17. Chronic Neurology Flashcards

1
Q

MS Definition

A

A chronic inflammatory multifocal, demyelinating disease of the central nervous system of unknown cause, resulting in loss of myelin, and oligodendroglial and axonal pathology

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2
Q

MS Common Symptoms and Signs

A

Symptoms depend on where in the CNS damage is

Optic neuritis
Motor weakness (with spasticity and hyper-reflexia), pyramidal signs
Sensory disturbances (Paraesthesiae, pain or sensory loss in limbs or trunk)
Fatigue

Lhermitte’s sign (electric shock radiating down back and triggered by neck flexion)

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3
Q

MS other symptoms

A

Urinary urgency and incontinence
Sexual dysfunction

Dysarthria
Paraesthesiae, pain (incl.trigeminal neuralgia) or numbness of face or tongue
Visual field defect - unilateral, Conjugate eye movement disorders: diplopia, nystagmus

Seizures
Psychiatric disturbances
Vertigo and nystagmus
Impairment of concentration or memory

Hemiparesis
Hemi sensory loss

Ataxic and spastic gait
Impaired coordination, action and intention tremor
Dysmetria

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4
Q

MS Invx

A

Fundoscopy - eye signs e.g. papillitis. Diplopia, nystagmus, internuclear ophthalmoplegia

Retro-bulbar optic neuritis (2/3)
Optic neuritis with papillitis (1/3)

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5
Q

Multiple Sclerosis Epidemiology

A

Around 2.5 millions worldwide
Higher prevalence among white people of Nordic origin - ‘Latitude effect’
Highest in UK, Sweden, Denmark

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6
Q

Multiple Sclerosis RF

A

AI PMHx
HLA-DLRB1*15
VItamin D levels (more sunlight)
Latitude

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7
Q

Multiple Sclerosis MRI

A

The demyelinated plaques in the white matter of the CNS are the pathological substrate of relapses

Areas of inflammation, with loss of myelin are scattered around the CNS.
The location and size of plaques determine the type and severity of symptoms (given rise to such varied symptoms)
Often plaques are silent, as may be in area of white matter that is of little importance. Or could appear in area of importance like the brainstem, possible leading to respiratory failure.

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8
Q

MS Pathophysiology

A

During an acute relapse, there is inflammation in response to myelin basic protein. The inflammation leads to demyelination, which causes delay of the nerve impulse and eventually the neurological symptoms. At first these completely resolve (treatment can speed up process- give steroids), but as disease progresses can often be left with residual symptoms.

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9
Q

3 types of MS phenotypes

A

Relapsing-remitting (RR) - 85%
Patients mostly fine, but suffer from relapses (acute symptoms) which then resolve; for most of these patients this eventually converts to SPMS (mean 10-15 years)

Secondary Progressive MS: gradually more and more disabled, may have more relapses superimposed on this, but often with incomplete recovery.

Primary progressive MS – progressing immediately, without the initial relapsing remitting stage

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10
Q

MS Dx

A

Clinical - Absence of alternative diagnosis
Dissemination in time (DIT)
Dissemination in space (DIS)

Based off:
Clinical history and examination 
Radiological evidence – MRI
Laboratory evidence – CSF
Electrophysiology – VEPs
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11
Q

How can we differentiate old and new lesions?

A

MRI with gadolinium contrast

During an acute attack, inflammation makes the BBB leaky (for 2-6 weeks) to allow immune cells into the CNS (normally brain is immune privileged). GAD also crosses the barrier = lights up any active lesions, and old lesions remain darker

Anything that lights up is at most 6 weeks old.

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12
Q

What is diagnostic of MS in the CSF?

A
Oligoclonal bands (95% sensitive) present in the CSF but not the serum
(B cells release IgG Ab targeting myelin)

NB if present in serum = infection/inflammation systemically

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13
Q

What are VEPs and what are they used for?

A

Visual evoked potentials (VEPs) – these look for subtle abnormalities in the visual pathways (commonly affected in MS) which may help clinical to pick up subclinical features even the patient was not aware of

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14
Q

A 28 year old Norwegian woman presents to A&E after she was unable to fell 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?

Multiple lesions on MRI that all enhanced with gadolinium
The patient’s symptoms reoccur 1 year later
The patient develops blurry vision in one eye a year later
The patient reports blurry vision currently
A 1 year follow up finds oligoclonal bands matched with the serum

A

Risk factors of being young, Nordic woman. Also demyelination can be precipitated by a hot bath

DIT
DIS

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15
Q

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?

Iron Deficiency Anaemia
Myasthenia Gravis
Lambert Eaton Myasthenic Syndrome
Carcinoma 
Horner’s Syndrome
A

This question demonstrates the classical presentation of myasthenia gravis – muscles fatiguing after use. Also a 40 year old woman which is typical group of people affected.
If it were not for the final sentence then IDA would be most likely statistically, but it wouldn’t produce the stereotypical ptosis on upwards gaze.
LEMS would be tiring at first and improve with use, so wrong way around for this question.
Carcinoma can obviously lead to tiredness, but firstly it is a little vague and secondly wouldn’t give the ptosis after a few seconds, likely provide some other symptoms too.
Horner’s syndrome is characterised by ptosis, but that is at rest.

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16
Q

Myasthenia Gravis Symptoms and signs

A
Symptoms - Muscles fatigue with use
Ptosis
Diplopia
Dysarthria
Dysphagia
±SOB

Signs
Fatigable muscles
Normal reflexes

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17
Q

Who does MG normally affect

A

It most commonly impacts young adult women (under 40) and older men (over 60) – as it is an autoimmune condition

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18
Q

What muscles does MG usually implicate

A

Those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing

Muscles that control breathing and neck and limb movements may also be affected.

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19
Q

MG Aetiology

A

Antibodies block, alter, or destroy nAChR or MuSK
May also have seronegative myasthenia

Muscles will fatigue with repeated use as more and more ACh is required to maintain contraction; in MG this happens quicker compared to normal person

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20
Q

MG Associations

A
Thymic hyperplasia (70%)
Thymoma (10%)
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21
Q

Mg Investigations

A

Bloods – anti-AChR or anti-MuSK
EMG -demonstrate muscle weakness, action potentials will gradually decrease over time
CT/MRI - for thymomas

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22
Q

Lambert Eaton Myasthenic Syndrome Symptoms

A

Symptoms – weakness where muscles improve with use
Difficulty walking (upper legs and hips)
Weakness in upper arms and shoulders
Similar symptoms to myasthenia gravis - mild weakness in eye, talking + chewing muscles etc
Autonomic: Dry mouth, constipation, incontinence

Signs
Muscles function better following use
Hyporeflexia

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23
Q

Lambert Eaton Myasthenic Syndrome Aetiology

A

Anti voltage gated calcium channels on nerve endings that are required to trigger exocytosis of Ach –> less Ach cannot cause normal contractions

Improves with repeated use as incoming stimulus leads to cumulative opening of the few calcium channels not blocked by antibodies

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24
Q

Lambert Eaton Myasthenic Syndrome Associations

A

Small cell lung cancer (paraneoplastic - producing Ab); older age of onset (averaging 60 years) and is caused by an accidental attack of the nerve terminal by the immune system as it attempts to fight the cancer. Tx of cancer removes LEMS

Autoimmune disease (onset = 35)

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25
Q

Lambert Eaton Myasthenic Syndrome Investigations

A

Bloods - Antibodies to voltage-gated calcium channels (VGCCs) have been reported in 75-100% of LEMS patients who have small cell lung cancer (SCLC) and in 50-90% of LEMS patients who do not have underlying cancer.
EMG
CT/MRI - lung cancer?

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26
Q

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?

Stroke
Multiple Sclerosis  
Parkinson’s disease
Motor Neuron Disease
Carpel Tunnel Syndrome
A

Motor Neuron Disease

The key thing is spotting the mixture of UMN (hyperreflexia and rigidity) and LMN signs (wasting).

Men are more likely to get MND

Stroke would be an acute onset, not progressive. MS would not really give wasting as it involved UMN’s, would also most likely be an acute attack.
Parkinson’s does have motor signs, but doesn’t give wasting as again it’s CNS not PNS. Also missing the classic triad.
Carpel tunnel syndrome can give arm/hand weakness, but no signs/symptoms outside of this.

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27
Q

MND Definition and Incidence

A

5-8/100,000
(AML/Charcot’s Disease)

Chronic neurodegenerative condition (hardening of the lateral corticospinal tracts) causing progressive muscle wasting, paralysis and death usually within 3-5 years due to respiratory failure

Progressive denervation and secondary muscle weakness of limbs, trunk, tongue and respiratory(Intercostal) muscles. Onset usually occurs in distal muscles of a single limb or may be bulbar, followed by widespread progression

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28
Q

MND Symptoms

A

Bulbar symptoms - dysphagia, impaired speech
Spastic weakness/paralysis of all skeletal musc –> respiratory failure
SOB
Changed cognitive function (15%)

Sparing of oculomotor, sensory and autonomic function (bladder, bowel, sexual function preserved)

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29
Q

Signs of MND

A

Wasting of:

  • Thenar hand muscles (base of the thumb
  • Tongue (bulbar onset)
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30
Q

What does bulbar mean?

A

Relating to the medulla oblongata (it’s shaped like a bulb)

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31
Q

What causes MND?

A

Unclear: sporatic + familial
Ubiquinated proteins in cytoplasm (normally marked for degradation by proteasome) but not destroyed –> builds up –> CS tract death.

97% of MND patients have ubiquitin inclusions positive for TDP-43 (protein in DNA/RNA processing normally in nucleus, but ends up in cytoplasm)

32
Q

MND Invx

A

Clinical Dx

  • EMG: fibrillation and fasciculations; motor units are polyphasic and have high amplitude and long duration.
  • Nerve conduction studies should show normal motor and sensory conduction in MND.
  • CT/MRI/blood tests to exclude other causes
33
Q

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?

Ataxic 
Hemiplegic
Shuffling 
Scissor 
Choreiform
A

Shuffling

Patient has classical triad of bradykinesia, rigidity and tremor, telling us it is likely Parkinson’s. Therefore answer is shuffling gait (shuffle as otherwise can lose balance) Patient obviously wouldn’t say “I’m struggling to initiate movement” that is the words of the GP, patient more likely to say “struggle to get going”

Ataxic gait is cerebellar sign, seen in Wernicke’s encephalopathy.
Hemiplegic is typically following a stroke
Scissor gait characteristic of cerebral palsy
Choreiform (dance like) typical of Huntington’s

34
Q

Parkinsons - 6M’s

A
Monotonous, hypotonic speech
Micrographia
HypomiMesis (expressionless face)
March a petit pas (chasing one's gravity)
Misery → depression 
Memory loss → dementia

Later: ANS e.g. dysphagia and drooling, anosmia etc, REM sleep disorder

35
Q

Tremor is absent in % of Parkinsons patients

A

30%

36
Q

How to test postural instability?

A

Push them –> fall

37
Q

What is Parkinson’s syndrome and what causes it?

A

Triad of bradykinesia, resting tremor and rigidity

  • Parkinson’s disease
  • Antipsychotics or antiemetics (Lower DA)
  • Atypical Parkinsonisms (multi-infarct/vascular - strokes in striatum)
38
Q

Full name of site of pathology in Parkinson’s

A

Substantia nigra pars compacta (midbrain)

39
Q

Compare Parkinson’s brain with normal - colour

A

Normal is darker, neurons produce Neuromelanin

40
Q

How much neurons to lose before symptoms in parkinson’s?

A

80%

41
Q

Pathophysiology of Parkinson’s

A

Alpha synuclein misfold –> accumulate in Lewy bodies and lewy dendrites –> neuron death in:
1. Nigrostriatal pathway - motor symptoms (striatum required for smooth, functional movement; inhibits oppositional movements).

Later:
2. Mesolimbic and mesocortical pathways –> cognitive symptoms.

42
Q

RF for Parkinsons

A

Age: 50% of those >80 have two or more clinical signs of Parkinsonism
Male
Countryside (pesticides?)
10% genetic

43
Q

Parkinson’s disease dementia vs Lewy Body disease

A

P’s D: Dementia develops many years after the onset of motor symptoms

44
Q

Lewy body dementia vs. Alzheimer’s

A

Hallucination (little people + animals)
Visuospatial dysfunction

aren’t as common in Alzheimer’s dementia

45
Q

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?

Pick’s disease
Lewy body dementia
Vascular dementia
Alzheimer’s dementia
Wernicke-Korsakoff syndrome
A

The factors that point to pick’s disease over the other options is that this patient is relatively young to have the other forms of dementia. They also have the classical symptoms of Pick’s – disinhibition and personality change. The fact he can chat to you about recent events and his sports team (effective way to test memory) tells us it not likely Alzheimer’s – as normally memory of recent events is the first thing to go
There’s no motor signs or symptoms of reduced thiamine – pointing us away from LBD and Wernicke’s

46
Q

What does dementia typically affect

A

Cognition and memory

  • Affect
  • Motivation and attention
  • Personality and behaviour
47
Q

The 5 As of Alzheimer’s dementia:

A
Amnesia (Episodic memory)
Anomia
Apraxia
Agnosia
Aphasia

± Depression
± Paranoid delusions

48
Q

Alzheimer’s symptoms

A

Memory: Poor day-to-day memory, repetitive, can get lost

Language: Word-finding problems, People’s names

Attention: Following conversations, especially in groups

Calculation: Partner/family take over accounts and bills

Executive Function: Household tasks, preparing meals

Praxis: Problems with dressing, manual tasks

49
Q

What is loss of memory in Alzheimer’s due to?

A

Atrophy of medial temporal lobes, where we normally have hippocampus

Later: global cortical atrophy

50
Q

Alzheimer’s pathophysiology

A

Amyloid precursor protein [APP] = transmembrane protein
Normal = a and γ secretase → normal degradation product
AD = b and γ secretase → abnormal product resistant to degradation → Ab
Ab accumulates outside the cell to form amyloid plaques

Interferes with neuronal communication (+ inflammation

Tau Tangles

51
Q

What else does Ab do?

A

(Tau = protein that supports microfilaments)

Ab triggers phosphorylation of tau, causing it to disassociate from the MF and accumulate into neurofibrillary tangles
Tangles + weakened microfilaments → ↓neuronal function and apoptosis → atrophy

→ degeneration of cholinergic nuclei → ↓ cortical ACh

52
Q

Key things for SBA (Alzheimers)

A

β Amyloid → extracellular plaques

Hyperphosphorylated tau → neurofibrillary tangles

Neuronal and synaptic loss

53
Q

Alzheimer RFs

A
Ages
Female
Trauma 
APOE (biggest genetic cause, involved in Ab clearance)/AD familial alzheimer's
Down's
Exercise and education is protective
54
Q

How does Trauma cause Alzheimer’s?

A

Chronic traumatic encelopathy (Punch-drunk syndrome) -> THI

–> chronic inflam, increase amyloid levels (Ab deposits in 30% of HI pts)

55
Q

Alzheimer’s Invx

A

Very few effective laboratory tests

Clinical diagnosis
CSF: tau (low) & beta amyloid (high)
Imaging: CT, MRI, (atrophy) PET, SPECT

Brain Tissue required for definitive diagnosis

56
Q

Vascular dementia symptoms

A

Location-specific deficits
Emotional and personality changes
Focal neurology
(sudden onset, step wise)

57
Q

Vascular dementia RF and pathophys

A

Infarction damaging the small and medium sized vessels

Vasculopaths, age, male, CVD

58
Q

Vascular dementia MRI

A

Hemosiderin deposits from previous infarcts

59
Q

Pick’s disease and pick bodies

A

Most common form of fronto-temporal dementia

Pick bodies: Hyperphosphyorlated tau protein

60
Q

Pick’s symptoms

A
Personality change
Disinhibition
Overeating, preference for sweet foods
Emotional blunting
Relative preservation of memory
61
Q

RF for pick’s, prognosis

A

Typically affects people younger than in other dementias
±FHx (although most are sporadic)
Death within 5-10yrs

62
Q

RF for pick’s, prognosis

A

Typically affects people younger than in other dementias
±FHx (although most are sporadic)
Death within 5-10yrs

63
Q

How to DDx dementias

A

Alzheimer’s
Insidious amnesia, language impairment

Lewy Body Dementia
Fluctuation, agitation, hallucinations, visuospatial dysfunction, Parkinsonism

Vascular Dementia
Stepwise decline, focal/motor/gait signs

Frontotemporal dementia
Lack of hygiene, personality change, poor comportment & planning

64
Q

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?

Multiple Sclerosis
Motor Neuron Disease
Korsakoff’s syndrome
Wernicke’s Encephalopathy 
Head trauma
A

Wernicke’s Encephalopathy

Patient has classic triad ACE: ataxia, confusion and eye signs – pointing us towards Wernicke’s encephalopathy. The spider naevi suggest patient may be alcoholic, which is likely a causative factor.
If untreated this could progress to Korsakoff’s, which is not the answer as they would not be confused and would be chronic, not acute
Head trauma can give ataxic gait and confusion, less likely to give eye signs. But probably second most likely on the list
MND and MS would rarely give confusion.

65
Q

Wernicke’s Encephalopathy signs

A

Ataxia (cerebellar dmg)
Confusion
Eye signs - ophthalmoplegia, nystagmus, diplopia, ptosis
10% has triad

66
Q

Why is ETOH so bad for W’s E

A

Poor diet

Prevents vitamin B-1 absorption and storage

67
Q

What is Thiamine used for?

A
  • Metabolism of carbohydrates, releasing energy.
  • Production of neurotransmitters including glutamic acid and GABA.
  • Lipid metabolism, necessary formyelin production.
  • Amino acid modification - production of taurine, of great cardiac importance.
68
Q

Why is ETOH so toxic?

A

Brain atrophy

Can Exacerbate Cognitive function in other dementias

69
Q

Invx for W’s E

A
Bloods 
Pabrinex
LFT
ECG before and after Tx
CT - lesions
Neuropsychological test to determine the severity of any mental deficiencies.
70
Q

W’s E prognosis

A

12% no cognitice sequelae, with LT Pabrinex
68% Karsakoff’s
20% Death

71
Q

Karsakoff’s features

A

Chronic
Alert
Amnesia and confabulation
Irreversible?

72
Q

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?

FBC
Karyotyping 
Whole genome sequencing 
CAG repeat testing
MRI head
A

CAG repeat testing

This man has symptoms suggestive of Huntington’s, the jerky movements one of the first symptoms to develop. The fact is father died young and had similar symptoms supports this. The typical genetic test for suspected Huntington’s is CAG repeat testing, if they have 40 or more repeats then Huntington’s is confirmed.
FBC wouldn’t explain these symptoms, Karyotyping is normally for aneuploidy like Down’s or translocation disorders.
Whole genome sequencing is for de novo mutations, where you can compare to the parents. Currently only used in research setting as very expensive.
MRI head might show atrophy of caudate but it is non-specific.

73
Q

Huntington’s symptoms

A
Motor: (hands and face first)
Chorea (jerky)
Athetosis (writhing hands)
Ataxia
Dysphagia
Cognitive
Lack of concentration
Depression
Dementia 
Personality changes, aggression
Difficulty eating, swallowing, can't protrude tongue
74
Q

Pathology of Hungtintons

A

Atrophy of medium spiny GABAergic neurons of mainly the caudate, but also putamen; (collectively = striatum) –> can’t inhibit movements –> chorea

Progression = global atrophy

75
Q

Genetic basis of Huntington’s

A

AD: Mutation of the HTT gene on short arm of chromosome 4, CAG

Sporadic: new genetic mutation-an alteration in the gene that occurs during sperm development and that brings the number of CAG repeats into the range that causes disease.

Normal (<35 codons) huntingtin protein is thought to stabilize neurons, preventing apoptosis from occurring and prolonging cell life.

> 40 codons = toxic (large glutamine blocks) - induces apoptosis in neurones (bc metab change sensed by mitochondria)

76
Q

CAG repeats significance

A

≤28: Normal range; individual will not develop Huntington’s disease

29-34: Individual will not develop Huntington’s disease but the next generation is at risk

35-39: Some, but not all, individuals in this range will develop Huntington’s disease; next generation is at risk

≥ 40: Individual will develop Huntington’s disease