, absence of postural tremors in the upper limbs and lack of response to levodopa.9–11 PSP is classically associated with these six extrapyramidal features/signs.9–11 Although not studied systematically, exceptions to these so-called cardinal features are asymmetry,12–14 peripheral rigidity,15 16 flexed posture,17 18 forward falls, tremors and levodopa responsiveness. However, these exceptions are uncommon and rarely reported in the literature.
Since the prognosis of patients of PSP is poor compared to patients with PD, it is important to differentiate PSP from PD in its early stages.19 The objective of this study was to describe extrapyramidal signs, particularly the prevalence of specific cardinal features, in patients with PSP.
METHODS Patients Consecutive patients diagnosed with PSP in the Neurology Unit of Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India, between August 2010 and April 2013 were recruited for this study. Each year around 30 000– 40 000 neurology patients are seen in SGPGIMS, a tertiary care super-speciality hospital which serves as a referral centre for patients from northern and north-eastern India. PSP inpatients and outpatients were included and all were under the care of the authors. When these patients first presented to the hospital, they were clinically examined by the authors and a history (including details on stepwise progression of the disease) was taken.
Inclusion and exclusion criteria Inclusion criteria were adapted from possible and probable National Institute for Neurological Disorders and Society for PSP (NINDS/SPSP) criteria.20 These included gradually progressive disorder with onset above 40 years of age with either vertical supranuclear palsy or slowing of vertical saccades and postural instability with falls within a year of disease onset. Supportive features included akinesia or rigidity, abnormal neck posture, early dysphagia and dysarthria, early onset of cognitive impairment including two or more of the following: apathy, impairment in abstract thought, decreased verbal fluency, utilisation or imitation behaviour, or frontal release signs. Supportive MRI features such as mid-brain tegmental atrophy leading to ‘morning glory’ and ‘humming bird’ signs, were also considered inclusion criteria. Exclusion criteria included recent history of encephalitis, alien limb syndrome, cortical sensory deficits, focal frontal or temporo-parietal atrophy, hallucinations or delusions unrelated to dopaminergic therapy, cortical dementia of Alzheimer type, prominent early cerebellar symptoms, unexplained dysautonomia, neuroradiological evidence of relevant structural abnormality and denial of consent for the study.
Clinical details History and examination A history of present and past illness was taken and a physical examination was performed by both
Pradhan S, et al. Postgrad Med J 2015;91:274–277. doi:10.1136/postgradmedj-2014-132696
Original article authors. Six cardinal extrapyramidal features of PSP were studied in detail. It was determined whether rigidity was predominantly axial (cardinal feature), equally axial and peripheral ( partial deviation) or predominantly peripheral (complete deviation). Similarly, it was evaluated whether there was symmetrical onset of rigidity (cardinal feature), initial asymmetrical rigidity becoming symmetrical within 1 year of onset of disease ( partial deviation), or asymmetrical rigidity persisting beyond 1 year (complete deviation). It was observed whether the posture was extended (cardinal feature), erect ( partial deviation) or flexed (complete deviation). It was also recorded if falls were backwards only (cardinal feature), both forwards and backwards ( partial deviation) or forwards only (complete deviation). Absence of tremors was considered a cardinal feature of the disease, the presence of tremors not amounting to pill-rolling was considered a partial deviation, and the presence of typical pill-rolling tremors either during walking or at rest was considered a non-cardinal feature of the disease. Unified Parkinson’s disease rating scale (UPDRS) scores were determined prior to treatment and then during follow-up after the administration of a levodopa-carbidopa combination to evaluate the response to levodopa. If there was a poor levodopa response or if there was a visible response for less than 3 months, it was classified as a cardinal feature. If there was a response for 3–6 months only, it was classified as a partial deviation, and if there was a good response even after 6 months, then it was classified as a complete deviation. Further analysis was carried out to determine how many of the six cardinal extrapyramidal features were present at the time of first diagnosis. For this purpose, cardinal features and features showing partial deviation were combined together and considered cardinal features of the disease, while complete deviations from normal were considered non-cardinal features. Data were collected from the history of present and past illness, physical examination and investigations.
Data analysis Simple data descriptors for continuous variables and counts and proportions for categorical variables were used to describe the clinical characteristics of the patients. SPSS V.20 was used.
Patient consent Although the study did not involve any alteration in patient evaluation or treatment, informed consent was taken from each patient or his/her close relative for the possible reporting of anonymised clinical findings in future for scientific purposes, according to the guidelines of the institutional ethical committee.
RESULTS Patient demographics A total of 28 cases satisfied the inclusion criteria for PSP. There were 16 (57%) males and 12 (43%) females. The mean (SD) age of patients was 64.9 (9.7) years with a median of 64 years.
Extrapyramidal features All PSP patients had rigidity: 19 (68%) had predominantly axial rigidity, five (18%) had almost equal axial and peripheral rigidity, and four (14%) had predominantly peripheral rigidity. The frequency of cardinal features, partial deviation from cardinal features and complete deviation from cardinal features among patients is given in table 1. The mean (SD) UPDRS score for all 28 patients was 106.11 (18.148) before levodopa treatment and 64.18 (16.984) after treatment, and the difference was 41.929 (11.835). Other clinical features of PSP such as blepharospasm were present in two (7%) patients, dystonia in eight (29%), dysphagia in nine (32%), masking in 13 (46%), dysarthria in 12 (43%) and cognitive impairment in 22 (79%). Analysis revealed that at the time of first diagnosis, four (14%) patients had all six cardinal extrapyramidal features, 11 (39%) had five features, eight (29%) had four features, four (14%) had three features and one (4%) had two features.
Laboratory findings
DISCUSSION
Patient MRI scans were performed using 3T-MRI. Blood samples were taken for blood tests (blood counts, liver, renal and thyroid function tests, and vitamin B12 and folic acid levels).
In this study of 28 PSP patients, we found that only 14% had all six of the extrapyramidal features classically associated with PSP. The mean age of patients was similar to that found in other
Table 1
Cardinal features and deviation from cardinal features in patients with progressive supranuclear palsy
Clinical feature
Cardinal/deviation from cardinal
Clinical feature
Frequency (percentage)
Rigidity
Cardinal feature Partial deviation from cardinal Complete deviation from cardinal Cardinal feature Partial deviation from cardinal Complete deviation from cardinal Cardinal feature Partial deviation from cardinal Complete deviation from cardinal Cardinal feature Partial deviation from cardinal Complete deviation from normal Cardinal feature Partial deviation from cardinal Complete deviation from cardinal Cardinal feature Partial deviation from cardinal Complete deviation from cardinal
Predominantly axial rigidity Equal axial and peripheral rigidity Predominantly peripheral rigidity Symmetrical onset of rigidity Asymmetrical onset of rigidity but symmetrical within 1 year Asymmetrical rigidity beyond 1 year Extended posture Erect posture Flexed posture Backward falls Forward as well as backward falls Forward falls Absence of tremors Tremors not amounting to pill-rolling Typical pill-rolling tremors Poor response or visible response for less than 3 months Response for 3–6 months only Good response even after 6 months
19 (68) 5 (18) 4 (14) 8 (29) 12 (43) 8 (29) 13 (46) 9 (32) 6 (21) 14 (50) 11 (39) 3 (11) 8 (29) 12 (43) 8 (29) 6 (21) 11 (39) 11 (39)
Symmetry or asymmetry
Posture
Direction of falls
Tremors
Response to levodopa
Pradhan S, et al. Postgrad Med J 2015;91:274–277. doi:10.1136/postgradmedj-2014-132696
275
Original article studies.5 6 21 Previous reports have shown that axial rigidity is more common in patients with PSP and is considered a cardinal feature. However, according to this study, PSP patients may also present with peripheral rigidity, which can be considered a deviation from the cardinal feature. A few studies have shown the presence of prominently peripheral rigidity in PSP.22 In this study, a significant number of patients presented with asymmetric onset of rigidity that became symmetrical within 1 year, while in some the asymmetric rigidity lasted for more than 1 year. Symmetric rigidity in PSP patients is more common than asymmetric rigidity. Asymmetrical involvement can be found in some PSP patients and is a deviation from the cardinal feature.12 14 Limb rigidity may occur in PSP.23 In this study, we found that predominantly lower limb rigidity is more common than predominantly upper limb rigidity in PSP patients. Several patients in this study had a flexed posture. Although considered a feature of Parkinson disease, some reports have mentioned flexed posture in PSP patients.17 18 At presentation, several patients had forward as well as backward falls and many patients had forward falls only, suggesting that a history of forward falls should not be negative for PSP. Half of the patients (50%) presented with falls/postural instability, while 50% presented with slowness of movement/ stiffness. In the former group, several patients had instant falls at presentation, without first having propulsion or retropulsion. Thus, there can be two different presentations of PSP. Although a previous report found tremors in only 12–16% of PSP cases,24 limb tremors (mainly postural tremors) were found in 71% of PSP patients in this study, while typical pill-rolling tremors were seen in 28.6%. This finding implies that the presence of tremors cannot be used to exclude a PSP diagnosis. In the present study, a large number of patients have shown good response to levodopa, some for more than 3 months. Very few other studies have shown good levodopa responsiveness in PSP.25 The six extrapyramidal features are important in the diagnosis of PSP. However, our findings suggest that deviations are quite common and therefore the cardinal features should not be taken as essential criteria for early diagnosis. Instead, these features should be followed in subsequent visits as some deviations are corrected over time. This study investigated only a few patients, so a longer follow-up period and further studies are needed to determine how patients with non-cardinal extrapyramidal features fare in the long term.
Current research questions ▸ Is the prognosis of progressive supranuclear palsy patients presenting with non-cardinal extrapyramidal features different from those presenting with cardinal extrapyramidal features? ▸ Can patients presenting with non-cardinal features be classified as a separate group? ▸ How do patients with non-cardinal extrapyramidal features fare regarding response to levodopa and other antiparkinsonian drugs?
Key references ▸ Tsuboi Y, Josephs KA, Boeve BF, et al. Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome. Mov Disord 2005;20:982–8. ▸ Bhidayasiri R, Tarsy D. Anterocollis in parkinsonism. Curr Clin Neurol 2012:134–5. ▸ Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (SteeleRichardson-Olszewski syndrome): report of the NINDS-SPSP International Workshop. Neurology 1996;47:1–9. ▸ Brooks DJ. Diagnosis and management of atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry 2002;72(Suppl I):i10–16. ▸ Constantinescu R, Richard I, Kurlan R. Levodopa responsiveness in disorders with parkinsonism: a review of the literature. Mov Disord 2007;22:2141–8; quiz 2295.
Contributors SP and RT certify that we are responsible for significantly contributing to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; and drafting the work or revising it critically for important intellectual content; and final approval of the version to be published; and that we have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Competing interests None declared. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
Main messages
2
▸ At presentation only 14% of patients with progressive supranuclear palsy (PSP) had all six cardinal features. ▸ At first diagnosis 47% patients had less than five of the cardinal features. ▸ Tremor, usually associated with Parkinson’s disease, was present in 71%, and pill-rolling tremor was infrequent. ▸ Almost 40% of patients with PSP remained responsive to levodopa after 6 months of therapy, suggesting the need for a review of advice about the use of levodopa in patients with PSP.
276
3 4 5 6
7 8
Alvarez-González E, Maragoto-Rizo C, Arteche-Prior M, et al. A clinical and epidemiological description of a series of patients diagnosed as suffering from progressive supranuclear palsy. Rev Neurol 2004;39:1006–10. Armstrong RA. Visual signs and symptoms of progressive supranuclear palsy. Clin Exp Optom 2011;94:150–60. Carrilho PE, Barbosa ER. Progressive supranuclear palsy in a sample of Brazilian population: clinical features of 16 patients. Arq Neuropsiquiatr 2002;60:917–22. Chiu WZ, Kaat LD, Seelaar H, et al. Survival in progressive supranuclear palsy and frontotemporal dementia. J Neurol Neurosurg Psychiatry 2010;81:441–5. Aiba I, Saito Y, Tamakoshi A, et al. Prognosis of patients with progressive supranuclear palsy. Rinsho Shinkeigaku 2005;45:565–70. Birdi S, Rajput AH, Fenton M, et al. Progressive supranuclear palsy diagnosis and confounding features: report on 16 autopsied cases. Mov Disord 2002;17:1255–64. Schrag A, Ben-Shlomo Y, Quinn NP. Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study. Lancet 1999;354:1771–5. Nath U, Ben-Shlomo Y, Thomson RG, et al. The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK. Brain 2001;124(Pt 7):1438–49.
Pradhan S, et al. Postgrad Med J 2015;91:274–277. doi:10.1136/postgradmedj-2014-132696
Original article 9
10
11 12
13
14
15 16
Litvan I, Mangone CA, McKee A, et al. Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. J Neurol Neurosurg Psychiatry 1996;60:615–20. Maher ER, Lees AJ. The clinical features and natural history of the Steele-Richardson-Olszewski syndrome ( progressive supranuclear palsy). Neurology 1986;36:1005–8. Macia F, Ballan G, Yekhlef F, et al. [Progressive supranuclear palsy: a clinical, natural history and disability study]. Rev Neurol (Paris) 2003;159:31–42. Oide T, Ohara S, Yazawa M, et al. Progressive supranuclear palsy with asymmetric tau pathology presenting with unilateral limb dystonia. Acta Neuropathol 2002;104:209–14. Takia M, Ishiia K, Fukuda T, et al. Evaluation of cortical atrophy between progressive supranuclear palsy and corticobasal degeneration by hemispheric surface display of MR images. AJNR 2004;25:1709–14. Tsuboi Y, Josephs KA, Boeve BF, et al. Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome. Mov Disord 2005;20:982–8. Deering R. Progressive Supranuclear Palsy: A Neurophysiological Report. 27 February, 2002. http://serendip.brynmawr.edu/bb/neuro/neuro02/web1/rdeering.html (1 June 2013). Kleinschmidt-DeMasters BK. Early progressive supranuclear palsy: pathology and clinical presentation. Clin Neuropathol 1989;8:79–84.
17
18 19 20
21 22 23 24 25
Pradhan S, et al. Postgrad Med J 2015;91:274–277. doi:10.1136/postgradmedj-2014-132696
Brigo F, Bovi T, Ferigo L, et al. Head drop in progressive supranuclear palsy: An unusual association with amyotrophic lateral sclerosis. Parkinsonism Relat Disord 2013;19:467–8. Bhidayasiri R, Tarsy D. Anterocollis in parkinsonism. Curr Clin Neurol 2012:134–5. Macleod AD, Taylor KS, Counsell CE. Mortality in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 2014;29:1615–22. Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP International Workshop. Neurology 1996;47:1–9. Baba Y, Putzke JD, Whaley NR, et al. Progressive supranuclear palsy: phenotypic sex differences in a clinical cohort. Mov Disord 2006;21:689–92. Rojo A, Pernaute RS, Fontán A, et al. Clinical genetics of familial progressive supranuclear palsy. Brain 1999;122:1233–45. Brooks DJ. Diagnosis and management of atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry 2002;72(Suppl I):i10–16. Masucci EF, Kurtzke JF. Tremor in progressive supranuclear palsy. Acta Neurol Scand 1989;80:296–300. Constantinescu R, Richard I, Kurlan R. Levodopa responsiveness in disorders with parkinsonism: a review of the literature. Mov Disord 2007;22:2141–8; quiz 2295.
277
Copyright of Postgraduate Medical Journal is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
