5- Neurology (Less acute- Parkinsons, Essential tremor and Multiple Sclerosis) Flashcards
Parkinsons background
Condition where there is a progressive reduction of dopamine in the basal ganglia, leading to disorders of movement
NOT RELATED TO THE CEREBELLUM
Parkinsons Pathophysiology
- Basal ganglia are a group of structures of the brain responsible for coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns
- The substantia nigra (part of the basal ganglia) produces dopamine
- Dopamine is essential for correct functioning of the basal ganglia
- In Parkinson’s there is a progressive fall in dopamine
Why is Parkinsons asymmetrical?
the initial pathology starts in one hemisphere and initially damages that hemisphere via the predominantly same-sided connections, leading to marked asymmetry
May be symmetrical if drug induce Parkinsons
Related syndromes i.e. Parkinson’s-plus syndromes
- Multiple system atrophy
- Dementia with lewy body
- Progressive supranuclear palsy
- Corticobasal degeneration
Causes/ risk factors for parkinsons
- Advancing age
- Male
presentation of parkinsons : key triad
involves bradykinesia plus at least one of; rigidity, tremor or postural instability
Characteristically asymmetrical triad
- Resting tremor (low frequency- pill rolling)
- Rigidity
- Bradykinesia
other presentations of parkinsons
Others
- Facial masking
- Stooped posture
- Forward tilt
- Reduced arm swing
- Shuffling gait
- Cogwheel rigidity
- Lead pipe
More
- Depression
- Sleep disturbance and insomnia
- Loss of smell – anosmia
- Postural instability
- Cognitive impairment and memory problem
investigations for parkinsons
- Clinical diagnosis
Rhomberg test and parkinsons
If Parkinson’s should not fall over due to not having a problem with vision or proprioception -> wide base
for sensory ataxia e.g. peripheral neuropathy
e.g. if you tell someone to close their eye who has peripheral neuropathy you have taken away 2/3 contributors of balance (vision and proprioception) -> will fall over
unilateral tremor
The tremor in Parkinsons has a frequency of 4-6 Hz, meaning it occurs 4-6 times a second.
- This is described as a “pill rolling tremor” because it looks like they are rolling a pill between their fingertips and thumb.
- It is more pronounced when resting and improves on voluntary movement.
- The tremor is worsened if the patient is distracted. Asking them to do a task with the other hand, such as miming the motion of painting a fence, can exaggerate the tremor.
“Cogwheel” Rigidity
- Rigidity is a resistance to passive movement of a joint.
- If you take their hand and passively flex and extend their arm at the elbow, you will feel a tension in their arm that gives way to movement in small increments (like little jerks).
- This is what leads to the cog wheel description.
Bradykinesia
Bradykinesia describes how their movements get slower and smaller. This presents in a number of ways:
- Their handwriting gets smaller and smaller (this is a classic presenting complaint in exams)
- They can only take small steps when walking (“shuffling gait”)
- They have difficulty initiating movement (e.g. from standing still to walking)
- They have difficulty in turning around when standing, having to take lots of little steps
- They have reduced facial movements and facial expressions (hypomimia)
parkinsons Pathophysiology
When thinking about Parkinsons disease in relation to the basal ganglia circuit start at the Substantia nigra
Parkinsons is caused by a decrease in dopamine
Normal dopamine action on the basal ganglia pathway
Dopamine excites the direct pathway (harbours D1 receptors) and inhibits indirect (harbours D2 receptors) pathway
1) Dopamine is stimulatory to the direct pathway via the D1 receptors
- Increase inhibition to Globus pallidus internus
- Decreasing GPi inhibition to the thalamus
- Overall increasing thalamus stimulation of the cortex
2) Dopamine is inhibitory to the indirect pathway via the D2 receptors
- Inhibition of inhibitory pathway
- Increase level of activity in the cortex
Hence overall excitation
Parkinson’s disease- loss of dopamine
- Therefore if we take dopamine away
- We get decreased cortex activity
Parkinson’s disease (decreased movement)
- Degeneration of dopaminergic neurones present in substantia nigra
- If we remove dopamine provided by the SN, then we lose net excitation on the cortex (dopamine stimulates direct pathway (which increases movement)and inhibits indirect pathway (which decreases movement))
- Therefore cortical activity decreases- corticospinal pathways aren’t stimulating LMN adequately
o Tremor
o Rigidity- reduction in proper coordination in flexors and extensors
o Bradykinesia- most easily explained by this pathway
o Psychiatric features- cognition circuit interlinked with the basal ganglia circuit
management of parkinsons
Aim: manage symptoms and minimise side effects
Patients describe themselves as “on” when the medications are acting and they are moving freely, and “off” when the medications wear out, they have significant symptoms and their next dose is due.
4 main classes of drugs used to treat Parkinsons
- Levodopa
- COMT inhibitors
- Dopamine agonists
- Monoamine Oxidase-B inhibitors
Levodopa
- Synthetic dopamine given orally to boost dopamine levels
- Usually given with carbidopa or benserazide (peripheral decarboxylase inhibitors) – which prevent levodopa being broken down before they cross the BBB. Therefore given as combination drugs
o Co-benyldopa (levodopa and benserazide)
o Co-careldopa (levodopa and carbidopa)
positives of levodopa
most effective treatment for symptoms
negatives of levodopa
- becomes less effective over time- therefore often reserved when other treatments are not working for symptom control
- patients develop dyskinesia
o dystonia- excessive muscle contraction
o chorea- jerking
o athetosis- involuntary twisting or writhing movements in the fingers, hands or feet
COMT inhibitors
- inhibitors of catechol-o-methyltransferase (COMT)
- COMT enzymes metabolise levodopa in the body and brain
- E.g. Entacapone -> usually taken with levodopa (and decarboxylase inhibitor e.g. carbidopa)
- Positive: extends effective duration of levodopa
Dopamine agonists
- Mimic dopamine in the basal ganglia, stimulating dopamine receptors
- Less effective than levodopa in reducing symptoms
- E.g. Bromocryptine, Cabergoline
- Role
o Used to delay use of levodopa
o Then use din combination to reduce dose of levodopa
Negatives
- Pulmonary fibrosis
Monoamine Oxidase-B Inhibitors
- Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline.
o The monoamine oxidase-B enzyme is more specific to dopamine and does not act on serotonin or adrenalin. - These medications block this enzyme and therefore help increase the circulating dopamine.
- Role
o Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose. - Examples are:
o Selegiline
o Rasagiline
Multiple system atrophy
This is a rare condition where the neurones of multiple systems in the brain degenerate. It affects the basal ganglia as well as multiple other areas. The degeneration of the basal ganglia lead to a Parkinson’s presentation. The degeneration in other areas lead to autonomic dysfunction (causing postural hypotension, constipation, abnormal sweating and sexual dysfunction) and cerebellar dysfunction (causing ataxia).
Dementia with Lewy Bodies
This is a type of dementia associated with features of Parkinsonism. It causes a progressive cognitive decline. There are associated symptoms of visual hallucinations, delusions, disorders of REM sleep and fluctuating consciousness.
Other Parkinsons plus syndromes not including Lewy body or Multiple system atrophy
Two other Parkinson’s-plus syndromes exist that involves a number of complex progressive neurological features:
* Progressive Supranuclear Palsy
* Corticobasal Degeneration
Essential tremor
Background
- Relatively common
- Associated with older age
- Associated with fine tremor affecting all voluntary muscles
- Most noticeable in the hands
causes of essential tremor
Causes/ risk factors
The exact cause of essential tremor is unknown. Studies show essential tremor is accompanied by a mild degeneration of the cerebellum, which is the part of your brain that controls movement.
Presentation of essential tremor
- Fine tremor
- Symmetrical
- More prominent on voluntary movement
- Worse when tired, stressed or after caffeine
- Improved by alcohol
- Absent during sleep
Management of essential tremor
No definitive treatment -> not harmful and does not require treatment if not causing functional or psychological problems.
Symptoms control
- Propranolol
- Primidone (barbiturate anti-epileptic medication)
The key differential diagnoses of a tremor are:
- Parkinson’s disease
- Multiple sclerosis
- Huntington’s Chorea
- Hyperthyroidism
- Fever
- Medications (e.g. antipsychotics)
Multiple sclerosis
Background
- Chronic and progressive condition that involves demyelination of the myelinated neruones in the CNS
- Caused by inflammatory process involving immune cells against myelin
- Symptoms improve in pregnancy and in postpartum period
Pathophysiology of MS
- Myelin covers axons of neurones in the CNS
o Increases speed of impulses along the neurone
o Myelin is provided by cells that wrap around the axons
–> Schwann cells -> PNS
–> Oligodendrocytes -> CNS - MS only affects CNS (oligodendrocytes)
- Inflammation around the myelin and infiltration of immune cells damages the myelin -> reducing the effectiveness of electrical conductance along CNS axons -> leading to symptoms of MS
MS: in early disease
- Re-myelination can occur and symptoms resolves
MS: in later disease
- Re-myelination is incomplete and symptoms gradually become more permanent
MS lesions
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. The key expression to remember to describe the way MS lesions change location over time is that they are “disseminated in time and space”.
Risk factors MS
- Typically presents in young adults <50 yo
- F>M
Causes of MS
- Multiple genes
- Epstein-Barr virus
- Low Vit D
- Smoking
- Obesity
Presentation of MS
Symptoms progress over more than 24 hours. At first presentation symptoms last day to weeks and then improve.
- Optic neuritis
- Eye movement abnormalities
- Focal weakness
- Focal sensory symptoms
- Ataxia
MS attack
When a patient presents with symptoms of a clinical “attack” of MS, for example, an episode of optic neuritis, there are usually other lesions of demyelination at the same time throughout the central nervous system, most of which are not causing symptoms.
investigations for MS
- Made by neurologist based on clinical picture and symptoms suggesting lesions that change location over time
- Symptoms have to be progressive over a period of 1 year
- Imaging: MRI scans can demonstrate typical lesions
- Lumbar puncture an detect “oligoclonal bands” in CSF
Management
of MS
Disease modification
- DMARDs and biologic therapy
Treating relapses
- Steroids: methylprednisolone
o 500mg orally daily for 5 days
o 1g intravenously daily for 3–5 days where oral treatment has failed previously or where relapses are severe
Symptom treatments
- Exercise to maintain activity and strength
- Neuropathic pain e.g. amitriptyline or gabapentin
- Depression e.g. SSRIs
- Urge incontinence e.g. anticholinergic medications such as tolterodine or oxybutynin
- Spasticity e.g. baclofen, gabapentin, physiotherapy
Ataxia and MS
Ataxia is a problem with coordinated movement. It can be sensory or cerebellar:
- Sensory ataxia is the result of loss of the proprioceptive sense, which is the ability to sense the position of the joint (e.g. is the joint flexed or extended). This results in a positive Romberg’s test and can cause pseudoathetosis.
- Cerebellar ataxia is the result of problems with the cerebellum coordinating movement. This suggestions cerebellar lesions.
Optic neuritis and MS
Optic neuritis is the most common presentation of multiple sclerosis. It involves demyelination of the optic nerve and loss of vision in one eye. This is discussed in more detail below.
presentation of ON
Unilateral reduced vision developing over hours to days. Key features are:
* Central scotoma. This is an enlarged blind spot.
* Pain on eye movement
* Impaired colour vision
* Relative afferent pupillary defect
Multiple sclerosis is the main cause of optic neuritis, however it can also be caused by:
- Sarcoidosis
- Systemic lupus erythematosus
- Diabetes
- Syphilis
- Measles
- Mumps
- Lyme disease
Management of ON
Patients presenting with acute loss of vision should be seen urgently by an ophthalmologist for assessment
- Steroids gold standard
prognosis of ON
Prognosis
- Recovery takes 2-6 weeks.
- Around 50% of patients with a single episode of optic neuritis will go on to develop MS over the next 15 years.
- Changes on an MRI scan help to predict which patients will go on to develop MS.
Eye movement abnormalities and MS
Background
- Patients may present with double vision due to lesions with the sixth cranial nerve (abducens nerve).
- There are two key phrases to remember to describe a sixth cranial nerve palsy:
1) Internuclear ophthalmoplegia
2) Conjugate lateral gaze disorder.
pathophysiology of MS and eye movement abnormalities
Unilateral lesions in the sixth nerve causes a condition called internuclear ophthalmoplegia
- Internuclear refers to the nerve fibres that connect between the cranial nerve nuclei that control eye movements (3rd, 4th and 6th cranial nerve nuclei).
- The internuclear nerve fibres are responsible for coordinating the eye movements to ensure the eyes move together.
- Ophthalmoplegia means a problem with the muscles around the eye.
Lesions in the sixth cranial nerve cause a conjugate lateral gaze disorder
- Conjugate means connected.
- Lateral gaze is where both eyes move together to look laterally to the left or right.
- It is disordered in a sixth cranial nerve palsy.
- When looking laterally in the direction of the affected eye, the affected eye will not be able to abduct.
- For example, in a lesion affecting the left eye, when looking to the left, the right eye will adduct (move towards the nose) and the left eye will remain in the middle as the muscle responsible for making it move laterally is not functioning.
Focal weakness in MS
- Bells palsy
- Horners syndrome
- Limb paralysis
- Incontinence
Focal sensory symptoms and MS
- Trigeminal neuralgia
- Numbness
- Paraesthesia (pins and needles)
- Lhermitte’s sign is an electric shock sensation that travels down the spine and into the limbs when flexing the neck. It indicates disease in the cervical spinal cord in the dorsal column. It is caused by stretching the demyelinated dorsal column.
Disease Patterns of MS
Highly variable between individuals
- Some patients may have mild relapsing-remitting episodes for life
- Whereas others have primary progressive MS that progresses without any improvement in symptoms.
There are certain classifications used to describe the pattern of MS in an individual.
These patterns are not separate conditions but part of a spectrum of disease activity.
1) Clinically isolated syndrome
2) Relapsing-remitting
3) Secondary progressive
4) Primary progressive
1) Clinically Isolated Syndrome
- 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.
1) Clinically Isolated Syndrome
- 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.
2) Relapsing-Remitting
- Most common pattern at initial diagnosis.
- It is characterised by episodes of disease and neurological symptoms followed by recovery.
- In MS the symptoms occur in different areas with different episodes. This can be further classified based on whether the disease is active and/or worsening:
-
Active: new symptoms are developing or new lesions are appearing on MRI
* Not active: no new symptoms or MRI lesions are developing -
Worsening: there is an overall worsening of disability over time
* Not worsening: there is no worsening of disability over time
3) Secondary Progressive
- Is where there was relapsing-remitting disease at first, but now there is a progressive worsening of symptoms with incomplete remissions.
- Symptoms become more and more permanent.
- Secondary progressive MS can be further classified based on whether the disease is active and/or progressing.
* Active: new symptoms are developing or new lesions are appearing on MRI
*** Not active: **no new symptoms or MRI lesions are developing -
Progressing: there is an overall worsening of disease over time (regardless of relapses)
*** Not progressing: **there is no worsening of disease over time
cerebellar lesions
e.g. cerebellar stroke or MS
Can present with vomiting, vertigo, difficulty walking etc
Classic symptoms and signs (Danish pneumonic)
- Dysdiadochokinesis
Deficit in rapid alternating movements e.g. asking patients to pronate and supinate rapidly - Ataxia
Gait - Nystagmus (fast phase towards lesion side)
Flickering movement of the eyes - Intention tremor
- Slurred speech
- Hypotonia in the limbs
Blood supply to cerebellum is from the vertebra basilar system
- Occlusion of the three cerebellar arteries produce similar syndrome (don’t forget the brainstem)
- Therefore should also examine cranial nerves in order to establish if brainstem involvement
