Neurology Flashcards
What does a sensory level suggest?
Location of injury is in spinal cord
What cell counts are significant on LP?
Lymphocyte >5
Polymorph >0
Will lesions in cranial nuclei in brainstem and anterior horn cell nuclei have UMN or LMN signs?
LMN, despite being within central nervous system
Pyramidal weakness
Weakness of
Upper limb extensors
Lower limb flexors
Frontal Lobe Signs
Primary motor cortex
Personality change
Primitive reflex (pout, moro, palmomental, glabellar tap)
Expressive dysphagia (dominant)
Anosmia
Optic nerve compression
Gait apraxia
Parietal Lobe
Primary sensory cortex
Gerstmann syndrome:
- Dominant, angular gyrus
- Acalculia, agraphia, L-R disorientation, finger agnosia (ALF)
Sensory, visual and spatial inattention (non dominant lesions)
Construction and dressing apraxia
Lower quadrantanopia
Temporal Lobe
Primary auditory cortex
Receptive aphasia (dominant)
Memory loss
Upper quadrantanopia
Foster Kennedy Syndrome
Tumour in frontal lobe
Altered vision in one eye
Papilloedema in opposite eye
Smell disturbance
Other frontal signs
Occipital Lobe
Homonymous Hemianopia
Anton’s Syndrome: cortical blindness with confabulation (bilateral lesions of occipital lobe)
Alexia without agraphia
What does the presence of quadrantanopia signify?
Cortical lesion
How to work out where the lesion is in quadrantanopia?
Flip everything
Up is down
Left is right
Broca Aphasia
Expressive, non fluent aphasia
Can comprehend, know what to say, but just can’t
Dominant frontal lobe
Wernicke’s Aphasia
Fluent, receptive aphasia
Not frustrated, can speak but incomprehensible
Dominant temporal lobe
Conduction Aphasia
Mix of Broca’s and Wernicke’s
Due to damage to the connection arcuate fasciculus)
Struggle with repetition, can comprehend some things,
Global Aphasia
Can’t comprehend, can’t express themselves
Left MCA stroke is classical cause
Transcortical aphasias
Can repeat things
So Transcortical motor: Broca’s but can repeat
Transcortical sensory: Wernicke’s but can repeat
Corticospinal Tract
Descending motor pathway
From primary motor cortex in frontal lobe → corona radiata → posterior limb and genu of internal capsule → pyramids → decussate in lower medulla
Blood supply from penetrating branches of MCA (M1)
Prone to damage from small vessel disease, hypertension.
Dense pure motor hemiparesis. No cortical signs. No aphasia, dysphasia, hemianopia/quadrantopia.
Thalamus
Largest nuclear mass of nervous system,
All sensory nerves come through here
PCA arterial supply
Pure sensory loss if stroke here
Pure Sensory Loss Stroke
PCA lesion affecting Thalamus
Pure dense motor stroke
M1 MCA affecting internal capsule if no additional cortical signs such as inattention, aphasia, etc.
Parts of Thalamus
Anterior: language, memory
Lateral: motor + sensory
Medial: arousal, memory
Posterior: visual
Think about where they’re pointing to. Can mimic other lesions
Spinothalamic Tract
Run contralateral in spinal cord
Decussate at level
Pain, temperature, crude touch
Peripheral nerve body is in dorsal root ganglion, synapse in dorsal horn
Another synapse in thalamus then to primary sensory cortex
Run generally lateral
Dorsal column
Run Ipsilateral in spinal cord
Proprioception, vibration, fine touch
Peripheral nerve penetrates into central nervous system up to lower medulla, running medially. Body still in dorsal root ganglion.
Decussates in lower medulla and synapses to 2nd order nerve here
Then again synapses in Thalamus
Rules of the Brainstem
Rule of 4s
- 4 Cranial nerves in the medulla, 4 in the pons and 4 above the pons
- 4 structures midline beginning with M
- 4 structures to side beginning with S
- The 4 motor nuclei are in the middle are those divide equally into 12 (except 1 and 2): 3, 4, 6, 12
Medial Brainstem Structures
Motor pathway, medial lemniscus, motor nucleus, medial longitudinal fasciculus
Lateral (Side) Brainstem Structures
Spinocerebellar pathways, spinothalamic pathways, Sensory nucleus of 5th CN, Sympathetic tract
Medial Longitudinal Fasciculus
Links CN III and VI to coordinate eye movements
Cranial Nerve I - Olfactory
Smell
CN II - Optic
Vision, afferent pathway for pupil
CN III - Oculomotor
Superior, inferior, medial rectus, inferior oblique, Levator palpebrae
Efferent pathway for pupil
CN IV - Trochlear
Superior oblique (depression (most in adduction) and intorsion)
CN V - Trigeminal
Facial sensation, muscles of mastication
CN VI - Abducens
Lateral rectus
CN VII - Facial
Muscles of expression, Stapedius, sensation to anterior 2/3 tongue
CN VIII - Vestibulocochlear
Hearing and balance
CN IX - Glossopharyngeal
Sensation: middle ear, posterior 1/3 tongue, some swallowing
?Carotid baroreceptor
CN X - Vagus
Sensation of pharynx, larynx, oesophagus, Thoracic and abdominal viscera
Motor: soft palate, larynx, pharynx
CN XI - Accessory
Sternocleidomastoid, Trapezius
CN XII - Hypoglossal
Tongue movement
Medial Lesion of brainstem
Abnormal eye movements, tongue movements, motor weakness in limbs, fine touch.proprioception/vibration loss
Lateral Lesion
Loss of pain/temperature sensation
Loss of facial sensation and movement, loss of hearing/balance
Eye movement for CN IV palsy
Look down and out, eye opposite direction looking is being tested.
Eye movement for CN VI palsy
Lateral gaze
Eye towards direction trying to look is being tested.
Lateral Medullary Syndrome
Ipsilateral facial numbness
Contralateral limb numbness
Ipsilateral Horner Syndrome
Ipsilateral dysmetria
Difficulty swallowing
Hiccups
Can have disinterest and vagueness if PICA artery stroke is causing it, get some cerebellar involvement
Staccato stroke syndrome
Tip of basilar lesion:
Medulla
Pons
Cortical
Brown Sequard
Ipsilateral LMN weakness and complete sensory loss at level of lesion
Ipsilateral UMN lesion below level
Ipsilateral loss of vibration and proprioception below lesion
Contralateral pain and temperature sensation 1-2 levels below
No bladder dysfunction
Central Cord Syndrome
Dysfunction of spinothalamic tracts on both sides at the level - “Cape sensory change”
As it enlarges, affects anterior horn cells → segmental LMN weakness at the level
Then UMN weakness below level
Typically seen after trauma, syrinx
Anterior Cord Syndrome
Loss of everything below level except proprioception and vibration (i.e. dorsal columns preserved)
Mostly due to ischaemia due to anterior spinal artery occlusion
Posterior Cord Syndrome
Loss of dorsal column only
Hyperacute treatment of ischaemic stroke without large vessel occlusion
0-4.5hr: CTB → Alteplase/Tenecteplase
4.5-9hr: CTP/MRI perfusion → Alteplase
Wake up: MRI/DWI and if markers to suggest <4.5hr (Ischaemia on DWI, normal FLAIR) → Alteplase
Risk Factors for haemorrhage post Thrombolysis
Happens regardless of tPA, but certain factors increase risk:
- Large infarcts
- Established infarct
- Grey matter infarcts
- Higher NIHHS
- Poor collaterals
- Hyperglycaemia
- Thrtombocytopaenia
Absolute contraindications to Thrombolysis
Extensive hypoattenuation on CT
Suspicion of SAH
Current or previous ICH
Intracranial neoplasms
Severe head trauma last 3 months
Intracranial or intraspinal surgery
Platelets <100
INR >1.7
APTT >40
Clexane last 24hr
Suspicion for current endocarditis
Active GI or internal bleed
Aortic arch dissection
Patients on which form of anticoagulation can be thrombolysed?
Dabigatran. Can be reversed fast enough to then thrombolyse.
Warfarin too slow to reverse
Apixaban’s reversal agent causes incomplete reversal
Choice of tPA
Tenecteplase superior to Alteplase on meta-analysis - standard of care for prior to 4.5hr
New study for Reteplase: superior to alteplase prior to 4.5hr
Indications for Clot Retrieval
Salvageable tissue and large vessel occlusion (ICA, M1, M2, ACA, PCA, Basilar)
Benefit even with large core
tPA eligible or ineligible (if eligible still give tPA)
Good premorbid function
No specific age cutoff
Management of large vessel occlusion stroke
If no access to clot retrieval, essentially as for stroke without large vessel occlusion.
0-4.5hr: CTA + CTP → Thrombectomy + Tenecteplase/Alteplase
4.5-9hr: Thrombectomy (or if not in centre with thrombectomy can give tPA if meets perfusion mismatch criteria, then transfer to centre with access to thrombectomy)
4.5-20hr: CTA + CTP → Thrombectomy
Predictors of good outcomes for clot retrieval
Younger
NIHHS Score
SBP
History of ischaemic stroke
Premorbid function
Location of thrombosis
Collaterals
Size of infarct (smaller better)
Time to treatment
Blood pressure targets in stroke
Too low = bad
Post tPA: keep below 185/110
No tPA: keep below 220/120
Intensive control <140 → worse outcomes
IV Labetalol 10mg often used
Hemicraniectomy in Ischaemic Stroke
When there is significant swelling.
For patients <60, with >50% MCA strokes, leads to 39% fewer deaths. But increases disability. (i.e. if you do survive you’re more impaired)
Works for older patients. but none >70 get back to mRS 0-2. In this group however it increases survival with no change in disability.
Who should be considered for an internal loop recorder post stroke?
Older patients
Higher CHADS-VASc
MRI characteristics
Left atrial cardiomyopathy
Benefit of DOACs over Warfarin in AF and Stroke
Dabigatran 150mg BD and Apixaban 5mg BD both superior to Warfarin
Rivaroxaban non inferior to warfarin
ICH risk lower for all
GI bleed more common in Riva and Dabi
Apixaban has mortality benefit
Embolic stroke of unknown cause - don’t anticoagulate: no benefit and increases bleeding
PFO
25% of population have it
PFO present in 50% of cryptogenic strokes
Most likely to be the cause if the patient is younger and has few other risk factors
Increases risk of perioperative stroke
Closure indicated in:
- <60 year olds
- With no other cause found and have atrial septal aneurysm or moderate to large right to left shunt
These patient should have closure + antiplatelets
When should Carotid Endarterectomy be done?
Patients with non disabling carotid artery territory stroke or TIA with ipsilateral carotid stenosis 70-99%
Consider if 50-69% and symptomatic (i.e. had a stroke in right territory)
Perform within 14 days, or within 3 months at the absolute most. Can be done as early as 48hr.
All then get usual secondary prevention
Asymptomatic stenosis only intervened upon if very high risk.
When to stent carotids post stroke
Selected patients with unfavourable anatomy, symptomatic restenosis, previous radiotherapy
Only in patients <70.
Don’t stent intracranial stenosis. No benefit over DAPT and risk factor management.
Most common vessels for dissection leading to stroke?
Carotid, Vertebral arteries
Post acute treatment for carotid/vertebral artery dissection leading to stroke
Aspirin
Most important risk factor to manage for stroke risk and when to do it
Hypertension (for both types)
Wait 48-72hr, then start. Risk benefit in reduction even if don’t have hypertension
Others:
Dyslipidaemia
Diabetes
Smoking
Alcohol
Antiplatelet use post stroke
Aspirin or Clopidogrel
DAPT if TIA or small stroke for 3 weeks then monotherapy
Long term DAPT increases bleeding risk without benefit
Ticagrelor better than Clopidogrel in patients who are CYP2C19 carriers (Reduces Clopidogrel metabolism, increases bleeding)
TIA Management
Workup like a stroke
DAPT for 21 days then monotherapy ongoing
If AF present, just start anticoagulation
Amaurosis Fugax
Form of TIA leading to transient monocular vision loss.
Descending curtain of visual loss
Never forget giant cell arteritis
Location of ICH and cause
Deep: Hypertension, other vascular risk factors
Lobar/peripheral: Cerebral Amyloid Angiopathy
Management of ICH
Intubate if dropping GCS
Aim for BP around 140 but not much lower
Manage hyperglycaemia
Reverse any anticoagulation (benefit limited for DOACs)
Don’t give platelets to reverse antiplatelet therapy
Can resume anticoagulation 4-8 weeks post, maybe longer if critical area/large
When to decompress ICH surgically
Cerebellar haemorrhage >3cm, deteriorating, brainstem compression, hydrocephalus
For supratentorial haemorrhage, only life threatening conditions where haemorrhage is 2cm from surface
If there is blood in ventricles and get blocked causing hydrocephalus, EVD is indicated
Management of CAA
Avoid anticoagulation, antiplatelet and thrombolysis
Hypertension control leads to 77% risk reduction
Risk Factors for Central Venous Sinus Thrombosis
Obesity
Thrombophilia (including OCP)
Local infection
Chronic inflammatory disease
Malignancy
Central Venous Sinus Thrombosis
Venous back pressure is the problem essentiall,y then CSF can’t be absorbed, there is ischaemia due to lack of venous outflow too.
Often present as intracranial hypertension.
Seizure with stroke, think CVST.
Management
Anticoagulation even if there is haemorrhage to prevent clot propagation. Clexane generally best, but Heparin sometimes used as more easily reversed/stopped.
DOACs long term. 3-6 months if severe, 6-12 if unprovoked.
Indefinite if severe thrombophilia or systemic thrombosis
Mechanical thrombectomy/direct fibrinolysis an option but no good evidence.
Hemicraniectomy if large
Other measures to bring down pressure - hypercapnia, etc.
Generally do reasonably well.
Internal Capsule Stroke
Classical Lacunar Syndrome
Typically pure motor
Due to M1 - Lenticulostriate artery occlusion
Can also get ataxic hemiparesis
Thalamic Stroke
Pure sensory lacunar syndrome
Basis Pontis Stroke
Dysarthria/clumsy hand
Causes of Transverse Myelitis
Primary Neurological conditions
- MS
- Neuromyelitis Optica (NMOSD)
- Myelin Oligodendrocyte glycoprotein associated disease (MOGAD)
- Acute demyelinating encephalomyelitis (ADEM)
Systemic inflammatory conditions: SLE, Sjogren’s Behcets, Sarcoid (Heerfordt syndrome)
OthersL Syphilis, TB, HIV, HSV, VZV, Paraneoplastic
Non Arteritic Ischaemic Optic Neuropathy
Cause of intrinsic optic neuropathy
Painless vision loss
Loss of blood flow to anterior aspect of the eye
Arteritic Ischaemic Optic Neuropathy
Typically painful vision loss, this is GCA
Leber’s Optic Neuropathy
Mitochondrial disorder which leads to fairly sudden onset vision loss
Optic Neuritis
Subacute onset with pain on eye movement
Visual acuity decreased, particularly colour vision. May be sparkles of light and a central scotoma can be present.
Relative Afferent Pupillary defect is classic finding
Disc swelling may or may not be present
Causes of bilateral Optic Disc Swelling
- Hypertension
- Raised ICP
- Bilateral optic neuritis/neuropathy → NMOSD
Papilloedema specifically means bilateral optic disc swelling secondary to raised intracranial pressure
MS Epidemiology
By far most common neuroimmiunology condition, develops in geneticslly suceptible individuals as result of environmental exposure.
Not hereditary, polygenetic, but there are clusters.
- HLA DR-2 (HLA-DRB1*15) Northern Europeans
- Female > Male
Environmental Factors
- EBV is key → new paper HOT TOPIC
- Smoking
- Latitude
- Sunlight exposure and Vitamin D is protective for MS
- Immigrants who migrate before adolescence acquire risk of the new country
- Obesity
EBV + defect in dendritic cells is likely the key mechanistic driver of MS
Risk factors for developing MS post CIS
- Younger age
- High cerebral lesion load
- Asymptomatic infratentorial or spinal cord lesions
- Gad enhancing lesions
- Oligoclonal bands in CSF
- Abnormal visual evoked potentials
McDonald’s Criteria
- 2 lesions in time and space
- Clinical diagnosis with radiological findings to help fulfil criteria
Time:
- 2 separate attacks, or even a history of an attack
- MRI with contrast enhancing and non enhancing lesions
- Oligoclonal bands (take up to a year to develop)
Space
- 2 different locations in the CNS through objective clinical evidence
- 2 different locations in the CNS through MRI
Acute MS Treatment
3 day Methylprednisolone pulse
No steroid taper required
Only benefit is accelerating recovery from relapse, but no benefit in terms of final outcomes i.e. no changes to disability or disease modification.
Can give oral with same outcomes.
Plasmapheresis for severe attacks
Interferon Beta
Modulate T and B cell function, reverses blood brain barrier disruption.
Reduces MS relapses 30% annually
Side Effects: Flu like symptoms, may worsen neurology. Depression, leukopaenia, liver abnormalities, thyroid disorders
Glatiramer
For MS
Stimulates Treg cells with synthetic mimics of MHC class II, rarely used now.
May be used in cancer patients.
Injection site reactions key
Teriflunomide
For MS
Dervied from leflunomide. Antimetabolite, interfering with de novo pyrimidine synthesis, inhibiting lymphocytes.
Similar efficacy to Interferon annual reuction of relapse around 30%
SEs: hair thinning, teratogenic.
Dimethyl Fumarate
For MS
Unknown mechanism, but lowers lymphocyte count
Reduces annual relapse rate by 53%, also reduces disability and reduces gad enhancing lesions
SEs: Flushing (use aspirin), diarrhoea, nausea.
Can cause PML
Fingolimod
Sphingosine-1-phosphate receptor modulator → inhibits migration of T and B cells from lymphoid tissue into peripheral circulation and CNS
(So low Lymphocytes in blood and some immunosuppression, but lymphocytes still there)
Reduces annual MS relapse rate by 54%, slows disability and gad enhancing lesions
SEs: First dose bradycardia, VZV reactivation, macular oedema, HTN, LFT derangement.
Monitoring for first dose due to bradycardia
Risk of rebound relapse with cessation (as Lymphocytes still present, just being held in lymphoid tissue)
Ozanimod
Another sphingosine-1-phosphate receptor modulate (subtypes 1 + 5) → more specific for lymphocyte migration
48% reduction of MS relapse
Dose escalation reduces bradycardia risk and macular oedema.
Cladribine
Purine antimetabolite targeting lymphocytes → immunomodulatory
Two 5 day courses then repeated a year later
58% MS reduction in relapse
SEs: VZV/HSV elapse, headaches, however increases malignancy risk if used past 2 years
Generally relapse starts to develop around 4 years, some get to 10 years. Need frequent MRIs to monitor.
Natalizumab
alpha4 beta1 integrin inhibitor → prevents leukocyte migration across BBB
Reduced annual MS relapse rate 68%, reduced disability, reduced new lesions
SEs: Anxiety, pharyngitis, peripheral oedema, PML, rebound relapse, anti drug antibodies
Progressive Multifocal Leukoencephalopathy
JC Virus related subacute demyelinating process. Polyomavirus, usually dormant, present in 50-60% of population.
Reactivated in immunosuppression, crosses BBB then destroys oligodendrocytes.
Subacute worsening of symptoms. Not inflammatory.
20% mortality risk. Increased risk with longterm use, previous immunosuppression. Check for JC virus prior to treatment, if positive don’t give. Check 6 monthly on treatment
Treat by stopping causative drug, PLEX,
Pembrolizumab used to allow immune system to respond to the infection. Also BK virus specific T cells can be done. Only do this if there is an additional cause that can’t be removed (e.g. haematological reason for immunosuppression).
Alemtuzumab
CD52 Inhibitor on lymphocytes → immunomodulatory effect
Reduces MS relapse 50% compared to IFN
SEs: ITP, Graves, anti-GBM, Infections
Ocrelizumab
Anti-CD20 → B cell depletion (same as Rituximab)
47% MS relapse reduction compared to IFN
SEs: increased risk of URTI, severe COVID, HBV reactivation, hypogammaglobulinaemia
Works in primary progressive MS but not on PBS
Siponimod
Works for secondary progressive MS
Selective sphingosine 1-phosphate receptor 1 +5 modulator (2nd gen fingolimod) → crosses BBB
Same first dose bradycardia as Fingolimod, VZV, macular oedema, HTN, LFT dernagement
Contraindicated with CYP2C93/3 → must do genotyping
Ofatumumab
CD-20 depleting agent
51-59% reduction in relapse compared to teriflunomide
SEs: URTI, UTI
Autologous SCT in MS
For highly active MS that breaks through high efficacy therapy
Similar efficacy to Ocrelizumab at 3 year mark.
65% have no disease activity at 10 years
Pregnancy and MS
Relapse risk drops during pregnancy
But increased risk postpartum, usually severe and starting treatment post delivery isn’t protective
IFN-beta and Glatarimer safe.
Natalizumab can continue to around 34 weeks then resume post partum.
Best option is CD20 depletion dosed just prior to conception (i.e. Ocrelizumab/Ofatumumab/Ritux)
Don’t use Fingolimod and Teriflunomide.
Neuromyelitis Optica Spectrum Disorders (NMOSD)
B cell mediated disease against AQP4 with complement activation.
Astrocytopathy
Optic neuritis (often bilateral), longitudinally extensive transverse myelitis (>3 levels), Area postrema syndrome (unexplained nausea, hiccups, vomiting). Acute brainstem syndrome.
Test for AQP4 (75-80% sensitive, >99% specific) and MOG (present in 50% of AQP4 -ve cases) antibodies. Few have oligoclonal bands.
IV Methylpred or PLEX for acute attack.
Long term: AZA, MMF, RTX.
Then disease specific MABs: Eculizumab (complement inhibitor), Inebilizumab (anti-CD19), Satralizumab (anti IL-6)
Eculizumab
Terminal complement inhibitor
Remarkably effective for NMOSD
NNT 2.5
Must have meningococcal vaccination prior
Myelin Oligodendrocyte Glycoprotein Associated Disease (MOGAD)
Pathophysiology not fully understood
MOG protein is in CNS
Demyelinating disease
1:1 gender ratio
Commonly post infectious/post vaccine
Test for MOG Ab in serum prior to immunosuppression
Need to have high PPV - lots of false positives with MOG Ab. Positive in lots of other things, not super specific
Optic neuritis (mostly anterior unlike MS and NMOSD), transverse myelitis, ADEM, brainstem lesions, cortical encephalitis
Treatment: IV Methylprednisolone with steroid taper. IVIG is treatment of choice. RTX, MMF other options
ADEM (Acute disseminated encephalomyelitis)
Monophasic disorder of the brain and sometimes cord
Mostly children or young adults
Encephalopathy is key
Usually preceded by viral infection or other systemic infection
Usually resolves after 3 months.
25% develop MS
Subset are MOG positive
Limbic Encephalitis
Hippocampus, Amygdala, Cingulate Gyrus
- Subacute psychiatric manifestations
- Poor short term memory
- Temporal lobe seizures
- MRI changes in unilateral or bilateral lobes
Rhomboencephalitis
Encephalitis of the brainstem
- Decreased conscious state
- Cranial nerve and brainstem signs
Cerebellitis/Cerebellar degeneration
Cerebellar symptoms and signs
Essentially present as a subacute onset of a movement disorder
Key infective causes of Encephalitis
HSV (esp 1)
Enterovirus
Flavivirus
HIV
Bacterial: Listeria, TB, Syphilis
Fungal: Cryptococcus
HSV Encephalitis
Most common cause in Australia
50% of patients > 50
Primarily HSV1, via trigeminal ganglion where reactivation goes to temporal lobe and back to original superficial site of infection
Acute to subacute onset of encephalitis.
Focal seizures very common
HSV PCR can be negative if done in first 48hr and MRI can also be normal early. But temporal lobe involvement classic. Lymphocyte predominant LP.
EEG: focal slowing, epileptiform discharges
IV Aciclovir for 14-21 days
No benefit (or harm) from Dexamethasone
Key infective cause of brainstem encephalitis
Listeria
Can cause microabscesses, moreso in immunocompetent patients.
Most testing is poorly sensitive
Cranial nerve exam going to be more sensitive.
Benpen for management
Japanese Encephalitis Virus
Bilateral Thalamic Encephalitis
Flavivirus
Most cases are asymptomatic but can be severe
Serum is more sensitive than CSF (moves into parenchyma so CSF can be negative)
NGS to test for it
Autoimmune versus Paraneoplastic Encephalitis
(key differentiators)
Paraneoplastic:
- T cell mediated
- Intracellular epitope
- Poorer prognosis
Autoimmune:
- B cell mediated
- Extracellular/Surface epitope
- Generally good prognosis
Paraneoplastic Antibodies
They are not causative, they are bystanders. Lots of overlap so just send the full panel. Panel is the anti-neuronal antibodies.
Hu:
- Limbic encephalitis, peripheral neuropathy
- Small cell lung cancer
Yo:
- Cerebellar degeneration
- Breast/Ovarian cancer
Ri:
- Opsoclonus myoclonus (random jerking of eyes), Rhomboencephalitis
- SCLC
Ma/Ta:
- Rhomboencephalitis
- Testicular cancer
KELCH-11
Cerebellar autoimmune encephalitis in testicular seminoma
NMDA Encephalitis
- 95% young people, and mostly women
- 50% have ovarian teratomas
- Older patients often have carcinoma, cancer less frequent in men and children
- 20% of HSV encephalitis develop NMDA encephalitis
Most common autoimmune encephalitis
B cell mediated, often linked to malignancy with antigen coming from the apoptotic tumour
Limbic encephalitis typically with preceding viral prodrome.
Orofacial dyskinesia, autonomic instability, insomnia, speech disturbance
Then drop GCS
Test on CSF. Serum has bulk false positives. MRI can be normal. Lymphocytes in CSF.
Remove cancer if present
Pulse MP, IVIG, RTX
Cyclo 2nd line
LGI1 Encephalitis
- Previously VGKC Encephalitis
- Cognitive and memory changes
- Faciobrachial dystonic seizures (First feature)
- Seizures
Disease of the elderly
Responds well to treatment, but recovery of cognition and memory often poor. (Hippocampal damage key)
Treatment:
- IVIG, steroids
- Can prevent cognitive change if treat when seizures present
Posterior Reversible Encephalopathy Syndrome
Predominantly due to hypertension exceeding limits of cerebral autoregulation.
Immunosuppression, pre-eclampsia, renal failure, autoimmune disease, infection can all cause it too.
MRI: white matter changes on MRI in posterior circulation
Acute mental state changes, headaches, visual change, seizures (most common symptom, 90%)
Treatment:
- Aggressive blood pressure management, get MAP + diastolic down
- Seizure management
- Treat other reversible causes
Differential for rest tremor
Idiopathic Parkinson’s Disease is key, and is less common in Parkinson’s Plus syndromes.
Others:
- Dystonic Tremor
- Essential Tremor (late)
Differential for postural tremor
- Essential tremor is key
- Dystonic tremor
- Enhanced physiological tremor (worsened by anxiety, drugs, hyperthyroidism - fine tremor)
- Drug induced tremor
- Neuropathies
Essential Tremor
A clinical syndrome. Thought to be pathology of connection between cerebellum, thalamus and cortex.
Bimodal presentation in 20s and 60s, and is a familial form which presents earlier. Pesticides and heavy metals classic triggers.
Bilateral, largely symmetrical postural and kinetic tremor of hands and forearms. May have concomitant head and jaw tremor. Alcohol tends to help but not diagnostic. Smoking also helps.
“yes yes” tremor
Exclude physiological/drug/dystonia
Essential Tremor treatment
Not everyone needs treatment
First line: propranolol, primidone, topiramate
Second line: Benzodiazepine, Gabapentin, zonisamide
Botox for head tremor (NEJM article this year)
Third line: DBS, Focal ultrasound (essentially burn a hole in the thalamus)
Holmes Tremor
Due to lesion just outside the red nucleus, blocking cerebellar outflow pathways.
Big kinetic tremor, coarse, fast.
Occurs in Wilson’s Disease, Stroke, MS.’
Responds to Levodopa
Dystonia
Cramping, twisting, patterned movements.
Due to sustained or intermittent muscle contractions.
“no no” tremor (repetitive contraction pulling head to the side)
Worsened by voluntary action, Worse if fighting the muscle that’s contracting
Chorea
Involuntary movements of limbs/trunk/neck/face, irregular, no repetition, unpredictable
Can look like fidgeting or multifocal myoclonus.
Can’t maintain motor activity
Drug induced chorea, termed dyskinesia, occurs in Idiopathic PD with too many drugs
Myoclonus
Fast, brief movements due to sudden increase or decrease in tone.
Asterixis is a negative myoclonus
Mostly metabolic, e.g. hepatic encephalopathy, CO2 narcosis, Cefepime
Idiopathic Parkinson’s Disease Background
Some genes associated: LRRK2 is key, others CHCHD2
Environmental risk factors: dietary dairy intake, pesticides, air pollution
Environmental protective factors: smoking, coffee
Idiopathic Parkinson’s Disease Pathophysiology
Synucleinopathy: insoluble forms of alpha synuclein accumulate, forming neuronal inclusions called Lewy Bodies.
These are toxic and lead to cell disruption.
Normally the proteins regulate synaptic vesicle transport.
Diagnosis of Parkinson’s Disease
Bradykinesia must be present
Accompanied by rigidity or rest tremor
Absence of absolute exclusion criteria and presence of at least two supportive criteria.
No red flags
Rigidity versus Spasticity
Rigidity: increased resistance to passive movement about a joint that is not velocity dependent
Spasticity: velocity dependent resistance to movement about a joint
What condition is likely if a patient has a movement disorder and can still ride a bike?
Parkinson’s Disease
Which form of Idiopathic Parkinson’s Disease has more falls?
Akinetic-rigid
What type of movement disorder is REM Sleep Behaviour Disorder suggestive of?
How to manage?
Synucleinopathy:
- Idiopathic Parkinson’s Disease
- Multiple Systems Atrophy
- Lewy Body Dementia
Treatment: SSRI makes it worse, so get rid of this.
Levodopa can make symptoms worse, particularly evening dose.
Melatonin and Clonazepam can help, Best evidence is for Melatonin
Benefits of Levodopa
Motor function
ADLs
Quality of life
Compared to other medications for Parkinson’s. By far best drug for Idiopathic Parkinson’s Disease.
Works for many years, but short acting so lots of doses needed.
Not disease modifying
Generally “honeymoon period” for a couple of years, in which management works easily. Then gets harder due to motor fluctuations.
Risk Factors for Motor Fluctuations in Parkinson’s Disease
Risk is higher with longer disease duration and higher levels of Levodopa used. Younger onset associated with higher risk.
Duration of Levodopa therapy is not associated.
Management: Divide dose to increase frequency, add COMT or MAO
Dyskinesia in Parkinson’s Disease
Chorea-type movement associated with too much Levodopa, linked to disease duration as well.
Treatment:
- Minimise dopaminergic medication dose/split into more frequent smaller doses
- Extended release Amantadine
Dopamine Agonists
Pramipexole (oral), Rotigotine (patch), Apomorphine (infusion)
Effective, but not as good as Levodopa. However long acting.
Good as a night time medication to help overnight and reduce early morning off.
SEs: Nausea, somnolenfe, dizziness, hallucinations, worsens delirium, impulse control disorders.
Due to delirium issues, best used in younger patients.
Must ask about impulse control problems before prescribing
Monoamine Oxidase B Inhibitors
Rasagiline, Selagiline
Essentially blocks breakdown of Dopamine to increase concentration
Probably slightly better than Dopamine Agonists.
Used for mild/early symptoms or young patients.
Cause insomnia and higher overall mortality.
Tyramine hypertensive crisis is serious complication to know: MOAI inhibits noradrenaline breakdown → adrenergic crisis
Management of Delirium in a Parkinson’s patient
Stop in this order (essentially order of potency)
- Anticholinergic medications
- Amantadine
- Dopamine agonists
- Monoamine oxidase inhibitors
- Levodopa
Management of Hallucinations in Parkinson’s Disease
Remove perpetuating agents
Quetiapine
Pimavanserin
Clozapine - best drug
Dementia with Lewy Bodies
Fluctuating cognition
Recurrent visual hallucinations, typically well formed and detailed (small animals, etc.)
Spontaneous features of parkinsonism, which respond poorly to L-Dopa
The delineation in terms of timing of movement and cognitive symptoms is less important rather than the phenotype above.
Very sensitive to neuroleptics.
Treat with anti-cholinesterases.
Mimics of Akinetic-Rigid Parkinson’s Phenotype
Neuroleptics
Vascular parkinsonism (see lower limb UMN signs)
Brain tumours
Carbon Disulphide
Mangansim
Huntingtons
Mimics of Tremor Phenotype
Dystonic tremor
Essential Tremor
FXTAS
Valproate toxicity
Functional
Progressive Supranuclear Palsy
Syndrome of supranuclear palsy, postural instability, dementia
Tauopathy
Slowed vertical saccades (specifically downgaze palsy), decreased blinking, staring gaze.
Wide based gait and axial rigidity, with early falls due to postural instability.
Personality changes and cognitive changes within first 2 years. FTD phenotype.
Pseudobulbar palsy - dysarthria, dysphasia
Minimal tremor, bradykinesia
MRI: hummingbird sign, mickey mouse sign.
20% responsive to L-dopa
most die within 5-8 years.
Multisystem Atrophy
Alpha synucleinopathy
Onset usually in 60s
Mean survival 6-10 years
Autonomic failue, Parkinsonism, Cerebellar signs
Erectile dysfunction, urinary dysfunction, REM sleep disturbance, dystonia, antecollis, pyramidal signs, dysphonia, parkinsonism
Corticobasal Syndrome
Wide phenotype, varying presentation. Syndrome can be casued by PSP, AD, FTD, etc.
But also Corticobasal Degeneration which is a specific Tauopathy involving basal ganglia degeneration.
Asymmetric progressive ideomotor apraxia affecting hand. Loss of two point discrimination, agraphia, rigidity, myoclonus.
Alien hand syndrome
Management of Restless Legs
- Correct any iron deficiency
- Levodopa
- Dopamine agonists (Pramipexole)
However augementation occurs with Levodopa and Dopamine agonists
Gabapentin/Pregabalin
Fragile X Associated Tremor Ataxia Syndrome (FXTAS)
Due to premutation of fragile X mental retardation 1 gene. Essentially 55-199 CGG repeats, (not enough to cause fragile X syndrome of intellectual disability, seizures, autism). Once pass 200 no protein, but below this the long protein is toxic.
F > M
Action tremor, cerebellar gait
Parkinsonism, moderate to severe STML, executive function deficit, neuropathy.
MRI: lesion in peduncles, corpus callosum.
Also linked to primary ovarian failure.
Huntington’s Disease
30-50 year olds
AD inherited expansion of CAG repeats on Huntingtin gene. Normal 6-26, Huntington >35, definite >40
Age of onset inversely linked to size of repeat → anticipation occurs with each generation
Long protein leads to degeneration of neurons.
Psychiatric: depression, irritability, psychosis, social withdrawal, OCD
Motor: INitial distal involuntary movements, chorea (face and axial), bradykinesia, dystonia
Cognitive: can predate motor, often executive dysfunction
Westphal Variant
Juvenile Huntington’s
High repeat count
Generally inherited from father
Can get seizures, progresses quickly
Spinocerebellar Ataxia
CAG repeat disorder
Many different SCAs, different inheritance
Predominantly Ataxia and upper motor neuron signs
Serotonin Syndrome
Mental status change: agitation, hypervigilance, delirium
Neuromuscular hyperactivity: hyperreflexia, rigidity, clonus (mostly lower limbs)
Autonomic hyperactivity: hypertension, tachycardia, diaphoresis, temp >40
Think of it as mostly UMN (pyramidal)
SSRI, SNRI, MOI, TCAs
Neuroleptic Malignant Syndrome
Due to antipsychotics (multiple drugs, rapid escalation, long acting), also cessation of them or PD drugs
Triad of:
- Autonomic dysfunction
- Altered conscious state
- Extrapyramidal symptoms
Highest specificity: hyperthermia, rigidity, elevated CK
Also a leukocytosis
What is the classic mutation in familial Motor Neuron Disease?
SOD1 - gain of function mutation
Also C9orf72 - phenotype of PSP/FTD symptoms
Pathophysiology of Motor Neuron Disease
Dying forward and dying backwards hypotheses
But essentially oxidative stress involving anterior horn leading to death of corticospinal tract and motor neurons
Most common Phenotype on MND
Limb onset with combination of upper and lower motor neuron signs in the limbs
Second most:
Bulbar onset, presenting with speech and swallowing difficulties, limb featues later
Primary lateral sclerosis with pure UMN
Also a pure LMN
MND Clinical
Mix of UMN and LMN
Asymmetric weakness, working proximally
Generally limb by limb
Split hand
Fasciculations (rare without weakness)
Pseudobulbar (UMN)
Respiratory muscle involvement
Prognosis
- 50% dead within 30 months
- 20% survive 5-10 years
- Poor prognosis: older age at onset, early resp muscle input, bulbar onset
Dementia in MND
- Tauopathy
- TDP-43-positive ubiquinated cytoplasmic inclusions
- Overlap with FTD - loss of executive function and verbal fluency
Investigations in MNDq
Decreased CMAP
Normal SNAP
EMG: fasciculations, fibrillations, positive sharp waves, chronic neurogenic changes
MRI: Corticospinal tract hyperintensity, rule out myelopathy
Riluzole
Indicated for MND
Inhibits Glutamate release
Disease modifying
Prolongs survival 3-6 months
Benefits of PEG in MND
Survival benefit, as not aspirating or dying from malnutrition
Regulation of horizontal and vertical linear movement
Utricle and Saccule
Regulation of rotational movement
Semicircular canal and ampulla
Peripheral Nystagmus
Loss of input from one vestibular apparatus makes brain think head is turning towards normal side, so eyes drift towards abnormal side then saccade back to centre
Tends to be unilateral
Central Nystagmus
Loss of input to maintain a fixed gaze, eyes drift back to centre, then rapidly saccade back to point of fixation
So often direction changing
Acute Vestibular Syndrome
- Acute, continuous dizziness lasting days
- Nausea, vomiting, nystagmus, head motion intolerance, gait unsteadiness
- Always symptoms
- Must have spontaneous nystagmus
Causes of Acute Vestibular Syndrome
Peripheral:
- Vestibular neuritis/labyrinthitis
Central
- Stroke: brainstem or cerebellar
- MS
- Rare: autoimmune, infection, metabolic, thiamine deficiency
Role of HINTS Plus exam
To discriminate between peripheral and central causes in acute vestibular syndrome only.
Not for episodic vestibular syndrome
Vestibular Neuritis
Presumed post infectious or viral (Ramsay Hunt Syndrome classic)
Clinical diagnosis, MRI normal
Resolves over weeks
Labyrinthitis if hearing involved → need to consider alternate aetiology (i.e. stroke)
Stroke and Acute Vestibular Syndrome
25% of all AVS, 96% are Ischaemic Strokes
No role for CT
Exam better than MRI DWI in first 48hr
So may need to repeat in a few days
HINTS Plus Exam
- Head Impulse Test
- Nystagmus
- Test for Skew deviation
- Neurological exam including hearing and gait
Nystagmus and Vestibular Neuritis
Dominantly fixed direction horizontal nystagmus (with torsional component).
Follows Alexander’s Law (worse towards fast phase)
Fixation tends to dampen it, so may need to attempt to remove it:
Cover one eye, shine torch in other eye → can show nystagmus. Can do the same with fundal exam
Stroke and Nystagmus
Dominantly vertical, torsional
Horizontal nystagmus that is direction changing (gaze evoked)
However half of all posterior fossa strokes have direction fixed horizontal nystagmus
Skew Deviation
Vertical double vision due to disruption of tracts in brainstem
Due to lesions in brainstem or cerebellum
Cover uncover test → correction present (i.e. eyes bounce up an down) → suggestive of central cause
HINTS Exam in Stroke
Vertical Nystagmus
Positive Test of Skew
No catch up Saccade on HIT
Anything focal on neurological exam
Head Impulse Test
Assessing Vestibulo-Ocular Reflex
Slow movement of head, then flick head back to centre
Catch up saccade: vestibular (eyes stay fixed with head, then catch up)
AICA stroke can lead to positive HIT as the Labyrinth knocked out → will have hearing loss
HINTS Exam in Peripheral AVS
All criteria must be met
Nystagmus: horizontal dominant, direction fixed, respects Alexander’s Law
No skew deviation
Positive head impulse test with catchup saccade
No other signs on neuro exam
Treatment of Vestibular Neuritis
1 week oral Prednisolone 60mg
Symptomatic
Any concern for VZV give antivirals
10-15% develop BPPV
Persistent postural perceptual dizziness may develop - functional
Spontaneous Episodic Vestibular Syndrome
No triggers, spontaneous. Tricky on first occasion, often worked up as AVS as don’t know it’s episodic.
Symptoms cannot be triggered by manoeuvres or exam
Causes: Vestibular Migraine, recurrent posterior circulation TIA (super uncommon), Meniere’s Disease
Consider medical causes: Vasovagal, arrhythmias, panic attacks, unstable angina, hypoglycaemia
Vestibular Migraine
Second most common cause episodic vestibular syndromes
Migraines can cause vestibular symptoms, and primary vestibular disease can cause migraines
Can develop nystagmus, and mixed picture
At least 5 episodes, 5min to 72hr. Hx of migraines, and migraine featues with at least 50% of vestibular episodes.
Treat like migraines. Can develop PPPD
Meniere’s Disease
Over diagnosed, not that common a cause of vertigo.
Endolymph ionic derangement and accumulation. Can become bilateral.
Spontaneous non triggered vertigo, hearing loss/tinnitus during attack, aural fullness.
Rule out other causes. Initialy episodic but can become fixed.
Direction fixed nystagmus, then swaps direction as resolving. Some HIT positive
Symptomatic treatment, vestibular rehab. Other things don’t help.
Key feature of triggered episodic vertigo
Can trigger the symptoms at bedside
Key differential for BPPV
Orthostatic hypotension
Others:
Central Paroxysmal positional vertigo (lesion causing compression with head movement)
BPPV
Most common cause of vestibular dysfunction. Any age, more common as get older.
Brief episodes, lasts less than a minute.
Most specific symptom: get dizziness when turn head while lying in bed
Dix-Hallpike
Usually delay 1-5s from doing movement and symptoms starting
Last <30s (fatigues as fluid movement settled)
Then nystagmus develops once symptoms have started. Mixed upbeat, torsional
Lack of latency, fatiguability suggestive of CPPV. Also downbeat in CPPV.
Central Paroxysmal Positional Vertigo
Central mimic of BPPV
Posterior fossa masses key issue, also stroke or demyelination in posterior fossa.
Superior Semicircular Canal Dehiscence
Rare, likely developmental. Thinning of temporal bone around semicircular canal.
Develop third window within the semicircular canals which becomes a pressure outlet essentially and sound waves move through the semicircular canals.
Triggered by sound, raised ICP.
Bone conducted sound is transmitted very well, e.g. can hear eyes move, heartbeat, pulsatile tinnitus, bowel sounds.
High resolution CT scan
Nystagmus between episodes.
Pathophysiology of Epilepsy
Paroxysmal depolarisation shift: rapidly repetitive action potentials not followed by refractory period leading to prolonged depolarisation.
Seizures occur when large numbers of neurons in one region undergo the same.
Types of Generalised Seizure
Tonic Clonic
Absence (a very specific syndrome)
Myoclonic
Atonic
Focal Seizure Features
Subjective sensory or psychic phenomena
Motor
+/- impaired awareness
+/- generalisation (focal to bilateral tonic-clonic
Incontinence and seizures
Urinary incontinence is non specific and commonly occurs in syncope
Faecal incontinence very rare in seizures, more likely in syncope
Provoked Seizure
Acute precipitant that may or may not occur: SAH, stroke, TBI, meningitis, Alcohol withdrawal, hypoglycaemia, hyponatraemia, uraemic encephalopathy, chronic liver disease
If can be reversed, may not need AED. If likely to have ongoing seizures then may need AED
Juvenile Myoclonic Epilepsy
2ndf most common form of epilepsy
7% have ICK mutation
Start during teens, normal development
Myoclonic jerks in early waking states
90% GTCS, 30% have absence
Worse with sleep deprivation and alcohol
3Hz spike/polyspike wave
Photic stimulation and hyperventilation
First line: Valproate
Women of child bearing age: Lamotrigine
Unlikely to go into remission
Childhood and Juvenile Absence Epilepsies
Onset 8-12 years old
Normal development
Absence seizures, occasional GTCS
80% of patients’ seizures resolve by adulthood
Sodium Valproate
Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
Most common form of epilepsy
Risk factors: prolonged febrile convulsions and CNS infections
Typical auras, focal seizures with impaired awareness, with or without automatisms
Can have dreamy states with perceived unreality or deja vu or jamais vu phenomena, gustatory/olfactory hallucinations, epigastric rising sensations
Eventually can evolve into bilateral TCS
MRI: unilateral (sometimes bilateral) hippocampal atrophy, T2 signal increase
60-90% of patients medically refractory → surgery (most common drug refractory epilepsy)
EEG Frequency
Alpha 9-12Hz: Normal
Beta 13-15Hz: Too much Benzos
Theta: 5-8Hz: Drowsy, encephalopathic
Delta 1-4Hz: Sleep or encephalopathic
Spike and wave pattern is epileptogenic pattern
Epilepsy versus Seizures
A disorder of the brain characterised by enduring predisposition to generate epileptic seizures
Risk of recurrence of seizures and when to treat
After 1st seizure: 46%
After 2nd seizure: 70%
Thus, treat after 2nd unprovoked seizure (as long as within a year or two)
Treat after first seizure if EEF is abnormal, neurological exam is abnormal, or MRI shows structural abnormality
Or if further seizures expected to be severe or vulnerable population
Focal Seizure AED choice
Carbamazepine
Lamotrigine
Carbamazepine not ideal in elderly, Lamotrigine probably better but Carbamazepine is first on PBS
Levetiracetam also effective, but more expensive
Absence Seizure AED Choice
Valproate
Ethosuximide for pure Absence seizures in kids
Idiopathic Generalised Epilepsy AED Choice
Valproate
Lamotrigine for women of child bearing age
Zonisamide
GTCS AED Choice
Valproate
Levetiracetam (inferior and more expensive)
AED to avoid in Mitochondrial Disorders
Valproate
Key serious risk of Carbamazepine
SJS in patients with HLA B*1502
Common in Han Chinese, Thai, Indian, Malay, Filipino, Indonesians
8% of population
OR 895 if mutation present
HLA A*3101 mutation in Europeans, but less serious
AED choice if rapid response needed
Phenytoin
Levetiracetam
Valproate
Otherwise start low and go slow
Role of drug levels in AEDs
Reference range is not therapeutic range. May be therapeutic below and toxic within.
Uses:
1. Establish an individual therapeutic concentration once working
2. Diagnose toxicity
3. Assess compliance
4. Guide dose adjustment (pregnancy, drug interactions, etc.)
Best combination of AED for refractory Epilepsy
Lamotrigine + Valproate
Drug resistant epilepsy
Those with ongoing seizures despite 2 or more AEDs tried
Refer to epilepsy unit
Consider surgery
10-28% reach seizure freedom with further adjustments
Predictors of high risk of seizure recurrence
Long duration of epilepsy prior to remission
Short seizure free interval before ceasing AEDs
Late age of onset
History of febrile seiures
>10 seizure before remission
Developmental delay
Ongoing EEG abnormalities
Epilepsy and Pregnancy
Oestrogen is neuroexcitatory
Progesterone is neuroinhibitory
Thus seizures more common during certain phases of menstrual cycle
Epilepsy may increase risk of infertility, and polypharmacy certainly does
Most AED induce hormonal contraception leading to rapid clearance. (Lamotrigine is key exception).
High mortality with seizures during pregnancy.
Typical congenital anomalies with AEDs
Neural Tube Defects
Congenital heart disease
Cleft lip/palate
Urogenital defects
Valproate key offender, plus Phenytoin.
Carbamazepine, Phenobarb, lamotrigine some risk.
Ideally go to monotherapy Lamotrigine. Levetiracetam being increasingly used.
Polypharmacy is the key problem.
AEDs undergoing increased clearance during pregnancy
Lamotrigine
Levetiracetam
Epilepsy and Osteoporosis
Epilepsy an independent RF for osteoporosis
2-6x higher rates if on an AED
Longer duration = higher risk
Increased Vit D metabolism, and lower oestrogen levels due to altered metabolism
Risk Factors for SUDEP
GTCS >2 years
Nocturnal seizures
treatment resistant (or not taking)
Long duration of epilepsy
Early age of onset
Dravet Syndrome (Sodium channel gene mutation)
Young people wth convulsive seizures mostly.
Possibly some centrally mediated cardiopulmonary dysfunction
Inter Ictal Psychosis
Chronic schizophrenia like psychosis
RF: bilateral temporal lobe epilepsy, age of onset, refractory disease
Responds to antipsychotics, and seizure activity doesn’t really influence psychosis
Post Ictal Seizures
2-10% of patients
Cluster of focal seizures with impaired awareness or GTCS followed by onset of psychosis hours to days afterwards, lasting for weeks
Definition of Status Epilepticus
5 minutes of continuous seizure, or two or more seizures between which there is incomplete recovery of consciousness
20% mortality
Seizures >30 minutes unlikely to terminate spontaneously → increased mortality
longer = harder to terminate
Implication of convulsive status epilepticus
Leads to permanent brain damage which becomes an epileptogenic focus → drivers further seizure activity → increased resistance to treatment
CO increases initially with raised BP, glucose and lactate
Then all start to drop after 30 minutes
Then becomes malignant with hyperthermia, rhabdo and multiorgan failure
Treatment of Status Epilepticus
First line: Lorazepam 2-4mg IV (fast, superior); Midazolam 10mg IM then repeat if still seizing
Second line: Phenytoin 15-20mg/kg; Valproate 20-40mg/kg; Keppra 20-60mg/kg
Third line: Midazolam loading then infusion or Propofol load and infusion
Serious consequence of sudden withdrawal of Benzodiazepines
Treatment resistant status epilepticus
Treatment of benzo refractory status
Keppra/Valproate/Phenytoin all similar
Non convulsive status
After or independent of convulsive seizure
Either focal status or absence status
Change in behaviour and cognition with no motor symptoms
EEG key
Risks: known Epilepsy Hx, structural brain abnormality, benzo withdrawal
Not life threatening, but can lead to neuronal damage.
Treat as for convulsive status
Pathophysiology of Migraine
Brainstem ion channel dysfunction, involved in regulation of sensory/pain inputs and cranial vascular tone
Menstruation and Migraine
Risk factor for migraine without aura specifically
Predictable, can manage around cycles and give prophylaxis/treatment on this basis
