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.     

Dopamine D2 receptor SPECT in corticobasal syndrome and autopsy-confirmed corticobasal degeneration

BackgroundCorticobasal degeneration (CBD) is a rare neurodegenerative disorder characterized by tau-positive neuronal and glial lesions in the cortex and striatum with neuronal loss in cortical regions and in the substantia nigra. Striatal dopamine D2 receptor binding in autopsy-confirmed CBD has not been studied before.MethodsWe performed D2 receptor single photon emission computerized tomography using ¹²³I-IBZM in nine patients with a clinically diagnosed corticobasal syndrome (CBS) and on ten healthy controls. Two of the patients subsequently came to autopsy and were diagnosed with CBD.ResultsOverall striatal D2 receptor binding was preserved in 8/9 patients, but more asymmetric than in controls. Overall striatal binding in pathologically confirmed CBD was reduced in one case and normal in the other, and was lower contralateral to the clinically more affected side in both.ConclusionThis first study on D2 receptor imaging in autopsy-confirmed CBD demonstrates that loss of postsynaptic striatal neurons in CBD is a variable finding. Given the heterogeneity of our findings in pathology-confirmed cases, D2 receptor imaging seems to be of little practical value in the diagnostic workup of patients with CBS.     

Clinical features of corticobasal degeneration

Coritcobasal degeneratin (CBD) has various neurological findings, such as cortical sign, parkinsonism, supranuclear palsy, myoclonus, and dementia. This disease used to be rare, but 20 years later, many case have been reported. Corticobasal degeneration is investigated from a wide range of specific analyses. It presents with a clinical resemblance to progressive supranuclear palsy (PSP) and it is important to determine whether CBD and PSP are the same entity. I will attempt to review the difference and similarities between PSP and CBD from a clinical standpoint.     

Early stage memory impairment,visual hallucinations,and myoclonus combined with temporal lobe atrophy predict Alzheimer’s disease pathology in corticobasal syndrome

Corticobasal syndrome (CBS) is a typical phenotype of corticobasal degeneration (CBD). However, autopsy series have shown that many CBS cases emerge from various types of non-CBD pathology. We report a 73-year-old Korean man who was clinically diagnosed with CBS whose underlying pathology was Alzheimer’s disease (AD) at autopsy (CBS-AD). This case suggests that early developing memory impairment and myoclonus, severe temporoparietal atrophy, and visual hallucinations may support a more specific prediction of CBS-AD.     

Bilateral upper limb rehabilitation with videogame-based feedback in corticobasal degeneration: a case reports study

Corticobasal degeneration (CBD) is a neurodegenerative disorder characterized by a combination of cortical and basal ganglia signs. We reported two cases treated with a bilateral upper limb rehabilitation tool with videogame based feedback for 3 time per week for 8 weeks. Both patients showed an improvement of pinch and grasp forces and motor function. However, both of them reported an increased upper limb pain. Bilateral upper limb mechanical device with exergame feedback was effective also in the two patients suffering of CBD for limiting the effects of apraxia by performing intensive purposeful task training.     

Corticobasal degeneration with primary progressive aphasia and accentuated cortical lesion in superior temporal gyrus: case report and review

A 57-year-old woman showed progressive sensory aphasia as an initial symptom, and then developed total aphasia within 6 years and, finally, severe dementia. Neuropathologically, the cerebral cortex was most severely affected in the superior and transverse temporal gyri, and subsequently in the inferior frontal gyrus, especially in the pars opercularis. The degeneration in the subcortical grey matter was most severe in the substantia nigra, and it was moderate to mild in the ventral part of thalamus, globus pallidus and striatum. Cytopathologically, in addition to achromatic ballooned neurons, massive tau-positive types of cytosekeletal abnormalities were observed both in neurons and glia, mainly in the degenerating region. This cytoskeletal pathology coincided with that reported in corticobasal degeneration (CBD). On Bodian staining, only a few neurofibrillary tangles were found in the entorhinal pre-alpha layer and substantia nigra. Pick’s bodies and senile plaques could not be found. This case is thought to represent a type of CBD, but with its cortical lesion focus located in the speech area instead of the frontoparietal region. A survey of 28 pathologically evaluated cases of CBD revealed two similar cases, both of which began with progressive aphasia and presented cortical degeneration in the superior temporal gyrus. An overview of CBD cases clarified the features in another group of cases, in which the cerebral accentuated focus was shifted forward from the central region, clinically resembling Pick’s disease. The clinical manifestations in CBD seem to be the expression of these diverse cortical lesions. Primary progressive aphasia may include cases of CBD with involvement of the language center. Received: 5 February 1996 / Revised, accepted: 13 May 1996     

Symmetric corticobasal degeneration (S-CBD)

BackgroundCorticobasal 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.ObjectiveTo 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.MethodsAll 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.ResultsFive 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.ConclusionsCBD 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.     

Markedly asymmetric presentation in multiple system atrophy

BackgroundMultiple system atrophy (MSA) presents with fairly symmetrical, levodopa unresponsive parkinsonism and additional features like autonomic dysfunction, cerebellar and corticospinal tract involvement. Marked asymmetry in atypical parkinsonism suggests alternative diagnosis like Corticobasal syndrome (CBS).MethodsWe describe five unusual cases, who presented initially with markedly asymmetric parkinsonism, rigid dystonic abnormal limb posturing and subsequently developed clinical and/or radiological features consistent with probable MSA-P.ResultsUsing the internationally accepted diagnostic criteria, the patients fulfilled the diagnostic criteria for probable MSA-P after 5 years from disease onset. Case 4 and 5 had characteristic MRI features and Case 2 was pathologically confirmed.ConclusionsWe use these cases to highlight that MSA-P MSA-P can present rarely with very marked asymmetry, dystonic limb and myoclonic jerks leading to a diagnosis of CBS at onset.     

Pathologically confirmed corticobasal degeneration presenting with visuospatial dysfunction

Corticobasal degeneration (CBD) typically manifests as progressive asymmetric rigidity and apraxia, although other non-motor presentations have been reported. We report two patients with pathologically diagnosed CBD who presented with prominent visuospatial dysfunction. The pathological changes were maximal in the visual association cortices, but absent in 31 cases of pathologically proven CBD with more typical antemortem features. Underlying CBD should be considered in the differential diagnosis of patients with findings reflecting posterior cerebral dysfunction.     

Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are characterized by their unique clinical features and neuronal pathology. Although astrocytic plaques and tufts of abnormal fibers have been suggested to be specific histopathologic markers, recent studies have revealed significant clinicopathologic overlap between CBD and PSP. Based on the distinctive camera lucida profile of astrocytic inclusions on Gallyas-Braak silver staining, we found that astrocytic plaques and tufts of abnormal fibers did not coexist in the same patient among 30 cases of clinically diagnosed CBD, PSP and atypical Parkinson’s disease. Using Tau immunohistochemistry it was difficult to verify the absence of tufts of abnormal fibers. A morphometric analysis revealed that the two groups classified by the presence or absence of astrocytic plaques and tufts of abnormal fibers exhibited significant differences in the density of ballooned neurons and neurofibrillary tangles and degeneration of the subcortical nuclei. Assessment using the NINDS neuropathologic criteria revealed that the cases with astrocytic plaques and tufts of abnormal fibers closely correspond to CBD and typical PSP, respectively. In addition, the cases lacking either of these two astrocytic inclusions had atypical PSP according to the NINDS criteria, and were associated with novel tau-positive astrocytes (spiny astrocytes). We thus conclude that astrocytic plaques and tufts of abnormal fibers are highly characteristic structures for CBD and typical PSP, respectively. We emphasize the importance of strict differentiation between different astrocytic inclusions not only for diagnosis, but also for further studies for elucidation of their role in the disease mechanisms of CBD and PSP. Received: 10 December 1997 / Revised, accepted: 23 March 1998     

Similarities and differences among progressive among progressive supranuclear palsy,corticobasal degeneration and Pick's disease

Corticobasal degeneration CBD) bears some resemblance to progressive supranuclear palsy (PSP) with regard to its widespread neuroal and glial cytoskeletal abnormalities. In addition, CBD and Pick's disease (PD) are both characterized by circumscribed cerebral atrophy and cortical ballooned neurons. Clinically, all three disease can present with a dementia and may be confused with each other. We examined the morphology and differential distribution of glial fibrillary tangles in PSP (n= 10), CBD (n= 3) and PD with Pick bodies (n= 2). Ballooned neurons were found in two cases of PSP but were much fewer than those found in the CBD or PD. Althought the subcortical lesions in PSP and CBD were similar, the involvement of the subthalamic and dentate nuclei was less severe in the latter. Gallyas-Breaak method revealed that tuft-shaped astrocytes were found almost exclusively in PSP, whereas astrocytic plaques were specific for CBD. None or few argyrophilic structures were visualized in PD. These findings indicate that each disorder is a distinct pathological entity. It is possible that a subpopulation of previous cases reported as unusual case of PD without Pick bodies may be additional examples of CBD.     

Creutzfeldt-Jakob disease presenting as corticobasal degeneration: a neurophysiological study

Abstract Creutzfeldt-Jakob disease (CJD) can occasionally present with a clinical picture resembling a corticobasal degeneration (CBD). Transcallosal inhibition, as tested by focal transcranial magnetic stimulation, is frequently absent or highly disrupted in CBD patients. We report a case of CJD presenting at the beginning of the disease as a CBD in which the ipsilateral silent period (iSP) was present and well detectable. This brief report shows that study of the iSP may be a useful diagnostic tool in order to differentiate CBD from syndromes presenting with similar clinical features.     

Is progressive upper-body apraxia a corticobasal syndrome?

Corticobasal degeneration (CBD) is characterized by various clinical manifestations including corticobasal syndrome, progressive supranuclear palsy-like syndrome and frontotemporal dementia. Focal cortical atrophy syndrome as the initial manifestation rarely occurs in CBD. Here, we present a 62-year-old man and a 70-year-old man who were admitted due to clumsiness in the arms. On initial neurological examination, they showed asymmetric limb apraxia without parkinsonism or global cognitive dysfunction. Brain MRI showed focal atrophy in the frontal and prefrontal cortices, and brain positron emission tomography scan revealed decreased metabolism in these same brain locations. Although these patients developed parkinsonism and dystonia within several years, the neurological signs were limited to the arms for a long period. “Progressive upper-body apraxia” may be a rare clinical manifestation of CBD which shows a benign clinical outcome. The patients described may enhance our understanding of the clinical heterogeneity of this disease.     

Epitope expression and hyperphosphorylation of tau protein in corticobasal degeneration: differentiation from progressive supranuclear palsy

Corticobasal degeneration (CBD) is a rare, progressive neurological disorder characterized by widespread neuronal and glial accumulation of abnormal tau protein. Using immunohistochemistry we analyzed tau epitope expression and phosphorylation state in CBD and compared them to cytoskeletal changes in Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Epitopes spanning the entire length of the tau protein were present in CBD inclusions. An antibody against the alternatively spliced exon 3 did not recognize cytoskeletal lesions in CBD, but did in AD and PSP. Tau epitopes from each region of the molecule were present in cytoskeletal inclusions in CBD, including gray matter astrocytic plaques, gray and white matter threads, and oligodendroglial inclusions. As in AD, tau from CBD was highly phosphorylated. Antibodies that recognized phosphorylated tau epitopes reacted with material from CBD in a highly phosphatase-dependent manner. Again, all types of inclusions contained phosphorylated epitopes. We conclude that abnormal tau protein in CBD comprises the entire tau molecule and is highly phosphorylated, but is distinguished from AD and PSP by the paucity of epitopes contained in the alternatively spliced exon 3.     

Clinical and pathologic evidence of corticobasal degeneration and progressive supranuclear palsy in familial tauopathy

BACKGROUND: Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are neurodegenerative tauopathies. Sporadic and familial cases of PSP and CBD have been noted, but both have not been reported in a single family. OBJECTIVE: To describe the clinical, oculomotor, balance, functional imaging, histopathologic, and genetic studies in a family with CBD and PSP. DESIGN: A report of the clinical and pathological features in a familial tauopathy. SETTING: University of Minnesota.Patients We evaluated 2 siblings and clinically assessed 20 additional family members. MAIN OUTCOME MEASURES: Demonstration of salient features in deceased and living family members. RESULTS: Histopathologically confirmed CBD in one sibling and PSP in another deceased sibling were demonstrated; both had clinical features of corticobasal syndrome. In addition, 3 siblings had probable PSP by clinical criteria. Genetic studies of 4 affected family members demonstrated the H1/H1 haplotype but did not reveal pathogenic tau mutations. The family history revealed consanguinity. CONCLUSIONS: This is the first report, to our knowledge, of CBD and PSP in 2 individuals in a single family who presented with corticobasal syndrome and had other affected siblings with clinical PSP. Despite clinical and pathologic heterogeneity, a unifying genetic etiology appears likely in this familial tauopathy.     

Characterising the uncommon corticobasal syndrome presentation of sporadic Creutzfeldt-Jakob disease

BackgroundCorticobasal syndrome (CBS), which encompasses cortical sensory loss, alien limb, bradykinesia, rigidity, limb apraxia and dystonia, is the classic presentation of corticobasal degeneration (CBD). It may occur in other neurodegenerative disorders including sporadic Creutzfeldt-Jakob disease (sCJD). Current CBD diagnostic criteria outline features of CBS but fail to distinguish CBD from other causative pathologies.ObjectivesTo characterise the CBS presentation of sCJD (sCJD-CBS) in the context of existing CBD diagnostic criteria.MethodData of two new cases of sCJD-CBS and seven patients identified from the Australian National Creutzfeldt-Jakob Disease Registry database was reviewed. Additional data from 11 published cases was incorporated to illustrate the natural history of sCJD-CBS. Comparison was made with pathologically diagnosed CBD cases with ante-mortem CBS presentation (CBD-CBS).ResultssCJD-CBS accounts for 1.8% of all Australian sCJD cases. Compared to CBD-CBS, disease progression is more rapid in sCJD-CBS (median time to diagnosis 48 vs.1.5 months, p < 0.001; and disease duration until death 68 vs. 5 months, p < 0.001). Although no clinical features separate the two, alien limb and myoclonus tend to occur early in sCJD-CBS following initial ‘sensory’ disturbance in the affected limb. Consistent with sCJD, distinctive diffusion weighted imaging (DWI) abnormalities on magnetic resonance imaging may also occur in sCJD-CBS.ConclusionsCJD should be suspected in patients presenting with CBS when clinical progression is rapid and accompanied by DWI abnormalities, even without cerebrospinal fluid 14-3-3 protein detection and electroencephalographic periodic sharp wave complexes. We propose the addition of rapid (<12months) progression to akinetic-mutism or death and DWI abnormalities as exclusions in future CBD diagnostic criteria.     

Clinicopathological and genetic correlates of frontotemporal lobar degeneration and corticobasal degeneration

Objective To correlate clinical diagnosis and genetic features with different pathological substrates in patients with frontotemporal lobar degeneration (FTLD) and corticobasal degeneration (CBD). Methods 32 cases with pathological proven FTLD or CBD were selected. Patients were classified clinically as frontotemporal dementia (FTD), progressive nonfluent aphasia (PNFA), semantic dementia (SD), CBD or FLTD with motor neuron disease (FLTDMND). Coding exons 1 and 9–13 of MAPT and exons 0–12 of the PGRN gene were screened by direct sequencing. Regarding the neuropathological findings, cases were classified as tau-positive, ubiquitinpositive tau-negative (FTLD-U), neuronal intermediate filaments inclusions disease (NIFID), dementia lacking distinctive histology (DLDH) or CBD. Results 17 patients were clinically diagnosed with FTD. Ten showed tau pathology, 3 FTLD-U, 1 NIFID and 3 DLDH. All patients clinically classified as FTLD-MND (6 patients) or SD (3 patients) were FTLD-U. Tau-positive pathology was the substrate of the three patients with PNFA. All three patients classified clinically as CBD presented neuropathologic features of CBD. The three individuals with familial history of early onset FTD and tau-positive pathology carried the P301L mutation in the MAPT gene. One out of 3 cases with FTLD-U and intranuclear inclusions carried a mutation in the PGRN gene. Conclusions We found that pathology underlying sporadic FTD is heterogeneous and not predictable. MAPT mutations and clinical diagnosis of PNFA and CBD were associated with tau-positive pathology. The presence of signs of lower MND and SD correlated with FTLD-U.A genetic study of MAPT is only recommended when familial history of early onset DFT is present. * Other members of the Catalan collaborative Study Group for FTLD are listed in the Appendix.     

A familial form of parkinsonism,dementia, and motor neuron disease: A longitudinal study

ObjectiveTo describe the clinical, positron emission tomography (PET), pathological, and genetic findings of a large kindred with progressive neurodegenerative phenotypes in which the proband had autopsy-confirmed corticobasal degeneration (CBD).MethodsFive family members, including the proband, were examined neurologically. Clinical information from the other family members was collected by questionnaires. Three individuals underwent PET with ¹¹C-dihydrotetrabenazine and ¹⁸F-fludeoxyglucose. The proband was examined post-mortem. Genetic studies were performed.ResultsThe pedigree contains 64 individuals, including 8 affected patients. The inheritance is likely autosomal dominant with reduced penetrance. The proband developed progressive speech and language difficulties at the age of 64 years. Upon examination at the age of 68 years, she showed non-fluent aphasia, word-finding difficulties, circumlocution, frontal release signs, and right-sided bradykinesia, rigidity, and pyramidal signs. She died 5 years after disease onset. The neuropathology was consistent with CBD, including many cortical and subcortical astrocytic plaques. Other family members had progressive neurodegenerative phenotypes – two were diagnosed with parkinsonism and behavioral problems, two with parkinsonism alone, one with amyotrophic lateral sclerosis alone, one with dementia, and one with progressive gait and speech problems. PET on three potentially affected individuals showed no significant pathology. Genetic sequencing of DNA from the proband excluded mutations in known neurodegenerative-related genes including MAPT, PGRN, LRRK2, and C9ORF72.ConclusionsFamilies with such complex phenotypes rarely occur. They are usually associated with MAPT mutations; however, in this family, MAPT mutations have been excluded, implicating another causative gene or genes. Further genetic studies on this family may eventually disclose the etiology.     

Levodopa-responsive parkinsonism in a patient with corticobasal degeneration and bilateral choroid plexus xanthogranulomas

Corticobasal degeneration (CBD) has substantial overlap of clinical features with other neurodegenerative diseases including Parkinson’s disease (PD). Its clinical diagnostic accuracy is the lowest among the common neurodegenerative diseases, and its antemortem diagnosis is more challenging when CBD is comorbid with another brain disease. We report an elderly male patient with multiple medical conditions and a family history of essential tremor. He presented with progressive tremor that was initially thought to be essential tremor and later diagnosed as PD despite head computerized tomography showing bilateral intraventricular masses and other minor changes. The clinical diagnosis of PD was supported by his responsiveness to low-dose levodopa. However, postmortem neuropathological examination revealed CBD and bilateral choroid plexus xanthogranulomas with mild ventricular enlargement and multifocal ependymal lining injury presumably due to mild hydrocephalus. CBD is typically levodopa-unresponsive, but hydrocephalus-associated parkinsonism is commonly levodopa-responsive. We raise awareness of the present comorbidity and atypical parkinsonism due to the choroid plexus xanthogranuloma-induced hydrocephalus for the clinical diagnosis and management of parkinsonism.     

Corticobasal degeneration and atypical progressive supranuclear palsy: their symptomatology, laboratory examination and differential diagnosis]

Corticobasal degeneration (CBD) and atypical progressive supranuclear palsy (PSP) were reviewed with special reference to their symptomatology, laboratory examination and differential diagnosis. In our survey of the autopsy cases of CBD in Japan, only about 60% of the pathologically confirmed CBD cases were correctly diagnosed clinically, meaning that atypical (non-classical) clinical forms are common in CBD. Concerning the autopsy cases of PSP in Japan, 75% of the PSP cases had correct clinical diagnosis. In literatures, the clinically atypical CBD includes (1) frontotemporal dementia, also with primary progressive aphasia and frontal lobe dementia as subforms, (2) PSP-like form, and (3) others. The clinically atypical PSP comprises (1) pure akinesia, (2) pure easy falling syndrome (Yuasa), (3) no postural instability, (4) no gaze palsy, (5) asymmetric parkinsonism, (6) no or severe dementia, etc.. PSP with cortical manifestations such as primary progressive aphasia and CBD-like features were also reported. The atypical CBD and PSP probably reflect the distribution of tau pathology different from that in typical forms. Except for the report that phosphorylated tau is increased in CSF in CBD, but not in PSP (Urakami et al), no reliable laboratory data have been available on clinical differentiation between atypical CBD and PSP.