Neurology Flashcards
1
Q
Hearing loss severity
A
Mild: 26-40 db Moderate: 40-55 db Moderate-severe: 55-70 db Severe: 70-90 db Profound: >90 db
2
Q
Molecule most rapidly depleted after neuronal injury
A

Phosphocreatine
3
Q
Necrosis (Asphyxia)
A
- Hypoxia/glucose deprivation disrupt cellular hemostasis and ATP depletion
- Loss of Na/K-ATPase -> membrane depolarization, influx of Na, Ca, H2O (cell swelling)
- Excess extracellular glutamate increases Ca entry into cells
- Activation of phospholipases, xanthine oxidase, nNOS
4
Q
Apoptosis (HIE)
A
Programmed cell death
1. Cytochrome C released from mitochondria activates caspase 8 & 9
2. Cell death by activation of caspases and endonucleases
3. Blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation
Therapeutic hypothermia can prevent this
5
Q
Oxidative stress (HIE)
A
- Reperfusion phase yields 02 radicals, NO
- Radicals react with proteins, lipids, DNA producing oxidative damage
- Lack of scavengers (glutathione, SOD, catalase, cholesterol)

6
Q
Failure to establish HR by 10 minutes results in ___
A
death or severe permanent disability
7
Q
Best predictor of intrauterine hypoxia
A
Metabolic acidosis on cord gas
8
Q
Best predictor of long-term outcome in asphyxia
A
Requirement for tube feeding at two weeks of age
9
Q
Long-term complications of kernicterus
A
TEAM (it takes a team to treat these babies) Teeth (dental enamel hypoplasia) Eye (upward gaze palsy) Auditory (aud neuropathy) Movement (athetoid CP)
10
Q
Minimal neuronal injury
A
Minimal ATP reduction followed by recovery
11
Q
Moderate neuronal injury
A
Biphasic depletion
Apoptosis
12
Q
Severe neuronal injury
A
Energy failure with predominant necrosis
13
Q
 Cerebral blood flow autoregulation
A
With decreasing gestational age, mean arterial pressure values approach the lower limits
14
Q
CO2 and cerebral blood flow
A
Increased CO2 -> increased CBF (dilates blood vessels)
Decreased CO2 -> decreased CBS (constriction)
15
Q
Arterial 02 content and cerebral blood flow
A
Increased O2 -> decreased CBF
Decreased O2 -> increased CBF
16
Q
Glucose and cerebral blood flow
A
Increased glucose -> decreased CBF
Decreased glucose -> increased CBF
17
Q
Calcium and cerebral blood flow
A
Increased calcium -> decreased CBF
Decreased calcium -> increased CBF
18
Q
Prostaglandins and cerebral blood flow
A
Increased prostaglandins -> increased CBF
Decreased prostaglandins -> decreased CBF
19
Q
CBF ___ with postnatal age
A
Increases
20
Q
Normal intracranial pressure
A
30-70 mmH2O
21
Q
Causes of increased intracranial pressure
A
Major intracranial hemorrhages Post hemorrhagic hydrocephalus Seizures Pneumothorax Tracheal suctioning
22
Q
Germinal matrix
A
Site of neuronal precursors between 10-20 weeks gestation
3rd trimester becomes site of glial precursors
23
Q
When does germinal matrix involute
A
By 36 weeks
24
Q
Intravascular factors and IVH
A
Increase or decrease in CBF
Fluctuating CBF
Platelet and coagulation problems
25
Extravascular factors and IVH
Deficient vascular support (decreased astrocytes)
Fibrinolytic activity
Postnatal decrease in tissue pressure
26
Cerebral autoregulation
Maintain stable cerebral blood flow in face of altering perfusion pressure
27
When does cerebral autoregulation fail?
High PCO2 (>70)
| After hypoxia/ischemia
28
Mechanism of brain injury in IVH
```
Hypoxic ischemic injury
Distraction of germinal matrix/glial precursors
Periventricular hemorrhagic infarct
PVL
PHH
```
29
IVH presentation: catastrophic syndrome
Deterioration in minutes to hours
Coma, respiratory abnormalities, generalized seizures, pupils fixed to light
Dropping hematocrit, bulging fontanelle, hypotension, metabolic acidosis
30
IVH presentation: saltatory syndrome
More subtle
Alteration in consciousness, hypotonia, respiratory problems
Evolves over several hours to days
31
IVH presentation: clinically silent
25-50% infants with IVH may fail to display a distinct constellation of signs indicative of the lesion
32
Why is grade 4 IVH different?
Venous infarction - pressure from IVH impedes blood through venous system -> hypoperfusion and infarction
Blood in ventricle releases vasoactive compounds with the same conclusion
33
When does 90% of IVH occur?
First three days of life
34
Percentage of neonates with grade 1/2 IVH with developmental abnormalities
10%
| Grade II worse than no hemorrhage
35
Percentage of neonates with grade 3 IVH with developmental abnormalities?
35-40%
36
Percentage of neonates with grade 4 IVH with developmental abnormalities?
80-90%
37
Causes of IVH in term neonates
Trauma and hypoxic events 50%
| 25% with no identifiable cause
38
Location of IVH in term neonates
Early - bleeding from choroid plexus or subependymal germinal matrix
Late - thalamus
39
Symptoms of IVH in term neonates
Irritability, stupor, apnea, seizures
| Seizures are focal or multifocal and present in 65%
40
HIE symptoms birth to 12 hours
```
Decreased consciousness
Ventilatory disturbances
Intact pupillary responses
Intact oculomotor responses (dolls eyes)
Hypotonia
Can see seizures
```
41
HIE symptoms 12-24 hrs.
```
Variable change in level of alertness
Typically when we see seizures start
Apneic spells
Jitteriness
Weakness
```
42
HIE symptoms 24-72 hrs.
Stupor or coma
Respiratory arrest
Brainstem ocular motor and pupillary disturbances
Can have catastrophic deterioration
43
HIE symptoms >72 hours
Persistent yet diminishing stupor
Disturbed sucking, swallowing, gag, tongue movements
Hypotonia
Weakness
44
How does therapeutic hypothermia help HIE?
```
Inhibition of apoptosis
Reduction in cerebral metabolism
Decreased leukotriene production
Preservation of endogenous antioxidants
Decreased intracellular acidosis
Reduction in glutamate release
Prevention of brain edema
```
45
Long-term outcomes with parasagittal injury
Vascular watershed areas
Spastic quadriparesis
Intellectual deficits
46
Long-term outcomes with selective neuronal necrosis
```
Cognitive deficits
Spastic quadriparesis
Choreoathetosis
Dystonia
Seizure disorder
Ataxia
Bulbar and pseudobulbar palsy
```
47
Long-term outcomes with basal ganglia injury
Onset of dystonia at 13 years (avg)
50% have history of normal neurological development
Intellect is normal in 80%
Progression of dystonia continues for a mean of 7years
48
Periventricular leukomalacia
Necrosis of white matter and a characteristic distribution with less severe injury peripherally
49
PVL is associated with injury to which cells?
Oligodendrocytes
50
Subdural hematoma
Due to tears and bridging veins
| Can be due to traumatic delivery
51
Four categories of cerebellar hemorrhage
Primary
Venus infarction
Extension of IVH
Subarachnoid hemorrhage into cerebellum
52
Caput succedaneum
Molding of head
| Crosses suture lines
53
Cephalohematoma
Subperiosteal bleeding
Limited by suture lines
Underlying linear skull fracture detected 10-25% of time

54
Subgaleal hemorrhage
Beneath aponeurosis covering scalp
Can spread beneath entire scalp and dissect into subQ tissue of the neck
Firm fluctuant mass, increases in size after birth
55
Diffuse neuronal injury
Insult is very severe and very prolonged
56
Cerebral cortex (nuclear) neuronal injury
Insult is moderate to severe and prolonged
57
Deep nuclear/brainstem neuronal injury
Insult is severe and abrupt
58
Ventral induction
5-6th week of gestation
Closure of neural tube -> procephalon/mesencephalon/
rhombencephalon
Associated with cleavage defects
59
Examples of ventral induction defects (brain)
Holoprosencephaly
Septo-optic dysplasia
Agenesis of the corpus callosum
60
Neuroepithelial cell proliferation/migration
7-20th week of gestation
| Migration from inside brain to outside of brain
61
Examples of neuronal proliferation defects
Microcephaly
| Megalencephaly
62
Examples of neuronal migration defects
```
Lissencephaly
Polymicrogyria
Schizencephaly
Cortical dysplasia
Periventricular heterotopia
```
63
Cortical organizations/connectivity
20th week
Cortical organization
Synaptic formations
T21, Fragile X, Rhett, Angelman syndrome, autism
64
Holoprosencephaly
Failure of cleavage of the two sides of the brain
Lobar (some cleavage anterior and posterior)
Semilobar (cleavage only posterior)
Alobar (no cleavage)

65
Genetics of Holoprosencephaly
Mutations in:
Sonic hedgehog gene
Fibroblast growth factor
Bone morphogenetic protein
66
What syndromes is holoprosencephaly associated with?
Trisomy 13
| Smith-Lemli-Opitz Syndrome
67
Septo-optic dysplasia
Septum pellucidum
Hypoplasia CN2
Pituitary insufficiency
68
Genes associated with Septo-optic dysplasia
HESX1
SOX2
SOX3
OXT2
69
Aprosencephaly
Failure of cleavage of prosencephalon -> no diencephalon
| Have midbrain and brainstem still
70
Genetics of agenesis of the corpus callosum
Frameshift mutation DCC Netrin 1 Receptor gene
71
Symptoms of agenesis of the corpus callosum
Autism
Stereotypies
Antisocial
72
Primary Microcephaly
- Microcephaly with normal to thin cortex, simple gyri
- Microlissencephaly (thick cortex)
- Microcephaly with polymicrogyria
Over 25 genes found
73
Secondary microcephaly
More common
| Infection, hypoxia, alcohol, radiation
74
Primary Megalencephaly
Too much proliferation, not enough pruning
Associated with autism
Distinguish from macrocephaly
Phosphatidylinositol-3-kinase (PI3K/AKT)
75
Secondary Megalencephaly
Deposition into white matter
| Seen with Canavan and Alexander syndromes
76
Hemimegalencephaly
One hemisphere is larger than the other - usually epileptogenic
Seen with linear sebaceous syndrome, tuberous sclerosis, neurofibromatosis
77
Type 1 lissencephaly
Classical lissencephaly
Thick cortex with agyria or pachygyria
Tangential and radial migration disorder
LIS1, DCX, RELN, ARX, 14-3-3e
78
Type 2 lissencephaly
Cobblestone lissencephaly
Loss of convolutions
TUBA1A, GPR56
79
Polymicrogyria
Two types in spectrum: abnormal four layer cortex and disorganized cortex
Due to persistence of reelin expression in Cajal-Ritzius cells
Associated with 22q11.2, Aicardi syndrome, Oculocerebrocutaneous syndrome, Sturge-Weber, Warburg micro
80
Schizencephaly etiology
Genetic, migrational, and environmental factors
| Possible ischemic episode in 7-8th week of gestation
81
Type 2 schizencephaly
Open lip
| Connecting the ventricle and meningeal surface, lined with polymicrogyria and separated lips
82
Type 1 Schizencephaly
Closed lip
| Gray matter lined cleft with lips in contact
83
Cortical dysplasia
As cells migrate out a trail is left
| Won’t see as a neonate, need myelin to see on imaging
84
Periventricular heterotopia
```
Bumpy appearance of ventricles
Nodules due to cells failing to migrate
Can have seizures
Filimin A (FLNA Xq28)
ADP ribosylation factor quinine nucleotide exchange (ARFGEF2)

```
85
When does myelination occur?
First eight months of life
| Caudal to rostral
86
Stages of myelination
Posterior before anterior
Proximal before distal
Primary sensory before motor
Projection pathways before cerebral association pathways
87
Do tone and movement develop first in the legs or the arms?
Legs first
88
Tonic labyrinth reflex
Head forward -> legs up
Head back -> arms out
Appears in utero
Gone by 3 years
89
Rooting/suck reflex
Appears at birth
| Gone by three months
90
Crossed adductor reflex
Appears at birth
| Gone by 7-8 months
91
Moro reflex
Appears at birth
| Gone at 5-6 months
92
Palmer grasp
Appears at birth
| Gone at six months
93
Plantar grasp
Appears at birth
| Gone at 9-10 months
94
Tonic neck reflex
Appears at birth
| Gone by 5-6 months
95
Galant reflex
Appears at birth
| Gone by six months
96
Cerebral palsy
Motor deficit that is not progressive
| Can’t reach Milestones
97
Which type of cerebral palsy is most common?
Spastic 85%
98
Subtypes of cerebral palsy
Spastic
Dyskinetic
Ataxic-hypotonic (cerebellar)
99
Types of spastic cerebral palsy
```
Diplegic (both legs)
Hemiplegic (ipsilateral arm+leg)
Quadriplegic (all 4 limbs)
Monoplegic (1 limb, usually arm)
Triplegic (3 limbs, usually 2 legs + 1 arm)
```
100
Types of dyskinetic cerebral palsy
Athetoid
Chorea
Dystonic
101
Symptoms associated with cerebral palsy
```
Developmental delay 50%
Visual defects
Hearing impairment
Speech and language delay
Feeding/swallowing difficulty
Seizures
```
102
Most common cause of neonatal seizures
Vascular (HIE, stroke, hemorrhage)
103
What kind of seizures appear at 24-72 hours of life?
```
HIE
Hypoglycemia
Stroke
Drug withdrawal
IVH
Trauma
```
104
What kind of seizures appear at 2-5 days of life?
Benign familial neonatal convulsions (fifth day fits)
| Hypocalcemia
105
What kind of seizures appear from 2-7 days of life?
```
Once babies start feeding
Ohtahara
EME
Glucose transporter type 1 deficiency
Galactosemia
Aminoacidopathies
Nonketotic hyperglycinemia

```
106
What kind of seizures appear from 4-7 days of life?
Benign idiopathic neonatal seizures
| Migrating partial seizures of infancy
107
Trace alternans on EEG
```
36-40 weeks
Sleep cycle (Active -> quiet -> active)
```
108
Trace discontinua on EEG
26-36 weeks
| Long pauses between bursts (up to 1 minute)
109
Neonatal seizures on EEG
Spike/wave pattern
110
Burst suppression on EEG
High amplitude bursts over a short period
| Long causes of low amplitude
111
Discontinuous EEG
22-28 weeks
| Left and right are not symmetric
112
Symptoms of benign neonatal seizures
```
5th day fits
90% occur days 4-6
Focal clonic seizures sometimes with apnea
Recur in a 24-48 hour span
Self resolve by six weeks of life
```
113
Genetics of familial neonatal seizures
Autosomal dominant
KCNQ2 and KCNQ3
Family history of similar seizures
114
Symptoms of familial neonatal seizures
```
First few days to several weeks of life
Focal, multifocal, tonic, clonic
Resolved by five months to two years
Self-limiting
Can treat with oxcarbazepine
```
115
Genetics of benign neonatal seizures
KCNQ2 mutation
116
Symptoms of Ohtahara syndrome
Early infantile epileptic encephalopathy
In utero to postnatal
Tonic spasms with burst suppression on EEG
High risk for infantile spasms and refractory epilepsy
117
Genetics of Ohtahara syndrome
Genetic or cortical malformation
| CDKL5, ARX, PLCB1, PNKP, SCN3A
118
Early myoclonic epileptic encephalopathy
Myocalnic seizures with burst depression on EEG
Associated with inborn errors of metabolism
 High risk for infantile spasms
119
KCNQ2 Encephalopathy
```
Severe epileptic encephalopathy
Seizures, hypotonia, no visual response
Tonic seizures
Multifocal sharp -> burst suppression
Sodium channel medications
```
120
Pyridoxine dependent epilepsy
Can’t make GABA
| Treat with pyridoxine
121
Phenobarbital
Hyperpolarizes cells
| Cl channels kept open via GABA-A receptors
122
Levetiracetam
SV2 release protein
| Blocks release of glutamate
123
Fosphenytoin
Sodium channel blocker
124
What is hypotonia?
Appendicular: reduced resistance to passive ROM in joints
Axial: impaired ability to sustain postural control/antigravity movement
125
What is weakness?
Reduction in the maximum power that can be generated
126
Do all weak infants have hypotonia?
Yes
127
Do all hypotonic infants have weakness?
No
128
Hypotonic with normal strength and reflexes
Central hypotonia
129
Hypotonic with weakness and areflexia
Peripheral hypotonia
130
Examples of central hypotonia
```
60-80%
HIE
Stroke
Fragile X
Prader Willi
Congenital syndromes
Metabolic disease
```
131
Examples of peripheral hypotonia
```
SMA
Congenital myotonic dystrophy
Congenital muscular dystrophy
Congenital myopathy
Congenital myasthenic syndrome
Pompe disease
Congenital neuropathy
Botulism
Brachial plexopathy
```
132
Mental status in hypotonia
Central: abnormal (seizures, encephalopathy)
Peripheral: normal
133
Cranial nerves in hypotonia
Central: localizing pattern
Peripheral: localizing pattern, extraocular muscle involvement, bulbar weakness
134
Motor deficits in hypotonia
Central: upper motor signs
- normal muscle bulk
- spasticity
- brisk reflexes
- hemideficits
```
Peripheral: lower motor signs
- reduced muscle bulk
- hypotonia
- decreased reflexes
- weakness with different patterns

```
135
Sensory deficits in hypotonia
Central: specific patterns
- hemisensory loss
- sensory level/sweat level
Peripheral: poor response diffusely
136
Findings with anterior horn deficits
```
Weakness
High arched palate
Bell shaped torso
Reduced muscle bulk
Absent reflexes
Fasciculations especially tongue

```
137
Findings with neuropathy
Weakness
Absent reflexes
Rare fasciculations
Sensory deficits
138
Findings with neuromuscular junction disorders
Weakness
Fatigability
Normal muscle bulk
Extraocular, bulbar, respiratory muscle involvement
139
Findings with muscle disorders
```
Weakness
Reduced muscle bulk
Pseudohypertrophy
Contractures
Proximal > distal most cases
Extraocular, bulbar, respiratory muscles involvement
```
140
Transient neonatal myasthenia gravis
10% of women with MG
Circulating antibodies against fetal isoform of AchR
Transient, outcome is good if baby survives
141
Congenital myasthenic syndrome
Rare
Fatigable weakness of eye movements, eyelids, swallowing, and proximal extremities since infancy
Albuterol and Pyridostigmine can help
Some worsened with Pyridostigmine
142
Congenital myopathy
Core myopathy most common histopathologic type
Nemaline myopathy most common presenting in infancy
RYR1 most common genetic type
Often have normal CK
143
What are people with RYR1 related myopathies at risk for?
Malignant hyperthermia
| Occurs with exposure to certain anesthetics
144
When does the germinal matrix start involuting?
32 weeks
145
What do you worry about if you see thalamic hemorrhage on imaging?
Cerebral sinovenous thrombosis
146
Syndromes associated with type 2 lissencephaly
Fukuyama type congenital muscular dystrophy
Muscle-Eye-Brain disease
Walker-Warburg syndrome
