Corticobasal Syndrome

Complex MONDO:0018696 Pathograph 3 Show in embeddings browser Neurodegenerative Disease Parkinsonism

Corticobasal syndrome (CBS) is an adult-onset, progressive neurodegenerative syndrome characterized by markedly asymmetric akinetic-rigid parkinsonism combined with cortical dysfunction — limb apraxia, cortical sensory loss, the alien limb phenomenon, focal limb dystonia, and myoclonus. CBS is the clinical phenotype most classically produced by corticobasal degeneration (CBD), a pathologically defined four-repeat (4R) tauopathy in which hyperphosphorylated 4R tau accumulates in neurons and glia, with astrocytic plaques as the pathognomonic lesion (distinguishing CBD from the tufted astrocytes of progressive supranuclear palsy). A central curatorial point is that CBS and CBD are not equivalent: only roughly half of clinically diagnosed CBS cases have CBD at autopsy, while Alzheimer disease, progressive supranuclear palsy, and frontotemporal lobar degeneration with TDP-43 can each present as CBS. Conversely CBD itself can present with non-CBS phenotypes (a nonfluent/agrammatic primary progressive aphasia, a frontal behavioral-dysexecutive-spatial syndrome, or a PSP-like Richardson syndrome). CBD/CBS is predominantly sporadic; the MAPT H1 haplotype is a shared risk locus with PSP, and rare familial cases occur (MAPT and GRN/progranulin mutations). There is no approved disease-modifying or symptomatic drug therapy; management is supportive.

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3
Pathophys.
1
Histopath.
9
Phenotypes
3
Pathograph
2
Genes
3
Medical Actions
⚙

Pathophysiology

3
4R-Tau Aggregation with Astrocytic Plaques
Corticobasal degeneration, the archetypal pathology of CBS, is defined by the accumulation of aggregated, hyperphosphorylated four-repeat (4R) tau in neurons and glia. The pathognomonic lesion is the astrocytic plaque, which distinguishes CBD from the tufted astrocytes of PSP; ballooned achromatic neurons, neuropil threads, and oligodendroglial coiled bodies are additional lesions. 4R tau predominance arises from alternative splicing of MAPT exon 10. This is the upstream initiating lesion.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology. astrocyte (astrocytic plaque) CL:0000127 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves astrocyte (astrocytic plaque), annotated with astrocyte (CL:0000127). CL:0000127 is a cell type from the Cell Ontology. oligodendrocyte (coiled body) CL:0000128 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves oligodendrocyte (coiled body), annotated with oligodendrocyte (CL:0000128). CL:0000128 is a cell type from the Cell Ontology.
Tau (amyloid) fibril formation GO:1990000 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Tau (amyloid) fibril formation, annotated with amyloid fibril formation (GO:1990000). GO:1990000 is a biological process from the Gene Ontology. ↑ INCREASED Tau hyperphosphorylation GO:0006468 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Tau hyperphosphorylation, annotated with protein phosphorylation (GO:0006468). GO:0006468 is a biological process from the Gene Ontology. ↑ INCREASED Disrupted microtubule cytoskeleton organization GO:0000226 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Disrupted microtubule cytoskeleton organization, annotated with microtubule cytoskeleton organization (GO:0000226). GO:0000226 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Network-Specific Tau Propagation and Asymmetric Neurodegeneration
Show evidence (3 references)
PMID:34316603 SUPPORT Human Clinical
"astrocytic plaques are pathognomonic of CBD, whereas PSP is characterized by tufted astrocytes."
Establishes the astrocytic plaque as the pathognomonic CBD lesion, distinguishing it from PSP.
PMID:31238088 SUPPORT Human Clinical
"Progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease or glial globular tauopathy belong to the group of 4R-tauopathies."
Places corticobasal degeneration within the 4R-tauopathies.
PMID:34316603 SUPPORT Human Clinical
"due to alternate splicing of exon 10 of the microtubule associated protein tau (MAPT) gene"
Explains that 4R tau predominance derives from MAPT exon 10 splicing.
Network-Specific Tau Propagation and Asymmetric Neurodegeneration
CBD behaves as a neural-network-specific disorder. Pathology begins in the dorsolateral prefrontal cortex and basal ganglia circuits, with the astrocytic plaque as the earliest lesion, and spreads to more posterior regions as the disease advances; tau seeding and propagation are strain- and network-specific. The result is progressive, characteristically asymmetric frontoparietal, basal ganglia, and nigral neurodegeneration.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology. astrocyte CL:0000127 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves astrocyte (CL:0000127). CL:0000127 is a cell type from the Cell Ontology.
Neuron apoptotic process GO:0051402 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Neuron apoptotic process (GO:0051402). GO:0051402 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Asymmetric Parkinsonism with Cortical Dysfunction (Corticobasal Syndrome)
Show evidence (3 references)
PMID:34316603 SUPPORT Human Clinical
"It initially affects the dorsolateral prefrontal cortex and basal ganglia circuits, with more posterior regions affected as the disease progresses."
Describes the network-specific spread of CBD pathology.
PMID:27797812 SUPPORT Model Organism
"tau seeding and propagation are strain- and neural network-specific"
Animal-model evidence that tau seeding and propagation are network-specific, supporting the network-based spread of CBD.
PMID:27797812 SUPPORT Human Clinical
"Relatively greater tau burden in the anterior frontal cortex, striatum and subthalamic nucleus suggests the striatal afferent connection to the dorsolateral prefrontal cortex and basal ganglia circuitry are the earliest neural network connections affected by corticobasal degeneration-related tau..."
Human preclinical cases identify the earliest network distribution of CBD tau pathology.
Asymmetric Parkinsonism with Cortical Dysfunction (Corticobasal Syndrome)
Asymmetric degeneration of frontoparietal cortex, basal ganglia, and substantia nigra produces the clinical corticobasal syndrome: an asymmetric, levodopa-resistant akinetic-rigid parkinsonism combined with cortical signs (limb apraxia, cortical sensory loss, alien limb phenomenon, focal dystonia, and myoclonus). Because phenotype tracks the topography and burden of tau pathology, CBD can also manifest as aphasic, behavioral, or PSP-like phenotypes rather than classic CBS.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology.
Show evidence (2 references)
PMID:42438177 SUPPORT Human Clinical
"Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
Summarizes the asymmetric motor and cortical clinical output of CBS.
PMID:34316603 SUPPORT Human Clinical
"multiple pathologies, such as CBD, Alzheimer's disease and progressive supranuclear palsy may underlie a patient with CBS."
Captures the clinicopathological heterogeneity: CBS is a syndrome with several possible underlying pathologies.
✶

Histopathology

1
Ballooned neurons and astrocytic tau plaques
CBD pathology includes ballooned neurons and tau-positive astrocytic plaques, with neuronal inclusions, neuropil threads, and oligodendroglial coiled bodies.
Show evidence (1 reference)
PMID:34316603 SUPPORT Human Clinical
"However, it is now evident that tau pathology in astrocytes is more important in discriminating PSP from CBD. Thus, astrocytic plaques are pathognomonic of CBD, whereas PSP is characterized by tufted astrocytes."
Defines the ballooned-neuron and astrocytic-plaque features of CBD pathology.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Corticobasal Syndrome Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

9
Eye 1
Supranuclear Gaze Palsy HP:0000605 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Supranuclear gaze palsy (HP:0000605). HP:0000605 is a phenotype from the Human Phenotype Ontology.
CBD can present as a progressive supranuclear palsy-like (Richardson) syndrome, and supranuclear gaze palsy reflects the clinical overlap between CBS and PSP as related 4R-tauopathies.
Show evidence (1 reference)
PMID:23359374 SUPPORT Human Clinical
"corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS)"
The progressive supranuclear palsy syndrome (PSPS) is enumerated as a CBD phenotype; supranuclear gaze palsy is the defining ocular sign of that overlapping presentation.
Musculoskeletal 1
Asymmetric Limb Rigidity HP:0002063 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Asymmetric limb rigidity, annotated with Rigidity (HP:0002063). HP:0002063 is a phenotype from the Human Phenotype Ontology.
Markedly asymmetric appendicular rigidity is a core feature of corticobasal syndrome and reflects the characteristically asymmetric basal ganglia and cortical degeneration.
Show evidence (1 reference)
PMID:42438177 SUPPORT Human Clinical
"Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
Names asymmetric limb rigidity as a defining clinical feature of CBS.
Nervous System 7
Limb Apraxia HP:0002186 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Limb apraxia, annotated with Apraxia (HP:0002186). HP:0002186 is a phenotype from the Human Phenotype Ontology.
Ideomotor limb apraxia (impaired skilled movement not explained by weakness, sensory loss, or incoordination) is one of the most characteristic cortical signs of CBS.
Show evidence (1 reference)
PMID:42438177 SUPPORT Human Clinical
"Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
Names apraxia as a defining clinical feature of CBS.
Limb Dystonia FREQUENT HP:0002451 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Focal limb dystonia, annotated with Limb dystonia (HP:0002451). HP:0002451 is a phenotype from the Human Phenotype Ontology.
Focal dystonia, often affecting an asymmetrically rigid and apraxic upper limb, is a common CBS feature and a target for botulinum toxin therapy.
Show evidence (2 references)
PMID:42438177 SUPPORT Human Clinical
"Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
Names dystonia as a defining clinical feature of CBS.
PMID:34316603 SUPPORT Human Clinical
"Dystonia is present in 40% of CBD patients"
Supports the FREQUENT band.
Myoclonus HP:0001336 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myoclonus (HP:0001336). HP:0001336 is a phenotype from the Human Phenotype Ontology.
Focal (often stimulus-sensitive) limb myoclonus is a recognized cortical sign of CBS.
Show evidence (1 reference)
PMID:42438177 SUPPORT Human Clinical
"Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
Names myoclonus as a defining clinical feature of CBS.
Asymmetric Akinetic-Rigid Parkinsonism HP:0001300 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Asymmetric akinetic-rigid parkinsonism, annotated with Parkinsonism (HP:0001300). HP:0001300 is a phenotype from the Human Phenotype Ontology.
The extrapyramidal core of CBS is an asymmetric, typically levodopa-resistant akinetic-rigid parkinsonism.
Show evidence (1 reference)
PMID:34316603 SUPPORT Human Clinical
"The most common presentation of CBD is the corticobasal syndrome (CBS), which is a constellation of cortical and extrapyramidal symptoms and signs."
Establishes the extrapyramidal (parkinsonian) component of CBS.
Alien Limb Phenomenon HP:0032506 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Alien limb phenomenon (HP:0032506). HP:0032506 is a phenotype from the Human Phenotype Ontology.
Alien limb phenomenon (involuntary, purposeful-appearing movement of a limb experienced as not under the patient's control) is one of the most recognizable cortical signs of CBS, though not present in all cases.
Show evidence (1 reference)
PMID:34316603 SUPPORT Human Clinical
"Corticobasal syndrome is characterized by cortical and extrapyramidal signs. Apraxia, cortical sensory deficits and alien limb phenomena are the most common cortical signs, whereas asymmetrical Parkinsonism, dystonia and myoclonus comprise the extrapyramidal signs."
Identifies alien limb phenomenon among the most common cortical signs of CBS.
Nonfluent/Agrammatic Aphasia HP:0002381 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Nonfluent/agrammatic aphasia, annotated with Aphasia (HP:0002381). HP:0002381 is a phenotype from the Human Phenotype Ontology.
CBD can present with, or CBS can be accompanied by, a nonfluent/agrammatic variant of primary progressive aphasia — one of the recognized CBD phenotypes.
Show evidence (1 reference)
PMID:23359374 SUPPORT Human Clinical
"corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS)"
Lists the nonfluent/agrammatic primary progressive aphasia phenotype among the four consensus CBD phenotypes.
Frontal Behavioral and Dysexecutive Impairment Impaired executive functioning HP:0033051 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Frontal-dysexecutive cognitive impairment, annotated with Impaired executive functioning (HP:0033051). HP:0033051 is a phenotype from the Human Phenotype Ontology.
A frontal behavioral-spatial syndrome with dysexecutive and visuospatial cognitive impairment is a recognized CBD phenotype and a common cognitive accompaniment of CBS.
Show evidence (1 reference)
PMID:23359374 SUPPORT Human Clinical
"corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS)"
Lists the frontal behavioral-spatial syndrome among the four consensus CBD phenotypes, capturing the frontal-dysexecutive cognitive presentation.
🧬

Genetic Associations

2
MAPT (Predominantly sporadic disease; the MAPT H1 haplotype is a shared common genetic risk locus with PSP, and rare familial CBD is caused by MAPT (tau-protein) mutations.)
Gene: MAPT hgnc:6893 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is MAPT (hgnc:6893). hgnc:6893 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: RISK_FACTOR
Show evidence (2 references)
PMID:34316603 SUPPORT Human Clinical
"A large genome-wide association study found significant genetic overlap between CBD and PSP in the MAPT H1 region"
Establishes the MAPT H1 region as a shared genetic risk locus for CBD and PSP.
PMID:34316603 SUPPORT Human Clinical
"CBD is a predominantly sporadic disease. Familial cases due to a microtubule associated tau protein (MAPT) mutation"
Documents that CBD is predominantly sporadic with rare MAPT-mutation familial cases.
GRN (Progranulin (GRN) mutations, a cause of frontotemporal lobar degeneration with TDP-43 pathology, can present clinically as corticobasal syndrome.)
Gene: GRN hgnc:4601 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is GRN (hgnc:4601). hgnc:4601 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE
Show evidence (1 reference)
PMID:34316603 SUPPORT Human Clinical
"Progranulin (PGRN) mutations can present with variable phenotypes, including CBS"
Establishes GRN/progranulin mutations as a cause of CBS (a non-CBD underlying pathology).
💊

Medical Actions

3
Symptomatic Pharmacotherapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: levodopa CHEBI:15765 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses levodopa, annotated with L-dopa (CHEBI:15765). CHEBI:15765 is a therapeutic agent from Chemical Entities of Biological Interest. clonazepam CHEBI:3756 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses clonazepam (CHEBI:3756). CHEBI:3756 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
No approved disease-modifying or symptomatic drug therapy exists for CBS. A levodopa trial is standard for the parkinsonian features but response is typically poor; myoclonus may be treated symptomatically (e.g., clonazepam or levetiracetam). Treatment is therefore symptomatic and supportive.
Show evidence (3 references)
PMID:42438177 SUPPORT Human Clinical
"with no approved symptomatic or disease-modifying drug treatments"
Documents that no approved symptomatic or disease-modifying drug therapy exists for CBS, so pharmacotherapy is off-label and symptomatic.
PMID:34316603 SUPPORT Human Clinical
"No disease-modifying treatment has been approved for CBD. However, many symptoms of CBS can be symptomatically treated. Parkinsonism in CBS can be treated with levodopa, with poor and only transient response"
Supports the poor and transient levodopa response.
PMID:34316603 SUPPORT Human Clinical
"Clonazepam is the first choice treatment for myoclonus"
Supports symptomatic clonazepam treatment of myoclonus.
Botulinum toxin for limb dystonia
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: Botulinum toxin type A CHEBI:3160 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses Botulinum toxin type A (CHEBI:3160). CHEBI:3160 is a therapeutic agent from Chemical Entities of Biological Interest.
Botulinum toxin can temporarily improve function in a dystonic affected limb.
Show evidence (1 reference)
PMID:34316603 SUPPORT Other
"Dystonia in CBS can be successfully treated with botulinum toxin, which can temporarily improve the functionality of the affected limb"
Directly supports symptomatic botulinum-toxin treatment of CBS dystonia.
Neurorehabilitation and Neurologic Music Therapy
Action: RehabilitationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Rehabilitation (NCIT:C15315). NCIT:C15315 is a clinical intervention from the NCI Thesaurus. NCIT:C15315
Platform: Behavioral / lifestyle
Multidisciplinary rehabilitation (physical, occupational, and speech therapy) is the mainstay of CBS management. Neurologic music therapy (NMT), alone or combined with high-definition transcranial direct current stimulation (HD-tDCS), has shown feasibility and preliminary benefit for upper-limb motor performance in a randomized controlled trial.
Show evidence (1 reference)
PMID:42438177 SUPPORT Human Clinical
"Both NMT alone and combined NMT + HD-tDCS were feasible in CBS and were associated with improvements in selected upper-limb motor outcomes"
Randomized-trial evidence supporting neurorehabilitation (neurologic music therapy, with or without HD-tDCS) for upper-limb motor performance in CBS.
🔬

Diagnosis

1
Asymmetric cortical atrophy on brain MRI
MRI supports the diagnosis by showing asymmetric peri-rolandic, posterior-frontal, and parietal cortical atrophy contralateral to the more severely affected side; imaging does not by itself establish CBD pathology.
Magnetic Resonance Imaging NCIT:C16809 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:34316603 SUPPORT Human Clinical
"The imaging hallmark of CBD is the asymmetrical cortical atrophy, which is more pronounced in the peri-rolandic region (anterior and posterior central gyrus), posterior frontal and parietal lobes, contralaterally to the clinically more severely affected side."
Describes the characteristic distribution of asymmetric cortical atrophy.
📈

Progression

1
Onset and course
Insidious adult onset (mean age at onset ~64 years) with gradual, relentless progression; probable-CBD clinical research criteria require insidious onset and gradual progression for at least 1 year with onset at age 50 or older. Mean survival is estimated at about 6.5 years.
Show evidence (2 references)
PMID:23359374 SUPPORT Human Clinical
"insidious onset and gradual progression for at least 1 year"
States the insidious-onset, gradually progressive course required by the probable-CBD criteria.
PMID:34316603 SUPPORT Human Clinical
"Mean survival is estimated at 6.5 years"
Provides the estimated mean survival for CBD.
📊

Prevalence

1
Worldwide
Point Prevalence 4.9–7.3 per 100,000 1–9 per 100,000
A population study projected prevalence between 4.9 and 7.3 per 100,000.
Show evidence (1 reference)
PMID:34316603 SUPPORT Human Clinical
"A single study projected a prevalence of 4.9–7.3 per 100.000"
Supports the structured prevalence range and band.
{ }

Source YAML

click to show 
name: Corticobasal Syndrome
creation_date: "2026-07-14T12:00:00Z"
category: Complex
description: >-
  Corticobasal syndrome (CBS) is an adult-onset, progressive neurodegenerative
  syndrome characterized by markedly asymmetric akinetic-rigid parkinsonism
  combined with cortical dysfunction — limb apraxia, cortical sensory loss, the
  alien limb phenomenon, focal limb dystonia, and myoclonus. CBS is the clinical
  phenotype most classically produced by corticobasal degeneration (CBD), a
  pathologically defined four-repeat (4R) tauopathy in which hyperphosphorylated
  4R tau accumulates in neurons and glia, with astrocytic plaques as the
  pathognomonic lesion (distinguishing CBD from the tufted astrocytes of
  progressive supranuclear palsy). A central curatorial point is that CBS and CBD
  are not equivalent: only roughly half of clinically diagnosed CBS cases have CBD
  at autopsy, while Alzheimer disease, progressive supranuclear palsy, and
  frontotemporal lobar degeneration with TDP-43 can each present as CBS.
  Conversely CBD itself can present with non-CBS phenotypes (a
  nonfluent/agrammatic primary progressive aphasia, a frontal
  behavioral-dysexecutive-spatial syndrome, or a PSP-like Richardson syndrome).
  CBD/CBS is predominantly sporadic; the MAPT H1 haplotype is a shared risk locus
  with PSP, and rare familial cases occur (MAPT and GRN/progranulin mutations).
  There is no approved disease-modifying or symptomatic drug therapy; management
  is supportive.
disease_term:
  preferred_term: Corticobasal Syndrome
  term:
    id: MONDO:0018696
    label: corticobasal syndrome
parents:
- Neurodegenerative Disease
- Parkinsonism
phenotypes:
- category: Neurological
  name: Asymmetric Limb Rigidity
  phenotype_term:
    preferred_term: Asymmetric limb rigidity
    term:
      id: HP:0002063
      label: Rigidity
  notes: >-
    Markedly asymmetric appendicular rigidity is a core feature of corticobasal
    syndrome and reflects the characteristically asymmetric basal ganglia and
    cortical degeneration.
  evidence:
  - reference: PMID:42438177
    reference_title: "A Randomized Controlled Trial of Dual Upper-Extremity Training [DUET]: Combining Neurologic Music Therapy with Noninvasive Brain Stimulation for Upper-Limb Performance in Corticobasal Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
    explanation: >-
      Names asymmetric limb rigidity as a defining clinical feature of CBS.
- category: Neurological
  name: Limb Apraxia
  phenotype_term:
    preferred_term: Limb apraxia
    term:
      id: HP:0002186
      label: Apraxia
  notes: >-
    Ideomotor limb apraxia (impaired skilled movement not explained by weakness,
    sensory loss, or incoordination) is one of the most characteristic cortical
    signs of CBS.
  evidence:
  - reference: PMID:42438177
    reference_title: "A Randomized Controlled Trial of Dual Upper-Extremity Training [DUET]: Combining Neurologic Music Therapy with Noninvasive Brain Stimulation for Upper-Limb Performance in Corticobasal Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
    explanation: >-
      Names apraxia as a defining clinical feature of CBS.
- category: Neurological
  name: Limb Dystonia
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Focal limb dystonia
    term:
      id: HP:0002451
      label: Limb dystonia
  notes: >-
    Focal dystonia, often affecting an asymmetrically rigid and apraxic upper
    limb, is a common CBS feature and a target for botulinum toxin therapy.
  evidence:
  - reference: PMID:42438177
    reference_title: "A Randomized Controlled Trial of Dual Upper-Extremity Training [DUET]: Combining Neurologic Music Therapy with Noninvasive Brain Stimulation for Upper-Limb Performance in Corticobasal Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
    explanation: >-
      Names dystonia as a defining clinical feature of CBS.
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Dystonia is present in 40% of CBD patients
    explanation: Supports the FREQUENT band.
- category: Neurological
  name: Myoclonus
  phenotype_term:
    preferred_term: Myoclonus
    term:
      id: HP:0001336
      label: Myoclonus
  notes: >-
    Focal (often stimulus-sensitive) limb myoclonus is a recognized cortical sign
    of CBS.
  evidence:
  - reference: PMID:42438177
    reference_title: "A Randomized Controlled Trial of Dual Upper-Extremity Training [DUET]: Combining Neurologic Music Therapy with Noninvasive Brain Stimulation for Upper-Limb Performance in Corticobasal Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
    explanation: >-
      Names myoclonus as a defining clinical feature of CBS.
- category: Neurological
  name: Asymmetric Akinetic-Rigid Parkinsonism
  phenotype_term:
    preferred_term: Asymmetric akinetic-rigid parkinsonism
    term:
      id: HP:0001300
      label: Parkinsonism
  notes: >-
    The extrapyramidal core of CBS is an asymmetric, typically levodopa-resistant
    akinetic-rigid parkinsonism.
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common presentation of CBD is the corticobasal syndrome (CBS), which is a constellation of cortical and extrapyramidal symptoms and signs."
    explanation: >-
      Establishes the extrapyramidal (parkinsonian) component of CBS.
- category: Neurological
  name: Alien Limb Phenomenon
  phenotype_term:
    preferred_term: Alien limb phenomenon
    term:
      id: HP:0032506
      label: Alien limb phenomenon
  notes: >-
    Alien limb phenomenon (involuntary, purposeful-appearing movement of a limb
    experienced as not under the patient's control) is one of the most
    recognizable cortical signs of CBS, though not present in all cases.
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Corticobasal syndrome is characterized by cortical and extrapyramidal signs. Apraxia, cortical sensory deficits and alien limb phenomena are the most common cortical signs, whereas asymmetrical Parkinsonism, dystonia and myoclonus comprise the extrapyramidal signs.
    explanation: Identifies alien limb phenomenon among the most common cortical signs of CBS.
- category: Neurological
  name: Nonfluent/Agrammatic Aphasia
  phenotype_term:
    preferred_term: Nonfluent/agrammatic aphasia
    term:
      id: HP:0002381
      label: Aphasia
  notes: >-
    CBD can present with, or CBS can be accompanied by, a nonfluent/agrammatic
    variant of primary progressive aphasia — one of the recognized CBD phenotypes.
  evidence:
  - reference: PMID:23359374
    reference_title: "Criteria for the diagnosis of corticobasal degeneration."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS)"
    explanation: >-
      Lists the nonfluent/agrammatic primary progressive aphasia phenotype among
      the four consensus CBD phenotypes.
- category: Neurological
  name: Frontal Behavioral and Dysexecutive Impairment
  phenotype_term:
    preferred_term: Frontal-dysexecutive cognitive impairment
    term:
      id: HP:0033051
      label: Impaired executive functioning
  notes: >-
    A frontal behavioral-spatial syndrome with dysexecutive and visuospatial
    cognitive impairment is a recognized CBD phenotype and a common cognitive
    accompaniment of CBS.
  evidence:
  - reference: PMID:23359374
    reference_title: "Criteria for the diagnosis of corticobasal degeneration."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS)"
    explanation: >-
      Lists the frontal behavioral-spatial syndrome among the four consensus CBD
      phenotypes, capturing the frontal-dysexecutive cognitive presentation.
- category: Neurological
  name: Supranuclear Gaze Palsy
  phenotype_term:
    preferred_term: Supranuclear gaze palsy
    term:
      id: HP:0000605
      label: Supranuclear gaze palsy
  notes: >-
    CBD can present as a progressive supranuclear palsy-like (Richardson)
    syndrome, and supranuclear gaze palsy reflects the clinical overlap between
    CBS and PSP as related 4R-tauopathies.
  evidence:
  - reference: PMID:23359374
    reference_title: "Criteria for the diagnosis of corticobasal degeneration."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS)"
    explanation: >-
      The progressive supranuclear palsy syndrome (PSPS) is enumerated as a CBD
      phenotype; supranuclear gaze palsy is the defining ocular sign of that
      overlapping presentation.
pathophysiology:
- name: 4R-Tau Aggregation with Astrocytic Plaques
  description: >-
    Corticobasal degeneration, the archetypal pathology of CBS, is defined by the
    accumulation of aggregated, hyperphosphorylated four-repeat (4R) tau in
    neurons and glia. The pathognomonic lesion is the astrocytic plaque, which
    distinguishes CBD from the tufted astrocytes of PSP; ballooned achromatic
    neurons, neuropil threads, and oligodendroglial coiled bodies are additional
    lesions. 4R tau predominance arises from alternative splicing of MAPT exon 10.
    This is the upstream initiating lesion.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: astrocyte (astrocytic plaque)
    term:
      id: CL:0000127
      label: astrocyte
  - preferred_term: oligodendrocyte (coiled body)
    term:
      id: CL:0000128
      label: oligodendrocyte
  biological_processes:
  - preferred_term: Tau (amyloid) fibril formation
    term:
      id: GO:1990000
      label: amyloid fibril formation
    modifier: INCREASED
  - preferred_term: Tau hyperphosphorylation
    term:
      id: GO:0006468
      label: protein phosphorylation
    modifier: INCREASED
  - preferred_term: Disrupted microtubule cytoskeleton organization
    term:
      id: GO:0000226
      label: microtubule cytoskeleton organization
    modifier: ABNORMAL
  downstream:
  - target: Network-Specific Tau Propagation and Asymmetric Neurodegeneration
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "astrocytic plaques are pathognomonic of CBD, whereas PSP is characterized by tufted astrocytes."
    explanation: >-
      Establishes the astrocytic plaque as the pathognomonic CBD lesion,
      distinguishing it from PSP.
  - reference: PMID:31238088
    reference_title: "Four-repeat tauopathies."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease or glial globular tauopathy belong to the group of 4R-tauopathies."
    explanation: >-
      Places corticobasal degeneration within the 4R-tauopathies.
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "due to alternate splicing of exon 10 of the microtubule associated protein tau (MAPT) gene"
    explanation: >-
      Explains that 4R tau predominance derives from MAPT exon 10 splicing.
- name: Network-Specific Tau Propagation and Asymmetric Neurodegeneration
  description: >-
    CBD behaves as a neural-network-specific disorder. Pathology begins in the
    dorsolateral prefrontal cortex and basal ganglia circuits, with the astrocytic
    plaque as the earliest lesion, and spreads to more posterior regions as the
    disease advances; tau seeding and propagation are strain- and
    network-specific. The result is progressive, characteristically asymmetric
    frontoparietal, basal ganglia, and nigral neurodegeneration.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  biological_processes:
  - preferred_term: Neuron apoptotic process
    term:
      id: GO:0051402
      label: neuron apoptotic process
    modifier: INCREASED
  downstream:
  - target: Asymmetric Parkinsonism with Cortical Dysfunction (Corticobasal Syndrome)
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It initially affects the dorsolateral prefrontal cortex and basal ganglia circuits, with more posterior regions affected as the disease progresses."
    explanation: >-
      Describes the network-specific spread of CBD pathology.
  - reference: PMID:27797812
    reference_title: "Astrogliopathy predominates the earliest stage of corticobasal degeneration pathology."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "tau seeding and propagation are strain- and neural network-specific"
    explanation: >-
      Animal-model evidence that tau seeding and propagation are network-specific,
      supporting the network-based spread of CBD.
  - reference: PMID:27797812
    reference_title: "Astrogliopathy predominates the earliest stage of corticobasal degeneration pathology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Relatively greater tau burden in the anterior frontal cortex, striatum and subthalamic nucleus suggests the striatal afferent connection to the dorsolateral prefrontal cortex and basal ganglia circuitry are the earliest neural network connections affected by corticobasal degeneration-related tau pathology.
    explanation: >-
      Human preclinical cases identify the earliest network distribution of CBD tau pathology.
- name: Asymmetric Parkinsonism with Cortical Dysfunction (Corticobasal Syndrome)
  description: >-
    Asymmetric degeneration of frontoparietal cortex, basal ganglia, and
    substantia nigra produces the clinical corticobasal syndrome: an asymmetric,
    levodopa-resistant akinetic-rigid parkinsonism combined with cortical signs
    (limb apraxia, cortical sensory loss, alien limb phenomenon, focal dystonia,
    and myoclonus). Because phenotype tracks the topography and burden of tau
    pathology, CBD can also manifest as aphasic, behavioral, or PSP-like
    phenotypes rather than classic CBS.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  evidence:
  - reference: PMID:42438177
    reference_title: "A Randomized Controlled Trial of Dual Upper-Extremity Training [DUET]: Combining Neurologic Music Therapy with Noninvasive Brain Stimulation for Upper-Limb Performance in Corticobasal Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Corticobasal syndrome (CBS) is a progressive neurodegenerative condition characterized by asymmetric limb rigidity, apraxia, dystonia, and myoclonus"
    explanation: >-
      Summarizes the asymmetric motor and cortical clinical output of CBS.
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "multiple pathologies, such as CBD, Alzheimer's disease and progressive supranuclear palsy may underlie a patient with CBS."
    explanation: >-
      Captures the clinicopathological heterogeneity: CBS is a syndrome with
      several possible underlying pathologies.
genetic:
- name: MAPT
  gene_term:
    preferred_term: MAPT
    term:
      id: hgnc:6893
      label: MAPT
  relationship_type: RISK_FACTOR
  association: >-
    Predominantly sporadic disease; the MAPT H1 haplotype is a shared common
    genetic risk locus with PSP, and rare familial CBD is caused by MAPT
    (tau-protein) mutations.
  notes: >-
    Microtubule-associated protein tau gene (17q21.31). The H1/H1 haplotype is
    enriched in pathologically confirmed CBD, mirroring PSP; rare causative MAPT
    mutations (e.g., N296N, G389R, P301S) have been reported in familial CBD and
    sporadic CBS.
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A large genome-wide association study found significant genetic overlap between CBD and PSP in the MAPT H1 region"
    explanation: >-
      Establishes the MAPT H1 region as a shared genetic risk locus for CBD and PSP.
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "CBD is a predominantly sporadic disease. Familial cases due to a microtubule associated tau protein (MAPT) mutation"
    explanation: >-
      Documents that CBD is predominantly sporadic with rare MAPT-mutation
      familial cases.
- name: GRN
  gene_term:
    preferred_term: GRN
    term:
      id: hgnc:4601
      label: GRN
  relationship_type: CAUSATIVE
  association: >-
    Progranulin (GRN) mutations, a cause of frontotemporal lobar degeneration
    with TDP-43 pathology, can present clinically as corticobasal syndrome.
  notes: >-
    GRN-related CBS is one of the non-CBD pathologies underlying the corticobasal
    syndrome and is enriched in familial CBS in some cohorts.
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progranulin (PGRN) mutations can present with variable phenotypes, including CBS"
    explanation: >-
      Establishes GRN/progranulin mutations as a cause of CBS (a non-CBD
      underlying pathology).
prevalence:
- population: Worldwide
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_low: 4.9
  rate_high: 7.3
  notes: >-
    A population study projected prevalence between 4.9 and 7.3 per 100,000.
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: A single study projected a prevalence of 4.9–7.3 per 100.000
    explanation: Supports the structured prevalence range and band.
progression:
- phase: Onset and course
  notes: >-
    Insidious adult onset (mean age at onset ~64 years) with gradual, relentless
    progression; probable-CBD clinical research criteria require insidious onset
    and gradual progression for at least 1 year with onset at age 50 or older.
    Mean survival is estimated at about 6.5 years.
  evidence:
  - reference: PMID:23359374
    reference_title: "Criteria for the diagnosis of corticobasal degeneration."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "insidious onset and gradual progression for at least 1 year"
    explanation: >-
      States the insidious-onset, gradually progressive course required by the
      probable-CBD criteria.
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Mean survival is estimated at 6.5 years"
    explanation: >-
      Provides the estimated mean survival for CBD.
diagnosis:
- name: Asymmetric cortical atrophy on brain MRI
  description: >-
    MRI supports the diagnosis by showing asymmetric peri-rolandic,
    posterior-frontal, and parietal cortical atrophy contralateral to the more
    severely affected side; imaging does not by itself establish CBD pathology.
  diagnosis_term:
    preferred_term: Magnetic Resonance Imaging
    term:
      id: NCIT:C16809
      label: Magnetic Resonance Imaging
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The imaging hallmark of CBD is the asymmetrical cortical atrophy, which is more pronounced in the peri-rolandic region (anterior and posterior central gyrus), posterior frontal and parietal lobes, contralaterally to the clinically more severely affected side.
    explanation: Describes the characteristic distribution of asymmetric cortical atrophy.
histopathology:
- name: Ballooned neurons and astrocytic tau plaques
  description: >-
    CBD pathology includes ballooned neurons and tau-positive astrocytic plaques,
    with neuronal inclusions, neuropil threads, and oligodendroglial coiled bodies.
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: However, it is now evident that tau pathology in astrocytes is more important in discriminating PSP from CBD. Thus, astrocytic plaques are pathognomonic of CBD, whereas PSP is characterized by tufted astrocytes.
    explanation: Defines the ballooned-neuron and astrocytic-plaque features of CBD pathology.
treatments:
- name: Symptomatic Pharmacotherapy
  description: >-
    No approved disease-modifying or symptomatic drug therapy exists for CBS. A
    levodopa trial is standard for the parkinsonian features but response is
    typically poor; myoclonus may be treated symptomatically (e.g., clonazepam or
    levetiracetam). Treatment is therefore symptomatic and supportive.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: levodopa
      term:
        id: CHEBI:15765
        label: L-dopa
    - preferred_term: clonazepam
      term:
        id: CHEBI:3756
        label: clonazepam
  evidence:
  - reference: PMID:42438177
    reference_title: "A Randomized Controlled Trial of Dual Upper-Extremity Training [DUET]: Combining Neurologic Music Therapy with Noninvasive Brain Stimulation for Upper-Limb Performance in Corticobasal Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "with no approved symptomatic or disease-modifying drug treatments"
    explanation: >-
      Documents that no approved symptomatic or disease-modifying drug therapy
      exists for CBS, so pharmacotherapy is off-label and symptomatic.
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: No disease-modifying treatment has been approved for CBD. However, many symptoms of CBS can be symptomatically treated. Parkinsonism in CBS can be treated with levodopa, with poor and only transient response
    explanation: Supports the poor and transient levodopa response.
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Clonazepam is the first choice treatment for myoclonus
    explanation: Supports symptomatic clonazepam treatment of myoclonus.
- name: Botulinum toxin for limb dystonia
  description: Botulinum toxin can temporarily improve function in a dystonic affected limb.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: Botulinum toxin type A
      term:
        id: CHEBI:3160
        label: Botulinum toxin type A
  evidence:
  - reference: PMID:34316603
    reference_title: "Corticobasal degeneration and corticobasal syndrome: A review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: Dystonia in CBS can be successfully treated with botulinum toxin, which can temporarily improve the functionality of the affected limb
    explanation: Directly supports symptomatic botulinum-toxin treatment of CBS dystonia.
- name: Neurorehabilitation and Neurologic Music Therapy
  description: >-
    Multidisciplinary rehabilitation (physical, occupational, and speech therapy)
    is the mainstay of CBS management. Neurologic music therapy (NMT), alone or
    combined with high-definition transcranial direct current stimulation
    (HD-tDCS), has shown feasibility and preliminary benefit for upper-limb motor
    performance in a randomized controlled trial.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: Rehabilitation
    term:
      id: NCIT:C15315
      label: Rehabilitation
  evidence:
  - reference: PMID:42438177
    reference_title: "A Randomized Controlled Trial of Dual Upper-Extremity Training [DUET]: Combining Neurologic Music Therapy with Noninvasive Brain Stimulation for Upper-Limb Performance in Corticobasal Syndrome."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Both NMT alone and combined NMT + HD-tDCS were feasible in CBS and were associated with improvements in selected upper-limb motor outcomes"
    explanation: >-
      Randomized-trial evidence supporting neurorehabilitation (neurologic music
      therapy, with or without HD-tDCS) for upper-limb motor performance in CBS.
notes: >-
  Curatorial note: this entry models the corticobasal SYNDROME (the clinical
  phenotype, MONDO:0018696), which is distinct from corticobasal DEGENERATION
  (the 4R-tauopathy pathology). The pathophysiology described is that of CBD, the
  most common substrate of CBS, but the clinicopathological dissociation (CBS may
  be caused by AD, PSP, FTLD-TDP, and others) is central and is captured
  explicitly. A knowledge-gap discussion on antemortem biomarkers that predict
  the underlying pathology of a given CBS patient is a good follow-up.