Parkinsons and MS Flashcards
1
Q
What bacteria can cause a chronic bacterial infection in the CNS?
A
TB
2
Q
What is acute encephalitis?
A
Infection of the brain parenchyma
3
Q
In a grossly pyogenic meningitis, what does the thick layer of suppurative exudate cover?
A
The leptomeninges (pia and arachnoid)
4
Q
What can be seen microscopically in grossly pyogenic meningitis?
A
Neutrophils in subarachnoid space
5
Q
When is viral meningitis most common?
A
Late summer/autumn
6
Q
What is the most common cause of viral (aseptic) meningitis?
A
Enteroviruses (eg. ECHO virus)
7
Q
What investigations can be carried out in viral meningitis?
A
Viral stool culture
Throat swab
CSF PCR
8
Q
What is the most common cause of viral encephalitis?
A
Herpes simplex virus
9
Q
What is another important cause of viral encephalitis? What important feature of their past medical history could suggest this?
A
Varicella zoster
History of shingles
10
Q
How do we treat the two main causes of viral encephalitis?
A
High dose aciclovir
11
Q
When must the commonest cause of viral encephalitis be treated?
A
<6 hours after admission
12
Q
What three travel related viruses can cause encephalitis?
A
West Nile
Japanese B encephalitis
Tick borne encephalitis
13
Q
What are the clinical features of viral encephalitis?
A
Insidious (sometimes sudden) Meningismus (meningism) Stupor/Coma Seizures and partial paralysis Confusion/Psychosis Speech and memory symptoms
14
Q
How can we investigate viral encephalitis?
A
LP
EEG
MRI
15
Q
What are the MRI findings in viral encephalitis?
A
Inflammed temporal lobe is brightest white:
- Uncus
- Adjacent parahippocampal gyrus
16
Q
What are the commonest causes of bacterial meningitis in neonates?
A
Listeria
Group B strep
E. coli
17
Q
What is the commonest cause of bacterial meningitis in children?
A
H. influenzae
18
Q
What is the commonest cause of bacterial meningitis in those aged 10-21?
A
Meningococcal
19
Q
What are the commonest causes of bacterial meningitis in those aged >21?
A
Pneumococcal > Meningococcal
20
Q
What are the commonest causes of bacterial meningitis in the elderly?
A
Pneumococcal > Listeria
21
Q
Those with a reduced cell-mediated immunity (eg. HIV) are more prone to what cause of bacterial meningitis?
A
Listeria
22
Q
Those who have undergone neurosurgery or have experienced open head trauma are at risk of what causes of bacterial meningitis?
A
Staph/
Gram negative bacilli
23
Q
In a patient with a cribiform plate fracture, what is the commonest cause of bacterial meningitis?
A
Pneumococcal
24
Q
Which of the following is not a common cause of bacterial meningitis in immunocompromised patients:
- Strep pneumonia
- Neisseria meningitidis
- Listeria
- H. influenzae
- Aerobic gram negative bacilli (inc. Psuedomonas)
A
H. influenzae
25
Which of the following is not a common cause of bacterial meningitis in patients with a skull base fracture:
- Staph. aureus
- Strep. pneumoniae
- H. influenzae
- Beta haemolytic GAS
Staph. aureus
26
Which of the following is not a common cause of bacterial meningitis in patients post-neurosurgery/open head trauma:
- Staph aureus
- Staph epidermidis
- Aerobic gram negative bacilli
- Strep. pneumoniae
Strep pneumoniae
27
Which of the following is not a common cause of bacterial meningitis in patients with a CSF shunt:
- Staph epidermidis
- Staph aureus
- Aerobic gram negative bacilli
- Neisseria meningitidis
- Proprionibacterium acnes
Neisseria meningitidis
28
What is a common cause of bacterial meningitis in AIDS patients?
Cryptococcus neoformans (when CD4 <100)
29
In patients with meningitis due to Neisseria meningitidis, where might bacteria be seen in the CSF?
Inside leucocytes
30
How do Neisseria meningitidis gain access to the meninges?
Via the bloodstream
31
What cause the symptoms in Neisseria meningitidis meningitis?
Endotoxin
32
Why are military recruits vaccinated against Neisseria meningitidis?
Prevents epidemics in training camps
33
What are some local disease features (apart from the meningitis) of Neisseria meningitidis?
Conjunctivitis
| Arthritis
34
What is the mortality rate of localised Neisseria meningitidis meningitis?
5%
35
What is the mortality rate of Neisseria meningitidis meningitis with septicaemia?
15%
36
What is the mortality rate of Neisseria meningitidis meningitis with fulminant septicaemia?
15-40%
37
What subtype of H. influenzae is the commonest cause of meningitis in children younger than 4 years?
Hib
38
What are the risk factors for pneumococcal meningitis?
```
Hospitalised patients
CSF skull fracture
Diabetes
Alcoholics
Young children
```
39
What is the gram stain and shape of Listeria?
Gram positive bacilli
40
What are the risk factors for Listeria Monocytogenes meningitis?
Neonates
Age >55 years
Immunosuppressed (esp. if due to malignancy)
41
What is the treatment for Listeria meningitis?
IV ampicillin/amoxicillin
42
How can we diagnose cryptococcal meningitis?
Serum and CSF cryptococcal antigen
43
How is cryptococcal meningitis treated?
IV amphotericin B/Flucytosine
| Fluconazole
44
Is CSF pleocytosis indicative of bacterial meningitis?
No
45
In what order to we collect CSF tubes?
Tube 1 - Haematology
Tube 2 - Microbiology
Tube 3 - Biochemistry
Tube 4 - Haematology
46
What cells are predominant in CSF in viral meningitis?
Lymphocytes
47
What cells are predominant in CSF in bacterial meningitis?
Polymorphs
48
What cells are predominant in CSF in TB meningitis?
Mostly lymphocytes
49
What is the protein level in viral meningitis?
Normal or slightly high
50
What is the protein level in bacterial meningitis?
High
51
What is the protein level in TB meningitis?
High or very high
52
What is the glucose level in viral meningitis?
Usually normal
53
What is the glucose level in bacterial meningitis?
Less than 70% of blood glucose
54
What is the glucose level in TB meningitis?
Less than 60% of blood glucose
55
What values for the following parameters are highly predicative (99% accuracy) of bacterial meningitis:
- WBC count
- Neutrophils
- Protein
- Glucose
- Glutamate (CSF/Serum)
```
WBC count >2000
Neutrophils >1180
Protein >220mg/dL (>0.22g/L)
Glucose <34mg/dL (<2.125mmol/L)
Glutamate <0.23
```
56
What are some non-infectious causes of neutrophilic pleocytosis and low CSF glucose?
Chemical meningitis (eg contrast)
Behcet syndrome
Drugs (NSAIDs, Sulfa, INH, IV Ig)
57
What is the other name for aseptic meningitis?
Encephalitis syndrome
58
What are some indications for hospital admission in meningitis?
```
Meningism
Impaired consciousness
Petechial rash
Febrile/Unwell and recent fit
Headahce
```
59
Which is done first on admission with suspected meningitis, LP or antibiotic therapy?
Antibiotics
60
What investigations are done immediately after empirical antibiotic therapy?
Throat swab
| Swab/aspirate any rash (microscopy and culture)
61
When would we undergo a CT prior to LP in meningitis?
```
Immunocompromised
CNS disease
New onset seizure
Papolloedema
Altered consciousness
Focal CNS deficit
```
62
What is the empirical antibiotic treatment for bacterial meningitis?
IV Ceftriaxone 2g bd
63
What antibiotic is added to the empirical treatment of bacterial meningitis if Listeria is suspected?
IV amoxicillin 2g qds
64
What is the empirical antibiotic treatment of bacterial meningitis if the patient has a penicillin allergy?
IV Chloramphenicol 25mg/kg 6-hourly qds WITH
| IV Vancomycin 500mg 6-hourly (or 1g 12-hourly)
65
What antibiotic is added to the empirical treatment of bacterial meningitis if Listeria is suspected and the patient has a penicillin allergy
IV Co-trimoxazole 120mg/kg into 4 divided doses/day
66
When are steroids given in bacterial meningitis?
To all patients with suspected meningitis
67
What steroid is given in bacterial meningitis?
IV Dexamethasone 10mg:
- With/Just before 1st antibiotic dose
- Then qds for 4 days
68
In what kind of meningitis do steroids have the most benefit?
```
Pneumococcal
Reduced chance of:
- Impaired consciousness
- Seizures
- Cardio-pulmonary failure
```
69
When would steroids not be given in meningitis?
Post-surgical meningitis
Immunosuppressed
Meningococcal or septic shock
Allergy
70
How can we assess prognosis in meningococcal disease?
```
Haemorrhagic distheses
Reduced consciousness
Multiorgan failure
Rapidly developing rash
Age >60
```
71
How can we assess prognosis in all types of meningitis?
```
Tachycardia
GCS <12
Low GCS, CN palsy
Seizures within 24 hours
Hypotension
Age >60
```
72
What are the contact prophylaxis regimens for meningitis for people older than 12 years?
```
PO Rifampicin 600mg 12-hourly for 4 doses
OR
PO Ciprofloxacin 500mg single dose
OR
IM Ceftriaxone 250mg single dose
```
73
What are the contact prophylaxis regimens for meningitis for people older than kids aged 3-11months?
PO Rifampicin 10mg/kg 12-hourly for 4 doses
OR
IV Ceftriaxone 125mg single dose
74
What are pyramidal/UMN features?
Pyramidal weakness:
- Weakness of extensors in upper limbs
- Weakness of flexors in lower limbs
Spasticity
75
What are hyperkinetic motor disease features?
```
Dystonia (sustained/repetitive muscle contractions resulting in twisting motions and abnormal posture)
Tics
Myoclonus
Chorea
Tremor
```
76
What is chorea?
Brief, irregular movements that move from one muscle to another
77
What are hypokinetic motor disease features?
Parkinsonism
| Parkinson's disease
78
What part of the brain do hyperkinetic and hypokinetic motor disease features arise from?
Basal ganglia
79
Where does ataxia arise?
Cerebellum
80
What is ataxia?
Loss of voluntary control of muscle coordination (including gait abnormality)
81
What are the features of Parkinson's?
Rigidity
Akinesia/Bradykinease
Resting tremor
Gait abnormalities
82
What is ballismus?
Chorea motions with large amplitude
83
What is tremor-dominant Parkinson's Disease?
Relative absence of other motor symptoms
84
What is non-tremor-dominant Parkinson's Disease?
Akinetic-rigid syndrome
| Postural instability gait disorder
85
Which type of Parkinson's Disease is associated with slower progression and less functional disability?
Tremor-dominant
86
What are some non-motor features of Parkinson's Disease?
```
Olfactory dysfunction
Cognitive impairment
Psychiatric symptoms
Sleep disorders
ANS dysfunction
Pain Fatigue
```
87
When are non-motor features of Parkinson's Disease common?
Early disease
88
What are the advanced stages of Parkinson's Disease associated with?
Emergence of complications due to long-term fluctuations
89
What are the symptoms of late-stage Parkinson's?
Axial motor symptoms:
- Postural instability
- Freezing of gait
- Falls
90
During what part of sleep do parasomnias occur in Parkinson's?
REM sleep
91
How can parasomnias be diagnosed in Parkinson's?
Overnight polysomnography
92
How are parasomnias in Parkinson's treated?
Clonazepam
Melatonin
(Both at bedtime)
93
What are the pathological hallmarks of Parkinson's?
Loss of dopaminergic neurones in substantia nigra
| Lowy body pathology
94
What are intracellular inclusions of alpha-synuclein?
Lewy bodies
95
What are the processes of neurones with intracellular inclusions of alpha-synuclein?
Lewy neurites
96
Where are insoluble misfolded alpha-synuclein deposits found?
Brain
Spinal cord
PNS
97
What is the sterotyped progression of Lewy body pathology?
6 stages:
- Starts in PSN
- Progressively affects CNS in a caudal to rostral direction in the brain
98
Where does the loss of dark black pigment occur in the brain in Parkinson's?
Substantia nigra
| Locus coeruleus
99
Where is the prevalence of Parkinson's higher?
Europe
| North and South America
100
What is the greatest risk factor for Parkinson's?
Agr
101
What is the M:F ratio of Parkinson's?
3:2
102
Onset before what age suggests a genetic cause of Parkinson's?
40 years
103
What is the greatest genetic risk factor for Parkinson's? What does in encode?
Mutations in GBA
Encodes Beta-Glucocerebrosidase:
- Lysosomal enzyme deficient in Gaucher's Disease
104
What mutation is the most common cause of dominant Parkinson's?
LRRK2
105
What mutation is the most common cause of recessive Parkinson's?
Parkin
106
What was the first gene associated with Parkinson's and what does it go?
SNCA
| Encodes the protein alpha-synuclein
107
What environmental factors are protective against Parkinson's?
```
Smoking
Coffee
NSAIDs
Calcium channel blockers
Alcohol
```
108
What environmental factors are associated with an increased risk of Parkinson's?
```
Pesticides
Prior head injury
Rural living
Beta blockers
Agricultural occupation
Well-water drinking
```
109
What is the main drug in symptomatic treatment of Parkinson's?
Levodopa
110
Give examples of dopamine agonists?
Ropinirole
Pramipexole
Cabergoline
111
Give an example of a MAO-B inhibitor?
Selegiline
112
When is Amantadine used in Parkinson's?
Relieves dyskinesias
113
When should treatment be initiated in Parkinson's?
When symptoms cause disability or discomfort
114
What drugs are better for the more severe symptoms of Parkinson's?
Levodopa
| Dopamine agonists
115
What are more effective therapies for tremor?
Anticholinergics
Trihexyphenidyl
Clozapine
116
What are the side effects of both Levodopa and Dopamine agonists?
Nausea
Daytime somnolence
Oedema (Greater in dopamine agonists)
117
What are additional side effects of dopamine agonists?
```
Pathological gambling
Hypersexuality
Binge eating
Compulsive spending
Hallucinations
```
118
When should dopamine agonists be avoided?
```
Patients with a history of:
- Addiction
- OCD
- Impulsive personality
Elderly
```
119
What is long-term levodopa therapy associated with?
Motor complications:
- Dyskinesias
- Fluctuations
120
How can levodopa-related side effects be reduced?
By adding:
- Dopamine agonist
- MAO B inhibitor
- Catechol-O-methyltransferase inhibitor
121
How is psychosis in Parkinson's managed?
Clozapine
122
How are visual hallucinations and delusions in Parkinson's patients with dementia treated?
Cholinesterase inhibitiors (eg. Rivastigmine)
123
How can psychotic symptoms in Parkinson's be managed without affecting motor function?
Primavansenin
124
Apart from moving, how else does bradykinesia affect a Parkinson's patient?
Hypomimia
Hypophonia
Micrographia
125
What is the frequency of the tremor in Parkinson's?
3-6Hz
126
How can the resting tremor be accentuated in Parkinson's?
Best observed when patient is focused on a mental task (eg count back from 100)
127
How can rigidity in Parkinson's be distinguished from spasticiy in UMN lesion?
The resistance to passive movement does not increase with faster passive movement
128
Where is the "cog-wheel" rigidity most apparent?
At the wrist
129
How can we accentuate rigidity in Parkinson's?
Froment's manoeuvre:
| - Ask patient to voluntarily move another body part
130
What is camptocormia?
Anterior truncal flexion in Parkinson's
131
What symptoms should be absent to diagnose pure Parkinson's disease?
Sensory
Pyramidal
Cerebellar
132
If a patient with suspected Parkinson's disease has changes in eye movement latency/speed/accuracy, what is a more likely diagnosis?
Progressive Supranuclear Palsy with Parkinsonism
133
What treatable causes of asthenia should be ruled out?
Hypothyroidism
| Anaemia
134
What part of the body does vascular Parkinson's affect predominantly?
Lower limbs
135
What cardinal feature of Parkinson's is uncommon is vascular Parkinson's?
Resting tremor
136
What other signs of brain vascular lesion may be present in vascular Parkinson's?
Spasticity
Hemiparesis
Pseudobulbar palsy
137
Symmetrical Parkinsonism, coarse postural tremor and presence of:
- Orolingual dyskinesias
- Tardive dystonia
- Akathisia (feeling of inner restlessness)
are signs of what?
Drug-induced Parkinsonism
138
What is the frequency of an essential tremor?
Up to 12Hz
139
What is the typical cause of an essential tremor?
Autosomal dominant inheritance
140
What is the usual age of onset of an essential tremor?
15 years
141
When does multi-system atrophy tend to onset?
6th or 7th decade
142
What is the core triad of features of Multi-System Atrophy?
Dysautonomia
Cerebellar features
Parkinsonism
143
What sort of tremor is seen in Multi-System Atrophy?
Jerky postural
144
What pyramidal signs are seen in Multi-System Atrophy?
Hyperreflexia
| Babinski positive
145
What other signs are seen in Multi-System Atrophy?
Severe dysarthria or dysphonia
Marked antecollis (excessive forward neck flexion)
Inspiratory sighing
Orofacial dystonia
146
What might an MRI in Multi-System Atrophy show?
"Hot cross bun signs":
- Cerebellar and pontine atrophy
- Hyperintense rim around putamen in T2 MRI
147
What gaze is typically affected in Progressive Supranuclear Palsy?
Vertical
148
What signs/symptoms are seen in Progressive Supranuclear Palsy?
```
Symmetric akinetic-rigid syndrome (mainly axial)
Poor gait and balance - Early falls
Pseudobulbar symptoms
Retrocollis
Staring (continuous frontalis activity)
```
149
What sort of response does Progressive Supranuclear Palsy have to levopdopa?
None
150
What causes Fragile X-Tremor Ataxia Syndrome?
Abnormal number of CGG repeats in FMR1 gene:
| - In the range of 55-200
151
What are the core symptoms of Fragile X-Tremor Ataxia Syndrome?
```
Cerebellar gait ataxia
Postural/Intention tremor
Variable Parkinsonism
Dysuatonomia
Frontal cognitive decline
Peripheral neuropathy
```
152
What is the typical age of onset of Fragile X-Tremor Ataxia Syndrome?
>50 years
153
How does Fragile X-Tremor Ataxia Syndrome tend to present in women?
Milder:
- Premature ovarian failure
- Early menopause
154
What MRI signs are seen in Fragile X-Tremor Ataxia Syndrome?
T2 hyperintensities in middle cerebral peduncles
155
What hyperkinetic movement disorder is a tremor?
Rhythmic sinusoidal oscillation of a body part
156
What hyperkinetic movement disorder is a tic?
Involuntary stereotyped:
- Movements OR
- Vocalisations
157
What hyperkinetic movement disorder is chorea?
Brief, irregular purposeless movements
| Movements flow from one body part to another
158
What hyperkinetic movement disorder is myoclonus?
Brief 'electric-shock' like jerks
159
What hyperkinetic movement disorder is dystonia?
Abnormal posture of affected body part
160
What typically causes a resting tremor?
Parkinson's
Drug-induced Parkinsonism
Psychogenic tremor
161
What typically causes a postural tremor?
Essential tremor
Enhanced physiological tremor
Tremor associated with neuropathy
162
What causes a kinetic tremor?
Cerebellar disease:
- Demyelination
- Haemorrhage
- Degenerative
- Toxic (eg. alcohol)
163
What can cause a head tremor?
Dystonia
| Cerebellar disease
164
What can cause a jaw tremor?
Dystonia
| Parkinson's disease
165
What can cause a palatal tremor?
Ataxia
Symptomatic
Essential tremor
166
If a tremor is present in yonger people (<45 years) what should be considered and how do we investigate?
Wilson's Disease:
- Copper
- Caeruloplasmin
167
What is the first line treatment for a dystonic tremor (including essential tremor)?
Propanolol
OR
Primidone
168
What are some secondary options for treatment of dystonic/essential tremor?
Atenolol
Gabapentin
Topiramate
Clonazepam
169
Is severely affected by a dystonic/essential tremor, what treatment can be offered?
Deep brain stimulation
170
What are primary dystonic syndromes?
Dystonia-Plus syndromes:
- Dopamine responsive dystonia
- Myoclonic dystonia
171
What are secondary dystonic syndromes?
Symptomatic
Heredodegenerative:
- Wilson's Disease
- Parkinson's Disease
172
What is the age at which a dystonic syndrome would be consider young-onset?
<28 years
173
What parts of the brain are usually affected in dystonia?
Basal ganglia:
- Putamen
- Globus pallidus
174
What are the three main phsyiological abnormalities in dystonia?
Loss/Reduction in reciprocal inhibition
Alterations in brain plasticity
Alterations in sensory function
175
What causes torsion dystonia?
DYT1 mutations
176
When does torsion dystonia usually onset?
<28 years (usually childhood)
177
Where does torsion dystonia usually start?
Lower limb (usually legs)
178
How long does it take for torsion dystonia to progress to generalised/multifocal dystonia?
5-10 years
179
What inheritance is torsion dystonia?
Autosomal dominant
180
How can cervical dystonia be treated?
Botox A or B
181
What is the procedure of choice in treating dystonia?
Deep brain stimulation
182
What inherited/degenerative disorders can cause chorea?
```
Huntington's Disease
Wilson's Disease
Neuroacanthocytosis
Benign Hereditary CHorea
Ataxia Telangiectasia
Spinocerebellar Ataxia Type 17
```
183
What infection can cause chorea?
HIV
184
What disease can display paroxysmal chorea?
Parkinson's Disease
185
What are some other causes of chorea?
```
Autoimmune
Metabolic
Drugs:
- Dopamine receptor blockers
- Levopdopa
- COC
```
186
How can chorea be treated?
Treat underlying cause
Symptomatic treatment:
- Terabenazine
- Dopamine receptor antagonists
187
What is the mode of inheritance of Huntington's Disease?
Autosomal dominant
188
What is Huntington's Disease characterised by?
Progressive behavioural disturbance
Dementia
Movement disorder - Usually chorea
189
What is the M:F ratio in Huntingtons?
Equal
190
Where are high prevalence populations for Huntingtons
```
Moray Forth (Scotland)
Venezuela
```
191
Where are there low rates of Huntington's?
Japan
| African Americans
192
What is the usual age of onset of Huntington's?
4th decade
193
What is the genetic mutation in Huntington's?
CAG triplet-repeat expansion disorder:
- Affects Huntingtin gene on chromosome 4
- Usually 20 in normal individuals (codes of glutamine)
194
How many repeats of the gene mutation must be present for Huntington's to definitely occur?
>=40
195
How many repeats of the gene mutation must be present to ensure Huntington's does not occur?
=<35
196
What is copropraxia?
Obscene gestures
197
What is echopraxia?
Copying others' movements
198
What is coprolalia?
Obscene words
199
What is echolalia?
Copying others' words
200
What is palilalia?
Repetition of the same word/phrase/syllable
201
When do primary tic disorders tend to start?
Childhood
202
What psychopathology may be associated with tics?
OCD
ADHD
Anxiety
Self-harm
203
What investigations are important in tics?
Copper
Blood for acanthocytosis
ASO titres
Uric acid
204
What developmental disorders can cause tics?
Down syndrome
Fragile X syndrome
Autism
205
What structural abnormalities can cause tics?
Post-encephalopathy
| Basal ganglia lesions (usually caudate nucleus)
206
What infections can cause tics?
Sydenham's Chorea (with rheumatic fever)
| Paediatric Autoimmune Neuropsychiatric Disorders Associated with Strep. (PANDAS)
207
What drugs and toxins can cause tics?
CO poisoning
Cocaine
Amphetamines
Anticonvulsants
208
What is the diagnostic criteria for Tourette Syndome?
```
Both of:
- Multiple motor tics
- >= 1 vocal tics
Tics must occur:
- Many times a day
- Nearly every day OR
- Intermittently for >= 1 year with <=3 months intervals of being tic-free
Age of onset <= 18 years
Exclusion of obvious secondary cause
```
209
What is the symptomatic treatment of the tics in Tourette?
Clonidine
| Tetrabenazine
210
What is an example of negative myoclonus?
Asterixis (liver flap)
211
What are causes of myoclonus plus dementia?
Alzheimer's
Lewy Body dementia
Creutzfeldt-Jakob Disease
212
What are causes of myoclonus plus Parkinsonism?
Corticobasal degeneration
Multiple System Atrophy
Spinocerebellar ataxias
213
What typically precipitates juvenile myoclonus epilepsy?
Alcohol
| Sleep deprivation
214
When are symptoms worst in juvenile myoclonus epilepsy?
In the morning
215
How is juvenile myoclonus epilepsy treated?
Sodium valproate
| Levetiracetam
216
What drug can aggravate juvenile myoclonus epilepsy?
Carbamazepine
217
When glutamate and aspartate are released in a head injury, what happens that increases the damage?
```
Intracelluar calcium release
Phospholipase activation
Breakdown of cell membrane:
- Cell swelling
- Apoptosis
```
218
What do the loss of the BBB and leucocyte infiltration cause in head injury?
Secondary inflammation
219
What does the loss of cerebral autoregulation of BP cause in head injury?
Secondary ischaemia
220
What does the loss of cerebral autoregulation of blood flow cause in head injury?
Metabolic de-coupling:
| - Even more ischaemia and oedema
221
What is the equation for cerebral perfusion pressure?
CPP = MAP - ICP
222
What CPP do we aim for in head injury?
>60 mmHg
223
What is normal adult ICP?
9-11 mmHg (12-15 cm H2O)
224
What is a common sign in anterior cranial fossa fracture?
'Raccoon' or 'Panda' eyes
225
What is a common sign in middle cranial fossa fracture?
'Battle signs' over mastoid
226
What focal signs can be present in head injury?
Lateralising motor signs
| CN iii palsy (pupillary light reflex)
227
What is a subfalcine herniation?
Frontal lobe scraped under falx cerebri
228
What is the first sign of a subfalcine herniation?
Leg weakness
229
What is a transtentorial (uncal) herniation?
Temporal lobe herniates and presses against brainstem and CN iii
230
What are the first signs of a transtentorial (uncal) herniation?
```
Coma (brainstem compression)
Pupil dilatation (reduced PNS supply via CN iii)
```
231
What is tonsillar herniation?
'Coning'
| Cerebellum herniates through foramen magnum and presses against brainstem
232
What are the signs in tonsillar herniation?
BP collapses
Cardiac arrest
Both result in death
233
What are the 'eye' scores in the GCS?
Spontaneously open = 4
Open to command = 3
Open to pain = 2
None = 1
234
What are the verbal response scores in the GCS?
```
Orientated = 5
Confused = 4
Inappropriate words = 3
Incomprehensible sounds = 2
None = 1
```
235
What are the motor response scores in the GCS?
```
Obeys commands = 6
Localises pain = 5
Flexion in response to pain = 4
Decorticate posturing (abnormal flexion) = 3
Decerebrate posturing (extension) = 2
None = 1
```
236
What is the definition of coma?
Doesn't open eyes
Doesn't obey commands
Doesn't speak
237
What GCS score indicates coma?
=<8
238
What kills a patient in head trauma?
Hypoxia
Hypotension
Increased ICP
239
How long after cardiovascular arrest does irreversible brain damage occur?
5 minutes
240
When should a CT be requested in head trauma?
A skull fracture OR
Not orientated (GCS <15) OR
With focal neurological signs OR
Taking anticoagulants (warfarin)
241
How does sedation help in head trauma?
Reduces cerebral metabolic rate
Reduces cerebral blood flow
Reduces ICP
242
How can we improve micro-circulation in head injury?
Mannitol
OR
Hypertonic saline
243
When is epilepsy most common following a head injury?
In the first 2 weeks
244
Where can CSF leak into following a head injury?
Nose
| Ear
245
Poor concentration, headache, poor memory and lethargy following a head injury are signs of what?
Post-concussion syndrome
246
How many patients are affected by cognitive problems following a head injury?
30%
247
How is Duchenne Muscular Dystrophy inherited?
X-linked recessive
248
Where is the mutation in Duchenne Muscular Dystrophy?
Xp21
249
What is the incidence in males of Duchenne Muscular Dystrophy?
1/3000
250
When and where does the weakness onset in Duchenne Muscular Dystrophy?
3-4 years of age
| Pelvic and shoulder girdles
251
At what age do most Duchenne Muscular Dystrophy patients become wheelchair bound?
10-12 weeks
252
What spinal feature is characteristic in Duchenne Muscular Dystrophy?
Lumbar hyperlordosis
253
What muscles hypertrophy in Duchenne Muscular Dystrophy? How are they often described?
Calf muscles
| 'Woody'
254
What is deficient in Duchenne Muscular Dystrophy?
Dystrophin
255
70% of Duchenne Muscular Dystrophy patients have what genetic abnormality?
Large scale deletions of dystrophin gene
256
30% of Duchenne Muscular Dystrophy patients have what genetic abnormality?
Point mutations
| Small insertions and deltions
257
What is Gower's sign?
Indicates proximal muscle weakness
| Patients have to 'walk' themselves up from sitting with their hands and arms
258
What investigations suggest Duchenne Muscular Dystrophy?
Raised serum CK
EMG
Muscle biopsy
259
What are some differentials for Duchenne Muscular Dystrophy?
Autosomal recessive limb girdle muscular dystrophies:
| - Some due to sarcoglycan deficiencies
260
What is the incidence of Huntington's Disease?
1/20000
261
What are the early clinical signs of Huntington's Disease?
```
Clumsiness
Agitation
Apathy
Anxiety
Abnormal eye movements
Depression
```
262
What macroscopic change is seen in Huntington's Disease?
Caudate nucleus atrophy
263
What percentage of cases of dementia are due to Alzheimer's Disease?
50-70%
264
What is the pathophysiology of Alzheimer's Disease?
Loss of cortical neurones
Intracellular neurofibrillay tangles
Extraceullar senile plaques
265
What are the extracellular protein deposits in Alzheimer's Disease?
Amyloid beta protein
266
Where are the extracellular protein deposits seen in Alzheimer's Disease formed from?
Fragments of the product of the amyloid precursor protein gene (Chromosome 21)
267
How does an autosomal dominant form of Alzheimer's Disease affect the age of onset?
Earlier
268
When is the onset of Alzheimer's Disease in Dowrr Syndome?
3rd or 4th decde
269
What mutations can result in Alzheimer's Disease?
```
APP mutations (Chromosome 21)
Presenilin 1 (Chromosome 14)
Presenilin 2 (Chromosome 1)
```
270
Where are glial cells derived from?
Neuroectoderm
271
Where are microglia derived from?
Mesoderm
272
Where do microglia originate?
Bone marrow
273
What cells does hypoxic damage to the CNS affect most
Neurones
274
How does hypoxia damage cells in the CNS
Activation of glutamate receptors
Uncontrolled calcium influx
Neurones can use anaerobic glycolysis
275
The following are signs of what sort of injury:
- Increased RNA and protein synthesis
- Cell body swelling
- Peripheral displacement of nucleus
- Enlargement of nucleolus
- Central chromatolysis
- Anterograde degeneration
- Breakdown of myelin
Axonal injury
276
What is gliosis?
Reactive response associated with prolifetation
277
What does gliosis result in?
Cell death
| Degeneration
278
What is the most important histological indicator of CNS injury?
Gliosis
279
What do astrocytes undergo in gliosis?
Hyperplasia
| Hypertrophy
280
What happens to nuclei in gliosis?
Enlarge
| Become vesicular
281
How does the cytoplasm appear in gliosis?
Bright pink
Irregular
Swathes around oddly placed nucleus
282
What are glial fibrils?
Extension of ramifying processes of cytoplasm
283
What is cytoplasmic expansion in gliosis associated with?
Increased production of glial fibrillay acidic protein
284
What happens in old gliosis lesions?
Nuclei become small and dark
| Nuclei lie in dense net of glial fibrils
285
How does gliotic tissue appear?
Translucent and firm
286
What are microglial nodules?
Microglia forming aggregates about foci of necrosis
287
What are neuronophagia?
Microglial congregations around portions of dying neurones
288
What percentage of cardiac output does the brain receive?
15%
289
How much of the oxygen in the body does the brain consume?
20%
290
How does the brain get ATP?
Active aerobic metabolism of glucose
291
What happens to the vasculature in the brain in response to hypertension?
Constricts
292
What is Weber's syndrome?
Vertebrobasilar pathology affecting the midbrain:
- Ipsilateral CN iii palsy
- Contralateral hemiparesis/hemiplagia
293
What is Global Hypoxic-Ischaemic Encephalopathy?
Parenchymal injuries with generalised decrease in blood flow
294
When does cerebral autoregulation fail?
When systolic BP <50 mmHg
295
What does mild ischaemic result in?
Preferential loss of selectively vulnerable neurones
296
What does moderate ischaemic result in?
Selective neuronal necrosis
| Glial and endothelial cells preserved
297
What does complete ischaemia result in?
Pan-necrosis
298
What groups of neurones are most vulnerable to hypoxic-ischaemic damage?
Pyramidal cells of hippocampus
Purkinje cells of cerebellum
Those within globus pallidus
299
What are the 'watershed areas'?
Junctions of arterial territories
300
Where do the 'watershed areas' receive blood from?
Dual supply from most distal arterial branches
301
What affects the 'watershed areas' first?
Hypotension
302
Give examples of 'watershed areas'.
Superior cerebral convexities:
- Ant. and Middle cerebral artery junctions
Posterior cerebellum:
- Ant. and Post. cerebellary artery junctions
303
What are the signs/symptoms of hypoxic-ischaemic encephalopathy?
Arrhythmias
Shock
Increased ICP
304
What age is the peak incidence of cerebral infarction?
70+ years
305
Where does thrombosis most commonly occur in cerebral infarction?
Bifurcation of common carotids
306
Where do most emboli arise in cerebral infarction?
Heart
| Atherosclerotic plaques in more proximal arteries
307
Where do most emboli occlusions occur in cerebral infarction?
Middle cerebral arteries
308
Apart from thrombosis and emboli, what else can cause occlusion?
Vasculitis
| Trauma
309
What causes of cerebral infarction does atheroma increase the risk of?
Basilar artery (usually);
- Thrombosis
- Aneurysm
310
How can hypertension result in cerebral infarction?
Atherosclerosis of small penetrating vessels:
| - Muscle in walls replaced with hyaline (weaker)
311
What infarcts does hypertension result in?
Lacunar infarcts
312
At what time do ischaemic neuronal changes occur in CVA?
5 to 20 hours
313
When does inflammation and extravasation of RBCs occur in CVA?
24 to 36 hours
314
At what time are necrotic areas following CVA visible macroscopically?
36 to 48 hours
315
What happens on day 3 following a stroke?
Macrophages infiltrate:
- Phagocytose necrotic debris
- Sharper demarcation of site of infarction
316
What happens in the 1st-2nd week following CVA?
Liquefaction of tissue and gliosis (Colliquative necrosis)
317
What happens a few months after a CVA?
Cavitation
| Completion of glial scar
318
Spontaneous saccular aneurysm rupture is more common in what sex?
Female
319
What conditions increase the incidence of Berry aneurysms?
```
PKD
Fibromuscular dysplasia
Coarctation of arota
Arteriovenous malformations in the brain
Collage iii developmental abnormality
```
320
Where do most saccular aneurysms arise?
Bifurcations (in internal carotid territory)
321
At what size are saccular aneurysms at greatest risk of rupture?
6-10cm
322
At what size do saccular aneurysms loss most risk of rupture but cause symptoms due to mass effect?
>=25cm
323
Why may parenchymal infarcts develop after an aneurysm rupture?
Arterial spasm
Mass effect due to:
- Haematoma
- Increased ICP
324
What symptoms is a subarachnoid haemorrhage associated with?
Severe headache
Vomiting
Loss of consciousness
325
In what sex are subarachnoid haemorrhages most common?
Female
326
How does the CSF appear in a subarachnoid haemorrhage?
Bloody
327
What can cause chronic hydrocephalus following a subarachnoid haemorrhage?
Organisation of blood in:
- Leptomeninges
- Arachnoid granulations
CSF flow obstruction
328
What substance is myelin rich in?
Phospholipid
329
What are metabolic causes of secondary demyelination?
Progressive Multifocal Leucoencephalopathy
| Contral Pontine Myelinosis
330
What infections can cause secondary demyelination?
Sub-acute Sclerosing Panencephalitis:
- Post measles complication (1/10000)
AIDS
331
What toxins can cause secondary demyelination?
Low-grade, non-fatal cyanide
CO (chronic, low-levels)
Solvents
332
What is the M:F ratio of MS?
1:2
333
What is the prevalence of MS?
1/1000
334
What is the defining feature of MS?
Episodes of neurological deficit separated by time and space
335
How does MS appear on a T1 weighted MRI?
Hypointense
336
How does MS appear on a T2 weighted MRI?
Hyperintense
337
What is one of the earliest clinical signs and is often the first sign at presentation in MS?
Optic neuritis
338
Apart from visual disturbance, what are some other common manifestations in MS?
Paraesthesia
Spasticity
Speech disturbance
Gait abnormalities
339
What vitamin might be related to MS?
Vitamin D
340
Why does the external surface of the brain appear normal in MS?
Grey matter has no myelin
341
On a cut surface of the brain, how do the demyelinated plaques appear?
Well-demarcated
Soft and pink in acute lesions
Firmer and pearly grey
342
Where are plaques common in MS?
CN ii and optic tract
Periventricular white matter
Corpus callosum
Brainstem and spinal cord
343
Where are acute MS plaques often centred around?
Veins
344
Why are chronic inactive MS plaques well-defined?
Astrocytic proliferation and gliosis are prominent
345
Where are chronic inactive MS plaques classically located?
Around lateral ventricles
346
What are shadow plaques in MS?
Plaques were the border between normal and affected white matter is ill-defined
347
What cells typically result in inflammation in MS?
Lymphocytes (T cells)
348
What type of glia are most common in MS gliosis?
Astrocytes
349
What metabolic conditions can result in secondary dementia?
Uraemia
| Hepatic failure
350
What conditions associated with paraneoplastic syndromes can commonly cause secondary dementias?
Small-cell lung cancer
| Some squamous cell carcinomas
351
What is Biswanger's Disease?
Vascular dementia due to white matter damage in hypertension
352
In what genetic condition is the risk of Alzheimer's Disease increased?
Down's Syndrome
353
How does Alzheimer's Disease tend to present?
Insidious impairment of higher functions:
- Mood
- Behaviour
354
What are some later signs of Alzheimer's Disease?
Disorientation
Memory loss
Aphasia
355
What do the later signs of Alzheimer's Disease indicate?
Severe cortical dysfunction
356
What macroscopic pathologies are seen in Alzheimer's Disease?
Marked decreased in brain size (cortical atrophy)
Widening of sulci
Narrowing of gyri
Secondary hydrocephalus (ventricular dilatation)
357
What lobe of the brain is often spared in Alzheimer's Disease?
Occipital
358
What is the main component of intracytoplasmic neurofibrillay tangles in Alzheimer's Disease? Why is it pathological?
Tau protein:
| - Abnormally phosphorylated
359
What effect do intracytoplasmic neurofibrillay tangles have on the cell?
Displace/Encircle nucleus
360
What is the main component of the extraceullar senile/neuritic plaques in Alzheimer's Disease? What is this cleaved to?
A-beta amyloid plaques:
| - Cleaved to beta-pleated sheet
361
Where are extracellular senile/neuritic plaques most common in Alzheimer's Disease?
Hippocampus
Cerebral cortex
Deep grey matter
362
Where is there excessive neuronal loss with astrocytosis in Alzheimer's Disease?
Hippocampus
Frontal lobe
Temporal lobe
363
What cells accumulate in amyloid?
Eosinophils
364
How does amyloid stain? What stain is used?
Congo Red stain:
| - Bright apple-green
365
On electron microscopy, how big is amyloid?
10-12nm fibrils
366
What are the hallmarks of Lewy Body Dementia?
Progressive dementia with:
- Hallucinations
- Fluctuating attention
- Parkinsonism
367
What do Lewy Bodies produce?
Ubiquitin
368
Where is the Huntingtin gene located?
Chromosome 4p16.3
369
What is Pick's Disease?
Progressive dementia characterised by:
| - Changes in character and social deterioration
370
When does Pick's disease usually present?
50-60years
371
What does Pick's Disease lead to?
Impaired:
- Intellect
- Memory
- Language
372
What are the macroscopic changes in Pick's Disease?
Extreme atrophy of temporal and frontal lobes
373
How much does the brain weight in Pick's Disease?
<1kg
374
What are the microscopic changes in Pick's Disease?
Neuronal loss and astrocytosis
Pick's cells (Swollen neurones)
Pick's bodies (Intracytoplasmic filamentous inclusions)
375
How quickly does Pick's Disease progress?
Rapidly:
| - 2-10 years from diagnosis to death (mean is 7)
376
Why does multi-infarct dementia often result in anxiety and depression?
Sufferers are aware of their deficits
377
What signs suggest multi-infarct dementia?
Abrupt onset
Stepwise progression
PMHx of hypertension and CVA
CT/MRI evidence of CVA
378
When does a diffuse axonal injury occur
At moment of injury
379
Where is the most common location of diffuse axonal injury?
Brainste,
380
What cells appear and where weeks after a diffuse axonal injury?
Clusters of microglia in white matter
381
What occurs in the 2-4 hours following a diffuse axonal injury?
Focal APP accumulation impairing axonal transport
382
What occurs in the 12-24 hours following a diffuse axonal injury?
Axonal varicosity -> Axonal swelling -> Brain swelling
383
What does calcium influx in diffuse axonal injury result in?
Activation of calpains
Cytoskeletal disruption
Disrupted antegrade flow
384
If an epidural haemorrhage goes untreated, what can happen?
Midline shift:
- Compression
- Herniation
385
What is a subfalcine herniation associated with?
Anterior cerebral artery compression
386
What type of respiration can result from herniation?
Cheyne-Stokes:
- Progressively deeper
- Sometimes faster
387
In what people are abscesses common?
IVDUs
388
What sort of cerebral oedema is due to:
- Defects in BBB
- Water, sodium and protein leak into extracellular space
Where does it occur?
Vasogenic
| White matter
389
What is the commonest cause of cytotoxic cerebral oedema?
Ischaemia
390
What causes hydrostatic cerebral oedema?
Low protein
Fluid flows into extracellular space -> Supped increase in ICP
Dilatation of capillary bed
391
In what condition is hydrostatic cerebral oedema seen?
Hypertensive encephalopathy
392
What type of cerebral oedema results from fluid forced into paraventricular white matter?
Interstitial
393
In what type of haemorrhage might patients experience a lucid interval before losing consciousness?
Epidural
394
Why are gyrud contours preserved in subdural haemorrhage?
Pressure is evenly distributed (unlike in an epidural haemorrhage)
395
Why is symptom onset of a subdural haemorrhage often slower?
Venous bleed
396
What typically causes chronic subdural haemorrhages?
Brain atrophy - Bridging veins become more vulnerable
397
What is the composition of a chronic subdural haemorrhage?
Liquefied blood:
- Yellowish
- Separated from brain by neomembrane
398
What contrast agents can be used in brain CT?
Niopam
Ultravist
Ominoaque
399
When do we take the scan to receive a CT angiogram?
During and immediately after bolus is pumped in
400
When do we take a scan to receive a CT venogram?
30 seconds later
401
After how long with a CT scan show enhancement where there has been BBB disruption (eg in tumours and inflammation)?
5 minutes
402
What substances can be used as contrast in MRI?
Paramagnetic (eg. Gadolinium):
- Magnevist
- Dotarem
403
What are the indications for angiography?
Investigation of spontaneous subarachnoid haemorrhage
Suspected aneurysm/AVM
Carotid stenosis
404
Where will blood be present on CT in a subarachnoid haemorrhage?
Ventricles
Sylvian fissures
Basal cisterns
Surface subarachnoid space
405
What is the gold standard investigation into a subarachnoid haemorrhage?
Digital subtraction angiography
406
What shows up as hyperintense on a T1 MRI?
Fat and the 4 Ms:
- Methaemoglobin
- Mineral deposition
- Melanin
- "Mush" (highly proteinaceous fluid)
407
What shows up as hypointense on T1 MRI?
Water
Air
Cortical bone
High flow (Arterial "flow voids")
408
What shows up as hyperintense on a T2 MRI?
```
Water (less tissue = more water):
- Fluid collection
- Oedema
- Demyelination
- Gliosis
- Some tumours
Fat (although it is usually suppressed)
```
409
What shows up as hypointense on a T2 MRI?
Some blood products (sub-acute haematoma)
Minerals
Air and bone
High flow
410
What is N-acetyl aspartate a marker of?
Neuronal density and neurometabolic fitness
411
What is N-acetly aspartate correlated to?
Rate of mitochondrial phosphorylation
412
What is the "Cho" peak formed of in MR spectroscopy?
Choline
Ach
Glycerophorycholine
Phosphocholine
413
What is the "Cr" peak formed of in MR spectroscopy?
Creatinine
| Phosphocreatinine
