Neurology Flashcards
What are the risk factors for developing Alzheimer’s disease?
Age
CVD
Depression
Low educational attainment
- Low social engagement and support
- head trauma, learning difficultie
What is dementia?
- a state characterised by impairment of 2 or more cognitive domains
- persisting for more than 6 months
- severe enough to impact on ability to function
- not primarily attributed to another mental disorder
what is mild cognitive impairment?
- a state characterised by impairment of one or more cognitive domains
- not severe enough to impact on ability to function
- synonymous with ‘prodromal’
(preclinical –> prodromal –> symptomatic)
(symptomatic is then alzheimer’s)
What are the cognitive domains?
- memory: semantic (worldly, no context)/episodic (autobiographical)
- visuospatial: perception/contruction/praxis
- language: naming/fluent/structure/comprehensive
- executive function: planning/ working memory/ inhibition
- social cognition/behavioural: theory of mind/empathy/insight
- attention: speed/multitasking
What genes put you at risk of AD?
APP and presenilin genes (PSEN1, PSEN2)
- APP on chromosome 21, so increased risk for people with down syndrome
alleles of apolipoprotein E4 = not as good at clearing beta plaques
What are the amyloid beta plaques and how do they contribute to AD?
- Senile plaques deposits of beta amyloid aggregate.
- Amyloid precursor protein is found on neurons (helps it to grow and repair after injury).
- If it is broken down normally by alpha secretase and gamma secretase it is soluble and easy to remove
- However if it is broken by beta secretase the leftover fragment isn’t soluble and creates a monomer called beat amyloid.
- These are sticky and can in between neurones and their signalling, They also increase inflammation which damages surrounding neurones
What are neurofibrillary tangles and how do they contribute to AD?
Neurons held together by cytoskeleton = is made up of microtubules a protein ‘tau’ makes sure they stay together.
Beta amyloid build-up outside the neurones initiates pathways which leads to the activation of kinase.
This leads to the phosphorylation of tau
The tau protein changes shape, stops supporting the microtubules, and clumps up with other tau proteins, forming neurofibrillary tangles
Neurones with tangles and non-functioning microtubules can’t signal as well, and sometimes end up undergoing apoptosis.
As neurones die, the brain starts to atrophy.
What are some of the symptoms of AD?
- Agnosia- can’t recognise things
- Apraxia can’t do basic motor skills
- Aphasia speech difficulties
- Cognitive impairment
- Agitation and emotional lability
- Depression and anxiety
- Sleep cycle disturbance:
- Motor disturbance: wandering is a typical feature of dementia
What are the symptoms of episodic memory loss?
Repetitive in conversation
- struggles to follow plot of TV shows
- May forget appointments
- increasingly reliant on partner, lists
- limited knowledge of current affairs
signs
- poor retention of address
- cannot recall breakfast
- cannot recall pictures from naming test
- Ribbot’s phenomena = better remote long term memory than what they did yesterday
What are causes of ‘rapid onset dementias’?
CJD
Vasculitis
Limbic encephalitis
SOl
seizures
infections
metabolic = Wernicke’s
Normal pressure hydrocephalus
usually treatable so want to diagnose quickly
How can the activities of daily life be affected in AD?
Loss of independence: increasing reliance on others for assistance with personal and domestic activities:
Early stages: problems with higher level function (e.g. managing finances, difficulties at work)
Later stages: problems with basic personal care (e.g. washing, eating, toileting) and motor function (e.g. walking, transferring)
What is the diagnostic criteria for AD?
Functional ability: inability to carry out normal functions
Impairment in 2 or more cognitive domains
Differentials excluded
What imaging is used for AD?
CT/MRI:
exclude other diagnosis
help determine type of dementia;
will show medial temporal lobe atrophy
What is the definitive diagnosis for AD
Brain biopsy after autopsy
What are the two cognitive assessments that can be performed to assess AD?
Mini mental state examination (MMSE)
Montreal cognitive assessment scale (MoCA)
Primary care: 6 Cognitive Impairment Test (6CIT)
ACE II
What is assessed in the cognitive assessments?
Attention and concentration
Recent and remote memory
Language
Praxis (planned motor movements)
Executive function
Visuospatial function
What is the treatment for AD?
Non-pharmacological:
programmes to improve/maintain cognitive function
Mild to moderate AD:
acetylcholinesterase inhibitors e.g., Donepezil and rivastigmine
Moderate to severe AD:
N-methyl-d-aspartic acid receptor antagonist memantine (anti-glutamate transmitter)
What is Parkinson’s disease (PD)
A neurodegenerative disorder characterised by the loss of dopaminergic neurons within the substantia nigra pars compacta (SNPC) of the basal ganglia.
What are the risk factors for developing PD?
Age: prevalence is 1% in 60-70 and 3% in those above 80
Gender: men are 1.5 times more likely than females to develop PD
Family history
Describe the pathophysiology of PD
progressive loss of dopamine-producing neurons meaning there is a reduction in the amount of dopamine produced at the substantia nigra
Loss of these neurons results in reduction in action of the direct pathway and a resultant increase in the antagonistic indirect pathway which has a restrictive action on movement.
Therefore bradykinesia and rigidity are key symptoms
There is also formation of protein clumps Lewy bodies
What are the 3 key presentations of PD?
Bradykinesia
Tremor
Rigidity
PD symptoms usually start unilaterally and then become bilateral later in the disease course.
What does the bradykinesia look like in PD?
Handwriting gets smaller
Only take small steps (shuffling gait)
Difficulty initiating movement
Difficulty turning around when standing
Reduced facial movements and expressions
What does the tremor look like in PD?
- A unilateral resting tremor.
- Described as pill rolling tremor looks like they are rolling pill between thumb and finger
- The tremor is worse at resting and when they are distracted like using the other hand
- Frequency of 4-6 times a second
What is the difference between an essential and Parkinson’s tremor?
Essential - active tremor + worsens with movement
Parkinson’s - pill rolling, resting tremor
What is the rigidity like in PD?
if you take their hand and passively flex and extend their arm at the elbow you will feel tension in their arm that gives way to movement in small increments (little jerks)
Described as cogwheel
What are some other symptoms of PD?
Depression
Sleep disturbance and insomnia no REM
Loss of sense of smell
Postural instability
Cognitive impairment and memory problems
What are the differences between a PD tremor and a benign essential tremor?
PD= asymmetrical
BET= symmetrical
PD= frequency= 4-6
BET= 5-8
PD= worse at rest
BET= better at rest
PD= improves with intentional movement
BET= worse
PD= no change with alcohol
BET= better with alcohol
What is used to diagnose PD?
PD is a clinical diagnosis and should be suspected in a patient with bradykinesia and at least one of the following:
- Tremor
- Rigidity
- Postural instability
What is the management for PD?
Motor symptoms NOT affecting quality of life:
A choice of one of the following:
- Dopamine agonist (non-ergot derived)
- Pramipexole, ropinirole - Monoamine oxidase B inhibitor
- Selegiline, rasagiline
- Stop breakdown of circulating dopamine - Levodopa
Motor symptoms affecting the quality of life:
- L.Dopa
Synthetic dopamine levodopa given with a drug that stops it being broken down.
These are peripheral decarboxylase inhibitors:
- Carbidopa and benserazide.
- Co-benyldopa (levodopa and benserazide)
- Co-careldopa (levodopa and carbidopa)
What is the prognosis for PD?
PD is a chronic and progressive condition with no cure.
Overall, life expectancy is reduced with the mortality being 2-5 times higher for those aged 70-89 years old. Also, the risk of dementia is up to 6 times higher in PD patients.
Management: Essential Tremor
The tremor is not harmful and does not require treatment if it is not causing functional or psychological problems.
Medications that may improve symptoms are:
- Propranolol (a non-selective beta blocker)
- Primidone (a barbiturate anti-epileptic medication)
What can cause vascular dementia?
Ischaemic stroke
Small vessel disease
Haemorrhage
Other: cerebral amyloid, which is a cause of small vessel disease.
Deposition of amyloid in small arteries.
CADASIL, which is due to mutation in the NOTCH3 gene and leads to arterial thickening and occlusion.
Describe the pathophysiology of VD?
- Once blood supply to the brain falls below the demands to the tissue, it’ considered an ischaemic stroke.
- The tissue damage is permanent because the dead tissue liquifies in a process called
*liquefactive necrosis** - Brain tissue necrosis leads to a loss of mental function in the area where the loss has occurred
How do the symptoms of VD appear?
They appear suddenly and the brain function decline is STEP-WISE e.g. it decreases with each stroke
Symptoms will vary depending on which vessels are affected in stroke/atherosclerosis
What is motor neurone disease?
Motor neurone disease is an umbrella term that encompasses a variety of specific diagnoses.
They are neurodegenerative diseases that affect both upper and lower motor neurones but sensory neurons are spared
What is the most common type of Motor Neurone Disease?
Amyotrophic lateral sclerosis (ALS) accounts for 50% of cases
What are some other types of MND?
Progressive muscular atrophy: LMN only
Primary lateral sclerosis: UMN only
Progressive bulbar palsy: affects muscles of talking and swallowing (second most common) LMN only
ALS: affects both UMN and LMN
What gene is implicated in some cases of ALS?
SOD1
What are the risk factors for MND?
Increasing age (over 60)
Male
Pesticides
Heavy metals
Rugby
What are the general symptoms of MND?
- Progressive weakness of the muscles throughout the body affecting the limbs, trunk, face and speech.
- The weakness is often first noticed in the upper limbs. There may be increased fatigue when exercising.
- They may complain of clumsiness, dropping things
more often or tripping over. They can develop slurred speech (dysarthria). - struggle to breathe especially at night due to only relying on diaphragm to breathe and it weakens earlier (wake up with headache)
What are the signs of LMN disease?
Muscle wasting
Reduced tone
Reduced reflex
Fasciculations
Loss of power
Babinski reflex negative
What is the cause of LMN injury?
motor neurone - MND< spinal muscular atrophy, polio infection
motor nerve roots - radiculopathy, guillain barre
motor nerves - neuropathies
Neuromuscular junction - myasthenia gravis
Muscles disorder - myositis, myopathies
What are the signs of a UMN lesion?
Increased tone (no UMN to stop actions of LMN)
Brisk reflexes
Rigidity + spasticity
Babinski reflex positive
What is never affected in MND?
Eye muscles (oculomotor movements)
Sensory function and sphincters (onuf’s nucleus)
What are the symptoms of MND?
Progressive weakness
Fatigue - nocturnal respiratory insufficiency (so wake up in night when CO2 builds up)
Falls
Speech and swallow issues
What are the investigations for MND?
MND is a clinical diagnosis
Electromyography: in MND there will be evidence of fibrillation potentials
Nerve conduction studies: may show modest reductions in amplitude
MRI spine: imaging can help exclude spinal pathology which may mimic MND, such as cervical cord compression and myelopathy
What are some differentials for MND?
MS
Polyneuropathies
Myasthenia gravis
GBS
What is the management for MND
No treatment - large amount of neurones have died before symptoms present
- Riluzole = prolongs survival by 2-4 months by protecting motor neuron damage form glutamate
Respiratory support: patients with reduced FVC can use non-invasive ventilation at home, usually BiPAP; prolongs survival by 7 months
Supportive treatment:
Antispasmodics: such as baclofen
What is the main cause of death in motor neurones disease?
death 75-80% within 5 years
- most commonly due to respiratory failure
What is Multiple Sclerosis?
An autoimmune cell-mediated demyelinating disease of the central nervous system
What are some risk factors for developing MS?
Vitamin D deficiency
Family history: HLA-DR2 is implicated; 30% monozygotic twin concordance
EBV infection: the virus with the greatest link to MS
Smoking
Obesity
Describe the pathophysiology of MS
(don’t fully know the cause)
T-cells get through the blood brain barrier and are activated by myelin. The T-cell then changes the BBB to allow more immune cells to get in the brain
MS is a type IV hypersensitivity reaction: T-cells release cytokines and these recruit more immune cells whilst also damaging the oligodendrocytes (+ axones)
B-cells will make antibodies that will destroy the myelin of the oligodendrocytes. leaving behind areas of plaque/sclera
How does MS progress over time?
- In early disease, re-myelination can occur and symptoms can resolve. (thin myelin forms so conduction reduced in heat)
- In the later stages of the disease, re-myelination is incomplete and symptoms gradually become more permanent.
- A characteristic feature of MS is that lesions vary in their location over time, meaning that different nerves are affected and symptoms change over time
MS lesions change location over time is that they are
What are the different types of MS?
Relapsing-remitting:
Secondary progressive
Primary progressive
Progressive relapsing
Clinically isolated syndrome (kind of counts)
What is Relapsing-remitting: MS?
The most common pattern 85% of cases
Episodic flare-ups separated by periods of remission. There isn’t full recovery after flare ups so disability increases over time.
60% will develop secondary within 15 years
What is secondary progressive MS?
Initially, the disease starts with a relapsing-remitting course, but then symptoms get progressively worse with no periods of remission
What is primary progressive MS?
Symptoms get progressively worse from disease onset with no periods of remission
Accounts for 10% of cases and is more common in older patients
What is Progressive relapsing MS?
One constant attack but there are bouts superimposed during which the disability increases even faster
What is clinically isolated syndrome MS?
This describes the first episode of demyelination and neurological signs and symptoms.
- MS cannot be diagnosed on one episode as the lesions have not been “disseminated in time and space”.
- Patients with clinically isolated syndrome may never have another episode or develop MS. If lesions are seen on MRI scan then they are more likely to progress to MS
What are the signs and symptoms of MS?
- Optic nerve affected:
Optic neuritis
Eye movement abnormalities- double vision VI nerve - Spinal cord affected:
- Focal weakness (incontinence, limb paralysis, Bells palsy)
- Focal sensory symptoms ( numbness, pins and needles,
- Lhermitte’s sign is an electric shock sensation that travels down the spine and into the limbs when flexing the neck.) - Cerebellar white matter affected
Ataxia - Cerebral hemispheres:
- large variety but can be silent - Medulla + pons
- dysarthria, double vision, vertigo, nysatgmus - Uhthoff’s phenomenon: worsening of symptoms following a rise in temperature, such as a hot bath
What is optic neuritis?
Demyelination of the optic nerve which present with:
- Unilateral reduced vision
- Central scotoma (enlarged blind spot)
- Pain on eye movement
- Impaired colour vision (red)
What is the primary investigation for MS and what would it show?
MRI of brain and spine:
- Will show demyelinating plaques called Dawson’s fingers
- High signal L2 lesions
- Old lesions will not enhance with contrast, whereas newer lesions will.
This provides evidence of dissemination of lesions in time and space which is required for a diagnosis of MS
What other investigations are done for MS?
Lumbar puncture
- can detect oligoclonal IgG bands in the CSF
Nerve conduction studies
- delayed conduction speeds
Evoked Potentials (VEP)
- measures speed of messages along nerves
What is the diagnostic criteria used to diagnose MS?
McDonald criteria
What is the McDonald criteria based on?
2 or more relapses and either:
- Objective evidence of two or more lesions
- Objective evidence of one and a reasonable history of a previous relapse
‘Objective evidence’ is defined as an abnormality on neurological exam, MRI or visual evoked potentials
What is used to treat a MS relapse?
Oral or IV methylprednisolone
(reduce time to recover from illness but don’t treat illness)
Plasma exchange: to remove disease-causing antibodies
What is used for maintenance of MS?
Disease-modifying drugs
Beta-interferon: decreases the level of inflammatory cytokines
Monoclonal antibodies e.g. alemtuzumab (anti-CD52) and natalizumab (anti-α4𝛃1-integrin)
Glatiramer acetate: immunomodulator drug which acts as a ‘decoy’
Fingolimod: a sphingosine-1-phosphate receptor modulator that keeps lymphocytes in lymph nodes so they can’t cause inflammation
What is used to treat muscle spasticity in MS?
- baclofen
- gabapentin
Why is stem cell transplant used in MS?
- use chemotherapy to kill off all their immune cells
and give them a stem cell transplant - MS is a inflammatory disease so new immune cells should not attack myelin
- doesn’t improve demyelination as damage is already done but stops the disease progressing
What are some complications of MS?
Genitourinary: urinary tract infections, urinary retention and incontinence
Constipation
Depression: offer mental health support if required
Visual impairment
Mobility impairment: offer physiotherapy, orthotics and other mobility aids
Erectile dysfunction
What is Huntington’s disease?
An autosomal dominant genetic neurodegenerative condition that causes a progressive a progressive deterioration in the nervous system.
What causes HD?
- It is a trinucleotide repeat disorder that involves a genetic mutation in the HTT gene on chromosome 4
- There is a repeat of CAG which codes for glutamine 36 times in a row so patients have 36 glutamine in a row on the Huntington protein
- These mutated proteins aggregate within neuronal cells of the caudate and putamen causing neuronal cell death.
- This leads to decreased ACh and GABA synthesis.
- This leads to dopamine increase leading to excessive movement
What is anticipation and how is it linked to HD?
It is a feature of trinucleotide repeat disorders. When copying the HTT gene, DNA polymerase can lose track of which CAG it’s on and so add extra CAGs. This is called repeat expansion.
This leads to successive generations having more repeats in the gene resulting in:
- Early age of onset
- Increased severity of the disease
What are the symptoms of HD?
Patients will be asymptomatic until 30-50.
Symptoms:
- Begin with Cognitive, psychiatric or mood problems
- Chorea (involuntary, abnormal movements)
- Eye movement disorders
- Dysarthria: speech difficulties
- Dysphagia: swallowing difficulties
- Dementia
How is diagnosis of HD made?
Made at a specialist genetic centre that looks for the number of CAG repeats.
This will involve pre and post test counselling
What is the treatment for HD?
No treatment
- supporting person and family
- maintaining quality of life = OT + PT
- speech and language therapy
- genetic counselling
- end of life care planning
What medications are given for symptoms relief in huntington’s?
Medications that can suppress the disordered movement:
Antipsychotics (e.g. olanzapine)
Benzodiazepines (e.g. diazepam)
Dopamine-depleting agents (e.g. tetrabenazine)
What is meningitis?
Meningitis refers to inflammation of the pia and arachnoid mater. Micro-organisms infect the cerebrospinal fluid (CSF).
What are the 3 main features of ‘meningism’?
Stiffness of the neck
Photophobia
Severe headache
What other symptoms would present with bacterial or viral meningitis?
Fever
Feel unwell
Rash (characteristically haemorrhagic in meningococcal meningitis)
What are the viral causes of meningitis?
80% viral
- Enteroviruses (including Echo virus, Coxsackie virus)
- Herpes simplex virus
- Mumps virus
- varicella zoster virus
- Lymphocytic chorio meningitis virus
And historically, Poliovirus (also an enterovirus)
What are the main bacterial causes of meningitis for each age group?
Neonates = E.coli, Group B strep, Listeria monocytogenes
Infants = N.meningitis + H.influenza, Strep pneumoniae
Adults = N.meningitis + S.pneumoniae
Elderly = S. pneumoniae + N.meningitis + listeris monocytogenes
What are the causes of fungal meningitis?
Cryptococcus neoformans
Candida
What are some risk factors for developing meningitis?
Immunocompromised: such as being in the extremes of age, infection (HIV), and medication (Chemotherapy) Listeria monocytogenes
M. Tuberculosis
Non-immunised: at risk ofH. influenza, pneumococcal and meningococcal meningitis
Crowded environments: students living in halls of residence are a commonly affected demographic
What is encephalitis?
Refers to inflammation of the cerebral cortex
What are the main clinical symptoms of encephalitis?
Lethargy + fatigue
Decreased level of consciousness
Fever
Focal neurology
Occasionally there may be fits
What are the viral causes of encephalitis?
Herpes simplex virus
Varicella zoster virus
Parvoviruses
HIV
Mumps virus
Measles virus
Where are the signs of encephalitis?
Pyrexia (fever)
Reduced GCS
Aphasia
Hemiparesis
Cerebellar signs
What are some behavioural changes that occur in encephalitis?
Memory disturbance
Psychotic behaviour
Withdrawal or change in personality
What are some investigations for encephalitis?
Throat swab
HIV serology
MRI of head will show evidence of inflammation will be normal in 1/3 of cases
Lumbar puncture and CSF investigation including a PCR for HSV
What is the treatment for encephalitis?
Aciclovir = should be given in all cases where it is suspected
Ganciclovirmay = be preferred in other herpesvirus infections, such as HHV-6
What CSF cell count results would signify a bacterial cause of infection?
a neutrophil predominant leucocytosis
a raised protein (from dying bacteria)
reduced CSF glucose to serum glucose ratio (metabolically active bacteria, use up glucose as a source of energy)
What are the two tests to look for meningeal infection?
Kernigs Test
Brudzinski’s Test
What is Kernigs Test?
Involves patient lying on their back and flexing one hip and knee to 90 degrees and then slowly straightening the knee whilst keeping the hip flexed. This causes the meninges to stretch
A positive test will be where there is spinal pain or resistance to the movement
What is Brudzinski’s Test?
Involves lying a patient on their back and gently using your hands to lift their head and neck off the bed and flexing their chin to their chest
A positive test is when a patient involuntarily flexes their hips and knees
What is another classic sign of meningococcus meningitis?
non-blanching rash
that everybody worries about as it indicates the infection has caused disseminated intravascular coagulopathy (DIC) and subcutaneous haemorrhages.
Other causes of bacterial meningitis do not cause this rash
What is the empirical antibiotic therapy used against bacterial causes of CNS infection in hospital?
IV cefotaxime or ceftriaxone
What medication should be prescribed alongside antibiotics for meningitis treatment?
IV dexamethasone (corticosteroids)
- reduce risk of long term neurological complications from some causes of meningitis
what medication should be given in primary care for meningitis?
IM benzylpenicillin
then admit the patient ASAP!!
What is the management for meningitis?
- Assess GCS
- blood culture
- broad spectrum antibiotics = Ceftriaxone or cefotaxime
- Steroids = IV dexamethasone
- lumbar puncture = definitive diagnosis
What are the contraindications for a lumbar puncture?
Abnormal clotting (platelets/coagulation)
Petechial rash
Raised intracranial pressure
GCS <9
Where is a lumbar puncture usually taken from?
Between L3/L4
Since spinal cord ends L1/2
When would you do a CT head before a lumbar puncture in meningitis?
Aged > 60
Immunocompromised
History of CNS disease
Seizures <1 week
GCS <14
Focal neurological signs
Papilloedema
Atypical history
What are close contacts of patients with meningitis offered?
Notified
Antibiotic prophylaxis = single dose of ciprofloxacin
What is the CSF count and culture characteristic for a viral meningitis infection?
Predominant lymphocyte response
Only moderately raised protein
CSF glucose more than 50% of the level of serum glucose
What antimicrobial agent is used to treat a viral meningitis or encephalitis infection?
IV aciclovir
How does an infection get into the brain?
- extra-cranial infection e.g. nasopharynx, ear, sinuses
- neurosurgical complications e.g. post op, infected shunts, trauma
- via blood stream e.g. bacteraemic
What is the pathophysiology of meningitis?
- bacteria in blood
- bacteria enter CSF and can be isolated from immune cells due to BBB
- replication
- blood vessels become leaky
- so WBCs can enter the CSF, meninges and brain
- meningeal inflammation +/- brain swelling
What types of meningitis are acute and which are more commonly chronic?
Bacterial and viral meningitis are usually acute
Fungal is more chronic
What will a lumbar puncture show for bacterial meningitis?
high pressure
cloudy
high WBCs
neutrophils
low glucose
high protein
What will a lumbar puncture show for viral meningitis?
normal or elevated pressure
clear
increased lymphocytes
high glucose
low protein
what will a lumbar puncture results show for fungal/TB meningitis?
elevated pressure
cloudy/fibrin web
Increased lymphocytes
low glucose
high protein
What is spinal cord compression SCC?
Results form processes that compress or displace arterial, venous and cerebrospinal fluid spaces as well as the cord itself.
What is the main cause of SCC?
Metastatic cancer lesions
Where are the metastasis most commonly from the cause SCC?
Breast
Lung
Prostate
Thyroid
Kidney
Myeloma
Lymphoma
What area of the spine is most commonly affected by metastasis in SCC?
Thoracic 60%
Lumbar 30%
Cervical 10%
What are some other causes of SCC?
Disc herniation
Disc prolapse
Primary spinal cord tumour
Infection
Haematoma
What are the symptoms of SCC?
Back pain
Progressive weakness of legs with UMN signs
Sensory loss 1-2 cord segments below level of lesion
UMN signs below level of lesion
LWN signs at the level of the lesion
What is a late sign of SCC?
Bladder and anal sphincter involvement: hesitancy, frequency and painless retention
What are the sensory ascending spinal tracts?
- dorsal column medial lemniscus system
- fine touch, vibration and proprioception - spinocerebellar tracts
- posterior = proprioceptive from lower limb
- cuneo = upper limbs
- anterior = lower limb
- rostral = upper ipsilateral - anterolateral systme
- anterior spinothalamic tract = crude touch, pressure
- lateral spinothalamic tract = pain + temperature
What does injury to DCMl pathway result in?
loss of proprioception and fine touch
- ipsilateral loss (if lesion in spinal cord)
- decussation in medulla oblongata
Gracillis = ground lower limbs
Cunneatus = upper limbs
What does injury to anterolateral system result in?
Impairment of:
pain and temperature (lateral)
Crude touch and pressure (anterior)
- contralateral loss (decussate in spinal cord)
What does injury to spinocerebellar tracts cause?
ipsilateral loss of muscle co-ordination (unconscious)
- likely to be injury alongside descending motor tracts
What are the motor descending spinal tracts?
Pyramidal tracts
- originate in cerebral cortex, carrying motor fibres to the spinal cord and brain stem
- voluntary control of musculature
Extrapyramidal tracts
- originate in brain stem, carrying motor fibres to the spinal cord
- responsible for the involuntary and automatic control of all musculature
No synapses = so all upper motor neurones
What is the function of descending motor tracts?
Corticospinal tracts – supplies the musculature of the body.
Corticobulbar tracts – supplies the musculature of the head and neck.
What are the two types of spinal cord injury?
- complete spinal cord injury
- total loss of motor and sensory function below level of injury - Incomplete spinal cord injury
- partial loss of motor and sensory function below level of injury
What would the features of a complete spinal cord compression be?
Loss of all motor and sensory function below the level
What are the types of incomplete spinal cord injury?
- anterior cord syndrome
- central cord syndrome
- Brown-Sequard syndrome
- Mixed syndromes
What would be the features of an anterior spinal cord compression?
Disruption of the anterior spinal cord:
- Loss of motor function below the level
- Loss of pain and temperature sensation
- Preservation of fine touch and proprioception
What would be the features of a posterior spinal cord compression?
Disruption of posterior spinal cord or posterior spinal artery (rare)
- Loss of fine touch and proprioception (posterior column)
- Preservation of pain and temperature sensation (anterior column)
What are the features of brown-sequard syndrome?
Hemi section of spinal cord:
- Ipsilateral paralysis
- Ipsilateral loss of vibration and proprioception
- Contralateral loss of pain and temperature
What is the primary investigation if suspecting a Spinal cord compression?
MRI of spinal cord
Biopsy/surgical exploration
What is the treatment for SCC?
Surgical decompression
- Laminectomy: removal of the lamina/spongy tissue between the discs to relieve pressure
- Microdiscectomy: removal of the herniated tissue from the disc
What is bilateral sciatica a red flag for?
Cauda equina syndrome
What is cauda equina syndrome?
It is a neurosurgical emergency which occurs when the bundle of nerves below the end of the spinal cord are compressed
What are the causes of Cauda Equina?
Lumbar disc herniation: the most common cause of CES
Trauma
Spinal tumour
Lumbar spinal stenosis: narrowing of the spinal cord may result in CES. This can be congenital or acquired e.g. spinal osteoarthritis (spondylosis), rheumatoid arthritis, and a slipped vertebra (spondylolisthesis)
Epidural abscess or haematoma
What are the key presentations of Cauda Equina Syndrome?
Saddle anaesthesia = (loss of sensation in the perineum) can you feel wiping after poo
Loss of sensation in bladder and rectum (not knowing when they’re full)
Urinary retention or incontinence
Faecal incontinence
What are the investigations for CES?
Examinations: PR exam, knee and ankle reflexes
MRI spine is gold standard
Bladder ultrasound: to determine whether there us urinary retention
What is the treatment for CES?
Emergency decompressive laminectomy: surgery should be performed within24-48 hoursof symptom onset.
The incidence of thromboemboli in patients with CES is remarkably high, therefore patients require adequate thromboprophylaxis
What is the main differential of CES?
Conus medullaris
What is Broca’s and Wernicke’s area?
Broca - motor control of speech
Wernicke - understanding of speech
What are mononeuropathies?
Lesions of individual peripheral or cranial nerves
- causes are usually local e.g. trauma or entrapment (tumour)
What are the types of mononeuropathies?
most affect the upper limb
- median nerve e.g. carpal tunnel syndrome
- ulnar = compression at elbow
- axillary neuropathy = shoulder dislocation/relocation
- radial neuropathy = spiral fractures of the radius
lower limb
- L5 radiculopathy = foot drop
Presentation: mononeuropathy
pain/paraesthesia/numbness in the distribution of the named nerve
examination
- majority of patients have no signs
Investigations: mononeuropathy
EMG
nerve conduction studies
What is Myasthenia Gravis?
A chronic autoimmune disorder of the postsynaptic membrane at the neuromuscular junction of skeletal muscle
What are the risk factors for developing Myasthenia Gravis?
Female 2x as common
Autoimmune: linked to rheumatoid and SLE
-Thymoma or thymic hyperplasia: 10-15% have a thymoma and 70% have thymic hyperplasia
What is the main cause of disease in Myasthenia Gravis?
Acetylcholine receptor antibodies present (85%)
These bind to the receptors on the post-synaptic membrane and prevent ACh from binding and causing muscle contraction
The problem is worsened during exercise as more of the receptors become blocked up. So the more the muscles are used the weaker they get. Gets better with rest
These antibodies also activate the complement system which damages cells further making the problem worse
What are the two other antibodies that can cause MG and how do they do it?
- Muscle specific kinase (MuSK)
- low-density lipoprotein receptor-related protein 4 (LRP4).
They are both proteins that are important for making the acetylcholine receptor. These antibodies lead to inadequate acetylcholine receptors causing MG
What are the signs of MG?
Proximal muscle weakness: often affecting the face and neck
Ptosis (drooping eyelid)
Complex ophthalmoplegia: cannot be isolated to one cranial nerve
Head drop: a rare sign due to weakness of cervical extensor muscles
Myasthenic snarl: a ‘snarling’ expression when attempting to smile
What are the symptoms of MG?
Muscle weakness that gets worse throughout the day
Diplopia: double vision
Slurred speech
Fatigue in jaw while chewing
What are the investigations for MG?
Look for presence of autoantibodies:
- Acetylcholine receptor (ACh-R) antibodies (85% of patients)
- Muscle-specific kinase (MuSK) antibodies (10% of patients)
- LRP4 (low-density lipoprotein receptor-related protein 4) antibodies (less than 5%)
CT/MRI of thymus gland to look for thymoma
What is another test that can be performed if unsure about MG?
Edrophonium test:
patients given IV Edrophonium chloride (neostigmine).
Will prevent breakdown of ACh by cholinesterase enzymes and improve symptoms temporarily
What are the treatments for MG?
First-line: Reversible acetylcholinesterase inhibitors (neostigmine/pyridostigmine)
Second-line: Immunosuppressants: prednisolone/azathioprine
Consider monoclonal antibodies (rituximab)
Thymectomy can also improve symptoms.
What is the main complication of MG?
Myasthenic crisis often triggered by another illness such as respiratory tract infection . Causes an acute worsening of symptoms and can lead to respiratory failure
What is the treatment for a Myasthenic crisis?
Patients may require non-invasive ventilation with BiPAP or full intubation and ventilation.
Medical treatment of myasthenic crisis is with immunomodulatory therapies such as IV immunoglobulins and plasma exchange.
What is the main differential for MG?
Lambert-Eaton myasthenic syndrome
What drugs should be avoided in MG?
Antibiotics;
- aminoglycosides (e.g. gentamicin)
- fluoroquinilones (e.g. ciprofloxacin)
- Macrolides (e.g. azithromycin)
- tetracyclines (e.g. doxycycline)
- quinolones
Neuromuscular blocking agents
Magnesium sulfate
penicillamine
Cardiac drugs - BB
neurological - lithium + phenytoin
What is Guillain-Barré syndrome?
An acute paralytic polyneuropathy. It is an autoimmune, rapidly progressive demyelinating condition of the peripheral nervous system
What are the risk factors for developing Guillain-Barré syndrome?
Male
Age 15-35 and 50-75
Malignancies
Vaccines (flu)
Infections
What are the most common infections that trigger Guillain-Barré syndrome?
Campylobacter jejuni (most common)
Cytomegalovirus
EBV
What causes Guillain-Barré syndrome?
A pathogenic antigen resembles myelin gangliosides in the peripheral nervous system.
The immune system targets the antigen and attacks the myelin sheath of sensory and motor neurones
It occurs in patches along the length of the axon so is called segmental demyelination
What antibodies are found in 25% of people with Guillain-Barré syndrome?
Anti-ganglioside antibodies (anti-GMI)
Describe the disease course of Guillain-Barré syndrome?
Symptoms usually start within 4 weeks of the preceding infection. The symptoms typically start in the feet and progresses upward.
Symptoms peak within 2-4 weeks, then there is a recovery period that can last months to years.
