Neurology Flashcards

Question

What are some movements that resemble neonatal seizures?

Answer 1

Benign nocturnal myoclonus jitteriness nonconvulsive apnea normal movement opisthotonos pathological myoclonus

Answer 2

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

Answer 3

tonic or clonic movements of the limbs are lacking

Answer 4

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

Answer 5

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

Answer 6

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

Answer 7

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

Answer 8

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

Answer 9

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)

Answer 10

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

Answer 11

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

Answer 12

Kernicterus, infantile Gaucher disease, and some aminoacidurias

Answer 13

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

Answer 14

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

Answer 15

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

Answer 16

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

Answer 17

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

Answer 18

treatment is unnecessary, and education and reassurance are usually sufficient if violent myoclonus with subsequent frequent arounsals which disrupts sleep --\> clonazepam may be considered

Answer 19

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

Answer 20

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

Answer 21

reduced stimulation decreases jitteriness newborns of addicted mother require sedation to facilitate feeding and to dec energy expenditure

Answer 22

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

Answer 23

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

Answer 24

clonazepam is effective in most cases

Answer 25

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

Answer 26

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

Answer 27

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

Answer 28

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

Answer 29

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

Answer 30

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

Answer 31

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

Answer 32

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

Answer 33

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

Answer 34

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

Answer 35

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

Answer 36

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

Answer 37

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

Answer 38

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

Answer 39

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

Answer 40

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

Answer 41

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

Answer 42

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)

Answer 43

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

Answer 44

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

Answer 45

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

Answer 46

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

Answer 47

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

Answer 48

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

Answer 49

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

Answer 50

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

Answer 51

premature delivery, growth retardation, microcephaly

Answer 52

tachycardia, tachypnea, hypertension, irritability, and tremulousness

Answer 53

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

Answer 54

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

Answer 55

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

Answer 56

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

Answer 57

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

Answer 58

perinatal asphyxia, maternal diabetes, intracranial hemorrhage

Answer 59

inborn errors of metabolism

Answer 60

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

Answer 61

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

Answer 62

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

Answer 63

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

Answer 64

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

Answer 65

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

Answer 66

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

Answer 67

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

Answer 68

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

Answer 69

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

Answer 70

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

Answer 71

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

Answer 72

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.

Answer 73

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.

Answer 74

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.

Answer 75

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.

Answer 76

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.

Answer 77

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.

Answer 78

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

Answer 79

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.

Answer 80

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

Answer 81

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

Answer 82

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

Answer 83

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

Answer 84

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

Answer 85

CT venogram or MRI venogram are standard diagnostic tests CT is more sensitive and accurate, but MRI is preferred due to absence of radiation

Answer 86

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.

Answer 87

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

Answer 88

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

Answer 89

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

Answer 90

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.

Answer 91

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.

Answer 92

Small haemorrhage - nil tx Surgical evacuation of large collections relieves brainstem compression

Answer 93

Rare disorder transmitted as an AR trait Genetic locus is unknown, but presumed cause is impaired glutamic decarboxylase activity

Answer 94

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

Answer 95

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

Answer 96

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

Answer 97

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.

Answer 98

ALDH7A1 mutation - assoc with folinic acid and pyridoxine dependent seizures

Answer 99

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

Answer 100

Characteristic peak on CSF electrophoresis confirms the diagnosis

Answer 101

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

Answer 102

Rare neurocutaneous syndrome involving the skin, teeth, eyes and CNS Genetic transmission is X-linked (Xq28) with lethality in the hemizygous male

Answer 103

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

Answer 104

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

Answer 105

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

Answer 106

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

Answer 107

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

Answer 108

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

Answer 109

temporal, temporoparietal, or parieto-occipital regions frontal, central or frontoparietal regions

Answer 110

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

Answer 111

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

Answer 112

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.

Answer 113

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

Answer 114

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

Answer 115

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

Answer 116

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

Answer 117

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

Answer 118

reassure family that child will not die during an attack

Answer 119

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

Answer 120

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

Answer 121

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

Answer 122

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.

Answer 123

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

Answer 124

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+

Answer 125

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

Answer 126

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

Answer 127

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