A.

COGNITIVE STRATEGY
In solving the scenario, we used the "group-individual learning" concept. We also collect informations from
our group tutor and look for existing evidence of informations regarding the scenario. We collect
informations from the anamnesis, physical examination, supporting examination and other examinations,
chronogically, to find the possibility of some diseases.

B. Answers of Learning Issues I

1. Anatomy and Physiology of Nervous System

Central nervous system can be divided into two parts, white and gray matter. Gray matter is an
area composed the body of neurons while white matter is composed by axons. neurons are
surrouded by the glial cells. There are 4 glial cells according to it’s function:

1. Microglia, an immune cells of the brain, acts like a macrophage but resides in tissue while
not needed but it will move when necessary.
2. Astrocyte, a cell that maintain the homeostasis of the brain by keeping the Kalium
concentrain in normal concentration, supporting the neuron cells, acting like a fibrocyte in
which they will repair and replace the damaged or died neuron, e.g. after a head trauma but
it doesn’t function like neuron.
3. Oligodendocyte, a cell that function like myelin sheath but only exist in CNS.
4. Ependymal cells, a cell that surrounds the ventricels of the brain, but recently it’s known
that ependymal cells could transform into the neuron cells in hippocampus. It may play a
role in memory.

Functionally, the nervous system is divided into two systems:

1. Somatic nervous system: This innervates the structures of the body wall (muscles, skin,
and mucous membranes).
2. Autonomic (visceral) nervous system (ANS): The ANS contains portions of the central and
peripheral systems. It controls the activities of the smooth muscles and glands of the
internal organs (viscera) and the blood vessels and returns sensory information to the brain.
 TELENCEPHALON

CEREBRUM

Cerebrum are 4 part of the lobes, i.e. frontal lobes, parietal lobes, temporal lobes, and
occipital lobes with 1 additional lobe, the insula. The cerebral cortex is organized into functional
regions. In addition to specific areas devoted to sensory and motor functions, there are areas that
integrate information from multiple sources. The cerebral cortex participates in advanced
intellectual functions, including aspects of memory storage and recall, language, higher cognitive
functions, conscious perception, sensory integration, and planning/execution of complex motor
activity.
  Broadmann Area

 Areas 3, 1 & 2 – Primary Somatosensory Cortex (frequently referred to as Areas 3, 1, 2 by

convention)
 Area 4 – Primary Motor Cortex
 Area 5 – Somatosensory Association Cortex
 Area 6 – Premotor cortex and Supplementary Motor Cortex (Secondary Motor Cortex)
(Supplementary motor area)
 Area 7 – Visuo-Motor Coordination
 Area 8 – Includes Frontal eye fields
 Area 9 – Dorsolateral prefrontal cortex
 Area 10 – Anterior prefrontal cortex (most rostral part of superior and middle frontal gyri)
 Area 11 – Orbitofrontal area (orbital and rectus gyri, plus part of the rostral part of the superior
frontal gyrus)
 Area 12 – Orbitofrontal area (used to be part of BA11, refers to the area between the superior
frontal gyrus and the inferior rostral sulcus)
 Area 13 and Area 14* – Insular cortex
 Area 15* – Anterior Temporal lobe
 Area 16 – Insular cortex
 Area 17 – Primary visual cortex (V1)
 Area 18 – Secondary visual cortex (V2)
 Area 19 – Associative visual cortex (V3,V4,V5)
 Area 20 – Inferior temporal gyrus
 Area 21 – Middle temporal gyrus
 Area 22 – Superior temporal gyrus, of which the caudal part is usually considered to contain
the Wernicke's area
 Area 23 – Ventral posterior cingulate cortex
 Area 24 – Ventral anterior cingulate cortex.
 Area 25 – Subgenual area (part of the Ventromedial prefrontal cortex)[4]
 Area 26 – Ectosplenial portion of the retrosplenial region of the cerebral cortex
 Area 27 – Piriform cortex
 Area 28 – Ventral entorhinal cortex
 Area 29 – Retrosplenial cingulate cortex
 Area 30 – Part of cingulate cortex
 Area 31 – Dorsal Posterior cingulate cortex
 Area 32 – Dorsal anterior cingulate cortex
 Area 33 – Part of anterior cingulate cortex
 Area 34 – Dorsal entorhinal cortex (on the Parahippocampal gyrus)
 Area 35 – Perirhinal cortex (in the rhinal sulcus)
 Area 36 – Ectorhinal area, now part of the perirhinal cortex (in the rhinal sulcus)
 Area 37 – Fusiform gyrus
 Area 38 – Temporopolar area (most rostral part of the superior and middle temporal gyri)
 Area 39 – Angular gyrus, considered by some to be part of Wernicke's area
 Area 40 – Supramarginal gyrus considered by some to be part of Wernicke's area
 Areas 41 and 42 – Auditory cortex
 Area 43 – Primary gustatory cortex
 Area 44 – Pars opercularis, part of the inferior frontal gyrus and part of Broca's area
 Area 45 – Pars triangularis, part of the inferior frontal gyrus and part of Broca's area
 Area 46 – Dorsolateral prefrontal cortex
 Area 47 – Pars orbitalis, part of the inferior frontal gyrus
 Area 48 – Retrosubicular area (a small part of the medial surface of the temporal lobe)
 Area 49 – Parasubicular area in a rodent
 Area 52 – Parainsular area (at the junction of the temporal lobe and the insula)

(*) Area only found in non-human primates.

Some of the original Brodmann areas have been subdivided further, e.g., "23a" and "23b"

 The Homonculus of Somatosensoric

Somatosensory pathway typically have three long neurons: primary, secondary, and tertiary. The
first always has its cell body in the dorsal root ganglion of the spinal nerve.

The second has its cell body either in the spinal cord or in the brainstem; this neuron’s ascending
axons will cross to the opposite side either in the spinal cord or in the brainstem. The axons of
many of these neurons terminate in the thalamus, and others terminate in the reticular activating
system or the cerebellum.
In the case of touch and certain types of pain, the third neuron has its cell body in the ventral
posterior nucleus of the thalamus and ends in the postcentral gyrus of the parietal lobe.
In the periphery, the somatosensory system detects various stimuli by sensory receptors, such as
by mechanoreceptors for tactile sensation and nociceptors for pain sensation. The sensory
information (touch, pain, temperature, etc.,) is then conveyed to the central nervous system by
afferent neurons, of which there are a number of different types with varying size, structure, and
properties.
Generally, there is a correlation between the type of sensory modality detected and the type of
afferent neuron involved. For example, slow, thin, unmyelinated neurons conduct pain whereas
faster, thicker, myelinated neurons conduct casual touch.

Ascending Pathways
In the spinal cord, the somatosensory system includes ascending pathways from the body to the
brain. One major target within the brain is the postcentral gyrus in the cerebral cortex. This is the
target for neurons of the dorsal column–medial lemniscal pathway and the ventral spinothalamic
pathway.
Note that many ascending somatosensory pathways include synapses in either the thalamus or the
reticular formation before they reach the cortex. Other ascending pathways, particularly those
involved with control of posture, are projected to the cerebellum, including the ventral and dorsal
spinocerebellar tracts.
Another important target for afferent somatosensory neurons that enter the spinal cord are those
neurons involved with local segmental reflexes.

Parietal Lobe: Primary Somatosensory Area

The primary somatosensory area in the human cortex is located in the postcentral gyrus of the
parietal lobe. This is the main sensory receptive area for the sense of touch.
Like other sensory areas, there is a map of sensory space called a homunculus at this location.
Areas of this part of the human brain map to certain areas of the body, dependent on the amount
or importance of somatosensory input from that area.
For example, there is a large area of cortex devoted to sensation in the hands, while the back has a
much smaller area. Somatosensory information involved with proprioception and posture also
target an entirely different part of the brain, the cerebellum.
Thalamus
The thalamus is a midline symmetrical structure within the brain of vertebrates including humans;
it is situated between the cerebral cortex and midbrain, and surrounds the third ventricle.
Its function includes relaying sensory and motor signals to the cerebral cortex, along with the
regulation of consciousness, sleep, and alertness.

Thalamic nuclei: The ventral posterolateral nucleus receives sensory information from the body.

Mapping the Primary Somatosensory Area

The cortical sensory homunculus is located in the postcentral gyrus and provides a representation
of the body to the brain.

Cortical Homunculus

Postcentral gyrus: The postcentral gyrus is located in the parietal lobe of the human cortex and
is the primary somatosensory region of the human brain.
This is the point-for-point correspondence of an area of the body to a specific point on the central
nervous system. Typically, the area of the body corresponds to a point on the primary
somatosensory cortex (postcentral gyrus).
This cortex is typically represented as a sensory homunculus which orients the specific body parts
and their respective locations upon the homunculus. Areas such as the appendages, digits, and face
can draw their sensory locations upon the somatosensory cortex.
Areas that are finely controlled, such as the digits, have larger portions of the somatosensory
cortex, whereas areas that are coarsely controlled, such as the trunk, have smaller portions. Areas
such as the viscera do not have sensory locations on the postcentral gyrus.

 The Homonculus of Somatomotoric

The somatomotor cortex is located in broadman area 4 (Primary motor cortex), and 6 and 8
(secondary motor cortex) somatomotor systems can be divided into pyramidal systems and
extrapyramidal systems
o Pyramidal system: movement initiation, voluntary, specific, smooth
o Extrapyramidal system: body position, muscle tone, movement inhibition / activation
 The Blood Supply of the Brain and Spinal Cord
o The brain receives blood from two sources: the internal carotid arteries, which
arise at the point in the neck where the common carotid arteries bifurcate, and the
vertebral arteries. The internal carotid arteries branch to form two major cerebral
arteries, the anterior and middle cerebral arteries. The right and left vertebral
arteries come together at the level of the pons on the ventral surface of the brainstem
 to form the midline basilar artery. The basilar artery joins the blood supply from
the internal carotids in an arterial ring at the base of the brain (in the vicinity of the
hypothalamus and cerebral peduncles) called the circle of Willis. The posterior
cerebral arteries arise at this confluence, as do two small bridging arteries, the
anterior and posterior communicating arteries. Conjoining the two major
sources of cerebral vascular supply via the circle of Willis presumably improves
the chances of any region of the brain continuing to receive blood if one of the
major arteries becomes occluded.
o The major branches that arise from the internal carotid artery—the anterior and
middle cerebral arteries—form the anterior circulation that supplies the forebrain.
These arteries also originate from the circle of Willis. Each gives rise to branches
that supply the cortex and branches that penetrate the basal surface of the brain,
supplying deep structures such as the basal ganglia, thalamus, and internal capsule.
Particularly prominent are the lenticulostriate arteries that branch from the middle
cerebral artery. These arteries supply the basal ganglia and thalamus. The posterior
circulation of the brain supplies the posterior cortex, the midbrain, and the
brainstem; it comprises arterial branches arising from the posterior cerebral,
basilar, and vertebral arteries. The pattern of arterial distribution is similar for all
the subdivisions of the brainstem: Midline arteries supply medial structures, lateral
arteries supply the lateral brainstem, and dorsal-lateral arteries supply dorsal-lateral
brainstem structures and the cerebellum (Figures 1.20 and 1.21). Among the most
important dorsal-lateral arteries (also called long circumferential arteries) are the
posterior inferior cerebellar artery (PICA) and the anterior inferior cerebellar
artery (AICA), which supply distinct regions of the medulla and pons. These
arteries, as well as branches of the basilar artery that penetrate the brainstem from
its ventral and lateral surfaces (called paramedian and short circumferential
arteries), are especially common sites of occlusion and result in specific functional
deficits of cranial nerve, somatic sensory, and motor function
BASAL GANGLIA (Nucleus caudatus + nucleus lenticularis (putamen + globullus palidus))
The term basal ganglia refers to masses of gray matter deep within the cerebral hemispheres (gray
among white). The basal ganglia include the caudate nucleus, the putamen , and the globus
pallidus.

Limbic System

DIENCEPHALON

Thalamus, Hipothalamus, Subthalamus, and epithalamus

Thalamus Hypothalamus Epithalamus Subthalamus

Function : Function : Function : Function :
• Sensoric • Eating • Sensoric Pineal body secrete
• Motoric • Autonomic • Motoric MSH (Melanocyte
• Limbic function • Reticular Stimulating
• Body Hormone)
Temperature
• Water balance
 • Anterior
Pituitary
function
• Circadian
rhythm
• Expression of
Emotion

MESENCEPHALON

MYELENCEPHALON AND METENCEPHALON

CEREBELLUM AND BRAINSTEM

SPINAL TRACT

THE CORTICOSPINAL TRACT

 The corticospinal, or pyramidal, tract is the major motor tract that controls voluntary
movement of the skeletal muscles, especially skilled movements of distal muscles of the limbs.
All structures from the cerebral cortex to the anterior horn cells in the spinal cord constitute the
upper portion of the system (upper motor neuron). The anterior horn cells and their associated
axons constitute the lower portion of the system (lower motor neuron).
SENSORIC SYSTEM AND MOTORIC SYSTEM

CEREBELLUM’S EFFERENT PATHWAY

 The cerebellum plays an important role in coordinating movement. It receives sensory
information and then influences descending motor pathways to produce fine, smooth, and
coordinated motion. The cerebellum is divided into three general areas:
archicerebellum (also called vestibulocerebellum), paleocerebellum (also called
spinocerebellum) and the neocerebellum (also called the cerebrocerebellum).
 The archicerebellum receives afferent signals from the vestibular apparatus and then sends
efferent fibers to the appropriate descending motor pathways.
 The paleocerebellum receives sensory information on limb position and muscle tone and
then modifies and coordinates these movements through efferent pathways to the
appropriate descending motor pathways.
 The neocerebellum receives input from the cerebral cortex and thus helps in the planning
of motor activity (e.g., seeing a pencil and then planning and executing the movement of
the arm and hand to pick it up).

CEREBELLUM’S AFFERENT PATHWAY

The cerebellum plays an important role in coordinating movement. It influences descending motor
pathways to produce fine, smooth, and coordinated motion.
 The archicerebellum sends efferent fibers to the appropriate descending motor pathways.
 The paleocerebellum modifies and coordinates these movements through efferent
pathways to the appropriate descending motor pathways.
 The neocerebellum helps in the planning of motor activity (e.g., seeing a pencil and then
planning andexecuting the movement of the arm and hand to pick it up).

SOMESTHETIC SYSTEM OF THE BODY

These tracts play a role in sensoric modulation in which the spinothalamic and spinnoreticular are
responsible for exteroseptive impulses and fasciculus gracilic and cuneatus (which will become
Medial Leminiscus after synapsing to dorsal column nuclei in medulla) bring proprioseptive
impulses.
 Pain, temperature, and pressure sensations below the head ultimately are conveyed to the
primary somatosensory cortex (postcentral gyrus) by the anterolateral system
(spinothalamic and spinoreticular tracts).
 The fasciculus gracilis and cuneatus of the spinal lemniscal system convey proprioceptive,
vibratory, and tactile sensations to the thalamus (ventral posterolateral nucleus), whereas
the lateral cervical system mediates some touch, vibratory, and proprioceptive sensations
(blue and purple lines show these dual pathways).
  Ultimately, these fibers ascend as parallel pathways to the thalamus, synapse, and ascend
to the cortex.

SKIN AND CUTANEOUS RECEPTORS AND PACCINIAN CORPUSCLE

1. Skin and Cutaneous Receptors

Cutaneous receptors respond to touch (mechanoreceptors), pain (nociceptors), and temperature

(thermoreceptors). Several different types of receptors are present in skin.
 Meissner’s corpuscles have small receptive fields and respond best to stimuli that are
applied at low frequency (i.e., flutter).
 The pacinian orpuscles are located in the subcutaneous tissue and have large receptive
fields. They respond best to high-frequency stimulation (i.e., vibration).
 Merkel’s discs have small receptive fields and respond to touch and pressure (i.e., indenting
the skin).
 Ruffini’s corpuscles have large receptive fields, and they also respond to touch and
pressure. Free nerve endings respond to pain and temperature.

2. Pacinian Corpuscle
 Pacinian corpuscles are mechanoreceptors that transduce mechanical forces (displacement,
pressure, vibration) into action potentials that are conveyed centrally by afferent nerve fibers.
As the viscoelastic lamellae are displaced, the unmyelinated axon terminal membrane’s ionic
permeability is increased until it is capable of producing a “generator potential.” As
demonstrated in the figure, pacinian corpuscles respond to the beginning and end of a
mechanical force while the concentric lamellae dissipate slow changes in pressure. In the
absence of the capsule, the generator potential decays slowly and yields only a single action
potential.

PROPRIOCEPTION: SPINAL EFFECTOR MECHANISM•

Position sense or proprioception involves input from cutaneous mechanoreceptors, Golgi tendon
organs, and muscle spindles (middle figure of upper panel). Both monosynaptic reflex pathways
(middle figure of upper panel) and polysynaptic pathways involving several spinal cord segments
(top and bottom figures of upper panel) initiate muscle contraction reflexes. The lower panel shows
the somatotopic distribution of the motor neuron cell bodies in the ventral horn of the spinal cord
that innervate limb muscles (flexor and extensor muscles of upper and lower limbs).

MUSCLE AND JOINT RECEPTORS

Muscle spindles and Golgi tendon organs send afferent signals to the brain to convey the position
of limbs and help coordinate muscle movement. Muscle spindles convey information on muscle
tension and contraction dynamic forces) and muscle length (static forces). The nuclear bag fibers
respond to both dynamic and static forces, whereas the nuclear chain fibers respond to static forces.
Intrafusal fibers maintain appropriate tension on the nuclear bag and nuclear chain fibers. If the
muscle tension is too great (e.g., overstretching of muscle or too heavy a load), activation of the
Golgi tendon organ causes a reflex relaxation of the muscle.
PROPRIOCEPTIVE REFLEX CONTROL OF MUSCLE TENSION•

Interaction of the muscle spindle and Golgi tendon organ during passive stretch of a muscle (panel
A) and during a contraction (panels B and C).

DERMATOMES
Sensory information below the head is localized to specific areas of the body, which reflect the
distribution of peripheral sensory fibers that convey sensations to the spinal cord through the dorsal
roots (sensory nerve cell bodies reside in the corresponding dorsal root ganglion). The area of skin
subserved by afferent fibers of one dorsal root is called a dermatome. This figure shows the
dermatome segments and lists key dermatome levels used by clinicians. Variability and overlap
occur, so all dermatome segments are only approximations.

Sensory information below the head is localized to specific areas of the body, which reflect the
distribution of peripheral sensory fibers that convey sensations to the spinal cord through the dorsal
roots (sensory nerve cell bodies reside in the corresponding dorsal root ganglion). The area of skin
subserved by afferent fibers of one dorsal root is called a dermatome. This figure shows the
dermatome segments and lists key dermatome levels used by clinicians. Variability and overlap
occur, so all dermatome segments are only approximations

PAIN

Pain is primarily a protective mechanism meant to bring to conscious awareness the fact that tissue
damage is occurring or is about to occur. Furthermore, storage of painful experiences in memory
helps us avoid potentially harmful events in the future.
Pain stimuli induce the excitaion of the afferen fiber that releases substance P and glutamate as
neurotransmitter but the roles are different. Substance P activates the ascending pathway from
afferent neuron and impulses continue to thalamus, then somatosensory cortex through the dorsal
sensory horn. Thalamus acts as a relay that will continue the impulses to the somatosensory cortex
and limbic system. Glutamate provides hyperexcitability by binding to NMDA receptor and
generating an action potential in the dorsal sensory horn by binding to AMPA receptor.

There are two types of pain, nociceptic pain, pain that arises from the trigger of nociceptic receptor
that could be induced mechanically, thermally, and polimodally, and neuropathic pain, condition
that causes tingling, numbness, and/or pain in parts of the body, notably the hands and feet.

Peripheral nerve palsies, or peripheral neuropathies, are regional losses of sensory and motor
function most often resulting from nerve trauma or compression. (You have experienced a mild,
temporary palsy if your arm or leg has ever “fallen asleep” after you leaned or sat in an
uncomfortable position.) The location of the affected dermatomes provides clues to the location of
injuries along the spinal cord, but the information is not precise. More exact conclusions can be
drawn if there is loss of motor control, based on the origin and distribution of the peripheral nerves
originating at nerve plexuses.

2. Pathophysiology of Seizure
Seizures are defined as finite episodes of disturbed cerebral function caused by
abnormal, excessive, and synchronous electrical discharges in groups of cortical neurons.
Various clinical phenomena may be apparent via observation, or the seizure may be
subclinical and thus remain clinically inapparent. Theoretically, any behavior or experience
of cerebral function may represent seizure activity, but in practice only certain patterns
frequently occur that allow for a classification schema.
Convulsion may be used clinically to refer to the motor manifestations of abnormal
electrical activity and is synonymous with generalized motor seizures. Nonconvulsive
seizure refers to seizure activity that does not involve motor symptomatology. Tonic refers
to a sustained stiffening of muscles that commonly accompanies many seizures. Clonic
means rhythmic movements or jerking of the muscles. Thus, tonic-clonic would accurately
describe a convulsion with initial stiffening of the body and extremities followed by
rhythmic contractions of muscle groups. Aura is commonly used to refer to any
premonitory subjective symptoms or sensation that the patient experiences before a seizure.
In actuality, an aura represents a focal seizure and a description of the aura may provide
valuable localizing information of the area of the brain where the generalized seizure
begins.
Provoked seizures can occur in anyone and do not constitute epilepsy. The terms
secondary seizures or acute symptomatic seizures are sometimes used to describe seizures
from a variety of identifiable causes, eg, electrolyte abnormalities, toxins, and tumors.
Epilepsy is present when seizures occur without a provoking factor because of an enduring
tendency to seizures. Altered brain physiology is always present in patients with epilepsy,
yet seizures occur essentially at random for entirely unknown reasons. Nevertheless, some
basic physiologic abnormalities causing the underlying tendency for seizures to occur are
known.
Seizures do not occur spontaneously under normal circumstances because neuronal
physiology maintains the stability of neuronal membranes and prevents rapid transfer of
the synchronous discharges that initiate a seizure. Several remarkable normal mechanisms
allow only a single action potential to pass in a time interval from one neuron to the next
as part of normal synaptic information transfer. Seizures can be provoked in a normal brain
by circumstances that disrupt this stability. For example, alterations of ion concentrations,
such as hyponatremia, cause a loss of the normal electrochemical gradients across cell
membranes that are needed to maintain stability; drug withdrawal from benzodiazepines,
barbiturates, and especially alcohol probably cause inhibitory GABA A receptors to be
sensitized so that neuronal activity that is normally harmless stimulates a seizure;
hypoglycemia alters cellular metabolism.
A seizure can be conceptualized as occurring when there is distortion of the normal
balance between excitation (E) and inhibition (I) in the brain (Stafstrom, 2010). This E/I
imbalance can result from an alteration at many levels of brain function, from genes and
subcellular signaling cascades to widespread neuronal circuits. The factors that alter E/I
balance can be genetic or acquired. Genetic pathologies leading to epilepsy can occur
anywhere from the circuit level (e.g., abnormal synaptic connectivity in cortical dysplasia)
 to the receptor level (e.g., abnormal ɤ-aminobutyric acid [GABA] receptor subunits in
Angelman syndrome) to abnormal ionic channel function (e.g., potassium channel
mutations in benign familial neonatal epilepsy [BFNE]). Similarly, acquired cerebral
insults can alter circuit function (e.g., structural alteration of hippocampal circuitry
following prolonged febrile seizures or head trauma). The developing brain is particularly
prone to seizures for a variety of physiological reasons (Berkovic, 2015). Even in the
normal developing brain, excitatory synaptic function develops before inhibitory synaptic
function, favoring enhanced excitation and seizure generation. In addition, early in life, the
neurotransmitter GABA causes excitation rather than inhibition (Ben-Ari, 2002; Pitkänen
et al., 2015). These observations partly explain why the very young brain is especially
susceptible to seizures. However, seizures cause less structural damage in the developing
brain than in the adult brain (Holmes and Ben-Ari, 1998).

3. Risk Factor and Predisposing Factor of Seizure

1. Epileptic Seizure

About half of epilepsy people had, has no exact cause. And the other half, it may caused
by various factors, including:

 Genetic influence: Some types of epilepsy, that classified by the type of seizure or
part of the brain that is affected, run in families. Researchers have linked some types
of epilepsy to specific genes. But genes are only part of the cause of epilepsy. Some
genes may make a person more sensitive to conditions that trigger seizures.
 Head trauma: Head trauma which is caused by injury can cause epilepsy.
 Brain conditions: Damage to the brain, such as brain tumors or strokes, can cause
epilepsy.
 Infectious diseases: Infectious diseases, such as meningitis, AIDS and viral
encephalitis, can cause epilepsy.
 Prenatal injury: Before birth, babies are prone to have brain damage. It may cause by
an infection, poor nutrition or oxygen deficiencies. This brain damage can result in
epilepsy.
  Developmental disorders: Developmental disorders, such as autism and
neurofibromatosis sometimes may associated with epilepsy.

Risk factors
Certain factors may increase the risk of epilepsy:
 Age: The onset is the most common in children and older adults, but this condition
can occur at any age.
 Family history: If there is a family history of epilepsy, it increased risk of developing
a epilepsy.
 Head injuries: Head injuries are responsible for some cases of epilepsy.
 Stroke and other vascular diseases: Stroke and other vascular diseases can lead to
brain damage that may trigger epilepsy.
 Dementia: Dementia can increase the risk of epilepsy in older adults.
 Brain infections: Infections such as meningitis, which causes inflammation in brain
or spinal cord, can increase the risk.
 Seizures in childhood: Children with febrile seizure commonly doesn't developed
epilepsy. The risk of epilepsy increases if a child has a long seizure, another nervous
system condition or a family history of epilepsy.

2. Non-Epileptic Seizure
This type of seizure is more prevalent in woman than in men, the onset is more
common in young adults (age 20 - 30). Non-epileptic seizure is most often caused by
mental stressor or a physical condition such as physical injury. The condition that may
increased the risk of this type of seizure are a heart condition, diabetes or othe metabolic
disorder, emotional pain, mental pain, physical or sexual abuse, and a major accident that
cause an injury in head. Non-epileptic seizure is more common in people with conditions
like depression and anxiety.

4. Pathophysiology of Epilepsy
 Epilepsy is defined as a brain disorder characterized by an enduring predisposition
to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social
consequences of this condition
The clinical signs and symptoms of seizures depend on the location of the epileptic
discharges in the cerebral cortex and the extent and pattern of the propagation of the
epileptic discharge in the brain. A key feature of epileptic seizures is their stereotypic
nature. (Loddenkemper et al., 2005)
Differential Diagnoses include : Frontal Lobe Epilepsy, Idiopathic Orthostatic
Hypotension and other Autonomic Failure Syndromes, Migraine Headache, Pediatric
Febrile Seizures, Pediatric First Seizure, Sleepwalking, Transient Global Amnesia,
Cardioembolic stroke, First Adult Seizure (Loddenkemper et al., 2005)

Pathophysiology
Seizures are paroxysmal manifestations of the electrical properties of the cerebral
cortex. A seizure results when a sudden imbalance occurs between the excitatory and
inhibitory forces within the network of cortical neurons in favor of a sudden-onset net
excitation. (Engel et al., 2006).
The brain is involved in nearly every bodily function, including the higher cortical
functions. If the affected cortical network is in the visual cortex, the clinical manifestations
are visual phenomena. Other affected areas of primary cortex give rise to sensory,
gustatory, or motor manifestations. The psychic phenomenon of déjà-vu occurs when the
temporal lobe is involved. (Engel et al., 2006)
The pathophysiology of focal-onset seizures differs from the mechanisms
underlying generalized-onset seizures. Overall, cellular excitability is increased, but the
mechanisms of synchronization appear to substantially differ between these 2 types of
seizure and are therefore discussed separately. (Engel et al., 2006)

Pathophysiology of focal seizures

The electroencephalographic (EEG) hallmark of focal-onset seizures is the focal

interictal epileptiform spike or sharp wave. The cellular neurophysiologic correlate of an
interictal focal epileptiform discharge in single cortical neurons is the paroxysmal
depolarization shift (PDS). The PDS is characterized by a prolonged calcium-dependent
depolarization that results in multiple sodium-mediated action potentials during the
depolarization phase, and it is followed by a prominent after-hyperpolarization, which is a
hyperpolarized membrane potential beyond the baseline resting potential. Calcium-
dependent potassium channels mostly mediate the after-hyperpolarization phase. When
multiple neurons fire PDSs in a synchronous manner, the extracellular field recording
shows an interictal spike. (Wolf et al., 2006)
If the number of discharging neurons is more than several million, they can usually
be recorded with scalp EEG electrodes. Calculations show that the interictal spikes need to
spread to about 6 cm2 of cerebral cortex before they can be detected with scalp electrodes.
(Berg et al., 2010)
Several factors may be associated with the transition from an interictal spike to an
epileptic seizure. The spike has to recruit more neural tissue to become a seizure. When
any of the mechanisms that underlie an acute seizure becomes a permanent alteration, the
person presumably develops a propensity for recurrent seizures (ie, epilepsy). (Berg et al.,
2010)
The following mechanisms (discussed below) may coexist in different
combinations to cause focal-onset seizures: Decreased inhibition, Defective activation of
gamma-aminobutyric acid (GABA) neurons, Increased activation If the mechanisms
leading to a net increased excitability become permanent alterations, patients may develop
pharmacologically intractable focal-onset epilepsy. . (Berg et al., 2010)
Currently available medications were screened using acute models of focal-onset
or generalized-onset convulsions. In clinical use, these agents are most effective at
blocking the propagation of a seizure (ie, spread from the epileptic focus to secondary
generalized tonic-clonic seizures). Further understanding of the mechanisms that
permanently increase network excitability may lead to development of true antiepileptic
drugs that alter the natural history of epilepsy. . (Berg et al., 2010)

Decreased inhibition

The release of GABA from the interneuron terminal inhibits the postsynaptic
neuron by means of 2 mechanisms: (1) direct induction of an inhibitory postsynaptic
potential (IPSP), which a GABA-A chloride current typically mediates, and (2) indirect
inhibition of the release of excitatory neurotransmitter in the presynaptic afferent
projection, typically with a GABA-B potassium current. Alterations or mutations in the
different chloride or potassium channel subunits or in the molecules that regulate their
function may affect the seizure threshold or the propensity for recurrent seizures.
Mechanisms leading to decreased inhibition include the following: Defective
GABA-A inhibition, Defective GABA-B inhibition, Defective activation of GABA
neurons, Defective intracellular buffering of calcium . (Berg et al., 2010)
Mechanisms leading to increased excitation include the following: Increased
activation of NMDA receptors, Increased synchrony between neurons due to ephaptic
interactions, Increased synchrony and/or activation due to recurrent excitatory collaterals. .
(Berg et al., 2010)

Pathophysiology of generalized seizures

The best-understood example of the pathophysiologic mechanisms of generalized

seizures is the thalamocortical interaction that may underlie typical absence seizures. The
thalamocortical circuit has normal oscillatory rhythms, with periods of relatively increased
excitation and periods of relatively increased inhibition. It generates the oscillations
observed in sleep spindles. The thalamocortical circuitry includes the pyramidal neurons
of the neocortex, the thalamic relay neurons, and the neurons in the nucleus reticularis of
the thalamus (NRT). (Fisher et al., 2005)
Altered thalamocortical rhythms may result in primary generalized-onset seizures.
The thalamic relay neurons receive ascending inputs from the spinal cord and project to
the neocortical pyramidal neurons. Cholinergic pathways from the forebrain and the
ascending serotonergic, noradrenergic, and cholinergic brainstem pathways prominently
regulate this circuitry. (Fisher et al., 2005)
The thalamic relay neurons can have oscillations in the resting membrane potential,
which increases the probability of synchronous activation of the neocortical pyramidal
neuron during depolarization and which significantly lowers the probability of neocortical
activation during relative hyperpolarization. The key to these oscillations is the transient
low-threshold calcium channel, also known as T-calcium current.
 In animal studies, inhibitory inputs from the NRT control the activity of thalamic
relay neurons. NRT neurons are inhibitory and contain GABA as their main
neurotransmitter. They regulate the activation of the T-calcium channels in thalamic relay
neurons, because those channels must be de-inactivated to open transitorily. (Fisher et al.,
2005)
T-calcium channels have 3 functional states: open, closed, and inactivated. Calcium
enters the cells when the T-calcium channels are open. Immediately after closing, the
channel cannot open again until it reaches a state of inactivation. (Fisher et al., 2005)
The thalamic relay neurons have GABA-B receptors in the cell body and receive
tonic activation by GABA released from the NRT projection to the thalamic relay neuron.
The result is a hyperpolarization that switches the T-calcium channels away from the
inactive state into the closed state, which is ready for activation when needed. The switch
to closed state permits the synchronous opening of a large population of the T-calcium
channels every 100 milliseconds or so, creating the oscillations observed in the EEG
recordings from the cerebral cortex . (Fisher et al., 2005)
Findings in several animal models of absence seizures, such as lethargic mice, have
demonstrated that GABA-B receptor antagonists suppress absence seizures, whereas
GABA-B agonists worsen these seizures. Anticonvulsants that prevent absence seizures,
such as valproic acid and ethosuximide, suppress the T-calcium current, blocking its
channels. (Fisher et al., 2005)
A clinical problem is that some anticonvulsants that increase GABA levels (eg,
tiagabine, vigabatrin) are associated with an exacerbation of absence seizures. An increased
GABA level is thought to increase the degree of synchronization of the thalamocortical
circuit and to enlarge the pool of T-calcium channels available for activation. (Fisher et al.,
2005)

DIAGNOSIS
The diagnosis of epileptic seizures is made by analyzing the patient's detailed
clinical history and by performing ancillary tests for confirmation. Physical examination
helps in the diagnosis of specific epileptic syndromes that cause abnormal findings, such
as dermatologic abnormalities (eg, patients with intractable generalized tonic-clonic
seizures for years are likely to have injuries requiring stitches). (Goodkin et al., 2007)
Potentially useful laboratory tests for patients with suspected epileptic seizures
include the following prolactin levels obtained shortly after a seizure to assess the etiology
(epileptic vs nonepileptic) of a spell; levels are typically elevated 3- or 4-fold and more
likely to occur with generalized tonic-clonic seizures than with other seizure types;
however, the considerable variability of prolactin levels has precluded their routine clinical
use, serum levels of anticonvulsant agents to determine baseline levels, potential toxicity,
lack of efficacy, treatment noncompliance, and/or autoinduction or pharmacokinetic
change, CSF examination in patients with obtundation or in patients in whom meningitis
or encephalitis is suspected (Goodkin et al., 2007)

Imaging studies
The following 2 imaging studies must be performed after a seizure: Neuroimaging
evaluation (eg, MRI, CT scanning), EEG (Goodkin et al., 2007)
The clinical diagnosis can be confirmed by abnormalities on the interictal EEG, but
these abnormalities could be present in otherwise healthy individuals, and their absence
does not exclude the diagnosis of epilepsy. Video-EEG monitoring is the standard test for
classifying the type of seizure or syndrome or to diagnose pseudoseizures (ie, to establish
a definitive diagnosis of spells with impairment of consciousness). This technique is also
used to characterize the type of seizure and epileptic syndrome to optimize pharmacologic
treatment and for presurgical workup. (Goodkin et al., 2007)
The patient's prognosis for disability and for a recurrence of epileptic seizures
depends on the type of epileptic seizure and the epileptic syndrome in question. Impairment
of consciousness during a seizure may unpredictably result in morbidity or even mortality.
(Rho et al., 2004)
Regarding morbidity, trauma is not uncommon among people with generalized
tonic-clonic seizures. Injuries such as ecchymosis; hematomas; abrasions; tongue, facial,
and limb lacerations; and even shoulder dislocation can develop as a result of the repeated
tonic-clonic movements. Atonic seizures are also frequently associated with facial injuries,
 as well as injuries to the neck. Worldwide, burns are the most common serious injury
associated with epileptic seizures. (Rho et al., 2004)

5. Infection of Central Nervous System related to seizures

Central nervous system (CNS) is one of our body system that includes spinal cords and brain. Our
body and mind are controlled by the CNS. If there is an infection In the CNS, it can affects our
body dramatically. CNS infection can caused by :

1. Meningitis
2. Encephalitis
CNS infection can tigger some complication such as increased intracranial pressure, cerebral
abscess, ventriculitis, hydrocephalus, cranial nerve injuries, and the most common is seizures.

Meningitis

Meninges is a layer that consist of dura mater, arachnoid mater, and pia mater that encircle the
neuroaxis. If there is an inflammation in the meninges, it is called meningitis. The inflammation
can be prior to bacterial infection, viral infection, or fungi infection. In adults the most common
microorganisms that caused meningitis are Streptococcus penumoniae and Neisseria meningitidis.
Other than that, HIV, Enterovirus, HSV, Parasitic infections such as Taenia solium can also induce
meningitis.
The pathogen such as virus or bacteria will entered the body, then it will invades the subarachnoid
space with various pathway, it can be through hematogenous pathway which the pathogen crosses
the BBB, Direct spread or it can be iatrogenic. Subsequently, our body will activates the immune
system, in this state our body will exhibit the complication and clinical features of meningitis.
Cytokines then being released, and making the capillary wall changes in the BBB. Further can
make the injured cell and nearby cells demaged and lead to increases of intracranial pressure,
cerebral edema, meningeal irritation, and neuronal death.

The symptoms of meningitis :

 altered mental status

 chills photophobia
 vision loss
 nausea and vomiting
 seizures.
The sign of Meningitis :

 Fever
 Decreased GCS
 Cranial nerve palsies
 Hemiparesis
 Nystagmus
 Headache
 Petechial rash

Meningitis, which is an inflammation, in the brain can change the permeability of the membarane,
which can lead to lowering the seizure threshold. In adult with community-acquired bacterial
meningitis, seizures can often be found. It is believe to be related to the severe inflammation,
structural CNS lesions, Pneumococcal meningitis, and other predisposing factors

Encephalitis

Encephalitis is an inflammation of the brain, the caused of encephalitis can be from virus such as
Herpes Simples 1 panencephalitis, Varicella Zoster Virus encephalitis, Enterovirus and arbovirus
polioencephalitis, HIV, Rabies, from Bacteria like Mycobacterium tuberculosis and Listeria
monocytogenes or it can also from parasites and fungi like cryptococcosis.

Sign and symptoms of encephalitis :

 Flu-like symptoms
 Headache
 Confusion or disorientation
 Seizures
 Change in personality and behaviour
 Hard in speaking
 Movement wakness
 Loss of consciousness
Encephalitis can be cured but it will leave a mark to the brain, it can caused a complications like :

 Memory loss
 Frequent seizure
 Personality and behavior change
 Problem with attention, concentration, planning, and problem solving
 Persistent tiredness

In a research that was conducted by Misra, et al in 2008, it is said that vora; encephalitis can
induce seizures not only in the acute stage but as well as rising the unprovokes seizures and
epilepsy. The comparison of seizures that happen in the relapse-late onset encephalitis with acute
encephalitis is (4%:1,8%).

Herpes Encephalitis which is due to herpes simplex virus infection, is the most common type
encephalitis in children who are older than 6 month and adult. Herpes simplex encephalitis can
caused a generalized seizure that may be preceded by focal seizures. Japanese encephalitis is the
most common arbo viral encephalitis worldwide. About 10 % of patient that are suffering from
Japanese encephalitis will experience seizure more often during the acute phase of the illness.

In a research conducted in 2009, proved that seizure more often occur in viral and bacterial
meningitis rather than viral meningitis. Also, The most frequent symptoms that someone with CNS
infection have that have seizure are headache, vomit, stiff neck, and drowsiness. The risk of
developing unprovoked seizure in patient with viral encephalitis and early seizure is 22 %.
Nevertheless patient with viral encephalitis but without early seizure have a risk almost half
percent of the former. For patient with bacterial meningitis and early seizure, their risk is about 13
% while for the one without early seizure have only 2.4%.

To sum up, Bacterial meningits can caused by Neiserria Meningitidis, S. Pneumoniae, and
Listeria. The CSF finding will likely bw low glucose, raised protein and polymorphs. While the
viral meningitis can caused by enterovirus, mumps, herpes simples, arbovirus, and the CSF finding
will be normal glucose, Rasied protein and lymphocytes. For the viral encephalitis, it is usually
due to herpes simplex, arbovirus, mumps, and measles infection.

6. Pathophysiology of Seizures Caused by Tumor and Trauma

The etiology of tumor-related seizures (TRS) is reviewed from the Karolinska Institute, Stockholm,
Sweden, and University of Pennsylvania, Philadelphia. Multiple causes are considered, involving host
and tumor factors. Morphological changes (aberrant neuronal migration, alterations in glial gap-
junction coupling), alkaline peritumoral pH, and ion level and amino acid changes (abnormal
glutaminergic transmission) in peritumoral brain tissue are probable factors in TRS pathophysiology.
Several alterations in enzymatic pathways (eg. lactate dehydrogenase, glutamine synthetase) are
observed in epileptic and neoplastic tissues. Cytokines, and tumor necrosis factor in particular, have
neuromodulatory effects, and are rapidly induced in glial cells following seizures.

One of the problems that can occur after a traumatic brain injury (TBI) is seizures. Most seizures happen in
the first several days or weeks after a brain injury. Some may occur months or years after the injury. About
70-80% of people who have seizures are helped by medications, and can return to usual activities. Seizures
can happen in 1 to 5 of every ten people who have had a TBI, depending on where the injury occurred in
the brain. The seizure usually happens where there is a scar in the brain as a consequence of the injury.

During a seizure there is a sudden abnormal electrical disturbance in the brain that results in one or more of
the following symptoms:

 Strange movement of your head, body, arms, legs, or eyes, such as stiffening or shaking

 Unresponsiveness and staring

 Chewing, lip smacking, or fumbling movements

 Strange smell, sound, feeling, taste, or visual images

 Sudden tiredness or dizziness

 Not being able to speak or understand others

A seizure in the first week after a brain injury is called an early post-traumatic seizure. About 25% of people
who have an early post-traumatic seizure will have another seizure months or years later. A seizure more
than seven days after a brain injury is called a late post-traumatic seizure. About 80% of people who have
a late post-traumatic seizure will have another seizure (epilepsy).

Having more than one seizure is called epilepsy. In some people this will be a problem they have for their
whole lives.

The cause of your brain injury can help doctors figure out how likely you are to have seizures.

 65% of people with brain injuries caused by bullet wounds have seizures

 Bleeding between the brain and the skull, which is called a subdural hematoma, also may cause a
seizure.

 Over 60% of people who need 2 or more brain surgeries after a brain injury experience seizures.

In a patient who had a seizure after a recent head injury, investigation of a seizure should focus on
determining whether an intracranial bleed or a change in clinical condition (eg, hyponatremia) has caused
the seizure. Early PTS should be treated promptly, but treatment for late PTS is not mandatory.

Seizures after stroke are classified as early or late onset, according to their timing after brain ischemia, in a
paradigm comparable to post-traumatic epilepsy. An arbitrary cut point of 2 weeks after the presenting
stroke has been recognized to distinguish between early- and late-onset poststroke seizures. Different
characteristics and mechanisms of poststroke seizures, according to their proximity to the onset of brain
ischemia, have been proposed, but no clear pathophysiological basis exists for the 2-week cut point.

Most early-onset seizures occur during the first 1 to 2 days after ischemia. Almost half (43%) of all patients
in the Stroke After Seizures Study experienced a seizure within the first 24 hours after stroke. In a series
restricted to early-onset seizures, 90% of the 30 patients had ictal activity within the first 24 hours. Most
seizures associated with hemorrhagic stroke also occur at onset or within the first 24 hours.

During acute ischemic injury, accumulation of intracellular calcium and sodium may result in
depolarization of the transmembrane potential and other calcium-mediated effects. These local ionic shifts
may lower the seizure threshold. Glutamate excitotoxicity is a well-established mechanism of cell death in
the experimental stroke model. Antiglutamatergic drugs may also have a neuroprotective role in ischemic
settings, aside from the role of treating seizures.

The size of regional metabolic dysfunction may also be relevant in causing early-onset seizures. In the
setting of large regions of ischemic hypoxia, high levels of excitotoxic neurotransmitters may be released
extracellularly. In studies of the postischemic brain in experimental animal models, neuronal populations
in the neocortex and hippocampus have altered membrane properties and increased excitability, which
presumably lower the threshold for seizure initiation. The ischemic penumbra, a region of viable tissue
adjacent to the infarcted core in ischemic stroke, contains electrically irritable tissue that may be a focus for
seizure activity.

In addition to focal ischemia, global hypoperfusion can cause seizure activity. Hypoxic-ischemic
encephalopathy is one of the most common causes of status epilepticus and carries a poor prognosis.
Particularly vulnerable to ischemic insult is the hippocampus, which is an especially epileptogenic area. In
late-onset seizures, by contrast, persistent changes in neuronal excitability occur. Replacement of healthy
cell parenchyma by neuroglia and immune cells may play a role in maintaining these changes. A gliotic
scarring has been implicated as the nidus for late-onset seizures, just as the meningocerebral cicatrix may
be responsible for late-onset post-traumatic epilepsy.

Cortical location is among the most reliable risk factors for poststroke seizures. Poststroke seizures were
more likely to develop in patients with larger lesions involving multiple lobes of the brain than in those with
single lobar involvement. However, any stroke, including those with only subcortical involvement, may
occasionally be associated with seizures. Earlier studies, relying on less sensitive neuroimaging techniques,
may not have detected concomitant small cortical lesions that could cause ictal activity. The mechanism by
which deep hemispheric subcortical lesions, most commonly due to small-vessel disease, cause seizures is
not understood.

In retrospective studies, risk factors for seizures after subarachnoid hemorrhage included middle cerebral
artery aneurysms, intraparenchymal hematoma, cerebral infarction, a history of hypertension, and thickness
of the cisternal clot. By contrast, clinical predictors for seizures after intraparenchymal hemorrhage have
been lacking. Vascular lesions may cause seizures by other mechanisms. Seizures due to arteriovenous
malformations and aneurysms typically occur when these lesions rupture, but these vascular lesions may
cause seizures by directly irritating adjacent brain parenchyma.
Finally, seizures associated with vascular lesions occur in the setting of significant reperfusion after
revascularization procedures, most commonly carotid endarterectomy for chronic severe extracranial
carotid stenosis. The reperfusion syndrome, first described by Sundt and colleagues, includes transient focal
seizure activity, atypical migrainous phenomena, and intracerebral hemorrhage, although the clinical triad
is often incomplete. Onset of this rare syndrome ranges from several days to 3 weeks after revascularization
and often is signaled by a new ipsilateral headache. Surgical correction of an arteriovenous malformation
may also cause intraoperative or postoperative hyperemia, with subsequent seizures or hemorrhage. By
contrast, arteriovenous malformations located in border-zone regions subject to relatively low flow rates
have a lower risk for hemorrhage.

The reperfusion syndrome has been attributed to impaired cerebral autoregulation. In the setting of chronic
hypoperfusion due to high-grade carotid stenosis, the arterioles responsible for normal autoregulation in the
downstream cerebral hemisphere become chronically dilated. Subsequently, when perfusion is improved
by a revascularization procedure, the vessels are incapable of vasoconstriction, and the brain parenchyma
is subjected to a massive augmentation of blood flow. The release of vasoactive neuropeptides from
perivascular sensory nerves may contribute to the development of the reperfusion syndrome, to oxidants
that develop before revascularization, and to an inflammatory response to the reestablishment of circulation.

7. Etiology of Psychogenic Seizure

Malingering

Malingering is pretending to be sick when you aren’t or pretending to be sicker than you are,
particularly when you have something to gain. Malingering is falsification or profound
exaggeration of illness (physical or mental) to gain external benefits such as avoiding work or
responsibility, seeking drugs, avoiding trial (law), seeking attention, avoiding military services,
leave from school, paid leave from a job, among others. It is not a psychiatric illness according to
DSM-5 (Diagnostic and Statistical Manual of Mental Diseases, Fifth edition). External
(secondary) gain is necessary for differentiating malingering from factitious disorder (a disorder
in which patient consciously creates physical or psychological symptoms to assume sick role,
the primary gain)

Etiology
Malingering has no specific etiology, but the causes include socio-economic conditions. It is
commonly reported among prisoners avoiding trial, students avoiding school, workers avoiding
work, homeless hoping for economic compensation/rations. Drug abusers commonly fake
sickness, painful conditions, or insomnia to receive drugs of abuse including opioids such as
nalbuphine, benzodiazepines, among others. Malingering is reported in people trying to avoid
military service. It has a close association with an antisocial personality disorder and histrionic
personality trait.

Pathophysiology

Malingering is associated with an anti-social personality disorder and histrionic personality trait.
To get an external (secondary) gain, the individual fakes an illness that can be of physical or
psychological nature. The patient consciously lies about his or her condition to get a benefit, and
upon achieving the benefit, they stop complaining. No medicine or intervention can cure
malingerers. Upon detailed history, the malingerer may exhaust their excuses and give up.

DSM-5 states that if any combination of the following 4 complains is present in a patient, then
malingering should be considered.

1. The medicolegal context of the presentation, for example, a lawyer sending his client for
evaluation or patient presents with an illness while facing trial

2. Marked discrepancy between the individual's "claimed stress or disability" and "objective
finding and observation"

3. Lack of compliance with diagnostic evaluation, treatment regimen and follow up care

4. Presence of anti-social personality disorder

History and physical

A careful and detailed history taking is necessary to rule out malingering.

1. Watch carefully for discrepancies in person's behavior while taking prolonged, detailed
history.

2. Dig deep into patient's personality (anti-social personality disorder, histrionic personality
traits).
 3. Find out about the legal status of the patient.

4. Ask rapid questions and see the incoherence between answers.

5. Ask an open-ended and leading questions. (Questioning about symptoms not related to the
"illness faked by the patient" may also induce a positive answer. The patient not knowing
much about the assumed disease may say yes to any question).

6. Watch for exaggeration of psychiatric symptoms like hallucinations and delusions.

Mental Status Exam

 Appearance and behavior: May appear disheveled, uncombed hair, untidy clothing, no eye
contact, no rapport building. Irritated hostile behavior

 Mood: Answers low or elated and never normal euthymic. Cannot mimic lack of effect,
anhedonia

 Thoughts: Exaggerated delusions, but cannot mimic formal thought disorders like
schizophrenia; confused at times with true psychiatric thought disorders as patient with
psychosis or schizophrenia can have bizarre delusions and unshakable beliefs

 Perception: Exaggerated hallucinations, both visual and auditory

 Insight: Have good insight about the disease. Almost always acknowledge suffering from
the disease they fake

 Cognition: Cannot be assessed properly at times, because the patient may be noncompliant
and may lie

Multiple examinations should be performed, and incoherences between the results should be noted.
Various tasks are given to patients and performance on different occasions are noted. The
inconsistent score in the same task performed multiple times suggest malingering.

Other areas to be investigated include:

 History of hospitalization, medication

 Current history of medication

  Family history

 Social history

Evaluation

The diagnosis of malingering is based on history, physical exam, and psychological tests. No
diagnostic laboratory tests are available to diagnose malingering. Laboratory studies are, however,
useful to exclude organic cause and genuineness of illness. These laboratory studies might include
the following:

1. Complete blood cell (CBC) count

2. Serum electrolytes.

3. Renal function tests

4. Liver function tests (LFTs)

5. Blood alcohol level

6. Blood and urine toxicology screen (may also rule in malingering in case of drug abusers
seeking opioids)

7. Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain
should be considered to rule out organic brain disorders

Other tests:

 The Minnesota Multiphasic Personality Inventory (MMPI)

 The F-scale

 Test of memory malingering

 The negative impression management scale

 Rey 15-item test

 The temporal memory sequence test

 Symptom and Disposition Interview (SDI)

Treatment

Do not confront the patient directly. Do not question the beliefs of the patient. Do not accuse the
patient of feigning his or her illness. Patient-doctor conflict, a lawsuit against the doctor, and
violence may result. Rather confront the patient indirectly. Offer a scientific explanation but do
not deny the beliefs of the patient. Invasive diagnostics and interventions ought to be avoided as
their harm outweigh benefits. The physician can help by encouraging:

 Behavioral therapy

 Psychotherapy

 Counseling
Somatization Disorder

Somatization disorder is a psychiatric condition marked by multiple medically unexplained

physical, or somatic, symptoms. In order to qualify for the diagnosis of somatization disorder,
somatic complaints must be serious enough to interfere significantly with a person's ability to
perform important activities, such as work, school or family and social responsibilities, or lead the
person experiencing the symptoms to seek medical treatment. Somatization disorder has long been
recognized by psychiatrists and psychologists, and was originally called Briquet's syndrome

Individuals with somatization disorder suffer from a number of vague physical symptoms,
involving at least four different physical functions or parts of the body. The physical symptoms
that characterize somatization disorder cannot be attributed to medical conditions or to the use of
drugs, and individuals with somatization disorder often undergo numerous medical tests (with
negative results) before the psychological cause of their distress is identified. They often use
impressionistic and colorful language to describe their symptoms, describing burning sensations,
pains that move from place to place, strange tastes on the tongue, tingling, or tremors. While many
symptoms resemble those associated with genuine diseases, some of the symptoms reported by
people with somatization disorder are not. The individual usually visits many different physicians,
but the information they provide about the patient's symptoms can be inconsistent. It is important
to note that while the physical symptoms of somatization disorder frequently lack medical
explanations, they are not intentionally fabricated. Somatization disorder can be dangerous, since
patients may end up taking several different medications, thereby risking harmful drug
interactions.

Causes

1. Defense against psychological Distress

One of the oldest theories about the cause of somatization disorder suggests that it is a way of
avoiding psychological distress. Rather than experiencing depression or anxiety, some individuals
will develop physical symptoms. Somatization disorder is a defense against psychological pain
that allows some people to avoid the stigma of a psychiatric diagnosis. While getting the care and
nurturing they need from doctors and others who are responsive to their apparent medical illnesses,
many patients are encouraged to continue their manipulative behavior.
 2. Heightened sensitivity to physical sensations

An alternative theory suggests that somatization disorder arises from a heightened sensitivity to
internal sensations. People with somatization disorder may be keenly aware of the minor pains and
discomforts that most people simply ignore. A similar theory has been offered to account for panic
disorder . Studies have shown that people with panic disorder are particularly sensitive to internal
sensations like breathing rate and heartbeats, which may lead them to react with intense fear to
minor internal changes. The physiological or psychological origins of this hypersensitivity to
internal sensations and their relevance to somatization disorder are still not well understood.

3. Catastrophic thinking about physical sensation

According to these thoughts, somatization disorder results from negative beliefs and exaggerated
fears about the significance of physical sensations. Individuals with somatization disorder are thus
more likely to believe that vague physical symptoms are indicators of serious disease and to seek
treatment for them. For instance, someone with somatization disorder may fear that a headache
signals a brain tumor, or that shortness of breath indicates the onset of asthma. When their doctors
can find no medical explanation for the symptoms, the patients may fear that they have a rare
disease; they frantically look for specialists who can provide a diagnosis. Anxiety causes them to
focus even more intensely on their symptoms, which in turn become more disabling. Many people
with somatization disorder reduce or eliminate many activities out of fear that exertion will worsen
their symptoms. With fewer activities to distract them from their symptoms, they spend more time
worrying about physical problems, resulting in greater distress and disability.

Symptoms

Gastrointestinal (GI) complaints, such as nausea, bloating, diarrhea, and sensitivities to certain
foods are common, and at least two different GI symptoms are required for the diagnosis. Sexual
or reproductive symptoms, including pain during intercourse, menstrual problems, and erectile
dysfunction are also necessary features for a diagnosis for somatization disorder. Other frequent
symptoms are headaches, pain in the back or joints, difficulty swallowing or speaking, and urinary
retention. To qualify for the diagnosis, at least one symptom must resemble a neurological
disorder, such as seizures , problems with coordination or balance, or paralysis.

Diagnosis

To receive a diagnosis of somatization disorder, the individual must have a history of multiple
physical complaints that began before age 30 and that continued for several years ( DSM-IV-TR ).
These symptoms must cause significant impairment to social, occupational or other areas of
functioning—or lead the patient to seek medical treatment.

Each of the following four criteria must be met.

 The individual must report a history of pain affecting at least four different parts or
functions of the body. Examples include headaches, back, joint, chest or abdominal pain,
or pain during menstruation or sexual intercourse.
 A history of at least two gastrointestinal symptoms, such as nausea, bloating, vomiting,
diarrhea, or food intolerance must be reported.
 There must be a history of at least one sexual or reproductive symptom, such as lack of
interest in sex, problems achieving erection or ejaculation, irregular menstrual periods,
excessive menstrual bleeding, or vomiting throughout pregnancy.
 One symptom must mimic a neurological condition. Examples include weakness,
paralysis, problems with balance or coordination, seizures, hallucinations , loss of
sensations such as touch, seeing, hearing, tasting, smelling—or difficulty swallowing or
speaking, or amnesia and loss of consciousness. Pseudo-neurologic symptoms like these
are the primary characteristics of another somatoform disorder known as "conversion
disorder."

If a thorough medical evaluation reveals no evidence of an underlying medical- or drug- or

medication-induced condition, the diagnosis of somatization disorder is likely. People with
genuine medical conditions can qualify for the diagnosis if the level of functional impairment
reported is more than would be expected based on medical findings. The symptoms must not be
intentionally produced. If the patient is feigning symptoms, a diagnosis of factitious
disorder or malingering would most likely be considered.
Treatment

1. Cognitive behavior therapy

Cognitive-behavioral therapy (CBT) for somatization disorder focuses on changing negative

patterns of thoughts, feelings, and behavior that contribute to somatic symptoms. The cognitive
component of the treatment focuses on helping patients identify dysfunctional thinking about
physical sensations. With practice, patients learn to recognize catastrophic thinking and develop
more rational explanations for their feelings. The behavioral component aims to increase activity.
Patients with somatization disorder have usually reduced their activity levels as a result of
discomfort or out of fear that activity will worsen symptoms. CBT patients are instructed to
increase activity gradually while avoiding overexertion that could reinforce fears. Other important
types of treatment include relaxation training, sleep hygiene, and communication skills training.
Preliminary findings suggest that CBT may help reduce distress and discomfort associated with
somatic symptoms; however, it has not yet been systematically compared with other forms of
therapy.

2. Medications

Antidepressant medications may help to alleviate symptoms of somatization disorder.

According to one study, patients with somatization disorder who took the
antidepressant nefazodone (Serzone) showed reductions in physical symptoms, increased activity
levels, and lower levels of anxiety and depression at the end of treatment.

Conversion Disorder

Conversion disorder is a psychiatric condition in which a person develops physical symptoms that
are not under voluntary control and are not explained by a neurological disease or another medical
condition. Conversion disorder is also called functional neurological symptom disorder, referring
to abnormal central nervous system functioning. Conversion disorder is a mental condition in
which a person has blindness, paralysis, or other nervous system (neurologic) symptoms that
cannot be explained by medical evaluation.

Causes

The onset of symptoms is usually sudden and can be associated with stress or a traumatic event.
Stressful life events are often present in people who develop conversion symptoms, but this is not
always the case. Conversion disorder can develop at any time throughout the lifespan. The onset
of non-epileptic seizures is most common in the third decade of life, and motor symptoms have
their peak onset in the fourth decade of life.

People who have conversion disorder are not making up their symptoms (malingering). Some
health care providers falsely believe that this disorder is not a real condition and may tell people
that the problem is all in their head. But this condition is real. It causes distress and cannot be
turned on and off at will. The physical symptoms are thought to be an attempt to resolve the conflict
the person feels inside. For example, a woman who believes it is not acceptable to have violent
feelings may suddenly feel numbness in her arms after becoming so angry that she wanted to hit
someone. Instead of allowing herself to have violent thoughts about hitting someone, she
experiences the physical symptom of numbness in her arms.

Symptoms

Conversion disorder can have many different presentations and symptoms. Motor symptoms
include weakness or paralysis, abnormal movements such as tremor, and difficulty walking.
Sometimes people experience sensory symptoms, such as altered, reduced, or absent skin
sensation, vision, or hearing. Conversion disorder can also take the form of “psychogenic” or “non-
epileptic” seizures, which include limb shaking and impaired of loss of consciousness but without
the electrical activity that occurs in the brain during a seizure. Other common symptoms include
episodes of unresponsiveness that resemble fainting or coma, reduced or absent speech volume,
changes in articulation when speaking (slurred speech), a sensation of a lump in the throat, and
double vision.
People with conversion disorder are not faking their symptoms, and despite not having a clear
physiological origin, the symptoms cause real distress and cannot be controlled at will. The
severity of the disability caused by conversion disorder can be similar to that experienced by
people with comparable medical diseases.

Diagnosis

The diagnosis of conversion disorder is based on a healthcare provider observing symptoms

consistent with the disorder. Other causes of similar symptoms should be ruled out to avoid a
misdiagnosis. It is best for a neurologist and a psychiatrist to work together on making the
diagnosis of the disorder. Current diagnostic criteria for conversion disorder include :

 One or more symptoms of neurological dysfunction

 No physical findings that may explain the symptoms

 No other disease is known that better explains the symptoms

 The symptom causes significant distress or impairment so that medical evaluation is desired
In some cases, people who are diagnosed with conversion disorder are later found to have another
neurological disease. In these cases, treatment and management should be based off of
recommendations established for that disease

Treatment

For some people, the symptoms of conversion disorder may improve with time, even without
treatment. This can occur after they receive a diagnosis of the disorder, reassurance that the
symptoms aren’t caused by an underlying problem, and validation that the symptoms are real.

Individuals with severe symptoms, symptoms that linger or keep coming back, or other mental or
physical health problems may require treatment. The specific type of treatment depends on the
particular signs and symptoms of the disorder and may include :

 Counseling (psychotherapy)
 Hypnosis

 Physical therapy

 Occupational therapy

 Treatment of related physical or psychological stressors

The focus of psychotherapy is to help the individual understand the emotional conflict behind their
physical symptoms, and to resolve this underlying psychological distress. Psychotherapy treatment
can include individual or group therapy, hypnosis, biofeedback, and relaxation training.

Physical therapy attempts to maximize physical functioning and prevent any secondary
complications that may result from physical symptoms, such as muscle weakness or stiffness that
follows periods of physical inactivity. Conversion disorder may also be treated through the use of
psychotropic medications that address underlying psychiatric problems, such as depression and
anxiety.

A positive prognosis can be expected when conversion symptoms have a sudden onset, are present
for a short amount of time, the individual is accepting of their diagnosis, and there are no additional
psychiatric disorders present.

8. Seizures caused by metabolic disorders

1. Hypoglicemia

During hypoglycemia, multiple metabolic derangements occur. Hypoglycemia

depletes acetate therefore within the neuronal cells oxaloacetate and a-ketoglutarate build
up.Oxaloacetate then forms Aspartate while a-ketoglutarate forms Glutamate. Glutamate
activates the NMDA receptor which allows Na and Ca influx. ATP depletion due to
hypoglycemia causes Na/K pump dysfunction allowing more Na into the cell down its
concentration gradient. This leads to cerebral cytotoxic edema while Ca influx causes
further intracellular dysfunction. Build up of Glutamate (excitatory neurotransmitter) along
with Ca-induced intracellular dysfunction leads to neurological complications including
confusion, coma, and seizure. Investigators showed that fasting and insulin infusion in rats
increased the incidence of barrel rotations, which is a characteristic phenotype of
hypoglycemic seizures in the animal. In particular, they showed a decreased release of
gamma amino-butyric acid (GABA) in the substantia nigra pars reticulate in rats with
seizures.

2. Hyperglicemia

Seizures induced by hyperglycemia was often encountered in clinical practice and

was characterized by hyperglycemia, no keto-acidosis, seizures resistant to anticonvulsant
treatment and seizure control associated with resolution of the hyperglycemia. Seizures
related to NKH are usually partial seizures. The accurate pathogenesis of seizures and
movement disorders related to NKHG remains still unclear. Currently, multiple factors,
such as vascular lesions, local brain damage, and metabolic factors may contribute to this
condition. The possible mechanisms are hyperglycemia or hyperosmolarity, a low level of
GABA, and focal ischemia. There a jurnal suggested that the Krebs cycle in NKH is
inhibited, GABA metabolism is increased, and the levels decreased, thus lowering the
threshold for seizure activity. Another hypothesis involved the decrease of seizure
threshold due to metabolic disturbance. Hyperosmolality and dehydration induced by
hyperglycemia or hypo-sodium accompanying hyperglycemia were suggested to trigger
focal seizures and lead to neurological deficit in some patients. Other authors suggested
that a previously existing cortical lesion of an ischemic nature might lead to these seizures
under altered metabolic conditions because hyperglycemia could result in reversible focal
ischemia without structural damage by decreasing local blood flow in certain cerebral
areas.

3. Hypocalcaemia

Hypocalcemia-induced seizures, in particular, have attracted much clinical

attention. These seizures likely occur in patients with predisposing endocrinological
abnormalities or renal insufficiency with overall poor calcium homeostasis. For example,
a seizure could be the first manifestation of chromosome22q syndrome due to low blood
calcium as a result of congenital hypoparathyroidism. Another example of hypocalcemic
seizures, and perhaps the most commonly seen, are drug-induced hypocalcemic seizures.
Biphosphonate may also induce hypocalcemic seizures due to a disturbance of calcium and
phosphate metabolism. Finally, the anticonvulsant phenytoin may paradoxically
exacerbate seizures when blood calcium is low. Therefore, clinicians are advised to check
calcium in cases of Anti-epileptic drug (AED) refractory seizures.

Although hypocalcemic seizures are widely documented in medical literature, the

underlying mechanism seems counterintuitive. From the presynaptic release of
neurotransmitters, to the electrical mechanical coupling in the myocyte, almost every step
in the neuromuscular function is predicated on calcium. However, clinical observations
clearly demonstrate an inverse relationship between excitability and blood calcium:
Hypocalcemia enhances neuronal excitability whereas hypercalcemia decreases
excitability. This paradox has not been adequately studied and explained.

4. Hypercalcemia
Seizure caused by hypercalcemia is rare, and the exact pathophysiology of
neuropsychiatric manifestations is still unknown. The role calcium plays in the
pathogenesis of epileptic discharges might be cerebral vasospasm resulting in cerebral
infarction, with subsequent focal or generalized seizures with encephalopathy, or
hypertensive encephalopathy resulting from the elevated vascular resistance caused by the
infusion of calcium or membrane instability. There is a literature stated that seizures
induced by hypercalcemia are related to reversible cerebral vasoconstriction.

5. Thiamine deficiency
Thiamine deficiency could be related to epileptogenesis by means of one of several
possible pathophysiological mechanisms; the exact way in which thiamine deficiency may
result in seizure activity is unknown, however, and remains hypothetical. Thiamine is an
important cofactor of three enzymes involved in carbohydrate metabolism. As a cofactor
of transketolase, vitamin B is of importance for the production of ribose through the
pentose phosphate shunt, and, therefore, indirectly for RNA production and protein
synthesis. In addition, thiamine is essential for the activity of the pyruvate-dehydrogenase
complex and of a-ketoglutarate dehydrogenase. Thus the oxidative decarboxylation
through the Krebs cycle and the production of adenosine 5'-triphosphate from that source
suffer severely in case of thiamine deficiency. Quite a different function of thiamine is its
hypothesized role in the electrogenesis and conductive activity along the neurolemma.
There a journal found that thiamine derivatives are copurified with specific proteins linked
to tetrodotoxin-sensitive receptors of sodium channels. Another indication that thiamine is
related to nerve cell membrane conduction is the fact that nerve fibers stimulated in vitro
may loose a considerable amount of thiamine pyrophosphate in the surrounding fluid.
These data point to a possible role of thiamine in the molecular aspects of bioelectrogenesis
and to a possible relationship between thiamine eficiency and changes in nerve cell
membrane stability. At the neurotransmitter level thiaimine deficiency may be
accompanied by a lowering of the concentration of y-ami-nobutyric acid (GABA) and 5-
hydroxytryptamine. GABA is synthesized from the Krebs cycle through the so-called
GABA shunt. Thiamine is indirectly involved in this reaction. There is a journal that
described the selective impairment of serotonin uptake by cerebellar and hypothalamic
synaptosomes in thiamine-deficient rats and the prompt reversal of serotonin uptake after
administration of high doses of thiamine.

6. Cobalamin deficiency
Neurological involvement often occurs along with macrocytic anemia but can occur
in the absence of anemia or macrocytosis. It is unclear why vitamin B12 deficiency leads
to neurological disease in some and hematological disease in others.
Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been postulated to
protect the vitamin B12-deficient patients against anemia and homozygosity for MTHFR
C677T gene could cause the dissociation between hematological and neurological disease
seen in some patients with vitamin B12 deficiency. Methylcobalamin is required in the
central nervous system for myelin synthesis.
Hence, a lack of cobalamin leads to either the destruction of myelin sheaths or
incorporation of abnormal fatty acids in myelin sheaths, thus leading to impaired neural
function and/or transmission. This may be the under lying cause of neurological symptoms
seen in vitamin B 12 deficiency. The exact mechanism involved in epileptogenesis due to
cobalamin deficiency is not clear. It is likely that cerebral neurons with destroyed myelin
 sheaths are more susceptible to the excitatory effects of glutamate. Cobalamin deficiency
may share similarities with multiple sclerosis in this regard.

9. Infections and Seizure

About 5% of patients with an infection of the central nervous system will
experience a seizure. A seizure may be the presenting symptom, or only one manifestation,
of the infection. Common infections of the central nervous system that may present with
seizures include: herpes simplex, cytomegalovirus, arbovirus, human immunodeficiency
virus, neurocysticercosis, malaria, toxoplasmosis, bacterial meningitis and brain abscess.
The seizures may be due to direct invasion of brain tissue by the infecting organism,
production of toxins by the organism or production of inflammatory mediators by the brain.
Infectious processes in the brain can lead to breakdown of the blood–brain barrier and brain
edema. Severe systemic infections can also be associated with seizures, even if the
infection is not present in the central nervous system. In this instance the seizures are most
likely due to hypoxia or other severe metabolic changes, such as hyponatremia, that are the
result of the overwhelming infection. In all cases, treatment for the seizures associated with
infection usually involves treatment of the underlying infection.
Bacterial infections in the central nervous system are less likely to cause seizures
than viral infections. However, generalized convulsions may occur with bacterial
meningitis. Compared to other bacteria, infections with Haemophilus influenzae are more
commonly associated with seizures. The mechanism of the seizures is not known. As with
other infectious processes, it has been postulated that the seizures are either a result of the
primary infection or due to the inflammatory response to the bacterial infection. To date
there is not much data for either possibility.
Encephalitis due to a viral infection of the brain can be associated with both focal
and generalized seizures. Viral encephalitis is characterized by neuronal and glial
degeneration, inflammatory infiltrate, edema, and tissue necrosis. Herpes simplex virus is
the most common pathogen associated with seizures in cases of viral encephalitis. But,
seizures occur in approximately 85% of children infected with Japanese encephalitis and
up to 10% of adults with West Nile virus. Equine encephalitis, St. Louis encephalitis,
cytomegalovirus and rabies have also been reported to cause seizures. Finally, it has been
estimated that 2–5% of HIV-infected patients have seizures due to the primary infection of
the brain by the virus.
The issues surrounding the relationship between herpes virus infections of the
central nervous system and seizures is a bit more complicated. Infection with herpes virus,
particularly herpesvirus 6B (HHV-6B) is quite common. Recently, it has been questioned
whether the association between acute infection with HHV-6B and seizures in infants less
that 1 month old is a causal relationship. It could be that the infection is causing the
seizures, but it is also possible that infants susceptible to the infection are those most likely
to have seizures. The evidence is not clear one way or the other. Herpesviruses can also
result in a latent or persistent infection. This persistent infection has been implicated in
febrile seizures and some forms of epilepsy – in the absence of symptomatic encephalitis.
HHV-6B has been found in resected tissue from a substantial proportion of patients
with temporal lobe epilepsy. The virus is found in astrocytes in this tissue. The current
hypothesis is that the presence of the virus is a result of an early infection and its continued
presence somehow lowers the seizure threshold or likelihood of developing epilepsy.
Herpes is easily reactivated, particularly by other viral infections. It is possible that
reactivation of the virus results in a series of consequences that result in a lowering of the
seizure threshold. One hypothesis is that reactivation of HHV-6 alters gene expression in
astrocytes, which in turn alters glutamate pathways. Thus the seizures could be due to an
action of the reactivated virus or a secondary action initiated by the presence of the virus
in the latent form. There is not enough data to state definitively one way or the other.
Other infections that involve the central nervous system have been reported to cause
seizures. Neurocysticercosis, infection of the central nervous system with the cyst form of
tapeworms, is the most common parasitic infection of the brain. In developing countries,
up to 50% of adult-onset epilepsy is due to neurocysticercosis. Malaria is estimated to
spread into the central nervous system in approximately one third of the cases and cerebral
malaria can present with seizures. The incidence of acute seizures in neurosyphilis is 14–
60%. Infectious diseases in which seizures have been reported, but are not typically the
presenting feature, include: rubeola, schistosomiasis, trichinosis, paragonimiasis,
echinococcosis, trypanosomiasis, typhus and amebiasis.
In summary, infections of the central nervous system are clearly associated with
seizures, either during the acute infection or as a delayed response. The mechanism
underlying these seizures are not understood and are most likely dependent on the
infectious agent and time course of the infection. In addition, inflammatory processes in
the brain have been implicated in a number of cases and could be the underlying cause of
seizures in some, if not all, infections.

Drug-induced Seizure
Seizures are a common toxic complication of numerous drugs and poisons, as well
as drug withdrawal syndromes. Studies have estimated that 6% of new‐onset seizures and
up to 9% of status epilepticus cases are due to drug toxicity. Several case series have
identified a variety of drugs and other substances associated with seizures. Antidepressants,
diphenhydramine, stimulants (including cocaine and methamphetamine), tramadol and
isoniazid account for the majority of cases. However, substances implicated in drug‐
induced seizures have evolved over time as new drugs enter the market. For example, a
California case series analyzing calls to the regional poison control centre found that over
a 10 year interval, newer antidepressants replaced tricyclics as the most common cause of
seizures and the frequency of cocaine and theophylline cases fell dramatically (with reports
of theophylline decreasing to zero). Causes of drug‐induced seizures also vary by
geographic region. In two recent US studies bupropion was the leading drug whereas a
Swiss study found mefenamic acid and citalopram were the most commonly reported
seizure‐causing drugs. In Iran and Austrialia tramadol overdose is a common cause of
seizures. In developing countries and agricultural regions herbicides and insecticides are
an important consideration.
Most drug‐induced seizures are self‐limited and do not cause permanent sequelae.
However, repeated or prolonged seizure activity may lead to irreversible neurological
injury as well as other life‐threatening complications such as hypoxia, hypotension,
pulmonary aspiration, hyperthermia, rhabdomyolysis and metabolic acidosis. In
retrospective studies of drug‐induced seizures reported to a regional poison control centre,
status epilepticus (defined as continuous seizure activity lasting more than 30 min or two
or more seizures without full recovery of consciousness between seizures) occurred in 3.6
% to 10% of cases. Thus, prompt treatment including good supportive care and
administration of effective anticonvulsant drugs are imperative.
Exposure to certain drugs and chemical substances can result in the abrupt onset of
altered mental status with or without localized or generalized motor activity (convulsions)
combined with epileptic‐like brain activity (seizures) seen on the electroencephalogram
(EEG). This altered EEG electrical activity is the result of abnormal neuronal discharges
that start in cortical or subcortical brain regions and may persist for an extended amount of
time. This is not epilepsy, which is a disease state associated with recurrent spontaneous
paroxysmal epileptic brain activity on EEG with or without associated motor activity.
While the clinical condition of patients with epilepsy certainly can be made worse (with
more severe or frequent seizures) by exposure to many drugs or chemicals, this is usually
not considered a primary drug‐induced seizure.
Drug‐induced seizures can occur as a direct result of altering neural pathways and
specific excitatory or inhibitory transmitters and receptors within those pathways.

Figure 1 offers a simplified representation of these processes. In Figure 1A, the normal
balance is represented between excitatory and inhibitory neural pathways, transmitters and
receptors. Gamma aminobutyric acid (GABA) mediated receptors and pathways are
inhibitory, while those involving glutamate are excitatory. Decreasing excitatory pathway
activity, neurotransmitters or receptor function, or increasing inhibitory actions, leads to
reduced neural activity that can manifest itself as clinical sedation (Figure 1B). Reducing
inhibitory pathways, neurotransmitters or receptor function by drugs or chemicals, or
increasing excitatory activity, can result in over activation and seizures (Figure 1C).
If the effect of a drug is to reduce GABA activity (e.g. isoniazid or a cephalosporin),
seizures can result. Drugs such as barbiturates or benzodiazepines can increase the
functional effect of GABA-mediated inhibitory activity and as a result prevent or terminate
drug-induced or drug-withdrawal seizures. Using this model, the sudden withdrawal of
high doses of drugs applied chronically that have a strong inhibitory neuronal function (e.g.
ethanol or barbiturates) can result in acute withdrawal seizures. This may be exacerbated
by up-regulation of the excitatory N-methyl-D-aspartate (NMDA) subtype of the glutamate
receptor/pathway.
Neuronal pathways are much more complex than represented in Figure 1. Besides
GABA and glutamate, central nervous system (CNS) neurotransmitter systems known to
be involved in seizure generation in animal models of epilepsy include norepinephrine,
dopamine, serotonin, acetylcholine, histamine and adenosine. Presynaptic and postsynaptic
adenosine receptor stimulation generates an inhibitory effect on many excitatory pathways
such as those that are glutamate mediated. Presynaptic adenosine receptor stimulation may
reduce the release of the excitatory neurotransmitter glutamate and postsynaptic adenosine
receptor stimulation may directly inhibit excitatory pathways. Adenosine type one (A1)
receptor antagonists like theophylline and caffeine can reduce seizure thresholds and
prolong seizures by interfering with mechanisms of seizure termination.
Because CNS neuronal interactions are complex, with both direct and indirect drug
and chemical effects, and variable pro- or anticonvulsant effects depending on
concentration, no single mechanism exists for explaining all cases of drug-induced
seizures. For example, in animal models both acetylcholine receptor antagonists and
acetylcholinesterase inhibitors can cause seizures. In animal models of nerve agent
poisoning there is an early phase in which anticholinergic agents are effective in
terminating seizures, followed by a phase in which these drugs are less effective and
prolonged epileptiform activity appears to be mediated by stimulation of NMDA receptors
by excitatory amino acids.
 Many drugs and toxins can also cause seizures as a result of indirect effects on brain
perfusion, oxygenation or metabolic disturbances. Toxic exposures can reduce brain blood
flow by depressing cardiac contractility, vasomotor tone, heart rate or inducing cardiac
arrhythmias. Pneumonia due to pulmonary aspiration of gastric contents or direct chemical
injury to lung parenchyma can cause hypoxaemia. Other poisons, such as carbon monoxide
and cyanide, can interfere with oxygen delivery or cellular oxygen utilization, simulating
cellular hypoxia. Electrolyte and metabolic disturbances such as hyponatraemia,
hypomagnesaemia and hypoglycaemia can also be an indirect cause of drug induced
seizures.
Some poisons can induce convulsive activity that resembles seizures but does not
originate in the cerebral cortex. Glycine is the major inhibiotry neurotransmitter of motor
neurons in the spinal cord and brain stem and contributes to the suppression of reflex arcs.
Strychnine competitively inhibits the action of glycine on postsynaptic receptors.
Strychnine poisoning results in so‐called ‘spinal seizures’ (involuntary muscle contraction,
myoclonus, hyperreflexia and opisthotonus) without loss of consciousness until the victim
becomes hypoxic due to impaired ventilation. Inhibition of presynaptic glycine release by
tetanus toxin produces an identical syndrome.

C. A LOGIC AND CRITICAL ANALYSIS OF PROBLEMS

After doing anamnesis, physical exam and lab examination on Ms. SM, 20 years old female who
came to the hospital with her sister with the chief complain of seizure, we then continue the
anamnesis and conclude that the seizure was a tonic seizure (no clonic movement) and is
generalized (both left and right extremities shows seizures). Heteroanamnesis with the person
accompanying the patient says that the seizure starts around 1 hour ago and persist continuously
after the sister show up in her room. During the seizure patient does not bite her tongue, no signs
of incontinence, the eye was closed. Patient does not have history of seizure, no epilepsy history
in family and from the patient. We also found that there is a risk factor of psychologic
abnormalities due to stressor from environment (includes the fact that the patient has problem with
her partner and shows academic decline) After the anamnesis, our group made 3 main field of
differential diagnosis which correlates to seizure Ms. SM experience. The 3 field is abnormality
in neurologic system (brain-peripheral system), psychological aspect and other system. The other
system includes abnormalities in metabolic function, infection and drug cause.

On the first field, neurologic abnormalities we include epilepsy, brain infection, tumor, trauma
background and stroke cause (ischemic and hemorrhagic stroke). For this field, we need additional
information to exclude this system as the data from anamnesis has not confirm that there is no
abnormalities in the brain system (other than the fact that neurologic examination shows normal
result which was the reason we exclude abnormalities in peripheral nervous system).

On the next field psychological aspect, we include 3 differential diagnosis which is seizure due to
factitious, somatization, and conversion disorder. We decided that we need to exclude other
structural diagnosis first before focusing on the diagnosis of psychological abnormalities
background. The one factor supporting this field was the fact that there is environmental stressor
and the patient show signs of psychogenic seizures.

The last field, the other aspect includes seizure due to abnormalities in metabolic function such as
hypoglycemic condition and hypothyroid, of both we need further blood examination to exclude.
The next thing we consider possible was infection, also need blood examination result to exclude.
The next differential diagnosis on this field is drug abuse or adverse effect, also need more data on
patient drug intakes and the last one is malingering, on which we need to dig more on patient
background data and motives, also we need to exclude all of the other diagnosis first.

D. OBSTACLES
The obstacles that we face throughout this tutorial is to unite each of our ideas or our assumption about this
case. Moreover, we really have no idea what the patient suffer on the first meeting, because there were so
little information that we’ve got, but after we received an additional information such as laboratory result,
we became more clear about this case.

E. LEARNING ISSUES II
1. Pathophysiology of Psychogenic Seizures

2. Risk Factor and Pre-disposing Factor of Psychogenic Factor

3. Management of Psychogenic Seizure

4. Information, Education and Communication and Psychosocial Aspect of Psychogenic Seizure

5. Differential Diagnosis of Psychogenic Seizure

6. Additional Examination to Eliminate Possibility of Stroke

7. Correlation of Stroke and Seizure

8. Correlation of Tumor and Seizure

9. Classification of Psychogenic Seizure

10. Criteria of Psychogenic Seizure

REFERENCES:

Alozai, U. and McPherson, P. (2018). Malingering. [online] Ncbi.nlm.nih.gov. Available at:

https://www.ncbi.nlm.nih.gov/books/NBK507837/ [Accessed 5 Dec. 2018].

Ben-Ari Y. 2002. Excitatory actions of GABA during development: The nature of the nurture. Nat
Rev Neurosci 3: 728–739.
Berkovic SF. 2015. Genetics of epilepsy in humans. Cold Spring Harb Perspect Med doi:
10.1101/cshperspect.a022400.
Chen, H. Y., Albertson, T. E., & Olson, K. R. (2015). Treatment of drug-induced seizures. British
journal of clinical pharmacology, 81(3), 412-9.
Chen, T., Huang, C., Chang, Y., Chen, Y., Chen, W. and Lai, S. (2004). Vasoconstriction as the
Etiology of Hypercalcemia-induced Seizures. Epilepsia, [online] 45(5), pp.551-554.
Available at: https://onlinelibrary.wiley.com/doi/full/10.1111/j.0013-9580.2004.57003.x
[Accessed 1 Dec. 2018].

Elsevier, 2016, Connections Between Infections and Seizures, retrieved December 1, 2018, from
http://scitechconnect.elsevier.com/connections-between-infections-seizures/
Englander J, Cifu DX, Diaz-Arrastia R. 2014. Seizures after Traumatic Brain Injury.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516165/. 1 Desember 2018 (11.01).
Han, P., Trinidad, B. and Shi, J. (2015). Hypocalcemia-Induced Seizure. ASN Neuro, [online]
7(2), p.175909141557805. Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374060/ [Accessed 1 Dec. 2018].

Holmes G, Ben-Ari Y. 1998. Seizures in the developing brain: Perhaps not so benign after all.
Neuron 21: 1231–1234.
K. Berger, F., Zieve, D. and Conaway, B. (2016). Conversion disorder: MedlinePlus Medical
Encyclopedia. [online] Medlineplus.gov. Available at:
https://medlineplus.gov/ency/article/000954.htm [Accessed 5 Dec. 2018].

Keyser, A. and De Bruijn, S. (1991). Epileptic Manifestations and Vitamin B1

Deficiency. European Neurology, 31(3), pp.121-125.

Ko, D.Y., 2017. Posttraumatic Epilepsy. https://emedicine.medscape.com/article/1184178-

overview. 1 Desember 2018 (11.05)
Kumar S. (2004). Recurrent seizures: An unusual manifestation of vitamin B12 deficiency. Neurol
India, [online] 52(1), pp.122-123. Available at:
http://www.neurologyindia.com/text.asp?2004/52/1/122/6721 [Accessed 1 Dec. 2018].

Liang, D., Bhatta, S., Gerzanich, V. and Simard, J. (2007). Cytotoxic edema: mechanisms of
pathological cell swelling. Neurosurg Focus, [online] 22(5), p.E2. Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740913/ [Accessed 1 Dec. 2018].

Luders HO, Burgess R, Noachtar S. Expanding the international classification of seizures to

provide localization information. Neurology 1993;43(9):1650–5.
Martini F H, Nath J L, Bartholomew E F (2012), Fundamentals of Anatomy and Physiology: The
Spinal Cord, Spinal Nerves, and Spinal Reflexes, Ninth Edition, San Francisco:
PEARSON.
Millichap, J.G., 2003. Pathophysiology of Seizures with Brain Tumors.
https://www.pediatricneurologybriefs.com/articles/10.15844/pedneurbriefs-17-10-3/. 1
Desember 2018 (10.50)
Minddisorders.com. (n.d.). Somatization disorder - causes, DSM, functioning, therapy, drug,
examples, person, people. [online] Available at: http://www.minddisorders.com/Py-
Z/Somatization-disorder.html [Accessed 5 Dec. 2018].

Mosewich RK, So EL. A clinical approach to the classification of seizures and epileptic
syndromes. Mayo Clin Proc 1996;71(4):405–14.
Netter F H, Craig J A, Pekins J, Hansen J T, Koeppen B M (2002), Atlas of Neuroanatomy and
Neurophysiology: Selections from the Netter Collection of Medical Illustrations, Teterboro
NJ: COMTan
Pitkanen A, Lukasiuk K, Dudek FE, Staley KJ. 2015. Epileptogenesis. Cold Spring Harb Perspect
Med doi: 10.1101/ cshperspect.a022822.
Psychology Today. (2018). Conversion Disorder | Psychology Today. [online] Available at:
https://www.psychologytoday.com/us/conditions/conversion-disorder [Accessed 5 Dec.
2018].

Rarediseases.info.nih.gov. (2017). Conversion disorder | Genetic and Rare Diseases Information

Center (GARD) – an NCATS Program. [online] Available at:
https://rarediseases.info.nih.gov/diseases/6191/conversion-disorder [Accessed 5 Dec. 2018].
Sherwood L (2010), Human Physiologi From Cells to System: The Central Nervous System, 7e.
Canada: BROOKS/COLE CENGAGE Learning.
Sherwood L (2010), Human Physiologi From Cells to System: The Peripheral Nervous System:
Afferent Division; Special Senses, 7e. Canada: BROOKS/COLE CENGAGE Learning.
Silverman, I.E., Restrepo, L., Mathews, G.C., 2002. Poststroke seizures.
https://jamanetwork.com/journals/jamaneurology/fullarticle/781335. 1 Desember 2018
(14.03)
Stafstrom CE. 2010. Pathophysiological mechanisms of seizures and epilepsy: A primer. In
Epilepsy: Mechanisms, models, and translational perspectives (ed. Rho JM, Sankar R,
Stafstrom CE), pp. 3–19. CRC, Boca Raton, FL.
Wang, X., Yu, H., Cai, Z., Wang, Z., Ma, B. and Zhang, Y. (2013). Nonketotic hyperglycemia-
related epileptic seizures. Epilepsy & Behavior Case Reports, [online] 1, pp.77-78.
Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150656/ [Accessed 1 Dec.
2018].

William P. Neil and Thomas M. Hemmen (2011). Neurologic Manifestations of Hypoglycemia,

Diabetes - Damages and Treatments, Prof. Everlon Rigobelo (Ed.), ISBN: 978-953-307-652-
2, InTech, Available at: https://www.intechopen.com/books/diabetes-damages-and-
treatments/neurologic-manifestations-ofhypoglycemia [Accessed 1 Dec. 2018].

Younes, S., Cherif, Y., Aissi, M., Alaya, W., Berriche, O., Boughammoura, A., Frih-Ayed, M.,
Zantour, B. and Sfar, M. (2014). Seizures and movement disorders induced by
hyperglycemia without ketosis in elderly. Iranian Journal of Neurology, [online] 13(3),
pp.172-176. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240936/
[Accessed 1 Dec. 2018].

https://www.mayoclinic.org/diseases-conditions/epilepsy/symptoms-causes/syc-20350093

https://www.cedars-sinai.edu/Patients/Health-Conditions/Non-Epileptic-Seizures.aspx

http://n.neurology.org/content/70/22_Part_2/2109

http://www.pathophys.org/meningitis/

http://www.soc.ucsb.edu/sexinfo/article/bacterial-meningitis

https://www.nhs.uk/conditions/encephalitis/

https://www.ncbi.nlm.nih.gov/pubmed/18754956

http://neurology-asia.org/articles/20043_004.pdf
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1676-26492009000200007

http://n.neurology.org/content/38/9/1407