Neurodegenerative diseases Flashcards
Name the descending tracts and what they do
MOTOR Lateral corticospinal tract - main voluntary motor - upper extremity motor pathway, more medial Ventral corticospinal tract - voluntary motor
Name the ascending tracts and what they do
SENSORY Dorsal columns - deep touch - vibratory - proprioception Lateral spinothalamic tract - pain - temperature Ventral spinothalamic tract - light touch
Risk factors for MS
HLA DLR1*15 allele More common in young white, women - nordic origin Associated with autoimmune conditions - psoriasis
Signs and sx of MS
Impaired coordination (action and intention tremor, ataxic gait)
Optic neuritis
Motor weakness (spasticity, pyramidal signs, spastic gait)
Sensory disturbances
Fatigue
What signs would be seen on fundoscopy for MS?
papillitis, diplopia, nystagmus, internuclear ophthalmoplegia
What is lost in MS?
Loss of myelin and oligodendroglial + axonal pathology (chronic inflammatory, demyelinating disease of CNS)
Types of MS
Relapsing-remitting (80-85%) - doesn't always convert to secondary progressive Primary progressive (15-20%) - progresses into clinical phenotype eventually Secondary progressive (follows RR after 10-15yrs) - clinical phenotype
*you can give steroids to relieve acute inflammation but as the disease progresses, you are left with residual sx
How is a MS diagnosis made?
Key to MS diagnosis:
- dissemination in space
- dissemination in time
- absence of alternative diagnosis
The following us used to aid diagnosis:
- clinical hx + examination
- radiological exam (MRI)
- lab evidence (CSF)
- electrophysiology (VEPs)
What contrast is used in MRIs for MS and why?
Gadolonium contrast used to distinguish between old and new lesions
Older lesions are darker than new
BBB leaks for up to 6 weeks after acute inflammation
What is present in CSF for MS?
Oligoclonal bands present in CSF but not serum (if matched, suggests inflammation is systemic)
- AI condition so B cells release IgG antibodies that target myelin
What causes myasthenia gravis?
‘Grave muscle weakness’, autoimmune condition
- antibody attacks ACh receptor so muscles unable to contract
- the more you use the muscle/need it, the more ACh required thus muscle fatigues
- MUSK (muscle-specific kinase) also leads to impaired transmission
How does myasthenia gravis present?
Muscle fatigue WITH USE
- ptosis, diplopia, dysarthria, dysphagia, +/- SOB
- normal reflexes
- relieved after periods of rest
Occurs in young adult women (<40yo)/older men (>60yo)
What are ix for myasthenia gravis?
Bloods = anti-AChR or anti-MUSK
- can be seronegative
EMG = demonstrates muscle fatigue
CT/MRI = look for thymomas* (pot. malignant)
*MG associated with thymic hyperplasia (70%) and thymoma (10%)
How does Lambert Eaton Myasthenic Syndrome present?
Difficulty swallowing Weakness in upper arms and shoulders Similar sx to MG Autonomic: dry mouth, constipation, incontinence Muscle function better after use Hyporeflexia
What causes LEMS?
Immune system attacks Ca2+ channels required to trigger ACh release
Decreased ACh means unable to form normal muscle contractions
Repeated use leads to cumulative openings of Ca2+ channels so eventually ACh increases
Which conditions are associated with LEMS?
Small cell lung cancer (50-60% cases)
- older onset, >60yo, smoker
Autoimmune conditions
- young age of onset, <35yo
Ix for LEMS
Bloods - anti-VGCC
EMG
CT/MRI - cancer detection
How may motor neurone disease present?
Impaired swallowing + speech Sparing of oculomotor, sensory + autonomic function (bladder, bowel, sexual function) Progressive muscle weakness Dysphagia SOB More common in men
Signs of MND
UMN
- increased tone, hyperreflexia, Babinski’s
LMN
- decreased tone, hyporeflexia, fasiculations, atrophy
- wasting of thenar hand muscles (base of thumb)
- wasting of tongue muscles (bulbar onset)
What protein builds up in MND?
Ubiqunated proteins in cytoplasm of motor neurones build up and kill corticospinal tracts
*90% of pts with ubiquitin inclusions +ve for TDP-43
What ix are done for MND?
Mainly to exclude other diagnoses
- EMG
- CT/MRI
- Bloods (B12, folate)
- Muscle biopsy
Classic triad of Parkinson’s
Bradykinesia
Rigidity; cogwheel
Rest tremor
6 Ms of Parkinson’s
Monotonous, hypotonic speech Micrographia hypoiMesis (expresionless face) March a petit pas (shuffling gait; lil steps) Misery => depression Memory loss => dementia
What pathways are affected in Parkinson’s?
Nigrostriatal pathway (required for smooth, functional movements) Mesolimbic + mesocortical pathways (cognitive sx)
- lack of dopaminergic neurones in substansia nigra
- alpha-synuclien deposition key protein deposited
RFs for Parkinson’s
Male
Age
FHx
Features of Parkinson’s disease dementia (PDD)
Amnestic, language deficits Visuospatial dysnfunction Hallucinations Fluctuations Aggresion/anxiety
- looks similar to Lewy Body dementia except has a LATER ONSET
- develops years after motor sx whilst Lewy Body doesn’t need motor sx
What is dementia?
Severe loss of memory and other cognitive abilities, leading to impaired daily function re of underlying cause
Cognitive abilities include:
- cognition and memory
- affect
- motivation and attention
- personality and behaviour
Types of dementia
Alzheimer’s
- insidious amnesia, language impairment
Vascular dementia
- stepwise decline, focal/motor/gait signs
Fronto-temporal (Pick’s disease)
- poor compartment and planning, personality change, lack of hygiene
Lewy Body dementia
- fluctuation, agitation, hallucinations, visuospatial, Parkinsonism
RFs for Alzheimer’s
Increased age (thus more prevalent in women)
Vascular RFs (DM, BP, dyslipidaemia)
Down’s syndrome
Presenilin 1+2 mutations (AD Alzheimer’s)
Sx of Alzheimer’s
Amnesia Anomia (word-finding problems) Apraxia (problems with dressing, manual tasks) Agnosia Aphasia \+/- depression, paranoid delusions
What would you find in a MRI of an Alzheimer’s pt?
Atrophy of medial temporal lobes where the hippocampus is
Pathophysiology of Alzheimer’s
Alzheimer’s amyloid precursor protein is broken down into abnormal beta and gamma secratase
These are resistant to degradation and form beta-amyloid that form amyloid plaques as more of the protein accumulates
This interferes with neuronal communication and inflammation, leading to dementia
Beta-amyloid also phosphorylates tau in the neuron, forming neurofibrillary tangles and weakened neurofilaments
This leads to decreased neuronal function and apoptosis thus atrophy of the brain so there is degeneration of cholinergic nuclei and decreased cortical ACh
Overall there is neuronal and synaptic loss thanks to extracellular plaques and hyperphosphorylated tau
Ix for Alzheimer’s
Clinical diagnosis mainly
CSF: tau and beta amyloid present if leaked into CSF
Imaging: atrophy in CT and MRI, can do PET, SPECT
Brain tissue is required for a definitive diagnosis, often confirmed via autopsy
How does vascular dementia present?
Sudden onset and stepwise deterioration as infarctions* lead to neuronal death, especially strokes
- location-specific deficits
- emotional and personality changes
- focal neurology
- increased age
- vasculopaths
- infarction of small + medium-sized vessels in MRI
RFs for vascular dementia
Female>male
Elderly
CVD risk factors
Haemosiderin deposits from previous infarcts
How does fronto-temporal dementia (Pick’s disease) present?
Personality changes Disinhibition Overeating, preference for sweet foods Emotional blunting Relative presentation memory 40-60 years old (2nd most common of younger onset) FHx
What pathophysiology is present in Pick’s disease?
TAUOPATHY
- hyperphosphorylated tau protein
- NO beta-amyloid
How does Wernicke’s encephalopathy present?
Ataxia (cerebellar damage)
Confusion
Eye signs (opthalmoplegia, nystagmus, diplopia, ptosis)
Complication of bariatric surgery, dialysis, alcoholic, malnourished patients = risk of vit B1 (thiamine)
Ix for Wernicke’s encephalopathy
Bloods => serum albumin + vit. B1
ECG => before and after treatment
CT => identify lesions from the disorder
Neuropsychology => determine severity of mental deficiency
Wernicke’s vs Korsakoff’s
Wernicke’s
- acute
- confusion
- cerebellar and eye signs
- reversible
Korsakoff’s
- chronic
- alert
- amnesia and confabulation (make up stories to fill in gaps due to amnesia; both anterograde and retrograde)
- irreverisble (20% recover)
What causes Huntington’s?
Mutation of Huntington gene (HTT), AD, chromosome 4
CAG repeats leads to degeneration and death of medium spiny GABAergic neurones in the caudate and putamen
What are the sx and signs of Huntington’s?
Motor: - chorea (rapid jerky involuntary movements) - athetosis (writhing movements of hands) - ataxia - dysphagia Cognitive: - lack of concentration - depression - dementia - personality changes; aggression
Ix for Huntington’s
CAG repeat testing <28 = fine 29-34 = fine, next gen. at risk 35-39 = may develop next gen. at risk >/= 40 = will develop
MRI/CT scan
- caudate/striatal atrophy (not specific to HT, may show later on in disease)
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
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 hyperreflexia. 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
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
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
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
