Progressive supranuclear palsy is a degenerative cerebral disease with a predominant lesion of the midbrain, nuclear-cortical pathways, subcortical formations. The components of the clinical picture are akinetic-rigid form of parkinsonism, ataxia, ophthalmoplegia, cognitive decline, pseudobulbar syndrome. Diagnosis is carried out according to clinical data, the results of cerebral MRI and cerebrovascular studies. In therapy, the drugs of choice are levodopa, memantine, antidepressants from the group of serotonin reuptake inhibitors.
ICD 10
G23.1
General information
Progressive supranuclear palsy (PSP) is a degenerative brain lesion of unclear etiology. Along with Alzheimer’s disease, multisystem atrophy, corticobasal degeneration, and Pick’s disease, PSP refers to taupathies characterized by the formation of tau protein inclusions in neurons and glial cells. Progressive supranuclear palsy was first described in detail in 1963-64 by Canadian neurologists Steele and Richardson in collaboration with pathologist Olshevsky, after whom the Steele-Richardson-Olshevsky syndrome is named. The prevalence of the disease according to various information sources varies between 1.4-6.4 cases per 100 thousand population. The manifestation of clinical symptoms occurs in the age period from 55 to 70 years, with age the probability of developing the disease increases. Males are more susceptible to the disease compared to women.
Causes
The etiofactors that trigger degenerative processes of a certain cerebral localization remain unknown. Most cases of the disease are sporadic. Separate family variants with presumed autosomal dominant inheritance were identified after 1995. Molecular genetic studies have shown that some forms of PSP are caused by defects in the tau-protein coding gene localized at the 17q21.31 locus. The most likely is a multifactorial mechanism of pathology occurring against the background of genetic predisposition.
Pathogenesis
The leading pathogenetic mechanism is considered to be dysmetabolism of cerebral intracellular proteins, accompanied by selective aggregation of individual proteins (tau protein, ubiquitin) in certain groups of brain cells. Pathological inclusions disrupt the vital activity of neurons, trigger the process of degradation and programmed death (apoptosis). Degenerative changes are selective, spread mainly to the midbrain, serrated cerebellar nuclei and subcortical structures: the black substance, pale ball, thalamus, reticular formation, subthalamic nucleus. To a lesser extent, the cortex of the prefrontal and temporal zones is affected.
The pathomorphological picture of PSP is represented by the presence of neurofibrillary glomeruli, glial inclusions, filamentous protein formations in the neurons of these cerebral structures. Macroscopically, atrophy of the midbrain is determined with a significant decrease in its sagittal size. The defeat of the midbrain causes supranuclear paralysis of the oculomotor musculature, degeneration of the cortical-bulbar tracts — pseudobulbar manifestations. Neurochemical studies reveal a reduced concentration of dopamine in the striatum, which underlies the Parkinsonian symptom complex.
Symptoms
Progressive supranuclear palsy is characterized by a nonspecific clinical debut. The symptoms of this period are represented by unusual fatigue, decreased performance, cephalgia, dizziness, low mood, narrowing of the circle of interests, sleep disorders, including insomnia at night and hypersomnia during the day. Subsequently, the symptoms of akinetic-rigid parkinsonism are added. Postural tremor is absent in most patients. Muscular rigidity is expressed mainly in the axial musculature — the muscles running along the cervical spine, connecting it with the skull. Patients complain of stiffness in the neck, back. An increase in tone in the posterior muscles of the neck leads to a typical “proud” position of the patient’s head. Parkinsonian ataxia is characteristic, due to a disorder in the coordination of the position of the trunk and lower extremities relative to the center of gravity. Difficulties in maintaining balance while walking lead to frequent falls backwards.
A distinctive feature of PSP is ophthalmoplegia, which occurs on average 2-3 years after the onset of the disease. Against the background of slow movement of the eyeballs, there is a paralysis of the gaze in the vertical plane, the patient cannot lower his eyes down. Due to the rare blinking, the patient feels discomfort, burning in the eyes. Blurred vision, convergence disorder, blepharospasm are possible. Progressive supranuclear ophthalmoparesis is accompanied by a restriction of looking down and up, over time it can lead to oculomotor disorders in the horizontal plane. With the development of complete ophthalmoplegia, a retraction of the upper eyelids is formed, which gives the face a surprised expression.
Pseudobulbar manifestations appear relatively early in the clinical picture of PSP: dysarthria, dysphagia, violent crying or laughter. There are changes in the personal and emotional sphere, patients become withdrawn, apathetic, demotivated, indifferent. Cognitive impairments in most cases join in the midst of the disease, in 10-30% of cases — at the stage of debut. It is characterized by intellectual decline, disorders of abstract thinking and memory, visual-spatial apraxia, elements of agnosia. Dementia is observed in 60% of patients with 3 years of experience of the disease.
Complications
In the initial period, the patient’s falls without the ability to coordinate their movements lead to bruises and fractures. A few years later, progressive oligobradikinetic syndrome bedridden patients. In the absence of proper care, immobility is dangerous with the development of joint contractures, pressure sores, and congestive pneumonia. Progressive pseudobulbar palsy causes choking with food with the risk of asphyxia, aspiration pneumonia. Nocturnal apnea can cause sudden death in a dream. A serious complication is the addition of intercurrent infections (pneumonia, cystitis, pyelonephritis), since there is a high risk of sepsis against the background of reduced immunity.
Diagnostics
Probable early criteria for PSP are the onset after the age of 40, progressive nature, paresis of horizontal gaze, pronounced postural instability with episodes of falls. A reliable diagnosis is possible in the presence of histologically confirmed pathognomonic changes in the brain tissues for PSP. The list of necessary diagnostic tests includes:
- Neurologist’s examination. In the neurological status, the leading syndrome is symmetrical oligobradykinesia. Hypomimia, retrocollis (pathological installation of the neck), vertical gaze paresis, symptoms of oral automatism, increased tendon reflexes are observed. Postural instability is expressed.
- Neuropsychological testing. It is carried out by a psychiatrist, neuropsychologist using special tests, tasks (MMSE scale, MOS, clock drawing test). It is required to assess the presence and severity of cognitive decline. Supranuclear paralysis is manifested by slow thinking, rapid exhaustion, moderate severity of intellectual disabilities.
- MRI of the brain. It reveals the expansion of the III ventricle, atrophic changes in the midbrain, basal ganglia, premotor zones of the frontal cortex and temporal regions. Allows to exclude intracerebral tumor, encephalitis, multiple sclerosis, stroke.
- Assessment of cerebral hemodynamics. Data on the blood supply to the brain can be obtained by duplex scanning, ultrasound, MRI of blood vessels. They are necessary to exclude dyscirculatory encephalopathy, vascular parkinsonism, vascular dementia.
Differential diagnosis is carried out with Parkinson’s disease, secondary Parkinsonism of traumatic, infectious, toxic, vascular etiology, Alzheimer’s type dementia, late form of neuroacanthocytosis. Supranuclear paralysis differs from classical Parkinson’s disease in the symmetry of Parkinsonism since its appearance, the rapid development of cognitive disorders, ophthalmoplegia, retrocollis, pronounced ataxia, and the small effect of dopaminergic therapy. It is possible to reliably differentiate progressive supranuclear palsy from other taupathies by the features of pathomorphological changes.
Treatment
An effective therapy capable of stopping the progressive degenerative process has not yet been found. Symptomatic treatment is carried out, aimed at alleviating the patient’s condition. The conducted pharmacotherapeutic studies were not accompanied by placebo control, and poorly prove the effectiveness of drug therapy. In the treatment of cognitive disorders, memantine, acetylcholinesterase inhibitors, and antidepressants with psychoactivating effects (fluoxetine, paroxetine) can be used to correct the psychoemotional sphere.
Most neurologists consider it necessary to prescribe starting dopaminergic therapy. In half of the patients, there is a certain relief of the condition against the background of taking levodopa drugs, but this effect lasts no more than two years. Antiparkinsonian pharmaceuticals of other groups (MAO inhibitors, dopamine receptor agonists, COMT inhibitors) have not shown their effectiveness.
Prognosis and prevention
With supranuclear paralysis, there is a non-stop progression of symptoms. The therapy does not have a significant effect on the course of the disease. The life expectancy of patients ranges from 5-15 years. The fatal outcome is caused by intercurrent infections, prolonged sleep apnea, aspiration pneumonia. Due to the lack of a clear understanding of the etiology and pathogenesis of nosology, the development of preventive measures is not possible, studies of the disease and its treatment methods are continuing.