The document describes a new fever affecting an unknown number of people. It was written by Aneesa Naadira Khan, who calls herself "crazy" for having a new idea about the fever. The fever is referred to as a "strange fever" and the author aims to briefly describe it. The cause and symptoms of the fever are not provided in the 3 sentences.

1. Problem 1: A strange fever
By Aneesa Naadira Khan
“A person with a new idea is a crank until the
idea succeeds.”
Call me crazy

2. Objective 1
Briefly describe the histology of the cerebral cortex

3. The cerebral cortex
 Has a thickness varying 1 to 4mm
 Is composed of glial cells and neurons
 Has six layers:
 I Molecular layer
 II External granular layer
 III External pyramidal layer
 IV Internal granular layer
 V Internal pyramidal layer
 VI Multiform (polymorphic layer)

4.  Layer 1 consists mainly of apical dendrites from pyramidal
cells from lower layers — plus axons synapsing on those
dendrites. It contains almost no neuron cell bodies.
 Layer 2 contains many small densely-packed pyramidal
neurons — giving it a granular appearance.
 Layer 3 contains medium-sized pyramidal neurons which
send outputs to other cortical areas.
 Layer 4 contains many spiny stellate (excitatory)
interneurons
 Layer 5 contains the largest pyramidal neurons, which
send outputs to the brain stem and spinal cord
(the pyramidal tract)
 Layer 6 consists of pyramidal neurons and neurons with
spindle-shaped cell bodies.

5.  6 layers of the cerebral cortex:
 Molecular (plexiform) layer
 apical dendrites of pyramidal cells
 large no. of synapses happen here
 OUTER granular layer
 stellate cells
 OUTER pyramidal cell layer
 pyramidal cells smaller
 INNER granular layer
 closely packed stellate cells
 horizontal fibres (of Baillarger)
 INNER pyramidal cell later (ganglionic layer)
 large pyramidal cells
 particularly in motor area
 inner fibres of Baillarger
 Multiform cell layer
 fusiform cells
 many nerve fibres entering white matter

9. Stellate (Granule) Cells
 These come in a wide assortment of shapes.
 They are typically small (< 10
micrometres) multipolar neurons.
 Their short axons do not leave the cortex.
 Stellate cells are the principal interneurons of
the neocortex.

10. Pyramidal Cells
 These cells are shaped as they are named.
 Pyramidal cells range in size from 10 micrometres in diameter to 70-100
micrometres of the giant pyramidal cells (Betz cells) of the motor cortex.
 A long apical dendrite leaves the top of each pyramidal cell and ascends
vertically to the cortical surface.
 A series of basal dendrites emerges from nearer the base of the cell and
spreads out horizontally.
 The apical dendrites of pyramidal cells are studded with dendritic spines.
 These are numerous small projections that are the preferential
site of synaptic contact.
 It has been suggested that dendritic spines may be the sites of synapses that are
selectively modified as a result of learning.
 Most or all pyramidal ells have long axons that leave the cortex to reach
either other cortical areas or to various subcortical sites.
 Therefore, pyramidal cells are the principal output neurons.

11. Fusiform Cells
 These are found in the deepest cortical layer.
 They are spindle-shaped with a tuft of
dendrites emerging from each end of
the spindle.
 They are, however, otherwise like pyramidal
cells with an axon that leaves the cortex.

12. Objective 2
Describe typical brain waves seen on the eeg and how
it is conducted

13. What is EEG?
 An electroencephalogram (EEG) is a painless
procedure that uses small, flat metal discs
(electrodes) attached to your scalp to detect electrical
activity in your brain. Your brain cells communicate via
electrical impulses and are active all the time, even
when you're asleep. This activity shows up as wavy
lines on an EEG recording.
From : myoclinic.com

14. During the procedure
 A standard noninvasive EEG takes about 1 hour. The patient will be
positioned on a padded bed or table, or in a comfortable chair. To
measure the electrical activity in various parts of the brain, a nurse or
EEG technician will attach 16 to 20 electrodes to the scalp. The brain
generates electrical impulses that these electrodes will pick up. To
improve the conduction of these impulses to the electrodes, a gel will be
applied to them. Then a temporary glue will be used to attach them to
the skin. No pain will be involved.
 The electrodes only gather the impulses given off by the brain and do
not transmit any stimulus to the brain. The technician may tell the
patient to breathe slowly or quickly and may use visual stimuli such as
flashing lights to see what happens in the brain when the patient sees
these things. The brain's electrical activity is recorded continuously
throughout the exam on special EEG paper.

15. Normal brain waves
 Alpha waves occur at a frequency of 8 to 12 cycles per second in a
regular rhythm. They are present only when you are awake but have
your eyes closed. Usually they disappear when you open your eyes or
start mentally concentrating.
 Beta waves occur at a frequency of 13 to 30 cycles per second. They
are usually associated with anxiety, depression, or the use of sedatives.
 Theta waves occur at a frequency of 4 to 7 cycles per second. They are
most common in children and young adults.
 Delta waves occur at a frequency of 0.5 to 3.5 cycles per second. They
generally occur only in young children during sleep.

16.  Beta waves (15-30 oscillations (or waves) per second (Hz)). This is the brain rhythm in the normal wakeful state
associated with thinking, conscious problem solving and active attention directed towards the outer world. You are
most likely in the "beta state" while you are reading this.
 Alpha waves (9-14 Hz). When you are truly relaxed, your brain activity slows from the rapid patterns of beta into
the more gentle waves of alpha. Fresh creative energy begins to flow, fears vanish and you experience a liberating
sense of peace and well-being. The "alpha state" is where meditation starts and you begin to access the wealth of
creativity that lies just below our conscious awareness. It is the gateway that leads into deeper states of
consciousness.
 Theta waves (4-8 Hz). Going deeper into relaxation and meditation, you enter the "theta state" where brain activity
slows almost to the point of sleep. Theta brings forward heightened receptivity, flashes of dreamlike imagery,
inspiration, and,sometimes, your long-forgotten memories. It can also give you a sensation of "floating".
 Theta is one of the more elusive and extraordinary realms we can explore. It is also known as the twilight state
which we normally only experience fleetingly as we rise up out of the depths of delta upon waking, or drifting off to
sleep. In theta, we are in a waking dream, and we are receptive to information beyond our normal conscious
awareness. Some people believe that theta meditation awakens intuition and other extrasensory perception skills.
 Delta waves (1-3 Hz). This slowest of brainwave activity is found during deep, dreamless sleep. It is also
sometimes found in very experienced meditators.

18. Objective 3
Explain the mechanism of action of anticonvulsants

19. Predominant MOA of anticonvulsant
drugs

20. Phenytoin
 Alters Na , K , and Ca conductance, membrane
potentials and the concentrations of amino acids and
the neurotransmitters norepinephrine, acetocholine
and y-aminobutyric acid (GABA)
 Blocks sustained high-frequency repetitive firing of
action potentials.
 It is a use-dependent effect on Na conductance
arising from preferential binding to and prolongation of
the inactivated state of the Na channel

21. Na channel blockers
Some antiepileptic drugs
stabilize inactive
configuration of sodium
(Na+) channel,
preventing high-
frequency neuronal
firing.
 During an action potential, these channels exist in the active state and allow influx of sodium ions. Once the activation
or stimulus is terminated, a percentage of these sodium channels become inactive for a period known as the refractory
period. With constant stimulus or rapid firing, many of these channels exist in the inactive state, rendering the axon
incapable of propagating the action potential.
 AEDs that target the sodium channels prevent the return of these channels to the active state by stabilizing them in the
inactive state. In doing so, they prevent repetitive firing of the axons

22. Na channel blockers
 Sodium channel blockade is the most common and
best-characterized mechanism of currently available
antiepileptic drugs (AEDs). AEDs that target sodium
channels prevent the return of the channels to the
active state by stabilizing the inactive form. In doing
so, repetitive firing of the axons is prevented.
Presynaptic and postsynaptic blockade of sodium
channels of the axons causes stabilization of the
neuronal membranes, blocks and prevents
posttetanic potentiation, limits the development of
maximal seizure activity, and reduces the spread of
seizures.

23. Calcium channel blockers
Low-voltage calcium
(Ca2+) currents (T-
type) are responsible
for rhythmic
thalamocortical spike
and wave patterns of
generalized absence
seizures. Some
antiepileptic drugs lock
these channels,
inhibiting underlying
slow depolarizations
necessary to generate
spike-wave bursts.
Calcium channels exist in 3 known forms in the human brain: L, N, and T. These
channels are small and are inactivated quickly. The influx of calcium currents in the
resting state produces a partial depolarization of the membrane, facilitating the
development of an action potential after rapid depolarization of the cell.
Calcium channels function as the " pacemakers " of normal rhythmic brain activity.
This is particularly true of the thalamus. T-calcium channels have been known to
play a role in the 3 per second spike-and-wave discharges of absence seizures.
AEDs that inhibit these T-calcium channels are particularly useful for controlling
absence seizures

24. enhancers
GABA is produced by
decarboxylation of glutamate
mediated by the enzyme
glutamic acid decarboxylase
(GAD). Some AEDs may act
as modulators of this
enzyme, enhancing the
production of GABA and
down-regulating glutamate
(see the image below).
Some AEDs function as an
agonist to chloride
conductance, either by
blocking the reuptake of
GABA (eg, tiagabine [TGB])
or by inhibiting its
metabolism as mediated by
GABA transaminase (eg,
vigabatrin [VGB]), resulting
in increased accumulation of
GABA at the postsynaptic
receptors.
Gamma-aminobutyric acid (GABA)-A receptor mediates chloride (Cl-) influx,
leading to hyperpolarization of cell and inhibition. Antiepileptic drugs may
act to enhance Cl- influx or decrease GABA metabolism.

25. GABA Receptor Agonists
 The benzodiazepines most commonly used for treatment of epilepsy are
lorazepam, diazepam, clonazepam, and clobazam. The first 2 drugs
are used mainly for emergency treatment of seizures because of their
quick onset of action, availability in intravenous (IV) forms, and strong
anticonvulsant effects. Their use for long-term treatment is limited
because of the development of tolerance.
 The 2 barbiturates mostly commonly used in the treatment of epilepsy
are phenobarbital (PHB) and primidone. They bind to a barbiturate-
binding site of the benzodiazepine receptor to affect the duration of
chloride channel opening. They have been used widely throughout the
world. They are very potent anticonvulsants, but they have significant
adverse effects that limit their use. With the development of new drugs,
the barbiturates now are used as second-line drugs for the treatment
of chronic seizures.

26. Glutamate blockers
 Glutamate receptors bind glutamate, an excitatory amino acid
neurotransmitter. Upon binding glutamate, the receptors facilitate
the flow of both sodium and calcium ions into the cell, while
potassium ions flow out of the cell, resulting in excitation.
 The glutamate receptor has 5 potential binding sites, as follows:
 The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
(AMPA) site
 The kainate site
 The N -methyl-D-aspartate (NMDA) site
 The glycine site
 The metabotropic site, which has 7 subunits (GluR 1-7)

27. GABA Transaminase Inhibitors
 Gamma-aminobutyric acid (GABA) is metabolized
by transamination in the extracellular
compartment by GABA-transaminase (GABA-T).
Inhibition of this enzymatic process leads to an
increase in the extracellular concentration of
GABA. Vigabatrin (VGB) inhibits the enzyme
GABA-T.

28. Objective 4
Discuss the pathophysiology of febrile convulsions and
epilepsy

29.  Febrile seizures occur in young children at a time in their development when the seizure threshold is low. This is a
time when young children are susceptible to frequent childhood infections such as upper respiratory infection, otitis
media, viral syndrome, and they respond with comparably higher temperatures. Animal studies suggest a possible
role of endogenous pyrogens, such as interleukin 1beta, that, by increasing neuronal excitability, may link fever and
seizure activity.[3]Preliminary studies in children appear to support the hypothesis that the cytokine network is
activated and may have a role in the pathogenesis of febrile seizures, but the precise clinical and pathological
significance of these observations is not yet clear.[4, 5]
 Febrile seizures are divided into 2 types: simple febrile seizures (which are generalized, last < 15 min and do not
recur within 24 h) and complex febrile seizures (which are prolonged, recur more than once in 24 h, or are
focal).[6]Complex febrile seizures may indicate a more serious disease process, such asmeningitis, abscess,
or encephalitis.
 Viral illnesses are the predominant cause of febrile seizures. Recent literature documented the presence of human
herpes simplex virus 6 (HHSV-6) as the etiologic agent in roseola in about 20% of a group of patients presenting
with their first febrile seizures. Shigella gastroenteritis also has been associated with febrile seizures. One study
suggests a relationship between recurrent febrile seizures and influenza A. [7, 8]
 Febrile seizures tend to occur in families. In a child with febrile seizure, the risk of febrile seizure is 10% for the
sibling and almost 50% for the sibling if a parent has febrile seizures as well. Although clear evidence exists for a
genetic basis of febrile seizures, the mode of inheritance is unclear. [9]
 While polygenic inheritance is likely, a small number of families are identified with an autosomal dominant pattern of
inheritance of febrile seizures, leading to the description of a "febrile seizure susceptibility trait" with an autosomal
dominant pattern of inheritance with reduced penetrance. Although the exact molecular mechanisms of febrile
seizures are yet to be understood, underlying mutations have been found in genes encoding the sodium channel
and the gamma amino-butyric acid A receptor.

30. Objective 5
Describe the role and synthesis of GABA in the brain

31. GABA-A
 GABA-A receptors are coupled to chloride
channels
 activation of GABA receptors will permit chloride
to diffuse into the cell, hyperpolarize the
membrane and decrease the excitability of the
cell.

32. GABA-B
 The GABA-B receptor is coupled to potassium
channels, forming a current that has a relatively
long duration of action compared with the chloride
current evoked by activation of the GABA-A
receptor.
 inhibit membrane excitability by opening
K+ channels and inhibiting Ca++ channels.

33. Role of GABA
 GABA is made in brain cells from glutamate, and
functions as an inhibitory neurotransmitter –
meaning that it blocks nerve impulses. Glutamate
acts as an excitatory neurotransmitter and when
bound to adjacent cells encourages them to ―fire‖
and send a nerve impulse. GABA does the
opposite and tells the adjoining cells not to ―fire‖,
not to send an impulse.

34. Synthesis of GABA