Corticobasal syndrome presenting Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET

doi:10.21203/rs.3.rs-3141095/v1

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Case Report

Corticobasal syndrome presenting Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET

https://doi.org/10.21203/rs.3.rs-3141095/v1

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Journal Publication

published 12 Dec, 2023

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Background:

Corticobasal syndrome (CBS) is a neurodegenerative disease diagnosed based on clinical manifestations such as asymmetrical parkinsonism, limb apraxia, and speech and language impairment. Foix-Chavany-Marie syndrome (FCMS) is a rare neurological disorder characterized by bilateral impairment of voluntary movement in the facial, pharyngeal, lingual, and masticatory muscles, leading to apraxia of speech. FCMS is commonly attributable to stroke. Transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy is also known as the pathological background of FCMS, while the pathological background of the majority of CBS cases are diverse tauopathies instead of TDP-43 proteinopathy. In this report, we describe a case of FCMS that finally received a diagnosis of CBS with suggested 4-repeat tauopathy.

Case presentation:

A 68-year-old female started experiencing difficulty speaking followed by difficulty writing, especially texting difficulty, several years before her visit. Her impairment had been gradually worsening, and she came to our hospital. On neurological examination, she demonstrated the facial apraxia, frontal lobe dysfunction, and upper motor neuron signs. Based on her clinical features, she was diagnosed with FCMS. Her symptoms exhibited rapid progression and myoclonus, parkinsonism, and left-side dominant cortical sensory deficit occurred, resulting in the fulfillment of diagnostic criteria for CBS after 9 months. Tau PET imaging displayed notable ligand uptake in the brainstem, subthalamic nuclei, basal ganglia, and bilateral subcortical frontal lobe, suggesting her pathological background was 4-repeat tauopathy. As a result of the progressive dysphagia, she became unable to eat and passed away at 12 months.

Conclusion:

We hereby present an atypical case of CBS presenting with rapidly progressive FCMS. TDP-43 proteinopathy was suspected based on the clinical symptoms in the early stages of the disease; however, tau PET suggested that her pathological background was 4-repeat tauopathy.

Corticobasal syndrome

Foix-Chavany-Marie syndrome

tau PET

aphasia

Foix-Chavany-Marie syndrome (FCMS), also known as anterior opercular syndrome, is a rare neurological disorder characterized by bilateral voluntary paralysis of the facial, pharyngeal, lingual, and masticatory muscles, accompanied by a dissociation between automatic and voluntary movements. While stroke is the predominant cause of FCMS, it can also be induced by neurodegenerative disorders [1]. Several reports on FCMS have described transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy as the background pathology [2, 3]. Here, we report a case of corticobasal syndrome (CBS) presenting rapidly progressive FCMS, for which tau positron emission tomography (PET) was considered useful for the diagnosis.

A 68-year-old right-handed woman had difficulty speaking for the last several years. Approximately seven months ago, she started making kana-dominant spelling mistakes specifically in her mobile text messages. Of note was that the frequency of errors in her mobile text messages exceeded those observed in her handwriting, suggesting dystextia. When she visited our hospital, she exhibited apraxia of speech, eyelid opening, oculomotor, and buccofacial movement. There was dissociation between spontaneous and voluntary movements of facial expression. Perseveration, pathological laughing, and increased limb tendon reflexes were prominent. Lower motor neuron signs were absent from all extremities and her tongue. Her Mini-Mental State Examination (MMSE) score was 19/30 and her Frontal Assessment Battery (FAB) score was 7/18, suggesting mild cognitive decline including frontal lobe dysfunction. Detailed neuropsychological evaluation by Western Aphasia Battery (WAB) for Japanese (shortened version) is shown in Table 1. Based on the observed irregular stagnation and distortion in her spontaneous speech, it appeared that she was suffering from apraxia of speech rather than dysarthria. Furthermore, although her comprehension of complex sentences was impaired, single-word comprehension remained intact. Brain magnetic resonance imaging (MRI) and perfusion single photon emission computed tomography (SPECT) showed bilateral atrophy and decreased cerebral blood flow in the frontotemporal lobe, including the anterior operculum (Fig. 1-A and C). In the dopamine transporter (DaT) scan, the specific binding ratio (SBR) calculated as the ratio of striatal specific to non-specific binding was 5.27 on the right and 5.29 on the left, within normal range for the same age group. Cervical MRI failed to show any lesions that might explain the increased tendon reflexes. Needle electromyography showed no obvious abnormalities suggestive of motor neuron diseases. After a while she also presented with dysphagia. She showed clinical signs of FCMS, the cause of which could not be determined, but a degenerative disease such as frontotemporal dementia - motor neuron disease was suspected.

Table 1. Result of Western Aphasia Battery for Japanese (shortened version).

Ⅰ: Spontaneous speech, Ⅱ: Auditory verbal comprehension, Ⅲ: Repetition, Ⅳ: Object naming, Ⅴ: Reading, Ⅵ: Writing. Asterisks denote items with mean – 2SD. Means and – 2SD for each of the lower test items in healthy subjects were as follows: Ⅰ - A: 97.0 ± 12.0 %, Ⅰ - B: 100 %, Ⅱ - A: 99.2 ± 4.4 %, Ⅱ - B: 96.0 ± 15.0 %, Ⅲ: 98.7 ± 6.0 %, Ⅳ: 99.0 ± 8.0 %, Ⅴ - A: 93.5 ± 26.6 %, Ⅴ - B: 100 %, Ⅴ - C: 100 %, Ⅵ - A: 96.7 ± 23.4 %, Ⅵ - B: 88.3 ± 50.0 %, Ⅵ - C: 95.0 ± 33.4 %. SD, standard deviation.

Her clinical symptoms continued to gradually worsen, and she presented with myoclonus, bradykinesia, postural instability, left-side neglect, and left-side dominant cortical sensory deficit nine months later. Tau PET with Florzolotau (¹⁸F) demonstrated remarkable uptake of the ligand around the brainstem, subthalamic nucleus, basal ganglia, and bilateral subcortical frontal lobe (Fig. 1-B), while amyloid PET with ¹¹C-PiB was negative by visual assessment. Based on neurological findings, she was ultimately diagnosed with probable CBS [4], and the tau PET image suggested that her pathological background was CBS-4R-tauopathy [5]. Ten months after her first diagnosis, she was hospitalized for a tibia fracture due to a fall. With the progression of her symptom, she exhibited severe dysphagia and communication difficulties, eventually becoming bedridden. After conducting a follow-up DaT scan, a decrease in striatal uptake was observed, with SBR measuring 3.14 on the right and 3.37 on the left, which were still within normal range but showed a rapid decline compared to the previous examination. As a result of the progressive dysphagia, she became unable to eat and passed away 12 months after her first diagnosis. Unfortunately, consent for an autopsy could not be obtained.

In this case, the initial symptom was her speech difficulty, which was followed by dystextia. Dystextia entails the phenomenon of the inability to compose and send text messages. The Japanese written language consists of both kana (syllabograms) and kanji (ideograms). Previous studies indicated that kana and kanji processings may occur in distinct brain regions, as evidenced by the occasional impairment of kana selectivity in cases of frontal or parietal lesions [6]. When constructing sentences in Japanese mobile text messages, individuals only need to select kana characters displayed on the screen and press the corresponding buttons, as opposed to handwriting where they must recall the letter configurations [7]. In instances of kana impairment, it is possible that the frequency of errors could be greater during text input compared to handwriting. While no case of CBS presenting with dystextia has been reported thus far, it may actually be considered an early manifestation of CBS, as in the present case.

When she was first examined, she exhibited hyperreflexia and was diagnosed with FCMS. Although there are few autopsy reports of FCMS, TDP-43 is known as the background pathology. Hence, we postulated that she was in the preliminary stage of motor neuron disease and would exhibit muscular weakness in the imminent timeframe. Nonetheless, upon subsequent observation, she did not exhibit the typical progression of motor neuron disease. Instead, she met the diagnostic criteria for probable CBS, and the tau PET findings suggested 4R-tauopathy. Although rare, degeneration of the corticospinal tract has been reported in 4R-tauopathies such as corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) [8]. Since it is challenging to distinguish pyramidal slowness from bradykinesia and spasticity from rigidity [9], upper motor neuron signs may be more prevalent in 4R-tauopathies than previously assumed.

Based on the classification of Primary Progressive Aphasia (PPA), this case was categorized as non-fluent/agrammatic variant PPA (nfvPPA) [10]. NfvPPA is frequently linked with tauopathy [11], whereas the underlying pathology of FCMS is generally associated with TDP-43. In the present case, a conclusive diagnosis of probable CBS was established, and the tau PET results indicated the presence of 4R-tauopathy, such as CBD and PSP. Although pathological findings are necessary for a diagnosis, globular glial tauopathy (GGT) was also considered in this case. GGT is a relatively recently described 4R-tauopathy with a variable clinical presentation that includes motor neuron disease and frontotemporal dementia. Limited studies have reported tau PET findings in GGT [12, 13]; nevertheless, the usefulness of tau PET for the antemortem diagnosis of GGT remains unclear.

In summary, we present an atypical case of CBS presenting with rapidly progressive FCMS. Despite the fact that initial symptoms were similar to the motor neuron disease, she eventually met the diagnostic criteria of probable CBS, with tau PET imaging supporting the presence of 4R-tauopathy as the background pathology. As CBS is a heterogeneous syndrome with various clinical presentations, it will be essential to accumulate more cases in order to understand this disease.

Words: 1106 (< 2500)

CBS

Corticobasal syndrome

FCMS

Foix-Chavany-Marie syndrome

TDP-43

transactive response DNA binding protein of 43 kD

PET

positron emission tomography

MMSE

Mini-Mental State Examination

FDB

Frontal Assessment Battery

WAB

Western Aphasia Battery

MRI

magnetic resonance imaging

DaT

dopamine transporter

SBR

specific binding ratio

CBD

corticobasal degeneration

PSP

progressive supranuclear palsy

PPA

Primary Progressive Aphasia

nfvPPA

non-fluent/agrammatic variant PPA

GGT

globular glial tauopathy

Ethics approval and consent to participate

The manuscript does not contain clinical studies or patient data. The PET study conducted for the present report was approved by the Niigata University Certified Review Board (UMIN 000050731). Written informed consent was obtained from the patient.

Consent for publication

Written informed consent was obtained from the patient’s next of kin for publication of this case report.

Availability of data and materials

Anonymized raw data supporting the findings of the present study may be shared by the corresponding author upon reasonable request.

Competing interests

Hitoshi Shimada holds patents on compounds related to the present report (JP 5422782/EP 12 884 742.3/CA2894994/HK1208672), and received honoraria for lectures from Eizai Co., Ltd., consultant fee from Splink Co., Ltd., and research fundings from Splink Co., Ltd. and Novartis Pharmaceutical Co., Ltd. All other authors declare that they have no conflict of interest.

Funding

This study was supported in part by JSPS KAKENHI Grant-in-Aid for Scientific Research (B) and (C) (Grant Numbers JP23H02825 and JP18K07543), JST FOREST Program (Grant Number JPMJFR220R, Japan), the Japanese Society of Neurology Novartis Pharma Grants for Basic Research 2022, Splink Co., Ltd., and APRINOIA Therapeutics Co., Ltd.

Authors’ contributions

(1) Research Project: A. Conception and Design; B. Acquisition of Data; C. Analysis and Interpretation of Data; (2) Manuscript: A. Writing of the First Draft; B. Review and Critique; (3) Other: A. Synthesizing of Radioligands. KN: 1A, 1B, 1C, 2A. YK: 1A, 1B, 2B. MH: 1B, 1C, 2B. AK: 1B, 2B, 3A. YN: 2B, 3A. YM: 2B, 3A. MW: 1B, 2B. HI: 1B, 2B. TT: 1A, 2B. HS: 1A, 1B, 1C, 2B.

Acknowledgements

The authors thank the patient and her caregivers in this study, as well as clinical research coordinators, PET operators, and research ethics advisers at Niigata University for their assistance with the current projects. We also thank Arndt Gerz and Mikhail Ratanov for their help in proofreading. We are grateful to APRINOIA Therapeutics (Suzhou, China) for providing the tosylate precursor used for ¹⁸F-florzolotau radiosynthesis. This study was supported in part by JSPS KAKENHI Grant-in-Aid for Scientific Research (B) and (C) (Grant Number JP23H02825 and JP18K07543), by Japanese Society of Neurology Novartis Pharma Grants for Basic Research 2022, by Splink Co., Ltd., and APRINOIA Therapeutics Co., Ltd..

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Competing interest reported. Hitoshi Shimada holds patents on compounds related to the present report (JP 5422782/EP 12 884 742.3/CA2894994/HK1208672), and received honoraria for lectures from Eizai Co., Ltd., consultant fee from Splink Co., Ltd., and research fundings from Splink Co., Ltd. and Novartis Pharmaceutical Co., Ltd. All other authors declare that they have no conflict of interest.

Download PDF

Journal Publication

published 12 Dec, 2023

Read the published version in BMC Geriatrics →

Editorial decision: Major revision
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Reviews received at journal
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Reviewers agreed at journal
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Reviewers invited by journal
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Editor assigned by journal
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Editor invited by journal
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Submission checks completed at journal
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You are reading this latest preprint version

Corticobasal syndrome presenting Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET

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Abstract

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Background

Case presentation

Discussion

Conclusions

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