Corticobasal Degeneration and Corticobasal Syndrome

Prevalence, Prognosis, and Definition

Corticobasal degeneration is a neurodegenerative disease of the brain caused by the accumulation of hyperphosphorylated 4-repeat tau isoforms. Corticobasal syndrome is a clinical diagnosis characterized by asymmetric cortical dysfunction, often affecting motor control of a limb, along with executive dysfunction, rigidity, a jerky postural tremor, myoclonus, dystonia, and a gait disorder; speech may be disrupted owing to apraxia or nonfluent aphasia. We now recognize that not all patients with corticobasal syndrome have underlying corticobasal degeneration pathology, and not all patients with corticobasal degeneration pathology present with corticobasal syndrome ( ); see Chapter 3 for a more general discussion of the issue of separating degenerative diseases from dementia syndromes. Corticobasal degeneration is a relatively rare disorder with a prevalence of about 2 per 100,000. From one literature review, the mean age of onset was 64 years, ranging from 45 to 77 years, with an average prognosis from diagnosis to death of about 6.6 years, ranging from 2 to 12.5 years ( ).

Criteria

Based on the clinical phenotypes of 129 autopsy-proven cases, a 2013 paper presented two sets of criteria for corticobasal degeneration: more specific clinical research criteria for sporadic probable corticobasal degeneration and broader, more inclusive criteria for possible corticobasal degeneration that may overlap with other tau-based pathologies ( Table 13.1 ) ( ). Both criteria are based on five clinical phenotypes that have been proven to be associated with the pathology of corticobasal degeneration ( Table 13.2 ). Definitions and explanations for many of the terms used in these criteria can be found in the Common Signs, Symptoms, and Stages section. Unfortunately, studies have found that these criteria are not highly sensitive or specific ( ).

It is worth noting that one of the clinical phenotypes associated with corticobasal degeneration is “progressive supranuclear palsy syndrome.” That this syndrome is one of the clinical phenotypes does not mean that progressive supranuclear palsy is a subset of corticobasal degeneration or that the two disorders are really the same. It does mean that some patients with underlying corticobasal degeneration pathology look very similar to patients with underlying progressive supranuclear palsy pathology.

Risk Factors, Pathology, and Pathophysiology

There are no known risk factors for developing corticobasal degeneration. A characteristic of this disorder is that the distribution of pathology and atrophy is asymmetric. Cortical regions affected are around the main sulci of the brain: parasagittal, peri-Rolandic, and peri-Sylvian. Subcortical structures affected include substantia nigra, and variably the globus pallidus, subthalamic nucleus, and thalamus. Under the microscope, the pathology consists of swollen achromatic neurons in amygdala and limbic structures, as well as ballooned neocortical achromatic neurons in specific layers (III, V, and VI) in frontal and parietal lobes ( Fig. 13.1 ). Hippocampal and temporal lobe regions are least affected. Corticobasal degeneration is associated with the accumulation of hyperphosphorylated 4-repeat tau protein isoforms in neurons and glia.

Common Signs, Symptoms, and Stages

Corticobasal syndrome classically starts with an impaired limb, which may present as an “alien limb,” but more often it presents as a stiff, clumsy, and useless hand. Retrospective autopsy studies show, however, that more patients actually present with cognitive, speech, behavioral, or gait abnormalities than those who present with limb abnormalities. Limb abnormalities are likely relatively specific for corticobasal degeneration but are not sensitive enough to allow one to rely upon this sign to detect the disorder. Presenting and early symptoms may include the following:

• Alien limb (not common but pathognomonic when it occurs): The affected limb is described as “having a mind of its own,” and patients report having little or no control over it. It may grasp, grope, wander, or take hold of objects, clothes, and people. Occasionally it may interfere with the function of the unaffected limb.

• Useless limb (common): The limb is not able to participate in functional activities, often because of varying combinations of rigidity, akinesia, dystonia, myoclonus, and apraxia.

• Focal/limb apraxias: Inability to perform skilled and/or learned movements unexplained by abnormalities such as weakness, incoordination, language difficulties, and so on. See Box 13.1 and Video 13.1 , Video 13.2 , Video 13.3 .

  Box 13.1

  Apraxia (see Video 13.1 , Video 13.2 , Video 13.3
  )

  A patient is said to have an apraxia when he or she is unable to perform a purposeful, coordinated movement despite normal strength and sensation. The patient’s actions often appear clumsy and uncoordinated. Apraxias come in a variety of types. Some of the more common are as follows.

  • Limb-kinetic apraxia refers to the loss of the ability to make precise independent finger movements, such as the pincer grasp that is needed to pick up a small coin off a flat surface.

  • Patients with ideomotor apraxia make errors in spatial movement, orientation, and/or timing of previously learned skilled movements. For example, when pantomiming cutting paper with scissors, he or she may not keep the scissors correctly oriented to the paper.

  • In conduction apraxia, patients show more difficulty imitating a skilled movement (such as a salute) than performing the movement to command.

  • Dissociation apraxia refers to the inability to pantomime to command, despite the ability to imitate and use objects perfectly.

  • Although the term ideational apraxia has been used to describe a variety of apraxias, its current meaning is an inability to correctly sequence a series of acts that lead to a goal (such as making a sandwich).

  • Patients with conceptual apraxia show errors in trying to use or pantomime using tools correctly, such that they may show hammering when asked to demonstrate the use of a screwdriver. Many of these patients also show deficits in semantic memory, having lost the meaning of these items.

• Rigidity: An increase in muscle tone causing resistance to movement of the joint.

• Akinesia : An inability to initiate movement owing to difficulty selecting and/or activating motor programs.

• Dystonia: Occurs when sustained muscle contractions cause abnormal postures or movements.

• Asterixis: A sudden involuntary loss of tone in a muscle group.

• Myoclonus: A brief, involuntary twitching of a muscle group.

• A jerky postural tremor: A “tremor” typically caused by frequent asterixis and myoclonus.

• Sensory symptoms: Includes numbness and tingling.

• Cortical sensory loss: Primary sensory abilities are normal, but there are deficits in the ability to use this information to make appropriate judgments. Patients can feel a touch, distinguish sharp from dull, warm from cold, and so on, but they are unable to identify a coin by feeling it (stereognosis, see Video 13.4 ) or a number when it is drawn in their hand (graphesthesia, see Video 13.5 ).

• Visuospatial deficits: Impairment in one or more visuospatial functions such as copying a cube or intersecting pentagons, left/right discrimination, neglect, simultagnosia (difficulty perceiving multiple objects at the same time), or directing limb movement via visual guidance. (See Chapter 11 .)

• Neglect: Ignoring one side of space. Often tested by presenting stimuli on both sides of the body simultaneously and ascertaining whether patients ignore stimuli on one side of the body in the absence of a primary sensory deficit. Left neglect is much more common than right. (See Chapter 11 .)

• Apraxia of speech: Abnormality of speech including slow speaking rate, abnormal prosody (some of the nonlinguistic aspects of speech such as emotion and intonation), and distorted sound substitutions. (See Chapter 9 .)

• Speech disturbance: The disturbance in speech can include orobuccal apraxia (apraxia of the mouth, lips, and tongue), apraxia of speech, halting and/or effortful speech. (See Chapter 9 .)

• Executive dysfunction: Impairments in planning, abstraction, problem solving, judgment, working memory, and goal-directed behavior.

• Behavioral disorder: Symptoms may include apathy, bizarre or antisocial behavior, personality changes, irritability, disinhibition, and hypersexuality. (See Chapter 10 .)

Over time the affected limbs become more rigid, with rapid movements such as pronation/supination and alternating finger tapping becoming impaired. Eventually even passive stretch may not be possible. Dystonia may become prominent, with the hand often becoming a clenched fist or having hyperextension of one or more fingers. Myoclonus is often seen in the fingers, which may increase with sensory stimulation and finger movements. Although all four limbs are commonly involved in the later stages, asymmetry is usually maintained.