Characteristics of clinical and neuroimage findings in patients with corticobasal syndrome / 中华神经科杂志

Objective:To investigate the clinical, neuropsychological, and neuroimage characteristics in patients with corticobasal syndrome (CBS), and to elucidate the exact diagnosis of CBS patients.Methods:Twelve CBS cases admitted to the Department of Neurology, Huashan Hosiptal,Fudan University from April 2019 to July 2021 were retrospectively enrolled in this study. Those data, including clinical features (demographic data and clinical characteristics of cortical dysfunction and movement disorder), neuropsychological assessment [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales score], brain magnetic resonance imaging (MRI) and multi-mode positron emission tomography (PET)/CT, were collected and carefully reviewed. Exact diagnosis of these patients was given according to the disease diagnosis criteria.Results:Cortical dysfunction and asymmetrical movement disorders were found in all cases, with poor response to levodopa. Patients suffered from cognitive impairment (MMSE score 16.16±9.82, MoCA score 13.44±7.35). The cranial MRI demonstrated significant asymmetric atrophy of frontal and parietal lobes, especially in the pre- and post-central gyrus. Fluorodeoxyglucose PET of 12 patients showed asymmetric frontal lobe and basal ganglia (especially caudate and putamen) hypometabolism (obviously on the contralateral side of the affected limb). Tau PET was implemented in 11 patients and displayed that abnormal tau protein deposition was positive in the cortex and/or subcortex in all patients. Of the 4 cases, who completed amyloid PET, amyloid protein deposition was positive in the cortex of 2 patients. As a result, 6 patients were diagnosed as progressive supranuclear palsy, 1 patient was diagnosed as corticobasal degeneration, and 5 patients were diagnosed as Alzheimer′s disease.Conclusions:The etiology of CBS is heterogeneous. The combination of clinical manifestation, cranial MRI and multi-mode PET/CT helps the differential diagnosis of CBS.

Pharmacological interventions in corticobasal degeneration: a review / Intervenções farmacológicas na degeneração corticobasal: uma revisão

ABSTRACT. Corticobasal degeneration (CBD) is a sporadic tauopathy that presents with a varied combination of motor, cognitive, and behavioral features, making its diagnosis difficult. CBD has high morbidity and poor prognosis, with no effective therapy at present. We searched the PubMed/MEDLINE database for articles published from 1990 to 2019, using the keywords "corticobasal degeneration" AND "treatment." The PRISMA method was adopted. Retrieved articles were characterized as having one of two methodological approaches: (1) studies aimed at primary tauopathy treatment and (2) symptomatic management. Review articles (based on CBD expert groups), case reports, case series, and pilot clinical trials were selected. Few attempts have been made to study drug options and drug efficacy in CBD systematically, and an effective treatment is not yet available. Treatment is symptomatic and based on similarity with other diseases due to the scarcity of studies specifically addressing CBD. CBD seems not to spark interest in more clinical trials for its low prevalence and reliability in clinical diagnosis.

RESUMO. A degeneração corticobasal (DCB) é uma tauopatia esporádica que se apresenta com uma combinação variada de características motoras, cognitivas e comportamentais, dificultando seu diagnóstico. O CBD tem alta morbidade e mau prognóstico, sem terapia efetiva no momento. Pesquisamos o banco de dados PubMed / MEDLINE para artigos publicados de 1990 a 2019, usando as palavras-chave "degeneração corticobasal" e "tratamento". O método PRISMA foi adotado. Os artigos recuperados foram caracterizados como tendo uma de duas abordagens metodológicas: (1) estudos voltados para o tratamento da tauopatia primária e (2) manejo sintomático. Artigos de revisão (baseados em grupos de especialistas em CBD), relatos de casos, séries de casos e ensaios clínicos piloto foram selecionados. Poucas tentativas foram feitas para estudar as opções de drogas e eficácia de drogas no CBD de forma sistemática, e um tratamento eficaz ainda não está disponível. O tratamento é sintomático e baseado na semelhança com outras doenças devido à escassez de estudos que abordem especificamente o CBD. O CBD parece não despertar o interesse em mais ensaios clínicos por sua baixa prevalência e confiabilidade no diagnóstico clínico.

Anesthetic management in corticobasal degeneration with central sleep apnea: A case report

Corticobasal degeneration (CBD) is a rare neurodegenerative disease characterized by dystonia, cognitive deficits, and an asymmetric akinetic-rigid syndrome. Little information is available regarding anesthetic management for CBD patients. Our patient was a 55-year-old man with CBD complicated by central sleep apnea (CSA). Due to the risk of perioperative breathing instability associated with anesthetic use, a laryngeal mask airway was used during anesthesia with propofol. Spontaneous respiration was stable under general anesthesia. However, respiratory depression occurred following surgery, necessitating insertion of a nasopharyngeal airway. Since no respiratory depression had occurred during maintenance of the airway using the laryngeal mask, we suspected an upper airway obstruction caused by displacement of the tongue due to residual propofol. Residual anesthetics may cause postoperative respiratory depression in patients with CBD. Therefore, continuous postoperative monitoring of SpO₂ and preparations to support postoperative ventilation are necessary.

Cognitive dysfunction in corticobasal degeneration / Disfunção cognitiva na degeneração corticobasal

ABSTRACT Corticobasal degeneration (CBD) was originally described as a distinct clinicopathological entity in 1967. Since then, different phenotypic presentations have emerged as possible manifestations of CBD histopathological findings. In addition, pathophysiological findings and the molecular basis have been delineated and several aspects of its cognitive manifestations have been clarified. Thus, not only the spectrum of what is currently designated as CBD has expanded, but overlap with other degenerative and even secondary disorders has made clinical diagnostic certainty even more challenging in the absence of specific and readily-available markers. Cognitive deficits in CBD are now recognized as a frequent initial presentation and may appear up to eight years before the motor symptoms, depending on the phenotypic variant. Characteristic cognitive features of CBD involve language deficits, visuospatial and executive dysfunctions, apraxia, and behavioral disorders. Semantic and episodic memories are usually preserved, while language is often impaired in the early stages.

RESUMO A degeneração corticobasal (DCB) foi originalmente descrita como uma entidade clínico-patológica distinta em 1967. Desde então, nossa compreensão sobre DCB evoluiu substancialmente. Diferentes apresentações fenotípicas emergiram refletindo possíveis manifestações das anormalidades histopatológicos da DCB. Adicionalmente, dados fisiopatológicos e moleculares foram delineados e aspectos das manifestações cognitivas foram explorados. Assim, não só o espectro do que é atualmente designado DCB foi expandido, mas a sobreposição com outras doenças degenerativas e até mesmo secundárias tornaram o diagnóstico clínico ainda mais desafiador na ausência de marcadores específicos e prontamente disponíveis. Déficits cognitivos na DCB são agora reconhecidos frequentemente como apresentações iniciais e podem surgir até 8 anos antes dos sintomas motores, dependendo da variante fenotípica. O quadro cognitivo envolve característicamente déficits de linguagem, disfunção visuoespacial e executiva, apraxia, e distúrbios comportamentais. Anormalidades da linguagem são frequentemente descritas nos estágios iniciais da DCB.

Corticobasal syndrome: a diagnostic conundrum / O enigmático diagnóstico da síndrome Corticobasal

ABSTRACT Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome of great interest to movement disorder specialists and behavioral neurologists. Although originally considered a primary motor disorder, it is now also recognized as a cognitive disorder, usually presenting cognitive deficits before the onset of motor symptoms. The term CBS denotes the clinical phenotype and is associated with a heterogeneous spectrum of pathologies. Given that disease-modifying agents are targeting the pathologic process, new diagnostic methods and biomarkers are being developed to predict the underlying pathology. The heterogeneity of this syndrome in terms of clinical, radiological, neuropsychological and pathological aspects poses the main challenge for evaluation.

RESUMO A síndrome corticobasal é classificada dentro do grupo das síndromes parkinsonianas atípicas, e atualmente desperta interesse em neurologistas especialistas em distúrbios do movimento e neurologia cognitiva e comportamental. Inicialmente considerada como uma síndrome tipicamente motora, hoje se reconhece a importância dos achados cognitivos na apresentação, podendo ocorrer mesmo na ausência de alterações motoras. Tal designação refere-se à síndrome clínica e é associada a várias patologias subjacentes. Tendo em vista que drogas modificadoras da doença estão focando na patologia de base, novos métodos diagnósticos de imagem e outros biomarcadores estão sendo desenvolvidos para predizer o processo patológico específico antemortem. A heterogeneidade clínica e patológica desta entidade, portanto, é o maior desafio a ser desvendado.

Corticobasal Degeneration Presenting as Non-Fluent/Agrammatic Primary Progressive Aphasia: A Case Report

BACKGROUND: Non-fluent agrammatic primary progressive aphasia (naPPA) is characterized by progressive non-fluent speech disorder and might be associated with taupathy such as corticobasal degeneration (CBD) and progressive supranuclear palsy. We report a case of overlap syndrome presented with language impairment, and diagnosed as naPPA with possible CBD. CASE REPORT: A 58-year-old woman visited a memory and dementia clinic, with a 10-month history of progressive language disturbance. She was diagnosed as naPPA and overlapping CBD, based on the clinical features and neuroimaging findings including florbetaben PET. CONCLUSIONS: naPPA is pathologically caused by taupathy, and might progress to asymmetrical parkinsonism and apraxia, suggestive of CBD. Overlapping clinical features in our case represent various phenotypes of taupathy.

Degeneración corticobasal: reporte de un caso / Corticobasal degeneration: a case report

Se presenta un caso de Degeneración Corticobasal en una paciente chilena de 48 años de edad. La evolución clínica fue progresiva, con parkinsonismo (rigidez, acinesia, alteraciones posturales, disartria), deterioro cognitivo, apraxia del vestir, apraxia constructiva e hipomimia. Además, la paciente presentaba afasia no fluente. Adicionalmente, fue diagnosticada con Síndrome Depresivo Crónico (SDC) y Trombosis Venosa Profunda (TVP) de la extremidad inferior izquierda. Se han descrito varios tipos de enfermedades neurodegenerativas en las últimas décadas, las cuales cumplen con distintas características patológicas y clínicas. Sin embargo, la diferenciación de estas, en la práctica, es compleja y se necesita de una apreciación clínica entrenada, evaluaciones clínicas detalladas, neuroimágenes y estudios de laboratorio para lograr llegar a un diagnóstico adecuado. Dentro de las principales enfermedades neurodegenerativas que se presentan con parkinsonismo encontramos las llamadas “taupatías”, que son la Degeneración Corticobasal (DCB) y la Parálisis Supranuclear Progresiva*(PSP)...

A case study of corticobasal degeneration in a Chilean 48 year old female patient is reported. The clinical course was progressive and included Parkinsonism (rigidity, akinesia, postural abnormalities, dysarthria), cognitive impairment, dressing apraxia, constructive apraxia and hypomimia. In addition, the patienth ad non Mfluent aphasia. Also, the patient was diagnosed with Chronic Depressive Syndrome and Deep Venous Thrombosis (DVT) of the left lower extremity. In recent decades, several types of neurodegenerative diseases* have been described. These diseases have different clinical and pathologic features. However, in practice, it is difficult to differentiate them from one another and, to reach an accurate diagnosis, advanced medical skills, detailed clinical evaluations of neuroimaging and laboratory studies are needed. “Tauopathies”, which are Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP) are among the major neurodegenerative diseases occurring with Parkinsonism...

An Autopsy Confirmed Case of Behavioral Variant Frontotemporal Dementia with Corticobasal Degeneration Pathology

A 63-year-old man presented with a 1.5-year history of progressive personality changes. Clinical evaluations revealed severe frontal dysfunction and bilateral frontal atrophy/glucose hypometabolism. He was diagnosed as probable behavioral variant frontotemporal dementia. He continued to decline, and died at the age of 66. At autopsy, numerous tau-positive gilial threads and coiled bodies were observed in the white matter. Tau-positive astrocytic plaques and neuronal cytoplasmic inclusions were also seen in cerebral cortices, which were compatible with corticobasal degeneration.

An Autopsy Confirmed Case of Behavioral Variant Frontotemporal Dementia with Corticobasal Degeneration Pathology

A 63-year-old man presented with a 1.5-year history of progressive personality changes. Clinical evaluations revealed severe frontal dysfunction and bilateral frontal atrophy/glucose hypometabolism. He was diagnosed as probable behavioral variant frontotemporal dementia. He continued to decline, and died at the age of 66. At autopsy, numerous tau-positive gilial threads and coiled bodies were observed in the white matter. Tau-positive astrocytic plaques and neuronal cytoplasmic inclusions were also seen in cerebral cortices, which were compatible with corticobasal degeneration.

Longitudinal Clinical Changes of Non-Fluent/Agrammatic Primary Progressive Aphasia as Tau Spectrum Disorder: A Case Report

BACKGROUND: Tauopathies are a group of diseases caused by the accumulation of hyperphosphorylated tau protein in the central nervous system. Previous studies have revealed that there is considerable overlap in clinical, pathological, and genetic features among different taupathies. CASE REPORT: We report a patient with non-fluent/agrammatic primary progressive aphasia at the initial assessment. Over time, other symptoms belonging to corticobasal degeneration and progressive supranuclear palsy appeared in this patient. CONCLUSIONS: Clinical overlapping features in these disorders may represent different phenotypes of a single disease process.

Clinicopathologic analysis of progressive non-fluent aphasia and corticobasal degeneration:case report and review / Estudo clínicopatologico de afasia progressiva não-fluente e degeneração córtico-basal: relato de caso e revisão

Objective: To investigate progressive non-fluent aphasia and histopathologically-proven corticobasal degeneration. Methods: We evaluated symptoms, signs, neuropsychological deficits, and radiology data longitudinally, in a patient with autopsy-proven corticobasal degeneration and correlated these observations directly to the neuroanatomic distribution of the disease. Results: At presentation, a specific pattern of cognitive impairment was evident with an extreme extrapyramidal motor abnormality. Follow-up examination revealed persistent impairment of praxis and executive functioning, progressive worsening of language performance, and moderately preserved memory. The motor disorder manifested and worsened as the condition progressed. Many of the residual nerve cells were ballooned and achromatic with eccentric nuclei. Tau-immunoreactive pathology was significantly more prominent in neurons in the frontal and parietal cortices and dentate nuclei than in temporal neocortex, hippocampi and brainstem. Conclusion: The clinical diagnosis of progressive non-fluent aphasia secondary to corticobasal degeneration hinged on a specific pattern of impaired cognition as well as an extrapyramidal motor disorder, reflecting the neuroanatomic distribution of the disease in frontal and anterior temporal cortices and the dentate nuclei.

Objetivo: Investigar o quadro clínico de afasia progressiva não-fluente e confirmação histopatológica de degeneração córtico-basal. Métodos: Foram avaliadas as alterações clínicas, neuropsicológicas e de neuroimagem, durante todo o curso clínico da doença. O diagnóstico de degeneração córtico-basal foi confirmado por estudo histopatológico. Essas observações foram diretamente relacionadas com a distribuição anatômica da doença. Resultados: Foi observada uma forma específica de prejuízo cognitivo associada com importante alteração extrapiramidal. Durante o curso clínico, surgiram apraxia e disfunção executiva, piora progressiva da linguagem e memória moderadamente preservada. As alterações extrapiramidais pioraram progressivamente à rigidez universal e postura distônica. As reações de imunohistoquímica para a proteína tau foram significativamente mais proeminentes nos neurônios residuais de aspecto baloniformes e acromáticos do córtex frontal e parietal e núcleo denteado do cerebelo do que nos do neocórtex temporal, hipocampo e tronco cerebral. Conclusão: O diagnóstico clínico de afasia progressiva não-fluente quando evolui para degeneração córtico-basal deve apresentar uma forma específica de prejuízo cognitivo, incluindo as alterações motoras, refletindo uma distribuição neuroanatômica da doença no córtex frontal e temporal anterior e no núcleo denteado do cerebelo.

Clinical features of dystonia in atypical parkinsonism / Características clínicas da distonia no parkinsonismo atípico

BACKGROUND: The association between Dystonia and Parkinson's disease (PD) has been well described especially for foot and hand dystonia. There is however few data on dystonic postures in patients with atypical parkinsonism. OBJECTIVE: To evaluate the frequency and pattern of dystonia in a group of patients with atypical parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP, and corticobasal degeneration - CBD) and to investigate whether dystonia could be the first presenting symptom at disease onset in those patients. METHOD: A total of 38 medical charts were reviewed (n=23/MSA group; n=7/CBD group; n=8/PSP group) and data values were described as means/standard deviations. The variables evaluated were sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopatherapy, Hoehn&Yahr scale >3 after three years of disease, and magnetic resonance imaging findings. RESULTS: The overall frequency of dystonia in our sample was 50 percent with 30.4 percent (n=7) in the MSA group, 62.5 percent (n=5) in the PSP group, and 100 percent (n=8) in the CBD group. In none of these patients, dystonia was the first complaint. Several types of dystonia were found: camptocormia, retrocollis, anterocollis, blepharoespasm, oromandibular, and foot/hand dystonia. CONCLUSION: In our series, dystonia was a common feature in atypical parkinsonism (overall frequency of 50 percent) and it was part of the natural history although not the first symptom at disease onset. Neuroimaging abnormalities are not necessarily related to focal dystonia, and levodopa therapy did not influence the pattern of dystonia in our group of patients.

INTRODUÇÃO: A associação de distonia e doença de Parkinson (DP) já foi bem estabelecida, principalmente para distonia focal em pé ou mão. Entretanto, há poucos dados quanto a distonia em pacientes com parkinsonismo atípico. OBJETIVO: Avaliar a freqüência e o padrão da distonia em um grupo de pacientes com parkisnonismo atípico (atrofia de múltiplos sistemas - AMS; paralisia supranuclear progressiva - PSP; degeneração corticobasal - DCB) e investigar se a distonia pode ser a manifestação inicial neste grupo. MÉTODO: Um total de 38 prontuários médicos foi revisado (n=23/grupo AMS; n=8/grupo PSP; n=7/grupo PSP) e os dados foram apresentados em médias/desvios padrões. As variaveis avaliadas foram: sexo, idade de início, duração da doença, primeiro sintoma, características clínicas da distonia e outros sinais neurológicos, resposta ao tratamento com levodopa, escala de Hoehn & Yahr >3 em 3 anos de doença, e achados de ressonância magnética. RESULTADOS: A frequência total de distonia em nosso grupo foi 50 por cento, sendo 30,4 por cento (n=7) no grupo AMS, 62.5 por cento (n=5) no grupo PSP e 100 por cento (n=8) no grupo DCB. Em nenhum dos pacientes, distonia foi o primeiro sintoma. Várias apresentações de distonia foram observadas: camptocormia, anterocólis, retrocólis, distonia oromandibular, em pé e mão. CONCLUSÃO: Em nossa série, distonia foi uma característica comum em pacientes com parkinsonismo atípico (freqüência de 50 por cento) e fez parte da história natural em todos os grupos, embora não tenha sido o sintoma inicial em nenhum deles. Anormalidades no exame de neuroimagem não necessariamente estão relacionadas a distonia focal, e o tratamento com levodopa não influenciou o padrão da distonia em nosso grupo de pacientes.

Progressive Nonfluent Aphasia With Ideomotor Apraxia and Rigidity in the Right Upper Extremity

A woman developed a slowly progressive speech disturbance at age 51. Three years latter she showed difficulty in calculation, reading and writing. At age 57, she complained of right shoulder pain. At age 58, neurological examination revealed rigidity, bradykinesia and ideomotor apraxia in the right upper extremity. This case demonstrats a clinical overlap between progressive nonfluent aphasia and corticobasal degeneration.

Severe Episodic Memory Impairment in a Patient With Clinical Features Compatible With Corticobasal Degeneration

Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder characterized by asymmetric parkinsonism associated with apraxia, cortical sensory loss, and alien-limb phenomenon. Neuropsychological testing in patients with CBD typically shows deficits in executive functions, praxis, language, and visuospatial functioning, but not in memory. We report a CBD patient with severely impaired memory function but relatively mild motor symptoms. Detailed neuropsychological assessment showed significant verbal and visual memory deficits accompanied by frontal executive dysfunctions. Our observations indicate that CBD can in rare cases present with severe episodic memory impairment associated with frontal executive dysfunctions in the early stage of illness.

Dementia with Parkinsonism

Parkinson's disease (PD) is a extrapyramidal movement disorder characterized by rigidity and bradykinesia. PD is one of the most common neurodegenerative disorders, affecting 1% of the population over the age of 60. Dementia is common and affects 40% of patients with PD during the course of the disease, the risk for the development of dementia being 6 times higher than in age-matched general population. In addition to motor abnormalities, there are several non-motor signs and symptoms that may create a considerable burden for patients and caregivers. Parkinsonism is a major feature of several dementing diseases. The parkinsonian disorders with dementia are Parkinson's disease dementia (PDD), parkinsonian-plus syndromes, sepcific heredodegenerative diseases, and secondary parkinsonisms. The parkinsonian-plus syndromes are neurodegenerative disorders charaterized by parkinsonism and at least one other nonparkinsonian neurological manfestation. This brief review concentrates on those disorders in which cognitive impairment/dementia and parkinsonism coexist: Parkinson's disease dementia, progressive supranuclear palsy, and corticobasal degeneration. The clinical and neuropsychological similarities and differences in these disorders are compared and contrasted along with Alzheimer's disease, Parkinson's disease, and dementia of Lewy bodies, highlighting the features critical for identifying the correct diagnosis.

Improvement of Apraxia and Hand Function with Transcranial Direct Current Brain Polarization in Patients with Corticobasal Degeneration

OBJECTIVE: To see whether anodal direct current (DC) polarization of the inferior parietal cortex (IPC) and the primary sensorimotor area (SM1) in corticobasal degeneration (CBD) patients leads to improvement of praxia and finger motion. METHOD: Twelve patients with CBD were enrolled. This single blind crossover study had three arms, anodal DC to IPC, anodal DC to SM1, and shame polarization on occipital area. DC was delivered for 40 minute at 2 mA with 25 cm2 sponge electrodes. Before and 20 min after the start of polarization, we performed the test of oral and limb apraxia (TOLA), finger tapping frequency, and grooved pegboard test. RESULTS: The total score of TOLA was increased 5.4+/-2.3% after anodal DC to IPC. The scores of limb apraxia and picture gesture subtests of TOLA, not of oral apraxia subtest, increased significantly after anodal DC to IPC compared to sham DC polarization (p<0.05). In anodal DC to SM1 group, the finger tapping frequency increased 15.5+/-14.1%, which was significantly greater than in sham group (p<0.05). CONCLUSION: These results showed beneficial effects of anodal DC polarization on apraxia and hand function in CBD patients. In addition, these effects for apraxia and hand movement were dependent on their stimulation sites of brain.

PET studies in Alzheimer Disease and Other Degenerative Dementias / 대한핵의학회잡지

Neurodegenerative disorders cause a variety of dementia including Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and Huntington's disease. PET scan is useful for early detection and differential diagnosis of these dementing disorders. Also, it provides valuable information about clinico-anatomical correlation, allowing better understanding of function of brain. Here we discuss recent achievements PET studies regarding these dementing disorders. Future progress in PET technology, new tracers, and image analysis will play an important role in further clarifying the disease pathophysiology and brain functions.

A Case with Corticobasal Degeneration Showing Asymmetric Apraxia with Concordant Hypometabolism on FDG-PET

Corticobasal degeneration (CBD) is characterized by asymmetric clinical manifestations including asymmetrical apraxia, alien limb movement and Parkinsonian symptoms. Cognitive function is relatively normal in the early course of illness. We report a 59 years old right-handed male with CBD. He showed asymmetrical ideomotor apraxia, alien limb movement and extrapyramidal symptom, such as cogwheel rigidity and bradykinesia, that were more severe in the right hand. These symptoms have deteriorated progressively for 2 years, but the cognitive function was relatively pre-served. Brain MRI revealed atrophic changes in both parietal lobes. FDG-PET showed an asymmetrical hypometabo-lism in supplementary motor area, parietal lobe, thalamus and basal ganglia, which was more severe in the left than the right hemisphere.