Neurology Flashcards
Acquired epileptic aphasia
Landau-Kleffner Syndrome
clinical: normal development then regression in ability to comprehend spoken language at 3-7 yrs
-retain socially appropriate interaction and play patterns
EEG: pattern of status epilepticus in sleep; 80% develop clinical seizures
treatment: AED, steroids, IVIg
prognosis: variable, some may regain language skills
Acute disseminated encephalomyelitis
definition: acute disseminated encephalomyelitis/post infectious encephalomyelitis
incidence: 1/100,000
pathophysiology: demyelinating AI disease of the CNS triggered by an environmental stimulus in susceptible individuals
- usually post a viral infection (coronavirus, coxsackie, CMV, EBV, HSV)
clinical:
- 4 weeks post febrile illness
- fever, headache, vomiting, meningismus
- rapid multifocial neurological deficits
- lasts 2 to 4 weeks
- 10% ongoing deficits
diagnosis:
- MRI: abnormalities vary in location often involve thalami/BG
- CSF: elevated protein
treatment:
- corticosteroids, IVIg, plasma exchange
Adrenoleukodystrophy
incidence: 1/40,000
genetics: XLR ABCD1 coding peroxisomal membrane, variable penetrance
genetic testing: gene sequencing
pathogenesis: peroxisomal disorder with progressive dysfunction adrenal cortex and CNS/PNS due to accummulation VLCFA
clinical 5 types:
-
Childhood cerebral: 4-8yrs rapidly progressive
- initial behavioural issues, auditory problems, poor vision, ataxia, seizures, spasticity/paralysis, hyperpigmentation gums - Adolescent: 10-21 yrs as above but slower
investigations:
- CT/MRI: lack of myelin in parieto-occipital lesions
- CSF: elevated proteins
- serum: elevated VLCFA, poor cortisol response
treatment: adrenal insuff, BMTx, Lorenzo’s oil, dietary restriction
Antiepileptic drug interactions
Antiepileptics
Antiepileptics associated weight gain
- Sodium valproate
- Gabapentin
- Carbamazepine
Chiari Malformations
definition: anatomic anomalies of the cerebellum, brainstem and craniocervical junction with downward displacement of the cerebellum
types:
- Chiari I: abnormally shaped cerebellar tonsils displaced below level foramen magnum
- Chiari II (Arnold Chiari): downward displacement cerebellar vermis and tonsils associated lumbosacral or thoracic myelomeningocele
- Chiari III: rare displacement cerebellar structures into encephalocoele
pathogenesis Chiari II:
- obstruction of CSF outflow through posterior fossa causing hydrocephalus
Ataxia telangiectasia
incidence: 1:100,000
- 2% caucasians carriers
defect: AR ATM gene defect Ch11q22-23 causing abnormal DNA repair/control
clinical onset <2yrs:
- neuro: ataxia, loss of ambulation, chorea, dystonia, poor speech
- eye: oculomotor apraxia, strabismus, nystagmus
- skin: telangiectasia to eyes/nose/ears/extremities 5yrs
- resp: sinopulmonary ix, pulmonary fibrosis
- immune: low IgA/IgG/IgE
- cancer: increased lymphoma, leukaemia, brain tumours (100x)
diagnosis: elevated AFP, MRI normal
prognosis: death by 25yrs
Becker muscular dystrophy
incidence: 1:100,000 (less common than DMD)
defect: X linked recessive dystrophin gene deletion
- not frameshift so you get some dystrophin production
clinical:
- onset later and milder than DMD
- slowly progressive muscle weakness of the LL and pelvis follow by UL weakness
- toe walking, calf hypertrophy and Gower’s manouver
- ambulatory until 15yrs
- cardiac involvement is more evident in BMD
diagnosis: elevated CK, muscle biopsy, genetic testing, EMG
Bell’s Palsy
incidence: 20/100,000
causes: OM, Lyme disease, VZV, HSV
clinical:
- ipsilateral paralysis of face usually over hours
- decreased secretion lacrimal gland (petrosal n.) and submandibular/sublingual nerve (chorda tympani n.)
- loss taste anterior 2/3 tongue
- loss sensation post auricular
- hyperacusis (stapedius)
treatment: prednisone
prognosis: full recovery 90%
Benign focal epilepsy of childhood with CTS
(Benign rolandic epilepsy)
incidence: 4-10yrs, most common childhood epilepsy
symptoms:
- sleep related face/arm movements
- simple partial hemimotor/sensory symptoms, drooling, anarthria, hemiconvulsions, GTCS
- NEVER DAYTIME SX
EEG: spikes in motor area and temporal lobes
prognosis: ALL outgrow, normal development 97%
treatment: carbamazepine
Brain tumour diagram
Carbamazepine
use: complex partial (1st), partial (1st), generalised
mechanism: blocks Na channels
side effects: rash, hepatotoxicity, leukopaenia
rare: worses absence/myoclonic/astatic, aplastic anaemia, thrombocytopaenia, hepatic dysfunction
monitor: FBC/LFTs 1st 3 months, levels
CYP450 inducer: increased metabolism ethosuximide, lamotrigine, topiramate, sodium valproate
- also increases OWN metabolism (autoinduction)
Causes flaccid paralysis
Paralysis from LMN lesion
Brainstem Stroke/encephalitis
Acute anterior poliomyelitis
Acute myelopathy
- SOL (spine occupying lesion)
- acute transverse myelitis
Peripheral neuropathy
- GBS
- post-rabies vaccine neuropathy
- heavy metals, biologic toxins, drugs
- acute porphyria
- critical illness neuropathy
Disorders of Neuromuscular transmission
- MG
Disorders of muscle
- hypokalemia, hypophosphataemia
- inflammatory myopathy
- acute rhabdomyolisis
- periodic paralysis
Causes of weakness
Central core congenital myopathy
defect: AD RYR1 gene producing Ca release from SR
- gene associated malignant hyperthermia
pathophysiology: uncoupling of excitation with calicium release
clinical: non-progressive, hypotonia, facial/proximal weakness, normal reflexes, hip dysplasia, kyphoscoliosis
diagnosis
- biopsy: lack of core staining
Charcot Marie Tooth disease
(Hereditary Motor Sensory Neuropathy)
definition: spectrum of disorders (CMT1-7) with mutation in one of several myelin structure, maintenance and formation genes
genetics (AD)
- CMT1a (50%): PMP22 gene duplication causing demyelinating neuropathy
clinical:
early distal weakness with absent reflexes, pes cavus, hammer toe then:
- distal calf atrophy with sensory (proprio/vibration) loss
- atrophy instrinsic muscles hand/feet
- kyphosis/scoliosis
diagnosis: genetic testing, nerve conduction
treatment: progesterone (increases PMP22), ascorbic acid, neurotrophin-3
Childhood absence seizures
onset: 3-12yrs
symptoms
- induced by hyperventilation
- brief acute onset staring without ictal period
- 40% have GTCS in adolescence
etiology: 30% family hx
EEG: bisynchronous 3hz spike +wave
prognosis: remission in 40% with treatment
treatment: ethosuximide most effective
- carbamazepine/phenytoin WORSEN SX
Childhood ataxia
congenital malformations
- chiari, Dandy-Walker, encephalocele, agenesis cerebellar vermis
infective
- post-infectious (usually viral eg. VZV, echovirus), acute labrynthitis, cerebellar abscess
toxic
- alcohol, thallium, toxic levels AED
metabolic
- abetaloproteinaemia (steatorrhoea/FTT)
degenerative
- ataxia telangiectasia, fredrich ataxia
migraine
- basilar, BPV
vascular
- ischaemic stroke, haemorrhagic stroke
clonazepam
use: absence (Lennon Gastaut), myoclonic, akinetic seizures, multifocal tic disorders
mechanism: enhances GABA, suppresses spike/wave discharge
- associated tolerance
side effects: neuro (amnesia, ataxia), behaviour, drowsiness, agitation, irritability, depression, respiratory depression
CYP450
Diazepam
Midazolam
use: status
mechanism: enhances GABA
side effects: drowsiness, coma
Dravet Syndrome
(Severe myoclonic epilepsy of infancy)
genetics: SCN1A
clinical: 1st year prolonged febrile seizures
- GTC both often hemiclonic
- initially normal development/EEG
- 1-4yrs: myoclonic, absence, clusters GTC
- developmental arrest with EEG slow/polyspikes
treatment: drug resistant
Eosinophilic granuloma
definition: benign histiocytosis in adolescents/adults
clinical: lytic lesions in bone associated with pathological fractures
Epilepsy syndromes and EEG
Erbs palsy
etiology: neonatal brachial plexus injury due to iatrogenic lateral traction of fetal head typically with shoulder dystocia
pathogenesis: C5/6 injury (50%), C5/6/7 (35%)
clinical:
- weakness deltoid and infraspinatus (C5) and biceps (C6)
- arm is adducted and internally rotated with forearm extended
- in C7 is involved they also have flexed fingers/wrist
Ethosuximide
use: absence (1st)
mechanism: blocks Ca channels
side effects: nausea, anorexia
rare: leucopaenia, pancytopaenia, rash
pharmacology: long half life
NO CYP450 effect
First seizure recurrence
normal EEG: 25%
abnormal EEG: 54%
abnormal exam/EEG: 67%
- 88% recurrences will occur within 2 years
Frederich ataxia
defect: AR GAA repeat expansion (>77) Ch9q13 encoding frataxin protein (mitochondrial Fe removal)
diagnosis: genetic testing for repeat
pathogenesis: deficiency causes excess Fe and oxidative damage
clinical degeneration:
- spinocerebellar tracts (proprioception)
- dorsal column (vibration/fine touch/proprioception)
- pyramidal tracts (corticospinal, corticobulbar)
also cerebellum, medulla
clinical:
- neuro: ataxia LL>UL <10yrs and progressive, Romberg +ve, loss of reflexes/proprioception/vibration, dysarthric speech
- skeletal: high arched feet, hammer toes, kyphoscoliosis
also: hypertrophic cardiomyopathy, DM 30%
Frontal Lobe Epilepsy
clinical: clusters of motor seizures often nocturnal
Gabapentin
use: adjuvant for poor control
mechanism: inhibits Ca channel
side effect: weight gain
rare: worsens myoclonic/absence, neurological sx
pharmacology: absorbed saturable AA uptake in GIT, inhibited antacids, renal excretion (unchanged)
half life: 5-7 hours (TDS dosing)
NO CYP450 effect
Genetic Epilepsy with Febrile Seizures
genetics: SCN1A
- eg. Dravet syndrome
clinical:
- febrile seizures >6 years
- GTC seizures in adolescence then remission
Herniation
central (midbrain): sunsetting
cingulate (sufalcine/frontal lobe): most common, coma
tonsillar: headache, neck stiffness, tilt, decreased GCS
transcalvarial (through #)
uncal (temporal): CNIII with PS input causing dilation of pupil
Hypomelanosis of ito
etiology: unknown sporadic
clinical:
- skin lesions 1st year: bizarre, patterned hypopigmented macules over body in demarcated whorls/streaks/patches in lines of Blaschko
- also: MR 70%, seizures 40%, microcephaly 25%, muscular hypotonia 15%, opthal defects 25%
Idiopathic intracranial hypertension
incidence: 1/100,000, obese women 15-44yrs
pathogenesis: signs of raised ICP without identifiable cause
clinical:
- symptoms of raised ICP: papiloedema, CNVI palsy
- headache: severe, lateral, throbbing
- transient visual changes: diplopia, visual field loss
- also: tinnitus, retrobulbar pain
associated conditions: Addison’s hypoPTH, OSA, anaemia, Behcet’s, SLE, PCOS, coag disorders
associated medications: GH, tetracycline, hyper vit A, nalidixic acid, nitrofurantoin, lithium, CS w/d, thyroxine
diagnosis:
- LP: raised ICP
- MRI: flattening posterior sclera, enhancing optic nerve
management: weight loss, low Na diet, carbonic anhydrase inhibitors, frusemide, surgical shunting
- NO steroids
prognosis: lasts months to years
Idiopathic occipital lobe epilepsy
(Gastaut syndrome)
onset: later childhood
symptoms:
- visual hallucinations, ictal blindness
- tonic deviation of eyes, nystagmus, eye fluttering
- diurnal seizures frequent but short
- consciousness preserved
EEG: frontal occipital discharges
prognosis: remission unlikely
Idiopathic occipital lobe epilepsy
(Panayiotopoul os syndrome)
onset: early childhood
symptoms:
- prolonged focal seizures, ictal vomiting/pallor/salivation
- associated ANS sx
- consciousness impaired
- head and eye version
- seizures infrequent
- associated sleep
EEG: frequent epileptic activity from occipital regions
prognosis: 25% single seizure, remission likely
treatment: AED only after 2nd seizure
Incontinentia pigmenti
defect: X-linked dominant mutation in NEMO gene encodes nuclear factor-kB essential modulator protein involved in immune, apoptosis and inflammation
- usually lethal in males so 97% patients are female
4 clinical stages:
stage I: erythematous streaks/plaques of vesicles on limbs/trunk in 1st week
stage II: blistering resolves with hyperkeratotic/verrucous plaques
stage III: hyperpigmented macules in whorls, patches, streaks in lines of blaschko
stage IV: hairless, anhidrotic, hypopigmented patches/streaks
also: CNS 30% (MR, seizures, microcephaly), dental anomalies 80%, nail anomalies 40%, eye defects 30%
Infantile botulism
organism: C.botulinum gram positive rod spore forming
pathogenesis: 1-12 months ingestion of spores invade GI tract and release toxins in vivo
- causes inhibition of release of acetyl choline in the NMJ
clinical: constipation, weakness, feeding difficulties, descending weakness, drooling, irritability, weak cry
treatment: botulinum antitoxin
Infantile spasms
onset: 3-7 months
characteristic: symmetric/synchronous spasms with brief contractions followed by a longer tonic phase
symptoms
- infantile spasms: frequent on waking
- hypsarrythmia on EEG: electrical chaos
- arrest of psychomotor development
west syndrome: triad of infantile spasms, hypsarrythmia and psychomotor developmental arrest
etiology: structural abnormalities, genetic, encephalopathy, T21, TS
treatment: prednisone
Juvenille absence epilepsy
onset: >10yrs
symptoms:
- infrequent absences but longer duration
- occurs on waking
- induced hyperventilation
- 15% myoclonic sx
etiology: polygenic
EEG: fast poly spike wave discharges
treatment: ethosuximide
prognosis: remission lower than CAE
Juvenille myoclonic epilepsy
incidence: 12- 18yrs, 10% all epilepsy
symptoms: early morning myoclonus
- can have GTCS on waking
- triggered sleep deprivation, fatigue, EtOH
etiology: genetic
EEG: 4-6Hz poly spike wave slow discharge
prognosis: lifelong but response to treatment
treatment: valproate
Klumpke’s palsy
etiology: brachial nerve injury with shoulder traction during birth
pathogenesis: C8/T1 injury (lease common)
clinical: isolated hand paralysis and Horner’s syndrome
Krabbe disease
(Globoid cell leukodystrophy)
defect: XLR deficiency of galactocerebrosidase (LSD)
pathophysiology: accummulation of loposomes
clinical:
- infantile: 5 months, irritable, DD, spasticity, absent reflexes, optic atrophy, microcephaly
j_uvenille:_ weakness, loss of skill/vision
diagnosis:
MRI: occipito-parietal changes
CSF: elevated protein
Lamotrigine
(Lamictil)
use: partial, GTCS, absence, tonic/atonic (1st)
mechanism: blocks Na channels, decreases GLUT release
side effect: rash (within 2 months)
rare: worses SMEI, SJS, hypersensitivity
half life: 22-37 hours
NO CYP effect
Leigh syndrome
definition: subacute necrotising encephalopathy
pathophysiology: altered mitochondrial metabolism
clinical: onset infancy
- dev delay, psychomotor regression, ataxia, dystonia, external opthalmoplegia, seizures, lactic acidosis, vomiting, weakness
diagnosis
histology: bilateral symmetric necrotizing lesions with spongy changes and microcysts in the basal ganglia, thalamus, brainstem, spinal cord
MRI: abnormal white matter signals in putamen, brainstem, basal ganglia
serum: elevated lactate
LP: elevate lactate/protein
prognosis: death within months of disease
Lennox Gastaut syndrome
incidence: 2-3% childhood epilepsy, M>F
onset: 3-5yrs
symptoms (triad):
- generalised seizures or atypical absence
- interictal EEG: <2.5Hz slow spike wave
- MR
etiology: 30% previously normal, some evolve from infantile spasms
EEG: slow spike wave
prognosis: intractable seizures, MR
treatment: valproate
Levetiracetam
(Keppra)
use: partial seizures adjunct
mechanism: unknown
side effects: sleep disturbance, psychosis, behavioural issues, fatigue
pharmacology: renal excretion
NO CYP450 effect
Localisation motor neuron disease
Long term neurological outcomes
- neonates-
Management seiziure
1st drug: 50% seizure free
2nd drug: 18% seizure free
- 33% remain drug resistant
Metachromic leukodystrophy
incidence: 1:100,000
defect: AR mutation ARSA gene coding arylsulfatase A
pathogenesis: accummulation of cerebroside sulfate destroying myelin
clinical 3 types:
-
Late infantile: 1-2yrs
- weakness, hypotonia, absent reflexes, bulbar palsy, ID
- within 1 yr can’t sit supported/decorticate posture and die by 6 yrs - Juvenile: 3-16yrs symptoms as above
- Adult: >16yrs with personality/psychiatric disturbances
investigations:
- slowed nerve conduction
- MRI: diffuse lack of white matter/cortical atrophy
treatment: BMTx
Migraine management
Abortive treatment
1st line: NSAIDS, naproxen
- avoid aspirin
2nd line: triptans (serotonin agonist)
Prophylaxis
1st line:
- <6yrs cryoheptadine (histamine/serotonin antagonist)
- >6yrs propranolol
- valproate/topiramate if not tolerating above
- amitriptyline if mixed disorder/depression
Mitochondrial myopathy
definition: group of disorders caused by mitochondrial respiratory chain dysfunction
pathophysiology: dysfunction of organs with aerobic metabolism
Disorders
Barth syndrome: XL cardiomyopathy, myopathy, cyclic neutropaenia
Leber hereditary optic neuropathy
Leigh syndrome: subacute necrotizing encephalomyopathy
MELAS: mitochondrial encephalopathy with lactis acidosis and stoke like symptoms
Pearson syndrome: sideroblastic anaemia and pancreatic dysfunction
diagnosis
serum: high lactate
biopsy: accummulation of mitochondria “ragged red fibres”
Moya Moya
incidence: 1/100,000 all ages but rare infancy
pathogenesis: chronic progressive cerebrovascular disease characterised by bilateral stenosis/occulsion of the arteries around the CoW
clinical: TIA, ischaemic stroke, haemorrhagic stroke, epilepsy
associations: meningitis, haem conditions, AI disease
imaging:
CT: infarction
MRI angio: stenosis or occlusive leasions in the distal internal carotid arteries and circle of willis
Myoclonic absence epilepsy
(Tassinari syndrome)
symptoms:
- behavioural arrest
- upward myoclonic jerking upper limbs
- proviked by hyperventilation
EEG: 3Hz spike wave
Prognosis: poor response to treatment
Myoclonic astatic epilepsy
onset: 1-8yrs
symptoms: myoclonic/myoclonic astatic seizures
- fall due to myoclonic jerk
EEG: paroxysmal 4Hz theta bursts with fast generalised spike/polyspikes
prognosis: variable
treatment: valproate
Myotonic dystrophy
incidence: 1/7,000
transmission: AD (mother 94%)
defect DMI1: CTG triplet repeat expansion >50 copies in gene DMPK for myotonic dystrophy protein kinase
defect DM2 (rarer/milder): CCTG repeat in ZNF9 gene
- with anticipation
defect DM3 (late form): Ch15
biopsy: increased interalised nuclei, atrophic muscle
clinical: myopathic facies, myotonia, weakness distal>proximal
- facies: scalloped, concave temporalis muscle, tented V upper lip, ptosis, high palate, long thin neck/tongue
- CNS: personality, MR 24%, dysphagia
- endocrine: delayed puberty, hypogonadism, DM, hypothyroidism
- eyes: cataracts, ptosis
- resp: hypoventilation, asp pneumo, anaesthetic complications
- cardiac: HB, arrhythmias, cardiomyopathy
- GI: dysphagia, constipation, megacolon, low IgG
severe neonatal form: polyhydramnios, weakness, hypotonia, respiratory distress
- usually babies to symptomatic mothers (DM1)
diagnosis:
- serum: CK in 100s
- DNA: abnormal CTG repeat
Nemaline congenital myopathy
incidence: most common congenital myopathy
genetics: heterogenous
pathophysiology: abnormalities in thin filaments of skeletal muscle
clinical: weakness proximal, hypotonia, motor delay, respiratory insufficiency, feed intolerance, EOM spared
- NO cardiac involvement
diagnosis:
- serum: elevated CK
- biopsy: rod bodies in muscle
Nerve conduction studies
measure 2 parameters:
latency: velocity of conduction
- decreased in demyelination
amplitude: measures peak conduction
- decreased in axonal loss
Neural tube defects
encephalocoele: midline defect skull with protrusion meninges/brain
myelomeningocoele: herniation of meninges/SC through vertebral defect
pathophysiology
- genetic: 1 child/parent 4%, 2 children 10%
- folic acid deficiency: 0.5mg low risk decreases 36%, 5mg high risk decreases 85%
- drugs: trimethoprim, anticonvulsants, MTX, clomiphene
- maternal comorb: DM, hyperthermia
Neuroleptic Malignant Syndrome
pathophysiology: increased calcium release from SR
causes: adverse effect to antiepileptic or antipsychotic
risk factors: increased rapid dose, potent drugs, NMDA meningitis
clinical: muscle rigidity, fever, autonomic instability, cognitive changes (delirium), altered GCS
management: cease agent, dantrolene
*serotonin syndrome is similiar but with decreased reflexes
Neuronal ceroid lipofucinosis
definition: lysosomal storage disease (most common neurodegenerative disease of children)
pathogenesis: abnormal accummulation of lipofuscin in organs
clinical:
- infantile: 1st with myoclonic seizures, MR, blindness, brown discolouration macula, ataxia, death <10yrs
- late infantile: 2-4yrs with dementia, ataxia, decreased VA and microcephaly
- juvenille: 5-10yrs, decreased VA, intellectual impairment
diagnosis:
histology: storage of autofluorescent substance in lysosomes
Nightmares
clinical:
- last 1/3 night in REM sleep
- mild-high autonomic arousal
- easily awoken
- sometimes increased sleep deprivation
- rarely FHx
Noctural seizures
clinical:
- non-REM>awake>REM
- usually sleep-wake transition
- variable autonomic arousal
- amnesic to event
- associated incontence, biting, drooling, postictal period
- increased with sleep deprivation
Optic neuritis
incidence: 6/100,000
pathogenesis: inflammatory and demyelination of the optic nerve
clinical:
- women (2/3) at 20-30 yrs
- monocular visual loss (10% bilateral more in children 12-15yrs) over hours to days
- eyes pain in 90%
associations: MS
PANDAS
Paediatric AI Neuropsychiatric Disorders
associated Group A Streptococcus
definition: OCD or tic exacerbations by Group A strep infections
pathogenesis: AI response with CNS manifestations
Parasomnias
age: 4-12 years
clinical:
- 1st 1/3 of sleep with slow wave sleep (non-REM)
- awakes abruptly with scream/agitation
- flushed, sweating and tachycardic
- may jump out of bed
- unresponsive to carming
- no memory of event
- increased sleep deprivation
- common FHx
investigations: if OSA, restless legs, safety, or >1/night
EEG: high amp, rhythmic delta or theta activity
management (only if problematic):
- behavioural techniques: wake prior to event
- medication: low dose benzo
Periventricular leukomalacia
pathogenesis: white matter injury from focal necrosis secondary to infection/ischaemia resulting cystic formation
- most common in premature infants as premature brain more vulnerable to vascular cellular factors
clinical: CP, ID, visual disturbances
Phenobarbitone
use: neonatal (1st), status
mechanism: enhances GABA, blocks Na channels, binds NMDA
side effects: rash, megaloblastic anaemia, osteomalacia, DD
rare: SJS, hepatic dysfunction
monitor: levels
pharmacology: renal excretion
CYP P450 inducer: increased metabolism carbamazepine, ethosuximide, lamotrigine, sodium valproate
Phenytoin
(dilantin)
use: status (1st), neonatal (1st), partial, GTCS
mechanism: blocks Na channels
side effects: hirsutism, megaloblastic anaemia
side effects: WORSENS absence seizures, hepatic dysfunction, LN, movement disorders, SJS, hepatic dys
monitor: levels
pharmacology: zero order, narrow TI
CYP450 inducer: increased metabolism carbamazepine, ethosuximide, lamotrigine, topiramate, sodium valproate
Pinealoma
pathophysiology: tumour pineal gland (control circadian rhythm)
- pineocytes, astrocytomas or germ cell
clinical: insomnia
- may be associated Parinaud’s syndrome: paralysis upward gaze, nystagmus, eyelid retraction and light near dissociation
Pompe disease
(congenital)
defect: glycogen storage disease II
- AR mutations in GAA causing lysosomal acid maltase deficiency
clinical: onset 4months
- cardiomyopathy respiratory compromise, severe generalised muscular hypotonia, macroglossia, hepatomegaly
diagnosis: (on Guthrie)
- serum: CK++++++
- biopsy: myopathy with glycogen within lysosomes
- EMG: myopathic changes
treatment:
- enzyme replacement (myozyme)
- high protein/low carb diet
Porencephaly
pathogenesis: congenital porencephalic cyst/s appear as a fluid-filled cavicuty in the cerebral hemisphere
- intra-axial and lined with white matter
Renally excreted antiepileptics
Most antiepileptics lipid soluble (cross BBB) and hepatic metabolism
3 EXCEPTIONS with renal metabolism: gabapentin, levetiracetam, vigabatrin
*Na valproate is water soluble but still hepatic metabolism
Reye Syndrome
incidence: 1/million
pathogenesis: inborn error of metabolism predisposing
clinical: days post viral illness (influenza A/B) or aspirin
- rapidly progressive encephalopathy
- vomiting, confusion, seizures and coma
- hepatomegally
diagnosis: mild elevated LFTs, increased PT, high ammonia/BGL, metabolic acidosis
Sensory innervation of the hand
Severe myoclonic epilepsy of infancy
onset: <1 yr
symptoms:
1st year: atypical hemiclonic generalised febrile seizures
2nd year: afebrile focal polymorphic seizures
etiology: sporadic mutations in SCN1A (Na channel)
EEG: initially normal then multifocal polyspike waves
prognosis: developmental regression, ataxia, temp/photic sensitivity trigger seizures
treatment: valproate, topiramate, clonazepam
Sodium valproate
use: GTC (1st), myoclonic (1st), absence, partial, akinetic
mechanism: enhances GABA, blocks Na channels
side effects: anorexia, amenorrhoea, weight gain, alopecia, hepatotoxicity
rare: pancreatitis, hepatic failure, hyperammonaemia
pharmacology: near complete bioavailability, liver failure (2nd drug/<3yrs)
half life: 8-12 hours
CYP inhibitor: decreased metabolism lamotrigine, carbamazepine, phenytoin, phenobarbitone
Spinal muscular atrophy
defect: AR mutation SMN1/SMN2 gene producing SMN protein
pathophysiology: loss of SMN protein causes loss of neurons from AHC and sx of motor nerves
types (see table)
clinical:
- progressive muscle wasting (proximal>distal)
- areflexia
- developmental delay
diagnosis:
- serum: CK normal/elevated
- genetic testing: SMN gene
- biopsy: perinatal denervation
- EMG: active denervation
Sturge Weber syndrome
NOT inherited
pathogenesis: vascular disorder of capillary vessels
- etiology unknown
clinical:
facial angioma: (port-wine stain) forehead/upper eyelid in distribution 1st/2nd trigeminal nerve, apparent at birth
- BUT 90% PWS NOT SWS
l_eptomeningeal angioma_: 90% when PWS involve upper and lower eyelids, 10% if one eyelid
ALSO
- ocular: glaucoma (bupthalmos: congenital open angle glaucoma 50%), vascular malformations
- neuro: seizures, focal deficiits, MR (50% adults), behaviour issues, visual field defect, hydrocephalus
- growth hormone deficiency
diagnosis:
- MRI: presence of leptomeningeal angioma
prognosis: depends on extent leptomeningeal angioma
Teeth
development in utero:
- dental lamina formed around the 4th to 6th week - development permanent teeth at 20th weeks
- calcification of the primary embryonic tooth at 3-4 months
eruption of Primary Teeth:
- 6 months- 2 years
- central/lateral incisors then the first primary molars, canines and the second primary molars
eruption of Permanent Teeth:
- upper and lower incisor teeth are exfoliated first 6 to 8yr and remaining canine 9 to 12yrs
- the initial permanent teeth to appear are the first permanent molars behind the last standing primary molar
Temporal Lobe Epilepsy
incidence: 10 yrs- adult
risk factors: febrile seizures, CNS infection, trauma
clinical: focal w/o changes in awareness
- autonomic, psychic or sensory
- 40% automatisms
neuroimaging: hippocampal atrophy, neoplasms, vascular, normal
prognosis: control in 70%
Topiramate
use: adjuvant poor control, migraines
use: blocks voltage dep Na channels, augments GABA
side effects: metabolic acidosis, nephrolithiasis (calcium phosphate stones), weight loss, cognitive dysfunction
CYP450 inducer: increased metabolism sodium valproate
Vigabatrin
use: infantile spasm
mechanism: increase GABA
rare: worsens GTC/absence/myoclonic, weight gain, visual field loss, psychosis, retinopathy
pharmacology: renal excretion
NO CYP450 effect
Landau Kleffner Syndrome
definition: acquired epileptic aphasia
incidence: 2-8yo
clinical: regression in language, associated seizures/behaviour disturbances
EEG: continuous status epilepticus of sleep
treatment: difficult
Tics
prevalence: 4-24%, M>F, onset 6-7 yrs, peak 13 yrs
pathogenesis: dopamine dysfunction basal ganglia
clinical: stereotyped, brief, repetitive, sudden motor or vocal head and upper body
prognosis: 50% resolve 18yrs
treatment: clonidine if QOL affected
RAPD
definition: pupils respond differently to light stimulus
pathogenesis: afferent pupillary defect
causes:
optic nerve disorders: neuritis, ischaemic, glaucoma, tumours, inflammation
orbital disease: compressive damage to nerve
MOST COMMON CAUSE IN CHILDREN: OPTIC GLIOMA
