Neuro 3 Flashcards
Types of Dementia
Alzheimer’s Dementia
Vascular Dementia
Lewy Body Dementia
Fronto-temporal Dementia (Pick’s disease)
Other Neurological Diseases
Parkinsonism/ Parkinson's Disease Huntington's Chorea Motor Neuron Disease Guillain-Barre Syndrome Myasthenia Gravis Neurofibromatosis Wernicke-Korsakoff Syndrome
Alzheimer’s Dementia - who?
Elderly (although early-onset subtype)
Alzheimer’s Dementia - RF
Age
Genetics
Down’s Syndrome
Alzheimer’s Dementia - Pathophysiology
Beta amyloid plaques - disrupts signalling
Tau neurofibrillary tangles - disrupts microtubules in neurons.
Decrease in cortical ACh
Alzheimer’s Dementia - Onset/Progression
Gradual, Progressive
Alzheimer’s Dementia - Presentation
5 A’s
+/- Depression
+/- Paranoid delusions
5 A's: Amnesia Anomia Apraxia Agnosia Aphasia
5 A’s of Alzheimer’s
Amnesia - remembering Anomia - naming Apraxia - doing Agnosia - recognizing Aphasia - speaking
Alzheimer’s Dementia - Genetics
Early Onset
Younger than 65 yrs old
Presenilin 1
Presenilin 2
APP gene
Alzheimer’s Dementia - Genetics
Late Onset
Older than 65 yrs old
Apolipoprotein E4
Which of the following is not classically a feature of Alzheimer’s Disease?
Amnesia Anomia Apraxia Ataxia Depression
Ataxia
Down’s Syndrome is associated with which form of dementia?
Alzheimer's dementia Pick's disease Lewy body dementia Frontotemporal dementia Vascular dementia
Alzheimer’s Dementia
APP
Amyloid Precursor Protein
–> helps neurons grow and repair; gets used, broken down and recycled.
Vascular Dementia - Who?
Elderly
Vasculopaths
Vascular Dementia - RF
M>F
Elderly
CVD risk factors
Vascular Dementia - Pathophysiology
Infarction of small and medium sized vessels
Vascular Dementia - Onset/Progression
Sudden onset
Stepwise deterioration
Vascular Dementia - Presentation
+/- Like Alzheimer’s
Location-specific deficits
Emotional and personality changes
Focal neurology
Pick’s Disease - Who?
40-60yrs
Pick’s Disease - RF
+/- FHx (although most sporadic)
Pick’s Disease - Pathophysiology
Pick Bodies: Hyperphosphorylated tau protein
Pick’s Disease - Onset/Progression
Death within 5-10 yrs
Pick’s Disease - Presentation
Personality change Disinhibition Emotional blunting Relative preservation of memory Overeating, preference for sweet foods
Silver staining Tau
An elderly gentleman is accompanied to the GPs with his daughter. She is distressed that ‘something’s happened to Dad, he’s changed …’. It transpires that he has started swearing at people in the street and flirting with all the women he meets. He scores well on an AMTS.
What is the likely Dx?
Pick’s disease Lewy body dementia Vascular dementia Alzheimer’s dementia CJD
Pick’s Disease
Lewy Body Dementia - Who?
Middle age to elderly
Lewy Body Dementia - RF
-
Lewy Body Dementia - Pathophysiology
Lewy Bodies: Eosinohilic intracytoplasmic neuronal inclusions composed of apha-synuclein and ubiquitin
Lewy Body Dementia - Onset/Progression
Fluctuating
Lewy Body Dementia - Presentation
Classic Presentation (2+ needed for Dx):
Fluctuating confusion and consciousness Visual hallucinations (people, animals) New onset Parkinsonism \+/- Repeated falls \+/- Syncope
Parkinsonism classic presentation
Classic Presentation:
Bradykinesia
Resting tremor (4-6Hz)
Rigidity (increased tone)
+/- postural instability
Parkinsonism - what else?
6 M’s:
Monotonous, hypotonic speech Micrographia hypomiMesis (expressionless face) March a petit pas (classic gait) Misery (depression) Memory loss (dementia)
Parkinsonism - Causes?
Idiopathic Parkinson’s Disease:
Asymmetric signs of Parkinsonism
Drug induced Parkinson’s:
Bilateral, symmetrical signs
Parkinson’s Plus:
Additional features present
Idiopathic Parkinson’s Disease - Pathophysiology
Decreased Dopamine - Degeneration of dopaminergic neurons in the substantia nigra
Parkinsonism - Signs
Cogwheel rigidity
(Lead-pipe rigidity and tremor)
March a petit pas
(Gait with little steps - as if chasing one’s centre of gravity)
Which of the following is not classically a feature of idiopathic Parkinson’s disease?
Athetosis Hypomimia March a petit pas Depression Micrographia
Athetosis
Parkinson’s Plus
Multiple system atrophy [MSA] - AKA Sky-Dragar Syndrome: Early autonomic features.
Progressive Supranuclear Palsy [PSP] - AKA Steele-Richardson-Olszewski Syndrome: Early postural instability and vertical gaze palsy.
Lewy Body Dementia: Early dementia and visual hallucinations.
Corticobasal ganglionic degeneration [CBD]: Alien limb phenomenon.
Vascular Parkinson’s: Legs particularly affected; Gait worse than tremor.
Huntington’s Chorea - Who?
About 40 yrs old - anticipated.
Huntington’s Chorea - Inheritance
Autosomal Dominant
Huntington’s Chorea - Genetics
HTT gene on Chr. 4
Anticipation: Age of onset links to number of CAG repeats.
Huntington’s Chorea - Presentation
Movement: Involuntary Movements. Chorea (purposeless, dance-like movements) and Athetosis (writhing movements of hands)
Cognitive: Dementia + Personality Changes
Mood: Depression
FHx: Increasingly early onset throughout generations
Huntington’s Chorea - Prognosis
No cure
No Rx slows progression
Death within 15 yrs of Dx
Huntington’s Chorea - Pathophysiology
Repeat Expansion:
Normal HTT gene = 10-35 CAG repeats
HD HTT gene = >36 CAG repeats
HTT –> Glutamine
Theory: Increased glutamine aggregates in caudate and putamen –> neuronal death.
Motor Neuron Disease
ALS - Motor Nerves Affected
Amyotrophic Lateral Sclerosis
(Lou Gehrig’s Disease)
UMN and LMN
Motor Neuron Disease
ALS - Presentation
UMN + LMN signs
Motor Neuron Disease
Progressive Muscular Atrophy Variant - Motor Nerves Affected
LMN only
Motor Neuron Disease
Progressive Muscular Atrophy Variant - Presentation
LMN signs only - e.g. flail arm/flail foot syndrome
Motor Neuron Disease
Progressive bulbar palsy variant - Motor Nerves Affected
Cranial Nerves XI - XII
Motor Neuron Disease
Progressive bulbar palsy variant - Presentation
Tongue: Flaccid, Fasciculating tongue
Jaw: Absent Jaw-Jerk
Voice: Nasal ‘Donald Duck’ Voice
Motor Neuron Disease Types
Amyotrophic Lateral Sclerosis [ALS] “Lou Gehrig’s”
Progressive Muscular Atrophy Variant
Progressive Bulbar Palsy Variant
Pseudobulbar Palsy
Primary Lateral Sclerosis Variant
Motor Neuron Disease
Pseudobulbar Palsy - Motor Nerves Affected
UMN lesion of cranial nerves IX - XII
Motor Neuron Disease
Pseudobulbar Palsy - Presentation
Tongue: Slow movements
Jaw: Brisk Jaw jerk
Voice: ‘Hot Potato’ Speech
Motor Neuron Disease
Primary Lateral Sclerosis Variant - Motor Nerves Affected
Loss of Betz cells in motor cortex - mainly UMN
Motor Neuron Disease
Primary Lateral Sclerosis Variant - Presentation
UMN pattern of weakness
Brisk reflexes
Extensor plantar response
No LMN signs
Multiple Sclerosis - Definition
Multiple lesions separated in time and space
Demyelinating disease of the CNS
Multiple Sclerosis - Pathophysiology
Type IV hypersensitivity reaction
Multiple Sclerosis - Who?
Female
20-40
White
Multiple Sclerosis - Presentation
PC of one neurological problem
PMH of unrelated neurological problem
+/- symptoms triggered/exacerbated by hot bath/shower - triggers demyelination
Multiple Sclerosis - O/E
Early signs - papillitis
Multiple Sclerosis - Types
Primary progressive MS - Steady accumulation of disability with no clear relapsing/remitting pattern.
Relapsing-remitting MS - Unpredictable clinical attacks with complete recovery in between attacks.
Progressive-relapsing MS - Steady declines in onset, with attack superimposed.
Secondary progressive MS - Initially relapsing and remitting MS that suddenly begins to have decline without periods of remission.
Relapsing and remitting –> Progressive
Papilloedema vs Papillitis
Papilloedema... Cause: Raised ICP Appearance on Fundoscopy: Blurred optic disc margin Vision: Normal Eye movements: No pain Bilateral
Papillitis…
Cause: MS (inflammation of optic nerve head)
Appearance on Fundoscopy: Blurred optic disc margin
Vision: Blurred
Eye movements: Pain on movement
Unilateral
Guillain-Barre Syndrome - RF
Recent URTI or Gastroenteritis (Campylobacter jejuni)
Guillain-Barre Syndrome - Pathophysiology
Autoimmune
Guillain-Barre Syndrome - Classic Presentation
Sudden onset
Ascending symmetrical muscle weakness and decreased sensation
LL > UL
Distal muscles > Proximal muscles
Guillain-Barre Syndrome - O/E
Flaccid paralysis
Absent reflexes
Guillain-Barre Syndrome - Complications
Respiratory failure (1/4)
Guillain-Barre Syndrome - Miller-Fisher Variant
(rare)
Opthalmoplegia
Ataxia
Arreflexia
Myasthenia Gravis - Antibody
AChR
Myasthenia Gravis - Key feature
Muscles fatigue with use
Myasthenia Gravis - Presentation
Drooping eyelids, slurred speech, swallowing difficulties
+/- SOB
Myasthenia Gravis - Reflexes
Normal
Myasthenia Gravis - Association
Thymic hyperplasia (70%) Thyoma (10%)
Neurofibromatosis Type 1 - Inheritance
Autosomal Dominant
Neurofibromatosis Type 1 - Gene
NF1
Chr.17
Neurofibromatosis Type 1 - Commoner?
Commoner
Neurofibromatosis Type 1 - Presentation
Cafe-au-lait spots Freckling in skin folds (axilla, groin, neck base, under breast) Neurofibromas Lisch nodules Spinal scoliosis
Neurofibromatosis Type 1 - Other features
Short stature
Mild learning difficulty
Cafe au lait spots Dx
Pre-pubertal: > 5 spots > 5mm each
Post-pubertal: > 5 sports > 15mm each
Neurofibromatosis Type 2 - Inheritance
Autosomal Dominant
Neurofibromatosis Type 2 - Gene
NF2
Chr.22
Neurofibromatosis Type 2 - Commoner?
Rarer
Neurofibromatosis Type 2 - Presentation
Sensorineural hearing loss: Bilateral vestibular Schwannomas (acoustic neruomas), becoming symptomatic by age 20
Neurofibromatosis Type 2 - Other features
No or fewer Cafe au lait spots than NF1
+/- Tinnitus
+/- Vertigo
Which of the following is not classically a feature of idiopathic neurofibromatosis type 1?
Cafe au lait spots Neurofibromas Auditory neuromas Lisch nodules Skin fold freckling
Auditory neuromas
Wernicke-Korsakoff Syndrome - Types
Wernicke’s encephalopathy
Korsakoff’s psychosis
Wernicke’s Encephalopathy - Cause
Thiamine Deficiency
Wernicke’s Encephalopathy - Who?
Alcoholics !
Malnourished
Elderly
Wernicke’s Encephalopathy - Acute/Chronic?
Acute
Wernicke’s Encephalopathy - Reversible?
Yes
Wernicke’s Encephalopathy - Presentation
Classic Presentation: ACE
Ataxia
Confusion
Eye signs: opthalmoplegia nystagmus
Korsakoff’s Psychosis - Cause
Thiamine deficiency
Korsakoff’s Psychosis - Who?
Alcoholics !
Malnourished
Elderly
Korsakoff’s Psychosis - Acute/Chronic?
Chronic
Korsakoff’s Psychosis - Reversible?
No (…?)
Korsakoff’s Psychosis - Presentation
Memory Loss
Confabulation
You are called to see a 40yo man in A&E. You try to take a Hx but the man in confused and unable to tell you much. O/E he has a cerebellar ataxia and nystagmus.
What is the likely Dx Multiple sclerosis Head trauma Korsakoff’s Wernicke’s Motor neuron disease
Wernicke’s
