Corticobasal Syndrome

Corticobasal syndrome (CBS) is a form of atypical parkinsonism (a parkinsonism-plus syndrome), which means that it shares some features with Parkinson's disease such as slowness of movement (bradykinesia), stiffness (rigidity), tremor, and postural instability (balance difficulties). It may also cause problems with memory and thinking. Corticobasal syndrome, however, is distinct from Parkinson's disease because of additional characteristic clinical features such as striking asymmetry and the presence of apraxia, myoclonus and sensory abnormalities, as well as its lack of response to treatment with levodopa.

CBS results in gradual loss of nerve cells (neurodegeneration) in the surface of the brain (the cerebral cortical areas) as well as deep structures (the basal ganglia). These brain regions are heavily involved in the control of movement, so corticobasal syndrome causes problems with mobility. In contrast to other types of atypical parkinsonism, the neurodegeneration in corticobasal syndrome is markedly asymmetrical, thus the symptoms usually start on one side of body and remain worse on that half throughout the course of the disease.

Signs and Symptoms

The most characteristic presenting feature of CBS is the gradual loss of use of one hand or leg (called "apraxia"). Patients may also experience abnormal postures of their limbs or neck (dystonia), painful rigidity, limb jerking (myoclonus), lack of movement (akinesia) and eventually irreversible contractures with only partial involvement of the contralateral side of the body.  In some cases, an affected limb may seem to have a "mind of its own", which can evolve into "alien" hand or limb, accompanied by the feeling that one's limb does not belong to the body and is feeling “foreign”.  Many patients hold the affected hand with the unaffected hand and make seemingly purposeful (“searching”) movements that the patient cannot control. This may be partly due to loss of sensation in the affected body part. 

Some patients also have language dysfunction (e.g. primary progressive aphasia) or slurred speech (dysarthria), difficulty opening or moving their eyes, as well as difficulties with their concentration and behavior. Although disorders of thinking and memory (cognitive changes) may be noted early in the disease, dementia usually occurs only in more advanced stages. There may be loss of inhibition and changes in behavior such that patients speak rudely or do not show empathy. On examination, there is often a loss of sensation in one or both sides of the body, even though patients typically do not complain of numbness.

The symptoms of CBS usually worsen over three to eight years and often result in great disability, including the inability to communicate or ambulate. Walking and balance difficulties occur later in patients with CBS in contrast to other forms of atypical parkinsonism such as progressive supranuclear palsy.

Diagnosis

There is no diagnostic test for CBS, but an experienced neurologist usually suspects the diagnosis based on a patient's history, physical examination and clinical course. Early in the disease, it can be challenging to differentiate CBS from other forms of parkinsonism, such as Parkinson's disease or progressive supranuclear palsy and in some cases, there is an overlap in clinical features between the different parkinsonian disorders. Imaging with CT or MRI may show asymmetrical shrinkage (atrophy) of the cerebral cortex (brain surface) on the side opposite to the more affected limbs. Brain scans, however, cannot yet reliably distinguish CBS from other neurodegenerative diseases. In some cases, the diagnosis of CBS cannot be confirmed until an autopsy examination of the brain is performed, which usually shows "ballooned" neurons, protein aggregations (neuronal inclusions) and other characteristic abnormalities resulting from abnormal accumulation of the tau protein (corticobasal syndrome is a “tauopathy”).  The term corticobasal degeneration is reserved for autopsy-confirmed CBS.

Cause

The cause of CBS is not yet known. Like other neurodegenerative diseases, patients with CBS accumulate misfolded proteins within specific brain cells. Mishandling of tau, a protein that normally acts to stabilize the cellular skeleton of neurons (nerve cells) and also accumulates in the brains of patients with Alzheimer disease, appears to play a major role but the details remain unclear. CBS is usually not an inherited condition. In some cases, there is a peripheral injury or acute central damage (e.g. brain stroke or trauma) suggesting an initial trigger for subsequent neurodegeneration, thus possibly explaining the striking and persistent asymmetry of clinical, imaging and pathological findings. 

Treatment

In contrast to other parkinsonian syndromes, levodopa almost never provides any meaningful improvement in the symptoms. Dystonia, painful muscle spasms and rigidity be reduced with muscle relaxants, such as clonazepam, and with botulinum toxin injections into affected parts of the body. Medications for memory loss, depression and anxiety may be useful in patients with these problems.

Other treatments for CBS include physical therapy and stretching exercises designed to maintain range of motion, relieve rigidity and to prevent contractures and deformities as well as to maintain good strength and condition of muscles. Devices which make walking safer, such as a cane or walker, can be helpful. Speech, physical, and occupational therapy may be beneficial. Because of swallowing problems, some patients require placement of a feeding tube (PEG) directly into the stomach to maintain adequate nutrition and prevent aspiration pneumonia. If general health and nutrition can be maintained, some corticobasal syndrome patients live for several years after the onset of symptoms, although their quality of life in the advanced stages of the disease is usually significantly impaired.

At present, there are no therapies that can reverse or even slow the progression of CBS. Furthermore, since CBS is quite rare, clinical drug trials are not available. Nonetheless, there is reason for hope. Because the biology of CBS may be related to other neurodegenerative diseases, it is possible that therapies designed for other conditions will also prove helpful for patients with CBS.

References

• Bruno et al. A General Neurologist's Practical Diagnostic Algorithm for Atypical Parkinsonian Disorders. Neurol Clin Pract. 2024 Dec; 14(6): e200345.
• Heilman KM. Upper Limb Apraxia. Continuum (Minneap Minn). 2021 Dec 1;27(6):1602-1623. 
• Lenka A, Jankovic J. Corticobasal syndrome: Are there central or peripheral triggers?. Neurology Clin Pract 2024 (in press).
• Pantelyat A. Progressive supranuclear palsy and corticobasal syndrome. Continuum (Minneap Minn). 2022 Oct 1;28(5):1364-1378. 
• Shir D, Pham NTT, Botha H, et al. Clinicoradiologic and Neuropathologic Evaluation of Corticobasal Syndrome. Neurology. 2023 Jul 18;101(3):e289-e299. 

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