Week 3 - Neuro-degenerative and neuro-developmental disorders Flashcards
(29 cards)
Fetal Alcohol Spectrum Disorder (FASD)
FASD
Definition, physical features, brain abnormalities and behavioural/cognitive impairments.
Encompasses physical malformations + intellectual impairment due to alcohol exposure in the utero.
Physical features (facial features):
* Smooth philtrum
* Thin upper lip
* Short eye opening width
* Flat midface, short nose
* Associated traits: low nasal bridge, small jaw, minor ear anomalies.
Brain abnormalities:
* Small size
* Abnormal gyri
* Misaligned cells
Behavioural and cognitive impairments:
* Learning disabilities, low IQ, hyperactivity and social difficulties.
* Symptoms vary based on severity and timing of alcohol exposure.
Fetal Alcohol Spectrum Disorder (FASD)
Prevalence and risk factors
- 1 in 100 to 1 in 700 in US newborns.
- Highest prevalence in children in foster care, prison populations and communities with high alcohol misuse.
- Especially harmful is alcohol is consumed in the first 3 months.
Fetal Alcohol Spectrum Disorder (FASD)
Not all-or-nothing
FASD exists on a spectrum:
* Minor facial differences + subtle behavioural problems
* To full-blown FAS with severe cognitive and physical issues
Severity depends on:
* Timing, amount and pattern of drinking
* Maternal health/nutrition
* Use of other substances
Fetal Alcohol Spectrum Disorder (FASD)
Cellular and genetic mechanisms
Alcohol disrupts cell division and maturation, and causes epigenetic changes.
Affected postassium channel: Kir2.1
* Allows K * flow across cell membranes
* Vital for maintaining resting membrane potential
* Blockage -> apoptosis (cell death) -> brain abnormalities.
* Alcohol inhibits kir2.1, contributing to FASD pathology.
Fetal Alcohol Spectrum Disorder (FASD)
Key takeaways
FASD teaches broader lessons about:
* Substance use in pregnancy
* Early developmental vulnerability
* Epigenetic and brain development
Neurological disorders
Multiple sclerosis
Multiple Sclerosis
Definition
It is a demyelinating disorder affecting myelinated motor and sensory fibers.
* A loss of myelin happens in patches which forms sclerotic plaques.
Neurological disorders
Symptoms
Multiple sclerosis
- Loss of sensation in face, limbs or body.
- Blurred vision
- Loss of motor control
Neurological disorders
Course
Multiple Sclerosis
- Often begins in adulthood and can vary.
- Symptoms often remit and relapse.
- Some forms progress rapidly, leading to severe disability within a few years.
Neurological disorders
Causes (still unclear)
Multiple Sclerosis
- Bacterial or viral infections
- Environmental triggers
- Autoimmune CNS response
- Often see in families (genetic predisposition).
Neurological disorders
Geographic prevalence
Multiple Sclerosis
- Most prevalent in northern europe.
- 50 per 100,000 in high incidence areas.
- Most common structural nervous system diseases (alongside Parkinson’s).
- Linked to vitamin D deficiency (crucial for myelin development in childhood and maintenance in adulthood).
- Progresses faster in females
Neurological disorders
Treatment and innovation
Multiple Sclerosis
Alemtusumab (lemtrada): targets immune cells that attack body tissue.
* Promising results in reducing symptoms.
Brain-computer interface tech: explored for improving mobility in those with severe or progressive MS.
Psychiatric and related disorders
Motor disorders
Motor disorders
Definition, main symptoms and the two main types
Basics:
* Motor disorders stem from basal ganglia dysfunction.
* Symptoms: movement and posture abnormalities.
* Common cognitive changes also occur as the disorders progress.
Two main types:
1. Hypokinetic-rigid syndrome: reduced movement (ex: Parkinson’s).
2. Hyperkinetic-dystonic syndrome: excessive, involuntary movements (ex: Tourette’s, Huntington’s).
Psychiatric and related disorders
Huntington’s disease (HD)
Hyperkinetic motor disorders
Definition, symptom, onset, early/late signs, death onset, neurobiology
Basics:
* Autosomal dominant disorder.
* Chorea = involuntary, dance like movements.
* Onset = typically between 30-50y
* Early signs = memory issues, personality changes, fidgeting.
* Late signs = cognitive decline, psychiatric symptoms.
* Death typically occurs 12y post onset.
Neurobiology:
* Cortical thinning + basal ganglia atrophy
* Death of ACh and GABA neurons -> loss of inhibition -> dopaminergic hyperactivity -> chorea.
* Genetics: 50% inheritance.
* Findings: poor performance on frontal lobe tasks and impairments in recent memory, executive function and information processing speed.
Psychiatric and related disorders
Tourette’s syndrome (TS)
Hyperkinetic motor disorders
Onset, tics, neurobiology, treatment
Onset: 2-15y
Tics:
* Start in face/head -> spread to limbs.
* Types: motor tics (facial, limb, body) and vocal tics (echolalia (repeating oters), coprolalia (swearing), palilalia (repeating self)).
* Often lessen with age.
* Associated with behaviours like impulsivity, compulsions and aggression.
Neurobiology:
* Likely subcortical origin, especially basal ganglia and frontoparietal circuits.
* Definits in visuospatial tasks, issues with drawing from memory, poor spatial working memory.
Treatment:
* Antidopaminergic agents.
Psychiatric and related disorders
Parkinson’s disease (PD): prevalence
Hypokinetic motor disorders
0.1-1% of global population
Psychiatric and related disorders
Parkinson’s disease (PD): Positive symptoms
Hypokinetic motor disorders
3
Tremor at rest:
* “pill-roling” hand movement.
* Stops during voluntary motion or sleep.
Muscular rigidity:
* Increased tone in flexor and extensor muscles.
* Passive movement meets resistance = cogwheel rigidity
Involuntary movements:
* Akathisia (restlessness)
* Oculogyric crisis = involuntary eye/head turning
* Poster shifts, twitches
Psychiatric and related disorders
Parkinson’s disease (PD): negative symptoms
Hypokinetic motor disorders
5
Postural disorders:
* Difficulty holding head/limbs in place - forward drooping.
* Trouble standing or sitting without support.
Righting disorders: difficulty rising or rolling over
Locomotive disorders:
* Problems initiating walking
* Festination = short, quick steps -> running gait
Speech disturbances: lack of vocal prosody, monotone voice.
Akinesia:
* Lack of movement
* Mask-like face, reduced spontaneous motion, blank staring.
Psychiatric and related disorders
Parkinson’s disease (PD): genetic risk
Hypokinetic motor disorders
- Most cases are not inherited, but 25% have a relative with the disease.
Psychiatric and related disorders
Parkinson’s disease (PD): progression
Hypokinetic motor disorders
Begins gradually - tremor in one hand, stiffness.
Progresses to:
* Mask-like facial expressions
* Slowed speech and movement
* Shuffling gait
* Drooling, difficulty swallowing
Progression varies:
* Rarely rapid (within 5 years), often 10-20 years to severe disability.
* On-off phenomenon = symptoms can temporarily vanish.
Psychiatric and related disorders
Parkinson’s disease (PD): neurobiological basis
Hypokinetic motor disorders
- Subtantia nigra = origin of dopamine pathways to cortex and basal ganglia
- Dopamine is the key neurotransmitter = 90%+ loss in PD brains.
- Marker = HVA in urine is drastically reduced.
- PD is defined by dopamine depletion but also involved reduced norepinephrine and degeneration in other basal ganglia nuclei.
Psychiatric and related disorders
Parkinson’s disease (PD): causes/types of parkinsonism
Hypokinetic motor disorders
Ideopathic, post-encephalitic, drug-induced, environmental toxins
Idiopathic PD (most common):
* Cause unknwon = may be genetic, age-related or viral
* Often starts after age 50.
Post-encephalitic PD:
* Linked to encephalitis lethargica
* Many recovered from the infection but developed PD after.
Drug-induced PD:
* Associated with tranquilisers
* Symptoms resemble PD but are often reversible.
Environmental toxins:
* MPTP (synthetic heroin) converts to MPP which destroys dopamine neurons.
* Young drug uses developed instant parkinsonism
* Suggests air/water pollution might contain similar toxins.
Psychiatric and related disorders
Parkinson’s disease (PD): treatment
Hypokinetic motor disorders
psychological support, physical therapy, pharmacological treatment, experimental and advanced treatments.
No cure exists - focus is on comfor, coping and quality of life
Psychological support and early counseling are vital for:
* Coping and understanding prognosis
Physical therapy:
* Heat/massage for cramps
* Exercise and training to maintain mobility
Pharmacological treatment:
* Goal: boot dopamine activity in remaining synapses and suppress overactivity in other brain areas due to dopamine deficiency.
* Medications: MAO inhibitors, L-dopa, anti-cholinergics.
Experimental and advanced treatments:
* Cell therapy: goal (increase dopamine-producing cells), approaches (transplanting stem cells and stimulating stem cells to become dopaminergic)
* Deep brain stimulation (DBS): electroduces implanted in brainstem regions to reduce tremor and akinesia, best used in combination with medication.
Psychiatric and related disorders
Parkinson’s disease (PD): psychological aspects
Hypokinetic motor disorders
Psychological symptoms, neuropsychological evidence, cognitive decline
Psychological symptoms:
* Vary across patients; often match motor symptom progression.
* Reduced feeling, libido, motive, attention
* Apathy = sitting still for hours, lacking will to act.
* Slow thinking, mistaken for poor understanding.
Neuropsychological evidence:
* Deficits similar to frontal-lobe or basal-ganglia damage.
* Likely due to degeneration of dopamine pathways to the frontal cortex.
* Not improved by drug therapy
Cognitive decline:
* May resemble Alzheimer’s in some patients even in non-demented PD patients.
Dementias
Dementias: demographics/prevalence
- Aging population in developed countries = increase in dementia.
- 20-50% of those over 80 are affected.
