PBL ILO’s Flashcards
Bamford classification of stroke
Bamford Classification of Ischaemic Stroke
Total Anterior Circulation Stroke
Large cortical stroke affecting the areas of the brain supplied by both the middle and anterior cerebral arteries
All 3 of the following must be present:
• Unilateral weakness (and/or sensory deficit) of the face, arm and leg
• Homonymous hemianopia
• Higher cerebral dysfunction (dysphasia, visuospatial disorder)
Partial Anterior Circulation Stroke
Less severe form of TACS
Only part of the anterior circulation has been compromised
2 of the following need to be present:
• Unilateral weakness (and/or sensory deficit) of the face, arm and leg
• Homonymous hemianopia
• Higher cerebral dysfunction (dysphasia, visuospatial disorder)*
*Higher cerebral dysfunction alone is also classified as PACS.
Posterior Circulation Syndrome
Involves damage to the area of the brain supplied by the posterior circulation e.g. Cerebellum and brainstem
1 of the following needs to be present:
• Cranial nerve palsy and a contralateral motor/sensory deficit
• Bilateral motor/sensory deficit
• Conjugate eye movement disorder (e.g. horizontal gaze palsy)
• Cerebellar dysfunction (e.g. vertigo, nystagmus, ataxia)
• Isolated homonymous hemianopia
Lacunar Stroke
Subcortical stroke
Occurs secondary to small vessel disease
No loss of higher cerebral function
1 of the following needs to be present:
• Pure sensory stroke
• Pure motor stroke
• Sensori-motor stroke
• Ataxic hemiparesis
Which part of the brain does the posterior cerebral arteries supply
• The posterior cerebral arteries supply a mixture of the medial and lateral areas of the posterior cerebrum.
Which area of the brain do the middle cerebral arteries supply
• The middle cerebral arteries supply the majority of the lateral cerebrum.
Which area of the brain do the anterior cerebral arteries supply
• The anterior cerebral arteries supply the anteromedial area of the cerebrum.
MCA stroke symptoms
MCA strokes typically present with the symptoms individuals associate most commonly with strokes, such as unilateral weakness and/or numbness, facial droop opposite to the lesion, and speech deficits ranging from mild dysarthria and mild aphasia to global aphasia.
ACA stroke symptoms
ACA strokes typically present with weakness and sensory loss in the lower leg and foot opposite to the lesion, incontinence and behaviour changes.
PCA stroke symptoms
PCA stroke may present with only a headache and mild visual changes such as vision loss, diplopia, inability to see half of the view, or difficulty reading perceiving colours, or recognizing familiar faces.
The cerebrum
The cerebrum is located within the bony cranium and extends from the frontal lobe anteriorly to the occipital bone posteriorly.
The cerebral cortex consists of many gyri and sulci which give it a wrinkled appearance. The gyri are the bulges or ridges on the cerebral cortex, while sulci are the deep furrows or grooves.
The cerebrum consists of two types of tissue - grey and white matter.
1. Grey matter forms the outer layer - the cerebral cortex
2. White matter forms the inner layer - consists of glial cells and myelinated axons.
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the brain - the grey matter contains around 15 billion neurons.
Lobes of the cerebrum and their jobs
Lobes of the cerebrum
The cerebral cortex is classified into 4 lobes
1. Frontal lobe
2. Parietal lobe
3. Temporal lobe
4. Occipital lobe
Frontal lobe
• Most anterior region
• Associated function: higher intellect, personality, mood, social conduct and language
• Broca (language retrieving) region located in the left frontal lobe
Parietal lobe
• Between the frontal lobe anteriorly and occipital lobe posteriorly
• Associated function: language and calculation and visuospatial functions
Temporal lobe
• Inferior to the frontal and parietal lobes
• Associated functions: memory and language, also hearing.
• Wernicke’s (language articulating) region is found in the left temporal lobe
• Location of the primary auditory cortex.
Occipital lobe:
• Most posterior region
• Associated functions: vision.
• Location of the primary visual cortex.
Functional organisations of the four lobes in the cerebrum
Functional organisation
In addition to the four lobes, the cerebral cortex is also divided into three functional areas as well
1. Sensory area: The sensory area processes information related to the senses such as touch, pain, smell, and hearing. 2. Motor area: The motor area is involved in initiating and controlling movements of the body such as walking or moving the arms and hands while eating. 3. Association area: The association areas of the brain are involved in various cognitive functions such as language and decision-making.
These functional areas are not just in one area of the cerebral cortex , rather they are spread throughout the whole of the cerebral cortex. Therefore, some of the lobes provide similar functions.
Vasculature of the cerebrum
Vasculature
The blood supply to the cerebral cortex can be simplified into 3 distinct arterial branches
• Anterior cerebral arteries - branches of the internal carotid arteries, supplying the anteromedial aspect of the cerebral cortex • Middle cerebral arteries - continuation of internal carotid arteries, supplying most of the lateral portions of the cerebrum • Posterior cerebral arteries - branches of the basilar arteries, supplying both the medial and lateral sides of the cerebrum posteriorly.
Venous drainage of the cerebrum is via a network of small cerebral veins.
These vessels empty into the dural venous sinuses - endothelial lined spaces between the outer and inner layers of the dura mater.
Long term management of a stroke
Long term management of stroke
· Secondary prevention
○ Clopidogrel 75mg once daily (alternatively aspirin & dipyridamole)
○ Atorvastatin 20-80mg (usually delayed at least 48 hours after event)
○ BP and diabetes control
○ Managing modifiable risk factors (smoking, obesity and exercise)
○ Address any underlying conditions
· Rehabilitation - requires multidisciplinary team
○ Nurses
○ SALT - assess swallow
○ Dieticians - malnutrition risk
○ Physiotherapy
○ Occupational therapy
○ Social services
○ Optometry
○ Psychology
○ Orthotics
Driving restrictions in acute stroke
Rationale for driving restrictions in acute stroke
· Legally not allowed to drive for at least 1 month after a stroke or TIA with no brain surgery or seizures (don’t need to tell the DVLA about this if your ability to drive is not affected)
○ Required to notify if stroke due to subarachnoid haemorrhage (brain bleed) - haemorrhagic stroke
· Personal responsibility to notify the DVLA of your attack - especially if you drive a LGV or PCV (notify asap)
· Might be able to drive again after a month - does depend on type of stroke and other health conditions e.g. epilepsy
· Physical effects of a stroke which may restrict driving:
○ Weakness in arms/legs
○ Pain, changes in sensation, weakness and problems with balance
· Vision problems:
○ Double or blurred vision, loss of central vision in one or both eyes, visual field loss
· Cognitive effects:
○ Difficult concentrating, understanding, solving problems or decision making
○ Perception of space and distance may have changed
○ Memory problems
· Seizures and epilepsy - if you have seizures after stroke, must stop driving - drive after 6 months or a year - up to the DVLA.
Upper and lower motor neurone lesions
The neurone that control muscle movement, known as motor neurone, are located in the brain, spinal cord, and peripheral nerves. These neurone work together to move muscles in your body.
The upper motor neurone are located in the brain and spinal cord, and the lower motor neurone are in the peripheral motor nerves.
The upper motor neurones originate in the cerebral cortex and travel down to the brain stem or spinal cord, while the lower motor neurones begin in the spinal cord and go on to innervate muscles and glands throughout the body. The upper motor neurones synapse in the spinal cord with anterior horn cells of lower motor neurones, usually via interneurons. The anterior horn cells are the cell bodies of the lower motor neurones and are located in the grey matter of the spinal cord.
Sometimes, motor neurone can become damaged, potentially impairing mobility. Injuries can cause damage to upper motor neurone, lower motor neurone, or both.
What causes upper motor neurone lesions?
Upper motor neurone lesions can have a variety of causes spanning physical trauma, illness, and vitamin deficiency. Several of the most common causes of upper motor neurone lesions include:
• stroke
• multiple sclerosis (MS)
• B12 vitamin deficiency
• Brown-Sequard syndrome (spinal hemiplegia)
• trauma to the brain or spinal cord
• tumours
• severe brain infection
• dementia
Additionally, amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, and primary lateral sclerosis cause both upper and lower motor neurone degeneration.
Typical signs of upper motor neurone lesions on a neuro exam
Upper motor neurone lesions
An upper motor neurone (UMN) lesion will be in the central nervous system (brain and spinal cord).
On neurological examination, typical signs of an upper motor neurone lesion include:
• Disuse atrophy (minimal) or contractures
• Increased tone (spasticity/rigidity) +/- ankle clonus
• Pyramidal pattern of weakness (extensors weaker than flexors in arms, and vice versa in legs)
• Hyperreflexia
• Upgoing plantars (Babinski sign) (extended big toe)
What causes lower motor neurone lesions?
The most common causes of lower motor neurone injuries are trauma to peripheral nerves that serve the axons, and viruses that selectively attack ventral horn cells.
Signs of a lower motor neurone lesion on a neuro exam
Lower motor neurone lesions
A lower motor neurone (LMN) lesion affects anywhere from the anterior horn cell to the muscle.
On neurological examination, typical signs of a lower motor neurone lesion include:
• Marked atrophy
• Fasciculations
• Reduced tone
• Variable patterns of weakness
• Reduced or absent weakness
• Downgoing plantars or absent response
Broca’s area
Broca’s Area
Broca’s area is responsible for speech production and articulation (motor speech) – finding the right words to use. Damage to Broca’s area causes:
○ Dysfluency
○ Impaired grammatical structure
○ Absence of small linking words
○ Slow, but comprehensible speech
Wernicke’s Area
Wernicke’s Area
Wernicke’s area is responsible for the comprehension of written and spoken language. Damage to this area causes:
○ Fluent speech lacking in meaningful content
○ Patients unaware of the scale of their aphasia
Angular Gyrus
Angular Gyrus
The angular gyrus region is responsible for reading and writing, it allows us to associate multiple types of language-related information (auditory, visual or sensory). Damage to this area may result in:
○ Alexia - inability to recognize or read written words or letters, typically as a result of brain damage
○ Agraphia - inability to write letters, symbols, words, or sentences, resulting from damage to various parts of the brain.
Primary Auditory Cortex
Primary Auditory Cortex
A lesion in the primary auditory cortex resulting in reduction of hearing sensitivity in both ears (mostly contralateral) and a loss of stereo perception of sound origin
Dual Stream Model of Neural Basis of Language
Dual Stream Model of Neural Basis of Language
The major network of language processing consists of two streams, the dorsal and ventral streams in the dominant hemisphere.
Dorsal Stream: associated with phonological processing via the superior longitudinal fasciculus (SLF) as a major trunk of the network
Ventral Stream: associated with semantic processing.
It is assumed that the network consists of intra-temporal network, such as the middle longitudinal fasciculus (MLF) and the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF) as an inter-lobe network.
Adding to the dural stream model, there is another system inside the frontal lobe for “driving of speech.” Recently named the frontal aslant tract (FAT) is probably associated with initiation and spontaneity of speech.
A 67 year old man comes to the emergency department with sudden onset vertigo and nausea starting 3 hours ago. He feels uncoordinated walking and has an ataxic gate. On examination there is dysdiadochokinesia and past pointing on the right side.
Dysdiadochokinesia - Inability to do rapid alternating movements
Which is most likely site of atherosclerosis?
A. Anterior communicating artery
B. Brachial artery
C. Common carotid artery
D. Middle cerebral artery
E. Vertebral artery
E. Vertebral artery
Symptoms of posterior circulation stroke
Question 2
A 67 year old man comes to the emergency department with sudden onset vertigo and nausea starting 3 hours ago. He feels uncoordinated walking and has a broad based uncoordinated gait and nystagmus.
Which other clinical features are consistent with the presentation (choose three)?
A. Chorea = uncontrollable jerky movements
B. Dysarthria = speech muscles weak
C. Dysdiadochokinesia
D. Intentional tremor
E. Resting tremor
F. Rigidity
B. Dysarthria = speech muscles weak
C. Dysdiadochokinesia
D. Intentional tremor
A 25 year old man comes to the emergency department after a head injury. He fell and hit his head after drinking alcohol heavily with friends. He only opens his eyes when you shout at him, has confused speech, will not follow commands, but can move all his limbs and tries to push you away when you attempt to examine him.
Calculate his GCS score
E3 V4 M5 = 12
Opens eyes to sounds 3/4
Confused speech 4/5
Localised motor response 5/6
A 67 year old woman comes to the emergency department with recued consciousness. She will not open her eyes, and does not open when you pinch her trapezius or apply supra-orbital pressure. She mutters something at you when you do the later though but no discernible words. She tries to push you away when you apply supra-orbital pressure.
Calculate her GCS score
E1 V2 M5 = 8
A 36 year old woman is brought to the emergency department after being hit by a car cycling. She will not open her eyes, makes no attempt to speak, when a you pinch her right trapezius muscle her right elbow, wrist and fingers flexes.
Calculate her GCS score
E1 V1 M3 = 5
67 year old man comes to the emergency department with right sided weakness and slurred speech starting two hours ago.
Which is the most appropriate next investigation ?
A. Carotid artery Doppler
B. Contrast CT scan brain
C. Contrast MRI brain
D. No contrast CT scan brain
E. Non contrast MRI brain
D. No contrast CT scan brain - can see haemorrhage
A 67 year old man comes to the emergency department with difficulty speaking, a droopy right mouth and weakness down his right upper and lower limb starting 1 hour ago
CT brain scan: Unremarkable. He has no previous medical history, takes no regular medications, his FBC, clotting, renal and liver function are normal, blood sugar is 5.6mmol/L
Which is the most appropriate management ?
A. Alteplase
B. Aspirin
C. Edoxaban
D. Enoxaparin
E. Warfarin
A. Alteplase - should be given within 4.5hrs of symptoms starting
Question 8
A patient comes to the emergency department with weakness and difficulty speaking. He will follow motor commands e.g. lift your arm, close your eyes, but has difficulty speaking, hesitating a lot and sometimes using inappropriate words in a sentence
Damage to which part of his brain is most likely causing the verbal symptoms ?
A. Broca’s area
B. Cerebellum
C. Internal capsule
D. Thalamus
E. Wernicke’s area
A. Broca’s area
What is the mechanism of action of Apixiban
A. Direct factor Xa inhibitor
B. Direct thrombin inhibitor
C. Enhances activity of antithrombin III
D. Inhibits binding of ADP to P2Y12 platelet receptors
E. Inhibits vitamin K epoxide reductase
A. Direct factor Xa inhibitor
A 34 year old man goes to the GP surgery after waking up with weakness down the left side of his face. He felt fine the night before, but woke up and found he had difficulty closing his left eye and his left lip was drooping. On examination there is weakness in his left lip, he has difficulty closing his left and eye and cannot elevate his left eyebrow.
Which is the most appropriate next step ?
A. Aciclovir
B. Arrange immediate referral to the emergency department
C. Aspirin
D. Prednisolone 30mg
E. Re-assurance only
D. Prednisolone 30mg - if symptoms presented in the last 72hrs (NICE)
You are asked to see a patient who had thrombolysis for an ischaemic stroke 24 hours ago because they have become unwell
How would you assess the patient ?
- Check tongue for swelling - in case of allergic reaction to thrombolytic agent used
- Another CT scan
- Neuro exam
- Any dizziness, vomiting
A 28-year-old man presents with a 12-hour history of high fever, severe headache, confusion, photophobia and neck stiffness. He has no significant past medical history and takes no regular medication. He is drowsy and looks unwell.
CSF results
Appearance: cloudy
Opening pressure: 30 cm H₂O
WBC: 936 cells/µL (>95% PMN cells)
Glucose level: < 40% of serum glucose
Protein level: 3 g/L
What is the most likely diagnosis?
The most likely diagnosis is bacterial meningitis. This patient has presented with meningeal symptoms, fever and confusion, which have progressed rapidly over the last 12 hours. The CSF is cloudy on inspection, the white cell count is significantly raised, and glucose levels are low.
The history and CSF results strongly suggest bacterial meningitis, and he should be treated empirically whilst culture results are awaited.
A 38-year-old woman presents with 24 hours of headache, photophobia, mild neck stiffness, and coryzal symptoms. She is fully orientated, and her observations are stable.
CSF results
Appearance: clear
Opening pressure: 23 cm H₂O
WBC: 150 cells /µL (primarily lymphocytes)
Glucose level: normal
Protein level: 90 mg/dL
What is the most likely diagnosis?
The most likely diagnosis is viral meningitis. This patient has presented with a history of meningitic symptoms alongside coryzal symptoms, suggesting a viral illness. The CSF findings are more suggestive of viral meningitis, given the clear appearance of the CSF, the mildly raised WCC (consisting mainly of lymphocytes), raised protein level and normal glucose. Further investigations, including CSF PCR, would be useful in identifying the specific causative virus.
A 52-year-old man presents with a sudden onset severe headache. The headache started 14 hours ago. Since the headache, he has felt nauseated. He is otherwise well and fully orientated. Clinical examination is largely unremarkable, but he does appear to have some mild neck stiffness.
CSF results
Appearance: yellowish
Opening pressure: 23 cm H₂O
WBC: normal
Red cell count: raised
Glucose level: normal
Protein level: 80 mg/dL
Xanthochromia: positive
What is the most likely diagnosis?
The most likely diagnosis is subarachnoid haemorrhage (SAH). The typical history of a sudden severe headache and meningitic symptoms (neck stiffness) strongly suggest SAH. CT head is the first-line investigation, however sensitivity decreases after six hours from symptom onset. As a result, lumbar puncture is used to rule out SAH.
The CSF typically shows a persistently raised red cell count (due to blood in the CSF from the initial bleed). Within several hours, the red blood cells in the cerebrospinal fluid are broken down, releasing their oxygen-carrying molecule heme, which is metabolised by enzymes to bilirubin, a yellow pigment. This yellow pigment can be detected, and its presence is called xanthochromia.
Describe neurogenic atrophy
Neurogenic atrophy is caused by an injury or disease affecting nerves that connect to your muscles. When these nerves are damaged, they can’t trigger the muscle contractions that are needed to stimulate muscle activity.
Symptoms common to neuromuscular disorders:
Some symptoms common to neuromuscular disorders include:
• Muscle weakness that can lead to twitching, cramps, aches and pains • Muscle loss • Movement issues • Balance problems • Numbness, tingling or painful sensations • Droopy eyelids • Double vision • Trouble swallowing • Trouble breathing
Types of neuromuscular disorders
Types of neuromuscular disorders include:
• Amyotrophic lateral sclerosis (ALS) • Charcot-Marie-Tooth disease • Multiple sclerosis • Muscular dystrophy • Myasthenia gravis • Myopathy • Myositis, including polymyositis and dermatomyositis • Peripheral neuropathy • Spinal muscular atrophy
Features of upper motor neurone lesions:
Site or the lesion
Muscle weakness
Muscle tone
Fasiculations
Tendon reflexes
Abdominal reflexes
Sensory loss
Electromyography
Features of upper motor neurone lesions:
Site or the lesion - cerebral hemisphere, cerebellum, brain stem, spinal chord
Muscle weakness - quadriplegia, hemiplegia, diplegia, paraplegia
Muscle tone - spasticity, rigidity
Fasciculation - absent
Tendon reflexes - hyperreflexia
Abdominal reflexes - absent depending on the involved spinal level
Sensory loss - cortical sensations
Electromyography - normal nerve conduction, decreased interference pattern and firing rate
Features of lower motor neurone lesions:
Site or the lesion
Muscle weakness
Muscle tone
Fasiculations
Tendon reflexes
Abdominal reflexes
Sensory loss
Electromyography
Site or the lesion - anterior horn cell, nerve roots, peripheral nerves, neuromuscular junction and muscles
Muscle weakness - proximal (myopathy), distal (neuropathy)
Muscle tone - hypotonia
Fasciculations - present (particularly tongue)
Tendon reflexes - hypo / areflexia
Abdominal reflexes - present
Sensory loss - peripheral sensations
Electromyography - abnormal nerve conductions, large motor units, fasciculations and fibrillations
Triad of features in Parkinson’s disease
There is a classic triad of features in Parkinson’s disease:
1. Resting tremor (a tremor that is worse at rest) 2. Rigidity (resisting passive movement) 3. Bradykinesia (slowness of movement)
Pathophysiology of Parkinson’s disease
Pathophysiology
The basal ganglia are a group of structures situated near the centre of the brain. They are responsible for coordinating habitual movements such as walking, controlling voluntary movements and learning specific movement patterns.
Dopamine plays an essential role in the basal ganglia function. Patients with Parkinson’s disease have a slow but progressive drop in dopamine production.
Spinal cord disorder examples
Spinal cord disorders are conditions that cause damage and deterioration to the spinal cord. These conditions may include:
Tumours
Spinal stenosis
Herniated discs
Abscess
Hematoma
Vertebral fractures
Degenerative disc disease
Features of Parkinson’s
Features
Tremor in Parkinson’s is worse on one side and has a 4-6 hertz frequency, meaning it cycles 4-6 times per second. It is described as a “pill-rolling tremor” due to the appearance of rolling a pill between their fingertips and thumb. It is more noticeable when resting and improves on voluntary movement. It gets worse when the patient is distracted. Performing a task with the other hand (e.g., miming the act of painting a fence) exaggerates the tremor.
Rigidity is resistance to the passive movement of a joint. Taking a hand and passively flexing and extending the arm at the elbow demonstrates tension in the arm that gives way to movement in small increments (like little jerks). The jerking resistance to movement is described as “cogwheel” rigidity.
Bradykinesia describes the movements getting slower and smaller and presents in several ways:
• Handwriting gets smaller and smaller (micrographia) • Small steps when walking (“shuffling” gait) • Rapid frequency of steps to compensate for the small steps and avoid falling (“festinating” gait) • Difficulty initiating movement (e.g., going from standing still to walking) • Difficulty in turning around when standing and having to take lots of little steps to turn • Reduced facial movements and facial expressions (hypomimia)
Other features include:
• Depression • Sleep disturbance and insomnia • Loss of the sense of smell (anosmia) • Postural instability (increasing the risk of falls) Cognitive impairment and memory problems
What is Myopathy
Myopathy is a general term referring to any disease that affects the muscles that control voluntary movement in the body.
The visual pathways and optic tracts
The visual Pathway
• The optic nerve transmits sensory visual information received from the retina to the visual cortex.
• The optic nerve is formed by the convergence of axons from the retinal ganglion cells. These cells receive impulses from the rods and cones.
Optic Tracts
• Within the middle cranial fossa the optic nerves from each eye unite and cross over to form the optic chiasm.
• Within the lateral halves the optic nerves remain ipsilateral.
• Action potentials received from the retina travel along these pathways and go into the brain
Each optic tract travels to its corresponding cerebral hemisphere and goes to the R and L Lateral Geniculate Nucleus. This is a relay system located within the thalamus
The axons running from the LGN carry visual information knows as the optic radiation
Optic radiation
Optic Radiation (remember everything is upside down until it reaches the brain)
The optic radiation pathway can be divided into upper and lower optic radiation
• Upper optic radiation – carries fibres from the superior retinal quadrants (corresponding to the inferior visual field quadrants). It travels through the parietal lobe to reach the visual cortex. • Lower optic radiation – carries fibres from the inferior retinal quadrants (corresponding to the superior visual field quadrants). It travels through the temporal lobe, via a pathway known as Meyers’ loop, to reach the visual cortex. • Once in the visual cortex the brain processes the visual data and responds appropriately i.e. by flipping it the right way round
Proprioception
Proprioception is transmitted through one of the ascending sensory pathways called
The Dorsal Column-Medial Lemniscal Pathway
The DMCL carries the sensory modalities of:
• Fine touch
• Vibration sense
• Proprioception
The name
• In the spinal cord, information travels via the dorsal (posterior) columns.
• In the brainstem, information is transmitted through the medial lemniscus.
First second and third order neurones are involved in this pathway.
First order
The first order neurones carry sensory information regarding touch, proprioception or vibration from the peripheral nerves to the medulla oblongata.
Arm = above T6 Leg = Below T6
• Signals from the upper limb (T6 and above) – travel in the fasciculus cuneatus (the lateral part of the dorsal column). They then synapse in the nucleus cuneatus of the medulla oblongata.
• Signals from the lower limb (below T6) – travel in the fasciculus gracilis (the medial part of the dorsal column). They then synapse in the nucleus gracilis of the medulla oblongata.
Second Order Neurones
• The second order neurones begin in the cuneate nucleus or gracilis. The fibres receive the information from the preceding neurones, and delivers it to the third order neurones in the thalamus.
• Within the medulla oblongata, these fibres decussate. They then travel in the contralateral medial lemniscus to reach the thalamus.
Third Order Neurones
• Lastly, the third order neurones transmit the sensory signals from the thalamus to the ipsilateral primary sensory cortex of the brain.
Dorsal column-medial lemniscus (DCML) spinal tract
Dorsal column-medial lemniscus (DCML)
The DCML pathway transports information about vibration, proprioception and fine touch. Information from these modalities is transported in the dorsal column, two large white matter tracts located between the dorsal grey horns of the spinal cord.
These dorsal columns are divided into two regions:
• Fasciculus gracilis (more medial): information from below T6-T8;
• Fasciculus cuneatus (more lateral): information from above T6-T8 but below the head.
Sensory Tracts in the Spinal Cord – Ascending and Descending Tracts
The central nervous system uses ascending and descending pathways to communicate with the external environment. Ascending pathways transport sensory information in afferent pathways from the body to the brain.
Descending tracts carry motor information in efferent nerves from upper motor neurons of cortical structures like the cerebellum and cerebrum. The descending tracts transmit this information to lower motor neurons, allowing it to reach muscles. Each pathway has upper motor neurons and lower motor neurons, typically neurons in descending tracts are UMNs and those leaving the spinal cord are LMNs.
Ascending:
• Dorsal column and the medial lemniscus (DCML)
• Spinothalamic tracts
• Spinocerebellar tracts
Descending:
• Pyramidal/ extra pyramidal tracts
• Corticospinal tracts
How are dorsal columns assessed in a neuro exam?
The dorsal columns are assessed by:
• Vibration: 128 Hz tuning fork
• Joint proprioception: small-joint movement (thumb, big toe)
• Light touch: cotton wool
Spinothalamic tract
Spinothalamic tract (anterolateral system)
The spinothalamic tract has two components, often referred to collectively as the anterolateral system. They are the anterior and lateral spinothalamic tracts (STT):
• Anterior STT: crude touch and pressure
• Lateral STT: pain and temperature
The nerve fibres cross at the anterior grey commissure at the level of the spinal nerve, but sometimes continue to cross in the 2-3 spinal levels superior
How are spinothalamic tracts assessed in a neuro exam?
The spinothalamic tracts are assessed by:
• Pain: pin-prick
• Temperature: cool and warm metal object
Spinocerebellar tracts
Spinocerebellar tracts
The spinocerebellar tracts transmit proprioceptive signals from the body to the brain. They transmit information about muscle stretch and the rate of muscle stretch from golgi tendon organs (GTO) and muscle spindle (MS) complexes. There are four of them:
• Dorsal (D) spinocerebellar: MS and some GTO from lower limb
• Cuneocerebellar (C): MS and some GTO from upper limb
• Ventral (V) spinocerebellar: GTO only from lower limb
• Rostral (R) spinocerebellar: GTO only from upper limb
There are three extra points to note with these pathways:
• The ventral spinocerebellar tract decussates twice, terminating in the IPSILATERAL cerebellum
• The other (spinocerebellar) tracts do not decussate and terminate in the IPSILATERAL cerebellum
• Each of these tracts can be group into the ventral spinocerebellar tract (ventral and rostral spinocerebellar tracts) and a dorsal spinocerebellar tract (cuneocerebellar and dorsal spinocerebellar tract)
The midbrain and superior cerebellar peduncle are only involved in the ventral spinocerebellar tract; the cuneocerebellar, and dorsal and rostral spinocerebellar all enter the cerebellum at the medulla through the inferior cerebellar peduncle
Corticospinal Tract (Part of the Pyramidal Tracts – Descending Tracts)
Pyramidal tracts
The pyramidal tracts are named as such due to their course through the pyramids of the medulla oblongata. The pyramidal tracts are responsible for the conscious, voluntary control of the body and face muscles.
They can be divided into two tracts that supply each of these areas:
• Corticospinal tract: cortex to spine (body)
• Corticobulbar tract: cortex to ‘bulb’ (Latin for ‘swelling or bulb of an onion’ like the head and neck)
Corticospinal Tract (Part of the Pyramidal Tracts – Descending Tracts)
Corticospinal tract (CST)
The CST communicates with three major cortical areas:
• Primary motor cortex: located in the precentral gyrus; execution of movements
• Premotor cortex: responsible for the control of behaviour, particularly of the trunk muscles
• Supplementary motor cortex: stabilisation and coordination of the body during bimanual movements
The fourth cortical area the CST communicates with is the posterior parietal cortex for integration with and modulation of incoming sensory information.
Neurons exiting the cerebral cortex in one of the three major regions above converge to form the white matter structure in the brain known as the internal capsule. The internal capsule is located between the basal ganglia and thalamus; two highly vascularised structures in the deep brain.
After passing through the internal capsule, the fibres continue to pass down through the centre of the crus cerebri of the midbrain, before entering the pons and medulla.
As the CST passes through the caudal medulla, it divides into the lateral and anterior corticospinal tracts:
• Lateral CST: decussate in the pyramid of the medulla
• Anterior CST: stay ipsilateral
These tracts then descend into the spinal cord, terminating in the ventral horn of the spinal cord where they synapse onto LMNs to supply the peripheral musculature.
The anterior CST remains ipsilateral and descends only to the cervical and upper thoracic spinal cord, where they decussate at the level of the nerve root they supply.
Management of an acute episode of MS
Management of an acute episode
NICE guidelines state that a relapse/attack can be diagnosed if a patient presents with:
• New symptoms or worsening of existing symptoms
• Subacute onset >24hrs
• Absence of fever/signs of active infection
Not all relapses require medical intervention.
If symptoms are severe, should consider medical intervention:
• Treatment of an acute attack/relapse requires high dose steroid therapy with methylprednisolone
○ 500mg Po for 5 days or 1g Po for 3-5 days
Plasmapheresis is also an option if the exacerbation is refractory to steroids
• Plasmapheresis → replacement of blood plasma. Take it out the vein, separate plasma from other cells, replace with plasma solution.
Flare ups may be caused by something other than an attack, such as an infection → treat underlying cause
Long term management of MS
Long-term management
Management of demyelinating process
Injectable disease-modifying agents:
• Beta-interferon
• Glatiramer acetate
Oral disease-modifying therapies (for relapsing MS):
• Dimethyl fumarate
• Fingolimod
• Cladribine
Monoclonal antibody therapies (treatment of RRMS):
• Alemtuzumab
• Natalizumab
** monoclonal antibodies carry dangerous side effects:
• Most notably, natalizumab can rarely cause progressive multifocal leukoencephalopathy via reactivation of the JC virus
Beta interferons
MS disease modifying drugs
Beta-interferons
• Recommended for treatment of ‘active’ relapsing MS → two or more relapses in the last two years
• How do beta-interferons work?
○ Your body makes its own interferons to dampen down inflammation. These are artificial interferons that reduce and my prevent inflammation that damages nerves in MS
Glatiramer acetate
MS disease modifying drug
Glatiramer acetate
• In England you can have this drug if:
○ You’ve had two relapses in the last two years
○ You’ve had one relapse in the last two years and MRI scans show new signs your MS is active
• How does glatiramer acetate work?
○ It is not clear how glatiramer acetate works. It seems to kill the immune cells that coat the myelin around nerves in the brain and spinal cord.
Dimethyl fumarate
MS disease modifying drugs
Dimethyl fumarate
• Recommended for people with ‘active’ relapsing MS. It won’t work if you don’t get relapses so you won’t be offered it if you have primary or secondary progressive MS
• How does dimethyl fumarate work?
○ Unsure on exact function, but it dampens down inflammation. May be helpful in reducing the inflammation that causes damage in the brain and spinal cord of people with MS
Fingolimod
MS disease modifying drugs
Fingolimod
• In England and Northern Ireland you can have it if:
○ You have the same or an increased number of relapses despite treatment with beta interferons, glatiramer acetate, dimethyl fumarate or teriflunomide
• How does fingolimod work?
○ T and B cells cause a lot of damage in MS. They normally kills viruses and bacteria that get into your body but in MS they damage your nerves.
○ Fingolimod stops them leaving you lymph nodes → means fewer get to the brain and spinal cord where they would attack the myelin
Cladribine
MS disease modifying treatment
Cladribine
• You can take cladribine if:
○ You have ‘highly active’ relapsing MS → two or more disabling relapses in the past year and MRI scans show you have more, or bigger lesions.
○ Despite taking a DMT, you’ve had a relapse in the past year and new or bigger lesions can be seen on your MRI scans
• How does cladribine work?
○ Kills T and B cells made by the immune system
○ Cladribine stops B cells especially from getting into the brain and spinal cord, so they cannot damage nerves there
Alemtuzumab
Disease modifying treatment for MS
Alemtuzumab
• Across the UK you can take alemtuzumab if you have relapsing MS and:
○ Despite already taking a DMT, you’ve still had a recent relapse and MRI scans show new signs that your MS is active
OR
○ You’ve had two or more relapses in the last year and you have new lesions on your MRI scans
• How does alemtuzumab work?
○ Kills T and B cells that attack the myelin in MS
○ Stops the cells from getting into the brain and spinal cord before they can damage the nerves there
Natalizumab
MS disease modifying treatment
Natalizumab
• In England you can have this drug if:
○ You have relapsing MS and you’ve had at least two relapses in the last year and MRI scans show new signs that your MS is active
• How does natalizumab work?
○ Sticks to T cells and stops them from getting into the brain and spinal cord where they would attack the myelin around the nerves there.
Symptom control of MS
Symptom control in advanced Multiple Sclerosis (MS) can be challenging due to the progressive nature of the disease and the wide range of symptoms that individuals may experience. Here are some common problems associated with symptom control in advanced MS:
1. Mobility Issues: As MS progresses, mobility can become severely impaired. Individuals may experience difficulty walking or may become wheelchair-bound. This can lead to a loss of independence and increased reliance on caregivers. Exercise can help to maintain activity and strength 2. Spasticity: Spasticity, or muscle stiffness and spasms, is a common symptom in advanced MS. It can be painful and limit range of motion, making daily activities more challenging. Spasticity and oscillopsia may be managed with baclofen or gabapentin 3. Fatigue: Fatigue is a pervasive symptom of MS and can become even more debilitating in advanced stages. Managing energy levels and finding ways to cope with extreme fatigue can be difficult. Fatigue may be managed with amantadine, modafinil or SSRI's 4. Pain: Pain can be a significant problem in advanced MS, and it may be neuropathic pain or related to musculoskeletal issues caused by mobility limitations. Neuropathic pain may be managed with medication (eg amitriptyline or gabapentin) 5. Bladder and Bowel Dysfunction: Advanced MS can lead to bladder and bowel control problems, including urinary urgency, incontinence, and constipation. These issues can be distressing and affect overall quality of life. Urge incontinence may be managed with antimuscarinic medications (eg solifenacin) 6. Cognitive Impairment: Cognitive changes, such as memory problems and difficulty with concentration and decision-making, can worsen in advanced MS, impacting daily functioning and independence. 7. Depression and Anxiety: Dealing with the progressive nature of MS and the challenges it presents can lead to increased rates of depression and anxiety in individuals with advanced MS. Depression may be managed with antidepressants, such as SSRI's 8. Swallowing Difficulties: Dysphagia, or difficulty swallowing, can occur in advanced MS, making it challenging to eat and increasing the risk of aspiration pneumonia. 9. Respiratory Issues: Weakness in the respiratory muscles can lead to breathing difficulties, especially during sleep. This can result in sleep apnea or a decreased ability to clear secretions from the airways. 10. Pressure Sores: Immobility and the inability to change positions easily can lead to pressure sores (bedsores), which can be painful and lead to serious infections. 11. Emotional and Social Isolation: The progressive nature of advanced MS can lead to social isolation and emotional distress due to limitations in mobility and participation in social activities. 12. Medication Management: Managing a complex medication regimen, including disease-modifying therapies, symptom management, and potential side effects, can be challenging. 13. Financial and Caregiver Burden: The cost of care for advanced MS and the strain it places on caregivers can be overwhelming for both individuals with MS and their families.
What is a lumbar puncture and what is it normally used for?
A lumbar puncture is usually required to obtain a sample of CSF for analysis. The most common indication for a diagnostic lumbar puncture is to investigate cases of suspected CNS infection (e.g. meningitis). CSF interpretation is also used to diagnose important non-infective pathologies, including subarachnoid haemorrhage.
Normal CFS and normal CFS ranges
Normal CSF
To understand CSF abnormalities in certain disease states, it is important to understand normal CSF composition.
Normal CSF is acellular. However, up to 5 white blood cells (WBCs) and 5 red blood cells (RBCs) per microlitre (µL) are considered normal after lumbar puncture.
White blood cell analysis in CSF usually separates WBCs into lymphocytes and polymorphonuclear leukocytes (PMNs).
PMNs include neutrophils, eosinophils, basophils and mast cells. In ‘normal’ CSF, WBCs should be predominantly lymphocytes. The presence of PMNs in the CSF, particularly neutrophils, suggests bacterial meningitis.
The blood-brain barrier is effective against large molecules (e.g. protein) but allows the passage of smaller molecules (e.g. glucose). As such, CSF is generally a low-protein fluid with copious glucose.
Normal CSF ranges (adults)
Appearance: clear and colourless
White blood cells (WBC): 0 – 5 cells/µL, predominantly lymphocytes.
Red blood cells (RBC): 0 – 5/µL
Protein: 0.15 – 0.45 g/L (or <1% of the serum protein concentration)
Glucose: 2.8 – 4.2 mmol/L (or ≥ 60% serum glucose concentration)
Opening pressure: 10 – 20 cm H2O
Bacterial meningitis and it’s CFS LP results
Bacterial meningitis
Bacterial meningitis typically presents with headache, fever, neck stiffness and photophobia. A characteristic non-blanching (petechial) rash is often present in meningococcal disease. Patients are often systemically unwell and require urgent treatment with IM/IV antibiotics following local antibiotic guidelines.3
Treatment should not be delayed to obtain CSF analysis. The presence of turbid CSF with high opening pressure, elevated polymorphonuclear leukocytes and low serum glucose is highly suggestive of bacterial infection. Gram stain and CSF culture / bacterial PCR confirm the diagnosis.
Gram staining
The appearance of causative bacterial organisms on Gram stain:3
• Gram-positive diplococci: pneumococcal infection (Streptococcus pneumoniae)
• Gram-negative diplococci: meningococcal infection (Neisseria meningitidis)
• Gram-positive rods / coccobacilli: listerial infection (Listeria meningitidis)
Viral meningitis and CFS results
Viral meningitis
Viral meningitis is typically more insidious in onset than bacterial infection but causes similar symptoms (headache, fever, neck stiffness and photophobia). Patients are less likely to be systemically unwell at the time of presentation. The most common causative agents are herpes viruses (HSV / VSV) and enteroviruses.5 Treatment is with an intravenous antiviral agent, most commonly aciclovir.
CSF with a markedly raised lymphocyte count and elevated protein but normal glucose is highly suggestive of viral infection. Diagnosis can be confirmed with a positive CSF viral PCR.
