Neurology Flashcards
Frontal Lobe function
- Difficulties with task sequencing
- Difficulties with executive skills
- Expressive aphasia (Broca’s) : located
in the posterior aspect of the frontal
lobe, in the inferior frontal gyrus - Anosmia
- Primitive reflexes
- Perseveration (repeatedly asking
same question or doing same task) * Changes in personality - Inability to generate a list
- Disinhibition
Parietal Lobe
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
* Gerstmann’s syndrome (lesion of dominant parietal):
o Alexia: in ability to read o Acalculia
oFinger agnosia oRight-left disorientation.
Temporal Lobe
Homonymous superior quadrantanopia
* Prosopagnosia (difficulty recognising
faces)
* Wernike’s (recepTive) aphasia * Memory impairment
* Auditory agnosia
Occipital Lobe
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
* 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)
DRIVING RULES (DVLA): Neurological aspect specific rules:
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’
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 (9)
Homonymous Quadrantanopias
Homonymous Quadrantanopias
* Superior: lesion of temporal lobe
* Inferior: lesion of parietal lobe
* Mnemonic = PITS (Parietal-Inferior, Temporal-Superior)
Bitemporal Hemianopia
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
Nystagmus causes
Causes:
* Visual disturbances
* Lesions of the labyrinth
* The central vestibular connections
* Brain stem or cerebellar lesions.
Nystagmus which changes with the direction of gaze
nvolvement of vestibular nuclei.
Pendular Nystagmus
mostly due to loss of macular vision, but could be in diffuse brain stem lesions.
Nystagmus Jerking on lateral gaze,
brain stem or cerebellum lesion.
- Nystagmus confined to one eye
nerve or muscle lesion, or medial longitudinal bundle lesion.
Nystagmus restricted to the abducting eye on lateral gaze (ataxic nystagmus)
due to a lesion
of the medial longitudinal bundle between the pons and mid-brain as in multiple sclerosis (MS).
Upbeat nystagmus
Cerebellar vermis lesions
Downbeat nystagmus - foramen magnum lesions
Arnold-Chiari malformation
Subdural Hemorrhage
Basics
* 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
Features
* Headache
* Classically fluctuating conscious level
* Raised ICP
Treatment
* Needs neurosurgical review
* Burr hole →
Subarachnoid Hemorrhage causes
Causes
* 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
Subarachnoid Hemorrhage 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
Subarachnoid Hemorrhage management
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 ↓ rebleedi
Extradural hematoma
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. The majority of epidural Hematomas occur in the temporal region where skull fractures cause a rupture of the middle meningeal artery.
Features
* Features of raised intracranial pressure
* Some patients may exhibit a lucid interval
Intracranial Venous Thrombosis
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
Features
* Headache (may be sudden onset)
* Nausea & vomiting
* Papilledema
Sagittal sinus thrombosis
May present with seizures and hemiplegia
* Parasagittal biparietal or bifrontal hemorrhagic infarctions are sometimes seen
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
Wernicke Encephalopathy pathophisology
yndrome caused by lesions in the medial thalamic nuclei, mammillary bodies, periaqueductal and periventricular brainstem nuclei, and superior cerebellar vermis, often resulting from inadequate intake or absorption of thiamine (Vitamin B1), especially in conjunction with carbohydrate ingestion.
Wernicke Encephalopathy features
Features
* Nystagmus
* Ophthalmoplegia
* Ataxia
* Confusion, altered GCS
* Peripheral sensory neuropathy
* Impairment of short-term memory
Wernicke Encephalopathy Investigations
Investigations
* ↓ Red cell transketolase * MRI
Marchiafava Bignami syndrome:
Corpus callosum degeneration from chronic alcohol excess
Urinary incontinence + gait abnormality + dementia
= normal pressure hydrocephalus
Idiopathic Intracranial Hypertension features
Features
* Headache
* Blurred vision
* Papilledema (usually present)
* Enlarged blind spot
* Sixth nerve palsy may be present
Idiopathic Intracranial Hypertension risk factors
Risk factors
* Obesity
* ♀sex
* Pregnancy
* Drugs (in this case it is not idiopathic): oral contraceptive pill, steroids, tetracycline, vitamin A
IIH Management
- 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
TIA - ABCD2 score of ≥4:
Aspirin (300 mg daily) started immediately
seen within 24hrs
TIA ABCD2 risk score ≤ 3:
Specialist assessment within 1 week of symptom
onset, including decision on brain imaging
* If vascular territory or pathology is uncertain,
refer for brain imaging
crescendo TIAs (≥2 episodes in a week)
treated as being at high risk of stroke, even though they may have an ABCD2 score of 3 or below.
Selected points relating to the management of acute stroke include:
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 (the 2009 Controlling hypertension and hypotension immediately post-stroke (CHHIPS) trial may change thinking on this but guidelines have yet to change to reflect this)
* ASA 300mg orally or rectally should be given as soon as possible if a hemorrhagic stroke has been excluded
* With regards to AF, the RCP state: ‘anticoagulants should not be started until brain imaging has excluded hemorrhage, and usually after 14 days from the onset of an ischemic stroke’
* If the cholesterol is > 3.5 mmol/l patients should be commenced on a statin
Thrombolysis
It is administered within 3 hours (SIGN recommend a window of 4.5 hours) of onset of stroke
symptoms (unless as part of a clinical trial)
* Hemorrhage has been definitively excluded (i.e. Imaging has been performed)
* If patient is awaked with stroke, do not thrombolyse (even if reached in < 3 hours), exact time
of stroke is unknown
Secondary Prevention stroke
. Clopidogrel
2. Dipyridamole MR + ASA
3. Dipyridamole MR
Anterior stroke
Contralateral hemiparesis and sensory loss, lower extremity > upper
* Disconnection syndrome (akinetic mute patient)
Middle stroke
Contralateral hemiparesis and sensory loss, upper extremity > lower
* Contralateral hemianopia
* Aphasia (Wernicke’s)
* Gaze abnormalities
Posterior stroke
Contralateral hemianopia with macular sparing
* Disconnection syndrome
Lacunar stoke
Present with either isolated hemiparesis, hemisensory loss or hemiparesis with limb ataxia
Lateral medulla (posterior inferior cerebellar artery- PICA)
- Ipsilateral: ataxia, nystagmus, dysphagia, facial numbness, cranial nerve palsy
- Contralateral: limb sensory loss
Pontine stroke
VI nerve: horizontal gaze palsy
* VII nerve
* Contralateral hemiparesis
Basilar Artery CVA
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
PACS (partial anterior circulatory stroke)
2 of the 3 elements above, or new higher cerebral
dysfunction.
TACS (total anterior circulatory stroke):
Higher cerebral dysfunction
Contralateral sensory/motor deficit
Visual field defect.
- LACS (lacunar stroke):
Pure motor or pure sensory syndrome or
Ataxic hemiparesis or
Dysarthria or
Clumsy-hand syndrome
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:
lso 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)
Pituitary Apoplexy:
sudden enlargement of pituitary tumour secondary to hemorrhage or infarction
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.
Brown-Séquard syndrome:
s a loss of sensation and motor function (paralysis and ataxia) that is caused by the lateral hemisection of the spinal cord.
Features:
* 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.
Syringomyelia
Syringomyelia - spinothalamic sensory loss (pain and temperature)
Syringomyelia Features
Maybe asymmetrical initially
* Slowly progressives, possibly over years
* Motor: wasting and weakness of arms
* Sensory: spinothalamic sensory loss (pain and temperature)
* Loss of reflexes, bilateral upgoing plantars
* Also seen: horner’s syndrome
Syringomyelia Localization of the lesion (for Part II):
At syrinx (there is anterior horn cell involvement) → lower motor
neuron pattern of weakness.
* At central decussating fibres (spinothalamic tract) → dissociated
sensory loss with late development of neuropathic arthropathy.
* At corticospinal tracts below the level of the syrinx results in
spastic paraparesis.
Transverse Myelitis:
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.
Subclavian Steal Syndrome:
s 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.
* 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.
Subacute Combined Degeneration of Spinal Cord 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
Von Hippel-Lindau: 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
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
Friedreich’s Ataxia
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
Friedreich’s Ataxia features
Neurological features
* Absent ankle jerks/extensor plantars
* Cerebellar ataxia
* Optic atrophy
* Spinocerebellar tract degeneration
Other features
* Hypertrophic obstructive cardiomyopathy (90%, most common cause of death)
* Diabetes mellitus (10-20%)
* High-arched palate
Tuberous Sclerosis (TS)
genetic condition of autosomal dominant inheritance. Like neurofibromatosis, the majority of features seen in TS are neuro-cutaneous
Tuberous Sclerosis Cutaneous features
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
Tuberous Sclerosis Neurological features
Neurological features
* Developmental delay
* Epilepsy (infantile spasms or partial)
* Intellectual impairment
Neurofibromatosis NF1
Café-au-lait spots (= 6, 15 mm in diameter) Axillary/groin freckles
Peripheral neurofibromas
Iris: Lisch nodules in > 90%
Scoliosis
It is caused by a gene mutation on chromosome 17 which encodes neurofibromin and affects around 1 in 4,000
Neurofibromatosis NF2
Bilateral acoustic neuromas
NF2 is caused by gene mutation on chromosome 22 and affects around 1 in 100,000
Hereditary Sensorimotor Neuropathy (HSMN)
HSMN type I
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
Amyotrophic lateral sclerosis
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
Progressive muscular atrophy
- LMN signs only
- Affects distal muscles before proximal
- Carries best 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
There are a number of clues which point towards a diagnosis of motor neuron disease:
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)
Lesions producing both upper motor and lower neuron signs
Causes
* Subacute combined degeneration of the cord
* Motor neuron disease
* Friedreich’s ataxia
* Syringomyelia
* Syringobulbia
* Taboparesis (syphilis)
* Conus medullaris lesion
Management: MND
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
First seizure investigation
Following their first seizure patients generally have both an electroencephalogram (EEG) and neuroimaging (usually a MRI).
Generalised tonic-clonic seizures treatment
sodium valproate
second line: lamotrigine, carbamazepine
Absence seizures* (Petit mal)
sodium valproate or ethosuximide
sodium valproate particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsy
Myoclonic seizures
sodium valproate
second line: clonazepam, lamotrigine
Focal seizures
carbamazepine or lamotrigine
second line: levetiracetam, oxcarbazepine or sodium valproate
Vigabatrin – rarley used anti-epileptic
40% of patients develop Visual field defects, which may be irreversible
* Visual fields should be checked every 6 months
AED cessation can be considered if
seizure free for > 2 years – Stop AEDs over 2-3 months
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.
Infantile Spasm (West syndrome):
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.
Distinguish functional from epileptic seizures:
- 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
Parkinson’s Disease
progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra, thus results in a classic triad of features: bradykinesia, asymetrical tremor and rigidity. The symptoms of Parkinson’s disease are characteristically asymmetrical
Bradykinesia, Tremor, Rigidity
Causes of Parkinsonism
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
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
Drugs causing Parkinsonism
Phenothiazines: e.g. Chlorpromazine
* Butyrophenones: haloperidol, droperidol
* Metoclopramide
Parkinsonism Management:
delay treatment until the onset of disabling symptoms and then to introduce a dopamine receptor agonist
Dopamine receptor agonists
MAOB
COMT
Dopamine receptor agonists
E.g. Bromocriptine, Pramipexole, Ropinirole, Cabergoline, Apomorphine
* Ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide*) 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
Adverse effects of L-Dopa
- Dyskinesia
- ‘On-off’ effect
- Postural hypotension
- Cardiac arrhythmias
- Nausea & vomiting
- Psychosis
- Reddish discolouration of urine upon standing
MAO-B (Monoamine Oxidase-B) inhibitors
e.g. Selegiline
* Inhibits the breakdown of dopamine secreted by the dopaminergic neurons
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)
*pergolide was wi
Multiple system atrophy:
Features
* Parkinsonism
* Autonomic disturbance (atonic bladder, postural hypotension)
* Cerebellar signs
Progressive Supranuclear Palsy
is degenerative disease involving the gradual deterioration and death of selected areas of the brain. Both ♂ and ♀ are affected approximately equally and there is no racial, geographical or occupational predilection. Approximately 6 people per 100,000.
Features
* Impairment of vertical gaze (down gaze worse than up gaze - patients may complain of difficultly reading or descending stairs)
* Parkinsonism
* Falls
* Slurring of speech
* Cognitive impairment
Management
* Poor response to L-dopa
Frontotemporal Lobar Degeneration (Pick Disease):
Progressive neurodegenerative disorder comprising of dementias.
* Insidious behavioral and cognitive symptoms: aggressiveness and inappropriate behavior,
stereotyped behavior, apathy and depression. Speech and language abnormalities begin early
and progress rapidly.
* Memory is less severely affected than in Alzheimer disease.
* Brain CT or MRI may show selective atrophy of the frontal and temporal lobes.
* Mini-Mental Score (MMSE): is often surprisingly high, and more formal neuropsychological
testing may be required to establish the typical cognitive deficits
* 50% of cases have an affected family member.
* A subgroup of patients with frontotemporal dementia has symptoms and signs of motor neuron
disease. This is evidenced by the lower motor neuron signs of impaired swallow, proximal limb
weakness and fasciculation’s indicating recent denervation.
* Treatment is supportive.
Essential tremor:
Features
* Postural tremor: worse if arms outstretched (usually 6-8 Hz)
* Improved by alcohol and rest
* Most common cause of titubation (head tremor)
Management
* Propranolol is first-line
* Primidone (anticonvulsant ) is sometimes used when propanolol is contraindicated
Creutzfeldt - Jakob disease (CJD): Basics & Features:
Rapidly progressive, severe and invariably fatal (usually within few months)
* Dementia
* Cerebellar ataxia
* Defuse myoclonic jerks
* Other neurological abnormalities.
Creutzfeldt - Jakob disease (CJD) - Investigation:
Investigation:
* The EEG patern is characteristic (diffuse non specific slowing periodic sharp wave complexes- PSWCs of 1 – 2 Hz), but diagnosis relies on either espiecalized tests for prion protein in CSF or direct brain biopsy.
* Pulvinar Sign on cranial MRI > 90% pathological in vCJD (Not Sporadic)
* Prion protien in tonsils
* 14-3-3 protien in CSF
ad Pathological changes
Macroscopic = widespread cerebral atrophy, particularly involving the cortex and hippocampus
* Microscopic = intraneuronal neurofibrillary tangles, neuronal plaques, deficiency of neurons
* Biochemical = deposition of type A-β-amyloid protein in cortex, deficit of Ach from damage to
an ascending forebrain projection
AD management
NICE now recommend the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer’s disease. Donepezil may cause bradycardia and atrioventricular node block.
* Memantine is reserved for patients with moderate - severe Alzheimer’s.
Hemiballism
occurs following damage to the subthalamic nucleus.
Features - Ballisic movements:
* Involuntary, sudden, jerking movements which occur contralateral to the side of the lesion
* Primarily affect the proximal limb musculature whilst the distal muscles may display more
choreiform-like movements.
* Symptoms may decrease during sleeping.
* Etiology: stroke in elders, infection or inflammatory in young.
* Antidopaminergic agents (e.g. Haloperidol) are the mainstay of treatment. Tetrabenazine may
be considered when long-term therapy is required.
Facial nerve Supply -
‘face, ear, taste, and tear’
* Face: muscles of facial expression
* Ear: nerve to stapedius
* Taste: supplies anterior two-thirds of tongue
* Tear: parasympathetic fibres to lacrimal glands, also salivary glands
Causes of bilateral facial nerve palsy
Sarcoidosis
* Guillain-Barre syndrome
* Polio, Lyme disease
Bell’s palsy features
Features
* Lower motor neuron facial nerve palsy - forehead affected*
* Patients may also notice post-auricular pain (may precede paralysis), altered taste, dry eyes
Multiple Sclerosis:
it is an UmL
- disseminated sclerosis or encephalomyelitis disseminate
- autoimmune disease in which the body’s immune response attacks a person’s central nervous system (brain and spinal cord), leading to demyelination.
- Disease onset usually occurs in young adults, and it is more common in ♀.
Relapsing-remitting MS
Characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity.
Deficits suffered during attacks may either resolve or leave sequelae. This describes the initial course of 85–90% of individuals with MS. When deficits always resolve between attacks, this is sometimes referred to as benign MS.
Secondary progressive MS
Describes those with initial relapsing-remitting MS, who then begin to have progressive neurologic decline between acute attacks without any definite periods of remission. Occasional relapses and minor remissions may appear. The median time between disease onset and conversion from relapsing-remitting to secondary progressive MS is 19 years.
Primary progressive MS
Describes the approximately 10–15% of individuals who never have remission after their initial MS symptoms. It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements. The age of onset for the primary progressive subtype is later than other subtypes.
Progressive relapsing MS
Describes those individuals who, from onset, have a steady neurologic decline but also suffer clear superimposed attacks. This is the least common of all subtype
Features of MS
Visual
* Optic neuritis: common presenting feature
* Optic atrophy
* Uhthoff’s phenomenon: worsening of
vision following rise in body temperature
(hot bath)
* Internuclear ophthalmoplegia
Sensory
* Pins/needles
* Numbness
* Trigeminal neuralgia
* Lhermitte’s syndrome: paraesthesiae in
limbs on neck flexion Motor
* Spastic weakness Cerebellar
* Ataxia, Tremor
Good prognosis features MS
♀sex
* Young age of onset
* Relapsing-remitting disease
* Sensory symptoms
* long interval between first two relapses
Treatment in multiple sclerosis
High dose steroids (e.g. IV methylprednisolone) may be given for 3-5 days to shorten the length of an acute relapse.
Baclofen is helpful in controlling spasticity.
β-interferon has been shown to ↓ the relapse rate by up to 30%.
MS β-interferon criteria
Relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided
* Secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)
* ↓ number of relapses and MRI changes. However doesn’t ↓ overall disability
Other drugs used in the management of multiple sclerosis include:
- Glatiramer acetate: immunomodulating drug
- Natalizumab: a recombinant monoclonal antibody that antagonises α4β1-integrin found on the
surface of leucocytes, thus inhibiting migration of leucocytes across the endothelium into parenchymal tissue
Ptosis + dilated pupil
third nerve palsy
Ptosis + constricted pupil
Horner’s
Causes of miosis (small pupil)
Horner’s syndrome
* Argyll-Robertson pupil
* Senile miosis
* Pontine hemorrhage
* Congenital
Argyll-Robertson:
Referred to as the “Whore’s Eye” because of the association with tertiary syphilis and because of the
convenient mnemonic that, like a prostitute, they “accommodate but do not react
Horner’s Syndrome: Features:
- Miosis (small pupil)
- Ptosis
- Enophthalmos (sunken eye) in reality the appearance is due to a narrow palpebral aperture
Argyll-Robertson: small irregular pupils that do not react to light but react to accommodation.
Causes: Multiple Sclerosis, Sarcoidoisis, DM
Referred to as the “Whore’s Eye” because of the association with tertiary syphilis and because of the
convenient mnemonic that, like a prostitute, they “accommodate but do not react”
rather than true enophthalmos
* Anhydrosis (loss of sweating one side)
Horner’s syndrome - anhydrosis determines site of lesion:
- Head, arm, trunk = central lesion: stroke, syringomyelia
- Just face = pre-ganglionic lesion: Pancoast’s, cervical rib
- Absent = post-ganglionic lesion: carotid artery
Causes of bilateral ptosis
Myotonic dystrophy
* Myasthenia gravis*
* Syphilis
* Congenital
Causes of unilateral ptosis (bilateral causes+)
Third nerve palsy
* Horner’s
Painful third nerve palsy
posterior communicating artery aneurysm
Third nerve palsy features
eatures
* Eye is deviated ‘down and out’
* Ptosis
* Pupil may be dilated (sometimes called a ‘surgical’ third nerve palsy) → PCA aneurysm
Weber’s syndrome:
ipsilateral third nerve palsy with
contralateral hemiplegia -caused by midbrain strokes
(cerebral peduncle)
Third nerve palsy causes
Diabetes Mellitus
* Vasculitis e.g. Temporal arteritis, SLE
* False localizing sign due to uncal herniation through tentorium
if raised ICP
* Posterior communicating artery aneurysm (pupil dilated)
* Cavernous sinus thrombosis
Myasthenia Gravis:
Autoimmune disorder resulting in insufficient functioning acetylcholine receptors.
Antibodies to acetylcholine receptors are seen in 90% of cases (antibodies are less commonly seen in disease limited to the ocular muscles).
eakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction.
Myasthenia Gravis features
Features
* Extraocular muscle weakness: diplopia
* Proximal muscle weakness: face, neck, limb girdle
* Ptosis
* Dysphagia
Myasthenia Gravis Associations
- Thymomas in 15%
- Autoimmune disorders: pernicious anemia, hypothyroidism, rheumatoid, SLE
- Thymic hyperplasia in 50-70%
Myasthenia Gravis Investigations
- Tensilon test: IV edrophonium ↓ muscle weakness temporarily
- CT thorax to exclude thymoma
- CK normal
Myasthenia Gravis Management
Long-acting anticholinesterase e.g. Pyridostigmine
* Immunosuppression: prednisolone initially (although sometimes it can worsen the symptoms)
* Thymectomy
drugs may exacerbate myasthenia:
β-blockers (theoretical worsening based on propensity to
cause side effects of fatigue and weakness)
* Gentamicin, Aminoglycosides and Tetracyclin
* Lithium
* Magnesium
* Penicillamine
* Phenytoin
* Quinidine, procainamide, verapamil, contrast agents.
* Chloroquine
* Prednisolone
Lambert-Eaton Myasthenic Syndrome
association with small cell lung cancer, and to a lesser extent breast and ovarian cancer.
caused by an antibody directed against pre-synaptic voltage gated calcium channel in the peripheral nervous system
Lambert-Eaton Myasthenic Syndrome Features
- Repeated muscle contractions lead to ↑ muscle strength* (in contrast to myasthenia gravis)
- Limb girdle weakness (affects lower limbs first). Proximal muscles more commonly affected.
- Hyporeflexia
- Autonomic symptoms: dry mouth, impotence, difficultly micturating
- Ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)
Lambert-Eaton Myasthenic Syndrome management
EMG
* Incremental response to repetitive electrical stimulation
Management
* Treatment of underlying cancer
* Immunosuppression, for example with prednisolone and/or azathioprine
* 3,4-diaminopyridine is currently being trialled**
* Intravenous immunoglobulin therapy and plasma exchange may be beneficial
Anti-Hu (imagine H sticks as 2 lungs or 2 brain hemispheres)
- Associated with small cell lung carcinoma and neuroblastomas
- Sensory neuropathy - may be painful
- Cerebellar syndrome
- Encephalomyelitis
Anti-Yo (imagine Y as lady’s private organ)
- Associated with ovarian and breast cancer
- Cerebellar syndrome
Anti-GAD antibody
- Associated with breast, colorectal and small cell lung carcinoma
- Stiff person’s syndrome or diffuse hypertonia
Glomus Jugulare Tumours
ighly vascular tumours derived from neural tissue and arising within the jugular foramen of the temporal bone.
♀:♂ ratio between 3 and 6:1 - Annual incidence is around 1 in 1.3 million.
Tend to present between 40 and 70 years of age.
Presents with deafness and pulsatile tinnitus
toscopic examination may reveal a characteristic pulsatile reddish-blue mass behind the
tympanic membrane.
Surgical resection is the treatment of choice, embolisation and radiotherapy have been used.
Demyelinating pathology
Guillain-Barre syndrome
* Chronic inflammatory demyelinating
polyneuropathy (CIDP)
* Amiodarone
* Hereditary sensorimotor neuropathies (HSMN)
type I
* Paraprotein neuropathy
Axonal pathology
Alcohol
* Diabetes mellitus (±demyelinating picture)
* Vasculitis
* Vit. B12 deficiency (±demyelinating picture)
* Hereditary sensorimotor neuropathies (HSMN)
type II
Predominately motor loss
Guillain-Barre syndrome
* Porphyria
* Lead poisoning
* HSMN - Charcot-Marie-Tooth
* CIDP
* Diphtheria
Predominately sensory loss
Diabetes
* Uremia
* Leprosy
* Alcoholism
* Vitamin B12 deficiency
* Amyloidosis
Alcoholic neuropathy
Secondary to both direct toxic effects and ↓ absorption of B vitamins
* Sensory symptoms typically present prior to motor symptoms
Vitamin B12 deficiency
Subacute combined degeneration of spinal cord
* Dorsal column usually affected first (joint position, vibration) prior to distal paraesthesia
Drugs causing a peripheral neuropathy
Antibiotics: nitrofurantoin, metronidazole
* Amiodarone
* Isoniazid
* Vincristine and most of the anti-cancer chemotherapy
* Tricyclic antidepressants
Autonomic Neuropathy features
eatures
* Impotence, inability to sweat
* Postural hypotension e.g. Drop of 30/15
mmHg
* Loss of ↓ in heart rate following deep
breathing
* Pupils: dilates following adrenaline
instillation
Autonomic Neuropathy
Causes
* Diabetes
* Guillain-Barre syndrome
* Multisystem atrophy (MSA), Shy-Drager
* Parkinson’s
* Infections: HIV, Chagas’, neurosyphilis
* Drugs: antihypertensives, tricyclics
* Craniopharyngioma
Guillain-Barre Syndrome pathogenesis
athogenesis
* Cross reaction of antibodies with gangliosides in the peripheral nervous system
* Correlation between anti-ganglioside antibody (e.g. Anti-GM1) and clinical features has been
demonstrated
* Anti-GM1 antibodies in 25% of patients
GBS Periciptating Organisms:
Periciptating Organisms:
* Campylobacter jejuni
* Chlamydia
* HBV
* Mycoplasma Pneumoniae
* CMV, EBV, HZV, HIV
GBS Management
Plasma exchange
* IV immunoglobulins
* Steroids and immunosuppressants have not been shown to be beneficial
* FVC regularly to monitor respiratory function
GBS Poor prognostic features
Age > 40 years
* Poor upper extremity muscle strength
* Rapid symptoms progression.
* Previous history of a diarrhoeal illness (specifically campylobacter jejuni)
* High anti-GM1 antibody titre
* Need for ventilatory support
Miller-Fisher syndrome
- Associated with areflexia, ataxia, ophthalmoplegia
- Usually presents as a descending paralysis rather than ascending as seen in other forms of
Guillain-Barre syndrome - Anti-GQ1b antibodies are present in 90% of cases
Herpes Simplex (HSV) Encephalitis **
Features
- Fever, headache, psychiatric symptoms, seizures, vomiting
- Focal features e.g. Aphasia
- Peripheral lesions (e.g. Cold sores) have no relation
to presence of HSV encephalitis
Herpes Simplex (HSV) Encephalitis Pathophysiology
HSV-1 responsible for 95% of cases in adults
* Typically affects temporal and inferior frontal lobes
Herpes Simplex (HSV) Encephalitis
Investigation
Investigation
* CSF: lymphocytosis, elevated protein
* PCR for HSV
* CT: medial temporal and inferior frontal changes
(e.g. Petechial hemorrhages) - normal in one-third of
patients
* MRI is better
* EEG pattern: lateralised periodic discharges (LPD,
not LAPD☺) at 2 Hz
Herpes Simplex (HSV) Encephalitis treatment
Treatment
* IV aciclovir
The prognosis is dependent on whether aciclovir is commenced early. If treatment is started promptly
the mortality is 10-20%. Left untreated the mortality approaches 80%
Sub-acute Sclerosing Panencephalitis
It is recognized to be the result of chronic measles infection.
Initially: decline in proficiency in school.
Followed by diffuse myoclonic jerks in association with focal and generalised seizures and visual deterioration due to choiroidoretinitis.
Followed by pyramidal signs, rigidity and progressive unresponsiveness.
Finally the patient lies decorticated followed by death.
HIV Neurocomplications:Encephalitis
Encephalitis
* May be due to CMV or HIV itself
* HSV encephalitis but is relatively rare in the context of HIV
* CT: edematous brain
HIV Neurocomplications: Cryptococcus
Most common fungal infection of CNS
* Headache, fever, malaise, nausea/vomiting, seizures, focal
neurological deficit
* CSF: high opening pressure, India ink test positive
* CT: meningeal enhancement, cerebral edema →
* Meningitis is typical presentation but may occasionally cause a
space occupying lesion
HIV Neurocomplications: . Progressive multifocal leukoencephalopathy (PML)
- Widespread demyelination
- Due to infection of oligodendrocytes by human papovirus (jc
virus) - Symptoms, subacute onset : behavioural changes, speech, motor,
visual impairment - CT: single or multiple lesions, no mass effect, don’t usually
enhance, Low attenuation diffusely - MRI is better - high-signal demyelinating white matter lesions are
seen in advanced HIV.
Toxoplasmosis
Accounts for around 50% of cerebral lesions in patients with HIV
* Constitutional symptoms, headache, confusion, drowsiness
* CT: usually single or multiple ring enhancing lesions, mass
effect may be seen
* Management: sulfadiazine and pyrimethamine
Myotonic dystrophy genetics
(also called dystrophia myotonica) is an inherited myopathy with features developing at around 20-30 years old. It affects skeletal, cardiac and smooth muscle. There are two main types of myotonic dystrophy, DM1 and DM2.
Genetics
* Autosomal dominant
* A trinucleotide repeat disorder
* DM1 is caused by a CTG repeat at the end of the DMPK (Dystrophia Myotonica-Protein
Kinase) gene on chromosome 19
* DM2 is caused by a repeat expansion of the ZNF9 gene on chromosome 3
Myotonic dystrophy DM1
DMPK gene on chromosome 19 - Distal weakness more prominent
Myotonic dystrophy DM2
- ZNF9 gene on chromosome 3
- Proximal weakness more prominent
- Severe congenital form is not seen
Myotonic dystrophy General features
Myotonic facies (long, ‘haggard’
appearance)
* Frontal balding
* Bilateral ptosis
* Cataracts
* Dysarthria
Myotonic dystrophy other features
*
Myotonia (tonic spasm of muscle) Weakness of arms and legs (distal initially) Mild mental impairment
Diabetes mellitus
Testicular atrophy
Cardiac involvement: heart block, cardiomyopathy
Dysphagia
Spastic Paraparesis:
Causes
* Demyelination e.g. Multiple sclerosis
* Cord compression: trauma, tumour
* Parasagittal meningioma
* Tropical spastic paraparesis
* Hereditary spastic paraplegia
* Transverse myelitis e.g. HIV
* Syringomyelia
* Osteoarthritis of the cervical spine
Trigeminal neuralgia
A unilateral disorder characterized by brief electric shock-like pains, abrupt in onset and termination, limited to one or more divisions of the trigeminal nerve
* The pain is commonly evoked by light touch, including washing, shaving, smoking, talking, and brushing the teeth (trigger factors), and frequently occurs spontaneously
* Small areas in the nasolabial fold or chin may be particularly susceptible to the precipitation of pain (trigger areas)
* The pains usually remit for variable periods
Management
* Carbamazepine (Tegretol®) is first-line
* Failure to respond to treatment or atypical features (e.g. < 50 years old) should prompt referral
to neurology
Neuropathic pain treatment
ICE issued guidance in 2010 on the management of neuropathic pain:
* First-line treatment*: oral amitriptyline or pregabalin
* If satisfactory pain reduction is obtained with amitriptyline but the person cannot tolerate theadverse effects, consider oral imipramine or nortriptyline as an alternative
* Second-line treatment: if first-line treatment was with amitriptyline, switch to or combine with
pregabalin. If first-line treatment was with pregabalin, switch to or combine with amitriptyline
- Other options: pain management clinic, tramadol (not other strong opioids), topical lidocaine
for localised pain if patients unable to take oral medication
Guidance on the management of diabetic neuropathy
First-line: oral duloxetine. Oral amitriptyline if duloxetine is contraindicated.
* Second-line treatment: if first-line treatment was with duloxetine, switch to amitriptyline or
pregabalin, or combine with pregabalin. If first-line treatment was with amitriptyline, switch to
or combine with pregabalin
* Other options: pain management clinic, tramadol (not other strong opioids), topical lidocaine
for localised pain if patients unable to take oral medication
Cluster headaches Features
- Pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours
- Clusters typically last 4-12 weeks
- Intense pain around one eye (recurrent attacks ‘always’
affect same side) - Patient is restless during an attack
- Accompanied by redness, lacrimation, lid swelling
- Nasal stuffiness
- Miosis and ptosis in a minority
Cluster headaches Management
Management
* Acute: 100% oxygen, subcutaneous sumatriptan (5-HT1D receptor agonist), nasal lidocaine
* Prophylaxis: verapamil, prednisolone
* Consider specialist referral
Acute migraine treatment
Standard analgesia - First-line therapy
* E.g. Paracetamol, ibuprofen, aspirin, may be poorly absorbed, often combined with anti-emetic e.g. Metoclopramide (to relieve associate nausea) → caution should be exercised with young patients as acute dystonic reactions may develop
Avoid aspirin in children < 16 years as risk of Reye’s syndrome
Triptans
* Second-line therapy
* Specific 5-HT1 agonists - opposes Vasodilation
Ergotamine
* α-blocker and a partial 5-HT1 agonist
* Now rarely used due to high incidence of adverse effects (e.g. Nausea and vomiting)
* Listed in the BNF as ‘less suitable for prescribing’
Prophylaxis migraine treatment
should be given if patients are experiencing ≥ 2 attacks/month. Treatment is effective in about 60% of patients
First-line
* β-blockers: propranolol 80-240mg OD
Also recommended in the SIGN guidelines
* Sodium valproate
* Topiramate (CKS recommend this is used under
specialist supervision)
* Gabapentin
* Amitriptyline
* Venlafaxine
The SIGN guidelines also suggest that stress management and acupuncture may be useful
5-HT2 antagonists
* Pizotifen: used less commonly now due to adverse effects (weight gain and drowsiness)
* Methysergide: very rarely used as associated with retroperitoneal fibrosis
Migraine and the combined oral contraceptive (COC) pill
- If patients have migraine with aura then the COC is absolutely contraindicated due to an increased risk of stroke (relative risk 8.72)
CSF raised lymphocytes
Viral meningitis/encephalitis
* TB meningitis
* Partially treated bacterial meningitis
* Lyme disease
* Behcet’s, SLE
* Lymphoma, leukemia
CSF raised protein
The following conditions are associated with raised protein levels
* Tuberculous, fungal and bacterial meningitis
* Viral encephalitis
* Guillain-Barre syndrome
* Spinal block (Froin’s syndrome)
EMG common findings:
- Polumyositis: reduced ampliyude and duration of motor unit
- MND: fibrillation due to denervation
- Myasthenia Gravis: diminished responses to repitative stimulations
- Lambert Eaton Myasthenia: enhanced responses to repitative stimulations.
- Myotonia Dystophia: High frequency action potentioals, Kamikaze discharge or dive bombers
frequency which is heard
