Neuro Flashcards
1st line medications to treat absence seizures
1) Ethosuximide
2) Sodium valporate
EEG findings in absence / petit mal seizures
Regular, symmetrical, generalised 3Hz spike and wave complexes of 3 cycles per second
Define encephalitis
Inflammation of the brain parenchyma
Most common cause of encephalitis
Viral (HSV, influenza, adenovirus, enterovirus, arbovirus)
- HSV most common (90% cases HSV-1, 10% HSV-2)
- CMV should be considered in the immunocompromised
Area of the brain most commonly affected in HSV encephalitis?
Medial temporal and inferior frontal lobes (in adults and children >3 months)
Generalised brain involvement in neonates
Causes of Encephalitis
Viral:
- HSV, influenza, adenovirus, enterovirus, arbovirus)
- HSV most common (90% cases HSV-1, 10% HSV-2)
- CMV should be considered in the immunocompromised
Bacterial:
- Lyme disease
- TB
- Listeria
- Legionella
- Syphilis
Parasites:
- Toxoplasmosis
Funagl:
- Candida
- Histoplasmosis
What infections can cause a secondary encephalitis?
Chickenpox
Measles
Mumps
Rubella
Flu A or B
EBV
Hep A or B
HIV
Enterovirus
Coronavirus
How does a secondary encephalitis present?
1-3 weeks post illness
Usually presents as an acute disseminated encephalomyelitis
x3 routes by which HSV infiltrates the CNS in HSE
1) Trigeminal or Olfactory tracts
2) CNS activation after recurrent infection
3) Latent HSV: CNS infection without a primary or recurrent infection
Pathophysiology of Herpes Simplex Encephalitis
HSV invades and replicates in neurones and glia, causing necrotising encephalitis with widespread haemorrhagic necrosis.
Duration of treatment for confirmed HSE?
14-21 days of IV Aciclovir (then needs repeat LP to confirm CSF is negative)
Drug of choice for CMV encephalitis?
Ganciclovir
What is the only indication to use corticosteroids in the treatment of encephalitis?
Encephalitis due to an immunologic reaction (e.g. Autoimmune encephalitis)
- Corticosteroids
- Plasma exchange or IVIG
Mortality rate of HSE?
70% in untreated HSE (often fatal within 7-14 days)
19% in treated HSE
Define meningoencephalitis
Inflammation of meninges and brain
Define myeloencephalitis
Inflammation of spinal cord and brain
Why should you use cefotaxime instead of Ceftriaxone to treat suspected meningitis in children <3 months
Ceftriaxone displaces bilirubin from albumin and can worsen jaundice
First line Abx choice for suspected bacterial meningitis?
> 3 months:
- Ceftriaxone
<3 months:
- Amoxicillin (listeria cover) and Cefotaxime
Contraindications for using corticosteroids (Dexamethasone) to treat severe bacterial meningitis?
<3 months
TB meningitis
>12 hours lapsed since first dose of Abx
When to follow up bacterial meningitis and what Ix should be done?
4-6 weeks post discharge
They all need a hearing test - high risk of sensorineural hearing loss and may need a cochlear implant
Define meningitis
Inflammation of the meninges caused by penetration of the blood-brain barrier and proliferation in the CSF by a particular pathogen
Most common form of meningitis
Viral meningitis (accounts for >50% cases)
Who is at the greatest risk of a bacterial meningitis?
Infants
What is the annual incidence of bacterial meningitis?
1-2 per 100,000
Risk factors for meningitis?
Immunosuppressed
CSF shunts/surgery
Renal or adrenal insufficiency
Thalassaemia
Cystic Fibrosis
Croweded living conditions
UNVACCINATED children
Common viral causes of meningitis
Enterovirus (most common)
Coxsackie virus
Echo virus
Measles
Mumps
HSV
VZV
Bacterial causes of meningitis
Neonates / <1 month old:
- Group B Strep
- E Coli
- Listeria
- Staph aureus
First 2 months of age:
- Group B Strep
- E Coli
- H influenzae
- Strep pneumoniae
Older infants / children:
- Meningococcus
- H influenzae
- Strep pneumoniae
TB is a risk at any age
LP findings in viral meningitis
AWPG
Appearance - clear
WCC - raised (lymphocytes)
Protein - normal or slightly raised
Glucose - normal or slightly reduced
LP findings in bacterial meningitis
AWPG
Appearance - Turbid
WCC - raised, usually polymorphs (typically >90%)
Protein - raised
Glucose - low (<40% serum glucose)
Same for TB although appearance can be turbid, viscous or clear
What is a normal CSF glucose level?
> 50% blood glucose ratio
Which infection can cause a subacute sclerosing panencephalitis?
Measles
What time period after measles infection would a subacute sclerosing panencephalitis develop?
2-10 years (median interval is 8 years)
Why are neonates/immature brains more excitable and likely to develop seizures?
Higher expression of NKCC1 and lower expression of KCC2 which causes a high neuronal chloride concentration. This causes GABA-ergic signalling to be excitatory rather than inhibitory and increases the brain’s excitability.
Ischaemia also increases NKCC1 expression
HIE reduces KCC2 expression
Types of neonatal seizure
Tonic -> stiffening of trunk/extremitiess
Multifocal clonic -> rhythmic clonic movements of different parts of the body
Focal clonic -> repetitive clonic movements of the same part of the body
Subtle -> stereotyped bicycling, tongue thrusting and swallowing movements
Myoclonic -> isolated repetitive brief (shock like) jerks of the body
Drug choice for neonatal seizures
1) Phenobarbitone
2) Phenytoin
3) Keppra or midazolam
What are the three conditions required for a seizure to occur?
Population of pathologically excitable neurones
Increase in excitatory glutaminergic activity through recurrent connections to spread the discharge
Reduction in the normal activity of GABA-ergic inhibitory projections
Types of generalised epileptic seizure
Absence / petit mal -> transient LOC with abrupt onset and termination where they stare off into space
Myoclonic -> brief, shock like jerks of limbs, neck or trunk
Tonic -> sudden stiffness in muscles
Tonic - clonic -> stiffness in muscles followed by general herking movements. LOC. may bite tongue, become cyanosed or incontinent of urine
Atonic -> part or all of the body becomes limp. Drop attacks.
Types of focal epileptic seizure
Focal seizure = activity arising from part of or in one hemisphere only
Frontal - motor phenomena
Temporal - auditory, taste or smell phenomena
Parietal - contralateral altered sensation
Occipital - positive or negative visual phenomena
Contraindications to a ketogenic diet
Carnitine deficiency
Beta oxidation defects
Porphyrias
Pyruvate carboxylase deficiency
1st line medication for most partial seizures
Oxcarbazepine
Keppra
1st line medication for generalised tonic-clonic seizures
Sodium Valporate
Alternative - Lamotrigine
1st line medication for myoclonic seizures
Sodium Valporate
2nd line - Topiramate or Keppra
1st line medication for atonic / tonic seizures
Sodium valporate
2nd line - lamotrigine
1st line medication for benign rolandic epilepsy / BECTS
Carbamazepine
Lamotrigine
Keppra
Sodium valporate
Teratogenic effects of sodium valporate / features of fetal valporate syndrome
Limb defects
Spina bifida
Cleft lip / palate
Heart defects (?VSD)
Reduced fetal growth
Dysmorphic - epicanthic folds, long thin upper lip, flat nasal bridge
Teratogenic effects of phenytoin / fetal hydantoin syndrome
Cleft palate / lip
Reduced growth
Mental deficiency
Congenital heart defects (VSD/ASD/PDA)
Hypoplastic nails and digits
Dysmorphic - indistinct philtrum, micrognathia, short palpebral fissures, epicanthic folds
Mutation most commonly seen in Rett syndrome
Sporadic mutation in MECP2 gene
Can also be X-linked dominant inheritance
Movement stereotypies seen in Rett syndrome
Hand wringing
Clapping
Hand to mouth movements
What cardiac condition is seen in Rett syndrome?
Long QT syndrome
- Note important to avoid medications which prolong the QTc
Which is the most common form of neurofibromatosis?
NF type 1 (makes up 96% of all NF cases)
Clinical / diagnostic features of NF type 1?
Cafe au lait macules (>6)
Lisch nodules (iris hamartomas) (>2)
Skin folding
Neurofibromas
Axillary freckling
Bone lesions (sphenoid dysplasia, scoliosis, long bone abnormalities)
Optic glioma
Inheritance pattern of NF type 1? (and which chromosome is affected?)
Autosomal dominant
Inheritance pattern of NF type 1? (and which chromosome is affected?)
Autosomal dominant
Mutation in NF1 gene on chromosome 17 (gene locus 17q11.2)
What is the biggest risk associated with NF type 1?
Overall risk of malignancy is 2.5-4 times that of the general population
This is because the mutation causes decreased production of neurofibromin which is a tumour suppressor protein
Which specific tumour is highly suggestive of NF2?
Posterior subcapsular tumours
Is there a cure / treatment for NF?
No
Which medication can reduce the size of plexiform neurofibromas?
Imatinib
Consequences / sequelae of NF type 1?
HTN (phaeochromacytomas or renal artery stenosis)
Epilepsy
Pathological bone fractures
Malignancy (brain tumours, leukaemia)
Learning difficulties +/- ADHD
Acute management of raised ICP
A-E approach;
- Protect airway if GCS <8
- 3ml/kg of 3% hypertonic saline (reduces cerebral oedema and improves cerebral perfusion)
- Nurse in midline and at 30 degrees
- IV Dex if RICP due to SOL
Acute management of status epilepticus
First line: IV Lorazepam or PR Diazepam - x2 doses
Second line: Phenytoin or Keppra
Last option: Rapid sequence induction / general anaesthesia
Inheritance pattern of tuberous sclerosis? (and which chromosome is affected?)
Autosomal dominant
Mutations in TSC1 and TSC2 genes found on chromosomes 9 and 16
Clinical features / diagnostic criteria of tuberous sclerosis
> 3 hypopigmented macules (ash leaf spots) - can use wood lamp to help visualise
3 angiofibromas
2 ungal fibromas
Shagreen patch
Retinal harmatomas
2 subependymal nodules (brain)
Subependymal giant cell astrocytoma (brain)
Cardiac rhabdomyoma
Lymphagiomyomatosis
2 angiomyolipomas (kidneys/liver)
Confetti skin lesions
3 dental enamel pits
Adenoma sebaceum (acne like rash)
Which neurocutaneous disorder requires regular suveillance?
TS
Need blood pressure, ECG + echo, U&E, EEG, MRI head, MRI abdomen
In which organs would you see growth of benign tumours / harmatomas in tuberous sclerosis
Brain
Heart
Kidneys
Lungs
Skin
Which medication is 1st line for infantile spasms caused by tuberous sclerosis
Vigabatrin
What do the TSC1 and TSC2 genes code for?
A mutation in which gene will cause more severe clinical manifestations?
TSC1 codes for hamartin
TSC2 codes for tuberin (MORE SEVERE CLINICAL MANIFESTATIONS)
Both are tumour suppressor genes
Organs affected in Friedrich’s ataxia
CNS
- Spinocerebellar tracts
- Dorsal columns
- Pyramidal tracts
- Cerebellum
- Medulla
Heart
- Hypertrophic cardiomyopathy
Pancreas
- DM
Inheritance / genetic abnormality causing Friedrich’s ataxia
Autosomal recessive
GAA repeat expansion in frataxin gene (FXN gene) - codes for the frataxin protein in mitochondria
Novel pharmacological therapies for Friedrich’s ataxia
trials have focussed on antioxidant therapy (reduce oxidative injury caused by iron deposits in mitochondria)
- Vitamin E or Co-enzyme Q10
Life expectancy in Friedrich’s ataxia
40-50
Life expectancy in NF type 1
Live long healthy lives (average life expectancy only reduced by 10-15 years)
Life expectancy in TS
Depends on clinical mainfestations of the disease - most have a normal life span
Typical clinical presentation of TS
Seizures and cutaneous signs
Timescales of neurological sequelae seen following measles infection
Encephalitis
- Usually 5 days following the rash
Acute disseminated encephalomyelitis (ADEM)
- 2 weeks following the rash
Subacute sclerosing panencephalitis
- 7-10 years following the infection
What has been shown to reduce the incidence of sensorineural hearing loss in Hib meningitis
Early administration of IV Dex
Cause of Angelman syndrome
Neurodevelopmental disorder caused by loss of expression of the maternally inherited UBE3A gene
Common presentation in juvenile myoclonic epilepsy
Myoclonic seizures (jerk like movements) soon after waking up / being clumsy first thing in the morning
Up to 80% will also develop generalised TC and absence seizures
Common presentation of frontal lobe epilepsy
Arm posturing / hypermotor activity during sleep
Common presentation of Panayiotopoulos syndrome?
Autonomic features (vomiting) are followed by tonic eye deviation, impairment of consciousness and sometimes evolution to secondary generalised tonic clonic seizure
Note low seizure frequency!
1st line drug for Panayiotopoulos syndrome
Nil - trick question
Most children go into spontaneous remission after a few seizures and don’t require treatment
Seizures seen in Lennox-Gastaut syndrome
Multiple seizure types including atonic, tonic, tonic-clonic and atypical absence seizures
Children also have cognitive impairment
Clinical presentation of language regression with EEG abnormalities seen in sleep
Landau-Kleffner syndrome
In which epilepsy syndrome do seizures most commonly occur at night?
Benign childhood epilepsy with centrotemporal spikes / benign rolandic epilepsy
