Neurology Flashcards
1
Q
Acquired epileptic aphasia
Landau-Kleffner Syndrome
A
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
2
Q
Acute disseminated encephalomyelitis
A
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
3
Q
Adrenoleukodystrophy
A
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
4
Q
Antiepileptic drug interactions
A
5
Q
Antiepileptics
A
6
Q
Antiepileptics associated weight gain
A
- Sodium valproate
- Gabapentin
- Carbamazepine
7
Q
Chiari Malformations
A
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
8
Q
Ataxia telangiectasia
A
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
9
Q
Becker muscular dystrophy
A
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
10
Q
Bell’s Palsy
A
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%
11
Q
Benign focal epilepsy of childhood with CTS
(Benign rolandic epilepsy)
A
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
12
Q
Brain tumour diagram
A
13
Q
Carbamazepine
A
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)
14
Q
Causes flaccid paralysis
A
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
15
Q
Causes of weakness
A
16
Q
Central core congenital myopathy
A
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
17
Q
Charcot Marie Tooth disease
(Hereditary Motor Sensory Neuropathy)
A
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
18
Q
Childhood absence seizures
A
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
19
Q
Childhood ataxia
A
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
20
Q
clonazepam
A
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
21
Q
CYP450
A
22
Q
Diazepam
Midazolam
A
use: status
mechanism: enhances GABA
side effects: drowsiness, coma
23
Q
Dravet Syndrome
(Severe myoclonic epilepsy of infancy)
A
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
24
Q
Eosinophilic granuloma
A
definition: benign histiocytosis in adolescents/adults
clinical: lytic lesions in bone associated with pathological fractures
25
Epilepsy syndromes and EEG
26
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
27
Ethosuximide
**use:** absence (1st)
**mechanism:** blocks Ca channels
**side effects:** nausea, anorexia
**rare:** leucopaenia, pancytopaenia, rash
**pharmacology:** long half life
**NO CYP450 effect**
28
First seizure recurrence
**normal EEG:** 25%
**abnormal EEG**: 54%
**abnormal exam/EEG:** 67%
- 88% recurrences will occur within 2 years
29
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%
30
Frontal Lobe Epilepsy
clinical: clusters of motor seizures often nocturnal
31
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**
32
Genetic Epilepsy with Febrile Seizures
**genetics:** SCN1A
- eg. Dravet syndrome
**clinical:**
- febrile seizures \>6 years
- GTC seizures in adolescence then remission
33
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
34
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%
35
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
36
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
37
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
38
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%
39
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
40
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
41
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
42
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
43
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
44
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
45
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**
46
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
47
Lennox Gastaut syndrome
**incidence:** 2-3% childhood epilepsy, M\>F
**onset:** 3-5yrs
**symptoms (triad):**
1. generalised seizures or atypical absence
2. interictal EEG: \<2.5Hz slow spike wave
3. MR
**etiology:** 30% previously normal, some evolve from infantile spasms
**EEG:** slow spike wave
**prognosis:** intractable seizures, MR
**treatment:** valproate
48
Levetiracetam
| (Keppra)
**use:** partial seizures adjunct
**mechanism:** unknown
**side effects:** sleep disturbance, psychosis, behavioural issues, fatigue
**pharmacology:** renal excretion
**NO CYP450 effect**
49
Localisation motor neuron disease
50
Long term neurological outcomes
- neonates-
51
Management seiziure
**1st drug:** 50% seizure free
**2nd drug:** 18% seizure free
- 33% remain drug resistant
52
Metachromic leukodystrophy
**incidence:** 1:100,000
**defect:** AR mutation ARSA gene coding arylsulfatase A
**pathogenesis:** accummulation of cerebroside sulfate destroying myelin
**clinical 3 types:**
1. _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
2. _Juvenile_: 3-16yrs symptoms as above
3. _Adult:_ \>16yrs with personality/psychiatric disturbances
**investigations:**
- slowed nerve conduction
- MRI: diffuse lack of white matter/cortical atrophy
**treatment:** BMTx
53
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
54
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"
55
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
56
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
57
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
58
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
59
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
60
Nerve conduction studies
**_measure 2 parameters:_**
**latency:** velocity of conduction
- decreased in demyelination
**amplitude:** measures peak conduction
- decreased in axonal loss
61
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
62
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
63
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
64
Nightmares
**clinical:**
- last 1/3 night in REM sleep
- mild-high autonomic arousal
- easily awoken
- sometimes increased sleep deprivation
- rarely FHx
65
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
66
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
67
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
68
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
69
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
70
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
71
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
72
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
73
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
74
Porencephaly
**pathogenesis:** congenital porencephalic cyst/s appear as a fluid-filled cavicuty in the cerebral hemisphere
- intra-axial and lined with white matter
75
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
76
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
77
Sensory innervation of the hand
78
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
79
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
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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
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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
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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
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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%
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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
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Vigabatrin
**use: i**nfantile spasm
**mechanism:** increase GABA
**rare:** worsens GTC/absence/myoclonic, weight gain, visual field loss, psychosis, retinopathy
**pharmacology:** renal excretion
**NO CYP450 effect**
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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
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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
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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_
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