Neurology Flashcards
which cerebral lobe is involved?
• Difficulties with task sequencing
• Difficulties with executive skills
• Expressive aphasia (Broca’s)
• Anosmia
Frontal lobe
Broca’s area: located in the posterior aspect of the frontal lobe, in the inferior frontal gyrus
which cerebral lobe is involved?
• Primitive reflexes
• Perseveration (repeatedly asking same question or doing same task)
• Changes in personality
• Inability to generate a list
• Disinhibition
Frontal lobe
which cerebral lobe is involved?
• Apraxias: loss of the ability to execute learned purposeful movements
• Neglect
• Astereognosis (unable to recognise object by feeling) = tactile agnosia
• Homonymous inferior quadrantanopia
• Sensory inattention
• Acalculia: inability to perform mental arithmetic
Parietal lobe
what is Gerstmann’s syndrome? where is the lesion?
Gerstmann’s syndrome (lesion of dominant parietal):
o Alexia: in ability to read
o Acalculia
oFinger agnosia
oRight-left disorientation.
which cerebral lobe is involved?
• Homonymous superior quadrantanopia
• Prosopagnosia (difficulty recognising
faces)
Temporal lobe
which cerebral lobe is involved?
• Wernike’s (recepTive) aphasia
• Memory impairment
• Auditory agnosia
Temporal lobe
which cerebral lobe is affected?
• Cortical blindness (blindness due to damage to visual cortex, may present as Anton syndrome: there is blindness but patient is unaware or denies blindness)
• Homonymous hemianopia
occipital lobe
which cerebral lobe is affected?
• Visual agnosia (seeing but not percieving objects - it is different to neglect since in agnosia the objects are seen and followed but cannot be named)
occipital lobe
which column is involved in joint position and light touch?
Dorsal column dysfunction: (joint position and light touch)
which column is involved in pinprick and temperature ?
Spinothalamic dysfunction: (pinprick and temperature)
DVLA rules for:
• First seizure with no abnormality of ix
- For patients with established epilepsy
• Stroke or TIA
• Multiple TIAs over short period of times
• Craniotomy e.g. For meningioma
• Pituitary tumour: craniotomy:
• trans-sphenoidal surgery ‘can drive when there is no debarring residual impairment likely to affect safe driving’
• Narcolepsy/cataplexy
• First seizure: 6 months off driving (if the licence holder has undergone assessment by an appropriate specialist and no relevant abnormality has been identified on investigation, for example EEG and brain scan where indicate). For patients with established epilepsy they must be fit free for 12 months before being able to drive.
• Stroke or TIA: 1 month off driving
• Multiple TIAs over short period of times: 3 months off driving
• Craniotomy e.g. For meningioma: 1 year off driving (With benign tumors and if there is no seizure history, licence can be reconsidered in 6 months if remains seizure free)
• Pituitary tumour: craniotomy: 6 months; trans-sphenoidal surgery ‘can drive when there is no debarring residual impairment likely to affect safe driving’
• Narcolepsy/cataplexy: cease driving on diagnosis, can restart once ‘satisfactory control of symptoms’
Syncope and DVLA rule
• Simple faint:
• Unexplained, low risk of recurrence:
• Explained and treated:
• Unexplained:
Syncope
• Simple faint: no restriction
• Unexplained, low risk of recurrence: 4 weeks off
• Explained and treated: 4 weeks off
• Unexplained: 6 months off
what is cataplexy?
Cataplexy describes the loss of muscular tone caused by strong emotion (e.g. laughter, being frightened).
Around two-thirds of patients with narcolepsy have cataplexy
Homonymous hemianopia:
-where is the lesion if the defect is incongruent?
-where is the lesion if the defect in congruent?
-where is the lesion if there is macula sparing?
Homonymous Hemianopia
• Incongruous defects = optic tract lesion
• Congruous defects (defect is approximately the same in each eye) :
optic radiation lesion or occipital cortex
• Macula sparing: lesion of occipital cortex
Homonymous quadrantanopia:
Where is the lesion if it is a superior quadrantanopia?
Where is the lesion if it is an inferior quadrantanopia?
• Superior: lesion of temporal lobe
• Inferior: lesion of parietal lobe
• Mnemonic = PITS (Parietal-Inferior, Temporal-Superior)
Bitemporal hemianopia:
-where is the lesion?
-if the lesion is an upper quadrant defect where is the compression and what is this commonly caused by?
-if the lesion is a lower quadrant defect where is the compression and what is this commonly caused by?
Lesion of optic chiasm
• Upper quadrant defect > lower quadrant defect = inferior chiasmal
compression, commonly a pituitary tumour
Lower quadrant defect > upper quadrant defect = superior chiasmal compression, commonly a craniopharyngioma
what are 4 causes of nystagmus?
• Visual disturbances
• Lesions of the labyrinth
• The central vestibular connections
• Brain stem or cerebellar lesions.
what does the medial longitudinal bundle do?
Medial Longitudinal Bundle → coordinates lateral rectus of one side with medial rectus of the other
what causes upbeat vs downbeat nystagmus?
Upbeat nystagmus: Cerebellar vermis lesions
Downbeat nystagmus - foramen magnum lesions
-Arnold-Chiari malformation
Subdural haemorrhage:
-when is this most commonly seen?
-what is this caused by?
• Most commonly secondary to trauma e.g. Old person/alcohol falling over
• Initial injury may be minor and is often forgotten
• Caused by bleeding from damaged bridging veins between cortex and venous sinuses
The combination of falls, alcohol excess, fluctuating episodes of confusion and focal neurology points towards a diagnosis of ?hemorrhage. The phrase ‘fluctuating conscious level’ is common in questions and should always bring to mind ?hemorrhage
subdural
what are three features of subdural haemorrhage?
Features
• Headache
• Classically fluctuating conscious level
• Raised ICP
what is the treatment for subdural haemorrhage?
Treatment
• Needs neurosurgical review
• Burr hole
what are 4 causes of subarachnoid haemorrhage?
• 85% are due to rupture of berry aneurysms (conditions associated with berry aneurysms include adult polycystic kidney disease, Ehlers-Danlos syndrome and coarctation of the aorta).
• AV malformations.
• Trauma.
• Tumours
what are 2 investigations for subarachnoid haemorrhage?
-if both were negative with a high level of suspicion, what should be done next?
Investigations
• CT: negative in 5%.
• LP: done after 12 Hrs (allowing time for
xanthochromia to develop) If the CSF examination did not reveal xanthochromia, or there was still a high level of clinical suspicion, then cerebral angiography would be the next step
what are 3 complications for subarachnoid haemorrhage?
Complications
• Rebleeding (in 30%)
• Obstructive hydrocephalus (due to blood in ventricles)
• Vasospasm leading to cerebral ischemia
what is seen on the ECG with subarachnoid haemorrhage?
Intracranial hemorrhage can cause changes in the ECG which are typically deep symmetrical T- wave inversion and prolonged QT interval
what is the management of subarachnoid haemorrhage?
• Neurosurgical opinion: no clear evidence over early surgical intervention against delayed intervention
• Nimodipine (e.g. 60mg / 4 hrly, if BP allows) has been shown to ↓ the severity of neurological deficits but doesn’t ↓ rebleeding
Extradural haemorrhage:
-where is the bleeding?
-what is this most commonly caused by?
-where is this most commonly seen?
Bleeding into the space between the dura mater and the skull.
Often results from acceleration-deceleration trauma or a blow to the side of the head (pterion region).
The majority of epidural Hematomas occur in the temporal region where skull fractures cause a rupture of the middle meningeal artery.
what are 2 features of extradural haemorrhage?
Features
• Features of raised intracranial pressure
• Some patients may exhibit a lucid interval
Intracranial venous thrombosis:
-what can these cause?
-what do 50% of patients have?
• Can cause cerebral infarction, much less common than arterial causes
• 50% of patients have isolated sagittal sinus thromboses - the remainder have coexistent lateral
sinus thromboses and cavernous sinus thromboses
what are three features of intracranial venous thrombosis?
Features
• Headache (may be sudden onset)
• Nausea & vomiting
• Papilledema
sagittal sinus thrombosis:
-how may this present?
Sagittal sinus thrombosis
• May present with seizures and hemiplegia
• Parasagittal biparietal or bifrontal hemorrhagic infarctions are sometimes seen
cavernous sinus thrombosis:
-what are the clinical features?
Cavernous sinus thrombosis
• Other causes of cavernous sinus syndrome: local infection (e.g. Sinusitis), neoplasia, trauma
• Ophthalmoplegia due to IIIrd, IVth and VIth nerve damage
• Trigeminal nerve involvement may lead to hyperaesthesia of upper face and eye pain
• Central retinal vein thrombosis
• Swollen eyelids
What cranial nerve palsies are assoc. with lateral sinus thrombosis?
Lateral sinus thrombosis
• VIth and VIIth cranial nerve palsies
what is the first line treatment for delirium if needed?
haloperidol 0.5mg then lorazepam
what is Marchiafava Bignami syndrome?
Marchiafava Bignami syndrome: Corpus callosum degeneration from chronic alcohol excess
what is the triad of normal pressure hydrocephalus?
A classical triad of features is seen
• Urinary incontinence
• Dementia and bradyphrenia (slowness of thought)
• Gait abnormality (may be similar to parkinson’s disease)
what is normal pressure hydrocephalus?
-what is this thought to be secondary to?
-what can cause this?
is a reversible cause of dementia seen in elderly patients. It is thought to be secondary to ↓ CSF absorption at the arachnoid villi. These changes may be secondary to head injury, subarachnoid hemorrhage or meningitis
what is seen on imaging in normal pressure hydrocephalus?
Imaging
• Hydrocephalus with an enlarged fourth ventricle
what is the management of normal pressure hydrocephalus?
Management
• Ventriculoperitoneal shunting
who does idiopathic intracranial hypertension affect?
Idiopathic Intracranial Hypertension (also known as pseudotumour cerebri and
formerly benign intracranial hypertension) is a condition classically seen in young, overweight ♀.
what are the features of idopathic intracranial hypertension?
• Headache
• Blurred vision
• Papilledema (usually present)
• Enlarged blind spot
• Sixth nerve palsy may be present
what are 4 risk factors for idiopathic intracranial hypertension?
• Obesity
• ♀sex
• Pregnancy
• Drugs (in this case it is not idiopathic): oral contraceptive pill, steroids, tetracycline, vitamin A
what are 3 investigations for idiopathic intracranial hypertension?
- CT Scan
- LP
- Cerebral MRI with MR Venography
what is the management for idiopathic intracranial hypertension?
-5 causes
• Weight loss
• Diuretics e.g. Acetazolamide
• Corticosteroids can be given
• Repeated lumbar puncture
• Surgery: optic nerve sheath decompression and fenestration may be needed to prevent damage
to the optic nerve. A lumboperitoneal or ventriculoperitoneal shunt may also be performed to ↓ intracranial pressure
describe the ABCD2 score in TIA
-is this still used?
The ABCD2 prognostic score has previously been used to risk stratify patients who present with a suspected TIA. However, data from studies have suggested it performs poorly and it is therefore no longer recommended by NICE Clinical Knowledge Summaries
Criteria
Points
Age ≥ 60 years - 1
Blood pressure ≥ 140/90 mmHg - 1
Clinical features
- Unilateral weakness - 2
- Speech disturbance, no weakness - 1
Duration of symptoms
- > 60 minutes - 2
- 10-59 minutes - 1
Patient has diabetes - 1
what to do in the management of TIA?
Immediate antithrombotic therapy: give aspirin 300 mg immediately, unless
1. the patient has a bleeding disorder or is taking an anticoagulant (needs immediate admission for imaging to exclude a haemorrhage)
2. the patient is already taking low-dose aspirin regularly: continue the current dose of aspirin until reviewed by a specialist
3. Aspirin is contraindicated: discuss management urgently with the specialist team
what is the management for patients if the patient has had more than 1 TIA or has a suspected cardioembolic source/ severe carotid stenosis?
If the patient has had more than 1 TIA (‘crescendo TIA’) or has a suspected cardioembolic source or severe carotid stenosis:
discuss the need for admission or observation urgently with a stroke specialist
what is the management if a patient has had a suspected TIA in the last 7 days?
If the patient has had a suspected TIA in the last 7 days:
arrange urgent assessment (within 24 hours) by a specialist stroke physician
what is the management if a patient has had a suspected TIA which occurred more than a week previously?
If the patient has had a suspected TIA which occurred more than a week previously:
refer for specialist assessment as soon as possible within 7 days
what drugs are used for antithrombotic therapy in TIA
clopidogrel is recommended first-line (as for patients who’ve had a stroke)
aspirin + dipyridamole should be given to patients who cannot tolerate clopidogrel
these recommendations follow the 2012 Royal College of Physicians National clinical guideline for stroke.
In Acute stroke:
-what should be kept within normal limits?
-what should not be lowered?
-what should be given ASAP after haemorrhagic stroke excluded?
-when should anticoagulants be initiated for atrial fibrillation?
-when should statins be used?
-blood glucose, hydration, oxygen saturation and temperature should be maintained within normal limits
-blood pressure should not be lowered in the acute phase unless there are complications e.g. Hypertensive encephalopathy
-aspirin 300mg orally or rectally should be given as soon as possible if a haemorrhagic stroke has been excluded
-with regards to atrial fibrillation, the RCP state: ‘anticoagulants should not be started until brain imaging has excluded haemorrhage, and usually not until 14 days have passed from the onset of an ischaemic stroke’
-if the cholesterol is > 3.5 mmol/l patients should be commenced on a statin. Many physicians will delay treatment until after at least 48 hours due to the risk of haemorrhagic transformation
when should thrombolysis be used in stroke?
Thrombolysis with alteplase should only be given if:
it is administered within 4.5 hours of onset of stroke symptoms (unless as part of a clinical trial) haemorrhage has been definitively excluded (i.e. Imaging has been performed)
11 absolute contraindications to thombolysis for stroke?
- Previous intracranial haemorrhage
- Seizure at onset of stroke
- Intracranial neoplasm
- Suspected subarachnoid haemorrhage
- Stroke or traumatic brain injury in preceding 3 months
- Lumbar puncture in preceding 7 days
- Gastrointestinal haemorrhage in preceding 3 weeks
- Active bleeding
- Pregnancy
- Oesophageal varices
- Uncontrolled hypertension >200/120mmHg
5 relative contraindications to thrombolysis for stroke?
- Concurrent anticoagulation (INR >1.7)
- Haemorrhagic diathesis
- Active diabetic haemorrhagic retinopathy
- Suspected intracardiac thrombus
- Major surgery / trauma in the preceding 2 weeks
when should thrombectomy be considered in stroke?
NICE recommend a pre-stroke functional status of less than 3 on the modified Rankin scale and a score of more than 5 on the National Institutes of Health Stroke Scale (NIHSS)
Which patients should be offerred thrombectomy as soon as possible and within 6 hours of symptom onset, together with intravenous thrombolysis (if within 4.5 hours)?
Offer thrombectomy as soon as possible and within 6 hours of symptom onset, together with intravenous thrombolysis (if within 4.5 hours), to people who have:
Acute ischaemic stroke and confirmed occlusion of the proximal anterior circulation demonstrated by computed tomographic angiography (CTA) or magnetic resonance angiography (MRA)
which patients should we:
Offer thrombectomy as soon as possible to people who were last known to be well between 6 hours and 24 hours previously (including wake-up strokes) and who…
Offer thrombectomy as soon as possible to people who were last known to be well between 6 hours and 24 hours previously (including wake-up strokes):
confirmed occlusion of the proximal anterior circulation demonstrated by CTA or MRA and if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion or diffusion-weighted MRI sequences showing limited infarct core volume
when should we:
Consider thrombectomy together with intravenous thrombolysis (if within 4.5 hours) as soon as possible for people last known to be well up to 24 hours previously (including wake-up strokes) and who…
Consider thrombectomy together with intravenous thrombolysis (if within 4.5 hours) as soon as possible for people last known to be well up to 24 hours previously (including wake-up strokes):
who have acute ischaemic stroke and confirmed occlusion of the proximal posterior circulation (that is, basilar or posterior cerebral artery) demonstrated by CTA or MRA and if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion or diffusion-weighted MRI sequences showing limited infarct core volume
What medicines should be used for secondary prevention in stroke?
Recommendations from NICE include:
clopidogrel is now recommended by NICE ahead of combination use of aspirin plus modified-release (MR) dipyridamole in people who have had an ischaemic stroke aspirin plus MR dipyridamole is now recommended after an ischaemic stroke only if clopidogrel is contraindicated or not tolerated, but treatment is no longer limited to 2 years' duration MR dipyridamole alone is recommended after an ischaemic stroke only if aspirin or clopidogrel are contraindicated or not tolerated, again with no limit on duration of treatment
when should carotid endarterectomy be considered in stroke?
With regards to carotid artery endarterectomy:
recommend if patient has suffered stroke or TIA in the carotid territory and are not severely disabled should only be considered if carotid stenosis > 70% according ECST** criteria or > 50% according to NASCET*** criteria
which cerebral artery has been affected in a stroke with:
• Contralateral hemiparesis and sensory loss, lower extremity > upper
• Disconnection syndrome (akinetic mute patient)
Anterior cerebral artery
which cerebral artery has been affected in a stroke with:
• Contralateral hemiparesis and sensory loss, upper extremity > lower
• Contralateral hemianopia
• Aphasia (Wernicke’s)
• Gaze abnormalities
Middle cerebral artery
what cerebral artery has been affected in a patient with:
• Contralateral hemianopia with macular sparing
• Disconnection syndrome
posterior cerebral artery
How does a lacunar stroke present?
Lacunar
• Present with either isolated hemiparesis, hemisensory loss or hemiparesis with limb ataxia
Describe lateral medullary syndrome
Lateral medulla (posterior inferior cerebellar artery- PICA)
• Ipsilateral: ataxia, nystagmus, dysphagia, facial numbness, cranial nerve palsy
• Contralateral: limb sensory loss
what is seen in a pontine stroke?
Pontine
• VI nerve: horizontal gaze palsy
• VII nerve
• Contralateral hemiparesis
basilar artery CVA:
-prognosis?
-how do these patients present?
-what visual sx?
-what syndrome can patients have?
-BP?
-what does management involve?
Basilar Artery CVA is typically associated with a poor prognosis
• Most of patients present with nausea, vertigo and vomiting
• Some present with motor deficits, dysarthria and speech involvement or headaches
• May present with visual disturbances. This includes abducens nerve palsy, conjugate gaze palsy,
internuclear ophthalmoplegia and ocular bobbing
• Locked-In Syndrome: patient is awake but is unable to respond in anyway except by vertical gaze and blinking (lesion is in ventral pons)
• 70% of patients presenting with basilar artery territory stroke are hypertensive.
• Management includes vigorous control of hypertension and antiplatelet agents.
what is LACS?
LACS (lacunar stroke):
Pure motor or pure sensory syndrome or
Ataxic hemiparesis or
Dysarthria or
Clumsy-hand syndrome.
what is PACS?
PACS (partial anterior circulatory stroke): 2 of the 3 elements below, or new higher cerebral
dysfunction.
Higher cerebral dysfunction
Contralateral sensory/motor deficit
Visual field defect.
what is TACS?
TACS (total anterior circulatory stroke): combination of the 3 elements
Higher cerebral dysfunction
Contralateral sensory/motor deficit
Visual field defect.
what is POCS?
POCS (posterior circulation syndrome):
Bilateral motor/sensory deficit or
Disorder of conjugate eye movement, or
Solitary visual field defect, or
Cerebellar dysfunction, or
Crossed cranial nerve and sensory/motor signs.
lateral medullary syndrome:
-what does this arise as a cause of?
-what are the cerebellar features?
-what are the brainstem features?
Lateral Medullary Syndrome: also known as Wallenberg’s syndrome, occurs following occlusion of the posterior inferior cerebellar artery, resulting in sensory and sympathetic disturbances
Cerebellar features
• Ataxia
• Nystagmus
Brainstem features
• Ipsilateral: dysphagia, facial numbness, cranial nerve palsy e.g. Horner’s
• Contralateral: limb sensory loss (pyramidal tract signs)
what is pituitary apoplexy?
Pituitary Apoplexy: sudden enlargement of pituitary tumour secondary to hemorrhage or infarction
what are the features of pituitary apoplexy?
Features
• Sudden onset headache similar to that seen in subarachnoid hemorrhage
• Vomiting
• Neck stiffness
• Visual field defects: classically bitemporal superior quadrantic defect
• Extraocular nerve palsies
• Features of pituitary insufficiency e.g. Hypotension secondary to hypoadrenalism
• Electrolytes disturbance.
what is the management of pituitary apoplexy?
Management: IV Hydrocortisone should be given to prevent adisonian crisis
what is brown-sequard syndrome?
-what is this caused by?
Brown-Séquard syndrome: is a loss of sensation and motor function (paralysis and ataxia) that is caused by the lateral hemisection of the spinal cord.
describe the features of brown sequard?
-loss of fine touch/vibration/proprioception on which side?
-hyper-reflexia and extensor plantar reflex on which side?
-loss of temperature and pain on which side?
-what other signs?
-what are the causes for this?
• Ipsilateral loss of fine touch, vibration and proprioception
• Ipsilateral hyper-reflexia and extensor plantar reflex
• Contralateral loss of pain and temperature sensation occurs affecting the side.
• Segmental anaesthesia at the level of the lesion
• Complete syndrome picture is rare and many patients may only exhibit some features.
• Trauma is a common cause; demyelination due to multiple sclerosis is another common cause
but any lateral cord lesion (ischaemia, hemorrhage, granuloma, tumour etc) may give this picture.
what is a syringomyelia?
-when do symptoms begin?
Syringomyelia is a developmental, slowly enlarging cavitaryexpansion of the cervical cord that produce progressive myelopathy. Symptoms begin insidiously in adolescence or early adulthood, progress irregularly, and may undergo spontaneous arrest for several years; most patients acquire a cervical-thoracic scoliosis.
• Development of cavity (syrinx) within the spinal cord
• If extends into medulla then termed syringobulbia
• Strongly associated (>50%) with the arnold-chiari malformation
what is the investigation used for syringomelia?
MRI is the investigation of choice
Myelography used to confirm the diagnosis but was associated with more deterioration
what is transverse myelitis?
-what signs are seen?
Transverse Myelitis: is an inflammatory lesion that can affect the cord. Constitutional symptoms such as headache and fever are common as is pain. Signs are indistinguishable from those caused by cord compression and again all sensory aspects are equally affected with no sparing of proprioception.
what is subclavian steal syndrome?
-what are neurological symptoms precipitated by?
Subclavian Steal Syndrome: is associated with retrograde flow in the vertebral artery due to proximal subclavian artery stenosis. Neurological symptoms are precipitated by vigorous exercise with the arm above the head, such as painting a wall.
Subclavian steal syndrome:
-what is diagnosis often confused with?
-what is the investigation of choice?
-what are the treatment option?
• Diagnosis is often confused with transient ischemic attacks or epilepsy.
• Duplex ultrasound and MRA are the investigations of choice.
• Endarterectomy and stenting are common surgical methods involved in relieving symptoms
associated with this condition.
what is subacute combined degeneration of the spinal cord?
Subacute Combined Degeneration of Spinal Cord, also known as Lichtheim’s disease, refers to degeneration of the posterior and lateral columns of the spinal cord as a result of vitamin B12 deficiency (most common), vitamin E deficiency or Friedrich’s ataxia. It is usually associated with pernicious anemia.
what are the features of subacute degeneration of the cord:
-limb signs?
-feet?
-what is it caused by?
-what is the treatment?
Features:
• Patchy losses of myelin in the dorsal and lateral columns.
• Present with progressive weakness of legs, arms, trunk,
tingling and numbness.
• Visual & Mental changes may also be present.
• Bilateral spastic paresis may develop and pressure, vibration
and touch sense are diminished.
• Positive Babinski sign may be seen.
• Prolonged deficiency (> 3 months) of vitamin B12 leads to
irreversible nervous system damage.
• If someone is deficient in vitamin B12 and folic acid, the vitamin B12 deficiency must be treated first to avoid
precipitating subacute combined degeneration of the cord.
• Therapy with vitamin B12 results in partial to full recovery,depending on the duration and extent of neurodegeneration
what is narcolepsy?
-what are the symptoms?
Narcolepsy is a condition causing excessive daytime somnolence and an overwhelming desire to sleep. Symptoms include excessive daytime sleepiness (EDS), involuntary sleep episodes –microsleeps- cataplexy (70%), sleep paralysis hallucinations - hypnagogic (at the onset of sleep) and hypnopompic (on awakening).
what is von hippel lindau syndrome?
-how is this inherited?
-what chromosome is assoc. with this?
-what are key features?
Von Hippel-Lindau (VHL) syndrome is an autosomal dominant condition predisposing to neoplasia. It is due to an abnormality in the VHL gene located on short arm of chromosome 3
Retinal and cerebellar hemangiomas are key features of Von Hippel-Lindau syndrome. Retinal hemangiomas are bilateral in 25% of patients and may lead to vitreous hemorrhage
what are the features of von hippel lindau syndrome?
• Cerebellar hemangiomas (Can secret crythyropiotiene that causes secondary polycythemia)
• Retinal hemangioma: vitreous hemorrhage
• Renal cysts (premalignant)
• Pheochromocytoma
• Extra-renal cysts: epididymal, pancreatic,
hepatic
• Endolymphatic sac tumours
what is friedreich’s ataxia?
-how is this inherited?
-what gene and chromosome are assoc?
-what is the typical age of onset?
Friedreich’s Ataxia is the most common of the early-onset hereditary ataxias. It is an autosomal recessive, trinucleotide repeat disorder characterized by a GAA repeat in the X25 gene on chromosome 9 (frataxin). Friedreich’s ataxia is unusual amongst trinucleotide repeat disorders in not demonstrating the phenomenon of anticipation. The typical age of onset is 10-15 years old
what are the neurological features of friedreichs ataxia?
Neurological features
• Absent ankle jerks/extensor plantars
• Cerebellar ataxia
• Optic atrophy
• Spinocerebellar tract degeneration
what are the non-neurological features of friedreichs ataxia?
Other features
• Hypertrophic obstructive cardiomyopathy (90%, most common cause of death)
• Diabetes mellitus (10-20%)
• High-arched palate
what is tuberous sclerosis?
-how is this inherited?
-where are the majority of features seen?
Tuberous Sclerosis (TS) is a genetic condition of autosomal dominant inheritance. Like neurofibromatosis, the majority of features seen in TS are neuro-cutaneous
what are the cutaneous features of tuberous sclerosis?
Cutaneous features
• Depigmented ‘ash-leaf’ spots which fluoresce under UV light
• Roughened patches of skin over lumbar spine (Shagreen patches)
• Adenoma sebaceum: butterfly distribution over nose
• Fibromata beneath nails (subungual fibromata)
• Café-au-lait spots may be seen
what are the neurological features of tuberous sclerosis?
Neurological features
• Developmental delay
• Epilepsy (infantile spasms or partial)
• Intellectual impairment
what are the non-cutaneous and non-neuro features of tuberous sclerosis?
Also
• Retinal hamartomas: dense white areas on retina (phakomata)
• Rhabdomyomas of the heart
• Gliomatous changes can occur in the brain lesions
• Polycystic kidneys, renal angiomyolipomata
neurofibromatosis 1 and 2:
-how are these inherited?
-chromosomes?
Neurofibromatosis: both types are inherited in an autosomal dominant fashion. NF1 is also known as von Recklinghausen’s syndrome. It is caused by a gene mutation on chromosome 17 which encodes neurofibromin and affects around 1 in 4,000. NF2 is caused by gene mutation on chromosome 22 and affects around 1 in 100,000
what are the features of neurofibromatosis type 1?
Café-au-lait spots (= 6, 15 mm in diameter) Axillary/groin freckles
Peripheral neurofibromas
Iris: Lisch nodules in > 90%
Scoliosis
what are the features of neurofibromatosis type 2?
Bilateral acoustic neuromas
what is hereditary sensorimotor neuropathy?
-how many types exist and how many of these are common to clinical practice?
-what are these due to?
Hereditary Sensorimotor Neuropathy (HSMN) is a relatively new term which encompasses Charcot-Marie-Tooth disease (also known as peroneal muscular atrophy). Over 7 types have been characterized - however only 2 are common to clinical practice
• HSMN type I: primarily due to demyelinating pathology
• HSMN type II: primarily due to axonal pathology
HSMN type 1:
-how is this inherited?
-what is this due to?
-when do features start?
-what are features?
-what happens to nerve conduction velocity?
HSMN type I
• Autosomal dominant
• Due to defect in PMP-22 gene (which codes for myelin) (PMP = Peripheral Myelin Protein)
• Features often start at puberty
• Motor symptoms predominate
• Distal muscle wasting, pes cavus, clawed toes
• Foot drop, leg weakness often first features
• Nerve Conduction Velocity is greatly ↓ <30m/second
what is motor neurone disease?
-what age does it usually present after?
-what are 4 patterns of disease?
Motor Neuron Disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognized including amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy and bulbar palsy. In some patients however, there is a combination of clinical patterns
Amyotrophic lateral sclerosis (50% of patients)
-what are the signs?
-what gene is responsible in familial cases?
-what does this code for?
• Typically LMN signs in arms and UMN signs in legs
• In familial cases the gene responsible lies on chromosome 21 and codes for superoxide
dismutase
what signs are seen in primary lateral sclerosis?
Primary lateral sclerosis
• UMN signs only
Progressive muscular atrophy:
-what are the signs?
-what muscles are affected?
-what is the prognosis?
Progressive muscular atrophy
• LMN signs only
• Affects distal muscles before proximal
• Carries best prognosis
Bulbar palsy:
-what are the signs?
-what is the prognosis?
Bulbar palsy
• Palsy of the tongue, muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei
• Carries worst prognosis
• Fasciculation
• Absence of sensory signs/symptoms (vague sensory symptoms may occur early in the disease
(e.g. Limb pain) but ‘never’ sensory signs)
• Lower motor neuron signs in arms and upper motor neuron signs in legs
• Wasting of the small hand muscles/tibialis anterior is common (tibialis anterior functions to
stabilise the ankle as the foot hits the ground during the contact phase of walking [eccentric contraction] and acts later to pull the foot clear of the ground during the swing phase [concentric contraction]. It also functions to ‘lock’ the ankle, as in toe-kicking a ball, when held in an isometric contraction)
-what should all of these prompt thought of?
motor neurone disease
Motor neurone disease:
-does this affect external ocular muscles?
-does this have cerebellar signs?
-abdominal reflexes?
-sphincter dysfunction?
• Doesn’t affect external ocular muscles
• No cerebellar signs
• Abdominal reflexes are usually preserved and sphincter dysfunction if present is a late feature.
what is the diagnosis of motor neurone disease?
The diagnosis of motor neuron disease is clinical, but nerve conduction studies will show normal motor conduction and can help exclude a neuropathy. Electromyography shows a ↓ number of action potentials with ↑ amplitude. MRI is usually performed to exclude the differential diagnosis of cervical cord compression and myelopathy
what is the treatement and prognosis for motor neurone disease?
Riluzole
• Anti-glutamate drug
• Used mainly in amyotrophic lateral sclerosis
• Prolongs life by about 3 months
• Expensive
Respiratory care
• Non-invasive ventilation (usually BiPAP) is used at night
• Studies have shown a survival benefit of around 7 months
Prognosis
• Poor: 50% of patients die within 3 years
what is the age distribution of the presentation of epilepsy?
Epilepsy is more likely to occur in young children or people over the age of 65 years; however it can occur at any time.
Epilepsy
what are the two main categories?
Basics
• Two main categories: generalised and partial seizures
• Partial seizures may progress to general seizures
• Other types: myoclonic, atypical absence, atonic and tonic seizures are usually seen in
childhood
describe the features of generalised seizures?
- no focal features, consciousness lost immediately
• Grand mal (tonic-clonic)
• Petit mal (absence seizures)
• Partial seizures progressing to generalised seizures
describe the features of partial seizures
-in patients who have automatisms, which part of the brain has the seizure activity most commonly?
- focal features depending on location
• Simple (no disturbance of consciousness or awareness)
• Complex (consciousness is disturbed)
• Temporal lobe → aura, déjà vu, jamais vu; motor → jacksonian
Complex partial seizures can take the form of
automatisms, such as chewing and swallowing, repeatedly scratching the head or searching for an object. Some people may even undress. They can occur as a result of seizure activity in any part of the brain but most commonly arise in the temporal lobes
what is the treatment for generalised tonic-clonic seizures?
Generalised tonic-clonic seizures
sodium valproate second line: lamotrigine, carbamazepine
what is the treatment for absence seizures? what may exacerbate these?
Absence seizures (Petit mal)
sodium valproate or ethosuximide
sodium valproate particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsy
carbamazepine may exacerbate
what is the treatment for myoclonic seizures - what may exacerbate myoclonic seizures?
Myoclonic seizures
sodium valproate
second line: clonazepam, lamotrigine
carbamazepine may exacerbate these
why should caution be exercised when combining sodium valproate with lamotrigine?
Caution should be exercised when combining sodium valproate and lamotrigine as serious skin rashes such as Steven- Johnson’s syndrome may be provoked.
what is a side affect of vigabatrin?
Vigabatrin – rarley used anti-epileptic
• 40% of patients develop Visual field defects, which may be irreversible
• Visual fields should be checked every 6 months
who do absence seizures affect?
Absence Seizures (Petit Mal) are a form of generalised epilepsy that is mostly seen in children. The typical age of onset of 3-10 years old and girls are affected twice as commonly as boys
Describe absence seizures:
-how long do they last?
-what may provoke the seizure?
-when do they occur?
-is there awareness?
-what is seen on EEG?
Features
• Absences last a few seconds and are associated with a quick recovery
• Seizures may be provoked by hyperventilation or stress
• The child is usually unaware of the seizure
• They may occur many times a day
• EEG: bilateral, symmetrical 3Hz (spike and wave) pattern
describe the management of partial seizures
Management
• Sodium valproate and ethosuximide are first-line treatment
• Good prognosis - 90-95% become seizure free in adolescence
Describe the management of focal seizures?
Focal seizures
carbamazepine or lamotrigine
second line: levetiracetam, oxcarbazepine or sodium valproate
when can anti-epileptic drugs be stopped? how does this happen?
AED cessation can be considered if seizure free for > 2 years – Stop AEDs over 2-3 months
In a patient who has been seizures free for 2 years what is the chance of recurrence and what increases this risk?
Therapy stopped: chance of recurrence in the next 2 years is 43%
Therapy cont.: 10%
Factors that have been shown to increase the risk of seizures include:
• Older age
• Use of multiple anticonvulsants
• History of myoclonic or tonic clonic seizure
• Previous abnormal imaging or EEG
• Seizure while on therapy.
Epilepsy in pregnancy:
-what should all women take who are thinking about pregnancy?
-what is the risk of congenital defect?
The risks of uncontrolled epilepsy during pregnancy generally outweigh the risks of medication to the fetus. All women thinking about becoming pregnant should be advised to take folic acid 5mg/day well before pregnancy to minimise the risk of neural tube defects. Around 1-2% of newborns born to non- epileptic mothers have congenital defects. This rises to 3-4% if the mother takes antiepileptic medication
In pregnancy:
-how many drugs should be aimed for to control
-how often should antiepileptic drug levels be checked?
-which drug is assoc. with neural tube defects?
-which drug is assoc. with cleft palate?
-which drug may need to be increased in pregnancy?
-which drug is considered the least teratogenic?
• Aim for monotherapy
• There is no indication to monitor antiepileptic drug levels
• Sodium valproate: associated with neural tube defects
• Phenytoin (Epanutin®): associated with cleft palate
• Lamotrigine: studies to date suggest the rate of congenital malformations may be low. The dose
of lamotrigine may need to be increased in pregnancy
• Carbamazepine: often considered the least teratogenic of the older antiepileptics
are antiepileptic drugs considered safe in breast feeding?
Breast feeding is generally considered safe for mothers taking antiepileptics with the possible exception of the barbiturates
what should pregnant women on phenytoin be advised to take in the last month of pregnancy to prevent clotting disorders in the newborn?
It is advised that pregnant women taking phenytoin are given vitamin K in the last month of pregnancy to prevent clotting disorders in the newborn
Infantile spasm AKA West syndrome
-when does this occur?
-what is this managed by?
-what is the triad?
• Occurs between 3-12 month of age, managed by Vegabatrin (S.E causes alopecia, ↓ visual acuity diplopia).
• West syndrome is the triad of infantile spasms, a pathognomonic EEG pattern (called hypsarrhythmia), and mental retardation - although the international definition requires only two out of these three elements.
what are non-epileptic attacks broadly divided into?
Non-epileptic attacks are broadly divided into:
• Hyperkinetic/thrashing attacks
• Akinetic/motionless attacks.
what should:
Asynchronous limb movements
• Undulating motor activity
• Purposeful movements
• Rhythmic pelvic movements
• Side-to-side head shaking
• Biting the tip of the tongue (as opposed to the side)
• Ictal crying
• Vocalisation during the ‘tonic–clonic’ phase
• Closed eyelids, resistance to eyelid opening
• Lack of cyanosis and rapid post-ictal reorientation
All point towards
pseudoseizure
what is the gold standard test for non-epileptic seizures?
Video telemetry
Prolactin is often elevated 15–20 min after a tonic–clonic seizure and should be normal in non-epileptic attacks, but there are a number of problems: serum rises are seen in syncopal episodes; it may be normal, especially in partial epileptic seizures; and the test is often badly carried out in practice (too early or too late).
what is parkinson’s disease caused by?
Parkinson’s Disease is a progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra
what is the triad of Parkinson’s disease?
-is it symmetrical/asymetrical?
bradykinesia, asymetrical tremor and rigidity. The symptoms of Parkinson’s disease are characteristically asymmetrical
describe the bradykinesia in Parkinson’s disease
Bradykinesia
• Poverty of movement also seen: mask-like face
• Difficulty in initiating movement
describe the tremor in Parkinson’s Disease
Tremor
• Most marked at rest, 3-5 Hz
• Typically ‘pill-rolling’
describe the rigidity in Parkinson’s Disease
Rigidity
• Lead pipe
• Cogwheel: due to superimposed
tremor
describe the other symptoms other than the triad of bradykinesia, tremor and rigidity in PD?
• Flexed posture
• Short, shuffling steps
• Micrographia
• Drooling of saliva
• Psychiatric features: depression is the most common feature (affects about 40%); dementia,
psychosis and sleep disturbances may also occur
• Impaired olfaction
• REM sleep behaviour disorder
• Parkinson’s disease
• Drug-induced e.g. Antipsychotics, metoclopramide - see below
• Progressive supranuclear palsy
• Multiple system atrophy
• Wilson’s disease
• Post-encephalitis
• Dementia pugilistica (secondary to chronic head trauma e.g. Boxing)
• Toxins: carbon monoxide, MPTP
are all causes of what?
Parkinsonion syndrome?
describe the different features that drug-induced parkinsonism has from Parkinson’s disease
Drug-induced Parkinsonism has slightly different features to Parkinson’s disease:
• Motor symptoms are generally rapid onset and bilateral
• Rigidity and rest tremor are uncommon
which three types of drugs can cause parkinson’s?
Drugs causing Parkinsonism
• Phenothiazines: e.g. Chlorpromazine
• Butyrophenones: haloperidol, droperidol
• Metoclopramide
does Domperidone cause extra-pyramidal side-effects?
Domperidone does not cross the blood-brain barrier and therefore does not cause extra-pyramidal side-effects
when is treatment started for parkinson’s disease?
Currently accepted practice in the management of patients with Parkinson’s disease (PD) is to delay treatment until the onset of disabling symptoms
what is the first line treatment for PD?
For first-line treatment:
if the motor symptoms are affecting the patient's quality of life: levodopa if the motor symptoms are not affecting the patient's quality of life: dopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAO‑B) inhibitor
what are the 5 drugs types used in Parkinson’s disease and how do they work?
-Dopamine receptor agonists
-Levodopa
-MAO-B inhibitor
-Amantadine
-COMT inhibitors
-Antimuscarinics
Dopamine receptor agonists (favored for patients > 75yrs old)
• E.g. Bromocriptine, Pramipexole, Ropinirole, Cabergoline, Apomorphine
• Ergot-derived dopamine receptor agonists (bromocriptine, cabergoline) have been
associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an ESR, creatinine and CXR should be obtained prior to treatment and patients should be closely monitored
• Ropinirole is least associated with tissue fibrosis.
• Patients should be warned about the potential for dopamine receptor agonists to cause impulse
control disorders and excessive daytime somnolence
Levodopa
• Usually combined with a decarboxylase
inhibitor (e.g. Carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine
• ↓ effectiveness with time (usually by 2 years)
• Unwanted effects: dyskinesia, ‘on-off’ effect
• Not used in neuroleptic induced parkinsonism
• Favoed for patients < 75yrs
MAO-B (Monoamine Oxidase-B) inhibitors
• E.g. Selegiline
• Inhibits the breakdown of dopamine secreted by the dopaminergic neurons
Amantadine
• Mechanism is not fully understood, probably ↑ dopamine release and inhibits its uptake at
dopaminergic synapses
COMT (Catechol-O-Methyl Transferase) inhibitors
• E.g. Entacapone
• COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an
adjunct to levodopa therapy
• Used in established PD
Antimuscarinics
• Block cholinergic receptors
• Now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson’s disease
• Help tremor and rigidity
• E.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)
For Levodopa:
Motor symptoms
ADLs
Motor Complications
Adverse events (excessive sleepiness, hallucinations and impulse control disorders)
Adverse effects?
More improvement in motor symptoms
More improvement in ADLs
More motor complications
Fewer specified adverse events
Adverse effects of L-Dopa • Dyskinesia
• ‘On-off’ effect
• Postural hypotension
• Cardiac arrhythmias
• Nausea & vomiting
• Psychosis
• Reddish discolouration of urine upon standing
