Neurology Flashcards
What level of spinal cord injury do you get autonomic dysreflexia?
Above T6
Spinal cord injury and cardiac complications
Increased risk of CAD (including dissection)
In the acute/aubacute setting- concerns with arrhythmias and haemodynamic instability
Peripheral neuropathy
mostly due to axonal neuropathies
- length dependent (there for LL affected first)
- reducec amplitude of evoked potentials with relatively preserved nerve conduction velocity
Parietal lobe lesion - non dominant
- anosognosia (deficit of self-awareness)
- hemisomatognosia (imperception for one half of the body)
- dressing apraxia (the incapacity of effectuating the acts of dressing correctly)
- prosopagnosia (the ability to recognize familiar faces, including one’s own face (self-recognition), is impaired,)
- Visual inattention
GERSTMAN SYNDROME:
Parietal lobe lesion - dominant:
-inferior parietal lobe
Angular and supramarginal gyri (Brodmann Area 39/40) - near temperoparietal junction
- Sx:
> Dysgraphria/agraphia
> acalculia/dysalculia
> finger agnosia
> L/R disorientation
> +/- aphasia
> +/- apraxia
MMN
Pure motor
Subacute
asymmetric
patchy
LMN signs
+/- conduction block and focal demyelination on NCS
Elevated Anti-GM1 (30-80% of pts)
Minimal response to steroids
but higher response to IVIG
PSP
Richardson’s syndrome
clinical sx
Classic features:
- early onset of falls
- classic PSP-RS have a **stiff and broad-based gait, with a tendency to have their knees and trunk extended **(as opposed to the flexed posture of idiopathic Parkinson disease) and arms slightly abducted.
- “drunken sailor gait.”
- supranuclear down gaze palsy and slow vertical saccades “can’t look down - improves with vestibula-ocula reflex
- postural instability
- **Frontal dementia **
PSP-P: tremor and asym onset, eye sx onset later - respond to Levodopa (better prognosis)
“Hummingbird” or “King penguin” sign
Suspect in pt >40
Predominant, otherwise unexplained impairment of episodic memory is suggestive of Alzheimer disease and is considered an exclusion criteria for the diagnosis of PSP.
PSP
Pathophysiology and radiology
- Tauopathy
- Midbrain atrophy
“hummingbird or king penguin” sign
Genetics – Normal brain tau contains six isoforms that are generated by the alternative splicing of a single tau gene (MAPT) on chromosome 17. Dominantly inherited mutations in the MAPT gene cause frontotemporal dementia with and without parkinsonism as well as PSP.
Marked reduction in D2 striatal receptors
Amantadine
- treat dyskinesia in Parkinson’s patients receiving levodopa, as well as extrapyramidal side effects of medications.
- mechanism: ?unknown ?NMDA antagonism
- SE: dry mouth, constipation, N?V, difficulty with sleep, abnormal dreams
Axonal neuropathy
NCS findings
- reduced amplitude of CMAPs
Demyelination
MCS findings
- slowing of conduction velocity
- Prolonged distal latency
- Temporal dispersion
CSF PCR for JC virus
Sensitivity and specificity
Low sensitivity 75%
High specificity 92%
if high pretest probability –> biopsy
MS treatment and pregnancy
Glatiramer, Dimethyl fumarate and ??Natalizumab Natalizumab: fetal haematological abnormalities (anaemia, thrombocytopenia if continued in 3rd trimester) If high risk of relapse, consider continuing until 3rd trimester.* are relatively safer in pregnancy whereas fingolimod, interferons and Teriflunomide are more dangerous
Wash out period prior to conception:
None: Glatiramer, IF beta, Dimethyl, Natalizumab
2 mo: fingolimod
4mo: alemtuzumab
6mo: Cladribine, Ocrelizumab and Ofatumumab
chlestyramine for Teriflunomide
Brachial neuritis
Common peroneal nerve lesion vs L5 radiculopathy
how to differentiate
Ankle inversion
- preserved in CPN injury
Ankle inversion is predominently done by tibialis posterior
Sleep related epilepsy
accounts for 10-15 of all epilepsy syndrome
- exclusively occurs in sleep
- nREM associated
- SHE: hypermotor epilepsy: nocturnal seizures in adolescents. Vigorous hyperkinetic and asymmetric tonic or dystonic features +/- impaired awareness
25% of SHE is inherited as autosomal dominant, with mutations in the CHRNA4 gene, which encodes for the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor, being described.
What causes global wasting of intrinsic muscles of the hand?
T1 lesion, which effects both ulnar and median nerve
Anti-epileptics and the channels they work on
Na: carbamazepine, phenytoin, topiramate, lamotrigine, lacosamide
Ca: Ethosuxamide, Lamotrigine
Glutamate: lamotrigine and topiramate
SV2A modulation: Keppra
EMG/NCS
Assess the peripheral nervous system:
CMAP: motor nerves
SNAP: sensory nerve action potential
Distal latency: prolonged in Carpal tunnel syndrome
Conduction velocity: prolonged in demyelination
Axonal polyneuropathy
commonly seen in diabetic polyneuropathy
- reduced amplitude of CMAPs and SNAPs
Radiculopathy
Proximal to DRG, therefore the SNAPs will be normal
reduced CMAPs proportional to the damage
Plexus lesions
NCS are similar to polyneuropathy as it will be distal to DRG
- reduction in both CMAPs and SNAPs
Conduction block
focal demyelination i.e. GBS
- stimulation proximal to the lesion results in reduction in CMAPs but when stimulated distally you get normal CMAPs
Carpal tunnel syndrome
prolonged sensory and motor distal lantency
NMJ disorder
Repetitive stimualtion:
decremental CMAPs: MG
incremental CMAPs: LES or botulism
EMG terms:
Fibrillations: represents a** single muscle fibre** that’s lost it’s innervation by the nerve, thus it’s dying - could be relation damage in the anterior horn cells, radiculopathy, plexopathy
- regular firing
**- always bad **
- can be due to denervation or myositis
- AXONAL neuropathies
i.e. alcohol
Fasciculations: due to entire motor unit. can visibly see it. A spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers.
- can be benign or anything that affects the peripheral nerve fibre
- classically seen in damage to anterior horn neurons
Motor unit potential (MUP):
- neurogenic: less number of MUPs, but bigger due sprouting
- myopathic: smaller MUPs, normal number i.e. DMD
Antibody in inclusion body myositis
Anti NT5c1a
Malignancy secondary to dermatomyositis
Anti p155
Which type of dementia is associated with MND?
FTD
Common mutation in familial MND?
C9ORF72
Poor clinical prognostic factors in ALS
- bulbar involvment
- resp subtype
- severity at baseline
- speed of progression
Subtypes that have a better prognosis in ALS
flail arm or leg syndrome
predominace in UMN or LMN
Worse prognosis for AIDP/GBS
Age >40
Male
Rapid onset
Resp involvement
Preceding diarrhoeal illness
High Anti GM1 titre
Weber’s syndrome
superior alternating hemiplegia
occlusion of the paramedian branches of the PCA or basilar artery
–> infarction of midbrain
ipsilateral occulomotor nerve palsy
contralateral hemiparesis or hemiplegia
Eyes: down and out
Myotonic dystrophy
AD inherited myopathy
20-30y/o
It affects skeletal, cardiac and smooth muscle
CTG repeat disorder
DM1 - **distal **weakness
DM2: prox. weakness
Associated with:
- cataracts
- dysarthria
- frontal balding
- bilateral ptosis
- myotonic facies
- - DM
- testricular atrophy
- cardiac: HB, CM
- dysphagia
DM1 is caused by a CTG repeat at the end of the DMPK (Dystrophia Myotonica-Protein Kinase) gene on chromosome 19
DM2 is caused by a repeat expansion of the ZNF9 gene on chromosome 3
MS and pregnancy
Pregnancy is protective against developing MS - more the better
MS activity increases in the 3 months post partum
Exclusive breastfeeding provides some reduction (30-50%) in MS disease activity postpartum
Where would the lesion be if someone can’t read but able to write and speak?
dominant occipital lobe
CN IV palsy
Trochlear nerve
Ipsilateral: up and out eye
due to inability to abduct, depress and internally rotate
The trochlear nerve is purely a motor nerve and is the only cranial nerve to exit the brain dorsally. The trochlear nerve supplies one muscle: the superior oblique. The cell bodies that originate the fourth cranial nerve are located in ventral part of the brainstem in the trochlear nucleus.
F waves
antidromic second CMAP
slight reduction in axonal neuropathy
highly reduced in demyelination
antiepileptic to use in juvenile myoclonic epilepsy
Sodium valproate
What is a visual sign associated with PML?
Homonomous hemianopia is an example of retrochiasmal visual field defect
RCVS, sometimes called Call-Fleming syndrome
Reversible cerebral vasoconstriction syndrome:
a weeks-long course of thunderclap headaches, sometimes focal neurologic signs, and occasionally seizures. A ‘sausage on string’ appearance is typical on CT angiogram.
Motor fluctuations on Levodopa in PD
Is associated with age of onset and duration of disease (rather than duration of treatment)
Annual incidence is 10%
Improved with increasing the frequency
What’s the median survival for ALS
3-5 years
PErinaud’s syndrome
damage to dorsal mid brain
clinical manifestation:
upward gaze palsy, convergence retraction nystagmus, bilateral lid retraction, Light-near dissociation
Occurs due to damage to dorsal pons
common cause: pineal gland tumour, haemorrhage or infarct
What’s most common clinical manifestation of ALS
- Asymmetric limb weakness
- Bulbar sx
MG - most sensitive test
Single fibre electromyography
Most specific test for MG
Anti ACh - R antibodies
Intraspinal location vs extraspinal location
Intra: C/T
Extra: L/S
Majjority of the spinal supply is by anterior spinal artery
Central cord syndrome presents with dissociative sensory loss
Chiari Malformation
Chiari I malformation (CM-I) is characterized by abnormally shaped cerebellar tonsils that are displaced below the level of the foramen magnum
*Chiari II malformation (CM-II), also known as Arnold-Chiari malformation, is characterized by downward displacement of the cerebellar vermis and tonsils, a brainstem malformation with beaked midbrain on neuroimaging, and a spinal myelomeningocele.
distinguish between radial nerve palsy and C7
C7 radiculopathy - wrist flexors are affected
Lamotrigine and pregnancy
Lamotrigine level is decreased in states of high estrogen i.e pregnancy, OCP
What is the average timeframe for death after developing cognitive disability in PD?
3 years
this is irrespective of age
Interestingly patients who develop Parkinsons at an older age are at a higher risk of mortality and developing dementia compared to younger patients
Posterior visuospatial symptoms correlate with dementia and mortality
What is the average timeframe for death after developing cognitive disability in PD?
3 years
this is irrespective of age
Interestingly patients who develop Parkinsons at an older age are at a higher risk of mortality and developing dementia compared to younger patients
Posterior visuospatial symptoms correlate with dementia and mortality
Tell me about Anti-NT5c1a
highly specific for IBM cf other myositis
only found in about 35 % of IBM
Other facts:
Vacuoles are not present in 20% of IBM
Anti NT5c1a can be seen in patients with SLE and sjogrens but WITHOUT muscle weakness. Anti NTC5c1a also has a prognostic role.
Conus medullaris
L1-2 involvement
Sudden
BILATERAL
less severe radicular pain
More severe back pain
Mixture of both UMN and LMN findings
Early faecal and urinary incontinence
Split hand syndrome
Split hand syndrome is a neurological syndrome in which the hand muscles on the side of the thumb (lateral, thenar eminence) appear wasted, whereas the muscles on the side of the little finger (medial, hypothenar eminence) are spared. Anatomically, the abductor pollicis brevis and first dorsal interosseous muscle are more wasted than the abductor digiti minimi. It is a specific sign for anterior horn cell disease such as ALS
What is:
- prosopagnosia
- anosognosia
- hemisomatognosia
what does the following finding suggestive of?
diffuse meningeal enhancement on brain MRI
RF for MS
female
caucasion
affected sibling (worse in monozygotic twins)
high altitude
low vit D
smoker
obese
** HLA-DRB1*15:01 confers the greatest risk.**
Pathogenesis of MS
Autoreactive T cells (esp Th17) migrate across BBB
reacte to antigen via APC
Secretion of proinflammatory cytokines
Stimulation of astrocytes and microglia
destruction of myelin –> exposed nerve results in axonal death
Ectopic B-cell follicles in meninges overlying grey matter lesion in MS
Grey matter lesions are common in progressive disease and correlates with cognitive impairment
VEP in MS
VEP: visual evoke potential
normal VEP - excludes optic nerve involvement
Core clinical characteristics of NMOSD
- optic neuritis
- acute myelitis
- Area postrema syndrome: intractable hiccups, nasuea, or vomiting
- Acute brainstem syndrome
- Symptomatic cerebral syndrome with NMOSD typical brain lesions
Core clinical characteristics of NMOSD
- optic neuritis
- acute myelitis
- Area postrema syndrome: intractable hiccups, nasuea, or vomiting
- Acute brainstem syndrome
- Symptomatic cerebral syndrome with NMOSD typical brain lesions
Differentiate NMOSD and MS
NMOSD: restricted to optic nerve and spinal cord
Severe attack
Longitudinal extensive central necrotic lesions
Pleocytosis during attacks
absent OCB
More female cf MS
Frequently have coexisting autoimmune conditions
NMOSD treatment
IVMP then Oral CS +/- PLEX
MMF, AZA
Rituximab (off label)
To note: MS treatment can be harmful: fingolimod, natalizumab, IF
Anti MOG disease
- Most common presentation is with bilateral (consecutive) optic neuritis.
- Also LETM and brainstem syndromes
Anti MOG disease
- Most common presentation is with bilateral (consecutive) optic neuritis.
- Also LETM and brainstem syndromes
Typically very severe
Steroid resposive –> good vision recovery
Treat like NMOSD if relapses off steroids
More recently identified in ~50% of
seronegative NMOSD patients.
* Also seen in CRION and MS patients.
Poor prognostic factors in MS
frequent relapse in the first 2 yrs of dx
short interval between the first 2 relapses
rapid early disability progression
high lesion load (esp spinal or infratentorial)
Cerebral atrophy
MALE
Later age of onset
Natalizumab
Tx for RRMS: alpha4 integrin (prevents bindinf to VAM1)
* 68% reduction in relapse rates
* 92% reduction in MRI activity
* 42% reduction in disease progression.
SE:
<5% hypersensitivity
* Increased risk of herpes virus reactivation (especially zoster)
* Risk of progressive multifocal leukoencephalopathy (PML)
caused by John Cunningham virus (JCV).
* If JCV serology positive, risk of PML related to:
* Any prior immunosuppression (highest risk).
* > 2 years on Natalizumab
* JCV index (level of positivity).
Alemtuzumab
Anti CD52 (found on all differentiated lymphocytes and monocytes)
Highly effective in reducing relapses (~50%
compared to IFNB-1a) and MRI activity
SE: Infusion reactions common
*Increased infection risk
* Risk of secondary autoimmunity
* Autoimmune thyroid disease (~30%)
* Risk of ITP, glomerular basement membrane disease,
autoimmune colitis etc
* Requires monitoring with monthly blood tests for 5 years (Bloodwatch program).
Given IV for 5 days (yr 1) then IV for 3 days
(yr 2).
Ocrelizumab
Anti CD 20 for RRMS and** PPMS**
Significant relative reduction in
relapses (~50% cw IFNB-1a)
* MRI activity reduction (94% cw IFNB1a)
* Reduced disability progression.
IN PPMS:
24% reduction in confirmed disability
progression cw placebo
SE:
*Infusion reaction common.
*Increased infection risk (beware Hep B reactivation).
* Estimated risk of PML (based on other anti-CD20+
therapies) ~1:30,000.
*Non-significant increased risk of malignancies in one
RCT (esp breast).
IV 6 mothly
Ofatumumab
Anti CD 20 for RRMS
Fully humanised
Reduced annualised relapse rate (0.11 vs 0.22)
* Reduced disability progression (8.1% vs 12%)
* Reduced new T2 lesions on MRI.
* Reduced NFL levels.
* NO change in brain volume.
SE:
2.5% serious infection
injection site reaction
Cladribine
For RRMS
* Deoxyadenosine analogue prodrug that selectively
targets lymphocytes due to preferential intracellular
activation.
~50% relative relapse rate reduction versus placebo
* Significant reduction in MRI activity and disability
progression.
* 48% of patients NEDA at 4 years after treatment
initiation.
Generally well tolerated:
SE:
Lymphopenia
short term risk of infection esp. zoster
Weight based oral dosing for 5-days, week 1
and week 5. Repeated year 2.
Fingolimod
ORAL, Binds to S-1-P receptors on lymphocytes
blocking their egress from lymph node. * Additional putative effect directly on astrocytes.
Relative relapse reduction of 54% cw placebo.
* Reduced MRI activity
* Slows disability progression
* Reduced brain atrophy
SE:
* First dose braydcardia.
* LFT derangements
* Lymphopenia
*Increased infection risk especially herpes viruses. can casue disseminated HSV or VZV
*Increased risk of non-melanomatous skin cancers.
* Annual skin checks
* PML risk ~1:10,000
Daily tab
Ozanimod: different R specificity, and lower risk of cardiac complications
Dimethyl fumarate
MS
activation of Nrf2 in he antioxidant pathways
SE: Flushin
GI upset
Lymphopenia
rate LFT derangements
Risk of PML 1:18,000
Least tolerated
Teriflunamide
Inhibits dihydroorotate dehydrogenase and interferes with pyrimidine synthesis.
* Relative relapse risk reduction of 32% cw placebo
* Reduced disability progression.
* Reduced brain atrophy rates
SE- hepatotoxicity, hair thinning, HTN, GT upset. Teratogenic!
ORal tab
Glatiramer Acetate
Synthetic polypeptide antigenically similar to myelin basic protein.
* ~30% relative reduction in relapse rates cw placebo.
SE: injection site reaction
used in pregnancy and breast feeding
IF beta 1a and 1b
Diverts immune system away from proinflammatory Th1 and Th17 pathways to a more anti-inflammatory Th2 pathway.
* Reduces annualised relapse rate by ~30%.
- Can delay conversion from CIS to RRMS.
- SE- flu-like symptoms, depression, LFT derangements
Siponimod
for SPMS
Like Fingolimod, selective sphingosine 1-phosphate rec modulator. Key differences include:
* Narrower spectrum of action on SIP receptors.
* Baseline pharmacogenomics (CYP2C9 genotyping) dictate starting dose.
* No cardiac monitoring needed unless pre-existing cardiac condition
SE: lymphopenia, increased LFT’s, (bradyarthymia), macular oedema, HTN, VZV reactivation, convulsions.
MS treatment and breastfeeding
Safest: GA, IFN
Likely safe- Natalizumab
Covid and MS
increased risk of severe covid outcomes
Older MS pt
male
higher EDSS
presence of comorbidities
MS pt on b-cell depleting therapy: Ocre, ofan
Recent methylpred
- ATAGI guidelines stipulate all MS patients are eligible for at least 4 covid-19 vaccines.
- MS patients who are on B-cell depleting therapies or SIP inhibitors are eligible for additional Covid-19 vaccinations, anti-viral treatments and Evusheld (tixagevimab and cilgavimab) due to blunted humoral responses.
MS RF
Both genetic and environmental factors contribute to the risk of MS
- 30 fold increase if Caucasian
* 3 fold increase if female
- 20 fold increase if affected sibling
- Up to 7 fold increase for Both genetic and environmental factors contribute to the risk of MS
- 30 fold increase if Caucasian
* 3 fold increase if female
- 20 fold increase if affected sibling
- Up to 7 fold increase for high latitude of residence
- 2 fold increase if low vitamin D levels
- 1.5 fold increase if smoker
- 1.3 fold increase if obese (females)
- 2 fold increase if low vitamin D levels
- 1.5 fold increase if smoker
- 1.3 fold increase if obese (females)
** HLA-DRB115:01 confers the greatest risk.
**
MS RF
Both genetic and environmental factors contribute to the risk of MS
- 30 fold increase if Caucasian
* 3 fold increase if female
- 20 fold increase if affected sibling
- Up to 7 fold increase for Both genetic and environmental factors contribute to the risk of MS
- 30 fold increase if Caucasian
* 3 fold increase if female
- 20 fold increase if affected sibling
- Up to 7 fold increase for high latitude of residence
- 2 fold increase if low vitamin D levels
- 1.5 fold increase if smoker
- 1.3 fold increase if obese (females)
- 2 fold increase if low vitamin D levels
- 1.5 fold increase if smoker
- 1.3 fold increase if obese (females)
** HLA-DRB115:01 confers the greatest risk.
**
What is the most common symptom in MS
sensory symptoms in limbs
Optic neuritis in the context of MS
in 21% of pt with MS, ON is the first presenting complaint
f>M
30s
Sx:
Monocular, central vision loss
Pain with movement or touch
altered colour vision (red/green in late stage)
reduced contrast sensitivity
Phosphenes
Uhthoff phenomenon
Poor prognosis:
- severe vision loss at presentation
- Longer lesions, NMO IgG
- African origin
- Children
- ## vision recovery over 6/12 - 12/12
Friedreich’s ataxia
- most common of the early-onset hereditary ataxias.
- AR
- GAA trinucleotide repeat on X25 gene on Chr 9
- DOES NOT SHOW ANTICIPATION
The typical age of onset is 10-15 years old. Gait ataxia and kyphoscoliosis are the most common presenting features.
Neurological features
absent ankle jerks/extensor plantars
cerebellar ataxia
optic atrophy
spinocerebellar tract degeneration
Other features
hypertrophic obstructive cardiomyopathy (90%, most common cause of death)
diabetes mellitus (10-20%)
high-arched palate
What is the treatment choice for childhood ansence epilepsy?
Ethosuximide
Drug of choice for focal epilepsy?
Lamotrigine; it’s better than carbamazepine, topiramate and gabapentin for focal seizrues
Lamotrigine and Valproate?
Rash
Carbamazepine and lamotrigine
lamotrigine level decreases
Levetiracetam
SVp2A inhibition –> reduce calcium current
Doesn’t interact with other AED
100% oral availability
95% renal excretion
ADR:
Fatigue, thrombocytopenia, blurred vision
**memory, irritability, mood swings, increased suicidality **
Brivaracetam - 2nd gen - only diff is less dizziness
Levetiracetam
SVp2A inhibition –> reduce calcium current
Doesn’t interact with other AED
100% oral availability
95% renal excretion
ADR:
Fatigue, thrombocytopenia, blurred vision
**memory, irritability, mood swings, increased suicidality **
Brivaracetam - 2nd gen - only diff is less dizziness
when will you used mTOR inhibitors?
Tuberous sclerosis epilepsy
General ADR of antiepileptics
drowsiness, fatigue, lethargy, insomnia, dizziness, hyponatraemia, irritability, paraethesia (esp. phenytoin)
particular issue with topiramate
issue with attention, language and causes weight loss
HLA B*1502
CBZ and PHY –> SJS
HLA B*3101
CBZ induced rash/DRESS
Lacosamide
inhibits sodium channel
Lacosamide binds to collapsin response mediator protein-2 (CRMP-2)
Perampanel
glutamnergic AMPA antagonist
ADR:
weight gain, aggression, dizziness and ataxia
Antiepileptic and pregnancy
Lamotrigine - major congenital malformation is similar to baseline 2.9%
Dose dependent defect with valproate and other AED
Folate is not protective for AED induced teratogenicity
Lamotrigine and Keppra are favourable
AED and pregnancy
concentration reduced for. lamotrigine, keppra, lacosamide
Topiramate reduced in 3rd tri and rebounds PP
CYP2C9*3
PHY –> SJS or DRESS
treatable autoimmune limbic encephalidities
Anti Potassium channel antibody - anti LGI1 (older male)
Anti NMDA antibody (young woman, teratoma)
Clinical clues for autoimmune epilepsies
Clinical clues
Limbic encephalitis
Faciobrachial seizures (esp LGI1)
Encephalopathy evolving rapidly, psychosis
Onset with status
EEG very basic
Spikes, sharp waves = epileptiform
Low sensitivitty ~40%
Odd #: left
Even # : right
Hepatic encephalopathy: triphasic waves
EEG very basic
Spikes, sharp waves = epileptiform
Low sensitivitty ~40%
Odd #: left
Even # : right
Hepatic encephalopathy: triphasic waves
SUDEP:
SUDEP:
- Most common cause of death is central hypoventilation
- RF:
○ Gender (male)
○ Uncontrolled generalised seizures (>2)
Nocturnal seizures
Juvenile myoclonic epilepsy (Janz syndrome)
typical onset is in the teenage years, more common in girls
infrequent generalized seizures, often in morning//following sleep deprivation
daytime absences
**sudden, shock-like myoclonic seizure **(these may develop before seizures)
often triggered by lack of sleep and flashing lights.
Tx. Valproate or lamotrigine
Seizures in most people with JME tend to improve after the fourth decade of life.
Seizures are generally well controlled with medications in up to 90% of people
AED commonly causes weight gain
Sodium valproate
which AED is associated with serious visual loss?
Vigabatrin
inhibiting the GABA-degrading enzyme, GABA transaminase, resulting in a widespread increase in GABA concentrations in the brain.
Key words for:
Dermatomyositis
Anti Mi
Anti TIF-1gamma - associated with malignancy
Clinical:
Gottron’s papules
Heliotroph rash (upper eye lid)
photosensitive rash - V sign and Shawl sign
mechanics hands
Histo:
perifascicular muscle atrophy
MRI-STIR: odema in patchy distribution
Key words for:
Anti synthetase syndrome
Antibodies again aminocyl transfer RNA synthatase
Antibodies: Anti-Jo1, Anti PL12
Histo: perifascicular necrosis, perimysium fragmentation and increased ALP activity
Clinical:
Inflammatory myositis, ILD, arthritis, raynauds, mechanic hands, fever
Key words for:
Immune mediated necrotising myopathies:
Elevated CK in the 100s, median 4700
Histo: myofibre necrosis and regeneration without lymphocytic infiltrate
Severe proximal muscle weakness
Ab:
Anti HMGCoA reductase
Ab negative immune mediated is associated with malignancy
Anti SRP: severe muscle involvement
Not all associated with statin
Polymyositis
dx of exclusion
subacute proximal muscle weakness, elevated CK, myopathic EMG
biopsy: endomysial inflammation with CD8+ infiltrate
Anti-Ro52
common myositis associated ab - non specific
Anti PMScl
Myositis/SSc overlap: associated with lung and oesophageal involvement
Anti Ku
another Myositis/SSc overlap: associated with joint involvment, raynauds, ILD
Anti U1RNP
Myosisis, Scleroderma, SLE and GN
Treatment overview for myositis
- Steroids
- AZA/MTX/MMF/CYC/TAC/IVIG/Ritux/Cyclophosphamide
Ritux: refractory DM/PM, Anti synthetase sx, ref, anti SRP antiby nec
Sporadic IBM
Most common muscle disease in >50
NT5C1A: predicts severe disease - and higher mortality
it’s not specific or sensitive
sx:
Quadriceps and distal fingers affected first
(MRI - ant. thigh muscle selectively involved)
reduced/absent knee reflex early in disease
slow progression
EMG/NCS: mixed muscle/nerve disease
Biopsy: endomysial inflammation (required)
rimmed vacuoles and proteinecous inclusions (not required)
Dystrophinopathies
Absence or decrease in the function of the dystrophin prtn in the sk m
X-linked recessive
prox. LL –> prox UL
Symmetrical weakness
disphragm and swallowing weakness occurs later in disease
Cardiac involvement, muscle cramps, myalgia, cognitive impairment
Duchenne: More severe phenotype, onset with 1st eyar of life. Loss of ambulation by 12-13
Becker MD: milder and variable phenotype, but more cardiac involvement
Dx: biopsy/genetic - absence of dystrophin
Tx:
1. Steroids - prolongs ambulation, preserved UL strength, reduce scoliosis, Cardio-pulm benefit
- female carriers may develop CM
Fascioscapulohumeral MD
Type 1 (95%) AD
hypomethylation of the subteleomeric region of Chr4q –> aberrant expression of DUX4 is a transcription factor
Asymmetric weakness of the orbicularis oculi, oris, rhomboids, serratus anterior, tricep, paraspinal, rectus abdominis, tibialis anterior
- weakness of the facial muscles, the upper arms and the hip girdle
Symptoms normal develop from the age of 15 to 30
Associated with retinal vasculopathy + hearing loss with large deletions
CK normal or mildly elevated
EMG/biopsy is not specific
Tx:
Supportive
Sporadic CJD
Creutzfeldt-Jakob disease (CJD) is rapidly progressive neurological condition caused by prion proteins. These proteins induce the formation of amyloid folds resulting in tightly packed beta-pleated sheets resistant to proteases.
Features
- dementia (rapid onset)
- myoclonus
Investigation
* CSF is usually normal
* EEG: biphasic, high amplitude sharp waves (only in sporadic CJD)
* MRI: hyperintense signals in the basal ganglia and thalamus
MELAS
mitochondrial encephalomyopathy, lactic acidosis, and stroke like syndrome
- typically parietal-occipital stroke/stroke-like events
- not in defined vascular territories
- cognitive impairment/dementia
- epilepsy and subclinical epilepsy
- myopathy
- elevated lactate in blood and CSF
Mutation in mitochondrial DNA tRNA LEu gene
Primary periodic paralysis
AD
typically presents early childhood
complete paralysis of all four limbs and absent reflexes
Abortive episodes
episodes may be triggered bt specific factors or situation
Continues episodes –> proximal muscle weakness
Hypokalaemic periodic paralysis
mutation in calcium channel CACNA1S (+/- SCN4A)
Triggered by carb or prolonged rest
Hyperkalaemic periodic paralysis
mutation in SCN4A (sodium channel)
Triggered by fasting or exercise
Myotonia in eyes and hands
PAINFUL
Andersen-Tawil sx
K+ channel KCNJ2
severe cardiac arrhythmias
facial and skeletal features
usually HYPOkalaemic
POMPE
Glycogen storage disease myopathies (type2)
AR
Mutation in GAA (acid alpha glucosidase) gene –> enzymatic acid maltase deficiency
Spectrum of severity in myopathy
Elevated CK
Tx:
High protein with complex carbs
Avoid strenuous exercise
Enzyme replacement: aglucosidase
Monitor for cardiac
MG
Background
80% have AchR antibodies (50% of occular MG)
very specific
to note some sero convert over a 6 month period
Genetic RF in HLA genes and CHRNA1
W:M 7:3 <40yo
M>W >50y/o
Antibody mediated T-cell dependent attack on the postsynaptic mb:
- bind to the alpha subunit
- block the binding
- increased internalisation of the receptor/degradation
- MAC formation and damage
Fatiguable
Thymus: thymoma in 15%, thymic hyperplasia ~65%
Anti-MuSK muscle specific TK
Block MuSK-LEP4 binding –> reduced AChR clustering at the end plate
found in a third of AChR neg MG, mostly women 85%
- atypical presentation (neck extensor, shoulder and resp muscles)
- severe bulbar, facial and ocular weakness - poor response to tx
- **PLEX **>IVIG
Anti LRP4
- 20% of double neg MG
Anti striational
-80% thymoma without MG
30% adult onset MG
antibodies are not used for monitoring
MG
Sx:
ptosis and binocular diplopia is the most common px symptoms
Bulbar weakness, facial weakness, weak neck flexion
Limb weakness (proximal) and symmetric
Fnger/wrist extension, ankle dorsiflexion also affected
Meds that trigger MG
Abx:
- amino glycosides, fluoroquinolones, tetracyclines, sulfonamides, penicillins, nitrofurantoin
CVS:
- betablocker, CCB, quinine, quinidine
Checkpoint inhibitors
IF alpha
Mag
D-penicillamine
MG tx
Stroids, IVIG or PLEX
- PLEX: fast onset in MG crisis
can’t use in sepsis or hypotension
- IVIG: moderate - severe exacerbation
improves after few days to weeks, effects last weeks to months
SE: flu like sx, aseptic meningitis, increased thrombosis risk
Pyridostgmine:
- used for symptomatic tx alone
- effetive 30-60mins later, last 3-4hrs
- Anti MuSK don’t respond
Corticosteroids
- effective within 2-3 weeks
- short term exac can occur esp bulbar weakness
Steroid sparing
- Azathioprine (effective after 4-8 months)
SE: myelosuppresion, toxic hepatitis, pancreatitis
Chest TPMT genotype
- MMF: inhibits monophosphaste dehydrogenase
- effective after 1-2 months
- SE: nausea, diarrhoea, abdominal pain, leukopenia, anaemia
Rituximab:
- significant improvement in severe or refractory cases
- esp in anti MuSK positive cases
Thymectomy
Eculizumab for anti AChR gen. MG
MG inx
Antibodies
Electrodiagnostic repetitive stimulation
single fibre electromyography - most sensitive
ice pack test - highly specific and sensitive for GM ptosis
Edrophonium test: rapid acting esterase inhibitor
CT chest
TFT: autoimmune thyroid disease often associated wiht MG
Other fun facts on MG
- if purely ocular and symmetric ptosis think chronic progressive external ophthalmoplegia
LEM
P/Q VGCC antibodies
less ACh release from presynaptic terminal
50/60s
male predominance
associated with SCLC
incrementation NCS - decrement with low rates 3Hz, increment with fast rate 20-50Hz
Tx:
3,4-diaminopyridine
IVIG/PLEX acutely
GBS
PNS
Classic: Acute onset of weakness and sensory sx in the LL that ascends to involve the UL/CN
ACUTE FLACCID PARALYSIS
M>F
Subtypes: AIDP, AMAN, AMSAN
>95% monophasic course
antecedent rsep or diarrhoel illness 4-6 weeks prior
Neuro nadir 2-4 weeks
recovery after 2-3 weeks from nadir
Pathology:
- complement activation
- upregulation of Fc receptor for IgG
- macrophage induced contact-dependent injury
- AIDP: schwann cell/myelin
- AMAN/AMSAN: axon
Antigangioside antibodies: relevant to AMAN and Miller Fisher sx
GBS triggers
Campy
CMB, EBV, mycoplasma, H. influenzae, hep E, Zika, Covid
Vaccine, pregnancy, immunosuppression, surgical
if someone develops GBS within 6-8 weeks of a vaccine, that vaccine should not be given
AIDP
most common >90% form of GBS
Initial presentation is sensory sx or pain (back pain is the most common sx - diffuse)
Predom. motor polyradiculopathy with acute progressive symmetric weakness involving proximal and distal muscles
Reduced or absent reflexes
you can get resp muscle involvement 30%
CN nerve >50%
dysautonomia
sphincter dysfunction can occur
Anti glycan ab: LM1 or GM1 only 25-30%
Miller Fisher
Ophthalmoplegia (diplopia), ataxia + areflexia
GQ1b antibodies in 80%
Bickerstaff brainstem encephalitis
ophthalmoplegia, ataxia, altered consciousness/hyperreflexia
CSF in GBS
Normal cell count
(some have WCC, but <50cell/mm3)
Elevated protein
IVIG can increase CSF WCC and protein
NCS/EMG in GBS
Early can be normal
prolonged F wave latencies or absent response
AIDP: sural sparing pattern, but UL sensory response absent or reduced
Prolonged distal latencies, reduced motor nerve conduction velocities, prolonged F wave, increased temporal dispersion, and conduction block at non compressible sites
AMAN: reduced cMAP
AMSAN:reduced cMAP amplitude and reduced sNAP amplitudes
NCS finding peak at 2 weeks of sx
GBS tx:
IVIG + PLEX
- equally efficacious
- 40-50% don’t have clinical response
- combined treatment is not superior
- don’t given second course of IVIG (increases AE incl VTE)
if worsens, consensus is to retreat with the original tx
IVIG is considered first line
-need to give 2 weeks of onset
PLEX: beneficial upto 4 weeks from onset
Poor prognostic factors for GBS
> 40
preceding diarrhoeal illness
short interval from onset to nadir
mechanical ventilation
high greade neuro deficit
persistly low cMAP amp
Variant of GBS associate with covid vax
- bilateral facial weakness (diplegia) with parasthesias
L5 damage would cause foot drop but not the loss of ankle jerk which is innervated via S1/tibial nerve. The same is true for common peroneal nerve
Tibial neuropathy would cause loss of ankle jerk, but weakness of plantarflexion (not dorsiflexion).
The femoral nerve innervates knee extensors and knee jerk
true
Millard Gubler syndrome
- unilateral lesion of the ventrocaudal pons may involve the basis pontis and te fascicles of CN VI and VII
Symptoms:
1. Contralateral hemiplegia (sparing the face)
2. Ipsilateral lacteral rectus palsy wtih diplopia - accentuated when pt looks to the side of the lesion
3. Ipsilateral peripheral facial paresis (due to CN VII involvement)
Femoral nerve (L2,3,4)
KNEE EXTENSION
KNEE JERK
SENSORY TO INNER ASPECT OF THIGH AND LEG
CRITICAL ILLNESS MYOPATHY
VS
CRITICAL ILLNESS POLYNEUROPATHY
CIM:
- proximal muscle
- failure to wean ventilator
- Normal sensation
- steroid use
- Sensory nerv amp: >80%
- Motor amp <80%
- Needle EMG: normal MUPs recruitment
- Short duration and low amp of MUPs +/- fibrillation potentials
- CK high
- Myopahty with myosin loss
CIP:
- Sensory <80%
- Motor <80%
- EPS: axonal motor and sensory poly neuropathy
- Reduced recruitment of normal MUPs
- Fibrillation and reduced recruitment of long duration, high amplitudes MUPs (late)
-CK normal
- neurogenic atrophy
