neuro

Embryo starts as a flat disk with 3 layers of cells. What are they called?

Endoderm (lining of viscera)

Mesoderm (Skeleton and muscles)

Ectoderm (Nervous system via neural plate)

Required features for GBS diagnosis

Progressive weakness in arms and legs (might start in legs only)

Areflexia (or decreased stretch reflexes)

Features that strongly support GBS diagnosis

▫ progression of signs/symptoms over days to 4 weeks

▫ symmetry of symptoms

▫ cranial nerve involvement (bilateral weakness of facial muscles)

▫ autonomic dysfunction

▫ high concentration of protein in cerebrospinal fluid

▫ nerve conduction study and electromyography (EMG) show

▫ e.g. nerve conduction block or reduced conduction velocity of action

potentials in motoneurones (indicative of demyelination)

What is the most common type of MS?

Relapsing remitting

What is chronic fatigue syndrome?

Disabling chronic fatigue and characteristic non-specific accompanying symptoms

What is akinesia?

Loss of movement

What is hypokinesia?

Insufficient movement

What is kinesia?

Movement

What is rigidity?

Increased muscle tone throughout range of passive movement

Primary movement disorder

• No known cause (‘idiopathic’)

• Abnormal movement is the major neurological abnormality

• Not caused by another recognised neurological condition

Secondary movement disorder

Abnormal movement caused by another recognised neurological condition, in which abnormal movement is a minor part

What are the 2 types of movement disorders and examples of them?

• Hyperkinetic: Essential tremor and Huntington’s disease

• Akinetic-rigid: Wilson’s disease and Parkinsonism

Wilson’s disease pathology

Mutations in the ATP7B gene (involved in copper transportation) → failure to excrete copper

What are the direct effects of ↑ copper on neurons: toxic (Wilson’s disease)

Formation of free radicals

• ↓ antioxidants

• mitochondrial damage

• disturbed protein biosynthesis

• can lead to apoptosis or cell death

• neurotoxicity is widespread throughout the nervous system but putamen appears to be particularly vulnerable

Indirect effects of ↑ copper on neurons (Wilson’s disease)

• Astrocyte degeneration

• Some oligodendrocyte involvement

Astrocytes

• most numerous type of glial cell in the central nervous system

• fill spaces between neurons, provide structural support

• regulate chemical environment between neurons (extracellular space)

• maintain blood-brain barrier

• form scar tissue after injury

Wilson’s disease diagnosis

• Blood test: measurement of serum concentration of ceruloplasmin (copper-binding protein)

• Examination of the eyes for Kayser- Fleischer (copper) rings

• Genetic test: ATP7B mutations

What is chorea?

Involuntary, irregular, purposeless, non-rhythmic, non-patterned movements that flow randomly from one body part to another)

Abnormal tremor

Rhythmical, regular oscillations of a body part

What is Huntington’s disease cause?

• Genetic mutation: Expanded polyglutamine stretch in the IT15 gene encoding a protein called huntingtin

• Autosomal dominant inheritance (i.e. abnormal gene from one parent can cause disease)

• Children have a 50% chance of inheriting the disorder

Neurodegeneration in Huntington’s disease?

• 30% reduction in total brain weight

• Significant degeneration in the striatum, globus pallidus, and deep layers of the cerebral cortex

What is pain?

Subjective perception of sensory information from nociceptors

Pathophysiology of shingles

• Step 1: contract chickenpox (or ‘varicella’)

• Step 2: following bout of chickenpox, virus stays in the body and remains dormant or ‘latent’ in dorsal root ganglia (i.e. where the cell bodies of the first order sensory neurons are located

• Step 3: reactivation of the latent virus = shingles (or ‘herpes zoster’)

Acute clinical manifestations of shingles

• Painful rash that is localised to the site (dermatome) corresponding to the affected dorsal root ganglion

• Can be accompanied by itching and tingling

• Rash is usually unilateral

• Thoracic and lumbar dermatomes most commonly affected

• Episode lasts 10-15 days

Most common complication of shingles

Post-herpetic neuralgia

• chronic neuropathic pain syndrome

• pain persists for >3 months after rash heals

• occurs in 25-50% of shingles cases in people aged >50 years

What is peripheral neuropathy?

Peripheral nerve damage

Why do the clinical manifestations differ between the different types of peripheral neuropathies?

• Depends on the peripheral nerve affected

• Depends on the type of neuron affected (motoneurone and/or sensory neuron)

Can you briefly describe the pathophysiology of carpal tunnel syndrome?

• Irritation and/or compression of the median nerve at the wrist by the flexor retinaculum and/or synovial tendon sheaths

• Can result from small carpal tunnel, over-use, inflammation, and/or other factors

What is conduction deafness?

Impaired conduction of sound from the outer ear to the cochlea

can result from

• excessive wax

• foreign objects

• rupture of the tympanic membrane (‘ear drum’)

• pathology of the ossicles

What is nerve deafness?

Impaired nerve function (‘nerve deafness’)

Associated with loss of hair cells in the cochlea or neurons in the cochlear branch of vestibulocochlear nerve (CN VIII)

caused by:

• e.g. exposure to loud sounds

• e.g. medications that are toxic to hair cells (e.g. some antimalarial and antibiotic medications)

Treatment for deafness

• Partial loss of hair cells = hearing aid (to amplify sound for remaining hair cells)

• severe bilateral loss of hair cells with intact cochlear branch of vestibulocochlear nerve (CN VIII) = cochlear implant

How does a cochlear implant work?

Step 1. Microphone on sound processor records sound and sound processor converts this into digital information

Step 2. Digital information is transferred to coil and then to an implanted receiver

Step 3. Receiver sends electrical signals down a wire to an electrode that has been implanted in the cochlea

Step 4. Electrode stimulates cochlear nerve at a location that is specific to the frequency of the sound that was detected by the microphone

Terminology associated with olfaction

• normosmia- normal odour detection

• hyposmia - reduced ability to detect odours

• anosmia - loss of ability to detect odours

• parosmia - distorted odour perception in the presence of an odour

• phantosmia - perception of an odour that is not present

What are the 3 categories of pathophysiology that underlie impaired olfaction?

• Obstruction of the nasal passage causing loss of odour conduction to the olfactory epithelium

• Damage to the olfactory epithelium

• Dysfunction of central nervous system structures involved in olfaction

What is the link between impaired olfaction and neurodegenerative disorders?

Axons from olfactory receptor cells provide a direct path for pathogens/toxins to enter brain

Hyposmia and Parkinson’s disease aetiology

hyposmia: early symptom and pre-dates onset of cardinal motor signs by

several years

• hyposmia: present in 90% patients

• Several biological and chemical risk factors for Parkinson’s disease are capable of entering the brain via olfactory route

• hypothesised pathology order: olfactory bulb → lower brainstem → basal nuclei → cerebrum

Cause of age related macula degeneration

Loss of cells in the macula

• wet’ type: rapid loss of cells caused by abnormal growth of blood vessels under the macula (resulting in leakage of blood and fluid)

• dry’ type: slow loss of photoreceptors in the macula

Symptoms of age related macula degeneration

Loss of sharp central vision

Cause of glaucoma

Inadequate drainage of fluid (aqueous humor) from posterior eye cavity leads to ↑ intraocular pressure which damages axons in the optic nerve

Symptoms of glaucoma

Loss of peripheral vision and in some severe cases blindness

Cause of retinopathy

Caused by diabetes-related blockage of small blood vessels in the retina and then growth of abnormal blood vessels that invade the space between the pigmented part and neural part of the retina

Symptoms of retinopathy

Results in loss of visual acuity due to damage of photoreceptors, leakage of blood into the posterior cavity, and abnormal growth of blood vessels

Anxiety disorder

Disorders that share features of excessive fear and anxiety and related behavioural disturbances

What is the hallmark feature of anxiety disorders?

Inappropriately large stress response to a stressor that is non-threatening and/or is not present

Describe one mechanism that can lead to an inappropriately large stress response in anxiety disorders

An overactive amygdala can trigger an exaggerated stress response by repeatedly activating the hypothalamic-pituitary-adrenal (HPA) axis.

1. Amygdala activation: The amygdala perceives potential threats and activates the hypothalamus, triggering the stress response.

2. HPA axis activation: The hypothalamus releases CRH (corticotropin-releasing hormone), stimulating the anterior pituitary to release ACTH (adrenocorticotropic hormone).

3. Cortisol release: ACTH stimulates the adrenal cortex to release cortisol (stress hormone).

4. Hippocampus dysfunction: The hippocampus normally helps regulate the stress response by providing negative feedback to the HPA axis. If its function is impaired, it becomes less effective at inhibiting the stress response.

5. Continuous cortisol release: Reduced negative feedback means the HPA axis remains activated, resulting in prolonged or elevated cortisol levels.

6. Effects on neurons: Chronically elevated cortisol can damage neurons, reduce dendritic branching and impair neurogenesis, particularly in the hippocampus. This further reduces the hippocampus's ability to regulate the stress response.

Overall: Amygdala overactivity + reduced hippocampal inhibition → prolonged HPA axis activation → elevated cortisol → neuronal changes → reduced regulation of the stress response.

How do SSRI medications act on neurons, and how are they thought to reduce symptom severity?

SSRIs (selective serotonin reuptake inhibitors) increase serotonin availability in the synapse.

1. Normally, serotonin is released from the presynaptic neuron and binds to receptors on the postsynaptic neuron.

2. Serotonin is then taken back up into the presynaptic neuron by serotonin transporters (SERT).

3. SSRIs block these transporters, reducing serotonin reuptake.

4. This leaves more serotonin in the synaptic cleft for longer, increasing its availability to bind to postsynaptic receptors.

Hallmark clinical manifestation of depression

Depressed mood and/or loss of interest or pleasure in nearly all activities for >2 weeks

Depressive disorders pathology - Monoamine hypothesis

Mood is associated with levels of serotonin and noradrenaline, which are types of monoamine neurotransmitters

• Evidence: drugs that ↓ serotonin, noradrenaline, adrenaline, dopamine = ↓ mood

• Evidence: drugs that ↑ serotonin and noradrenaline = ↑ mood

Depression may result from a deficit in the serotonergic and/or noradrenergic diffuse modulatory systems?

What do SSRI’s (selective serotonin reuptake inhibitors): do?

Block reuptake of serotonin

What do tricyclics do?

Block reuptake of noradrenaline and serotonin

What do monoamine oxidase (MAO) inhibitors do?

Prevent enzymatic breakdown of noradrenaline and serotonin

What structural changes are evident in the brains of people with schizophrenia and what might these structural changes represent?

• ↓ gray matter (e.g. ↓ thickness of cerebral cortex)

• ↑ volume of ventricles

• ? signs of neurodegenerative illness

3 symptoms of ADHD

• inattention: difficultly in maintaining focus, disorganised, lacking persistence (not due to defiance or lack of comprehension)

• hyperactivity: excessive motor activity when it is not appropriate (e.g. fidgeting)

• impulsivity: hasty and/or risky actions without forethought

Pathology of ADHD

• ↓ total cerebral volume

• ↓ thickness of cerebral cortex

• ↓ volume of caudate nucleus that normalises in early adolescence

Altered dopaminergic neurotransmission

• evidence: improvement in symptoms with use of psychostimulant medication(↑ dopamine in synaptic cleft)

• evidence: polymorphisms in genes associated with dopamine re-uptake transporter and dopamine D4 receptors

3 symptoms of ASD

• persistent deficits in social communication

• persistent deficits in social interaction across multiple contexts

• restricted, repetitive patterns of behaviours, interests, or activities (e.g. lining up toys, excessive adherence to routines and resistance to change)

What are the most robust pathological and pathophysiological changes associated with ASD?

• ↑ brain volume (overgrowth) during infancy and early childhood but not in adulthood

Abnormal serotonergic neurotransmission

• serotonin modulates several developmental events (e.g. cell division, proliferation, migration, and differentiation of neurons in the cerebral cortex, neuroplasticity in the cerebral cortex, and synaptogenesis)

• children with autism spectrum disorder lack the usual peak in serotonin synthesis that occurs in children aged ~2 years and have ↓ serotonin receptors (5-HT2A) in the cerebral cortex

Addiction

Chronic brain disease associated with disruption of reward, motivation, memory, learning, executive function, self-regulation, and mood and stress circuitry

Reward

Subjective value of an object, stimulus, or situation that has the potential to induce goal-oriented behaviour

Motivation

A brain process triggered by intrinsic and/or extrinsic drivers that induce an animal or person to move towards a goal.

types of diffuse modulatory systems

• noradrenergic

• serotonergic

• dopaminergic

• cholinergic

Pathology and pathophysiology ADHD

• ↓ total cerebral volume

• ↓ thickness of cerebral cortex

• ↓ volume of caudate nucleus that normalises in early adolescence

What are the most robust pathological and pathophysiological changes associated with Autism spectrum disorder?

• ↑ Brain volume (overgrowth) during infancy and early childhood, but not in adulthood

• Abnormal serotonergic neurotransmission