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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Márta Balaskó and Gyula Bakó Molecular and Clinical Basics of Gerontology Lecture 17 NEUROLOGICAL DISORDERS IN THE ELERLY PART II

The most common aging-associated neurological disorders (outline) Disorders of cerebral blood flow (stroke) Neurodegenerative diseases affecting motor (and later cognitive) functions (e.g. Parkinson s diasease) Other, more frequent neurological disorders also present in old individuals with high prevalence: - myasthenia gravis - headache - dizziness (vertigo) in the elderly Peripheral neuropathies

Neurodegenerative diseases affecting motor functions: classification Earlier definitions: extrapyramidal disease, diseases of the basal ganglia Types: Hypokinetic syndromes - Parkinson s disease - Symptomatic parkinson syndromes - Multiple system atrophy Hyperkinetic syndromes - Huntington chorea - Creutzfeldt-Jakob disease

Parkinson s diasease Movement-related disease of unknown origin including shaking, rigidity, slowness of movement and difficulty with walking with dementia in the later phases. Huntington-chorea A neurodegenerative autosomal dominant genetic disorder that affects muscle coordination (with abnormal involuntary writhing movements = chorea) with cognitive decline and dementia. Creutzfeldt-Jakob disease A rare, degenerative, invariably fatal brain disorder Neurodegenerative diseases affecting motor functions TÁMOP-4.1.2-08/1/A-2009-0011

Parkinson s disease: etiology prevalence TÁMOP-4.1.2-08/1/A-2009-0011 A disease with progressive movement disorder Special progressive cell death of the substantia nigra with consequent dopamine deficiency The origin of the cellular damage is unknown Risk factors: AGE Noxious effects (CO poisoning, infections, pesticides) Mutations of the tau-gene Prevalence: 100-200/100,000 population It is more frequent in males (1.5 : 1)

Neurotransmitter imbalance in Parkinson s disease TÁMOP-4.1.2-08/1/A-2009-0011 Balance between dopamine and glutamate/acetylcholine Imbalance as a result of dopamine deficiency Glutamate Acetylcholine Dopamine Glutamate Acetylcholine Dopamine

Parkinson s disease: early symptoms Symptoms: Asymmetry: one-sided motor symptoms - tremor (at rest and aggravated by sustained effort), - rigidity of muscles (cogwheel phenomenon upon passive movement of limbs), - hypo- and bradykinesis (difficulty in initiating movement and getting frozen during the course of it), - lack of expression in the face (mask-like face, diminished eye blinking) - postural abnormalities - slow and monotonous speech Upon levodopa administration symptoms improve Long-term (levodopa) treatment itself also leads to

Parkinson s disease: late symptoms Motor functions postural instability (after 8-10 years) Autonomic functions seborrheic oily skin orthostatic hypotension gastrointestinal disorders (dysphagia, constipation) sphincter disturbances impotence enhanced sweating Cognitive decline intellectual impairment occurs invariably (mechanism unknown)

Secondary (symptomatic) parkinsonism TÁMOP-4.1.2-08/1/A-2009-0011 Different types of secondary Parkinsonism show somewhat similar symptoms as Parkinson s disease, but they do not react to levodopa. The progression is frequently more rapid. Infections: complications of viral encephalitis Atherosclerosis of cerebral vessels: vascular Parkinsonism Toxins: Carbon monoxide, Manganese Drugs: neuroleptic drugs, reserpine, metoclopramide, methyldopa Metabolic disorders: parathyroid disorders, cerebral hypoxia Tumors Head trauma Other degenerative disorders: e.g. striatonigral degeneration, Olivopontocerebellar atrophies, Shy-Drager syndrome

Huntington disease (chorea) Characteristics: 5-10/100,000 population Autosomal dominant inheritance (huntingtin, chromosome 4) Onset: 40-50 years of age Mean survival does not exceed 15 years Main symptom: involuntary abnormal choreiform writhing movements Psychiatric symptoms are present from the beginning (affective disorders, schizoform symptoms) No available treatment

Creutzfeldt-Jakob disease Characteristics: Prevalence: rare: 1 / 1,000,000 population Cause: prion (infectious agent composed of protein in a misfolded form) Onset is usually about the age of 60 years (50-70) Triade of symptoms: - dementia (starts with failing memory, mental deterioration) - characteristic EEG findings - myoclonus Other symptoms occur during progression: involuntary movements and muscle weakness, blindness, coma. Progression: 0.5-1 year survival

The most common aging-associated neurological disorders (outline) Disorders of cerebral blood flow (stroke) Neurodegenerative diseases affecting motor functions (e.g. Parkinson s disease) Other, more frequent neurological disorders also present in old individuals with high prevalence: - myasthenia gravis - headache - dizziness (vertigo) in the elderly Peripheral neuropathies

General characteristics An autoimmune neuromuscular disease affecting acetylcholine receptors Leading symptoms: fluctuating muscle weakness and fatiguability that ameliorates upon rest The disease affect predominantly: - ocular (ptosis), - bulbar (swallowing, chewing, speech) - facial muscles (lack of facial expression) - Neck - skeletal muscles - respiratory muscles (diaphragm), respiratory failure Myasthenia gravis

Pathomechanism of myasthenia gravis Nerve endings spread along muscle Nerve Muscle Antibody Surface of muscle fiber Some receptors are blocked or damaged by antibodies A nerve ending Acetylcholine is released from nerve ending Neuromuscular junction (gap between nerve and muscle) Receptor on surface of muscle fiber Some receptors are stimulated by acetylcholine

Myasthenia gravis in the elderly Special characteristics in the elderly It progresses to a severe, fatal disease more frequently sooner Complete remission occurs rarely Crises presents higher risk for lethal outcome Immunosuppressive treatment is more frequently needed More frequent drug side-effects Comorbidities (e.g. hypothyroidism 15%)

Head-aches in the elderly Primary (60-70% of all head-aches) Migraine (much less prevalent than in the young) Tension head-ache (frequent) Cluster head-ache (predominantly in males, above 60 years) Secondary (they are more prevalent in the elderly) Intracranial vascular diseases Intracranial tumor, inflammation Other disease-associated forms (e.g. ear-throat and nose, diseases of the locomotor system) Drug-induced (e.g. nitrate) Immune disease-associated (arteritis temporalis) Trauma-associated (chronic subdural hematoma)

Dizziness in the elderly Characteristics: Very frequent complaint in the elderly 30% of people older than 65 years experience dizziness in some form, increasing to 50% in the very old (older than 85 years) Above 80 years of age: females 66%, males 33% It is often associated with depression, Anxiety increases the prevalence 45-70% of the elderly suffer a fall at least once a year (dizziness is often found in the background)

Dizziness in the elderly: causes Vertebrobasilar circulatory disorders (the most frequent cause among the elderly) Degenerative diseases or ischemia affecting the vestibular organ Degeneration of mechanoreceptors in the neck region Diminished physical activity due to some other disease, immobilization Oscillations of blood pressure Exsiccosis (hypovolemia)

The most common aging-associated neurological disorders (outline) Disorders of cerebral blood flow (stroke) Neurodegenerative diseases affecting motor (and later cognitive) functions (e.g. Parkinson s disease) Other, more frequent neurological disorders also present in old individuals with high prevalence: - myasthenia gravis - headache - dizziness (vertigo) in the elderly Peripheral neuropathies

Peripheral neuropathy in the elderly Peripheral neuropathy is a widespread damage of the peripheral nervous system. Prevalence: 2400/100,000 (2.4%), rising with age to 8000/100,000 (8%). In the elderly, losses of vibratory sensation in the lower extremities and ankle reflexes are common. Causes: (40-70% idiopathic or autoimmune): diabetes mellitus (most frequent known cause in Europe) aging, alcoholism, HIV, toxin exposure, metabolic abnormalities, vitamin B 12, B 1 deficiencies, side effects of drugs Consequences: sensory, motor, autonomic deficits Symptoms include also paresthesia, pain, weakness, paralysis, distortion of the feet, orthostatic hypotension, disorders of