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Magnetic resonance imaging of the brain in patients with corticobasal degeneration typically shows focal or asymmetric atrophy, usually maximal in the frontoparietal cortex. Many patients who are diagnosed with corticobasal degeneration using current diagnostic criteria do not have classical corticobasal degeneration pathology. Our case is remarkab...
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... In the case report described by Engelen et al. neurological symptoms ( Table 1) were associated with decreased left internal carotid artery (ICA) flow. Acute appearance of these symptoms suggest vascular, rather than neurodegenerative, etiology, as CBD tends to have insidious onset (Engelen et al., 2011). Marques et al. described the occurrence of unexplained hemiplegia with consecutive homolateral CBS in two patients with metabolic disorders and prior endarterectomy due to ICA stenosis. ...
... Patients with vascular CBS tend to present a rapid onset of the symptoms, comparing to primarily insidious clinical phenotype of CBD. Moreover, their neurological state may deteriorate in a precipitous manner, as subsequent vascular episodes occur (Engelen et al., 2011). The presence of the time gap between a stroke and the appearance of neurological symptoms should not be perceived as an argument against vascular basis of CBS, as additional silent cerebrovascular accidents, typical for high-risk patients, may collectively contribute to exacerbation of their health state (Koga et al., 2019). ...
Corticobasal syndrome (CBS) is a clinical entity, classified as an atypical parkinsonism, characterised by both motor and higher cortical dysfunctions. The clinical manifestation of CBS is associated with several pathologies, among which corticobasal degeneration (CBD) is the most common. The aim of our study was to elaborate on the possible vascular pathogenesis of CBS and consider types of vascular lesions in these cases. Several cases of vascular CBS are described in the literature. The majority of presented patients were affected by internal carotid artery stenosis and ischemic strokes; few cases were associated with vascular malformations or autoimmune diseases. Vascular CBS is preceded by an abrupt onset. The clinical manifestation does not significantly differ with non-vascular CBS. Patients with vascular CBS are usually elderly; often with coexistent hypertension, dyslipidemia and diabetes mellitus. Inferring from our observations, cerebral hypoperfusion can play a significant role in neuropathological changes in neurodegenerative diseases. To our knowledge our paper is the first comprehensive review of vascular CBS and we are positive that our observations show that further research concerning the vascular pathogenesis of tauopathic atypical parkinsonisms is required.
... MRI is more sensitive for the detection of SDH. Small hematomas can be managed conservatively with surveillance imaging; however, neurosurgical treatment is recommended for larger hematomas or hematomas that are causing a neurologic deficit [28]. ...
... MRI showed asymmetric atrophy mimicking the characteristic appearance of CBS due to neurodegenerative cause. However, vessel imaging revealed ipsilateral ICA occlusion [28,31]. The incidence of CBS due to large vessel occlusion is unknown, and it remains unclear whether vessel imaging should be obtained in all patients who present with the clinical and radiographic features of CBS. ...
Purpose of Review
This article discusses the diagnostic evaluation and management of reversible dementia syndromes. It highlights clinical syndromes and explores the recent literature implicating certain reversible factors in Alzheimer’s disease pathogenesis.
Recent Findings
The prevalence of fully reversible dementia is low, but there is growing awareness for potentially reversible contributors to neurodegenerative disease. In particular, exposure to anticholinergic medications, obstructive sleep apnea, and depression have emerged as potentially modifiable targets in the pathogenesis of preclinical and early Alzheimer’s disease. Treatment of these factors may not only reverse any direct cognitive effects but also prevent downstream neurodegeneration.
Summary
There is substantial opportunity to improve outcome in patients with dementia due to reversible etiologies. Even in the setting of primary neurodegenerative disease, conscientious effort is required to recognize and address reversible contributors.
... 10 Corticobasal syndrome secondary to cerebrovascular disease is much less common and only reported in a few case reports in patients with ipsilateral ICA occlusions or following carotid endarterectomy. [11][12][13] The precise mechanisms underlying cerebral atrophy related to chronic hypoperfusion are still incompletely understood; however, by using positron emission tomography, Yamauchi and colleagues demonstrated evidence of increased oxygen extraction, termed misery perfusion, in tissues supplied by a stenotic carotid artery. 14 This response serves as an early compensatory response to decreased CBF but over time is highly predictive of focal atrophy. ...
Cerebral atrophy is a common finding in elderly patients; however, cerebrovascular disease causing progressive focal cerebral atrophy and dysfunction is unusual. In this report, we present 3 cases of hemicerebral atrophy due to ipsilateral internal carotid artery (ICA) stenosis or occlusion mimicking neurodegenerative conditions. Patient 1 had a frontal dysexecutive syndrome potentially consistent with a diagnosis of behavioral variant frontotemporal dementia; however, neuroimaging revealed a chronically occluded left ICA and a pattern of atrophy restricted to the left middle cerebral artery territory, suggestive of a vascular etiology. Patient 2 presented with progressively worsening seizures and right-sided weakness consistent with left hemispheric dysfunction, with radiographic evidence of left hemicerebral atrophy. Angiography revealed a chronic dissection of the left ICA leading to left cerebral hypoperfusion. Patient 3 had asymmetric parkinsonism, alien limb, and cognitive impairment consistent with a diagnosis of corticobasal syndrome. His imaging, however, revealed atrophy and encephalomalacia within the anterior circulation watershed territories with chronic, severe stenosis of the left ICA suggestive of a chronic hypoperfused state. In this case series, we report 3 examples of hemicerebral atrophy secondary to chronic ipsilateral ICA vascular disease with diverse progressive clinical symptoms mimicking primary neurodegenerative conditions. This case series highlights the importance of considering chronic hypoperfusion and large-vessel severe stenosis or occlusion in patients with cognitive impairment and evidence of asymmetric brain atrophy. In addition to symptomatic treatment, the management of vascular risk factors including treatment with antiplatelet agents, statins, and revascularization procedures can be considered.
... , AD 12) , PSP 12) , PD 20) , FTLD-TDP 31) , FTLD-FUS 32) , Atypical 4 repeat tauopathy 33) , neurofilament inclusion body disease 34) 2) Genetic disorder MAPT gene mutation 35) , PGRN gene mutation 36) , LRRK2 gene mutation 37) , CSF1R gene mutation 38) , C9orf72 gene mutation 39) , ataxin-8 gene mutation 40) 3) Others CJD 12) , Carotid artery occlusion 41) , Fahr disease 42) , Neurosyphilis 43) , CPM 44) , Anti-phospholipid antibody syndrome 45) , Thalamic tuberculoma 46) , CTX 47) CBD; corticobasal degeneration, AD; Alzheimer disease, PSP; progressive supranuclear palsy, PD; Parkinsonʼs disease, FTLD; frontotemporal lobar degeneration, TDP; transactive response DNA binding protein of 43 kD, FUS; fused in sarcoma, MAPT; microtubule-associated protein tau, PGRN; progranulin, LRRK2; Leucine-rich repeat kinase 2, CSF1R; Colony stimulating factor 1 receptor, SCA8; Spinocerebellar ataxia type 8, CJD; Creutzfeldt-Jakob disease, CPM; Central pontine myelinolysis, CTX; Cerebrotendinous xanthomatgosis. For a diagnosis of CBS (corticobasal syndrome), the patient should satisfy all mandatory criteria, two major criteria (in italics) and two minor criteria. ...
Experts use the term corticobasal syndrome (CBS) for patients with a clinical diagnosis of corticobasal degeneration (CBD), and reserve CBD for those whose conditions have been diagnosed on the basis of neuropathological analyses. Several studies demonstrated that patients with CBD may also present with progressive supranuclear syndrome (PSPS), aphasia, Alzheimer disease-like dementia or behavioral change, suggesting that CBS is merely one of the presenting phenotypes of CBD. Although previous CBD diagnostic criteria reflected only CBS, the international consortium proposed new diagnostic criteria for CBD in 2013 (Armstrong's criteria). The new criteria include 4 CBD subtypes; CBS, frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA)，and PSPS. These subtypes were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD (cr-CBD) and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies (p-CBD). Two studies have already revealed that the sensitivity and specificity of the criteria were not high. Because therapeutic interventions that target abnormally-phosphorylated tau have started, further refinement of the criteria is needed via biomarker researches with prospective study designs.
... Corticobasal syndrome (CBS) is a progressive disease that includes a heterogeneous neuropathological spectrum comprising corticobasal degeneration (CBD), Alzheimer disease (AD), progressive supranuclear palsy (PSP or Richardson's syndrome) and frontotemporal lobar degeneration, Creutzfeldt-Jacob disease, and vascular degenerative diseases [1][2][3]. In the majority of cases, CBD is the underlying disease. ...
Corticobasal syndrome (CBS) is a progressive disease that includes a heterogeneous neuropathological spectrum. In the majority of cases, corticobasal degeneration (CBD) is the underlying disease. Clinical heterogeneity is reflected in the clinical presentation of the syndrome and consequently misdiagnosis is common. Our case is of interest because the symptoms, the poor response to L-dopa and the I123 Ioflupane CIT SPECT (DAT-SCAN) results were typical for CBD. However, the magnetic resonance imaging appearance suggested the possibility of a disease of vascular etiology. A 63-year-old woman presented in our outpatient clinic with symptoms of progressive clumsiness in the right arm when performing movements demanding fine motor skills, and mild speech difficulties. The brain magnetic resonance imaging (MRI) report described ischemic lesions in the left subcortical parietal areas, in the centrum semiovale, in periventricular white matter, cingulated gyrus bilaterally and moderate ventricle dilatation. A comprehensive neuropsychological study suggested mixed cortical and subcortical involvement. A DAT-SCAN examination showed a diminished dopamine transporter uptake in the left lenticular nucleus, suggesting parkinsonisn. For this patient, CBS-CBD was the most probable diagnosis, whereas vascular CBS was not excluded. This case report illustrates the low diagnostic sensitivity in predicting CBD and the overlap with other related neurodegenerative diseases. Finally, it demonstrates that in CBS, different underlying pathologies can be found at the same individual.
The spectrum of tauopathy encompasses heterogenous group of neurodegenerative disorders characterized by neural or glial deposition of pathological protein tau. Clinically they can present as cognitive syndromes, movement disorders, motor neuron disease, or mixed. The heterogeneity in clinical presentation, genetic background, and underlying pathology make it difficult to classify and clinically approach tauopathy. In the literature, tauopathies are thus mostly highlighted from pathological perspective. From clinical standpoint, cognitive syndromes are often been focussed while reviewing tauopathies. However, the spectrum of tauopathy has also evolved significantly in the domain of movement disorders and has transgressed beyond the domain of primary tauopathies. Secondary tauopathies from neuroinflammation or autoimmune insults and some other “novel” tauopathies are increasingly being reported in the current literature, while some of them are geographically isolated. Because of the overlapping clinical phenotypes, it often becomes difficult for the clinician to diagnose them clinically and have to wait for the pathological confirmation by autopsy. However, each of these tauopathies has some clinical and radiological signatures those can help in clinical diagnosis and targeted genetic testing. In this review, we have exposed the heterogeneity of tauopathy from a movement disorder perspective and have provided a clinical approach to diagnose them ante mortem before confirmatory autopsy. Additionally, phenotypic variability of these disorders (chameleons) and the look-alikes (mimics) have been discussed with potential clinical pointers for each of them. The review provides a framework within which new and as yet undiscovered entities can be classified in the future.
Tauopathies are a group of heterogenous neurodegenerative disorders those affect extrapyramidal, cognitive, behavioral and pyramidal networks in varied proportions and clinically present with isolated or in different combinations of movement disorders, dementia and motor neuron disease. Pathologically they are characterized by neuronal and/or glial inclusions of the microtubule-binding protein, tau. In the literature, tauopathy has been discussed mostly as a pathological entity with its detailed pathological intricacies. Recently, tau has been described as a ‘propagon’ because of its prion-like seeding or ‘permissive templating’ and propagation capacity.1,2 Interestingly, such a propagation of abnormal protein generally follows a spatio-temporal template (connectome). There is evidence of variant or ‘strain’ specificity for this prion-like intercellular transmission3 and targeting a particular vulnerable neural network that clinically manifests as a particular phenotype (‘molecular nexopathy’)4. Such a targeted interaction between the abnormal protein and the vulnerable neural network depends on and can be modified by multiple factors like the biochemical property of the abnormal protein according to its post translational modification, intrinsic susceptibility of the network targeted, genetic, epigenetic factors and environmental influence. Adding to this complexity, coexistence of other abnormal protein (like associated TDP43 with tau) also influence this network targeting and thus can modify the phenotypic presentation. Such a heterogeneity in clinical presentation and intermingling of the phenotypes often make it difficult for the clinician to diagnose it clinically before pathological validation. Recent advances in genetics and correlation studies among clinical, radiological and pathological findings have unfolded the vast spectrum of tauopathy. Classic 4R-tauopathy like progressive supranuclear palsy (PSP) itself can present with varied clinical phenotype.5 The complex overlap of typical or atypical parkinsonism with behavioral or language predominant cognitive dysfunction and upper motor or lower motor dominant (UMN/LMN) motor neurone disease (MND) is a real challenge for the clinician. Diverse phenotypic presentation of the same or different mutations of the tau gene (MAPT) further adds to this complexity.6 Pathological confirmation of the diagnosis of tauopathy mostly depends on autopsy findings. In vivo biomarkers like CSF tau and tau-PET imaging are still research based tools. But each of these tauopathies has some clinical and radiological signatures that can predict the underlying genetics and pathology. Secondary tauopathy from autoimmune insult like in anti-IgLON5 disease and Nodding syndrome, brings up the topic of complex interaction between autoimmunity and neurodegeneration.
In this review, we have discussed ‘parkinsonism in familial tauopathy’, a puzzle for the clinician, by differentiating the phenotypic presentations of common genetic factors, to promote targeted genetic testing. We have gone through the clinical and radiological clues for diagnosing classic 4R- and 3R- primary tauopathies. The clinical phenotypes (‘chameleons’) and look-alikes (‘mimics’) of these entities have been mentioned. Subsequently, secondary tauopathies, some emerging ‘novel’ tauopathies and geographically isolated tauopathies are highlighted.
Atypical parkinsonism comprises typically progressive supranuclear palsy, corticobasal degeneration, and mutilple system atrophy, which are distinct pathologic entities; despite ongoing research, their cause and pathophysiology are still unknown, and there are no biomarkers or effective treatments available. The expanding phenotypic spectrum of these disorders as well as the expanding pathologic spectrum of their classic phenotypes makes the early differential diagnosis challenging for the clinician. Here, clinical features and investigations that may help to diagnose these conditions and the existing limited treatment options are discussed.
Copyright © 2015 Elsevier Inc. All rights reserved.
Abstract Corticobasal degeneration (CBD) is a distinct neurodegenerative disorder characterized by widespread neuronal and glial accumulation of abnormal tau protein. The core characteristic clinical features of the disorder include progressive asymmetric akinetic-rigid syndrome with apraxia and features indicative of cortical dysfunction (e.g., cortical sensory loss, alien limb sign, and myoclonus) and basal ganglionic dysfunction (e.g., akinesia and dystonia). Pathological examinations of CBD patients have indicated that several proteinopathies, such as tauopathies, amyloidopathies, TDP-opathies, α-synucleinopathies, and prionopathies, may underlie the same clinical phenotype. Because of this considerable clinicopathologic heterogeneity, experts use the term corticobasal syndrome (CBS) for patients with a clinical diagnosis of CBD, and reserve CBD for those whose conditions have been diagnosed on the basis of neuropathological analyses. In this review, we have focused on the clinical aspects of CBS, including its clinical presentation, diagnostic criteria, and pathological backgrounds that are difficult to predict on the basis of clinical presentation alone. Future studies need to further characterize the natural history of CBS patients by performing serial assessments of clinical, neuropsychological, laboratory, and neuroimaging features, since this information will be necessary for designing future disease-modifying therapies that specifically target dysfunction of the 4-repeat tau protein.
Abstract Focal asymmetric cortical atrophy with ballooned neurons, nigral degeneration, and tau-positive neuronal and glial lesions in both the gray and white matter, particularly astrocytic plaques in the affected cerebral cortex, are characteristic features of corticobasal degeneration (CBD). Since the clinical manifestations of CBD are diverse, several neurological diseases can present with clinical findings that are thought to be specific to CBD. These clinical conditions are referred to as corticobasal syndrome (CBS). CBS includes Alzheimer's disease, progressive supranuclear palsy, Pick's disease, Lewy body disease, frontotemporal lobar degeneration, and Creutzfeldt-Jakob disease. In cases of clinically diagnosed CBS, the consistent histopathological finding appears to be asymmetric frontal and parietal cortical degeneration.
