Corticobasal syndrome etiologies in a young Filipino patient: A case report and literature review.

While corticobasal syndrome (CBS) has long been associated with corticobasal degeneration (CBD), only 24-57% of CBS patients will have the classic histopathologic findings of CBD postmortem. Here, we present a 28-year-old male who had a 3-year history of progressive right sided predominant, atypical parkinsonism, limb dystonia, stimulus sensitive myoclonus, apraxia, aphasia, alien limb phenomenon, and cognitive impairment, typical of CBS, who, based on Armstrong criteria will qualify as possible CBD. In conclusion, among young patients presenting with CBS, tauopathies are still the most common causes, but inherited metabolic and white matter diseases as well as other non-tau associated neurodegenerative conditions should also be ruled out. Nevertheless, since most of these are diagnosed histopathologically, accurate and complete clinical findings, in addition to extensive metabolic work ups, imaging and genetic tests may be needed to clinch the cause of this syndrome.

Prado MB Jr ，Adiao KJ 《-》

Comparing classic-onset corticobasal syndrome to speech/language-onset corticobasal syndrome.

Patients with classic-onset corticobasal syndrome (CBS) present with asymmetric limb apraxia and parkinsonism. We have, however, observed patients who initially present with speech and/or language (SL) problems and several years later develop CBS (i.e., SL-onset CBS). We aimed to compare clinical, neuroimaging and pathological characteristics of classic-onset CBS with SL-onset CBS. We conducted a retrospective cohort study of 62 patients who met criteria for CBS (17 presented with classic-onset CBS and 45 had SL-onset CBS). We compared demographics, clinical characteristics, and grey and white matter volume loss with SPM12 between groups and assessed pathology and corticobasal degeneration (CBD) pathological lesion counts in patients who had died and undergone autopsy. Median age at CBS diagnosis was 66.4 years in classic-onset CBS and 73.6 years in SL-onset CBS. Classic-onset CBS had higher frequencies of dystonia, myoclonus, and alien limb phenomenon, while SL-onset CBS had a higher frequency of vertical supranuclear gaze palsy. Both groups showed smaller frontoparietal volumes than controls, with SL-onset CBS having greater volume loss in the left supplementary motor area than classic-onset CBS. All three classic-onset CBS cases with autopsy (100 %) had CBD pathology while 8/21 of SL-onset CBS cases (38 %) had CBD. Pathological lesion burden (including astrocytic plaques) did not differ between classic-onset and SL-onset CBS. Classic-onset and SL-onset CBS appear to be different syndromes, with the former being a more profuse motor syndrome. The more widespread volume loss in SL-onset CBS likely reflects longer disease course.

Garcia-Guaqueta DP ，Stephens YC ，Ali F ，Utianski RL ，Duffy JR ，Clark HM ，Thu Pham NT ，Machulda MM ，Lowe VJ ，Dickson DW ，Whitwell JL ，Josephs KA ... -  《-》

Progressive aphasia, apraxia of speech and agraphia in corticobasal degeneration: A 12-case series clinical and neuropsychological descriptive study.

Despite initial underreporting of language dysfunctions in corticobasal syndrome (CBS), aphasia is now recognized as a frequent feature of this disease. Aphasia in CBS seems clinically overlying to a non-fluent/agrammatic primary progressive aphasia (nfaPPA), which is also a clinical phenotype associated with corticobasal degeneration (CBD) pathology. However, the clinical features of aphasia in CBS still remain poorly delineated, resulting in misjudgements in the differential diagnosis from a PPA presentation of the disease. To investigate the language disorders of this syndrome, also through a systematic examination of recoding skills (reading, written spelling and repetition) and articulatory disturbances, which have been rarely examined in previous studies. We present a clinical and neuropsychological descriptive study of the language impairments in a case series of 12 aphasic patients with a clinical diagnosis of CBS. Language assessment was conducted by means of the Esame NeuroPsicologico dell'Afasia, a comprehensive Italian battery for language functions, the Token Test, and the Apraxia of Speech Rating Scale. The language profile of the patients showed a severe expressive language disorder, characterized by non-fluent speech, apraxia of speech (AoS) with predominant stuttering-like dysfluencies, spatial/apraxic agraphia, lack of word-finding and defective sentence repetition. Severe limb apraxia, visual-spatial deficit and alien hand syndrome were also present. Neuroimaging showed bilateral left asymmetric atrophies and hypometabolism in the frontal premotor, parietal posterior and temporal areas. These findings suggest that aphasia in CBS might present as a 'mixed PPA', instead of an nfaPPA as previously stated, showing a combination of features of the nfa and logopenic variants of the PPA, associated with AoS, stuttering and agraphia, which might be additional important cognitive markers for the clinical diagnosis of CBS and discriminating features of an nfaPPA presentation of a CBD. These results might also suggest specific intervention areas in the rehabilitation of patients with CBS. What this paper adds What is already known on the subject Language disorders in CBS patients usually present clinically overlying to an nfaPPA, which is also a clinical phenotype associated with CBD pathology, according to recent diagnostic criteria. However, the clinical features of aphasia in CBS still remain poorly delineated, and this raises difficulties and misjudgements for clinicians in the differential diagnosis from a PPA presentation of the disease. What this paper adds to existing knowledge This study shows that the language profile of our CBS patients was characterized by severe expressive language disorders, with non-fluent speech, apraxia of speech (AoS) with predominant stuttering-like dysfluencies, spatial/apraxic agraphia, lack of word-finding, and defective sentence repetition. These findings suggest that aphasia in CBS might present as a 'mixed PPA', rather than an nfaPPA as previously stated, showing a combination of features of the nfa and logopenic variants of the PPA associated with AoS, stuttering and agraphia. What are the potential or actual clinical implications of this work? These results suggest that AoS, stuttering and agraphia might be important additional cognitive markers for the clinical diagnosis of CBS, and discriminating features of an nfaPPA presentation of a CBD. The language disorders exhibited in the present study might also support speech and language therapists in targeting specific intervention areas in the rehabilitation of patients with CBS.

Ruggeri M ，Biagioli C ，Ricci M ，Gerace C ，Blundo C ... -  《-》

Neuropathology and emerging biomarkers in corticobasal syndrome.

Corticobasal syndrome (CBS) is a clinical syndrome characterised by progressive asymmetric limb rigidity and apraxia with dystonia, myoclonus, cortical sensory loss and alien limb phenomenon. Corticobasal degeneration (CBD) is one of the most common underlying pathologies of CBS, but other disorders, such as progressive supranuclear palsy (PSP), Alzheimer's disease (AD) and frontotemporal lobar degeneration with TDP-43 inclusions, are also associated with this syndrome.In this review, we describe common and rare neuropathological findings in CBS, including tauopathies, synucleinopathies, TDP-43 proteinopathies, fused in sarcoma proteinopathy, prion disease (Creutzfeldt-Jakob disease) and cerebrovascular disease, based on a narrative review of the literature and clinicopathological studies from two brain banks. Genetic mutations associated with CBS, including GRN and MAPT, are also reviewed. Clinicopathological studies on neurodegenerative disorders associated with CBS have shown that regardless of the underlying pathology, frontoparietal, as well as motor and premotor pathology is associated with CBS. Clinical features that can predict the underlying pathology of CBS remain unclear. Using AD-related biomarkers (ie, amyloid and tau positron emission tomography (PET) and fluid biomarkers), CBS caused by AD often can be differentiated from other causes of CBS. Tau PET may help distinguish AD from other tauopathies and non-tauopathies, but it remains challenging to differentiate non-AD tauopathies, especially PSP and CBD. Although the current clinical diagnostic criteria for CBS have suboptimal sensitivity and specificity, emerging biomarkers hold promise for future improvements in the diagnosis of underlying pathology in patients with CBS.

Koga S ，Josephs KA ，Aiba I ，Yoshida M ，Dickson DW ... -  《-》

Symmetric corticobasal degeneration (S-CBD).

Corticobasal degeneration (CBD) is a neurodegenerative disease characterized pathologically by neuronal loss, gliosis and tau deposition in neocortex, basal ganglia and brainstem. Typical clinical presentation is known as corticobasal syndrome (CBS) and involves the core features of progressive asymmetric rigidity and apraxia, accompanied by other signs of cortical and extrapyramidal dysfunction. Asymmetry is also emphasized on neuroimaging. To describe a series of cases of CBD with symmetric clinical features and to compare clinical and imaging features of these symmetric CBD cases (S-CBD) to typical cases of CBS with CBD pathology. All cases of pathologically confirmed CBD from the Mayo Clinic Rochester database were identified. Clinical records were reviewed and quantitative volumetric analysis of symmetric atrophy on head MRI using atlas based parcellation was performed. Subjects were classified as S-CBD if no differences had been observed between right- and left-sided cortical or extrapyramidal signs or symptoms. S-CBD cases were compared to 10 randomly selected typical CBS cases. Five cases (2 female) met criteria for S-CBD. None had limb dystonia, myoclonus, apraxia or alien limb phenomena. S-CBD cases had significantly less asymmetric atrophy when compared with CBS cases (p=0.009); they were also younger at onset (median 61 versus 66 years, p<0.05) and death (67 versus 73 years, p<0.05). Family history was present in 40% of S-CBD cases. CBD can have a symmetric presentation, clinically and radiologically, in which typical features of CBS, such as limb apraxia, myoclonus, dystonia and alien limb phenomenon, may be absent.

Hassan A ，Whitwell JL ，Boeve BF ，Jack CR Jr ，Parisi JE ，Dickson DW ，Josephs KA ... -  《-》