Parkinsonism and Related Disorders 21 (2015) 335e336
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Palatal tremor in progressive supranuclear palsy: A case report Keywords: PSP Progressive supranuclear palsy Palatal tremor Palatal myoclonus
Palatal tremor (PT) is an uncommon movement disorder, and an exceptional finding even in a movement disorders clinic. It is characterized by rhythmic contractions of the soft palate. When there is no attributable structural cause, it is termed essential PT. On the other hand, symptomatic PT has been associated with lesions affecting the triangle of Guillain-Mollaret (GM). This comprises of nucleus ruber, inferior olivary nucleus and contralateral dentate nucleus, with PT most commonly resulting from vascular, demyelinating or mass lesions. PT has only rarely been reported in neurodegenerative diseases, mostly in multiple system atrophy and Alexander's disease and typically in association with ataxia [1]. We present a clinical case of progressive supranuclear palsy (PSP) with PT and discuss potential pathophysiological mechanisms in light of the imaging findings. A 76-year-old woman presented with a three-year history of difficulty walking with frequent falls. She increasingly required assistance with most of daily activities, and her family noted a decline in cognitive functioning. Previous medical history included depression and euthyroid nodular goiter. She had no risk factors for cerebrovascular disease. On examination she had a supranuclear gaze palsy affecting vertical more than horizontal eye movements, slow saccades, prominent axial rigidity with only a mild limb rigidity and bradykinesia more marked on the left. There was no ataxia. Her posture was erect, she was unable to walk unassisted and there was no recovery on the pull test. Her MMSE score was 18/30. Additionally, a PT of approximately 2 Hz was observed (Video). It did not affect any other cranial muscles, and neither tremor nor myoclonus were observed elsewhere. On direct questioning, the patient denied audible “clicks”. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.parkreldis.2014.12.032. She was diagnosed as probable PSP, supported further by characteristic imaging findings. Brain MRI showed midbrain atrophy (Fig. 1a), in addition to generalized cortical atrophy. Both inferior olivary nuclei exhibited increased signal on FLAIR, without hypertrophy (Fig. 1b). Susceptibility-weighted sequence revealed decreased signal in both dentate nuclei, suggestive of iron accumulation (Fig. 1c). No lesions were observed in the GM triangle. FDG PET of the brain revealed a metabolic pattern typical for PSP e http://dx.doi.org/10.1016/j.parkreldis.2014.12.032 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
decreased metabolism in frontal areas and in the caudate nuclei with normal cerebellar signal (Suppl. Fig. 1). Thyroid tests were normal, as were B12 and folate. CSF analysis was unremarkable, including negative PCR for Tropheryma whipplei and negative serology for borreliosis (immunofluorescence test) and syphilis (VDRL). Comprehensive autonomic nervous system testing was unremarkable. PT is an atypical finding in PSP, previously reported only in two (pathologically confirmed) cases [2]. This unusual disease manifestation warrants additional clinical investigations. In our case, we excluded Whipple's disease or neurosyphilis. Clinical phenotype including absence of autonomic symptoms and signs and the metabolic pattern on FDG PET speak against the diagnosis of multiple system atrophy. Furthermore, MRI did not show support for other potential neurodegenerative causes such as Alexander's disease and neuronal brain iron accumulation (NBIA), as well as vascular or structural lesions in the GM triangle. Clinical features of essential and symptomatic PT may overlap. In our case the ear clicks were not audible and there was brain stem and cerebellar pathology with olivary hyperintensity on neuroimaging, all favoring symptomatic PT. Notably, our patient did not have hypertrophy of the inferior olivary nuclei, the usual feature of symptomatic PT that is thought to be a consequence of trans-synaptic olivary degeneration. However, olivary hypertrophy is only a transient pathological finding in symptomatic PT
Fig. 1. A) Midbrain atrophy demonstrated on midsagittal T1-weighted MRI. B) Hyperintense signal in inferior olivary nuclei on FLAIR. C) Decreased signal in dentate nuclei on SWI. Axial images are displayed in radiological view.
336
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 335e336
that usually develops six months after olivary deafferentation and is then followed by atrophy after a few years. In contrast, a hyperintense MRI signal, as seen in our patient, is a consistent feature which precedes hypertrophy and remains even in the atrophy stage [3]. Hence, our patient's MRI findings are consistent with either the early or the late imaging correlates of symptomatic PT. Only assumptions are possible as to what could be the causative mechanism of PT in our patient, or in PSP in general. PT in two previously reported cases of PSP was attributed to either hypoxic injury in the setting of pre-existing dentate nucleus degeneration or demyelination and gliosis in the superior cerebellar peduncle along with degeneration in the dentate nucleus [2]. In the present case, there was no history of hypoxia and no changes of MRI signal in superior cerebellar peduncles to support any of the two mechanisms. Instead, altered MRI signal suggestive of iron accumulation was observed in both dentate nuclei, perhaps an epiphenomenon of the degenerative process. Interestingly, iron deposition in the dentate nuclei was previously associated with PT in neuroferritinopathy [4]. Structural changes in the dentate nuclei are consistent with the putative pathophysiology of PT, causing an interruption of the inhibitory pathway from the dentate to the contralateral inferior olivary nucleus. Thus, there might be a link between iron accumulation in the dentate nuclei and PT in this particular patient. However, the pathophysiological relevance of iron accumulation in PSP is not as clear as in neuroferritinopathy. For example, a recent high-field MRI study did not confirm increased iron accumulation in PSP post-mortem brains compared to healthy controls [5]. We demonstrate that PT may accompany the clinical phenotype of otherwise typical PSP. Although apparently a rare feature of the disease, it might be that PT is habitually overlooked on neurological examination, due to inability of PSP patients to widely open the mouth (related to akinesia) and the absence of audible clicks on which they could complain.
Acknowledgments We thank the patient and her caregivers for their consent to publish the case report and the accompanying video. Appendix A. Supplementary data Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.parkreldis.2014.12.032.
References [1] Kulkarni PK, Muthane UB, Taly AB, Jayakumar PN, Shetty R, Swamy HS. Palatal tremor, progressive multiple cranial nerve palsies, and cerebellar ataxia: a case report and review of literature of palatal tremor in neurodegenerative disease. Mov Disord 1999 Jul;14(4):689e93. [2] Suyama N, Kobayashi S, Isino H, Iijima M, Imaoka K. Progressive supranuclear palsy with palatal myoclonus. Acta Neuropathol 1997 Sep;94(3):290e3. [3] Goyal M, Versnick E, Tuite P, Cyr JS, Kucharczyk W, Montanera W, et al. Hypertrophic olivary degeneration: metaanalysis of the temporal evolution of MR findings. AJNR Am J Neuroradiol 2000 Jun-Jul;21(6):1073e7. [4] Wills AJ, Sawle GV, Guilbert PR, Curtis AR. Palatal tremor and cognitive decline in neuroferritinopathy. J Neurol Neurosurg Psychiatr 2002 Jul;73(1):91e2. [5] De Reuck JL, Deramecourt V, Auger F, Durieux N, Cordonnier C, Devos D, et al. Iron deposits in post-mortem brains in patients with neurodegenerative and cerebrovascular diseases: a semi-quantitative 7.0 T magnetic resonance imaging study. Eur J Neurol 2014 Jul;21(7):1026e31.
Rok Berlot, Maja Kojovic* Department of Neurology, University Medical Centre Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia *
Corresponding author. Tel.:þ386 1 522 23 11. E-mail addresses: [email protected] (R. Berlot), [email protected] (M. Kojovi c). 15 October 2014
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Palatal tremor in progressive supranuclear palsy: A case report Keywords: PSP Progressive supranuclear palsy Palatal tremor Palatal myoclonus
Palatal tremor (PT) is an uncommon movement disorder, and an exceptional finding even in a movement disorders clinic. It is characterized by rhythmic contractions of the soft palate. When there is no attributable structural cause, it is termed essential PT. On the other hand, symptomatic PT has been associated with lesions affecting the triangle of Guillain-Mollaret (GM). This comprises of nucleus ruber, inferior olivary nucleus and contralateral dentate nucleus, with PT most commonly resulting from vascular, demyelinating or mass lesions. PT has only rarely been reported in neurodegenerative diseases, mostly in multiple system atrophy and Alexander's disease and typically in association with ataxia [1]. We present a clinical case of progressive supranuclear palsy (PSP) with PT and discuss potential pathophysiological mechanisms in light of the imaging findings. A 76-year-old woman presented with a three-year history of difficulty walking with frequent falls. She increasingly required assistance with most of daily activities, and her family noted a decline in cognitive functioning. Previous medical history included depression and euthyroid nodular goiter. She had no risk factors for cerebrovascular disease. On examination she had a supranuclear gaze palsy affecting vertical more than horizontal eye movements, slow saccades, prominent axial rigidity with only a mild limb rigidity and bradykinesia more marked on the left. There was no ataxia. Her posture was erect, she was unable to walk unassisted and there was no recovery on the pull test. Her MMSE score was 18/30. Additionally, a PT of approximately 2 Hz was observed (Video). It did not affect any other cranial muscles, and neither tremor nor myoclonus were observed elsewhere. On direct questioning, the patient denied audible “clicks”. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.parkreldis.2014.12.032. She was diagnosed as probable PSP, supported further by characteristic imaging findings. Brain MRI showed midbrain atrophy (Fig. 1a), in addition to generalized cortical atrophy. Both inferior olivary nuclei exhibited increased signal on FLAIR, without hypertrophy (Fig. 1b). Susceptibility-weighted sequence revealed decreased signal in both dentate nuclei, suggestive of iron accumulation (Fig. 1c). No lesions were observed in the GM triangle. FDG PET of the brain revealed a metabolic pattern typical for PSP e http://dx.doi.org/10.1016/j.parkreldis.2014.12.032 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
decreased metabolism in frontal areas and in the caudate nuclei with normal cerebellar signal (Suppl. Fig. 1). Thyroid tests were normal, as were B12 and folate. CSF analysis was unremarkable, including negative PCR for Tropheryma whipplei and negative serology for borreliosis (immunofluorescence test) and syphilis (VDRL). Comprehensive autonomic nervous system testing was unremarkable. PT is an atypical finding in PSP, previously reported only in two (pathologically confirmed) cases [2]. This unusual disease manifestation warrants additional clinical investigations. In our case, we excluded Whipple's disease or neurosyphilis. Clinical phenotype including absence of autonomic symptoms and signs and the metabolic pattern on FDG PET speak against the diagnosis of multiple system atrophy. Furthermore, MRI did not show support for other potential neurodegenerative causes such as Alexander's disease and neuronal brain iron accumulation (NBIA), as well as vascular or structural lesions in the GM triangle. Clinical features of essential and symptomatic PT may overlap. In our case the ear clicks were not audible and there was brain stem and cerebellar pathology with olivary hyperintensity on neuroimaging, all favoring symptomatic PT. Notably, our patient did not have hypertrophy of the inferior olivary nuclei, the usual feature of symptomatic PT that is thought to be a consequence of trans-synaptic olivary degeneration. However, olivary hypertrophy is only a transient pathological finding in symptomatic PT
Fig. 1. A) Midbrain atrophy demonstrated on midsagittal T1-weighted MRI. B) Hyperintense signal in inferior olivary nuclei on FLAIR. C) Decreased signal in dentate nuclei on SWI. Axial images are displayed in radiological view.
336
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 335e336
that usually develops six months after olivary deafferentation and is then followed by atrophy after a few years. In contrast, a hyperintense MRI signal, as seen in our patient, is a consistent feature which precedes hypertrophy and remains even in the atrophy stage [3]. Hence, our patient's MRI findings are consistent with either the early or the late imaging correlates of symptomatic PT. Only assumptions are possible as to what could be the causative mechanism of PT in our patient, or in PSP in general. PT in two previously reported cases of PSP was attributed to either hypoxic injury in the setting of pre-existing dentate nucleus degeneration or demyelination and gliosis in the superior cerebellar peduncle along with degeneration in the dentate nucleus [2]. In the present case, there was no history of hypoxia and no changes of MRI signal in superior cerebellar peduncles to support any of the two mechanisms. Instead, altered MRI signal suggestive of iron accumulation was observed in both dentate nuclei, perhaps an epiphenomenon of the degenerative process. Interestingly, iron deposition in the dentate nuclei was previously associated with PT in neuroferritinopathy [4]. Structural changes in the dentate nuclei are consistent with the putative pathophysiology of PT, causing an interruption of the inhibitory pathway from the dentate to the contralateral inferior olivary nucleus. Thus, there might be a link between iron accumulation in the dentate nuclei and PT in this particular patient. However, the pathophysiological relevance of iron accumulation in PSP is not as clear as in neuroferritinopathy. For example, a recent high-field MRI study did not confirm increased iron accumulation in PSP post-mortem brains compared to healthy controls [5]. We demonstrate that PT may accompany the clinical phenotype of otherwise typical PSP. Although apparently a rare feature of the disease, it might be that PT is habitually overlooked on neurological examination, due to inability of PSP patients to widely open the mouth (related to akinesia) and the absence of audible clicks on which they could complain.
Acknowledgments We thank the patient and her caregivers for their consent to publish the case report and the accompanying video. Appendix A. Supplementary data Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.parkreldis.2014.12.032.
References [1] Kulkarni PK, Muthane UB, Taly AB, Jayakumar PN, Shetty R, Swamy HS. Palatal tremor, progressive multiple cranial nerve palsies, and cerebellar ataxia: a case report and review of literature of palatal tremor in neurodegenerative disease. Mov Disord 1999 Jul;14(4):689e93. [2] Suyama N, Kobayashi S, Isino H, Iijima M, Imaoka K. Progressive supranuclear palsy with palatal myoclonus. Acta Neuropathol 1997 Sep;94(3):290e3. [3] Goyal M, Versnick E, Tuite P, Cyr JS, Kucharczyk W, Montanera W, et al. Hypertrophic olivary degeneration: metaanalysis of the temporal evolution of MR findings. AJNR Am J Neuroradiol 2000 Jun-Jul;21(6):1073e7. [4] Wills AJ, Sawle GV, Guilbert PR, Curtis AR. Palatal tremor and cognitive decline in neuroferritinopathy. J Neurol Neurosurg Psychiatr 2002 Jul;73(1):91e2. [5] De Reuck JL, Deramecourt V, Auger F, Durieux N, Cordonnier C, Devos D, et al. Iron deposits in post-mortem brains in patients with neurodegenerative and cerebrovascular diseases: a semi-quantitative 7.0 T magnetic resonance imaging study. Eur J Neurol 2014 Jul;21(7):1026e31.
Rok Berlot, Maja Kojovic* Department of Neurology, University Medical Centre Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia *
Corresponding author. Tel.:þ386 1 522 23 11. E-mail addresses: [email protected] (R. Berlot), [email protected] (M. Kojovi c). 15 October 2014
