Neurodegenerative Disorders Flashcards
Alzheimer’s Disease Vascular Dementia Parkinson’s disease Huntington’s disease Motor neurone disease Multiple sclerosis Muscular dystrophies
What is Alzheimer’s disease?
A progressive neurodegenerative disorder and the most common cause of dementia, characterized by memory loss, cognitive decline, and behavioral changes
Key pathophysiological changes in Alzheimer’s disease?
Brain atrophy
Amyloid plaques
Neurofibrillary tangles (Tau protein accumulation)
Reduced cholinergic activity
Neuroinflammation
List the main risk factors for Alzheimer’s disease
Advanced age
Family history
Apolipoprotein E4 (APOE4) genotype
Cardiovascular risk factors (e.g., hypertension, diabetes, obesity)
Head trauma
Low educational attainment
What are early symptoms of Alzheimer’s disease?
Forgetting recent events
Difficulty finding words
Trouble performing complex tasks
Mild confusion and spatial disorientation
How do symptoms progress in Alzheimer’s?
Worsening memory loss
Impaired judgment
Behavioral changes (agitation, aggression)
Loss of motor and verbal skills
Dependency in activities of daily living
What cognitive screening tools are used to assess Alzheimer’s disease?
Mini-Mental State Examination (MMSE)
Montreal Cognitive Assessment (MoCA)
Addenbrooke’s Cognitive Examination (ACE-III)
What imaging studies are useful in diagnosing Alzheimer’s?
MRI brain: Shows cortical atrophy, especially in the medial temporal lobes.
What blood tests are done to rule out reversible causes of dementia?
Thyroid function tests
Vitamin B12 and folate levels
Calcium levels
Liver and kidney function tests
What are the drug treatments for Alzheimer’s disease?
Mild to moderate cases: Acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine)
Moderate to severe cases: Memantine (NMDA receptor antagonist)
Non-pharmacological management strategies for Alzheimer’s?
Cognitive stimulation therapy
Structured daily activities
Support for caregivers
What advanced care planning is recommended for Alzheimer’s?
Lasting power of attorney
Advance care directives
Discussion of end-of-life care preferences
What are common behavioral symptoms in Alzheimer’s disease?
Depression
Anxiety
Agitation
Psychosis (hallucinations or delusions)
How are behavioral symptoms managed in dementia patients ?
Non-pharmacological approaches: Music therapy, environmental adjustments, caregiver training
Medications (if necessary): SSRIs for depression, antipsychotics (e.g., risperidone) for severe agitation
What lifestyle changes may reduce the risk of Alzheimer’s?
Regular physical activity
Healthy diet (e.g., Mediterranean diet)
Cognitive engagement (e.g., puzzles, reading)
Cardiovascular risk control
What is Vascular Dementia?
A type of dementia caused by reduced blood supply to the brain, leading to cognitive decline. It is the second most common type of dementia.
What is the underlying mechanism of Vascular Dementia?
It results from ischaemia or hemorrhage causing damage to brain tissue, often due to strokes or small vessel disease.
List key risk factors for Vascular Dementia.
Hypertension
Diabetes
Smoking
Hyperlipidaemia
Atrial fibrillation
Obesity
Sedentary lifestyle
Cardiovascular diseases
Which lifestyle modifications can reduce the risk of developing Vascular Dementia?
Managing hypertension, regular exercise, healthy diet, smoking cessation, and controlling diabetes.
What are the typical symptoms of Vascular Dementia?
Stepwise progression of cognitive decline
Early executive dysfunction (e.g., planning and decision-making difficulties)
Memory impairment
Focal neurological signs (e.g., hemiparesis, dysarthria)
How does Vascular Dementia differ from Alzheimer’s disease in presentation?
It often presents with a stepwise progression and prominent executive dysfunction early on, while Alzheimer’s typically starts with memory loss.
Name conditions that should be considered in the differential diagnosis of Vascular Dementia.
Alzheimer’s disease
Lewy body dementia
Frontotemporal dementia
Normal pressure hydrocephalus
Delirium
Depression
Nutritional deficiencies (e.g., B12 deficiency)
What investigations are used to diagnose Vascular Dementia?
Blood tests (e.g., FBC, U&E, LFT, glucose, lipid profile)
Neuroimaging (MRI or CT to detect vascular lesions and strokes)
Cognitive assessments (e.g., MMSE, MoCA)
Why is MRI preferred in diagnosing Vascular Dementia?
MRI is more sensitive in detecting small vessel disease and ischaemic changes.
What is the primary aim of managing Vascular Dementia?
To prevent further vascular damage and manage symptoms, as the condition is not curable.
List key management strategies for Vascular Dementia.
Controlling risk factors (e.g., managing blood pressure, glucose, and cholesterol)
Antiplatelet therapy (e.g., aspirin) for stroke prevention if indicated
Lifestyle modifications (e.g., regular exercise, healthy diet)
Cognitive rehabilitation
Support for patients and caregivers
What is the prognosis of Vascular Dementia?
Progressive decline over time, with variability depending on the underlying vascular disease and stroke recurrence.
What is Parkinson’s Disease (PD)?
Parkinson’s Disease is a progressive neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra, resulting in reduced dopamine in the basal ganglia.
What are the hallmark motor symptoms of Parkinson’s Disease?
Bradykinesia, rigidity, resting tremor, and postural instability.
What is the pathophysiology of Parkinson’s Disease?
Loss of dopamine-producing neurons in the substantia nigra pars compacta and formation of Lewy bodies (alpha-synuclein deposits).
Describe the resting tremor associated with Parkinson’s Disease.
A “pill-rolling” tremor that occurs at rest and decreases with intentional movement.
What are some non-motor symptoms of Parkinson’s Disease?
Depression, anxiety, cognitive impairment, autonomic dysfunction (e.g., constipation, orthostatic hypotension), and sleep disturbances.
How is Parkinson’s Disease diagnosed clinically?
Diagnosis is based on motor symptoms (bradykinesia with rigidity or tremor) and response to dopaminergic therapy.
What imaging technique can help confirm Parkinson’s Disease?
DaTscan (dopamine transporter imaging), showing reduced dopaminergic function.
What are some causes of secondary parkinsonism?
Drug-induced (e.g., antipsychotics), vascular parkinsonism, and exposure to toxins (e.g., manganese, carbon monoxide).
Name four medication classes used to treat Parkinson’s Disease.
Levodopa/Carbidopa, dopamine agonists, MAO-B inhibitors, and COMT inhibitors.
What is the first-line treatment for motor symptoms of Parkinson’s Disease?
Levodopa/Carbidopa, which is converted to dopamine in the brain.
What are dopamine agonists, and name examples used in PD?
Drugs that mimic dopamine effects; examples include ropinirole and pramipexole.
What is the role of deep brain stimulation (DBS) in Parkinson’s Disease? Change
DBS targets motor symptoms in advanced stages of Parkinson’s Disease, improving quality of life.
List complications of long-term Levodopa use in Parkinson’s Disease.
Motor fluctuations (“on-off” phenomena) and dyskinesias (involuntary movements).
What is Parkinsonism? How does it differ from Parkinson’s Disease?
Parkinsonism refers to a group of disorders with similar motor symptoms but can have other causes, like drugs or vascular damage, unlike idiopathic Parkinson’s Disease.
Name some Parkinsonian syndromes other than idiopathic Parkinson’s Disease.
Multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD).
What are some autonomic symptoms in Parkinson’s Disease?
Constipation, urinary urgency, orthostatic hypotension, and erectile dysfunction.
Describe gait changes observed in Parkinson’s Disease.
Short, shuffling steps with reduced arm swing and freezing episodes during movement initiation.
What is the role of COMT inhibitors in Parkinson’s Disease treatment?
They extend the duration of Levodopa’s action by inhibiting its breakdown (e.g., entacapone).
What are the key features of the Parkinsonian triad?
Tremor, rigidity, and bradykinesia.
What are Lewy bodies, and where are they found in Parkinson’s Disease?
Protein aggregates primarily containing alpha-synuclein, found in dopaminergic neurons in the substantia nigra.
What is Huntington’s Disease?
A genetic neurodegenerative condition caused by a mutation in the HTT gene.
Leads to progressive loss of motor control, cognitive decline, and psychiatric symptoms.
What causes Huntington’s Disease?
Expansion of CAG repeats in the HTT gene on chromosome 4.
The longer the repeat, the earlier the onset and more severe the symptoms.
Abnormal huntingtin protein causes neuronal dysfunction and cell death, particularly in the basal ganglia and cortex.
Which areas of the brain are affected in Huntington’s Disease?
Mainly the basal ganglia (caudate nucleus and putamen).
Leads to disturbances in motor, cognitive, and emotional regulation.
How is Huntington’s Disease inherited?
Autosomal dominant inheritance.
Each child of an affected parent has a 50% chance of inheriting the disease.
Shows genetic anticipation (earlier onset in subsequent generations with increased repeat expansions).
What are the main motor symptoms of HD?
Chorea (involuntary, jerky movements).
Dystonia (muscle rigidity).
Bradykinesia (slow movements).
Impaired voluntary motor control, leading to falls and reduced mobility.
What are the cognitive features of HD?
Progressive dementia.
Difficulties with planning, problem-solving, and concentration.
Memory impairment
What psychiatric symptoms are associated with HD?
Depression.
Anxiety.
Irritability and aggression.
Psychosis (less common).
What is the average age of onset of HD?
Typically between 30 and 50 years, though juvenile forms occur with more severe repeat expansions.
How is Huntington’s Disease diagnosed?
Clinical examination: Chorea, cognitive changes, and family history.
Genetic testing: Confirms the number of CAG repeats in the HTT gene.
Imaging (supportive):
MRI or CT: Shows atrophy of the caudate nucleus and putamen.
Is there a cure for Huntington’s Disease?
No cure; treatment is symptomatic and supportive.
What are the pharmacological treatments for HD?
Chorea:
Tetrabenazine (dopamine-depleting agent).
Antipsychotics (e.g., haloperidol or risperidone) for severe cases.
Psychiatric symptoms:
SSRIs or other antidepressants for depression and anxiety.
Antipsychotics for psychosis or severe agitation.
What supportive care is important in HD?
Physiotherapy to maintain mobility and prevent falls.
Occupational therapy to improve daily function.
Speech and language therapy for dysphagia and communication difficulties.
Nutritional support to manage weight loss due to chorea and swallowing issues
What is the typical disease progression of HD?
Symptoms worsen over 10-25 years.
Leads to severe motor disability, loss of speech, and dependence on caregivers.
Common causes of death: Aspiration pneumonia, cardiovascular disease, or infection.
What is the role of genetic counseling in HD?
Offered to individuals with a family history of Huntington’s Disease.
Pre-symptomatic genetic testing is available but requires careful psychological support.
What ethical considerations are involved in HD?
Testing of minors is not typically performed unless there are clinical symptoms.
Discussions about the implications of a positive test for family planning.
What is Motor Neurone Disease (MND)?
MND is a group of progressive neurodegenerative disorders affecting motor neurons in the brain, brainstem, and spinal cord, leading to muscle weakness and atrophy.
What are the types of Motor Neurone Disease?
Amylotrophic Lateral Sclerosis (ALS), Progressive Bulbar Palsy (PBP), Primary Lateral Sclerosis (PLS), Progressive Muscular Atrophy (PMA).
What is Amyotrophic Lateral Sclerosis (ALS)?
Most common form, affecting upper and lower motor neurons.
Progressive Bulbar Palsy (PBP)
Affects cranial nerves, causing speech and swallowing issues.
Primary Lateral Sclerosis (PLS)
Purely upper motor neuron involvement.
Progressive Muscular Atrophy (PMA)
Purely lower motor neuron involvement.
What is the typical age of onset for MND?
Most cases develop between 50 and 70 years old, with a slight male predominance.
What causes MND?
The exact cause is unknown, but factors include:
Genetic mutations: Such as SOD1, C9orf72 (common in familial cases).
Glutamate toxicity: Excess glutamate may contribute to neuronal death.
Oxidative stress and mitochondrial dysfunction also play roles.
Which neurons are affected in MND?
Upper motor neurons (UMNs) in the corticospinal tract and lower motor neurons (LMNs) in the anterior horn cells of the spinal cord.
What are the hallmark features of UMN?
Spasticity, hyperreflexia, clonus. & No sensory or sphincter involvement.
What are the hallmark features of LMN?
Muscle wasting, fasciculations, flaccidity. No sensory or sphincter involvement.
Which symptoms are seen in ALS?
Progressive limb weakness, difficulty swallowing (dysphagia), slurred speech (dysarthria), and respiratory muscle weakness.
What are “bulbar symptoms”?
Symptoms related to cranial nerve dysfunction, including dysphagia, dysarthria, and tongue wasting.
What tests are used to diagnose MND?
Electromyography (EMG): Shows evidence of denervation and reinnervation.
Nerve conduction studies (NCS): Help exclude neuropathies.
MRI brain/spine: Rules out mimicking conditions (e.g., multiple sclerosis).
Genetic testing: If familial MND is suspected.
What is the diagnostic criteria for ALS?
Based on El Escorial criteria, including clinical, electrophysiological, and neuroimaging findings
What is the mainstay of pharmacological treatment in MND?
Riluzole: Extends survival by reducing glutamate-mediated toxicity.
Edaravone: May slow progression in some patients.
What supportive measures are available for MND?
Nutrition: PEG feeding for dysphagia.
Respiratory support: Non-invasive ventilation (e.g., BiPAP) for respiratory insufficiency.
Physiotherapy and occupational therapy: Maintain mobility and independence.
Speech therapy: Helps with communication and swallowing difficulties.
How is end-of-life care managed in MND?
Focuses on symptom control, including pain management, respiratory support withdrawal when appropriate, and addressing psychosocial needs.
What is the typical prognosis for MND?
The prognosis varies; ALS has a median survival of 3–5 years from symptom onset. Prognosis is better for PLS and PMA.
What factors influence prognosis in MND?
Early respiratory involvement and bulbar onset indicate poorer prognosis.
Slower progression and limb-onset disease are associated with longer survival.
What is the underlying pathophysiology of Multiple Sclerosis (MS)?
MS is an autoimmune, inflammatory, demyelinating disease of the central nervous system (CNS), primarily affecting the brain and spinal cord. It involves T-cell mediated destruction of myelin sheaths and axons, leading to neurological dysfunction.
What is the role of plaques in MS?
MS is characterized by focal areas of demyelination called plaques, which disrupt the conduction of electrical signals in the CNS. These plaques are seen in white matter and can involve grey matter as the disease progresses.
What are the known risk factors for MS?
Female sex (more common in women)
Age (most cases diagnosed between 20-40 years)
Genetic predisposition (e.g., HLA-DRB1 gene variants)
Low vitamin D levels
Smoking
Epstein-Barr Virus (EBV) infection
What are the typical presenting symptoms of MS?
Sensory symptoms (e.g., paresthesia, numbness)
Optic neuritis (painful visual loss in one eye)
Motor symptoms (e.g., limb weakness, spasticity)
Ataxia and tremor
Fatigue
Lhermitte’s sign (electric shock-like sensation on neck flexion)
What are the types of MS based on disease progression?
Relapsing-remitting MS (RRMS): Episodes of relapse with periods of remission.
Secondary progressive MS (SPMS): RRMS that progresses without remission.
Primary progressive MS (PPMS): Steady progression from onset without relapses.
Progressive-relapsing MS (PRMS): Progressive disease with acute relapses.
Which imaging modality is most useful in diagnosing MS?
MRI is the gold standard for MS diagnosis. Key findings include hyperintense lesions on T2-weighted images and gadolinium-enhancing lesions in active disease.
What is the role of lumbar puncture in MS?
Lumbar puncture may reveal oligoclonal bands in the cerebrospinal fluid, indicating intrathecal antibody production.
What blood tests are useful in MS evaluation?
Routine blood tests exclude mimics of MS, such as B12 deficiency and autoimmune diseases (e.g., lupus).
What is the McDonald criteria used for?
The McDonald criteria diagnose MS based on dissemination of lesions in time and space via clinical episodes and MRI findings.
What is the acute treatment for MS relapses?
High-dose intravenous or oral corticosteroids (e.g., methylprednisolone) reduce inflammation during acute relapses.
Name disease-modifying therapies (DMTs) used in MS.
First-line: Interferon-beta, glatiramer acetate
Oral therapies: Fingolimod, dimethyl fumarate
Monoclonal antibodies: Natalizumab, ocrelizumab, alemtuzumab
How is symptomatic management tailored in MS?
Fatigue: Amantadine, exercise
Spasticity: Baclofen, tizanidine
Neuropathic pain: Gabapentin, amitriptyline
Urinary symptoms: Anticholinergics for overactive bladder, intermittent self-catheterization for retention
What are the common complications associated with MS?
Depression and anxiety
Secondary infections (e.g., UTIs)
Physical disability
Increased risk of osteoporosis due to immobility and steroid use
What is Uhthoff’s phenomenon?
Temporary worsening of MS symptoms triggered by heat or exercise.
What factors are associated with a worse prognosis in MS?
Male sex
Older age at onset
PPMS subtype
Early motor or cerebellar involvement
What are muscular dystrophies?
A group of genetic disorders characterized by progressive muscle weakness and wasting due to defects in muscle proteins and muscle cell degeneration.
Name the most common forms of muscular dystrophy.
Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), Myotonic Dystrophy, Facioscapulohumeral Dystrophy (FSHD), and Limb-Girdle Muscular Dystrophy (LGMD).
What causes DMD?
A mutation in the dystrophin gene (DMD gene) on the X chromosome, leading to absent dystrophin protein.
Describe the key clinical features of DMD.
Onset before 5 years old.
Gower’s sign (using hands to rise from the floor).
Calf pseudohypertrophy (enlarged calves due to fat and fibrosis).
Delayed motor milestones, such as walking.
Progressive muscle weakness, starting in proximal muscles.
What complications are associated with DMD?
Cardiomyopathy.
Respiratory failure.
Scoliosis.
Learning disabilities.
What is the management for DMD?
Corticosteroids to slow progression.
Physiotherapy and mobility aids.
Cardiac and respiratory support.
How does BMD differ from DMD?
BMD has a later onset (teens to adulthood).
Mutations result in reduced dystrophin rather than its absence.
Slower progression and milder symptoms compared to DMD.
What are the typical clinical features of BMD?
Muscle weakness, particularly in proximal lower limbs.
Cardiomyopathy.
Preservation of walking ability into adulthood.
What is the genetic cause of Myotonic Dystrophy?
Type 1: CTG trinucleotide repeat expansion in the DMPK gene.
Type 2: CCTG repeat expansion in the CNBP gene.
Key clinical features of Myotonic Dystrophy?
Myotonia (difficulty relaxing muscles).
Weakness in distal muscles.
Cataracts, cardiac conduction abnormalities, and endocrine issues.
Cognitive impairment.
What is the “anticipation phenomenon” in Myotonic Dystrophy?
Symptoms worsen and appear earlier in successive generations due to increasing repeat expansion.
What is the typical presentation of facioscapulohumeral muscular dystrophy (FSHD)?
Asymmetric weakness in facial, shoulder, and upper arm muscles.
Scapular winging.
Relative sparing of lower limbs.
What genetic defect is associated with FSHD?
Deletion of D4Z4 repeats on chromosome 4.
What muscles are primarily affected in LGMD?
Proximal muscles of the shoulders and hips.
How is LGMD inherited?
Autosomal recessive (most common).
Autosomal dominant forms exist.
What is the typical onset and progression of LGMD?
Onset varies widely, and progression depends on the subtype but generally leads to difficulty with climbing stairs, lifting arms, and walking.
How are muscular dystrophies diagnosed?
Clinical assessment (muscle weakness pattern, family history).
Genetic testing for specific mutations.
Muscle biopsy showing dystrophic changes.
Creatine kinase (CK) levels elevated in many types.
What are the general principles of managing muscular dystrophies?
Multidisciplinary approach involving neurology, physiotherapy, cardiology, and respiratory specialists.
Use of assistive devices (e.g., wheelchairs).
Genetic counseling.
What are common complications across all muscular dystrophies?
Respiratory failure.
Cardiomyopathy.
Joint contractures.
Reduced mobility and independence.
Define dementia.
Dementia is progressive cognitive impairment due to degenerative or vascular disease sufficient to impair daily activities.
Mild cognitive impairment (MCI) refers to _________ but does not significantly affect _________.
cognitive decline; daily activities.
What are the three main components of the dementing syndrome?
Cognitive decline.
Behavioral changes (e.g., mood, hallucinations, delusions, aggression).
Physical decline.
Match the following lobes to their primary functions:
Temporal lobe.
Parietal lobe.
Frontal lobe.
Occipital lobe.
Temporal lobe: Memory and emotional circuits (medial); word and picture meaning (lateral).
Parietal lobe: Spatial awareness, sensory function, reading/writing/calculation.
Frontal lobe: Personality, behavior, executive function, motor areas.
Occipital lobe: Vision and visual recognition.
The _________ circuit is involved in limbic memory, while the angular gyrus in the parietal lobe is key for _________
medial temporal; reading, writing, and calculation.
List the four main causes of dementia.
Alzheimer’s disease.
Vascular dementia.
Frontotemporal dementia.
Lewy body dementia.
What are three common symptoms of Alzheimer’s disease?
Amnesia.
Visual and spatial disorientation.
Dysphasia.
What are common signs of vascular dementia?
Mental and physical decline.
Pseudobulbar palsy.
Shuffling gait.
Stigmata of vascular risk.
Name three clinical features of Lewy body dementia.
Parkinsonism (rigidity, bradykinesia, tremor).
Fluctuating confusion.
Visual hallucinations.
What are two hallmark features of frontotemporal dementia?
Personality changes.
Dysexecutive syndrome (frontal cognitive impairment).
True/False: Frontotemporal dementia is associated with early motor signs.
False (motor signs are absent initially).
What are the subtypes of frontotemporal dementia?
Behavioral variant FTD.
Semantic dementia.
Primary progressive aphasia.
What are key elements to cover in the history for dementia?
Concentration and attention.
Memory and orientation.
Reading, writing, comprehension.
Mood and behavior.
Activities of daily living.
What physical examination findings may be observed in dementia?
Myoclonus.
Primitive reflexes.
Astereognosis.
Finger agnosia.
