Neurology

Question 1

What are the types of seizures?

Answer 1

Seizures falls within two main categories: generalised (affecting all parts of the cerebral cortex) or partial/focal (affecting one region or lobe or hemisphere, but can spread to other regions and lead to a secondary generalised seizure).

In generalised epilepsy, there tends to be a loss of consciousness (not necessarily, such as in myoclonic seizures). Types of generalised epilepsy include:

• Tonic-clonic seizure (grand maI) -A tonic phase (sustained muscle contraction) followed by a clonic phase (random jerks and contractions).
• Absence seizure (petite mal)- patient remains ‘absent’ just staring for a few minutes.
• Myoclonic seizure - brief jerks of a muscle or muscle group.
• Clonic - a monoclonus that is regularly repeating.
• Tonic - Sustained muscle contraction, the patient goes stiff causing them to fall backwards.
• Atonic - Loss of muscle tone, causing the patient to drop to the floor forwards.

Partial/focal seizures can be further divided into simple partial (where consciousness is preserved) or complex partial (where there is an alteration of consciousness).

Question 2

What are the causes of Epilepsy?

Answer 2

The majority of cases are idiopathic. These fall within primary epilepsy syndromes: idiopathic generalised epilepsy, temporal lobe epilepsy, juvenile myoclonic epilepsy.

Sometimes, seizures can occur secondary to a cause, including:

• Tumour
• Infection (e.g. meningitis, encephalitis, abscess)
• Inflammation (e.g. vasculitis, rarely MS)
• Toxic/metabolic(Na imbalance, hyper/hypoglycaemia, hypocalcaemia, hypoxia, porphyria, liver failure)
• Drugs, including withdrawal from alcohol or benzodiazepines.
• Vascular, Trauma, Congenital abnormalities.

Question 3

What are the clinical features of Focal Seizures?

Answer 3

• Frontal lobe seizure: motor convulsions. May demonstrate Jacksonian march (convulsions start from fingers or mouth, and spread). There may be a post-ictal flaccid weakness. On the other hand, may have sensory seizure where strong sensations are felt in one part of the body, face or limbs.
• Temporal lobe seizure: patient experiences an aura, Déjà vu, or hallucinations of smell or taste.
• Frontal lobe complex partial seizure: loss of consciousness, with associated automatisms and rapid recovery.

Question 4

What are the clinical features of Generalised Seizures?

Answer 4

• Tonic-clonic: Vague symptoms before attack such as irritability. Tonic phase (sustained muscle contraction) followed by a clonic phase (random jerks and contractions). Associated faecal or urinary incontinence, tongue biting. Typical post-ictal phase of altered consciousness, lethargy, confusion, headache, back pain, stiffness.
• Absence: Starts in childhood. Characterised by loss of consciousness but maintenance of posture. The child often reported as staring blankly. No post-ictal phase.

Question 5

What is status epilepticus?

Answer 5

Status epilepticus refers to a seizure (unless stated assume a generalised tonic-clonic seizure) that lasts for more than 30 minutes

Question 6

What are the complications of Epilepsy?

Answer 6

Fractures in tonic-clonic seizures. Hypoxia/brain damage if status epilepticus is not controlled.

Question 7

How can Epilepsy be investigated?

Answer 7

Bloods:

• Glucose as hyperglycaemia or hypoglycaemia can cause seizures.
• FBC to look for generalised infections.
• U&Es as electrolyte imbalances, particularly Na+ imbalances or uraemia can cause seizures.
• Serum prolactin can help differentiate generalised seizures from non-epileptic seizure disorder, as seizures increase serum prolactin by greater than twice baseline.

EEG (Electroencephalogram) can help classify the seizure disorder.

A head CT/MRI should be performed to look for any lesions, which could explain the seizure.

Question 8

How is Epilepsy managed?

Answer 8

Patient education is very important. This includes avoiding triggers and keeping a seizure diary. Recommended supervision for swimming or climbing. Driving is only permitted if not had a seizure in more than 6 months. Important to

Only starting anti-convulsant therapy after >2 unprovoked seizures. Start treatment a with single anti-epileptic drug (AED), at the lowest possible dose. There are numerous anti-convulsant agents, but the SANAD trial suggests:

• Lamotrigine or carbamazepineas first line treatment for focal seizures
• Sodium valproate should be used for generalised seizures (supported by 2017 Cochrane review).

Other commonly used agents include phenytoin, levetiracetam, clobazam, topiramate, gabapentin, vigabatrin, ethosuximide (absence).

Other treatments:

• Epilepsy surgery is often explored in medically refractory patientswith localisation-related epilepsywho have proven symptomatic or cryptogenic focal-onset epilepsy.
• Neurostimulation devices - devices such as deep brain stimulation (DBS), vagus nerve stimulation, and responsive neurostimulation (RNS) may be used.

Question 9

What is the definition and epidemiology of Encephalitis

Answer 9

Encephalitis is defined as inflammation of the brain parenchyma associated with neurological dysfunction. It is not very common, only 2500 cases in a year in the UK. High-risk groups include neonates (<1y) and elderly (>65y).

Question 10

What is the aetiology of encephalitis?

Answer 10

Viruses are the main cause of encephalitis, with herpesvirus the most common group of viruses.

Immune-mediated encephalitis can be the cause of a third of cases, with antibodiesusually against NMDA receptors.

However, a cause is only found in half of cases.

Question 11

What are the clinical features of Encephalitis?

Answer 11

Patients present with fever in infective causes, as well as a rash. The rash may be a vesicular eruption if caused by enteroviruses, HSV or VZV. A maculopapular rash is indicative of EBV (after treatment with ampicillin), measles, HHV-6 and other viruses. Lots of other rashes for different causes.

Altered mental state is a key manifestation of the disease, which can range from mild somnolescence (sleepiness), hemiparesis, ataxia to coma. These can be focal neurological deficits such as aphasia, hemianopia, brisk tendon reflexes, Babinski sign.

Seizures are also common. Generalised tonic-clonic seizures, partial complex seizures and focal seizures with secondary generalisation are very frequently seen at some point in the clinical course.

Patients also tend to have other symptoms caused by a viral infection, such as cough or gastrointestinal disturbances.

Meningism (photophobia, headache, neck stiffness) can develop, resulting in meningoencephalitis.

Question 12

Describe the diagnosis of encephalitis

Answer 12

Bloods:

• FBC often shows elevated WBC
• U&Es may show hyponatraemia in some causes.
• LFTs may be elevated in certain causes.
• Blood cultures may detect and confirm systemic bacterial infections

CSF sample should be taken and analysed. Depending on aetiology, there may have elevated white cell count, normal/elevated protein, normal/low glucose, or normal/elevated RBCs. PCR can identify viruses.

Throat swab or nasopharyngeal aspirate to detect respiratory viruses.

MRI of the brain is the imaging study of choice or may need CT brain.

EEG should be done in all patients with persistent altered mental status or seizures.

Question 13

What is the management of encephalitis?

Answer 13

All cases of encephalitis should be admitted and fully evaluated. Some patients with milder symptoms and signs can be managed in a regular nursing unit. All other patients, and in particular those with complications should be managed in an ICU, preferably a neuro-intensive care unit. Supportive management for all patients may include:

• Endotracheal intubation and mechanical ventilation
• Circulatory and electrolyte support
• Prevention and management of secondary bacterial infections
• DVT prophylaxis

Viral aetiologies

In most cases, the aetiology is suspected to be viral, and so the patient should be started on acyclovir until the cause is determined. As most cases are secondary to HSV this has strong evidence.

In immunocompromised patients, ganciclovir and Foscarnetare added to cover CMV, and continued until ruled out.

Non-viral aetiologies

Patients with suspected autoimmune encephalitis should be treated aggressively initially with intravenous corticosteroids (methylprednisolone sodium succinate), immune globulin, or plasma exchange. Cases with persistent altered mental status should be treated with rituximab and/or cyclophosphamide.

Confirmed bacterial encephalitis should be treated with appropriate antibiotics.

Question 14

Describe the management of elevated intracranial pressure

Answer 14

In patients with elevated ICP, management with corticosteroids and mannitol should be considered. Initial measures are:

• Elevation of the head of the bed to 30° to 45°
• Avoiding compression of the jugular veins
• Hyperventilation to a PaCO2 of around 30. Subsequently, hyperosmolar therapy with mannitol boluses or hypertonic saline can be used to decrease ICP.
• Shunting or surgical decompression (by craniectomy) is indicated in some cases where medical management (corticosteroids, mannitol) has failed to control elevated ICP, and for impending uncal herniation.

Question 15

What are the types of childhood epilepsy syndromes?

Answer 15

• Infantile Spasms (West Syndrome): Age of onset 3-12 months; Violent flexor spasms of the head, trunk and arms followed by extension of arms (salaam attacks) lasting 1-2s, often in bursts of 20-30.
  
  • Most have underlying neurological cause.
  • Most will lose skills and develop learning disability and continuing epilepsy.
• Childhood absence epilepsy: Age of onset 4-12 years; Good prognosis, 80% remission in adolescence, the remainder develop juvenile absence epilepsy and juvenile myoclonic epilepsy.
• Benign Rolandic epilepsy (Benign epilepsy with centro-temporal spikes): Age of onset 4-10 years; Tonic-clonic seizures in sleep, or simple focal seizures with abnormal feelings in the tongue and distortion of the face. 15% of all childhood epilepsies, remits in adolesence.
• Juvenile absence epilepsy: Age of onset 10-20 years; Absences, and generalised tonic-clonic seizures, often with photosensitivity. Learning is impaired. Lifelong treatment.
• Juvenile myoclonic epilepsy: Age of onset 10-20 years; Myoclonic seizures, generalised tonic-clonic seizures, typically shortly after waking. For example throwing drinks of cereal in the morning due to myoclonus. Lifelong treatment.

Question 16

What is the definition and epidemiology of Guillian-Barrè?

Answer 16

Guillain-Barre Syndrome (GBS) is a type of acute post-infectious polyneuropathy characterised by symmetric and ascending flaccid paralysis. In affected patients, cross‑reactive autoantibodies attack the host’s own axonal antigens, resulting in inflammatory and demyelinating polyneuropathy.

It is quite rare, affecting up to 2 per 100,000.

Question 17

What is the aetiology of Guillian-Barrè syndrome?

Answer 17

About ⅔ of GBS patients experience symptoms of an upper respiratory or gastrointestinal tract infection 1–4 weeks prior to the onset of GBS.

• Campylobacter enteritis is the most common disease associated with GBS.
• Cytomegalovirus is the most common virus associated with GBS

Question 18

What are the clinical features of Guillian-Barre syndrome?

Answer 18

Initial symptoms include back and limb pain, esp. paraesthesias affecting distal extremities.

Advanced symptoms include:

• Ascending flaccid paralysis: Bilateral flaccid paralysis spreads from the lower to the upper limbs in a“stocking‑glove” distribution.
• Cranial nerve involvement: frequently bilateral facial nerve involvement (facial diplegia). Facial weakness and speech problems occur in 50% of patients.
• Landry paralysis: involvement of the respiratory muscles. Weakness can cause respiratory distress requiring ventilation.

As with lower motor neurone signs, there is reduced or absent muscle reflexes.

Neuropathic pain develops in about ⅔ of patients

Question 19

What are the subtypes of Guillain-barre syndrome?

Answer 19

Question 20

Describe the investigation results of Guillain-Barre syndrome

Answer 20

• The cerebrospinal fluid analysis shows albuminocytologic dissociation: elevated protein levels and normal cell counts in cerebrospinal fluid (CSF); CSF cell counts higher than 50 cells per μl CSF indicate that GBS is unlikely!
• Serological screening:
  
  • To identify potential pathogens (e.g., Campylobacter jejuni)
  • Detection of antibodies directed against gangliosides (e.g., anti‑GM1 antibodies)
• EMGs: reduced nerve conduction velocity due to demyelination : increased F‑wave latency

Question 21

Describe the management and prognosis of Guillian-Barrè syndrome

Answer 21

Supportive management:

• Monitor cardiac and respiratory function: in some cases, intensive care unit (ICU) treatment and intubation may be indicated
• DVT prophylaxis

High dose of intravenous immunoglobulins or plasmapheresis (equivalent outcome in adults, but the only choice recommended in children)

Although GBS is considered an autoimmune disease, glucocorticoids are not recommended for treatment. They have not shown to hasten recovery or affect the long-term outcome.

Prognosis

Spontaneous recovery - sometimes full, occasionally incomplete - is usual. Up to 70% of patients with GBS have a good prognosis: Disease progression peaks 2–4 weeks after the onset of symptoms.

Question 22

Define Horner’s syndrome

Answer 22

This is a rare condition that results from disruption of the sympathetic nerves supplying the eye. There is the triad of:

• Partial ptosis (upper-lid drooping)
• Moderate miosis (pupillary constriction)
• Hemifacial anhidrosis (absence of sweating).

Question 23

What is the aetiology of Horner’s syndrome?

Answer 23

Horner’s syndrome disruption of the sympathetic arc supplying the eye, and can be due to disease processes at multiple levels. At the level of the:

• Brainstem/spinal chord: tumour (ganglioma), infarction,
• T1 root: brachial plexus lesion, neurofibromatosis
• Cervical sympathetic chain: Pancoast tumour (lung apex)
• Internal carotid artery: dissection or occlusion

Can also be caused by migraine or cluster headaches, as well as rarer causes such as MS.

NEUROANATOMY REMINDER:

Sympathetic innervation to the eye consists of a 3-neuron arc. First order sympathetic fibres originate in the hypothalamus and descend through the brainstem to level C8-T2 of the spinal cord, where they synapse on preganglionic sympathetic fibres.

Second order fibres leave the cord at level T1 and ascend the sympathetic chain over the apex of the lung to synapse in the superior cervical ganglion at the level of the bifurcation of the common carotid artery (C3-C4).

Third order (postganglionic) fibres pass alongside the internal carotid artery, sending branches to the blood vesselsand sweat glands of the face. They then pass via the cavernous sinus to enter the eye via the superior orbital fissure. They pass via the long ciliary nerves to supply the dilator pupillae and levator palpebrae.

Question 24

What are the clinical features of Horner’s syndrome?

Answer 24

Patients may report the inability to open eye fully on the affected side (ptosis). Other two of the classical triad is miosis and anhidrosis.

If there is facial flushing this points to a pregnaglionic lesion, whereas orbital pain/headache points to a postganglionic lesion.

There may be other symptoms depending on the underlying cause such as head/neck pain if associated with carotid artery dissection.

Question 25

What is the aetiology of Meningitis?

Answer 25

* **Bacterial**: * Neonates: Group B Streptococci, *E. coli*, *Listeria monocytogenes* * Children: *Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae* * Adults: ***Neisseria meningitidis**, **Streptococcus pneumoniae**,* Tuberculosis. * Elderly: *Streptococcus pneumoniae* and ***Listeria monocytogenes*** * **Viral**: Enteroviruses, mumps, HSV, VZV, HIV. * Fungal: Cryptococcus (with HIV) * Others: Aseptic meningitis (not due to infection).

Question 26

What are the clinical features of Meningitis?

Answer 26

* Patients present with a **severe headache**, **photophobia** (hours to days onset), **neck stiffness** (absent in some patients) **or back ache** and **fever** and **vomiting**. * Patients are also often **irritable**, **drowsy** and **confused**. They can also present with psychiatric distrubance. * **Focal neurological signs** complicate meningitis in 15% **Seizures** are a presenting feature in 30% of patients. A careful history should reveal risk factors such as recent travel, or exposure to rodents or ticks. On examination there are signs of: * Infection: **fever**, **tachycardia**, **hypotension**, and **non-blanching petechial skin rash** (indicative of *Neisseria meningitidis*). * Meningism: **photophobia**, **neck stiffness**, positive Kernig's sign (patient supine with hip flexed at 90o, knee cannot be fully extended) and Brudzinski's sign (Passive flexion of neck causes flexion of both legs and thighs).

Question 27

What are the potential complications of Meningitis?

Answer 27

* Septicaemia * Shock * DIC * Renal failure * Fits * Peripheral gangrene * Cerebral oedema * Cranial nerve lesions, cerebral venous thrombus, hydrocephalus.

Question 28

What are the investigations for Meningitis?

Answer 28

A **CT scan** is necessary in certain patients **before a lumbar puncture**. This is to exclude causes that would lead to increased cranial pressure (which would lead to herniation during CSF removal). If the patient has recent **neurological deficit**, new-onset **seizures**, **papilledema**, **abnormal level of consciousness**, or is immunocompromised, perform a head CT before CSF removal. A **lumbar puncture** should otherwise be the first test, to analyse the **CSF** for microscopy, culture and sensitivity testing. * In **bacterial** meningitis, the CSF will appear **cloudy**, and have **↑neutrophils**, **↑**protein and ↓**glucose**. * Whereas in **viral** meningitis, there will be ↑**lymphocytes** and **↑protein** but **normal glucose**. Measure opening pressure: opening pressure is often raised (**\>20cm** CSF) in meningitis. In patients where LP is delayed, two sets of **blood cultures** should be sent off. **PCR** can be used to amplify bacterial DNA and diagnose bacterial meningitis over viral meningitis.

Question 29

Describe the management of Meningitis

Answer 29

1. Start with an A-E approach, **stabilising the patient** and giving oxygen. Patient is best managed in **ITU**. 2. **Immediate IV antibiotics** (even before LP and blood cultures) if meningitis is suspected. * **Ceftriaxone** (kills **meningococcus** and **pneumococcus**, but **not listeria**) 2g IV BD * If \>50 years or immunocompromised: add **amoxicillin** 2g IV 4-hourly (to kill **listeria**) 3. Organise CT scan prior to LP (safest option) 4. Make a definitive diagnosis with LP. Use LP to alter antibiotic therapy if necessary 5. **Dexamethasone** is given shortly after or with the first dose of antibiotics, and continued for 4 days. Has been shown to **improve outcome** and **mortality**. Avoid if HIV cause is suspected. 6. Arrange for **contacts** (including medical/nursing staff) to have prophylaxis. **Notify public health England**. If viral meningitis cause is confirmed, continue supportive care and consider **antiviral therapy**. Observe for and if necessary, treat complications.

Question 30

What is the definition and epidemiology of a Stroke?

Answer 30

A stroke is a **rapid permanent neurological deficit from cerebrovascular insult.** Also defined clinically as a focal or global impairment of CNS function developing rapidly and lasting \>24h (see TIA). Can be subdivided into location (e.g. anterior circulation or posterior circulation) or by pathological process (infarction, haemorrhage). Strokes are common. Annual incidence is **2 in 1000**. It is the **third most common cause of death in developed countries.**

Question 31

What is the aetiology of a Stroke?

Answer 31

**Infarction** (80%): * **Thrombosis** secondary to **atherosclerosis** of the vessel causing partial or full occlusion\*\*.\*\* Commonly affects small cerebral vessels (**lacunar infarcts**) and less commonly affects the large vessels (e.g. middle cerebral artery). * **Emboli**: Thrombus forming elsewhere such as the **heart (due to atrial fibrillation)** and lodging in the cerebral arteries. Also due to **intimal flap** of a **carotid dissection**. Rarely thromboemboli from the venous circulation, fat, air, non-bacterial endocarditis. * Hypotension: If below the autoregulatory range maintaining cerebral blood, infarction results from the 'watershed zones' between different cerebral artery territories. * Others: **vasculitis**, **cocaine**. **Haemorrhage** - primary intracerebral haemorrhage or subarachnoid haemorrhage (SAH) (20%): **Severe hypertension**, Charcot-Bouchard **microaneurysm rupture**, **amyloid angiopathy**, arteriovenous malformations. Less commonly trauma, tumours. Patients tend to have a family history (pointing to anatomical anomaly).

Question 32

What are the risk factors for a Stroke?

Answer 32

For infarction stroke: Hypertension, older age, male sex, FHx of stroke, Hx of ischaemic stroke or other atheromatous events, smoking, diabetes. Diseases such as atrial fibrillation, carotid artery stenosis, sickle-cell disease.

Question 33

What are the general clinical features of a Stroke? (not asking specifically about stroke syndromes)

Answer 33

**Sudden onset** deficits (within seconds). Patients usually present with **weakness**, **sensory,** visual or **cognitive impairment**, impaired **coordination** or **consciousness**. The loss of function depends on the area of brain tissue involved in the ischaemic process. **Haemorrhagic** stroke can present with a combination of **_headache_**, **_meningism_**, **vomiting**, and **loss of consciousness** if acute onset. However, it is not possible to differentiate between haemorrhagic and ischaemic strokes from clinical examination alone or with the aid of scoring systems. A CT scan is required.

Question 34

What are the differentials to consider for a stroke?

Answer 34

Strokes tend to commence suddenly and the deficit is as its peak established within 24 hours. Many conditions may masquerade as a stroke: * **Space occupying lesion** - consider if the evolution of symptoms is longer than 24 hours or progresses in a stuttering way over days in weeks. * **Subdural haematoma** should be suspected if the levels of consciousness is variable * **Abscess** of the brain, or **encephalitis** should be suspected if the patient presents with pyrexia. * Focal migraine, psychogenic, Todd's paresis (post-seizure) or hypoglycaemic attack can also present similarly to a stroke. An alternative diagnosis is more likely in those aged \<45 years, in absence of risk factors, presence of seizures, papilloedema, pyrexia, or fluctuating levels of consciousness.

Question 35

What are the features of an anterior circulation stroke?

Answer 35

* **_Anterior cerebral artery_** syndrome is often due to embolic stroke and presents with **contralateral leg weakness** (motor cortex) and **confusion** (frontal lobe). * **_Middle cerebral artery (MCA):_** **contralateral facial weakness** and **hemiparesis** usually of **arms** (motor cortex), **hemi-sensory loss** (loss of feeling in contralateral face and arm) (somatosensory cortex). Receptive and/or expressive **dysphasia**. Dyslexia, dysgraphia, dyscalculia.

Question 36

What are the features of a lacunar stroke?

Answer 36

* Internal capsule or pons: **Pure sensory** and/or **motor deficit**. * Thalamus: **Loss of consciousness**, **hemisensory deficit**. * Basal ganglia: **Hemichorea**, parkinsonism.

Question 37

What are the features of a posterior circulation stroke?

Answer 37

* Posterior cerebral: **Contralateral homonymous hemianopia** * Anterior inferior cerebellar artery: **Vertigo**, ipsilateral **ataxia**, ipsilateral deafness, ipsilateral facial weakness. * Posterior inferior cerebellar artery: **Vertigo**, ipsilateral **ataxia**, ipsilateral **Horner's syndrome**, hemifacial loss, dysarthria and contralateral **spinothalamic sensory loss**. * Basilar artery: **combination of cranial nerve** pathology and **impaired consciousness**.

Question 38

What are the investigations for a Stroke?

Answer 38

A **CT-head** should be performed **as soon as possible** to **detect/rule out intercranial haemorrhage**. In most cases, CT-head is **normal** within the first few hours of a ischaemic stroke. However, a haemorrhage is seen as a **darkness** (hypoattenuation) of the brain parenchyma. An **MRI** of the brain is good at detecting an **infarct stroke** as well as a haemorrhagic stroke. However, many centres do not have a head-MRI available. Diffusion-weighted imaging can differentiate between old (\>2 weeks) stroke and new ones. While CT/MRI transport is being organised, a cannula should be placed in order to sample blood: * **Serum glucose** (to exclude hyper- or hypo- glycaemia) * Serum **U&Es** (to exclude electrolyte disturbances and renal failure) * **Cardiac enzymes** (to exclude concomitant MI) * **FBC** to look at anaemia and possible thrombocytopaenia * **Prothrombin Time and PTT** is required to exclude coagulopathy prior to thrombolytics. An **24h ECG** should be done to identify any **arrhythmias** which pre-dispose to embolism and **exclude acute MI**. **CT/MRI angiography** to detect artery dissections or intracranial stenosis.

Question 39

Describe the management of an ischaemic stroke

Answer 39

All patients should receive CT imaging and be admitted to a **specialist acute stroke unit** for specialist monitoring and treatment. **THROMBOLYSIS:** If **\<4.5h** from **onset of symptoms** and **currently with significant neurological deficit** and **haemorrhage excluded** on CT-head, intravenous **thrombolysis** with **tPA** (**alteplase**) should be considered. Check for (long list) of contraindications such as clotting disorder or recent history of head trauma, or previous MI, stroke, or head trauma within last 3 months. Give **aspirin 300mg** as soon as haemorrhage has been excluded and **24 hours after** tPA to prevent further strokes. **THROMBECTOMY**: **Stent retrievers** (catheter to remove thromboembolus in large vessel occlusion) should be considered for patients who match the criteria and performed ideally within the **first 6 hours**. If presents \>4.5h from onset, or there are contraindications for tPA, administer **aspirin** alone. **DVT prophylaxis** is important for those with infarct stroke, as DVT/PEs are responsible for 10% of stroke deaths. This is done with **heparin/dalteparin** and **early mobilisation**. **Long-term antiplatelet** of choice is **clopidogrel** which is given lifelong after ischaemic stroke. Second-line is aspirin + dipyridamole. **Supportive care** in a specialised stroke ward has been shown to decrease mortality and disability after 1 year. **Supplemental oxygen** should be provided. **Swallowing assessment** is important because swallowing impairment in stroke is associated with an increased risk of **aspiration pneumonia** and death.

Question 40

What are the potential complications following a Stroke?

Answer 40

*Cerebral complications* * **Transtentorial herniation** is the most common cause of death in the first week. It is due to raised ICP secondary to **cerebral oedema**. * **Haemorrhagic transformation** occurs in 30% of ischaemic stroke usually 12h to 4 days after the event. * **Acute hydrocephalus** due to compression of the aqueduct of Sylvius by oedema or blood. * **Seizures** may complicate 20% of infarcts are most common in haemorrhagic or cortical stroke. * SIADH occurs in 10-15% of strokes. *Systemic complications* * **Aspiration is common** - dysphagia occurs in at least half of all cases of stroke. * **Immobility**. * **Infections** (e.g. pneumonia, UTI, from pressure sores) are a common cause of death after stroke. * **DVT** incidence is comparable to that following a hip or knee arthroplasty. PE accounts for 25% of early deaths following a stroke. * **Cardiovascular events** (arrhythmias, MI, cardiac failure) * Death

Question 41

What is the definition of a TIA?

Answer 41

A TIA is a **transient episode of neurological dysfunction** caused by focal brain, spinal chord, or retinal **ischaemia**, **without acute infarction**. This has replaced the old definition of lasting less than 24h. The majority of TIAs resolve in the first hour.

Question 42

What is the aetiology of a TIA?

Answer 42

* **Cardioembolic events** (most common) - when an intracardiac embolus forms secondary to **stasis** from **impaired ejection fraction** or **atrial fibrillation**. The precipitating factor may be a thrombogenic nidus within the heart such as an infectious vegetation or artificial valve. Rarely, thrombus can pass from the venous system across a cardiac shunt to create paradoxical emboli. * In situ **thrombosis** of an intracranial artery as a result of an unstable plaque. * Small-vessel occlusion, occlusion due to hypercoagulability, dissection, vasculitis, vasospasm, or sickle-cell occlusive disease. * Often **uncertain mechanism**.

Question 43

What are the clinical features of a TIA?

Answer 43

The **patient** or the **caregiver** will report a **focal neurological deficit** that only lasts for a **brief duration**. The deficit tends to be **unilateral** as TIAs tend to affect areas of the brain controlling function of the **contralateral side** of the body. On examination: patient may present with an **increased BP** which often happens as a protective mechanism to maintain cerebral blood flow. Note an **absence of positive symptoms** such as shaking, scomata, spasms - as these suggest seizure, migraines etc.

Question 44

What are the investigations for a TIA?

Answer 44

**Bloods** are mainly to exclude other disorders: * **Glucose** - important to exclude hypoglycaemia. Glucose \<3.3 mmol/l suggests hypoglycaemia as cause. * U&Es - severe disturbances may explain symptoms. * FBC - usually normal. An **ECG** may show **atrial fibrillation** - should be done for all patients who have had a TIA. **MRI** should be done as an initial evaluation in some cases particularly if vascular territory or pathology is uncertain. It is helpful but not universally recommended because it is not available in some areas, and cost-effectiveness has been called into question. **Fasting lipid profile** is useful as guidelines recommend treatment with statin therapy. **Angiography** may show presence of stenosis.

Question 45

Describe the management of a TIA

Answer 45

Whereas previous advice involved using risk scores such as the ABCD2 score, latest NICE guidelines advise against the use of such scores to inform urgency or referral of patients with suspected TIAs. The immediate management of a suspected TIA is: * Offer **aspirin (300 mg daily)**, unless contraindicated, to people who have had a suspected TIA, to be started **immediately**. * Common contra-indications are to patients already taking another anticoagulant or aspirin daily, or has a bleeding disorder. * **Refer immediately** people who have had a suspected TIA for specialist assessment and investigation, to be seen within 24 hours of onset of symptoms. ***Do not routinely* arrange a CT scan** as NICE has concluded it is rarely beneficial and simply prolongs hospital stay, unless an alternative diagnosis is being considered. An MRI scan is often done in TIA clinic (on same day as assessment) to determine the territory of ischaemia, or to detect haemorrhage or alternative pathologies. As soon as a TIA is confirmed, patients should be started on **secondary prevention** usually with **clopidogrel** long-term. Studies show combination of clopidogrel and aspirin to be more effective at reducing incidence of stroke. (NEJM 2013;369:11) A **lipid lowering agent** such as **simvastatin** should be considered for all patients with atherosclerotic risk factors. **Lifestyle modifications** and **antihypertensive therapy** should also be offered if appropriate.

Question 46

What are the clinical features of Tension Headache?

Answer 46

A tension headache can either be **episodic** or **chronic**. It is **very common**. It is frequently described as a **tight band** around the **head**, often radiating into the **neck**. The source of the pain is believed to be chronic contraction of the head and neck muscles. The patient usually has a background of **stress and worry**, sometimes with clinically significant anxiety or depression. The patient may be worried about it being a brain tumour, fuelling the stress and anxiety further. They are **rarely disabling** and are **not associated with autonomic dysfunction**.

Question 47

Describe the management of Tension Headache

Answer 47

Treatment usually starts by helping the patient **understand** the nature of the headache, with **reassurance** (after careful neurological examination). Advise them to take simple **analgesics** such as **paracetamol** or **aspirin**. Underlying **depression** should be treated. *Chronic* **Antidepressants** such as **amitriptyline** have been shown to help treat tension headaches, even if dose is lower than needed to treat depression. Non-drug **relaxing therapies** such as **relaxation training, EMG biofeedback, cognitive behavioural therapy** can be used.

Question 48

What are the clinical features of Cluster Headache?

Answer 48

A cluster headache is considered to be **one of the most painful conditions** known to humanity. Predominantly **affect men** more than women, and 1 in 500. They tend to occur in clusters, **repetitively**, **once or twice a day**, for **several weeks**. After, they have a **long interval** of a year or more until it recurs in the same way. The attacks themselves are **brief**, lasting **30-120 minutes**. They often occur at the same time in each 24h cycle. The pain is **extremely severe** and tends be felt around **one eye**. It is usually accompanied by ipsilateral signs of **autonomic dysfunction** including **redness**, **swelling**, **nasal congestion** or **Horner's syndrome**. The patient may also complain of nausea, vomiting, photophobia, and a migranous aura.

Question 49

Describe the diagnosis and management of cluster headache

Answer 49

**A brain CT/MRI is done to exclude secondary causes** and is often normal in primary cluster headaches. However, abnormalities can point towards a secondary cause. Management * Acute: **100% oxygen** (80% response rate within 15 minutes), **subcutaneous triptan** (75% response rate within 15 minutes) * Prophylaxis: **verapamil** (calcium channel blocker) is the drug of choice. There is also some evidence to support a tapering dose of prednisolone * NICE recommend seeking specialist advice from a neurologist if a patient develops cluster headaches with respect to neuroimaging

Question 50

What is the definition and epidemiology of Migraine?

Answer 50

A migraine is a **severe episodic headache** that may have a prodrome of focal neurological symptoms (aura) and is associated with systemic disturbance. Can be classified as a **common migraine** (without aura) or **classical migraine**(with aura). Migraines are very common, affecting **15% of women** and **6% of men**. Usual onset is **adolescence or early adulthood**.

Question 51

What are the clinical features of Migraine?

Answer 51

A migraine produces **episodes** of headaches, which can be described **as severe** and **pulsating,** often on one side of the head (more common in adolescents), but can also be bilateral. It is also often felt at the **front of the head**. The patient is usually fine in between episodes. The migraine usually lasts **for several hours** (some patients experience intermittent episodes for days). Patients also tend to experience **nausea**, **vomiting**, **photophobia** and **phonophobia** during the migraine episode. Classically (although uncommonly) preceded by an **aura**, which may include: * **Visual symptoms** (most commonly) such as **zigzag** lines and/or **scotoma** — visual aura is the most common type of aura. * **Sensory symptoms** such as unilateral **pins and needles** or **numbness**. * **Speech** and/or language symptoms such as **dysphasia**. Completely normal examination features.

Question 52

What are the triggers for a migraine?

Answer 52

* **Stress** and fatigue (even relaxation after stress) * Skipping meals * Binge eating * **Specific foods** (cheese, citrus etc) * Specific **drinks** (**caffeine**, **wine**) * **Menstruation** or ovulation * **Oral contraceptive**.

Question 53

Describe the management of Migraine

Answer 53

Acute treatment: * First-line: offer combination therapy with an **oral triptan (5HT1 agonist)** and an \*\*NSAID/\*\*paracetamol * For young people aged 12-17 years consider a nasal triptan in preference to an oral triptan * If the above measures are not effective or not tolerated add an antiemetic - a non-oral preparation of **metoclopramide**\* or **prochlorperazine** and consider adding a non-oral NSAID or triptan Adequate **hydration** is also important as dehydration can cause migraines. Prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients. * NICE advise **either topiramate or propranolol**'according to the person's preference, comorbidities and risk of adverse events'. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives

Question 54

What is the definition and epidemiology of Myasthenia Gravis?

Answer 54

Myasthenia gravis is an **autoimmune condition affecting the neuromuscular junction**, causing skeletal muscle weakness. It is more common in **females** at **younger** ages, but **males** in the **elderly**.

Question 55

What is the aetiology and associated conditions of Myasthenia Gravis?

Answer 55

It is most commonly caused by **autoantibodies** (Type II Hypersensitivity) to **nicotinic acetylcholine receptor** (nAChR) on the **neuromuscular junction**, preventing acetylcholine from binding. * It is associated with **other autoimmune conditions** such as Grave's disease, Rheumatoid Arthritis, SLE. * It is also associated with **thymoma** (most common primary tumour in the anterior mediastinum) in **10-15% of patients** as well as **thymic hyperplasia** in 65% of patients. Thought to be related to pathophysiology as myoid cells in the thymus express AChR. A **paraneoplastic** subtype (**Lambert-Eaton myasthenic syndrome**) is caused by autoantibodies against pre-synaptic calcium ion channels - commonly due to Small Cell lung cancer.

Question 56

What are the clinical features of Myasthenia Gravis?

Answer 56

**Muscle weakness** that **worsens throughout the day** or with **repetitive use**. However, in Lambert-Eaton syndrome it is the opposite, with weakness improving after repetitive use. Patients most often complain of ocular symptoms such as **drooping** of the **eyelids (bilateral** ptosis) or **diplopia**. They also have bulbar symptoms such as **dysarthria** (difficulty articulating speech), **dysphagia**, **facial weakness/paresis** (myasthenic snarl). Patients can also complain of **proximal muscle weakness**, commonly difficulty walking up the stairs. However, **without muscle wasting**, and with **normal reflexes** and **intact sensations**. Uncommonly, patients can have **shortness of breath**. If this is so severe as to need **ventilation**, it is called a Myasthenia gravis crisis.

Question 57

What are the investigations for Myasthenia Gravis?

Answer 57

Bloods: * **CK** (to exclude myopathies) * **Serum acetylcholine receptor (AChR) antibodies** (positive in 80%) * Muscle-specific tyrosine kinase antibodies (another cause of myasthenia gravis) or Calicum channel antibodies (Lambert-Eaton) * Consider testing for other autoimmune disorders, such as thyroiditis, SLE, and/or rheumatoid arthritis! **Repetitive nerve stimulation** and **conduction** studies. The repetitive nerve stimulation will show a **decremental response** in Myasthenia Gravis. While the opposite (an incremental response) will be seen in Lambert-Eaton syndrome. In cases of myasthenia gravis, it is important to perform a **CT chest** in order to look for a thymoma. Removal of a thymoma may improve the condition in certain patients and prevents malignant transformation. The **Tensilon test** (generally not done anymore as can cause bradycardia) is administering a short-acting anticholinersterase, to see if symptoms improve. **Single-fibre EMG** may show 'jittering'.

Question 58

Describe the management of Myasthenia Gravis

Answer 58

* Long-acting **cholinesterase inhibitors** e.g. **pyridostigmine** provides symptomatic relief. * If symptoms persist, immunosuppression with prednisolone initially. * **Thymectomy can be beneficial even if thymoma not present.**

Question 59

What are the differences between Myasthenia Gravis and Lambert-Eaton syndrome?

Answer 59

LEMS is a rare autoimmune disease that reduces neuromuscular transmission and leads to muscle weakness. There are a few differences between LEMS and MG: * The auto-antibodies are **directed to presynaptic voltage-gated sodium channels**. * In contrast to muscle weakness worsening with use, in Lambert-Eaton, **muscle weakness improves with use**. * Whereas MA is associated with thymomas, LEMS is associated with **small-cell lung carcinoma**.

Question 60

What is the definition and epidemiology of Multiple Sclerosis?

Answer 60

MS is defined as an **inflammatory demyelinating disease** characterised by the presence of **episodic neurological dysfunction** in at least **2 areas of the CNS** (brain, spinal cord, and optic nerves) **separated** in **time** and **space**. * MS is the most common cause of neurological disability in young adults, affecting 1 in 1000 patients. * Most commonly diagnosed between the ages of **20-40 years** and affecting **females** more than males (2:1).

Question 61

What are the different types of Multiple Sclerosis?

Answer 61

There different types of MS (not biologically based, but clinically retrospectively): * **Relapsing-remitting MS** - commonest form. Characterised by clinical attacks of demyelination with **complete recovery in between attacks**. * **Secondary progressive MS** - \>50% of patients with relapsing-remitting MS develop an accumulative progressive course. * **Primary-progressive MS** - **steady accumulation** of disability with no clear relapsing-remitting pattern. * **Clinically isolated syndrome** - single clinical attach of demyelination (does not qualify as MS), but 10-50% progress to developing MS. * **Marburg variant** - severe fulminant variant of MS leading to advanced disability to death within a period of weeks. Distinct from acute disseminated encephalopathy (ADEM).

Question 62

What is the aetiology of Multiple Sclerosis?

Answer 62

Unknown aetiology with autoimmune basis. **EBV exposure** and **prenatal vitamin D levels** have been found to be associated with MS in epidemiological studies. A **Type IV hypersensitivity** reaction to **myelin**.

Question 63

What are the symptoms of Multiple Sclerosis?

Answer 63

Symptoms depend on the site of inflammation. Common ones include: * **Optic neuritis** (commonest) **in one eye** - **Impaired visual acuity** (described as looking through jelly), **loss of colour discrimination** and **pain** moving the affected eye. * Particular **sensory phenomena** such as pins and needles, odd sensations, numbness, burning. * **Motor** symptoms such as **weakness** in limbs causing **foot drop** or spasms. (UMN signs as affects the CNS - **increased tone,** brisk **reflexes**) * **Autonomic** symptoms are also common, causing **urinary urgency**, hesitancy, **incontinence** (urinary and faecal) and **impotence**. * Psychological symptoms of **depression** and **psychosis**.

Question 64

What are the examination findings of Multiple Sclerosis?

Answer 64

**Fundoscopy** may reveal **optic neuritis**. In chronic disease there may be optic atrophy. **Visual field** examination may reveal central or field defects. There may be a **abnormal RAPD** (relative afferent pupillary defect). Can **elicit motor signs** (UMN) such as **increased tone, reflexes, weakness**. There may be cerebellar signs such as **dysdiadochokinesia**, **intention tremor**, **ataxic wide-based gait**, scanning speech. May elicit **Lhermitte’s phenomenon**: (Electric shock-like sensation in arms and legs precipitated by neck flexion).

Question 65

What are the investigations for Multiple Sclerosis?

Answer 65

Diagnosis is made from **two or more CNS lesions** with corresponding symptoms, separated by time and space. **MRI** of **brain and cervical spine** with **gadolinium** to look for **plaques** indicating MS. A **lumbar puncture** can be done to look for other inflammatory causes of symptoms. **Oligoclonal bands** and increased **CSF immunoglobulins** point to MS. **Evoked potentials** may show **slow delayed conduction velocity**. VEPs (visual electrode potentials) are slow in ~90% of MS patients.

Question 66

Describe the management of Multiple Sclerosis acute flare-up

Answer 66

Patients with relapsing-remitting and secondary progressive MS experience exacerbations, for which the first line treatment is **high-dose glucocorticoids** such as **methylprednisolone** usually for 3-5 days. * If symptoms decrease: End glucocorticoid therapy by slowly tapering the dose. * Second line: **plasmapheresis**

Question 67

What are the disease modifying drugs that are used in the management of Multiple Sclerosis?

Answer 67

Question 68

How do you treat spasticity in multiple sclerosis?

Answer 68

Spasticity: **baclofen** and **gabapentin** are first-line. Other options include dantrolene and tizanidine. **Physiotherapy** is important.

Question 69

How do you treat fatigue in multiple sclerosis?

Answer 69

Fatigue: * Once other problems (e.g. anaemia, thyroid or depression) have been excluded NICE recommend a trial of **amantadine** * Other options include **mindfulness training and CBT**

Question 70

How do you treat bladder dysfunction in multiple sclerosis?

Answer 70

**Bladder dysfunction** may take the form of urgency, incontinence, overflow etc. * Guidelines stress the importance of getting an **ultrasound first to assess bladder emptying** - anticholinergics may worsen symptoms in some patients. * If **significant residual volume** → intermittent **self-catheterisation** * if no significant residual volume → **anticholinergics** such as oxybutynin may improve urinary frequency.

Question 71

What are some common causes of neuropathic pain?

Answer 71

Examples include: * Diabetic neuropathy * Post-herpetic neuralgia * Trigeminal neuralgia * Prolapsed intervertebral disc

Question 72

Describe the management of neuropathic pain

Answer 72

NICE updated their guidance on the management of neuropathic pain in 2013: * First-line treatment\*: **amitriptyline** (TCA), **duloxetine** (SNRI), **gabapentin** or **pregabalin** * If the first-line drug treatment does not work try one of the other 3 drugs * **Tramadol** may be used as '**rescue therapy**' for exacerbations of neuropathic pain * **Topical capsaicin** may be used for **localised neuropathic** pain (e.g. post-herpetic neuralgia) * Pain management clinics may be useful in patients with resistant problems \*for some specific conditions the guidance may vary. For example carbamazepine is used first-line for trigeminal neuralgia *