Neurology Flashcards
Stroke
Stroke is also called cerebrovascular accident (CVA). Cerebrovascular accidents are either:
Ischaemia or infarction of the brain tissue secondary to a disrupted blood supply (ischaemic stroke)
Intracranial haemorrhage, with bleeding in or around the brain (haemorrhagic stroke)
Ischaemia refers to an inadequate blood supply. Infarction refers to tissue death due to ischaemia.
The blood supply to the brain may be disrupted by:
A thrombus or embolus
Atherosclerosis
Shock
Vasculitis
Transient ischaemic attack (TIA) involves temporary neurological dysfunction (lasting less than 24 hours) caused by ischaemia but without infarction. Symptoms have a rapid onset and often resolve before the patient is seen. TIAs may precede a stroke. Crescendo TIAs are two or more TIAs within a week and indicate a high risk of stroke.
Stroke presentation
A sudden onset of neurological symptoms suggests a vascular cause (e.g., stroke). Stroke symptoms are typically asymmetrical. Common symptoms are:
Limb weakness
Facial weakness
Dysphasia (speech disturbance)
Visual field defects
Sensory loss
Ataxia and vertigo (posterior circulation infarction)
Stroke risk factors
Previous stroke or TIA
Atrial fibrillation
Carotid artery stenosis
Hypertension
Diabetes
Raised cholesterol
Family history
Smoking
Obesity
Vasculitis
Thrombophilia
Combined contraceptive pill
TOM TIP: The combined contraceptive pill carries a tiny increased risk of stroke. The risk is higher in patients with migraines with aura, smokers over 34 years or those with a history of stroke or TIA.
FAST tool
The FAST tool is used as a simple way to identify stroke in the community:
F – Face
A – Arm
S – Speech
T – Time (act fast and call 999)
ROSIER tool
The ROSIER tool (Recognition Of Stroke In the Emergency Room) gives a score based on the clinical features and duration. Stroke is possible in patients scoring one or more.
Managing TIA
Symptoms should have completely resolved within 24 hours of onset. Initial management involves:
Aspirin 300mg daily (started immediately)
Referral for specialist assessment within 24 hours (within 7 days if more than 7 days since the episode)
Diffusion-weighted MRI scan is the imaging investigation of choice.
Managing Stroke
The information here is summarised from the NICE guidelines (updated 2022) on stroke. Initial management involves:
Exclude hypoglycaemia
Immediate CT brain to exclude haemorrhage
Aspirin 300mg daily for two weeks (started after haemorrhage is excluded with a CT)
Admission to a specialist stroke centre
Thrombolysis with alteplase is considered once haemorrhage is excluded (after the CT scan). Alteplase is a tissue plasminogen activator that rapidly breaks down clots. It may be given within 4.5 hours of the symptom onset, based on local protocols and by an appropriately trained team. Patients need close monitoring for complications, particularly intracranial or systemic haemorrhage, with access to immediate imaging if bleeding is suspected.
Thrombectomy is considered in patients with a confirmed blockage of the proximal anterior circulation or proximal posterior circulation. It may be considered within 24 hours of the symptom onset and alongside IV thrombolysis.
In patients with an ischaemic stroke, lowering the blood pressure can worsen the ischaemia. High blood pressure treatment is only indicated in hypertensive emergency or to reduce the risks when giving intravenous thrombolysis. Blood pressure is aggressively treated in patients with a haemorrhagic stroke.
Assessing for underlying causes of stroke
Patients with a TIA or stroke are investigated for carotid artery stenosis and atrial fibrillation with:
Carotid imaging (e.g., carotid ultrasound, or CT or MRI angiogram)
ECG or ambulatory ECG monitoring
Anticoagulation is initiated for atrial fibrillation (after excluding haemorrhage and finishing two weeks of aspirin).
Surgical interventions are considered where there is significant carotid artery stenosis. The options are:
Carotid endarterectomy (recommended in the NICE guidelines)
Angioplasty and stenting
TOM TIP: The top risk factors to remember are atrial fibrillation and carotid artery stenosis. All patients with a TIA or stroke will have carotid imaging and ECGs to identify these.
Secondary prevention of stroke
Clopidogrel 75mg once daily (alternatively aspirin plus dipyridamole)
Atorvastatin 20-80mg (not started immediately – usually delayed at least 48 hours)
Blood pressure and diabetes control
Addressing modifiable risk factors (e.g., smoking, obesity and exercise)
Rehabilitation of stroke
Stroke patients require a period of adjustment and rehabilitation involving a multi-disciplinary team of:
Stroke physicians
Nurses
Speech and language (SALT) to assess swallowing
Dieticians in those at risk of malnutrition
Physiotherapy
Occupational therapy
Social services
Optometry and ophthalmology
Psychology
Orthotics
Intracranial bleeds
Intracranial haemorrhage refers to bleeding within the skull. There are four types:
Extradural haemorrhage (bleeding between the skull and dura mater)
Subdural haemorrhage (bleeding between the dura mater and arachnoid mater)
Intracerebral haemorrhage (bleeding into brain tissue)
Subarachnoid haemorrhage (bleeding in the subarachnoid space)
Intracerebral haemorrhage and subarachnoid haemorrhage account for 10-20% of strokes.
Risk factors for intracranial bleeds
Head injuries
Hypertension
Aneurysms
Ischaemic strokes (progressing to bleeding)
Brain tumours
Thrombocytopenia (low platelets)
Bleeding disorders (e.g., haemophilia)
Anticoagulants (e.g., DOACs or warfarin)
Presentation of intracranial bleeds
Sudden-onset headache is a key feature. They can also present with:
Seizures
Vomiting
Reduced consciousness
Focal neurological symptoms (e.g., weakness)
Glasgow Coma Scale
The Glasgow Coma Scale (GCS) is a universal assessment tool for the level of consciousness. It is scored based on eyes, verbal response and motor response. The maximum score is 15/15, and the minimum is 3/15. A score of 8/15 needs airway support, as there is a risk of airway obstruction or aspiration, leading to hypoxia and brain injury.
Score
Eyes
Verbal Response
Motor Response
6
–
–
Obeys commands
5
–
Oriented
Localises pain
4
Spontaneous
Confused
Normal flexion
3
Speech
Inappropriate words
Abnormal flexion
2
Pain
Incomprehensible sounds
Extends
1
None
None
None
Extradural haemorrhage
Extradural haemorrhage occurs between the skull and dura mater and is usually caused by a rupture of the middle meningeal artery in the temporoparietal region. It can be associated with a fracture of the temporal bone. On a CT scan, they have a bi-convex shape and are limited by the cranial sutures (they do not cross the sutures, which are the points where the skull bones join together).
A typical history is a young patient with a traumatic head injury and an ongoing headache. They have a period of improved neurological symptoms and consciousness, followed by a rapid decline over hours as the haematoma gets large enough to compress the intracranial contents.
Subdural haemorrhage
Subdural haemorrhage occurs between the dura mater and arachnoid mater and is caused by a rupture of the bridging veins in the outermost meningeal layer. On a CT scan, they have a crescent shape and are not limited by the cranial sutures (they can cross over the sutures).
Subdural haemorrhages may occur in elderly and alcoholic patients, who have more atrophy in their brains, making the vessels more prone to rupture.
Intracerebral haemorrhage
Intracerebral haemorrhage involves bleeding in the brain tissue. It presents similarly to an ischaemic stroke with sudden-onset focal neurological symptoms, such as limb or facial weakness, dysphasia or vision loss.
They can occur spontaneously or secondary to ischaemic stroke, tumours or aneurysm rupture.
They can occur anywhere in the brain tissue:
Lobar intracerebral haemorrhage
Deep intracerebral haemorrhage
Intraventricular haemorrhage
Basal ganglia haemorrhage
Cerebellar haemorrhage
Subarachnoid haemorrhage
Subarachnoid haemorrhage involves bleeding in the subarachnoid space, where the cerebrospinal fluid is located, between the pia mater and the arachnoid membrane. This is usually the result of a ruptured cerebral aneurysm.
The typical history is a sudden-onset occipital headache during strenuous activity, such as heavy lifting or sex. The sudden and severe onset leads to the “thunderclap headache” description.
Principles of managing intracranial bleeds
Immediate imaging (e.g., CT head) is required to establish the diagnosis. Bloods should include a full blood count (for platelets) and a coagulation screen.
Initial management will involve:
Admission to a specialist stroke centre
Discuss with a specialist neurosurgical centre to consider surgical treatment
Consider intubation, ventilation and intensive care if they have reduced consciousness
Correct any clotting abnormality (e.g., platelet transfusions or vitamin K for warfarin)
Correct severe hypertension but avoid hypotension
Smaller bleeds may be managed conservatively with close monitoring and repeat imaging.
Surgical options for treating an extradural or subdural haematoma are:
Craniotomy (open surgery by removing a section of the skull)
Burr holes (small holes drilled in the skull to drain the blood)
Subarachnoid haemorrhage
Subarachnoid haemorrhage involves bleeding in the subarachnoid space, where the cerebrospinal fluid is located, between the pia mater and the arachnoid membrane. This is usually the result of a ruptured cerebral aneurysm.
Subarachnoid haemorrhage has a very high mortality (around 30%) and morbidity, making it essential not to miss.
Subarachnoid haemorrhage risk factors
It is more common in:
Aged 45 to 70
Women
Black ethnic origin
General risk factors include:
Hypertension
Smoking
Excessive alcohol intake
Subarachnoid haemorrhage is particularly associated with:
Family history
Cocaine use
Sickle cell anaemia
Connective tissue disorders (e.g., Marfan syndrome or Ehlers-Danlos syndrome)
Neurofibromatosis
Autosomal dominant polycystic kidney disease
Subarachnoid haemorrhage presentation
The typical history is a sudden-onset occipital headache during strenuous activity, such as heavy lifting or sex. The sudden and severe onset leads to the “thunderclap headache” description. It may feel like being struck over the back of the head.
Other important features include:
Neck stiffness
Photophobia
Vomiting
Neurological symptoms (e.g., visual changes, dysphasia, focal weakness, seizures and reduced consciousness)
Investigating subarachnoid haemorrhage
CT head is the first-line investigation. Blood will cause hyper-attenuation in the subarachnoid space. However, a normal CT head does not exclude a subarachnoid haemorrhage. CT is less reliable more than 6 hours after the start of symptoms.
Lumbar puncture is considered after a normal CT head. The NICE guidelines (2022) recommend waiting at least 12 hours after the symptoms start before performing a lumbar puncture, as it takes time for the bilirubin to accumulate in the cerebrospinal fluid (CSF). With a subarachnoid haemorrhage, a CSF sample will show:
Raised red cell count (a decreasing red cell count on successive bottles may be due to a traumatic procedure)
Xanthochromia (a yellow colour to the CSF caused by bilirubin)
CT angiography is used after confirming the diagnosis to locate the source of the bleeding.
Managing subarachnoid haemorrhage
Patients should be managed by a specialist neurosurgical unit. Patients with reduced consciousness may require intubation and ventilation. Supportive care involves a multi-disciplinary team during the initial stages and recovery.
Surgical intervention may be used to treat aneurysms. The aim is to repair the vessel and prevent re-bleeding. This can be done by endovascular coiling, which involves inserting a catheter into the arterial system (an endovascular approach), placing platinum coils in the aneurysm and sealing it off from the artery. An alternative is neurosurgical clipping, which involves cranial surgery and putting a clip on the aneurysm to seal it.
Nimodipine is a calcium channel blocker used to prevent vasospasm. Vasospasm is a common complication following a subarachnoid haemorrhage, resulting in brain ischaemia.
Managing complications of subarachnoid haemorrhage
Hydrocephalus refers to increased cerebrospinal fluid, causing expansion of the ventricles. Treatment options include:
Lumbar puncture
External ventricular drain (a drain inserted into the brain ventricles to drain CSF)
Ventriculoperitoneal (VP) shunt (a catheter connecting the ventricles with the peritoneal cavity)
Seizures are treated with anti-epileptic drugs.
Multiple Sclerosis
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.
Multiple sclerosis typically presents in young adults (under 50 years) and is more common in women.
Pathophysiology of multiple sclerosis
Myelin covers the axons of neurones and helps electrical impulses travel faster. Myelin is provided by cells that wrap themselves around the axons:
Oligodendrocytes in the central nervous system
Schwann cells in the peripheral nervous system
Multiple sclerosis affects the central nervous system (the oligodendrocytes). Inflammation and immune cell infiltration cause damage to the myelin, affecting the electrical signals moving along the neurones.
When a patient presents with symptoms of an MS attack (e.g., an episode of optic neuritis), there are often other demyelinating lesions throughout the central nervous system, most of which are not causing symptoms.
In early disease, re-myelination can occur, and the symptoms can resolve. In the later stages of the disease, re-myelination is incomplete, and the symptoms gradually become more permanent.
A characteristic feature of MS is that lesions vary in location, meaning that the affected sites and symptoms change over time. The lesions are described as “disseminated in time and space”.
Causes of multiple sclerosis
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
Onset of multiple sclerosis
Symptoms usually progress over more than 24 hours. Symptoms tend to last days to weeks at the first presentation and then improve. There are many ways MS can present, depending on the location of the lesions.
Optic neuritis and MS
Optic neuritis is the most common presentation of multiple sclerosis. It involves demyelination of the optic nerve and presents with unilateral reduced vision, developing over hours to days.
Key features are:
Central scotoma (an enlarged central blind spot)
Pain with eye movement
Impaired colour vision
Relative afferent pupillary defect
A relative afferent pupillary defect is where the pupil in the affected eye constricts more when shining a light in the contralateral eye than when shining it in the affected eye. When testing the direct pupillary reflex, there is a reduced pupil response to shining light in the eye affected by optic neuritis. However, the affected eye has a normal pupil response when testing the consensual pupillary reflex.
Other causes of optic neuritis include:
Sarcoidosis
Systemic lupus erythematosus
Syphilis
Measles or mumps
Neuromyelitis optica
Lyme disease
Patients presenting with acute loss of vision need urgent ophthalmology input. Optic neuritis is treated with high-dose steroids. Changes on an MRI scan help to predict which patients will go on to develop MS.
Eye Movement Abnormalities and MS
Lesions affecting the oculomotor (CN III), trochlear (CN IV) or abducens (CN VI) can cause double vision (diplopia) and nystagmus. Oscillopsia refers to the visual sensation of the environment moving and being unable to create a stable image.
Internuclear ophthalmoplegia is caused by a lesion in the medial longitudinal fasciculus. The nerve fibres of the medial longitudinal fasciculus connect the cranial nerve nuclei (“internuclear”) that control eye movements (the 3rd, 4th and 6th cranial nerve nuclei). These fibres are responsible for coordinating the eye movements to ensure the eyes move together. It causes impaired adduction on the same side as the lesion (the ipsilateral eye) and nystagmus in the contralateral abducting eye.
A lesion in the abducens (CN VI) causes a conjugate lateral gaze disorder. Conjugate means connected. Lateral gaze is where both eyes move to look laterally to the left or right. When looking laterally in the direction of the affected eye, the affected eye will not be able to abduct. For example, in a lesion involving the left eye, when looking to the left, the right eye will adduct (move towards the nose), and the left eye will remain in the middle.
Focal neurological symptoms and MS
Multiple sclerosis may present with focal weakness, for example:
Incontinence
Horner syndrome
Facial nerve palsy
Limb paralysis
Multiple sclerosis may present with focal sensory symptoms, for example:
Trigeminal neuralgia
Numbness
Paraesthesia (pins and needles)
Lhermitte’s sign
Lhermitte’s sign describes an electric shock sensation that travels down the spine and into the limbs when flexing the neck. It indicates disease in the cervical spinal cord in the dorsal column. It is caused by stretching the demyelinated dorsal column.
Transverse myelitis refers to a site of inflammation in the spinal cord, which results in sensory and motor symptoms depending on the location of the lesion.
Ataxia and MS
Ataxia is a problem with coordinated movement. It can be sensory or cerebellar.
Sensory ataxia is due to loss of proprioception, which is the ability to sense the position of the joint (e.g., is the joint flexed or extended). This results in a positive Romberg’s test (they lose balance when standing with their eyes closed) and can cause pseudoathetosis (involuntary writhing movements). A lesion in the dorsal columns of the spine can cause sensory ataxia.
Cerebellar ataxia results from problems with the cerebellum coordinating movement, indicating a cerebellar lesion.
Disease patterns in MS
The disease course is highly variable between individuals. Some patients have mild relapsing-remitting episodes for life, while others have symptoms that progress without any improvement. There are classifications used to describe the patterns, which are not separate conditions but part of a spectrum of disease activity.
Clinically isolated syndrome describes the first episode of demyelination and neurological signs and symptoms. Patients with clinically isolated syndrome may never have another episode or may go on to develop MS. Lesions on an MRI scan suggest they are more likely to progress to MS.
Relapsing-remitting MS is the most common pattern when first diagnosed. It is characterised by episodes of disease and neurological symptoms followed by recovery. The symptoms tend to occur in different areas with each episode. It can be further classified based on whether the disease is active or worsening:
Active: new symptoms are developing, or new lesions are appearing on the MRI
Not active: no new symptoms or MRI lesions are developing
Worsening: there is an overall worsening of disability over time
Not worsening: there is no worsening of disability over time
Secondary progressive MS is where there was relapsing-remitting disease, but now there is a progressive worsening of symptoms with incomplete remissions. Symptoms become increasingly permanent. Secondary progressive MS can be further classified based on whether the disease is active or progressing.
Primary progressive MS involves worsening disease and neurological symptoms from the point of diagnosis without relapses and remissions. This can be further classified based on whether it is active or progressing.
Diagnosing MS
The diagnosis is made by a neurologist based on the clinical picture and symptoms suggesting lesions that change location over time. Other causes for the symptoms need to be excluded.
Investigations can support the diagnosis:
MRI scans can demonstrate typical lesions
Lumbar puncture can detect oligoclonal bands in the cerebrospinal fluid (CSF)
Managing MS
A specialist multidisciplinary team (MDT) manages multiple sclerosis, including neurologists, specialist nurses, physiotherapists and occupational therapists.
Disease-modifying therapies aim to induce long-term remission with no disease activity. Many options target various aspects of the immune system to reduce relapses and disease progression.
Relapses may be treated with steroids. The NICE guidelines (2022) suggest either:
500mg orally daily for 5 days
1g intravenously daily for 3–5 days (where oral treatment has previously failed or where relapses are severe)
Symptomatic treatments include:
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
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.
Amyotrophic lateral sclerosis (ALS) is the most common and well-known type of motor neurone disease. Stephen Hawking had amyotrophic lateral sclerosis.
Progressive bulbar palsy is the second most common form of motor neurone disease. It primarily affects the muscles of talking and swallowing (the bulbar muscles).
Other types to be aware of are progressive muscular atrophy and primary lateral sclerosis.
Pathophysiology of MND
Motor neurone disease involves a progressive degeneration of both the upper and lower motor neurones. The sensory neurones are spared.
The exact cause is unclear, although several mechanisms have been considered. Many genes have been linked with an increased risk of developing the condition. Family history is important as around 5-10% of cases are inherited. There seems to be an increased risk with smoking and exposure to heavy metals and certain pesticides.
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).
Signs of lower motor neurone disease:
Muscle wasting
Reduced tone
Fasciculations (twitches in the muscles)
Reduced reflexes
Signs of upper motor neurone disease:
Increased tone or spasticity
Brisk reflexes
Upgoing plantar reflex
Diagnosing MND
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.
Managing MND
There are no effective treatments for halting or reversing the progression of the disease.
Riluzole can slow the progression of the disease and extend survival by several months in ALS.
Non-invasive ventilation (NIV) can be used to support breathing when the respiratory muscles weaken.
Management of the condition involves supporting the person and their family:
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
Patients with motor neurone disease tend to die of respiratory failure or pneumonia.
Parkinson’s disease
Parkinson’s disease is a condition where there is a progressive reduction of dopamine in the basal ganglia of the brain, leading to disorders of movement. The symptoms are characteristically asymmetrical, with one side affected more than the other.
There is a classic triad of features in Parkinson’s disease:
Resting tremor
Rigidity
Bradykinesia
Pathophysiology of Parkinson’s disease
The basal ganglia are a group of structures situated in the middle of the brain. They are responsible for coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns. Part of the basal ganglia called the substantia nigra produces a neurotransmitter called dopamine. Dopamine is essential for the correct functioning of the basal ganglia. In Parkinson’s disease, there is a gradual but progressive fall in the production of dopamine.
Presentation of Parkinson’s disease
The typical patient is an older aged man around the age of 70.
Unilateral Tremor
The tremor in Parkinsons has a frequency of 4-6 Hz, meaning it occurs 4-6 times a second. This is described as a “pill rolling tremor” because it looks like they are rolling a pill between their fingertips and thumb. It is more pronounced when resting and improves on voluntary movement. The tremor is worsened if the patient is distracted. Asking them to do a task with the other hand, such as miming the motion of painting a fence, can exaggerate the tremor.
“Cogwheel” Rigidity
Rigidity is a resistance to passive movement of a joint. If you take their hand and passively flex and extend their arm at the elbow, you will feel a tension in their arm that gives way to movement in small increments (like little jerks). This is what leads to the cogwheel description.
Bradykinesia
Bradykinesia describes how their movements get slower and smaller. This presents in a number of ways:
Their handwriting gets smaller and smaller (this is a classic presenting complaint in exams)
They can only take small steps when walking (“shuffling gait”)
They have difficulty initiating movement (e.g. from standing still to walking)
They have difficulty in turning around when standing, having to take lots of little steps
They have reduced facial movements and facial expressions (hypomimia)
Other Features
There are a number of other features that often affect patients with Parkinson’s disease:
Depression
Sleep disturbance and insomnia
Loss of the sense of smell (anosmia)
Postural instability
Cognitive impairment and memory problems
Parkinson’s Disease v Benign Essential Tremor
TOM TIP: A common exam task challenges you to distinguish between the tremor of Parkinson’s disease and benign essential tremor. The table below gives some tips on this:
Parkinson’s Tremor
Benign Essential Tremor
Asymmetrical
Symmetrical
4-6 hertz
5-8 hertz
Worse at rest
Improves at rest
Improves with intentional movement
Worse with intentional movement
Other Parkinson’s features
No other Parkinson’s features
No change with alcohol
Improves with alcohol
Parkinson’s-plus Syndromes
Multiple System Atrophy
This is a rare condition where the neurones of multiple systems in the brain degenerate. It affects the basal ganglia as well as multiple other areas. The degeneration of the basal ganglia lead to a Parkinson’s presentation. The degeneration in other areas lead to autonomic dysfunction (causing postural hypotension, constipation, abnormal sweating and sexual dysfunction) and cerebellar dysfunction (causing ataxia).
Dementia with Lewy Bodies
This is a type of dementia associated with features of Parkinsonism. It causes a progressive cognitive decline. There are associated symptoms of visual hallucinations, delusions, disorders of REM sleep and fluctuating consciousness.
Others
Two other Parkinson’s-plus syndromes exist that involves a number of complex progressive neurological features:
Progressive Supranuclear Palsy
Corticobasal Degeneration
Diagnosing Parkinson’s disease
Parkinson’s disease is diagnosed clinically based on symptoms and examination. The diagnosis should be made by a specialist with experience in diagnosing Parkinson’s. NICE recommend using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
Managing Parkinson’s disease
Treatment is initiated and guided by a specialist, and is tailored to each individual patient and their response to different medications. There is no cure, so treatment is focused on controlling symptoms and minimising side effects.
Patients describe themselves as “on” when the medications are acting and they are moving freely, and “off” when the medications wear out, they have significant symptoms and their next dose is due.
Levodopa
This is synthetic dopamine given orally to boost their own dopamine levels. It is usually combined with a drug that stops levodopa being broken down in the body before it gets the chance to enter the brain. These are peripheral decarboxylase inhibitors. Examples are carbidopa and benserazide.
Combination drugs are:
Co-benyldopa (levodopa and benserazide)
Co-careldopa (levodopa and carbidopa)
Levodopa is the most effective treatment for symptoms but becomes less effective over time. It is often reserved for when other treatments are not managing to control symptoms.
The main side effect of dopamine is when the dose is too high patients develop dyskinesias. Theses are abnormal movements associated with excessive motor activity. Examples are:
Dystonia: This is where excessive muscle contraction leads to abnormal postures or exaggerated movements.
Chorea: These are abnormal involuntary movements that can be jerking and random.
Athetosis: These are involuntary twisting or writhing movements usually in the fingers, hands or feet.
COMT Inhibitors
The main example of this is entacapone. These are inhibitors of catechol-o-methyltransferase (COMT). The COMT enzyme metabolises levodopa in both the body and brain. Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.
Dopamine Agonists
These mimic dopamine in the basal ganglia and stimulate the dopamine receptors. They are less effective than levodopa in reducing symptoms. They are usually used to delay the use of levodopa and are then used in combination with levodopa to reduce the dose of levodopa that is required to control symptoms. One notable side effect with prolonged use is pulmonary fibrosis. Examples are:
Bromocryptine
Pergolide
Carbergoline
Monoamine Oxidase-B Inhibitors
Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline. The monoamine oxidase-B enzyme is more specific to dopamine and does not act on serotonin or adrenalin. These medications block this enzyme and therefore help increase the circulating dopamine. Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose. Examples are:
Selegiline
Rasagiline
Benign Essential Tremor
Benign essential tremor is a relatively common condition associated with older age. It is characterised by a fine tremor affecting all the voluntary muscles. It is most notable in the hands but affects many other areas, for example causing a head tremor, jaw tremor and vocal tremor.
Features of benign essential tremor
Fine tremor
Symmetrical
More prominent on voluntary movement
Worse when tired, stressed or after caffeine
Improved by alcohol
Absent during sleep
Differential diagnosis of tremor
Benign essential tremor is diagnosed clinically based on the presenting features. It is important to look for features to exclude other causes of a tremor.
The key differential diagnoses of a tremor are:
Parkinson’s disease
Multiple sclerosis
Huntington’s Chorea
Hyperthyroidism
Fever
Medications (e.g. antipsychotics)
Managing benign essential tremor
There is no definitive treatment for benign essential tremor. The tremor is not harmful and does not require treatment if not causing functional or psychological problems.
Medications that can be tried to improve symptoms are:
Propranolol (a non-selective beta blocker)
Primidone (a barbiturate anti-epileptic medication)
Epilepsy
Epilepsy is an umbrella term for a condition where there is a tendency to have seizures. Seizures are transient episodes of abnormal electrical activity in the brain. There are many different types of seizures.
A diagnosis of epilepsy is made by a specialist based on the characteristics of the seizure episodes.
Investigating epilepsy
An electroencephalogram (EEG) can show typical patterns in different forms of epilepsy and support the diagnosis.
An MRI brain can be used to visualise the structure of the brain. It is used to diagnose structural problems that may be associated with seizures and other pathology such as tumours.
Other investigations can be used to exclude other pathology, particularly an ECG to exclude problems in the heart.
Types of seizures
There are many types of seizures. There are different first line treatments for epilepsy with different types of seizures. The aim of treatment is to be seizure free on the minimum anti-epileptic medications. Ideally they should be on monotherapy with a single anti-epileptic drug. Treatment is initiated and guided by a specialist.
Generalised Tonic-Clonic seizures
These are what most people think of with an epileptic seizure. There is loss of consciousness and tonic (muscle tensing) and clonic (muscle jerking) episodes. Typically the tonic phase comes before the clonic phase. There may be associated tongue biting, incontinence, groaning and irregular breathing.
After the seizure there is a prolonged post-ictal period where the person is confused, drowsy and feels irritable or depressed.
Management of tonic-clonic seizures is with:
First line: sodium valproate
Second line: lamotrigine or carbamazepine
Focal seizures
Focal seizures start in temporal lobes. They affect hearing, speech, memory and emotions. There are various ways that focal seizures can present:
Hallucinations
Memory flashbacks
Déjà vu
Doing strange things on autopilot
One way to remember the treatment is that they are the reverse of tonic-clonic seizures:
First line: carbamazepine or lamotrigine
Second line: sodium valproate or levetiracetam
Absence seizures
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 10-20 seconds. Most patients (> 90%) stop having absence seizures as they get older. Management is:
First line: sodium valproate or ethosuximide
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. Management is:
First line: sodium valproate
Second line: lamotrigine
Myoclonic seizures
Myoclonic seizures present as sudden brief muscle contractions, like a sudden “jump”. The patient usually remains awake during the episode. They occur in various forms of epilepsy but typically happen in children as part of juvenile myoclonic epilepsy. Management is:
First line: sodium valproate
Other options: lamotrigine, levetiracetam or topiramate
Infantile spasms
Infantile spasms
This is also known as West syndrome. It is a rare (1 in 4000) disorder starting in infancy at around 6 months of age. It is characterised by clusters of full body spasms. There is a poor prognosis: 1/3 die by age 25, however 1/3 are seizure free. It can be difficult to treat but first line treatments are:
Prednisolone
Vigabatrin
Sodium Valproate
This is a first line option for most forms of epilepsy (except focal seizures). It works by increasing the activity of GABA, which has a relaxing effect on the brain. Notable side effects:
Teratogenic so patients need careful advice about contraception
Liver damage and hepatitis
Hair loss
Tremor
There are a lot of warning about the teratogenic effects of sodium valproate and NICE updated their guidelines in 2018 to reflect this. It must be avoided in girls or women unless there are no suitable alternatives and strict criteria are met to ensure they do not get pregnant.
Carbamazepine
This is first line for focal seizures. Notable side effects are:
Agranulocytosis
Aplastic anaemia
Induces the P450 system so there are many drug interactions
