Neurology Flashcards
Define Alzheimer’s Disease
Alzheimer’s disease is a chronic, neurodegenerative disorder characterized by the progressive accumulation of abnormal protein deposits, primarily amyloid plaques and tau tangles, in the brain.
This leads to the deterioration of cognitive function, memory loss, and various behavioural and psychological symptoms.
Define Dementia
Define MCI
- A state characterised by impairment of 2 or more cognitive domains
- presenting for more than 6 months
- severe enough to impact on function
- That is not primarily attributable to underlying condition
MCI: impairment of 1 or more cognitive domain that is not severe enough to impact function
What is the Epidemiology of Alzheimer’s Disease?
Increasing prevalence with age
Women more commonly affected than men
APOE Gene
Alzheimer’s is the most common cause of dementia (>50%)
What is the pathophysiology of Alzheimer’s Disease?
Amyloid Plaques: The accumulation of beta-amyloid protein fragments outside nerve cells in the form of plaques is a hallmark feature. These abnormal protein deposits are believed to disrupt neuronal communication, trigger inflammation, and ultimately lead to cell death.
Tau Tangles: Inside nerve cells, abnormal tau protein accumulates, forming neurofibrillary tangles.
Neuronal Loss and Brain Atrophy: As the disease progresses, significant neuronal loss occurs, particularly in brain regions responsible for memory and cognitive function, such as the hippocampus and the cerebral cortex.
Give some risk factors for Alzheimer’s Disease
Age: Advanced age is the most significant risk factor >65yrs
Genetic Predisposition: apolipoprotein E (APOE) gene, Down’s syndrome
Family History: Having a first-degree relative with Alzheimer’s disease
Cardiovascular Risk Factors: Conditions like hypertension, diabetes, obesity, and hypercholesterolemia
Lifestyle Factors: Physical inactivity, smoking, and a diet high in saturated fats may contribute to increased risk.
Traumatic Brain Injury: A history of head injuries, particularly repeated concussions, has been linked to a higher risk of developing Alzheimer’s disease.
Low Educational Attainment: Lower levels of education may be associated with an increased risk.
What are some clinical features of Alzheimer’s Disease?
Cognitive impairment
- memory loss
- generally affects recent events more than distant memories
- difficulty learning new information
- the person may defer to family members when answering questions,
- vague with dates
- problems with reasoning and communication
- difficulty in making decisions/executive function
- nominal dysphasia
Behavioural and Psychological Symptoms of Dementia (BPSD):
- Aggitation
- Depression
- Psychosis
- Apathy
- Disinhibition
Give some examples of behavioural changes you may see in Alzheimer’s Disease?
Agitation
Aggression
Apathy
Mood swings
Irritability
Give some examples of Psychological symptoms you may see in Alzheimer’s Disease?
Hallucinations
Delusions
Paranoia (in later stages)
What are some differential Diagnoses for Alzheimer’s Disease?
Vascular Dementia
Lewy Body Dementia
Frontotemporal Dementia
Mild Cognitive Impairment (MCI)
Normal Age related Decline
What are the first line investigations for Alzheimer’s Disease?
History - Cognitive decline questionnaire (MMSE)
Examination - Neurological Exam
Blood tests - Confusion Screen
What are the lab tests involved in a confusion screen?
- FBC (e.g. infection, anaemia, malignancy)
- U&Es (e.g. hyponatraemia, hypernatraemia)
- LFTs (e.g. liver failure with secondary encephalopathy)
- Coagulation/INR (e.g. intracranial bleeding)
- TFTs (e.g. hypothyroidism)
Calcium (e.g. hypercalcaemia) - B12 + folate/haematinics (e.g. B12/folate deficiency)
- Glucose (e.g. hypoglycaemia/hyperglycaemia)
- Blood cultures (e.g. sepsis)
What are the diagnostic investigations for Alzheimer’s Disease?
Once reversible courses of confusion are eliminated and dementia is still suspected:
Brain imaging - MRI or PET scan
CSF Analysis
What is the management of Alzheimer’s Disease?
Non-pharmacological:
- Psychological Interventions
- Cognitive stimulation therapy
Pharmacological:
- Acetylcholinesterase inhibitors (Donepezil or Rivastigmine)
- NDMA antagonists (memantine)
- If they have BPSD - low dose anti-psychotic (risperidone)
There is no curative treatment
Define Parkinson’s Disease?
Parkinson’s disease is a chronic, progressive, degenerative neurological condition
There is a progressive reduction in dopamine in the basal ganglia which leads to disordered control of bodily movements.
What is the epidemiology of Parkinson’s disease?
The second most common neurodegenerative disorder after Alzheimer’s disease
What is the aetiology of Parkinson’s disease?
Unknown however the pathophysiology is well established and correlated to lewy body dementia
What are some risk factors for developing Parkinson’s Disease?
Male (twice as common)
Increasing age (>65 years)
Family History - though it isn’t a genetic condition this can increase risk
Previous Head injury
What are some protective factors for Parkinson’s disease?
Smoking
Caffeine intake
Physical activity
What is the characteristic triad of Parkinson’s disease?
Resting tremor
Rigidity (resisting passive movement)
Bradykinesia (slowness of movement)
What are the clinical features of Parkinson’s disease?
Motor Features:
- Asymmetrical Pin-rolling Tremor - worse on one side
- Rigidity - “Cogwheel Rigidity, Lead pipe arm”
- Bradykinesia - Shuffling gait, Micrographia, Poverty of movement
Other Features:
- REM Sleep Behaviour Disturbance and insomnia
- Anosmia (loss of sense of smell)
- Autonomic Dysfunction - Postural hypotension, constipation and ED.
- Psychiatric features - Depression, Hallucinations, Anxiety
- Postural instability (a Late feature of Parkinson’s)
- Hypomimia (lack of facial expression)
What are some different presentations of Bradykinesia in Parkinson’s disease?
- 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)
Symmetry, Hertz, At Rest, Movement, Additional features, Alcohol
What are the features of the Parkinson’s Tremor?
Asymmetrical
4-6 Hertz
Worse at rest
Improves with intentional movement
Additional Features Present
No change with Alcohol
Symmetry, Hertz, At Rest, Movement, Additional features, Alcohol
What are the features of a Benign Essential Tremor?
Symmetrical
6-12 Hertz
Improves at rest
Worse with intentional movement
Additional Features Absent
Improves with Alcohol
What are some Parkinson’s-Plus Syndromes?
What are the characteristic features?
Multiple System Atrophy
- Presents with early autonomic dysfunction
- Constipation, Postural hypotension, Sweating, Sexual dysfunction.
- Postural instability compared to PD
Lewy Body Dementia
- Early and prominent cognitive dysfunction before parkinsonism traits.
- Visual Hallucinations
Progressive Supranuclear Palsy
- Verticle Gaze Palsy
- Postural instability
Corticobasal Degeneration
What are some differential Diagnoses for Parkinson’s Disease?
- Benign Essential Tremor
- Multiple System Atrophy (MSA): Very prominent autonomic dysfunction, early postural instability, poor response to levodopa
- Dementia with Lewy Bodies (DLB): Early and prominent cognitive dysfunction, visual hallucinations, fluctuating cognition
- Progressive Supranuclear Palsy (PSP): Early gait instability and falls, vertical gaze palsy, prominent axial rigidity
- Corticobasilar Degeneration: May have predominant apraxia, aphasia and ‘alien hand’ syndrome
- Normal Pressure Hydrocephalus (NPH): Presents with Magnetic gait, urinary incontinence and memory problems
- Wilson’s Disease: May be associated with signs of liver disease
- Dementia Pugilistica: Secondary to repeated head trauma
What are some side effects of Levodopa?
LEVODOPA:
Lunacy - psychosis, hallucinations
End dose weaning
inVoluntary movements - dyskinesia, Chorea, Athetosis
Orthostatic hypotension
Dry mouth/drooling
On off phenomenon
Palpitations
Anorexia
Give an example of a Catechol-o-methyltransferase (COMT) inhibitor?
Entacapone
Tolcapone
Give an example of a Monoamine Oxidase B (MOA) inhibitor?
Selegiline
Rasagiline
What are the investigations for Parkinson’s Disease?
Parkinson’s disease is primarily a clinical diagnosis, supported by positive response to treatment trials.
An absolute failure to respond to 1-1.5g of levodopa daily almost excludes a diagnosis of idiopathic Parkinson’s disease.
Other investigations such as MRI Head or a Dopamine Transporter Scan (DaT scan) can be considered in atypical cases.
The NICE guidelines recommend that the diagnosis is made using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria
What is the management of Parkinsons?
Motor Sx
Persistent Sx
Non-responsive
Motor Symptoms significantly affecting QoL
- First line: Levodopa (often in combination with decarboxylase inhibitors is first line)
- Dopamine agonists tend to be added later down the line for most people.
Motor Symptoms not affecting QoL
- Dopamine Agonists (non-ergot derived)
- Levodopa (+decarboxylase inhibitors)
- Monoamine Oxidase Inhibitors
Patients have symptoms despite optimal Levodopa Treatment then use adjuncts:
- Dopamine Agonists
- MOA inhibitors
- COMT inhibitors
- Amantadine (when motor symptoms persist and adjuncts haven’t helped)
If people have fluctuating symptoms but tend to respond well to medications then you can use Deep Brain Stimulation to improve the length of time the medications work for
Give Some examples of Dopamine Agonists and a key side effect?
Non-Ergo:
- Rotigotine
- Ropinirole
- Apomorphine
Non-ergo DAs are used in parkinsons disease
Ergot:
- Bromocriptine
- Pergolide
- Cabergoline
Side effect of Pulmonary Fibrosis in prolonged use of Ergot dopamine agonists hence no the main ones used are non-ergot
All can cause hallucinations and impulse disorders (Gambling)
Define Essential Tremor?
Benign essential tremor is a relatively common condition chronic neurological condition associated with older age.
Autosomal Dominant Inheritance in > 50% of cases
It is characterised by a fine tremor affecting all the voluntary muscles. It is most notable in the hands but can affect other areas, for example, causing a head tremor, jaw tremor and vocal tremor.
What is the Epidemiology of Essential Tremor?
ET is one of the most prevalent movement disorders, with the incidence increasing with age.
The condition may manifest at any age, from childhood to adulthood.
The age of onset tends to be earlier in those with a positive family history.
What is the Aetiology of Essential Tremor?
Aetiology is complex and not fully understood
Multifactorial - Genetic and Environmental Factors
50% of cases - ET is inherited via an Autosomal Dominant Trait
What are some medications combined with levodopa?
What are some medications for the autonomic features of Parkinson’s?
Levodopa is always combined with Dopa-Decarboxylase inhibitors to prevent peripheral metabolism of L-Dopa
Levodopa (combined with Decarboxylase inhibitors Carbidopa / Benserazide)
- Co-beneldopa (levodopa and benserazide), with the trade name Madopa
- Co-careldopa (levodopa and carbidopa), with the trade name Sinemet
Specific Autonomic Symptoms
- REM Sleep disorder: Modafinil
- Orthostatic Hypotension: Midodrine
- Drooling: Glycopyrronium bromide
What are the clinical Features of Essential Tremor?
A postural or kinetic tremor, which predominantly affects the upper limbs distally.
Additional symptoms may include:
- Involvement of the head, lower limbs, voice, tongue, face, and the trunk, although less common.
- Increased tremor amplitude over time, causing difficulty with tasks such as writing, eating, holding objects, dressing, and speaking.
- Exacerbation of tremor during situations of anxiety, stress, and social interaction.
- Potential development of severe psychosocial disability, including depression, particularly in patients with head and voice tremors.
Improved with Alcohol Consumption
What are some differential diagnoses for Essential Tremor?
- Parkinson’s disease: Resting tremor, bradykinesia, rigidity, postural instability.
- Hyperthyroidism-associated tremor: Palpitations, heat intolerance, weight loss, anxiety.
- Dystonic tremor: Abnormal posturing, muscle contractions, worsened by voluntary movement.
What are the investigations for Essential Tremor?
Mainly a Clinical Diagnosis
Further investigations, such as blood tests or neuroimaging, may be warranted to rule out other potential causes of tremor.
What is the Management of Essential Tremor?
No definitive treatment for Essential Tremor
Medications that may improve symptoms are:
- Propranolol is first line
- Primidone (a barbiturate anti-epileptic medication)
- Topiramate
Define Motor Neurone Disease?
Motor neurone disease is a term that encompasses a variety of specific diseases affecting the motor nerves.
Motor neurone disease is a progressive, eventually fatal condition where the motor neurones stop functioning.
There is no effect on the sensory neurones. Sensory symptoms suggest an alternate diagnosis.
What is the epidemiology of MND?
2:1 Male predominance
Mean age of Onset 50-60 yrs
90% of cases are Sporadic with only 10% familial
Notable overlap with Frontotemporal Dementia
What are some potential genetics of MND?
Associated with the misfolding of the TDP-43 Protein
2% of cases associated with a mutation in the SOD-1 gene
What are some risk factors for MND?
Increased age >60 yrs
Male
FHx
Smoking
RUGBY
What is the most common type of Motor neurone Disease?
Amyotrophic Lateral Sclerosis (ALS)
Accounts for 50% of cases
What are the different types of MND?
Amyotrophic Lateral Sclerosis (ALS): UMN and LMN signs
Progressive Muscular Atrophy (PMA): LMN signs only (best prognosis)
Primary Lateral Sclerosis (PLS): UMN signs only
Progressive Bulbar Palsy (PBP): CN9-12 affected. Speech and swallowing issues (worst prognosis)
What is the Pathophysiology of MND?
Degenerative condition selectively affecting motor neurons (cortical and bulbar tracts) mainly in the anterior horn cells, motor cortex or cranial nerve nuclei
There is relentless and UNEXPLAINED destruction of UMN and anterior horn cells in the brain and spinal cord
Causes both UMN and LMN dysfunction
- UMN and LMN affected but no sensory or sphincter loss – distinguishes from MS
- Never affects eye movements – distinguishable from myasthenia gravis
What are the signs of Upper Motor neuron lesions?
Hypertonia
Rigidity + spasticity
Hyperreflexia
Babinski Reflex Positive - Big toe goes up when stroking foot
Power:
Arms - Flexors > Extensors
Legs - Flexors < Extensors
What are the signs of Lower Motor neuron lesions?
Hypotonia
Flaccidity + muscle wasting
Hyporeflexia
Fasciculations
Babinski Reflex Negative - big toe goes down when stroking foot
Generally loss of power
What is not affected in MND?
Eye muscles and Sphincters generally spared (affected in MS and Myasthenia Gravis)
Sensory function (affected in MS and polyneuropathies)
Give a characteristic presentation of MND?
The typical patient is a late middle-aged (e.g., 60) man,
possibly with an affected relative.
There is an insidious, progressive weakness of the muscles throughout the body, affecting the limbs, trunk, face and speech.
The weakness is often first noticed in the upper limbs. There may be increased fatigue when exercising.
They may complain of clumsiness, dropping things more often or tripping over. They can develop slurred speech (dysarthria).
What are the clinical signs of MND?
- Fasciculations
- Asymmetric limb weakness is common in ALS
- Mixed UMN and LMN signs
- Dysarthria / Dysphagia
- Split Hand Sign - Disproportionate wasting of thenar muscles compared to hypothenar muscles.
What are some differential Diagnosis of MND?
- Multiple Sclerosis
- Myasthenia Gravis
- Thyrotoxicosis
- Brainstem lesions (TIA/Stroke)
- Cervical Spondylopathy
- Paraproteinaemias
How is MND Diagnosed?
What are some observed findings?
The diagnosis needs to be made very carefully. It is based on the clinical presentation after excluding other conditions. It should only be made by a specialist when there is certainty. The diagnosis is often delayed, causing stress.
- LMN/UMN signs in 3 regions
- Nerve conduction studies will show normal motor conduction and can help exclude a neuropathy.
- Electromyography shows a reduced number of action potentials with increased amplitude.
- MRI is usually performed to exclude the differential diagnosis of cervical cord compression and myelopathy
What are some investigations to rule out reversable differential diagnoses of MND?
TFTs: Rule out Thyrotoxicosis
Protein Electrophoresis: Rule out Paraproteinemia’s
MRI brain and spinal cord: Assess for brainstem lesions or Cervical Spondyloarthropathy
EMG and Nerve conduction studies: Rule out Myasthenia gravis or multifocal mononeuropathy.
What is the management of MND?
Symptom control?
No effective treatments for halting or preventing progression of MND
Riluzole can slow progression by a couple of months
NIV (non-invasive ventilation) BIPAP can be used to support breathing
PEG is the preferred way to support nutrition
Symptom Control:
- MDT input
- Baclofen for muscle spasticity
- Benzodiazepines for breathlessness due to anxiety
What is the prognosis of MND
What are some management considerations to make due to the prognosis?
- PMA has the best prognosis
- PBP has the worst prognosis
- Average prognosis is 2-3 years after diagnosis
Considerations
- Breaking bad news effectively and supportively
- Multidisciplinary team (MDT) input to support and maintain their quality of life
- Symptom control (e.g., baclofen for muscle spasticity and antimuscarinic medical for excessive saliva)
- Benzodiazepines may help breathlessness worsened by anxiety
- Advanced directives to document their wishes as the disease progresses
- End-of-life care
Define Multiple Sclerosis (MS)
Multiple sclerosis (MS) is a chronic and progressive autoimmune condition involving demyelination in the central nervous system.
The immune system attacks the myelin sheath of the myelinated neurones.
What is the pathophysiology of MS?
Multiple sclerosis affects the central nervous system (the oligodendrocytes)
- Type IV Hypersensitivity Rxn
- T-cell mediated – T cells activate B cells to produce auto-antibodies against Basic myelin protein of oligodendrocytes
- The Abs will bind to the basic myelin protein and target oligodendrocytes for destruction by macrophages
- T Lymphocytes manage to cross the BBB, they can cause a cascade of destruction to the neuronal cells (oligodendrocytes) in the brain by recruiting other immune cells
- This results in plaques of demyelination and inflammation and therefore conduction disruption along axons
- In early disease, the myelin sheath can regenerate and symptoms somewhat resolve, however the new myelin is less efficient and temperature dependent
- Therefore Symptoms are exacerbated by heat
What are some causes of MS?
The cause of the multiple sclerosis is unclear, but there is growing evidence that it may be influenced by:
Multiple genes
Epstein–Barr virus (EBV)
Low vitamin D
Smoking
Obesity
What is the Epidemiology of MS?
- 3 times more common in women
- most commonly diagnosed in people aged 20-40 years
- much more common at higher latitudes (5 times more common than in tropics)
What is characteristic about the symptom onset in MS?
- Symptoms usually progress over more than 24 hours.
- 75% have significant Lethargy
- Symptoms tend to last days to weeks at the first presentation and then improve.
- Later in the disease the symptoms become more permanent
There are many ways MS can present, depending on the location of the lesions.
What is the most common presentation of MS?
Optic Neuritis: demyelination of the optic nerve and presents with unilateral reduced vision, developing over hours to days
Key features include:
- Central scotoma (an enlarged central blind spot)
- Pain with eye movement
- Impaired colour vision
- Relative afferent pupillary defect
What are some other causes of Optic Neuritis?
Sarcoidosis
Systemic lupus erythematosus
Syphilis
Measles or mumps
Neuromyelitis optica
Lyme disease
What are the clinical manifestations of MS?
Visual
Sensory
Motor
Cerebellar
Other
Visual
- optic neuritis: common presenting feature
- optic atrophy
- Uhthoff’s phenomenon: worsening of vision following rise in body temperature
- internuclear ophthalmoplegia
Sensory
- pins/needles
- numbness
- trigeminal neuralgia
Lhermitte’s syndrome: paraesthesiae in limbs on neck flexion
Motor
- spastic weakness: most commonly seen in the legs
Cerebellar
- ataxia: more often seen during an acute relapse than as a presenting symptom
tremor
Others
- urinary incontinence
- sexual dysfunction
- intellectual deterioration
What is Uhthoff’s Phenomenon?
A worsening of neurological symptoms related to a demyelinating disorder such as multiple sclerosis when the body overheated in hot weather, exercise, fever, saunas, or hot tubs
What are the classifications of MS?
Multiple sclerosis may be divided into two groups:
Relapsing-remitting (which may become secondarily progressive)
Primary progressive
- Relapsing remitting MS makes up 80% of disease at presentation, compared with primary progressive which is <10%.
- The remaining 10% fall into a difficult to classify intermediate group of progressive-relapsing disease.
What investigations are done in MS?
2 main tests?
Other?
Clinical History and Examination
MRI Scan
- high signal T2 lesions
- periventricular plaques
- Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum
Lumbar Puncture
- IgG Oligoclonal Bands in CSF
Visual Evoked Potentials
- Delayed but well preserved waveform
What diagnostic Criteria is used in MS?
McDonald Criteria:
- 2 or more attacks + 1 Objective clinical Lesion
OR
- 1 attack + 2 Objective clinical Lesions
Objective clinical lesions must be disseminated in time and space demonstrated by MRI or positive CSF findings
For the purposes of the McDonald’s criteria, there must be lesions in two of the four regions of the central nervous system which satisfy dissemination in space; juxtacortical, subcortical, infratentorial and spinal cord.
What is the Acute management for MS?
Glucocorticoids
- 500mg orally daily for 5 days
- 1g Methylprednisolone intravenously daily for 3–5 days (where oral treatment has previously failed or where relapses are severe)
What is the Chronic management of MS?
Additional Management?
Disease Modifying therapies:
Biologics:
- Natalizumab is first line
- Ocrelizumab, Alemtuzumab
Symptomatic Control:
- Exercise to maintain activity and strength
- Fatigue may be managed with amantadine, modafinil or SSRIs
- Neuropathic pain may be managed with medication (e.g., amitriptyline or gabapentin)
- Depression may be managed with antidepressants, such as SSRIs
- Urge incontinence may be managed with antimuscarinic medications (e.g., solifenacin)
- Spasticity may be managed with baclofen or gabapentin
- Oscillopsia may be managed with gabapentin or memantine
What may indicate a worse prognosis in MS?
Older age of Onset
Male Gender
Primary Progressive MS
High relapse rate
Smoking
Comorbidities
Define Muscular Dystrophy
Muscular dystrophy refers to a group of inherited genetic disorders characterized by the progressive degeneration and weakening of the body’s muscles.
The disease is categorized into various types, the most common being Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy, distinguished primarily by the severity and onset age.
What is the Epidemiology of Muscular Dystrophy?
- The most common form of muscular dystrophy is Duchenne muscular dystrophy (1 in 3,500-6,000 male births)
- Becker muscular dystrophy is less common, (1 in 18,000-30,000 male births)
These conditions are X-linked recessive disorders, males are predominantly affected while females are usually carriers.
What is the aetiology of Muscular Dystrophy?
Mutations in the dystrophin gene, leading to reduced expression of dystrophin, a crucial protein involved in muscle contraction and stability.
In Duchenne’s, the protein is virtually absent
In Becker’s, the protein is expressed at lower levels or the protein is dysfunctional.
What are the clinical features of Duchenne’s Muscular Dystrophy?
- Presents in early childhood with muscle wasting and weakness
- Children usually become wheelchair-bound before puberty and often succumb to respiratory failure by their early twenties
- May present with hypertrophic calves, as degenerated muscle is replaced by fat
- Notable signs include a positive Gower’s manoeuvre and difficulty in lifting the child due to proximal muscle weakness
What are the clinical features of Becker’s Muscular Dystrophy?
- Presents later in childhood with muscle wasting and weakness
- Patients commonly become wheelchair-bound in their teens and can survive into their thirties
What are some differential Diagnoses for Muscular Dystrophy?
Limb-Girdle Muscular Dystrophy: Characterized by weakness and wasting of the proximal muscles, specifically around the hips and shoulders. (autosomal inheritance)
Spinal Muscular Atrophy
Myopathies
What are the investigations for Muscular Dystrophy?
- Creatine Kinase Measurement - First line screening as levels are significantly raised in muscular dystrophy
- Genetic Testing is Gold standard for diagnosis
- Muscle Biopsy
What is the management of Muscular Dystrophy?
MDT input to maximise quality of life and minimise disease progression.
- Glucocorticoids slow muscle degeneration
- Physical Therapy to maintain mobility
- Genetic Counselling
What is the prognosis of Muscular Dystophy?
- Patients with Duchenne’s muscular dystrophy typically survive into their early twenties
- Patients with Becker’s muscular dystrophy can live into their thirties.
- The leading causes of mortality are respiratory complications and dilated cardiomyopathy.
Define Huntington’s Chorea?
Huntington’s disease (also called Huntington’s chorea) is an autosomal dominant genetic condition that causes progressive neurological dysfunction.
What is the epidemiology of Huntington’s disease?
It is one of the most common hereditary neurodegenerative disorders
1 in 10,000-20,000
What are the Genetics of Huntington’s disease?
It is a trinucleotide repeat disorder involving a genetic mutation in the HTT gene on chromosome 4, which codes for the huntingtin (HTT) protein.
CAG > 38 repeats
Give some examples of other Trinucleotide repeat disorders?
Fragile X syndrome
Spinocerebellar ataxia
Myotonic dystrophy
Friedrich ataxia
What is Anticipation in genetics?
Anticipation is a feature of trinucleotide repeat disorders, where successive generations have more repeats in the gene, resulting in:
Earlier age of onset
Increased severity of disease
What is the pathophysiology of Huntington’s disease?
Faulty Huntingtin protein builds up in the striatum causing cell death and loss of cholinergic and GABA-nergic neurons 🡪 decreased ACH and GABA synthesis in striatum
Less GABA causes less regulation of dopamine to striatum causing increased dopamine levels resulting in excessive thalamic stimulation and subsequently increased movement (chorea)
What is the presentation of Huntington’s disease?
Features typical develop after 35 years of age
- chorea
- personality changes (e.g. irritability, apathy, depression) and intellectual impairment
- dystonia
- saccadic eye movements
- Dysarthria/Dysphagia
What are the movement disorders associated with Huntington’s disease?
Chorea (involuntary, random, irregular and abnormal body movements)
Dystonia (abnormal muscle tone, leading to abnormal postures)
Rigidity (increased resistance to the passive movement of a joint)
Eye movement disorders
Dysarthria (speech difficulties)
Dysphagia (swallowing difficulties)
What are some differential Diagnosis for Huntington’s disease?
Parkinson’s disease: Characterized by bradykinesia, resting tremor, rigidity, and postural instability
Wilson’s disease: Presents with liver disease, Kayser-Fleischer rings in the eye, and neurological symptoms such as dystonia, tremor, and dysarthria
Huntington’s disease-like disorders (HDL1, HDL2, HDL3, and HDL4): Present with a similar clinical picture but have different genetic backgrounds
Neuroacanthocytosis syndromes: Characterized by movement disorders and spiculated red blood cells (acanthocytes)
What are the investigations for Huntington’s disease?
Neuroimaging: MRI and CT scans may show loss of striatal volume and an enlarged frontal horn of the lateral ventricles in severe disease stages.
Genetic Testing: confirmatory and allows for predictive testing in at risk family members
What is the management of Huntington’s disease?
No curative or preventative treatments
- Breaking bad news effectively and supportively
- Genetic counselling regarding relatives, pregnancy and children
- Multidisciplinary team (MDT) input to support and maintain their quality of life
- Physiotherapy to improve mobility, maintain joint function and prevent contractures
- Speech and language therapy where there are speech and swallowing difficulties
- Tetrabenazine may be used for chorea symptoms
- Antidepressants (e.g., SSRIs) for depression
- Advanced directives to document their wishes as the disease progresses
- End-of-life care
What is the prognosis for a patient with Huntington’s disease?
What are the common complications?
The prognosis for Huntington’s disease is poor, with an invariable decline in physical and cognitive abilities.
Death usually occurs due to complications:
Aspiration pneumonia
suicide is the second most common cause of death
Define a Brain Abscess?
A brain abscess is a pus-filled swelling in the brain.
It usually occurs when bacteria or fungi enter the brain tissue after an infection or severe head injury.
Causes of Brain Abscesses?
- Extension of sepsis from middle ear or sinuses,
- Trauma or surgery to the scalp
- Penetrating head injuries
- Embolic events from endocarditis
What are the clinical features of Brain Abscesses?
The presenting symptoms will depend upon the site of the abscess (those in critical areas e.g. motor cortex) will present earlier. Abscesses have a considerable mass effect in the brain and raised intracranial pressure is common.
- headache - often dull, persistent
- fever - may be absent and usually not the swinging pyrexia seen with abscesses at other sites
- focal neurology - e.g. oculomotor nerve palsy or abducens nerve palsy secondary to raised intracranial pressure
Other features consistent with raised intracranial pressure
- Nausea
- Papilloedema
- Seizures
What are the investigations for a Brain Abscess?
- FBC
- ESR/CRP
- Neuroimagining: MRI may show a ring enhancing lesion with surrounding oedema
What is the management for a Brain Abscess?
Surgery: a craniotomy is performed and the abscess cavity debrided
IV antibiotics: IV 3rd-generation cephalosporin + metronidazole
Intracranial pressure management: e.g. dexamethasone
Define Meningitis?
Inflammation of the meninges from both infective and non-infective causes.
This is a notifiable condition to PHE
What are the different infective causes of Meningitis?
Viral:
Enterovirus (coxsackie)
HSV2
VZV
Bacterial:
N. Meningitidis
S. pneumonia
Fungal: Cryptococcus Neoformans (primary in the immunosuppressed population)
Parasitic: Amoeba, Toxoplasma Gondii
What is the most common cause of meningitis in children and adults?
Neisseria meningitidis
Streptococcus pneumonia
What is the most common cause of meningitis in neonates?
Group B Streptococcus - Streptococcus Agalactiae
E.coli
Strep. pneumonia
Listeria
What are some non-infective causes of Meningitis?
- Malignancies such as leukemia, lymphoma, and other tumors
- Chemical meningitis
- Certain drugs, including NSAIDs and trimethoprim
- Systemic inflammatory diseases such as sarcoidosis,
- Systemic Lupus Erythematosus, Behcet’s disease.
What is the most common cause of meningitis?
Viral infection (Most commonly enteroviruses)
More common but less severe than bacterial causes.
What are the main risk factors for meningitis?
Extremes of age (Infant/elderly)
Immunocompromised
Pregnancy
Travel
Crowded environment - barracks/uni
Non-vaccinated
What vaccines are available for meningitis coverage?
N. Meningitidis - Men B + Men C + Men ACWY
S. pneumoniae - PCV Vaccine
What are the symptoms of Meningitis?
Meningism:
Headache, Fever, Neck stiffness
Non-Blanching Purpuric Rash
Nausea + Vomiting
Seizures
Photophobia
Purpuric Rash - Bacterial Meningitis
Non-Blanching Purpuric Rash - Meningococcal Septicaemia
What does the Non-blanching Purpuric Rash indicate in Meningitis?
Bacterial Meningococcal Septicaemia:
This rash indicates the infection has caused disseminated intravascular coagulopathy (DIC) and subcutaneous haemorrhages.
What is the presentation of Meningitis in Neonates?
Neonates and babies can present with very non-specific signs and symptoms:
- Hypotonia
- Poor feeding
- Lethargy
- Hypothermia
- Bulging Fontanelle.
What are the clinical signs of meningitis?
Kernig’s Sign:
When the hip is flexed and the knee is at 90°, extension of the knee results in pain
Brudzinski Sign:
Severe neck stiffness causes the hips and knees to flex when the neck is flexed
What are the primary investigations in meningitis?
1st Line: Bloods
FBC - raised WCC
CRP - raised
Blood glucose - compared with CSF
Blood culture - to determine viral/bacterial
CT Head - Look for Brain Lesions/Abscesses/CIs for LP
Lumbar Puncture (LP) + CSF Analysis (Gold Standard)
What are some contraindications for a lumbar puncture?
Raised ICP
GCS <9
Focal Neurological signs
In Paediatric cases of fever and general unwellness what does NICE recommend as an important investigation?
A Lumber Puncture in all children:
- Under 1 month presenting with fever
- 1 to 3 months with fever and are unwell
- Under 1 year with unexplained fever and other features of serious illness
Where is a lumbar puncture usually taken from?
Between L3/L4
Since spinal cord ends L1/2
What are some differential diagnoses for Meningitis?
- Encephalitis
- Subarachnoid Haemorrhage
- Brain Abscess
- Sinusitis
- Migraine
What would the results of CSF analysis be in Bacterial, Viral and Fungal Meningitis?
Fungal:
- Lymphocytosis
- Increased Protein Concentration
- Decreased Glucose Concentration
What is the management of Bacterial Meningitis in the community?
STAT dose of IM Benzylpenicillin and immediate transfer to hospital
In True Penicillin allergy then immediate transfer to hospital
What is the management of Bacterial Meningitis in the Hospital?
Ideally perform a blood culture and a lumbar puncture prior to starting Abx unless the patient is acutely unwell.
Broad Spec Abx - Cover All Likely Organisms:
1st Line - Ceftriaxone or Cefotaxime (as they get through the BBB)
WTIH OR AFTER
IV Dexamethasone - Prevent neurological sequelae
2nd Line: Chloramphenicol
Once Blood cultures have been done then can tailor Abx:
Eg. IV Benzylpenicillin for N.Meningitidis
What antibiotics should be used to treat bacterial meningitis in children?
Under 3 Months: Cefotaxime and Amoxicillin (covers for listeria)
Over 3 Months: Ceftriaxone
What Post Exposure Prophylaxis should be done in Meningitis cases?
Contact Tracing:
- This risk is highest for people that have had close prolonged contact within the 7 days prior to the onset of the illness.
- The risk decreases 7 days after exposure. Therefore, if no symptoms have developed 7 days after exposure they are unlikely to develop the illness.
A single dose of ciprofloxacin. It should be given as soon as possible and ideally within 24 hours of the initial diagnosis.
What is the management of Viral Meningitis?
Usually only requires Supportive treatment
Acyclovir can be used to treated suspected or confirmed HSV/VZV infections
What are some complications of Meningitis?
- Hearing loss is a key complication
- Seizures and epilepsy
- Cognitive impairment and learning disability
- Memory loss
- Cerebral palsy, with focal neurological deficits such as limb weakness or spasticity
- Septic Shock and DIC
- Coma and Death
Define Encephalitis?
Encephalitis is a pathological condition characterised by inflammation of the brain parenchyma, also known as the “encephalon”.
What is the aetiology of Encephalitis?
- Predominantly Viral Infection
- Bacterial and fungal pathogens can also lead to encephalitis (Rarely in the UK)
- Autoimmune Encephalitis - NMDA receptor antibodies
What are the most common Viral causes of Encephalitis?
Herpes Simplex Virus Type 1 (HSV-1)
Others:
- HSV-2
- CMV
- EBV
- VZV
- HIV
What are the clinical features of Encephalitis?
Altered Mental Status
Fever
Flu-like prodromal illness
Seizures
Acute onset Focal neurological deficits
Headaches
Behavioural changes
What investigations are done in Encephalitis?
Encephalitis should be suspected in any patient presenting with sudden onset behavioural changes, new seizures, and unexplained acute headache
- A routine panel of blood tests
- Blood cultures and viral PCR
- Lumbar Puncture + Cerebrospinal fluid (CSF) analysis with viral PCR
- Consideration for malaria blood films in case of exposure risk
CNS Imaging: CT/MRI
What may be seen on MRI in Encephalitis?
Temporal lobes affected
Bilateral Multifocal Haemorrhage
What is the management of Encephalitis?
Intravenous antiviral medications are used to treat the suspected or confirmed underlying cause:
Aciclovir treats herpes simplex virus (HSV) and varicella zoster virus (VZV)
Ganciclovir treats cytomegalovirus (CMV)
Supportive management of complications:
Anti-convulsant for seizures
What are some side effects of Aciclovir?
Common
- Generalised fatigue/malaise
- Gastrointestinal disturbance
- Photosensitivity and urticarial rash
Others:
- Acute renal failure
- Haematological abnormalities
- Hepatitis
- Neurological reactions
What are some complications of Encephalitis?
Lasting fatigue and prolonged recovery
Change in personality or mood
Changes to memory and cognition
Learning disability
Headaches
Chronic pain
Movement disorders
Sensory disturbance
Seizures
Hormonal imbalance
Define Guillain-Barre Syndrome?
Guillain-Barré syndrome is an acute immune-mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni)
What is the pathophysiology of GBS?
Guillain-Barré is thought to occur due to a process called molecular mimicry.
Antibodies against the pathogen aslo react to gangliosides (anti-ganglioside antibodies) which are components of cell membranes and myelin sheath.
This leads to demyelination and a peripheral polyneuropathy
What are the clinical forms of GBS?
- Acute inflammatory demyelinating polyneuropathy
- Acute motor axonal neuropathy
- Acute Sensory and motor axonal neuropathy
- Miller-Fisher variant characterised by ophthalmoplegia, ataxia, and areflexia
What is Miller-Fischer Syndrome?
Variant of Guillain-Barre syndrome
associated with ophthalmoplegia, areflexia and ataxia.
- The eye muscles are typically affected first
- Usually presents as a descending paralysis rather than ascending
- Anti-GQ1b antibodies are present in 90% of cases
What is the Aetiology of GBS?
Typically occurs 1-3 weeks following an infection
- Campylobacter jejuni
- Cytomegalovirus
- Epstein Barr Virus
What is the symptomatic progression of GBS?
- Gastroenteritis
- 1-3 weeks later: Neurological Symptoms start
- 2-4 weeks later: Symptoms Peak
- Months to years: Recovery period
What are the clinical features of GBS?
Symptoms occuring 3-4 weeks post infection:
- Progressive ascending symmetrical limb weakness
- Lower back pain due to radiculopathty
- Paraesthesia preceding motor symptoms
- hyporeflexia
- Cranial Nerve Signs - Ophthalmoplegia, facial nerve palsy.
- Autonomic Dysfunction - Urinary retention, diarrhoea, Arrhythmias
- Potential respiratory distress in severe cases
What are some differential Diagnoses for Guillain Barre Syndrome?
Brainstem strokes
Polio
Lyme Disease
CMV
HIV
TB
Transverse Myelitis
Myasthenia Gravis
Lambert Eaton Myasthenic Sydrome
What criteria is used to diagnose GBS?
Brighton Criteria
What are the investigations for GBS?
First line
Other?
Nerve Conduction studies
- Reduced signal conduction velocity
- Prolonged distal motor latency
- Increased F wave latency
Lumbar Puncture + CSF analysis
- raised protein with normal cell count and glucose
Other:
- Spirometry
- Monitoring of FVC for respiratory muscle involvement
- Serological - Anti-ganglioside antibodies
What is the management of GBS?
Management for Severe cases: (eg inability to walk)
- IV Immunoglobulins are first line
- Plasmapheresis is second line
Other:
- Supportive care
- VTE Prophylaxis - TEDS + LMWH
- Monitoring FVC for respiratory failure
- Analgesia - NSAIDS or Opiates for Radiculopathy pain
- Manage complications
What is the leading cause of death in GBS?
Pulmonary Embolism hence the VTE prophylaxis
What is the prognosis of GBS?
Recovery can take months to years
Most patients make a fully recovery
5% mortality due to respiratory or cardiovascular complications
Define Bulbar Palsy?
A subtype of lower motor neurone lesion impacting the Glossopharyngeal, Vagus and Hypoglossal cranial nerves.
This leads to impairments of speech and swallowing
What is the aetiology of Bulbar Palsy?
- Motor Neurone Disease - primarily PBP
- Myasthenia Gravis
- Guillain Barre Syndrome
- Brainstem Stroke - Lateral medullary Syndrome or Wallenberg’s Syndrome
- Syringobulbia - Fluid-fillled cavity within the spinal cord.
What are the clinical features of Bulbar Palsy?
- Absent or normal Jaw Jerk Reflex
- Absent Gag Reflex
- Flaccid fasciculating tongue
- Nasal speech (often quiet)
- Signs of the underlying cause
What are some differential diagnoses for Bulbar palsy?
- Pseudobulbar Palsy: Upper motor neurone lesion of cranial nerves causing dysarthria and dysphagia
- Brainstem tumour
- Multiple Sclerosis
- Polymyositis and Dermatomyositis: Muscle weakness of the pharyngeal muscles
What are the investigations for Bulbar Palsy?
Aim at establishing underlying aetiology
- Neurological Examination - Cranial Nerve Exam
- EMG and Nerve Conduction Studies - Help diagnose MG or MND
- Blood tests and antibody screening
- MRI to identify brainstem lesions or presence of a syrinx
- Lumbar puncture to rule out infective or autoimmune causes
What is the management of Bulbar Palsy?
Symptomatic relief and management of underlying cause
- Speech and swallowing therapy
- Nutritional support due to Dysphagia and poor oral intake
- Regular Monitoring to assess progression and manage complications
- Pharmacological management of underlying cause
Define Cerebellar Syndrome?
A cluster of clinical manifestations resulting impaired function of the cerebellum.
VIITAMIN C
What are some causes of Cerebellar Dysfunction?
- Vascular: Stroke of posterior circulation
- Infectious: Lyme disease, Cerebellar Abscess
- Inflammatory: Multiple Sclerosis
- Traumatic: Trauma to posterior fossa
- Alcohol
- Metabolic: Hypothyroidism
- Iatrogenic: Phenytoin, Carbamazepine
- Neoplastic: Primary and Secondary Tumours
- Congenital: Friedrich’s Ataxia, Spinocerebellar Ataxias (eg. SPG7)
VANISHED
What are the clinical Manifestations of Cerebellar Dysfunction?
Vertigninous Symptoms
Ataxia
Nystagmus
Intention Tremor
Slurred Staccato Speech (dysarthria)
Hypotonia
Exaggerated Broad Based Gait
Dysdiadochokinesia
What symptoms arise from cerebellar vermis lesions?
Truncal Ataxia
Gait instability
Few cerebellar signs in the limbs
What symptoms arise from cerebellar hemisphere lesions?
VANISHED signs in Ipsilateral Limb
What are some differential diagnoses for Cerebellar Dysfunction?
- Stroke
- Multiple Sclerosis
- Posterior Fossa Tumour
- Alcoholism
- Medication side effects: Phenytoin, Carbamazepine
- Tumours
- Hereditary conditions
What are the investigations for Cerebellar Dysfunction?
History: Alcohol intake, Head injury, infection
Neuroimaging: CT or MRI to identify stroke, tumour, trauma
Serological Tests: Identify infectious or inflammatory causes
Lumbar Puncture: Evidence of infection, inflammation or malignancy
Genetic Testing: Diagnose hereditary conditions
What is the management of Cerebellar Dysfunction?
Treat Underlying Cause
- Medications - manage symptoms
- Surgery to remove tumours or address trauma
- Rehabilitation therapies - physical, speech, occupational
- Lifestyle modifications - Alcohol cessation
What is Herpes Zoster Ophthalmicus?
Herpes zoster ophthalmicus (HZO) describes the reactivation of the varicella zoster virus in the area supplied by the ophthalmic division of the trigeminal nerve.
It accounts for around 10% of case of shingles.
What are the clinical features of Herpes Zoster Ophthalmicus?
- Vesicular rash around the eye, which may or may not involve the actual eye itself
- Hutchinson’s sign: rash on the tip or side of the nose. Indicates nasociliary involvement and is a strong risk factor for ocular involvement
What is the management of Herpes Zoster Ophthalmicus?
-
Oral antiviral treatment for 7-10 days
- Ideally started within 72 hours
- Intravenous antivirals may be given for very severe infection or if the patient is immunocompromised
- Topical antiviral treatment is not given in HZO
- Topical corticosteroids may be used to treat any secondary inflammation of the eye
- Ocular involvement requires urgent ophthalmology review
What are some complications of Herpes Zoster Ophthalmicus?
- Ocular: Conjunctivitis, Keratitis, Episcleritis, Uveitis
- Ptosis
- Post herpatic Neuralgia
What is Ramsay Hunt Syndrome?
Herpes Zoster Oticus is caused by the reactivation of the varicella zoster virus in the geniculate ganglion of the Facial nerve
What are the clinical features of Ramsay Hunt Syndrome?
- Auricular Pain - often the first feature
- Vesicular rash around the ear canal, pinna and can extend to the anterior 2/3rds of the tongue and hard palate
- Facial Nerve Palsy
- Vertigo and tinnitus
What is a typical patient presenting with Ramsay Hunt Syndrome?
Patient with facial nerve palsy, auricular pain and a vesicular rash around their ear
What is the management of Ramsay Hunt Syndrome?
Treatment should be initiated within 72 hours
Oral Aciclovir and Corticosteroids (prednisolone)
May also require lubricating eye drops
Define Cerebral Palsy?
A Permanent disorder of movement and posture due to a non-progressive lesion of the motor pathways in the developing brain.
It is not a progressive condition, however the nature of the symptoms and problems may change over time during growth and development.
There is huge variation in the severity and type of symptoms, ranging from completely wheelchair bound and dependent on others for all activities of daily living, to para-Olympic athletes with only subtle problems with coordination or mobility.
What is the Epidemiology of Cerebral Palsy?
2/3 in 1000
What are some causes of Cerebral Palsy?
Antenatal (80%):
- Maternal infections: Rubella, CMV, Toxoplasmosis
- Trauma during pregnancy
- Cerebral Malformation
Perinatal (10%):
- Birth asphyxia (Hypoxic Ischemic Encephalopathy)
- Pre-term birth
- Intrumental Delivery
Postnatal (10%):
- Meningitis
- Intraventricular Haemorrhage
- Kernicterus (Severe neonatal jaundice)
- Head injury
What are the types of Cerebral Palsy?
Spastic: hypertonia (90%) (increased tone) and reduced function resulting from damage to upper motor neurones
- Hemiplegic
- Diplegic
- Quadriplegic
Dyskinetic: problems controlling muscle tone, with hypertonia and hypotonia, causing athetoid movements and oro-motor problems. This is the result of damage to the basal ganglia.
Ataxic: problems with coordinated movement resulting from damage to the cerebellum
Mixed: a mix of spastic, dyskinetic and/or ataxic features
Spastic CP is also known as pyramidal CP. Dyskinetic CP is also known as athetoid CP and extrapyramidal CP.
What are some clinical features of Cerebral Palsy?
- Motor Problems
- Abnormal tone early infancy
- Delayed motor milestones
- Abnormal gait - Hemiplegic/Diplegic Gait
- Feeding difficulties.
What are some non-motor problems associated with Cerebral Palsy?
- Learning Difficulties (60%)
- Epilepsy (30%)
- Squints (30%)
- Hearing Impairments (20%)
What are some differential diagnoses to Cerebral Palsy?
- Muscular Dystrophies
- Metabolic Disorders
- Hereditary spastic paraplegia
- Juvenile idiopathic arthritis
What are some investigations performed in suspected Cerebral Palsy?
Clinical Diagnosis often
- Neuroimaging: MRI to visualise the extent and nature of the brain lesions
- Genetic Testing: considered for differential diagnoses when there is a suspicion of an underlying genetic disorder
What is the management of Cerebral Palsy?
Requires a Multidisciplinary Team Approach
-
Paediatricians: Optimise Medications:
- Muscle Relaxants - Baclofen
- Anti-epileptic Drugs
- Glycopyrronium Bromide - For excessive drooling
- Surgery: Musculoskeletal deformity correction / Tendon release
- Physiotherapy: Stretch and strengthen muscles and maximise function
- Occupational Therapy: Manage patients everyday lives and ADLs
- Speech and Language Therapy: Aid with speech and swallowing problems as some patients may require an NG or PEG tube (requires dieticians)
What are some complications of Cerebral Palsy?
- Learning disability
- Epilepsy
- Kyphoscoliosis
- Muscle contractures
- Hearing and visual impairment
- Gastro-oesophageal reflux
Define Hypoxic Ischaemic Encephalopathy (HIE)?
A form of brain damage that occurs due to antenatal or perinatal hypoxia
What is the epidemiology of HIE?
1-2 per 1000
Incidence is higher in premature and low birth weight infants
What are some causes of Hypoxic Ischaemic Encephalopathy?
Pre-partum
- Placental Abruption
- Maternal Shock
Intrapartum
- Intrapartum haemorrhage
- Cord compression
- Prolapsed cord
- Nuchal Cord
Post Partum
- Prolonged Respiratory Arrest
What is the pathophysiology of Hypoxic Ischaemic Encephalopathy?
A lack of oxygen in the foetal circulation which leads to an insufficient oxygen supply to the brain
This ischaemia culminates in irreversible brain damage both from primary neuronal death and secondary reperfusion injury
What are the clinical features of HIE?
Presentation varies along with the degree of neurological damage.
Mild: Irritability, Slight changes in behaviour
Severe: Hypotonia, Poor responsiveness to stimuli, Severe prolonged seizures
What are some differential diagnoses for HIE?
Meningitis
Metabolic Disorders
Intracranial Haemorrhage
Drug withdrawal
What are the investigations performed in suspected HIE?
EEG Monitoring: Evaluate seizure activity and brain function
Multiple MRI Scans: To assess extent of brain injury and areas affected
What is the management of HIE?
Depends on presentation and systemic complications:
- Respiratory Support
- Anticonvulsant therapy: To control Seizures
- Careful fluid balance: To prevent further complications
- Cooling Therapy: To induce mild hypothermia and prevent further damage from secondary reperfusion injury
Define Malaria?
Malaria is an infectious disease caused by members of the Plasmodium family of protozoan parasites.
Protozoa are single-celled organisms.
The most severe and dangerous type is Plasmodium falciparum, which accounts for about 80% of malaria cases in the UK.
How is Malaria spread?
Through bites from the Female Anopheles Mosquitoes that carry the disease
What are the different types of plasmodium that can cause Malaria?
- Plasmodium falciparum (the most common and severe form)
- Plasmodium vivax
- Plasmodium ovale
- Plasmodium malariae
- Plasmodium knowlesi
What is the lifecycle for Malaria?
- Inoculation of parasites (sporozoites) passed from the blood to the liver
- Asexual division in the liver maturing into Schizonts
- Parasite emerges from the liver to infect red blood cells as mature Merozoites
P. vivax and P. ovale lay down Hypnozoites in the liver that remain dormant and are immune to conventional anti-malarial drugs and so can reactivate years later
- Infected RBCs rupture releasing loads of merozoites into the blood and cause Haemolytic Anaemia
How many hours do P. vivax, P. ovale and P. falciparum infect RBCs for before they rupture?
P. vivax and P. ovale - 48 hours cyclical fever spikes
P. falciparum - More frequent and irregular fever spikes
What are some protective factors for malaria?
Sickle Cell Disease
G6PD Deficiency
HLA-B53
Absence of Duffy Antigens
What are the clinical features of Malaria?
Non-specific symptoms:
Fever (often cyclical every 48 hours)
Fatigue
Myalgia
Headache
Nausea and Vomiting
Signs:
Pallor due to haemolytic anaemia
Hepatosplenomegaly
Jaundice due to the rupture of RBCs
What is the gold standard investigation for Malaria?
Malaria Blood Film:
- Thick - Sensitive to Malaria
- Thin - Used to determine Species
3 Negative samples taken over 3 consecutive days are required to exclude malaria due to the cyclical release of parasites from the blood every 48-72 hours.
What is the management of Malaria?
Anti-malarials:
Artesunate or Chloroquine
- Quinine plus Doxycycline
- Quinine plus clindamycin
There are increasing rates of resistance to chloroquine where Artesunate should be used
Artesunate is AVOIDED in pregnancy
What is the treatment for complicated malaria often due to P. falciparum infection?
- Admitted to HDU/ICU and monitored for complications
- Artesunate is first line
Quinine dihydrochloride may also be used
What are some complications of P. falciparum Malaria?
- Cerebral malaria: seizures, coma
- Acute renal failure: blackwater fever, secondary to intravascular haemolysis, mechanism unknown
- Acute respiratory distress syndrome (ARDS)
- Hypoglycaemia
- Disseminated intravascular coagulation (DIC)
What are the features of Cerebral Malaria?
Altered consciousness that can range from confusion to deep coma
Seizures
Neurological deficits
This is a medical emergency that requires urgent intervention
What are the different Primary Brain Tumours?
- Gliomas (Astrocytoma, Ependymoma, Oligodendroma, Glioblastoma
- Meningioma
- Schwannoma
- Pituitary adenoma
What is the most common Primary Brain Tumour in Adults and in Children?
Adults: Glioblastoma followed by Meningioma
Children: Astrocytoma and Craniopharyngioma
What is the most common form of brain tumour?
Metastatic brain cancer
What are the cancers that will most commonly spread to the brain to cause metastatic brain cancer?
Lung cancer (Most common)
Breast
Bowel
Skin (melanoma)
Kidney
What are the clinical features of brain tumours?
Wide range of symptoms depending on location and size
- Headaches: Often severe and constant that are worse in the mornings and when lying down
- Nausea and Vomiting accompanying the headaches
- Seizures: often the first sign of a brain tumour
- Cognitive changes: Memory loss, confusion, difficulty concentrating
- Focal Neurological Deficits: Motor and sensory symptoms
- Visual changes: if pressing on the optic chiasm or nerve
- Personality changes: irritability, mood swings, depression
What are the red flag signs for brain tumours?
New Headaches:
- Severe and persistent
- Woken by headache
- Worse in morning
- Worse Lying down
- Associated with N+V
- Exacerbated by coughing, sneezing and drowsiness
Features of raised ICP (papilloedema)
Focal neurology (motor, sensory, visual)
What is a Glioblastoma Multiforme?
Glioblastoma (GBM), also referred to as a grade IV astrocytoma, is a fast-growing and aggressive brain tumour
Most common primary tumour in adults
Often fatal within 1 year of Dx
- On imaging they are solid tumours with central necrosis and a rim that enhances with contrast.
- Disruption of the blood-brain barrier and therefore are associated with vasogenic oedema.
- Histology: Pleomorphic tumour cells border necrotic areas
What is a meningioma?
Second most common primary brain tumour in adults
Benign extrinsic tumours arising from the meninges.
CT/MRI scan with show contrast enhancement
What is a Pilocytic Astrocytoma?
Finding on histology?
Most common primary brain tumour in children
Has Rosenthal fibres (corkscrew eosinophilic bundles) on histology
What is a Medulloblastoma?
- A medulloblastoma is an aggressive paediatric brain tumour that arises within the infratentorial compartment. It spreads through the CSF system. Treatment is surgical resection and chemotherapy.
- Histology: Small, blue cells. Rosette pattern of cells with many mitotic figures
What is an Ependymoma?
- Commonly seen in the 4th ventricle
- May cause hydrocephalus
- Histology: perivascular pseudorosettes
What is an Oligodendroma?
Findings on histology
- Benign, slow-growing tumour common in the frontal lobes
- Histology: Calcifications with ‘fried-egg’ appearance
What is a Haemangioblastoma?
- Vascular tumour of the cerebellum
- Associated with von Hippel-Lindau syndrome
- Histology: foam cells and high vascularity
What is a Craniopharyngioma?
Derived from?
Presentation?
Most common paediatric supratentorial tumour
Solid/cystic tumour of the sellar region (Sellar turcica) derived from Rathke’s pouch
- Presents with Hormonal disturbance, hydrocephalus and bitemporal hemianopia
What are the investigations for a brain tumour?
MRI head - locate tumour
Biopsy - determine grade
Fundoscopy - Papilloedema due to raised ICP
NO LP as this is CI in raised ICP
What is the management of brain tumours?
Depends on Type, Grade and Site:
Tx is non-curative except for Grade I tumours
Surgical removal if possible/reduce ICP (dexamethasone to reduce oedema)
Chemotherapy/Radiotherapy Before/during/after surgery.
(Radiotherapy is mainstay of treatment)
Palliative Care
What are the differential Diagnoses of a brain tumour?
Aneurysm
Abscess
Cyst
Haemorrhage
Idiopathic intracranial hypertension
What are Pituitary Tumours?
- Pituitary gland – sits in pituitary fossa (behind nose and below base of brain)
- Tumours are almost always benign and usually curable
- Excessive effects of tumour
- Local effects of tumour – bitemporal hemianopia
- Inadequate hormone production by the remaining pituitary gland
- Treated with Transsphenoidal surgical resection
What is an Acoustic Neuroma?
Vestibular Schwannoma (previously termed acoustic neuroma)
- A benign tumour of schwaan cells forming the myelin sheath arising from the auditory (vestibulocochlear) nerve often found at the cerebellopontine angle.
Where do acoustic neuromas occur?
From the vestibulocochlear nerve at the cerebellopontine angle
(sometimes referred to as cerebellopontine angle tumours)
What are the clinical features of an Acoustic Neuroma?
40-60 years presenting with gradual onset classically presenting with:
- Unilateral sensorineural Hearing loss (often first symptom)
- Vertigo
- Unilateral Tinnitus
- Absent Corneal Reflex
Other features:
- Dizziness or imbalance
- Sensation of fullness in the ear
- Facial nerve palsy - due to compression if the tumour grows large enough
What is the pathophysiology of the features of Vestibular Schwannomas?
Features can be predicted by the affected cranial nerves
- cranial nerve VIII: vertigo, unilateral sensorineural hearing loss, unilateral tinnitus
- cranial nerve V: absent corneal reflex
- cranial nerve VII: facial palsy
What condition is associated with vestibular schwannomas?
Neurofibromatosis type II
Bilateral acoustic neuromas
What are the investigations for an Acoustic neuroma?
MRI of the cerebellopontine angle is the investigation of choice
Audiometry: pattern of sensorineural hearing loss
What may be seen on histology in an Acoustic neuroma?
Antoni A or B patterns
Verocay bodies
What is the treatment for an Acoustic Neuroma?
Observation (watch and wait)
Radiotherapy to reduce growth
Surgery to remove the tumour
What are some complications of an Acoustic Neuroma?
- Vestibulocochlear nerve injury, with permanent hearing loss or dizziness
- Facial nerve injury, with facial weakness
Define Bell’s Palsy?
Defined as an acute, unilateral lower motor neuron palsy causing facial nerve paralysis without sparing the extraocular muscles and muscles of mastication.
Often Idiopathic
What is the Aetiology of Bell’s Palsy?
Largely idiopathic
Viral infections have been implicated as a particular cause
- Reactivation of HSV 1
- EBV
- VZV
What are the clinical features of Bell’s Palsy?
Acute (but NOT sudden; around 72 hours) onset of unilateral lower motor neurone facial weakness
- lower motor neuron facial nerve palsy → forehead affected
- in contrast, an upper motor neuron lesion ‘spares’ the upper face
- post-auricular pain (may precede paralysis)
- altered taste
- dry eyes
- hyperacusis
What are some other causes of facial nerve palsy?
- Bell’s palsy (pregnancy, DM)
- Ramsay Hunt syndrome
- Parotid gland tumour
- Otitis media, cholesteatoma
- Cerebello-pontine angle tumour
- Stroke
What are the investigations for Bell’s Palsy?
Primarily a clinical diagnosisof exclusion
- Full Blood Count
- ESR and CRP
- Viral Serology
- Lyme serology
- Otoscopy
- EMG
- MRI/CT
What is the management of Bell’s Palsy?
1st line
Supportive Mx?
- Prompt administration (Within 72 hours) of Oral steroids: 50mg of oral prednisolone or prednisone once daily for 10 days, followed by a taper.
- Aciclovir can be considered in select cases
Supportive Treatments:
- Artificial tears and ocular lubricants
- Eye patch
What is the prognosis of Bell’s Palsy?
Complete Recovery: 70-80% within 34 months
Incomplete recovery: some patients may experience residual weakness or persistent facial symptoms
Increased age and severity are associated with increased risk of incomplete recovery.
Define Epilepsy
Epilepsy is an umbrella term for a neurological condition where there is a tendency to generate epileptic seizures.
>2 episodes more than 24 hours a part
Define a seizure
Seizures are transient episodes of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
What is the epidemiology of Epilepsy?
- Epilepsy affects approximately 50 million people worldwide, making it one of the most common neurological diseases.
- Incidence rates vary depending on age, with higher rates in the very young and the elderly.
- Both males and females are affected equally.
What is an epileptic seizure?
Paroxysmal event in which changes of behaviour, sensation or cognitive processes are caused by excessive (too much voltage), hypersynchronous neuronal discharges in the brain (unprovoked)
What is a Pseudoseizure (non-epileptic seizure)?
Paroxysmal event in which changes in behaviour, sensation and cognitive function caused by mental processes associated with psychosocial distress
What is the aetiology of Epilepsy?
Epilepsy can be idiopathic, cryptogenic, or symptomatic.
Factors such as genetic predisposition, brain trauma, tumours, strokes, infectious diseases, or developmental disorders can contribute to the onset of epilepsy.
What are some risk factors for Epilepsy?
Family History
Head Trauma
Premature babies
Cerebral Infections
Dementia (10x more likely)
Drug use - cocaine
Cerebrovascular events
VITAMIN DE
List some causes of seizures?
Vascular - Stroke, HTN
Infection - Meningitis, Encephalitis
Trauma/Toxins - Drugs/alcohol
Autoimmune - SLE
Metabolic - Hypocalcaemia, Hypoglycaemia, Hypo/hypernatraemia
Idiopathic - Epilepsy
Neoplasms
Dementia + Drugs (cocaine)
Eclampsia + everything else
What are the different types of Seizure?
- Generalised Seizure: Excessive neuronal activity across the whole brain
- Focal (partial) seizure: Excessive neuronal activity in a specific part of the brain
- Simple Focal
- Complex Focal
- Focal-Bilateral
What is a generalised Seizure?
A seizure that starts within both hemispheres of the brain at onset.
They are bilateral
ALWAYS a loss of consciousness
What are the different types of a Generalised Seizure?
Non-Motor:
- Absence seizures (petit mal): brief pauses for less than 10 seconds.
Motor:
- Tonic-clonic (Grand mal) seizures: characterized by loss of consciousness, stiffening (tonic), and jerking (clonic) of limbs. Post-ictal confusion is common.
- Myoclonic seizures: sudden jerks of a limb, trunk, or face.
- Atonic seizures: sudden loss of muscle tone, causing the patient to fall, with consciousness retained.
What is an Absence Seizure?
- Absence seizures typically happen in children.
- The patient becomes blank, stares into space and then abruptly returns to normal.
- During the episode they are unaware of their surroundings and won’t respond.
- These typically only lasts 10 to 20 seconds.
What is an Atonic Seizure?
What condition is typically associated with Atonic Seizures?
- Atonic seizures are also known as drop attacks.
- They are characterised by brief lapses in muscle tone.
- These don’t usually last more than 3 minutes.
- They typically begin in childhood.
- They may be indicative of Lennox-Gastaut syndrome.
What is Todd’s Paralysis?
Period after an epileptic seizure in which the patient experiences temporary paralysis
What are Focal Seizures?
Seizures that originate within one side of the brain and are usually confined to one region.
They may progress to secondary lobes (Focal-bilateral seizures)
What are the different types of Focal Seizure?
With impaired consciousness (complex):
- Patients lose consciousness, usually post an aura or at seizure onset.
- Commonly originate from the temporal lobe,
- post-ictal symptoms such as confusion are common.
Without impaired consciousness (simple):
- Patients retain consciousness, experiencing only focal symptoms.
- Post-ictal symptoms are absent
Evolving to a bilateral
- convulsive seizure (‘secondary generalised’):
- patients first experience a focal seizure that evolves into a generalized seizure, typically tonic-clonic.
What are the symptoms of a focal seizure that arises from the Temporal Lobes?
They affect hearing, speech, memory and emotions. There are various ways that focal seizures can present:
- Hallucinations (auditory, gustatory, olfactory)
- Memory flashbacks
- Déjà vu
- Automatisms (Lip smacking, grabbing, plucking)
What is the Jacksonian March?
Where Focal Seizures may start with one muscle group being affected however this then spreads to involve other muscle groups as the abnormal electrical activity spreads.
Associated with Frontal lobe focal seizures
How are seizures classified?
Where the seizures began
Level of awareness during the seizure
Other features of the seizure e.g. motor
What are the characteristics of an Epileptic Seizure?
- Duration – 30-120 seconds
- Positive ictal symptoms – excess of something
- Seeing/hearing something that isn’t there
- Feeling touch when you aren’t being touched
- Positive postictal symptoms
- May occur from sleep
- May be associated with other brain dysfunction – bleeds, stroke, tumours etc.
- Tongue Biting
- Incontinence
- Typical seizure phenomena – lateral tongue bite, déjà v
What are the characteristics of a Pseudoseizure (non-epileptic)?
- Situational
- Duration 1 – 20 mins
- Dramatic motor phenomena or prolonged atonia (Pelvic Thrusting)
- Eyes closed
- Ictal crying and speaking
- Surprisingly rapid or slow postictal recovery
- History of psychiatric illness, other somatoform disorders
What are some differential diagnoses for Epilepsy?
- Syncope: characterized by a sudden, transient loss of consciousness and postural tone followed by spontaneous recovery. Triggered by low blood flow to the brain.
- Transient Ischemic Attack (TIA): brief episodes of focal neurologic dysfunction caused by ischemia that does not cause lasting brain injury. Symptoms depend on the brain area affected.
- Migraines: characterized by recurrent headaches often accompanied by a variety of symptoms such as visual disturbances (auras), nausea, vomiting, dizziness, extreme sensitivity to sound, light, touch and smell, and tingling or numbness in the extremities or face.
- Panic Disorder: sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath, numbness, or a feeling that something terrible is going to happen.
What are the investigations for seizures and epilepsy?
Electroencephalogram (EEG) shows different wave patterns for different forms of epilepsy
MRI brain is used to diagnose structural pathology (e.g., tumours).
Additional investigations can be considered to exclude associated pathology:
- ECG
- Serum electrolytes, including sodium, potassium, calcium and magnesium
- Blood glucose for hypoglycaemia and diabetes
- Blood cultures, urine cultures and lumbar puncture where sepsis, encephalitis or meningitis is suspected
When is Neuroimaging indicated in the investigations of seizures?
The first seizure is in children under 2 years old
Focal seizures
There is no response to first line anti-epileptic medications
What are the goals of epilepsy treatment?
- Aim for optimum quality of life through seizure control, balanced against potential side effects, particularly teratogenesis in women of childbearing age.
- Initiation of medication may not always be appropriate after a “provoked” first seizure; discuss such cases with a specialist.
- The choice of antiepileptic drugs involves complexity due to the lack of head-to-head trials comparing different medications.
- Interactions with other medications, particularly with phenytoin and carbamazepine, should be considered.
- Issues regarding teratogenicity, particularly with valproate, which carries a high risk of neural tube defects, should be considered. Lamotrigine is a better choice for women of childbearing age.
What is the management of Focal seizures?
Monotherapy up to 3rd line should be considered and then adjunctive therapy
1st Line: Lamotrigine or Levetiracetam
2nd Line: Carbamazepine, Oxcarnazepine, Zonisamide
3rd Line: Lacosamide
What is the management for Generalised Tonic-clonic seizures?
1st Line: Male = Sodium Valproate, Female = Lamotrigine/Levetiracetam
2nd Line: Lamotrigine, Levetiracetam
Lamotrigine or Levetiracetam is first line in women of childbearing age who can have children
What is the management of an Generalised Absence Seizure?
1st Line: Ethosuximide
2nd Line: Sodium Valproate (male), Levetiracetam/Lamotrigine (female)
What general advice should be given to patients and families presenting with seizures?
recognising, managing and reporting further seizures. Avoid situations where a seizure will put the patient at risk
- Take showers rather than baths
- Be very cautious with swimming unless seizures are well controlled and they are closely supervised
- Be cautious with heights
- Be cautious with traffic
- Be cautious with any heavy, hot or electrical equipment
What are some notable side effects of sodium valproate?
Teratogenic, so patients need careful advice about contraception
Liver damage and hepatitis
Hair loss
Tremor
What are some notable side effects of Carbamazepine?
Agranulocytosis
Exacerbate Absence seizures
Aplastic anaemia
Induces the P450 system so there are many drug interactions
What does this show?
CT head showing an Extradural Haemorrhage
What does this show?
A Subdural Haemorrhage
What does this show?
Subarachnoid Haemorrhage
What condition is shown here?
Horner’s Syndrome:
- Ptosis
- Miosis
- Anhidrosis
What condition is this?
Neurofibromatosis
What is this cutaneous sign and what condition does it suggest?
Cafe-au-lait spot
Suggests neurofibromatosis
May also suggest other conditions such as Familial Cafe au lait spots, McCune-Albright syndrome or Legius syndrome
