Neurology

Question 1

A static abn in development from birth suggest a …

Answer 1

congenital, intrauterine or perinatal cause

Question 2

A loss of skills (regression) over time strongly suggests an…

Answer 2

underlying degenerative disease of the CNS, such as an inborn error of metabolism

Question 3

Describe the upper limits of normal for gross motor, fine motor, social skills and language at 3 months of age?

Answer 3

Question 4

Describe the upper limits of normal for gross motor, fine motor, social skills and language at 6 months of age?

Answer 4

Question 5

Describe the upper limits of normal for gross motor, fine motor, social skills and language at 9 months of age?

Answer 5

Question 6

Describe the upper limits of normal for gross motor, fine motor, social skills and language at 12 months of age?

Answer 6

Question 7

Describe the upper limits of normal for gross motor, fine motor, social skills and language at 18 months of age?

Answer 7

Question 8

Describe the upper limits of normal for gross motor, fine motor, social skills and language at 24 months of age?

Answer 8

Question 9

Tay-Sachs occurs more commonly in which ethnic group?

Answer 9

Ashkenazi Jewish population

Question 10

Consanguineous marrianges have higher rates of …

Answer 10

metabolic and degenerative disorders of the CNS

Question 11

Describe the rate of average head growth in premature infants

Answer 11

0. 5cm in first 2 weeks
1. 75cm in 3rd week

1cm in 4th week and every week thereafter until 40th week of development

Question 12

What is the average head circumference of term infants at birth, 6 months, and 1 yr?

Answer 12

34-35cm at birth

44cm at 6 months

47cm at 1yr

Question 13

Broad causes of microcephaly?

Answer 13

May develop in utero or postnatally and may, for example be related to intrauterine infection, drug exposure, or to perinatal or postnatal injury

Question 14

Broad causes of macrocephaly?

Answer 14

most commonly familial, but may be from disturbane of growth, neurocutaneous disorder (e.g. NF), chromosomal defects (e.g. Kleinfelter syndrome), or storage disorder

Question 15

What is a meningocele?

Answer 15

Meninges herniates through a defect in the posterior vertebral arches or anterior sacrum

The spinal cord is usually
normal and assumes a normal position in the spinal canal, although there may be
tethering of the cord, syringomyelia, or diastematomyelia. A fluctuant midline
mass that might transilluminate occurs along the vertebral column, usually in the
lower back. Most meningoceles are well covered with skin and pose no
immediate threat to the patient

Question 16

What is a myelomeningocele? What is the incidence?

Answer 16

Most severe form of dysraphism

Involves the vertebral column and spinal cord

Incidence is 1 in 4000 live births

Question 17

Cause of myelomeningocele?

Answer 17

Unknown

As with all NTC defects, including anencephaly, a genetic predisposition exists; risk of recurrence after one affected child is 3-4% and increases to 10% with two prior affected children

Epidemiologic evidnce and presence of substantial familial aggregation of anencephaly, myelominingocele and craniorachischisis indicate heredity, on a polygenic basis, as a sig contributor to etiology of myelomeningocele as well

Folate is intricately involved in the prevention and etiology of NTDs

Question 18

Prevention of myelomeningocele?

Answer 18

Folic acid

Drugs that antagonise folic acid, such as trimethoprim and anticonvulsants carbamazepine, phenytoin, phenobarbital, and primidone, increase risk of myelomeningocele

Valproic acid causes NTDs in about 1-2% of pregnancies when given during pregnancy

Question 19

Clinical manifestations of myelomeningocele?

Answer 19

Dysfunction including skeleton, skin, gastrointestinal and genitourinary tract dysfunction

Question 20

Myelomeningocele most common location and symptoms?

Answer 20

Can be located anywhere along the neuaxis, but lumbosacral region accounts for at least 75% of the cases

Lesions in low scaral region cause bowel and bladder incontinence assoc w/ anesthesia in the perineal area but with no impairment of motor function

newborns with defect in midlumbar or high lumbothoracic region typically have either a sac-like cystic structure covered by a thin layer of partially epithelialised tissue

Question 21

Exam findings in myelomeningocele?

Answer 21

flaccid paralysis of the lower extremities, absence of deep tendon reflexes, lack of response to touch and pain, high incidence of lower-extremity deformities (clubfeet, ankle and/or knee contractures, and subluxation of the hips)

Myelomeningocele above the mid-lumbar region tends to produce LMN signs due to abn and disruption of the conus medullaris and above spinal cord structures

Question 22

Seizure patterns in newborns?

Answer 22

Apnea with tonic stiffening of body

focal clonic movement of one limb or both limbs on one side

multifocal clonic limb movement

myoclonic jerking

paroxysmal laughing

tonic deviation of the eyes upward or to one side

tonic stiffening of the body

Question 23

What is the most common paroxysmal neurological disorder of the newborn?

Answer 23

Seizures

Occurs in 1.8%-3.5% of live birth

Question 24

How do uncontrolled seizures contribute to further brain damage?

Answer 24

Brain glucose decreases during prolonged seizures and excitatory amino acid release interferes with DNA synthesis

Question 25

What are some movements that resemble neonatal seizures?

Answer 25

Benign nocturnal myoclonus

jitteriness

nonconvulsive apnea

normal movement

opisthotonos

pathological myoclonus

Question 26

Signs of seizure activity in paralyzed (MV) neonates?

Answer 26

rhythmic increases in systolic arterial BP, HR, and oxygenation desaturation should alert physicians to the possibility of seizures

Question 27

What does the term ‘subtle seizure’ mean?

Answer 27

tonic or clonic movements of the limbs are lacking

Question 28

Clinical features of focal clonic seizures in newborns?

Answer 28

Repeated, irregular slow clonic movements (1-3 jerks/second) affecting 1 limb or both limbs on one side

Rarely do such movements sustain for long periods and they do not ‘march’ as though spreading along the motor cortex

in an otherwise alert and responsive full-term newborn, unifocal clonic seizures always indicate a cerebral infarction or hemorrhage, or focal brain dysgenesis

In newborns with states of dec consciouisness, focal clonic seizures may indicate a focal infarction superimposed on a generalised encephalopathy

Question 29

Diagnosis of focal clonic seizures in newborns?

Answer 29

EEG: unilateral focus of high-amplitude sharp waves adjacent to the central fissure

discharge can spread to involve contigeous areas in the same hemisphere and can be associated with unilateral seizures of the limbs and adverse movements of the head and eyes

Interictal EEG: may show focal slowing, sharp waves, or amplitude attenuation

Newborns should get an MRI w/ diffusion weighted images. US is acceptable for neonates who are too unstable

Question 30

Clinical features of multifocal clonic seizures in newborns?

Answer 30

migratory jerking movements noted in first one limb and then another

facial muscles may be involved

migration appears random and does not follow expected patterns of epileptic spread

sometimes prolonged mvmts occur in one limb suggesting a focal rather than a multifocal seizure - detection of multifocal nature comes later, when nursing notes appear contradictory concerning side or limb affected

usually assoc w/ severe, generalised cerebral disturbances such as HIE, but may represent benign neonatal convulsions when noted in an otherwise healthy neonate

Question 31

Diagnosis of multifocal clonic seizures in newborns?

Answer 31

Standard EEG usually detects multifocal epileptiform activity. 24hr video-EEG monitoring is the best diagnostic test to confirm diagnosis

Question 32

Clinical features of myoclonic seizures in newborns?

Answer 32

Brief, nonrhythmic extension and flexion mvmts of the arms, legs, or all limbs characterise myoclonic seizures

uncommon seizure pattern in the newborn, but presence suggests severe, diffuse brain damage

Question 33

Diagnosis of myoclonic seizures in newborn?

Answer 33

nil specific EEG pattern

myoclonic jerks often occur in babies born to drug-addicted mothers –> ?seizure vs. jitteriness, or myoclonus

myoclonus noticed in an otherwise normal newborn may be a normal involuntary motion (benign myoclonus of drowsiness)

Question 34

clinical features of tonic seizures in newborns?

Answer 34

extension and stiffening of the body, usually associated with apnea and upward deviation of the eyes

tonic posturing w/o the other features is rarely a seizure manifestation

Question 35

diagnosis of tonic seizures in newborns?

Answer 35

often a Sx of intraventricular hemorrhage and an indication for US study

tonic posturing also occurs in newborns w/ forebrain damage, not as a seizure manifestation, but as a disinhibition of brainstem reflexes

Prolonged disinhibition results in decerebrate posturing, an extension of the body and limbs assoc w/ internal rotation of the arms, dilation of the pupils, and downward deviation of the eyes

decerebrate posturing is often a terminal sign in premature infants w/ intraventricular hemorrhage caused by pressure on the upper brainstem

tonic seizures and decerebrate posturing look similar to opisthotonos, a prolonged arching of the back not necessarily assoc w/ eye mvmts. Cause of opisthotonus is likely meningeal irritation. It occurs in kernicterus, intantile Gaucher disease and some aminoacidurias

Question 36

When might opisthotonus occur in?

Answer 36

Kernicterus, infantile Gaucher disease, and some aminoacidurias

Question 37

Clinical features of apnea in newborns?

Answer 37

irregular resp pattern w/ intermittent pauses of 3-6 seconds, often followed by 10-15 seconds of hyperpnea –> common occurrence in premature infants

nil assoc w/ changes in HR, BP, temp, or skin colour

immaturity of bran-stem resp centers causes this resp pattern, termed periodic breathing

incidence of periodic breathing correlates directly w/ degree of prematurity

apneic spells are more common during active than quiet sleep

Apneic spells of 10-20s are usually assoc w/ a 20% reduction in HR

Longer episodes usually assoc with a 40% or greater reduction in HR

frequency of apneic spells correlates w/ brainstem myelination

apnea w/ bradycardia is unlikely to be a seizure

apnea w/ tachycardia raises possibility of seizure and should be eval w/ simultaneous video EEG recording

Question 38

Diagnosis of apneic spells in neonates?

Answer 38

typically sign of brainstem immaturity and not a pathological condition

sudden onset apnea and states of dec consciousness, esp in premature newborns, suggests an intracranial hemorrhage w/ brainstem compression –> immediate US exam is in order

apneic spells are almost never a seizure unless assoc w/ tonic deviation of eyes, tonic stiffening of the body, or characteristic limb mvmts

prolonged apnea w/o bradycardia, and esp w/ tachycardia, is a seizure until proven otherwise

Question 39

Management of apnea in newborns?

Answer 39

short episodes do not need intervention. The rare epileptic apnea requires the use of anticonvulsant agents

Question 40

Clinical features of benign nocturnal myoclonus

Answer 40

sudden jerking mvmts of limbs during sleep occur in normal people of all ages

appear primarily during early stages of sleep as repeated flexion mvmts of fingers, wrists, and elbows

jerks do not localise consistently, stop with gentle restraint, and end abruptly with arousal

when prolonged, usual misdiagnosis is focal clonic or myoclonic seizures

Question 41

diagnosis of benign noctural myoclonus in newborns?

Answer 41

distinction between noctural myoclonus and seizures or jitteriness is that benign nocturnal myoclonus occurs solely during sleep, is not activated by a stimulus, and the EEG is normal

Question 42

management of benign nocturnal myoclonus in newborns?

Answer 42

treatment is unnecessary, and education and reassurance are usually sufficient

if violent myoclonus with subsequent frequent arounsals which disrupts sleep –> clonazepam may be considered

Question 43

clinical features of jitteriness in newborns?

Answer 43

excessive response to stimulation

touch, noise, or motion provokes a low-amplitude, high-frequency shaking of the limbs and jaw

common assoc w/ a low threshold for the moro reflex, but can occur in the absence of any apparent stimulation and be confused with myoclonic seizures

Question 44

diagnosis of jitteriness in newborns?

Answer 44

usually occurs in newborns w/ perinatal asphyxia, along with the occurrence of seizures

EEG monitoring, absence of eye mvmts or alteration in resp pattern, and presence of stimulus activation distinguishes jitteriness from seizures

newborns of addicted mothers and newborns w/ metabolic disorders are often jittery

Question 45

management of jitteriness in newborns?

Answer 45

reduced stimulation decreases jitteriness

newborns of addicted mother require sedation to facilitate feeding and to dec energy expenditure

Question 46

clinical features of hyperekplexia

Answer 46

exaggerated startle to tactile or auditory stimulation

often assoc w/ freq falls when ambulatory, and hypertonia more than normal or low muscle tone

7-12% of these newborns may have seizures

apnea and developmental problems are frequent comorbidities

three genes involed, all of which affect the glycinergic neurotransmission

Question 47

diagnosis of hyperekplexia

Answer 47

Dx made based on phenotype

Gene positive cases present at birth, but about 50% of the cases w/o known genetic etiology present after the first month of life

Question 48

management of hyperekplexia

Answer 48

clonazepam is effective in most cases

Question 49

Seizures occuring during the first 24 hours, and especially in the first 12 hours in newborns are usually due to?

Answer 49

HIE

Sepsis, meningitis, and SAH are next in frequency, followed by intrauterine infection, and trauma

direct drug effects, IVH at term, and pyridoxine and folinic acid dependency are relatively rare causes of seizures, but important to consider as they are treatable conditions

Question 50

More common causes of seizures during period from 24-72 hours after birth are? DDx in this period of time?

Answer 50

IVH in premature newborns, SAH, cerebral contusion in large full-term newborns, and sepsis and meningitis at all gestational ages

Cause of unifocal clonic seizures in full-term newborns is often cerebral infarction or intracerebral hemorrhage

MRI w/ diffusion weighted images is diagnostic

cerebral dysgenesis may cause seizures

metabolic disorders: newborns are usually lethargic and feed poorly before onset of seizures - seizures are rarely the first clinical feature

Question 51

Causes of seizures beyond 72 hours of age in neonates?

DDx during this period?

Answer 51

initiation of protein and glucose feedings makes inborn errors of metabolism, esp aminoaciduria, a more imp consideration

Conditions that cause early and late seizures include cerebral dysgenesis, cerebral infarction, intracerebral hemorrhage, and familial/genetic neonatal seizures

Question 52

What is maple syrup urine disease?

Answer 52

Almost complete absence (< 2% of normal) of branched-chain keto-acid dehydrogenase (BCKD) causes the neonatal form of MSUD

Question 53

Genetic abnormality in maple syrup urine disease?

inheritance pattern?

Answer 53

BCKD (branched-chain deto-acid dehydrogenase) is composed of six subunits, but the main abn in MSUD is deficiency of the E1 subunit on chromosome 19q13.1-q13.2

Leucine, isoleucine, and valine cannot be decarboxylated, and accumulate in blood, urine, and tissues

Autosomal recessive

Question 54

Clinical features of maple syrup urine disease in newborns?

Answer 54

affected newborns appear healthy at birth but lethargy, feeding difficulty, and hypotonia develop after protein ingestion

progressive encephalopathy develops by 2-3 days postpartum

encephalopathy includes lethargy, intermittent apnea, opisthotonos, and sterotyped mvmts such as ‘fencing’ and ‘bicycling’

Coma and cenrtal resp failure may occur by 7-10 days of age

seizures begin in second week and assoc w/ development of cerebral oedema

once seizure start they continue with inc frequency and severity

w/o therapy, cerebral oedema becomes worse and results in coma and death within 1 month

Question 55

Diagnosis of maple syrup urine disease in newborns?

Answer 55

Inc plasma concentrations of the three branch-chained amino acids - valine, isoleucine, leucine

measure of enzyme in lymphocytes or cultured fibroblasts serve as a confirmatory test

Heterozygotes have diminished levels of enzyme activity

Question 56

Management of maple syrup urine disease in newborns?

Answer 56

Hemodialysis may be needed to correct life-threatening metabolic acidosis

trial of thiamine (10-20mg/kg/day) improve condition in a thiamine-responsive MSUD variant

stop intake of all-natural protein, and correct dehydration, electrolyte imbalance, and metabolic acidosis

a special diet, low in branched-chain amino acids, may prevent further encephalopathy if started immediatedly by NG tube

newborns diagnosed in first 2 weeks and treated rigorously have the best prognosis

Question 57

What is glycine encephalopathy?

Inheritance pattern of this disease?

Answer 57

Defect in the glycine cleavage system causes glycine encephalopathy (nonketotic hyperglycinemia)

Autosomal recessive

Question 58

Clinical features of glycine encephalopathy in newborns?

Answer 58

irritable and refuse feeding anytime from 6hrs to 8days after delivery

onset of sx is usually within 48 hours, but delays be a few weeks occur in milder allelic forms

Hiccupping is an early and continuous feature; some mother relate that child hiccupped in utero as a prominent symptoms

progressive lethargy, hypotonia, resp disturbance, and myoclonic seizures follow

some newborns survive the acute illness, but cognitive impairment, epilepsy, and spasticity characterise the subsequent course

milder forms: onset of seizures occurs after the neonatal period. developmental outcome is better, but does not exceed moderate cognitive impairment

Question 59

Diagnosis of glycine encephalopathy

Answer 59

During acute encephalopathy, EEG demonstrates burst-suppression pattern, which evolves into hypsarrhythmia during infancy

MRI may be normal or show agenesis or thinning of corpus callosum

Delayed myelination and atrophy are later findings

hyperglycinemia and esp elevated conc of glycine in the CSF in the absence of hyperammonemia, organic acidemia, or valproic acid treatment establishes the dx

Question 60

Management of glycine encephalopathy in newborns?

Answer 60

No tx has proven to be effective

HD provides only temporary relief of the encephalopthy, and diet therapy has not been successful in modifying the course

Diazepam, a competitor for glycine receptors, in combination with choline, folic acid, and sodium benzoate, may stop the seizures

Oral sodium benzoate at 250-750mg/kg/day can reduce plasma glycine conc into normal range

this substantially reduces but does not normalise CSF glycine concentration

Carnitine 100mg/kg/day may inc glycine conjugation with benzoate

Dextromethorphan 5-35mg/kg/day divided into four doses is helpful in lowering levels of glycine

Question 61

Describe urea cycle disturbances in newborns that may present with seizure activity/neurological impairment?

What is the inheritenace of these?

Incidence of urea cycle disorders?

Answer 61

Carbamoyl phosphate synthetase (CPS) deficiency, ornithine transcarbamylase (OTC) deficiency, citrullinemia, argininosuccinic acidemia, and argininemia (arginase deficiency) are disorders caused by defects in enzyme systems responsible for urea synthesis

Similar syndrome results from def of the cofactor producer N-acetylglutamate synthesis (NAGS)

arginase deficiency does not cause symptoms int he newborn

OTC is X-linked trait; transmission of all others is by AR inheritence

Estimated prevalence of all urea cycle disturbances is 1: 30, 000

Question 62

Clinical features of urea cycle disorders?

Answer 62

Due to ammonia intoxication

progressive lethargy, vomiting, and hypotonia develop as early as first day after delivery, even before initiaiton of protein feeding

progressive LOC and seizures follow on subsequent days

Vomiting and lethargy correlate with plasma ammonia conc greater than 200ug/dL (120umol/L)

coma correlates with conc greater than 300ug/dL (180umol/L) and seizures with those greater than 500ug/dL (300umol/L)

death follows quickly in untreated newborns

newborns with partial deficiency of carbamoyl phosphatase synthetase (CPS) and female carrier of ornithine transcarbamylase deficiency may become symptomatic after ingesting a large protein load

Question 63

Diagnosis of urea cycle disturbances?

Answer 63

suspect in every newborn with a compatible clinical syndrome and hyperammonemia w/o organic acidemia

determine blood ammonia conc and plasma acid-base status

hyperammonemia can be life threatening, and dx within 24hrs is essential

plasma ammonia conc of 150mmol/L strongly suggests a urea cycle disorder

quantitative plasma amino acid analysis helps differentiate the specific urea cycle disorder, but other still require liver biopsy to determine level of enzyme activity

most common cause of hyperammonemia is difficult phlebotomy with improper sample processing

accurate serum ammonia testing requires good venepuncture, sample placement on ice, and rapid processing

Question 64

Management of urea cycle disorders in newborns?

Answer 64

Tx cannot await specific diagnosis w/ symptommatic hyperammonaemia due to urea cycle disorders

reduce plasma ammonia conc by limiting nitrogen intake to 1.2-2g/kg/day and using essential amino acids for protein

allow alternative pathway excretion of excess nitrogen with sodium benzoate and phenylacetic acid; reduce amount of nitrogen in diet; reduce catabolism by introducing calories supplied by carbohydrates and fat

arginine conc are low in all inborn errors of urea synthesis except for arginase deficiency and require supplementation

episodes of hyperammonemia may occur and may lead to coma and death. in such cases IV sodium benzoate, sodium phenylacetate, and arginine, coupled with nitrogen-free alimentation, are appropriate

If response to drug therapy is poor, then peritoneal dialysis or HD is indicated

Question 65

What are benign familial neonatal seizures?

Answer 65

suspect in neonates or infants with multifocal brief motor seizures and otherwise normal function, esp when a FHx of similar events is present

Question 66

Genetic defect in benign familial neonatal seizures?

Answer 66

Mutations that affect the potassium or sodium channels

mutation is located on the gene KCNQ2 (locus 20q13.3) found in 50% of cases, KCNQ3 (locus 8q24) found in 7% of cases, and SCN2A (locus 2q23-q24.3)

Question 67

Clinical features of benign familial neonatal seizures?

Answer 67

brief multifocal clonic seizures develop during the first week, sometimes assoc w/ apnea

delay of onset may be as long as 4 weeks

with or s/o tx, seizures usually stop spontaneously within the first months of life

febrile seizures occur in up to 1/3 of affected children. some have febrile seizures w/o first having neonatal seizures

epilepsy develops later in life in as many as 1/3 of affected newborns

seizure types include nocturnal GTC seizures and simple focal orofacial seizures

Question 68

diagnosis of benign familial neonatal seizures

Answer 68

suspect when seizures develop w/o apparent cause in a healthy newborn

labs are normal

eeg: multifocal epileptiform discharges and may be normal interictally

FHx of neonatal seizures is critical to dx but may await discovery until interviewing the grandparents; parents are freq unaware that they had neonatal seizures

detection of a causative mutation (KCNQ2, KCNQ3, SCN2A) may abbreviate further diagnostic testing and reassure as most cases are benign

predictive testing in siblings or children of affected family members wound not change management

Question 69

management of benign familial neonatal seizures?

Answer 69

Tx with anticonvulsants

Oxcarbazepine at 20mg/kg/day for a few days and titrated to 40mg/kg/day can be helpful

duration of tx needed is unclear

levetiracetam is often ineffective

Question 70

what is bilirubin encephalopathy?

Answer 70

kernicterus - yellow discoloration of brain that is esp severe in the basal ganglia and hippocampus, occurs when the serum unbound or free fraction of (unconjugated) bilirubin becomes excessive

Question 71

clinical features of bilirubin encephalopathy in newborns?

Answer 71

Hypotonia, lethargy and poor sucking reflex occur within 24 hours of delivery

bilirubin staining of brain is evident in newborns dueing this first clinical phase

2nd/3rd day: febrile and how inc tone and opisthotonic posturing. seizures are not a constant feature but may occur at this time

characteristic of the third phase is apparent improvement with normalisation of tone

evidence of neurological dysfunction beings to appears toward the end of the second month, and the symptoms become progressively worse throughout infancy

in premature newborns, clinical features are subtle and may lack the phases of inc tone and opisthotonos

typical clinical syndrome after the first year includes extrapyramidal dysfunction, usually athetosis, which occurs in virtually every case; disturbances of vertical gaze, upward more often than downward in 90%; high-frequency hearing loss in 60%; and mental retardation in 25%

survivors often develop a choreoathetoid form of cerebral palsy

Question 72

diagnosis of bilirubin encephalopathy in newborns?

Answer 72

newborns w/ haemolytic disease - basis for a presumed clinical diagnosis is a significant hyperbilirubinemia and a compatible evolution of symptoms

Dx is difficult in critically ill premature newborns, in whom cause of brain damage is more often asphyxia than kernicterus

MRI may show trageted areas in the basal ganglia

Question 73

management of bilirubin encephalopathy in newborns?

Answer 73

phototherapy or exchange transfusion, prevents kernicterus

once kernicterus has occurred, further damage can be limited, but not reversed, by lowering serum bilirubin concentration

diazepam and baclofen are often needed for mgmt of dystonic postures assoc w/ cerebral palsy

Question 74

symptoms of opiate withdrawal in newborns?

Answer 74

tend to occur earlier in full term (first 24 hrs) than in premature (24-48 hrs) newborns

jitteriness present only during the waking states which can shake an entire limb

irritability, a shrill, high-pitched cry, and hyperactivity follow

newborn seems hungry but has difficulty feeding and vomits afterward

diarrhea and other sx of autonomic instability are common

myoclonic jerking is present in 10-25% of newborns undergoing withdrawal –> whether this is seizures or jitteriness is unclear

definite seizures occur in <5% of newborns

Question 75

maternal cocaine use in pregnancy is assoc with?

Answer 75

premature delivery, growth retardation, microcephaly

Question 76

Feature of cocaine intoxication in newborns?

Answer 76

tachycardia, tachypnea, hypertension, irritability, and tremulousness

Question 77

Definiteion of hypocalcaemia in newborns?

Answer 77

Blood calcium conc less than 7mg/dL (1.75 mmol/L)

Question 78

Onset of hypocalcaemia in first 72 hours after delivery is associated with?

Answer 78

LBW, asphyxia, maternal diabetes, transitory nronatal hypoparathyroidism, maternal hyperparathyroidism, and DiGeorge syndrome (DGS)

Later-onset hypocalcemia occurs in kids fed improper formulas, in maternal hyperparathyroidism, and in DGS

Question 79

Describe the link between hypocalcaemia and DiGeorge syndrome?

Answer 79

DGS is assoc w/ microdeletions of chromosome 22q11.2

disturbance of cervical neural crest migration into the derivatives of the pharyngeal arches and pouches explans the phenotype

organs derived from the third and fourth pharyngeal pouches (thymus, parathyroid gland, and great vessels) are hypoplastic

Question 80

Clinical features of DiGeorge syndrome?

Answer 80

22q11.2 syndrome covers several similar phenotypes: DGS, velocardiofacial syndrome (VCFS), and Shprintzen syndrome.

CATCH describe the phenotype of cardiac abn, T-cell deficit, clefting (multiple minor facial anomalies) and hypocalcaemia

identifical of most kids with DGS is in the neonatal period with a major heart defect, hypocalcemia, and immunodeficiency

Dx of kids with VCFS comes later due to cleft palate or craniofacial deformities

Initial Sx of DGS may be due to CHD, hypocalcaemia, or both. Jitteriness and tetany usually begin in the first 48hrs after delivery

peak onset of seizure is on 3rd day, but a 2 week delay may occur

many affected newborns die of cardiac causes during the first month; survivors fail to thrive and have frequent infections secondary to the failure of cell-mediated immunity

Question 81

Diagnosis of Digeorge syndrome?

Answer 81

Newborns with DGS come to medical attention due to seizures and heart disease

Seizures or a prolonged QT interval brings attention to hypocalcemia

molecular genetic testing confirms the dx

hypocalcaemia generally responds to PTH or to oral calcium and vitamin D

Question 82

Causes of neonatal hypoglycaemia?

Answer 82

Question 83

Early onset neonatal hypoglycaemia is generally associated with?

Answer 83

perinatal asphyxia, maternal diabetes, intracranial hemorrhage

Question 84

Late onset neonatal hypoglycaemia is generally associated with?

Answer 84

inborn errors of metabolism

Question 85

Hypoglycaemia is rare and mild among newborns with which metabolic disorders?

Answer 85

rare amd mild among newborns with classic MSUD, ethylmalonic-adipic aciduria, and isovaleric acidemia

Question 86

hypoglycaemia is severe among newborns with which metabolic disorders? (3)

Answer 86

3-methylglutaconic aciduria, glutaric aciduria type 2, and disorders of fructose metabolism

Question 87

clinical features of mild HIE?

Answer 87

newborn is lethargic but conscious immediately after birth

jitteriness and sympathetic overactivity (tachycardia, dilatation of pupils, decreased bronchial and salivary secretions)

muscle tone is normal at rest

tendon reflexes are normoreactive or hyperactive, and ankle clonus is usually elicited

moro reflex is complete, and a single stimulus generates repetitive extension and flexion mvmts

seizures are not an expected feature, and their occurrance suggests concurrent hypoglycaemia, a secondary condition, or a more significant HIE

Question 88

clinical features of severe HIE?

Answer 88

stuporous or comatose immediately after birth, resp effort is usually periodic and insufficient to sustain life

seizures begin within first 12 hours

hypotonia is severe, and tendon reflexes, the moro reflex, and the tonic neck reflex are absent

sucking and swallowing are depressed or absent, but pupillary and oculovestibular reflexes are present

most of these newborns have frequent seizures, which may appearon EEG w/o clinical signs

Question 89

Diagnosis of HIE?

Answer 89

Mild HIE: EEG background rhythms are normal or lacking in variability.

Severe HIE: background is abn and shows suppression of background amplitude

degree of suppression correlates well with severity of HIE

worst case is a flat EEG or one with a burst-suppression pattern

bad outcome: amplitude remains suppressed for 2 weeks or a burst-suppression pattern is present at any time

Epileptiform activity may also be present but is less predictive of the outcome than is background suppression

MRI w/ diffusion-weighted images help determine extent of injury. Basal ganglia and thalamus are often affected by HIE

Question 90

Management of HIE?

Answer 90

attention to derangements in several organs and correction of acidosis

control of seizures, maintaining adequate ventilation and perfusion

either whole body or selective head cooling

continuous EEG monitoring needed as seizures are often subclinical in newborns

Question 91

What is isovaleric acidemia?

What is the inheritance pattern?

Answer 91

Isovaleric acid is a fatty acid derived from leucine

Isovaleryl-CoA dehydrogenase converts isovaleric acid to 3-methylcrotonyl-CoA

Genetic transmission is AR inheritence

Heterozygote states is detectable in cultured fibroblasts

Question 92

Clinical features of isovaleric acidemia?

Answer 92

two phenotypes: acute overwhelming disorder of the newborn vs. chronic infantile form

acute disorder: newborn normal at birth but within a few days –> lethargy, feed refusal, vomits. Clinical syndrome similar to MSUD except urine smells like ‘sweaty feet’ instead of maple syrup

60% of affected newborns die within 3 weeks

Survivors have a clinical syndrome identical to the chronic infantile phenotype

Question 93

Diagnosis of isovaleric acidemia?

Answer 93

excretion of isovaleryl-lysine in urine detects isovaleric acidosis

assays or isovaleryl-CoA dehydrogenase activity utilise cultured fibroblasts, and molecular testing is available

clinical phenotype correlates not with percentage of residual enzyme activity, but with ability to detoxify isovaleryl-CoA with glycine

Question 94

Management of isovaleric acidemia?

Answer 94

dietary restriction of protein, esp leucine –> dec occurrence of later psychomotor retardation

L-Carnitine is a beneficial supplement to diet of some kids with isovaleric acidemia

Acutely ill newborns –> oral glycine + protein restriction and carnitine –> reduced mortality

Arachidonic acid, docosahexaenoic acid, and vit B12 may become deficient –> may need supplementation in pts tx w/ dietary restriction of protein

Question 95

What is methylmalonic acidemia?

What mode of inheritance?

Answer 95

D -Methylmalonyl-CoA is racemized to L -methylmalonyl-
CoA by the enzyme D -methylmalonyl racemase and then
isomerized to succinyl-CoA, which enters the tricarboxylic
acid cycle.

The enzyme D -methylmalonyl-CoA mutase cat-
alyzes the isomerization.

The cobalamin (vitamin B 12 )
coenzyme adenosylcobalamin is a required cofactor.

autosomal recessive inheritance

Mutase deficiency is
the most common abnormality. Propionyl-CoA, propionic
acid, and methylmalonic acid accumulate and cause hyper-
glycinemia and hyperammonemia

Question 96

Clinical features of methylmalonic acidaemia?

Answer 96

Affected children appear normal at
birth.

In 80% of those with complete mutase deficiency,
the symptoms appear during the first week after delivery;
those with defects in the synthesis of adenosylcobalamin
generally show symptoms after 1 month.

Symptoms
include lethargy, failure to thrive, recurrent vomiting, dehy-
dration, respiratory distress, and hypotonia after the
initiation of protein feeding.

Leukopenia, thrombocytope-
nia, and anemia are present in more than one-half of
patients. Intracranial hemorrhage may result from a bleed-
ing diathesis.

The outcome for newborns with complete
mutase deficiency is usually poor. Most die within 2 months
of diagnosis; survivors have recurrent acidosis, growth
retardation, and cognitive impairment

Question 97

Diagnosis of methylmalonic acidaemia?

Answer 97

Suspect the diagnosis in any newborn with
metabolic acidosis, especially if associated with ketosis, hyper-
ammonemia, and hyperglycinemia. Demonstrating an
increased concentration of methylmalonic acid in the urine
and elevated plasma glycine levels helps confirm the diagno-
sis. The specific enzyme defect can be determined in
fibroblasts. Techniques for prenatal detection are available.

Question 98

Management of of methylmalonic acidaemia?

Answer 98

Some affected newborns are cobalamin
responsive and others are not. Management of those with
mutase deficiency is similar to propionic acidemia. The
long-term results are poor. Vitamin B 12 supplementation
is useful in some defects of adenosylcobalamin synthesis,
and hydroxocobalamin administration is reasonable while
awaiting the definitive diagnosis. Maintain treatment with
protein restriction (0.5–l.5 g/kg/day) and hydroxocobala-
min (1 mg) weekly. As in propionic acidemia, oral supple-
mentation of L -carnitine reduces ketogenesis in response to
fasting.

Question 99

What is propionic acidemia?

Mode of inheritance?

Answer 99

Propionyl-CoA forms as a catabolite of methionine, threo-
nine, and the branched-chain amino acids. Its further car-
boxylation to D -methylmalonyl-CoA requires the enzyme
propionyl-CoA carboxylase and the coenzyme biotin. Isolated deficiency of propionyl-CoA carboxylase
causes propionic acidemia. Transmission of the defect is
autosomal recessive.

Question 100

Clinical features of proprionic acidemia?

Answer 100

Most affected children appear nor-
mal at birth; symptoms may begin as early as the first
day after delivery or delayed for months or years. In new-
borns, the symptoms are nonspecific: feeding difficulty,
lethargy, hypotonia, and dehydration. Recurrent attacks
of profound metabolic acidosis, often associated with
hyperammonemia, which respond poorly to buffering is
characteristic. Untreated newborns rapidly become dehy-
drated, have generalized or myoclonic seizures, and become
comatose.
Hepatomegaly caused by a fatty infiltration occurs in
approximately one-third of patients. Neutropenia, throm-
bocytopenia, and occasionally pancytopenia may be
present. A bleeding diathesis accounts for massive intracra-
nial hemorrhage in some newborns. Children who survive
beyond infancy develop infarctions in the basal ganglia.

Question 101

Diagnosis of propionic acidemia?

Answer 101

Consider propionic acidemia in any new-
born with ketoacidosis or with hyperammonemia without
ketoacidosis. Propionic acidemia is the probable diagnosis
when the plasma concentrations of glycine and propionate
and the urinary concentrations of glycine, methylcitrate,
and β-hydroxypropionate are increased. While the urinary
concentration of propionate may be normal, the plasma
concentration is always elevated, without a concurrent
increase in the concentration of methylmalonate.
Deficiency of enzyme activity in peripheral blood leuko-
cytes or in skin fibroblasts establishes the diagnosis. Molec-
ular genetic testing is available. Detecting methylcitrate, a
unique metabolite of propionate, in the amniotic fluid
and by showing deficient enzyme activity in amniotic fluid
cells provides prenatal diagnosis.

Question 102

Management of propionic acidemia?

Answer 102

The newborn in ketoacidosis requires
dialysis to remove toxic metabolites, parenteral fluids to
prevent dehydration, and protein-free nutrition. Restricting
protein intake to 0.5–l.5 g/kg/day decreases the frequency
and severity of subsequent attacks. Oral administration of
L -carnitine reduces the ketogenic response to fasting and
may be useful as a daily supplement. Intermittent adminis-
tration of nonabsorbed antibiotics reduces the production
of propionate by gut bacteria.

Question 103

What HSV serotype is associated with genital herpes?

Answer 103

HSV-2 is assoc w/ 80% of genital herpes and HSV-1 with 20%

Question 104

Describe the transmission to neonates of HSV-2?

Answer 104

Transmission of HSV to the new-
born can occur in utero, peripartum, or postnatally.

85% of neonatal cases are HSV-2 infections acquired
during the time of delivery.

highest risk for perinatal
transmission occurs when a mother with no prior HSV-1
or HSV-2 antibodies acquires either virus in the genital
tract within 2 weeks prior to delivery (first-episode primary
infection). Postnatal transmission can occur with HSV-1
through mouth or hand by the mother or other caregiver.

Question 105

Clinical features of HSV infection in newborns?

Answer 105

1/3 have disseminated disease, 1/3 have localised brain involvement, 1/3 have localised involvement of the eyes, skin or mouth

About 50% of infections involve the CNS

overall mortality rate is over 60%, and 50% of survivors have permanent neurological impairment

Sx onset: as early as 5th day, but usually in second week

Vesicular rash present in 30%, usually on scalp after vertex pres, and on buttock after breech

conjunctivitis, jaundice, bleeding diasthesis may be present

First Sx of encephalits are irritability and seizures

seizures may be focal or generalised and are frequently only partially responsive to therapy

Neuro degen is progressive and characterised by coma and quadriparesis

Question 106

Diagnosis of HSV encephalitis?

Answer 106

Culture m/c/s from vesicles, mouth, nasopharynx, rectum, or CSF

PCR is standard for diagnosing herpes encephalitis

EEG: multifocal spikes, initially more than the periodic triphasic pattern seen in older populations

Periodic pattern of slow waves usually suggests a destructive underlying lesion similar to stroke

CSF: lymphocytic leukocytosis, RBC, elevated protein concentration

Question 107

Management of HSV encephalitis?

Answer 107

C/S considered in all women with active genital herpes infection at term, whose membranes are intact or ruptured for <4hrs

IV acyclovir - 60mg/kg/day divided TDS for 14 days in skin/eye/mouth disease and for 21 days for disseminated disease

If have CNS HSV - repeat LP at end of IV therapy to determine if CSF if normalised

Tx continues until PCR is negative

ARF is most sig adverse effect of IV acyclovir

mortality remains >/=50% in newborns with disseminated disease

Question 108

Causes of cerebral venous thrombosis in newborns?

Answer 108

coagulopathy, polycythaemia, sepsis

when involving the superior saggital sinus - can occur w/o known predisposing factors, probably due to trauma even in relatively normal deliveries

Question 109

Clinical features of cerebral venous thrombosis?

Answer 109

focal seizures/lethargy any time during first month

ICP remains normal, lethargy slowly resolves, and seizures tend to respond to anticonvulsants

Long-term outcome is uncertain and likely depends on extent of hemorrhagic infarction of the hemisphere

Question 110

Diagnosis of cerebral venous thrombosis?

Answer 110

CT venogram or MRI venogram are standard diagnostic tests

CT is more sensitive and accurate, but MRI is preferred due to absence of radiation

Question 111

Management of cerebral venous thrombosis?

Answer 111

Anticoagulation - decrease risk of
thrombus progression, venous congestion leading to hem-
orrhage and stroke, and facilitate re-canalization of the
venous sinus

Response to therapy varies widely, and dos-
ages of low molecular weight heparin frequently require
readjustment to maintain therapeutic anti-Xa levels of
0.5–1 U/mL. A starting dose of 1.7 mg/kg every 12 hours
for term infants, or 2.0 mg/kg every 12 hours for preterm
infants, may be beneficial.
Ultimately therapeutic deci-
sions must incorporate treatment of the underlying cause
of the thrombosis, if known.

Question 112

Clinical features of primary subarachnoid hemorrhage in newborns

Answer 112

likely originates from tearing of superficial veins by shearing forces during prolonged delivery with head molding

mild HIE often assoc s/ SAH - newborn is usually well, when suddenly unexpected seizure occurs on 1st or 2nd day of life

LP performed usually due to suspected sepsis, reveals blood in CSF

RCC in 1st and last tube typically show similar counts in SAH, and show clearing numbers in traumatic taps

most newborns do not suffer long term sequelae

Question 113

Diagnosis of subarachnoid hemorrhage in newborns?

Answer 113

CT is useful to document the extent of hem-
orrhage. Blood is present in the interhemispheric fissure
and the supratentorial and infratentorial recesses. EEG
may reveal epileptiform activity without background sup-
pression. This suggests that HIE is not the cause of the sei-
zures, and that the prognosis is more favorable. Clotting
studies are needed to evaluate the possibility of a bleeding
diathesis

Question 114

Management of primary subarachnoid haemorrhage in newborns?

Answer 114

Seizures usually respond to anticonvul-
sants. Specific therapy is not available for the hemorrhage,
and posthemorrhagic hydrocephalus is uncommon

Question 115

Clinical features of subdural haemorrhage in newborns?

Answer 115

Blood collects in the posterior fossa and may pro-
duce brainstem compression. The initial features are those
of mild to moderate HIE. Clinical evidence of brainstem
compression begins 12 hours or longer after delivery. Char-
acteristic features include irregular respiration, an abnor-
mal cry, declining consciousness, hypotonia, seizures, and
a tense fontanelle. Intracerebellar hemorrhage is sometimes
present. Mortality is high, and neurological impairment
among survivors is common.

Question 116

Pathophys of subdural haemorrhage in newborns?

Answer 116

Subdural hemorrhage is usually the
consequence of a tear in the tentorium near its junction
with the falx. Causes of tear include excessive vertical mold-
ing of the head in vertex presentation, anteroposterior elon-
gation of the head in face and brow presentations, or
prolonged delivery of the after coming head in breech pre-
sentation.

Question 117

Diagnosis of subdural hemorrhage in newborns?

Answer 117

MRI/CT/US

Question 118

Management of subdural hemorrhage in newborns?

Answer 118

Small haemorrhage - nil tx

Surgical evacuation of large collections relieves brainstem compression

Question 119

What is the cause of pyridoxine dependency?

What is the mode of inheritance?

Answer 119

Rare disorder transmitted as an AR trait

Genetic locus is unknown, but presumed cause is impaired glutamic decarboxylase activity

Question 120

Clinical features of pyridoxine dependency in newborns?

Answer 120

seizures soon after birth - multifocal clonic progressing rapidly to status epilepticus

presentations of prolonged seizures and recurrent episodes of status epileptics are typical, but recurrent self-limited events including partial seizures, generalised seizures, atonic seizures, myoclonic events, and infantile spasms also occur

Seizures only respond to pyridoxine

Seizure-free interval up to 3/52 may occur after pyridoxine discontinuation

Outcome improved and cognitive deficits dec w/ early diagnosis and tx

Intellectual disability is common

Question 121

Atypical features of pyridoxine dependency?

Answer 121

Atypical features: late-onset seizures (up to 2 years), seizures initailly responding to antiepileptics and then do not, seizure that do not initially respond to pyridoxine but then become controlled, and prolonged seizure-free intervals occuring after stopping pyridoxine

Question 122

Diagnosis of pyridoxine dependency in newborns?

Answer 122

Suspect in newborns with an
affected older sibling, or newborns with daily seizures
unresponsive to anticonvulsants, with a progressive course,
and worsening EEGs

infantile-onset
variety: intermittent myoclonic seizures, focal clonic sei-
zures, or generalized tonic-clonic seizures. The EEG is con-
tinuously abnormal because of generalized or multifocal
spike discharges and tends to evolve into hypsarrhythmia.
An IV injection of pyridoxine 100 mg stops the clinical sei-
zure activity and often converts the EEG to normal in less
than 10 minutes. However, sometimes 500 mg is required.
When giving pyridoxine IV, arousals may look like
improvement in EEG since hypsarrhythmia is a pattern
seen initially during sleep. Comparing sleep EEG before
and after pyridoxine is needed to confirm an EEG response.

CSF neurotransmitter testing is available to confirm the
diagnosis.

Genetic testing may confirm mutations of the aldehyde
dehydrogenase 7A1 (ALDH7A1) gene, which encodes
antiquitin

Question 123

Management of pyridoxine dependency?

Answer 123

Lifelong dietary supplement of pyridoxine 50–100 mg/day prevents further seizures. Subsequent
psychomotor development is best with early treatment,
but this does not ensure a normal outcome. The dose needed
to prevent mental retardation may be higher than that
needed to stop seizures.

Question 124

What mutation is responsible for folinic acid dependency seizures?

Answer 124

ALDH7A1 mutation - assoc with folinic acid and pyridoxine dependent seizures

Question 125

Clinical features of folinic acid dependent seizures?

Answer 125

infants develop seizures during the first week of life that are not responsive to anticonvulsants or pyridoxine

Question 126

Diagnosis of folinic acid dependent seizures?

Answer 126

Characteristic peak on CSF electrophoresis confirms the diagnosis

Question 127

Management of folinic acid dependent seizures?

Answer 127

Treat the disorder with folinic acid (not folic acid) supplementation 2.5-5mg twice daily

Question 128

What is incontinentia pigmenti (Bloch-Sulzberger syndrome)?

What is mode of transmission?

Answer 128

Rare neurocutaneous syndrome involving the skin, teeth, eyes and CNS

Genetic transmission is X-linked (Xq28) with lethality in the hemizygous male

Question 129

Clinical features of incontinenti pigmenti (Bloch-Sulzberger syndrome)?

Answer 129

F:M 20:1

erythematous and vesicular rash resembling epidermolysis bullosa present on flexor surfaces of limbs + lateral traunk at birth or soon thereafter

rash persists for first few months and a cerrucous eruption that lasts for weeks or months replaces the original rash

between 6-12 months of age, deposits of pigment appears in prev area of rash in bizarre polymorphic arrangements

pigmentation later regresses and leaves a linear hypopigmentation

alopecia, hypodontia, abn tooth shape and dystrophic nails may be associated

some pts have retinal vascular abn that predispose to retinal detachment in early childhood

neuro disturbance occur in few than half of cases

newborns: prominent features is onset of seizures on 2nd or 3rd day, often confined to one side of the body

residual neurological handicaps may include cognitive impairment, epilepsy, hemiparesis, and hydrocephalus

Question 130

Diagnosis of incontinenti pigmenti (bloch-sulzberger syndrome)?

What gene abn is looked for?

Answer 130

clinical findings and biopsy of skin rash are diagnostic. bases for diagnosis are clinical findings and molecular testing of the IKBKG gene

Question 131

management of incontinenti pigmenti (bloch-sulzberger syndrome)?

Answer 131

neonatal seizures caused by incontinenti pigmenti usually respond to standard anticonvulsant drugs

blistering rash requires topical medication and oatmeal baths

regular ophthal exam are needed to diagnose and treat retinal detachment

Question 132

Where is levetiracetam excreted? Is it liver metabolised?

Answer 132

Not liver metabolised, excreted unchanged in the urine. no drug-drug interactions exist

Can be used as initial therapy in newborns with seizures

Maintenance dose dependent on renal clearance. Reduce dosage and dosing interval in neonates with hypoxic injury w/ associated lower renal function

Question 133

What are the main causes of paroxysmal disoders in infants (children less than 2 years old)?

Answer 133

Seizures, especially febrile convulsions are the main cause of PNDs, but apnea and syncope (breath-holding spells) are relatively common also

Question 134

What questions should be asked when trying to determine if an infant has had a seizure?

Answer 134

What was the child doing before the spell?

Did anything provoke the spell?

Did the child’s color change?

If so, when and to what color?

Did the eyes move in any direction?

Did the spell affect one body part more than other parts?

In addition to getting a home video of the spell, ambulatory or prolonged video-EEG monitoring is the only way to identify the nature of unusual spells

Question 135

Seizures characterised by dec motor activity with indeterminate changes in the level of consciousness arise from the [….], while seizures with motor activity usually arise from the […]

Answer 135

temporal, temporoparietal, or parieto-occipital regions

frontal, central or frontoparietal regions

Question 136

Definition of infant apnea?

Answer 136

Cessation of breathing for 15s or longer, or for less than 15s if accompanied by bradycardia

Premature newborns with respiratory distress syndrome may continue to have apneic spells as infants, esp if they are neurologically abnormal

Question 137

What are apneic seizures?

Answer 137

Apnea alone is rarely a seizure manifestation

frequency of apneic seizures relates inversely to age, more often
in newborns than infants, and rare in children.

Isolated
apnea occurs as a seizure manifestation in infants and young
children, but when reviewed on video, identification of
other features becomes possible.

Overall, reflux accounts
for much more apnea than seizures in most infants and
young children. Unfortunately, among infants with apneic
seizures, EEG abnormalities only appear at the time of apnea.
Therefore, monitoring is required for diagnosis

Question 138

Breath-holding spells with LOC occur in almost […] of infants and young children

Answer 138

5%

Question 139

Cause of breath-holding spells?

What inheritance patterns?

Answer 139

Cause is a disturbance in central autonomic regulation probably transmitted by AD inheritance with incomplete penetrance

Approximately 20%–30% of parents of affected
children have a history of the condition. The term breath-
holding is a misnomer because breathing always stops in
expiration. Both cyanotic and pallid breath-holding occurs;
cyanotic spells are three times more common than pallid
spells. Most children experience only one or the other, but
20% have both.
The spells are involuntary responses to adverse stimuli.
In approximately 80% of affected children, the spells begin
before 18 months of age, and in all cases they start before
3 years of age. The last episode usually occurs by age 4 years
and no later than age 8 years.

Question 140

Clinical features of cyanotic syncope?

Answer 140

usual provoking stimulus for cyanotic spells is anger, pain, frustration or fear

cyanosis develops rapidly, followed quickly by limpness and LOC

crying may not precede cyanotic episodes provoked by pain

if lasts for only seconds, infant may resume crying on awakening. most spells are longer and are assoc w/ tonic posturing of the body and trembling movement of the hands or arms

eyes may rolls upward

movements are mistaken for seizures by even experienced observers, but they are likely brain-ste release phenomenon. Concurrent EEG shows flattening of the record, not seizure activity

after a prolonged spell, child first arouses and then goes to sleep. once an infant begins having breath-holding spells, freq inc for several months and then declines, and finally ceases

Question 141

Diagnosis of cyanotic breath holding spells?

Answer 141

sequence of cyanosis, apnea, and LOC is critical

cyanotic syncope and epilepsy are confused due to lack of attention to precipitating event

questioning should focus on precipitating events, absence of breathing, facial color, and FHx

family often has a history of breath-holding spells or syncope

between attacks, EEG is NAD

during an episode, EEG first shows diffuse slowing and then rhythmic slowing followed by background attenuation during the tonic-clonic, tonic, myoclonic, or clonic activity

Question 142

Management of cyanotic breath holding spells?

Answer 142

Educate and reassure

leave chid in supine position with airway protection until recovers consciousness

picking up child prolongs the spell

if spells occur in response to discipline or denial of a childs wishes, comfort child but remain firm in their decision

Question 143

Clinical features of pallid syncope?

Answer 143

provocation is usually a sudden, unexpected, painful event

child rarely cries but instead becomes white and limp and loses consciousness

parents often start giving CPR

after initial limpness, body may stiffen, and clonic movements of the arms may occur

as in cyanotic syncope, these movements represent a brainstem release phenomenon, not seizure activity

duration of spell is difficult to determine as observer is so scared that second feel like hours. afterward child often falls asleep and is normal on awakening

Question 144

Diagnosis of pallid syncope?

Answer 144

Pallid syncope is the result of reflex asystole

pressure on the eyeballs to initiate a vagal redlex provokes an attack

do not recommend provoking an attack as an office procedure

history alone is diagnostic

Question 145

management of pallid syncope?

Answer 145

reassure family that child will not die during an attack

Question 146

What are the three possibilities for infants that present with fever and seizure?

Answer 146

1. nervous system infection
2. underlyingseizure disorder in which stress of fever triggers the seizure, although subsequent seizures may be afebrile
3. simple febrile seizure, a genetic age-limited epilepsy in which seizures occur only with fever

Question 147

What is Dravet Syndrome?

Answer 147

Kids that have complex febrile seizures evolving into difficult to control epilepsies, exacerbated by antizeisure medication with sodium blocking MOA - carbamazepine, oxcarbazepine, phenytoin, or lamotrigine

Question 148

Seizure presentation in Dravet syndrome?

Answer 148

first seizures are usually febrile, usually prolonged, can be generalised or focal clonic in type

febrile and nonfebrile seizures recur, sometimes as status epilepticus

generalised myoclonic seizures appear after 1 year of age

partial, complex seizures with secondary generalisation may also occur

conincident with the onset of myoclonic seizures are the slowing of developemtn and the gradual appearance of ataxia and hyperreflexia

Question 149

Diagnosis of Dravet syndrome?

Answer 149

The diagnosis is based on the phenotype. Up
to 80% patients have a mutation on SCN1A (locus 2q24)
with a negative effect on sodium channel function. Genetic
testing (positive in 80% of cases) is helpful and may prevent
further unnecessary EEGs or imaging studies.

Question 150

Management of Dravet syndrome?

Answer 150

Avoidance of sodium channel drugs is a
benefit, if not already clinically detected. Medications such
as levetiracetam,
divalproex sodium, topiramate, zonisa-
mide, rufinamide, and management with a ketogenic diet
are good alternatives. Cannabinoids have shown similar
benefits in this epileptic syndrome. De novo mutations
are rare and genetic counseling is recommended. Prenatal
counseling and genetic testing of the patient’s siblings
should be considered

Question 151

What is GEFS?

Answer 151

Generalized epilepsy with febrile sei-
zures plus (GEFS+) is suspected in patients with family his-
tories of generalized epilepsies and febrile seizures with different phenotypes. It is associated with mutations that
affect the sodium channel and GABAa receptor. Mutations
are found on SCN1A (locus 2q24), SCN1B (locus 19q13.1),
and GABRG2 (locus 5 q34). There is also a childhood
absence epilepsy with febrile seizures phenotype associated
with mutations in GABRG2 (locus 5q34), likely another
phenotype of GEFS+

Question 152

Diagnosis of GEFS
+?

Answer 152

The diagnosis is based on the phenotype,
which is highly variable regarding manifestations, progno-
sis, and response to treatment. For this reason, genetic test-
ing is of limited utility at this time

Question 153

Management of GEFS+?

Answer 153

Wide spectrum antiseizure medications
are recommended: divalproex sodium, lamotrigine,
levetiracetam, zonisamide, topiramate, clobazam, and
perampanel

Question 154

Seizure types with greatest probability of cognitive impairment in descending order are…

Answer 154

myoclonic, tonic-clonic, complex partial, and simple partial