Neurology Flashcards
Gerstmanns Syndrome
Stroke at the angular gyrus of the dominant parietal lobe
Alcalculia
Finger Agnosia - cannot name fingers
Agraphia - cannot write, but can copy (Alexia)
L)/R) dissassociation
Non-dominant parietal lobe infarct
Inattention
Neglect
Apraxia
Impaired spacial perception
PCA infarct
Non- Dominant Parietal infarct
Inattention
Neglect
Apraxia
Spatial unawareness
Foot Drop
Due to Peroneal Nerve injury (branch of Sciatic nerve)
- Common peroneal - Dorsiflexion and eversion
- Deep peroneal - Just dorsiflexion
(The other branch of the sciatic nerve is the Tibial Nerve which supplies plantarflexion)
Internuclear Opthalmoplegia
Interruption Medial longitudinal fasiculus which carries information about the direction that the eyes should move in midbrain
- Leading eye nystagmus
- Failure of adduction of other eye
- Normal convergence
- Ipsilateral lesion to adduction deficit
- Bilateral is most suggestive of MS
Anton Syndrome
Lesion is in Bilateral occipital lobes supplied by Posterior cerebral artery – Presents with bilateral visual loss and unawareness or denial of blindness.
S1 radiculopathy
- Inability to plantar flex (walk on toes) “S1/S2 I stand on my shoe” via Tibial Nerve (branch sciatic nerve)
- Loss of sensation plantar aspect of lateral aspect foot
- Loss of ankle jerk reflex
Diagnosis GBS
Nerve Conductive Study and EMG - but may not be diagnostic in first week
Elevated CSF protein level (Albumino-cytological dissociation)
Mild increase in CSF WCC
Antiganglioside GM1 antibodies
GQ1b antibodies in Miller Fisher Syndrome
MRI findings PSP
Midbrain atrophy on MRI presenting as “Mickey Mouse “ and “Hummingbird” Signs
Progressive Supranuclear Palsy
Vertical gaze ophthalmoplegia
Early Falls with Axial rigidity
Facial dystonia
Asymmetrical Parkinsons
Poor response to L-Dopa
Lewy body Dementia
Early Dementia
Parkinsons
Dream-like behaviour with visual hallucinations
Corticobasal degeneration
Parkinsons Plus syndrome
Asymmetrical Parkinsons
Fronto-temporal dementia
Alien Limb Phenomenan
Apraxia
Multi-systems atrophy
Parkinsons Plus
Severe Autonomic dysfunction - Urinary retention, Postural hypotension
Cerebellar dysfunction
Pathological laughter and crying
Less likely to have hallucinations and cognitive dysfunction
Hot Cross Bun sign on MRI - increased T2 pons
mulTi-sysTem aTrophy = T similar to Hot Cross Bun sign
Shy- Drager Syndrome
Variant of Multi-system Atrophy (Parkinson’s Plus syndrome) - with severe autonomic dysfunction
Hemiballismus
Rare movement disorder characterised by a large movement of an entire limb on one side of the body.
Acute development of hemiballismus caused by focal lesions in the contralateral basal ganglia and subthalamic nucleus
HINTS exam
Head Impulse test
- positive; correctional saccade in peripheral, negative in central
Nystagmus
- Bidirectional in Central
- Towards the pathological side in Peripheral
Test of vertical skew
Meineres Disease
- Vertigo
- Head Impulse - Saccade positive
- Unidirectional Nystagmus
- Aural Fullness
- Tinnitus
- Sensori-neural hearing loss
Acute stroke MRI
DWI - hyperintense region indicating poor perfusion
ADC - Hypodense region indicating poor free water flow
Ab in Myasthenia Gravis
Attack post-synaptic ACh receptors
Anti-AchR (90%, or only 50% in ocular MG), cause increase internalisation & degradation of receptors
Anti -MUSK (10%), cause clustering of AchR on endplate, more frequently respond to PLEX > IVIG
Management for MG
Pyrodistigmine - for symptom relief only - not for crisis!
Thymectomy - even if no pathology but refractory to treatment
IVIG
PLEX - better response with MUSK +
Steroids - cautiously as can cause crisis
Immunosuppression - AZA, Mycophenolate, Rituximab
Acute Disseminated encephalomyelitis (ADEM)
- Post- Vaccination or viral illness
- Anti-MOG myelin oligodendrocyte glycoprotein)
- Rapidly progressive neurological decline in young patient who is apyrexial
- Clinical evidence of demyelination with PNS and CNS signs
- Mimics MS or transverse myelitis on imaging
- Rx with steroids
Syndromes/Signs associated with MS
- Optic Neuritis
- Intranuclear Ophthalmoplegia
- C-spine dermatome pruritus
- MS hug - neuropathic pain at torso
- Trigeminal Neuralgia
- Dyschromatopsia - Impaired colour vision (red becomes dark and bleached)
- Transverse myelitis - inflammation of spinal cord mimicking Cauda equina
- Cerebellar ataxia - with cerebellar lesions
- Lhermittes sign; Lhermittes sign; intense burst of pain like an electric shock that runs down back on flexion of neck “barber chair sign”; indicates dorsal column demyelination in c-spine
- Worsening of neurological signs with increased body tempretures
Lhermittes sign
Intense burst of pain like an electric shock that runs down back on flexion of neck “barber chair sign”; indicates dorsal column demyelination in c-spine
McDonald Criteria
For MS - Dissemination in space AND time
MS lesions; Dissemination in Space
Spinal
Infra tentorial
Periventricular
Juxtacortical
MS - Dissemination in Time
Differing neurological attacks of > 24 hours duration or multiple plaques of differing intensities on MRI scan
OR oligoclonal bands
Expanded Disability Status Scale
Used for disability in MS;
0; normal
1; minimal signs, no disability
2; minimal disability
3; moderate disability
4; severe disability
5; disability affecting ADLs
6; Assistance required to walk
7; Wheelchair bound
8; Bed bound
9; Unable to communicate/eat
10; Death
MS drugs
“DONT ForGet Preload In ACS”
Maintenance;
Dimethyl Fumurate - mechanism not well understood
Ocrelizumab - Anti-CD20
Natalizumab - Anti- alpha 4 integrin
Teriflunomide - Pyrimidine synthesis inhibition
Fingolimide - S1P inhibition to inhibit lymphocyte migration from LN
Glatiramer - Shunts Th1 to Th2
Peg IFN
Interferon Beta
Immune reconstitution;
Alemtuzumab - Anti-CD52
Cladrabine - Inhibits purine synthesis
Stem Cell Transplant
Side effects/benefits of MS drugs
DONT ForGet Preload In ACS
Dimethyl Fumurate - Best in pregnancy
Ocrelizumab - works for progressive MS
Natalizumab - JC virus/PML
Teriflunomide - teratogenic, alopecia
Fingolomide - Heart block, Macular oedema, CI CVD
Glatiramer - panic attacks & flushing, safe in pregnancy
Peg IFN & IFN Beta - Hepatitis, Flu-like illness, Depression
Alemtuzumab - Autoimmune conditions, thyroiditis, haemolytic anaemia, Anti-GBN GN, ITP, Breast Ca, Melanoma
Cladribine - Increased Cancer risk, PML
Anti- MOG
Anti- myelin oligodendrocyte glycoprotein
- Acute disseminated encephalopathy in children
- Neuromyelitis optica in adults
(Mimics transverse myelitis and MS)
Type 1 Charcot Marie Tooth
- Hereditary sensory and motor neuropathy
- Hypertrophy of myelin producing “onion rings” on biopsy
- Demyelinating
- Slow Nerve conduction
- Onset in Childhood
Type 2 Charcot Marie Tooth
- Hereditary Motor and Sensory neuropathy
- Non-demylinating
- Caused by direct damage to nerve axons
- Does not affect nerve conduction velocity
- Weakness of foot and leg predominate
- Less prominent sensory changes/deformity
- Onset adolescence
Hereditary neuropathies with pressure palsies
- Mutation in PMP22 gene causing insufficient maintenance of myelin sheath. Most commonly on chromosome 17.
- Persistant symptoms when pressure applied to nerves i.e. perineal, ulnar nerve palsies
Anti-Hu
Paraneoplastic encephalitis associated with small cell lung cancer
Lambert Eaton Syndrome
- Antibodies against pre-synaptic VGCC
- Improves with exertion
- Associated with SCLC, Males, 50-60 years
- Weakness, Areflexia & Autonomic dysfunction
- NCS with low CMAP which increases with exercise
- Rx;
- 3-4 diaminopyradine (blocks K+ depolarising channels to increase Calcium channel opening)
- IVIG
- PLEX
Anti-NMDA Encephalitis
- Young Female
- Ovarian teratoma, Sex Cord stromal tumours, SCLC
- Extrema delta brush delay on NCS
- MRI showing mesial-temporal hyperintensities
- CSF; Increased protein, lymphocytic pleocytosis, Anti-NMDA ab, Oligoclonal bands
Huntingtons
- Triplet repeat disorder - CAG repeats > 27 - full penetrance > 40 repeats - causes mutant Huntington gene
- Affects Basal ganglia
- Caudate atrophy on MRI
Rx with Tetrabenzine
Types of inclusions in Neurological conditions
Tau
- PSP
- Corticobasal degeneration
- Picks disease/frontotemporal dementia
Synuclein
- Parkinsons Disease
- Lewy body dementia
- Multisystem Atrophy
Amyloid
- Alzheimers
- Vascular Dementia
Prion
- CJD
Creutzfeldt-Jakob disease (CJD)
CJD sporadic
CJD Variant - Acquired “Mad Cow Disease”
Progressive dementia, neuropsychiatric changes, mutism, ataxia with death within 1 year
Motor Neurone Disease
Motor neurone denervation due to glutamate excitotoxicity spreads UMN -> LMN
- SOCD1
- C9ORF 72 -> associated with coexisting frontotemporal dementia
Risk Factors for MND
Low BMI
Healthy, Fit
FHx (SOCD1, C9ORF 72)
Split Hand Syndrome
Associated with MND
Wasting at First dorsal interosseous (flexor digitorium mini inervated by ulnar N) & Adductor policies brevis inervated by Median N
Types of MND
Amyotrophic lateral Sclerosis (ALS) - UMN +LMN
ALS plus - UMN + LMN + executive dysfunction
ALS-FTD - UMN + LMN + Frontoremporal dementia
Primary lateral sclerosis - UMN only
Primary muscular atrophy - LMN (remember because LMN denervation causes muscle atrophy!)
PMA + mild sensory change = Kennedy syndrome
Management MND
- Riluzole - Na channel blocker to decrease Glutamate release and decrease glutamate excitotoxicity -> slows progression of disease
- Endaravone - Free Radical Scavanger
- NIV - increases survival and QOL if commenced before bulbar dysfunction - indications
- SNIP < 30
- Low MIP indicative of diaphragm
- Low MEP indicative of abdominal muscles
Genetic predisposition Alzheimers Disease
APO E4 - Late onset Alzheimer’s and cardiovascular disease
Presenilin 1 and 2, Amyloid Precurser Protein - Early onset Alzheimers disease
APO E2 - protective Gene!
Treatment Alzheimers Disease
Donepezil - Ach Esterase inhibitor - Increases Ach in synaptic cleft
Memantine - Glutaminergic NMDA receptor antagonist
Types Muscular Dystrophy
- Duchenne - absence dystrophin protein, X linked, males affected, female carriers. Severe disease beginning in infancy
- Beckers - Milder form, variable dystrophin protein phenotype, more cardiomyopathy
- Fascioscapular - facial weakness, scapula winging
- Oculopharyngeal - Ptosis and difficulty swallowing
- Emery Drifiuss - weakness shoulder and upper limb
- Myotonic Dystrophy - Autosomal dominant, Percussion myotonia, endocrine abnormalities, Cataracts, cardiomyopathy, cognitive impairment
Type 1 Myotonic Dystrophy
Autosomal Dominant
3 x CTG repeats on DMPK gene
Onset < 10 years of age
Features
- Facial weakness (not prominent in Type 2)
- Distal muscle weakness (Type 2 is proximal)
- Cardiomyopathy common
- Grip Myotonia
- Dive Bomber on EMG
Type 2 Myotonic Dystrophy
Autosomal dominant
CCTG repeat on CNBP gene (Previously ZnF9)
Onset over 10 years of age
Features
- Milder disease
- Diabetes
- Proximal muscle weakness
Myotonic dystrophy complications
Diabetes
Gynacomastia
Testicular Atrophy
Cognitive impairment
Cardiomyopathy
Hatchet face
Frontal balding
Facial muscle atrophy
Hypothyroidism
Increased cancer risk
IBS
Types of Epilepsy
Focal - most commonly due to mesial-temporal sclerosis at hippocampus
Generalised idiopathic epilepsy; Na valproate as first line treatent
Frontal Lobe epilepsy; Nocturnal motor symptoms
Levetiracetam
“Keppra”
- Blocks SV2A-mediated pre-synaptic vesicle release of neurotransmitter
- Causes mood changes including aggression & Suicidal ideations
Na channel blockers in treatment of epilepsy
- Phenytoin
- Topiramate
- Lamotrigine
- Carbamazepine
Others;
- Keppra; SV2A modulator
- Topiramate also works to potentiate GABA & as mild diuretic by inhibiting carbonic anhydrase
- Vigabatrin; Potentiates GABA
- Lamotrogine also inhibits NMDA glutamate receptor & blocks Ca channels
Rx generalised epilepsy
Keppra
Na Valproate
Rx focal seizures
- Carbemazepine
- Lamotrigine
Rx epilepsy in pregnancy
Lamotrigine
Na Valproate
- Inhibits GABA transaminase
- Used for focal seizures in non-childbearing age women
- Causes weight gain
- Causes hyperammoneic encephalopathy
- Teratogenic
Drugs metabolised by CYP3A4
- Lamotrogine
- Carbamazepine
- Paracetamol (with 2E1)
- Simvastatin and Atorvastatin (therefore cannot be used for Leukodystrophy associated with Protease inhibitors in HIV - must Rx w Pravastatin which is not a CYP 3A4 substrate)
Inhibitors CYP3A4
Increased metabolism Carbamazepine
SICKFACES.COM
Sodium Valproate
Isonazid
Cimetidine (H2 receptor antagonist)
Ketaconazole
Fluconazole
Alcohol and Grapefruit juice
Chloramphenicol
Erythromycin
Sulphonamides
Ciprofloxacin
Omeprazole
Metronidazole
Inducers of CYP3A4
Decreases concentration carbamezepine & Lamotrigine
Decreases efficiency of OCP
CRAPGPS
- Carbemazepine (increases own metabolism!)
- Rifampicin
- Alcohol
- Phenobarbitone
- Griseofulvin (for ring worms)
- Primidone, Phenytoin
- St John’s wart
Na Valproate and Lamotrigine
Na Valproate decreases clearance of Lamotrogine - therefore combination is good in refractory epilepsy
Lamotrigine
Side effects
- SJS
- Ataxia
- Can aggravate myoclonic jerks of infancy
- Concentration increased by Na Valproate & decreased by OCP
- Really excreted
Rx absence seizures
Ethosuxamide or Lamotrigine
Rx Juvenile myoclonic Epilepsy
Na Valproate, or Lamotrigine if child bearing age
Third Nerve Palsy
“Down and Out”, Ptosis, Miosis
Surgical - Pupil involved - commonly due to PCOM Aneurysm
Medical - Pupil spared - commonly due to diabetes of vasculitis such as GCA
Webers Syndrome - Ipsilateral 3rd Nerve palsy due to midbrain infarct at Occulomotor nucleus, along with contralateral hemiplegia due to disruption of corticospinal tracts (sometimes can have Parkinson’s due to Substantia nigra involvement) - often due to HTN
- Uncal herniation
- Cavernus sinus thrombosis
Aphasia
Brocas - Expressive, non-fluent, comprehends
Wernickes (Brodman area 22) - Receptive, fluent, does not comprehend
Connected by arcuate fasciculus
PICA/Lateral medullary/Wellenbergs syndrome
- Ipsilateral facial pain and temp loss
- Contralateral body pain and temp loss
- Vertigo, Ataxia, ipsilateral nystagmus
- Ipsilateral Horners
- Dysphagia & ipsilateral loss of taste
Brainstem anatomy
Midbrain - 2 3, 4
Pons - 5, 6, 7, 8
Medulla - 9, 10, 11, 12
Contraindication to thrombolysis in acute stroke
- Intracranial Haemorrhage
- Extensive Hypodense region suggestive of subacute bleed
- Active bleeding
- BP > 180/100
- Recent GU/GI Surgery
- Recent trauma
- Brain tumour
- Aortic dissection
- BSL < 2.7
- Infective endocarditis
- Pl < 100
- INR > 1.2
- DOAC use < 48 hours
Complicated by unilateral, contralateral, orolingual oedema -> bradykinin induced
Thrombectomy indications
ICA or M1 infarct within 6 hours
Acute haemorrhagic stroke management
- BP target of 140mmHg
- Reverse anticoagulation
- Idarucizumab for Dabigatran
- Factor Xa for Apixaban and Rivaroxaban
- Vitamin K for warfarin
- Prothrombin X (factors II, IX and X)
AVOID platelet transfusion!
Genetic predisposition MS
HLA DR B1 501
(3 x risk)
Parkinsons Medications
- Selegiline - MOA B inhibitors - decreases Dopamine degradation - serotonin syndrome
- Amantadine - NMDA receptor antagonist to reduced glutamate excitotoxicity - Livedo reticularis, hallucinations
- Benztropine - Ach R antagonist - cholinergic side effects
-Pramipexole, Cabergoline, Rotigotine Patch - Dopamine Agonists, moderate disease in young patients - Compulsive behaviours (most common with pramipexole)
- L-Dopa with carbidopa - Dopamine replacement - for moderate disease in older patients - most severe motor fluctuations within 5 years - Punding, compulsive behaviours
- Entacapone - COMT inhibitors to decrease degradation of dopamine - counteracts motor fluctuations and “off periods”
- Apomorphine - Similar structure to Dopamine - decreases off-time - risk of subcutenous nodules, haemolytic anaemia, sleep attacks (cannot drive!)
- Duodopa - continuous levodopa-carbidopa infusion - Increased risk melanoma, peritonitis, neuropathies. CI heart failure, acute angle glaucoma, arrhythmias, Hx stroke, Use of MOA, dementia
- Deep brain stimulation @ sub thalamic nucleus and internal globes pallidus
Anti-synthetase syndrome
- Raynauds
- ILD
- Dermatomyositis
- Non-erosive arthritis
- Mechanics hands
- Anti-Jo
- Anti-PL-12
Associated with malignancy like all dermatomyositis and polymyositis
Immune mediated necrotising myopathy
- Isolated, severe proximal myopathy (i.e. no skin or other organ involvement)
- Due to autoimmune attack on HMG-CoA reductase even in absence of statin use
- Very high CK in ‘thousands’
- Myonecrosis on biopsy
Inclusion body myositis
- Proximal and distal myopathy
- Only mildly raised CK
- Biopsy showing endomysial inclusion
- Only inflammatory myopathy most common in Men - ALL others female predominant
- EMG showing myopathic and neuropathic process
- Treatment resistance - slow progression 5 - 15 years
