Final Flashcards
(334 cards)
1
Q
What are the five lobes of the cerebral hemispheres and their primary functions?
A
Frontal: Motor control, decision-making, personality
Parietal: Sensory integration, spatial awareness
Temporal: Hearing, memory, language
Occipital: Vision
Insula: Interoception, emotion, taste
2
Q
Name and describe the main parts of the diencephalon.
A
Thalamus: Sensory relay center
Hypothalamus: Autonomic and endocrine regulation
Pineal gland: Regulates circadian rhythms (melatonin production)
3
Q
What structures make up the brainstem and what are their functions?
A
Midbrain: Visual/auditory processing, motor coordination
Pons: Relay between cerebrum and cerebellum; sleep and respiration
Medulla: Autonomic functions (heart rate, breathing)
4
Q
What does the cerebellum do?
A
Coordinates voluntary movements, posture, balance, and motor learning.
5
Q
How do neurons communicate with each other?
A
Via synaptic transmission using neurotransmitters that bind to specific receptors on the postsynaptic cell.
6
Q
What’s the difference between a neuron and a nerve?
A
Neuron: A single nerve cell
Nerve: A bundle of axons from many neurons
7
Q
What are glial cells? Name two types.
A
Non-neuronal cells supporting and insulating neurons. Types: Astrocytes (blood-brain barrier, nutrients), Microglia (immune defense).
8
Q
What is the blood-brain barrier (BBB)?
A
A selective barrier formed by endothelial cells that protects the brain from harmful substances in the blood while allowing nutrients to pass.
9
Q
Difference between motor and sensory neurons?
A
Motor: Carry signals from CNS to muscles
Sensory: Carry signals from sensory receptors to CNS
10
Q
What is the function of brain ventricles?
A
They produce and circulate cerebrospinal fluid (CSF), cushioning the brain and removing waste.
11
Q
What are the three primary germ layers and what do they form?
A
Ectoderm: Nervous system, skin
Mesoderm: Muscles, bones, circulatory system
Endoderm: Internal organs (gut, lungs, etc.)
12
Q
Define neurulation.
A
The formation of the neural tube from the ectoderm, which becomes the brain and spinal cord.
13
Q
What is an inducing factor?
A
A signaling molecule that instructs cells to take on specific fates (e.g., BMP, Shh).
14
Q
What is a morphogen?
A
A type of inducing factor whose effects vary depending on concentration (e.g., Shh, BMP).
15
Q
What is a transcription factor?
A
A protein that binds DNA and regulates gene expression, crucial for cell fate decisions.
16
Q
What did Spemann and Mangold discover?
A
They found an “organizer” region in the mesoderm that induces neural plate formation by releasing factors that block BMP signaling.
17
Q
What role does Sonic Hedgehog (Shh) play?
A
Shh is secreted by the notochord and floor plate, promoting ventral neural identities (e.g., motoneurons).
18
Q
What is BMP’s role in dorsoventral patterning?
A
BMPs promote dorsal fates (e.g., sensory neurons); inhibition allows default neural fate.
High BMP → cells become epidermis or dorsal neurons (like sensory neurons).
BMP blocked → cells become neural tissue (default pathway).
19
Q
What are rhombomeres and what determines their identity?
A
Segmental units of the hindbrain, patterned by Hox genes in response to morphogens like retinoic acid.
20
Q
What happens if Hoxb1 is deleted?
A
Rhombomere 4 (R4) takes on R2 characteristics, altering motoneuron migration.
21
Q
How does regional specialization of the brain occur?
A
Through intrinsic programs (transcription factors) and extrinsic cues (e.g., sensory input during critical periods).
22
Q
What’s the significance of reprogramming sensory cortices?
A
Shows neural plasticity; cortical regions can adapt function based on input (e.g., auditory cortex rewired to process vision).
23
Q
What are the two main modes of cell division in the neuroepithelium and their outcomes?
A
Symmetric Division: Produces two progenitor cells → amplifies progenitor pool
Asymmetric Division: Produces one progenitor and one differentiated cell (neuron or glia) → depletes progenitors
Environmental signals influence division type.
24
Q
What determines whether a neuroepithelial cell becomes a neuron or glial cell?
A
Neighboring cell signaling (Notch/Delta pathway)
Intrinsic properties and extrinsic cues like transcription factors
Notch high → glia, Notch low/Delta high → neurons
25
How do Delta and Notch signaling regulate neuronal differentiation?
Delta (ligand) activates Notch (receptor) on neighboring cells
When a cell has high Notch activation, it suppresses its own Delta expression → that cell becomes a glial cell (or remains a progenitor, depending on context).
A cell with low Notch / high Delta keeps sending Delta signals → it becomes a neuron.
Feedback loop creates cellular diversity from a uniform population.
26
What transcription factors are important in neuronal/glial differentiation?
bHLH (basic helix-loop-helix) transcription factors
Promote neuronal fate by influencing Delta expression and suppressing glial gene programs.
27
Where do excitatory cortical neurons originate and how do they migrate?
Origin: Cortical ventricular zone
Migrate radially along radial glia
“Inside-out” layering: older neurons are deeper, younger neurons migrate past to superficial layers.
28
Where do cortical interneurons originate and how do they migrate?
Origin: Ganglionic eminences
Migrate tangentially across cortex before integrating
Diverse timing and routes → increased cortical complexity
29
Why is a neuron’s “birthday” important?
It determines its final position and identity in the cortex. Earlier-born neurons form deeper layers, later-born migrate past them to form outer layers.
30
What are neural crest cells and what do they become?
Migratory cells from the neural tube
Become sensory neurons, autonomic neurons, Schwann cells, melanocytes, etc.
31
What did the Le Douarin graft experiments show?
Neural crest cells can change fate based on environmental cues during migration
Grafted cells take on identity of new location
32
What three factors determine neuronal diversity?
Proliferative zone origin
Transcription factor expression
Migration pattern
33
How do neurons acquire specific neurotransmitter phenotypes?
The cells or tissues that neurons connect to (their targets) can send signals back to the neuron that influence its identity, including which neurotransmitter it uses.
Example: IL-6-like molecules induce some sympathetic neurons to switch from NE to ACh when innervating sweat glands
34
What growth factors influence glial development?
PDGF (Platelet Derived Growth Factor): Promotes oligodendrocyte lineage
CNTF (Ciliary Neurotrophic Factor): Promotes astrocyte fate
Self-renewal signals maintain progenitor pool postnatally
35
What is the neurotrophic factor hypothesis?
Neurons are overproduced, and only those that successfully connect with targets and receive neurotrophic factors (e.g., NGF) survive
Neuronal activity influences responsiveness to these factors
36
Name three ways target tissues influence developing neurons.
Phenotype selection (e.g., neurotransmitter type)
Survival signals via neurotrophins
Axonal guidance and connectivity
37
What is the function of the axon growth cone?
Motor role: Axon elongation via actin-myosin interactions, polymerization/depolymerization of actin
Sensory role: Detects environmental cues with membrane receptors, guiding growth toward or away from stimuli
38
Describe the three structural parts of a growth cone.
Central core: Microtubules, mitochondria, organelles
Filopodia: Thin, actin-rich projections; sensory function with receptors for cues
Lamellipodia: Actin-myosin meshwork between filopodia; supports motility
39
What was Paul Weiss’s hypothesis?
on axon pathfinding
Stereotropism: Mechanical guidance based on structural paths
Resonance hypothesis: Axons form connections where electrical activity is congruent (experience-dependent)
40
What is Roger Sperry’s hypothesis?
chemospecificity hypothesis
Axons are guided by molecular labels to specific targets
Connections are not random and depend on chemical cues, even if the target is moved
Proven by frog eye rotation experiment: axons reconnected to original tectal targets despite rotation
41
What are the four types of axon guidance mechanisms?
Contact attraction (e.g., cadherins)
Contact repulsion (e.g., ephrins)
Long-distance attraction (e.g., netrins)
Long-distance repulsion (e.g., semaphorins)
42
What are short-range vs long-range cues in axon guidance?
Short-range: Membrane-bound or ECM-associated (e.g., ephrins)
Long-range: Diffusible molecules forming gradients (e.g., netrins, semaphorins)
43
How do retinal ganglion cell axons reach their targets in the brain?
Exit retina along basal lamina and glial cells
Enter optic stalk guided by attractants
Nasal axons cross at chiasm; temporal axons remain ipsilateral
Travel via optic tract to tectum, LGN, or SC
Layer-specific cues halt growth and trigger arborization
44
What role do ephrins and Eph receptors play in retinal map formation?
Create gradients across retina and tectum
Direct axons to precise locations, forming retinotopic maps
45
What are the key molecular players in spinal cord midline crossing?
BMP: Repels axons laterally
Netrin (via DCC receptor): Attracts axons to midline
Slit (via Robo receptor): Repels axons from midline once crossed
Frizzled (Wnt pathway): Guides axons rostrally after midline crossing
46
What happens once an axon reaches its target?
Synapse formation initiated via neuroligin and neurexin
Synaptic pruning occurs: excess connections are eliminated
"Use it or lose it" principle: Synapse maintenance is activity-dependent
47
What is synaptic pruning and why is it important?
Selective elimination of excess synapses
Optimizes neural circuit efficiency and learning capacity
48
What are cell adhesion molecules (CAMs) and their role in synapse formation?
CAMs (e.g., cadherins) stabilize contact between growth cone and dendrite
Recruit presynaptic and postsynaptic proteins needed for mature synapse
49
What does BSSC stand for, and why is it important in studying respiratory development?
BSSC stands for Brainstem-Spinal Cord. It's a preparation used in rodent models to study the neural control of breathing. It allows researchers to observe rhythmic respiratory patterns and neural connections in isolated systems.
involves isolating the brainstem and spinal cord, preserving their neural connections, and allowing them to generate respiratory rhythms
50
What is the significance of the rhythmic slice preparation in respiratory research?
The rhythmic slice contains the pre-Bötzinger complex (PreBot), a region that generates spontaneous inspiratory rhythms. It allows observation of rhythmic activity even when isolated from other brain regions.
51
What is the rat gestational designation for embryonic and postnatal stages, and what is the gestation period?
Embryonic = E, Postnatal = P. The gestational period in rats is 21 days.
52
What structure does the pleuroperitoneal fold (PPF) develop into?
The PPF develops into the primordial diaphragm.
53
What are the 'costal' and 'crural' components of the diaphragm?
These terms refer to anatomical regions of the diaphragm—'costal' is the peripheral part attached to ribs; 'crural' refers to the central tendon region near the spine.
54
What is the ventricular zone, and why is it relevant in neural development?
It's the inner layer of the developing neural tube where neural progenitor cells originate, crucial for early nervous system development.
55
What is the significance of phrenic motor neurons (PMNs) extending dendrites into the white matter?
This positioning allows PMNs to receive descending axonal input from medullary respiratory centers, enabling rhythmic respiratory activity.
56
How do phrenic axons reach the diaphragm during development?
They migrate toward the pleuroperitoneal fold using short-range cues (like the body wall), then separate from the brachial plexus and target muscle precursors.
57
How is myotube formation restricted in the diaphragm during development?
Myotube formation in the diaphragm is limited to areas innervated by the phrenic nerve. This ensures muscle develops only where it will be functional, allowing the diaphragm to contract effectively for breathing.
58
Describe the dendritic reorganization of PMNs after E17.
After embryonic day 17, premotor neuron dendrites stop spreading out widely. Instead, they shrink and bundle together, reorienting themselves from side-to-side to front-to-back. This change likely helps the neurons fire in a coordinated way to control movement more effectively.
This reflects a shift from exploration and connectivity to precision and coordination.
59
Why might PMN number reduce between E15 and E17?
Possible reasons include:
- alleviating spatial constraints --> Reducing neuron number through programmed cell death (apoptosis) helps free up space
- ongoing migration --> Some PMNs may still be migrating to their final positions during this window. Thus, neurons might not be gone, just not yet settled into the phrenic motor nucleus.
- reducing dendritic density for improved efficiency. --> Pruning some neurons and dendrites reduces redundant or unneeded inputs, making the network more efficient and coordinated.
60
What hypothesis were Allan and Greer testing?
That phrenic motor neurons are mature at the onset of phrenic activity at embryonic day 17 (E17), before birth.
61
Why study PMN and diaphragm development before birth, given neonates don't breathe in utero?
Respiratory activity begins before birth, and PMNs are mature at birth—so maturation must occur prenatally.
62
What was the major conclusion of the Allan Greer study?
Even though phrenic motor neurons are still structurally immature at E17, they can already start working together. Their early coordination likely happens through gap junctions (direct electrical links) or widespread neural branches—not through fully mature chemical synapses or dendritic organization.
63
What was a key critique of the methodology used in the Allan Greer study?
The DiI labeling technique may not capture all PMNs due to incomplete retrograde labeling.
64
Why is a fully functioning respiratory system at birth critical?
Because failure of breathing at birth is incompatible with life. Each component of the respiratory system must develop in parallel to ensure readiness for the transition to air breathing.
65
What changes are seen in preBötzinger complex (preBot) activity during prenatal development?
In both brainstem-spinal cord and brainstem slice preparations, there is an increase in respiratory frequency as development progresses.
66
What are key signs of diaphragm maturation around the onset of FBMs?
Increased muscle fiber density and cross-sectional area.
67
What in vitro indicators show increasing neuromuscular maturity?
Patch clamp recordings show increasing PMN firing rates, and end plate potentials become more frequent, indicating improved neuromuscular transmission.
End plate potentials (EPPs) are the electrical signals that occur at the neuromuscular junction (NMJ) when a motor neuron releases acetylcholine onto a muscle fiber.
As the NMJ matures, these signals occur more often (indicating consistent neurotransmitter release),
68
What do in vivo ultrasound studies reveal about FBMs?
FBMs increase with age and shift from single to clustered events, becoming more prominent and patterned (e.g., sinusoidal) near birth.
69
What mechanical and physiological processes occur during FBMs?
During FBMs, the fetus activates breathing muscles, which stretch the lungs in a rhythmic way. The closed glottis traps fluid, creating positive pressure that expands the lungs and airways. These mechanical and physiological actions are critical for proper lung development before birth.
70
When do FBMs start in humans, and when do they become regular?
FBMs begin at 10–12 weeks gestational age and become regular around 28 weeks.
71
What are the functions of FBMs according to rodent studies?
- Lung Development and Maturation --> The stretching and distension of fluid-filled lungs during FBMs stimulates the growth and branching of lung tissue.
- encourages alveolar development and production of surfactant, a substance essential to keep the lungs from collapsing after birth.
- Activating the diaphragm and other respiratory muscles helps strengthen and coordinate them.
- help train the neural networks that control breathing, including the phrenic motor neurons and brainstem respiratory centers. helps establish synchrony and timing needed for effective breathing.
- Maintaining Fluid Balance and Pressure in the Lungs
- FBMs help develop the airway structure and muscle tone needed to handle the transition from fluid-filled to air-filled lungs at birth.
72
What insights come from sheep studies regarding FBMs?
FBMs are abolished during hypoxia but can return after 12–16 hours, suggesting an adaptive suppression to minimize oxygen use. This supports their role in developmental maturation.
73
How do FBMs change during labor?
FBMs decrease significantly (<10%) to prevent aspiration, influenced by placental and hormonal changes such as increased PCO₂, catecholamines, and decreased pH and temperature.
74
What characterizes the first breath?
It is deep and long, creating hydrostatic pressure to clear airways, increase pulmonary blood flow, and close the ductus arteriosus. Postnatal breathing becomes rapid and irregular.
75
What role does surfactant play in birth readiness?
Secreted by type II alveolar cells starting at 24–28 weeks; sufficient by 35 weeks to prevent alveolar collapse, enabling premature infants to breathe independently.
76
What hypothesis did Kobayashi et al. test?
That timing and age-dependent in vitro changes in respiratory activity correlate with in vivo behavior (FBMs).
77
Describe the methods used by Kobayashi et al.
Pregnant rats were anesthetized; fetal FBMs were recorded using ultrasound. Stimuli (e.g., doxapram, aminophylline) and hypoxia were administered via maternal injection, and FBMs characterized by diaphragm/thoracic wall movement.
78
What were three key findings of Kobayashi study?
(1) FBMs change from single to clustered between E15–E21.
(2) Stimulants increased clustered FBMs, especially at E20.
(3) Hypoxia reduced FBMs at E20, but recovery occurred post-normoxia.
79
Why is it important to understand FBM characteristics and onset?
To track lung growth/maturation, guide respiratory development studies, and understand neural inspiratory drive.
80
What inspiratory profile differences exist between in vivo and in vitro models?
In vivo: clustered patterns dominate late gestation;
In vitro: predominantly single, low-frequency activity, lacking supramedullary and peripheral influences.
81
Why examine neuromodulation of FBMs?
To explore how neuromodulators like doxapram and aminophylline alter respiratory rhythm, and how hypoxia depresses it—important for understanding developmental vulnerabilities.
82
What major conclusions did the kyobashi study reach?
FBMs begin later in rats than in some species but align with in vitro findings. The full network and supramedullary structures are essential for episodic breathing. Peripheral chemoreceptors likely immature until ~E20.
83
What were two flaws in the Kobayashi paper?
(1) Could not track the same fetus longitudinally—individual variation.
(2) No direct PO₂ measurements in dam or fetus—unclear hypoxic exposure. Other flaws: no fetal sleep state control, no dose-response testing.
84
What are common postnatal breathing irregularities?
Apneas (long pauses in breathing), often linked to maternal factors (e.g., hypoglycemia, alcohol, narcotics), leading to drops in O₂ and long-term breathing changes.
85
How does prenatal nicotine exposure affect neonatal respiration?
It blunts chemoreflexes, reduces tongue muscle responses, and alters XII motor neuron firing, suggesting CNS-level disruption of respiratory control.
86
What is the clinical definition of SIDS (Sudden Infant Death Syndrome)?
SIDS is the sudden, unexplained death of an infant between 1 month and 1 year of age, which remains unexplained after thorough investigation (Willinger et al., 1991).
87
What is the leading cause of death in infants aged 1 month to 1 year in the U.S.?
SIDS (CDC, 2012).
88
When does SIDS most commonly occur?
Peak incidence is between 2–4 months of age (AAP, 2011).
89
List major risk factors associated with SIDS.
Preterm birth (<39 weeks), male sex (~60% of cases), African American, American Indian, and Alaskan Native ethnicity (AAP, 2011; Heron, 2012).
90
What are common myths about SIDS that are incorrect?
It is not caused by vaccines, cribs, hereditary factors, apnea monitors, or immunizations; and co-sleeping does not prevent it.
91
What are the three components of the Triple Risk Hypothesis for SIDS (Filiano & Kinney, 1994)?
(1) A critical developmental period, (2) a vulnerable infant, and (3) an exogenous stressor.
92
What campaign led to a 50% reduction in SIDS deaths?
The “Back to Sleep” (now “Safe to Sleep”) campaign, encouraging infants to sleep on their backs (AAP, 2005).
93
How much does stomach sleeping increase SIDS risk?
Between 1.7 to 12.9 times greater risk (AAP, 2005).
94
What is now the number one risk factor for SIDS following the Safe to Sleep campaign?
Maternal smoking (Knopik, 2013).
95
How does prenatal nicotine exposure affect infants?
It alters brain regions responsible for cardiorespiratory, arousal, and homeostatic control.
96
How is heat stress linked to SIDS?
Hyperthermia is often found in SIDS victims; infants have immature thermoregulation (Bach, 2022; Wailoo, 1989).
97
What hypothesis was tested regarding nicotine and heat stress in SIDS?
That chronic nicotine exposure causes severe breathing deficits during heat stress at a critical developmental period (P10–12 in rodents).
98
What model was used to test SIDS-related hypotheses in the lab?
P10–12 rodents were exposed to nicotine and/or heat stress and evaluated using plethysmography under normothermic and hyperthermic conditions.
99
What were the four experimental groups in the SIDS study?
(1) Control + normal temp, (2) Nicotine + normal temp, (3) Control + heat stress, (4) Nicotine + heat stress.
100
What outcomes did researchers measure in the nicotine/heat stress rodent model?
Breathing irregularities and mortality rates in response to hypoxia and hypercapnia during heat exposure.
101
What did the study conclude about nicotine and heat stress in SIDS?
Nicotine and heat stress jointly contribute to breathing deficits and mortality during a critical developmental period.
102
What does recent research suggest about human milk and SIDS risk?
Breastfeeding for at least 2 months significantly reduces SIDS risk (Hauck et al., 2011; Thompson et al., 2017).
103
What hypothesis connects breastfeeding to gut microbiota and SIDS?
That human milk promotes healthy infant gut microbiota, which in turn may reduce SIDS risk (Carr et al., 2021).
104
What potential confounding factors complicate breastfeeding studies on SIDS?
Bedsharing and socioeconomic status (Bartick et al., 2022).
105
What methods were proposed for future studies on breast milk and infant gut health?
Collect breast milk and fecal samples monthly for 6 months, analyze bacterial DNA using PCR/sequencing, and survey feeding behaviors and demographics.
106
What are limitations of rodent models in SIDS research?
(1) Cannot fully replicate human complexity.
(2) Other components of tobacco smoke are not included.
(3) Inflammatory stressors were not accounted for.
107
What are key limitations in the breastfeeding study?
(1) Cannot establish causality.
(2) High dropout risk in human studies.
(3) SIDS is rare and may not occur in the sample.
108
How do these studies advance knowledge on SIDS?
They identify interaction between developmental vulnerability and external stressors, guiding public health practices and future research directions.
109
What is immunohistochemistry/immunofluorescence and what is it used for?
A method used to label specific proteins within tissues or cells using antibodies. It allows visualization of protein distribution/localization and is semiquantitative.
110
Describe the labeling process used in immunofluorescence.
It involves two antibodies: a primary antibody that binds the target protein and a secondary antibody conjugated to a fluorophore, which binds the primary antibody. This enhances signal detection.
111
Why are goat, rabbit, and donkey antibodies used in immunofluorescence?
They are used due to species-specific interactions that help prevent cross-reactivity and improve target specificity in multi-label experiments.
112
What are fluorophores and why are they important in immunofluorescence?
Fluorophores are molecules that absorb light at one wavelength and emit light at another. They enable visualization of labeled structures under a fluorescence microscope.
113
What anatomical marker is used to identify preBötC neurons?
NK1 receptor (NK1R), which binds Substance P.
114
What marker identifies motor neurons?
Choline acetyltransferase (ChAT), an enzyme involved in the synthesis of acetylcholine.
115
How can NK1R and ChAT be used together in imaging studies?
NK1R (green) and ChAT (red) can be colabeled to show differentiation between motor neurons and preBötC neurons.
- Motor neurons will show yellow.
- PreBötC neurons (which are usually ChAT-negative but NK1R-positive) will show green only.
116
What is BrdU and how is it used in developmental studies?
BrdU (5-Bromo-2’-deoxyuridine) is a thymidine analog incorporated into DNA during the S-phase of dividing cells. It is used to determine when cells are born (neurogenesis).
117
How is BrdU detected in tissue?
Through immunofluorescence using antibodies against BrdU conjugated to a fluorophore.
118
How can BrdU help determine the birthdate of preBötC neurons?
BrdU is injected at various embryonic stages. Postnatal analysis shows when specific neurons (e.g., NK1R+ but ChAT–) were born based on BrdU presence.
119
At what embryonic day are preBötC neurons born, and how was this determined?
Around embryonic day E12.5. Determined by injecting BrdU and identifying NK1R+ BrdU+ ChAT– neurons in the preBötC region at later stages (e.g., E17).
120
What is shown in Figure 8 regarding neuron identity and birthdate?
Yellow cells (NK1R+ and BrdU+) in the preBötC indicate these neurons were born at E12.5 and are not motor neurons (ChAT–).
121
Why are the results in Figure 8 important?
They confirm that preBötC neurons are distinct from nearby motor neurons and have a specific developmental timeline, supporting the study’s hypothesis.
122
What hypothesis were Pagliardini et al. testing?
That preBötC neurons arise at a specific embryonic stage and are molecularly distinct from motor neurons.
123
Were the methods used by Pagliardini et al. appropriate for testing their hypothesis?
Yes. They used specific molecular markers (NK1R, ChAT), BrdU birthdating, and immunofluorescence to temporally and anatomically identify preBötC neurons.
124
What are the relevant respiratory nuclei that should be labeled in a brainstem diagram?
PreBötzinger complex, nucleus ambiguus (controls motor functions in the head and neck, including swallowing, speaking, and breathing), and possibly the ventral respiratory group (VRG).
125
What should be included in a summary of in vitro recordings from Pagliardini et al. study?
In vitro recordings demonstrated rhythmic activity in preBötC neurons consistent with their role in generating respiratory rhythm. This supports the identity and function of preBötC neurons.
126
What are glia, and what are the main types?
Glia are non-electrical, non-excitable, non-vascular, homeostatic support cells in the CNS. Types include:
Macroglia: astrocytes, oligodendrocytes, ependymal cells, radial glia, Schwann cells, NG2 glia
Microglia: immune cells of the CNS
127
What are the general functions of glial cells?
Structural support
Myelination (oligodendrocytes in CNS, Schwann cells in PNS)
Synaptic plasticity (microglia)
Neurotransmitter uptake (astrocytes)
Ion homeostasis
Immune surveillance
Blood-brain barrier (astrocytes and pericytes)
Energy metabolism (astrocyte-neuron lactate shuttle)
Developmental guidance
128
What is the function of oligodendrocytes and what makes them unique?
Oligodendrocytes myelinate multiple axons in the CNS, enhancing saltatory conduction. Derived from NG2 glia, they are abundant and capable of regeneration.
129
What are ependymal cells and their function?
Ciliated neuroepithelial cells lining the ventricles/central canal. They produce cerebrospinal fluid (CSF) and facilitate substance exchange between CSF and CNS.
130
What are radial glia and their role in brain development?
The first glial cells from neural progenitors. They guide neuronal migration and later differentiate into astrocytes and oligodendrocytes.
131
What are Schwann cells and how do they differ from oligodendrocytes?
Schwann cells myelinate axons in the PNS. Unlike oligodendrocytes, each Schwann cell myelinates one axon segment.
132
What makes NG2 glia (oligodendrocyte precursor cells) unique?
Proliferative and multipotent
Can become oligodendrocytes or astrocytes (especially after injury)
Active in adulthood
Likely play neuromodulatory and neuroprotective roles
133
What are the main metabolic and regulatory roles of astrocytes?
Glutamate recycling: via glutamate/Na+ cotransport and conversion to glutamine
Lactate shuttle: converts excess Na+ from transport into lactate, which fuels neurons
Neurotrophic signaling: affects survival/maturation of oligodendrocytes
BBB integrity: structural and functional maintenance
K+ uptake: high expression of potassium channels
Synaptic modulation: interacts with and refines circuits
134
Describe the developmental pathway of astrocytes.
BMP signals ectoderm → neural crest
Post-neurogenesis, radial glia switch to producing glia
Delta-Notch signaling → astrocyte fate
Ciliary neurotrophic factor (CNTF) enhances differentiation
Final fate: protoplasmic (gray matter) or fibrous (white matter) astrocytes
135
What is the origin and role of microglia in the CNS?
Derived from mesoderm (yolk sac lineage), unlike other glia (ectoderm-derived)
Invade CNS in embryonic and postnatal waves
Functions:
Immune surveillance
Synaptic pruning
Respond to damage/infection
Modulate neural development
136
How does microglial morphology change with age?
Young microglia: small body, long thin processes
Aged microglia: enlarged cell body, shorter/thicker processes
137
What is astrogliosis and how does it manifest?
Astrogliosis is a protective but potentially harmful response of astrocytes to CNS injury. It involves cell enlargement, changes in protein expression, inflammatory signaling, and scar formation, all of which help define the brain’s response to damage (e.g., trauma, ischemia). Features:
Hypertrophy
Increased GFAP/vimentin (plays a role in maintaining the structural integrity of astrocytes. )
Release of neurotrophic factors
Glial scar formation
Modulation of BBB
Proinflammatory cytokine release
138
What is microglial activation (microgliosis)?
triggered by damage to the central nervous system (CNS) or pathogenic insults
Reactive state of microglia post-injury. Includes:
Hypertrophy
Phagocytosis
Release of pro-/anti-inflammatory molecules
Triggers astrogliosis
139
How do microgliosis and astrogliosis interact?
Microglial activation can stimulate astrocyte reactivity. Together, they balance inflammation, neuroprotection, and repair. Excessive activation can exacerbate pathology.
140
What is Spinal Muscular Atrophy (SMA)?
SMA is an autosomal recessive neuromuscular disorder that leads to the loss of motor neurons in the anterior horn of the spinal cord, resulting in progressive muscle weakness, hypotonia, and atrophy.
141
What is the global incidence and carrier frequency of SMA?
SMA occurs in approximately 1 in 11,000 births, and 1 in 50 people are carriers.
142
What is the most common cause of death in severe SMA?
Respiratory failure due to severe muscle weakness.
143
What genes are involved in SMA?
SMN1 and SMN2 on chromosome 5.
144
How does SMN2 contribute to SMA pathology?
SMA causes the loss of SMN1, forcing the body to only use SMN2. Because SMN2 makes so little functional protein, it can’t fully compensate for the loss of SMN1. This deficiency in SMN protein causes motor neuron degeneration, which leads to SMA.
145
Why is SMN2 copy number important?
The number of SMN2 copies partially compensates for the lack of SMN1. More SMN2 copies usually correlate with milder disease.
146
What characterizes SMA Type 0?
Prenatal onset, no fetal movement, life expectancy <6 months.
147
What are the signs of SMA Type I?
Onset before 6 months; cannot sit independently; hypotonia; absent reflexes; high mortality by age 2.
148
What are the signs of SMA Type II?
Onset 7–18 months; can sit, cannot walk; joint contractures, tremors, risk of respiratory issues.
149
What are the signs of SMA Type III?
Onset before age 3; can walk but may need a wheelchair later; scoliosis and poor mobility are possible.
150
What are the signs of SMA Type IV?
Onset after age 18; mild symptoms; typically no walking or respiratory issues.
151
Is there a cure for SMA?
No cure exists, but there are treatments that slow disease progression and improve quality of life.
152
What is Nusinersen?
A treatment that enhances SMN2 splicing to produce more functional SMN protein.
153
What is Risdiplam?
An oral medication that also promotes exon 7 inclusion in SMN2 transcripts.
154
What is Onasemnogene abeparvovec?
A gene therapy that replaces the faulty SMN1 gene with a functional copy.
155
How does prognosis vary by SMA type?
Type 0: Often fatal despite treatment
Type I: May survive early childhood with intervention
Type II: Many survive into adulthood
Type III: Normal lifespan with support
Type IV: Lifespan usually unaffected
156
Why is early intervention critical in SMA?
Most motor neuron loss in Type I SMA occurs before 6 months, so early treatment is crucial.
157
Is newborn screening available in the U.S.?
Yes, as of 2024, all 50 states and D.C. screen for SMA at birth.
158
What is Neurofibromatosis (NF)?
NF is a genetic disorder that causes the growth of noncancerous tumors on nerve tissue, affecting the skin, central, and peripheral nervous systems.
159
What gene is primarily affected in Neurofibromatosis Type 1?
The NF1 gene, located on chromosome 17q11.2, which produces neurofibromin, a protein involved in cell growth regulation.
160
What is the birth incidence of Neurofibromatosis?
NF occurs in about 1 in 3,300 births, with no race or sex preference.
161
How is NF inherited?
NF1 and NF2 are autosomal dominant disorders, meaning one copy of the altered gene is enough to cause the condition.
162
What are the three main types of NF?
NF1 (most common)
NF2
NF2-related Schwannomatosis
163
What are hallmark features of NF1?
Café au lait spots
Neurofibromas (benign skin or nerve tumors)
Lisch nodules on the iris
Learning disabilities and ADHD
Optic pathway gliomas
164
What behavioral or cognitive conditions are associated with NF1?
ADHD (28% prevalence, more in males)
Learning disabilities (affect ~50% of NF1 patients)
165
What other health risks are increased with NF1?
Cardiovascular disease
Hypertension
Breast cancer in women
Gastrointestinal disease
166
How common is NF2?
Very rare, affecting 1 in 25,000 individuals.
167
What tumors are common in NF2?
Schwannomas on the vestibulocochlear nerve (hearing loss, balance issues)
Meningiomas (tumors on the meninges)
Ependymomas (tumors in the spinal cord)
168
What gene is mutated in NF2 and what does it do?
The NF2 gene on chromosome 22, which encodes merlin, a protein that helps regulate cell growth.
169
What distinguishes NF2 Schwannomatosis from other types?
Symptoms appear later in life (teens to 30s)
Involves both vestibular and non-vestibular schwannomas, especially on the head and neck.
170
What is the molecular consequence of NF1 mutation?
Loss of neurofibromin activity leads to RAS pathway hyperactivation, increasing tumor formation through PAK1.
171
What happens when both NF2 alleles are inactivated?
The merlin protein is no longer produced, disrupting cell cycle control and increasing tumor growth.
172
Is there a cure for Neurofibromatosis?
No, but several treatments can help manage symptoms and improve quality of life.
173
What is the typical life expectancy for someone with NF?
About 40–72 years, which is 10–15 years shorter than average, depending on the type and severity.
174
What are some common treatments for NF?
Surgery (for severe or cosmetic neurofibromas)
Chemotherapy (e.g., vinblastine, vincristine)
Behavioral therapy (for ADHD)
Pain management
Hearing aids or cochlear implants (for NF2-related hearing loss)
175
What is Anencephaly?
A severe neural tube defect (NTD) where major parts of the brain, skull, and scalp fail to form due to improper closure of the cranial neural tube during early embryonic development.
176
When does the neural tube normally close?
Between day 23 and day 26 of embryonic development.
177
What is the outcome for infants born with anencephaly?
Most are stillborn or die within hours to days after birth.
178
What is the global prevalence of anencephaly?
Approximately 1 to 5 cases per 1,000 live births, with higher rates in areas lacking folic acid food fortification.
179
What are common physical features of anencephaly at birth?
Absence of major parts of the brain and skull
Exposed brain tissue
Abnormal facial features (e.g., flattened forehead, cleft palate)
Malpositioned ears
180
What are some physiological complications in infants with anencephaly?
Lack of consciousness
No sensory response or voluntary movement
Difficulty or failure to regulate breathing, heartbeat, and temperature
181
What prenatal sign may suggest anencephaly?
Polyhydramnios (excess amniotic fluid) may be detected during pregnancy.
182
What is the most important preventable cause of anencephaly?
Folic acid deficiency before and during early pregnancy.
183
What gene mutation is commonly linked to anencephaly?
MTHFR (methylenetetrahydrofolate reductase), which impairs folate metabolism.
184
Name other maternal risk factors for anencephaly.
Maternal diabetes
Obesity
Antiepileptic medications
Exposure to high temperatures or pesticides
Family history of neural tube defects
185
How is anencephaly diagnosed prenatally?
Through ultrasound and maternal blood screening.
186
Is there a cure or treatment for anencephaly?
No. Since major brain structures are absent, corrective treatment is not possible. Only supportive care is offered.
187
How effective is folic acid in preventing anencephaly?
Adequate folic acid intake before and during early pregnancy can reduce the risk of anencephaly by up to 70%.
188
What is the recommended prevention strateg for anencephaly?
Folic acid supplementation (400–800 mcg/day pre-conception and in early pregnancy)
Maternal diabetes and weight management
Avoiding teratogenic medications/environmental exposures
189
What is the definition of epilepsy?
Epilepsy is a neurological disorder characterized by uncontrollable, excessive electrical signals in the brain, leading to seizures.
190
What are seizures, and how are they classified in epilepsy?
Seizures are abnormal electrical activity in the brain. They can be:
Focal (partial): Begin in one brain area, can be with or without loss of consciousness.
Generalized: Involve the entire brain, such as absence, tonic, atonic, clonic, myoclonic, and tonic-clonic seizures.
191
What are common signs and symptoms of epilepsy?
Jerking of arms and legs
Staring spells
Confusion
Loss of consciousness
Psychological changes
192
What are the common types of generalized seizures?
Absence (staring spells)
Tonic (stiff muscles)
Atonic (loss of muscle tone)
Clonic (rhythmic jerking)
Myoclonic (brief twitches)
Tonic-clonic (grand mal: stiffening, shaking, loss of consciousness)
193
What are major causes of epilepsy?
Genetic factors: Mutations in ion channel genes (e.g., potassium, calcium channels).
Structural brain abnormalities: Abnormal synapse formation or cortical development issues.
Brain injury: Strokes or trauma can lead to excitatory imbalances and seizures.
Unknown: ~20% of cases have no clear cause.
194
How is epilepsy diagnosed?
EEG: Detects abnormal electrical patterns (interictal epileptiform discharges).
Imaging: MRI, PET, SPECT, MEG help identify seizure foci or structural problems.
195
What are the main treatment options for epilepsy?
Antiseizure medications (ASMs): Phenytoin, carbamazepine, valproate, lamotrigine, levetiracetam.
Electrical stimulation: Vagus nerve stimulation (VNS), responsive neurostimulation (RNS), deep brain stimulation (DBS).
Surgery: For cases with a localized seizure focus.
Ketogenic diet: Used when other treatments fail.
196
How do antiseizure medications (ASMs) work?
ASMs regulate neuronal excitability by stabilizing ion channels and preventing excessive firing.
197
What is vagus nerve stimulation (VNS) in epilepsy treatment?
An implanted device stimulates the vagus nerve to regulate brain activity and reduce seizures.
198
What is responsive neurostimulation (RNS)?
A device detects abnormal electrical signals and delivers targeted electrical stimulation to prevent seizures.
199
What is deep brain stimulation (DBS) in epilepsy management?
Electrodes are implanted in specific brain areas to deliver controlled electrical signals and help prevent seizures.
200
Is epilepsy curable?
No, epilepsy is not curable, but it is often manageable with medications, electrical stimulation, surgery, and dietary interventions.
201
What is the global prevalence of epilepsy?
Approximately 50 million people worldwide have epilepsy, making it one of the most common neurological disorders.
202
What is epileptogenesis?
The process by which the brain becomes prone to generating seizures, often after brain injury, stroke, or due to genetic or developmental factors.
203
203
What role does glutamate play in epilepsy after a brain injury?
Brain injury can cause excessive glutamate release, leading to calcium buildup in neurons, increased excitability, and seizures.
204
What is Rett Syndrome?
Rett Syndrome is a rare genetic neurological and developmental disorder that primarily affects females. It occurs in about 1 in 10,000 to 1 in 23,000 girls worldwide. It usually presents between 6 to 18 months of age and is marked by the loss of motor and communication skills after a period of seemingly normal development.
205
What causes Rett Syndrome?
Rett Syndrome is caused by a mutation in the MECP2 gene located on the X chromosome. This gene codes for the MeCP2 protein, which is important for regulating gene expression in the brain and maintaining neural connections.
206
What are the hallmark symptoms of Rett Syndrome?
Key symptoms include:
Loss of motor skills (e.g., walking, hand use)
Loss of speech
Repetitive hand movements (e.g., hand-wringing, clapping)
Breathing irregularities (e.g., hyperventilation, breath-holding)
Seizures (common in later stages)
Scoliosis and joint contractures in later stages
207
What are the four stages of Rett Syndrome?
Stage 1: Early Onset (6-18 months)
Subtle delays (e.g., reduced eye contact, delayed motor milestones)
Stage 2: Regression (1-4 years)
Loss of skills (speech, hand use), repetitive movements, breathing problems
Stage 3: Plateau (2-10 years)
Symptoms stabilize, some functional improvement (e.g., eye gaze)
Stage 4: Late Motor Deterioration (10+ years)
Increased motor issues (e.g., scoliosis, joint problems), but cognitive and social abilities often remain stable
208
What is the typical prognosis for individuals with Rett Syndrome?
There is no cure for Rett Syndrome. However, with appropriate care and therapy, individuals can live into their 40s and beyond. Those with milder symptoms may have a relatively longer life expectancy, but without management, complications can lead to early death.
209
What treatments are available for Rett Syndrome?
Trofinetide: The only FDA-approved medication, helps with brain inflammation and synaptic function
Physical therapy: Improves motor skills and mobility
Occupational therapy: Teaches adaptive skills (e.g., using assistive devices)
Speech therapy: Supports alternative communication (e.g., eye gaze, communication devices)
Supportive care: Includes managing breathing problems, scoliosis, and seizures
210
Why does Rett Syndrome primarily affect females?
Since Rett Syndrome is caused by a mutation in the MECP2 gene on the X chromosome, males who inherit the mutation usually do not survive infancy, as they lack a second X chromosome to compensate. Females with the mutation often survive because they have one healthy X chromosome.
211
How does the MECP2 mutation affect the brain?
The mutation leads to the production of a non-functional MeCP2 protein, which disrupts the regulation of other genes critical for neuron development, synaptic function, and brain plasticity. This causes impaired neural connections and is the basis of the neurological symptoms.
212
What is Congenital Central Hypoventilation Syndrome (CCHS)?
CCHS is a rare, lifelong neurodevelopmental disorder that disrupts the automatic control of breathing, especially during sleep. Individuals with CCHS do not respond normally to high carbon dioxide (CO₂) or low oxygen (O₂) levels.
213
What causes CCHS?
CCHS is caused by mutations in the PHOX2B gene, which is essential for developing neurons that control automatic breathing. Most cases involve polyalanine repeat mutations (PARMs), and the mutations are usually inherited from asymptomatic parents.
214
How does CCHS affect breathing?
CCHS impairs the brain’s ability to respond to high CO₂ or low O₂, especially during non-REM sleep, leading to hypoventilation. Breathing can slow or stop entirely, which is life-threatening without intervention.
215
What are the main signs and symptoms of CCHS?
Hypoventilation during sleep (slowed or absent breathing)
Cyanosis and respiratory failure in infants
Fatigue and concentration problems in older children
Gastrointestinal issues (Hirschsprung’s disease)
Cardiac arrhythmias and eye movement abnormalities
Risk of respiratory arrest, especially after sedatives or anesthesia
216
How is CCHS diagnosed?
Diagnosis is based on clinical presentation (hypoventilation, cyanosis, etc.) and genetic testing for PHOX2B mutations. Early detection is crucial for life-saving interventions.
217
How is CCHS treated?
Lifelong assisted ventilation (e.g., tracheostomy with mechanical ventilation or non-invasive ventilation)
Monitoring of oxygen and carbon dioxide levels
Routine neurocognitive assessments to detect cognitive issues from hypoxia
There is no cure, but proper management allows a normal life expectancy.
218
What is the prognosis for individuals with CCHS?
With appropriate lifelong ventilation support, individuals with CCHS can have a normal life expectancy. However, untreated cases are at risk for severe complications and sudden death, especially during sleep.
219
Why is CCHS considered a genetic disorder?
CCHS is inherited in an autosomal dominant pattern with incomplete penetrance, meaning it can be passed from asymptomatic parents to children. This highlights the importance of family genetic testing.
220
What are some additional complications associated with CCHS?
Some individuals with CCHS also have:
Hirschsprung’s disease (gastrointestinal motility disorder)
Cardiac arrhythmias (irregular heartbeats)
Eye movement abnormalities (such as strabismus)
221
What is Neurofibromatosis (NF)?
NF is a genetic neurodevelopmental disorder characterized by the growth of multiple tumors on or near nerves, affecting the brain, spinal cord, skin, eyes, and bones. It has three types: NF1, NF2, and Schwannomatosis (SWN).
222
What are the three types of Neurofibromatosis?
NF1 (most common, ~96% of cases)
NF2 (rarer, ~1 in 33,000)
Schwannomatosis (SWN) (rarest, ~1 in 40,000 to 1.7 million)
223
What causes NF1?
NF1 gene mutation on chromosome 17
Leads to loss of neurofibromin, a protein that regulates the Ras pathway
Without neurofibromin, the Ras pathway becomes overactive, promoting tumor growth
224
What are the key features of NF1?
Café-au-lait spots (skin patches)
Axillary/inguinal freckling
Neurofibromas (benign nerve tumors)
Lisch nodules (iris bumps)
Learning disabilities
Bone abnormalities
Mutation in the NF2 gene on chromosome 22
Results in a lack of merlin protein, which normally regulates the Hippo pathway to control cell growth
Without merlin, schwannomas form, especially on the vestibulocochlear nerve
225
What causes Schwannomatosis (SWN)?
Mutations in two genes on chromosome 22, plus post-fertilization mutations
Leads to loss of tumor suppression and uncontrolled cell growth
226
What are the key features of NF2?
Bilateral vestibular schwannomas (tumors on both vestibulocochlear nerves)
Hearing loss and balance problems
Vision changes
Muscle weakness
227
What are the key features of Schwannomatosis (SWN)?
Multiple schwannomas without vestibular nerve involvement
Chronic pain, numbness, tingling, and weakness
Tumor size and number do not correlate with symptom severity
228
How is Neurofibromatosis treated?
Surgical removal of tumors when possible
Radiation therapy (occasionally, for local control)
Two FDA-approved drugs (MEK inhibitors) for NF1-related tumors:
Selumetinib (Koselugo)
Mirdametinib (Gomekli)
Supportive care for symptom management
229
What is the prognosis for NF?
NF1: Reduced life expectancy (~15 years less)
NF2: Median survival ~15 years after diagnosis
SWN: Normal life expectancy, but often diagnosed late due to mild early symptoms
230
What is Autism Spectrum Disorder (ASD)?
A neurodevelopmental disorder characterized by challenges in social communication, social interaction, and restricted or repetitive patterns of behavior, interests, or activities.
231
What does the term “spectrum” in ASD imply?
It reflects the wide range of symptoms, skills, and levels of impairment or disability that individuals with ASD can have.
232
What are the two main diagnostic criteria for ASD according to the DSM-5?
1) Persistent deficits in social communication and social interaction
2) Restricted, repetitive patterns of behavior, interests, or activities
233
Name three specific social communication difficulties common in ASD.
- Difficulty with back-and-forth conversations
Reduced sharing of interests or emotions
Trouble understanding nonverbal cues (e.g., facial expressions)
234
Give three examples of restricted or repetitive behaviors in ASD.
- Repetitive movements (e.g., hand-flapping)
Insistence on sameness or routines
Highly restricted, fixated interests
235
What are some early signs of ASD that may appear in infancy?
Lack of eye contact, delayed speech development, lack of interest in social interaction, and unusual responses to sensory input.
236
At what age is ASD typically diagnosed?
Most children are diagnosed after age 2, though signs can be observed earlier.
237
What are some common co-occurring conditions with ASD?
Intellectual disability, ADHD, anxiety, epilepsy, and gastrointestinal disorders.
238
Is there a single known cause of ASD?
No; ASD is believed to result from a combination of genetic and environmental factors.
239
How is ASD diagnosed?
Through behavioral evaluations and developmental screenings, often by a team including pediatricians, psychologists, and speech-language pathologists.
240
Can ASD be cured?
No; ASD is a lifelong condition, but early intervention and support can significantly improve outcomes.
241
What types of therapies are often used to support individuals with ASD?
Behavioral therapy (e.g., ABA)
Speech therapy
Occupational therapy
Social skills training
242
What does “neurodiversity” mean in the context of ASD?
The view that neurological differences like ASD are natural variations of the human brain and should be respected as such.
243
What is meant by “masking” in individuals with ASD?
When individuals hide or suppress autistic traits to fit into social norms, often leading to stress or burnout.
244
What is the gender ratio in ASD diagnosis?
ASD is about 4 times more common in males than in females, though females may be underdiagnosed.
245
What are the three main symptoms of ADHD?
Inattention, hyperactivity, and impulsivity.
246
Define "inattention" in the context of ADHD.
Trouble paying attention, especially to details; easily distracted; difficulty finishing tasks; often forgetful or loses things.
247
Define "hyperactivity" in ADHD.
Excessive movement, energy, and talking; difficulty staying still or quiet; constant fidgeting or restlessness.
248
Define "impulsivity" in ADHD.
Acting without thinking; difficulty with self-control; interrupting others; impatience.
249
What are signs of inattention in a child with ADHD?
- Can't pay attention to details
Struggles to concentrate or complete tasks
Difficulty listening
Frequently loses things
Forgets daily activities
250
What are signs of hyperactivity and impulsivity in ADHD?
- Fidgeting/squirming
Inability to stay seated
Loud play
Impatience
Interrupting or intruding on others
251
What are the three subtypes of ADHD?
Inattentive type: Primarily inattentive symptoms
Hyperactive-Impulsive type: Primarily hyperactive and impulsive symptoms
Combined type: All three symptoms present
252
Why is ADHD hard to diagnose in young children?
Many preschoolers naturally show similar behaviors, but most grow out of them. ADHD symptoms must persist and impair function to be diagnosed.
253
What is the minimum number of symptoms required to diagnose ADHD?
Children under 16: At least 6 symptoms
Ages 17 and up: At least 5 symptoms
Symptoms must appear in multiple settings and last over 6 months.
254
What is the latest age by which ADHD symptoms must appear?
Symptoms must be present before age 12 to support an ADHD diagnosis.
255
What other conditions can mimic ADHD symptoms?
Stress, sleep disorders, anxiety, and depression.
256
What two main categories contribute to the causes of ADHD?
Genetics and prenatal environmental factors.
257
How do genetics contribute to ADHD?
Account for up to 70% of ADHD risk
Involve genes affecting dopamine, serotonin, norepinephrine, and synaptic function
Impact brain areas like the prefrontal cortex and amygdala
258
How can maternal smoking during pregnancy influence ADHD risk?
Nicotine disrupts fetal neurotransmitter systems and impairs brain development, increasing ADHD risk.
259
What is the role of maternal immune activation (MIA) in ADHD development?
Inflammatory responses during pregnancy may damage fetal brain tissue, increasing ADHD susceptibility.
260
How common is ADHD in children?
In 2022, 11.4% (7 million) of U.S. children aged 3–17 were diagnosed with ADHD.
261
Is there a cure for ADHD?
No; it is managed with treatment focused on symptom control and functional improvement.
262
How is ADHD diagnosed?
Clinically—based on behavioral symptoms. There are no definitive lab tests or imaging.
263
What type of medication is typically used to treat ADHD?
Stimulants, such as lisdexamfetamine (LDX/Vyvanse).
264
What is anencephaly?
A severe neural tube defect where major parts of the brain, skull, and scalp fail to form due to failure of neural tube closure at the cranial end during embryonic development.
265
When does the cranial neural tube normally close during development?
Between day 23 and day 26 of embryonic development.
266
What is the typical outcome for infants born with anencephaly?
They are usually stillborn or die within hours to days after birth.
267
What is the global prevalence of anencephaly?
Approximately 1 to 5 per 1,000 live births, with higher rates in areas lacking folic acid fortification.
268
Name at least four major risk factors for anencephaly.
Folic acid deficiency
Maternal diabetes
Genetic mutations (e.g., MTHFR)
Use of antiepileptic medications
269
What vitamin deficiency is most associated with increased risk of anencephaly?
Folic acid (Vitamin B9) deficiency.
270
What are the hallmark signs and symptoms of anencephaly at birth?
Absence of major portions of brain/skull
Exposed brain tissue
Abnormal facial features (e.g., cleft palate)
No consciousness or voluntary movement
Often results in stillbirth or rapid neonatal death
271
What prenatal sign may suggest anencephaly during pregnancy?
Polyhydramnios (excess amniotic fluid).
272
How does maternal diabetes increase the risk of anencephaly?
Through hyperglycemia-induced oxidative stress and disrupted cell signaling, which interfere with neural tube closure.
273
How does maternal obesity contribute to anencephaly risk?
Likely through altered glucose metabolism and inflammation affecting neurodevelopment.
274
Why are antiepileptic drugs a risk factor for anencephaly?
They interfere with folate metabolism and neural cell development.
275
Is there a cure or corrective treatment for anencephaly?
No; the condition is fatal due to absence of critical brain structures.
276
What kind of care is provided to newborns with anencephaly?
Supportive care (comfort measures), but not life-sustaining interventions like mechanical ventilation.
277
What is the most effective prevention strategy for anencephaly?
Folic acid supplementation before conception and during early pregnancy.
278
What diagnostic tools are used prenatally to detect anencephaly?
Ultrasound and maternal blood screening.
279
What causes Fragile X Syndrome?
A mutation in the FMR1 gene on the X chromosome, which leads to a deficiency or absence of the FMRP protein.
280
What is the role of the FMR1 gene in Fragile X Syndrome?
It codes for FMRP (Fragile X Mental Retardation Protein), which regulates protein synthesis in the brain.
281
How is Fragile X Syndrome inherited?
X-linked dominant inheritance. However, due to X-inactivation, females may show milder symptoms.
282
How common is Fragile X Syndrome?
Males: 1 in 4,000–7,000
Females: 1 in 6,000–11,000
283
What are common comorbidities of Fragile X Syndrome?
Autism spectrum disorder, intellectual disability, anxiety, hyperactivity, speech and motor deficits.
284
What cognitive and behavioral symptoms are seen in Fragile X Syndrome?
Intellectual disability, autistic behaviors (e.g., stimming), seizures, anxiety, sleep issues, aggression, hyperactivity.
285
What are key physical features of males with Fragile X Syndrome?
Large ears and face
Flexible joints (especially fingers, wrists, elbows)
Low muscle tone
Flat feet
High-arched palate
Macroorchidism (large testicles)
286
What type of mutation occurs in Fragile X Syndrome?
CGG trinucleotide repeat expansion in the FMR1 gene.
287
What are the FMR1 repeat ranges and their classifications?
Normal: 5–44 repeats
Intermediate: 45–54 repeats
Premutation: 55–200 repeats
Full mutation: >200 repeats
288
Why are symptoms often less severe in females with Fragile X Syndrome?
Due to X-inactivation, one X chromosome is randomly silenced, potentially silencing the mutated copy.
289
What is the life expectancy for individuals with Fragile X Syndrome?
Normal life expectancy.
290
Is there a cure for Fragile X Syndrome?
No, there is currently no cure.
291
What types of treatment are used for Fragile X Syndrome?
Therapies: speech, physical, cognitive-behavioral
Medications: to manage symptoms (e.g., anxiety, hyperactivity)
Early intervention is important
292
What is cerebral palsy (CP)?
A group of disorders caused by injury to the central nervous system during the prenatal, perinatal, or early postnatal period, leading to impaired voluntary movement and balance control.
293
How common is cerebral palsy in the U.S.?
About 1 in 345 live births.
294
Is cerebral palsy progressive?
No. While symptoms may change with age, the brain injury does not worsen over time.
295
What are the main types of movement disorders in CP?
Spasticity (di-, hemi-, or quadriplegia)
Dyskinesia
Ataxia
Combinations of these
296
What are common comorbidities associated with CP?
Pain, intellectual disability, epilepsy, hip displacement, incontinence, sleep disorders, difficulty walking or speaking.
297
What are key early signs of CP in infants (up to 5 years)?
Exaggerated reflexes
Floppy or stiff limbs
Irregular posture
Uncontrollable or delayed movements
Unsteady walking
298
What tendencies in infancy may suggest early CP?
Favoring one side of the body
Trouble feeding or swallowing
Delayed motor milestones
Weak or absent reflexes
Difficulty focusing the eyes
299
What MRI findings are common in CP (6–24 months)?
Clefts in cerebral tissue
Hydrocephalus
Periventricular leukomalacia
300
What are major causes of cerebral palsy?
Infections during pregnancy
Genetic/developmental abnormalities
Inflammation and white matter damage
Birth complications, e.g., hypoxia or severe jaundice
301
How does maternal infection contribute to CP?
It activates the fetal immune system, releasing pro-inflammatory cytokines that damage brain cells.
302
What brain structure is most vulnerable to injury in CP?
The white matter, which transmits movement signals.
303
Is life expectancy affected in people with CP?
Most children survive into adulthood, but severely affected individuals may have reduced life expectancy.
304
What early milestones predict the ability to walk independently?
Sitting by 24 months
Crawling by 30 months
305
What are poor prognostic indicators for walking in CP?
No head control by 20 months
No postural reflexes by 24 months
Not crawling by age 5
306
Is there a cure for cerebral palsy?
No, but therapies can help manage symptoms and improve quality of life.
307
What are common therapy types used for CP?
Physical therapy (e.g., constraint-induced movement therapy, or CIMT)
Speech therapy (e.g., More Than Words program)
Mobility aids (e.g., canes, walkers)
Educational and cognitive training for learning disabilities
308
What is constraint-induced movement therapy (CIMT)?
A rehab method where the unaffected limb is restricted to promote use and strengthening of the affected limb.
309
What is Spina Bifida?
A congenital condition where the neural tube fails to close completely during early fetal development.
310
What are the three main types of Spina Bifida (from least to most severe)?
Occulta – Mildest, often asymptomatic.
Meningocele – Meninges protrude through the spine.
Myelomeningocele – Most severe; spinal cord/nerves protrude.
311
How common is Spina Bifida in the U.S.?
~1 in 1,278 babies per year.
312
Name at least five signs or symptoms of Spina Bifida.
Hydrocephalus
Paralysis/mobility issues in lower limbs
Learning disabilities
Bowel/bladder incontinence
Sleep apnea
Tethered spinal cord
Chiari malformation type II (in infants with myelomeningocele)
313
What is the believed cause of Spina Bifida?
Multifactorial – includes low maternal folate (B-9), genetic factors (e.g., MTHFR gene), and environmental influences.
314
What gene is implicated in folate processing and linked to Spina Bifida risk?
MTHFR gene – affects folate metabolism and neural tube development.
315
List at least four risk factors for Spina Bifida.
Uncontrolled maternal diabetes
Folate deficiency
Obesity
Family history of neural tube defects
High maternal core body temperature
Female and/or Hispanic/white ethnicity
316
When and how is Spina Bifida often diagnosed prenatally?
Between the 16th–18th week of pregnancy via:
MSAFP (Maternal Serum Alpha-Fetoprotein) blood test
Follow-up: Ultrasound and amniocentesis if MSAFP is abnormal
317
What are common treatment approaches for Spina Bifida?
Prenatal surgery (repair before birth)
Postnatal surgery (close spinal opening)
Maternal management: Control diabetes/obesity, increase B-9 intake
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How does prognosis differ by type of Spina Bifida?
Occulta: Typically normal life, no major complications
Myelomeningocele: Challenges include mobility issues, bladder/bowel dysfunction, risk of hydrocephalus
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explain the delta/notch pathway from start to finish
In the neural tube, random differences in Delta expression lead to high-Delta cells activating Notch in their neighbors, inhibiting neuronal differentiation around them. Neurogenin accelerates this process by directly increasing Delta expression, pushing the cell to become a neuron, while inhibiting surrounding cells from doing the same.
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What is lissencephaly?
Lissencephaly is a rare brain malformation characterized by a "smooth brain" due to absent or incomplete development of the brain's folds (gyri) and grooves (sulci).
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What causes lissencephaly?
It is caused by defective neuronal migration during embryonic development, often due to genetic mutations.
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Which genes are commonly associated with lissencephaly?
Mutations in genes such as LIS1 (PAFAH1B1) and DCX (Doublecortin) are commonly involved.
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What are the main types of lissencephaly?
Classic (type I): Smooth cortex with four layers instead of six
Cobblestone (type II): Bumpy surface from overmigration of neurons beyond the brain’s outer surface
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What are typical symptoms of lissencephaly?
Seizures, severe developmental delays, muscle spasticity or hypotonia, feeding difficulties, and intellectual disability.
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How is lissencephaly diagnosed?
Through neuroimaging (especially MRI) and genetic testing to identify causative mutations.
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Is there a cure for lissencephaly?
No cure exists; treatment is supportive and symptom-based (e.g., seizure control, therapy).
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What is congenital toxoplasmosis?
A parasitic infection caused by Toxoplasma gondii, passed from mother to fetus during pregnancy, potentially leading to neurological and ocular damage.
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How is congenital toxoplasmosis transmitted?
Through transplacental passage during acute maternal infection with T. gondii, typically from ingesting contaminated food or water.
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What are common severe symptoms of congenital toxoplasmosis in affected infants?
Seizures, hydrocephalus, cerebral calcifications, chorioretinitis, microphthalmia, hepatosplenomegaly, and developmental delays.
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What are common mild or later-onset symptoms?
Learning disabilities, motor delays, hearing loss, and endocrine abnormalities.
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How is congenital toxoplasmosis diagnosed?
Through serologic testing for T. gondii IgM and PCR testing during pregnancy or after birth.
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What treatments are available during pregnancy?
Spiramycin before 18 weeks gestation; sulfadiazine, pyrimethamine, and folinic acid afterward if infection is confirmed.
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What is the postnatal treatment approach?
A combination of sulfadiazine, pyrimethamine, and leucovorin for up to a year to improve neurological outcomes.
