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

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

NEUROLOGICAL

DISORDERS IN THE ELERLY

PART II

Márta Balaskó and Gyula Bakó

Molecular and Clinical Basics of Gerontology – Lecture 17

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

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

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

Neurodegenerative diseases affecting

motor functions: classification

Neurodegenerative diseases affecting motor functions

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

Parkinson’s disease: etiology prevalence

• 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

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 dyskinesis

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

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

Myasthenia gravis

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

Pathomechanism of myasthenia gravis

A nerve ending

Acetylcholine is released from

nerve ending Neuromuscular junction (gap between

nerve and muscle)

Some receptors are blocked or damaged

by antibodies

Some receptors are stimulated by

acetylcholine Surface of

muscle fiber Antibody

Muscle Nerve

Nerve endings spread along

muscle

Receptor on surface of muscle fiber

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 B₁₂, B₁ 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

sweating, gastric dysmotility, impotence, incontinence, etc.