BRAIN DISEASE DEFINITION SYMPTOMS/TYPES NEUROPATHOLOGY MEDICATIONS

ALZHEIMER’S DISEASE The most common form of dementia

affecting the elderly

MEMORY LOSS

PERSONALITY CHANGES

PARANOIA

Atrophy at these Areas:

LIMBIC SYSTEM

1. Hippocampus (glutamate)

2. Entorhinal cortex (glutamate)

CHOLINERGIC BASAL NUCLEUS OF MEYNERT

MEDIAL SEPTUM

SEROTONERGIC ANTERIOR RAPHE

NORADRENERGIC LOCUS CERULEUS

NEOCORTEX

Lesion formation from:

Extracellular deposits of fibrous amyloid protein

1. Amyloid peptide forms senile plaques

2. It is made from APP

3. APP regulate neurite formation, cell adhesion and

ion transport (Cu and Zn)

4. Mutant APP751 forms β-amyloid plaques,

tau-positive tangles which leads to memory

impairments

5. APP could either be cleaved byα-APP secretase to

lead to harmless results or β-APP secretase to

generate β-amyloid proteins

6. Aggregated β-amyloid proteins are known to kill

neurons by apoptosis

7. Mutations in presenelin 1 and 2 genes may lead to

early forms of Alzheimer’s disease.

Intracellular deposit of hyper phosphorylated tau

proteins, forming NFTs (Neurofibrillary tangles).

1. Tau proteins bind to β-tubulins to stabilize

microtubules involved in axoplasmic transport.

2. Hyper phosphorylated tau proteins assembles to

form paired helical filaments which forms NFTs

3. Tau load is the best predicator for cognitive decline

in AD

Neuroinflammation

Presence of activated microglial cells and astrocytes

Amyloid fibres not only being toxic to neurons directly,

it also indirectly activates microglia to secrete

molecules to kill neurons.

TACRINE

ARICEPT

MEMANTINE

PARKINSON’S DISEASE A very severe neurodegenerative disorder RIGIDITY

AKINESIA

TREMOR AT REST

EMOTIONALLY FLAT

Loss of dopamine neurons in the SNc and dopamine

terminals in the striatum

Over-excitation of cholinergic neurons in the striatum

(akinesia)

Increased glutamate activity in subthalamic

nucleus????

L-DOPA (+ CARBIDOPA)

BENZTROPINE

BROMOCRIPTINE

SCHIZOPHRENIA A disease of abnormal thought,

perception, behaviour and attention.

DEREALIZATION

DEPERSONALIZATION

Schizophrenic symptoms due to over activity of dopamine

systems and down decrease in activity of glutamate

systems in the mesolimbic/cortical systems.

TYPICAL:

CHLORPRAMAZINE

HALOPERIDOL

ATYPICAL

CLOZAPINE

RISPERIDONE

POSITIVE SYMPTOMS NEGATIVE SYMPTOMS

Delusions

Auditory

Hallucinations

Withdrawal

Flattened Mood

ANXIETY An unpleasant state accompanied by

apprehension, worry, fear,

nervousness etc.

GENERALIZED ANXIETY DISORDERS

OCDs

PHOBIAS

PANIC ATTACKS

INCREASED SEROTONIN RELEASE FROM THE RAPHE

NUCLEUS

DECREASED ACTIVITY OF GABAA RECEPTORS

ANTI-ANXIOLYTICS

DIAZEPAM (BENZODIAZEPINE)

MIDAZOLAM (BENZODIAZEPINE)

FLUMAZENIL (BZ ANTAGONIST)

BUSPIRONE

DEPRESSION An episodic, recurrent illness with

periods of spontaneous remission

UNIPOLAR

Decrease in mood, appetite, libido

Tiredness

ENDOGENOUS DEPRESSION: unknown origin

REACTIVE DEPRESSION: Life/environment

based

BIPOLAR

Mood Fluctuates between depression and

mania

Genetic basis

MANIA: Heightened mood/euphoria,

irritability, poor insight into sudden irrational

decisions and some cases delusions and

hallucinations

SIMPLE MONOAMINE THEORY

Depression is a result of decrease in brain monoamines

(NA, DA, 5-HT)

Thus Monoamine Inactivation Systems:

Re-uptake into the neurons

Metabolism by MAOA and MAOB enzymes

Anti-depressants inhibit the above two systems

ANTI-DEPRESSANTS

LITHIUM CARBONATE

1ST GENERATION 2ND GENERATION

TRICYCLICS

AMITRIPTYLLINE

IMIPRAMINE

MAO INHIBITORS

PHENELZINE

MAO INHIBITORS

MOCLOBEMIDE

SSRI

FLUOXETINE

PAROXETINE

EPILEPSY A group of brain disorders

characterised by abnormal

synchronous high frequency and

neuronal discharge (seizure) that is

spontaneous and recurrent.

Types of seizures (epilepsy):

PARTIAL SEIZURES

Localised to some brain regions, have a

“Focus”.

- Simple: No loss of consciousness

- Complex: Loss of consciousness

GENERALISED SEIZURES

Takes place everywhere, have no “Focus”.

- Petit Mal: Absence seizure, spike and wave,

common in children.

- Grand Mal: Tonic/Clonic seizures. Involves:

1. Trunk & limb movements

2. Jerking of muscles

Insufficient GABAA activity.

Excessive neuronal discharge

IDIOPATHIC

No known cause

SYMPTOMATIC

Result of tumour/infection/injury

ANTI-EPILEPTICS

PHENOBARBITONE

PHENYTOIN

CARBAMAZEPINE

SODIUM VALPORATE

DIAZEPAM

LAMOTRIGINE

MEMANTINE (SE)

STATUS EPILEPTICUS (SE)

Medical emergency

>20min (prolonged + seizure) get to brain

damage

Can be partial/convulsive SE or Absence SE

HUNTINGTON’S DISEASE A neurodegenerative genetic disorder

that affects muscle coordination and

leads to cognitive decline and

psychiatric problems.

BEHAVIOURAL/COGNITIVE CHANGES

HYPERKINESIA

HYPOKINESIA AT LATE STAGE

INVOLUNTARY MOVEMENTS

Loss of GABAergic projection neurons in the striatum

N/A

AMYOTROPHIC LATERAL

SCLEROSIS (AKA

ALS/MOTOR NEURON

DISEASE)

Adult onset chronic

neurodegenerative disorder with the

characteristic of degeneration of

upper and lower motor neurons.

MUSCLE WASTING

WEAKNESS

SPASTICITY

PARALYSIS

DEATH DUE TO RESPIRATORY MUSCLE

PARALYSIS

GLUTAMATE EXCITOTOXICITY

1. Loss of astrocytic EAAT2 (removes glutamate from the

synapse) in the motor neuron and spinal cord

2. Increases glutamate levels at the synapses

3. Causes over action of neuronal NMDA receptors and

AMPA receptors

4. Increases intracellular Ca2+ as well as Na+/Cl- ions

5. Influx of water

6. Death of motor neurons

7. Symptoms of ALS

RILUZOLE

OBESSIVE COMPULSIVE

DISORDERS

Anxiety disorders characterized by

intrusive thoughts that produce

uneasiness, apprehension, fear or

worry, repetitive actions aimed at

reducing the associated anxiety.

REPETITIVE ACTIONS (COMPULSIONS)

REPETITIVE THOUGHTS (OBSESSIONS)

Mutation in the serotonin transporter.

Mutation causes gain-of-function leading to increased

serotonin

Unclear????

SSRIs (FLUOXETINE)