Neurology Flashcards
MS - pathophys, Epid, Clinical, Ix, Dx, Tx, Cx?
immune-mediated disorder characterized by activation of T-helper cells induce B-cells to produce Ab and cytokines that drive an inflammatory process directed at myelin and erosion of BBB, resulting in demyelination and axonal damage.
Epid:
F>M
20-40 y
Aetiology:
Genetics
Environmental - toxins, EBV
relapses triggered by infections, surgical procedures
Clinical
visual disturbance in one eye
peculiar sensory phenomena - odd sensations of a patch of wetness, burning, tingling, hemibody sensory loss, Lhermitte’s sign (electric shock like sensations extending down the cervical spine radiating to limbs)
foot dragging or slapping
Ix:
MRI brain - hyperintensitits in periventricular white matter
MRI spinal cord - demyelinating lesions in spinal cord, particul cervical spinal cord
TSH - exclude alternative Dx
Vit B12 - exclude alternate Dx
ant-NMO ab - present in neuromyelitis optica
CSF - oligoclonal bands and elevated CSF IgG present in 80%
evoked potenitals - prolongation of conduction, asymmetrical prolongation in visual evoked potenitals
Dx:
Dissemination in space and time
2 or more attacks, objective clinical evidence of 2 or more lesions or objective clinical evidence of 1 leision with reasonable historical evidence of prior attack
Tx:
1st line - Methylprednisolone
2nd line - IVIG
With severe worsening quadriplegia - plasma exchange
relapse remitting MS - immunomodulators, low dose anticonvulsants for sensory symptoms, antisapcity medication for increased muscle tone
Cx: UTI Osteopenia and OP Depression Visual impairment Erectile Dysfucntion (ED) Cognitive impairment Impaired mobility
What is the most common CNS tumour? Tx?
Glioblastoma
Tx: Surgical resection + concurrent Chemo (Temzolamide - oral alkylating agent) and stereotactic RTx
Types of nerve fibres?
A- myelinated
subtypes a (propioception), b (touch, pressure, motor), y (motor to muscle spindles), o (pain, cold, touch)
B - myelinated (paraganglionic autonomic)
C - unmyelinated slow conducting (pain)
Large fibres are concerned primarily with propioceptive sensation, somatic motor function, conscious touch and pressure.
Small fibres - pain and temperature sensations and autonomic function
What features indicate a poor prognosis in Bell’s palsy?
Older age > 60 y
Severe complete paralysis
Hyerpacusis
Altered taste
EMG evidence of axonal degeneration
Which antiepileptic drug reduces the serum levels of lamotrigine?
Phenytoin
Carbamazepine
(Think BS CRAP GPS)
What signs will a right Parietal stroke will produce?
Homonymous hemianopia
Hemispatial neglect
- cannot draw clockface
Dressing apraxia
What signs will an occipital infarct produce?
Homonymous heminopia with macular sparing
Pt with receptive aphasia. Which lobe affected?
Temporal (Wernicke’s area)
Which area is affected in global aphasia?
Perisylvian area
Triad of normal pressure hydrocephalus? MRI findings? Tx?
Dementia
Gait impairment - gait ataxia
Urinary incontinence
MRI:
Ventriculomegaly
Tx:
CSF drainage
Surigcal placement of ventriculoperitoneal shunt
Which antibodies are associated with paraneoplastic syndromes?
(sub-acute progressive neurological disease)
Anti Hu and Anti-Yo antibodies in CSF
why does Sodium valproate cause lamotrigine toxicity?
Valproate causes a significant rise in plasma concentration of lamotrigine by competitively inhibiting glucoronidation. Lamotrigine is extensively metabolsised by N-gluocoronidation
Which SSRI has been shown to improve motor recovery post stoke?
Fluoxetine
- serotonin mediated suppression of post stroke hyper-excitability (lancet 2011)
Meniere disease: Triad?
Vertigo
Unilateral low freq hearing loss
Tinnitus - associated with fullness
(Nystagmus to opposite side affected)
Acoustic neuroma: Presentation? Imaging of choice?
Nystgamus - rapid
Slowly progressive symptoms of hearing loss
Tinnitus
Loss of corneal reflex
MRI:
detect tuomours as small as 1-2 mm
What Tx is Dx for BPPV? Tx?
Hallpike manoeuvre
Tx with Epsley manoeuvre
What features predict a stroke mimic?
known CI
LOC or seizure at onset
Migration of symptoms
Positive symptoms e.g. paraesthesia, jerks
Brown Sequard Syndrome: Presentation?
Characterised by:
Ipsilateral motor deficit below the level of the lesion
Ipslateral impairment of vibration and position sense below the level of the lesion
Contralateral loss of pain and temperature from one or two segments below the lesion
Syringomyelia, subacute degeneration of cord and Friedrich’s ataxia can cause cerebellar signs and patchy sensory loss but would be bilateral.
painful eye with decreased visual acuity and relative afferent pupillary defect. Dx?
Optic neuritis
Most likely underlying cause is MS.
Myasthenia Gravis. Pathophy? Presentation? NCS demonstrate? Tx?
Antibody to the neuromuscular junction AChR or MuSK
Presentation:
fluctuating fatigable symmetric painless weakness
Fluctuating dysarthria
ptosis
Bulbar symptoms - Difficulty chewing, slurred speech
NCS:
Reduced amplitude
Tx:
Pyridostigmine (ACh inhibitor)
Thymectomy
Which symptoms in PD are not related to levodopa?
Falls, instability, gait disturbance Dysphagia, speech disturbance Incontinence, constipation Insomnia, REM sleep behaviour disorder Depression, cognition, pain
Tx for PD?
◦Dopamine Gold Standard
L-Dopa is 1st line Tx for:
- severe motor impairment
- >60 y, especially with CI
Levodopa +/- entacopone (COMT inhibitor acts by reducing extra cerebral metabolism of dopamine). COMT responsible for metabolism.
levodopa is the main precursor in dopamine synthesis.
- superior benefits in motor function, ADLs and QOL compared with other classes
- decreased chance of requiring add on therapy
Dopamine agonists: Stimulate dopamine by binding directly to receptors in the striatum
Non ergot
- pramiprexole, discontinuation in 8% due to AE e.g. somnolence, GIT, Impulse control disorder
- ropinirole
- transdermal rotigotine
Ergot derived
- cabergoline
- bromocriptine
- pergolide
- complications of heart valve and retroperitoneal fibrosis
AE: impulse control disorder, punding (repeated pointless actions)
MAO B inhibitors - rasigiline and selegeline ◾mild benefit ◾may slow progression of disease AE: hepatic dysfunction, higher overall mortality
◾apomorphine◾SC injection, powerful
◾moderate motor benefit
◾defer onset of motor fluctuations
◾AE: impilse control disorders, sleppiness, psychosis
◾Rotigotine - transdermal patch
◦Stalevo◾triple medication consisting of Levodopa, carbidopa and entacapone
Wallenberg’s syndrome (aka lateral medullary syndrome). What? Clinical features?
Due to occlusion of the posterior inferior cerebellar artery
– Ipsilateral loss of facial pain and temperature(due to trigeminal spinal nucleus and tract involvement).
– Contralateral loss of pain and temperature(due to damage to the spinothalamic tract).
– Ipsilateral palatal, pharyngeal, and vocal cord paralysis with dysphagia and dysarthria (due to involvement of the nucleus ambiguus).
– Ipsilateral Horner syndrome (due to affection of the descending sympathetic fibers).
– Ipsilateral cerebellar signs and symptoms (due to involvement of the inferior cerebellar peduncle and cerebellum).
– Vertigo, nausea, and vomiting (due to involvement of the vestibular nuclei).
– Occasionally, hiccups (singultus) attributed to lesions of the dorsolateral region of the middle medulla and diplopia (perhaps secondary to involvement of the lower pons).
What is Foster Kennedy Syndrome?
due to an inferior frontal lobe tumour.
It causes optic atrophy in one eye and papilloedema in the other.
What is Gerstmann syndrome?
Gerstmann syndrome causes agraphia, acalculia, finger agnosia, left right disorientation.
CT/MRI should precede LP in which group of pts?
1) presence of papilledema on physical examination
2) history of recent head trauma
3) known or suspected intracranial lesions (immunosuppressed, known malignancy)
4) focal neurologic findings.
5) depressed level of consciousness
Which mutation occurs in familial form of ALS?
SOD1 mutation
What is Kennedy’s syndrome? Presentation?
– X-linked lower motor neuron disorder
– No UMN signs.
– Associated with gynaecomastia and infertility.
Underlying molecular defect is an expanded trinucleotide repeat (-CAG-) in the first exon of the androgen receptor gene on the X chromosome
– X-linked lower motor neuron disorder
– No UMN signs.
– Associated with gynaecomastia and infertility.
Underlying molecular defect is an expanded trinucleotide repeat (-CAG-) in the first exon of the androgen receptor gene on the X chromosome
MOA of riluzole?
sodium channel blocker that inhibits glutamate release.May slow progression of disease marginally.
Does not prolong survival
UMN signs only? Dx
Primary lateral sclerosis
LMN signs only?
Primary muscular atrophy
ALS. Presentation?
UMN LMN Bulbar dysfunction Respiratory failure Cramps and fasciculation NORMAL SENSATION
majority of anti-epileptics block Na channels except?
Tiagabine
GABA re-uptake inhibitor
MOA of Vigabatrin? indication
GABA transaminase inhibitor
Refractory complex partial seizures
Partial seizures with or without secondary generalisation
Which antiepileptic may cause OP?
Other AE of this anti-epileptic?
Phenytoin
Osteoporosis, ataxia, nystagmus, gingival hyperplasia, coursening of facial features, loss of libido, hormone dysfucntion, bone marrow hypoplasia.
Which of anti-epileptic has the most teratogenic effect in pregnancy?
NaValproate
Major malformations, such as congenital heart disease, neural tube defects, urogenital defects and cleft lips or palates, occur in about 3-7% of women with epilepsy who take antiepileptic drugs, although a substantially higher risk is attributed to high doses of valproate (greater than 1400 mg/day).
Which anti-epileptic drugs may cause visual field changes?
Vigabatrin
- visual field changes!
Drowsiness(most common), neuropsychiatric symptoms, weight gain
Which anti-epileptics cause weight gain and weight loss?
Gain:
Vigabatrin
Pregabalin
Valproate.
Loss:
Topiramate
Which AED may cause renal calculi?
Topiramate
Which AED may cause insulin resistance?
Valproate causes insulin resistance and changes in sex hormone levels (anovulatory cycles, amenorrhea and PCOS).
Also causes metabolic abnormalities such as hypocarnitinemia, hyperglycinemia and hyperammonemia
Presentation of PCA aneurysm?
Headache painful 3rd nerve palsy 3rd nerve palsy - eye deviated down and out -ptosis - pupils maybe dilated
Which AED does not affect the OCP?
Sodium Valproate (Cyp inhibitor)
Which AED may aggravate juvenile myoclonic epilepsy and should be avoided?
Tx?
Carbamazepine
Tx: NaValproate
What is the most common symptom of excess Levodopa?
Nausea and vomiting
Common AE: orthostatic hypotension dyskinesia anorexia agitation insomnia drowsiness depression hallucinations confusion
MOA of amantadine?
Indications?
Amantadine enhances dopamine release and blocks cholinergic receptors.
Acts as NMDA antagonist.
Indications:
PD
Influenza A
MOA of COMT inhibitors?
prolong dopamine activity by blocking breakdown
Domperidone crosses BBB. T/F
False.
Safe to use in PD.
Indications:
N/V
Gastroparesis (idiopathic or diabetic)
Smoking is protective against PD. T/F
True
List the dopamine agonist. AE?
Pramiprexole
Apomorphine
AE:
Impulse control disorder
Somnolence
Psychosis
Radial nerve supplies (C5-8)? Presentation of lesion?
Supplies triceps, brachioradialis. extensors of the hand
Lesion: wrist drop absent sensation over the anatomical snuff box weakness of finger and thumb extension loss of triceps reflex
Median nerve (c6-T1). Supplies? Presentation of lesion?
Supplies all the muscles of the forearm except flexor carpi ulnaris and ulnar half of flexor digitorum
Lesion:
Carpel tunnel syndrome
failure of flexion of index finger - cubital fossa lesion
Loss of sensation over the palmar aspect of thumb, index and middle and lateral half of ring finger
weakness of abduction/opposition of thumb
Ulnar nerve (C8-T1. Supply? Presentation of lesion?
Supplies all the small muscles of the hand (except LOAF), flexor carpi ulnaris and ulnar half of flexor digitorum profundus
Presentation:
Clawing of ring finger
loss of sensation over the palmar and dorsal aspect of the little finger and medial half of ring finger
weakness of small finger flexion, abduction and adduction
If the peripheral nerve lesion involves more than one nerve and distribution of the sensory loss is wider (e.g. involves the distal forearm). Where is the lesion?
Brachial plexopathy.
Pt post ortho Sx. Foot drop and ankle reflex absent. Where is the lesion?
Sciatic Nerve.
if reflexes were intact, think of common peroneal or L5 radiculopathy
Cervical spinal cord compression. Presentation?
Upper cervical
C5
C8
Upper cervical
- UMN signs in UL and LL
C5
- UMN in UL and LL
- biceps jerk lost
- LMN weakness and wasting of rhomboids, deltoids, biceps and brachioradialis
- brachioradialis jerk inverted
C8
- UMN signs in LL
- LMN weakness and wasting of intrinsic muscles of hands
Haemophilia pt develops haematoma. Weak knee extension, absent knee jerk and loss of sensation over inner aspect of thigh and leg. lesion?
Femoral nerve (L2, 3, 4)
Which antibiotic reduces the therapeutic effects of NaValproate?
Carbapenem (imipenem, meropenem, ertapenem)
Unknown mechanism
List the 4 pre-requisites to exclude before a pt is considered brain dead
1) Clinical or neuroimaging evidence of an acute CNS catastrophe that is compatible with the clinical diagnosis of brain death.ie: the cause of brain death should be known.
2) Exclusion of complicating medical conditions that may confound clinical assessment (no severe electrolyte,acid base or endocrine disturbance)
3) No drug intoxication or poisoning, which may confound the clinical assessment.
4) Core temperature >32 degrees celcius.
Why should phenytoin be avoided in Asians (Han chinese, Thai and malay)?
More likely to have HLA-B 1502 allele which sig increases the risk of severe skin reactions.
Routine testing is not recommended.
Where is the lesion- difficulty making the ok sign?
right anterior interosseous nerve
Ventral (motor) tract? Dorsal (sensory) tracts?
Ventral (front-V shape) - corticospinal (motor) and spinothalamic tract (pain and temp)
Dorsal - Dorsal comum meniscus (sensory, vibration), spinocerebellar (limb and joint propioception)
Which drugs cause an i) axonal neuropathy ii) demyelinating neuropathy?
axonal - ethanol, pyridoxine, thalidomide
demyelinating - Cholorquine, Procainamide, Perhexiline, Tacrolimus
GBS is associated with which abs?
Anti-ganglioside (GM1, GD1a, GT1a and GQ1b)
GQ1b
What are the hallmarks of Supranucelar palsy?
Distinctive eye findings (impairment of vertical gaze movement, square wave jerks, slow saccades and a spuranuclear gaze paresis)
Facial dystonia
Axial rigidity
How to differentiate Multi systems atrophy (MSA) from PD?
- poor initial response to l-dopa
- autonomic failure
- speech and bulbar dysfunction
- early falls
- progression (50% wheelchair by 5 y)
- preserved cognition
Hallmarks of corticobasal ganglionic degeneration?
- asymmetric dystonic syndrome with apraxia
- cortical sensory loss
- tremor
- myoclonus
- dementia
Clinical findings of a sciatic nerve lesion?
Loss of knee flexion
Loss of ankle dorsiflexion (L4 deep peroneal)
Loss of toe extension (L5 deep peroneal)
Loss of sensation on dorsum of foot and sole
Loss of ankle jerk (sciatic nerve)
Clinical hx typically - hip dislocation, fracture or replacement, prolonged bed rest, deep seated pelted mass, performs syndrome
Clinical features of frontal lobe damage?
Attention disorder, ditractability, poor attention
poor memory
perservation, concrete thinking -> leads to difficulty with arithmetic calculations, serial sevens or carryover subtraction
aphasia, urinary, faecal incontinence
Epilepsy
Reduced activity, lack of drive, inability to plan ahead, lack of concern
Patient having difficulty drawing animals, all the animals look the same. Where is the lesion?
Lateral temporal lobe/cortex.
Pt has a semantic problem, having lost the sense of what features make an animal distinct from other animals.
Which lobe is responsible for visuospatial function?
Non dominant parietal lobe
What is the 1st line Tx for Juvenile Myoclonic Epilepsy? What medication will exacerbate myoclonic epilepsy?
Valproate and topiramate
Lamotrigine may exacerbate myoclonus
MCA infarct. Clin pres? Which segment of MCA affected?
Dense hemoplegia
Hemianopis
Aphasia if dominant
M1 of MCA segment. Increased attenuation of the proximal portion of the MCA is typically seen within 90 minutes
ACA infart. Clin Pres?
Sensory and Motor deficits of LL predominantly.
Medical frontal lobe affected.
What sign is classic of a lacunar infarct?
Pure motor deficit
What is the pathophys of Lewy body disease?
Misfolding and intracellular aggregation of alpha synuclein.
Extracellular aplha synuclein is internalised into neighbouring cells and degraded into lysosomes.
In Lewy body a higher proportion of excreted alpha synuclein is in aggregated form which promotes further aggregation ind is pro inflammatory.
ACHR-Ab negative MG with positive MusSK Ab is not associated with underlying thymoma. T/F
True
50% of patients with REM sleep behaviour disorder progress to Parkinson’s D? Tx?
True
Clonazepam or benzo suppress REM
Steps in Apnea Testing for the declaration of Brain Death?
- Pre-oxygenate pt to 100% FiO2
- Ensure pt is not hypoxic via ABG
- Disconnect the ventilator but supply oropharyngeal O2
- Monitor the patient for any signs of respiration
- Obtain ANGs at selected intervals q3-4 min
- Stop the test and return to mechanical ventilation if
- haemodynamic instability occurs or
- the patient exhibits attempts to breathe or
pCO2 is > 60 mmHg or rises > 20 mmHg above baseline in the setting of arterial pH
Pregabilin - MOA, Indications, AE?
Binding to vgated calcium channels in the CNS to modulate calcium influx and inhibit release of excitatory neurotransmitters
Indications
Adjuvant treatment in focal seizures with or without secondary generalisation
Neuropathic pain
AE
dizziness, drowsiness, confusion, irritability, visual disturbanve, ataxia, tremor, insomnia, euphoria, odema
Gradually reduce dose over one week
Smoking is associated with increased risk of cerebral aneurysm rupture. T/F
False
What RF are associated with cerebral aneurysm rupture?
Age > 70 y
Aneurysm size > 7 mm
HT
ACA, Posterior circulation and posterior communicating aneurysm
Earlier SAH from another aneurysm
How long does HSV remain positive after antiviral therapy?
Positive for first week of antiviral therapy
Clinical Presentation of HSV encephalitis? Tx If no Dx after first PCR of CSF what is the next step
Severe headache
Fever
Impaired consciousness or cognitive state
No meningism or photophobia
Tx: Aciclovir 10 mg/kg TDS
Next step
- Repeat MRI and LP after 3 days
Convalescent serological tests at weeks 1,2, and 6 for HSV, flavivirus or VZV
Clin Pres of Anterior spinal artery syndrome and tracts affected?
Loss of motor function - corticospinal
Loss of sensation - spinothalamic
Vibration and position sensation spared - posterior columns
Clin Pres of Central Cord syndrome and tracts affected?
Loss of pain and temperature in one or more adjacent dermatomes bilaterally at the level of the lesion
- cape or vest like distribution across neck, shoulders or trunk
As the central lesion enlarges it effects
- the anterior horn cells, causing segmental lower motor neuron weakness at the level of the lesion
- lateral corticospinal tracts causing UMN weakness and temperature and sensation loss below the lesion
Arm weakness > LL - corticospinal
Preserved vibration, light touch and joint position - dorsal column
Clin Pres of Brown Sequard syndrome and tracts affected?
Loss of motor function, vibration, position and deep touch sensation on same side as cord damage
Loss of pain, temp and light touch on opposite side
Which nerve roots are affected in caudal equina syndrome?
Mechanical compression of sacral and lumbar roots between L2 and S1
Which Abs are highly specific with mid sensitivity to Inclusion Body Myositis?
Abs against 5 nucleotidase 1A (anti-cN1A)
What is the difference between Duchenne and Becker’s muscular dystrophy?
Duchenne = large deletion of dystrophin gene, child hood onset
Becker’s = smaller deletion of dystrophin gene
Both are X-linked R
What is the time course for NCS and EMG changes in radial nerve lesion?
Nerve conduction studies
- motor conduction fails on D3-7
- sensory conduction fails on D6-10
EMG
- reduced recruitment of normal morphology motor units on day 3-7
- Fibirllations, positive sharp waves develop on D10-42
- Regenrating units appear in months
Which epilepsy syndrome is drug resistant?
Mesial temporal sclerosis (atrophy of hippocampus on MRI)
Meniere disease. When does it begin, triad?
3-4th decade
Triad : episodic vertigo, tinnitus and low frequency hearing loss
Exlcude neurosyphilis as a cause of hearing loss by checking serum VDRL or RPR
Aminoglycoside toxicty: symptoms and Dx test?
Sensorineural loss and intermittent mild vertigo
Corrective saccade indicates a positive test
What is Uhthoff phenomenon?
worsening of MS symptoms due to increased heat e.g. fever.
heat increases conduction block in demyelinated pathways.
e.g. worsening vision
Neuroleptic malignant syndrome: What? Aetiology? Clinical? Ix? Tx?
Idiosyncratic response to potent neuroleptics resulting in autonomic dysfunction, extrapyramidal symptoms and high fever.
Clinical:
Characterised by 3 features
hyperthermia - accompanied by tachycardia, diaphoresis, labile BP
extrapyramidal signs - muscle rigidity or dystonia, elevated muscle enzyme levels
delirium
Aetiology:
D2 receptor blockers e.g. risperidone and atypical neuroleptics
Ix:
CK elevated
Tx:
Discontinuing causative drugs
Supportive measures
Doapmine agonist bromocriptine can reverse the syndrome
Dantrolene - muscle relaxant can inhibit the excessive muscle contractions that generate myoglobinemia
Which anti epileptics are broad spectrum? For all seizure types
NaValproate
Lamotrigine
Levetiracetam
Topiramate
Clobazam
Which anti epileptics are narrow spectrum? Focal without alteration in consciousness and focal evolving to bilateral convulsive seizure.
Carbamaepine
Ganapentin
Lacosamide
Oxcarbazepine
Phenobarbital
Phenytoin
Pregabilin
Primidone
Tx for absence seizures?
Ethosuximide
Tx for juvenile myoclonic epilepsy?
NaValproate
What is paraneoplastic syndromes?
An immune reaction to the primary tumour generating autos that cross react with epitopes on specific NS structures.
Anti-NMDA encephalitis is associated with which tumour?
Ovarina teratomas
US or MRI of pelvis if suspected
Define the following aphasia syndromes?
Broca
Wernicke
Global
Conduction
Transcortical motor
Transcortical sensory
Mixed transcortical
Broca
- Nonfluent aphasia with intact comprehension
Wernicke
- Fluent aphasia with impaired comprehension
Global
- nonfluent aphasia with impaired comprehension. Both Broca and Wernicke’s affected
Conduction
- poor repetition but fluent speech
- intact comprehension
- can’t repeat phrase: No ifs ands or buts
- damage to arcuate fasiculus
- Damage to left superior temporal lobe and/or left supra marginal gyrus
Transcortical motor
- nonfluent aphasia with good comprehension and repetition
Transcortical sensory
- poor comprehension with fluent speech and repetition
Mixed transcortical
- non fluent speech, poor comprehension and good repetition
What is Gerstmann syndrome?
Destruction to the inferior parietal lobule of the dominant hemisphere results in Gerstmann syndrome.
•4 primary symptoms1. Dysgraphia/agraphia: deficiency in the ability to write
- Dyscalculia/acalculia: difficulty in learning or comprehending mathematics
- Finger agnosia: inability to distinguish the fingers on the hand
- Left-right disorientation
• Associated with lesions in the dominant hemisphere (usually left) including the angular and supramarginal gyri near the temporal and parietal lobe junction.
Clinical signs of 3rd nerve palsy?
Ptosis
Eyes pointing down and out.
Clinical signs of optic neuritis?
Relative afferent pupillary defect where the pupils appears to dilate in response to light, if the light is swung between the eyes rapidly
Treatment of essential tremor?
- 1st line - propanolol
- 2nd line - Primidone, MOA unknown
- 3rd line - combination of propranolol and primidone
- Atenolol or metoprolol if asthma or bronchospasm in pts unable to tolerate primidone
- Tremor resolves with EtOH and symmetrical - help differentiate from others.
What is the function of the angular gyrus?
Involved in translating visual patterns in words and lettrs into meaningful information such as what is done during reading.
A lesion in the dominant hemisphere (left) results in Gerstmann syndrome (dysgraphia, acalculia, finger agnosia and L-R disorientation, dysphagia)
Pt has numbness in neck. Bilateral and isolated to dermatomal region. Pain and sensation decreased in this same region. Motor function and neuro exam otherwise NAD. dx? Common causes?
Central cord lesion
Manifest as sensory disorder with disruption of spinothalamic tract.
Motor spared.
Dermatomes above and below are normal.
As lesion grows, corticospinal and anterior horn may be involved.
Causes:
Syringomyelia
Intramedullary tumour
Hyperextension in a pt with cervical spondylosis
What spinal cord syndrome will a knife lesion usually cause?
Brown sequard
What cord lesion will a disc herniation cause?
posterior cord function and nerve roots
Pt has UMN and LMN signs with no sensory deficits. Dx?
Amytrophic lateral sclerosis
Acoustic Schwannoma. Symptoms?
Hearing loss and constant vertigo
Restless leg syndrome. Symptoms. Common cause of secondary RLS?
Urge to move the legs accompanied by an uncomfortable and unpleasant sensation in the legs.
Periodic limb movement while asleep
Fe deficiency a widely recognised cause of secondary RLS.
CRF- uraemia
PVD
DM
Medications - antihistamines, dopamine antagonists, TCA, mirtazepine
Hall pike manoeuvre. How do you perform it?
Place the head in extension
Rotate to 45 degrees while the patient is sitting
Have the patient lay down quickly on her back with her head held in extension (head hanging off the examination table)
2-10 second of latency before the onset of rotational nystagmus confirms the diagnosis
Treatment for GBS?
IVIG
Steroids NOT used.
Presentation of trigeminal neuralgia? Tx?
Lancinating pain of the face, triggered by eating.
Common in patients with MS otherwise iodiopathic
Tx: Carbemazepine is the 1st line Tx
What symptoms does dislocation of the stapes cause?
Hearing loss
Not specifically with dizziness
Vestibular neuritis. Symptoms?
Ear pain Tinnitus Monophasic Position dependent Symptoms last for hours to days
How does Botulism manifest? Cause?
Neurotxin produced by Clostridium botulinum
Causes weakness that is bilateral and descending in nature with symmetrical cranial nerve neuropathies
No fever, confusion or pleocytosis
West Nile virus infection. Cause, symptoms, Ix?
Caused by a bite from an infected culex mosquito
Most patients are asymptomatic
Age > 50 and immunosuppressed are at increased risk of meningoencephalitis and neuroinvasive disease involving anterior horn cells of the spinal cord.
Fever, altered mental state, flaccid paralysis with arreflexia.
Neurocysticercosis. Cause, presentation?
Caused by Taenia solium infection, parasitic worm. Transmitted by consumption of undercooked pork or by ingesting eggs via faecal-oral transmission.
Characterised by seizures.
Multiple cyst in brain.
Tx:
Albendazole and dexamethasone
GBS:
Pathophys
Characterised by what symptoms
Patho:
T cell driven AI response
Associated IgG and complement deposition on Schwann cell.
Progressive (days), symmetric muscle weakness that starts in the lower extremities (ascending paralysis) and accompanied by reduced or absent reflexes.
Pain typically located in the back and extremities and can be the presenting feature.
Paraesthesia, pain and paralysis are also common on initial presentation
Dysautonomia in 70% of pts
- tachy, urinary retention, HTN alternating with hypotension, brady, ileus, loss of sweating
Important to perform PFTs as patient at risk of acute respiratory failure
LP, EMG and NCS are normal in the 1st week of presentations in 50% of pts.
HIV serology as may present with a GBS like syndrome.
Recommended Tx for a patient with 70-90% stenosis of the carotid artery on a BG of MI presenting with recurrent TIAs.
Carotid stenting because carotid endarterectomy is associated with a higher risk of MI in the peri-procedural period.
Stenting is associated with a higher risk of stroke.
Otherwise carotid endarterectomy recommended.
Stenting has been shown to be as effective.
Tx within 2 weeks of symptoms have better outcomes.
Eye movement and corresponding muscles?
LR6 SO4 rest 3
Lateral rectus CNVI
Superior oblique CNIV
Multiple systems atrophy characterised by?
Neurodegenerative disorder affecting multiple systems.
ANS, extrapyramidal system and cerebellum
Parkinsonian features, ataxia and AN dysfunction
DDx of thunderclap headaches
SAH most common cause Cervical artery dissection Cerebral venous thrombosis Reversible cerebral vasoconstriction syndrome - think of this if headache recur over a few days Pituitary apoplexy
Ix of thunderclap headache?
CT brain with no contrast within the 1st 12 hrs
LP if CT -ve or equivocal
- high ICP may be a clue to cerebral venous thrombosis where 25% of CT scans are -ve
What is the following imaging useful for Dx in thunderclap headache: MRI Brain MRI brain with gad MRA/CTA brain MRV/CTV brain MRA/CTA neck Catheter angiography
MRI Brain
- ischaemic stroke, cerebral oedema, pituitary apoplexy
MRI brain with gad
- intracranial hypotension
- meningitis
MRA/CTA brain
- aneurysm
- intracranial dissection
- Reversible cerebral vasoconstriction syndrome
MRV/CTV brain
- Central venous sinus thrombosis
MRA/CTA neck
- cervical artery dissection
Catheter angiography
- aneurysm
- Reversible cerebral vasoconstriction syndrome
- arterial dissection
- Central venous sinus thrombosis
Pt post MVA with right sided headache, right Horner’s syndrome and left arm weakness. Location of Pathology?
Carotid dissection.
Horner’s syndrome or cranila nerve palsies due to:
- stretching of sympathetic nerve and cranial nerve fibres by an enlarged carotid artery and cervical root injury caused by compression from an enlarged vertebral artery
Sympathetic fibres (carotid plexus, nerve to sweat gland, nerve to dilator muscle and tarsal muscle)
Pt post MVA with right sided headache, right facial numbness, vertigo, vomiting and right sided Horner’s syndrome. Location of pathology?
Brainstem stroke
Neurological manifestations of the following Vitamin deficiencies: Vitamin B1 Vit B6/pyridoxine VitB12/cobalamin Folate Vitamin E
Vitamin B1/thiamine def (wernicke’s encephalopathy)
- ataxia with minimal lim dysmetria
- opthalomoplegia: horizontal paralysis > other directions
- encephalopathy
- nystagmus: horizontal > vertical
(opthalmoplegia corrects within hours of receiving IV thiamine)
Vit B6/pyridoxine
- painful sensorimotor neuropathy
Excess Vit B6 can cause a peripheral neuropathy
VitB12/cobalamin
- subacute degeneration of the spinal cord.
- Large fibre sensory neuropathy
- depression and psychosis
- encephalopathy
- dementia
- optic neuropathy
Folate
-subacute degeneration of the spinal cord
Vitamin E
- weakness and ataxia from spinocerebellar tract degeneration
- opthalmoplegia
- large fibre neuropathy
How can you distinguish between a common peroneal nerve lesion and L5 radiculopathy?
Common peroneal nerve lesion (behind popliteal and crosses at fibula)
- foot drop due to weak dorsiflexion from deep peroneal nerve
- weak foot eversion (superficial peroneal nerve)
- injuries from prolonged bed rest, crossing legs, hyperflexion of the knee
L5 radiculopathy:
- weak dorsiflexion
- weak big toe extension
- weak foot inversion (posterior tibialis) and eversion
- lesions due to lumbosacral spine pathology therefore SLR +ve
- normal reflexes
- sensory loss over lateral aspect of leg and foot
- extensor digitorum longus supplied by deep peroneal nerve L5
Muscles of foot eversion.
Nerve supply?
Peroneus longus and brevis
Supplied by superficial peroneal nerve; L5 and S1
Loss of sensation of dorsum of foot (sparing web space between first MTJ and 2nd MTJ.
Muscles of dorsiflexion of toes.
Nerve supply?
Muscles of dorsiflexion of foot. Nerve supply?
Extensor digitorum longus
Tendons of the lateral four toes can be seen during dorsiflexion.
Supplied by deep peroneal nerve: L5, S1
Tibialis anterior
Supplied by deep peroneal nerve L4,5
Muscles of foot inversion.
Innervation?
Tibialis posterior
Supplied by tibial nerve; L4/5
Convulsive syncope. Presentation?
Prodrome phase
- lightheadedness
- visual, auditory surroundings fading away
- blurred vision
- generalised weakness
- tonic clonic movements a consequence of cerebral hypoperfusion. Always happen after a few seconds and never during the fall.
Presentation of Raised intracranial pressure
Symptoms of raised ICP:
Horizontal diplopia due to false localising CN VI palsy
Pulsatile tinnitus nay be reported
Symptoms of papilloedema:
Transient visual obscurations, lasting up to 30s and described as black out of vision in one eye or both of the eyes.
These obscurations may be predominantly or uniformly orthostatic.
Progressive loss of vision in one or both eyes.
Herpes Zoster Oticus (Ramsay Hunt Syndrome). Cause, Presentation, Prognosis?
Occurs when Herpes Zoster affects the trigeminal nerve and adjacent CN VII and VIII.
Triad of:
peripheral facial paralysis
ear pain
vesicles in the external auditory canal
Prognosis poor. Recovery variable over months.
Korsakoff syndrome. Symptoms?
Develops from Wernike encephalopathy - 80% of pts with WE who alcohol abuse develop Korsakoff
Antegrade and retrograde amnesia
confabulation
Pt with symptomatic R ICA stenosis 75%. What Mx is best evidenced?
Aspirin.
Always started before CEA and continued 3/12 after.
Acute vestibular syndrome. Symptoms. DDx?
Spontaneous, continuous vertigo lasting hours to days.
DDx:
Vestibular neuritis
- isolated spontaneous vertigo with NO hearing loss
Labrynthitis
Stroke
Migraine
Meniere’s - rare, 3% vertigo, associated hearing loss , tinnitus or fullness in the ear.
Bilateral vestibulopathy. Main cause?
50% of cases are due to ototoxic medication. Gent accounting for 15-50%.
Gentamicin ototoxicty is vestibular, not cochlear therefore producing permanent loss of balance but not of hearing.
Complication of intercurrent illness in MS pts?
Pseudo relapse - worsening or unmasking of pre-exisiting neurological manisfestations in association with intercurrent illness (particularly febrile) or metabolic derrangement.
What are the 3 types of peripheral nerve fibres?
A fibre
- large, myelinated
- alpha: efferents to skeletal muscle and afferents to muscle spindle, golgi tendon organs.
- beta: efferent to muscle spindles and afferent to muscle spindles, touch and kinaesthesia
- gamma: efferents to muscle spindles
- delta: pain and temperature afferents
B fibre
- small diameter, thinly myelinated
- preganglionic autonomic fibres
C- fibre
- small diameter, non myelinated
- pain, temp, itch afferents and post ganglionic autonomic
NCS findings in GBS?
Increased distal motor latency
Slowing of motor conduction velocities
Conduction block, dispersion.
Focal seizures with or without secondarily generalised tonic clonic seizures. Antiepileptic Tx?
Narrow spectrum drugs: 1st line Carbemazapine Gabapentin Oxcarbazepine Phenytoin Pregabilin Tiagabine Eslicarbazepine Vigabatrin
In elderly, Lamotrigine and Keppra alternative options as carb is not ideal
Generalised seizures. Antiepileptic Tx?
Valproate
Absence:
Ethosuximide
Rufinamide
If rapid response required, use medications which can be loaded e.g. valproate, phenytoin, keppra
Focal and generalised seizures. Antiepileptic Tx?
Broad spectrum; Valproate Benzodiazepine Felbamate Phenonbarb Primidone Lamotrigine levetiracetam Topiramate Zonisamide
Hippocampal sclerosis (aka Mesial temporal sclerosis). Cause, Presentation, Tx?
Characterised by temporal lobe epilepsy with hippocampal atrophy on MRI.
Most common underlying cause of temporal lobe epilepsy.
Presentation:
complex partial seizures with epigastric or psychic auras are the most common manifestation
Auras of taste and smell are less common are relatively specific for TLE
Tx:
Drug resistant
Epidural haemmorhage. Cause, presentation?
Cause:
Nearly always a result from direct head injury causing fracture of the temporal bone and laceration of the middle meningeal artery.
Presentation:
headache
Mental status abnormalities
rapid neurological decline with ipsilateral pupillary dilatation
Tx:
Surgical evacuation otherwise death within a few hours
Subdural haemmorhage. Cause, presentation, Tx?
Injury to small bridging veins between the cortex and the dura.
Presentation:
Indolent
acute develops over hours
chronic develops over weeks to months
Tx:
Surgical intervention of clinical or neuroimaging evidence of pressure on adjacent brain tissue
Cause of Intracerebral vs. subarachnoid haemmorhages.
Intracerebral
- HT or stroke
- trauma
Subarachnoid
- ruptured cerebral aneursym
- trauma
Tx of PML in MS?
Stop Natalizumab
Plasma exchange to remove natilizumab
Miller Fisher syndrome is a variant of GBS. Autoantibody associated?
Gq1b 90-95%
Which autoab are associated with the following subtypes of GBS? Bickerstaff Brainstem encephalitis Acute motor axonal neuropathy Sensory GBS Bulbar Palsy
Bickerstaff Brainstem encephalitis
- GQ1b, 66%
Acute motor axonal neuropathy
- GD1a, GM1
Sensory GBS
- GD1b
Bulbar Palsy
GT1a
CIPD.
Presentation
Tx
Weakness of both proximal and distal muscles
Majority have sensory symptom findings - numbness and tingling. Neuropathic pain may be present.
Deep tendon reflexes absent or depressed.
Tx:
Corticosteroids
Plasma exchange
IVIG
Mulitfocal Motor Neuropathy.
Presentation
Autoab associated
Presentation:
Asymmetric limb weakness, usually in the distribution of individual peripheral nerves
Onset of weakness is usually in the upper extremeties
Over time pt develops atrophy and EMG evidence of axon loss
Deep tendon reflexes are usually decreased but intact in unaffected areas
anti-GM1 in 40-80%
Motor conduction block has been regarded as a core aspect of MMN.
What is the most common presentation of vasculitic neuropathies?
Mononeuritis mulitplex
- PAN
- cryoglobulinaemia
What is Heerfordt syndrome?
Facial palsy combined with uveitis, fever, parotid enlargement and transverse myelitis.
Neuropathy associated with sarcoid.
What is Parsonage Turner syndrome?
A multifocal immune mediated inflammatory peripheral NS disorder.
Acute sudden onset pain radiating from shoulder to the upper arm.
Affected muscles become weak and atrophied, usually upper trunk and long thoracic nerve.
Middle aged men but can affect anyone.
Tx:
Steroids and analgesics
Diabetic neuropathy. features?
Distal syymetric polyneuropathy
Slowly progressive sensory predominant neuropathy
Sensory loss in toes and feet that results from length dependent dysfunction of nerve fibres.
Small fibre loss leading to pain, 25%
Diabetic autonomic neuropathy. Features?
Resting tachycardia Orthostatic hypotension exercise intolerance Abnormla sweat patterns Gastric motor abnormlaities Errectile dysfunction T1Dm>T2DM Infreq seen in pts with typical diabteic distal sensory neuropathy More common in pts with pred small fibre neuropathy
What is Diabetic amyotrophy?
Diabetic lumbosacral and cervical neuropathy
Males > 50y
Severe unilateral pain in the back, hip or thigh that spreads to involve the entire limb and can involve the other leg within weeks to months
Shortly after the onset of pain, proximal weakness can be detected.
Profound atrophy of the thigh can be seen.
Weakness involves multiple root levels and peripheral nerves.
Freq associated with weight loss.
Occurrence is not related to glucose control or duration of diabtets.
What is the commonest cause of an isolated CN IV nerve palsy?
Diabetes
What is HSV-2 lumbrosacral radiculopathy?
MRI findings
CSF
Tx
Radicular pain, paraesthesia, genital discomfort and lower extremity weakness.
Involvememnt of cauda equina or conus medullaris may result in associated urinary retention.
MRI:
nerve root enlargement with associated T2 hyperintensity and T1 contrast enhancment in nerve roots and spinal cord
CSF: positive HSV2 pcr, elevated protein, normla glucose, lymphocytic pleocytosis
Tx:
Valacyclovir
What neuropathy is associated with HIV?
Distla, symmetric, sensory predominant polyneuropathy affecting small sensory fibres in isolation or both small and large sensory fibres occurs in 20-60%.
Don’t usually have motor symptoms.
Paraprotiens and corresponding neuropathy associated: MGUS Waldentrom's MM POEMs Amyloidosis
MGUS:
IgM
Distal large fibre sensory predominant
Demyelinating
Waldentrom’s:
IgM
Distal large fibre sensory
Axonal>demyelinating
Hallmark of IgM neuropathies is prolonged distal latencies implying terminal nerve involvement
MM:
IgG predominant
Length dependent sensorimotor
Aoxonal
POEMs:
IgG, IgA, Lambda
CIDP like
Demyelinating
Amyloidosis:
Lambda
Sensorimotor and small fibre
Axonal
immunoglobulin light chain amyloidosis. What type of neuropathy and autonomic symptoms does it typically cause?
Painful length dependent peripheral neuropathy with generalised autonomic failure - orthostatic hypotension
Parkinson’s Tx:
If too Parkinsonian
If motor fluctuations and dyskinesia
If too Parkinsonian
- increase the dose
If motor fluctuations and dyskinesia
- break up the dose into increased frequencies
Never stop medmications abruptly as this can lead to a Parkinsonian crisis
What is multisystem atrophy characterised by?
Tria
Alpha synuclein disorder
Triad of autonomic failure, parkinsonism, cerebellar signs
Antiepileptic. Failure to 1st Tx. next step?
reach optimal dose.
Gradually switch to another monotherpay.
May go dual therpay if severe epilepsy and unlikely to respond to monotherpay or dual combination is efficacious.
Combinations of Na channel blockers are not effective. Use another drug with diff MOA.
Valproate and Lamotrigine are the best known combination
When to stop antiepileptic therapy?
After 2-4 years f seizure freedomSlow tiration over 2-3 months, 6 months for benzos.
Predictors of higher risk recurrence are:
Adolescent onset epilepsy incl juvenile myoclonic epilepsy
focal seizure
underlying neuro disodrer
Predictors of lower than average risk of recurrence:
Childhood onet epilepsy
Idiopathic generalised epilepsy
Which antiepileptic can worsen absence and myoclonic seizures?
Carbemazepine
Note: HLA 1502 and SJS in Han Chinese
HLA A*3101 and hypersensitivity reaction in Europeans
Phenytoin
If you develop a rash on Carbemazapine, what is the risk of rash with other AED?
Phenytoin 58%
Oxcarazepine 33%
Phenobarb 27%
Lamotrigine 20%
AED: MOA and AE Carbamazapine Leviteracetam Phenytoin NaValproate
Carbamazapine: Na channel blocker AE - hyponatraemia, rash, blood dyscrasia - concentration dependent: diplopia, dizziness, drowsiness, nausea, lethargy, unsteadiness
Leviteracetam:
Inhibits presynaptic CC reducing neurotransmitter release abd acting as a neuromodulator
AE:
Psychosis in 10% of pts
Dose dependent - Sedation, behavioural disturbances
Phenytoin:
Na channel blocker
AE:
Ataxia, nystagmus, diplopia (dose related)
skin thickening, acne, coarsening of facial features
Can worsen absence and myoclonic seizures
NaValproate:
PIP3 reduction
Na channel blocker
Increases GABA
AE:
weight gain
teratogenic
PCOS like syndrome
Which AED causes weight gain?
NaValproate
Why is there an increased risk of OP and Osteopenia with AEDs?
Accelerated metabolism of Vit D and lower oestrodial levels.
2-6 x higher rates of bone fractures
Neuromyelitis Optica aka Devic's disease What Epid Diagnostic criteria Ab associated Tx Complications
relapsing remitting B cell mediated disease
Epid:
High predominance in Asian and African decent
Dx Criteria:
1. Optic neuritis
2. Acute myelitis
AND at least 2 supportive criteria:
1. Continguous spinal cord lesion on MRI that extends over three vertebral segments
2. Brain MRI does not satisfy Dx criteria for MS
3. NMO-IgG is seropositive
AQP4 antibodies 70% sensitive and more than 90% specific for NMO
- predicts risk of future relapses
- 30% ARRR
- Eculuzimab (Phase III)
Complications:
More severe disease than MS
50% are blind in at least one eye or required ambulatory assistance within 5 years of disease onset
Longitudinally extensive centrally located necrotic spinal cord
Multiple Sclerosis: Epid Pathophys 4 Types Diagnostic criteria MRI criteria LP findings
AI inflammatory demyelination and axonal degeneration
Epid:
HLA-DR2 (HLA-DRb1*15) in northern europeans
Develops in genetically susceptible individuals as a result of environmental exposure (EBV, smoking, latitude)
F>M
Pathophys:
Plaques (focal demyelination) through time and space, T cell mediated damage to oligodendrocytes
B cell involvement
Early axonal loss
Types:
Relapse remitting (RRMS) most common
- 90% F:M 2:1
Secondary progressive (SPMS)
- 50-75% within 15 years
Primary progressive MS (PPMS)
- 10% overall
- 20% of males
- no relapse
Progressive relapsing MS
-
Multiple sclerosis Tx:
Acute
Non acute
Acute attack:
IV methylpred 500 mg -1 g for 3/7 OR
Oral 1 g methylpred for 3/7 (was not inferior to IV, Lancet, 2015)
Non acute Tx only effective in RR MS:
Start with most efficacious drug and monitor closely for AE.
1st line Tx: Interferon Beta (Modulates T cell and B cell function) - Injectable
Other Tx:
Glatiramer Acetate - Modulates T cell and B cell function
Teriflunomide - synthetic polypeptides resembling MHC class II molecules, stimulates reg T cells that resemble myelin reactive T cells.
Dimethyl Fumurate/BG12 - Hydrolysed to its metabolite monomethyl fumarate (MMF)
Laquinimod - unknown
Fingolimod - Sphingosine-1-phosphate receptor modulator
Natalizumab - Targets a4B1-intergrin
Multiple sclerosis drugs: MOA, AE Interferon Beta (SC) Glatiramer Acetate (SC) Teriflunomide (PO) Dimethyl Fumurate/BG12 (PO) Laquinimod (PO) Fingolimod (PO) Natalizumab (Infusion) Alemtuzumab (infusion)
Interferon Beta (1st line)- injectable MOA: - Modulates T cell and B cell function - decreases expression of matrix metalloproteinases - reverses BBB disruption - alters expression of a number of cytokines Efficacy - annually reduces relapses, 30% SE: Flu like symptoms, may worsen neurology Injection site reaction Subset will develop Ab Depression, leukopenia, LFTs and thyroid disorders Subset will develop ANTIBODIES
Glatiramer Acetate - injectable
MOA:
synthetic polypeptides resembling MHC class II molecules
functions as an altered peptide ligand MHC class II molecules and stimulates reg T cells that resemble myelin reactive T cells.
Efficacy:
annually reduces relapses, 30%. Same as interferon beta
AE:
Injection site reaction, post injection systemic reactions
No constitutional symptoms like IFN-B
Teriflunomide - Oral MOA: derived leflunomide Antimetabolite that interferes with the de novo synthesis of pyrimidines. Inhibits mitochondrial enzyme dihydro-orotate dehydrogenase. Unknown mechanism in MS Efficacy: Reduction in annual relapse 31%, disability progression 31% and MRI lesions 80% AE: Hair thinning, GIT, TERATOGENIC
Dimethyl Fumurate/BG12- Oral
MOA:
Hydrolysed to its metabolite monomethyl fumarate (MMF).
Unknown mechanism
Efficacy:
Reduction in annual relapse 53%, disability progression 38% and MRI lesions 90%
AE:
Flushing and diarhhoea common
N/abdo pain
Cases of PML in pts treated for psoriasis
Laquinimod- Oral MOA: unknown Crosses CNS, reduces leukocyte trafficking into the CNS or the modulation of inflammatory cytokine production Efficacy: Reduction in annual relapse 23%, disability progression 36% and MRI lesions 37% AE: Mild LFT derrangement
Fingolimod - Oral
MOA:
Sphingosine-1-phosphate receptor modulator
Inhibits the migration of T cells from lymphoid tissue into the peripheral circulation and CNS
Efficacy:
Reduction in annual relapse 54%, disability progression 30% and MRI lesions 82%
AE:
First-dose bradycardia
Herpes virus dissemination
Macular oedema
HTN
Natalizumab - Infusion MOA: Targets a4B1-intergrin Inhibits the leucocyte migration across the BBB by blocking the interaction between a4-integrin on leucocytes and vascular cell adhesion molecule 1 on endothelial cells Efficacy: Reduction in annual relapse 68%, disability progression 42% and MRI lesions 92% AE: Anxiety Pahrygitis periperhal odema Infusion related symtpoms 6% develop persistent anti-natalizumab neutralising antibodies PML
Alemtuzumab - yearly infusion
MOA:
Targets CD52 expressed in lymphocytes and monocytes and causes rapid and profound lymphopenia
Efficacy:
Reduced risk of relapse ad sustained accumulation of disability by 50% compared to IFN-B.
AE:
Infusion reactions
Induce other AI diseases- ITP, Grave’s, Anti-GBM, increased infection (URTI, Herpes)
PML.
Presentation
Aubacute worsening of visual, motor or cognitive changes and/or gradually enlarging T2 hyperintensities with minimal or no gad enhancement.
90% will have worsening disability and 25% mortality.
IRIS post PML.
What?
When does it occur?
Paradoxical deterioration in clinical status attributed to recovery of the immune system viral for controlling JCV.
New contrast enhancement in PML lesions consistent with inflammatory breakdown of BBB.
Occurs 2-5 weeks after plasma exchange and can persist for months.
MS and pregnancy. Risk of relapse?
Relapses are reduced in pregnancy.
Increased risk post partum
- starting Tx post delivery does not protect against relapses in post partum period
Women who are pregnant have a better long term outcome than those who have not been pregnant.
Pregnancy associated with increased risk of conversion of radiologically isolated syndrome to 1st event.
Tx of Multiple sclerosis in pregnancy?
Monthly IVMP for 6 months reduces relapses.
COntinuing Tx during preg if high risk of severe relapses.
Drugs that can be used are:
Interferon B
Glatiramer - safe with breast feeding too
Natalizumab - crosses placenta and can have an immune effect
Alemtuzumab - crosses placenta
MS Drugs to avoid during pregnancy?
Fingolimod - teratogenic
Teriflunomide - teratogenic and present in semen
Dimethyl fumerate - teratogenic
Best tolerated AED in pregnancy?
Lamotrigine
Which AED causes defects in pregnancy?
Phenytoin - cleft palate Topiramate - cleft palate Carbemazepine - posterior cleft palate Valproate - neural tube defects, facila clefts, hypospadias, cog decline Phenobarb - cardiac malformations
Which AED causes cognitive decline in children?
Valproate - dose dependent associated with low IQ socres
Phenytoin
Phenobarb
Mycophenalate safe in pregnancy?
No, teratogenic
Large vessel athersclerosis and CEA. Pts > 70 years have better outcomes?
True
Which antiviral cause a painful sensory axonal neuropathy?
Zalcitabine
Didanosine
Stavudine
What is the first sign of advanced disease in PD?
Visual hallucinations
Huntington’s disease.
Inheritance
Pathophys
Presentation
AD
Due to expansion of CAG repeats, Hungtinton > 35, definite phentoype > 40 repeats
Ch4p16.3 in the huntington gene
Presentation Psychiatric: Depression irritability psychosis social withdrawal OCD
Motor: Initial distal involuntary movements Chorea, face and axial bradykinesia and rigidity Dystonia can be the first sign
Cognitive:
Can predate motor and vary in severity
Executive function
Sudden unexpected death in epilepsy (SUDEP).
Cause?
Who does it affect?
Usually young with convulsive seizures
poor adherence to medications or poor seizure control
tends to occur at night
cause unknown - may result from brainstem mediated effects of seizures on pul, cardiac and arousal functions.
Risk of seizure after:
1st
2nd
1st = 46% 2nd = 70%
Tx for following seizure types: Focal Generalised Idiopathic generalised Absence Don't know
Focal = carbamazepine Generalised = valproate Idiopathic generalised = valproate Absence = ethos ot valproate Don't know = valproate
Parkinsons disease:
Pathophys
Criteria
Pathophys:
a-synuclein is a neuronal protien, likely toxic leading to cell disruption. Found within Lewy bodies.
(this is opposed to Tau protein found in other Parkinsonian disorders)
Dx criteria:
Inclusion criteria:
Bradykinesia AND at least one of the following:
Muscular rigidity
4-6 Hz rest tremor
Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction
Supportive criteria: 3 or more required for diagnosis of definite PD - unilateral onset - rest tremor present - progressive disorder - persistent asymmetry affecting side of onset most - excellent response to levodopa -severe levodopa induced chorea -levodopa response for more than 5 years -clinical course of 10 years or more
EEG rhythms
Alpha 9-12 Hz = normal Beta 13-15 Hz = too much benzos Theta 5-8 Hz = drowsy or encephalopathic Delta 1-4 Hz = sleep or encephalopathic Spike and wave = epileptogenic
Aneurysmal bleeding. Ix to confirm after CT negative?
CSF spec for bilirubin
Diabetic neuropathic arthropathy most likely affects which area?
Mid foot
Clinical finding suggestive of spinal canal stenosis?
Lower extremity numbness with prolonged weight bearing
Motor neuron disease: Variants Mean age Mutation Pathophy Presentation Tx
variants are:
- ALS - mixed UMN and LMN
- 40% have fronto-temporal dementia - Spinal muscle atrophy - predominant LMN
- Primary lateral sclerosis - UMN predominant, better prognosis
- Progressive bulbar palsy
Mean age:
55y
Mutation:
SOD1 in familial ALS
Pathophys:
Anterior horn cell degeneration
Loss of motor brainstem nuclei
Diffuse loss of corticol neurons
Presentation: UMN LMN Slit hand syndrome- thinner and first dorsal interosseous wasting SENSATION SPARED
Tx:
Riluzole - inhibits glutamate release from pre-synaptic terminals, stabilises the inactive state of voltage depends Na channels, inhibits high affinity uptake of GABA.
Neurotransmitters.
Inhibitory
Excitatory
Inhibitory = GABA. 3 receptors A, B and C Excitatory = Glutamate, 2 major eceptors, GPCR and ionotropic (ligand gated on channels e.g. NMDA, AMPA)
What are the 2 cholinergic recptors?
Where is ACh found?
Muscurinic (GPCR) and nicotinic
ACh found at the neuromuscular junction in autonomic ganglia and postganglioninc parasympathetic nerve target junctions.
Also found in the basal forebrain complex and postmesenchepalic cholinergic complex.
What are the NA receptors?
Where is NA found?
alpha - NE greater affinity
beta - E greater affinity
NE neurons found in the locus coeruleus and other medullary pontine nuclei
Where is 5HT found? Receptors?
Brainstem in the midline raphe nucle which project to portions of the hypothalamus, limbic system, neocorte and cerebellum.
7 receptors, most are GPCR (muscarinic)
