What Is 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 stiffness (rigidity), tremor at rest, slowness of movement (bradykinesia) and postural instability (balance difficulties). It may also cause problems with memory and thinking. Corticobasal syndrome, however, is distinct from Parkinson's disease in regards to other clinical features and its response to treatment.
Corticobasal syndrome was first described by Rebeiz and colleagues in 1968. There are some variations of the name of corticobasal syndrome such as corticobasal disease or corticobasal ganglionic degeneration. The name implies the parts of the brain damaged. corticobasal syndrome 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 corticobasal syndrome 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, muscle jerking (myoclonus), and eventually irreversible muscle contractures, all involving the same side of the body. They may have myoclonus of one hand while at rest or with activity. On occasion, an affected limb can seem to have a "mind of its own" and make seemingly purposeful movements that the patient cannot control. This problem, known as "alien" hand or limb, is sometimes accompanied by the feeling that one's limb is somehow foreign. 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 loss of sensation in one or both sides of the body, even though patients typically do not complain of numbness. The symptoms of corticobasal syndrome usually worsen over three to eight years and often result in great disability, including the inability to communicate or ambulate. Walking and balance difficulties, however, occur later in patients with corticobasal syndrome compared with other forms of atypical parkinsonism such as progressive supranuclear palsy.
There is no diagnostic test for corticobasal syndrome, but a 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 corticobasal syndrome 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 corticobasal syndrome from other similar neurodegenerative diseases. In some cases, the diagnosis of corticobasal syndrome 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 cause of corticobasal syndrome is not yet known. Like other neurodegenerative diseases, patients with corticobasal syndrome accumulate misfolded proteins within specific brain cells. Mishandling of tau, a protein that normally acts to stabilize the cellular skeleton of neurons (nerve cells), appears to play a major role but the details remain unclear. Corticobasal syndrome is usually not an inherited condition.
As with the other atypical parkinsonian syndromes, treatment with levodopa and related medications sometimes lessens muscle rigidity and improves mobility, but results are often disappointing. Muscle spasms and jerking can 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 corticobasal syndrome include physical therapy and stretching exercises designed to 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 corticobasal syndrome. Furthermore, since corticobasal syndromes quite rare, clinical drug trials are sometimes not available for affected patients. Nonetheless, there is reason for hope. Because the biology of corticobasal syndrome may be related to other neurodegenerative diseases, it is possible that therapies designed for other conditions will also prove helpful for patients with corticobasal syndrome.
Baizabal-Carvallo JF, Jankovic J. Parkinsonism, movement disorders and genetics in frontotemporal dementia. Nat Rev Neurol. 2016 Mar;12(3):175-85.
Bhatia KP, Stamelou M. Nonmotor Features in Atypical Parkinsonism. Int Rev Neurobiol. 2017;134:1285-301.
Borroni B, Garibotto V, Agosti C, et al. White matter changes in corticobasal degeneration syndrome and correlation with limb apraxia. Arch Neurol. 2008;65:796-801.
Deutschländer AB, Ross OA, Dickson DW, Wszolek ZK. Atypical Parkinsonian syndromes: a general neurologist's perspective. Eur J Neurol. 2017 Aug 12.
Dutt S et al. Progression of brain atrophy in PSP and CBS over 6 months and 1 year. Neurology. 2016 Nov 8;87(19):2016-25.
Fahn S, Jankovic J. Principles and Practice of Movement Disorders. Churchill Livingstone, Elsevier, Philadelphia, PA, 2007:1-652. (Accompanied by a DVD of movement disorders.)
Graham NL, Bak T, Patterson K, Hodges JR. Language function and dysfunction in corticobasal degeneration. Neurology. 2003;61:493-9.
Jankovic J, eds. Neurology in Clinical Practice, 5th ed., Butterworth-Heinemann (Elsevier), Philadelphia, PA, 2008.
Jankovic J, Shannon KM. Movement disorders. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders, 5th ed., Lippincott Williams and Wilkins, Philadelphia, PA, 2007:1-720. (Accompanied by a CD video atlas.)
Kouri N, Whitwell JL, Josephs KA, Rademakers R, Dickson DW. Corticobasal degeneration: a pathologically distinct 4R tauopathy. Nat Rev Neurol. 2011;7:263-72.
Koyama M, Yagishita A, Nakata Y, Hayashi M, Bandoh M, Mizutani T. Imaging of corticobasal degeneration syndrome. Neuroradiology. 2007;49:905-12.
Lee SE, Rabinovici GD, Mayo MC, et al. Clinicopathological correlations in corticobasal degeneration. Ann Neurol. 2011;70:327-40.
Ling H, O'Sullivan SS, Holton JL, et al. Does corticobasal degeneration exist? A clinicopathological re-evaluation. Brain. 2010;133:2045-57.
Mahapatra RK, Edwards MJ, Schott JM, Bhatia KP. Corticobasal degeneration. Lancet Neurol. 2004;3:736-43.
Murray R, Neumann M, Forman MS, et al. Cognitive and motor assessment in autopsy-proven corticobasal degeneration. Neurology. 2007;68:1274-83.
Peigneux P, Salmon E, Garraux G, et al. Neural and cognitive bases of upper limb apraxia in corticobasal degeneration. Ann Neurol. 2001;57:1259-68.
Shelley BP, Hodges JR, Kipps CM, et al. Is the pathology of corticobasal syndrome predictable in life? Mov Disord. 2009;24:1593-9.
Thomas M, Jankovic J. Parkinson-plus syndromes. In: Noseworthy J, editor-in-chief. Neurological Therapeutics: Principles and Practice, 2nd ed., Informa Healthcare, Milton Park, Abingdon, Oxon, UK, 2006:2803-26.
Vanek Z, Jankovic J. Dystonia in corticobasal degeneration. Mov Disord. 2001; 16:252-7.
Wenning GK, Litvan I, Jankovic J et al. Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination. J Neurol Neurosurg Psychiatry. 1998 Feb;64(2):184-9.
Williams DR. Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau. Intern Med J. 2006;36:652-60.