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Camptocormia or Pisa syndrome in multiple system atrophy
Clinical Neurology and Neurosurgery 108 (2006) 699–704
Case report
Camptocormia or Pisa syndrome in multiple system atrophy Jarosław Sławek a,∗ , Mirosława Derejko b , Piotr Lass c , Mirosława Dubaniewicz d a
b
Department of Neurosurgery, Division of Functional Neurosurgery and Movement Disorders, Medical University, ul. D˛ebinki 7, 80-211 Gda´nsk, Poland Department of Neuroelectrophysiology, Institute of Psychiatry and Neurology, ul. Sobieskiego 9, 02-957 Warszawa, Poland c Department of Nuclear Medicine, Medical University, ul. D˛ ebinki 7, 80-211 Gda´nsk, Poland d Department of Radiology, Medical University, ul. D˛ ebinki 7, 80-211 Gda´nsk, Poland Received 28 June 2005; accepted 8 July 2005
Abstract Although a mild stooped posture is a hallmark of parkinsonism, extreme trunk forward flexion is not common. This phenomenon was described in different etiological entities and called camptocormia. Other similar presentations called Pisa syndrome and antecollis were described mainly in extrapyramidal disorders. Authors present two cases of probable multiple system atrophy (MSA) with predominant parkinsonism and Pisa syndrome (or camptocormia). Both of them were previously misdiagnosed as idiopathic Parkinson’s disease (PD) and one was reported 1 year earlier. The typical clinical presentation fulfilling the diagnostic criteria for multiple system atrophy, rapid progression with lack of responsiveness to l-DOPA and apomorphine and typical MRI putaminal pathology observed in both cases allowed us to make a diagnosis. Accuracy of clinical diagnosis in multiple system atrophy is still very poor. Therefore, unusual or rare clinical presentations may support the final diagnosis. The camptocormia, Pisa syndrome and antecollis may represent the continuum of the same motor phenomenon and most of the authors refer them to unusual form of axial dystonia. According to many clinical presentations on different forms of camptocormia/Pisa syndrome authors conclude that not etiology, but the localization of specific lesion, probably within putamen is responsible for that form of dystonia. In cases of parkinsonism and severe forward flexion of trunk multiple system atrophy, diagnosis should be considered. © 2005 Elsevier B.V. All rights reserved. Keywords: Camptocormia; Dystonia; Parkinson’s disease; Multiple system atrophy; Pisa syndrome
1. Introduction Camptocormia or bent spine has been characterized by extreme forward flexion of thoracolumbar spine with passive dropping of both arms. Typically, the symptoms increase while patient is walking and disappear in recumbent position [1]. Camptocormia is a motor phenomenon of heterogeneous etiology. It may be the result of intradural hematoma, vertebral infection, spinal cord malignancies, myositis of paraspinal muscles, sodium valproate toxicity, psychogenic origin or in some cases may be idiopathic [2–6]. This phenomenon was also observed in extrapyramidal disorders such ∗
Corresponding author. Tel.: +48 58 340 01 08; fax: +48 58 340 01 08. E-mail addresses: [email protected], [email protected] (J. Sławek). 0303-8467/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2005.07.004
as post-encephalitic parkinsonism, autosomal recessive juvenile parkinsonism (caused by mutations in the parkin gene), idiopathic Parkinson’s disease (PD) and multiple system atrophy (MSA), after pramipexole exposure and referred presumably to the sort of unusual axial dystonia [7–11]. Pisa syndrome is another (but clinically similar) form of rapidly evolving and severe axial dystonia with forward, but also laterally orientated trunk flexion. Initially, it was described as a motor phenomenon appearing a several days after starting of neuroleptic treatment [12]. A similar picture may also occur as a subtype of tardive dystonia or motor presentation of Alzheimer’s disease (AD) and MSA [13,14]. However, in MSA, more characteristic motor presentation is head ptosis or antecollis, Kan and Colosimo gave similar descriptions of their patients with Pisa syndrome and diagnosis of MSA [13,15].
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The authors have described the case of camptocormia in PD with improvement after unilateral pallidotomy. Although published in 2003, the paper was accepted in August 2002 and till the end of 2003, we observed the evolution of symptoms and signs, which had changed our previous diagnosis of PD into MSA. At the same time, another similar case was referred to our department, emerging the question that Pisa syndrome, camptocormia or generally severe flexion dystonia of the trunk are more often than suspected symptoms of probable MSA [16].
2. Case reports 2.1. Patient no. 1 In the previous report, authors described a 49-year-old woman who developed resting tremor followed by the cogwheel rigidity and loss of dexterity of the left hand 5 years earlier. Marked bradykinesia, dysarthria and involvement of the right side developed within the next 6 months. Laboratory tests and neuroimaging (CT, MRI and rCBF SPECT) were normal and response to l-DOPA with benserazide was between moderate and good, after increasing the dosage to 600 mg/day. After 3 years, her posture was markedly stooped with deterioration of gait and with postural instability and
falls. There were no cerebellar symptoms. Despite increasing the dosage of l-DOPA with benserazide to 1400 mg/day, she developed severe and painful forward trunk flexion with predominance to right side, which increased during walking and disappeared completely in the recumbent position (Fig. 1). The occurrence of trunk flexion (diagnosed as camptocormia) was not related to time and dosage of l-DOPA intake. MRI of brain and thoracic and lumbar spine were normal. Due to deterioration, she underwent right side pallidotomy in May 2001, with decrease of left extremities rigidity and hypokinesia and almost immediate improvement of posture with markedly reduced trunk flexion. Despite of initial good effect, in the following months she started to deteriorate rapidly with only subjective response to l-DOPA, and autonomic disturbances like severe constipation and urine incontinence have appeared. Therefore, she was again admitted to clinic for apomorphine testing and presumably further treatment with subcutaneous infusion with external pump. Unfortunately, we did not observe any motor improvement till dose of 7.5 mg in single injection and afterwards during a week observation of continuous subcutaneous infusion of apomorphine, with even slight deterioration and somnolence at higher dosages. At that time (almost one and a half year after surgery), the forward trunk flexion following also the neck anteflexion returned and deteriorated in the next months. The MRI scan performed at that time revealed putaminal atrophy and hypointensity
Fig. 1. The clinical presentation of severe forward, with right side predominance trunk flexion similar to descriptions of both camptocormia or Pisa syndrome (patient no. 1).
J. Sławek et al. / Clinical Neurology and Neurosurgery 108 (2006) 699–704
Fig. 2. MRI scans (T2 weighted images, 0.5T), patient no. 1. The hyperintense rim at the lateral putaminal edge.
with hyperintense lateral rim (T2 weighted images, 0.5T), the characteristic MRI features of MSA as published by Schrag et al. and Yekhlef et al. [17–19] (Fig. 2). At the time of report she was almost anarthric, able to walk only a few steps with assistance, had severe general rigidity, bradykinesia, dysphagia, risus sardonicus and severe, mentioned above forward flexion of the neck and trunk. She was classified as being at stage 5 according to Hoehn–Yahr scale and 20% according to Schwab-England Activities of Daily Living scale. Till now, any symptoms of cognitive decline and dyskinesia have not been observed, even after high l-DOPA dosages. The relatively earlier onset of the disease, rapid progression, lack of response to dopaminergic therapy after 6–7 years, autonomic dysfunctions and characteristic MRI findings have changed our initial diagnosis from PD into MSA with predominant parkinsonism (MSA-P). 2.2. Patient no. 2 A 63-year-old woman developed painful rigidity and loss of dexterity of right extremities in 1999, followed by slight resting tremor of right hand and dysarthria. During the next 3 years, the typical for PD symptoms of bradykinesia, gait disturbances, stooped posture and instability was developed and have become bilateral. Computed tomography scans were normal. From 1999, l-DOPA with benserazide was started with moderate effect and due to relatively rapid progression, was increased up to 1300 mg/day in 2002; but in the last 2 years, the initial beneficial effect was lost. Concomitant treatment with amantadine 200 mg/day and piribedil up to 150 mg/day were also ineffective. There were no dyskinesia, nor other motor fluctuations (e.g. wearing off). The depression was diagnosed and treated with fluoxetine 20 mg/day and later sertraline 50 mg/day without effect. No cognitive
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Fig. 3. MRI scans (T2 weighted and FLAIR images, 1.5T), patient no. 2. The hypointensivity of putamen and lateral hyperintense rim.
declines were observed at that time. In 2003, she progressed rapidly, still with asymmetry of symptoms (more pronounced rigidity of right extremities), Babinski’s sign on the left side and urine incontinency. She could walk only a few steps with assistance. Cerebellar symptoms were not observed. She was classified as being at stage 4 according to Hoehn–Yahr scale and 50% according to Schwab-England Activities of Daily Living score. The UPDRS motor score (III) did not deteriorate after cessation of anti-parkinsonian medications, suggesting the l-DOPA unresponsiveness. MRI scan performed in 2003 revealed the putaminal changes similar to those described in case 1 with more marked hypointensity (T2 weighted images, 1.5T) and hyperintensive rim at lateral edge of putamen (FLAIR images) (Fig. 3). Therefore, we have changed our previous diagnosis from PD to MSA-P. At the same time, she developed very markedly stooped posture with forward trunk, but not neck flexion of almost 60◦ maximally, with predominance to the right side, resembling that in patient no. 1 and diagnosed as camptocormia (or Pisa syndrome) (Fig. 4). The flexed posture deteriorated while walking and was accompanied by very severe back pain and all those symptoms disappeared in recumbent position. Plain X-ray examination showed the degenerative changes of the lumbar vertebral column.
3. Discussion Severe trunk forward flexion in extrapyramidal disorders was described in post-encepahilitic parkinsonism by Martin, in Parkinson’s disease by Djaldetti et al., Friedman and by Inzelberg et al. in Arabic Israeli family with parkin mutations [7–9,11]. Our case no. 1 (formerly presented as PD) fulfilled the United Kingdom Parkinson’s Disease Society Brain Bank criteria for diagnosis of idiopathic PD at the
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Fig. 4. The clinical presentation of forward and right trunk flexion (camptocormia or Pisa syndrome) in patient no. 2.
time of former description [16,20]. Nevertheless, from the beginning, patient presented with some relatively atypical but acceptable for diagnosis of PD symptoms like: younger age at onset, postural instability, relatively fast progression and lack of dyskinesias (despite high dosages of l-DOPA). Revisiting the case, 18 months later after initial description, we have changed our previous diagnosis into MSA-P. Diagnosis of MSA may be a significantly difficult task in the patients presenting only with parkinsonian signs. In some cases, the clinical presentation may be undistinguishable from idiopathic PD up to the time of death [21]. The accuracy of clinical diagnosis of MSA appears relatively poor in general, with up to 55% of postmortem confirmed cases being misdiagnosed even at last neurological evaluation [22]. Especially the form of MSA-P, representing mostly the striatonigral degeneration (SND) is usually mistaken for PD due to a number of overlapping symptoms as: asymmetry, resting
tremor and positive response (at least initially) to l-DOPA. Published criteria have improved the clinical diagnostic accuracy, but in fact it is still relatively low [23]. Therefore, we still need to investigate some specific clinical features that differentiate MSA from PD and other atypical parkinsonian syndromes. A number of warning signs (“red flags”) have been proposed, among them are disproportionate antecollis, respiratory stridor, “cold hand sign” and recently described “risus sardonicus” [24]. The MRI abnormalities published in recent years may also help us to make a proper diagnosis. The typical for MSA-P changes includes a hyperintense rim at the lateral putaminal edge (due to gliosis), putaminal atrophy and hyperintensity (mainly on 0.5T scans), atrophy and signal decrease of the globus pallidus (mainly on 1.5T scans) as a result of iron content higher than in PD. Although highly diagnostic, those putaminal abnormalities occurred in only 54% of patients with MSA, therefore, their sensitivity is relatively low, but specificity and positive predictive value very high (for hyperintense putaminal rim 91 and 84%, respectively) [18]. Moreover, these findings are probably not early in the course of disease. One may conclude, when specific changes are seen, MRI is useful to support a clinical diagnosis of MSA versus PD. Two presented cases, however, diagnosed only clinically, had showed those specific MRI changes that may support the diagnosis of MSA. The differentiation based on anal sphincter EMG findings or biochemical test with clonidine is also of limited value, due to similar features found in PD or progressive supranuclear palsy. The presented cases fulfill now the criteria for the diagnosis of probable (no pathological data, still alive) MSA, according to Litvan et al. consensus criteria published in 2003 [23]. If possible, the autopsy confirmation will be presented by authors subsequently. The unusual clinical features as antecollis or severe, asymmetrical, forward trunk flexion whatever the name (camptocormia or Pisa syndrome) may alert the neurologists and may improve the diagnosis at early stage. This may become more important once drugs are developed to slow the rate of disease progression. The pathogenesis or nature of camptocormia and/or Pisa syndrome remains unclear. Most of the authors refer the abnormal trunk flexion to dystonic contractions of paraspinal and/or abdominal muscles. In most cases of parkinsonism, no obvious relationship between bent spine and administration of l-DOPA was observed. Dystonia is a typical complication of PD, in most cases presenting as an early morning dystonia as a result of the lack of l-DOPA. Therefore, there is a possibility of other central mechanisms, may be not of dopaminergic origin, underlying this phenomenon. The investigation of real nature of camptocormia is more complicated due to the observations of myositis of paraspinal muscles described by several authors, also in PD and nonPD patients [25–28]. The disadvantage of our report is the lack of EMG or biopsy examination in presented cases. Nevertheless, as in the case of head ptosis, histological changes in the paraspinal muscles are seen in those with an obvious extrapyramidal cause, suggesting that these changes may be
J. Sławek et al. / Clinical Neurology and Neurosurgery 108 (2006) 699–704
non-specific, resulting from mechanical strain rather than a specific myopathic disorder [1]. There are interesting reports on camptocormia published by Nieves et al. and Nandi et al. [29,30]. Former one described the acute onset dystonic camptocormia caused by right side vascular lenticular lesions in two cases. It may confirm the dystonic nature of camptocormia, because lenticular lesion produces dystonia more often than any other movement disorders [29]. The report by Nandi et al., concerning the case of 39-year-old man with camptocormia of unknown origin, treated successfully with bilateral pallidal stimulation may support this notion. Although the etiology of camptocormia was unknown in that case, the improvement was achieved after bilateral pallidal stimulation. What is of the major interest, the symptoms recurred after stimulation was switched off. It has been shown that pallidal stimulation improves a wide variety of dystonic conditions [28]. Therefore, this report and our previous report on MSA patient with bent spine improvement after unilateral pallidotomy (patient no. 1) may support the view of dystonic nature of camptocormia and probably also Pisa syndrome [13,16]. The similar case of Pisa syndrome due to pathologically confirmed MSA-P with laterality of putaminal lesions was recently described by Hozumi et al. [31]. In both the clinical case studies by Colosimo [13], the case of Hozumi et al. [31] and our case no.1, akinetic-rigid parkinsonian symptoms dominated on the side opposite to the direction of the lean. It was not observed in our case no. 2, where right side rigidity was more prominent and patient leaned to the right. It may suggest that dominance of one-side putaminal changes decides on the lean direction and it may be related to the different localization of changes responsible for limb rigidity. The lack of response of Pisa syndrome to l-DOPA therapy may support this view. The diagnosis of atypical parkinsonism is one of the major contraindications for functional neurosurgery [32]. Our case no. 1 was misdiagnosed and underwent surgery at the time of diagnosis of PD. However, successful in terms of camptocormia, MSA still should not be treated as indication for surgical therapy. Poor clinical results of pallidotomy in MSA patients may be confirmed by Pereira et al. observations that internal globus pallidus firing rates are different (lower) in MSA [33]. The characteristic clinical presentation of camptocormia is the same in PD and other cases with distinct etiology. Therefore, in conclusion one may suggest that not etiology, but specific localization of pathology is responsible for this unusual form of axial dystonia. Despite some differences it may be postulated that there is a continuum of symptoms like antecollis, camptocormia and Pisa syndrome, reflecting the specific localization (presumably putaminal) of pathology [1]. The specific location of MRI findings in MSA-P patients may support this hypothesis. The conditions of camptocormia and Pisa syndrome are clinically difficult to distinguish and may reflect the same clinical problem. In parkinsonian patients with pronounced forward flexion of trunk (whatever the name), the diagnosis of MSA has to be considered.
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References [1] Umapathi T, Chaudhry V, Cornblath D, Drachman D, Griffin J, Kuncl R. Head drop and camptocormia. J Neurol Neurosurg Psychiatry 2002;73:1–7. [2] Kiuru S, Livanainen M. Camptocormia: a new side effect of sodium valproate. Epilepsy Res 1987;1:254–7. [3] Reichel G, Kirchofer U, Stenner A. Camptocormia – segmental dystonia. Proposal of a new definition for an old disease. Nervenarzt 2001;72:281–5. [4] Rosen JC, Frymoyer JW. A review of camptocormia and an unusual case in the female. Spine 1985;10:325–7. [5] Sinel M, Eisenberg MS. Two unusual gait disturbancies: astasia, abasia and camtocormia. Arch Phys Med Rehabil 1990;71:1078– 80. [6] Zwecker M, Iancu I, Zeilig G, Ohty A. Camptocormia: a case of possible paraneoplastic etiology. Clin Rehabil 1998;12:157–60. [7] Djaldetti R, Mosberg-Galli R, Sroka H, Merims D, Melamed E. Camptocormia (bent spine) in patients with Parkinson’s disease—characterization and possible pathogenesis of an unusual phenomenon. Mov Disord 1999;3:443–7. [8] Friedman JH. Episodic camptocormia in PD. Mov Disord 2001;6:1201. [9] Inzelberg R, Hattori N, Nisipeanu P, Abo Mouch S, Blumen SC, Carasso RL, et al. Camptocormia, axial dystonia, and parkinsonism: phenotypic heterogeneity of a parkin mutation. Neurology 2003;60:1393– 4. [10] Levin OS, Amosova NA. Camptocormia induced by pramipexole in patients with multiple system atrophy. Atypical Parkinsonian Disorders International Meeting, Innsbruck, Austria, February 19–21, 2003:60 pp. [11] Martin JP. Curvature of the spine in post-encephalitic parkinsonism. J Neurol Neurosurg Psychiatry 1965;28:395–400. [12] Suzuki T, Koizumi J, Moroji T, Sakuma K, Hori M, Hori T. Clinical characteristics of the Pisa syndrome. Acta Psychiat Scand 1990;82:454–7. [13] Colosimo C. Pisa syndrome in a patient with multiple system atrophy. Mov Disord 1998;3:607–8. [14] Patel S, Tariot PN, Hamill RW. Pisa syndrome without neuroleptic exposure in a patient with dementia of the Alzheimer type. J Geriatr Psych Neurol 1991;4:48–51. [15] Kan AE. Striatonigral degeneration. Pathology 1978;10:45–52. [16] Sławek J, Derejko M, Lass P. Camptocormia as a form of dystonia in Parkinson’s disease. Eur J Neurol 2003;10:107–10. [17] Schrag A, Kingsley D, Phatourus C, Mathias CJ, Lees AJ, Daniel SE, et al. Clinical usefulness of magnetic resonance imaging in multiple system atrophy. J Neurol Neurosurg Psychiatry 1998;65:65– 71. [18] Schrag A, Good CD, Miszkiel K, Morris HR, Mathias CJ, Lees AJ, et al. Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology 2000;54:697–702. [19] Yekhlef F, Ballan G, Macia F, Delmer O, Sourgen C, Tison F. Routine MRI for the differential diagnosis of Parkinson’s disease, MSA, PSP and CBD. J Neural Transm 2003;110:151–69. [20] Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–4. [21] Colosimo C, Albanese A, Hughes AJ, de Bruin VM, Lees AJ. Some specific clinical features differentiate multiple system atrophy (striatonigral variety) from Parkinson’s disease. Arch Neurol 1995;52:294– 8. [22] Osaki Y, Ben-Schlomo Y, Wenning GK, Daniel SE, Hughes A, Lees AJ, et al. Do published criteria improve clinical diagnostic accuracy in multiple system atrophy? Neurology 2002;59:1486– 91. [23] Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, Mc Keith I, et al. SIC task force appraisal of clinical diagnostic criteria for parkinsonian disorders. Mov Disord 2003;5:467–86.
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[24] Wenning GK, Geser F, Poewe W. The “risus sardonicus” of multiple system atrophy. Mov Disord 2003;10:1211. [25] Laroche M, Delisle MB, Aziza R, Lagarrigue J, Mazieres B. Is camptocormia a primary muscular disease? Spine 1995;20:1011–6. [26] Rondot P, Lacroix S, Said G. Camptocormia associated with Parkinson’s disease. J Neurol 2001;248(Suppl. 2):37. [27] Wunderlich S, Csoti I, Reiners K, G¨unther-Lengsfeld T, Schneider C, Becker G, et al. Camptocormia in Parkinson’s disease mimicked by focal myositis of the paraspinal muscles. Mov Disord 2002;3:598– 600. [28] Sch¨abitz WR, Glatz K, Schuhan C, Sommer C, Berger C, Schwanninger M, et al. Severe forward flexion of the trunk in Parkinson’s disease: focal myopathy of the paraspinal muscles mimicking camptocormia. Mov Disord 2003;4:408–14.
[29] Nandi D, Parkin S, Scott R, Winter JL, Joint C, Gregory R, et al. Camptocormia treated with bilateral pallidal stimulation. J Neurosurg 2002;97:461–6. [30] Nieves AV, Miyasaki JM, Lang AE. Acute onset dystonic camptocormia caused by lenticular lesions. Mov Disord 2001;1:177–80. [31] Hozumi I, Piao YS, Inuzuka T, Matsuyama Z, Yamada Y, Hara A, et al. Marked asymmetry of putaminal pathology in an MSA-P patient with Pisa syndrome. Mov Disord 2004;4:470–86. [32] Defer GL, Widner H, Goetz C, Brooks D, Fahn S, Freeman T, et al. Core assessment program for surgical interventional therapies in Parkinson’s disease (CAPSIT-PD). Mov Disord 1999;14:572–84. [33] Pereira LCM, Palter VN, Lang AE, Hutchinson WD, Lozano AM, Dostrovsky JO. Neuronal activity in the globus pallidus of multiple system atrophy patients. Mov Disord 2004;12:1485–92.
Case report
Camptocormia or Pisa syndrome in multiple system atrophy Jarosław Sławek a,∗ , Mirosława Derejko b , Piotr Lass c , Mirosława Dubaniewicz d a
b
Department of Neurosurgery, Division of Functional Neurosurgery and Movement Disorders, Medical University, ul. D˛ebinki 7, 80-211 Gda´nsk, Poland Department of Neuroelectrophysiology, Institute of Psychiatry and Neurology, ul. Sobieskiego 9, 02-957 Warszawa, Poland c Department of Nuclear Medicine, Medical University, ul. D˛ ebinki 7, 80-211 Gda´nsk, Poland d Department of Radiology, Medical University, ul. D˛ ebinki 7, 80-211 Gda´nsk, Poland Received 28 June 2005; accepted 8 July 2005
Abstract Although a mild stooped posture is a hallmark of parkinsonism, extreme trunk forward flexion is not common. This phenomenon was described in different etiological entities and called camptocormia. Other similar presentations called Pisa syndrome and antecollis were described mainly in extrapyramidal disorders. Authors present two cases of probable multiple system atrophy (MSA) with predominant parkinsonism and Pisa syndrome (or camptocormia). Both of them were previously misdiagnosed as idiopathic Parkinson’s disease (PD) and one was reported 1 year earlier. The typical clinical presentation fulfilling the diagnostic criteria for multiple system atrophy, rapid progression with lack of responsiveness to l-DOPA and apomorphine and typical MRI putaminal pathology observed in both cases allowed us to make a diagnosis. Accuracy of clinical diagnosis in multiple system atrophy is still very poor. Therefore, unusual or rare clinical presentations may support the final diagnosis. The camptocormia, Pisa syndrome and antecollis may represent the continuum of the same motor phenomenon and most of the authors refer them to unusual form of axial dystonia. According to many clinical presentations on different forms of camptocormia/Pisa syndrome authors conclude that not etiology, but the localization of specific lesion, probably within putamen is responsible for that form of dystonia. In cases of parkinsonism and severe forward flexion of trunk multiple system atrophy, diagnosis should be considered. © 2005 Elsevier B.V. All rights reserved. Keywords: Camptocormia; Dystonia; Parkinson’s disease; Multiple system atrophy; Pisa syndrome
1. Introduction Camptocormia or bent spine has been characterized by extreme forward flexion of thoracolumbar spine with passive dropping of both arms. Typically, the symptoms increase while patient is walking and disappear in recumbent position [1]. Camptocormia is a motor phenomenon of heterogeneous etiology. It may be the result of intradural hematoma, vertebral infection, spinal cord malignancies, myositis of paraspinal muscles, sodium valproate toxicity, psychogenic origin or in some cases may be idiopathic [2–6]. This phenomenon was also observed in extrapyramidal disorders such ∗
Corresponding author. Tel.: +48 58 340 01 08; fax: +48 58 340 01 08. E-mail addresses: [email protected], [email protected] (J. Sławek). 0303-8467/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2005.07.004
as post-encephalitic parkinsonism, autosomal recessive juvenile parkinsonism (caused by mutations in the parkin gene), idiopathic Parkinson’s disease (PD) and multiple system atrophy (MSA), after pramipexole exposure and referred presumably to the sort of unusual axial dystonia [7–11]. Pisa syndrome is another (but clinically similar) form of rapidly evolving and severe axial dystonia with forward, but also laterally orientated trunk flexion. Initially, it was described as a motor phenomenon appearing a several days after starting of neuroleptic treatment [12]. A similar picture may also occur as a subtype of tardive dystonia or motor presentation of Alzheimer’s disease (AD) and MSA [13,14]. However, in MSA, more characteristic motor presentation is head ptosis or antecollis, Kan and Colosimo gave similar descriptions of their patients with Pisa syndrome and diagnosis of MSA [13,15].
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J. Sławek et al. / Clinical Neurology and Neurosurgery 108 (2006) 699–704
The authors have described the case of camptocormia in PD with improvement after unilateral pallidotomy. Although published in 2003, the paper was accepted in August 2002 and till the end of 2003, we observed the evolution of symptoms and signs, which had changed our previous diagnosis of PD into MSA. At the same time, another similar case was referred to our department, emerging the question that Pisa syndrome, camptocormia or generally severe flexion dystonia of the trunk are more often than suspected symptoms of probable MSA [16].
2. Case reports 2.1. Patient no. 1 In the previous report, authors described a 49-year-old woman who developed resting tremor followed by the cogwheel rigidity and loss of dexterity of the left hand 5 years earlier. Marked bradykinesia, dysarthria and involvement of the right side developed within the next 6 months. Laboratory tests and neuroimaging (CT, MRI and rCBF SPECT) were normal and response to l-DOPA with benserazide was between moderate and good, after increasing the dosage to 600 mg/day. After 3 years, her posture was markedly stooped with deterioration of gait and with postural instability and
falls. There were no cerebellar symptoms. Despite increasing the dosage of l-DOPA with benserazide to 1400 mg/day, she developed severe and painful forward trunk flexion with predominance to right side, which increased during walking and disappeared completely in the recumbent position (Fig. 1). The occurrence of trunk flexion (diagnosed as camptocormia) was not related to time and dosage of l-DOPA intake. MRI of brain and thoracic and lumbar spine were normal. Due to deterioration, she underwent right side pallidotomy in May 2001, with decrease of left extremities rigidity and hypokinesia and almost immediate improvement of posture with markedly reduced trunk flexion. Despite of initial good effect, in the following months she started to deteriorate rapidly with only subjective response to l-DOPA, and autonomic disturbances like severe constipation and urine incontinence have appeared. Therefore, she was again admitted to clinic for apomorphine testing and presumably further treatment with subcutaneous infusion with external pump. Unfortunately, we did not observe any motor improvement till dose of 7.5 mg in single injection and afterwards during a week observation of continuous subcutaneous infusion of apomorphine, with even slight deterioration and somnolence at higher dosages. At that time (almost one and a half year after surgery), the forward trunk flexion following also the neck anteflexion returned and deteriorated in the next months. The MRI scan performed at that time revealed putaminal atrophy and hypointensity
Fig. 1. The clinical presentation of severe forward, with right side predominance trunk flexion similar to descriptions of both camptocormia or Pisa syndrome (patient no. 1).
J. Sławek et al. / Clinical Neurology and Neurosurgery 108 (2006) 699–704
Fig. 2. MRI scans (T2 weighted images, 0.5T), patient no. 1. The hyperintense rim at the lateral putaminal edge.
with hyperintense lateral rim (T2 weighted images, 0.5T), the characteristic MRI features of MSA as published by Schrag et al. and Yekhlef et al. [17–19] (Fig. 2). At the time of report she was almost anarthric, able to walk only a few steps with assistance, had severe general rigidity, bradykinesia, dysphagia, risus sardonicus and severe, mentioned above forward flexion of the neck and trunk. She was classified as being at stage 5 according to Hoehn–Yahr scale and 20% according to Schwab-England Activities of Daily Living scale. Till now, any symptoms of cognitive decline and dyskinesia have not been observed, even after high l-DOPA dosages. The relatively earlier onset of the disease, rapid progression, lack of response to dopaminergic therapy after 6–7 years, autonomic dysfunctions and characteristic MRI findings have changed our initial diagnosis from PD into MSA with predominant parkinsonism (MSA-P). 2.2. Patient no. 2 A 63-year-old woman developed painful rigidity and loss of dexterity of right extremities in 1999, followed by slight resting tremor of right hand and dysarthria. During the next 3 years, the typical for PD symptoms of bradykinesia, gait disturbances, stooped posture and instability was developed and have become bilateral. Computed tomography scans were normal. From 1999, l-DOPA with benserazide was started with moderate effect and due to relatively rapid progression, was increased up to 1300 mg/day in 2002; but in the last 2 years, the initial beneficial effect was lost. Concomitant treatment with amantadine 200 mg/day and piribedil up to 150 mg/day were also ineffective. There were no dyskinesia, nor other motor fluctuations (e.g. wearing off). The depression was diagnosed and treated with fluoxetine 20 mg/day and later sertraline 50 mg/day without effect. No cognitive
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Fig. 3. MRI scans (T2 weighted and FLAIR images, 1.5T), patient no. 2. The hypointensivity of putamen and lateral hyperintense rim.
declines were observed at that time. In 2003, she progressed rapidly, still with asymmetry of symptoms (more pronounced rigidity of right extremities), Babinski’s sign on the left side and urine incontinency. She could walk only a few steps with assistance. Cerebellar symptoms were not observed. She was classified as being at stage 4 according to Hoehn–Yahr scale and 50% according to Schwab-England Activities of Daily Living score. The UPDRS motor score (III) did not deteriorate after cessation of anti-parkinsonian medications, suggesting the l-DOPA unresponsiveness. MRI scan performed in 2003 revealed the putaminal changes similar to those described in case 1 with more marked hypointensity (T2 weighted images, 1.5T) and hyperintensive rim at lateral edge of putamen (FLAIR images) (Fig. 3). Therefore, we have changed our previous diagnosis from PD to MSA-P. At the same time, she developed very markedly stooped posture with forward trunk, but not neck flexion of almost 60◦ maximally, with predominance to the right side, resembling that in patient no. 1 and diagnosed as camptocormia (or Pisa syndrome) (Fig. 4). The flexed posture deteriorated while walking and was accompanied by very severe back pain and all those symptoms disappeared in recumbent position. Plain X-ray examination showed the degenerative changes of the lumbar vertebral column.
3. Discussion Severe trunk forward flexion in extrapyramidal disorders was described in post-encepahilitic parkinsonism by Martin, in Parkinson’s disease by Djaldetti et al., Friedman and by Inzelberg et al. in Arabic Israeli family with parkin mutations [7–9,11]. Our case no. 1 (formerly presented as PD) fulfilled the United Kingdom Parkinson’s Disease Society Brain Bank criteria for diagnosis of idiopathic PD at the
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Fig. 4. The clinical presentation of forward and right trunk flexion (camptocormia or Pisa syndrome) in patient no. 2.
time of former description [16,20]. Nevertheless, from the beginning, patient presented with some relatively atypical but acceptable for diagnosis of PD symptoms like: younger age at onset, postural instability, relatively fast progression and lack of dyskinesias (despite high dosages of l-DOPA). Revisiting the case, 18 months later after initial description, we have changed our previous diagnosis into MSA-P. Diagnosis of MSA may be a significantly difficult task in the patients presenting only with parkinsonian signs. In some cases, the clinical presentation may be undistinguishable from idiopathic PD up to the time of death [21]. The accuracy of clinical diagnosis of MSA appears relatively poor in general, with up to 55% of postmortem confirmed cases being misdiagnosed even at last neurological evaluation [22]. Especially the form of MSA-P, representing mostly the striatonigral degeneration (SND) is usually mistaken for PD due to a number of overlapping symptoms as: asymmetry, resting
tremor and positive response (at least initially) to l-DOPA. Published criteria have improved the clinical diagnostic accuracy, but in fact it is still relatively low [23]. Therefore, we still need to investigate some specific clinical features that differentiate MSA from PD and other atypical parkinsonian syndromes. A number of warning signs (“red flags”) have been proposed, among them are disproportionate antecollis, respiratory stridor, “cold hand sign” and recently described “risus sardonicus” [24]. The MRI abnormalities published in recent years may also help us to make a proper diagnosis. The typical for MSA-P changes includes a hyperintense rim at the lateral putaminal edge (due to gliosis), putaminal atrophy and hyperintensity (mainly on 0.5T scans), atrophy and signal decrease of the globus pallidus (mainly on 1.5T scans) as a result of iron content higher than in PD. Although highly diagnostic, those putaminal abnormalities occurred in only 54% of patients with MSA, therefore, their sensitivity is relatively low, but specificity and positive predictive value very high (for hyperintense putaminal rim 91 and 84%, respectively) [18]. Moreover, these findings are probably not early in the course of disease. One may conclude, when specific changes are seen, MRI is useful to support a clinical diagnosis of MSA versus PD. Two presented cases, however, diagnosed only clinically, had showed those specific MRI changes that may support the diagnosis of MSA. The differentiation based on anal sphincter EMG findings or biochemical test with clonidine is also of limited value, due to similar features found in PD or progressive supranuclear palsy. The presented cases fulfill now the criteria for the diagnosis of probable (no pathological data, still alive) MSA, according to Litvan et al. consensus criteria published in 2003 [23]. If possible, the autopsy confirmation will be presented by authors subsequently. The unusual clinical features as antecollis or severe, asymmetrical, forward trunk flexion whatever the name (camptocormia or Pisa syndrome) may alert the neurologists and may improve the diagnosis at early stage. This may become more important once drugs are developed to slow the rate of disease progression. The pathogenesis or nature of camptocormia and/or Pisa syndrome remains unclear. Most of the authors refer the abnormal trunk flexion to dystonic contractions of paraspinal and/or abdominal muscles. In most cases of parkinsonism, no obvious relationship between bent spine and administration of l-DOPA was observed. Dystonia is a typical complication of PD, in most cases presenting as an early morning dystonia as a result of the lack of l-DOPA. Therefore, there is a possibility of other central mechanisms, may be not of dopaminergic origin, underlying this phenomenon. The investigation of real nature of camptocormia is more complicated due to the observations of myositis of paraspinal muscles described by several authors, also in PD and nonPD patients [25–28]. The disadvantage of our report is the lack of EMG or biopsy examination in presented cases. Nevertheless, as in the case of head ptosis, histological changes in the paraspinal muscles are seen in those with an obvious extrapyramidal cause, suggesting that these changes may be
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non-specific, resulting from mechanical strain rather than a specific myopathic disorder [1]. There are interesting reports on camptocormia published by Nieves et al. and Nandi et al. [29,30]. Former one described the acute onset dystonic camptocormia caused by right side vascular lenticular lesions in two cases. It may confirm the dystonic nature of camptocormia, because lenticular lesion produces dystonia more often than any other movement disorders [29]. The report by Nandi et al., concerning the case of 39-year-old man with camptocormia of unknown origin, treated successfully with bilateral pallidal stimulation may support this notion. Although the etiology of camptocormia was unknown in that case, the improvement was achieved after bilateral pallidal stimulation. What is of the major interest, the symptoms recurred after stimulation was switched off. It has been shown that pallidal stimulation improves a wide variety of dystonic conditions [28]. Therefore, this report and our previous report on MSA patient with bent spine improvement after unilateral pallidotomy (patient no. 1) may support the view of dystonic nature of camptocormia and probably also Pisa syndrome [13,16]. The similar case of Pisa syndrome due to pathologically confirmed MSA-P with laterality of putaminal lesions was recently described by Hozumi et al. [31]. In both the clinical case studies by Colosimo [13], the case of Hozumi et al. [31] and our case no.1, akinetic-rigid parkinsonian symptoms dominated on the side opposite to the direction of the lean. It was not observed in our case no. 2, where right side rigidity was more prominent and patient leaned to the right. It may suggest that dominance of one-side putaminal changes decides on the lean direction and it may be related to the different localization of changes responsible for limb rigidity. The lack of response of Pisa syndrome to l-DOPA therapy may support this view. The diagnosis of atypical parkinsonism is one of the major contraindications for functional neurosurgery [32]. Our case no. 1 was misdiagnosed and underwent surgery at the time of diagnosis of PD. However, successful in terms of camptocormia, MSA still should not be treated as indication for surgical therapy. Poor clinical results of pallidotomy in MSA patients may be confirmed by Pereira et al. observations that internal globus pallidus firing rates are different (lower) in MSA [33]. The characteristic clinical presentation of camptocormia is the same in PD and other cases with distinct etiology. Therefore, in conclusion one may suggest that not etiology, but specific localization of pathology is responsible for this unusual form of axial dystonia. Despite some differences it may be postulated that there is a continuum of symptoms like antecollis, camptocormia and Pisa syndrome, reflecting the specific localization (presumably putaminal) of pathology [1]. The specific location of MRI findings in MSA-P patients may support this hypothesis. The conditions of camptocormia and Pisa syndrome are clinically difficult to distinguish and may reflect the same clinical problem. In parkinsonian patients with pronounced forward flexion of trunk (whatever the name), the diagnosis of MSA has to be considered.
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