Corticobasal degeneration is a separate clinical form of a selective degenerative process with a predominant lesion of the frontal-parietal cortex and subcortical ganglia. Clinical manifestations of the pathology are polymorphic, including parkinsonism, praxis disorder, tremor, myoclonia, focal dystonia, speech disorders. Corticobasal degeneration is diagnosed according to the results of neurological examination, neuropsychological testing, PET and MRI of the brain. Etiopathogenetic therapy of the disease has not been developed, treatment is symptomatic.
ICD 10
G31.0 Limited brain atrophy
General information
Corticobasal degeneration (CBD) was first described in 1968. The disease was named in connection with a combination of degenerative changes in the cerebral cortex and basal (subcortical) structures. Along with Alzheimer’s disease, progressive supranuclear paralysis (PSP), Pick’s disease, multisystem atrophy, CBD refers to taupathies accompanied by the accumulation of tau protein in cerebral cells. Since oligobradykinesia is one of the leading clinical symptom complexes, in clinical neurology, corticobasal degeneration is considered a variant of parkinsonism-plus. The exact prevalence of CBD is unknown, some studies indicate that the pathology accounts for 0.9% of all cases of Parkinsonism. The peak incidence occurs at the age of 50-60 years.
Causes
Etiological factors of the occurrence of CBD, the causes of selective lesion of cortical-subcortical structures have not been determined. The disease has a sporadic character, according to unconfirmed data, there are isolated family cases. Some researchers suggest a connection between the pathological metabolism of individual intracellular proteins and changes in the genetic apparatus of nerve cells. The polyethological nature of the disease development is likely, in which the combined effect of several etiofactors leads to the realization of a genetically determined disorder.
Pathogenesis
The main pathogenetic mechanism is recognized as a violation of protein metabolism in brain tissues. The result of dysmetabolism is the aggregation of a number of proteins inside neurons, glial cells. Protein inclusions alter the normal vital activity of cells, possibly triggering the mechanism of their self-destruction (apoptosis). The pathological process has a selective localization, mainly the fronto-parietal areas of the cortex, the nigra substance, the striatum, the ventrolateral thalamic nucleus, the serrated nuclei of the cerebellum are affected. The macroscopic picture is represented by asymmetric atrophic processes of this localization. Microscopically, a decrease in the number of nerve cells, demyelination of fibers, and intra-neuronal inclusions of tau protein are determined. A pathognomonic sign of CBD is the presence of unpainted balloon-like neurons in the affected areas.
Symptoms
The clinical picture reflects the progressive lesion of the cortex and basal ganglia. The sequence of development and the combination of syndromes can be different, which forms polymorphism and significant variability of manifestations. Often the first symptom is a feeling of numbness, awkwardness in the limb (more often in the upper one), a disorder of complex types of sensitivity in it: the ability to recognize objects by touch (stereognosis), to distinguish several simultaneously acting stimuli (discriminatory feeling). These changes extend to the ipsilateral limb, then to the opposite side. In half of the cases, the syndrome of an “alien” limb (more often a hand) occurs in combination with its involuntary movements.
The symptoms of parkinsonism are present in 100% of patients, are asymmetric in nature with a predominance of akinetic-rigid manifestations. Other extrapyramidal disorders are noted: various forms of muscular dystonia, myoclonia, postural tremor, less often — chorea, athetosis. In many patients, corticobasal degeneration occurs with a typical tonic condition of the upper limb with flexion and reduction of the shoulder, forearm, hand and fingers. In some cases, patients are forced to carry a ball in their hand to prevent damage to the brush with the nails of sharply bent fingers. Oculomotor disorders are represented by some limitation of the amplitude of movements, obvious paresis of the eye is observed in 20% of cases. Cerebellar ataxia, frontal symptoms are possible: paratonia, sucking, grasping reflexes.
With the onset of symptoms in the lower limb, gait disorders appear in the first year of the disease, with the localization of the first manifestations in the arm — after 3 years. Frontal dysbasia with frequent falls is determined. Pyramidal insufficiency is limited by the appearance of stop symptoms, hyperreflexia. In most cases, dysarthria occurs, which has a mixed cortical-subcortical character, in 20-30% of cases — dynamic aphasia. In 85% of patients, apraxia is noted — a violation of the program of sequential execution of actions. Intellectual decline usually develops after the formation of pronounced motor disorders. At the same time, there are cases when corticobasal degeneration manifested as cognitive disorders, and dementia was the leading symptom of the disease.
Complications
The patient’s falls caused by dysbasia are dangerous for serious injury with bruises and fractures. Subsequently, progressive parkinsonism and apraxia deprive the patient of the possibility of self-service, are the cause of deep disability. Local musculotonic disorders are complicated by the development of contractures. Gradually, the ability to move independently is lost. Constant bed rest contributes to the development of bedsores and a number of infectious complications: cystitis, ascending pyelonephritis, congestive pneumonia, sepsis.
Diagnostics
Corticobasal degeneration is diagnosed based on the following clinical criteria: L-DOPA-resistant Parkinsonism, apraxia, the phenomenon of “alien” limbs, muscular dystonia, myoclonia, rough tremor. Diagnosis is possible if there are three signs out of six. The diagnosis is reliably verified according to the data of pathomorphological examination of cerebral tissues. During the diagnostic search , the following studies are carried out:
- Neurological examination. In the debut of CBD, a neurologist reveals local sensory disorders, astereognosis, a violation of the skin-kinesthetic sense of one limb. Subsequently, dysbasia, hypokinesia, muscle rigidity and dystonia, speech disorders, pyramidal insufficiency, hyperkinesis are determined.
- Neuropsychological testing. A neuropsychologist’s examination is necessary to assess the level of cognitive impairment. In typical cases, corticobasal degeneration is characterized by the late development of dementia, the absence of mental disorders. Apraxia of complex motor acts comes to the fore.
- Cerebral MRI. At the initial stages, MRI of the brain does not visualize pathological changes. During the period of clinical peak, atrophy is revealed, most pronounced in the fronto-parietal cortex, thalamus, caudate nucleus, shell.
- Assessment of cerebral circulation. The examination is necessary for the differential diagnosis of CBD from vascular parkinsonism, dyscirculatory encephalopathy. Duplex scanning of cerebral vessels, ultrasound of extracranial and intracranial vessels make it possible to exclude chronic cerebral ischemia as an etiofactor of the degenerative process that has arisen.
At the onset of symptoms, corticobasal degeneration requires differentiation with Parkinson’s disease, in the future – with clinically similar brain tumors, degenerative diseases: Gallervorden–Spatz disease, Peak, Alzheimer’s disease, PSP, dementia with Lewy bodies. CBD differs from Parkinson’s disease in the presence of cortical symptoms, speech disorders, and resistance to DOPA therapy. With PSP, ophthalmoplegia is expressed, there are no myoclonia and focal cortical dysfunction. Alzheimer’s disease is characterized by a predominance of atrophic and hypometabolic changes in the frontotemporal cortex.
Treatment
Treatment options for CBD are limited because the etiology of the disease remains unclear. Mainly symptomatic therapy is used. There is no therapeutic scheme that can stop the progression of degeneration yet. Treatment is aimed at alleviating the patient’s condition, reducing the severity of symptoms. Combination therapy with the inclusion of the following components is generally accepted:
Antiparkinsonian treatment. In some patients, L-DOPA pharmaceuticals give a moderate effect for several years, so therapy begins with their use. In some cases, dopamine receptor agonists are effective.
Symptomatic therapy. With pronounced intentional tremor, myoclonia, clonazepam is prescribed, with postural tremor — beta-blockers. Progressive aphasia is an indication for the use of cholinesterase inhibitors. The removal of muscle tonic tension in focal dystonia is facilitated by the injection of botulinum toxin.
Physical therapy. Special therapeutic gymnastics is necessary to prevent the development of joint contractures. Exercises facilitate the condition of muscular dystonia, help to prolong the patient’s motor activity.
Prognosis and prevention
Corticobasal degeneration is characterized by a steady progression of neurological manifestations. On average, after 5 years, cognitive and motor disorders bedridden the patient. The life expectancy of most patients does not exceed 10 years from the time of the onset of symptoms. The cause of death is usually bronchopneumonia. The development of preventive measures is not possible until the etiology of CBD is established.
