Corticobasal syndrome

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Research question: What is Corticobasal sydrome? How is it diagnosed? What are effective treatments or management path?

Date: 6/7/22 Requestor: Peta-Leanne redacted: s22(1)(a)(ii) - irrelevant material Endorsed by (EL1 or above): Naomi redacted: s22(1)(a)(ii) - irrelevant material Researcher: Stephanie redacted: s22(1)(a)(ii) - irrelevant material Cleared by: Stephanie redacted: s22(1)(a)(ii) - irrelevant material

1. Contents

Corticobasal syndrome ……………………………………………………………………………………………….. 1

1. Contents ……………………………………………………………………………………………………….. 1
1. Summary ………………………………………………………………………………………………………. 2
1. Corticobasal syndrome ……………………………………………………………………………………. 2
- 3.1 Background ………………………………………………………………………………………………… 2
- 3.2 Symptoms ……………………………………………………………………………………. 3
- 3.3 Diagnosis ……………………………………………………………………………………. 3
- 3.4 Imaging ……………………………………………………………………………………. 4
- 3.5 Treatment ……………………………………………………………………………………. 5
1. References/Bibliography ………………………………………………………………………………….. 6
1. Version control ……………………………………………………………………………………. 6

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2. Summary

Corticobasal syndrome (CBS) is a rare, slowly progressive, neurodegenerative disorder. Diagnosis of CBS is made by a neurologist based on clinical signs and symptoms. While pathological changes may be evident on MRI, the absence of changes does not exclude the disorder. Common manifestations of CBS are asymmetric progressive rigidity, apraxia, limb dystonia and frontal-cognitive deficits. CBS progresses to disability and loss of independence, with a poor long-term prognosis – average life expectancy post-diagnosis is 7 years. Death is typically related to complications of being bedridden such as pneumonia aspiration, pulmonary embolus and sepsis infection. There are no effective treatments to stop or slow progression of the disease. Clinical management is aimed at improving functional ability where possible and reducing the life-threatening risks from increasing immobility.

3. Corticobasal syndrome

3.1 Background

Corticobasal syndrome is a rare, progressive neurodegenerative disorder (Mennella & Schub, 2018; Stasio et al, 2019). Prevalence of CBS is estimated to be 4.9-7.3:100,000 (Constantinides et al, 2019; Wilson et al, 2021), and average life expectancy after diagnosis is 7 years (Constantinides et al, 2019; Wilson et al, 2021). Death is typically from complications from being bedridden, such as aspiration pneumonia, pulmonary embolism, or sepsis infection (Mennella & Schub, 2018). Typical age of presentation for CBS is between 50-70 years old (Wilson et al, 2021).

While some literature refers to CBS as corticobasal degeneration (CBD) or cortical basal ganglionic degeneration (Mennella & Schub, 2018), CBS requires a clinical diagnosis whereas CBD has pathological diagnostic criteria (Parmera et al, 2016; Wilson et al, 2021). Another difference is CBD diagnostic criteria has a particular age of onset and excludes anyone with a positive family history or known tau-protein mutation, which is not the case for CBS diagnosis (Constantinides et al, 2019).

CBS is a disorder of movement, cognition and behaviour (Wilson et al, 2021). It has a gradual onset of neurologic symptoms in the absence of stroke or tumour, and progression of the disease is slow (Mennella & Schub, 2018; Wilson et al, 2021). Patients who experience a dramatic presentation or rapid degeneration should have other diagnoses considered, for example Creutzfeldt-Jacob disease or Hashimoto’s encephalitis (Wilson et al, 2021).

Multiple pathologies may underlie CBS, such as CBD, Alzheimer’s disease, frontotemporal degeneration or progressive supranuclear palsy (Constantinides et al, 2021; Wilson et al, 2021). It is believed CBS results from abnormal levels of tau protein accumulating in certain brain cells leading to degeneration (Mennella & Schub, 2018).

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3.2 Symptoms

Onset of CBS is gradual. Neurological degeneration manifests in motor, sensory, cognitive and behavioural signs and symptoms (Mannella & Schub, 2018). Presenting symptoms of CBS can vary between individuals as different parts of the brain may be affected (Monash Health, n.d.). Limb symptoms are typically asymmetrical early in the disease course, however eventually progress to the whole body (Mannella & Schub, 2018).

Most common symptoms reported in the literature include:

Limb apraxia – disorder of skilled movement evident as an inability to execute purposeful movement (Mannella & Schub, 2018); occurs in approximately 70-80% of CBS cases, usually asymmetrical
Alien-limb – loss of control over a limb such that it seems to have a mind of its own (Mannella & Schub, 2018); occurs in approximately 50% of cases of CBS (Constantinides et al, 2019; Wilson et al, 2021)
Extrapyramidal dysfunction manifest as focal or asymmetric rigidity or focal or asymmetric limb dystonia early in the disease course (Mannella & Schub, 2018; Wilson et al, 2021); rigidity is evident in over 73% of cases (Wilson et al, 2021)
Dystonia is present in 40% of cases, with 80% being upper limb; usually presents in first two years of disease course and related to myoclonus (Constantinides et al, 2019)
Parkinsonism evident as slowed, awkward voluntary movements with additional involuntary movements, generally asymmetrical (Constantinides et al, 2019; Wilson et al, 2021)
Tremors are typically not present, but if evident they are then usually a positional or action tremor; can be irregular with myoclonic quality (Constantinides et al, 2019)
Postural instability
Aphasia – typically non-fluent, slowed, effortful and/or groping apraxia of speech and grammatical errors, sometimes there will be difficulty with word retrieval and sentence repetition (Wilson et al, 2021)
Cognitive deficits from frontal lobe executive dysfunction (Mannella & Schub, 2018)
Persistent pain may be a common non-motor symptom (Mannella & Schub, 2018)

3.3 Diagnosis

Diagnosis of CBS is difficult due to overlapping features of other disorders, the lack of diagnostic tests and biological markers to confirm a CBS diagnosis, and the heterogenous presentation of the syndrome (Constantinides et al, 2021; Monash Health, n.d.; Parmera et al, 2016).

Table 1 shows Cambridge clinical criteria for CBS. For a positive diagnosis, patients must display all mandatory criteria, and two of both major and minor criteria (Wilson et al, 2021).

Table 1

Cambridge clinical criteria, modified Bak and Hodges, for CBS diagnosis (Wilson et al, 2021)


Mandatory criteria	Insidious onset
	No sustained response to levodopa treatment
Major criteria	Akinetic rigid syndrome
	Limb apraxia
	Speech and language impairment
Minor criteria	Focal or segmental myoclonus
	Asymmetric dystonia
	Alien limb syndrome
	Cortical sensory loss or dyscalculia
	Frontal executive dysfunction
	Visuospatial defects

3.4 Imaging

It should be noted that CBS diagnosis can be supported, but not refuted, by features of imaging (Wilson et al, 2021). Although cortical and subcortical changes on MRI have been well described in the literature, it is unclear at what stage of the disease these findings have been identified.

Neural changes identified by imaging will depend on the underlying pathology responsible for the CBS (Constantinides et al, 2019). Most commonly, MRI will demonstrate asymmetric cortical changes such as grey matter atrophy or dysfunction evident as hypometabolism or hypoperfusion (Wilson et al, 2021). Changes particularly affect frontal-parietal regions encompassing the premotor, motor and sensory association cortices, and typically develop contralateral to the more affected side of the body (Wilson et al, 2021). Perirolandic patterns of change relate directly to the symptoms of CBS, and the finding of asymmetrical perirolandic atrophy or hypometabolism on imaging supports the clinical diagnosis of CBS (Wilson et al, 2021). (N.b. The perirolandic region of the brain is also known as the central lobe or paracentral area. It incorporates the primary motor cortex, primary somatosensory cortex (the main sensory receptive area) and paracentral lobule (motor and sensory region) (Zuo et al, 2020)).

3.5 Treatment

There are no effective treatments to stop or slow the progression of CBS (Mennella & Schub, 2018; Stasio et al, 2019; Wilson et al, 2021). The goal of treatment is to improve motor and cognitive-behavioural symptoms (Parmera et al, 2016) or reduce the risk of life-threatening complications such as falls, aspiration pneumonia, or sepsis (Mennella & Schub, 2018).

Management options/goals noted in the literature include (Constantinides et al, 2019; Mennella & Schub, 2018; Monash Health, n.d.):

Botulinum toxin injections to temporarily improve the functionality of the affected limb and decrease pain and cramping or dystonic muscles
Myoclonus may be helped by medications like clonazepam (tranquiliser)
Physiotherapy/physical therapy – improve everyday functionality such as walking and balance problems, prevent contractures and improve rigidity, advise on assistive technology to support independence
Occupational therapy – can advise on positional aides to support posture while eating, drinking, communication; provide home safety advice to minimise risk from falls; assess and advise on pressure relieving equipment such as specialised seating and mattresses
Speech therapy – assess speech and language decline; swallowing difficulties are common, which can lead to loss of enjoyment of food, poor nutrition, or aspiration therefore support from a speech pathologist may be beneficial
Dietician for management of nutrition if difficulties occur with swallowing or mood changes prevent the person from eating well
Depression and anxiety – mood changes can be supported via prescribed medication or a social worker/psychologist
There is little evidence of effective therapy to improve cognition or prevent cognitive decline

4. References/Bibliography

Constantinides, V. C., Paraskevas, G. P., Paraskevas, P. G., Stefanis, L., & Kapaki, E. (2019). Corticobasal degeneration and corticobasal syndrome: A review. Clinical Parkinsonism & Related Disorders, 1, 66-71. https://doi.org/10.1016/j.prdoa.2019.08.005

Di Stasio, F., Suppa, A., Marsili, L., Upadhyay, N., Asci, F., Bologna, M., Colosimo, C., Fabbrini, G., Pantano, P., & Berardelli, A. (2019). Corticobasal syndrome: neuroimaging and neurophysiological advances. European Journal of Neurology, 26, 701-710. http://doi:10.1111/ene.13928

Mennella, H. D. A.-B., & Schub, T. B. (2018). Corticobasal syndrome. CINAHL Nursing Guide.

Monash Health. (n.d.). Corticobasal degeneration [fact sheet]. Accessed from https://monashhealth.org/services/movement-disorders-program/understanding-movement-disorders/corticobasal-degeneration/

Parmera, J. B., Rodriguez, R. D., Neto, A. S., Nitrini, R., & Dozzi Bruck, S. M. (2016). Corticobasal syndrome: A diagnostic conundrum. Dementia & Neuropsychologia, 10(4), 267-275. http://doi: 10.1590/s1980-5764-2016dn1004003

Raypole, C., (2019). Understanding extrapyramidal symptoms and the medications that cause them. Healthline. Accessed from https://www.healthline.com/health/symptom/extrapyramidal-symptoms

Wilson, D., Le Heron, C., & Anderson, T. (2021). Corticobasal syndrome: a practical guide. Practical Neurology, 21(4), 276-285. http://dx.doi.org/10.1136/practneurol-2020-002835

Zuo, F., Hu, K., Kong, J., Zhang, Y., & Wan, J. (2020). Surgical management of brain metastases in the perirolandic region. Frontiers in Oncology, 10. https://doi.org/10.3389/fonc.2020.572644

5. Version control

Version	Amended by	Brief Description of Change	Status	Date
1.0	SJP131	Document created	Cleared	6/7/22