CLINICAL PROFILE OF SEIZURES IN ADULTS PATIENTS ADMITTED IN A TERTIARY CARE
HOSPITAL IN KANCHIPURAM DISTRICT, TAMIL NADU
Dissertation Submitted to
THE TAMIL NADU DR.M.G.R. MEDICAL UNIVERSITY in partial fulfilment of the requirement for the award of
degree of
MD GENERAL MEDICINE BRANCH - I
REG. NO.: 201711804
KARPAGA VINAYAGA INSTITUTE OF MEDICAL SCIENCES & RESEARCH CENTER
MADHURANTHAGAM
THE TAMILNADU DR. M.G.R. MEDICAL UNIVERSITY,
CHENNAI, TAMILNADU MAY 2020
CERTIFICATE
Certified that this dissertation entitled is “CLINICAL PROFILE OF SEIZURES IN ADULTS PATIENTS ADMITTED IN A TERTIARY CARE HOSPITAL IN KANCHIPURAM DISTRICT, TAMIL NADU” is a bonafide work done by Dr. SHAIKH ASIF MOHD YUSUF, Post graduate student, Karpaga Vinayaga Institute of Medical Sciences, Madhuranthagam, during the academic year 2017 – 2020.
Dr.SUFALA SUNIL VISWAS RAO, M.D,
PRINCIPAL,
Karpaga Vinayaga Institute of Medical Sciences,
Madhuranthagam Tk,
Kanchipuram Dist– 603308, Tamil Nadu, India.
Prof. Dr.P.V.BHASKAR REDDY MD.,
Professor of General medicine
Karpaga Vinayaga Institute of Medical Sciences,
Madhuranthagam Tk,
Kanchipuram Dist– 603308, Tamil Nadu, India.
DECLARATION BY THE CANDIDATE
I, hereby declare that this dissertation entitled “CLINICAL PROFILE OF SEIZURE IN ADULTS ADMITTED IN A TERTIARY CARE HOSPITAL IN KANCHEEPURAM DISTRICT, TAMIL NADU” submitted by me for the degree of M.D is the record work carried out by me during the period from July 2017to July 2019 under the guidance of Dr. R. Kulothungan, Professor of the Department of General medicine, Karpaga Vinayaga Institute of Medical Sciences and has not formed the basis of any degree, diploma or fellowship titles in this or any other university or other similar institution of higher learning.
Place: Dr. SHAIKH ASIF MOHD YUSUF
Department of General medicine
Signature of guide
Prof. Dr. R.KULOTHUNGAN
Professor,Departmentof General medicine,
Karpaga Vinayaga Institute of Medical Sciences and Research Center Madhuranthagam
CERTIFICATE – II
His is to certify that this dissertation work titled “CLINICAL PROFILE OF SEIZURES IN ADULTS PATIENTS ADMITTED IN A TERTIARY CARE HOSPITAL IN KANCHIPURAM DISTRICT, TAMIL NADU” of the candidate DR. SHAIKH ASIF MOHD YUSUF with registration Number 201711804 for the award of M.D. in the branch of GENERAL MEDICINE. I personally verified the urkund.com website for plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 19 percentage of plagiarism in the dissertation.
Guide & Supervisor sign with Seal.
Prof. Dr. R. KULOTHUNGAN
Professor,Departmentof GENERAL MEDICINE,
Karpaga Vinayaga Institute of Medical Sciences and Research Center, Madhuranthagam
IEC CERTIFICATE
ACKNOWLEDGEMENT
I sincerely thank Dr. R. ANNAMALAI, Managing Director, KarpagaVinayaga Institute of Medical Sciences for his kindness in helping us with all available resources.
I wish to thank Dr. SUFALA SUNIL VISWAS RAO, Principal, Karpaga Vinayaga Institute of Medical Sciences for her support and guidance.
It is beyond words to express my sincere thanks and gratitude to my Professorand Unit Chief and my Guide,Dr. R. KULOTHUNGAN Professor, KIMS who consistently guided me in each and every step of my thesis work. His kind support and encouraging words are great pillars of mysuccess.
I wish to proudly thank my Associate professor Dr. SAKTHIVADIVEL for his valuable advice and support. I feel happy to thank for the encouragement, guidance and support rendered by her all through my works.
LIST OF ABBREVIATIONS
CNS Central nervous system E/I Excitation/inhibition
GABA Gamma-Aminobutyric Acid
NMDA N-methyl-D-aspartate
K+ Potassium
Na+ Sodium
Ca++ Calcium
ILAE’s International League Against Epilepsy GTCS Generalized tonic-clonic seizures
FS Focal seizures
SE Status epilepticus
GEFSþ Generalized epilepsy with febrile seizures plus BFNE Benign familial neonatal epilepsy
LGS Lennox–Gastaut syndrome
LKS Landau–Kleffner syndrome
WS West syndrome
DS Dravet syndrome
JME Juvenile myoclonic epilepsy
Hz Hertz
ADNFLE Autosomal dominant nocturnal frontal lobe epilepsy BFNC Benign familial neonatal convulsions
ADPEAF Autosomal dominant partial epilepsy with auditory features
PME Progressive myoclonus epilepsy
CT Computed tomography
MRI Magnetic resonance imaging
EEG Electroencephalogram
SPECT Single-photon emission-computed tomography
MEG Magnetoencephalography
CGH Comparative genomic hybridization
AIGE Adult onset idiopathic generalized epilepsy PSS Post stroke seizures
TIA Transient ischemic attacks
SAH Subarachnoid haemorrhage
MCA Middle cerebral artery
FFA Free fatty acid
AEDs Antiepileptic drugs
SSECTL Single small enhancing CT lesions
ICT Intracranial tension ATT Anti tuberculous therapy EITB Electroimmuno-transfer blot
CSF Cerebrospinal fluid
ELISA enzyme-linked immunosorbent assay GCSE Generalized convulsive status epilepticus ICU Intensive care unit
IEC Institutional ethics committee
Hb Haemoglobin
CONTENTS
SL.NO. TITLE PAGE NO.
1. INTRODUCTION 1
2. AIMS AND OBJECTIVES 3
3. REVIEW OF LITERATURE 4
4. MATERIALS AND METHODS 72
5. OBSERVATION AND ANALYSIS 77
6. DISCUSSION 93
7. LIMITATION OF STUDY 98
8. SUMMARY AND CONCLUSION 99
9. REFERENCES 100
9. ANNEXURES
ANNEXURE 1-PROFORMA 114
ANNEXURE 2A - CONSENT (ENGLISH) 121
ANNEXURE 2B - CONSENT (TAMIL) 122
MASTERCHART 123
INTRODUCTION
A seizure (latin word “to take possession of”) is a paroxysmal event due to abnormal, excessive, hypersynchronous discharge from an aggregate of centralnervous system neurons1.
About 50 million people suffer from seizure disorders worldwide2. Seizure disorders affect 0.3-0.5% population worldwide, about 1.5- 5.0%may have a seizure in their lifetime 1,3. The prevalence in India is estimated to be around 5.33%4. The prevalence is fairly uniform at different age group reaching about 6-8 case per thousand individuals by adolescentsexcept for an increase by 80 years where prevalence reaches 23 per thousand4.
Seizures beginning in the adult life needed special attention as regards to their etiology as these are likely to be due to an identifiable secondary causes. Some of the important causesaretrauma, alcohol withdrawal, drug abuse, central nervous system (CNS) infections, space- occupying lesions and in older adults cerebrovascular accidents, tumours, metabolic disorders, Alzheimer’s etc. are commonly observed.
In addition, the etio-clinical profile of seizures in adults necessitate decisions about the initiation and discontinuation of medical treatment that are different from those in younger patients1,5.
Etiological analysis of epilepsy is made with proper medical history, clinical examination, biochemical profile and neuroimaging studies, the epilepsy can be treated accordingly thus helps in reducing the morbidity and mortality associated with it.
Present study was undertaken to evaluate the clinical profile and etiological analysis of new onset epilepsy in adults of more than 18 years of age in tertiary care hospital.
AIMS AND OBJECTIVES:
1) To study about various causes of seizures in adults at tertiary care hospital.
2) To study biochemical & imaging abnormalities in seizures disorder.
Revised:
1) To study clinical profile and various causes of seizures in adults at tertiary care hospital.
2) Analysis of biochemical & imaging abnormalities in seizures patients.
REVIEW OF LITERATURE
Definition6:
A “seizure” (from the Latin sacire, "to take possession of") is defined as paroxysmal alteration of neurologic function which caused by the hypersynchronous and excessive discharge of neurons in the brain.
From the Greek word “epilambanein” the term “epilepsy” comes whichmeans “to seize” or “to take hold of”.
“Epileptic seizure” is used to distinguish a seizure caused by abnormal neuronal firing from a non-epileptic event. “Epilepsy” is the condition of recurrent, unprovoked seizures. A seizure triggered by insult (e.g., fever, hypoglycemia)doesnot full fill the definition of epilepsy because it is a short-lived secondary condition, not a chronic state. Therefore, a seizure is the event and epilepsy is the disorder.
History of seizure7:
The history of epilepsy is intermingled with the history of human existence; the first reports on epilepsy can be traced back to the Assyrian texts, almost 2,000 B.C7.
Approximately 500 years before Hippocrates, Atreya, the father of Indian Medicine, recognized that disturbance of mind is epilepsy, rather than an effect of supernatural phenomena. Hippocrates in his book “On Sacred Disease” described the first neurosurgery procedure referring that craniotomy should be performed at the opposite side of the brain of the seizures, in order to spare patients from “phlegma” that caused the disease8,9
The ideas of supernatural causation slowly died out only to be replaced by another set of bizarre misnomers. Obstetrician to Queen Victoria, Sir Charles Locock, Credited crowded teeth, menstruation and masturbation with causing seizures.
At the beginning of the 18th century, the view that epilepsy was an idiopathic disease deriving from brain and other inner organs prevailed. One should mention the important work in this field by William Culen (1710–1790) and Samuel A. Tissot whose work set the base of modern epileptology describing accurately various types of epilepsies.
In 1857, Sir Locock (1799–1875) discovered the anticonvulsant
In 1912, Hauptmann (1881–1948), a German physician, introduced phenobarbital in the therapy of epilepsy, one of the first antiepileptic drugs. The next drug introduced in the therapy of epilepsy was phenytoin in 1938. During the 1950s, new drugs came up such as carbamazepine in 1953 [117], primidone in 1954, ethosuximide in 1958 by Vossen [118], sodium valproate in 1963 by Meunier et al. The last decade newer antiepileptic drugs such as vigabatrin (1989), lamotrigine (1990), oxcarbazepine (1990), gabapentin (1993), felbamate (1993), topiramate (1995), tiagabine (1998), zonisamide (1989 in Japan and 2000 in the USA), levetiracetam (2000), stiripentol (2002), pregabalin (2004), rufinamide (2004), lacosamide (2008), eslicarbazepine (2009), and perampanel (2012) were used.
Genetics: The first connection between heredity and epilepsy was made in 1903 by Lundborg (1868–1943), a Swedish physician. The most important evolution, however, in the field of the genetics of epilepsy, took place during the last twenty years; in 1989, Leppert was the first to identify the link between chromosome 20 and idiopathic human epilepsy syndrome in a family with benign familial neonatal convulsions.
Epilepsy still remains a field of active research, occupying different medical specialties. The growing evidence on the connection
between various genes and epilepsies is the cutting edge of modern epilepsy research, and in the next decades new exciting discoveries are going to change epileptology.
EPIDEMIOLOGY OF EPILEPSY
Globe10,11
At the global level, it is estimated that nearly 70 million people suffer from epilepsy. The estimated proportion of the general population with active epilepsy (i.e. continuing seizures or with the need for treatment) at a given time is between 4 and 10 per 1000 people.
INDIA
Prevalence:It is the proportion of people with seizure in given population at aspecified time. The overall prevalence rate in India is 3.0- 11.9 per 1,000 populations.
Incidence:The number of new cases of seizure occurring during a given time interval,usually one year, in a specified population is called as incidence. Incidence rate in India is (0.2-0.6 per 1,000 populations per year)
The community-based studies recorded a higher frequency for generalized seizures ranging from 79 to 54.5%. Within generalized epilepsy, tonic-clonic was the commonest type12,13,14. There is a differential distribution of epilepsy among various socio-demographic
and economic groups with higher rates reported for the male gender, rural population, and low socioeconomic status. Approximately 75% of epilepsy begins during childhood, suggestive of susceptibility to develop seizures in developing brain. However, a changing pattern in the age- specific occurrence of epilepsy with preponderance towards the older age group is noticed due to socio-demographic and epidemiological transition10.
The prognosis for seizure control is good and over 70% will enter remission.There is an increased risk of premature death particularly in patients with chronicEpilepsy15.
Pathophysiology of Epilepsy
Physiologically a seizure developed when there is distortion of the normal balance between excitation (E) and inhibition (I) in the brain.
This E/I imbalance can result from an alteration at many levels of brain function, from genes to widespread neuronal circuits. The factors that alter Excitation/Inhibition balance can be genetic or acquired16.
Focal seizure activity can start in a region of cortex and then
Initiation phase of seizure is characterized by twoconcurrent following events,
(1) High-frequency bursts of action potentials and (2) Hyper-synchronization
The bursting activity is caused by a long-lasting depolarization of the neuronal membrane due to influx of extracellular Ca2+, this leads to the opening of voltage dependent Na+channels, influx of Na+ &
generation of repetitive action potentials.Followed by hyperpolarizing after-potential mediated by GABA receptors/K+channels, depending on the cell type. The spike discharge on the EEG is due to synchronized bursts from a sufficient number of neurons. Normally, intact hyperpolarization created by Inhibitorsprevents the spread of bursting activity. There is a recruitment of surroundingneurons via one of the following four mechanisms, including:
Increase in extracellular K+, blunts hyperpolarization and depolarizes neighboring neurons;
1. Enhanced neurotransmitter release due to accumulation of Ca++ in presynaptic terminals;
2. Depolarization-induced activation of the NMDA receptor, which causes additional Ca++ influx and neuronal activation;
3. Changes in tissue osmolarity and cell swelling.
The factors that alter Excitation/Inhibition balance could 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 GABA receptor subunits in Angelman syndrome) to abnormal ionic channel function (e.g., potassium channel mutations in benign familial neonatal epilepsy [BFNE]). Similarly, acquired pathologies are cerebral insults which can alter circuit function (e.g., structural alteration of hippocampal circuitry following prolonged febrile seizures)17.
The developing brain is particularly prone to develop seizures for a variety of physiological reasons18. Even in the normal developing brain, excitatory synaptic function develops before inhibitory synaptic function, favoring enhanced excitation and seizure generation.
Additionally, early in life GABA neurotransmitter causes excitation rather than inhibition19,20. This observation is partly explained why very
Basic mechanisms of other precipitating factors of seizures such as fever, alcohol withdrawal, infection and hypoxia are not as well understood.The generalized spike-and-wave discharges in absence seizures are due to scillatoryrhythms which are normally generated during sleep by the circuits connecting the thalamus and cortex. This involves an interaction between GABA-B receptors, T-type calcium channels, and potassium channels located within the thalamus. This modulation of these receptors and channels can induce absence seizures.
Alcohol causes intoxication through effects on diverse ion channels andneurotransmitter receptors, including GABA-A receptors- particularly thosecontaining δ subunits that are localized extra- synaptically and mediate tonicinhibition and N-methyl-D-aspartate (NMDA) receptors.
Alcohol dependence results from compensatory changes during prolonged alcohol exposure, including internalization of GABAA receptors, which allowsadaptation to these effects.
Withdrawal seizures are due to reflect unmasking of these changes and mayalso involve specific withdrawal-induced cellular
events, such as rapid increases inα4 subunit–containing GABAA receptors that confer reduced inhibitory function.
During a seizure, the demand for blood flow to the brain increases to carry off CO and to bring substrate for metabolic activity of the 2 neurons, as the seizure prolongs, the brain suffers more from ischemia that may result in neuronal destruction and brain damage21.
Mutation in several genes may be linked to some types of epilepsy. Genes that code for protein subunits of voltage-sensitive and ligand-activated ion channels have been associated with the generalized epilepsy and infantile seizure syndromes22.
Classification23
Grand mal and petit mal were most common words to described seizures from decades. In 1981, classification was developed has divided into partial (focal) onset and generalized onset seizures. The partial seizures were further divided into simple partial seizures and complex partial seizures. Generalized seizures were divided into various subcategories.
Old classification served well but had several drawbacks as follow, these concerns led to the ILAE’s (International League Against Epilepsy) current revision.
Several important seizure types were not specifically listed such as focal clonic seizures.
It was impossible to classify a seizure if the onset was not known.
Many of the terms, such as psychic seizures or complex partial seizure were confusing.
ILAE’s new classification has two classification versions as below:
A) Classification of seizure types basic version B) Classification of seizure types expanded version A) Classification of seizure types basic version
1) Defining where seizures begin: The first step is to separate seizures by how they begin in the brain.
Dividing seizures into those that start focally in one hemisphere or side of the brain versus those that engage networks in both sides of the brain at the onset.
If onset is unknown, the seizure falls into the unknown onset category.
2) Describing awareness in focal seizures:
Focal Aware (replaces the term simple partial): A seizure is
“focal aware” if awareness is intact, even if the person is unable to talk or respond during the seizure.
Focal Impaired Awareness (replaces the term complex partial seizure)- A seizure is classified as “focal impaired awareness” if awareness is impaired at any time during the seizure.
A seizure can start focally in the brain and spread to both sides of the brain, resulting in a ”focal to bilateral tonic- clonic seizure.” This used to be called a secondarily generalized tonic-clonic seizure. The word “generalized” is now only used if seizures are known to affect both sides of the brain at once in the beginning of a seizure.
The term aura is often used to describe symptoms a person may feel in the beginning of a seizure and is not in the new
Figure 1: Classification of seizure type basic version (ILAE 2017)
Describing motor and other symptons in focal seizures:
A focal motor seizure means some type of movement occurs during the event. For example, twitching, jerking, or stiffening movements of a body part or automatisms.
A focal non-motor seizure includes other symptoms such as changes in sensation, emotions, thinking, or experiences.
A seizure therefore can be focal motor (the word “onset” is implied) or focal non-motor.
It is also possible for a focal aware or impaired awareness seizure to be sub-classified as motor or non-motor onset.
Describing generalized onset seizures: Seizures that start in both sides of the brain, called generalized onset, can be motor or non-motor (absence). The generalized tonic-clonic seizure term is still used to describe seizures with stiffening (tonic) and jerking (clonic). This loosely corresponds to “grand mal.” The generalized absence seizure corresponds to the old term “petit mal.” These seizures involve brief changes in awareness, staring, and some may have automatic or repeated movements like lipsmacking.
B) Classification of seizure types expanded version
The expanded classification keeps the framework of the basic classification, but adds more seizure types as subheadings.
Focal motor onset seizure types include automatisms, atonic, clonic, epileptic spasm, hyperkinetic, myoclonic and tonic seizures. Several of these types also appear in the generalized onset categories.
Focal non-motor onset seizures include autonomic, behavior arrest, cognitive, emotional, and sensory seizures. Since seizures often have several different symptoms and behavioral signs, the seizure is named for the first prominent symptom or sign. This has been the usual clinical practice, because seizure onset marks the part or network of the brain involved in generating the seizure. Other regions become involved as the seizure spreads.
Below are brief descriptions of each seizure type.
Focal onset seizuresmay occur with or without impairment of awareness, except that atonic and epileptic spasm seizures usually do not show obvious impairment of awareness.
Focal automatisms seizure: A seizure with automatic fumbling behavior, such as lip-smacking, hand-rubbing, picking at objects, walking in circles, repeatiting meaningless phrases, or undressing.
Focal atonic seizure: Focal, for example in one arm or leg, sudden loss of muscle tone and strength, resulting in a transiently limp limb.
Focal clonic seizure: Sustained rhythmically jerking of one part of the body or face.
Focal epileptic spasms: Sudden flexion or bending of the trunk with flexion or extension of the limbs lasting less than a few seconds. These often occur in clusters. The term infantile spasms applies to epileptic spasms occurring during infancy. Video-EEG monitoring and a brain MRI may be needed to determine whether onset of epileptic spasms is focal or generalized.
Hyperkinetic seizure: A seizure with vigorous thrashing or pedaling movements. Even though both sides of the body are usually involved with these seizures, the EEG often shows a focal and frontal lobe origin.
Some people used to call these hypermotor seizures.
Focal myoclonic seizure: Irregular and brief lightning jerks of limbs or face on one side of the body.
Focal tonic seizure: Stiffening of arm, leg, or neck producing a forced posture during the seizure.
Focal autonomic seizure: A seizure whose primary effect is on autonomic nervous system functions, such as heart rate, blood pressure, sweating, skin color, hair standing on end (piloerection), and gastrointestinal sensations.
Focal behavior arrest seizure: In this seizure type, movement stops, sometimes called a freeze or a pause. Because brief behavior arrest is common and hard to recognize as being abnormal, a seizure should only be classified as a focal behavior arrest seizure if the behavior arrest is the main feature through the entire seizure.
Focal cognitive seizure: This type of seizure refers to impaired cognition (thinking) during a seizure. The impairment might affect language, spatial perception, ability to calculate math, or other cognitive functions. Do not count loss of awareness or memory (unless only memory is impaired) as a focal cognitive seizure, because awareness is used to describe other seizure types.
Focal emotional seizure: This seizure type begins with spontaneous fear, anxiety, or less often joy. There may be involuntary laughing or crying, each of which might or might not be accompanied by a subjective emotion. Gelastic and dacrystic seizures would fit into this group.
Focal sensory seizure: Sensory seizures can consist of tingling or numbness, visual symptoms, sounds, smells, tastes, tilting or spinning sensations (vertigo), and hot-cold feelings.
Generalized onset seizures are not characterized by level of awareness, because awareness is almost always impaired.
Generalized tonic-clonic: These are the main seizure type in 10% of all persons with epilepsy. Also a common seizure type resulting from metabolic derangements. Immediate loss of awareness, tonic phase (stiffening of all limbs), followed by clonic phase (sustained rhythmic jerking of limbs and face). Duration is typically for 1 to 3 minutes. The seizure may produce a cry at the start, tongue biting, falling and incontinence. The postictal phase is characterized by muscular flaccidity, unresponsiveness, and excessive salivation. Further bladder
tonic phase shows a progressive increase in generalized low-voltage fast activity which followed by high-amplitude andpolyspike discharges.
The high-amplitude activity is interrupted by slow waves to create a spike-and-wave pattern in the clonic phase.
Generalized clonic: Rhythmical sustained jerking of limbs and/or head with no tonic stiffening phase.
Generalized tonic: Stiffening of all limbs, without clonic jerking.
Generalized myoclonic: Irregular, unsustained jerking of limbs, face, eyes, or eyelids.
Generalized myoclonic-tonic-clonic: cause is unknown commonly occurs in early adolescence. This seizure is like a tonic-clonic seizure, but it is preceded by a few myoclonic jerks on both sides of the body.
Such seizures are commonly seen in people with the syndrome of juvenile myoclonic epilepsy.
Generalized myoclonic-atonic: These seizures may be seen in children with Doose syndrome. This seizure presents with a few myoclonic jerks, followed by a limp drop.
Generalized atonic: This is an epileptic drop attack, with sudden loss of muscle tone and strength and a fall to the ground or a slump in a chair.
Atonic seizures usually last only seconds.
Generalized epileptic spasms: Brief seizures with flexion at the trunk and flexion or extension of the limbs.
Generalized typical absence: Sudden onset when activity stops with a brief pause and staring, sometimes with eye fluttering and head nodding or other automatic behaviors. If it lasts for more than several seconds, awareness and memory are impaired. Recovery is immediate. The EEG during these seizures always shows generalized spike-waves.
Generalized atypical absence: may have slower onset and recovery and more pronounced changes in tone. Atypical absence seizures can be difficult to distinguish from focal impaired awareness seizures, but it usually recover more quickly and the EEG patterns are different.
Generalized myoclonic absence: A seizure with a few jerks and then an absence seizure.
Generalized eyelid myoclonia: precipitated by closing the eyes or by light characterized by jerks of the eyelids and upward deviation of the eyes.
Unknown Onset Seizures:
Clinicians using the classification will identify a seizure as focal or generalized onset if there is about an 80% confidence level about the type of onset. This means that there is significant confidence on the seizure onset and type. Seizures without enough confidence about onset are labeled of unknown onset. The most important seizures of unknown onset are tonic-clonic, epileptic spasm, and behavior arrest (which could be either a focal impaired awareness or absence seizure).
Table1: Changes in Terms used for seizure.
Old terms New terms
Unconscious (still used, not in name)
Impaired awareness (surrogate)
Partial Focal
Simple partial Focal aware
Complex partial Focal impaired awareness Dyscognitive (word discontinued) Focal impaired awareness
Psychic Cognitive
Secondarily generalized tonic- clonic
Focal to bilateral tonic-clonic Arrest, freeze, pause, interruption Behavior arrest
EPILEPSY SYNDROME:
Epilepsy refers to a group of clinical characteristics that consistently occur together, with similar seizure type(s), age of onset, EEG findings, triggering factors, genetics, natural history, prognosis, and response to antiepileptic drugs (AEDs).
Examples of epilepsy syndromes according to age of onset
Neonatal
Benign familial neonatal epilepsy (BFNE)
Infancy
West syndrome
Dravet syndrome
Childhood
Generalized epilepsy with febrile seizures plus(GEFSþ)
Childhood absence epilepsy
Lennox–Gastaut syndrome
Landau–Kleffner syndrome
Adolescence and adulthood
Juvenile myoclonic epilepsy
1) Benign familial neonatal epilepsy (BFNE):
BFNE is a neonatal epilepsy syndrome in which begin in the first week of life. Seizures are focal clonic or focal tonic, often accompanied by apnea. They usually stop after a few days or weeks. The key to the diagnosis is a family history of newborn or infantile seizures that
resolved. The prognosis of BFNE is good, although ∼10%–15% of affected infants continue to have seizures beyond the neonatal period, even into adulthood24.
BFNE is the first epilepsy syndrome explained by a mutation in a voltage-gated ion channel gene. BFNE has been linked to two genes:
KCNQ2 on chromosome 20q and KCNQ3 on chromosome 8q. These genes code for voltage-gated potassium channel subunits, which regulate the M-current, a muscarine-activated neuronal current that turns off potassium channels25. The M-current stabilizes resting membrane potential; its dysfunction leads to increased neuronal excitability and seizures. It is not known why seizures in BFNE affect neonates and then resolve because the genetic defect is present throughout life.
2) West syndrome (WS):
WS is an age-specific disorder, beginning primarily in the first year of life and characterized by the triad of epileptic spasms, an interictal EEG pattern called hypsarrhythmia and intellectual disability.The duration of an epileptic spasm is intermediate between a myoclonic jerk and a tonic seizure. Spasms often occur in clusters of
head nods, forceful flexion, or extension of the trunk and limbs. They frequently occur during sleep transitions, especially on awakening.
The interictal EEG pattern in WS is called hypsarrhythmia, a disorganized, “chaotic” pattern of very high voltage slow waves and spikes over multiple cortical areas. The classic ictal EEG pattern is a generalized slow wave followed by background voltage attenuation in all channels, accompanied by a clinical spasm.
Most cases of WS have an identifiable cause, such as hypoxia- ischemia, brain hemorrhage, brain infection, developmental brain anomaly, or inborn metabolic error.
WS is an epileptic encephalopathy with a poor prognosis. At least two-thirds of affected children have intellectual disability. With age, the seizures often change from spasms to other seizure types, such as those seen in Lennox–Gastaut syndrome (see below). Several animal models of IS have been reported recently, raising hope that elucidating the pathophysiology of IS will lead to more efficacious treatments26,27,28.
3) Febrile seizures plus:
Children with febrile seizures plus (FS+) have febrile seizures beyond the age at which febrile seizures usually stop (∼5 yr). In addition, these children may develop additional afebrile seizure types, including GTC, absence, and myoclonic. Therefore, this syndrome differs from ordinary febrile seizures and represents a genetic predisposition to epilepsy. In FS+, the outcome is variable; seizures resolve in some children, but persist in others. In different families, genetic defects have been identified in neuronal sodium channels29 and GABA receptors30. Many patients with FS+ have mutations in the α1 subunit of the voltage-gated sodium channel gene, SCN1A31.
4) Dravet syndrome (DS):
DS is a rare epilepsy syndrome in which children present with seizures before 18 month of age32. The initial seizure often occurs with a fever and has a hemiclonic semiology. Later, other seizure types occur and the child shows developmental regression. About 70%–80% of patients with DS have a mutation in the SCN1A gene, mostly sporadic and causing nonfunctional sodium channels33.
5) Lennox–Gastaut syndrome (LGS)1
LGS occurs in children and is defined by the following triad: (1) multiple seizure types; (2) an EEG showing slow (<3 Hz) spike-and- wave discharges and a variety of other abnormalities; and (3) impaired cognitive function in most of cases. Lennox-Gastaut syndrome is associated with CNS disease or dysfunction from a variety of causes, including developmental abnormalities, perinatal hypoxia/ischemia, trauma, infection, and other acquired lesions. The multifactorial nature of this syndrome suggests that it is a nonspecific response of the brain to diffuse neural injury. Unfortunately, many patients have a poor prognosis due to the underlying CNS disease.
6) Landau–Kleffner syndrome (LKS):
LKS is also called acquired epileptic aphasia which is a rare epilepsy in which a child loses previously acquired language abilities because of seizures or epileptiform abnormalities on EEG. In its pure form, LKS occurs in previously normal children with normal language development who gradually lose the ability to understand spoken language and produce speech34. Nuero-imaging studies are negative.
Although PET studies have shown bitemporal abnormalities which
supporting the hypothesis that language-related brain regions are dysfunctional in LKS35. EEG abnormalities in LKS may include generalized and focal/multifocal spikes/spike waves.
7) Juvenile myoclonic epilepsy (JME)1
It is ageneralized seizure disorder with unknown cause, appears in early adolescence and is characterized by bilateral myoclonic jerks that may be single or repetitive. They are most frequent in the morning after awakening and can be provoked by sleep deprivation. Consciousness is preserved unless the myoclonus is especially severe. Many patients also experience GTCS, and up to one-third have absence seizures. Seizures are exacerbated by fatigue, sleep deprivation, and alcohol use.Theinterictal EEG in JME shows bursts of fast (3.5- to 6-Hz) spike- wave complexes. The seizures respond well to appropriate anticonvulsant medication. As there is often a family history of epilepsy, genetic linkage studiessuggesta polygenic cause.Although responsible gene has not yet been identified but some the studies linked JME to chromosome 6p (a locus dominantly inherited)36.
Table2: Examples of Genes Associated With Epilepsy Syndromes1
Gene (Locus)
Function of Gene Clinical Syndrome
Comments CHRNA4
(20q13.2)
Nicotinic acetylcholine receptor subunit;
alterations in Ca2+ flux; this mayreduce
amount of GABA
release in
presynaptic terminals
Autosomal dominant
nocturnal frontal lobe epilepsy (ADNFLE);
childhood onset;
short, nighttime seizures with dominant motor movements
First identified in a large Australian family; other families found to have mutations in
CHRNA2 or
CHRNB2.
KCNQ2 (20q13.3)
Voltage-gated potassium
channel subunits;
mutation in pore regions may cause
a 20–40%
reduction of potassium
currents, which will lead to impaired
repolarization
Benign familial neonatal
convulsions (BFNC);
autosomal dominant
inheritance; onset in 1st week of life in infants who are otherwise normal;
remission usually within weeks to months; long-term epilepsy in 10–
15%
Rare; other families found to have mutations in KCNQ3; sequence and functional homology to KCNQ1, mutations of which cause long QT syndrome
and a
cardiacauditory syndrome
SCN1B (19q12.1)
beta-subunit of a voltage-gated sodium channel;
mutation disrupts disulfide
bridge that is crucial for structure of extracellular
Generalized
epilepsy with febrile seizures plus (GEFS+);
autosomal dominant inheritance;
presents with febrile seizures at
Incidence
uncertain; GEFS+
identified in other families with mutations in other sodium channel subunits (SCN1A and
SCN2A) and
Gene (Locus)
Function of Gene Clinical Syndrome
Comments domain; mutated
Beta-subunit leads to slower sodium channel inactivation
median 1 year, which may persist
>6 years, then variable seizure
types not
associated with fever
GABAA receptor subunit (GABRG2 and GABRA1);
significant phenotypic heterogeneity within same
family, including members with febrile seizures only
LGI1 (10q24)
Leucine-rich glioma-
inactivated 1 gene; previous evidence for role in glial tumor progression;
protein homology
suggests a
possible role in nervous system development
Autosomal
dominant partial epilepsy with auditory features (ADPEAF); a form of idiopathic lateral temporal lobe epilepsy with auditory
symptoms or aphasia as a major simple partial seizure
manifestation; age of onset usually between 10 and 25 years
Mutations found in approximately 50%
of families containing two or more subjects with idiopathic
localization-related epilepsy with ictal auditory symptoms, suggesting that at least one other gene may underlie this syndrome. LGI1 is the only gene identified so far in temporal lobe epilepsy
CSTB (21q22.3)
Cystatin B, a noncaspase
cysteine protease inhibitor; normal protein may block neuronal
apoptosis by
Progressive myoclonus
epilepsy (PME) (Unverricht-
Lundborg disease);
autosomal
Overall rare, but relatively common in Finland and Western
Mediterranean (>1 in 20,000); precise role of cystatin B in
Gene (Locus)
Function of Gene Clinical Syndrome
Comments cathepsins), or
controlling proteolysis
onset between 6 and 15 years, myoclonic
seizures, ataxia, and progressive cognitive decline;
brain shows neuronal
degeneration
mutations of cystatin B have similar syndrome
Doublecortin (Xq21-24)
Directly regulates microtubule
polymerization and bundling
associated with severe mental retardation and seizures
in males;
subcortical band heterotopia with more subtle findings in females
(presumably due to random X- inactivation);
Rare but of uncertain
incidence, recent increased
ascertainment due to
improved imaging techniques.
THE CAUSES OF SEIZURES AND EPILEPSY:
Shift in the normal balance of excitation and inhibition within the CNS causes seizures. The cause of epilepsy is completely unknown. The word epilepsy does not indicate anything about the cause or severity of the person's seizures, some cases of epilepsy are induced by genetic factors, but it can also result form brain injuries caused by blows to the head, stroke, infections, high fever or tumors37. For instances, not
everyone who has a serious head injury (a clear cause of seizures) will develop epilepsy38. A penetrating head injury is associated with upto a 45% risk of subsequent epilepsy.
Certain epilepsy syndromes termed as reflex epilepsy need specific precipitants or trigger for seizures to occur like reading, flashing lights and precipitants like emotional stress, sleep deprivation sleep it self, heat stress, alcohol and febrile illness are examples of precipitants cited by patients with epilepsy. Notably the influence of various precipitants varies with the epilepsy syndrome39. The menstrual cycle in epileptic women can influence patterns of seizure recurrence, catamenial epilepsy in the seizure linked to the menstrual cycle40.
There are different causes of epilepsy that are common in different age groups1;
In neonatal period and early infancy, the most common causes are hypoxic–ischemic encephalopathy, CNS infections, trauma, congenital CNS abnormalities and metabolic disorder.
In late infancy and early childhood, the most common febrile
In child hood well defined epilepsy syndromes are generally observed.
In adolescence and adult hood the causes are more likely to be secondary to any CNS lesion.
In old persons, cerebrovascular disease is the most common cause, the other causes, includes CNS tumors, head trauma and other degenerative diseases like dementia1
Causes of seizures1:
Table3: Causes of seizures Neonates
(<1 month)
Intracranial hemorrhage and trauma Perinatal hypoxia and ischemia
Metabolic disturbances (hypoglycemia, hypocalcemia, hypomagnesemia, pyridoxine deficiency)
Acute CNS infection Developmental disorders Drug withdrawal
Genetic disorders Infants and
children
(>1 month and
<12 years)
Genetic disorders (metabolic, degenerative, primary epilepsy syndromes)
Febrile seizures
Developmental disorders CNS infection
Trauma Idiopathic Adolescents
(12–18 years)
Idiopathic Trauma Infection Brain tumor
Illicit drug use Genetic disorders Young adults
(18–35 years)
Idiopathic Trauma
Alcohol withdrawal Brain tumor
Illicit drug use Older adults
(>35 years)
Cerebrovascular disease Brain tumor
Metabolic disorders (uremia, hepatic failure, electrolyte abnormalities, hypoglycemia, hyperglycemia)
Alcohol withdrawal
Alzheimer’s disease and other
degenerativeneurodisease Idiopathic
DIAGNOSTIC EVALUATION:
History and Examination1
The history and neuroclinical details were important factors in the diagnosis of seizures. The history should focus on risk and precipitating factors. Clues for a predisposition to seizures include a history of febrile seizures, earlier auras or brief seizures. Epileptogenic factors such as head trauma and stroke should be identified. Precipitating factors such as sleep deprivation, electrolyte or metabolic derangements, acute
The general physical examination includes a search for signs of infection or systemic illness. Examination of the skin may reveal signs of neurocutaneous disorders such as tuberous sclerosis or neurofibromatosis. A finding of organomegaly may indicate a metabolic storage disease, and limb asymmetry may provide a clue to brain injury early in development.
Electroencephalogram (EEG)6:
It can detect abnormal electrical activity, such as focal spikes or waves, or diffuse bilateral spike waves. A routine EEG will preferably, include wakefulness and sleep because in different states of consciousness the prevalence of epileptiform abnormalities varies. A patient hyperventilate for 3 min has a high yield of leading to an absence seizure, related to the seizure-provoking effect of alkalosis41. Photic stimulation may elicit paroxysmal epileptiform activity or even a generalized seizure in a person susceptible to generalized epilepsy42. Video-EEG monitoring for hours-days can differentiate an epileptic seizure from a nonepileptic event. The diagnosis of epilepsy is based on clinical information and the EEG should be regarded as confirmatory, not diagnostic. The standard teaching is “treat the patient, not the EEG”.
Neuroimaging:
Computed tomography (CT) and magnetic resonance imaging (MRI) scans are important adjuncts to the clinical examination and EEG in the evaluation of a person with seizures. Neuroimaging techniques are especially sensitive for central nervous system (CNS) structural lesions.
Focal neurologic findings on examination (e.g., unilateral weakness, asymmetric reflexes) mandate neuroimaging.
MRI is more likely to show an abnormality in a patient with focal seizures, abnormal neurologic findings, or focal discharges on EEG.
MRI is more sensitive than CT and is therefore preferred, especially for the detection of cortical malformation, dysgenesis, or hippocampal sclerosis. Quantitative, computer-assisted volume analysis of the temporal lobes may detect asymmetries that are not readily apparent on visual analysis of the scan. CT is valuable in the acute setting to detect hemorrhage, calcification, or tumors.
Several new imaging techniques are available to aid in the assessment of epilepsy43. MRI abnormalities can be correlated directly with EEG activity. Functional MRI (fMRI) takes advantage of blood
interictal or ictalepileptiform activity and localize language and memory. Magnetic resonance (MR) spectroscopy measures the concentrations of a variety of neurochemicals in different brain regions and can sometimes assist in localizing a seizure focus. Positron emission tomography (PET) images the brain’s regional use of glucose with asymmetries suggesting areas of interictal or ictal abnormality. Single- photon emission-computed tomography (SPECT) compares local blood flow discrepancies, information that is most useful when recorded during a seizure. Magnetoencephalography (MEG) assesses the brain’s dynamic electromagnetic fields and can better localize epileptic dipoles, including those tangential to the scalp, which can be missed by conventional EEG44. These advanced modalities are used mainly in epilepsy centers for presurgical evaluations45.
Metabolic evaluation:
The type of seizure and syndrome dictates the extent of the metabolic workup46. For example, a child with IS or Lennox–Gastaut syndrome is more likely to have a metabolic or degenerative disorder than one presenting with simple partial seizures. In metabolic disorders, seizures are typically accompanied by other abnormalities, such as developmental delay, unexplained vomiting, or coma. In neonatal
seizures, a metabolic evaluation is mandatory, including a screen of serum amino acids and urine organic acids, and blood lactate to screen for mitochondrial disease. In addition to its more common use to evaluate CNS infection, cerebrospinal fluid can be analyzed for glucose transporter defects (GLUT1 deficiency syndrome)47 and rare (but sometimes treatable) neurotransmitter defects48.
Genetic testing:
As the genetic basis of epilepsies becomes progressively unraveled, clinical testing will occupy an increasingly pivotal role in the clinic49,50. At this point, genetic testing is available for several single genes, as well as complex genetic disorders51,52. A basic karyotype can be performed to evaluate for a chromosomal anomaly, especially in a patient with dysmorphic features. If a specific syndrome is suspected, an epilepsy panel of selected genes can be ordered (e.g., SCN1A for Dravet syndrome [DS]). Comparative genomic hybridization (CGH) microarray evaluates targeted chromosomal regions for copy number variants.
When a genetic diagnosis is highly suspected, but other work up is unrevealing, the clinician can consider whole exome sequencing of the
SEIZURES IN ADULT:
ADULT ONSET IDIOPATHIC GENERALIZED EPILEPSY (AIGE):
It is generally thought to have a focal basis and symptomatic etiology54. However in some patients, IGE is suspected because of typical generalized tonic - clonic, myoclonic or absence seizures, a family history of seizures, the generalized spike- wave complexes on EEG, normal brain imaging55.Two hospital based studies recently reported that 34.8% and 13.4% of IGE cases had seizure onset in adulthood56,57 .The IGE typically appears within first two decades of life.
The annual age specific incidences of IGE patients aged 15- 24 years were 3.6 per 1,00,000 and 25- 34 years were 3.5 per 1,00,000.Whereas the incidences of IGE patients aged 5- 9 years were 10.7 per 1,00,000 and 10- 14 years were 15.3 per 1,00,00058. Patients with AIGE have a good prognosis, with good to excellent seizure control with a single AED56.
The patients with AIGE can be divided into three groups on the basis of seizure type
Adult onset absence epilepsy: absence seizures as well as tonic – clonic seizures occurs in these patients.
Adult onset myoclonic epilepsy: myoclonic jerks and tonic- clonic seizures occurs in these patients.
Adult onset tonic – clonic epilepsy: only tonic clonic seizures occurs in these patients
POST-STROKE SEIZURES (PSS):
Seizure is an important complication after stroke.Incidence of seizures after stroke varies from 4.1% to 12.5%59. Post stroke epilepsy incidence in India is13%60.
Temporal relation of stroke and seizures: Seizure may occur before or at the onset of or weeks to months after a stroke.
The incidence of epilepsy prior to stroke was 4.5% when compared to 0.6% in the matched control group61. These seizures occur weeks or even years before the presenting stroke. This increased incidence of epilepsy in stroke patients may be 29 attributed to subclinical cerebral vascular disease Thus, the onset of seizures in adult or elderly population may be warning sign for further strokes.
Post stroke seizures classification:
Early onset seizures: seizures occurring within 2 weeks following stroke onset Late onset seizures: seizures occurring after 2 weeks. This differentiation helps to determine the need and duration of treatment these patients with an AED’s59.
A) Post stroke early seizures:
The incidence of epileptic seizures in acute stroke is 4.4% in patients with transient ischemic attacks (TIA), lobar infarcts and extensive hemorrhages. Seizures occur within 24 to 48 hours after the stroke. In a prospective study of 1000 patients with stroke and TIA the incidence of early seizures was (15.4%) in patients with supratentorial lobar or extensive hemorrhages, followed by SAH(8.5%), carotid artery cortical infarction (6.5%), and hemispheric TIA’s (3.7%)62 .The commonest site of infarction among the patients with cortical infarcts and early epilepsy is in the MCA territory. Predictably, subcortical and deep cerebral, brain stem infarcts, and infratentorial hemorrhages are not associated with increased risk for seizures. Incidence of seizures is low (1%) in lacunar infarcts. Cerebral embolism patients experience more
seizures than thrombotic infarct patients63. Patients with stroke and early seizures had larger lesions(>10 mm) on cerebral CT scan.
In acute stage, almost 60% of seizures are focal and 40% are of generalized tonic - clonic type. Of the focal seizures, 75% are simple focal motor while remaining 25% become generalized. In 0.7 to 1.1% of patients with stroke early seizures presenting with status epilepticus (SE). In certain instances, PSS present as only subtle clinical findings, such as focal, intermittent eye deviation or nystagmus, mild facial twitching, or focal sensation changes; other PSS cases may only have worsening of motor deficit, impaired speech or fluctuating stroke recovery. Moreover, patients with PSS may have no focal motor or sensory signs, and only present with altered mental status and behaviour arrest. These cases of subclinical/non-convulsion seizures or SE can only be confirmed by electroencephalogram (EEG)64.
Predictive factors of early seizures:
The presence of precipitating factors like hypoglycemia, hyperglycemia, hypernatremia ,hyponatremia, hypomagnesemia, hypocalcemia, infections and renal failure increases the incidence of
history of diabetes and atrial fibrillation. However, the major predictors of early seizures in new onset stroke patients are cortical involvement in neuro- imaging studies, initial stroke severity and acute confusional state at the onset of stroke65. Primary generalized seizure is common with late onset seizures (56%).But early onset seizures, which are generally simple partial in nature. Status epilepticus is more common in early onset than late onset seizures66.
In a prospective study, Strzelczyk et al,evaluated 264 consecutive patients with stroke, and defined seven risk items, weighted differently, then established the Post-Stroke Epilepsy Risk Scale. The scale showed moderate sensitivity (70%) and positive predictive value (87.5%), and relatively high specificity (99.6%) and negative predictive value (98.8%)67.
Table 4: Seven items of the Post-Stroke Epilepsy Risk Scale
Pathophysiology of early post stroke seizures:
In infarct, in the ischemic penumbra ionic imbalances, enhanced release of excitotoxic glutamate, breakdown of membrane phospholipids and release of FFA play an important role in epileptogenesis59.
Risk of recurrence:There is 11% to 39% risk of recurrent seizures in patients with early stroke seizures. Lesions involving more than one lobe, patients with large hemorrhagic strokes, and cortical infarcts are at higher risk of developing seizures later68.
Management: Seizures can be controlled with monotherapy alone. If the stroke patient presents with status epilepticus or if there is early recurrence of seizures treatment with AED therapy is indicated69.
B) Post stroke late seizures:
It occurs after first 2 weeks of stroke. It also may begin months to a year after a stroke. The incidence is about 15%70. Nearly 24% of seizures occur within three weeks and 93% in two years.
Pathophysiology of late post stroke epilepsy:
The mechanisms behind late-onset PSS may be secondary gliotic scarring with associated changes in membrane properties, chronic inflammation, neurodegeneration, altered synaptic plasticity, eventually leading to hyperexcitability, and increased synchronisation of neuronal activities.
Management:Carbamazepine and Phenytoin have high treatment success in post stroke epilepsy.
SINGLE SMALL ENHANCING CT LESIONS (SSECTL):
In Indian patients with new onset seizures the commonest imaging abnormality is spontaneously resolving single, small, enhancing lesion in CT71.
Atleast 26% of Indian patients with focal epilepsy have SSECTL reported by Wadia et al72. The lesion could have either a disc or a ring like enhancement of size less than 20mm. The surrounding perifocaloedema may be mild to moderate and usually there is no mass effect. In 1985 Setiet al, however reported the spontaneous resolution of these lesions73.
By the help of stereotactic brain biopsy Rajshekar et al, have made an attempt to answer the controversy regarding the etiology of these lesions. He showed after histopthological diagnosis that, majority of these lesions are cysticercus granuloma and few of them are tuberculoma. They form the clinical and radiological criteria of SSECTL to diagnose the lesion to be a solitary cysticercusgranuloma.These lesions itself acts as antigen and production of inflammatory cytokines, causing cytotoxic and vasogenicoedema, which acts as an epileptogenic foci in dying phase of cyst74.
Diagnostic criteria for solitary cerebral cysticercus granuloma (SCCG)75
Clinical criteria
1. Seizure as initial symptom (partial or generalized).
2. No features of persistent raised ICT.
3. No evidence of progressive neurologic deficit
4. No evidence of active systemic illness like tuberculosis and/or focus of pyogenic infections, primary malignancy.
CT criteria:
1. solitary lesion
2. Should enhance after contrast injection 3. <20 mm in diameter
4. Absence of severe cerebral edema.
Management of SSECTL: AED therapy is the mainstay of treatment.
An addition of short course of oral prednisolone (1mg/kg/day for ten days followed by tapering over 2 weeks) helps in prevention of seizure recurrence and also in early disappearance of lesion71. After a period of 10- 12 weeks follow up CT scan should be done in every patient to document the resolution of granuloma. If the patient has not had a seizure in the preceding 3 months, soon after a documented resolution of granuloma early discontinuation of AEDs is recommended75.
If the lesion enlarges in size on follow up CT scan Anti tuberculous therapy (ATT) may be considered.
If clinically malignancy is suspected Surgical excision of the enlarging lesion for histopathological examination is recommended, as SSECTL in few patients could be due to meningioma and other primary bone tumours75.
NEUROCYSTICERCOSIS:
It is a common parasitic disease of the CNS. Neurocysticercosis is caused by ‘cysticercus cellulose’ the encysted larval stage of the tapeworm TaeniaSolium. For many years the parenchymal cysts may remain dormant and the death of larva and subsequent intense inflammatory reaction induced by larval antigens produces symptoms (e.g. seizures). Subsequently, the cyst transforms into active granuloma.
The cyst then shrinks and granuloma eventually calcify or frequently disappears completely76.
Figure 4: Neurocysticercosis is caused by Taeniasolium .Neurologic infection can be classified on the basis of the location and viability of the parasites. When the parasites are in the ventricles, they often cause obstructive hydrocephalus. Left: MRI showing a cysticercus in the lateral ventricle, with resultant hydrocephalus. The arrow points to the scolex within the cystic parasite. Center: CT showing a parenchymal cysticercus, withenhancement of the cyst wall and an internal scolex ( arrow). Right: Multiple cysticerci, including
In brain parenchyma, the cysticercus cyst typically goes through four stages of involution
1) Vesicular 2) Colloidal
3) Granular – nodular and 4) Calcific.
The first 2 stages are considered to represent the live parasite, and last two stages, the dying or dead forms of the parasite. A live cyst is asymptomatic, evolving no or minimal host immune response. In India, majority of patients of neurocysticercosis have single enhancing lesions but the multiple enhancing CT/MRI lesions are also not uncommon77. These single or multiple lesions pose a challenge to clinicians and radiologists. The clinical features and imaging of neurocysticercosis and tuberculoma are exceedingly similar and it is difficult to differentiate these two conditions78.
The distinction between tuberculoma and single cysticercus granuloma is important because single cysticercus granuloma is a benign and self limiting condition, but tuberculoma is an active infection which requires prolonged therapy with potentially toxic drugs79.
Table5:Diagnostic Criteria for Human Cysticercosis1
Diagnosis is confirmed by either one absolute criterion or a combination of two major criteria, one minor criterion, and one epidemiologic criterion. A probable diagnosis is supported by the fulfillment of1:
1) One major criterion plus two minor criteria;
2) One major criterion plus one minor criterion and one epidemiologic criterion; or
3) Three minor criteria plus one epidemiologic criterion.
Unequivocal evidence of neurocysticercosis is histopathological demonstration of the parasite. Following lesions are highly suggestive of neurocysticercosis in neuroimaging, solitary cysticercusgranuloma ,spontaneous resolution or eventual calcification after several months80.
Electroimmuno-transfer blot (EITB)assay is the current serological assay of choice for the diagnosis of neurocysticercosis. This assay has a specificity of 100% and a sensitivity of 94% to 98% for patients with 2 or more cystic or enhancing lesions. But frequent false negative results in patients with a solitary intracranial cysticercus lesion, in whom less than 50% test positive. The sensitivity and specificity of EITB is also low in patients with calcified lesions81.
CSF ELISA for neurocysticercosis is 95% specific and 87%
sensitive. It is a useful supportive tool for the diagnosis. But in contrast Serum ELISA has a large number of false negative and false positive results.
TUBERCULOMA OF BRAIN
It account for 20 to 30% of intracranial space occupying lesions in India82.Tuberculoma develop in brain when the initial ―Rich focus‖
does not rupture into the meninges but expands locally with in the brain parenchyma. It may also originate in the meninges, and may be found in the superficial cortex. This meningeal form may resemble a meningioma83.
Patients with tuberculoma most often present with seizures (60 to 100%), signs and symptoms of raised ICT (56- 93%) and focal neurological deficits (33- 68%).Tuberculomas may also be multiple or military84.
There may be multiple caseating granulomas in the brain, although most of the patients (66- 73%) have single or multiple large granulomas with necrotic centre85.
Imaging features:
During the initial phase, edema and necrosis may appear as low attenuating areas on CT scan, There may be high attenuation, contrast
