Neurology Flashcards
1
Q
What is the classic triad of Parkinson’s Disease?
A
Resting tremor (rolling pill tremor)
Rigidity (cogwheel rigidity)
Bradykinesia
2
Q
Who would you suspect PD in?
A
Men above 70 years old
3
Q
Risk factors for PD
A
- Increasing age
- History of familial PD in younger disease
- Male sex
- Head trauma
4
Q
Basic pathology of PD
A
Gradual + progressive fall in dopamine production (from substantia nigra) -> disorders of movement (characteristically asymmetrical)
5
Q
Key presentations of PD
A
C PUB
C- Cogwheel rigidity
P - Postural instability (stooped posture + forward tilt)
U - Unilateral pill rolling tremor
B - Bradykinesia
6
Q
How is a diagnosis of PD made?
A
Clinical diagnosis (history and clinical examination)
7
Q
Differential diagnoses for PD
A
Benign essential tremor
Dementia with Lewy Bodies
Alzheimer’s disease with Parkinsonism
Drug-induced Parkinsonism
8
Q
Properties of unilateral tremor in PD
A
Asymmetrical
4-6 Hz
Worse at rest
Improves with intentional movement
No change with alcohol
9
Q
Name some signs of bradykinesia in PD
A
Micrographia
Shuffling gait
Hypomima
10
Q
When is levodopa prescribed in PD
A
Last line - effectiveness reduces over time
11
Q
Name a combination drug of levodopa and a peripheral decarboxylase inhibitor used in PD
A
Co-careldopa (levodopa + carbidopa)
12
Q
Name 3 S/E of levodopa dose being too high
A
Dystonia (abnormal postures or exaggerated movements)
Chorea (abnormal involuntary movements)
Athetosis (involuntary twisting or writhing movements)
13
Q
Name a COMT inhibitor (used in PD)
A
Entacapone
14
Q
What are COMT inhibitors used for?
A
In PD - to extend the duration of levodopa
15
Q
Name a dopamine agonist
A
Bromocryptine
Cabergoline
Pergolide
16
Q
Name a monoamine oxidase-B inhibitor
A
Selegiline or rasagiline
17
Q
Complications of PD
A
Levodopa-induced dyskinesia
Dementia
Bladder dysfunction
Orthostatic hypotension
Dysphagia
18
Q
What type of genetic disease is Huntington’s disease?
A
Autosomal dominant
Also a trinucleotide repeat disorder - anticipation
19
Q
What is genetic anticipation and what neurological condition displays it?
A
Huntington’s disease
Anticipation = where successive generations have more repeats in the gene -> results in earlier age of onset + increased severity
CAG expansion of the first exon in the Huntingtin gene (HTT)
20
Q
When does Huntington’s present in life?
A
Typically mid-life
(But can be any age)
21
Q
What are the earlier symptoms of Huntington’s
A
Cognitive, psychiatric and mood problems (personality change, irritability and impulsivity)
22
Q
What are the signs of Huntington’s
A
Chorea (involuntary abnormal movements)
Eye movement disorders (slowed rapid eye movements)
Dysarthria (speech difficulties)
Dysphagia (swallowing difficulties)
Loss of coordination
Deficit in fine motor coordination
23
Q
Testing for Huntington’s
A
- CAG repeat testing
- Rest is clinical
24
Q
What is the treatment for slowing or stopping the progression of Huntington’s?
A
None - just supportive
25
Management for Huntington's disease
Speech and language therapy
Genetic counselling
End of life care planning
Antidepressants for depression
26
Two main complications of Huntington's disease
Depression -> suicide
Dysphagia -> aspiration pneumonia
27
Typical life expectance after the onset of Huntington's disease?
15-20 years after symptom onset
Death due to aspiration pneumonia + suicide
28
Define MS
T-cell mediated inflammatory demyelinating disorder of the CNS - characterised by the presence of episodic neurological dysfunction in at least 2 areas of the CNS (brain, spinal cord, optic nerves - **separated in time and space**
29
What individual are you most likely to diagnose MS in?
Females under 50
(disease of the young)
Effects x2 women
30
Causes of MS
* Multiple genes (polygenic)
* EBV
* Low vitamin D
* Smoking
* Obesity
31
What type of hypersensitivity reaction underpins MS pathology?
Type IV (cell-mediated)
32
Very basic MS pathology
T-cell mediated
T cells = activate B cells to produce auto-antibodies against myelin -> demyelination -> disruption of conduction along axon
33
What does **'disseminated in time and space** mean in MS?
Key characteristic in MS
Lesions vary in their location over time
Therefore symptoms change over time
34
What is **Uhtoff's phenomenon** in MS
Worsening of neurological symptoms in MS when the body gets overheated
35
Name a clinical sign in MS examination
| Involves the neck
Lhermitte's sign
Bending neck forward -> electric shock runs down back -> radiates to limbs
36
Name the group of symptoms in MS
* Optic neuritis (loss of vision in one eye)
* Eye movement abnormalities (double vision)
* Focal weakness (e.g. limb paralysis or incontinence)
* Focal sesnory symptoms (e.g. numbness, paraesthesia, Lhermitte's sign)
* Ataxia (sensory or cerebellular)
37
Name the disease patterns of MS (4)
* Clinically isolated syndrome
* Primary progressive MS
* Relapsing-remitting MS
* Secondary progressive MS
38
Investigations for MS
* MRI brain and spinal cord (demonstrate demyelinating lesions) - first line
* Lumbar puncture ('oligoclonal bands' in CSF)
39
3 Differential diagnoses for MS
Fibromyalgia
Sjorgren syndome
Vitamin B12 deficiency
Peripgeral neuropathy
Amyotrophic lateral sclerosis (ALS)
40
Management for MS
* Immunomodulators (interferon beta 1a (IM) or 1b (SC)) + rituximab
* Relapses - IV methylprednisolone
* Symptomatic treatments (neuropathic pain - amitriptyline or ganapentin, spasticity - gabapentin)
41
Complications of MS
* Depression
* Visual impairment
* Erectile dysfunction
* Cognitive impairment
* Impaired mobility
42
Lesions in which cranial nerve cause double vision in MS?
CN VI (abducens)
(Sixth cranial nerve palsy -> muscles around eye cannot move eye laterally)
| M**S** - **S**ixth cranial nerve
43
Define epilepsy
Umbrella term for a condition where there is a tendency to have seizures
44
Define seizure
Transient episodes of abnormal electrical activity in the brain
45
What type of seizures present as a loss of consciousness + tonic (muscle tensing) + clonic (muscle jerking) episodes?
Generalised tonic-clonic seizure
46
What might the patient do in a tonic-clonic seizure?
* Tongue-bitting
* Groaning
* Irregular breathing
47
What is a post-ictal period?
Occurs after a seizure
Patient becomes confused, drowsy, irritable or depressed
48
First and second line management for a generalised tonic-clonic seizure
* First line: Sodium valproate
* Second line: Carbamazepine or Lamotrigine
49
What region of the brain do focal sezuires begin in?
Temporal lobes
| Focal seizures affect hearing, speech, memory, emotions
50
A patient has seizures and experiences:
* Hallucinations
* Memory flashbacks
* Deja vu
* Doing strange things on autopilot
What type of seizure are they experiencing?
Focal seizure
51
What is the first line and second management for focal seizures?
* First line: Carbamazepine or Lamotrigine
* Second line: Sodium valproate
52
Name 2 investigations for epilepsy
* Electroencephalogram (EEG)
* MRI brain (diagnose structural pathology)
53
Differential diagnoses for seizures
DRIFT 3R
* Drugs
* Rum (alcohol withdrawal)
* Illness (chronic)
* Fever
* Trauma
* 3 antis (antihistamine, anticonvulsants, antidepressants)
* Rat poison
54
Name an important contraindication for sodium valproate
Teratogenic
Avoid in pregancy and young women!
55
Why do you have to be carreful when prescribing carbamazepine?
Many drug interactions!
(It induces the P450 system)
56
What is status epilepticus?
* Continuous seizure for **more than 5 mins**
OR
* **3 seizures** in **1 hour**
MEDICAL EMERGENCY
57
Complications of status epilepticus
Permanent brain damage -> death
58
Treatment of status epilepticus in hospital and the community
* Hospital: ABCDE approach + IV lorazopam
* Community: Rectual diazepam
59
Define Guillian-Barre syndrome
An acute paralytic neuropathy - that affects the peripheral nervous system
60
What key symptoms does Guillian-Barre syndrome produce?
Acute, symmetrical ascending weakness
Also may cause sensory problems
61
Name 3 main triggers for Guillian-Barre syndrome
* Camplyobacter jejuni
* EBV
* CMV
62
What is the key term that underpins Guillan-Barre pathophysiology?
MOLECULAR MIMICRY
B-cells produce antibodies that target the myelin sheath and axon of motor nerve cells
63
A patient presents with:
* Symmetrical ascending weakness (starting at feet, moves up)
* Reduced relexes
* Neuropathic pain
* Peripheral loss of sensation
* Facial nerve weakness
Suspected diagnosis?
Guillian-Barre syndrome
64
What is the key presentation of Guillian-Barre syndrome?
**Symmetrical ascending weakness** (starting at feet - moves up the body)
65
A patient presents with gastritis and within 4 weeks complains of loss of sensation and neuropathic pain in feet. Diagnosis?
Guillian-Barre syndrome
66
What are 2 confirmatory tests for Guillian-Barre syndrome?
* Nerve conduction studies (reduced signal through the nerves)
* Lumbar puncture (elevated CSF proteins)
67
What is the management for Guillian-Barre syndrome
* IV immunoglobulins (IVIG)
* Plasma exchange (alternative to IVIG)
* Supportive care
* VTE prophylaxis (DOAC, LMWH)
68
Name a couple of complications of Guillian-Barre Syndrome
* Respiratory failure
* Paralysis
* DVT
* Fatigue
* Psychological problems
69
The Brighton criteria is used to diagnose which neurological condition?
Guillian-Barre syndrome
70
Patient presents with a mild ache across forehead (band-like headache pattern around the headache). Normal neurological examination and NO associated features N+V. Diagnosis?
Tension headache
71
Name some causes of a tension headache
* Stress
* Missing meals
* Dehydration
* Alcohol
* Depression, anxiety
* Eyestrain
* Noise
72
Which muscles are thought to cause ache in a tension headache?
* Frontalis
* Temporalis
* Occipitalis
73
Describe the characteristic features of a tension headache
Dull, non-pulsatile, bilateral constricting pain
74
Differentials for a tension headache
* Chronic migraine
* Giant cell arteritis
* Brain tumour
* Pituitary tumour
* Medicine overuse headache
75
Possible complication of a tension headache
Peptic ulcer
(secondary ulcer to NSAID use)
76
Define migraine
Complex neurological condition that causes headache + other associated symptoms
77
Types of migraine
* Migraine without aura
* Migraine with aura
* Silent migraine (aura with no headache)
* Hemiplegic migraine (temporary weakness on one side of the body)
78
How long does a migraine typically last?
4 to 72 hours
79
Patient presents with a unilateral pounding or throbbing headache with nausea and vomiting, and a discomfort to lights and loud noises. All investigations come back normal. Diagnosis?
Migraine
80
Symptoms of a migraine
* Moderate-to-severe intensity
* Pounding or throbbing in nature
* Usually unilateral - but can be bilateral
* **Photophobia** (discomfort with lights)
* **Phonophobia** (discomfort with loud noises)
* **Aura** - with or without
* Nausea + vomiting
81
Patient presents with sparks and blurring of vision followed by a headache. All investigations come back normal. Diagnosis?
Migraine with aura
82
What is aura?
Visual changes associated with migraines
* Sparks in vision
* Blurring in vision
* Lines across vision
* Loss of different visual fields
83
Patient presents with unilateral weakness in limbs, ataxia and a throbbing painful sensation in head. There are aslo changes in conscious. CT head comes back normal . Diagnosis?
Hemiplegic migraine
84
Name the 5 stages of a migraine
* Prodromal
* Aura
* Headache
* Resolution
* Postdromal
85
Differentials for a migraine
* Tension headache
* Cluster headache
* Medication-overuse headache
* Subarachnoid haemorrhage (SAH)
* Giant cell arteritis
* Headache after head or neck trauma
* Stroke (if hemiplegic migraine)
86
Name the 3 drug classes used in the first line management of a migraine
* Analgesics
* Triptans
* Antiemetics
87
What is sumatriptan and when is it used?
A triptan - used in migraine
88
What is metoclopramide used for?
An antiemetic
89
What is promethazine
An antiemetic (antihistamine)
90
Name some migraine prophylaxis used to reduce frequency + severity of attacks
* Propanolol
* Topiramate
* Amitryptyline
91
Complications of a migraine
* Depression
* Complications of pregnancy
* Chronic migraine
92
Key medication for a migraine
Triptans
E.g sumatriptan
93
Describe the presentation of a cluster headache
Severe unbearable unilateral headaches around one eye
94
Typical person to present with a cluster headache
50 y/o male smoker
95
Patient presents with:
* Read, swollen watering eye
* Miosis (pupil constriction)
* Ptosis (Eye drooping)
* Nasal discharge
* Headache around one eye
All investigations come back normal. Diagnosis?
Cluster headache
96
First line investigations for a cluster headache
* MRI brain (normal)
* ESR (normal)
* Pituitary function tests (normal)
97
Differentials for a cluster headaches
* Migraine
* Trigmenial neuralgia
* Subarachnoid haemorrhage
* Giant cell arteritis
98
What is the acute management for a cluster headache?
* Triptans (sumatriptan injected s/c)
* High flow 100% oxygen
99
Second line management for a cluster headache
* Intranasal zolmitriptan
* Intranasal lidocaine
100
Cluster headache prophylaxis
* Verapamil
* Lithiuum
* Prednisolone
101
Complications of cluster headaches
Depression
102
What condition involves an intense stabbing paroxysmal pain in the trigeminal nerve (CN V)?
Trigeminal neuralgia
103
Main cause of trigeminal neuralgia
**Vein or artery compressing the trigeminal nerve**
Other causes:
- Local pathology pressing on trigeminal nerve (more common in younger people)
- Aneurysms
- Meningeal inflammation
- Tumours - vestibular schwannoma
- 5th nerve lesion
- Brainstem → tumour, MS, infarction
- Cerebellopontine angle – acoustic neuroma, other tumour
104
Risk factors for trigeminal neuralgia
* Multiple sclerosis (demyelinating disorder)
* Increased age
* Female sex
105
Pathophysiologiy of trigeminal neuralgia
Compression of the trigeminal nerve -> results in demyelination + excitation -> erratic pain signalling
106
What can trigger an attack of trigeminal neuralgia?
Facial or oral mechanical stimulation. E.g.:
* Touching/moving tongue
* Chewing
* Brushing teeth
* Blowing nose
* Hot/cold drinks
107
Describe the pain involved in trigeminal neuralgia
* Recovering paroxysmal attacks
* Severe intensity
*** Sharp, stabbing, shooting, electric shock
*** Usually unilateral
108
Investigations for trigeminal neuralgia
First line: clinical diagnosis Other:
* MRI
* Trigeminal reflex testing
* Intra-oral x-ray
109
Differentials for trigeminal neuralgia
* Dental caries
* Dental fracture
* Migraine
* Temporal arteritis
110
Management for trigeminal neuralgia
* First line: Carbamazepine orally
* Second line: Phenytoin, gabapentin
* Microvascular decompression
111
Define myasthenia gravis
Autoimmune condition that causes skeletal weakness
112
What disease is linked to myasthenia gravis
Thymoma
113
What type of hypersensitivity reaction underpins myasthenia gravis?
Type II hypersensitivity reaction
114
Pathology that underpins myasthenia gravis
Ach receptor antibodies = bind to post-synaptic neuromuscular junction receptors
Blocks the receptor -> ACh is unable to stimulate the receptor -> cannot trigger muscle contraction
115
Antibodies involved in myasthenia gravis
* ACh receptors
* Muscle-specific kinase (MuSK)
* Low-density lipoprotein receptor-related protein (LRP4)
116
When does myasthenia gravis improve and worsen?
* Worsens with activity
* Improves with rest
117
Symptoms of mysathenia gravis
The symptoms most affect the ***proximal muscles*** and small muscles of the head and neck. It leads to:
- Extraocular muscle weakness causing double vision (***diplopia***)
- Eyelid weakness causing drooping of the eyelids (***ptosis***)
- Weakness in facial movements
- Difficulty with swallowing
- Fatigue in the jaw when chewing
- Slurred speech
- Progressive weakness with repetitive movements
118
Examination of myastheia gravis
Elicit atiguability in the muscles:
* Repeated blinking
* Prolonged upward gazing
* Repeated abduction of one arm 20 times
119
First line investigations for myasthenia gravis
* Serum ACh receptor antibody analysis
* Muscle-specific tyrosine kinase (MuSK) antibodies
* Low-density lipoprotein receptor-related protein (LRP4)
* Serial pulmonary function tests (FVC + NIF)
120
When is the edrophonium test performed?
Diagnosis of myasthenia gravis
121
First-line treatment of myasthenia gravis
* Neostigmine or pyridostigmine
* Prednisolone or azathioprine
* Rituximab
122
Management of myasthenic crisis
* Non-invasive ventilation
* Full intubation + ventilation
* Immunomodulatory therapies (IV immunoglobulins, plasma exchange)
123
Which head presents as a dull, non-pulsatile, bilateral constricting pain (not severe, like a band around their head)?
Tension headache
124
How does a migraine persent?
* Moderate-to-severe intensity
* Pounding or throbbing
* Usually unilateral
* Photophobia or phonophobia
* Can be preceeded by aura
125
What is aura?
Visual changes associated with migraines
* Sparks in vision
* Blurring in vision
* Lines across vision
* Loss of different visual fields
126
Patient presents with unilateral throbbing headache, unilateral weakness of the limbs, ataxia and changes in conscious
Hemiplegic migraine
(can mimic a stroke)
127
Name some prodromal stage symptoms of a migraine
Yawning, fatigue, mood changes, followed by aura
128
First line management for a migraine
* NSAID
* Antiemetic (metaclopramide)
* Triptans (sumatriptan) - in severe cases
129
When do you use triptans?
As migraine starts
(e.g. sumatriptan)
130
Name 3 drugs used in migraine prophylaxis
* Propanolol
* Amitriptyline
* Topiramate (teratogenic)
131
What trigger in women may trigger a migraine?
Menstrual cycle
(may warrant prophylaxis)
132
Name some acute diagnosis differents of a migraine
* Subarachnoid haemorrhage (SAH) (CT)
* Giant cell arteritis (jaw claudication, inflammatory markers)
133
What headache can be described as a 'suicide headache'?
Cluster headache
(suicide = a complication)
134
Typical patient to present with a cluster headache?
30-50 year old male smoker
135
Describe the symptoms of a cluster headache
One-sided **sharp, stabbing, burning**, orbital/supraorbital, temporal head pain
136
Describe the signs of a cluster headache
* Red swollen, watering eye
* Pupil constriction (miosis)
* Eye drooping (ptosis)
* Nasal discharge
* Facial sweating
137
First line investigations for a cluster headache
* MRI brain (with contrast) (normal)
* ESR (normal)
* Pituitary function tests (normal)
138
One clinical exam to perform on a patient with a headache
Fundoscopy
(check for papilloedema - rasied intracranial pressure)
139
Complications for headaches
Depression!
140
Most common cause of trigeminal neuraglia
Vein or artery compressing the trigeminal nerve
(Results in demyelination + excitation -> results in erratic pain)
141
Triggers for trigeminal neuralgia attacks
Facial or oral mechanical stimulation
* Touching/moving tongue, lips, face
* Chewing
* Shaving
* Brushing teeth
* Blowing nose
* Hot/cold drinks
142
Patient presents with severe sharp, stabbing, shooting, electric shock pain in face, usually unilateral. Occurs in more than one distribution of the trigeminal nerve. Recovering paroxysmal attacks (1s-2min)
Trigeminal neuralgia
143
A sign of trigeminal neuralgia
Facial muscle spasms/autonomic symptoms
144
Differential diagnoses of trigeminal neuralgia
- Dental caries
- Dental fracture
- Migraine
- Temporal arteritis
- Mandibular osteomyelitis
145
First line and second line management of trigeminal neuralgia
* First line: Carbamazepine
* Second line: Phenytoin, gabapentin (analgesic targeted for neuropathic pain)
146
Surgical interventions for trigeminal neuralgia
* Microvascular decompression
* Ablative surgery
147
Define epilepsy and a seizure
* Epilepsy = umbrella term to describe when there is a tendency to have seizures
* Seizure = transient episodes of abnormal brain activity
148
Name some seizures
* Generalised tonic-clonic
* Focal
* Absence
* Atonic
* Myoclonic
149
Patient has a loss of conscious with muscle tensing and jerking. They also bite their tongue, wet themselves, and are breathing irregularly. Diagnosis?
Generalised tonic-clonic seizure
150
What is a post-ictal period?
Period after a seizure, presents confused, drowsy, irritable or depressed
151
First and second line management for a generalised tonic-clonic seizure
* Sodium valproate
* Lamotrigine or carbamazepine
152
Where do focal seizures start in the brain?
Temporal lobes
153
Differences between a focal aware seizure and a focal impaired awareness seizure
* Focal aware seizure = consciousness preserved
* Focal impaired awareness seizures = loss of awareness, memory loss of seizure, impaired responsieness during seizure
154
What can a focal seizure evolve into?
bilateral tonic-clonic seizure
(formally known as secondary generalised tonic-clonic seizure)
155
Patient presents with a sense of deja vu and then hallucinates. Their hearing and speech are also affected. Diagnosis?
Focal seizure
156
Management for a focal seizure?
* First line: Carbamazepine or lamotrigine
* Second line: sodium valproate
157
Difference between management of a focal seizure and a generalised tonic-clonic seizure
The first line and second line are swapped
158
A child randomally becomes blank, stares into space, then abruptly returns to normal (unaware of surroundings) - lasting 10-20s
Absence seizure
159
First line management of an absence seizure
Sodium valproate or ethosuximide
160
A child randomly drops to the floor and is there for less than 3 minutes. Diagnosis?
Atonic seizure
161
Management foran atonic seizure
* First line: sodium valproate
* Second line: Lamotrigine
162
A patient suddenly has brief muscle contractions (like a 'suden jump') - they remain awake during the episode. Diagnosis?
Myoclonic seizure
163
First and second line management for myoclonic seizures
* First line: Sodium valproate
* Second line: Lamotrigine
164
Diagnosis of epilepsy requirements
At least 2 unprovoked seizures occurring 24 hours apart
165
Investigations for epilepsy
* Clinical examination + history
* Electroencephalogram (EEG)
* MRI brain
166
Differential diagnoses for epilepsy
DRIFT 3R
* Drugs
* Rum (alcohol withdrawal)
* Illness (chronic)
* Fever
* Trauma
* Antis
* Rat poison
167
A female of child-bearing age with epilspsy needs to be prescribed medication, which one are you going to avoid?
Sodium valproate
(Highly teratogenic)
168
Side effects for carbamazepine
* Aplastic anaemia
* Induces the P450 system (so many drug interactions
169
What is status epilepticus?
Continuous seizure activity for over 5 mins -> permanent brain damage -> death
Or 3 seizures in an hour
170
How do you treat status epilepticus in the community and hospital?
* Community: Buccal midazolam
* Hospital: IV lorazepam (then IV phenytoin or IV phenobarbital if persists)
171
Progression of brain atrophy in AD
Medial temporal lobe -> limbic system -> widespread throughout brain
172
Describe the onset of AD
Insidious, progresses steadily
(deteriorating course over 8-10 years)
173
Describe the early, intermediate and advanced stages of AD
* Early: Recent memory impairment, impaired reasoning, concentration loss, sleep disturbance
* Intermediate: Behavioural psychological symptoms, motor task completion difficulties
* Advanced: Complete debilitation (urinary/faecal incontinence)
174
First line investigations for AD
* Mini Mental State Examination
* MRI head (generalised atrophy with medial temporal lobe)
175
Differential diagnoses for AD
* Delirium
* Depression
* Vascular dementia
* Dementia with Lewy bodies
* Frontotemporal dementia
* Parkinson's disease dementia
176
First line management for AD
* Cholinesterase inhibitor (oral rivastigmine or donepezil)
* Anti-glutamate (memantine)
177
Name a cholinesterase inhibitor
* Rivastigmine
* Donepezil
178
Define Alzheimer's disease
Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder characterised by a global, non-reversible impairment in cerebral functioning.
179
Which lobes area affected in frontotemporal dementia?
* Frontal
* Temporal
180
How does frontotemporal dementia usually present?
* Disruption in **personality + social** conduct
OR
* Primary **language** disorder
181
What do 50% of people with frontotemporal dementia also display?
Parkinsonism
182
When is the typical onset of frontotemporal dementia?
45-65 years
183
What specifc-protein cellular inclusions are involved in frontotemporal dementia?
Tau protein build-up → stop neuronal signalling → neuron apoptosis
184
What genetic mutation is a risk factor for frontotemporal dementia?
MAPT gene
185
What two types of motor disease are associated with frontotemporal dementia?
* Parkinsonism
* Motor neuron disease
186
What are the signs and symptoms of frontotemporal lobe dementia?
- **Frontal lobe involvement →behaviour/emotional changes**
- Disinhibition, emotional blunting, apathy/empathy-loss, compulsive behaviour, family/friend dissociation (argumentative/hostile behaviour)
- **Temporal lobe involvement → language impairment, emotional disturbance**
- Difficulty finding correct word, progressive aphasia, impaired word comprehension
- **Later stages → cognitive decline**
- Worsening memory, inability to learn new things, concentration loss
187
A patient presents with:
* Changes in personality and social behaviour
* Progressive loss of language comprehension
* Memory impairment, disorientation, apraxia
* Self-neglect and abandonment of social activity and contacts
Possible diagnosis?
Frontotemporal dementia
188
What are the Ix for frontotemporal dementia?
* Formal cognitive testing
- Frontotemporal rating scale (FRS)
- MMSE (not great)
* Brain MRI
- Atrophy in the front and/or anterior temporal lobes
- (usually left-right asymmetry)
189
When investigating frontotemporal dementia, if a brain MRI becomes back normal or intermediate. What imaging should you request? What would it show if positive?
**Brain fluorodeoxyglucose (FDG-PET) scan**
* Focal hypo-metabolism in the frontal and/or anterior temporal lobes (frequently asymmetrical)
190
What is the non-pharmacological and pharmacological treatments of frontotemporal dementia?
Non-pharmacological:
* Physical exercise
* Occupational therapy
* Increased supervision
Pharmacological:
* Benzodiazepine or antipsychotoc (**lorazepam**, risperidone)
* SSRI (**citalopram** or sertraline)
* **Trazodone** (sleep disturbances)
191
Possible complications for frontotemporal dementia
* Irresponsible/compulsive spending
* Dangerous driving
* Falls
* Problems with family relationships
192
What protein is responsible for Lewy body dementia and where is it found?
* Alpha-synuclein protein aggregation → Lewy bodies → apoptosis
* Cortex + substantia nigra
193
What are the key presentation of Lewy Body dementia?
* **Cognitive impairment**
- Attention, executive, visuospatial functions, memory (later)
* **Visual hallucinations**, disordered speech
* **Parkinsonism**
- Resting tremor
- Stiffness, slow movement
- Reduced facial expressions
* **REM sleep behavioural disturbance**
194
Imaging for Lewy body dementia. What does it show?
* CT/MRI head
* **Generalised cortical atrophy**
(preservation of the medial temporal lobe (particularly the hippocampus)
* CT PET
195
What are the first and second line treatments for Lewy Body dementia?
First line:
* Supportive care
* Cholinesterase inhibitor (rivastigmine or **donepezil**)
* SSRIs (sertraline or citalopram)
* Sleep disturbance → **clonazepam**
* Severe motor symptoms → dopaminergic agent (carbidopa/**levodopa**)
Second line:
* **Memantine** (orally)
* Antipsychotic (**risperidone**)
196
Name an antipsychotic
Risperidone
197
Name a cholinestarse inhibitor
* Rivastigmine
* Donepezil
198
Complications of Lewy Body dementia
* (Aspiration) Pneumonia
* Dysphagia
* Antipsychotic sensitivity
* Urinary incontinence
* Falls
199
What drug is effective for REM sleep behavioural disorder in Lewy body dementia?
Clonazepam
200
What are some causes of vascular dementia?
Cerebrovascular changes: E.g. **Infarction, haemorrhage**
* **Cerebral artery atherosclerosis**
* Carotid artery/heart embolisation
* Chronic hypertension → cerebral arterioles sclerosis
* **Vasculitis**
201
Name a couple of Rx for vascular dementia
* Age > 60 yrs
* Obesity
* Hypertension
* Cigarette smoking
202
Where does the damage occur in vascular dementia?
Grey + white matter
203
What are the key presentations of vascular dementia?
- Prominent executive function deficit
- Progressive stepwise cognitive function impairment
- Late-onset memory impairment
204
What does damage in the frontal lobe lead to?
Executive dysfunction
205
What does damage in the left parietal lobe lead to?
* Aphasia
* Apraxia
* Agnosia
206
What does damage in the right parietal lobe lead to?
* Hemineglect (unaware of one side of body)
* Confusion
* Agitation
* Visuospatial difficulty
207
What does damage in the temporal lobe do?
Anterograde amnesia
208
Ix for vascular dementia
* **Brain CT/MRI**
- Cerebrovascular lesions (**multiple cortical, subcortical infarcts**)
* ECG (AF may be present)
* Vitamin B12 (rule out for cognitive decline)
* Carotid duplex/doppler ultrasound (reveal carotid plaques/carotid stenosis)
* **Echocardiogram** (reveal cardiogenic emboli)
209
What is the management for vascular dementia?
* Antiplatelet therapy (prevent further infarction)
- **Aspirin** or **clopidogrel** (orally)
* Lifestyle modification
* Concomitant AD → **Memantine** OR acetylcholinesterase inhibitor (donepezil or **rivastigmine**)
* Vadcular risk factor control (atorvastatin)
* Depression/agitation (**sertraline**)
210
How is vascular dementia characterised?
Chronic progressive multifaceted impairment of cognitive function
211
Descrbe the onset of a stroke
SUDDEN ONSET
212
Define an ischaemic stroke?
* Neurological dysfunction
* Caused by **focal** cerebral, spinal or retinal infarction
* (Cell death due to lack of blood supply)
213
What are the 5 types of ischaemic stroke? (Classification)
TOAST Classification
- **Large artery atherosclerosis**
- **Small artery strokes**
- **Cardioembolic infarction**
- Formation of emboli in heart → lodging in brain arteries
- AF, MI, IE
- Other determined pathology
- Undetermined pathology
214
What proportion of strokes are ischaemic?
80%
215
Name some causes of ischaemic stroke
* Large artery stemosis
* Cardioembolic (AF, MI, IE)
* Atherothromboembolism (e.g. from cartotid artery)
* Shock (reduced blood flow throughout body)
* Vasculitis
216
Rx for iscahemic stoke
- **Older age (esp. >55)**
- **Hypertension**
- **Smoking**
- Male sex
- Same risk factors as atherosclerosis → atherosclerotic plaque → occlusion of cerebral artery → ischaemic stroke
217
Pathophysiology of an ischaemic stroke
- Blood vessel occlusion → decreased blood supply in specific brain area → hypoperfusion → tissue hypoxia → infarction
- ↓blood flow → ↓oxygen + glucose in brain → ↓ATP production → cell death
218
Pathology of thrombosis in ischaemic stroke
* Obstruction in blood vessel
* **Narowing** of blood vessel due to atherosclerotic plaque → gradual reduced blood flow
* Damage to **atherosclerotic fibrous cap** → **platelet + clotting cascade activation** → thrombus formation with sudden stop to blood flow
219
Key generalised presentations of an ischaemic stroke
* **Unilateral weakness** or paralysis in face, arm, leg
* **Dysphasia** (difficulty in speech - slurred)
* **Ataxia**
* **Visual disturbance**
220
What is the scoring system for assessing the risk of an ischaemic stroke?
ABCD2
* A - Age
* B - Blood pressure
* C - Clincial presentation
* D - Duration of symptoms
* D - Diabetes
221
First line and other Ix for ischaemic stroke
First line:
* **CT head** (no contrast)
* Blood (exclude **hypoglycaemia**)
* ECG +/- hour tape
- AF or MI
Gold-standard:
* **Diffusion-weighted MRI head** (more sensitive)
Other:
* **Carotid doppler**
* Echo
* CT or MRI angiogram
222
What is the first line treatment for an ischaemic stroke?
Within 4.5 hours:
* Thrombolysis (**IV altepase**)
Within 6-24 hours:
* **Thrombectomy** (mechanical removal of clot)
| BP should not be lowered during stroke - risk reducing perfusion
223
What does ROSIER stand for and when is it used?
Recognition of Stroke in the Emergency Room
224
4 potential mechaisms for ischaemic stroke
* **Embolism**: an embolus originating somewhere else in the body (e.g. the heart) causes obstruction of a cerebral vessel, resulting in hypoperfusion to the area of the brain the vessel supplies.
* **Thrombosis**: a blood clot forms locally within a cerebral vessel (e.g. due to atherosclerotic plaque rupture).
* **Systemic hypoperfusion**: blood supply to the entire brain is reduced secondary to systemic hypotension (e.g. cardiac arrest).
* ** Cerebral venous sinus thrombosis**: blood clots form in the veins that drain the brain, resulting in venous congestion and tissue hypoxia.
225
Which regions of te brain are supplied by the anterior cerebral arteries?
Anteromedial area of cerebrum
226
Which region of the brain is supplied by the middle cerebral arteries?
Lateral cerebrum
227
Which regions of the brain are supplied by the posterior cerebral arteries?
Posterior cerebrum
228
Based on the initial presenting symptoms + clinical signs - what classification system is used in ischaemic stroke?
Bamford classification
229
What are the principal management of an intracranial bleeds?
* ** Immediate CT head to establish the diagnosis
* Check FBC and clotting
* Admit to a specialist stroke unit**
* Discuss with a specialist neurosurgical centre to consider surgical treatment
* Consider intubation, ventilation and ICU care if they have reduced consciousness
* Correct any clotting abnormality
* Correct severe hypertension but avoid hypotension
*
230
What is an intracerebral haemorrhage?
* Blood vessels rupture → intraparenchymalblood accumulation
231
Pathology of an intracerebral haemorrhage
Blood vessel trauma → **rupture** → creates blood of blood → **tissue + surrounding blood vessel compression** → **hypoxia** in downstream tissue → damage due to compression → **oxygen lack**
232
Causes of intracerebral haemorrhage
- **Hypertension (most common)**
- **Atherosclerosis**
- Vascular abnormalities
- Cerebral amyloid angiopathy
- Vasculitis
- **Secondary to ischaemic stroke**
- Blood flow blockage → reperfusion → increased chance of blood vessel rupture → bleeding into dead tissue
233
Rx for intracerebral haemorrhage
- Male sex
- Black individuals (African descent)
- Heavy alcohol use, amphetamines, cocaine abuse, antithrombotic medications
234
General presentation of an intracranial haemorrhage
- Begin slowly → worsen gradually
- Enlargement of haematoma (within few hours) → increased intracranial pressure
- Altered consciousness
- Headache
- Nausea + vomiting
- Unequal pupil size
235
Sx if there a stroke in the anterior/middle cerebral artery
Numbness + sudden muscle weakness
236
Sx if there a stroke in the posterior cerebral artery
Impaired vision
237
Sx if there a stroke in Broca's area
Slurred speech
238
Sx if there a stroke in Wernicke's area
Difficulty understanding speech
239
What is a major complication of intracerebral haemorrhage?
Hydrocephalus
240
Ix for intracerebral haemorhage
- Head CT (no contrast)
- Trauma → multifocal bleedings
- CT angiography
- Unifocal/multifocal enhancement of contrast
- Diffusion-weighted MRI (T2-WI)
- Bloods:
- Prothrombin time
- FBC (platelet count)
241
Treatment of intracerebral haemorrhage
| Not sure on this
- With anticoagulant usage → **Vitamin K, unactivated prothrombin**
- **Enalapiril** (hypertension)
- **Phenytoin** (seizures)
- **Antipyretics** (fever reduction)
**Surgery:**
- If haemorrhage >3cm / brainstem compression
- Craniotomy with clot removal
- **Endoscopic evacuation**
242
If a patient presents with a thnderclap headache, what is the main worrying possible diagnosis?
Subarachnoid haemorrhage
243
Where does a subarachnoid haemorrhage occur?
Between the **pia mater** + **arachnoid mater**
(In the **subarachnoid space**)
244
Pathology of a spontaneous haemorrhage
Spontaneous event/injury → rupture of blood vessel in **subarachnoid space** → release of **blood into CSF** →** rapid increase in intracranial pressure**
245
Causes of subarachnoid haemorrhage
- **Traumatic → head injury**
- Spontaneous → arterial origin (more common)
- Arteriovenous blood vessel malformations
- Rupture of saccular ‘berry’ aneurysms (e.g. anterior half of circle of Willis)
246
What is a symptom of raaised intracranial pressure?
THUNDERCLAP HEADACHE
- ‘Worst ever’ headache
- May be only symptom
N+V
247
What is a major complication of a subarachnoid haemorrhage?
ASPEPTIC MENINGITIS
- Bleeding into subarachnoid space filled with CSF → blood degradation → irritation of meninges → development of aseptic meningitis
- Neck pain + stiffness
- Photophobia
- Brudzinksi’s (force neck flexion → spontaneous knee, hip flexion)
248
If a patient who has thought to have a subarachnoid haemorrhage, is experiencing neck pain + stiffness and photophobia. What might have they developed?
Aseptic meningitis
(Meningeal irritation)
249
What cranial nerve may be affected in increased intracranial pressure? How might this present?
**Increased intracranial pressure** → **abducens** nerve paralysis → eye pointing out → **diplopia**
250
Complications of a subarachnoid haemorrhage
- Vasospasm → delayed ischaemia
- **Hydrocephalus**
- Clogging of CSF drainage
- Re-bleeding
- Sympathetic hyperactivity due to increased intracranial pressure
- **SAH (’sympathetic surge’)**
- Sudden life-threatening increase in blood pressure - due to vasoconstriction
- **Meningitis (irritation from presence of blood)**
- Seizures
251
Ix for subarachnoid haemorrhage
- **Head CT (non-contrast)**
- Hydrocephalus (’Mickey Mouse’ ventricular system appearance
- MRI
- Visualise arteriovenous malformations (not detected by angiography)
- **Lumbar puncture**
- Increase **erythrocytes** in all samples
- CSF centrifugation → yellow coloration (due to erythrocytes breakage)
- **Fundoscopy** (optic disc swelling)
252
Tx for subarachnoid haemorrhage
- Antihypertensive therapy
- Beta-blockers
- Hydralazine
- **Calcium channel blockers**
- ACEi
- Intracranial pressure treatment
- Osmotic or **loop diuretics**
- Prior all procedures: IV midazolam (initial treatment)
- Vasoconstriction treatment
- Calcium channel blocker
- Seizure treatment (phenytoin, phenobarbital)
**Keep blood pressure <140 mmHg to avoid re-bleeding**
253
Where does a subdural haemorrhage occur?
Intracranial bleeding with blood accumulation between dura mater + arachnoid membrane
254
Causes of a subdural haemorrhage
- Head trauma (most common)
- Acceleration-deceleration (coup-contrecoup injury)
- Shaken baby syndrome
- Spontaneous (vascular malformations)
255
Risk factors for a subdural haemorrhage
- Brain atrophy elderly → bridging veins stretch
- Infants, alcohol abusers → thinner wall of bridging veins
- Epilepsy, anticoagulant drugs, thrombocytopenia
256
Sign and symptoms of a subdural haemorrhage
- **Loss of consciousness **after trauma/in ensuing days due to haematoma expansion
- Acute subdural haematoma
- **Sudden, severe headache**, with nausea + vomiting
- **Unequal pupils**
- **Difficulties in speech** + swallowing
- Palsies of cranial nerves
- Chronic (present 14 days after injury)
- Impaired cognitive skills
- Altered consciousness
- Headaches
- Contralateral/ipsilateral hemiparesis (depends on haematoma location)
- **Optic disc swelling**
257
How does a subdural haemorrhage appear on a head CT?
Cresent shape
258
Management of a subdural haemorrhage
**Medications:************************
- Diuretics (decrease intracranial pressure)
- Vitamin K (anticoagulation reversal)
- Lower risk of haematoma enlargement
****************Surgery:****************
- If clot thickness > 10mm, midline shift > 5mm, intracranial pressure > 20 mmHg
- **Burr Hole**
- **Decompressive craniectomy**
- Craniotomy
- Blood vessel ligation
259
What is used for anticoagulation reversal to lower the risk of haematoma enlargement?
Vitamin K
260
What can used to decrease intracranial pressure?
Loop diuretics
261
What is an extradural (epidural) haemorrhage?
Nervous tissue compression - due to accumulation of blood in the epidural space
Types: Intracranial + spinal
262
Causes of an epidural haemorrhage
- Neurosurgical procedures complication
- Trauma
**Intracranial epidural haematoma**
- Head trauma → pterion skull fracture (most common)
- Blood vessel malformations
**Spinal epidural haematoma**
- Trauma (e.g. lumbar puncture/epidural anaesthesia)
263
How does an epidural haemorrhage initially present?
Initial state of consciousness
* Lucid state
* Delayed neurological deterioration - consequence of enlarging haematoma compression
264
What are the signs of increased intracranial pressure?
- Headache
- Nausea + vomiting
- **Cushing reflex (↑blood pressure, ↓heart rate, irregular breathing)**
- Focal signs
- Weakness of extremities on opposite side
- Dilated pupil on injured side - due to compression of CN III
265
A patient presents with a broken skull with a haematoma + altered conscioussness. Possible diagnosis?
Intracranial epidural haematoma
266
A patient presents with radicular back pain (resembles pain from herniated discus), sensory defects and urinary + faecal incontinence. What is a possible diagnosis?
Spinal epidural haematoma
267
How does an epidural haematoma present on a NCCT?
Biconvex haematoma
(+skull fracture)
268
Treatment of an epidural haemorrhage
**Medications:**
- Mannitol, other osmotic diuretics
- ↑urine excretion, ↓intracranial pressure
- Anticoagulation reversal
**Surgery:**
- Craniotomy (evacuation of blood mass)
- Laminectomy (↓blood in spinal epidural haematoma)
269
What is meningitis?
Inflammation of the meninges surrounding the brain + spinal cord
270
Non-infective causes of meningitis
* Paraneoplastic
* Drug side effects
* Autoimmune (e.g. vasculitis, SLE)
271
Mnemonic for bacterial causes for meningitis
**E**xplaing **B**ig **H**ot **N**eck **S**tiffness
- **E**. coli, Group **B** streptococcus (infants)
- **H**aemophilus influenzae (older infants, kids)
- **N**eisseria meningitidis (young adults)
- **S**treptococcus pneumoniae (elderly)
272
Name two diplococci bacteria that cause meningitis
- Strep **p**neumoniae – most common in adults
- Gram **P**OSITIVE diplococci
- **N**eisseria meningitidis
- Gram **N**EGATIVE diplococci
273
Name a parasitic cause of meningitis
P. Falciparum
274
What are 4 risk factors for meningitis
SPIT:
* Students
* Pregnancy
* Immunocompromised
* Travel
275
What are the three major presentations for meningitis?
* Fever
* Headache
* Neck stiffness ('meningism')
276
What are 2 clinical signs (tests) for meningitis?
* Kernig's sign
* Brudzinksi's sign
277
What are some signs of meningitis?
* **Non-blanching/blanching purpuric rash**
- Glass test
- Non-blanching: meningococcal septicaemia - bacterial meningitis
* **Photophobia/phonophobia**
* **Papilloedema** (swelling of optic disc on fundoscopy)
- **Usually bilateral**
278
What is the immediate/first line treatment for meningitis?
**IM benzylpenicillin**
(before investigations)
279
First line treatment/investigations for meningitis
* IM bensylpenicillin
* Assess GCS
* Blood culture (BEFORE antibiotics)
* Broad-spectrum antibiotics
- First line: Cefotaxime or ceftriaxone
- Immunocompromised: + amoxicillin
- Recent travel: + vancomycin
* Steroids: IV dexamethasone
* LUMBAR PUNCTURE (diagnostic)
- Microscopy
- Gram stain
- Culture
- Viral PCR
- Consider Acid Fact Bacilli (TB)
* CT head
280
Contraindications for a lumbar in meningitis
* **Abnormal clotting**
* **Petechial/purpura**
- Because suggests bloodborne virus so could introduce bacteria into CSF
* **Raised intracranial pressure (papilloedema)**
281
DDx for meningitis
- ‘**Worst headache ever**’ → **subarachnoid haemorrhage** (especially if trauma, ‘**thunderclap onset**’)
- Migraine
- Encephalitis
- Flu and other illnesses
- Sinusitis
- Brain abscess
- Malaria
282
Name 3 major complications of meningitis
* **Cerebral oedema**
* **Cerebral abscess**
* Venous sinus thrombosis
283
What is the protein level in CSF in meningitis?
High protein content
284
What is encephalitis?
* Encephalitis = inflammation of brain parenchyma
* Associated with neurological dysfunction
- Altered state of consciousness
- Seizures
- Personality changes
- Cranial nerve palasies
- Speech problems
- Motor + sesnory deficits
285
What is the most common cause of encephalitis?
* Viral - **HERPES SIMPLEX** (most common)
* Varicella zoster (chicken pox)
286
Which lobes are primarily affected in encephalitis?
* **Frontal + temporal** lobes
Results in:
* Decreased consciousness
* Confusion
* Focal signs
287
Pathology of encephalitis
* **Peripheral nerve conduits** to brain parenchyma (for virus - herpes simplex virus)
* **Haematogenous spread** (transer of infections from distant sites)
288
Presentation of encephalitis
* Preceding **'flu-like'** illness
Then (triad): **ACUTE ONSET FEBRILE ILLNESS** + ALTERED MENTAL STATUS
* **Altered GCS** (confusion, drowsiness, coma)
- Seizure, memory loss
* **Fever**
* **Headache**
289
What neurological condition could lead to encephalitis?
**Meningitis**
(Patient may meningism presentation aswell as encephalitis)
290
Ix for encephalitis
* **Lumbar puncture**
- CSF for viral PCR, serology
- Raised lymphocytes
* **CT head** (if lumbar puncture is contraindicated)
* **MRI** after lumbar puncture
- Show swelling/ inflammation ± midline shifting due to raised ICP
* **Blood cultures**
* **Throat swab**
* **HIV** testing
- Acute phase viraemia can cause encephalitis
* **EEG**
291
What is the treatment for encephalitis?
* **Aciclovir IV**
* Supportive care
* Carbamazepine (seizures)
* IM benzylpenicillin (meningitis)
292
Complications of encephalitis
* Raised intracranial pressure
* Seizures
* Coma
293
What should be administered as soon as you suspect encephalitis?
Aciclovir
294
What is motor neuron disease?
* Umbrella term
* Prossive → ultimately fatal
* **Motor neurons stop functioning **
295
What happens to the motot + sesnory neurons in motor neuron disease?
* Motor neurons = stop functionng
* Sensory neurons = not affacted
- Patients should have no sensory symptoms
296
What is amytrophic lateral sclerosis (ALS)?
* = motor neuron disease
* Loss of motor neurons in **motor cortex + anterior horn**
* UMN + LMN signs = most common
297
How does amytrophic lateral sclerosis (ALS) present?
- Progressive focal wasting
- Weakness + fasciculation (muscle twitching) spreading to other limbs
- Cramps
- Spasticity
- Brisk reflexes
298
How does primary lateral sclerois present?
**UMN signs only **
* Slow progressive tetraparesis
* Pseudobulbar palsy
299
How does progressive muscular atrophy present?
**LMN signs only**
* Weakness + fasciculations in one limb → progressing to adjacement spina segments
300
How does progressive bulbar palsy present>
UMN + LMN + Cranial nerve 9,10,11,12 signs
Lower cranial nuclei affected causing:
* Dysarthria (difficultly speaking)
* Dysphagia
* Nasal regurgitation of fluids
* Choking
301
Who is motor neuron disease most likely to present in?
Middle aged men
302
Where do upper motor neurons start and travel through?
* **UMN** = in the **motor cortex** (in pre-frontal gyrus)
* Axons travel through hemispheres into spinal cord - via **corticospinal tract**
303
Where do lower motor neurons start?
**LMNs** = sit in **motor nuclei** in various parts in the **brain stem** + all way down the **spinal cord** in cord in **columns** in the **ventral horn** of the **spinal grey matter**
304
Read: Organistaion of movement
- **Idea of movement** – **association areas** of cortex
- Activation of **upper motor neurons** in the **pre-central gyrus**
- Impulses travel to **lower motor neurons** and their motor units via the **corticospinal (pyramidal) tracts**
- **Modulating activity of the cerebellum and basal ganglia**
- Hence why individuals with cerebellar and basal ganglia disorders can’t control movements properly
- **Further modification** of movement depending on **sensory feedback**
305
Read: Regulation of muscle tone
- **Stretch receptors** in muscle (**muscle spindles**) innervated by **gamma motor neurons**
- **Muscle stretched** 🡪 **afferent impulses** from muscle spindles which 🡪 **reflex partial contraction of muscle**
- **Disease states e.g. spasticity and extrapyramidal rigidity alter muscle tone by altering the sensitivity of this reflex**
306
What gene is implicated in motor neuron disease pathology?
**SOD-1** gene mutation
Suggests** oxidative stress + free radicals** are implicated in the **destruction**
307
Name 3 Rx for motor neuron disease
* **Smoking**
* Exposure to **heavy metals**
* Certain **pesticides**
308
Pathology of motor neuron disease
- **Degenerative** condition affecting **motor neurons** – mainly the **anterior horn cells**
- There is relentless and unexplained **destruction of UMN and anterior horn cells in the brain and spinal cord**
- **Causes both UMN and LMN dysfunction**
- **UMN and LMN affected but no sensory or sphincter loss – distinguishes from MS**
- **Never affects eye movements – distinguishable from myasthenia gravis**
309
What signs/symptoms distinguish motor neuron disease from MS and myasthenia gravis?
MS vs MND: **MND** = UMN + LMN affected but **no sensory** or **sphincter loss**
Mysthenia gravis vs MND: **MND =** **never affected the eyes**
310
Read: Diseases that affect final common pathways
* Motor neurons of the brainstem or spinal cord → Motor neuron disease, spinal cord/brainstem compression
* Spinal rooys → tumours
* Peripheral nerve → axonal degeneration or demyelinating
* NMJ → Myasthenia Gravis
311
Onset of motor neuron disease
Insidious + progressive onset
312
Name a sign of motor neuron disease
Slurred speech (dysarthria)
313
Name some general motor neuron disease symptoms
- **Insidious, progressive weakness of the muscles throughout the body**
- Limbs
- Trunk
- Face
- Speech
- **Weakness = often first noticed in the upper limbs**
- May have increased fatigue when exercising
- Complain of clumsiness (dropping things, tripping over)
- **Headache in morning (nocturnal hypercapnia)**
314
What are some symptoms of lower motor neuron disease?
EVERYTHING GOES **DOWN**!
- **Reduced muscle tone** (flaccid)
- **Fasciculations** (twitches in the muscles)
- **Reduced reflexes** (hyporeflexia)
- **Muscle wasting**
- **Bulbar** → speech + swallowing muscles
- Upper limb → hand muscles
- Lower limb
- **Bilateral foot drop** (from wasting of tibialis anterior muscle) → prominent tibial bones
- **Respiratory** → weakness of breathing muscles
- Diaphragm = higher up
- Most patients = die from **respiratory issues**
315
What are some symptoms of upper motor neuron disease?
EVERYTHING GOES **UP**
- **Increased tone** (spasticity)
- **Hyperreflexia → Brisk reflexes**
- Upgoing/extensor plantar responses (**positive Babinski sign**)
- When you stroke sole of foot, normally big toe should go down
- Goes up in UMN lesions
- **Characteristic pattern of limb muscle weakness (pyramidal pattern)**
- Upper limb extensor muscles = weaker than flexors
- Lower limb flexor muscles = weaker than extensors
- Finer, more skilful movements most severely impaired
- **Pyramidal drift**
- Hold hands out → one arm will ‘drift away’
316
What does a positive Babinski sign indicate?
(Upgoing/extensor plantar responses)
- When you stroke sole of foot, normally big **toe should** go down
- Goes up in **UMN lesions**
317
What is pyramidal shft? When is it found?
Hold hands out → one arm will ‘drift away’
Found in **upper motor neuron disease**
318
What is the diagnosis criteria for motor neuron disease?
Diagnosis = based on clinical presentation + excluding other conditions that can cause motor neurone symptoms
* Definite = LMN + UMN signs in **3 regions**
319
What Ix should you request for UMN lesions?
* **MRI spine + brain**
* Blood tests for metabolic disorders
* **Lumbar puncture: CSF examinations** (e.g. oligoclonal bands (MS))
320
What Ix should you request for LMN lesions?
* **MRI brain + spine**
* **Neurophysiology nerve conduction studies/electromyography**
* Blood tests
- **Raised creatinine kinase** (due to muscle destruction)
- Peripheral neuropathy screen
- Auto-antibodies
* **Lumbar puncture** (exclude inflammatory causes)
321
Read: Diagnostic tips for motor neuron disease
* Non sensory loss → rule out MS or myelopathy
* No disturbances in eye movements → rule out myasthenia gravis or multiple sclerosis (MS)
* No spincter disturbances → rules out MS
322
Differential diagnoses for motor neuron disease
- **Multiple sclerosis (MS)**
- UMN and LMN affected but **no sensory or sphincter loss** – distinguishes from MS
- **Myasthenia gravis**
- Never affects **eye movements** – distinguishable from myasthenia gravis
- ********Cervical spine lesion********
- May present with UMN + LMN signs in arms + legs
- **Idiopathic multifocal motor neuropathy**
- Presents with weakness → predominantly in hands
- Profuse fasciculation
323
Differential diagnoses for motor neuron disease
- **Multiple sclerosis (MS)**
- UMN and LMN affected but **no sensory or sphincter loss** – distinguishes from MS
- **Myasthenia gravis**
- Never affects **eye movements** – distinguishable from myasthenia gravis
- **Cervical spine lesion**
- May present with UMN + LMN signs in arms + legs
- **Idiopathic multifocal motor neuropathy**
- Presents with weakness → predominantly in hands
- Profuse fasciculation
324
Is there a cure for motor neuron disease?
No
325
What is the first line drug in motor neuron disease?
**Riluzole**
* (sodium channel blocker → inhibits glutamate release)
* Can slow disease progression → extend survival by a few months in ALS
326
Give two examples of symptom management for motor neuron disease
* **Dysphagia** → **NG/PEG tube**
* **Drooling** (due to bulbar palsy) → oral **amitryptyline**
* **Spasticity** → **baclofen**
* Joint pain → analgesia
* **Non-inasive ventilation (NIV)**
- Supports breathing at night (for **nocturnal hypercapnia**)
327
Complications of motor neuron disease
* **Respiratory failure** or **pneumonia**
- Patients usually die of this
* Aspiration pneumonia
328
What is the median survival for ALS?
3-5 years
329
Name a cause of an upper motor lesion
* **S**troke
* **I**nfection
* **T**umour
(**Any injury to the brainstem or spinal cord** = can cause upper motor neuron lesions)
* Specifically the **WHITE MATTER** of the spinal cord (where the upper motor neurons are travelling through)
330
Where can damage occur to cause a lower motor neuron lesion?
Any **damage** to the **spinal cord (grey matter)** or **axons leaving** the spinal cord to the **skeletal muscle**
- Specifically to the **VENTRAL GREY MATTER** of the spinal cord (the anterior horn of the spinal cord)
-** Anterior horn of the spinal cord** = where the **UMNs** and **LMNs** **synapse** (where the **LMNs = start**)
331
A patient presents with muscle weakness, but no atrophy. Reflexes are increased w/ a positive Babinski sign. Patient does no experience fasciculations. When holding their hands out, one arm will drift away. Possible diagnosis?
Upper motor lesion
| **Pyramidal drift** = Hold hands out → one arm will ‘drift away’
332
A patient presents with muscle weakness and atrophy. They have diminshed/absent deep tendon reflex. They also have flaccid paralyis w/ no plantar response. They alos experience fasiculations. Possible diagnosis?
Lower motor neuron lesion
333
CN I (Olfactory) Palsy Sx
Anosmia - can't smell
334
CN II (Optic nerve) paslsy Sx
Visual defect - depends on location
335
CN III (oculomotor) palsy Sx
* Ptosis = drooping of eyelids
* Fixed pupil dilation
* Eye down + out
336
Causes of a CNIII palsy
* Raised ICP
* Diabetes
* Hypertension
* Giant cell arteritis
337
CN IV (trochlear) palsy Sx
Diplopia (double vision) on looking down (e.g. walking down the stairs)
338
CN V (trigeminal) palsy Sx
* Jaw deviates to the side of the lesion
* Loss of corneal reflex
- Involuntary blinking of the eyelids elicited by stimulation of the cornea
339
CN VI (abducens) palsy Sx
Eyes abducted
340
Causes of CN VI (abducen's) palsy?
* MS
* Wernicke's encephalopathy
* Pontine stroke (fixed small pupils)
341
CN III, IV, VI (3,4,6) Palsy
Non-functioning eye
Causes:
* Stroke
* Tumours
* Wernicke's encephalopathy
342
CN VII (facial) palsy Sx
Facial droop + weakness
343
Name a major cause of CN VII (facial) nerve palsy and the treatment
Bell's palsy
(dribbling at side of mouth)
Management = steroids
344
Difference in presentation between Bell's palsy and stroke
* Bell's palsy → forehead + lip droop
* Stroke → Lip droop
345
CN VIII (vestibulocochlear) palsy Sx
* Hearing impairment
* Vertigo + lack of balance
346
CN IX (glossopharyngeal) and CN X (vagus) palsy Sx
* Gag reflex issue
* Swallowing issues → uvula = deviates from the side of the lesion
* Vocal issues
347
CN XI (accessory) palsy
Cannot shrug shoulder or shake head
348
CN XII (hypoglossal) palsy Sx
Tongue deviates towards side of lesion
349
What is Brown-Sequard syndrome?
Hemisection of the spinal cord
350
Name some causes of spinal cord compression
* Trauma
* Spinal cord tumours
* A prolapsed intervertebral disc (herniation)
* Epidural or subdural haematoma
* Inflammatory disease (esp. rheumatoid arthritis)
* Spinal infection
* Cervical spondylitic myelopathy
* Spinal manipulation
351
Where is the most common site for a prolapsed intervertebral disc (herniation)
**L4-L5** and **L5-S1**
(Large disc herniations can cause cauda quina syndrome)
352
What are the sensory and motor symptoms of spinal cord compression
**Sensory symptoms = sensory loss + paraesthesia**
* Light touch + proprioception + joint position sense = reduced
**Motor symptoms = fatigue + gait disturbance**
353
What is the presntations of:
* Cervical spine
* Thoracic spine
* Lumbar spine
* **Cervical spine lesion → quadriplegia + artifical ventilation = required**
- Injury above level C3,C4, C5 (the segmental level of the phrenic nerve) → causes paralysis of the diaphragm → artificial ventilation is required
* **Thoracic spine lesion → paraplegia**
* Lumbar spine lesions → can affect L4, L5 and sacral nerve roots
354
What is the investigation for spinal cord compression?
MRI spine
355
What is metastatic spinal cord compression?
When a metastatic lesion = compresses the spinal cord (before the end of the spinal cord and the start of the cauda equina)
* It is an oncological emergency
356
What is the difference between metastatic spinal cord compression and cauda equina syndrome?
* Cauda equina syndrome = presents with LMN signs (reduced muscle tone + reduced reflexes)
* Metastatic spinal cord compression = UMN signs seen (increased tone, brisk reflexes, upping plantar responses)
- Spinal cord = being compressed higher up
357
Where is compression in sciatica?
L5/S1 root compression
358
What is radicular pain?
Radiating shooting pain
359
Name a spinal and non-spinal cause of sciatica
* Spinal: Spinal disc herniation
* Non-spinal: Pregnancy
360
How does sciatica present?
Unilateral sudden shooting pain radiating from lumbar spine down leg (side , back) to foot
* Pain: Lower back, buttock, hip and foot
* Numbness, muscle weakness, burning sensation
361
What Ix/tests do you perform for sciatica?
* MRI/x-ray
* Straight leg raising test
* Crossed straight leg raising test (higher specificity)
362
First and second line management for sciatica
* Fist line: Analgesia (**NSAIDs**)
* Secon line: Surgical decompression, spinal disc repair (severe symptoms)
363
What is cauda equina syndrome?
- Cauda equina = formed by the **nerve roots distal to the termination of the spinal cord at L2/L3**
- Cauda equina syndrome = caused by compression of the lumbosacral nerve roots of the cauda equina
- CES is a **neurosurgical emergency**, and delays in diagnosis and treatment may lead to permanent disability.
364
Caues of cauda equina syndrome
* **Lumbar disc herniation** at **L4/L5** and **L5/S1**
* Tumours
* **Spondylolisthesis** (anterior displacement of a vertebra out of line with the one below)
* Abscess
* Trauma
365
What is the cauda equina?
* Cauda equina = collection of roots - that travel through the spinal canal AFTER the spinal cord terminate around **L2/L3**
* The nerve roots = exit either side of the spinal column at their vertebral level
- (L3, L4, L5, S1, S2, S3, S4, S5 and Co)
366
What does the cauda equina supply?
- **Sensation → lower limbs + perineum + bladder + rectum**
- **Motor innervation → lower limbs + anal** and **urethral sphincters**
- **Parasympathetic innervation → bladder + rectum**
367
What os the treatment of metastatic spinal cord compression?
- High dose dexamethasone (to reduce swelling in the tumour and relieve compression)
- Analgesia
- Surgery
- Radiotherapy
- Chemotherapy
368
What is the menomic for cauda equina syndrome presentation?
SPINE
* S- Saddle anaesthesia
* P - Pain
* I - Incontinence
* N - Numbness
* E - Emergency
**BLADDER DYSFUNCTION = essential component of CES**
369
Other Sx of cauda equina syndrome
Signs:
* **Fasciculations**
* Urinary retenion
Symptoms:
* **Saddle anaesthesia **
* **Less bladder + bowel control**
* **Erectile dysfunction**
* Lumbosacral pain
* **Leg weakness - flaccid + areflexic**
* Paraplegia
370
What are the first and gold-standard investigations for cauda equina syndrome?
First line:
* Digital rectum examination
* Examination (knee flexion, straight leg raising)
Gold standard:
* MRI lumbar spine (without contrast)
371
Treatment for cauda equina syndrome
- Immediate hospital admission → **MRI spine**
- Neurosurgical input → **lumbar decompression surgery** of the spinal cord
372
Complications of cauda equina syndrome
- **Bladder dysfunction**
- Bowel dysfunction
- Sexual dysfunction
- Back and/or leg pain
- Sensory pain
- Leg weakness
373
Define syncope
Event of **temporarily losing consciousness** - due to a d**isruption of blood flow to the brain** → often leading to a **fall**
374
What are the 3 major criteria for syncope?
* Loss of consciousness
* Loss of consciousness = must be TRANSIENT (self-limiting)
* Caused by GLOBAL CEREBRAL HYPOFUSION (almost always means BP)
375
Name some causes of primary syncope (simple fainting)
- **Dehydration**
- **Missed meals**
- **Extended standing** in a **warm environment**, such as a school assembly
- A** vasovagal response to a stimuli**, such as sudden surprise, pain or the sight of blood
376
Pathophysiology of syncope
* Strong stimulus (emotional event, painful sensation, change in temp) → **stimulates vagus nerve** → stimulates parasympathetic nervous system
* Blood vessels delivering blood to the brain = relax → BP in the cerebral = drops → hypoperfusion of brain tissue → patient = loses consciousness and ‘faint’
377
Ix for syncope
* ECG (arrhythmia + long QT syndrome)
* Bloods (FBC: Anaemia; Electrolytes: Arrhythmias + seizure; Blood glucoese)
* Neurological examination
* **Lying and standing blood pressure**
* **Tilt-table testing**
378
What is tilt table testing used to diffrentiate between?
Vasovagal syncope + Postural (orthostatic) hypotension syncope
379
What is Lambert-Eaton Myasthenic Syndrome?
Rare **autoimmune** disorder of the neuromuscular junction
Pesents like myasthenia gravis - but **less severe** +** weakness improves with exercise**
380
What primarily causes Lamber-Eaton Myasthenic Syndrome?
Small Cell Lung Cancer (Paraneoplastic)
381
Pathology of Lambert-Eaton Myasthenia Syndrome
Antibodies produced that damage the voltage-gated calcium channels in the presynaptic terminals of the NMJ (not enough ACh release)
382
Presentation of Lambert-Eaton Myasthenia Syndrome
**- Symptoms develop very slowly
- Proximal muscle weakness → proximal leg muscle weakness**
- **Eyes**
- Diplopia
- Ptosis
- **Oropharyngeal muscles**
- Slurred speech
- Dysphagia (swallowing problems)
- **Autonomic dysfunction**
- Dry mouth
- Dizziness
- Impotence
- Blurred vision
- **Reduced tendon reflexes**
383
Ix for Lambert-Eaton Myasthenic Syndrome
* Nerve conduction studies
* Chest CT scan (underlying malignancy)
* Anti-P/Q voltage-gated calcium channel serology (positive)
384
Treatment for Lambert-Eaton Myasthenia Syndrome
* Treat uderlying cause
* **Amifampridine** orally
* Immunosuppressants (**prednisolone** or **azathioprine**)
385
What is a meningioma?
Benign brain tumour
386
What is a glioblastoma?
Highly malignant brain tumour
387
How do brain tumours present?
* Often asymptomatic
* Focal neurolofical symptoms
* Raised intracranial pressure
388
A patient has had an unusual change in personality and behaviour. Where would the location of a brain tumour be?
Frontal lobe
(Frontal lobe = responsible for personality + higher-level decision making)
389
What is a key symptom of raised intracranial pressure?
Headache:
* Constant
* Nocturnal
* Worse on waking
* Worse on coughing, straining or bending forward
* Vomiting
390
What is a key examination finding for raised intracranial pressure?
Papilloedema on fundoscopy
391
Name a couple of causes of raised intracranial pressure
Brain tumours
Intracranial haemorrhage
Idiopathic intracranial hypertension
Abscesses or infection
392
Apart from headache, what are some other features of raised ICP?
* Altered mental state
* Visual field defects
* Seizures (particularly focal)
* Unilateral ptosis
* Third and sixth nerve palsies
* Papilloedema (on fundoscopy)
393
Name common cancers that metastasise to the brain
* Lung
* Breast
* Renal cell carinoma
* Melanoma
394
What is a glioma?
Tumuours of the glial cells in the brain or spinal cord
395
What is the most malignant glioma?
**Gliobastoma multiforme**
(Also most common)
396
What is a meningioma?
Tumours growing from the cells of the meninges in the brain + spinal cord
* Usually benign
* Mass effect - can lead to raised intracranial pressure + neurological symptoms
397
What visual defect can pituitary tumours cause if large enough?
Bitemporal hemianopia
(Press on the optic chiasm)
398
What brain tyumour is associated with hearing loss, tinnitus and balance problems?
Acoustic neuroma (AKA Vestibular Schwannoma)
399
What is the general management of brain tumours
* Palliative care
* Chemotherapy
* Radiotherapy
* Surgery
400
Carpal tunnel syndrome is caused by the compression of which nerve?
Median nerve
401
What causes bilateral carpal tunnel syndrome?
* Rheumatoid arthritis
* Diabetes
* Acromegaly
* Hypothyroidism
402
Which finger is not affected in carpal tunnel syndrome?
Little finger
403
What are the sensory symptoms of carpal tunnel syndrome?
* Pain
* Numbness
* Paraesthesia (pins + needles, tingling)
* Burning sensation
404
What are the motor symptoms of carpal tunnel syndrome?
* Weakness of thumb movements
* Weakness of grip strength
* Difficulty with fine movements
* Wasting (atrophy of thenar muscles)
405
What does a positive Phalen's test indicate?
Carpal tunnel syndrome
- Position triggers the sensory symptoms of carpel tunnel
- Numbness + paraesthesia in the median nerve distribution
406
What does a positive Tinel's test indicate?
Carpal tunnel syndrome
- Tap the wrist at where the median nerve travels through the carpal tunnel (in the middle - at the point where the wrist meets the hand)
- Position triggers the sensory symptoms of carpel tunnel
- Numbness + paraesthesia in the median nerve distribution
- TOM TIP: Think of tapping a tin can (Tinel’s) to remember the difference between Phalen’s and Tinel’s test.
| Think of tapping (Tinel’s) to remember between Phalen’s & Tinel’s test.
407
What are the two clinical examination tests for carpal tunnel syndrome?
* Phalen's
* Tinel's
408
What is the diagnostic test for carpal tunnel syndrome?
Nerve conduction studies (electromyography)
409
Managment for carpal tunnel syndrome
* Wrist splints
* Steroid injections (hydrocortisone or methylprednisolone acetate)
* Surgical decompression
410
Injury in to the radial nerve results in which condition?
Wrist drop
- = Inability to extend the wrist (+ fingers) → due to weakness or paralysis of the POSTERIOR FOREARM MUSCLES
411
Claw hand is a result from what?
* Ulnar nerve palsy
* Charcot-Marie-Tooth Disease
412
What is a radiculopathy and give an example?
* Radiculopathy = compression of nerve root + LMN
* Sciatica = lumbar radiculopathy
(cranial nerves = peripheral - because they have Schwann cells)
413
What is a mononeuropathy and give an example?
* Mononeuropathy = affects 1 nerve
* Carpal tunnel syndrome (medial nerve) = most common
* Cranial mononeuropathies (III or VII cranial nerve palsy)
414
What is a polyneuropathy and give an example?
Polyneuropathy = multiple/systemic - can be motor, sensory, sensorimotor and autonomic
* Multiple sclerosis
* Guillain-Barre
* Diabetes
415
What are the 6 mechanisms that cause nerve malfunction?
* Demyelination
* Axonal degeneration
* Compression
* Infarction (micro-infarction of the nvasa nervorum)
* Infiltration
* Wallerian degeneration
416
What are the causes of peripherpheral neuropathy?
DAVID:
* D - Diabetes
* A - Alcohol
* V- Vitamin B12 deficiency
* I - Infective
* Drugs - isoniazid
417
Name two systemic onditions that commonly cause axonal peripheral neuropathy
* Diabetes
* Vitamin B12 deficiency
418
Name the motor symptoms of peripheral neuropathies
- Muscle cramps
- Weakness
- Fasciculations (muscle twitches)
- Muscular atrophy → excessive atrophy → high arched feet (pes cavus)
419
What anti-neuralgics can you give for peripheral neuropathies?
GAP:
* Gabapentin
* Amytriptyline
* Pregabalin
420
Ix for peripheral neuropathies
- Clinical examination
- Reduced or absent reflexes
- Sensory deficit
- Weakness → muscle atrophies
- Neurological examination (nerve conduction studies/QST)
- Demyelinating → slow conduction velocities
- Axonal → reduced amplitudes of the potential
421
What is mononeuritis multiplex?
Used to describe a distinctive clinical presentation of progressive motor + sensory deficits in the distribution of specific peripheral nerves
422
How does Brown Sequard syndrome present>
- Contralateral: pain + temperature loss
- Ipsilateral: hemiparesis/hemiplegia + proprioception/vibration sense loss
423
Management ofr Brown-Sequard Syndrome
- Supportive - physical + occupational therapy
- Steroids - reduce swelling + inflammation
424
What is Charcot-Marie-Tooth disease?
- a group of hereditary **peripheral neuropathies** with different genetic abnormalities.
- Usually **autosomal dominant** pattern
425
Presentation of Charcot-Marie-Tooth syndrome?
- Walking difficulties
- Pes cavus (high foot arches)
- Steppage gait
- Diffuse deep tendon hyporeflexia or areflexia
- Reduced muscle strength
- Reduced sensation
426
What is Duchenne Muscular Dystrophy?
* Muscular dystrophy = umbrella term for genetic conditions - that cause **gradual weakening + wasting of muscles**
* Duchenne muscular dystrophy (DMD) = caused by **************************************************defective dystrophin gene************************************************** on the ************************x-chromosome************************
- Caused by **non-sense/frameshift mutation**
- ************************************DMD = CONGENITAL MYOPATHY************************************
- **DMD** → **D**oesn’t **M**ake **D**ystrophin
427
Management of DMD
- **Oral steroids → slow progression of muscle weakness (prednisolone)**
- Creatinine supplementation → improve muscle strength slightly
- Physiotherapy + exercise + psychological support
