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Pisa syndrome in progressive supranuclear palsy: A case report
Parkinsonism and Related Disorders 21 (2015) 1115e1116
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Pisa syndrome in progressive supranuclear palsy: A case report Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.parkreldis.2015.07.005. Keywords: Progressive supranuclear palsy Pisa syndrome Dystonia
Pisa syndrome (PS) is an abnormal posture characterized by a tonic flexion of the trunk to one side, which is typically mobile (it resolves, for example, on lying down). PS is rare in patients with progressive supranuclear palsy (PSP); only one case of PSP with PS has been reported [1]. We here described another case of a patient with PSP who developed PS. A 72-year-old man presented with a 2-year history of gait disturbance and postural instability with recurrent falls. He had no family history of neurodegenerative disorder. On examination, he was alert but apathetic. His Mini Mental State Examination score was 10 out of 30 points. His Frontal Assessment Battery (FAB) score was 3 out of 18 points (prehension behavior, 3/3). His score of the Japanese Version of the Montreal Cognitive Assessment (MoCA-J) was 4 out of 30 points (naming, 3/3; orientation, 1/6). Neither aphasia nor apraxia signs were observed. There was predominantly right-side grasp reflex. His vertical ocular movements in voluntary gaze as well as smooth pursuit ocular movements were slow and severely limited. His horizontal gaze and smooth pursuit of a visual target were also slow, saccadically fragmented, and hypometric predominantly to the left side. He had severe bradykinesia with symmetric rigidity and was unable to walk without assistance. He had an abnormal posture of the trunk, leaning to the right, which became more marked (by at least 10 ) when sitting on a wheelchair (Fig. 1A, B; see Video). This posture was alleviated in the supine position. There was no ataxia. The alien hand phenomenon, cortical sensory loss, tremor, and myoclonus were absent. Midsagittal T1weighted MRI of the brain showed the characteristic prominent atrophy of the midbrain and anterior cingulate gyrus (Fig. 1C), without marked atrophy of the pons. There was no asymmetrical cortical atrophy (not shown). 123I-N-isopropyl-4-iodoamphetamine (I-IMP) brain single-photon emission computed tomography (SPECT) showed reduced perfusion predominantly in the bilateral anterior cingulate gyri, predominantly left lateral frontal cortex, caudate, and midbrain, and normal cerebellar signals (Fig. 1D). On the basis of the clinical findings of vertical supranuclear gaze palsy and early onset of postural instability with falls, he was diagnosed as having probable PSP. http://dx.doi.org/10.1016/j.parkreldis.2015.07.005 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
The characteristic clinical sign in this patient is PS in addition to the common features of PSP. A mild asymmetry does not represent an exculsion criteria [1]. SPECT findings such as a hypoperfusion in the frontal areas, caudate nuclei as well as midbrain support the PSP diagnosis in this patient [2]. Regarding the differential diagnoses in this patient, his clinical phenotype and MRI findings did not support the corticobasal syndrome (CBS) diagnosis, although autopsy findings were not available. Eye movement abnormalities are common particularly in patients with spinocerebellar ataxia 1 (SCA1), SCA2, SCA6, and SCA7. Our patient's clinical and imaging findings did not indicate the diagnosis of SCAs. The pathophysiology of PS has not been fully understood, but several causes have been proposed. A possible cause could be an imbalance in a dynamic interplay among neurotransmitters, which include dopamine, acetylcholine, noradrenaline, and serotonin, and their roles in modulating the axial muscle tone [1]. Recently, Castrioto et al. have reviewed the data supporting the central and peripheral hypotheses in an attempt to clarify the mechanisms underlying the development of PS in Parkinson's disease (PD) [3]. The central hypothesis refers to ganglial dysfunction and abnormal integration of sensory information as the causes of PS, whereas the peripheral hypothesis suggests paraspinal muscle hyperactivity and myopathy as the causes. In animal model studies, asymmetry of dopaminergic activity between two sides of the basal ganglial loop leads to rotational behavior and postural deviation towards the more dopamine-depleted striatum, that is, toward the less affected hemibody [3]. In PD patients, the introduction, increase, or decrease in dopaminergic medications can induce or reverse PS, supporting the hypothesis that asymmetry in the functioning of the basal ganglial loop might contribute to the development of this syndrome [3]. Interestingly, a significant loss of cholinergic neurons in the pedunculopontine nucleus (PPN) pars compacta, a putative cholinergic nucleus, has been demonstrated in PSP patients [4]. The globus pallidus delivers neuronal information processed in the basal ganglia to the PPN, which is involved in postural control and locomotion, as well as to the thalamus [5]. We hypothesize that any asymmetry or dysregulation of the pathway involving the PPN, as well as dopaminergic dysfunction, results in the asymmetric alteration of the trunk muscles in this patient. Other mechanisms such as alterations in perception of postural verticality and impairment in vestibular function may also be involved in the pathogenesis of PS in this patient [3]. His neuropsychological evaluation revealed fronto-subcortical dysfunction. In addition, there was mild asymmetry of hypoperfusion in his frontal regions, especially in the lateral frontal cortices (left > right) on SPECT images of his brain.
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Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1115e1116
Fig. 1. (A) Tonic flexion of the trunk to the right was present in standing position. (B) When sitting, right flexion of the trunk was marked. (C) Midsagittal T1-weighted MRI of the brain demonstrating frontal lobe and midbrain atrophies without pontine atrophy. (D) 123I-IMP SPECT showing hypoperfusion in bilateral anterior cingulate gyri (arrowheads), predominantly left lateral frontal cortex, caudate (arrowheads), and midbrain (arrows).
Finally, we hypothesize that the pathophysiology of PS involves asymmetrical alteration in the cortico-striato-pallido-thalamocortical circuits, which caused by fronto-subcortical impairment in this patient. Disclosures Funding sources and conflicts of interest: The authors report no sources of funding nor conflicts of interest. Financial disclosures for previous 12 months: The authors declare that there are no disclosures to report. References [1] P. Solla, A. Cannas, E. Costantino, G. Orofino, L. Lavra, F. Marrosu, Pisa syndrome in a patient with progressive supranuclear palsy, J. Clin. Neurosci. 19 (2012) 922e923. [2] A. Varrone, M. Pagani, E. Salvatore, D. Salmaso, V. Sansone, M. Amboni, et al., Identification by [99mTc]ECD SPECT of anterior cingulate hypoperfusion in progressive supranuclear palsy, in comparison with Parkinson's disease, Eur. J. Nucl. Med. Mol. Imaging 34 (2007) 1071e1081. rennou, P. Krack, B. Debû, The pathogenesis of [3] A. Castrioto, C. Piscicelli, D. Pe Pisa syndrome in Parkinson's disease, Mov. Disord. 29 (2014) 1100e1107. [4] K. Jellinger, The pedunculopontine nucleus in Parkinson's disease, progressive supranuclear palsy and Alzheimer's disease, J. Neurol. Neurosurg. Psychiatry 51 (1988) 540e543. [5] S.M. Lee, C.H. Loo, Y.H. Choi, Primary progressive freezing of gait in a patient with CO-induced parkinsonism, Mov. Disord. 25 (2010) 1513e1515.
Kazuyuki Noda* Department of Neurology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan Sumihiro Kawajiri Department of Neurology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan Yuji Tomizawa Department of Neurology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan Nobutaka Hattori Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan Yasuyuki Okuma Department of Neurology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan *
Corresponding author. E-mail address: [email protected] (K. Noda). 7 November 2014
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Pisa syndrome in progressive supranuclear palsy: A case report Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.parkreldis.2015.07.005. Keywords: Progressive supranuclear palsy Pisa syndrome Dystonia
Pisa syndrome (PS) is an abnormal posture characterized by a tonic flexion of the trunk to one side, which is typically mobile (it resolves, for example, on lying down). PS is rare in patients with progressive supranuclear palsy (PSP); only one case of PSP with PS has been reported [1]. We here described another case of a patient with PSP who developed PS. A 72-year-old man presented with a 2-year history of gait disturbance and postural instability with recurrent falls. He had no family history of neurodegenerative disorder. On examination, he was alert but apathetic. His Mini Mental State Examination score was 10 out of 30 points. His Frontal Assessment Battery (FAB) score was 3 out of 18 points (prehension behavior, 3/3). His score of the Japanese Version of the Montreal Cognitive Assessment (MoCA-J) was 4 out of 30 points (naming, 3/3; orientation, 1/6). Neither aphasia nor apraxia signs were observed. There was predominantly right-side grasp reflex. His vertical ocular movements in voluntary gaze as well as smooth pursuit ocular movements were slow and severely limited. His horizontal gaze and smooth pursuit of a visual target were also slow, saccadically fragmented, and hypometric predominantly to the left side. He had severe bradykinesia with symmetric rigidity and was unable to walk without assistance. He had an abnormal posture of the trunk, leaning to the right, which became more marked (by at least 10 ) when sitting on a wheelchair (Fig. 1A, B; see Video). This posture was alleviated in the supine position. There was no ataxia. The alien hand phenomenon, cortical sensory loss, tremor, and myoclonus were absent. Midsagittal T1weighted MRI of the brain showed the characteristic prominent atrophy of the midbrain and anterior cingulate gyrus (Fig. 1C), without marked atrophy of the pons. There was no asymmetrical cortical atrophy (not shown). 123I-N-isopropyl-4-iodoamphetamine (I-IMP) brain single-photon emission computed tomography (SPECT) showed reduced perfusion predominantly in the bilateral anterior cingulate gyri, predominantly left lateral frontal cortex, caudate, and midbrain, and normal cerebellar signals (Fig. 1D). On the basis of the clinical findings of vertical supranuclear gaze palsy and early onset of postural instability with falls, he was diagnosed as having probable PSP. http://dx.doi.org/10.1016/j.parkreldis.2015.07.005 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
The characteristic clinical sign in this patient is PS in addition to the common features of PSP. A mild asymmetry does not represent an exculsion criteria [1]. SPECT findings such as a hypoperfusion in the frontal areas, caudate nuclei as well as midbrain support the PSP diagnosis in this patient [2]. Regarding the differential diagnoses in this patient, his clinical phenotype and MRI findings did not support the corticobasal syndrome (CBS) diagnosis, although autopsy findings were not available. Eye movement abnormalities are common particularly in patients with spinocerebellar ataxia 1 (SCA1), SCA2, SCA6, and SCA7. Our patient's clinical and imaging findings did not indicate the diagnosis of SCAs. The pathophysiology of PS has not been fully understood, but several causes have been proposed. A possible cause could be an imbalance in a dynamic interplay among neurotransmitters, which include dopamine, acetylcholine, noradrenaline, and serotonin, and their roles in modulating the axial muscle tone [1]. Recently, Castrioto et al. have reviewed the data supporting the central and peripheral hypotheses in an attempt to clarify the mechanisms underlying the development of PS in Parkinson's disease (PD) [3]. The central hypothesis refers to ganglial dysfunction and abnormal integration of sensory information as the causes of PS, whereas the peripheral hypothesis suggests paraspinal muscle hyperactivity and myopathy as the causes. In animal model studies, asymmetry of dopaminergic activity between two sides of the basal ganglial loop leads to rotational behavior and postural deviation towards the more dopamine-depleted striatum, that is, toward the less affected hemibody [3]. In PD patients, the introduction, increase, or decrease in dopaminergic medications can induce or reverse PS, supporting the hypothesis that asymmetry in the functioning of the basal ganglial loop might contribute to the development of this syndrome [3]. Interestingly, a significant loss of cholinergic neurons in the pedunculopontine nucleus (PPN) pars compacta, a putative cholinergic nucleus, has been demonstrated in PSP patients [4]. The globus pallidus delivers neuronal information processed in the basal ganglia to the PPN, which is involved in postural control and locomotion, as well as to the thalamus [5]. We hypothesize that any asymmetry or dysregulation of the pathway involving the PPN, as well as dopaminergic dysfunction, results in the asymmetric alteration of the trunk muscles in this patient. Other mechanisms such as alterations in perception of postural verticality and impairment in vestibular function may also be involved in the pathogenesis of PS in this patient [3]. His neuropsychological evaluation revealed fronto-subcortical dysfunction. In addition, there was mild asymmetry of hypoperfusion in his frontal regions, especially in the lateral frontal cortices (left > right) on SPECT images of his brain.
1116
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1115e1116
Fig. 1. (A) Tonic flexion of the trunk to the right was present in standing position. (B) When sitting, right flexion of the trunk was marked. (C) Midsagittal T1-weighted MRI of the brain demonstrating frontal lobe and midbrain atrophies without pontine atrophy. (D) 123I-IMP SPECT showing hypoperfusion in bilateral anterior cingulate gyri (arrowheads), predominantly left lateral frontal cortex, caudate (arrowheads), and midbrain (arrows).
Finally, we hypothesize that the pathophysiology of PS involves asymmetrical alteration in the cortico-striato-pallido-thalamocortical circuits, which caused by fronto-subcortical impairment in this patient. Disclosures Funding sources and conflicts of interest: The authors report no sources of funding nor conflicts of interest. Financial disclosures for previous 12 months: The authors declare that there are no disclosures to report. References [1] P. Solla, A. Cannas, E. Costantino, G. Orofino, L. Lavra, F. Marrosu, Pisa syndrome in a patient with progressive supranuclear palsy, J. Clin. Neurosci. 19 (2012) 922e923. [2] A. Varrone, M. Pagani, E. Salvatore, D. Salmaso, V. Sansone, M. Amboni, et al., Identification by [99mTc]ECD SPECT of anterior cingulate hypoperfusion in progressive supranuclear palsy, in comparison with Parkinson's disease, Eur. J. Nucl. Med. Mol. Imaging 34 (2007) 1071e1081. rennou, P. Krack, B. Debû, The pathogenesis of [3] A. Castrioto, C. Piscicelli, D. Pe Pisa syndrome in Parkinson's disease, Mov. Disord. 29 (2014) 1100e1107. [4] K. Jellinger, The pedunculopontine nucleus in Parkinson's disease, progressive supranuclear palsy and Alzheimer's disease, J. Neurol. Neurosurg. Psychiatry 51 (1988) 540e543. [5] S.M. Lee, C.H. Loo, Y.H. Choi, Primary progressive freezing of gait in a patient with CO-induced parkinsonism, Mov. Disord. 25 (2010) 1513e1515.
Kazuyuki Noda* Department of Neurology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan Sumihiro Kawajiri Department of Neurology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan Yuji Tomizawa Department of Neurology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan Nobutaka Hattori Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan Yasuyuki Okuma Department of Neurology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan *
Corresponding author. E-mail address: [email protected] (K. Noda). 7 November 2014