Neurodegenerative diseases Flashcards
Neurodegenerative diseases
What is multiple sclerosis?
A chronic inflammatory multifocal, demyelinating disease of the CNS with unknown cause, leading to loss of myelin, and oligodendroglial and axonal pathology
(autoimmune disease attacking myelin)
What are the symptoms of MS?
Optic neuritis- blurred vision
Motor weakness
Sensory disturbances
Fatigue
Depends on the location of demyelination
What are the signs of MS?
Retrobulbar neuritis Papillitis Diplopia Nystagmus Internuclear ophthalmoplegia Intention tremor/ataxia/dysmetria Lhermitte's sign
What are the features of retrobulbar neuritis?
Pt reports blindness
Fundoscopy shows no abnormality
(Pt sees nothing, Dr sees nothing)
What are the features of papillitis?
Hyperaemia and oedema of the optic disc
What are the features of internuclear ophthalmoplegia
The affected eye has an inability to adduct and the contralateral eye can abduct, but with nystagmus
Pt will complain of horizontal diplopia
What is Lhermitte’s sign?
Shock radiating down spine upon neck flexion
What is the epidemiology of MS?
Latitude effect (more prevalent in higher latitude)
What are the risk factors of MS?
Psoriasis/AI conditions
HLA DLR B1*15
What are the types of MS?
Relapsing-remitting MS
Primary progressive MS
Secondary progressive MS
What is relapsing-remitting MS?
The patient will have symptomatic episodes of MS, whilst feeling fine between relapses
What is primary progressive MS?
There is a constant progression of worsening symptoms
What is secondary progressive MS?
The Pt starts off as RRMS, but developings into PPMS
What are the investigations for MS?
Diagnosis is based off of:
- Clinical Hx/Exam
- MRI
- CSF
- VEPs- visual evoked potential is delayed
How is MS diagnosed?- key features
Clinical diagnosis. No one specific test.
Need to tick the following:
- absence of alternative diagnosis
- disseminated in time- If you have one flare of MS- 1x CT showing demyelinating plaques, isn’t diagnostic. Need =>2 events.
- disseminated in space- affects different parts of the body
Which contrast is beneficial for an MRI scan of a MS Pt?
Gadolinium- light up areas of active inflammation
Shows active flares of MS- white shows acute
What should you expect to find in the CSF for MS?
Oligoclonal bands in the CSF, but not in the serum
Autoimmune so B cells involved in pathophysiology - secrete immunoglobulins which destroy myelin
- If found in serum = infection
- If only found in CSF = MS
What is myasthenia gravis? What causes it
Weakness in muscles through repeated use
Antibodies in the NMJ block ACh receptors, preventing the binding of ACh to its receptor –> can’t stimulate them after short amount of use
What are the 2 common types of myasthenia gravis antibodies?
AChR antibody
MuSK antibody
What are the signs of myasthenia gravis?
Muscles fatigue with use - Ptosis - Diplopia - Dysarthria - Dysphagia - SOB Muscles get fatigued so neuro exam may be normal at first but if muscles used repeatedly then they become abnormal
What are the signs of myasthenia gravis?
Fatiguable muscles
Normal reflexes
What is the epidemiology of myasthenia gravis?
Common in women<40 and men>60
What are the investigations of myasthenia gravis?
Bloods: anti-AChR, anti-MuSK
EMG- shows reducing amplitude of response
CT/MRI - check thymus
What are the associations of myasthenia gravis?
Thymic hyperplasia- 70%
Thyoma- 10%
What is Lambert-Eaton Myasthenic Syndrome?
Muscle weakness with improvement on use
Don’t work well at start but as axons increasingly fire more VGCCs open and the muscle is eventually stimulated
Affects VGCCs- antibodies bind and block so inhibit acetylcholine release and muscle contraction
What are the symptoms of LEMS?
Difficulty walking
Weakness in upper arm/shoulder
Similar to MG symptoms
Dry mouth, constipation, incontinence (autonomic)
What are the signs of LEMS?
Muscles get better with use
Hyporeflexia
What pathologies are associated with LEMS?
- Small cell lung cancer- LEMS can be a paraneoplastic syndrome
- Autoimmune conditions
What are the investigations for LEMS?
Bloods: anti-VGCC
EMG
CT/MRI
What is motor neurone disease (AKA amyotrophic lateral sclerosis)?
Chronic neurodegenerative condition causing muscle wasting, paralysis, and death
What are the symptoms of MND?
Progressive muscle weakness –> wheelchair-bound
Impaired swallowing and speech (bulbar signs)
Spastic weakness and paralysis in skeletal muscle
Respiratory failure (weak intercostals)- cause of death usually muscle in chest wall
Sparing of the oculomotor, sensory, and autonomic function (aka bowel, bladder, sexual function intact)
Does MND present with UMN or LMN signs?
Both UMN and LMN signs
What are the signs of MND?
UMN + LMN signs- classic combination
Wasting of thenar muscles
Wasting of bulbar muscles of the tongue
What is the cause of MND?
Ubiquinated proteins in the motor neurons kills the cells- accumulation of misfolded proteins –> apoptosis
Leads to death of corticospinal tracts
97% of Pts have ubiquitin inclusions positive for TDP-43
What are the investigations for MND?
Clinical diagnosis
Can do the following: EMG- see fasciculations CT/MRI B12/folate HIV Lyme disease seroloy
These are done to rule out other causes
What are the 4 types of MND?
Progressive muscular atrophy (LMN)
Progressive bulbar palsy (CN)
Pseudobulbar palsy (UMN)
Primary lateral sclerosis (UMN)
Which nerves are affected in progressive muscular atrophy and what is the typical presentation?
LMN only
LMN signs only- flail arm/foot syndrome
Which nerves are affected in progressive bulbar palsy
and what is the typical presentation?
CN XI-XII
Flacid fasciculations of tongue
Absent jaw jerk
Nasal voice (Donald Duck)
Which nerves are affected in pseudobulbar palsy
and what is the typical presentation?
UMN lesion of CN IX-XII
Slow tongue movements
Hyper-reflexic jaw jerk
“Hot potato” speech
Which nerves are affected in primary lateral sclerosis and what is the typical presentation?
Loss of Betz cells in motor cortex, mainly UMN UMN weakness pattern Brisk reflexes Extensor plantar respones No LMN signs
What are the types of Parkinsonism?
Parkinsonism = collection of signs and symptoms, can be caused by:
- Parkinson’s disease- death of dopamine neurones
- Drug induced
- Atypical Parkinsonisms- eg PSP
What is Parkinson’s disease?
Loss of dopaminergic neurones in the substantia nigra pars compacta in the midbrain
What are the clinical features of Parkinson’s?
Classic Parkinsonism triad + 6 M’s:
- Monotonous, hypotonic speech (get quieter)
- Micrographia
- hypoMimesis
- March a petit pas (shuffling gate, little steps)
- Misery- depression
- Memory loss- dementia
Cogwheel rigidity (used in tone assessment), postural instability, lack of arm swinging
What is the classic Parkinsonism triad?
Resting tremor
Bradykinesia
Rigidity
What are the causes of drug induced Parkinsonism?
Drugs that lower dopamine levels
- antipsychotics
- antiemetics
What is the cause of Parkinson’s disease?
- Misfolds of alpha-synuclein accumulate to form Lewy bodies/neurites
- Degenerative - progessive death of dopaminergic neurones in substantia nigra
- This eventually triggers cell death
The damage to which pathway causes the motor symptoms in Parkinson’s?
Nigrostriatal
The striatum is required for smooth function movement, and inhibition of oppositional movement
The damage to which pathway causes the cognitive symptoms in Parkinson’s?
Mesolimbic and mesocortical
What are the risk factors for Parkinson’s?
Male 4:1
Aging
FHx
links to insecticide
What are the types of atypical Parkinsonism’s?
Multiple system atrophy Progressive supranuclear palsy Corticobasal degeneration Vascular Parkinson's Lewy body dementia
What is multiple system atrophy?
Collective term for 3 conditions
Cerebellar and cortical atrophy
Papp-Lantos bodies
What is progressive supranuclear palsy?
Early postular instability and vertical gaze palsy
What is corticobasal degeneration?
Alien limb phenomenon
Pt is unaware of moving their limb
What is vascular Parkinson’s?
Caused by a stroke
Legs particularly affected
Gait worse than tremor
What is Lewy body dementia?
Early dementia and visual hallucinations
Due to Lewy body deposition in the cortex
What is Parkinson’s disease dementia?
Very similar to Lewy body dementia
Differential- dementia develops many years after the onset of motor symptoms
Amnestic, language deficits Visuospatial dysfunction Hallucinations Fluctuations Aggression/anxiety
What is dementia?
Severe loss of memory and other cognitive abilities which leads to impaired daily function, regardless of the underlying cause
Issues with:
- cognition, memory
- mood
- motivation + attention
What is the main risk factor for dementia?
Age- why women is more common than men (survive longer)
What are the typical signs of Alzheimer’s?
6 As:
Amnesia- Starts short term memory loss
Anomia- naming things, people
Attention- following conversations, esp groups
Apraxia- doing specific tasks eg brushing teeth
Agnosia- recognising
Aphasia- speaking
+/-depression
+/-paranoid delusions
What is the main investigation for Alzheimer’s and what will the result be?
MRI head
Visual atrophy of the cortex and medial temporal lobes (where the hippocampi are located)
Global atrophy- entirety of brain eventually atrophies
Hippocampus involved in encoding memories, so people struggle to form new memories
Can still retrieve old memories
What is the cause of Alzheimer’s?
BETA AMYLOID + TAU
AMYLOID PRECURSOR PROTEIN usually spliced by alpha and gamma secretase
In Alzheimers, BETA SECRETASE replaces ALPHA SECRETASE
Product is insoluble (amyloid beta)
Forms BETA AMYLOID PLAQUES, which can impair brain function
Microtubules in the neuron contains Tau
TAU PROTEINS get phosphorylated, clumping together, forming neurofibrillary tangles
What may be seen in histology of an Alzheimer’s brain?
Extrcellular plaques (B amyloid) Neurofibrillary tangles (hyperphosphorylated Tau) Neuronal and synaptic loss
What are the risk factors for Alzheimer’s?
Age
DM/BP/dyslipidaemia/diet
Female 2:1
APOE gene
Autosomal dominant Alzheimer’s disease
Down syndrome- 21 chromosome is where amyloid protein gene is –> increased risk of amyloid plaques
Trauma (chronic traumatic encephalopathy)
What are the investigations for Alzheimer’s?
Clinical diagnosis MMSE- severe decline in memory section CSF: tau and beta amyloid Imaging: CT/MRI/PET Require brain tissue biopsy for definitive diagnosis- never done
What are the risk factors for vascular dementia?
Any cardiovascular risk factor: eg. smoking, exercise etc Female>male Elderly Vasculopaths
What is the presentation of vascular dementia?
Sudden onset Step-wise deterioration- microinfarcts cause progressive loss of cognition Location specific deficits Focal neurology Emotional/personality changes
What will an MRI show in a Pt with vascular dementia?
Haemosiderin deposition
What is Pick’s disease?
The most common form of fronto-temporal dementia
Involves Tau but not amyloid beta
What is the presentation of Pick’s disease?
Classical frontal lobe changes: Personality change Disinhibition Overeating, preference for sweet foods Emotional blunting Relative preservation of memory
What are the risk factors of Pick’s disease?
40-60yrs
FHx
What is Wernicke’s encephalopathy?
Acute presentation of neurocognitive manifestations due to a thiamine/B1 deficiency, commonly due to XS alcohol
What is the classic physical signs triad of Wernicke’s?
Ataxia
Confusion
Eye signs (ophthalmoplegia., nystagmus, diplopia, ptosis)
What are the investigations for Wernicke’s?
Bloods- albumin, B12
ECG
CT
What is the management for Wernicke’s?
Pabrinex
What are the clinical features of Korsakoff’s psychosis?
Chronic presentation
Pt is alert
Amnesia and confabulation
What is Huntington’s disease?
Autosomal dominant mutation of the Hungtingtin gene (HTT) causing CAG repeats
Expansion of CAG trinucleotide - >40
What are the symptoms of Huntington’s?
Motor:
- chorea (dance-like movements)
- athetosis (writhing movement of the hands)
- ataxia
- dysphagia
Cognitive:
- lack of concentration
- depression
- dementia
- personality changes, aggression
What will you see on an MRI of a Pt with Huntington’s?
Global atrophy of the brain
Loss of the striatum - gray matter below ventricles
How many CAG repeats are needed for a Pt to be guaranteed to develop Huntington’s?
40+
<35 codons = normal
A 28 year old Norwegian woman presents to A&E after she was unable to feel the hot water on her left leg whilst taking a bath. CSF analysis demonstrated oligoclonal bands that were unmatched with the serum. Which of the following would most likely confirm a diagnosis of Multiple Sclerosis?
A. Multiple lesions on MRI that all enhanced with gadolinium
B. The patient’s symptoms reoccur 1 year later
C. The patient develops blurry vision in one eye a year later
D. The patient reports blurry vision currently
E. A 1 year follow up finds oligoclonal bands matched with the serum
C. The patient develops blurry vision in one eye a year later
Need dissemination in time and space.
A 40 year old woman visits her GP complaining of tiredness. On questioning, she reports getting tired when climbing the stairs or during a conversation. She often has to stop what she is doing to regain her energy. The GP asks her to look upwards, and after a few seconds she begins to develop ptosis. What is the most likely diagnosis?
A. Iron Deficiency Anaemia B. Myasthenia Gravis C. Lambert Eaton Myasthenic Syndrome D. Carcinoma E. Horner’s Syndrome
B. Myasthenia Gravis
A 50 year old man visits his GP complaining of weakness in his right arm. He reports the weakness has gradually developed over the last 2 months. On inspection, the GP notices wasting of his tongue and hyper-reflexia. His right arm is rigid. What is the most likely diagnosis?
A. Stroke B. Multiple Sclerosis C. Parkinson’s disease D. Motor Neuron Disease E. Carpel Tunnel Syndrome
D. Motor Neuron Disease
A 70 year man is referred to a neurologist by his GP. The referral letter notes that the man has slowly been struggling to get around and carry out basic activities like cooking dinner, finding he struggles to initiate movement. The letter also notes that the patient has a resting tremor and rigid upper arms. When the neurologist calls the patient into the room, what gait does he expect the patient to most likely have?
A. Ataxic B. Hemiplegic C. Shuffling D. Scissor E. Choreiform
C. Shuffling
ataxic = cerebellar dysfunction hemiplegic = stroke scissor = cerebral palsy choreiform = HD
A 55 year old gentleman is accompanied to the GP by 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 is able to chat to you about current events and his favourite sport team’s latest match. What is the most likely diagnosis?
A. Pick’s disease B. Lewy body dementia C. Vascular dementia D. Alzheimer’s dementia E. Wernicke-Korsakoff syndrome
A. Pick’s disease
Type of fronto-temporal dementure. Typically presents younger than other dementia.
personal unawareness of personality changes
You are called to see a 40 year old man in A&E. You try to take a history but the man in confused and unable to tell you much. On examination he has numerous spider naevi on his chest, an ataxic gait and nystagmus. What is the most likely diagnosis?
A. Multiple Sclerosis B. Motor Neuron Disease C. Korsakoff’s syndrome D. Wernicke’s Encephalopathy E. Head trauma
D. Wernicke’s Encephalopathy
classic triad- confused, ataxic gait, nystagmus
Not Korsakoff’s because this is the acute stage
A 40 year old man starts to make random jerky movements at points throughout the day. Worried about this, he visits his GP. Upon questioning, he informs the GP that his father died in his 40s, but he was too young to remember why, although he did have similar symptoms. What test should be arranged?
A. FBC B. Karyotyping C. Whole genome sequencing D. CAG repeat testing E. MRI head
D. CAG repeat testing
A 70 year old man has confusion and falls, worsening over nearly 1 year. There is no history of vascular disease. Examination shows bradykinesia, resting tremor, and a shuffling gait. What is the most likely diagnosis?
A. Parkinson’s Disease
B. Alzheimer’s Disease
C. Frontotemporal Dementia
D. Vascular Dementia
A. Parkinson’s Disease
Epidemiology of MS
Higher prevalence in Northern hemisphere
thought to be association with Vit D deficiency
scandinavian countries esp
when do you suspect MS?
- optic neuritis
- young person with sensory changes
- demyelinated plaques in white matter of CNS on CT
UMN symptoms
weakness no strophy hyperreflexes no fascicultions hypertonia present extensor response
LMN symptoms
weakness atrophy hyporeflexia fasciculations hypotonia absent extensor response
typical symptoms of PD dementure
- amnestic, language deficits
- visuospatial dysfunction- inability to draw clock + put numbers in right place
- hallucinations- little men
- fluctations
- aggression/anxiety
Describe the symptoms onset of Lewy body dementure
Usually dementia symptoms start before Parkinson’s.
These 2 usually start within a year of each other
What is protective of alzheimers?
constantly accessing memorable information- education and use of brain
What test can determine type of dementia?
MMSE
What area of the brain is most affected by small vessel disease? eg vascular dementia
Ventricles
Describe how CAG repeats determine prognosis in Huntington’s
<28 = normal 29-34 = next gen at risk 35-39 = 40+ = increasing CAG repeats decreases age of onset
