Corticobasal Degeneration

Original Editor - Mason Trauger
Top Contributors - Mason Trauger and Kim Jackson

Introduction

Corticobasal degeneration (CBD), sometimes called corticobasal ganglionic degeneration (CBDG), is a form of Parkinsonism, more specifically a Parkinson-Plus Syndrome. Parkinson-Plus Syndromes are a group of neurodegenerative disorders that present with symptoms typical of Parkinson's Disease (PD) (bradykinesia, apraxia, resting tremor, rigidity, etc.); however, they do not typically respond well to PD pharmacological management and have additional symptoms such as cognitive deficits, dementia, and cranial nerve involvement. The following video provides a brief (~3.5 minute) overview of CBD:

Clinically Relevant Anatomy and Pathophysiology

Corticobasal degeneration is a type of tauopathy affecting regions throughout the cerebral cortex (with greater impacts to the frontoparietal cortex) and basal ganglia (specifically the striatum and substantia nigra). Common histopathologic findings with CBD are neuronal loss and "ballooned" achromatic neurons.

Although the etiology of CBD is unknown, there are known trends associated with progressive neurodegenerative tauopathies. Tau is a protein that assists in providing structural stability to neuronal axons. These proteins can either over-accumulate (aggregation; gain of function) and become toxic to neurons and glia, or can lose function, resulting in a loss of stability and inability to transport cellular contents. In CBD, tau proteins appear to aggregate, and result in the formation of astrocytic plaques primarily in the cortex.

Epidemiology

Due to the difficulty of antemortem diagnosis, the proposed numbers are likely to be underestimates.

• Annual incidence rate: 0.62 to 0.92 cases per 100,000 people
• Prevalence: 5 to 7 per 100,000

The age of symptom onset appears to range between 45 and 72.2 years, with a mean of 63.7 years

Clinical Presentation

All Parkinsonisms present with symptoms of Parkinson's, including apraxia, rigidity, bradykinesia, tremor, and postural instability. CBD is one pathological cause of the clinical condition known as Corticobasal Syndrome (CBS). Although there are multiple clinical criteria to diagnose CBS, the following are commonly used presentation criteria:

• Asymmetric presentation with insidious onset/gradual progress
• Orobuccal/limb apraxia
• Cortical sensory deficits
• Alien limb phenomena
• Limb rigidity or akinesia
• Limb dystonia
• Limb myoclonia
• Behavioral and cognitive impairments
  • Executive function and memory; with preserved episodic memory
• Language dysfunction:
  • Decreased speech fluency
  • Speech apraxia
  • Aphasia
• Visuospatial dysfunctions including:
  • Visual agnosia
  • Oculomotor apraxia
  • Optic ataxia

Diagnostic Procedures

Diagnosing CBD is difficult due to the aforementioned collection of pathologies composing corticobasal syndrome. This term tends to be preferred at this time, as there is a relatively high rate of antemortem mis-diagnosis of CBD. However, some diagnostic findings are consistent with the pathology of CBD.

Imaging such as an MRI, and to a lesser degree, a CT scan, can be used to assist in CBD diagnosis. The following are common CBD findings on MRI:

• asymmetric cortical atrophy (commonly posterolateral and medial frontal regions)
• bilateral atrophy of the basal ganglia
• atrophy of the corpus callosum
• preserved brainstem anatomy

Nuclear medicine studies such as single-photon-emission computed tomography (SPECT) and positron-emission tomography (PET) may also demonstrate clinical features of CBD. A common pattern found in patients with CBD on PET scan is asymmetric frontoparietal hypometabolism, with the contralateral hemisphere to the onset of symptoms having the most hypometabolic clusters.

The following is a ~15 minute podcast which describes the clinico-radiologic and pathologic evaluation of corticobasal syndrome:

Medical Management

Presently, there is no cure for CBD; all medical interventions at this time are directed at symptom management, rather than disease management.

Pharmacological management: due to the resemblance to Parkinson's Disease, dopaminergic agonists such as levodopa or rotigotine are used to treat the motor effects of atypical parkinsonism. Although transdermal rotigotine may be effective in reducing these symptoms, it does not specify subtype efficacy; additionally, only 24% of patients with CBD demonstrated improvements with levodopa intervention. Dopaminergic interventions are also used sparingly due to the high likelihood of inducing adverse psychotic events. Benzodiazepams such as clonazepam, appear to be effective in combatting symptoms of myoclonus and dystonia. Ultimately, most effects of these drugs are considered unsatisfactory for the population as a whole.

Botulinum Toxin Injections: In cases of dystonia, injections of botulinum toxin can provide pain relief and prevent skin damage, with the most promising effects on wrist dystonia.

Physiotherapy Management

Based on the clinical presentation culminating in deficits in balance, communication, cognition, gross and fine motor control, a multidisciplinary approach is encouraged to address these functional deficits. Physiotherapy, Occupational Therapy, and Speech Therapy all have a role in patient care; communication/referral between specialties should be performed as appropriate.

The literature treating Parkinson-Plus Syndromes is relatively scant. However, recommendations for a comprehensive treatment plan involve:

• Encourage regular walking to maintain mobility and cardiovascular fitness
• Implementation of a fall prevention program
• Progressive strengthening with resistance training through early stages of disease progression
• Utilization of motor learning principles (strategy training, avoiding initial dual tasking, constant, distributed, blocked practice, part training)

CurePSP presented an hour-long webinar on physical therapy intervention on progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy:

The following are open-access case studies for patients with CBD:

• Improved mobility, cognition and disease severity in Corticobasal Degeneration of an African-American male after 12 weeks of Adapted tango: a case study
• Long-Term Exercise Training for an Individual With Mixed Corticobasal Degeneration and Progressive Supranuclear Palsy Features: 10-Year Case Report Follow-up
• Virtual Reality Training Helpful in Motor and Cognition in Corticobasal Syndrome: A Case Report PET Study

Differential Diagnosis

The differential diagnosis list of CBD includes:

• Progressive Supranuclear Palsy
• Multiple System Atrophy
• Parkinson's Disease
• Pick's Disease
• Alzheimer's Disease
• Lewy Body Disease
• Creutzfeldt-Jakob Disease

Outcome Measures

The Cortical Basal ganglia Functional Scale (CBFS) is a novel rating scale assessing daily living experiences of individuals with 4 repeat tauopathies such as CBD. This scale is purported to have excellent clinimetric properties (test-retest reliability intraclass coefficient =0.93) to assess disability in physical, cognitive, and psychiatric domains. The scale is currently owned by the International Parkinson and Movement Disorder Society; one can view and request permission to use the scale at the following link: https://www.movementdisorders.org/MDS/MDS-Rating-Scales/Cortical-Basal-ganglia-Functional-Scale-CBFS.htm

Any other outcome measure(s) selected for a patient with CBD will be not be validated for their diagnosis; however, based on the functional impairments, the following are some of the numerous options to track change over time:

• Berg Balance Scale
• Functional Gait Assessment
• Dynamic Gait Index
• 10 Metre Walk Test
• Timed Up and Go Test (TUG)
• Mini-Mental State Examination

Prognosis

Corticobasal degeneration has a rapid decline in function until death, with mortality being associated with the development of sepsis and pneumonia from immobility and dysphagia.After symptom onset, life expectancy ranges from 2 to 13 years, with a median survival range of 6 to 8 years.

Resources

• USCF's A Healthcare Provider's Guide To Corticobasal Syndrome (CBS)
• CurePSP's Allied Health Professional Guide to Progressive Supranuclear Palsy, Corticobasal Degeneration, and Multiple System Atrophy
• Patient Education Sheets Provided by the International Parkinson and Movement Disorder Society