NEUROLOGY AND NEUROSURGERY - Y. V. ALEKSEEENKO - 2014

EXTRAPYRAMIDAL DISORDERS

Parkinsonism and Parkinson's Disease

The parkinsonian symptom complex (hypertonic hypokinetic) typically arises from damage primarily to the pallidal segment of the extrapyramidal system and is etiologically heterogeneous. The most common form is idiopathic—Parkinson's disease (accounting for up to 80%)—along with postencephalitic, vascular, post-traumatic, toxic, and drug-induced variants of secondary parkinsonism. A distinct group comprises cases where parkinsonism manifests as part of a neurodegenerative Central Nervous system disorder (corticobasal degeneration, multiple system atrophy, progressive supranuclear palsy, etc.), known as "parkinsonism plus" syndromes.

Parkinson's disease is one of the most prevalent chronic degenerative disorders of The Nervous System, characterized primarily by motor impairment accompanied by a range of autonomic, cognitive, affective, and other symptoms. Most frequently, the condition is multifactorial in origin, driven by a combination of genetic predisposition and exposure to known or unidentified environmental toxins. Genetically linked Parkinson's disease accounts for less than 510% of cases. While parkinsonism predominantly affects older adults, it can occasionally present at a younger age (early-onset or juvenile form).

The underlying causes of sporadic forms remain largely unknown. The pathology is driven by progressive neurodegeneration involving the loss of dopaminergic Neurons (apoptosis) and The formation of Lewy bodies within deep Brain structures, most notably the substantia nigra. However, standard pathomorphological criteria for diagnosing Parkinson's disease with high sensitivity and Specificity have yet to be universally established.

The spatiotemporal progression of neurodegenerative processes—gradually involving neurons of the Medulla Oblongata, the olfactory tract, the Brainstem, the substantia nigra, the hippocampus, the temporal mesocortex, and neocortical structures—accounts for the wide spectrum of clinical manifestations in parkinsonism (H. Braak et al.). This explains why characteristic motor deficits are accompanied by impairments in Olfaction, internal organ innervation, somatosensory and visceral pain modulation, Sleep architecture, emotional regulation, memory, and cognitive Functions.

The disease features an extended latent period, a pre-motor phase, and a phase of overt motor symptoms. Clinically apparent motor deficits typically emerge only after the loss of at least 60–80% of dopaminergic neurons.

There are four cardinal motor signs of Parkinson's disease: hypokinesia (delayed movement initiation, progressive reduction in speed and amplitude of sequential movements); increased Muscle tone (rigidity); and tremor. The fourth sign, postural instability (impaired balance control), generally develops several years after disease onset.

In addition to motor deficits, patients experience a wide array of non-motor symptoms that can manifest at various stages of Parkinson's disease. These include neuropsychiatric and autonomic symptoms, sleep disorders, sensory disturbances, and other Clinical Features (K. R. Chaudhuri, D. G. Healy, A. H. V. Schapira, 2006). Their combination creates a complex picture of mosaic affective, autonomic, and sensory dysfunction that significantly diminishes patients' quality of life and limits their functional independence.

Neuropsychiatric Symptoms

   • Depression, apathy, anxiety

   • Anhedonia

   • Attention deficit

   • Hallucinations, illusions

   • Dementia

   • Obsessive behavior (potentially medication-induced)

   • Confusion

   • Delirium (potentially medication-induced)

   • Panic attacks

Sleep Disorders

   • Restless legs syndrome and periodic limb movement disorder

   • Rapid eye movement (REM) sleep behavior disorder, loss of REM atonia

   • Non-REM-related movement disorders

   • Excessive daytime sleepiness

   • Vivid dreams

   • Insomnia

   • Sleep-related breathing disorders Autonomic symptoms

   • Urinary disturbances (urgency, nocturia, urinary frequency)

   • Sweating / thermoregulatory dysfunction

   • Orthostatic hypotension

   • Shoulder girdle pain

   • Sexual dysfunction (hypersexuality - frequently medication-induced, erectile dysfunction)

   • Dry eyes (xerophthalmia)

   • Sialorrhea

   • Constipation

Sensory and other symptoms

   • Pain

   • Paresthesias

   • Olfactory disturbances

   • Fatigue

   • Diplopia

   • Blurred Vision

   • Seborrhea

   • Weight loss

   • Weight gain

Non-specific signs of the premotor phase of Parkinson's disease may include constipation, excessive daytime sleepiness, fatigue, hyposmia, as well as hypersalivation, forgetfulness, etc. Rapid eye movement (REM) sleep behavior disorder — characterized by loss of muscle atonia, motor restlessness, violent behavior, and other symptoms — can precede The Development of Parkinson's disease by 3–11 years.

The key Features of the motor symptom phase in parkinsonism are considered to be hypokinesia, rigidity, tremor, and postural instability. The most prominent, although not obligatory, symptom is involuntary tremor of the distal limbs, HEAD, lower jaw, or Tongue at a frequency of 4-6 Hz. Parkinsonism is typically characterized by a resting tremor, which is most pronounced at rest. It worsens with anxiety and, conversely, diminishes during active movements and disappears during sleep. In some cases, characteristic finger movements such as "pill-rolling" or "counting coins" are observed.

Parkinsonism is also characterized by muscle rigidity (increased muscle tone of a plastic type), which is readily detected during passive limb movements. In this case, muscle resistance remains constant throughout the entire range of motion and is independent of its speed. Occasionally, the "cogwheel" phenomenon is observed, which manifests as a sensation of ratchet-like, intermittent resistance during the assessment of passive range of motion and muscle tone. Muscle rigidity in patients with Parkinson's disease frequently causes back and shoulder girdle pain.

Hypokinesia is an obligate sign of parkinsonism, which consists in delayed movement initiation, a gradual decrease in speed and amplitude during repetitive movements (bradykinesia), and, furthermore, a reduction in the volume of associated movements (syncinesias), movement diversity, individual motor characteristics, along with the breakdown and simplification of motor stereotypes (oligokinesia). Hypokinesia is quite frequently the earliest sign of parkinsonism, yet it poses certain diagnostic challenges because patients perceive it as a vague, difficult-to-explain discomfort when performing routine movements, self-care tasks, and everyday activities (buttoning clothes, tying shoelaces, etc.).

Parkinsonism is frequently accompanied by postural instability, which is an impaired ability to maintain balance when changing posture. This phenomenon has recently been regarded as the fourth cardinal sign of parkinsonism, although it typically manifests several years after the onset of the disease.

The combination and gradual progression of primary (nuclear) signs of parkinsonism lead to quite characteristic abnormalities in complex motor activities and behavior. Hypomimia, reduced blinking frequency, a tendency to freeze in various postures, and difficulty initiating movement or changing body position are frequently observed. A characteristic "begging" posture is common, featuring a dropped head, arms and legs slightly flexed at the elbow and knee joints, and forearms held close to the torso. The patient struggles to keep the body's center of gravity within the base of support, and phenomena such as propulsion, lateropulsion, or retropulsion may occur. Paradoxical kinesia may also emerge—a sudden improvement in motor activity triggered by emotional stimuli. Gait becomes slow, shuffling, and short-stepped. During walking, a lack of associated movements (acheirokinesis) is noticeable. Speech becomes quiet, monotonous, and progressively fading, with a characteristic development of phonation disorders (dysphonia). Motor and psychic restlessness, along with an urge to move constantly (akathisia), also develop.

The Diagnosis of parkinsonism is based on clinical signs. Diagnostic criteria include the presence of hypokinesia and at least one of the other three key features: tremor, muscular rigidity, or postural instability. The diagnosis is usually straightforward in patients over 55 years of age, characterized by asymmetrical development of parkinsonian signs (tremor, bradykinesia, or rigidity), progressive motor disorders, and a good response to replacement therapy. To rule out Hydrocephalus, multi-infarct state, Wilson's disease, and other structural-metabolic central nervous system disorders, an MRI is recommended, along with Blood serum ceruloplasmin testing, 24-hour urinary copper measurement, and an ophthalmologic examination. The reliability of the diagnosis becomes questionable in the absence of tremor, acute onset or stepwise progression of motor disorders, or in young patients.

In addition, There is a set of criteria that strongly argues against Parkinson's disease. These include a history of repeated strokes with stepwise progression of parkinsonian symptoms; a history of recurrent TRAUMATIC BRAIN INJURIES or encephalitis; oculogyric crises; neuroleptic Treatment at the time of symptom onset; prolonged remission; strictly unilateral symptoms lasting more than 3 years; downward gaze palsy; early and rapidly progressive autonomic failure; cerebellar signs; early-onset dementia; Babinski signs; cerebellar atrophy or communicating hydrocephalus; lack of response to high doses of levodopa; and exposure to parkinsonism-inducing toxic substances.

The predominance of specific primary motor impairments allows for the identification of the main Clinical forms of Parkinson's disease: tremorous, rigid-tremorous, and akinetic-rigid. The course of the disease is typically progressive. The staging of Parkinson's disease, taking into account the severity of motor impairments, is determined using the specialized Hoehn and Yahr scale.

Effective management of Parkinson's disease is possible through symptomatic replacement therapy, which compensates for dopaminergic system deficiencies in various ways, as well as neuroprotection aimed at slowing disease progression. For this purpose, medications are used that increase dopamine synthesis in the brain, stimulate dopamine release from presynaptic terminals and block its reuptake, prevent dopamine breakdown, stimulate postsynaptic dopamine receptors, and counteract progressive neuronal death.

Class="center">Staging/Severity of Motor Impairments in Parkinson's Disease (Hoehn and Yahr Scale)

Pharmacological Agents Used in the Treatment of Parkinsonism

In the Cytology/cytology/16.html">Early stages of the disease, dopamine agonists, amantadine, selective monoamine oxidase B inhibitors, catechol-O-methyltransferase inhibitors, and anticholinergic agents are widely used. When pronounced motor disorders are present, levodopa preparations are prescribed, which can be combined with dopamine agonists. Combining levodopa with a decarboxylase inhibitor makes it possible to reduce the levodopa dose and thereby lower the risk of side effects. Maintaining a steady blood concentration of medications throughout the 24-hour cycle is crucial to minimizing the risk of dyskinesia and severe fluctuations in motor activity.

If conservative therapy proves ineffective, neurosurgical treatment may be an option. This involves stereotactic ablation of specific groups of thalamic nuclei, the globus pallidus, etc., as well as chronic high-frequency deep brain stimulation using implanted electrodes.

Essential Tremor

Essential tremor is a common hereditary nervous system disorder with an Autosomal dominant inheritance pattern. Molecular genetic studies have established its genetic heterogeneity, yet not all mutant genes responsible for essential tremor have been precisely identified to date. Its prevalence in the general population reaches up to 5.6%. The disease has a relatively benign course characterized by slow progression throughout life. The primary clinical manifestation is hand tremor with a frequency of 6–12 Hz, and less commonly, tremor of the head, Lips, voice, trunk, or legs.

Unlike Parkinson's disease, essential tremor is typically characterized by a single symptom—tremor. Unlike the resting tremor seen in Parkinson's disease, essential tremor emerges During Muscle contraction and limb movement, most frequently in the hands. In a small number of cases, tremor may be accompanied by writing difficulties (writer's cramp), mild Torticollis, and a slight increase in limb muscle tone that never reaches the level of true rigidity. While Parkinson's disease progresses rapidly and severely limits patients' functional independence over time, individuals with essential tremor tend to have a normal Life expectancy and maintain a relatively high quality of life.

High doses of vitamin B₆ are thought to help slow the progression of the disease. The beta-blocker propranolol noticeably reduces tremor severity; it is administered in long-term courses of 10–20 mg twice daily under the monitoring of Heart rate and blood pressure. Mild herbal sedatives are also recommended. Newer antiepileptic drugs (topiramate, levetiracetam, etc.) and atypical antipsychotics (clozapine) are sometimes used to treat essential tremor, though the results of their efficacy remain mixed. It has long been known that small amounts of alcohol can temporarily reduce tremor in many patients with this condition. However, given the potential medical and socio-economic consequences of alcohol consumption and the risk of developing alcohol dependence, this therapeutic recommendation is considered unacceptable by most specialists.

Unlike most other hereditary neurological disorders, Genetic Counseling regarding reproductive options for essential tremor yields a favorable outlook, and prenatal DNA Diagnostics are not performed.

Huntington's Disease

Huntington's disease is an inherited, slowly progressive nervous system disorder with an autosomal dominant inheritance pattern, manifested by choreic hyperkinesia, psychiatric disturbances, and dementia. The prevalence of this condition ranges from 3 to 7 per 100,000 population across various countries. The Huntington's disease Gene, which encodes the huntingtin protein, is located on the short arm of chromosome 4. The disease typically begins after the age of 30 with choreic hyperkinesia, predominantly affecting facial Muscles, alongside cognitive impairment. Patients develop expressive grimaces involving tongue protrusion and frowning, as well as bizarre limb movements that over time transform into choreoathetosis and dystonia, gradually leading to marked muscle rigidity. Limb paresis and other gross focal neurological deficits are absent. Oculomotor abnormalities with vertical, horizontal, or combined nystagmus are characteristic. In juvenile forms of Huntington's disease, bradykinesia, muscle rigidity, and seizures may serve as the initial symptoms. As the disease progresses, speech and swallowing difficulties gradually develop. THE SPECTRUM OF psychiatric and behavioral disorders is dominated by attentional deficits, unmotivated mood swings, disinhibition, impaired insight into one's condition, delusional symptoms, and dementia. A positive family history is crucial for diagnosis, and early detection is possible through molecular genetic testing, including prenatal diagnosis. Symptomatic therapy utilizes dopamine antagonists, while neuroleptics and dopamine agonists are occasionally employed.

Hepatolenticular Degeneration

Hepatolenticular degeneration (Wilson's disease, Westphal-Wilson-Konovalov disease) is an inherited autosomal recessive disorder caused by a mutation in a gene on the long arm of chromosome 13, which encodes a hepatic P-type ATPase involved in ceruloplasmin synthesis and copper elimination from body Tissues. This enzymatic defect results in the accumulation of copper in various Organs and tissues, primarily the Liver, the Basal Ganglia of the brain, the cornea, and the Kidneys. This leads to the blockade of sulfhydryl groups in oxidative Enzymes and disrupts redox processes in the tissues of target organs. The prevalence of the disease is 2–3 cases per 100,000 population. The clinical picture comprises neurological and visceral symptoms, characterized by marked clinical polymorphism. The leading manifestations include an extrapyramidal symptom complex, pseudobulbar disorders, progressive cognitive decline, impaired liver function, and Kayser-Fleischer rings in the cornea. Most patients develop truncal and limb muscle rigidity, leading to gait, swallowing, and speech disturbances. Various hyperkinesias occur, including tremor, limb athetosis, and torsion dystonia. Epileptic seizures, pyramidal signs, and psychiatric disorders may also appear. A pathognomonic sign of hepatolenticular degeneration is the Kayser-Fleischer corneal ring, detected via ophthalmoscopy and caused by copper-containing pigment deposits at the periphery of the cornea. Blood serum tests reveal a significant decrease in ceruloplasmin, while urine tests show a characteristic increase in 24-hour copper excretion. Family history data, typical clinical manifestations, Kayser-Fleischer rings, and relevant laboratory findings help suspect and diagnose hepatolenticular degeneration. Molecular genetic testing is available. Effective treatment is achievable through lifelong administration of thiol compounds that facilitate the elimination of excess copper from the body (unithiol, d-penicillamine, etc.), along with dietary management and symptomatic therapy.

Clinical Problems

Option 1

A 28-year-old male complains of hand tremors that become particularly noticeable during fine motor tasks, emotional stress, or when under the observation of others. He first noticed mild hand trembling at the age of 15 when feeling anxious. Since then, it has slightly worsened, which he tends to attribute to intensive workloads and chronic sleep deprivation. He notes that the tremor diminishes after consuming small amounts of alcohol or taking sedatives. There are no other neurological symptoms. Instrumental neurological examinations (EEG, Echo-EG) revealed no abnormalities. His medical history includes occasional colds. His father, examined over the past decade, exhibits mild tremors of the hands and head.

   • Identify the primary neurological disorders.

   • Formulate the topical diagnosis.

   • Formulate the preliminary clinical diagnosis.

   • Outline the main directions for Differential diagnosis.

   • Describe the instrumental examination protocol.

   • List the known etiopathogenetic variants of tremor.

   • Indicate other possible symptoms of extrapyramidal system involvement.

   • Specify the diagnostic criteria for essential tremor.

   • What is The Role of heredity in the development of this disease?

   • Describe the treatment Methods for the disease.

   • Formulate recommendations for the patient.

   • Determine the prognosis of the disease.

Case 2

A 48-year-old woman has experienced periodic headaches and hand tremors over the past four years. The tremor worsens in the presence of strangers or when anxious, and becomes less noticeable during movement. She is concerned about a decrease in strength and a sensation of muscle tension in her arms and legs, difficulty performing fine and precise movements, and changes in her handwriting. The onset of the disease was gradual, which she associates with stress and emotional distress at work. Her condition has deteriorated recently. Upon examination, notable features include a fixed stare, infrequent blinking, and masked facies (hypomimia). There is slowness and simplification of movements, a lack of gesturing during conversation, a tendency to "freeze" in fixed postures, and an absence of associated arm swing during walking. She turns her head by rotating her entire torso. Her speech is monotonous. Examination reveals oral automatism signs, a slight increase in muscle tone in the arms and legs with a sensation of intermittent resistance during passive movements in the limb joints. She has noted elevated blood pressure for several years.

   • List the main neurological disorders.

   • Determine the leading neurological symptom complex.

   • Name its core components that determine the patient's condition.

   • Indicate the signs of hypokinesia.

   • Characterize the changes in muscle tone.

   • What are the Characteristic Features of tremor in parkinsonism?

   • Formulate the preliminary clinical diagnosis.

   • Determine the directions for differential diagnosis.

   • Outline the scheme and objectives of the instrumental neurological examination.

   • What is the role of heredity in the development of this disease?

   • What autonomic disorders are observed in this disease?

   • List the possible psychiatric disorders associated with this disease.

   • Name the main clinical forms of parkinsonism.

   • Indicate the treatment methods for the disease.

   • What complications and severe neurological deficits may occur as the disease progresses?

   • Formulate recommendations for the patient.

   • Determine the prognosis of the disease.

Option 3

A 38-year-old man presents with involuntary facial grimaces, as well as rapid, random, and bizarre movements predominantly in the shoulder girdle and arms. These movements are aggravated during social interaction and goal-directed activities. When alone, resting, or sleeping, the hyperkinesia diminishes or disappears completely. Speech and self-care are impaired due to numerous excessive and hard-to-control movements. The condition began with facial muscle twitching that appeared about three years ago following a traumatic brain injury caused by a blast wave. Later, the movements gradually spread to the neck and shoulder girdle. Recently, the patient's relatives have noticed behavioral changes, forgetfulness, and inappropriate emotional responses.

   • List the main neurological disorders.

   • Identify the leading neurological symptom complex.

   • Describe the signs of choreic hyperkinesia.

   • Formulate a preliminary clinical diagnosis.

   • Outline the directions for differential diagnosis.

   • Outline the scheme and objectives of further examination.

   • What role does heredity play in the development of this disease?

   • How can The history of remote trauma be interpreted?

   • Indicate the treatment methods for the disease.

   • Determine the prognosis of the disease.