Editor’s Note

Dear Colleagues,

Greetings of the season!

It's a great pleasure to present you this issue of TAPIJ, which contains valuable articles
that expands your existing knowledge of medicine.

We have two excellent review articles in this issue of TAPIJ. The article on “Approach to
diagnosis and treatment of Epilepsies” details on its pathogenesis, diagnostic aspects, treatment
options and management in the clinical settings. Another review article on the “Stress and
Diabetes” emphasizes the role of stress on insulin resistance.

We also have four detailed, interesting case reports of idiopathic CD4 lymphocytopenia,
renal failure - a reversible cause of complete heart block, an interesting case of hyponatremia and
a covariance case of pulmonary thromboembolism with quadriplegia. These case reports will
elucidate the possible pathogenesis and management of diseases.

Besides these, we have our usual articles on Toxicology, ECG and Dermatology sections.

Hence, I can assure you that this edition of TAPIJ with its articles on various aspects of
medicine will boost your clinical and academic knowledge.

With warm regards,

Dr. Vijay Viswanathan

i
 Contents
Review Articles

1. Stress and Diabetes 1

Padma V
2. Approach to diagnosis and treatment of Epilepsies 6
Chandra SR, Sahana S, Thomas Gregor Issac

Case Reports

3. A Case of Idiopathic CD4 lymphocytopenia 15

Vignesh Kumar C, Jemima Bhaskar, Malathy AR
4. Renal failure - A reversible cause of complete heart block 20
Nandhakumar V, Kalaichelvan U, Ulhas. M. Pandurangi
5. An interesting case of Hyponatremia 22
Jaiganesh M
6. A covariance case of pulmonary thromboembolism with quadriplegia
due to sensory motor neuropathy with cortical venous thrombosis 25
Devarajan TV, Anu Deenadayalu

Toxicology

7. Toxicology Clinics-Bench to Bedside. Corrosive Poisoning - Current Best Practice 29

Senthil Kumaran S, Balamurugan N, Karthikeyan V

Dermatology

8. Dermatology photo feature 33

Jayakar Thomas, Tamilarasi S

ECG – Section

9. Diagnose the ECG 35

Ulhas Pandurangi

Miscellaneous

10. Errata 36
11. Instructions of Authors 37
12. Application Forms 40

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 TAPI Journal Vol. 6, Issue 2, April - July 2014
Review Article

Stress and Diabetes

Padma V*
*Professor of Medicine, Sree Balaji Medical College, Chrompet.

Abstract more energy and increased concentration to

Stress is a condition, which causes manage stress by an increase in the levels of
disruption of homeostasis through physical or glucose from the liver, muscle and fat reserves.
psychological stimuli. In patients with diabetes,
Chronic stress
stress-induced increase of glucose is not
Chronic stress causes anger, hostility,
metabolized properly. Stress may increase glucose
depression, anxiety, eating disorders and sleeping
levels, decrease glucose levels or might have no
problems which later develop into diabetes.
effect in diabetic patients. The pathophysiological
changes that happen in patients with diabetes due 30% of diabetics are known to have
to stress will be discussed in this review article. depression, which in turn causes poor self care,
health complications, decreased quality of life and
Keywords: Stress, endoplasmic reticulum, C-Jun
increased health care costs. 15% of the patients
N–terminal kinases, Tumor necrosis factor alpha,
with depression have diabetes. Diabetic patients
IkB kinase.
on insulin therapy, also known to have depression
Introduction of around 50% and the risk of diabetes increases
Stress is “a particular pattern of disturbing to 25% in the patients on antidepressants.
psychological and physiological reactions that Screening for depression in diabetes is now
occur when an environment event threatens becoming a national recommendation in UK/US.
important motives and taxes one's ability to cope”. Depression increases the risk of diabetes
Stress causes a lot of medical health problems like and vice versa. 14% of diabetic patients have
acid peptic disease, alcoholism, asthma, diabetes, anxiety, which is also associated with poor diabetic
fatigue, tension, headache, hypertension, insomnia, control.
irritable bowel syndrome, psychoneuroses, sexual
dysfunction and skin diseases like psoriasis, lichen 10-20% of type 1 diabetics in early teens
planus, urticaria, pruritus, neurodermatitis, etc. and 20-40% of type 1 diabetics in late teens are
associated with eating disorders like bulimia.
Sources of stress are
1) External sources - job, financial problems and Stress Hyperglycemia
relationship problems. Transient increase in blood glucose
caused by stress resolves spontaneously and leads
2) Internal sources - how we perceive the stress.
to a reduction in insulin secretory capacity and its
Stress can be either physical or sensitivity. Stress hyperglycemia may be a clue to
psychological. Physical stress like surgery, illness incipient diabetes.
and injury are known to cause hyperglycemia. On
the other hand, psychological stress is likely to Pathogenesis
cause hypo or hyperglycemia in type 1 diabetes Stress causes diabetes in many ways:
patients and hyperglycemia in type 2 diabetes 1. Stress causes comfort eating, which leads to
patients. obesity. Inflammatory signaling pathways act
on the endoplasmic reticulum (ER) causes
Acute stress
overloading of the functional capacity of the
Acute stressful events increase
norepinephrine and epinephrine levels, which give

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

ER, that leads to ER stress and thus causing induces the deranged metabolic equilibrium.
insulin resistance. Obesity is associated with a state of aberrant
2. Increased mitochondrial production of immune activity and increasing risk for associated
reactive oxygen species (ROS) triggers inflammatory diseases, including atherosclerosis,
inflammatory signals which cause protein and diabetes, airway inflammation and fatty liver
lipid oxidation and hyperglycemia1. disease. It has been demonstrated that obesity
overloads the functional capacity of the ER and
3. Stress blocks the body from releasing insulin
that this ER stress leads to insulin resistance by
in type 2 diabetes patients.
the activation of inflammatory signaling
4. It produces ketoacidosis or hypoglycaemia in pathways4, 5. Increased glucose metabolism can
type 1 diabetes. lead to a rise in the mitochondrial production of
5. There is a decrease in antioxidant levels due to ROS in obesity, which activates inflammatory
increased lipid and protein oxidation. pathways6. JNK has recently emerged as a central
6. Decrease in levels of albumin, transferrin, metabolic regulator, playing an important role in
ceruloplasmin and haptoglobins. the development of insulin resistance in obesity7.
7. Stress increases cortisol level, which leads to In obesity, JNK activity, is found to be elevated in
hyperglycemia and obesity by causing a boost the liver, muscle, and fat tissues. Loss of JNK1
in appetite. prevents the development of insulin resistance and
diabetes in both genetic and dietary mouse models
8. Hyperglycemia causes a decrease in NADPH
of obesity.
which regulates the growth and death of the
beta cells. NADPH is an essential antioxidant Adipocytes secrete adipokines, which is
in which all the cellular antioxidants ultimately the pathogenesis of several components of
depend on. metabolic syndrome. Deranged HP axis increase
9. Studies using experimental models suggested the circulating cortisol and visceral fat. This
that the overproduction of TNF-alpha in promotes the release of increased free fatty acids
adipose tissue is an important feature of and thus causes insulin resistance.
obesity and contributes significantly to insulin During obesity, there is an elevation in
resistance2, 3. the levels of certain adipokines such as TNF-
The body handles stress in three ways: alpha, IL-6, leptin and Visfatin (a B cell growth
a) Fight or flight stage - acute stress response. factor). TNF-alpha and IL-6 levels are known to
promote insulin resistance. Leptin has multiple
b) Resistance stage - the stressful stage has
effects on immune function and also suppresses
disappeared, but still the body releases higher
appetite and promotes fatty acid oxidation.
levels of stress hormones.
c) Exhaustion stage - chronic stress. The Adiponectin promotes insulin sensitivity
immune system is affected, causing infection. and has antiinflammatory action. Resistin induces
Long term effects of fighting stress deplete endotoxemia/ inflammation and has variable
the body’s energy stores, causes fatigue, action in obesity. It regulates fasting blood glucose
depression, insomnia, poor appetite, level.
hypertension, diabetes, and dyslipidemia, Chemokines like IL-1, IL-IR, IL-8, IL -10,
contributing to coronary artery disease. IL-18, Monocyte Chemotactic Protein-1 levels,
soluble TNF Receptor, C-reactive protein and
Obesity
haptoglobin were also increased in obesity. IL-8,
The chronic stressful state promotes
MCP-1 and IL-18 are proatherogenic whereas
hypothalamic-pituitary (HP) axis dysfunction. It is
a systemic low grade inflammatory state that

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 TAPI Journal
J Vol. 6,
6 Issue 2, A
April - July 20
014

soluble TNF
T Receptoor, C-reactive protein andd Overrexpression of o C/EBP beeta protein in i the
haptoglob
bin are proinflaammatory cytokines. beta cells of transgenic mice leaads to diabetees and
prevention of accuumulation of this
t protein in n mice
norm malized beta cell mass an nd insulin levels10.
Macrrophages in adipose tisssue are likeely to
contribute to the production n of inflamm matory
mediiators either alone or in concert with
adipo ocytes, which suggests a po
otentially impo ortant
influuence of maccrophages in promoting in nsulin
resisttance11, 12 .
In beta cells, TNF-aalpha and eleevated
levells of free faatty acids stiimulates inhibitory
phossphorylation of serine residues
r of IRS-1
Fig..1. Potential mechhanism of beta celll failure18 (insuulin receptor substrate-1). This phosph horyla-
Inncreased environmenttal stresss tion reduces both the ability off IRS-1 to associate
destabilizees HP axis in geneticallly susceptiblee with the insuulin recepto or and tyrrosine
individuals and causees obesity. In I obesity, a phossphorylation of o IRS-1 in response
r to in
nsulin
decrease in n sex steroidss and growth hormone, thee thereeby inhibitin ng downstreaam signalingg and
malfunctio on of HP axxis and increaased levels off insullin action13.
cortisol arre reported. This rettardation of insulin recceptor
Prolonged exposure to inflaammation duee down nstream signaaling leads to o insulin resistance.
to obesityy leads to inccreased plasmma lipid levelss Receent studies have
h shown thet crucial ro ole of
and the in ncidence of insulin
i resistaance which in
n metaabolic stress in
n the activatio
on of inflamm matory
due course results in fatty liiver disease, signaaling pathwayss.
atheroscleerosis, and diab
betes. The ER stress path hway is a central
c
H
Hence, obesityy promotes states of both h proccess which actiivates both JN NK and IKK. JNK,
chronic low-grade in nflammation and insulin n a miitogen activated protein kiinase gets actiivated
resistance.. It has beeen reported that, in thee by means of various strress stimuli and
absence ofo obesity, infusion
i of animals with h inflammmatory sign nals. Whereass IKK, an en nzyme
inflammattory cytokiness or lipids can
n cause insulin
n comp plex, is invollved in propaagating the cellular
resistance8. respoonse to inflammmation. Inhiibition of ER stress
pathw way via chaaperones or other mechaanisms
Stress and
d Beta cell couldd potentially disable inflaammatory response
D
Diabetes is a multifactoriaal disease. Inn and rescue
r insulin
n action10. Extrracellular meddiators
both types of diabetes, there is a losss of beta celll like cytokines andd lipids or in ntracellular sttresses
function caused by reeducing secreetory capacityy like ER stress orr excess ROSS (reactive oxygen o
and enhan nced apoptossis. Oxidative stress causess speciies) productiion by mito ochondria acttivates
impairmen nt of beta cell function n by reactivee inflammmatory path hways like JNK and IKK. These T
oxygen and
a nitrogen species. Beeta cells aree pathw ways lead to the
t production of inflamm matory
extremely sensitive tow
wards oxidativve stress. Thee mediiators through h transcriptioonal regulation n and
most imp portant target in beta cellss to oxidativee direcct inhibition of insulin signaaling.
insult are KATP chann nels and cell metabolism9.
Other pathways
p likee those meddiated
Loss of functional KATP channells causes an n
throuugh the SO OCS (suppreessor of cyttokine
upregulation of antioxidant enzymes.
signaaling) protein
ns and iNO OS (nitric oxide

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

synthase) are also involved in inflammation- mitochondria, which inflicts oxidative damage,
mediated inhibition of insulin action. increased production of proinflammatory
Transcription factors from the PPAR (peroxisome cytokines and thus activates inflammatory
proliferator activated receptor) and LXR (liver X signaling cascades inside endothelial cells14.
receptor) families, promote nutrient transport and Endothelial injury in the adipose tissue might
metabolism and antagonize inflammatory activity. attract inflammatory cells such as macrophages to
LXR families are nuclear receptors, which regulate this site and further exacerbate the local
lipid metabolism in liver. inflammation.

Conclusion
Stress responses mediate insulin
resistance by inhibiting insulin receptor signaling
pathways. Other pathways, molecules, and
alternative mechanisms and the role of alterations
in mitochondrial function have yet to be
uncovered.
Several studies have been reported on the
association between diabetes and polymorphisms
in the promoters of TNF-alpha and IL-615, 16,
although the well-accepted polymorphism with
type 2 diabetes is found in the gene encoding
PPAR17. Altered activity of PPAR affects
susceptibility to inflammation in obesity. Genetic
variations in the FABP, JNK, IKK, or ER stress
pathways or any other loci are known to modulate
the extent of inflammation and thus insulin
resistance. It defines the risk of individuals for
developing metabolic complication of obesity.
Fig. 2. Possible mechanisms that contribute to β‑cell failure in Besides, diabetes and cardiovascular disease,
diabetes19. inflammation have become an emerging criteria
FABPs (fatty acid binding proteins) seize for linking obesity to airway inflammation and
ligands of these transcription factors and promote asthma, cancer, fatty liver and other pathologies.
to a more inflammatory environment. The cell Henceforth, a better understanding of the
must strike a balance between metabolism and mechanisms that lead from obesity to
inflammation. When there is a state of over inflammation will help to design novel therapies
nutrition, the processes required for response to to reduce the morbidity and mortality of obesity.
nutrients and nutrient utilization, like References
mitochondrial oxidative metabolism and 1. Wellen KE, Hotamisligil GS. Inflammation, stress, and
increasing protein synthesis in the ER, can induce diabetes. J Clin Invest. 2005; 115:1111-9.
the inflammatory response of JNK and thus 2. Hotamisligil GS, Arner P, Caro JF, Atkinson RL,
contributes to insulin resistance1. A second Spiegelman BM. Increased adipose tissue expression of
mechanism that initiates inflammation in obesity is tumor necrosis factor-alpha in human obesity and
insulin resistance. J Clin Invest. 1995; 95:2409-15.
oxidative stress. In hyperglycemia condition,
3. Kern PA, Saghizadeh M, Ong JM, et al. The expression
increased glucose uptake by endothelial cells and
of tumor necrosis factor in human adipose tissue.
adipose tissue causes excess production of ROS in

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Regulation by obesity, weight loss, and relationship to 13. Aguirre V, Werner ED, Giraud J, et al. Phosphorylation
lipoprotein lipase. J Clin Invest. 1995; 95:2111-9. of Ser307 in insulin receptor substrate-1 blocks
4. Ozcan U, Cao Q, Yilmaz E, Lee AH, et al. Endoplasmic interactions with the insulin receptor and inhibits insulin
reticulum stress links obesity, insulin action, and type 2 action. J Biol Chem. 2002; 277(2):1531-7.
diabetes. Science. 2004; 306:457-61. 14. Brownlee M. Biochemistry and molecular cell biology of
5. Nakatani Y, Kaneto H, Kawamori D, et al. Involvement diabetic complications. Nature. 2001; 414:813–820.
of endoplasmic reticulum stress in insulin resistance and 15. Vozarova B, Fernández-Real JM, Knowler WC, et al.
diabetes. J Biol Chem. 2005; 280:847-51. The interleukin-6 (-174) G/C promoter polymorphism
6. Lin Y, Berg AH, Iyengar P, Lam TK, et al. The is associated with type-2 diabetes mellitus in Native
hyperglycemia-induced inflammatory response in Americans and Caucasians. Hum Genet. 2003; 112:409-
adipocytes: the role of reactive oxygen species. J Biol 13.
Chem. 2005; 280:4617-26. 16. Dalziel B, Gosby AK, Richman RM, et al. Association
7. Hirosumi J, Tuncman G, Chang L, et al. A central role of the TNF-alpha -308 G/A promoter polymorphism
for JNK in obesity and insulin resistance. Nature. 2002; with insulin resistance in obesity. Obes Res. 2002; 10:401-
420(6913):333-6. 7.

8. Yu C, Chen Y, Cline GW, et al. Mechanism by which 17. Florez JC, Hirschhorn J, Altshuler D. The inherited
fatty acids inhibit insulin activation of insulin receptor basis of diabetes mellitus: implications for the genetic
substrate-1 (IRS-1)-associated phosphatidylinositol 3- analysis of complex traits. Annu Rev Genomics Hum Genet.
kinase activity in muscle. J Biol Chem. 2002; 277:50230-6. 2003; 4:257-91.
9. Drews G, Krippeit-Drews P, Düfer M. Oxidative stress 18. Popa S, Mota M. 2013. Beta-Cell Function and Failure
and beta-cell dysfunction. Pflugers Arch. 2010; 460:703- in Type 2 Diabetes, Type 2 Diabetes, Prof. Kazuko
18. Masuo (Ed.), ISBN: 978-953-51-1171-9, InTech, DOI:
10.5772/56467.
10. Matsuda T, Kido Y, Asahara S, Kaisho T, et al. Ablation
of C/EBPbeta alleviates ER stress and pancreatic beta 19. Kitamura, T. The role of FOXO1 in β-cell failure and
cell failure through the GRP78 chaperone in mice. J Clin type 2 diabetes mellitus. Nat Rev Endocrinol. 2013;
Invest. 2010; 120:115-26. 9:615–623.
11. Weisberg SP, McCann D, Desai M, et al. Obesity is
associated with macrophage accumulation in adipose
tissue. J Clin Invest. 2003; 112:1796-808.
12. Xu H, Barnes GT, Yang Q, Tan G, Yang D, et al.
Chronic inflammation in fat plays a crucial role in the
development of obesity-related insulin resistance. J Clin
Invest. 2003; 112:1821-30.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014
Review Article

Approach to diagnosis and treatment of Epilepsies

Chandra SR*, Sahana S**, Thomas Gregor Issac***
*Professor of Neurology, Department of Neurology; **Project Officer, #512' DHATHRI' 13th Cross, ISRO layout,
Bangalore 560078; ***Junior Resident, Department of Clinical Neurosciences, National Institute of Mental Health
and Neurosciences, Karnataka, India

Introduction epilepsy. It may be genetically determined,

International league against epilepsy congenital conditions like migration disorders,
defines epilepsy as a disorder of the brain heterotopias, hamartomas, vascular lesions,
characterized by an enduring predisposition to metabolic disorders or acquired conditions like
generate seizures and requiring occurrence of at CNS infections, which includes parasitic like
least one unprovoked seizures (old definition cysticercosis, fungal, viral, bacterial (chronic as
required two)1. It is a situation characterized by well as acute), vascular diseases like hemorrhage
paroxysmal alteration in motor, sensory, psychic and infarction, perinatal hypoxic ischaemic
or autonomic functions due to paroxysmal cerebral damage, head trauma and tumours.
cerebral dysrhythmia. “Epilepsy” is derived from a Sturge-Weber syndrome and tuberous sclerosis
Greek word, which means ‘to seize’ or ‘lay hold usually lead to epilepsy in early life. Convulsions
on’. An ancient Ayurvedic literature of Charaka may occur in the infants of diabetic mothers or as
Samhita (around 1,000-800 BC), called it as a result of accidental injection of local anesthetic
APASMARA, a disorder which takes the person into a child’s brain during episiotomy, or it may be
away from consciousness2. 10% of all people will pyridoxine dependent and deficient convulsions.
get at least one fit in their lifetime and one third of Convulsions can occur in the first few
them progress to epilepsy. Patients are categorized days after birth due to birth anoxia or bleed; first
as low risk if only one seizure occurs and medium few weeks due to CNS infections, hypocalcemia
risk if 2 to 3 seizures, or abnormal EEG, or or other metabolic disturbances and those
neurological abnormality. High risk if more than 2 occurring after the second week of life, usually
of the features are present. indicate developmental abnormalities of the brain.
Study done on 25,000 persons in Central Late onset seizures are often due to ischaemia,
Travancore gave the prevalence rate as 5/1,000 trauma, tumours and degenerative diseases.
persons3. The International League Against Febrile seizures, alcohol, substance abuse and
Epilepsy gives the incidence as 50-100/100,000 drugs are the other causes of seizures in adult age
population and form a serious potentially life group.
threatening emergency1. Epilepsy is a
Pathogenesis
heterogeneous condition with many etiologies
The cortical neurons become abnormally
and different factors, including etiology, age of
excitable due to disorder of ion channels,
onset, seizure control, and adverse effects related
neurotransmitters, receptors, etc. The property of
to the treatment. Epileptic encephalopathies are
neurons is to get excited. Epilepsy results when a
characterized by slow or regression of
single or group of neurons becomes abnormally
development that is attributed to epileptic activity.
excitable. An epileptic neuron is a deafferented as
Etiology of Epilepsy its dendritic spines are damaged. It has a more
Nearly 70% of the cases are idiopathic. excitatory post synaptic potential than inhibitory
(Primary or idiopathic epilepsy). In the remaining post synaptic potential and has more glutamate
cases, the etiology varies and is multi-factorial than glycine. It has poor autoregulation and the
depending upon the age of onset and the type of tight junctions are often defective and so

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

submitted to an unregulated exposure to systemic  With psychic manifestations.

metabolic fluctuations. These changes slowly B. Complex partial seizures
influence neighbouring neurons to abnormal  With simple partial features at onset
activity and the time taken for an epileptic neuron followed by impairment of consciousness
to become converted to an epileptic focus capable  With impairment of consciousness at
of putting the whole brain to abnormal activity is onset.
called maturation time. From the epileptic focus C. Partial seizures evolving to secondarily gene-
activities spread along anterior, posterior ralised seizures
commissures and corpus callosum as well as via
 Simple partial seizure – generalised
superior and inferior longitudinal association seizure
fibres. There is also electrical spread to
 Complex partial seizure – generalised
paroxysmal depolarization shift in addition to a
seizure
chemical front produced by excitatory
 Simple partial seizure – complex partial
neurotransmitters. Arrest takes place by substrate
seizure – generalised seizure.
exhaustion and diencephalocortical inhibition.
Generalized epilepsies are due to electrical activity,  Generalised Seizures
mostly of genetic nature4. Seizures are classified as A. Absence seizures
symptomatic when have a demonstrable structural B. Myoclonic seizures
cause and cryptogenic when there is a presumed C. Clonic seizures
structural cause. They are called epileptic D. Tonic seizures
syndromes, when seizures are one of the E. Tonic-clonic seizures
manifestations of a group of symptoms and signs.
F. Atonic seizures
Epileptic encephalopathy is the term applied to
seizure associated regression. Most genetic  Unclassified Seizures
epilepsies are polygenic in inheritance and some 2. Classification of epilepsies and epileptic
are single gene related like benign familial neonatal syndromes
convulsions linked to chromosome 20q, the A. Localization related (focal, local, partial) epi-
abnormal gene being KCNQ2. Others are lepsies and syndromes
CHRNA4 (20q13) associated with frontal lobe  Idiopathic with age related onset
seizures, SCN 1B (19q12.1) with febrile seizures
 Benign childhood epilepsy with
plus syndrome, LGI1 (10q24) with autosomal centrotemporal spikes
dominant partial seizures and deafness, CSTB
 Childhood epilepsy with occipital
(21q22.3) with Unverricht Lundborg disease,
paroxysms
EPM2A (6q24) with Lafora body disease and
DOUBLECORTIN (Xq21-24) with  Primary reading epilepsy.
Lissencephaly.  Symptomatic
 Chronic progressive epilepsiapartialis
Classification of Epilepsies
continua of childhood
1. Classification of Epileptic Seizures  Syndromes characterized by seizures with
 Partial Seizures specific modes of precipitation
A. Simple partial seizures  Temporal lobe epilepsies
 With motor manifestations  Frontal lobe epilepsies
 With somatosensory or special sensory  Parietal lobe epilepsies
manifestations  Occipital lobe epilepsies
 With autonomic manifestations  Cryptogenic.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

B. Generalised epilepsies and syndromes D. Special syndromes

 Idiopathic with age related onset  Situation related seizures
 Benign neonatal familial convulsions  Febrile convulsions
 Benign myoclonic epilepsy of infancy  Isolated seizures or status epilepticus
 Childhood absence epilepsy (pyknolepsy)  Seizures occurring only when there is an
 Juvenile absence epilepsy acute metabolic or toxic event caused by
 Juvenile myoclonic epilepsy (impulsive factors such as alcohol, drugs, eclampsia
petit mal) and non ketotic hyperglycemia.
 Epilepsy with grand mal seizures on Treatment Planning In Epilepsy
awakening Before planning treatment, it is important
 Other generalised idiopathic epilepsies to decide the following: Whether it is a seizure or
not defined above a seizure mimic like syncopes, non-epileptic
 Epilepsies with seizures precipitated by attacks, cataplexy, drop attacks, etc. Once the
specific modes of activation. seizure is confirmed we have to assess the chances
 Cryptogenic of recurrence. Find out any specific precipitating
 West syndrome (infantile spasms, Salam factors like use of substances and drugs, sleep
seizures) deprivation, starvation, reflex like sunlight,
 Lennox-Gastaut syndrome television, sound, eating, bathing, etc. If there is a
precipitating factor, the aim is to avoid that and if
 Epilepsy with myoclonic/astatic seizures
it is found that a patient with the first episode of
 Epilepsy with myoclonic absences. seizure belongs to the high risk group of
 Symptomatic recurrence, he should be initiated on monotherapy
 Nonspecific etiology based on the seizure type.
 Early myoclonic encephalopathy
 Early infantile epileptic
encephalopathy with suppression
burst
 Other symptomatic generalised
epilepsies.
 Specific syndromes
 Epilepsies, which form part of the
clinical profile of certain neurological
disorders.
C. Epilepsies and syndromes, undetermined Fig. 1. Expert Consensus Guidelines for the treatment of
whether focal or generalised Epilepsy
 With both generalised and focal seizures Studies, which deal with the management
 Neonatal seizures of first unprovoked seizures are the First Seizure
 Severe myoclonic epilepsy of infancy Trial Group (FIRST Study) wherein 24% of the
treated group and 42% of the untreated group had
 Epilepsy with continuous spike and wave recurrence at 2 years and in the Multi-Centre
during slow wave sleep Study of Early Epilepsy and Single Seizure (MESS
 Acquired epileptic aphasia Study) where 32% of treated and 39% of
 Other undetermined epilepsies not untreated had recurrence at 2 years. However,
included above. both groups had no better difference in the long

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

term. When the patient has more than one For absence seizures, the drugs of choice
unprovoked seizure, the treatment options for are ethosuximide and sodium valproate. In case
initiating the antiepileptic drugs/therapy (AED) is of atypical absence and atonic seizures, the drugs
as follows: of choice are valproate, clonazepam and
Preventative measure has to be taken to lamotrigine. Alternatives are topiramate,
avoid the epileptogenic AEDs for specific seizure clonazepam, zonisamide, felbamate.
types.
Myoclonic seizures can be a part of
In partial seizures, drugs such as generalized seizures and sodium valproate,
gabapentin, lamotrigene, leviteracetam, and clonazepam and clobazam are the drugs of choice.
vigabatrin are avoided. In generalized seizures, Myoclonic jerks when associated with partial
drugs like gabapentin and tiagabine can produce seizures, they are treated as partial seizures.
non-convulsive status. Benzodiazepines are
avoided in tonic seizures. During myoclonic In progressive myoclonic epilepsy
seizures, gabapentin, lamotrigene, tiagabine, syndrome, high dose of piracetam is used in
vigabatrin, diphenylhydantoin and carbamazepine addition to valproate, clonazepam and clobazam.
are avoided.
If myoclonic seizures are associated with
Patients are counseled regarding the ceroid lipofuschinosis, antioxidants are used, while
probability, that about 20% of the seizures may in Unveritch Lundborg syndrome, N-Acetyl
not be easily controlled. They are advised to cysteine is used. In myoclonic seizures associated
adhere to restrictions with reference to avoid the
with mitochondrial cytopathy, sodium valproate
specific precipitating factors. Sleep deprivation,
and phenobarbitone is avoided as they can be
starvation, excessive consumption of cerebral
stimulants like cocoa containing food, alcohol and fatal. Mitochondrial cocktail consisting of co-
fixed flickers, watching television as well as the enzyme Q10, levo carnitine, vitamin B1, vitamin
precipitants cause reflex epilepsies. Treatment E, vitamin C, alpha lipoic acid, vitamin B6,
once initiated, compliance to treatment has to be vitamin K and benzodiazepines are used6.
maintained by both patient and caregiver along Infantile spasms may be symptomatic or
with necessary education regarding the expected
idiopathic and the drug of choice is adreno
efficacy, safety and side effects of the drugs5.
corticotrophic hormone ideally when the slam
Treatment of choice differs based on seizure attacks are associated with hypsarrhythmic EEG.
type It is given as intramuscular injections at 1-3
 Partial Seizures mg/kg or 40 IU per day, which can be raised up
This includes simple, complex and to 120 IU. Remission is induced in at least 70% of
secondarily generalized seizures. Drugs of choice the patients in about 3 weeks. Then it is continued
are carbamazepine, oxcarabamazepine, clobazam, for 3 months and tapered. Relapse occurs in about
clonazepam and primidone. The alternatives drugs 30% of the patients after discontinuation. Then it
used are lamotrigine and phenobarbitone. is followed up with sodium valproate and/or
benzodiazepines. Oral steroids can be given
Gabapentin, topiramate, tiagabine, instead of ACTH at 1-2 mg/kg body weight and
levetiracetam and zonisamide can be used as add- continued for 3-5 months. Though there is a good
on therapy. effect on the progression of encephalopathy in
 Primary Generalised Tonic Clonic these patients by an unknown mechanism, the side
Seizures effect profile is often severe.
Drugs of choice are valproate, phenytoin, Benefits of extended release AEDs
leviteracetam, and phenobarbitone. Alternatives include fewer fluctuations in blood levels and
are lamotrigine, topiramate and primidone.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

hence improved seizure control tolerability, less sunlight, reading, hearing music, startle and eating.
frequent dosing and Improved compliance. Avoidance of precipitating factors and
prophylactic anticonvulsants serve to prevent the
Interactions between anti-seizure drugs
attacks. Photochromic glasses can be used for
Carbamazepine when combined with
photosensitive epilepsies. In pharmacotherapy,
phenytoin/phenobarbitone reduces the efficacy by
clonazepam, clobazam, valproate, leviteracetam
increasing its metabolism. Phenytoin when
and zonisamide were used to treat reflex epilepsy.
combined with primidone increases its toxicity by
conversion to phenobarbital. Valproic acid when  Epilepsy and Pregnancy
combined with clonazepam may precipitate non Pregnancy poses special risk to both
convulsive status epilepticus. Phenobarbital mother and child. Status epilepticus may
decreases the metabolism and increases toxicity complicate 1–2% of epileptics during labor.
of phenytoin. Seizures can cause fetal loss in addition to hypoxia
induced changes in intrauterine growth. Overall
Interaction with other drugs and fetal anomalies are more in epileptic parents. The
enhanced toxicity: teratogenic antiepileptics are better avoided and
polytherapy is reduced to monotherapy whenever
1 Antibiotics Phenytoin, phenobarbitone,
possible and sustained release preparations are
carbamazepine.
safer than multidosing. It is better to monitor free
2 Anticoagulants Phenytoin and drug levels regularly during pregnancy. Risks of
phenobarbitone. AEDs during pregnancy include fetal congenital
3 Cimetidine Displaces phenytoin, valproat malformations and developmental delay.
and benzodia zepines Teratogenicity has been established for valproate
4 Isoniazid Increases toxicity of which is associated with maximum teratotoxicity
phenytoin in the form of open neural canals. Phenytoin
5 Oral Antiepileptics toxicity produces fetal hydantoin syndrome characterized
contraceptives increased and efficacy by cleft lip, cleft palate, microcephaly and
(OCPs) of OCPs reduced hirsuitism. Minor congenital malformations occur
6 Salicylates Displaces phenytoin and in 6-20% and major abnormalities occur in 4-6%
valproate of infants exposed to these drugs in utero,
compared to 3% in babies of epileptic mothers
7 Theophylline Carbamazepine and
not exposed to drugs.
phenytoin.
Administration of 5 mg folate daily, early
Compliance in Epilepsy in pregnancy may reduce this risk. Perinatal death
Successful treatment requires patient rates of the baby may rise from 1–3.9% in
compliance and noncompliance in the primary controls to 1.3–7.8% in the case of epileptic
cause of breakthrough seizures. mothers. Low birth weight (7-10%) and
Identify and address the reasons for prematurity (4-11%) is associated with higher
noncompliance. Compliance declines as the incidence of epilepsy. Mental retardation is 8% if
number of daily doses increases and maximum only mother is affected, 4% if only the father is
compliance is achieved at once daily dosing7. affected and 25% if both are affected8.

Drugs in Special Situations Management of Women with Epilepsy

 Reflex Epilepsy  Marital and pre-conception counselling

These are epilepsies precipitated by Currently epilepsy as such is not

specific stimuli. The common stimuli are hot considered a reason for divorce. Whenever
water bath of the head, photic stimulation such as possible safer AEDs are initiated like lamotrigine,
flickering light and TV watching, exposure to levitiracetam and carbamazepine. Monitoring of

10
 TAPI Journal Vol. 6, Issue 2, April - July 2014

serum alpha-fetoprotein (AFP) in the mother for include mitochondrial cocktail (see previous
neural tube defects is recommended in addition to paragraph)6.
first trimester anomaly scanning. Oral
 Treating Epilepsy in Renal failure
supplementation of vitamin K 20 mg/day
throughout pregnancy reduces the risk of There is an alteration in the
hemorrhagic disease of the newborn. As an pharmacokinetics profile of AEDS in renal
alternative, 3 doses of 10 mg vitamin K in the last disease. Gastroparesis postpones absorption.
trimester to the mother and 1-2 mg IM to the Decrease in gut cytochrome P-450 metabolism
baby at birth can be given. Elective lower segment and in P-glycoprotein active transport results in
caesarean delivery is done in those with risk of more drug entering the portal circulation.
status epilepticus. 4 mg lorazepam intravenously Albuminuria and acidosis reduce plasma albumin
over 4 minutes is used to treat seizures and and binding affinity leading to increased free drug
pethidine is avoided. Concurrent administration of fraction. Reduced glomerular filtration and tubular
oral contraceptives along with AEDS may lower secretion increased half life of the drugs. Kidneys
serum levels of anti-epileptic drug and precipitate readily excrete water-soluble, low-protein-bound
seizures, therefore, AEDs reduces the efficacy of molecules with a small distribution volume, such
contraceptives. as gabapentin, vigabatrin, levetiracetam, and
topiramate so they can be used safely. In status
Catamenial epilepsy is treated with epilepticus, benzodiazepines combined with
acetazolamide 500mg daily or clobazam 10 mg phenytoin and fosphenytoin can be rapidly
twice daily for 5 days, before the onset of administered IV. Therapeutic range of phenytoin
menstruation. being 5-10 μg/ml and free phenytoin 1-2 μg/mL.
During hemodialysis gabapentin, vigabatrin,
topiramate, phenobarbital, and levetiracetam will
require a supplemental dose. Highly protein
bound AEDs like carbamazepine and valproate,
are less likely to require supplemental doses.
Antibiotics get trapped in the intracranial
compartment and dose adjustments are needed
for those with epileptic potential. In patients with
Fig. 2. Effective and toxic level of some common AEDs kidney stones, drugs like topiramate and
zonisamide are avoided.
Other special situations
 Endocrine Disorders
 Epilepsy and Porphyria
Carbamazepine, phenytoin, and
AEDs induce hepatic metabolism, phenobarbital (enzyme-inducing properties) may
increasing heme synthesis and therefore have considerable long-term influence on
precipitate porphyric crisis. Gabapentin and hormonal status.
levetiracetam are safe in patients with porphyria
having seizures. When there is a crisis, it is treated They may be implicated in certain bone,
with glucose and hematin infusion. Diazepam may lipid, thyroid, and sex hormone abnormalities.
control seizures9. Some of the new AEDs are less likely to have
such effects. Significant changes on the thyroid
 Seizures in Mitochondrial Cytopathy hormone system, i.e., the total and free thyroxine
Anticonvulsants, which are potential levels were significantly lower in children treated
mitochondrial poisons, can be fatal. Therefore, with phenytoin, primidone, and carbamazepine.
avoid phenobarbitone and sodium valproate and Among children and adolescents receiving

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

carbamazepine and oxcarbamazepine rapid loading is avoided. There is a less risk of

monotherapy. New AEDs with negligible enzyme- arrhythmia, hypotension with IV valproate.
inducing properties - lamotrigine, levetiracetam,
 Liver disease
gabapentin and pregabalin should be considered in
patients with clinically significant thyroid In patients with liver disease, metabolism
dysfunctions10. of AEDs is altered along with the loss of
hepatocytes, disruption of liver blood flow,
 Systemic Lupus Erythematosis (SLE) increased free AED levels and hypoalbuminemia.
Convulsions resulting from a flare of Barbiturates, sedation and hypothermia is used for
cerebral lupus may not require anticonvulsant severe intracranial hypertension. Midazolam can
therapy because they are frequently solitary and be used for clustered attacks. The dosage is
self-limited. If several seizures occur over 24 to 48 titrated to keep EEG in burst-suppression for at
hours or more, AEDs can be prescribed for a least 10 seconds. Lowering ammonia levels with
limited duration. Hydantoins and ethosuximide lactulose can stop the seizures.
drugs are mostly not prescribed, as they can
 Organ transplant
induce lupus. Carbamazepine, valproic acid,
Seizures occur due to periods of critical
primidone, and lamotrigine are occasionally
illness, various toxic, metabolic, electrolyte, and
reported to cause lupus. Drug-induced SLE
infectious abnormalities. Unique to this,
typically occurs months after anticonvulsant population with immunosuppressive toxicity cause
therapy is initiated and remits after seizure. Acute seizure management consists of
discontinuation of the offending agent. AEDs do lorazepam, diazepam and midazolam. Rapid IV
not exacerbate idiopathic SLE. Drugs of choice loading of antiepileptic is done with extreme
will be bezodiazepines and leviteracetam11. caution in patients with significant hepatic or
pancreatic dysfunction. IV administration of
 Immune compromised stated (HIV)
levetiracetam may prove advantageous to the
Seizures occur due to HIV infection by transplant population with 1-2 seizures during the
itself, mass lesions, meningitis, encephalitis, peritransplantation period, with 1 to 3 month
ischemia, metabolic derangement, and drugs. course of AED. Patients with epileptogenic brain
Treating the cause and selection of the appropriate lesions or metabolic and electrolyte imbalances
AED and consideration of the effects of co- need longer course.
administered HAART is required. Phenytoin rash Carbamazepine, oxcarbazepine, pheno-
occurs more commonly. Valproic acid may barbitone, and phenytoin may reduce cyclosporine
increase viral replication. Benzodiazepines might (CsA), tacrolimus, and corticosteroid blood levels
cause displacement of protein by HAART agents with a delayed effect of up to 10 days.
and increase free drug concentration and toxicity. Levetiracetam is advantageous in the setting of
Ideal choice of drug in these patients is severely ill transplant patients. Levetiracetam is
phenobarbitone, gabapentin, topiramate, not protein-bound or is not dependent on liver
levetiracetam, and pregabalin. cytochrome P450. 66% of it is excreted
unchanged in the urine, while 24% undergoes
 Heart Disease enzymatic hydrolysis. Valproic acid is best avoided
Phenytoin causes hypotension and in liver recipients and carbamazepine should not
arrhythmia, if it is given as rapid IV. Therefore, in be used in bone marrow recipients because it may
patients with known heart disease, not >25 cause myelosuppression. Seizures in
mg/min is advisable and fosphenytoin is found to cardiopulmonary transplant patients will need long
be a better choice. Drugs such as topiramate, term monotherapy with any one of the following
: phenytoin, fosphenytoin, or oral valproate
levetracetum, lamotrigine and gabapentin are safe.
carbamazepine, oxcarbazepine, or lamotrigine.
Phenobarbitone carries risk of hypotension so

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

 Hematological Disorders ketosis is mediated by stimulating the inhibitory

Carbamazepine can induce leucopoenia, γ-aminobutyric acid (GABA) pathways. Ketogenic
and valproate can produce abnormal platelet Diet is initiated by First 5 days, moderate fasting
function. Phenytoin produces megaloblastic followed by administration of the diet with 30%
anemia and pseudolymphoma and rarely of calorific requirement is from the fat. Adverse
lymphomas. Therefore, phenobarbitone and effects are dehydration, hypoglycemia,
leviteracetam are the drugs of choice. hyperlipidemia, constipation, osteoporosis,
carnitine depletion, renal stones hypoproteinemia
 Seizures and Megavitamin Therapy and pancreatitis. The duration to continue the
Seizures in patients with pyridoxine ketogenic diet depends on clinical response, but 3
dependent convulsions, glutaric acidurias, methyl months are needed for optimal seizure control. If
malonic aciduria, homocysteinuria and propionic seizures are under control for 2 years, then can be
aciduria respond to megavitamin therapy and not weaned off gradually. Compliance is difficult.
AEDs.
Choice of drugs based on other general
 Epilepsy in elderly parameters
The prevalence of epilepsy in the elderly If the patient is suffering from migraine
was reported as 87/ 1,00,000 in 65 -69 age group. with seizures, sodium valproate or topiramate is
It is symptomatic and mostly vascular. Lower the drug of choice. In obese patients, valproate is
doses than young is enough to treat epilepsy, as avoided, topiramate and zonisamide are
their metabolism is slow. Depending on prescribed. In anxious patients, leviteracetam is
comorbidities, drugs need modification. not prescribed. Drugs like phenytoin and
valproate are not recommended in case of young
 Epilepsies in children
female patients, in order to avoid cosmetic side
Lennox Gestaut Syndrome (LGS) effects. In hyperactive children, phenobarbitone
It constitutes 1-4% of childhood and primidone are avoided.
epilepsies. Multiple types of seizures, with mental
Other non pharmacological treatment
retardation and abnormal EEG with generalized
options are vagal stimulation, deep brain
slow spike-and-wave discharges (1.5-2.5 Hz). LGS
stimulation and surgery-specific or palliative.
can be classified as Idiopathic (22-30%) or
Symptomatic (70-78%). The mean age at onset of Withdrawal of AEDs
epilepsy is 26-28 months. Seizure control does not Withdrawal is still the biggest controversy
improve cognition. Sodium valproate, felbamate, as it might cause increased seizure frequency and
topiramate, rufinamide, lamotrigene and ketogenic severity. Withdrawal is easier for absence, but not
diet are useful. Most often, palliative surgery is for partial or generalized tonic-clonic seizures.
needed. Withdrawal of barbiturates and benzodiazepines is
West Syndrome very difficult. Patients with structural, genetic,
epileptic syndromes, neuro-developmental
Treatment options are ACTH, steroids
problems. myoclonic and multiple seizures may
and ketogenic diet.
not be able to do well without drugs. Patients
Clinical Uses of Ketogenic Diet: Induction of mild who needed polypharmacy, and relapsed following
ketosis by instituting ketogenic diet has been previous withdrawal needs caution.
found to decrease the frequency of seizures in
children. Status Epilepticus (SE)
It is defined as seizure which requires
Diet that constitutes 80% of energy from intervention to come to normality. Previously, it
fat is used to produce ketosis. The effect of was classified as recurrent seizures without gain of

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

consciousness in between or a single seizure Conclusion

lasting more than 5 minutes. Epilepsy is one of the neurological
diseases that can be managed with good result in a
Classification – SE is classified into convulsive
large number of patients, provided proper care is
and nonconvulsive types. Convulsive status may
taken in the diagnosis of epilepsy and reassessing
be absence/ tonic/ clonic/ myoclonic/ tonic-
the phenotype during every visit. Appropriate
clonic types.
monotherapy should be chosen and titrated to
Non Convulsive SE - is a state of maximum tolerated levels. Rational polytherapy
electromechanical dissociation, where the should be used only when needed. Compliance to
epileptiform discharges are evident on the EEG drugs, adherence to restrictions, management of
and are not accompanied by clinical the behavioral issues and care during special
manifestations. situations will ensure good quality of life in at least
Time management is a critical factor in 70% of these patients.
the management of SE. First 10 minutes are used
References
in restoring airway, breathing and circulation. 1. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE
Lorazepam, which is more effective than Official Report: A practical clinical definition of
diazepam is recommended, because of its longer epilepsy. Epilepsia. 2014; 55:475–482.
duration of action of more than 4 hrs and less 2. Pierce JMS. A disease once sacred. A history of the
respiratory depression. Simultaneously a loading medical understanding of epilepsy. Brain. 2002; 125:441-
dose of IV phenytoin 0.5-1gm (18-30 mg/kg) in 442.
saline is given over 20 minutes, at the rate of 3. Radhakrishnan K, Nayak SD, Kumar SP, Sarma PS.
Profile of antiepileptic pharmacotherapy in a tertiary
50mg/minute or fosphenytoin (150mg equivalent
referral center in South India: a pharmacoepidemiologic
to 100mg of phenytoin) is given in dose of 15 to and pharmacoeconomic study. Epilepsia 1999; 40: 179-
20mg/kg at a rate of 75 to 150mg/min. 85.
Phenobarbitone given IV in doses of 0.8 to 4. Huff JS, Fountain NB. Pathophysiology and definitions
1gm/kg in 24 hrs (20mg/kg at100mg/min) is of seizures and status epilepticus. Emerg Med Clin North
effective, if further seizures occur. In intractable Am. 2011; 29:1-13.
cases, thiopental anaesthesia was given as IV 5. Karceski S, Morrell MJ, Carpenter D. Treatment of
injection of 0.3 to 0.6 gm. Assisted ventilation is epilepsy in adults: expert opinion, 2005. Epilepsy Behav.
2005; 7 Suppl 1:S1-64; quiz S65-7.
mandatory, when penobarbitone or thiopentone is
6. Tarnopolsky MA. The mitochondrial cocktail: rationale
given. Levitiracetam (3rd line) is given in a dose of
for combined nutraceutical therapy in mitochondrial
20 to 30mg/kg as bolus IV over 15 minutes cytopathies. Adv Drug Deliv Rev. 2008; 60(13-14):1561-7.
followed by maintenance of 1500mg b.d. orally or 7. Karceski S. Taking epilepsy medications consistently:
IV. Sodium Valproate (3rd line) is given as 15 to why it makes a difference. Neurology. 2014; 82(8):e71-2.
30 mg/kg as loading dose and maintained as 8. Nulman I, Laslo D, Koren G. Treatment of epilepsy in
500mg t.d.s. Lacosamidein doses (50mg/min) is pregnancy. Drugs. 1999; 57(4):535-44. Erratum in Drugs.
repeated twice a day. Buccal application or intra 1999; 57(6):870.
nasal spray or rectal Diazepam can be tried in 9. Ruiz-Giménez J, Sánchez-Alvarez JC, Cañadillas-
children. Consider the reversible factors like Hidalgo F, Serrano-Castro PJ; Andalusian Epilepsy
Society. Antiepileptic treatment in patients with epilepsy
hyponatremia, hypoglycemia, acidosis,
and other comorbidities. Seizure. 2010; 19(7):375-82.
hypocalcemia, hypoxia, hypomagnesemia, and
10. Cansu A. Antiepileptic drugs and hormones in children.
hyperthermia. Emergency investigations include Epilepsy Res. 2010; 89:89-95.
blood gases, glucose, renal and hepatic functions, 11. Ong MS, Kohane IS, Cai T, Gorman MP, Mandl KD.
calcium, magnesium, full blood count and Population-level evidence for an autoimmune etiology
screening for the presence of a clot. Toxicology of epilepsy. JAMA Neurol. 2014; 71:569-74.
screening may be done in suspected cases. ECG
has to be done as soon as the patient arrives.

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Case Report

A Case of Idiopathic CD4 lymphocytopenia

Vignesh Kumar C*, Jemima Bhaskar**, Malathy AR***
*Senior Resident in Internal Medicine, **Associate Professor of Medicine,
***Professor of Medicine, ESI Medical College, PGIMSR and Model Hospital, Chennai

Abstract field with 100% lymphocytes, CSF Glucose was

Opportunistic infections are infrequent in 11mg/dl, protein was 348mg/dl and chloride
immunocompetent individuals. If such an event 113mg/dl. Acid-Fast Bacilli (AFB) smear and
occurs, the search should be intensified to identify India ink preparation were found to be negative.
an uncommon cause. Such intensive search can Cryptococcal antigen was detected in CSF by
unveil a reasonably common occurrence of an Latex agglutination. HIV screening showed
uncommon entity. A 40 year old male with no negative. CSF culture results revealed no growth.
high risk behavior was admitted with chronic He was diagnosed to have cryptococcal meningitis
headache and fever with some personality and was treated with intravenous amphotericin B
changes. He was evaluated to have cryptococcal and flucytosine for duration of 4 weeks and
meningitis and was treated with antifungals. He discharged after one month with an advice to
was found to be HIV negative and he was continue fluconazole 800mg for 6 months. On
discharged. He had a relapse of meningitis and review after one week, he had personality changes,
was treated with a prolonged course of but no focal sensory or motor deficit or neck
antifungals. An intensive search for an uncommon stiffness. HIV test was repeated and was found to
cause for immunodeficiency identified a be negative. Immunoglobulin profile was
persistently low CD4 count, which satisfies the performed to identify a cause for
criteria for Idiopathic CD4 lymphocytopenia. immunodeficiency and was within normal range.
A CD4 count was found to be 268 cells/[Link].
Keywords: Cryptococcal meningitis, Idiopathic CD4
MRI of the brain showed asymmetric enlargement
Lymphocytopenia
of the lateral ventricles, left larger than right,
Case Report enlarged choroid plexuses, periventricular
A 40-year-old male patient presented with extravasation of CSF, leptomeningeal
illness of persistent fever for the past 6 weeks enhancement and edema in bilateral posterior
along with holocranial headache for which he had basal ganglia. He continued on the tablet,
taken multiple courses of antibiotics. He had no fluconazole. On review after another 3 weeks, his
significant medical illness in the past and had no sensorium had deteriorated and he had dysarthria,
higher risk behavior. He was hemodynamically neck stiffness, extrapyramidal signs in the form of
stable, conscious, oriented and the systemic rigidity of all 4 limbs and static tremors. Release
examination was normal. He had no neck stiffness reflexes such as glabellar tap and palmomental
or focal neurological deficits. Fundus examination reflexes were present. His extraocular movements
revealed no papilledema. Complete haemogram, were full and plantar were flexor. A repeat CT
renal parameters, liver function tests and chest brain showed isolated enlargement of frontal horn
X-ray was within normal limits. Fever of left lateral ventricle and MRI brain with
investigations like MP-QBC test, IgM titres for contrast was suggestive of choroids plexitis and
Leptospira and blood and urine cultures were also ventriculitis. Repeat CSF analysis showed CSF
found to be negative. CT scans for brain revealed glucose - 30mg/dl, protein 848mg/dl, cell count
asymmetric dilatation of the lateral ventricles. of 35 cells with 100% lymphocytes and latex
Cerebrospinal Fluid (CSF) analysis results are as agglutination positive for cryptococcus. He was
follows: 155 white blood cells per high-power started once again on the injection amphotericin B

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

for an extended period of 6 weeks with the Discussion

periodic monitoring of renal parameters and Idiopathic CD4 lymphocytopenia (ICL)
potassium levels. He was provided supportive was first defined in 1992 by the Centers for
care, including physiotherapy, bladder care and Disease Control and Prevention (CDC) as:
back care. His sensorium improved, fever and  CD4 T-lymphocyte depletion (number of
headache was subsiding and complete resolution absolute CD4+ T-lymphocyte level
of extrapyramidal signs occurred. A repeat CD4 decrease to <300 cells/[Link] or <20%
count was done after 6 weeks and was found to be of total lymphocytes) at a minimum of
284 cells/[Link], this fulfills the criteria for two separate time points at least 6 weeks
idiopathic CD4 lymphocytopenia. He was apart;
ambulant at the end of 5 weeks and was
 no serological evidence of HIV infection;
discharged with an advice to continue tablet,
fluconazole 800 mg daily for 6 months with  an absence of any defined
monitoring of CD4 count at the end of every 6 immunodeficiency or therapy associated
months. He presented for review after 3 months with depressed levels of CD4 T-cells.1-4
and was doing well, but subsequently lost to The pathogenesis may be multifactorial.
follow-up as he left to his native place in North- To explain this syndrome, researchers have
East India and could not be traced. proposed several hypotheses:
 diminished generation of T-cell
precursors;
 increased T-cell apoptosis;
 biochemical failure of the CD3-T-cell
receptor (TCR) pathway by p56 Lck
(a lymphocyte-specific tyrosine kinase)
alteration;
 defective production of cytokines;
 CD4 T-cell antibodies.5
The clinical spectrum of ICL ranges from
an asymptomatic laboratory abnormality to life-
Fig. 1. CT Brain shows asymmetric lateral ventricles threatening complications that imitate the clinical
course of AIDS patients. ICL is typically revealed
by the emergence of opportunistic infection,
including Cryptococcus, Mycobacteria, Pneumocystis
Carini, Candidiasis and Cytomegalovirus. Malignancies
were reported in 18.1% of the patients among
which lymphoma with its subtypes was the most
common. Autoimmune diseases were reported in
14.2% patients6. Sjogren’s disease was the most
commonly reported autoimmune diseases in ICL
patients and it has been suggested to screen all
patients with ICL for Sjogren’s syndrome7.

Fig. 2. MRI Brain shows cystic dilatation of left lateral ventricle

with periventricular CSF leak

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

increase their chance of recovery as defective

production of the proinflammatory cytokines
IFN-γ and TNF-α in patients with CD4
lymphopenia is likely to be a key mechanism
responsible for the increased risk of invasive
cryptococcal infections in patients with ICL15.
Allogeneic bone marrow transplantation resulted
in restoration of CD4+ T lymphocyte counts in
one patient with ICL complicated by
opportunistic infections and aplastic anemia16.
Fig. 3. Graphical representation of most common infections in
Cryptococcal meningoencephalitis has
Idiopathic CD4 lymphocytopenia6
been the most frequently encountered
HIV is the most important differential manifestation of cryptococcosis. Most patients
diagnosis of CD4 lymphocytopenia. Transient with cryptococcal meningitis are
CD4 lymphocytopenia has been estimated to immunocompromised. The most common forms
occur in 0.4‑4.1% of healthy HIV‑negative of immunosuppression, other than HIV include
individuals8. Infections, malignancies, medications glucocorticoid therapy, solid organ
and autoimmune diseases can lead to transient transplantation, cancer (particularly hematologic
CD4 lymphocytopenia. Opportunistic bacterial9, malignancy), sarcoidosis and hepatic failure. In a
viral, parasitic, and fungal diseases may depress multicenter retrospective study of 157 cases of
CD4 cell counts. CNS cryptococcosis in HIV-negative patients, 30
17
Due to the rarity of this condition, no percent had no apparent underlying condition .
specific guidelines exist for prophylaxis, Clinical presentation of cryptococcal
monitoring, and treatment. Therefore, the meningoencephalitis in HIV seronegative patients
management is based on the experience with HIV is variable. Some patients present with an acute
treatment. Prophylaxis against opportunistic illness and some have symptoms for up to several
infections is advised by means of the protocols months. Most patients present with signs and
advocated for HIV‑1 infected patients with symptoms of subacute meningoencephalitis viz.,
advanced disease. Monitoring every four months fever (in approximately 50 percent of cases)
17,18
,
with CD4 counts might be sufficient for stable headache, lethargy, personality changes, and
patients without apparent infections. Once these memory loss developing over 2 to 4 weeks.
patients develop signs of infection, they need Patients may also present with disseminated
close attention6. A few investigators reported disease.
successful treatment with IL‑2 for opportunistic
infection associated with ICL. The idea of IL-2 A lumbar puncture is necessary to
came from its use in HIV patients with definitively diagnose cryptococcal
CD4+ lymphopenia. IL‑2 has showed significant meningoencephalitis, although this procedure
increase in CD4 counts and possible clinical should be delayed in the setting of focal
improvement in immunological function. Limited neurologic signs, papilledema, or impaired
data have shown it to be relatively safe and mentation pending the results of radiographic
potentially effective treatment, especially when imaging. MRI is more effective than CT for
19
combined with conventional treatment regimens10- identifying CNS cryptococcal lesions .
14. Recombinant IFN-γ in severe cryptococcal Radiographic images frequently show no
infections restores the Th1-type cytokine abnormality or cerebral atrophy without
20
production and boosts antifungal defense and obstruction or hydrocephalus. Mass lesions are

17
 TAPI Journal Vol. 6, Issue 2, April - July 2014

seen in about 10 percent of patients with CNS chronic headache, particularly if the patients also
cryptococcal infections18. Choroid plexus have one of the following characteristics: fever,
involvement in the form of unilateral or bilateral weakness or anorexia, neurological complaints, or
enlargement of the choroid plexus that enhances abnormal neuroradiologic findings. Imaging
on contrast, with trapping of the temporal horns, findings of a strongly enhancing choroid plexus,
is a rare manifestation in immunocompetent cystic lesions in the basal ganglia, meningeal
hosts. Gelatinous pseudocysts and enhancement and an intraventricular lesion in
cryptococcomas in the choroid plexus are such a patient should suggest a diagnosis of
relatively specific for CNS cryptococcosis. cryptococcal infection.
Choroid inflammation can progress to
References
ependymitis, intraventricular synechiae, loculation
1. Centers for Disease Control (CDC). Unexplained CD4+
or enlargement, and entrapment of the temporal T-lymphocyte depletion in persons without evident HIV
horn owing to the obstruction of flow by infection--United States. MMWR Morb Mortal Wkly Rep.
cryptococci21. 1992; 41:541.
2. Smith DK, Neal JJ, Holmberg SD. Unexplained
Treatment of cryptococcal meningitis in
opportunistic infections and CD4+ T-lymphocytopenia
non HIV, non organ transplant patients include an without HIV infection. An investigation of cases in the
induction therapy with amphotericin B (0.7-1.0 United States. The Centers for Disease Control
mg/kg per day) plus flucytosine (100 mg/kg per Idiopathic CD4+ T-lymphocytopenia Task Force. N
day) for 4 weeks or amphotericin B (0.7-1.0 Engl J Med. 1993; 328:373.
mg/kg per day) alone for 4 to 6 weeks, followed 3. Ho DD, Cao Y, Zhu T, et al. Idiopathic CD4+ T-
by consolidation therapy with fluconazole (400- lymphocytopenia - immunodeficiency without evidence
800 mg per day) for 8 weeks and maintenance of HIV infection. N Engl J Med. 1993; 328:380.

therapy with Fluconazole (200 mg per day) for 4. Spira TJ, Jones BM, Nicholson JK, et al. Idiopathic
CD4+ T-lymphocytopenia--an analysis of five patients
6-12 months22, 23. The role of steroids in the
with unexplained opportunistic infections. N Engl J Med.
treatment of cryptococcal meningitis in non-HIV 1993; 328:386.
individuals remain controversial24, 25.
5. Luo L, Li T. Idiopathic CD4 lymphocytopenia and
Five cases of cryptococcal meningitis in opportunistic infection-an update. FEMS Immunol Med
immunocompetent patients have been reported, Microbiol. 2008; 54:283-9.

however estimation of CD4 count was not done 6. Ahmad DS, Esmadi M, Steinmann WC. Idiopathic CD4
Lymphocytopenia: Spectrum of opportunistic infections,
as a part of their study26. Four cases of Idiopathic
malignancies, and autoimmune diseases. Avicenna J Med.
CD4 lymphocytopenia have been reported in 2013;3:37-47
India, all of which presented with cryptococcal
7. Kirtava Z, Blomberg J, Bredberg A, et al. CD4+
infection27-30. Three had cryptococcal meningitis T‑lymphocytopenia without HIV infection: increased
and one had disseminated cryptococcal infection prevalence among patients with primary Sjogren’s
with cavernoesophageal fistula30. Among them syndrome. Clin Exp Rheumatol. 1995; 13:609‑16
three of them survived and one expired29. 8. DeHovitz JA, Feldman J, Landesman S. Idiopathic
CD4+ T‑lymphocytopenia. N Engl J Med. 1993;
Conclusion 329:1045‑6.
CNS cryptococcosis is uncommon in 9. Fantin B, Joly V, Elbim C, et al. Lymphocyte subset
non-immunosuppressed hosts, but it causes counts during the course of community‑acquired
significant mortality and long-term morbidity. It is pneumonia: evolution according to age, human
often not considered during the evaluation of immunodeficiency virus status, and etiologic
microorganisms. Clin Infect Dis. 1996; 22:1096‑8.
non-immunosuppressed patients. Cryptococcal
meningitis should be included in the differential 10. Wilhelm M, Weissinger F, Kunzmann V, Muller JG,
Fahey JL. Idiopathic CD4+ T cell lymphocytopenia
diagnosis for all the patients who present with
evolving to monoclonal immunoglobulins and

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progressive renal damage responsive to IL‑2 therapy. 20. Graybill JR, Sobel J, Saag M, et al. Diagnosis and
Clin Immunol. 2001; 99:298‑304. management of increased intracranial pressure in
11. Yilmaz‑Demirdag Y, Wilson B, Lowery‑Nordberg M, patients with AIDS and cryptococcal meningitis. The
et al. Interleukin‑2 treatment for persistent cryptococcal NIAID Mycoses Study Group and AIDS Cooperative
meningitis in a child with idiopathic CD4(+) T Treatment Groups. Clin Infect Dis. 2000; 30:47.
lymphocytopenia. Allergy Asthma Proc. 2008; 29:421‑4. 21. Kumari R, Raval M, Dhun A. Cryptococcal choroid
12. Warnatz K, Draeger R, Schlesier M, Peter HH. plexitis: rare imaging findings of central nervous system
Successful IL‑2 therapy for relapsing herpes zoster cryptococcal infection in an immunocompetent
infection in a patient with idiopathic CD4+ T individual. Br J Radiol. 2010; 83:e14-7.
lymphocytopenia. Immunobiology 2000; 202:204‑11. 22. Perfect JR, Dismukes WE, Dromer F, et al. Clinical
13. Cunningham‑Rundles C, Murray HW, Smith JP. practice guidelines for the management of cryptococcal
Treatment of idiopathic CD4 T lymphocytopenia with disease: 2010 update by the infectious diseases society of
IL‑2. Clin Exp Immunol. 1999; 116:322‑5. America. Clin Infect Dis. 2010; 50:291.

14. Trojan T, Collins R, Khan DA. Safety and efficacy of 23. Brouwer AE, Rajanuwong A, Chierakul W, et al.
treatment using interleukin‑2 in a patient with idiopathic Combination antifungal therapies for HIV-associated
CD4(+) lymphopenia and Mycobacterium cryptococcal meningitis: a randomised trial. Lancet 2004;
avium‑intracellulare. Clin Exp Immunol. 2009; 156:440‑5. 363:1764.

15. Netea MG, Brouwer AE, Hoogendoorn EH, et [Link] 24. Saag MS, Graybill RJ, Larsen RA, et al. Practice
patients with cryptococcal meningitis and idiopathic guidelines for the management of cryptococcal disease.
CD4 lymphopenia: defective cytokine production and Infectious Diseases Society of America. Clin Infect Dis.
reversal by recombinant interferon- gamma therapy. Clin 2000; 30:710–8.
Infect Dis. 2004; 39:e83-7. 25. Lane M, McBride J, Archer J. Steroid responsive late
16. Petersen EJ, Rozenberg-Arska M, Dekker AW, et al. deterioration in Cryptococcus neoformans variety gattii
Allogeneic bone marrow transplantation can restore meningitis. Neurology 2004; 63:713–4.
CD4+ T-lymphocyte count and immune function in 26. Sanchetee P. Cryptococcal meningitis in
idiopathic CD4+ T-lymphocytopenia. Bone Marrow immunocompetent patients. J Assoc Physicians India. 1998;
Transplant. 1996; 18:813. 46: 617-619.
17. Pappas PG, Perfect JR, Cloud GA, et al. Cryptococcosis 27. Sharma A, Lal V, Modi M, et al. Idiopathic CD4
in human immunodeficiency virus-negative patients in lymphocytopenia presenting as refractory cryptococcal
the era of effective azole therapy. Clin Infect Dis. 2001; meningitis. Ann Indian Acad Neurol. 2010; 13:136-8.
33:690. 28. Jha S, Ghosh P, Agarwal V. Cryptococcal meningitis
18. Cox, GM, Perfect, JR. Cryptococcus neoformans var unmasking idiopathic CD4 lymphocytopenia. Neurol
neoformans and gattii and Trichosporon species. In: India. 2007; 55:312-4.
Topley and Wilson's Microbiology and Microbial 29. Nair JP, Athavale AU, Gawande S, et al. Disseminated
Infections, 9th ed, Ajello, Edward (Ed), Arnold Press, Cryptococcosis with Caverno-Oesophageal Fistula in a
London 1997. Case of Idiopathic CD4+ T-Lymphocytopenia, J Assoc
19. Charlier C, Dromer F, Lévêque C, et al. Cryptococcal Physicians India. 2014; 62:66-69.
neuroradiological lesions correlate with severity during 30. Augustine R, Khalid M, Misri ZK, Hegde S. Idiopathic
cryptococcal meningoencephalitis in HIV-positive CD4+ T-lymphocytopenia - a diagnostic dilemma. J
patients in the HAART era. PLoS One. 2008; 3:e1950. Assoc Physicians India. 2010; 58:45-7.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014
Case Report

Renal failure ‐ A reversible cause of complete heart block

Nandhakumar V*, Kalaichelvan U, Ulhas. M. Pandurangi**
* Cardiology Registrar; **Senior Consultant Cardiologist & Electrophysiologist,
The Madras Medical Mission, Mogappair, Chennai‐37. India.
Email: arrhythmiaheartfailureacademy@[Link]

Case Study His arterial blood gas analysis report revealed the
A 64 year old gentleman presented with partial pressures of oxygen (pO2) - 86mm Hg and
acute onset of progressive breathlessness for the carbon dioxide (pCO2) - 29mm Hg and the blood
past one week. His clinical examination revealed pH-7.22. His bicarbonate (HCO3) level was found
the pulse rate of 35 beats per minute, blood to be 11meq/L. The results of hematogram and
pressure of 180/80mmHg, facial puffiness and general biochemistry analyses are as follows:
bilateral pedal edema. hemoglobin was 9.8g/dl, total count was
7900/mm3, blood urea 52mg/dl, serum creatinine
He was a known case of diabetes,
3.6mg/dl, sodium 135meq/L, potassium 5.5
hypertension, chronic kidney disease and lumbar
meq/L, calcium 7.8mg/dl , phosphate 5.5mg/dl
spondylosis. His medication includes metoprolol
and magnesium 2.0 mg/dl. His chest X-ray and
50mg twice a day, clinidipine 10mg twice a day
echocardiogram were within normal limits.
and anti diabetic drugs [glimepiride and
metformin]. Significant bradycardia due to complete
heart block was considered responsible for the
On admission, his electrocardiogram patient symptoms. A temporary pacemaker (VVI
(ECG) revealed a complete heart block with an mode) was implanted to achieve a ventricular rate
atrial rate of 70 beats per minute and slow of 80 beats per minute [Fig. 2].
irregular ventricular rate of 30-50 beats per
minute. The QRS complexes were wide and not
of uniform morphology suggestive of unstable
ventricular escape rhythm [Fig. 1].

Fig. 2. Temporary Ventricular Pacing.

Metoprolol was stopped and clinidipine
was continued. Soon after achieving the pacing, a
remarkable improvement in the rhythm of the
Fig. 1. Complete heart block with an atrial rate of 70 beats per patient was noted. His blood pressure was almost
minute and irregular, slow ventricular rate of 30-50 beats per normalized even after withholding
minute, the QRS complexes were wide and not of uniform antihypertensive drugs. Over a period of 6 days,
morphology suggestive of unstable ventricular escape rhythm. we observed a gradual improvement in his urine

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

output and normalization in the levels of arterial

blood gases as well as electrolytes. Concomitantly,
the intrinsic sinus rhythm and A-V conduction
also showed improvement [Fig. 3, 4]. There was a
gradual acceleration of sinus rate, intermittent A-V
conduction and normalization of QRS complexes.
The patient was observed for 2 more days and
maintenance of stable sinus rhythm with normal
A-V conduction were confirmed [Fig. 5] and the
patient was discharged in a stable condition.

Fig. 5. Day 6- Normalization of rhythm including heart rate,

PR interval and also QRS complexes.

Discussion
In a case of acquired complete heart
block one should always look for the reversible
causes. The common reversible causes are:
1. Drug induced
2. Acute myocardial infarction
3. Myocarditis
4. Electrolyte/ Acid-Base imbalance
5. Metastasis, infiltration, compression or trauma
of the conduction system.
Fig. 3. Day 2- intrinsic rhythm: evidence for resolving CHB- In case of chronic kidney disease, the
intermittent A-V conduction (the second and third QRS pathologic process of myocardial fibrosis and
complexes in the rhythm strip appear to be the result of metastatic calcification may alter the mechanical
conducted P waves). and electrical components of the myocardium and
conduction system which become sensitive to the
adverse effects of acid-base imbalances. The
milieu of metabolic acidosis, hyperkalemia,
hyperphosphatemia and hypocalcaemia in our
patient of chronic kidney disease who was also on
rate limiting drug (metoprolol) predisposed to the
development of complete heart block.
Though our patient showed gradual
improvement in A-V conduction leading to
avoidance of permanent pacemaker, he will be
watched over closely since the chances of
recurrence of complete heart block are high either
because of progression of primary conduction
disease or worsening of renal function eventually
or both.
Fig. 4. Day 3- Intrinsic Rhythm-2:1 A-V Block, Wide QRS Lesson from this case report
(RBBB, Left Axis Deviation) In a case of the acquired complete heart
block, always look for the reversible causes.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014
Case Report

An Interesting case of Hyponatremia

Jaiganesh M*, M.D., Postdoctoral Fellowship (Diabetology)
*Consultant Physician and Diabetologist, M. V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research
Centre [WHO Collaborating Centre for Research, Education and Training in Diabetes]
No. 4, West Madha Church Road, Royapuram, Chennai‐600 013. Tamil Nadu.

Abstract S1, S2 + and no murmurs. Examination of her

A 70 year old female, a known case of respiratory system revealed RS: NVBS, and no
type 2 diabetes and hypertension reported to the added sounds. Results of other examinations are
hospital with giddiness, fecal and urinary abdomen - soft, no organomegaly, CNS: skull
incontinence and an abnormal gait since 2- 3 days. defect present, X-ray and ECG analysis were
On examination, the patient appeared drowsy, normal. Her ECHO study exposed normal LV
disoriented and confused. With no other signs of systolic function.
pallor, cyanosis, clubbing, pedal edema, and Laboratory investigations revealed: TSH
dehydration. Exhaustive investigations revealed was 3.0 μIU/ml, serum urea was 27mg/dl, serum
the hypoosmolar hyponatremia condition and uric acid was 2.3mg/dl, and creatinine level was
thus, presenting an interesting case of the 1.1mg/dl instead of 1.3mg/dl and serum glucose
syndrome of inappropriate antidiuretic hormone level in fasting were 123mg/dl and postprandial
secretion (SIADH). was 218mg/dl. The results of urine examination
Keywords: Sodium, Antidiuretic hormone, are as follows: Pus cells: 6-8, Epithelial cells: 2-3,
Hyponatremia, Giddiness, Tolvaptan. Specific gravity: 1.025, pH: 6.0, Proteins: ++,
Glucose: ++ and Ketones: nil. Her arterial blood
Case Report gas analysis reports showed normal. The sodium
level was 108 mEq/L, reporting a state of
Presentation
hyponatremia. The MRI study revealed the
A 70 year old female with a 17-year
features suggestive of age related atrophic changes
history of type 2 diabetes and 12-year history of
and lacunar infarcts. The neurologist's opinion
hypertension presented with giddiness, fecal and
was the metabolic encephalopathy due to
urinary incontinence and an abnormal gait in the
hyponatremia. Hyponatremia was treated by the
last 3, 2, and 2 days respectively. She had a past
administration of 3% saline at the rate of 25 ml
surgical history of brain tumor- Glioma, which
/hr. The level of sodium was raised to 118
was excised 3 years back. She also had an
mEq/L, but in the subsequent day, sodium levels
intermittent history of drowsiness and lethargy.
were again reduced to 112 mEq/L. Further,
Previously, she had 3 repeated admissions in other
laboratory investigations revealed: serum
hospitals for hyponatremia. There was no history
osmolarity was 242 mosmol/l, urinary Na was +
of head injury, radiation exposure, and acute CNS
45 mmol/l and urine osmolarity was 237
or lung infections.
mosmol/l. These findings lead to the suspicion of
On examination, the patient appeared SIADH and was diagnosed as chronic SIADH
drowsy, disoriented and confused. There were no since the laboratory investigations met the criteria
signs of pallor, cyanosis, clubbing, pedal edema, for SIADH (Table 1) and there was a prior
and dehydration and her levels of jugular venous repeated admissions for hyponatremia.
pressure (JVP) was normal.
Antihyperglycemic drugs and
Her systemic examination revealed a antihypertensive drugs (amlodipine) were given to
normal heart rate and rhythm evidenced by CVS: stabilize her glycemia and blood pressure. Fluid

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

intake was restricted to 800ml/day and tolvaptan Pathophysiology

(15mg/day) was prescribed to treat SIADH. The Vasopressin (ADH) is secreted from the
patient was discharged in a stable condition, with a posterior pituitary gland in response to:
sodium level of 133 mEq/L. Tolvaptan was a) decrease in plasma volume (dehydrated state),
discontinued and the patient was advised to be on b) increases in the plasma osmolality, and c)
fluid restriction, 1.2 L/day. As these patients have cholecystokinin (CCK) secreted by the small
a permanent risk of worsening hyponatraemia, the intestine. During dehydration, posterior pituitary
patient was advised to take regular check ups to gland secretes ADH to increase the water
determine the sodium levels. During the patient reabsorption in the collecting ducts of the kidney
follow up visits, the sodium levels were found to nephron. This action prevents the water loss in
be normal. the kidneys and helps to normalize the blood
Diagnosis osmolality. In SIADH, the inappropriate secretion
Syndrome of Inappropriate Secretion of of ADH cause excess dilution of plasma
Anti-Diuretic Hormone (SIADH) electrolyte (sodium) concentration which creates a
hypoosmolar hyponatremia state. Hyponatremia
Discussion in SIADH is not primarily due to serum sodium
The syndrome of inappropriate deficiency, but as a result of excess water retention
antidiuretic hormone secretion (SIADH), also and is usually detected as a low sodium level on
called as Schwartz-Bartter syndrome and laboratory testing.
syndrome of immoderate antidiuresis (SIAD), is SIADH is usually treated with fluid
characterized by an extreme release of antidiuretic restriction (in particular water).
hormone (ADH) from the posterior pituitary
gland or another source. The clinical features of Diagnosis
SIADH include anorexia, nausea, muscle aches, In a patient with clinical euvolemia, the
generalized muscle weakness, myoclonus, following laboratory investigations are performed
hyporeflexia, ataxia pathological reflexes, tremor, to determine the serum and urine sodium and
asterixis and Cheyne-Stokes respiration, dysarthria, osmolality, low serum osmolality, high urine
lethargy, confusion, delirium, seizures, and coma sodium (>40 mmol/L) and urine osmolality (>100
(due to cerebral edema). mOsm/kg, often > serum osmolality), and to
confirm the SIADH (Table 1).
Pathogenesis
The common causes of SIADH are Table 1. Diagnostic criteria for SIADH
meningitis, head injury, subarachnoid hemorrhage, 1. Euvolemic hyponatremia <134 mEq/L with
cancers, brain tumor/surgery, lung cancer plasma osmolality, POsm <275 mOsm/kg
(especially small-cell lung cancer, as well as other 2. Urine osmolality >100mOsm/kg of water
small-cell malignancies of other organs), during hypotonicity2
infections, brain abscess, pneumonia, lung abscess, 3. Urine sodium concentration >40 mEq/L with
and Guillain-Barré syndrome. Intake of drugs like normal dietary salt intake.
chlorpropamide, ciprofloxacin, clofibrate, 4. Clinical euvolemia without edema or ascites.
moxifloxacin, phenothiazine, ifosfamide, No evidence of dehydration, low blood urea
nitrogen (BUN), normal serum creatinine, low
vincristine, oxcarbazepine, cyclophosphamide,
uric acid, normal acid-base and K+ balance,
oxytocin, carbamazepine, selective serotonin
5. Normal adrenal and thyroid function.
reuptake inhibitors, morphine and amitriptyline
can cause hyponatraemia. Other causes include The differential diagnosis involves
hypothyroidism and sarcoidosis. psychogenic polydipsia, congestive heart failure,
cirrhosis and cerebral salt wasting syndrome.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

Management High index of suspicion and application

The treatment for SIADH includes: of criteria for SIADH is required in cases of
a) Treating the possible underlying causes, euvolemic hyponatremia. This can help in the
b) Long-term fluid restriction of 1,200–1,800 early detection of SIADH and management.
mL/day3 in order to increase serum sodium References
through decreasing total body water, 1. Rose BD, Post TW. Clinical Physiology of Acid-Base
c) For very symptomatic patients (severe and Electrolyte Disorders, 5th ed, McGraw-Hill, New
York 2001. p.703.
confusion, convulsions, or coma) hypertonic
2. Babar SM. SIADH associated with ciprofloxacin. Ann
saline (3%) 1–2 ml/kg IV in 3–4 hr is advised.
Pharmacother. 2013; 47:1359-63.
d) Drugs like Conivaptan4 (an antagonist of both 3. Rivkees SA. Differentiating appropriate antidiuretic
V1A and V2 vasopressin receptors), hormone secretion, inappropriate antidiuretic hormone
Demeclocycline4 (used in chronic situations when secretion and cerebral salt wasting: the common,
fluid restrictions are difficult to maintain), uncommon, and misnamed. Curr Opin Pediatr. 2008;
Tolvaptan (an antagonist of the V2 vasopressin 20:448-52.
receptor) and demeclocycline (a potent inhibitor 4. Zietse R, van der Lubbe N, Hoorn EJ. Current and
of Vasopressin (ADH/AVP) action) is also used future treatment options in SIADH. NDT Plus. 2009; 2
(Suppl_3):iii12-iii19.
to treat SIADH.
5. Ashrafian H, Davey P. A review of the causes of central
Hyponatremia should be managed with pontine myelinosis: yet another apoptotic illness? Eur J
extreme caution, as administration of hypertonic Neurol. 2001; 8(2):103-9.
saline may abruptly lead to a rapid dilute diuresis
and over-rapid rise in serum sodium. A rapid rise
in the sodium level may cause central pontine
myelinolysis5. Hyponatremia should be corrected
at a rate of no more than 12 mEq/L/day of
sodium to prevent central pontine myelinolysis.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014
Case Report

A covariance case of pulmonary thromboembolism with quadriplegia

due to sensory motor neuropathy with cortical venous thrombosis
Devarajan TV*, Anu Deenadayalu**
*Emeritus Professor of Medicine, AVMC, Pondicherry and Senior Consultant Physician,
** Observer, Department of General Medicine, Apollo First Med Hospitals, 154,
Poonamallee High Road, Kilpauk, Chennai‐600010, Tamilnadu, India.
Email: drtvd@[Link]; rdvaish@[Link].

Abstract embolism arises from cortical venous thrombosis

A case of pulmonary thromboembolism in very many cases. Pulmonary thromboembolism
with quadriplegia, a unique clinical entity, is caused is notoriously difficult to diagnose and has earned
by sensory-motor neuropathy with cortical venous its reputation as “the great masquerader”4. In
thrombosis. We present a case study of 51 year patients who have deep venous thrombosis, the
old female with a known case of endogenous thrombus can reach pulmonary artery and cause
depression. She had complaints of fever with pulmonary thromboembolism. The prevalent
chills, abdominal distension and breathlessness. cause of pulmonary thromboembolism is the deep
She was diagnosed to have pulmonary vein thrombosis, which carry a high mortality. The
thromboembolism by classical ECG changes and autopsy series shows that pulmonary embolism
was confirmed by CT chest angiography. While remains the cause of undiagnosed death in around
undergoing treatment, she developed quadriplegia 40% - 70% of patients2. Even with advanced
due to sensory-motor neuropathy and recovered diagnostic modalities, it is difficult to diagnose
after intravenous immunoglobulin with rapid pulmonary thromboembolism. The causes of
resolution of symptoms. A week later, she venous thrombosis and pulmonary
developed convulsions due to cortical venous thromboembolism range from by injury,
thrombosis. MRI brain with MRA and MRV infections, malignancy, dehydration, collagen
investigations showed a positive laboratory report disease, drugs, blood dyscrasias and
and disclosed decreased protein C level, as the coagulopathies. After the advent of High
causative factor. We herein report a rare clinical resolution chest CT (HRCT), MRI Brain with
presentation of non-specific and inaccurate MRA and MRV, and lab investigations, it became
combination of pulmonary thromboembolism due easy to detect infections, coagulopathies and
to deep vein thrombus and sensory-motor blood dyscrasias. Early diagnosis and treatment is
neuropathy resulting in quadriplegia with a considered necessary for a successful outcome5, 6.
favourable outcome.
Case Report
Introduction A 51 year old female with a known case
Pulmonary thromboembolism due to of endogenous depression with diabetes mellitus
deep vein thrombosis in the legs is a well known was admitted to the hospital with a 8 day fever,
entity1. The incidence of cerebral venous constipation, slurred speech, facial tremors and
thrombosis and dural sinus thrombosis showed abdominal distension (Fig. 1a and 1b).
lower limb deep vein thrombosis in 2.5% and Several days prior to the current
pulmonary thromboembolism in 2.5% only2. admission, she was treated as an outpatient with
Deep vein thrombosis can also cause paradoxical an intravenous antibiotics, anticonvulsants, and
embolism via right-to-left shunts into the arterial antidepressants. On examination, we noticed, her
circulation, which may result in stroke3. While temperature was 105 degree Fahrenheit and pulse
reviewing literature, it is seen that the pulmonary rate was 110/minute. She was tachypnoeic with

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

abdominal distension. She had one episode of

convulsion after admission. Urgent surgical and
gynaecology opinion was obtained with no
abnormality. ECG (Fig. 2b) revealed the features
of pulmonary thromboembolism - S1, Q3, T3
phenomenon which was later confirmed by
HRCT chest (Fig. 3a and b). Furthermore, she Fig. 1. (a and b) - On admission, the patient had
also had a feature of acute respiratory distress abdominal distension and pain
syndrome requiring assisted ventilation (Fig. 1b).
She was given intravenous heparin, IV antibiotics.
Heparin was later changed over to oral
anticoagulants. She improved gradually and was
mobilized. She was tested for serological markers
of autoimmune disease which revealed the
reduction in the levels of activated protein C and
protein S. Other markers such as antinuclear Fig. 2a - X-ray chest shows ARDS; b- ECG shows Q3,
antibody, anti extractable nuclear antigen T3 phenomenon of pulmonary thromboembolism
antibody, anti double stranded DNA antibody,
thrombophilia, homocysteine levels, Lupus
anticoagulant, anticardiolipin antibodies, immuno-
globulin IgG and IgM, and anti thrombin III
activity were found to be negative (Table.1).
Her blood culture reports, showed the
presence of Klebsiella and Pseudomonas, which
was treated with intravenous antibiotics,
vancomycin and meropenom.
Fig. 3. (a and b) - HRCT reveals pulmonary thromboembolism
During the recovery period in the ICU,
she developed quadriplegia. Her nerve conduction
study results revealed the sensory motor
neuropathy. Cerebrospinal fluid analysis was done
which showed a total protein content of 0.78 g/l.
Cell count was lower side, revealing albumino
cytological dissociation, suggestive of infective
polyneuropathy was confirmed by nerve
Fig. 4. (a and b) - MRI brain with MRA and MRV shows
conduction studies. left jugular vein thrombosis
Hence, she was started on intravenous
immunoglobulins for five days, 0.4 g/kg, and she
made a rapid recovery. She became afebrile and
her sensorium improved. Tracheostomy was done
and she was slowly weaned off from the
ventilator. Her muscle power, improved in all the
four limbs. She had persistent hypocalcaemia,
hypokalemia, hypomagnesaemia which were Fig. 5a - Before discharge; b - Three months after discharge
corrected accordingly.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

The following day, she had another Discussion

setback when she became drowsy, febrile with The above patient presented had features
fever and convulsions. MRI Brain with MRA and of pulmonary thromboembolism caused by deep
MRV revealed a cortical venous thrombosis vein thrombosis. Under observation, she is also
involving left internal jugular vein with lacunar complicated with the occurrence of quadriplegia
infarcts (Fig. 4 a and b). She was again initiated due to sensory motor neuropathy, and further
on intravenous heparin and broad spectrum developed cortical venous thrombosis. The
antibiotics for gram negative sepsis. mortality rate, for the above combination is very
high in all over the world. It has been reported
She was mobilized gradually made to walk
that the patients with cortical venous thrombosis
with support and was discharged with stable vitals
developed pulmonary thromboembolism with a
(Fig. 5b). She was started on long term oral
high mortality.
anticoagulants with an advice to monitor the
international normalization ratio (INR), Among the possibilities, the symptoms
physiotherapy, anticonvulsants, antidepressants and a history of sudden withdrawal of
and antidiabetic medications. The final diagnosis antipsychotic drugs and the patient presented with
was pulmonary thromboembolism, sensory motor hyperpyrexia and convulsions misguided us
neuropathy with quadriplegia, respiratory failure, towards the neuroleptic malignancy syndrome.
gram negative sepsis, status epileptics, But the reports of lab investigations did not
hypokalemia, and hypomagnesium with cortical support this syndrome.
venous thrombosis.

Table 1. Test results of this case report

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

With earlier diagnosis, assisted ventilation,

good ICU care, IV immunoglobulin, IV
antibiotics, heparin and supportive measures could
save the patient. Our patient had pulmonary
thromboembolism due to deep vein thrombosis,
later developed cortical venous thrombosis.
Incidence of sensory motor neuropathy with the
above combination is not yet reported. This could
be a coincidence or cause.
References
1. Bousser MG. Cerebral venous thrombosis: nothing,
heparin, or local thrombolysis?. Stroke. 1999; 30:481-3.
2. Cakmak S, Nighoghossian N, Desestret V, Hermier M,
et al. Pulmonary embolism: an unusual complication of
cerebral venous thrombosis. Neurology. 2005; 65:1136-7.
3. David Green. Prevention and treatment of venous
thromboembolism in neurologic and neurosurgical
patients, consultative hemostasis and thrombosis
(Second Edition) 2007; Pages 685-690.
4. Samuel Z. Goldhaber. Deep Vein Thrombosis and
Pulmonary Embolism, Consultative Hemostasis and
Thrombosis (Second Edition) 2007, Pages 245– 256.
5. Bettmann MA, Lyders EM, Yucel EK et al. Expert
Panel on Cardiac Imaging. Acute chest pain: suspected
pulmonary embolism [online publication]. Reston (VA):
American College of Radiology (ACR); 2006. 5p.
6. Goldhaber SZ. Pulmonary embolism. Lancet.
2004;17:1295– 305.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014
Toxicology

Toxicology Clinics‐Bench to Bedside

Corrosive Poisoning ‐ Current Best Practice
Senthilkumaran S*, Balamurugan N, Karthikeyan V
*Head, Department of Emergency and Critical Care Medicine, Sri Gokulam Hospitals, Salem.
E‐mail: maniansenthil@[Link].

Corrosives are the substances that cause 3. What are the possible mechanisms of
both functional and histological damage when toxicity in corrosive agents?
ingested or come into contact with body surfaces Most corrosive agents cause direct
by chemical reactions. They are broadly classified chemical injury. Acidic agents cause protein
as alkalis (pH >7) or acids (pH <7). Originally denaturation resulting in coagulative necrosis.
referring to acids, the term corrosives are now Alkaline agents are more dangerous as they cause
used synonymously with caustics, a term originally liquefactive necrosis resulting in deep and
applied to alkalis. progressive mucosal burns. Other corrosive agents
like oxidants may have reducing, oxidizing,
1. What are the commonly available
denaturing or defatting actions.
corrosive agents?
The commonly available corrosive agents are: 4. What are the influencing factors for
 Strong acids and alkalis chemical injury?
 Concentrated weak acids and alkalis  The pH of the compound/agent
 Concentration
 Oxidizers (with neutral pH)
 Volume ingested
 Alkylating agents
 Presence or absence of food in the
 Dehydrating agents stomach
 Halogens and organic halides
5. What are all the clinical features
 Phenol suggestive of a severe corrosive injury?
2. Mention the sources of some corrosive Corrosive ingestion may result in
agents? immediate symptoms of injury to the
Table 1. Sources of the corrosive agents gastrointestinal tract:
Compounds Source  Mouth and throat pain
Alkali
 Drooling of saliva
Sodium hydroxide Detergents, drain and oven
cleaners, button batteries  Odynophagia
Sodium hypochlorite Bleach  Vomiting
Ammonium Toilet bowl and glass  Abdominal pain
hydroxide cleaners, anti-rust products
Sodium Detergents Upper airway injury is the most important
tripolyphosphate immediate life-threat.
Acids
Laryngeal injury and edema presents with:
Hydrochloric acid Metal cleaners
Sulfuric acid Drain cleaners, car batteries
 Progressive stridor
Hydrofluoric acids Rust remover, petroleum  Hoarseness
industry  Respiratory distress
Nitric acid Engraving, electroplating

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

6. What are the corrosive agents that cause  Do not administer oral fluids
severe systemic toxicity in addition to
 Do not administer activated charcoal
direct corrosive injury?
Corrosive agents that can cause severe  Do not attempt pH neutralization
systemic toxicity are furnished below:  Do not perform gastric lavage
Table 2. Corrosive agents and systemic toxicity 10. When will you insert a nasogastric tube in
Corrosive agent Systemic toxicity corrosive poisoning?
Large-volume acid ingestions may benefit
Glyphosate Metabolic acidosis, Shock,
Multiple organ dysfunction
from a nasogastric tube suction if performed
syndrome (MODS) rapidly after ingestion. The pyloric sphincter
spasm may prolong contact time of the agent to
Hydrofluoric acid Hypocalcemia
the gastric mucosa for up to 90 minutes. It may
Mercuric chloride Renal failure, Shock prevent small intestine exposure and may be of
Oxalic acid Hypocalcemia, Renal failure particular value following ingestion of zinc
Phenol Coma, Seizures, Hepatotoxicity, chloride, mercuric chloride, or hydrogen fluoride,
Renal failure unless signs of perforation are present. In case of
Picric acid Renal failure alkali, mucosal exposure results in a quick and
Potassium Methemoglobinemia, Multi- deep liquefactive necrosis. Blind insertion may
permangante organ failure result in the perforation of damaged tissues and
hence, it is contraindicated.
Silver nitrate Methemoglobinemia
11. When to perform upper gastrointestinal
7. What are the key components of risk (UGI) endoscopy?
assessment? Endoscopy has been called ‘sine qua non’
 Agent(s) - (including pH of corrosive for evaluating patients with corrosive poisoning. It
agents) is generally agreed that patients with intentional
 Dose(s) - (including concentration and corrosive ingestions should undergo early
volume for corrosive agents) endoscopy, as ingestions with suicidal intent carry
 Time(s) of ingestion high risk of clinically important injury. In
 Patient factors (co- morbidities) accidental ingestions, particularly in children, the
 Clinical progression decision to perform endoscopy should be based
on signs and symptoms. Currently, early
8. What are the three things to consider endoscopy is recommended after an accidental
while examining the patient’s with corrosive ingestions in adult and pediatric patients
corrosive injuries?
with any obvious signs or symptoms of serious
 The absence of lip or oral burns does not
injury. Early endoscopy permits early grading of
exclude significant gastro- esophageal
injuries and helps to determine the treatment plan
burns.
and disposition and nutritional support.
 Neutral pH of saliva does NOT mean
corrosive ingestion did not occur 12. How early UGI endoscopy should be
done?
 Signs and symptoms correlate poorly with
Tissue friability after a corrosive injury
the extent of gastrointestinal injury.
increases significantly in 24 to 48 hours of post-
9. What are the things one should avoid injury and is maximal between days 5 and 14.
during decontamination of a corrosive Most experts agree that endoscopy should be
ingestion? done within first several hours after ingestion;
 Do not induce vomiting ideally UGI endoscopy shall be performed within

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

12 hours and not exceeding 24 hours of post followed by a continuous infusion of 8 mg/hour
ingestion to avoid iatrogenic perforation. for 72 hours.

13. How are the endoscopic findings of 17. What are the determinants for disposition?
corrosive injuries graded? Disposition is determined by the risk
The endoscopic findings of corrosive assessment and the patient’s clinical progression.
injuries are graded as follows:
The possibilities are:
 Grade 0 — Normal 1. The patient if asymptomatic at 4 hours of
 Grade I — Mucosal edema and post-ingestion, a trial of oral fluids may be
hyperemia given. If this is tolerated well, the patient
 Grade IIA — Superficial ulcers, bleeding can be discharged. Some experts suggest
and exudates endoscopy following corrosive ingestion,
 Grade IIB — Deep focal or even in asymptomatic patients.
circumferential ulcers 2. The patient if symptomatic (e.g. throat
 Grade IIIA — Focal necrosis pain, drooling, pain on attempting to
swallow his own saliva, or has vomiting or
 Grade IIIB — Extensive necrosis
abdominal pain), the patient is kept on nil
14. Is there any role for antibiotics in the per mouth and admitted for an
treatment of corrosive injury to the observation and an endoscopy within 24
gastrointestinal tract? hours.
No. Antibiotics are not warranted for 3. If the patient has airway compromise,
corrosive poisoning, unless there is an evidence of take measures to secure the airway and
gastrointestinal perforation such as mediastinitis arrange for ICU admission.
or peritonitis and subsequent severe sepsis.
4. If the patient has an evidence of
15. Is there a role for corticosteroids in the gastrointestinal perforation, sepsis or
treatment of the gastrointestinal tract hemodynamic instability, then arrange for
corrosive injury? an urgent surgical assessment.
The use of corticosteroids for the
treatment of gastrointestinal corrosive injuries 18. What are the complications of corrosive
from alkaline agents is controversial. However, injury to the gastrointestinal tract?
there is no evidence that corticosteroids are  Esophageal perforation and mediastinitis
effective in preventing esophageal stricture  Perforation of the stomach or small
formation. Furthermore, there are concerns that intestine resulting in peritonitis
corticosteroids may actually increase mortality in  Septic shock and MODS
Grade III injuries, by increasing the risk of  Esophageal strictures occur in 30% of
infection or conceal the symptoms and signs of patients with Grade IIB or III injury on
perforation. endoscopy
16. Is there any role for proton pump inhibitor  Esophageal carcinoma may occur over 40
in corrosive injury to the gastrointestinal years after a Grade II or III corrosive
tract? injury
Yes, there is a definite role. Proton pump
inhibitor suppresses gastric acid secretions and 19. What are the common pitfalls observed?
thereby prevents erosion. It should be  Failure to identify the substance ingested,
administered in a dose of 80 mg as bolus IV, measure the pH of the material ingested,

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 TAPI Journal Vol. 6, Issue 2, April - July 2014

or seek information on its potential for Acknowledgments

corrosive injury. We thank Prof. P. Thirumalaikolandu
 Unintentionally inducing vomiting by subramanian, M.D and Dr. N. Rajesh, M.D, D.M.
giving excessive amounts of oral fluid for (Gastro) for the critical review.
dilution References:
 Failure to appreciate antacids and 1. Murray L, Daly FFS, Little M, and Cadogan M.
feedings that will obscure endoscopic Corrosives; in Toxicology Handbook, Elsevier Australia,
2007.
evaluation
2. Dowsett RP, Linden CH: Corrosive Poisoning. In Rippe
 The false assumption that an absence of JM, Irwin RS. Intensive Care Medicine. Fifth Edition,
oropharyngeal burns precludes the Lippincott Williams and Wilkens, Philadelphia, 2003.
presence of significant GI injury in
patients with ingestions.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014
Dermatology

Dermatology Photo Feature

Jayakar Thomas*, Tamilarasi S**
* Professor & Head, ** Resident, Department of Skin & STD, Sree Balaji Medical College & Hospital, Chennai.

An 85- year-old woman presented with Description/Clinical picture

painless bilateral upper and lower eyelid swelling, Active blepharochalasis patients are with
for 25 years with no history of trauma. On recurrent episodes of non painful and non
examination, we observed the presence of a few erythematous edema of the upper eyelids. These
telangiectatic vessels, edema in both upper eyelids, swelling are generally non pitting and relatively
and a thin loose wrinkled atrophic skin in both refractory to the antihistamines and
lower eyelids. Systemic examination was normal. corticosteroids. The lower eyelids are also
involved in severe cases. The duration of an acute
Diagnosis
attack ranges between a few hours to days with an
Blepharochalasis
average of 2 days.
Pathogenesis After several episodes of edema, the
Pathogenesis of blepharochalasis is still eyelids become wrinkled, redundant, discoloured,
controversial and several theories exist. thinned and laced by tortuous vessels, which have
Blepharochalasis, namely the onset of eyelid a characteristic appearance of tissue paper. Ptosis
edema is idiopathic and the spontaneous seen in blepharochalasis, is acquired and non
resolution is strongly suggestive of localized symmetric and with good levator function.
idiopathic angioedema with sequelae that result
from stretching and atrophy of tissues. In the late stage, a total dehiscence of the
attachment of upper and lower eyelids to the
The fragmentation of elastic fibres might lateral and medial canthal tendon may occur.
be caused by the mechanical distortion as a result
of the repeated episodes of stretching following On microscopic examination, atrophy,
edema. fragmentation and markedly decreased amounts of
elastic fibres in the dermis were observed.
Recent studies using immune- Capillaries are dilated and increased in number.
fluorescence have shown that the patients with Epidermal thickness varies from normal to thin
blepharochalasis have immunoglobulin A (IgA) and atrophic. Perivascular inflammatory infiltrate
antibodies directed against elastic fibres, which
supports immune related mechanisms.

33
 TAPI Journal Vol. 6, Issue 2, April - July 2014

composed of lymphocytes, histiocytes, mast cells Treatment of blepharochalasis is primarily

and plasma cells were also observed. surgical with the hope of achieving functional and
cosmetically acceptable results. Surgical
Differential diagnoses are recurrent
management should be performed when
angioedema, hereditary angioedema, contact
blepharochalasis is in a quiescent phase to avoid
dermatitis, Aschers syndrome, floppy eyelid
the recurrent bout of swells that further lead to
syndrome, dermatochalasis and lax eyelid
ptosis and lid atrophy.
syndrome.
Upper blepharoptosis is preferably
Management corrected through the repair of levator dehiscence
No pharmacological agents have proven or levator advancement.
to be beneficial in the treatment of
blepharochalasis. Lateral canthoplasty is often found to be
effective.
Antihistamines, steroids, sympatho-
mimetics, mast cell stabilizers and cool
compresses are used to modify the symptoms of
acute attacks, but the appropriate remedy to treat
the blepharochalasis is still not yet determined.

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 TAPI Journal Vol. 6, Issue 2, April - July 2014
ECG - Section

Diagnose the ECG

Ulhas M. Pandurangi*
*Senior Consultant Cardiologist & Electrophysiologist, The Madras Medical Mission, Chennai, Tamil Nadu.

What is the diagnosis?

Answer:
The ECG demonstrates sinus rhythm, The combination of RBBB and leftward
bradycardia (45 beats per min), PR interval of axis should intensify the suspicion of biventricular
190msec, incomplete right bundle branch block hypertrophy. An ECG is diagnostic of
(RBBB) pattern and QRS duration of 80msec. The biventricular hypertrophy, if R and S are of equal
QRS axis is leftward. magnitude throughout the precordial leads and
QRS axis is leftwards in a normal positioned heart
The combination of bradycardia and wide
(situs solitus, levocardia).
QRS should always raise the suspicion of A-V
block. If the morphology and the axis of QRS are Hence the diagnosis of the ECG is sinus
suggestive of significant conduction defects as in bradycardia and biventricular hypertrophy.
this ECG viz. an incomplete RBBB pattern,
leftward axis and upper limit of PR interval, the
suspicion of A-V block becomes very strong and
needs to have a closer scrutiny at the blocked P
waves which may fall sometimes on the T waves.

35
 ERRATA

The editors and the publisher apologize for the following errors
that happened in our earlier issue
(TAPI Journal Vol. 6, January-March 2014).

1. The issue no. was wrongly printed as 4 instead of 1.

2. In Page i, under the Section toxicology, the article title had been
published incorrectly. It should read as “Toxicology Clinics-Bench
to Bedside. Toxic Hypoglycemia: Manifestation and Management
Part-1” instead of as shown.

36
37
38
The Journal of the Association of Physicians of India
(Tamil Nadu State Chapter)

Honorary Editor:
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All the contributors and co-authors are entitled to receive a free copy of the
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Prepare your manuscripts now!

Please email your articles in Microsoft word format to:
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