Corticobasal Syndrome

Corticobasal Syndrome 

• Corticobasal syndrome (CBS) refers to a pathologically heterogenous clinical syndrome of atypical parkinsonism with markedly asymmetric limb rigidity and dystonia, along with several other features including limb apraxia, myoclonus, cortical sensory deficits, and alien limb phenomena. 
• •Corticobasal degeneration (CBD) was the term previously used to describe the clinical entity now known as CBS as well as a specific tauopathy underlying approximately half of CBS cases.
• Now, CBS describes the specific clinical syndrome, and CBD describes the most common pathologic cause of CBS. Just as CBS is pathologically heterogenous, so too is CBD clinically heterogenous.
• CBD pathology is characterized by widespread deposition of 4-repeat hyperphosphorylated tau in neurons as well as in the glia (where the 4-repeat tau forms astrocytic plaques) of cortical gray and white matter as well as in the basal ganglia, diencephalon, and upper brainstem. 
• CBD can underlie not only CBS but also clinically classic progressive supranuclear palsy, presenting with early falls and supranuclear gaze palsy, behavioral variant frontotemporal dementia, posterior cortical atrophy, and even the nonfluent/agrammatic variant of primary progressive aphasia.

Epidemiology & Demographics

• •CBS epidemiology is poorly defined. It has a case prevalence of approximately 2/100,000 and, according to a Russian study, an annual incidence rate of 0.02/100,000. 
• •Mostly commonly presentation is in the 5th to 7th decades of life. 
• •Affects males and females equally.
• •Average survival from diagnosis is approximately 7 yr.

What causes Corticobasal Syndrome & what increases the Risk of this condition?

Sporadic neurodegenerative disease that may be due to one of several pathologic substrates (from most to least common) such as corticobasal degeneration, Alzheimer disease, progressive supranuclear palsy, and frontotemporal lobar degeneration with ubiquitin and TDP-43 positive inclusions. 

Genetic susceptibility variants have been identified related to genes affecting the tau protein in patients with corticobasal degeneration and progressive supranuclear palsy pathologies. 

Pathophysiology

Neurodegeneration causing asymmetric neuronal loss and atrophy of frontoparietal cortex, especially in the perirolandic region but also affecting subcortical structures such as the striatum, thalamus, and brainstem

Clinical Manifestations

What are the Presenting Signs & Symptoms of Corticobasal Syndrome?

• •May present with either motor or cognitive complaints.
• •Motor complaints may include limb clumsiness or incoordination.
• •Cognitive complaints may include memory loss, behavioral changes, or language difficulties.
• •The clinical hallmarks of CBS include a significantly asymmetric rigidity and bradykinesia (parkinsonism) without tremor and with poor to no response to levodopa, typically manifesting first in an upper limb.
• •Focal limb dystonia or hemidystonia is common at presentation and may progress to a fixed contraction.
• •Apraxia:
  • 1.Ideomotor: Impairment in miming hand gestures and in mimicking tool use in the absence of primary sensory-motor or language dysfunction
  • 2.Limb-kinetic: Impaired fine motor movements of the fingers and hand
• •Cortical sensory loss:
  • 1.Agraphesthesia: Impairment in recognizing a number or letter traced on the skin of the hand or finger
  • 2.Astereognosis: Impairment in object identification by active touch without use of other sensory modalities
  • 3.Loss of two-point discrimination
• •Alien limb syndrome: A condition in which a limb or limbs appear to be acting on their own, not under any volitional control.
• •Falls and nonfluent aphasia may be early features in a substantial minority of patients.

 Diagnosis

• •Careful physical examination looking for characteristic findings, especially in a patient presenting with loss of dexterity or limb clumsiness.
• •MRI of the brain without contrast is characterized by asymmetric atrophy in frontoparietal cortical areas, especially posteromedial frontal and perirolandic cortex and dorsal insula. 

Diagnostic Criteria 

• •Proposed clinical phenotype of corticobasal syndrome associated with the pathology of corticobasal degeneration
• •Probable corticobasal syndrome:
  • 1.Asymmetric presentation with insidious onset and gradual progression of two of the following: (a) Limb rigidity or akinesia, (b) limb dystonia, (c) limb myoclonus; plus two of the following: (d) Orobuccal or limb apraxia, (e) cortical sensory deficit, (f) alien limb phenomena (more than simple levitation)
• •Possible corticobasal syndrome:
  • 1.Either symmetric or asymmetric presentation with insidious onset and gradual progression of one of the following: (a) Limb rigidity or akinesia, (b) limb dystonia, (c) limb myoclonus; plus one of the following: (d) Orobuccal or limb apraxia, (e) cortical sensory deficit, (f) alien limb phenomena (more than simple levitation)

History & Physical Examination

• •History of limb clumsiness, stiffness, or incoordination should raise the possibility.
• •Physical examination should include a complete neurologic examination with additional tests of the following:
  • 1.Check for presence of bradykinesia—slowness of initiation of voluntary movement with progressive reduction of speed and amplitude of repetitive actions such as finger or foot tapping. 
  • 2.Check for presence of lead pipe rigidity—a velocity-independent increase in tone.
  • 3.Check for limb dystonia or dystonic posturing or a limb.
  • 4.Tests for apraxia:
    • a.Ideomotor apraxia: Ask the patient to mimic certain hand movements and to mime brushing teeth, brushing hair, cutting with scissors. The patient should mime holding the tool rather than using the hand as the tool itself.
    • b.Limb-kinetic apraxia: Ask the patient to make fine finger movements; loss of coordination indicates apraxia.
    • c.Orobuccal apraxia: Ask the patient to mimic blowing out candle or licking crumbs off limbs.
    • d.Apraxia of speech: May be tested in patients having difficulty with language fluency and pronunciation but with intact written communication.
  • 5.Tests of cortical sensory loss:
    • a.Agraphesthesia: Trace letters or numbers on the palm of the hand or the fingertips.
    • b.Astereognosis: Place objects such as different types of coins in patient’s hand with eyes closed and ask patient to identify the objects using only touch.
    • c.Alien limb: Observation of limb movements that are reported to be beyond the volitional control of the patient.

How is Corticobasal Syndrome diagnosed?

Laboratory Tests

Laboratory tests typically ordered for workup of dementia, such as complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, and vitamin B₁₂ level, may be ordered.

Imaging Studies

MRI of the brain without contrast shows asymmetric frontoparietal atrophy.

Diagnostic Procedures

• •Neurologic examination
• •MRI of the brain without contrast
• •Neuropsychologic testing

Differential Diagnosis

Differential Diagnosis Compared with Corticobasal Syndrome

Condition	Description	Differentiated by
Parkinson disease	Typical motor features include a levodopa-responsive, asymmetrically presenting syndrome of bradykinesia with at least one of the following: 4-6 Hz supination-pronation resting tremor, rigidity, or postural instability plus nonmotor symptoms such as depression, anxiety, REM sleep disorder, constipation, anosmia	•Levodopa responsive•Pill rolling supination-pronation tremor common•No cortical dysfunction•No alien limb syndrome
Progressive supranuclear palsy	Symmetric levodopa-nonresponsive parkinsonism characterized by axial greater than limb rigidity, no resting tremor, early severe postural instability and falls, eventual development of a supranuclear gaze palsy, inability to look vertically volitionally with preserved vertical eye movements when the head is moved up and downDementia, dysphagia, dysarthria with a growling voice, and facial dystonia with a deep, furrowed brow are common	•Symmetric with axial rigidity and no response to levodopa•No cortical dysfunction•Early falls•Early dysphagia and dysarthria
Multisystem atrophy	Symmetric parkinsonism with early, severe dysautonomia affecting multiple aspects of the autonomic nervous system as well as ataxia	•Symmetric presentation•Late development of laryngeal stridor is common in MSA•Only minority with modest levodopa responsiveness•Cortical deficits very uncommon

Treatment

• •Supportive care
• •Occupational therapy
• •Physical therapy
• •Speech therapy

First-Line Treatment

Supportive care

Pharmacologic Therapy

No effective drug therapies exist.

Nonpharmacologic & Supportive Care

Palliative care may be appropriate as the disease progresses.

Persistent Or Recurrent Disease

CBS is a relentlessly progressive neurodegenerative disease.

Follow-Up

Monitoring

Regular follow-up for disease progression and referral to appropriate therapies, including palliative care

Complications

• •Painful limb dystonia
• •Loss of ability to perform activities of daily living due to apraxia, dystonia, rigidity, cortical sensory loss, or aphasia
• •Falls and associated injury
• •Dysphagia and aspiration pneumonia

Prognosis

Average time from diagnosis to death is approximately 7 yr.

Referral

Movement disorders or behavioral neurologist for confirmation of diagnosis

Alarm Signs & Symptoms

Extremely rapid progression may indicate Creutzfeldt-Jakob disease.

References

• 1. Armstrong M.J., et al.: Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 80: pp. 496-503.
• 2. Kouri N., et al.: Corticobasal degeneration: a pathologically distinct 4R tauopathy. Nat Rev Neurol 2011; 7: pp. 263-272.
• 3. Coyle-Gilschrist I.T.S., et al.: Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes. Neurology 2016; 86: pp. 1736-1743.
• 4. Winter Y., et al.: Incidence of Parkinson’s disease and atypical parkinsonism: Russian population-based study. Mov Disord 2010; 25: pp. 349-356.
• 5. Kouri N., et al.: Corticobasal degeneration: a pathologically distinct 4R tauopathy. Nat Rev Neurol 2011; 7: pp. 263-272.
• 6. Lee S.E., et al.: Clinicopathological correlations in corticobasal degeneration. Ann Neurol 2011; 70 (2): pp. 327-340.
• 7. Greene P.: Progressive supranuclear palsy, corticobasal degeneration, and multisystem atrophy. Continuum (Minneap Minn) 2019; 25 (4): pp. 919-935. Movement Disorders.
• 8. Lee SE et al: Clinicopathological correlations in corticobasal degeneration, Ann Neurol 70(2):327-340, 2011.
• 9. Armstrong M.J., et al.: Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 80: pp. 496-503.
• 10. Zesiewicz T.A.: Parkinson disease. Continuum (Minneap Minn) 2019; 25 (4): pp. 896-918. Movement Disorders.