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302: Scientific Bases of Medicine > Neurology > Flashcards

Neurology Flashcards

1
Q

What is Multiple Sclerosis?

A
  • MS is an autoimmune, inflammatory, demyelinating & degenerative condition of the central nervous system.
  • The immune trigger is unknown but the targets are myelinated Central Nervous System (CNS) Tracts.
  • In regions of inflammation, breakdown of the blood–brain barrier occurs and destruction of myelin ensues, with axonal damage, gliosis and the formation of sclerotic plaques.
  • Plaques (MS lesions) may form in the CNS white matter in any location (and also in grey matter); thus, clinical presentations may be diverse.
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2
Q

What is the physiological theory behind MS?

A
  • It’s a B cell and T cell disorder
  • activated T cells enter the CNS → release chemicals that cause inflammation and de-myelination
  • T-cells also activate B cells → these B cells go on to produce antibodies and stimulate the other proteins that cause further damage to the CNS
  • there is initial damage to that region which presents as clinical i.e optic nerve neuritis but is also proceeded by re-myelination which presents as clinical recovery
    • however, there can be some deficit, especially with subsequent attacks → more neuronal damage and brain atrophy which can be seen in MRI scans
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3
Q

What is the epidemiology of Multiple Sclerosis?

A
  • It’s the leading cause of the nontraumatic disabling neurological conditions in you adults
  • Starts between 20-40 y/o
    • 5% of cases occur in childhood (rare in under 10y/o)
  • ~2.5 million people are affected worldwide
    • 100,000 people in the UK have MS (~1/600)
    • the lifetime risk in the general population is ~1:30
  • Women are twice as likely to develop MS as men
  • MS incidence is higher in colder climates Vit D deficiency?
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4
Q

What are the Genetic factors in the occurrence of Multiple Sclerosis?

A
  • Most common in the white population
  • Northern European descent
  • HLA DRB1*1501 on chromosome 6p21
  • Non-HLA genes also identified (IL7RA &IL2RA)
  • Familial recurrence rate of about 20%
  • Siblings 5%; parents 2% & children 2%
  • Reduction in risk changes from 3% in first degree relatives to 1% in 2nd & 3rd relatives
  • However, alteration in the risk of MS depending on the age of migration

suggests it’s not only genetic factors but also environmental

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5
Q

What is the link between Viral infection and Multiple Sclerosis?

A
  • 40% of new clinical symptoms are associated with a viral infection
  • 10% of infections in MS patients are followed by a relapse
  • Relative risk of contracting MS increases with age of infection with measles, mumps, rubella and EBV (up to age 12-15 years old)
  • EBV infection as young adult – 8x risk of MS
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6
Q

What is a Clinically Isolated Syndrome?

A
  • A clinically isolated syndrome (CIS) is an acute or subacute neurological syndrome
  • A CIS is usually the first clinical event in an MS patient
  • MS will develop in 80% of patients with a CIS, however, a CIS is not entirely predictive of MS hence other differentials need to be considered as a CIS covers a broad spectrum of syndromes
    • MS is not the only recurrent demyelinating disease i.e adrenoleukodystrophy
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7
Q

Which CIS symptoms are characteristic of MS?

A
  • Painful optic neuritis
  • Partial acute transverse myelitis
  • Lhermitte’s symptom
  • Bilateral internuclear ophthalmoparesis (INO)
  • Paroxysmal dysarthria\ataxia
  • Tonic seizures
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8
Q

What is Lhermitte’s syndrome?

when does it occur?

A

An electric shock like sensation that affects the spine and neck. It is often sporadic, does not last long and may recur

  • this is seen in MS, cervical spondylosis, cervical tumour and b12 deficiency
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9
Q

Explain dissemination in time and space in relation to Multiple sclerosis

A

Dissemination in space: looking for one or more lesions in the following regions the periventricular, cortical, Infratenorial, spinal cord

Dissemination in time: a new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, with reference to a baseline scan, irrespective of the timing of the baseline MRI. The simultaneous presence of symptomatic gadolinium-enhancing and non-enhancing lesions at any time (shows newer and older lesions, occurring within 6>8 weeks)

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10
Q

What is Uhtoff’s phenomenon?

A

When symptoms of MS are brought on by a period of increased body temperature

i.e visual disturbances after taking a hot shower, sauna, or having a fever

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11
Q

What is the typical and atypical presentation of optic neuritis in MS?

A
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12
Q

What is the typical and atypical presentation of Isolated Brain Stem Syndrome

A
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13
Q

What is the typical and Atypical presentation of Isolated Spinal Cord Syndrome?

A
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14
Q

What are the differentials for individuals presenting atypically with Optic Neuritis

A

Atypical presentation → no pain, retinal exudates, retinal haemorrhages severe disc swelling, no visual recovery

  • Ischaemic Optic Neuritis (ON)
  • hereditary ON
  • Infiltrative ON
  • Inflammatory (sarcoid, lupus)
  • infection (syphilis, Lyme, viral)
  • Toxic/Nutritional
  • Retinal disorders
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15
Q

What are the differentials for individuals presenting atypically with isolated Brain Stem Syndrome

A

Atypical presentation → hyperacute onset, vascular territory signs e.g lateral medullary syndrome (sensory deficits), age >50, trigeminal neuralgia, fluctuating ocular/bulbar weakness, non-remitting, fever, meningism

  • Ischaemic haemorrhagic (cavernous angioma)
  • Infiltrative
  • Inflammatory (sarcoid, lupus)
  • Infection (syphilis, listeria, Lyme, viral)
  • Toxic
  • Nutritional
  • Central pontine myelinolysis
  • Neuromuscular
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16
Q

What are the differentials for individuals presenting atypically with Isolated Spinal Cord Syndrome

A

Atypical presentation → hyperacute onset or insidiously progressive, complete transverse myelitis, sharp sensory level, radicular pain, areflexia, failure to remit

  • Compression e.g intervertebral disc, tumuor
  • Ischemia/ infarction
  • Other inflammatory disease e.g neuromyelitis optica, sarcoid, lupus, Sjorgens
  • Infection e.g syphilis, lym, viral, TB
  • Toxic/nutritional/metabolic e.g B12 deficiency, NO toxicity, copper deficiency
  • Arteriovenous malformation
  • non-cord mimics e.g Guillain-Barré syndrome, myasthenia gravis
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17
Q

What is the EDSS and what is it used for?

A

Expanded Disability Status Scale

  • when an EDSS of 3 is reached the disease becomes irreversible
  • the earlier txt starts the better the chances of delaying progression of the disease to this state
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18
Q

What is the long term implication of MS attack relapses?

A

the lower the number of relapses within the first 2 years of diagnosis the longer the time they have an EDSS less than 6 therefore the better their mobility

The interval between the attacks can also be predictive of disability from the disease onset

Patients with a short interval (0–2 years) reached DSS 6 and DSS 8 quicker than those with a long interval (e.g. 3–5 years or 6+ years)

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19
Q

How can the baseline Brain MRI lesions be used to diagnose MS or predict prognosis?

A
  • the presence of a single lesion on a baseline MRI scan increases the risk of conversion to CDMS by around 80% versus 20% on those with a normal MRI
  • If you have one or more lesions it didn’t really change this risk very much
  • Those with more lesions tended to have a greater disability. But this trend showed great variability
  • The location of the lesion can be an indicator of a long-term disability: ptx with at least 2 infratentorial lesions had a worse outcome at follow-up
  • Lesion volume continues to increase for at least 20-years in relapse onset MS patients and the rate of lesion growth is 3 times higher in those who developed Secondary Progressive MS than those who remain Relapsing-Remitting MS
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20
Q

What can we learn from the appearance of grey and white matter on MRI scans about the prognosis of multiple sclerosis

A

GM, but not WM, fractions correlated with disability & lesion load

GM atrophy rate (expressed as a fold increase from the control subjects) increased with the disease stage

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21
Q

What is epilepsy?

A
  • a recurring unprovoked (spontaneous) seizures
  • acute symptomatic seizures are provoked by acute insults such as
    • stroke, infection, alcohol withdrawal, or a metabolic disturbance
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22
Q

What types of seizures are there?

A
  • Primary generalized onset: electrical discharges appear to start over the whole brain at the same time on EEG
  • Partial/focal onset: electrical discharge appears to start in one cortical region and then may remain localized or may spread over the whole brain - secondary generalized
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23
Q

What are the classifications of Idiopathic (Primary) Generalized seizures?

A
  • Limited repertoire of seizures
  • Tonic-clonic seizures (“grand mal”)
  • Absences (“petit mal”)
  • Tonic seizures
  • Atonic seizures
  • Myoclonic seizures
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24
Q

Give an overview of what Idiopathic Generalized Seizures are?

A
  • Onset in childhood or adolescence
  • Usually no focal symptoms/signs
  • Often a number of seizure types cluster
  • A polygenic cause is presumed with no identifiable structural lesion on imaging
  • Generalized (all leads) spike and wave discharges on EEG may be induced by hyperventilation, and on photosensitivity testing
  • Provoked by sleep deprivation
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25
Q

What is Juvenile Myoclonic Epilepsy (JME? - give an overview

A
  • Commonest form of primary generalized epilepsy 3-12% all epilepsy
  • Juvenile onset, probably lifelong
  • Early morning myoclonic jerks (ask)
  • Photosensitive, sleep deprivation triggers
  • +/- absences
  • generalized tonic-clonic seizures – occur without warning
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26
Q

Give an overview of the presentation of Generalised Tonic-Clonic Seizures “grand mal”

A
  • sudden onset without warning in primary generalised epilepsy
  • Tonic phase
    • continuous muscle spasm, fall, cyanosis, tongue biting, incontinence
  • Clonic phase
    • rhythmic jerking slows and gets larger in amplitude as the attack progresses
    • Ends; the duration is typically 1-3 minutes
  • Post-ictal (post-seizure) phase
    • coma, drowsiness, confusion, headache
    • muscle aching
    • red/blue, wakes in ambulance/A&E
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27
Q

Give an overview of Absences “petit mal”

A
  • Abrupt, short, 5-20 seconds
  • Multiple times/day, can lead to learning difficulties
  • Unresponsive, amnesia for the gap, rapid recovery
  • Tone preserved (or mildly reduced)
  • If absences only, tend to remit in adulthood (childhood absence epilepsy)
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28
Q

What ways are there Focal Onset Seizure?

A
  • a simple partial seizure where the patient is aware (used to be an aura)
    • focal seizure with awareness
  • a complex partial seizure- aura/warning with a level of reduced awareness
    • focal seizure with reduced awareness
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29
Q

Where d partial seizures frequently present themselves in the lobe?

A
  • Temporal lobe - 70%
  • Frontal lobe - 25%
  • Occipital lobe - 4%
  • Parietal lobe - 1%
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30
Q

Give temporal lobe seizures by aetiology

A
  • Hippocampal sclerosis: 50%
    • have a history of febrile convulsion
  • Tumour: 18%
  • Birth Hypoxia: 10%
  • Vascular: 10%
  • Post Traumatic: 8%
  • Other: 4%
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31
Q

What are the symptoms and signs of temporal lobe epilepsy?

A
  • hallucinations of taste, speech and /or smell, visual distortion; memory déjà vu and jamais vu
  • epigastric rising sensation (over humpback bridge)
  • fear, elation, low mood
  • pallor/ flushing/ heart rate changes (can mimic panic/hyperventilation attacks)
  • automatisms- semi-purposeful limb movements
  • Oral automatisms- lip-smacking, chewing movements
  • dystonic posturing (limb rises)
  • speech disturbance (dominant hemisphere onset) last 1-3 minutes typically
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32
Q

What are the symptoms of a frontal lobe seizure?

A
  • brief 10-30 seconds, rapid recovery, frequent
  • predominantly nocturnal
  • forced head /eye deviation to the contralateral side
  • motor activity often bizarre, thrashing
  • often misdiagnosed as non-epileptic
  • ictal EEG (during the seizure) is often normal
  • Jacksonian spread with Todd’s paresis
  • automatisms, dystonic posturing for example
  • a fencing posture (overlap TLE)
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33
Q

What are Parietal lobe epilepsy symptoms?

A
  • positive sensory symptoms (unlike TIA/stroke)
  • tingling, pain
  • distortion of body shape/image
  • Jacksonian march of positive sensory symptoms
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34
Q

What are Occipital lobe epilepsy symptoms?

A
  • typically simple visual hallucinations -balls of coloured or flashing lights
  • amaurosis (blackout or whiteout) at onset -25%
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35
Q

What anti-epileptic drugs make myoclonic jerks and absences worse?

A
  • Phenytoin
    • treats tonic-clonic seizures
    • safe to use in status epilepticus (when a seizure lasts more than 5 minutes or are close together)
  • Carbamazepine,
  • Gabapentin,
  • Pregabalin
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36
Q

Which type of seizure patient would you give a scan to?

A
  • Jacksonian motor or sensory seizures
  • Patients with focal neurological deficit (including a temporary unilateral Todds paresis)
  • Alcohol withdrawal seizure; only scan if subdural haematoma suspected fall, hit head, found on the floor, bruising on head
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37
Q

What is the physiological representation of Epilepsy?

A
  • Epilepsy represents a hyperexcitation or a failure of inhibitory regulation, either focally (e.g. motor cortex, temporal cortex) or generally (whole cortex at once)
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38
Q

How are epileptic episodes physiological caused?

A
  • Na+ channel inactivation too slow in excitatory neurons
  • Reduced number of functional Na+ channels in inhibitory neurons
  • Reduced number of functional K+ channels in excitatory neurons
  • Mutated ion channels: voltage-gated and ligand-gated ion channels
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39
Q

How do Na+ channel dysfunctions lead to epilepsy?

A

Na+ channel inactivation too slow in excitatory neurons

  • e.g., generalized epilepsy with febrile seizures plus (GEFS+)
  • a point mutation in part of Na+ channel (β subunit) –> abnormally slow inactivation
    • action potential repolarization impaired

Reduced number of functional Na+ channels in inhibitory neurons

  • e.g., generalized epilepsy with febrile seizures plus (GEFS+)
  • missense mutations or truncated protein results in reduction or loss of Na+ channel function
    • action potential generation impaired
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40
Q

How do K+ channelopathies lead to epilepsy?

A

Reduced number of functional K+ channels in excitatory neurons

  • e.g., benign familial neonatal convulsions
  • defect in KCNQ2 or KCNQ3 K+ channel subunit –> impaired activation
    • action potential repolarization impaired
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41
Q

Explain the development of Focal (partial) seizures

A
  • synchronized ‘paroxysmal depolarizing shift’ (PDS, 20 to 40 mV, lasting 50 to 200 ms) overcomes inhibition
  • increased extracellular K+ due to neuronal damage or reduced uptake by the astrocytes as well as glutamate release from neurons or astrocytes contribute to PDS
  • during the PDS trains of action, potentials occur
  • hippocampal neurons have similar responses under normal conditions, making the hippocampus more prone to seizures than the neocortex
  • Focal seizures may spread to other brain regions along the normal neuronal pathways and may also show secondary generalization if the activity spreads to the thalamus (tonic clonic seizure)
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42
Q

Explain the development of Primary Generalized seizures.

A
  • Primary generalized seizures reach the cerebral cortex via normal neuronal pathways from the thalamus
    • e.g. tonic clonic seizure; absence; juvenile myoclonic epilepsy
  • pathways originate in the brainstem and are normally involved in regulating the sleep/wake cycle and arousal of the cerebral cortex
  • Ca2+ channels and inhibitory GABA receptors in thalamic neurons have been implicated in ‘spike and wave’ seizures, showing that inhibition (the wave) is preserved
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43
Q

What is the general action of Anti-epileptic drugs?

A
  • work to inhibit Glutamate
    • this is an excitatory molecule in the brain
  • work to increase GABA activity
    • this is an inhibitory molecule in the brain
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44
Q

What AEDs work by inhibiting the excitatory process in neurons?

A
  • Phenytoin, Carbama/ Oxcarba-zepine, Eslicarbazepine acetate, Lamotrigine, Lacos/ Zonis-amide
    • inhibits voltage-gated Na+ ion channel
  • Ethosuximide
    • inhibits Ca2++ entry into postsynaptic neuron
  • Retigabine
    • increases excite of K+ from the postsynaptic neuron
  • Perampanel
    • inhibits the AMPA receptor which glutamate binds to and allows NA+ into the postsynaptic neuron
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45
Q

What AEDs work by increasing the activity of the inhibitory process in neurons?

A
  • Levetiracetam
    • increases activity of SV2A- regulates action potential-dependent neurotransmitter release
  • Retigabine
    • increases the activity of KCNQ K+ channels in the pre and postsynaptic neuron
  • Gabapentin, Pregabalin
    • inhibit alpha-2-beta-subunit of Ca2+ channels in the presynaptic neuron
  • Tiagabine
    • Inhibits GAT-1 in presynaptic neurons and on glial cells
  • Benzodiazepines, Barbiturates
    • increases activity of GABAA more Cl- moved into the postsynaptic neuron
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46
Q

Perampanel as an AED

A
  • non-competitive blockade of AMPA glutamate receptor
  • release of glutamate cannot overcome the block
  • reduce spread/generalisation of seizure
  • can also affect behaviour and mood
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47
Q

What role or lack thereof does GABA play in the occurrence of a full-blown seizure?

A
  • Focal epilepsy characterised by intermittent high amplitude discharges at site of epileptic focus during inter-ictal (seizure) periods.
  • Two phases:
    • synchronous depolarisation (caused by strong excitatory inputs to the region of the focus),
    • followed by a period of hyperpolarisation, (activation of GABA inhibition)
  • Transition from inter-ictal discharges to full-blown seizure is a decrease in the hyper-polarisation phase
    • failure of inhibition to kick in, therefore treating with GABA stimulants helps control the seizure
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48
Q

What drugs enhance GABA-ergic synaptic transmission?

A
  • sodium valproate (sodium channels)
  • benzodiazepines (clobazam, lorazepam)
  • barbiturates/ primidone pro drug
  • tiagabine (inhibits GABA re-uptake)
  • vigabatrin (inhibits GABA –T breakdown)
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49
Q

What is Levetiractem?

A
  • high-affinity synaptic vesicle protein-2A ligand that modulates glutamate neurotransmitter release
  • rapidly up titrated and is effective
  • IV formulation; no drug-drug interactions
  • keeps patients alert but causes mood lowering/agitation side-effects
  • brivaracetam second-generation version
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50
Q

What drugs would be suitable for Primary Generalized Epilepsy?

A

First line

  • Sodium valproate
  • Lamotrigine

Second line

  • levetiracetam, topiramate, zonisamide, benzodiazepines
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51
Q

What drugs would be suitable for Partial (focal onset) epilepsy?

A

First line

  • Carbamazepine
  • Lamotrigine
  • all other AEDs have efficacy
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52
Q

Go over the toxicity effects of Benzodiazepines

A

Dose related (acute)

  • Drowsiness
  • Ataxia
  • Hyperactivity
  • cognitive impairment

Long term

  • Tolerance/ Dependence
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53
Q

Go over the toxicity effects of Phenytoin

A

Dose-related (acute)

  • Ataxia
  • Diplopia
  • Nystagmus

Long-term

  • Gingival hyperplasia
  • Osteomalacia
  • Cerebellar atrophy
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54
Q

Go over the toxicity effects of Sodium Valproate

A

Dose-related (acute)

  • Sedation
  • Tremor

Long-term

  • Hair thinning
  • Weight gain
  • Menstrual irregularities
  • Encephalopathy
  • Parkinsonism

(is an enzyme inhibitor)

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55
Q

Give an overview of the Motor Control of Hierarchy

A
  • High for strategy: Association areas of Neocortex and basal ganglia
  • Medium for tactics: Motor Cortex and Cerebellum
  • Low for execution: Brainstem and Spinal Cord
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56
Q

Give an overview of the corticospinal tracts from the motor cortex to the skeletal muscles

A
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57
Q

rubro = red

Give an overview of the Rubrospinal tract

A
  • predominentley innervates the flexor muscles in the upper limb
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58
Q

Give an overview of the Vestibulospinal tract

A
  • originates in the vestibular nuclei of the medulla which relay sensory information from the vestibular labyrinth in the inner ear
  • Medial Vestibulospinal pathway activates the cervical spinal circuits that control neck and back muscle guides
    • guides head movements
    • helps keep eyes stable as the body moves
  • Lateral vestibulospinal projects ipsilaterally far down the lumbar spinal cord
    • helos maintain an upright and balanced posture
    • facilitates the extensor motor neurons of the legs
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59
Q

Give an overview of the Tectospinal tract

A
  • Originates in the superior colliculus in the midbrain
  • The superior colliculus receives information from the retina and the visual cortex used to construct the map of the world around us
    • allows the direction of the head and eyes so that the appropriate point of space is imagined on the fovea
  • The neurons decussate immediately and lie close to the midline into the cervical region of the spinal cord
    • help control muscles of the neck, upper trunk and shoulder
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60
Q

Give an overview of the Reticulospinal tract

A
  • Reticulospinal tract descends in two separate pathways
    • Pontine (medial)
    • Medullary (lateral)
  • both facilitate the extension of the limbs
  • the pathway runs from the brainstem, the reticular formation is under the cerebral aqueduct and fourth ventricle
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61
Q

What are the 5 descending pathways in the spinal cord

A
  • Tectospinal and medial vestibulospinal
    • Control head and neck movements.
  • Lateral vestibulospinal and reticulospinal
    • Activate extensor muscles in arms and legs.
  • Rubrospinal
    • Activates flexor muscles in arms.
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62
Q

Explain the meaning of different Posturing in Coma

A
  • Decorticate posturing: the lesion is above the red nucleus
    • the rubrospinal neurons are disinhibited and therefore facilitate flexors in the upper limbs (lesions above the red nucleus)
  • Decerebrate posturing: the rubrospinal neurons are disrupted and therefore upper limbs are extended (lesions below the red nucleus)
  • Noxious stimuli allow us to understand where the lesion is
    • supraorbital pressure
    • nail bed stimulation
    • sternal stimulation
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63
Q

What is the impact of damage to the motor cortex and corticospinal tract

  • loss of descending inhibition
A
  • Typical Posture
    • some preserved upper limb flexion
    • lower limb extension
  • Increased tone (spasticity),
  • Brisk Reflexes:
  • Extensor Plantar/Babinski reflex: abnormal extension of toes (up till age 2 is normal)
  • Clonus
  • Patient maintains a posture
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64
Q

What is the blood supply of the brain?

A
  • Anterior Cerebral artery –> Frontal
  • Middle Cerebral Artery –> Temporal and Parietal
  • Posterior Cerebral Artery –> Occipital
  • Anterior choroidal artery + Branch of Internal Carotid –> centre of the brain
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65
Q

What is the consequence of the middle cerebral artery occlusion?

A
  • a Proximal lesion would affect the internal capsule
    • leading to complete hemiparesis
  • a Distal lesion may spare the leg area of the motor cortex
    • (secondary swelling and ischaemia may compromise function)
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66
Q

What is the consequence of an Anterior Cerebral Artery stroke?

A
  • this supplies the medial part of the frontal lobes including leg area of the motor cortex
    • leg (crural) paresis
    • frontal sing e.g abulia: loss or impairment of the ability to make decisions or act independently
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67
Q

What is a Jacksonian Seisxre (March)

A
  • partial onset of a simple motor seizure becoming secondarily generalised
  • strongly associated with a structural abnormality in or close to the motor cortex
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68
Q

What is the role of the Posterior Parietal Cortex?

A
  • Area 5- somatosensory afferents
  • Area 7- visual pathway afferents
  • Mental body/ environment image
    • Damage results in neglect (can perceive but do not attend)
  • Exploratory movements
    • Eg turning object in hand (looking and feeling)
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69
Q

What inputs allow for motor planning?

A
  • Visual, Auditory, Somatosensory, Vestibular, Gustatory

all feed into the Heteronodal which allows for motor planning

  • the prefrontal cortex plans for movement after receiving information from the other cortices in the brain
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70
Q

Give an overview of the Premotor Area (PMA)

A
  • Importance in control of visually guided movements
    • origination of the hand in relation to the object to be grasped (prehension)
    • Damage: may cause perseveration of motor activity despite lack of success
  • receives input from the cerebellum is involved in planning movements based on visual cues, mostly involved in
    • control of postural and proximal limb muscles
  • lesions in the PMA disrupts response to visual cues
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71
Q

What is Apraxia?

A

Inability to carry out purposeful movements in the absence of paralysis or paresis. There is great difficulty in the sequencing and execution of movements

  • Ideational (Parietal) apraxia: unable to report sequence
    • show me how to make a peanut butter sandwich
  • Ideomotor (SMA) apraxia: unable to use the tool
    • show me how to hold and use a pair of scissors
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72
Q

What is Dystonia?

A

Sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures or positions. If only occurs with certain actions, said to be ‘task specific’.

  • though manifestation is motor, the primary abnormality is likely to be disrupted sensory processing mediated by the basal ganglia
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73
Q

What is the role of the Anterior Cingulate Gyrus

A

implicated in

empathy, impulse control, emotion, and decision-making

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74
Q

What is the role of the Basal ganglia

A

Positive feedback loop with the cortex to select wanted movements and deselect unwanted movements.

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75
Q

What is the function of the Cerebellum

A
  • Coordination of muscles in order to make smooth movements.
  • Balance
  • Motor learning
  • Cognitive functions
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76
Q

Recreate this sagittal section of the Cerebellum and the cerebellar peduncles

A
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77
Q

Gross anatomy of the cerebellum

A
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78
Q

What are the three functional separations of the cerebellum?

A
  • Spinocerebellum
    • Vermis,
    • Fastiguel & Interposed nuclei: motor execution
  • Cerebrocerebelllum
    • Dentate nucleus: motor planning
  • Vestibulocerbellum
    • Flocculus, Nodulus
    • Vestibular nuclei: balance and eye movements
79
Q

Explain the Spinocerebellums role in the cerebellar

A
  • functions in the control of muscle tone/posture
  • takes in information via the spinocerebellar tracts from the midbrain
  • the cerebellum puts out information through efferent neurons
    • from the reticular formation down the reticulo and vestibulospinal tracts
80
Q

Explain the Cerebrocerebellums role and pathway in the cerebellar?

A
  • Planning movements
  • afferent fibres from the cortex travel through the corticopontine tract synapse and continue on the pontocerebellar tract
  • efferent fibres go back to the cortex from the Dentate cerebellar nuclei to the thalamus then the cortex
81
Q

Explain the Vestibulocerebellums pathway and role in the cerebellum?

A
  • involved in balance and eye movements
  • information from the ear from the vestibular nerve to the flocculondular lobe
  • efferent fibres synapse and decussate at the vestibular nuclei. travel down the vestibulospinal tract down the spine and up to the extraocular muscle nuclei in the midbrain
82
Q

Explain the pathways that enter/leave the cerebellum through the cerebellar peduncles

A

Superior cerebellar peduncle

  • Dentate nuclei: to thalamus and
  • Interposed nuclei: to red nucleus
  • Fastigial nucleus: to vestibular nuclei

Middle Cerebellar peduncle

  • Descending Corticospinal fibres synapse at the pons and enter the cerebellum

Inferior cerebellar peduncles

  • Ascending fibres from the inferior olive and proprioceptive information from eh spinocerebellar tract
83
Q

What are the effects of lesions to the Cerebrocerebellum pathway

A
  • Dysmetria: movement is not stopped in time (overshoot)
  • Dsynergia: decomposition of complex movements
  • Dysdiadochokinesia: reduced ability to perform rapidly alternating movements
  • Intentional tremor: tremor arising when trying to perform a goal-directed movement
  • Dysarthria – articulation inco.ordination: incoordination in the respiratory muscles, muscles of the larynx, etc. Uneven speech strength and velocity.
84
Q

Explain the Vestibular-ocular pathway from this diagram

A
85
Q

What are the effects of a lesion to the vestibulocerbellar pathway?

A
  • Nystagmus- involuntary, rhythmical, repeated oscillations of one or both eyes, in any or all directions of view
    • movement of the eyes minimises the ability to focus the eyes on one point (fixation).
86
Q

What are the effects of a lesion in the spinocerebellar pathway?

A
  • Gait ataxia (unsteadiness of walking), and disturbance of limb tone (hypotonia) and posture
87
Q

What are the cell layers of the cerebellar cortex?

A
  • MPG-W
    • Molecular: Stellate cell, Parallel fibre
    • Purkinje: Purkinje cell, Basket cell
    • Granular: Granule cell, Golgi cell, Mossy fibre, climbing fibre from the inferior olive, Purkinje cell axon
    • White matter: Mossy fibre, climbing fibre from the inferior olive
88
Q

Explain Motor learning via Long-term depression

A
  • the release of DAG and IP3 causes increased intracellular Ca2+ and activation of PKC
  • this triggers clatherin-dependent internalization of postsynaptic AMPA receptors
  • this weakens the parallel fibre synapse
89
Q

What are some Inherited genetic causes of cerebellar dysfunction?

A
  • Frederich’s ataxia
  • Spinocerebellar degeneration
    • (Ataxia may occur if major connections disrupted)
  • Ataxia-telengiectasia
  • Von Hippel Lindau
90
Q

What is Acquired Symmetrical Ataxia, give examples

A

Cerebellar atrophy

  • Alcohol
  • Metabolic (B12/Thyroid/Coeliac)
  • Drugs (eg phenytoin)
  • Degenerative (familial, MSA)
  • Immune (paraneoplastic)
91
Q

What is the vascular anatomy of the cerebellum

A
92
Q

Give examples of focal cerebellar pathology

A
  • Metastasis
  • PICA (Posterior inferior cerebellar artery) territory stroke
  • MS
93
Q

Describe the organization of the peripheral vestibular system

A
  • the endolymph in the chochlear duct is continuous with he endolymph on the apical surface of the vestibular hair cells
94
Q

What are the otolith organs? Explain their orientation and their structure

A
  • they are sensory cells in the otolith organs (sacculus and utriculus cells) are embedded in a gelatinous sheet covered with crystals of calcium carbonate
    • they sense linear and gravitational accelerations of the head
    • the four otolith organs are not exactly perpendicular to enable them to resolve and tilt
  • the six semicircular canals are oriented at right angles to one another to detect head rotation in all directions
95
Q

What are the two types of vestibular hair cells?

A
  • Type II vestibular hair cells
    • receive afferent and efferent information
    • appear to be more sensitive
  • Type I vestibular hair cells
    • surrounded by an afferent nerve calyx and are not directly contacted by efferent nerve fibres
96
Q

What is the role of the semicircular canal receptors?

A
  • they detect rotation of the head
    *
97
Q

What is Nystagmus?

A
  • Slow eye movements followed by fast ones during continued head rotation - the fast phase defines the direction of the nystagmus
  • physiological nystagmus occurs in the head rotation due to the vestibulo-ocular reflex
  • Spontaneous nystagmus is when the eyes move rhythmically from side to side in the absence of any head movements
    • this occurs when one of the canals is damage
    • no firing takes place instead of the reduced firing that would happen in physiological nystagmus
98
Q

What is the use of Caloric testing?

A
  • water is used to test the function of the brainstem in an unconscious patient - uses ocular reflexes
  • using slightly warmer or colder warmer than body temp generates currents in the canal that mimics endolymph movement induced by turning the head
    • affects the firing rates of the associated vestibular nerve
      • warmer water = higher frequency
      • cooler water = decreased rate
    • the net difference generates an eye movement
99
Q

The Central vestibular pathway

A
100
Q

What are causes of vestibular disorders?

A
  • Ear infection
  • Head injury
  • Whiplash
  • Ageing
  • certain drugs: AMinoglycoside antibiotics (gentamicin)
101
Q

What are disorders of the vestibular system?

A
  • Patient complains of “dizziness”
    • Light-headed à check cardiovascular
    • Vertigo (spinning) à check vestibular
  • Trauma
    • Esp. CN VIII, e.g. motorcycle accident
  • Benign paroxysmal positional vertigo (BPPV)
    • vertigo caused by changes in head position
  • Ménière’s disease
    • Progressive disease
    • episodes of vertigo, tinnitus and progressive hearing loss, usually in one ear
    • Excess fluid in inner ear
102
Q

Explain the location and organization of the olfactory epithelium

A
  • ciliated receptor cells send their own afferent axons to the brain
  • olfactory information is coded by the pattern of stimulation that the brain learns to interpret
103
Q

Explain the mechanism of olfactory transduction

A
  • Olfactory transduction depends on a second messenger process, with cAMP being activated in response to an odorant molecule
  • This leads to opening of cAMP-dependent ligand-gated ion channels
    • non-selective cation channels, permeable to Na+ and Ca2+
    • Na+ and Ca2+ influx (inward current in the figure) depolarizes the olfactory receptor cells, signalling the binding of an odorant molecule, and leading to action potentials
    • The Ca2+ influx indirectly opens Cl- channels which, due to the unusually high intracellular Cl- concentration of the olfactory receptors, contributes to the depolarization
104
Q

What are the central pathways of the olfactory system?

A
105
Q

What is Hyposmia and Anosmia?

A
  • reduced or increased olfaction- very common
  • Causes:
    • upper resp. tract infection
    • older age
    • nasal polyps
    • diabetes mellitus
    • head trauma, high dose radiation at nasal epithelium, some drugs
106
Q

Organization of the gustatory system

A
107
Q

Explain the mechanism of taste transduction

A
  • Salt sensation depends on the equilibrium potential for Na+ ions across the taste receptors
  • Sour sensation depends on pH (acidity), with H+ ions (protons) closing K+ channels either directly or indirectly via a cAMP as a second messenger.
    • his leads to depolarization of the taste receptors
  • Sweet sensation comes about via a second messenger system that closes K+ channels, leading to depolarization of the taste receptors
  • Bitter and umami sensation are due to a second-messenger induced increase in intracellular Ca2+ in the receptors. The Ca2+ increase leads to neurotransmitter release
108
Q

The central pathways of the gustatory system?

A
  • Taste is signalled by cranial nerves VII (front 2/3 of the tongue), IX and X (both rear 1/3 of the tongue) to the nucleus of the solitary tract in the brainstem.
  • Fibres (red lines) from second-order taste neurons project ipsilaterally to the ventral posterior nucleus of the thalamus.
  • Thalamic efferents (green lines) then project to the insula, defining the primary gustatory cortex which, in turn, projects (black lines) to the orbitofrontal cortex, sometimes defined as a secondary cortical taste area.
  • The parabrachial nuclei of the pons are shown in orange. The parabrachial nuclei have a dorsal thalamocortical projection and also a ventral projection that terminates in amygdalar and hypothalamic nuclei, among others.
109
Q

Clinical issues in gustation

A
  • 80% of taste disorders are smell disorders

True taste disorders

  • prior upper respiratory tract infection
  • head injury
  • poor oral hygiene

less obvious daignosis

110
Q

What are the clinical features of motor neurone disease: Amyotrophic Lateral Sclerosis (ALS)?

A
  • Early symptoms
    • Asymmetric hand weakness → dropping of objects
    • Cramping of upper extremities
    • Dysarthria, dysphagia, dysphonia develop later
  • Atrophy → decreased strength, decreased muscle bulk, abnormal tone causing fasiculations
    • weakness → inability to ambulate leads to wheelchair use
  • Late symptoms
    • resp[iratory weakness → dyspnoea → respiratory infection
    • Recurrent bouts of cough, fever chill → pneumonia
111
Q

What is the pathology and cause of Amyotrophic Lateral Sclerosis (ALS)

A
  • progressive degenerative motor neurone disease with upper and lower motor neuron signs
  • Protein aggregation → neuronal injury, death → retrograde neuronal degeneration → gliosis (change in glial cells)
  • Supreoxide dismutase 1 (SOD1): antioxidant protein encoded on chromosome 9 is seen in 20% of familial ALS
    • gain of function mutation → misfolding → protein aggregation → direct neuronal injury, unfolded protein response → death
    • interference with: organelle autophagy, proteasome function, axonal transport, mitochondrial function
  • C9orf72 proteins is involved in some way
  • Hexanucleotide repeat expansion involved in dead neurons
  • TDP-43, FUS: an RNA binding genes cause abnormal RNA accumulation _> abnormal protein accumulation → neuronal injury
112
Q

How is Motor Neurone ALS diagnosed?

A
  • raised creatine kinase due to muscle atrophy
  • heavy-metal levels and Lyme disease tests negative
  • EL Escorial criteria
  • Family history
113
Q

What is the El Escorial criteria?

A
  • Evidence of lower motor neuron disease by clinical/ electrophysiological/ neuropathic examination
  • Evidence of upper motor neuron disease by clinical examination
  • Progressive spread of signs/s and symptoms within/ outside of body region as determined by history/ examination

All three are required to make a diagnosis of ALS

114
Q

What are upper and lower motor neurone signs seen in ALS

A
115
Q

What are Nerve/ Nerve root causes of Foot drop?

A
  • CPN compression/trauma
  • Sciatic n. compression/trauma
  • L5 radiculopathy
  • L4 radiculopathy
  • Diabetes, vasculitis, leprosy, other inflammatory neuropathies, malignant infiltration, Charcot- Marie-Tooth
116
Q

What are Muscular causes of Foot drop?

A
  • Distal muscular dystrophy
  • Inclusion body myopathy
117
Q

What are upper motor neuron causes of foot drop?

A
  • Spinal cord lesions (esp. conus)
  • Para-saggital meningiomas
118
Q

Why does spinal cord compression occur anatomically?

A

Ends at L1 / L2 interspace

Cervical spine: cord levels correspond to vertebrae

Thoracic spine: the cord level (clinical) lower than vertebral level

T12/L1 disc will compress the conus (sacral cord segments)

119
Q

What are examination findings in cord compression?

A
  • High cervical spine compression
  • Clumsy slow fingers
  • Quadriplegia
  • Respiratory problems
  • Bladder & bowel dysfunction
  • Thoracic spine disease
  • Paraplegia
  • Sensory level
  • Bladder & bowel dysfunction
  • Traps for the unwary
  • Triple flexion response to pain
  • Gait ataxia may be the only feature
120
Q

What are key factors of Cauda Equina syndrome?

A
  • Cauda Equina syndrome is a sacral sensory & sphincter syndrome
  • If weakness occurs, it often only affects ankle and toe plantar flexion (S1/S2) with accompanying loss of ankle reflexes
  • It may be painless
  • Decompression undertaken later than 48 hours after clinical presentation yields very poor results
121
Q

What is meningitis?

A

Inflammation of the meninges and subarachnoid space – classic triad of symptoms: headache, fever and neck stiffness — and pleocytosis (an increased cell count, particularly of leukocytes) in the CSF

122
Q

What is Encephilitis?

A

Inflammation of the brain cortex parenchyma - behavioural changes, focal neurological abnormalities and impairment of consciousness

123
Q

What is meningoencephalitis?

A

Central nervous system infection with clinical features of both meningeal and parenchymal disease.

124
Q

What is Aseptic meningitis?

A
  • inflammation of the meninges not due to pyogenic bacteria
125
Q

What is the global epidemiology of community-acquired bacterial meningitis?

A
  • Bacterial meningitis is associated with high mortality and morbidity worldwide, with an estimated 16 million cases in 2013, causing 1.6 million years lived with disability each year
  • Incidence rates of community-acquired bacterial meningitis in high-income areas (such as Europe, the United States and Australia) are 1–3 per 100,000 population per year
  • Reported case fatality rates are high and vary with patient age, causative pathogen and country income
  • Meningitis caused by Streptococcus pneumoniae has the highest case fatality rates: 20–37% in high-income countries and up to 51% in low-income countries. Case fatality rates for meningococcal meningitis are distinctly lower, in the range of 3–10% worldwide
126
Q

What is the epidemiology of community-acquired bacterial meningitis in adults?

A
  • Bacterial meningitis is associated with high mortality and morbidity worldwide, with an estimated 16 million cases in 2013, causing 1.6 million years lived with disability each year
  • Incidence rates of community-acquired bacterial meningitis in high-income areas (such as Europe, the United States and Australia) are 1–3 per 100,000 population per year
  • Reported case fatality rates are high and vary with patient age, causative pathogen and country income
  • Meningitis caused by Streptococcus pneumoniae has the highest case fatality rates: 20–37% in high-income countries and up to 51% in low-income countries. Case fatality rates for meningococcal meningitis are distinctly lower, in the range of 3–10% worldwide
127
Q

What is the aetiology of community-acquired bacterial meningitis?

A
  • Causative pathogens depend on the age of the patient and predisposing factors
  • Neonates: early (first week of life – vertical transmission) vs. late (second to sixth week of life) - Streptococcus agalactiae (group B streptococcus, GBS) and Escherichia coli
  • Children: Vaccination against Haemophilus influenzae type b, Neisseria meningitidis serogroup C and 7-, 10- and 13-valent pneumococcal conjugate vaccines has reduced the incidence of bacterial meningitis in children - currently N. meningitidis serogroup B causes most cases in both children and adults
128
Q

What is the effect of conjugate vaccines and the incidence of bacterial meningitis infections?

A
  • reduces the incidence of bacterial infections
129
Q

What are the clinical characteristics of community-acquired bacterial meningitis? in Neonated and children?

A
  • Neonates: nonspecific symptoms: irritability, poor feeding, respiratory distress, pale or marble skin and hyper- or hypotonia (low diagnostic accuracy – low threshold to perform a LP)
  • Children: fever, chills, vomiting, photophobia and severe headache; the younger the patient with bacterial meningitis, the more subtle and atypical are the symptoms
  • Some signs or symptoms are associated with specific pathogens: petechial and purpuric rash are usually signs of meningococcal disease, although a rash has also been described in pneumococcal meningitis
  • In all children with suspected bacterial meningitis CSF examination should be performed, unless contraindications for LP are present
130
Q

What are the clinical characteristics of community-acquired bacterial meningitis? in Adults

A

Adults: headache, fever, neck stiffness and altered mental status are common signs and symptoms at admission

A petechial rash is identified in 20–52% of patients and is indicative of meningococcal infection in over 90% of patients

131
Q

What CSF investigations would indicate community-acquired bacterial meningitis?

A
  • CSF
  • A positive CSF culture is diagnostic for bacterial meningitis and enables in vitro testing of the antimicrobial susceptibility patterns, after which antibiotic treatment can be optimized
  • Gram staining, latex agglutination, immunochromatographic antigen testing and PCR could provide additional information, especially when the CSF culture is negative
  • Classic abnormalities of CSF composition in bacterial meningitis are a pleocytosis of mainly polymorphic leukocytes, low glucose concentration, low CSF to blood glucose ratio and elevated protein levels
  • The CSF lactate concentration is a widely available, cheap and rapid diagnostic test
132
Q

What Seruminvestigations would indicate community-acquired bacterial meningitis?

A
  • Serum
  • Serum concentrations of C-reactive protein (CRP) and pro-calcitonin are highly discriminatory between paediatric bacterial and viral meningitis
  • Blood cultures are valuable for detection of the causative organism and establish susceptibility patterns if CSF cultures are negative or unavailable
133
Q

What are causes of Aseptic meningitis?

A
  • Viral pathogens are the most common aetiology of aseptic meningitis
  • Non-infectious causes:
    • drug-induced (e.g., amoxicillin, nonsteroidal anti-inflammatory medications or trimethoprim-sulfamethoxazole)
    • neoplastic,
    • neurosarcoidosis,
    • rheumatoid arthritis, systemic lupus erythematosus, or
    • vasculitis (e.g., Kawasaki disease)
134
Q

How does Viral meningitis present and what are the causes?

A
  • Viral meningitis exhibits a summer-to-fall seasonality in temperate climates and a year-round incidence in tropical and subtropical areas
  • Non-polio human enteroviruses (NPEV) are the leading recognizable cause of viral meningitis (Picornaviridae)
  • NPEV have a worldwide distribution and humans as the only natural reservoir
  • The majority of meningitis cases are due to Enterovirus species B, Echovirus A71 (species A), and Coxsackievirus A9 and B5 (species B)
  • Herpes Simplex viruses (HSV, Herpesviridae) account for 0.5 - 17% of viral meningitis cases
  • Mups cirus
  • Causative pathogens are primarily transmitted through the faecal-oral route, and less commonly via respiratory secretions
135
Q

What is the link between Herpes simplex viruses and Meningitis?

A

Herpes simplex viruses (HSV) (Herpesviridae), account for approximately 0.5% to 18% of viral meningitis cases

HSV type 1 (HSV-1) is the most commonly identified cause of sporadic encephalitis worldwide

HSV type 2 (HSV-2) is associated with benign recurrent aseptic meningitis and recurrent benign lymphocytic meningitis (RBLM)

136
Q

What is the pathogenesis of Viral meningitis?

A
137
Q

What is the clinical presentation of Viral meningitis, Which causes present with specific symptoms?

A
  • Fever
  • Headache
  • Neck stiffness
  • Arthralgia/myalgia
  • Nausea/ vomiting
  • Photophobia (mainly non-polio human enteroviruses)
138
Q

What are meningeal signs of Viral meningitis?

A
  • Kernig’s sign – With the patient’s hips and knees flexed, a positive sign is when the patient resists extension of the knee. The test was originally performed with a patient seated on the edge of the bed and feet dangling over the side
  • Brudzinski’s sign – Flexion of the supine patient’s neck causes the patient to flex both hips and knees; therefore, retracting the legs toward the chest
  • Nuchal rigidity – Neck stiffness denoting involuntary resistance to passive neck flexion
139
Q

What will CSF result show in Non-polio human enterovirus of viral meningitis?

A
  • WBC (cells/mm3) normal CSF <5
    • in NPEV 9–2590 raised
  • Lymphocytes (%) normal CSF 0–30
    • in NPEV 24–100 raised
  • Glucose (mg/dL) normal CSF 45–80
    • in NPEV 45–80 normal
  • Protein (mg/dL) normal CSF 15–45
    • in NPEV 277–1540 raised
140
Q

What will CSF results show in HSV/VZV viral meningitis?

A
  • WBC (cells/mm3) normal CSF <5
    • in infection 46-1860 raised
  • Lymphocytes (%) normal CSF 0–30
    • in infection 80–100 raised
  • Glucose (mg/dL) normal CSF 45–80
    • in infection 32-80 normal/ slightly low
  • Protein (mg/dL) normal CSF 15–45
    • in infection 404-3215 very raised
141
Q

What will CSF results show in lymphocytic choriomeningitis virus viral meningitis?

A
  • WBC (cells/mm3) normal CSF <5
    • in infection 415-1715 more likely to be raised
  • Lymphocytes (%) normal CSF 0–30
    • in infection 95–100 more likely to be raised
  • Glucose (mg/dL) normal CSF 45–80
    • in infection 43-68 normal but lower end of spectrum
  • Protein (mg/dL) normal CSF 15–45
    • in infection 128-240 raised but not very high
142
Q

What will CSF results show in mumps viral meningitis?

A
  • WBC (cells/mm3) normal CSF <5
    • in infection 77-1600 raised
  • Lymphocytes (%) normal CSF 0–30
    • in infection 77–100 more likely to be raised
  • Glucose (mg/dL) normal CSF 45–80
    • in infection NR
  • Protein (mg/dL) normal CSF 15–45
    • in infection 40-74 barley raised
143
Q

How is Viral meningitis diagnosed?

A

The gold standard tool for the diagnosis of viral meningitis is the polymerase chain reaction (PCR), which detects and quantifies viral DNA or RNA in the CSF

Alternative specimens, such as blood, throat or nasal swabs, or stool samples might be used instead, particularly in cases of suspected NPEV infections

Diagnosis of mumps virus, herpesvirus, arboviruses, and human immunodeficiency virus (HIV) infections can be achieved using serological assays, although the results might be negative at early stages of the disease

144
Q

What are HIV-associated opportunistic infections of the CNS

A
  • Asian and Pacific regions
    • Cryptococcal meningitis, cerebral toxoplasmosis, tuberculous meningitis, Japanese encephalitis B
  • Sub-Saharan Africa
    • Tuberculous meningitis, cryptococcal meningitis, cytomegalovirus, malaria
  • Europe and North America
    • Progressive Multifocal Leukoencephalopathy, toxoplasmic encephalitis, cryptococcal meningitis
  • South America
    • Cerebral toxoplasmosis, tuberculous meningitis, cryptococcal meningitis;
      Chagas disease is reported in southern US states and South America
145
Q

What is Measles?

A
  • The measles virus is a non-segmented, negative-sense RNA virus and a member of the Morbillivirus genus in the family of Paramyxoviridae
  • The genome of about 16000 nucleotides encodes six structural proteins, the nucleoprotein, phosphoprotein, matrix, fusion, haemagglutinin, and large protein, and two non-structural proteins V and C encoded within the phosphoprotein gene
146
Q

Explain the pathogenesis of measles

A
  • Respiratory route of transmission - respiratory droplets and small particle aerosols that remain suspended in the air for up to 2 h
  • R0 of 9-18 – high contagiousness
  • Incubation period: 12.5 days
  • The infectious period begins several days before and lasts for several days after the onset of rash, coinciding with peak levels of viraemia and when cough and coryza are most intense, facilitating transmission
147
Q

How does Measles present?

A
  • Fever and maculopapular rash
  • Cough, coryza, conjunctivitis
  • Koplik’s spots appear on the buccal mucosa as small white papules and provide an opportunity to clinically diagnose measles a day or two before the rash
  • The rash appears 3–4 days after the onset of fever,
    • → first on the face and behind the ears → spreads to the trunk and extremities, coinciding with development of the adaptive immune response
148
Q

What are CNS complications of measles/

A

Acute disseminated encephalomyelitis (ADEM) - a demyelinating autoimmune disease that is triggered by measles virus and occurs within days to weeks in approximately one in 1000 cases

Measles inclusion body encephalitis (MIBE) - a progressive measles virus infection of the brain that results in neurological deterioration and death in individuals with impaired cellular immunity within months of the acute illness

Subacute sclerosing panencephalitis (SSPE) - a delayed complication of measles that occurs in about 1:10 000 to 1:100 000 cases 5–10 years after the acute illness, caused by the host response to production of mutated virions with defective assembly and budding

149
Q

How is measles diagnosed and what are potential differentials?

A
  • The differential diagnosis includes rubella, dengue fever, parvovirus B19 infection, human herpesvirus 6 infection …
  • The most common laboratory method for confirming measles is detection of measles virus–specific IgM antibodies in a blood specimen
  • A real-time PCR assay for measles virus RNA in urine, blood, oral fluid, or nasopharyngeal specimens can identify infection with a sensitivity of 94% and a specificity of 99% before measles IgM antibodies are detectable, and it allows genotyping of the measles virus
150
Q

Who are most at risk for complications from measles infection?

what complications are there?

A

Young infants, adults older than 20 years, pregnant women, and those who are immunocompromised or undernourished, particularly children with vitamin A deficiency are most at risk of complications

  • Pneumonia
  • Laryngotracheobronchitis (croup) and otitis media
  • Diarrhoea
  • Keratoconjunctivitis
151
Q

How are headaches classified?

A
  • Primary headaches
    • Migraine
    • tension-type
    • Trigeminal autonomic cephalagis
    • other primary headache disorders
  • Secondary headaches
152
Q

What are the phases of migraine?

A
  • Prodrome: few hours to days
  • Aura: 5- 60 minutes
  • Migraine attack: 4-72 hours
  • Postrdome: 24-48 hours

can last days

153
Q

How does a Prodromeof a migraine present?

A
  • Fatigue/cognitive change:
    • Concentration difficulty, fatigue, memory
      impairment, depression, elation, irritability.
  • Homeostatic alterations:
    • Food cravings, thirst, frequency of urination,
      yawning, sleep disturbance
  • Sensory sensitivites/nonpainful migrainous
    symptoms:
    • Neck stiffness, photophobia,
      phonophobia, osmophobia, nausea.
154
Q

What are physiological changes that happen in the brain during the prodrome of a migraine?

A
  • Dysfunction of the Orexinergic system involved
    in regulating feeding, sleep/wake cycle, stress
    and motivation.
  • Increased ADH secretion – thirst/urination
  • Increase sensitivity of TCC – Neck stiffness.
  • PET and functional MRI :
    show changes in the connectivity within the
    hypothalamus. The hypothalamus can often be
    viewed as the “generator”of migraine –
    homestatic alterations
  • Changes in connectivity with other regions of
    the brain – fatigue/cognitive change
  • Increased activity in the occipital lobe – visual
    sensitivities
  • Activation of brainstem – nasuea
  • Differences in thalamic and thalamo-cortical
    activity – allodynia, aberrant sensory
    processing
155
Q

How does an Aura of migraine present?

A
  • Visual (most common)
    – Zig-zag lines, visual fortification
  • Speech
    – Dysphasia
  • Sensory disturbance
    – (negative and positive
    symptoms)

→ caused by where cortical spreading depression occurs

→ some people have aura without migraines and vice versa

156
Q

What is Cortical Spreading Depression?

A

Cortical spreading depression (CSD) is considered the electrophysiological substrate of the migraine aura. CSD is a spreading depolarization that tends to start in the occipital lobe and spreads forward over the cerebral hemisphere at a rate of about 2–4 mm/min.

157
Q

What is the Diagnostic criteria for migraines?

A
  • A: At least five attacks fulfilling criteria B-D
  • B: Headache attacks lasting 4-72 hr (untreated or unsuccessfully treated)2;3
  • C: Headache has at least two of the following four characteristics:
      1. unilateral location
      2. pulsating quality
      3. moderate or severe pain intensity
      4. aggravation by or causing avoidance of routine physical activity (eg, walking or
        climbing stairs)
  • D: During headache at least one of the following:
      1. nausea and/or vomiting
      2. photophobia and phonophobia
  • E: Not better accounted for by another ICHD-3 diagnosis
158
Q

What are important factors to find out in history about headaches?

A

• Presenting headache
– Constant or episodic
– Site: Unilateral or bilateral/holocranic
– Headache load: Frequency/duration/severity
• Character of pain: Throbbing, stabbing etc
• Precipitating factor
• Previous history of headaches

159
Q

What neuromodulators or implicated in the causes of headaches?

A
  • Sertonoing: low levels of serotonin are associated with migraines
  • Dopamine: dopamine hypersensitivity leads to associated symptoms of migraine: nausea vomiting yawning
  • CGRP (calcitonin gene-related peptide): CGRP is released from the C-fibres and acts on the CGRP receptors located on the A-delta fibres → this has a role in modulating pain transmission
160
Q

How is the trigeminovascular system activated within the dura?

A

Trigeminal C-fibres are activated which leads to
CGRP release
• CGRP release causes vasodilatation leading to
release of proteins which results in neurogenic
inflammation.
• Neurogenic inflammation activates A-delta
fibres which transmit signal back to the
brainstem.

161
Q

What is the relation between hormones serotonin and migraines

A
  • migraines are more common in females and are more prevalent around menstruation and menopause due to a decrease in oestrogen
    • reduced during pregnancy due to an increase in oestrogen
  • the net effect of oestrogen is to increase serotonin levels therefore migraines are more likely when oestrogen levels decreased causing serotonin also decrease
162
Q

What is the relation between high oestrogen and migraines?

A
  • Oestrogen facilitates the glutaminergic system.
    • – Glutaminergic pathways are involved in the induction of Cortical
      spreading depression.
      – Therefore high oestrogen levels (as in pregnancy) is associated with a
      higher frequency of migraines with aura (NB overall migraine
      frequency is reduced)
  • Prostaglandin secretion is highest during menstruation which is
    involved in signalling pain. This contributes to menstrual
    migraines.
163
Q

What are lifestyle changes in the treatment for migraine?

A
  • avoidance of triggeers
  • hydrate, reduce caffeine, alcohol
  • regular meals
  • good sleep hygeine
  • excercise
164
Q

What are pharmacological treatments for migraine?

A
  • Abortive treatments:
    • Triptans – Decrease CGRP release
    • NSAIDs – Decrease prostaglandin secretion
    • Paracetamol
    • Antiemetics – Decrease Dopamine centrally
  • Preventatives:
    Oral drugs
    • Anti-hypertensives: Propranolol (women of child bearing age)
    • Anti-epileptics: Topiramate
    • Antidepressants
    Injectables
    • Botox – blocks release of neurotransmitters
    • CGRP antagonists – blocks CGRP pathway
165
Q

What novel medications are there for the treatment of migraines?

A

Ditans (Lasmiditan)
• 5HT-1F receptor agonist
• Inhibits peptide release
• Does not affect 5HT-1B,D so no
cardiovascular effects
• Not contraindication in those with
IHD/CVAA

Gepants (Umbrogepant, Rimgepant)
• CGRP receptor antagonist (small
molecule)
• Oral tablet
• Abortive and preventative
• Redefines concept of episodic vs
chronic
• No issue of overuse headache

166
Q

What are primary headache types and how do they generally present?

A
167
Q

How do Tension headaches present? and what are their common causes?

A
  • Pain > 4 hours, noo migrainous features, often bilateral (band across the forehead) and prefer to be still
  • Caused by: stress, anxiety, depression, lack of sleep, poor posture
    • accumulate to reaching a threshold for triggering a headache
168
Q

What are red flags in a clinical assessment of a headache?

A

• Age: Greater than 50 yrs
• Onset: Thunderclap < 5mins, NDPH
• Severity: “worst headache of their life”
• Progression: Rapid or developing associated features.
• Triggers: Provoked by valsalva, exercise, sex, postural change.
• Systemic symptoms: Rash, weight loss, fever, neck stiffness.
• Risk factors: HIV, Suspected malignancy, surgery, shunt in situ, inflammatory disorders,
recent head injury.
• Neurological signs: optic nerve swelling, hemiparesis, altered consciousness, visual field
defect, cranial nerve palsies, seizures.
• Raised ICP features: N&V, Position dependent, Visual obscurations, pusalatile tinnitus, worse with
Valsalva maneouvres

169
Q

What are common causes of secondary headaches?

A
  • Brain tumour
  • Brain haemorrhage
  • Giant cell arthritis:
    • Age > 50 years
      Raised ESR, CRP
      Scalp tenderness
      Jaw claudication
      Associated with polymyalgia
      Rheumatica
      Can lead to blindness
  • Reversible Cerebral vasoconstriction Syndrome
    • sudden, intense headache, “thunderclap” headache
    • seen in postpartum, serotonergic medication and use of stimulants
  • Idiopathic intracranial hypertension
    • often occur in obese females, have visual changes
    • caused by impaired lymphatic drainage and increased venous sinus pressure
  • Low-pressure headache: headache worse on sitting/standing up, relieved by lying down
  • Hypertensive encephalopathy/PRES: acute rise in BP can cause high levels of hydrostatic pressure leading to increased interstitial fluid this can manifest in seizures
    • seen in later stages of pregnancy
  • Trigeminal neuralgia: Paroxzysmal pain typically in V2 and v3 dermatomes. Commonly shooting pain triggered by touch, wind talking and brushing teeth
170
Q

how does Giant Cell arthritis present?

A

Age > 50 years
Raised ESR, CRP
Scalp tenderness
Jaw claudication
Associated with polymyalgia
Rheumatica
Can lead to blindness

171
Q

How does trigeminal neuralgia present?

A

Paroxysmal pain typically in V2 and V3 dermatomes of the cranial nerve 7. Commonly shooting pain triggered by touch, wind talking and brushing teeth

172
Q

How does Reversible Cerebral vasoconstriction Syndrome present?

A
  • sudden, intense headache, “thunderclap” headache
  • seen in postpartum, serotonergic medication and use of stimulants
173
Q

What is Guillain-barre syndrome ad explain the disease pathogenesis?

A

Immune-mediated demyelination of the peripheral nervous system often triggered by infection - classically Campylobacter jejuni

  • cross-reaction of antibodies with gangliosides in the peripheral nervous system
  • correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated
  • anti-GM1 antibodies in 25% of patients
174
Q

What is Miller Fisher syndrome?

A
  • cross-reaction of antibodies with gangliosides in the peripheral nervous system
  • correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated
  • anti-GM1 antibodies in 25% of patients
175
Q

How does Guillain-Barre syndrome present?

A

progressive symmetrical weakness of the limbs often in an ascending fashion

this is in conjunction with diminished reflexes and normal sensation

176
Q

What areas does Subacute combined degeneration affect and what symptoms does it cause?

what is the underlying pathology?

A
  • Damage to the posterior columns - loss of proprioception, light touch and vibration sense (sensory ataxia and a positive Romberg’s test).
  • Damage to lateral columns - spastic weakness and upgoing plantars (UMN signs).
  • Damage to peripheral nerves - absent ankle and knee jerks (LMN signs).

→ caused by B12 deficiency, may present with macrocytic anaemia, b12 should be replaced before folate else it can precipitate combined degeneration of the cord

177
Q

What is Autonomic dysreflexia?

A

occurs in patients who have had a spinal cord injury at, or above T6 spinal level. Briefly, afferent signals, most commonly triggered by faecal impaction or urinary retention (but many other triggers have been reported) cause a sympathetic spinal reflex via thoracolumbar outflow.

The usual, centrally mediated, parasympathetic response however is prevented by the cord lesion. The result is an unbalanced physiological response, characterised by extreme hypertension, flushing and sweating above the level of the cord lesion, agitation, and in untreated cases severe consequences of extreme hypertension have been reported, e.g. haemorrhagic stroke.

Management of autonomic dysreflexia involves removal/control of the stimulus and treatment of any life-threatening hypertension and/or bradycardia.

Fecal impaction/ urinary retention are the most common triggers

178
Q

What is Myasthenia gravis?

A

autoimmune disorder resulting in insufficient functioning acetylcholine receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases*. Myasthenia is more common in women (2:1)

179
Q

What are the clinical features of Myasthenia gravis?

A

fatigability - muscles become progressively weaker during periods of activity and slowly improve after periods of rest:

  • extraocular muscle weakness: diplopia
  • proximal muscle weakness: face, neck, limb girdle
  • ptosis
  • dysphagia
180
Q

What conditions are associated with Myasthenia gravis?

A
  • thymomas in 15% (thymic carcnioma)
  • autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE
  • thymic hyperplasia in 50-70%
181
Q

WHat investigations are done for Myasthenia gravis?

A
  • single fibre electromyography: high sensitivity (92-100%)
  • CT thorax to exclude thymoma
  • CK normal
  • autoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine kinase antibodies
  • Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used any more due to the risk of cardiac arrhythmia
182
Q

What is the management for Myasthenia gravis?

A
  • long-acting acetylcholinesterase inhibitors
    • Pyridostigmine is first-line
  • immunosuppression is usually not started at diagnosis, but the majority of patients eventually require it in addition to long-acting acetylcholinesterase inhibitors:
    • Prednisolone initially
    • Azathioprine, Cyclosporine, Mycophenolate mofetil may also be used
  • thymectomy
183
Q

What is the glasgow coma scale in adults

A
  • Motor response
    6. Obeys commands
    5. Localises to pain
    4. Withdraws from pain
    3. Abnormal flexion to pain (decorticate posture)
    2. Extending to pain
    1. None
  • Verbal response
    5. Orientated
    4. Confused
    3. Words
    2. Sounds
    1. None
  • Eye opening
    4. Spontaneous
    3. To speech
    2. To pain
    1. None
184
Q

What are cluster headaches?

A

headaches that are very painful and typically occur in clusters lasting several weeks, and occur typically once a year

they are common in men (3:1) and in smokers

Alcohol may trigger an attack and there is some relation to nocturnal sleep

185
Q

What are features of Cluster headaches

A
  • pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours
  • clusters typically last 4-12 weeks
  • intense sharp, stabbing pain around one eye (recurrent attacks ‘always’ affect same side)
  • patient is restless and agitated during an attack
  • accompanied by redness, lacrimation, lid swelling
  • nasal stuffiness
  • miosis and ptosis in a minority
186
Q

What is the management of cluster headaches?

A
  • acute: 100% oxygen (80% response rate within 15 minutes), subcutaneous triptan (75% response rate within 15 minutes)
  • prophylaxis: verapamil is the drug of choice. There is also some evidence to support a tapering dose of prednisolone
  • NICE recommend seeking specialist advice from a neurologist if a patient develops cluster headaches with respect to neuroimaging
187
Q

What situations should anti-emetics be used in

A
  • Ondansetron for chemotherapy-induced nausea
  • Haloperidol for intracranial causes (raised ICP, direct effect of tumour)
  • Prochlorperazine for vestibular causes
  • Metoclopramide for gastrointestinal causes
188
Q

What is the immediate management of Status epilepticus

A
  • ABC
    • airway adjunct
    • oxygen
    • check blood glucose
  • First-line drugs are IV benzodiazepines such as diazepam or lorazepam
    • in the prehospital setting PR diazepam or buccal midazolam may be given
    • in hospital IV lorazepam is generally used. This may be repeated once after 10-20 minutes
  • If ongoing (or ‘established’) status it is appropriate to start a second-line agent such as phenytoin or phenobarbital infusion
  • If no response (‘refractory status’) within 45 minutes from onset, then the best way to achieve rapid control of seizure activity is induction of general anaesthesia.
189
Q

What is status epilepticus defined as?

A
  • a single seizure lasting >5 minutes, or
  • >= 2 seizures within a 5-minute period without the person returning to normal between them
190
Q

What are the features of a third nerve palsy?

A
  • eye is deviated ‘down and out’
  • ptosis
  • pupil may be dilated (sometimes called a ‘surgical’ third nerve palsy)
191
Q

What are causes of Third nerve Palsy?

A
  • diabetes mellitus
  • vasculitis e.g. temporal arteritis, SLE
  • false localizing sign* due to uncal herniation through tentorium if raised ICP
  • posterior communicating artery aneurysm
    • pupil dilated
    • often associated pain
  • cavernous sinus thrombosis
  • Weber’s syndrome: ipsilateral third nerve palsy with contralateral hemiplegia -caused by midbrain strokes
  • other possible causes: amyloid, multiple sclerosis
192
Q

What are features of Lambert Eaton Syndrome

A
  • repeated muscle contractions lead to increased muscle strength (in contrast to myasthenia gravis)
    • in reality, this is seen in only 50% of patients and following prolonged muscle use muscle strength will eventually decrease
  • limb-girdle weakness (affects lower limbs first)
  • hyporeflexia
  • autonomic symptoms: dry mouth, impotence, difficulty micturating
  • ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)
193
Q

What is Lambert-Eaton syndrome?

A

myasthenic syndrome is associated with small cell lung cancer and to a lesser extent breast and ovarian cancer

it can also occur independently as an autoimmune disorder/

it is caused by antibodies directed against presynaptic voltage-gated calcium channels in the peripheral nervous system

194
Q

What is the management of Lambert-Eaton syndrome?

A
  • treatment of underlying cancer
  • immunosuppression, for example with prednisolone and/or azathioprine
  • 3,4-diaminopyridine is currently being trialled
    • works by blocking potassium channel efflux in the nerve terminal so that the action potential duration is increased. Calcium channels can then be open for a longer time and allow greater acetylcholine release to the stimulate muscle at the end plate
  • intravenous immunoglobulin therapy and plasma exchange may be beneficial

302: Scientific Bases of Medicine (9 decks)

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