New Content Flashcards
(295 cards)
1
Q
define health disparities
A
Social determinants of health (SDOH), i.e. poverty, racism,
and their consequences, impact health outcomes in
Black, Hispanic and Latinx, and other marginalized
populations.
2
Q
what are barriers to access
A
- gaps in health insurance coverage
- challenges traveling to in person services
- limited availability of Telehealth resources
3
Q
what are barriers to quality
A
- unequal availability of diagnostic and treatment resources
- uneven distribution of specialty care
- limited healthcare workforce diversity
- limited language services
4
Q
What type of study design is most appropriate to help
uncover factors that contribute to the higher risk for
stroke in a segment of the US population?
A. A double-blind randomized controlled trial
B. A single-blind randomized controlled trial
C. Cohort study
D. Case study
A
C. Cohort study
5
Q
describe the REGARDS study
A
- Reasons for Geographic and Racial Differences in Stroke (REGARDS) project, sponsored by the National Institutes of Health (NIH), is a national cohort study focusing on learning more about the factors that
increase a person’s risk of having a stroke. - Between 2003-2007, the study enrolled 30,239 black and white participants from the continental United States.
- For over a decade, the study has followed its participants to understand why Southerners and Black Americans have higher rates of stroke and related diseases that affect brain health.
- found that this was especially true for black individuals
6
Q
why do we need diverse healthcare providers
A
- one study showed that black healthcare providers reduce mortality for black patients
- infant mortality of black infants halved (reduced) when they had a black doctor
7
Q
What is a common motor deficit experienced by TBI patients?
A
Bimanual coordination deficits (difficulties in coordinating movements of both hands), including slower reaction times and decreased motor speed.
8
Q
How do structural brain abnormalities relate to TBI motor deficits?
A
White and grey matter changes in the brain are linked to impaired motor control.
9
Q
What imaging method was used in the TBI study to assess brain activity?
A
Functional magnetic resonance imaging (fMRI).
10
Q
How did TBI patients’ brain activation differ during movement preparation?
A
descreased activation in right superior frontal gyrus and visual cortex
11
Q
What was the pattern of brain activation in TBI patients during movement execution?
A
They exhibited overactivation in frontal, parietal, occipital, and subcortical areas.
12
Q
What does overactivation in TBI patients during movement execution suggest?
A
It indicates compensatory mechanisms due to impaired predictive motor control.
13
Q
What brain areas showed increased activation in TBI patients during execution?
A
Execution Phase: Increased activation in multiple brain regions, requiring greater cognitive effort for motor execution.
Specifically, left dorsolateral prefrontal cortex, left orbitofrontal cortex, inferior and superior parietal lobes, and cerebellum crus II
14
Q
How did augmented visual feedback impact task performance for TBI patients?
A
Both TBI patients and healthy controls performed better with augmented visual feedback.
15
Q
What was the key difference in feedback response between TBI patients and controls?
A
TBI patients showed less differentiation in brain activation between feedback conditions.
16
Q
Which brain areas were more active in healthy controls than TBI patients in response to feedback?
A
Primary motor cortex, cerebellum, and superior parietal lobe.
17
Q
What does reduced neural differentiation in TBI patients indicate?
A
neural differentiation –> specific brain waves related to a function
This indicates that their brain activity is less specialized or distinct when engaging in different cognitive or motor tasks.
18
Q
How do TBI patients compensate for motor control difficulties?
A
By recruiting additional brain regions, requiring increased cognitive effort.
19
Q
What is the primary goal of the study (MS)?
A
To identify early MRI predictors of long-term outcomes in relapse-onset multiple sclerosis (MS), including secondary progressive MS, physical disability, and cognitive performance.
20
Q
Why are demographic and clinical factors insufficient for predicting MS progression?
A
They have limited predictive value for individual patients and do not fully capture disease variability.
21
Q
What type of patients were included in the MS study?
A
Patients with clinically isolated syndrome (CIS) suggestive of MS, recruited within three months of onset.
22
Q
Which early MRI measures were studied as predictors of MS progression?
A
The study counted lesions present in multipke areas (brain stem, spinal cord, and cerebellum) to see if there was a relationship.
23
Q
What were the two strongest MRI predictors of secondary progressive MS after 15 years?
A
Baseline gadolinium-enhancing lesions and spinal cord lesions.
24
Q
What does the presence of gadolinium-enhancing lesions indicate?
A
Active inflammation and a higher risk of long-term disability.
25
How did new spinal cord lesions over time affect prognosis?
They were associated with an increased risk of developing secondary progressive MS.
26
What percentage of patients had progressed to secondary progressive MS after 15 years?
15% of patients.
27
What percentage of patients remained with CIS and did not develop MS?
27% of patients.
28
How common was significant physical disability among MS patients after 15 years?
Physical disability was generally low (median EDSS score of 2), but a subset had severe disability.
29
Which MRI measure was associated with poorer cognitive performance at 15 years?
Baseline gadolinium-enhancing lesions.
30
What tests were used to assess cognitive function in the study?
Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT).
31
What was a key predictor of reduced walking speed at 15 years for MS?
Baseline gadolinium-enhancing and spinal cord lesions.
32
How can these MS findings be used in clinical practice?
MRI findings can help counsel patients on long-term prognosis and personalize treatment plans.
33
Why is spinal cord MRI particularly important in MS prognosis?
Spinal cord lesions strongly predict secondary progression and physical disability.
34
What is the primary research question of the tourettes study?
Whether individuals with Gilles de la Tourette syndrome (GTS) exhibit enhanced habit formation due to an imbalance between goal-directed and habitual behavioral control.
35
What behavioral characteristic do tics and habits share?
Both are driven by stimulus-response associations and are often performed automatically, without sensitivity to the desirability of the outcome.
36
What neurological system is thought to contribute to tic generation in GTS?
The sensorimotor cortico-striatal network.
37
What type of learning paradigm was used in the tourettes study?
A three-stage learning task:
1. instrumental learning --> associating action with reward
2. outcome --> understanding changing rewards
3. slip of action task --> assessing habit formation
38
What did the ‘slip-of-action’ test measure?
The balance between goal-directed and habitual control by evaluating whether participants could suppress responses to devalued outcomes.
39
How were participants grouped in the tourettes study?
Into unmedicated GTS patients, medicated GTS patients, and healthy controls.
40
How did unmedicated GTS patients perform on the ‘slip-of-action’ test?
They relied more on habitual, outcome-insensitive behavior and were more likely to respond to devalued stimuli.
41
How did tic severity correlate with habitual responding?
In unmedicated GTS patients, greater engagement in habitual responses correlated with more severe tics.
42
How did medicated GTS patients compare to unmedicated patients and controls?
They performed at an intermediate level, suggesting that dopamine antagonist treatment may reduce habitual control.
43
What structural connectivity was associated with habitual behavior in GTS patients?
Increased connectivity within the right motor cortico-striatal network.
44
What brain region's connectivity predicted tic severity in unmedicated patients?
Stronger structural connectivity between the supplementary motor cortex and the sensorimotor putamen.
45
How does dopamine contribute to habit formation and tics?
abnormal reinforcement signals to the sensorimotor striatum may lead to excessive habit formation and contribute to tic generation.
46
What effect do dopamine antagonists have on habit formation?
They may reduce reliance on habitual control, but the effects vary depending on the specific medication.
47
What treatment approach is supported by the findings tourettes?
Habit reversal therapy, which has been shown to reduce tics and alter cortico-striatal activity.
48
Why is understanding habit formation important for GTS treatment?
Because tics may be reinforced by excessive habit learning, interventions targeting habit formation could improve symptom management.
49
What is epilepsy?
Epilepsy is a neurological disorder characterized by an increased likelihood of seizures due to abnormal brain activity.
50
What is an epileptic seizure?
A seizure is a sudden burst of abnormal electrical activity in the brain that can cause convulsions, loss of awareness, or other symptoms.
51
What are interictal spikes?
Interictal spikes are brief, abnormal bursts of electrical activity in the brain that occur between seizures in epilepsy patients.
52
What is the primary goal of epilepsy research?
The primary goal is to predict and prevent seizures by identifying early warning signs in brain activity.
53
How are interictal spikes related to seizures?
The relationship is complex and subject-specific; some patients show increased spike rates before seizures, while others show a decrease.
54
What did the study find about pre-ictal spike rates?
In 9 out of 15 subjects, spike rates significantly changed before seizures—some increased, while others decreased.
55
What is the significance of interictal spikes in seizure prediction?
Changes in interictal spike patterns may serve as biomarkers for cortical excitability, helping predict seizure likelihood.
56
How do circadian rhythms affect seizures?
Seizures tend to follow daily cycles, with some patients experiencing seizures predominantly during specific times of the day.
57
What evidence supports longer-term seizure cycles?
Some patients showed weekly or monthly seizure patterns, suggesting the influence of hormonal or other regulatory mechanisms.
58
What was observed about the timing of seizures?
Many subjects had seizures clustered at specific times of day, indicating a possible link to sleep cycles.
59
What is one hypothesis about the role of interictal spikes?
Some researchers believe that spikes might help prevent seizures by regulating brain activity, while others think they contribute to seizure onset.
60
How does interictal spiking relate to cortical excitability?
Both spikes and seizures may be influenced by the same factors regulating brain excitability, leading to similar temporal patterns.
61
What is a potential clinical implication of interictal spike monitoring?
Spikes could serve as a marker for identifying seizure risk, improving prediction strategies and treatment timing.
62
How was the data for the epilepsy study collected?
Data was obtained from intracranial EEG recordings of 15 patients over periods ranging from 6 months to 2 years.
63
What algorithm was used for spike detection?
A template-matching algorithm identified spikes by comparing EEG patterns with predefined spike templates.
64
What statistical methods were used in the study?
Autocorrelation, cross-correlation, and rank-sum tests were used to analyze spike and seizure patterns.
65
What is idiopathic rapid eye movement sleep behavior disorder (iRBD)?
iRBD is a sleep disorder characterized by abnormal movements and vocalizations during REM sleep, often associated with dream enactment.
66
Why is iRBD important in neurodegenerative research?
Most individuals with iRBD eventually develop a synucleinopathy, such as Parkinson’s disease (PD) or dementia with Lewy bodies (DLB), making it an early indicator of neurodegeneration.
67
What was the primary aim of the iRBD study?
To quantitatively assess gait and balance impairments in polysomnography-confirmed iRBD patients across different walking and balance conditions.
68
How many participants were included in the iRBD study?
38 participants (24 iRBD patients and 14 healthy controls).
69
What walking tasks were used to assess gait?
Participants completed five walking trials: normal pace, fast pace, counting backward from 100 by 1s, naming animals, and subtracting 7s from 100.
70
What additional balance tests were performed in iRBD study?
Participants completed static balance tests with eyes open and closed, as well as single-leg stance trials.
71
Did iRBD patients show gait impairments during normal walking?
No, significant differences were found only under fast-paced and dual-task conditions.
72
How did iRBD patients respond differently to dual-task walking?
Unlike healthy controls, iRBD patients did not widen their step width but instead showed increased step width variability.
73
What gait abnormalities were observed in iRBD patients during fast-paced walking?
iRBD patients exhibited greater step length asymmetry compared to healthy controls.
74
Were there differences in balance between groups?
iRBD patients had increased anterior–posterior sway during the eyes-closed balance test, suggesting subtle proprioceptive impairments.
75
What do these gait and balance impairments suggest about iRBD?
They likely reflect early neurodegenerative changes in brainstem regions involved in both REM sleep regulation and gait coordination.
76
How might the iRBD findings be useful in clinical settings?
Gait assessments under dual-task and fast-paced conditions could serve as early screening tools for identifying individuals at risk of developing Parkinson’s disease.
77
Why is asymmetry in gait significant for early detection of PD?
Asymmetry in step length and arm swing is a known early marker of Parkinson’s disease, reflecting early dopamine-related motor deficits.
78
What is epilepsy?
A neurological disorder characterized by an enduring predisposition to generate epileptic seizures and associated cognitive, psychological, and social consequences.
79
What causes epileptic seizures?
Abnormal, excessive, or synchronous neuronal activity in the brain.
80
What are the three main types of seizure onset?
1. Focal onset – Begins in localized brain regions.
2. Generalized onset – Involves both hemispheres from the start.
3. Unknown onset – Insufficient clinical data to determine origin.
81
What are some possible causes of epilepsy?
Acquired causes (e.g., stroke, traumatic brain injury), infections (e.g., neurocysticercosis), autoimmune diseases, and genetic mutations.
82
What is the 2017 International League Against Epilepsy (ILAE) classification framework?
A diagnostic system that categorizes epilepsy based on seizure type, epilepsy type (focal, generalized, unknown), epilepsy syndrome, and underlying etiology.
83
What tools are used for epilepsy diagnosis?
Clinical history, electroencephalography (EEG), neuroimaging (MRI/CT), and genetic testing.
84
What are some common non-epileptic seizure mimics?
Syncope, panic attacks, migraines, sleep disorders (e.g., REM sleep behavior disorder), and psychogenic non-epileptic seizures (PNES).
85
How common is epilepsy worldwide?
Epilepsy affects approximately 65 million people globally.
86
What is the incidence and prevalence of epilepsy?
The global prevalence is 6.4 cases per 1,000 persons, and the annual incidence is 67.8 cases per 100,000 person-years.
87
In which age groups is epilepsy most common?
Highest in infants/early childhood and older adults (>50–60 years).
88
What factors contribute to a higher epilepsy burden in low-income and middle-income countries (LMICs)?
Higher rates of birth injuries, neuroinfections, and limited access to medical care.
89
What is the first-line treatment for epilepsy?
Anti-seizure drugs (ASDs), with more than 20 approved by the FDA and EMA.
90
What percentage of epilepsy patients have drug-resistant epilepsy?
About one-third of patients fail to achieve seizure control with medication.
91
What are the treatment options for drug-resistant epilepsy?
Epilepsy surgery, neurostimulation devices, dietary therapies (e.g., ketogenic diet), and clinical trials for new ASDs.
92
What is the gold standard surgical treatment for drug-resistant epilepsy?
Resective epilepsy surgery, which removes the seizure focus.
93
What is epileptogenesis?
The process by which normal brain circuits transform into epileptic networks capable of generating seizures.
94
What is ictogenesis?
The mechanisms that generate and sustain seizures.
95
What are some known mechanisms of epileptogenesis?
- Neuronal plasticity (e.g., mossy fiber sprouting)
Glial dysfunction (e.g., astrocyte and microglia activation)
Blood-brain barrier (BBB) breakdown
Neuroinflammation and oxidative stress
96
How do animal models contribute to epilepsy research?
Rodent and non-mammalian models (e.g., zebrafish) help study seizure mechanisms and test new therapies.
97
What is SUDEP?
Sudden Unexpected Death in Epilepsy, occurring primarily during sleep and often following a generalized tonic-clonic seizure (GTC).
98
What are the main risk factors for SUDEP?
- Frequent GTC seizures (>3 per year)
Lack of seizure control
Nocturnal seizures
Young adult age
99
How can SUDEP be prevented?
Seizure control (medication, surgery, neurostimulation), nocturnal monitoring, and avoiding sleep deprivation.
100
What is Restless Legs Syndrome (RLS)?
RLS is a sleep-related sensorimotor disorder characterized by an urge to move the legs, occurring during rest, worsening in the evening or night, and improving with movement.
101
Who first described RLS?
Sir Thomas Willis in the 17th century, followed by Karl-Axel Ekbom, who provided a detailed clinical description.
102
What is another name for RLS?
Willis–Ekbom syndrome.
103
At what ages does RLS typically onset?
RLS has a bimodal onset, peaking at around 20 years and again at 40 years.
104
Is RLS more common in men or women?
RLS is 30–50% more prevalent in women than men.
105
What is the prevalence of RLS in different populations?
5–13% in Europe and North America; 1–3% in most Asian populations.
106
What are the two main classifications of RLS?
Primary (idiopathic) and secondary (symptomatic).
107
What conditions are commonly associated with secondary RLS?
Iron deficiency, kidney disease, cardiovascular diseases, diabetes, and neurological disorders.
108
What are periodic limb movements (PLM), and how are they related to RLS?
PLM are involuntary leg movements that occur in sleep (PLMS) or wakefulness (PLMW); at least 80% of RLS patients experience PLMS.
109
What are some hypothesized mechanisms underlying RLS?
Brain iron deficiency, dysfunction in the dopaminergic and nociceptive systems, and altered adenosine and glutamatergic pathways.
110
How does iron deficiency contribute to RLS?
Brain iron deficiency disrupts dopamine regulation, affecting neurotransmission and leading to symptoms.
111
How is the dopaminergic system involved in RLS?
A hyperdopaminergic state is observed, yet dopamine agonists initially relieve symptoms before leading to augmentation.
112
What are the essential diagnostic criteria for RLS?
1) Urge to move legs, 2) Symptoms worsen with rest, 3) Symptoms improve with movement, 4) Symptoms occur mainly at night, 5) Symptoms are not solely due to another condition.
113
What are common conditions mistaken for RLS?
Leg cramps, positional discomfort, akathisia, polyneuropathy, and venous disorders.
114
Why is RLS often misdiagnosed?
Low physician awareness, difficulty in describing symptoms, and confusion with insomnia.
115
What are the first-line pharmacological treatments for RLS?
Dopamine agonists (e.g., pramipexole, ropinirole) and α2δ ligands (e.g., gabapentin, pregabalin).
116
What is augmentation in the context of RLS treatment?
A worsening of symptoms due to long-term use of dopaminergic medications.
117
What are non-pharmacological approaches to managing RLS?
Exercise, lifestyle modifications, iron supplementation, cognitive-behavioral therapy, and sleep hygiene practices.
118
What are some common comorbidities associated with RLS?
Cardiovascular disease, diabetes, iron deficiency, multiple sclerosis, Parkinson’s disease, and depression.
119
How does RLS affect quality of life?
It disrupts sleep, increases the risk of mood disorders, and can lead to significant daily impairment.
120
What is the relationship between RLS and pregnancy?
RLS affects up to 20% of pregnant women, peaking in the third trimester and often resolving after childbirth.
121
What is Multiple Sclerosis (MS)?
MS is a chronic, inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) caused by complex gene–environment interactions.
122
What is the pathological hallmark of MS?
The accumulation of demyelinating lesions in the white and grey matter of the brain and spinal cord.
123
What immune cells are involved in MS pathology?
T cells, B cells, and myeloid cells infiltrate the CNS, leading to inflammation and neurodegeneration.
124
At what age does MS typically onset?
Between 20 and 40 years of age, though it can occur in childhood or adolescence.
125
What is the gender prevalence of MS?
MS is more common in women, with a female-to-male ratio of approximately 3:1.
126
What environmental factors contribute to MS risk?
Epstein–Barr virus (EBV) infection, smoking, low vitamin D levels, obesity during adolescence, and high latitude.
127
How does smoking affect MS?
Smoking increases the risk of MS, accelerates disability progression, and promotes conversion from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS).
128
What are the main subtypes of MS?
1) Clinically Isolated Syndrome (CIS)
2) Relapsing–Remitting MS (RRMS)
3) Secondary Progressive MS (SPMS)
4) Primary Progressive MS (PPMS)
129
What characterizes RRMS?
Recurrent episodes of neurological dysfunction (relapses) with varying degrees of recovery.
130
What differentiates PPMS from RRMS?
PPMS is characterized by progressive neurological decline from onset without relapses.
131
What are common early symptoms of MS?
Optic neuritis, sensory disturbances, motor impairment, and brainstem or cerebellar dysfunction.
132
How is MS diagnosed?
Through clinical evidence of demyelinating lesions disseminated in space and time, supported by MRI, cerebrospinal fluid (CSF) analysis, and evoked potentials.
133
What role does MRI play in MS diagnosis?
MRI detects demyelinating lesions, assesses disease activity, and monitors treatment response.
134
What is the significance of cerebrospinal fluid (CSF) analysis in MS?
The presence of oligoclonal bands (OCBs) in the CSF supports an MS diagnosis.
135
What are first-line disease-modifying therapies (DMTs) for MS?
Interferon-beta, glatiramer acetate, and oral immunomodulators (e.g., fingolimod, dimethyl fumarate).
136
What is the significance of B-cell-targeting therapies in MS?
Anti-CD20 therapies (e.g., ocrelizumab) reduce relapses and disability progression, highlighting the role of B cells in MS pathology.
137
How can non-pharmacological approaches help manage MS?
Physical therapy, lifestyle modifications, vitamin D supplementation, and smoking cessation can improve outcomes.
138
What conditions are commonly comorbid with MS?
Cardiovascular disease, depression, osteoporosis, and sleep disorders.
139
How does MS affect life expectancy?
MS reduces life expectancy by 7–14 years, though this gap is narrowing with better treatments.
140
What are major causes of mortality in MS patients?
MS-related complications, infections, and suicide.
141
What is Amyotrophic Lateral Sclerosis (ALS)?
ALS is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons, leading to muscle weakness and paralysis.
142
What are upper and lower motor neurons?
Upper motor neurons project from the cortex to the brainstem/spinal cord, while lower motor neurons project from the brainstem/spinal cord to muscles.
143
How does ALS affect cognitive function?
Up to 50% of ALS patients develop cognitive or behavioral impairment, with 13% presenting with frontotemporal dementia (FTD).
144
What is the incidence of ALS in Europe?
2–3 cases per 100,000 individuals.
145
How does ALS incidence vary globally?
It is higher in European populations (>3 per 100,000) but lower in East Asia (~0.8 per 100,000).
146
What are some environmental risk factors for ALS?
Smoking, exposure to toxins (e.g., cyanotoxins), and possibly intense physical activity.
147
What percentage of ALS cases are familial?
About 10% of ALS cases are familial.
148
What is the most common genetic cause of ALS?
C9orf72 repeat expansion, associated with both ALS and FTD.
149
Name some other genes linked to ALS.
SOD1, TARDBP, FUS, and TUBA4A.
150
What are the two main types of ALS onset?
Spinal-onset (limb weakness) and bulbar-onset (speech/swallowing difficulties).
151
What are early symptoms of ALS?
Muscle weakness, cramps, spasticity, dysphagia, dysarthria, and fasciculations.
152
How does ALS typically progress?
It leads to progressive muscle weakness, paralysis, respiratory failure, and eventual death.
153
What criteria are used to diagnose ALS?
The El Escorial and Airlie House criteria, requiring upper and lower motor neuron degeneration with disease progression.
154
What diagnostic tools are used for ALS?
Electromyography (EMG), MRI, and cerebrospinal fluid (CSF) analysis.
155
Why is ALS difficult to diagnose?
It mimics other neuromuscular diseases, and no single definitive test exists.
156
What are the FDA-approved disease-modifying treatments for ALS?
Riluzole and Edaravone.
157
What is the function of Riluzole?
It reduces glutamate toxicity and prolongs survival by ~3 months.
158
What supportive treatments are used for ALS symptoms?
Muscle relaxants for spasticity, speech therapy for dysarthria, and non-invasive ventilation for respiratory support.
159
What is the average survival time after ALS diagnosis?
2–5 years, but some patients live much longer.
160
What staging systems are used for ALS?
The King’s clinical staging system and the Milano–Torino (MITOS) system.
161
What are negative prognostic factors for ALS?
Bulbar-onset disease, rapid progression, cognitive impairment, and weight loss.
162
What is deep brain stimulation (DBS)?
DBS is a neuromodulation therapy that delivers electrical stimulation to specific brain regions to treat movement disorders like Parkinson’s disease (PD).
163
What is the limitation of conventional DBS (cDBS)?
cDBS provides continuous stimulation, which can lead to unnecessary energy use, side effects, and only partial efficacy.
164
How does adaptive DBS (aDBS) differ from cDBS?
aDBS adjusts stimulation in real time based on brain activity, optimizing therapeutic effects while reducing power consumption.
165
What was the main objective of the parkinson's study?
To test whether aDBS can be more effective and energy-efficient than cDBS in Parkinson’s disease patients.
166
How many patients participated in the study?
Eight patients with advanced PD.
167
What feedback signal was used to control aDBS?
Local field potential (LFP) beta-band activity recorded from the subthalamic nucleus (STN).
168
What conditions were compared in the study?
aDBS, cDBS, no stimulation, and random intermittent stimulation.
169
How did aDBS compare to cDBS in terms of motor improvement?
Motor scores improved by 66% (unblinded) and 50% (blinded) with aDBS, which was 27–29% better than cDBS.
170
What was the impact of aDBS on energy consumption?
aDBS reduced stimulation time by 56%, significantly lowering energy use.
171
Did random intermittent stimulation show similar benefits as aDBS?
No, aDBS was significantly more effective, showing that beta-band-triggered stimulation was key.
172
What are the potential benefits of aDBS for patients?
Fewer side effects, longer battery life, and improved symptom control.
173
What neurological biomarker was crucial for aDBS function?
Beta oscillations (13–30 Hz) in the STN LFP, which correlate with motor impairment.
174
What future improvements could be made to aDBS?
More advanced machine learning classifiers and phase-specific stimulation could further enhance efficacy.
175
What is the global prevalence of Parkinson’s disease?
It affects 2-3% of the population over 65 years old.
176
How does Parkinson’s disease incidence change with age?
The incidence increases 5-10 times from the sixth to the ninth decade of life.
177
Which gender is more affected by PD?
Men are affected about twice as often as women.
178
What environmental factors increase PD risk?
Exposure to pesticides and traumatic brain injury increase risk, while smoking and caffeine consumption appear protective.
179
What are the hallmark neuropathological features of PD?
Loss of dopaminergic neurons in the substantia nigra and intracellular Lewy bodies composed of α-synuclein.
180
How does α-synuclein aggregation contribute to PD?
It disrupts neuronal function, spreads in a prion-like manner, and contributes to neurodegeneration.
181
What are some molecular mechanisms involved in PD pathogenesis?
Mitochondrial dysfunction, oxidative stress, calcium homeostasis imbalance, axonal transport defects, and neuroinflammation.
182
How does mitochondrial dysfunction play a role in PD?
PD is associated with complex I deficits in the electron transport chain, leading to energy failure and oxidative damage.
183
What is the role of neuroinflammation in PD?
Microglial activation and immune response contribute to disease progression by promoting α-synuclein misfolding.
184
What clinical criteria are used for PD diagnosis?
The MDS criteria require bradykinesia plus at least one additional symptom (rigidity or tremor), with exclusion of alternative causes.
185
What imaging techniques aid in PD diagnosis?
- DaTscan SPECT for dopamine transporter imaging
- PET scans for dopamine metabolism
- Neuromelanin MRI to detect substantia nigra degeneration
186
What cerebrospinal fluid (CSF) biomarker is associated with PD?
Reduced α-synuclein levels in CSF suggest PD, but no clinically definitive biomarker exists yet.
187
What is the importance of prodromal symptoms in PD?
Non-motor symptoms like REM sleep behavior disorder (RBD), hyposmia, and constipation may precede motor symptoms by decades.
188
What is the gold standard treatment for PD motor symptoms?
Levodopa (L-DOPA), a dopamine precursor that replenishes striatal dopamine.
189
Why do PD patients develop motor complications with L-DOPA?
Due to pulsatile dopamine stimulation, leading to motor fluctuations and dyskinesias.
190
What adjunct therapies help improve L-DOPA efficacy?
- COMT inhibitors (entacapone, tolcapone)
- MAO-B inhibitors (rasagiline, selegiline)
- Dopamine agonists (pramipexole, ropinirole)
191
What surgical treatment is available for advanced PD?
Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) or globus pallidus interna (GPi).
192
What are the current experimental therapies for PD?
- Gene therapy to restore dopamine production
- Stem cell therapy for dopaminergic neuron replacement
- Anti-α-synuclein immunotherapy to prevent toxic aggregation
193
What is a major challenge in PD research?
Identifying early biomarkers to enable disease-modifying treatments before significant neurodegeneration occurs.
194
What is amyotrophic lateral sclerosis (ALS)?
ALS is a fatal neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons.
195
What is the blood–brain barrier (BBB), and why is it important in ALS treatment?
The BBB is a protective barrier that limits the entry of drugs into the brain, making targeted delivery of therapeutics for ALS difficult.
196
What are some existing methods to bypass the BBB for ALS treatment?
Surgical injections, drug modifications for transcellular transport, and chemical disruption (e.g., mannitol), but these methods can have off-target effects or require invasive procedures.
197
What is MR-guided focused ultrasound (MRgFUS)?
A non-invasive technique that uses ultrasound waves and microbubbles to temporarily open the BBB, allowing targeted drug delivery.
198
How does MRgFUS achieve BBB permeabilization?
Ultrasound interacts with intravenously injected microbubbles, causing mechanical disruption of the BBB without thermal injury.
199
Why is MRgFUS advantageous over traditional BBB bypass methods?
It is non-invasive, precisely targeted, temporary, and reversible, reducing the risks of surgical procedures.
200
What was the primary objective of this first-in-human trial for ALS?
To evaluate the safety, feasibility, and reversibility of MRgFUS-induced BBB opening in ALS patients.
201
How many participants were included in the study?
Four ALS patients (two men, two women, median age 61 years).
202
What brain regions were targeted using MRgFUS?
The primary motor cortex, specifically the arm or leg control regions, as mapped using functional MRI (fMRI).
203
How was BBB opening confirmed?
Through gadolinium-enhanced MRI, which showed contrast agent leakage at the targeted site immediately after sonication.
204
Was MRgFUS successful in opening the BBB?
Yes, all four patients exhibited transient and reversible BBB opening without serious adverse effects.
205
What happened to the BBB permeability after the procedure?
The BBB returned to normal within 24 hours, as shown by MRI scans.
206
What adverse events were observed in ALS study?
Mild-to-moderate side effects such as headache, scalp pain, and muscle discomfort, but no serious adverse events like hemorrhage or seizures.
207
Did MRgFUS affect ALS progression?
No accelerated disease progression was observed over the 60-day follow-up period.
208
How could MRgFUS enhance ALS treatment in the future?
It could facilitate the delivery of gene therapy, antibodies, neurotrophic factors, and stem cells to the motor cortex.
209
Why is targeted drug delivery important in ALS?
ALS affects specific brain regions, and non-targeted drug delivery can lead to systemic side effects or inefficacy.
210
What future research directions were suggested for ALS?
- Larger clinical trials to confirm safety and efficacy.
- Testing MRgFUS with drug administration for ALS.
- Investigating blood-spinal cord barrier opening for spinal cord-targeted therapies.
211
explain the origins of research and development funding
in the 1870s, alexander graham bell developed the telephone with funding from the wealthy father of one of his students.
there was a huge explosion of government funding for research after WWII
212
where is the majority of funding from for research labs
Majority: federal sources
2. private sources
3. startup funds
Least: other (ex., funding from universities)
213
how does the government fund research
- taxpayer dollars
- NIH
214
what is the NIH
national institute of health
- the primary funding agency for biomedical research in the U.S. (and the largest funder of biomedical research in the world)
- Began as a one-room “Laboratory of Hygiene” in 1887
215
how many institutes and centers does NIH have
27
216
what is one example of how NIH research has helped
NIH-funded research was behind every single new
drug approved by the FDA from 2010-2016 (Galkina et
al., 2018)
217
what is the Primary NIH grant: R01
- is the original and historically oldest grant mechanism used by NIH. The R01 provides support for health-related research and development based on the mission of the NIH.
- No specific dollar limit unless specified (typically ~$500,000)
- Generally awarded for 3 to 5 years of work
218
what are some examples of indirect costs used for research grants
Costs which are not specific to one research project - shared across groups, reduce redundancy
● Building upkeep and resources
● Utilities
● Hiring of staff/support
● Safety (biocontainment, disposal, etc.)
● Facilities
● Equipment
● Regulatory Compliance
219
IACUC
is responsible for oversight
of the animal care
220
IRB
assess the ethics and safety of research studies involving human subjects, such as behavioral studies or clinical trials for new drugs or medical devices
221
What are the key characteristics of REM sleep?
REM sleep is characterized by muscle atonia, rapid eye movements, an activated EEG pattern, and vivid dreaming.
222
What is REM sleep behavior disorder (RBD)?
RBD is a parasomnia where patients lose REM sleep atonia, leading to dream enactment behaviors such as talking, shouting, punching, or kicking.
223
What is REM sleep without atonia (RSWA), and how is it related to RBD?
RSWA is excessive muscle tone during REM sleep, which is the core physiological abnormality in RBD.
224
What are common dream enactment behaviors in RBD?
Patients may act out dreams involving fighting, running, grabbing, or defensive movements, often leading to injury.
225
What are the two main types of RBD?
1. Idiopathic RBD (iRBD) – Occurs without an underlying neurological disease but is a strong predictor of future neurodegeneration.
2. Symptomatic (or secondary) RBD – Associated with α-synucleinopathies (e.g., Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy) or antidepressant use.
226
What percentage of iRBD patients develop a neurodegenerative disease?
Around 80–90% of iRBD patients eventually develop an α-synucleinopathy, often within 10–15 years.
227
What neurological disorders are most commonly linked to RBD?
Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
228
What is the estimated prevalence of iRBD in the general population?
Approximately 1% of people over 60 years old have iRBD.
229
What are the strongest risk factors for iRBD?
- Age (more common in individuals over 50)
- Male sex (higher prevalence in men, though this may be due to diagnostic bias)
- Pesticide exposure
- Head trauma
- Smoking history
230
What role do genetics play in RBD?
Variants in GBA, SNCA, and LRRK2 genes—also linked to Parkinson’s disease—are associated with increased RBD risk.
231
What brain regions are implicated in RBD pathophysiology?
The sublaterodorsal nucleus (SLD) and ventral medulla, which regulate REM sleep atonia, are affected by neurodegeneration.
232
How does α-synuclein pathology contribute to RBD?
Misfolded α-synuclein aggregates in the brainstem disrupt normal REM sleep regulation, leading to RSWA and dream enactment.
233
What experimental evidence supports RBD as a brainstem disorder?
Lesions in the pons and medulla of animal models induce RBD-like behaviors during REM sleep.
234
What is the gold standard diagnostic test for RBD?
Video polysomnography (vPSG), which confirms RSWA and abnormal REM sleep behaviors.
235
What screening tools are available for RBD?
- RBD Screening Questionnaire (RBDSQ)
- RBD Single Question (RBD1Q)
- Mayo Sleep Questionnaire (MSQ)
236
What other conditions can mimic RBD?
- Sleepwalking (NREM parasomnias)
- Nocturnal seizures
- Obstructive sleep apnea (OSA)
- PTSD-related nightmares
237
What are the first-line pharmacological treatments for RBD?
- Clonazepam (reduces dream enactment behaviors but may cause sedation)
- Melatonin (safer alternative, especially for older adults or those with cognitive impairment)
238
What are common non-pharmacological strategies for RBD?
- Removing sharp objects from the bedroom
- Padding furniture and using bed rails
- Placing a mattress on the floor to prevent injuries
239
How can sleep disorders like obstructive sleep apnea affect RBD treatment?
Untreated OSA can worsen RBD, so CPAP therapy should be considered before prescribing clonazepam.
240
Why is RBD considered a prodromal marker of neurodegeneration?
It often precedes Parkinson’s disease, DLB, or MSA by 10–15 years, making it a key early indicator of α-synucleinopathies.
241
What are the strongest clinical predictors of conversion to Parkinson’s disease or DLB?
- Severe olfactory loss
- Mild motor impairment
- Dysautonomia (e.g., constipation, low blood pressure)
- Color vision deficits
242
How might RBD be useful in future clinical trials?
Since RBD patients have a high risk of neurodegeneration, they could be ideal candidates for early neuroprotective therapies aimed at slowing disease progression.
243
What is a traumatic brain injury (TBI)?
A structural injury and/or physiological disruption of brain function caused by an external force.
244
What are the three main severity classifications of TBI?
Mild, moderate, and severe, based on factors like loss of consciousness, post-traumatic amnesia, and Glasgow Coma Scale score.
245
What are the two main types of TBIs?
Penetrating TBI, where an object breaches the skull, and closed-head TBI, where the skull remains intact.
246
What are the most common causes of TBI?
Falls and road traffic accidents, which together account for more than 50% of cases.
247
What is mild TBI also known as?
Concussion.
248
What are common symptoms of mild TBI?
Headache, dizziness, nausea, memory problems, irritability, and emotional lability.
249
What percentage of mild TBI patients recover within 7–10 days?
80–90% of patients.
250
What is post-concussive syndrome (PCS)?
Persistent symptoms lasting >3 months after mild TBI, affecting about 10–15% of patients.
251
What is the most well-studied mechanism of TBI?
Diffuse axonal injury (DAI), caused by stretching and tearing of axons.
252
What types of forces contribute to TBI?
Linear acceleration, rotational acceleration, and impact deceleration.
253
What are common neuropathological features of TBI?
Axonal injury, microglial activation, neuroinflammation, and tau pathology.
254
What is chronic traumatic encephalopathy (CTE)?
A neurodegenerative disease linked to repetitive concussions and subconcussive hits, particularly in contact sports and military personnel.
255
What is the hallmark neuropathological feature of CTE?
Perivascular accumulation of hyperphosphorylated tau in neurons and astrocytes, especially at the depths of cortical sulci.
256
How is CTE diagnosed?
Post-mortem neuropathological examination (no validated biomarkers for diagnosis in living patients).
257
What is traumatic encephalopathy syndrome (TES)?
The clinical counterpart of CTE, proposed for diagnosing patients with progressive neurological symptoms and a history of head trauma.
258
What imaging techniques are used to assess TBI?
CT scan (for detecting hemorrhage) and MRI (for detecting axonal injury and microhemorrhages).
259
What is diffusion tensor imaging (DTI), and how does it help in TBI diagnosis?
DTI detects white matter integrity and can identify diffuse axonal injury even when conventional MRI appears normal.
260
What are potential fluid biomarkers for TBI?
Tau, neurofilament light (NF-L), S100B, GFAP, and UCH-L1, which reflect neuronal and astrocytic damage.
261
What role does amyloid-beta (Aβ) play in TBI?
Some TBI cases exhibit Aβ plaques similar to Alzheimer’s disease, possibly accelerating neurodegeneration.
262
What neurodegenerative diseases have been linked to TBI?
Alzheimer’s disease, Parkinson’s disease, and CTE.
263
How does TBI increase the risk of dementia?
TBI may accelerate tau and amyloid pathology, increasing the likelihood of cognitive decline.
264
What factors increase the risk of poor long-term outcomes after TBI?
Older age, repeated injuries, genetic susceptibility (e.g., APOE ε4 allele), and psychiatric conditions.
265
What measures can help prevent TBI?
Helmet use, seatbelt enforcement, improved sports regulations, and military blast protection.
266
What is the standard treatment for severe TBI?
Neurosurgical intervention, intracranial pressure monitoring, and intensive care management.
267
How is mild TBI managed?
Rest, symptom management, cognitive rehabilitation, and gradual return to activity.
268
What is Gilles de la Tourette syndrome (GTS)?
A childhood-onset neurodevelopmental disorder characterized by multiple motor tics and at least one phonic tic lasting more than a year.
269
What is the estimated prevalence of GTS in children and adolescents?
Approximately 1%.
270
At what age do tics typically develop in GTS?
Before 10 years of age, usually between 4–6 years.
271
What are the core diagnostic features of GTS?
Multiple motor tics and at least one phonic tic persisting for more than a year.
272
Name two pathognomonic but less common features of GTS.
Coprolalia (involuntary swearing) and echophenomena (involuntary repetition of sounds or movements).
273
What diagnostic criteria are commonly used for GTS?
DSM-5 and ICD-10 criteria.
274
Name three common comorbid conditions associated with GTS.
ADHD, OCD, and anxiety disorders.
275
How does the presence of comorbid conditions affect the severity of GTS?
It can increase the severity of symptoms and impact quality of life.
276
Is GTS primarily genetic, environmental, or both?
Both; it is a polygenic disorder with environmental contributions such as perinatal factors and immune responses.
277
What neurotransmitter is most strongly implicated in GTS?
Dopamine.
278
Name two other neurotransmitters involved in GTS pathophysiology.
Glutamate and GABA.
279
What are the first-line treatments for GTS?
Psychoeducation, behavioral therapy, and pharmacotherapy when necessary.
280
Name one pharmacological treatment used for severe tics in GTS.
Haloperidol (a neuroleptic/antipsychotic).
281
What alternative treatment is used for severe, refractory cases of GTS?
Deep brain stimulation (DBS).
282
What is Restless Legs Syndrome (RLS)?
A common sensorimotor disorder characterized by unpleasant sensations and an urge to move the legs, usually in the evening or night.
283
What is the estimated prevalence of RLS?
6%–12% of the general population.
284
What temporary relief can patients with RLS experience?
Movement or walking can provide temporary relief from symptoms.
285
Which brain imaging technique was used in this study to evaluate RLS patients?
Diffusion Tensor Imaging (DTI).
286
What major structural brain change was identified in patients with RLS?
Decreased segregation in the brain network compared to healthy controls.
287
Which brain regions showed significant local structural connectivity changes in RLS patients?
Middle frontal gyrus, superior frontal gyrus, orbital frontal gyrus, postcentral gyrus, pulvinar anterior thalamic nucleus, and supplementary motor area.
288
How did global structural connectivity differ in RLS patients?
Patients showed lower transitivity (0.031 vs. 0.033 in healthy controls, p = 0.035), indicating decreased network segregation.
289
What measures were positively correlated with RLS severity?
Characteristic path length, radius of graph, and diameter of graph.
290
What measures were negatively correlated with RLS severity?
Mean clustering coefficient, global efficiency, small-worldness index, and transitivity.
291
What criteria were used to diagnose primary RLS in this study?
The International Restless Legs Syndrome Study Group (IRLSSG) criteria.
292
Name two sleep-related scales used to assess patients in this study.
Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI).
293
What was the gender distribution in the RLS patient group?
More than two-thirds of the patients were women.
294
What does this study suggest about the role of the sensorimotor network in RLS?
Alterations in sensorimotor connectivity may play a pivotal role in the pathophysiology of RLS.
295
How does this study contribute to the understanding of RLS?
It provides evidence of altered structural connectivity, supporting the idea that RLS is a network disorder.
