Neuro Flashcards
wTypes of strokes:
Ischaemic stroke
Haemorrhagic stroke
Can also get a transient ischemic attack
What is a stroke
WHO definiton: rapidly developing clinical signs of focal/general disturbance of cerebral function with symptoms lasting 24hours or longer or leading to death, with no apparent cause other than vascular origin
patients with similar symptoms due to: tumours, subdural haemotoma, poisoning, trauma are not considered strokes
Stroke vs TIA
TIA: brief episode of neurological dysfunction typically lasting less than 1 hour (up to 24hour) with a vascular cause and with no evience of infarction (cell death) on imaging
Stroke: rapidly developing clinical signs of focal/general disturbance of cerebral function with symptoms lasting 24hours or longer or leading to death, with no apparent cause other than vascular origin
Ischaemic Stroke
87% of strokes are ischaemic
occurs due to blockage of blood flow
Ischaemic tissue is weaker and at a bleeding risk -> risk of haemorrhagic transformation
Mechanisms of ischaemic stroke
Circle of Willis anatomy
Signs and symptoms of ischaemic stroke (Bamford (oxford) classification)
Based on clinical findings
Internal carotids: Anterior circulation
Vertebral arteries: Posterior circulatoin
- Total Anterior Circulation Syndrome
Entire anterior circulation of one side - proximal middle cerebral artery often
All 3 of: 1. Unilateral motor/sensory deficit (2/3 of arm, leg, face)
2.Higher dysfunction: dyshagia, visuospatial disturbance, reduced consciousness
3.Homonymous hemianopia - Partial Anterior Circulation Syndrome
Part of anterior circulation of one side
2/3 of above symptoms
OR partial motor/sensory deficit (one limb)
OR higher dysfunction alone - Posterior Circulation Stroke
Can also involve cerebellum and brainstem
cerebellar signs
cranial nerve and contralateral motor and sensory deficits
bilateral motor/sensory deficits alone
isolated homonymous hemianopia - Lacunar Stroke Syndrome
Subcortical Infarcts <2cm
Occlusion of penetrating arteries
1.Pure motor
2.Pure Sensory
3.Ataxic Hemiparesis
4.Dysarthria/clumsy hand syndrome
5.Mixed Sensorymotor
Diagnosis for ischaemic stroke
Treatment for ischaemic stroke
Secondary Prevention of Ischaemic Stroke
What is a haemorrhagic stroke
15-20% are haemorrhagic
result from vessel rupture
Types of haemorrhagic stroke:
- Intracerebral haemorrhage
i)Intraparenchymal: bleeding within brain tissue
ii)intraventricular: bleeding into the ventricles - Subarachnoid haemorrhage
*These intracranial bleeds are considered strokes, others (epidural/subdural) are not considered strokes
Causes of intracerebral haemorrhage
hypertension
arteriovenous malformations
cerebral amyloid angiopathy
Vascular tumpurs
Vasculitis
Can also be secondary to an ischaemic Stroke
Causes of subarachnoid haemorrhage
85% of spontaneous subarachnoid haemorrhage are due to rupture of an aneurysm
-Anterior communicating artery 35%
-Internal Carotid 30%
-Middle Cerebral artery 22%
15% due to arteriovenous malformation, coagulopathy, intraparenchymal extension
Signs and symptoms of haemorrhagic stroke
Diagnosis of haemorrhagic stroke
Treatment/management for haemorrhagic stroke
- Stabilisation - e.g airway
- Blood Pressure
NICE: 1. Presentation within 6h and SBP 150-220mmHg -> reduce to 130-140mmHg and maintain for 7 days - Presentation after 6h or SBP 220mmHg + -> consider reducing to 130-140mmHg and maintain for 7 days
Exclusions:
1.Underlying structural cause (AVM, Aneurysm)
2.Low GCS (Below 6)
3.Likely to undergo neurosurgery
4.Poor prognosis
Agents used:
Labetalol
Nimodipine/nicardipine
Enalapril
Hydralazine
- Raised intracranial pressure
Positional change: Bed to 30
Osmotic agents: Mannitol
Hyperventilation therapy - Surgical
Decompressive craniectomy
Aspiration
Secondary Prevention of Haemorrhagic Stroke
What is a TIA (Transient Ischaemic Attack)
Brief period of ischaemia due to emboli/stenosis of brain in the carotid artery
Infarction is very unlikely in a TIA
Causes of TIA
Modifiable:
Alcohol
Hypertension
Smoking
Hyperlipidaemia
Diabetes Mellitus
Obesity
High Fat diet
Stress
Unmodifiable:
Age
Family History
Male
Pathogenesis
Emboli in carotid artery and plaques leads to impaired perfusion of brain tissue
Symptoms of TIA
Contralateral hemiparesis
Dysarthria
Vision problems
Gait disturbance
Carotid bruit on physical exam -> due to atherosclerosis of carotid artery
Diagnosis of TIA
Carotid ultrasound
CT of head
Treatment of a TIA
Aim is to prevent a stroke
-Antiplatelet medication: clopidagrel
-Decrease lipids via statins
Surgery: carotid endarterectomy (surgical removal of plaque and correction of stenosis if stenosis >70%)
Stroke Diagnosis
Acute Treatment/Management of Stroke
Chronic/Long Term Treatment of Stroke
Prevention of Stroke
What are stroke syndromes
Collections of signs and symptoms resulting from strokes in different regions of the brain/CNS
What does the anterior cerebral artery supply
medial & superior frontal and parietal lobes
corpus callosum
basal ganglia
Signs and symptoms of anterior cerebral artery stroke syndrome
- Contralateral weakness
Legs > Arm/Face
Motor homuniculus distribution - Contralateral Sensory deficits
- Abulia
Absence of willpower or the inability to act decisively - Speech Disturbance
Transcortical motor aphasia: non-fluent, difficulty intiating speech
Transcortical Mixed aphasia: speaking + comprehension impairment - Urinary Incontinence
Voluntary bladder control areas affected - Ipsilateral ataxia + contralateral leg weakness
- Bilateral ACA involvement
Bilateral leg weakness
Frontal disinhibition
-Primitive reflexes return e.g grasping, suck reflexes
-Personality changes
What does the middle cerebral artery supply
Temporal Lobe
Anterolateral Frontal lobe
Parietal Lobe
Middle Cerebral Artery - Superior division syndrome
Middle Cerebral Artery - Inferior Division Syndrome
Middle Cerebral Artery - Gerstmann Syndrome
Middle Cerebral Artery- Ataxic hemiparesis
No facial Involvement/speech disturbance
What does the posterior cerebral artery supply
Occipital lobe
Inferior Temporal Lobe
Thalamus
Midbrain
PCA Stroke Syndrome - Alexia without agraphia
PCA Stroke Syndrome - Unilateral Occipital Lobe
PCA Stroke Syndrome - Anton Syndrome (Cortical Blindness)
PCA Stroke Syndrome - Balint Syndrome
PCA Stroke Syndrome - Thalamic Pain Syndrome (Dejerine Roussy Syndrome)
PCA Stroke Syndrome - Claude Syndrome
PCA Stroke Syndrome - Weber Syndrome
Basillar/Vertebral Artery Stroke Syndrome
Types of Intracranial Haemorrhage
Extra-Axial Haemorrhage: Bleeding that occurs within the skull but outside the brain tissue
Epidural
Subdural
Subarachnoid
Intra Axial Haemorrhage (Inside Brain tissue)
Intracerebral
Intraventricular
What is an epidural haemorrhage?
Bleeding between the skull and the dura mater
Source of blood is often arterial (Middle meningeal artery)
Causes:
Skull fractures (70-95%). Head trauma includes: motor vehicle accidnet, fault, assault
Clinical Manifestations of an epidural haemorrhage
Altered consciouscness
Headache
Vomiting
Confusion/seizures
Aphagia
What is a subdural haemorrhage
Bleeding between the dura mater and subarachoid membrane
Source of blood often tearing of the bridging veins
Clinical Manifestations of a subdural haemorrhage
Coma (50%)
Lucid interval -> Progressive neuro decline -> Coma
What is a subarachnoid haemorrhage
Haemorrhage within arachnoid space
Source of blood from rupturing of aneurysm (cerebral artery)
Causes:
Rupture of sacular aneurysm -> subarachnoid haemorrhage
Clinical Mainfestations of subarachnoid haemorrhage
Sudden severe headache
Loss of consciousness/Seizure
Nausea/Vomiting
Meningismus
Types of intracerebral haemorrhage
Lobar haemorrhage
Thalamic haemorrhage
Pontine hameorrhage
Cerebellar haemorrhage
Intracerebral haemorrhage
Second most common cause of stroke
Aetiology:
Hypertension
Embolism
Brain tumour
Bleeding Disorder
Drugs
Clinical Manifestations
Neurological signs and symptoms (Depending on area)
Headache
Nausea/Vomiting
Decreased loss of consciousness
Intraventricular haemorrhage
Bleeding confined to the ventricular system of the brain
Most often occurs as a secondary phenomenon when intracerebral haemorrhage ruptures or when subarachnoid haemorrhage extends to the ventricles
Diagnosis of intracerebral haemorrhage
CT scan
MRI
Angiography
Treatment for intracerebral haemorrhage
Drugs
-for hypertension
-to relieve intracranial pressure
Surgery
-Craniotomy: part of skull removed to drain blood and relieve pressure
-Stereotactic aspiration: aspirate off blood and relieve pressure
Pathophisiology of intracerebral haemorrhage
Diagnosis of subarachnoid haemorrhage
Treatment of subarachnoid haemorrhage
Diagnosis of epidural haemorrhage
Treatment for epidural haemorrhage
Diagnosis for a subdural haemorrhage
Treatment for a subdural haemorrhage
What is multiple sclerosis?
Chronic and progressive autoimmune demyelinating disease of the nerve cells in the brain, spinal cord characterised by various neurological disorders
Cell-mediated (Type IV) hypersensitivity reaction
Pathophisiology of MS
Type IV hypersensitivity
1.T cell crosses blood brain barrier. Becomes activated by myelin
2.T cell changes blood brain barrier, expressing more receptors for immune cells to cross blood brain barrier
3. Cytokines (IL-1, IL-6, TNF - alpha, INF- gamma) released by T cells dilates blood vessels (allowing more cells to get in) and directly damages oligodendrocytes
4. Attracts B cells which produce antibodies that mark myelin sheath proteins, And macrophages which use those antibody markers to engulf and destroy oligodendrocytes.
5. Without oligodendrocytes, no myelin covers the neurons leaving sclera
6. Attacks happen in bouts
Early on: remyelination occurs
Overtime: Irreversible
Causes of MS
Types of MS
Charcot’s neurological triad
Symptoms of MS
Vary, depends on location of plaques
Affects 20-40 years old
Worsen over weeks;linger for months
Charcot’s neurological triad
Also (see pic)
Diagnosis of MS
Treatment for RRMS
Treatment for Progressive MS
What is Guillain-Barre Syndrome
Autoimmine demyelinating disorder that leads to progressive paralysis
Most common cause of acute flaccid, neuromuscular paralysis worldwide
Causes of Guillain-Barre Syndrome
Pathophysiology of Guillain-Barre Syndrome
Symptoms of Guillain-Barre Syndrome
Guillain-Barre Syndrome diagnosis
Treatment of Guillain-Barre Syndrome
What is Parkinson’s Disease
Neurodegenerative condition resulting from loss of dopaminergic neurons in the brain, characterised by associated motor symptoms
Part of brain involved in regulating motor signalling
Basal Ganglia
Direct vs Indirect pathway of basal ganglia
Direct facilitates movement
Indirect terminates movement
Pathophysiology of Parkinson’s Disease
Thought that the degeberation of neurons in substantia nigra pars compacta is due to the accumulation of Alpha’s Nuclein (protein involved in regulation of the synaptic vesicles and release of neurotransmitters)
Close Link to Lewys Body dementia
Signs and symptoms of Parkinson’s Disease
Appear when 50% of neurons have been lost
1.Bradykinesia
2.Rigidity (muscle stiffening): Cog wheel rigidity, Lead Pipe rigidity
3.Hypomimia - Expressionless Face
4.Tremors (Pill Rolling Tremor) - Mostly resting
5.Gait Disturbance - Shuffling gait. Also at an increased risk of falls
= Collectively these symtpoms are known as Parkinsonism (80% of Parkinsin’s Disease). Others include
-Drug induced
-Multi-system atrophy
-Progressive Supranuclear Palsy
-Normal Pressure Hydrocephalus
Other symptoms include:
6. Autonomic disturbance: Hypersalivation, constipation/incontinence
7. Cognitive Impairment
Causes of Parkinson’s Disease
Most cases are idiopathic
1.Genetics:
-2x risk in 1st degree relatives
-10-15% of cases are familial: Autosomal Dominant, Autosomal recessive
- Environmental
-Rural living
-Exposure to industrial chemicals
-Infections: Encephalitis - Age- mean age 60
-5-15% before 40
-1% of people over 60 - Males : Females (1.5:1)
Diagnosis of Parkinson’s Disease
Clinical Diagnosis
Movement Disorder Society Parkinson’s Disease Criteria:
1.Bradykinesia + Resting Tremor/Rigidity
+
2. 2 Supportive Criteria
+
3. No exclusion or red flag criteria
Dat Scan: Radioactive Isotope + SPECT scan
Treatment for Parkinson’s Disease
- Medication
- Deep Brain stimulation:
-Pulse generator placed under skin
-Electrodes placed in vicinity of basal ganglia
Parkinsons Disease: On/Off phenomenon
Initially medication may treat symptoms well however as time goes on there is less of an effect and the on/off phenomenon inevitably appears with the use of levodopa. Overtime the window for controlled symtpoms known as the on phase gets tighter. While off is a state of rigidity and uncontrolled symptoms. The switch from on to off and vice versa can happen quickly. This kinesias are involuntary movements that are a side effect that can occur when patients flip between on and off known as diphasic dyskinesia. It can also occur following levadopa medication giving peak dopamine levels known as peak dose dyskinesia.
What is Huntington’s Disease
Huntington disease, or HD, is a rare neurodegenerative disease that involves a repeated sequence of DNA that causes an abnormal protein to form, leading to abnormal movements and cognitive problems.
Autosomal Dominant genetic disorder
Cause of HD
Mutation in a single gene called huntingtin. This is a dominant mutation. Thus if 1 parent has the disease, their child has a 50% chance of developing it too.
The huntingtin gene contains a DNA sequence that consists of nucleotides (CAG) in repitition - known as trinucleotide repeat. When the gene is mutated an excess no of repeats can occur and a mutated form of huntington protein is created.
The higher the noof repeats the greater the risk of disease, and all people with 36 or more repeats in the huntingtin gene will develop Huntington’s disease. Mutated Huntingtin proteins ahve a tendency to group together, forming clusters within neuros that are not easily removed by brai enzymes. Accumulation in the brain is associated with increased neurodegeneration.
Symptoms of HD
Regions affected by Huntington’s
Diagnosis of Huntington’s Disease
MRI
EEG
Treatment for HD
What is dementia?
Progressive neurodegenerative disease characterised by cognitive decline that causes impairment in daily functioning
Types of dementia
1.Alzheimer’s Disease
2.Vascular dementia
3.Dementia with Lewy Bodies
4.Frontotemporal dementia
Signs and symptoms of dementia
Symptoms get progressively worse over time
Cognitive Decline >=1 of:
1.Memory
2.Executive Function
3.Language
4.Attention
5.Visuospatial function
Alzheimer’s disease
70% of dementia
Caused due to the accumulation of insoluble proteins in the brain:
beta amyloid plaques: extracellular
hyperphosphorylated Tau protein (normally involved in microtubules): intracellular neurofibrillary tangles
Beta amyloid may be found in non-dementia brains
-Increased quantity in Alzheimer’s
-Mostly hippocampus , parietal, temporal lobes
Symptoms of Alzheimer’s disease
1.Short term memory loss
2.Difficulty finding words
3.Disorientation
4.Poor insight
Vascular Dementia
Involves reduced blood flow to neurons giving ischaemia and cell death
1.Multi Infarct Dementia
Series of small strokes that together cause symptoms
- Subcortical dementia
Small penetrating arteries affected (small vessel disease) - Stroke related dementia
30% of ischaemic strokes
Function decreases in a step-wise manner
Risk Factors for Vascular dementia
1.Smoking
2.Diabetes
3.AF
4.Dyslipidaemia
5.Hypertension
6.Age
Risk doubles every 5 years
Risk Factors for Vascular dementia
1.Smoking Diabetes
Prominent symptoms of Vascular dementia
Impairment in :
Planning
Organising
Judgement occur early on
Dementia with Lewy Bodies
10%
Lewy Bodies: Spherical, intracellular deposits formed from alpha synuclein + ubiquitin
Primary abnormality in Parkinson’s Disease dementia
Symtpoms of dementia with Lewy Bodies
Core symptoms
1. Flucuating cognition
2. Visual hallucinations (2/3)
3. Parkinsonian Features: Bradykinesia, rigidity, falls, autonomic dysregulation(orthostatic hypotension, incontinence/constipation)
Suggestive symptoms
1.REM sleep disturbances
2.Sensitivity to antipyschotics
Frontotemporal dementia
Second most common dementia in under 65s: mean age of onset 53
Involved proteins:
1.TDP 43 (DNA binding protein)
2.Tau protein (microtubule protein)
Types:
1.Behavioural variant (BvFTD) Pick’s disease
Most common
Personality/behavioural changes early
-Disinhibition/social withdrawal
Pick Bodies: Spherical intracellular collections of tau fibrils
- Semantic Variant
Difficulty finding correct words
impaired comprehension
Fluent Aphasia
3.Non fluent variant
Progressively more hesitant speech
=2 + 3 are primary progressive aphasia
Risk Factors for dementia
- Age is the largest risk factor
-Age 65 = 2%
-Age 85 = 40% - Genetics:
-10-30% increased risk in 1st degree relative
-Early Onset dementia (<65years): Trisomy 21,
5% of alzheimer’s overall (and majority of early onset) has autosomal dominant inheritance with near complete penetrance
Early genes: Late genes: - APP Ch21 1. Apolipoprotein E: E4 variant (1 allele = 50%)(2 allele = 90%) 2. Presenilin 1 Ch14
- Presenilin 2 Ch 1
- Gender: F>M
- Cognitive Reserve
Social isolation
Left education early
Low job complexity - Vascular Risk Factors
Diagnosis of dementia
Post mortem brain biopsy traditionally only mode of confirmation
-Rarely done on living people
-PET scan can demonstrate histological features of Alzheimer’s
1.Clinical History + Physical Exam
2.Mental State Examination: MMSE/MOCA
3.Lab investigations:
Blood typically normal
Vitamin B12/Folate
Thyroid Function Tests
Electrolyte Panels
Infection (e.g Lyme’s disease + neurosyphilis)
- CT head
Exclusion of chronic intracranial bleed or normal pressure hydrocephalus
Cerebral atrophy - Genetic Testing
What is the most common cause of death in dementia
Pneumonia
Treatment for dementia
No cure currently
1 year mortality 30-40%. 5 year mortality 65%
1.Medication
Cholinesterase inhibitors: donepezil, galantamine, rivastigmine)
NMDA antagonists: memantine
= slow cognitive decline but effect on survival unclear
- Risk Reduction (Especially vascular)
- Behavioural + Environmental support
Maintain familiarity
Monitor personal comfort
Attention redirection
4.Mental Health Support
5.Aerobic exercise
Types of CNS infections:
Meningitis (bacterial, viral and fungal)
Encephalitis
What is meningitis
Inflammation of the leptomeninges (arachnoid and pia maters)
What is meningoencephalitis
Meningitis : Inflammation of the leptomeninges
+
Encephalitis : Inflammation of the brain
Pathophisiology of meningitis
Inflammation triggered by:
1.Autoimmune disease: Lupus
2.Adverse reaction to medication: Intrathecal therapy (injected directly into CSF)
3.Infection (most common): Neisseria meningitidis, Herpes simplex
2 routes an infection takes to reach CSF and leptomeninges
1.Direct spread (Pathogen gets inside skull/spinal column and penetrates the meninges and eventually CSF):
Through overlying skin
Up through nose
Anatomical defect: congenital (spina bifida). acquired (skull fracture)
2. Haemotogenous spread
Through binding to surface receptors/areas of damage/vulnerable spots
Pathogen recognised by CSF and produces more white blood cell. 1ul Greater than 5 WBC -> meningitis
Meningitis: Common causative organisms table
Symptoms of meningitis
Stiif and Painful Neck
Fever
Altered Mental Status
Headache
Photophobia & Phonophobia
Malaise & Fatigue
Nausea/Vomiting
Anorexia
Skin Rash
Cold Extremities
Papilledema: Swelling of optic nerve due to increased ICP
Seizures
Cranial Nerve Palsies
Diagnosis for meningitis
Kernig’s sign
Brudzinski’s sign
Lumbar puncture (needle between L3 & L4 takes CSF): Measure pressure, analyse WBC, protein & glucose
PCR: Look for HIV, Enterovirus, HSV, TB
Western Blot: Borrelia burgdorferi
Thin Blood Smear: Malaria
Treatment for meningitis
What is encephalitis?
Condition involving inflammation of the brain parenchyma
May be due to a variety of causes
Epidemiology & Risk Factors for developing encephalitis
Causes of encephalitis
Pathogenesis of encephalitis
Clinical Features of encephalitis
Other Features:
Meningitis signs and symptoms
Nuchal rigidity (“Stiff neck”)
Brudzinski’s sign
Kernig’s sign
Diagnosis of encephalitis
Treatment of encephalitis
Primary vs Secondary type headache
Tension type headache
Most ubiquitus headache and is the most common reason why OTC analgesics are purchased
Location: Bilateral
Character: Pressure or toghtness which waxes and wanes
Duration: Variable
Associated symptoms: None
Migraine headache
A disorder of recurrent attack
Location: Unilateral (70%)
Character:
gradual onset, crescendo pattern, moderate-severe intensity
Duration: 4-72 hours
Associated symptoms: nausea, vomiting, photophobia, phonophobia, aura
Cluster headache
Form of trigeminal autonomic cephalgia
0.1% of population
“Suicide headache” - excruciating
Unilateral -Eye/Temple
<4hr duration
Sweating, tearing, hypermia, ptosis, rhinorrhea, restlessness
Cyclical/Consistent timing
Precipitated by alcohol
More common in men and smokers
Episodic: episodes present on 7-365 days of the year with at least 1 month complete remission
Chronic: pain ongoing beyond 1 year, less than 1 month complete remission
Treatment :
Acute:
1. Oxygen therapy
2. Triptans
Prevention:
1. Verapamil (CCB)
2. Lithium
3. Topiramate
4. Deep Brain/Occipital Nerve stimulation
What is trigeminal neuralgia
Neurological condition involving recurrent episodes of facial pain
Pathophysiology of trigeminal neuralgia
Signs and symptoms of trigeminal neuralgia
Diagnosis of trigeminal neuralgia
Clinical diagnosis
MRI to rule out secondary causes (lesions)
Treatment for trigeminal neuralgia
1st line therapies:
Carbamazepine
Oxcarbazepine
What are seizures
Transient occurence of signs and symptoms due to abnormally excessive or synchronous neuronal activity within the brain
Classification of seizures
1st: where the seizure originated in the brain
Generalised: Involve both hemispheres of the brain
Focal: Originate from an area on one hemisphere
*If seizures begin on one hemisphere and then involve both sides, they are known as focal to bilateral seizures
2nd: whether or not patient keeps their awareness during the seizure
Generalised seizures are automatically considered to affect awareness, only applies to focal seizures
Focal Aware = Simple
Focal Unaware = Complex
3rd: Motor/Non-motor involvement during the seizure
Generalised seizures may feature stiffening and jerking
Focal Seizures can have movements twitching, jerking and stiffening + automatic movements like licking lips or rubbing hands
Focal seizures: one group of muscles may be affected but abnormal movement can spread to other muscle groups . Due to abnormal neuronal activity of brain also moving to a diff area - JACKSONIAN MARCH.
Generalised non-motor seizures are known as absent seizures where individuals will rpimarily have changes in awareness and stay
Focal non-motor seizures typically have other symptoms that happen first (aura) e.g changes in emotion/sexperiences/thinking
Types of generalised seizures
What is status epilepticus
> 5 mins seizure duration
Medical emergency
Benzodiazepine, phenytoin, phenobarbital
What is the postictal phase
Following a seizure there is a postictal phase
Lasts min-hours
Confusion
Tiredness
Headache
Speech difficulty
10% pyschosis
Amnesia
Causes of Seizures. Provoked or Unprovoked?
VITAMINS
Diagnosis of seizures
Management of seizures
- Follow up - specialist clinic
Antiepileptic drugs: valproate, lamotrigine, levetiracetam
Differential diagnosis for seizures
What is an upper motor neuron
Neuron located within brain/brainstem
Axon travels down spinal cord
Innervates alpha & gamma motor neurons in ventral horn
What is a lower motor neuron
Alpha & Gamma motor neurons located in the ventral horn of the spinal cord
Axon travels to periphery to innervate muscle
UMN vs LMN lesions
Signs of upper vs lower motor neuron lesions
What is myastenia gravis
Acquired autoimmune condition involving neuromuscular blockade and subsequent muscle weakness
It is a type II hypersensitivity reaction
Most common neuromuscular junction disorder affecting skeletal muscles
Classic presentation of myasthenia gravis
Fluctuating muscle weakness and fatigue of heavilt used muscle groups
-Worsens with activity and improves with rest
-Weakness worse in the afternoon hours
-Weakness involves muscles of the eyes, extremities and throat
Extraocular Muscle Weakness
-Ptosis, Diplopia (often none in morning): Unilater or bilateral
-Often intial finding
-Most common symptom
Ocular MG -> Generalised MG
Continuing see pic
Pathophysiology of myasthenia gravis
Autoantibodies produced against acetylcholine receptors & other muscle components
Myasthentic crisis
Myasthenia gravis : exacerbating factors
Types of myasthenia gravis
Differential Diagnosis of Myasthenia Gravis
Lamber-Eaton Syndrome (Paraneoplastic)
Guillain Barre Syndrome
Motor Neuron Disease
Course of Myasthenia Gravis
Investigations for Myasthenia Gravis
Treatment for Myasthenia Gravis
What is motor neurone disease
Cluster of major degenerative diseases
Characterised by selective loss of neurons in motor cortex, cranial nerve nuclei and anterior horn cells
Upper and lower motor neurones are affected, but there’s NO sensory loss or sphincter disturbance – distinguishes from MS and polyneuropathies
Never affects eye movements – distinguishes from myasthenia
Relentless and unexplained destruction of upper motor neurones and anterior horn cells
Most will die in 3yrs from respiratory failure due to bulbar palsy and pneumonia
Causes of motor neurone disease
Most are sporadic with no family history
Rare familial cases
Mutations in the free radical scavenging enzyme copper/zinc superoxide dismutase (SOD-1)
Suggests that oxidative stress and free radicals play a role in destruction of motor neurones
Clinical presentation (symptoms and signs) of motor neurone disease
4 clinical patterns:
ALS/amyotrophic lateral sclerosis – 50%
Loss of motor neurons in motor cortex AND anterior horn of cord
Weakness + UMN signs e.g. upgoing planters
+ LMN wasting/fasciculation
Worse prognosis if – bulbar onset, older, reduced FVC
Split hand sign- thumb’s side of the hand seems to separate from the rest owing to excessive wasting around it
Progressive bulbar palsy – 10%
Only affects cranial nerves IX-XII
LMN lesion of the tongue and muscles of talking and swallowing –
Flaccid, fasciculating tongue
Jaw jerk is normal or absent
Speech is quiet, hoarse or nasal
Progressive muscular atrophy – 10%
Anterior horn cell lesion only
No UMN signs
Affects distal muscle groups before proximal
Primary lateral sclerosis
Loss of Betz cells in motor cortex
Mainly UMN signs
Marked spastic leg weakness and pseudobulbar palsy
No cognitive decline
Suspect MND in
>40yrs
Stumbling spastic gait, foot-drop ± proximal myopathy
Weak grip and shoulder abduction
UMN signs – spasticity, brisk reflexes, upgoing plantars
LMN signs – wasting, fasciculation of tongue, abdomen, back, thigh
Diagnostic tests and results for motor neurone disease
Brain/spinal cord MRI excludes structural causes
Lumbar puncture excludes inflammatory ones
Treatment for motor neurone disease
Antiglutamatergic drugs – riluzole
Drooling – propantehline, amitriptyline
Dysphagia – blend food, NG tube
Spasticity – baclofen, diazepam
Joint pains and distress – follow analgesic ladder
Respiratory failure – non-invasive ventilation at home may allow palliation
What is a spinal cord compression
Metastatic spinal cord compression (MSCC) is an oncological emergency that describes when tumours (usually having spread from another part of the body) grow in the spinal column and compress the spinal cord.
L1-L2 anything below is cauda equina syndrome
Causes of spinal cord compression
Spinal metastases
-Lung
-breast
-myeloma
-lymphoma
-prostate
Signs and symtpoms of spinal cord compression
Diagnosis of spinal cord compression
MRI
Management of spinal cord compression
What is cauda equina syndrome
Cauda equina syndrome is a condition caused by damage to the bundle of peripheral nerves protruding from the bottom of the spinal cord, called the cauda equina.
Causes of cauda equina syndrome
Symptoms of cauda equina syndrome
Diagnosis of cauda equina syndrome
Treatment of cauda equina syndrome
Spinal cord lesions summary
What is syncope
Reversible loos of consciousness due to inadequate blood flow to the brain
-Fast onset
-Short duration
-Spontaneous recovery
Causes of syncope
Diagnosis of syncope
Causes of syncope (PASS OUT)
symptoms of syncope
Blacking out.
Feeling lightheaded.
Falling for no reason.
Feeling dizzy.
Feeling drowsy or groggy.
Fainting, especially after eating or exercising.
Feeling unsteady or weak when standing.
Changes in vision, such as seeing spots or having tunnel vision.
Headaches.
Treatment for syncope
Medicines for syncope include:
Midodrine.
Fludrocortisone
Limb neuropathies..
- Carpal tunnel syndrome
- ‘Wrist drop’
- ‘Claw hand’
- ‘Foot drop’
What is carpal tunnel syndrome
Cindition involving impingement (or entrapment) of the median nerve in the wrist
Most common entrapment neuropathy
Pathophysiology of carpal tunnel syndrome
Median nerve becomes compressed in the carpal tunnel due nto bone growth and/or soft tissue proliferation
Risk factors for carpal tunnel syndrome
Clinical Features of Carpal Tunnel Syndrome
Diagnosis of Carpal Tunnel Syndrome
Treatment for carpal tunnel synrome
What is a foot drop? (Peroneal Nerve Injury)
The patient is unable to lift the front of the foot up due to weakness or paralysis of the tibialisi anterior muscle which lifts the foot up
Signs of a foot drop
When the patient with foot drop walks, the foot slaps down onto the floor
Steppage gait means that the patient slaps his foot down onto the floor because the foot drops, and his gait will show that he is raising the thigh up in an exagerrated fashion while walking
Causes of a foot drop
Usually results from an injury to the common peroneal nerve. This nerve is susceptible to injury at any point of its course
Conditions causing foot drop:
1.L4-L5 disc herniation: Herniated disc compressing the L5 nerve root may cause foot drop
2.Lumbrosacral plexus injury can occur from a pelvic fracture with displacement of the sacriliac joint
3.Hip/Knee dislocation
4.Neglected compartment syndrome
Systemic causes: diabetes, ischaemia, inflammatory conditions
Causes of a foot drop
Usually results from an injury to the common peroneal nerve. This nerve is susceptible to injury at any point of its course
Conditions causing foot drop:
1.L4-L5 disc herniation: Herniated disc compressing the L5 nerve root may cause foot drop
2.Lumbrosacral plexus injury can occur from a pelvic fracture with displacement of the sacriliac joint
3.Hip/Knee dislocation
4.Neglected compartment syndrome
Systemic causes: diabetes, ischaemia, inflammatory conditions
Treatment of foot drop
Non operative treatment:
Observation
Therapy
Stretching
Range of motion of the ankle
AFO bracing
Surgery:
Nerve repair/grafting if there is laceration of the nerve
If the injury is chronic, you will do a posterior tibial tendon transfer to the lateral cuniform, in addition to achilles tendon lengthening
Split posterior tibial tendon transfer
What is wrist drop
characterisitic deformity of a radial nerve lesion
The wrist remians in the palamr flexion due to weakness of the dorsiflexions. It is seen in radial nerve palsy
Causes of wrist drop
Radial nerve = big
Trauma
-Shoulder dislocation
-Fractures (Humerus, supracondylar, monteggia)
Compression
-Saturday Night Palsy
-Crutch Palsy
Treatment for wrist drop
Tendon transfer operation
What is claw hand
Ulnar nerve palsy
Claw hand is a condition that causes curved or bent fingers
Causes of claw hand
Causes may include:
Congenital abnormality
Genetic diseases, such as from Charcot-Marie-Tooth disease
Nerve damage in the arm
Scarring after a severe burn of the hand or forearm
Rare infections, such as leprosy
Diagnosis of claw hand
Medical History
Physical Examination
Electromyography
Treatment for claw hand
Physical therapy
Surgery
What causes amaurosis fugax
Atherosclerotic emboli in the eye
Heart disease, especially irregular heartbeat
Alcohol abuse
Cocaine use
Diabetes
Family history of stroke
High blood pressure
High cholesterol
Increasing age
Smoking (people who smoke one pack a day double their risk for a stroke)
Amaurosis fugax can also occur because of other disorders such as:
When can amaurosis fugax occur
Amaurosis fugax can also occur because of other disorders such as:
Other eye problems, such as inflammation of the optic nerve (optic neuritis)
Blood vessel disease called polyarteritis nodosa
Migraine headaches
Brain tumor
Head injury
Multiple sclerosis (MS), inflammation of the nerves due to the body’s immune cells attacking the nervous system
Systemic lupus erythematosus, an autoimmune disease in which the body’s immune cells attack healthy tissue throughout the body
What is Lambert-Eaton Syndrome
Rare Autoimmune Neuromuscular junction disorder -> presynaptic neurons
This is due to a decreased Ach release and therefore reduced contraction
Improves temporarily after repeated use
Majority of Lambert-Eaton Syndrome cases are associated with
Small Cell Lung Cancer
Also associated with:
Hashimoto’s thyroiditis
Diabetes Mellitus type 1
Causes of Lambert-Eaton Syndrome
Autoimmune response against voltage-gated Ca2+ chnnels
Affects somatic and parasympathetic nervous system
Type II hypersensitivity reaction: antibody production against its own protein
Antibodies bind and block most Ca2+ channels: Low Ca2+ with neuron -> no Ach release -> no muscle contraction
With repeated stimulation -> enough Ca2+ gets through -> Ach release -> muscle contraction
Signs and symptoms of Lambert-Eaton Syndrome
Symmetrical weakness of proximal muscles
-Shoulders, hips and thighs
-Difficulty climbing stairs and standig up
Reduced reflexes
Warming-up phenomenon: weakness is relieved temporarily after repeated use
Advanced stages: weakness in the respiratory muscles -> respiratory failure
Most have autonomic symptoms: dry mouth, constipation, blurred vision, urinary problems, fainting
Diagnosis of Lambert Eaton Syndrome
Treatment of Lambert Eaton Syndrome
What is brown Sequard Syndrome
Condition that results from damage (resection) to one half of the spinal cord on either side
This hemisection causes damage of the spinal cord tracts
This syndrome results in weakness or paralysis (hemiparaplegia) on one side of the body and a loss of sensation (hemianesthesia) on the opposite side
Damages:
Descending Corticospinal tracts
Ascending dorsal column tracts
Spinothalamic tracts
How does sensory stimuli reach brain
A sensory stimuli passes through three neurons
The lateral branch of the 1st order neuron carries info to the dorsal root
The second order neuron crosses over to the opposite side of the spinal cord
Third order neuron located in the ventral posterior region of the thalamus to the sensory cortex of the brain
What causes Brown Sequard Syndrome
Symptoms of Brown Sequard Syndrome
Diagnosis of Brwon Sequard Syndrome
MRI
Treatment of Brown Sequard Syndrome
What is Charcot-Marie-Tooth syndrome
Group of hereditary, progressive neurlogical disorders of the PNS, impaired sensory/motor function
Inherited
Worsen overtime
Pathophysiology of Charcot-Marie-Tooth Syndrome
Defective proteins in myelin sheath or axon -> signals fail to reach target tissues: sensory & motor
Types of Charcot-Marie-Tooth Syndrome
CMT1: Autosomal dominant
Mutations in PMP22 & MPZ: Encode proteins part of myelin sheath (made by schwann cells)
Slows down electrical impulses
CMT2: Autosomal dominant
Mutations in MFN2: Encodes Mitofusin-2 (expressed in neuronal mitochondria)
When defective: mitochondrial function (-> neuronal death)-> disrupted
in both CMT1 & CMT2, motor neurons are affected, muscles begin to atrophy (“use it or lose it”). When sensory nerves are affected the feet and toes are first affected
Symptoms of Charcot-Marie-Tooth Syndrome
Diagnosis of Charcot-Marie-Tooth
Treatment of Charcot-Marie-Tooth
Duchenne muscular Dystrophy (D mnemonic)
Diagnosis of duchenne muscular dystrophy
presence of risk factors
imbalance of lower limb strength
lower extremity musculotendinous contractures
delayed motor milestones
Diagnostic investigations of duchenne muscular dystrophy
Treatment for muscular dystrophies
stage 1: ambulatory
1ST LINE –
corticosteroids
stage 2: non-ambulant
1ST LINE –
supportive therapies to maintain activities of daily living
stage 3: ventilator-supported
1ST LINE –
inspiratory and expiratory respiratory muscle assistance
What is depression
A mental state of low mood
Diagnostic and Statistic Manual of Mental Disorders (DSM V)
Causes/Risk Factors of depression
Multifactorial
1. Genetics
High concordance rates in twins
Family History
- Environmental
Stressful life events
Childhood abuse
Substance abuse/medical conditions
Diasthesis-Stress model:
See pic
Pathophysiology of depression
Not entirely understood
- Monoamine theory: lack of monoamine neurotransmitters (serotonin, dopamine, norepinephrine)
Decrease in serotonin is not equal to depression in healthy individuals
Anti-depressants restore levels quickly, but take weeks to improve clinical symptoms - Hypothalamic-Pituitary Axis Disturbance
Increase Cortisol, decrease dexamethasone suppression
Link to growth + thyroid hormones - Immune system
Excessive cytokine release
Improvement of symptoms with NSAIDs
Close link between asthma and depression
Epidemiology of depression
- Lifetime risk ~ 12%
- Female : Male 2:1
Different pyschosocial pressures
Hormonal Diff - Mean onset ~ 40 years
Becoming increasingly common in younger ages
Diagnosis of depression
Treatment for depression
Combinations more effective
1.Lifestyle
2.Pyschotherapy *Favoured in U18s: CBT, interpersonal therapy
3.Medication:
SSRI: Setraline, citalopram, fluoxetine
SNRI: Duloxetine, venlafaxine
Atypical: mitrazapine
TCA (amitriptyline)
MAOI (selegiline)
Vit D
COX-2 inhibitors (Celecoxib)
- Electroconvulsive therapy
Electrically Induced Seizure
50% effective in treatment resistant MDD. 50% relapse in 12 months
Primary vs Secondary brain tumours
Primary: Tumour in the brain that arose from associated tissue
Secondary: Tumour in the brain that metastasised there from elsewhere
Types of primary brain tumours
Glioma
Meningioma
Pituitary adenoma
Clinical Presentation of primary brain tumours
Progressive focal neurological deficit: Symptoms depend on location (frontal lobe -> personality change etc). Speed of deterioration is proportional to growth of tumour Raised intracranial perssure: Headaches (worse on cough/leaning forward), vomiting and papilloedema. Epilepsy: Focal or generalised General cancer symptoms: Weight loss, malaise, anaemia etc
False localising signs: Raised ICP or the presence of a tumour can cause healthy structures to affect adjacent ones. E.g., Downward displacement of temporal lobe -> III or VI CN palsy
Pathophysiology of primary brain tumours
Progressive focal neurological deficit: Mass effect of the tumour and oedema -> impact functionality of site associated with tumour. Can destroy tissue -> rapid deterioration Raised ICP: As tumour grows -> downward displacement of the brain -> pressure on the brainstem (drowsiness) -> respiratory depression -> coma -> death. False localising signs possible (see left) Epilepsy: Tumour creates unusual electrical impulses -> seizures
Causes of primary brain tumours
Derived from the skull itself, or adjacent structures. 95% of primary tumours are Gliomas or Meningiomas (others include neurofibromas and lymphomas)
Causes of secondary brain tumours
Metastases from: Bronchus, Breast, Kidney, Thyroid, Stomach, Prostate
Epidemiology of Primary brain tumour
About 10% of all neoplasms
Diagnosis of primary brain tumour
CT and MRI. Positron Emission Tomography to find occult metastasis
Treatment of primary brain tumours
Surgery: Exploration, removal or biopsy (meningiomas can be fully removed without incident)
Radiotherapy: Gliomas and radiosensitive metastases
Medical: Cerebral oedema can be reduced with corticosteroids. Epilepsy treated with anticonvulsants.
What is peripheral neuropathies
Neuropathy of the peripheral nerves
Types of peripheral neuropathies
3 types: autonomic, motor and sensory
Clinical Presentation of peripheral neuropathies
Can be asymptomatic. Diabetes: Long history of paresthesia (glove stocking), pain, weakness and wasting, autonomic symptoms; incontinence, sexual dysfunction). Usually present as foot ulcers (constant damage due to paresthesia)
Pathophysiology of peipheral neuropathies
Diabetes: Hyperglycaemia damages 3 cell types; retinal endothelium, mesangial cells in glomeruli and schwann cells in perpheral nerves (these cell types cannot regulate their glucose well, so constant hyperglycaemia causes excessive oxidation -> damage)
Aetiology of peripheral neuropathies
Acute: Guillain barre Chonic: Diabetes, alcohol
Diagnosis of peripheral neuropathies
Nerve conduction studies. FBC. Diabetes: As in DM
Treatment for peripheral neuropathies
Diabetic control. Amitriptyline for neuropathic pain.
