Context: Characterization of heat stroke cases on arrival to hospital may lead to early recognition and improved management. Delay in treatment leading to high rate of mortality and poor outcomes so a high index of clinical suspicion in appropriate setting is warranted. Aims: Recurring seasonal(summer) outbreak of heat stroke among children from Muzaffarpur district, Bihar was investigated to describe clinico-epidemiological features. Materials and Methods: A retrospective study involving 50 patients of classic heat stroke admitted to Sri Krishna Medical College and Hospital (SKMCH) Muzaffarpur in June 2005 and June 2011 were carried out. These patients had presented with a rectal temperature of more than 40°C and central nervous system disturbance. The patients were treated with standard regimen of management of heat stroke and sponging in ICU after emergency resuscitation. Results: A total of 50 case records were studied of children below12 years of age. Case fatality ratio was 60% .The disease had peak incidence in June. Previously healthy, rural children (mean age-3.78 yr) of very low socio-economic background were found most vulnerable. The main presenting feature ware high fever (100%), convulsion (100%), unconsciousness (100%), decebrate rigidity (50%), tachycardia (80%), and tachypnea (80%). No one had splenomegaly. Cerebrospinal fluid (CSF) was under high pressure but normal otherwise in all cases. Biochemical investigation reveled hyponatremia (50%), hypokalemia (5%), mild raised SGPT (30%), blood urea (40-50mg/dl) (40%) with normal creatinine. Smear for malarial parasites were negative. CT scan of head done in 20 cases; 10- showed feature of generalized cerebral edema while rest was normal. ECG showed non-specific ST-T changes and tachyarrhythmia. Moderate to severe residual neurologic deficit was observed in 20% of survivors. Male to female ratio was 1.5:1.No infective organism or its antigen or antibody was found in the any of the samples tested locally or at various apex virological centers of India. Conclusions: Heat stroke is a medical emergency with serious complication and requires prompt treatment. It is associated with multi-organ dysfunction with high mortality and substantial neurological squeals.
Keywords: Clinico-pathological aspect, heat stroke, potentially fatal, rapid cooling
Recently a number of outbreaks have been reported in newspapers and newsmagazines of India bearing headlines, ‘mystery disease’, or convulsive disease caused by ‘mystery virus’. ,,, Many outbreaks were not investigated as per outbreak protocol.  In India, since Japanese B Encephalitis (JE) virus is the mostly recognized common cause of encephalitis, especially in outbreak, physician, and public health and administrative officials have a tendency to attribute all the epidemic of febrile convulsive disorder in children to this virus. During any outbreak investigation, the primary and most important aim of investigators is to isolate a virus or its antigen or antibody from a requisite sample. Many a times they fail to get positive result with the available and known resources and label it as “mysterious disease.” ,,, Epidemiological, physical and environmental consideration is conspicuous by its absence in such investigations  Sometimes there is an ‘outbreak of encephalopathy’, but even after innumerable tests of samples, investigators fail to conclude the known viral etiology of encephalitis and keep other possible explanations and etiologies in consideration. Thus, the mystery of undiagnosed outbreaks persists. ,
Weather in this area of north Bihar is quite hot and humid from mid-April to mid-July every year with frequent heat waves, sometimes sustain heat wave are frequent. In June 2005 and in June 2011, probably heat waves were more sustained affecting more than 300 children in with a high mortality of 100 in 2005 and 50 in 2011 alarming health, civic and administrative bodies along with media persons. The common media reports were outbreak of “mysterious disease,” “acute encephalitis syndrome” (AES), “brain fever” or “encephalitis.” , The team of investigators (pediatrician, epidemiologist, entomologist and neurologist) from National Institute of Communicable Diseases (NICD) New Delhi, National Institute of Virology (NIV) Pune, Rajendra Medical Research Institute (RMRI) Patna, Team from Madurai, Tamil Nadu, Safdarjung Hospital and Lady Harding Medical College New Delhi, have done camp several times in this region but they fail to isolate any virus, bacteria or other infective organism in these outbreaks.
The final report of 2011 outbreak submitted by Directorate General of Health Services, conclude “clinic-epidemiological and environmental evidence support the diagnosis of ‘Acute Encephalitis Syndrome’ which has significant mortality, affecting predominantly rural population with poor sanitation.” However, it is unlikely to be Japanese B Encephalitis virus, West Nile virus, Cerebral Malaria, NIPAH virus or Chandipura virus .Since the critically ill patients had presented with abrupt onset of high fever and feature of acute encephalopathy (like convulsion, unconsciousness and decebrate posturing). They were admitted in Sri Krishna Medical College Hospital and other secondary level private hospitals of Muzaffarpur. Overall picture of these cases were suggestive of heat stroke. The outbreak of heat stroke in Muzaffarpur anticipated when temperature rises 38°C-44°C and remains sustained for 3 to 4 days between 38°C-44°C along with daytime heat wave. Every year during these summer months, health authority serves an emergency notice to all health centers to tackle the expected emergency.
Heat stroke (HS) was first documented in 24BC by the Romans, but was not demonstrated to result in multi-organ dysfunction until 1946.  It is life threatening medical emergency – defined clinically as core temperature > 40°C accompanied by central nervous system dysfunction.  It is an important treatable form of multiple organ dysfunction syndrome (MODS) resulting from thermo-regulatory failure coupled with an exaggerated acute phase response and possibly altered expression of heat shock protein.  It is a diagnosis of exclusion such as drug withdrawal syndrome, neuroleptic malignant syndrome, septicemia, cerebral malaria, CNS infection, thyroid storm, drug toxicity (anticholinergic).  Despite the advances in last 50 years, mortality due to HS continues to be as high as 10 to 50 %  There are two forms of heat stroke – classical heat stroke, occurs in ‘epidemic form’ during period of high environmental temperature and humidity as in summer heat waves and affects very young and elderly. It usually affects infants and young children due to immature thermoregulatory system, lower rate of sweating and poor acclimatization. Exertion in hot humid climate may result in exertional heat stroke, which affects fit, young, and healthy individuals  Failure to normal cardiovascular adaption to severe heat stress, exaggerated acute phase response and attenuated heat-shock proteins response are the main reasons which leads to HS. 
This paper on classical HS is to study the clinico-pathophysiological aspect of the disorder and wish to highlight the condition to increase the awareness of clinicians and paramedical personnel to this potentially fatal but treatable condition
The study area in India is located between 26° and 26.07° N, 85°, and 85/.45° E. The cases were reported from different blocks/regions of Muzaffarpur like Meenapur, Kanti, Bochahan, Aurai, Gayaghat, kudhani, katra Motipur, Paru, Marwan,Sahibgang and Musshari and from and joining district like Sithamadhi and Sheohar. The most affected blocks were Meenapur, Musshari, and Kanti (76%). These blocks are heavily cultivated by litchi garden spread over thousands of acre [Figure 1]. The population is mostly rural. Average annual rainfall is 11.87 cm. The climatic condition in May – June is extremely hot and humid the temperature ranges from 28°c to 40-44°c with a high humidity ranging from 56% to100 %.
This study was a retrospective case note review study of the patients admitted in Sri Krishna Medical College Muzaffarpur, in June 2005 and in June 2011. A total of 85 acute encephalopathy cases were admitted and 50 cases were selected who met the diagnostic criteria of Heat Stroke. The remaining 35 patient, treated outside before admission, were excluded from study. Following criteria were used to select a case of HS:
Outbreak investigations were initiated immediately after initial resuscitation to exclude the other causes of acute encephalopathy. The requisite clinical sample (blood, urine, nasal swab, throat swab, rectal swab, and CSF) sent to NIV, Pune and NCDC, New Delhi for virological testing, by Directorate of Health Services, Bihar. Postmortem brain needle biopsy (2 cases) by nasal route and postmortem liver biopsy (1 case) also done. Predesigned Proforma was used to collect information from the cases. Clinical investigations included recording history, clinical findings, and result of routine laboratory investigations, review of hospital records and collection of various sample like blood and CSF from patients.
Epidemiology and demography:
There are various epidemiological risk factors, that strongly favor the seasonal outbreaks of heat stroke in children in Muzaffarpur:(i) The climate between April and June, is hot(28/40°C) and humid (56- 90% ) and most outbreaks have occurred at the height of temperature (38°c-40°c) and humidity (70%-80%),(ii) the number of cases suddenly drop, even to zero with fall of temperature due to rain .(iii) May-June is the season of ‘litchi'(a type of flashy and juicy fruit) in this area. Many children expand their whole day outdoor playing, eating, and collecting litchi (iv) ) being from low socioeconomic families, some get engaged themselves as child labor for plucking and packing litchi, (v) Most of the houses in this area are surrounded by farmland, litchi garden or any other plantation that contribute to air moisture through transpiration and evaporation raising humidity further, (vi) Victims were from villages with overcrowded housing, poor electric power supply, poor hygiene and ventilation.
All patients presented with abrupt attack of fever, convulsion, followed by coma, decerebrate rigidity, opisthotonic posturing, dystonia and death (within 48-72 hours of illness). More alarmingly, some patient died within 5-10 hours of convulsion. There was no prodromal symptom at all. The duration of illness before admission was less than 48 h in 58.2% cases. No rash or exanthema was recorded in any child. Every parent had stated that the child was completely normal before this abrupt fever and convulsion.
Main presenting features were high fever (100%), convulsion (100%), and unconsciousness (100%). Clinical examinations revealed a temperature of >104°C, tachycardia (80%), tachypnea (80%) with respiratory distress, hypotension (28%), anhidrotic (80%), hot and dry skin.
All the children were unconscious. Dilated poorly reacting pupils and absent Doll’s eye movement were seen in 30% and 50%, respectively. Half of them had bilateral decerabrate rigidity and extensor planters while rest had absent tendon reflex (50%) and flaccidity (50%). None of the patients had any sign of meningeal irritation [Table 2].
Systemic examinations were unremarkable with soft abdomen and no splenomegaly, few had mild diarrhea, no skin rashes or bleeding noted at any point of time.
Forty patients (80%) had polymorphonuclear leukocytosis (13000-17000/cu mm). Coagulation profile was not done since no patient had shown bleeding tendency. Smears for malarial parasites were negative
It reveled mild hyponatremia (126-134meq/l) in 50%, hypokalemia (2-2.3meq/l) in 5%, mildly raised SGPT (50-100IU/L) in 30%, subtle raised blood urea (40-50mg/dl) in 40% and with normal creatinine. Muscle enzymes (CPK-MM) were within normal limit [Table 3].
Lumber puncture was done within 24 h of admission. Opening pressure was high but CSF turned out to be normal (cells, sugar and protein level were in range).
Various specimens of urine, throat swab, blood, and CSF were tested for bacterial and viral cultures. They were turned out negative for growth of any pathogen.
Computerized tomography (CT) of head was done in 20 cases; 10 had features of diffuse cerebral edema while in rest it was normal.
ECG showed non-specific ST changes and tachyarrhythmia.
Virological report of NIV Pune and NICD New Delhi
The requisite clinical samples (31 CSF,59 sera, 19 nasal swab, 48 throat swab,44 rectal swab,2 urine samples, 2 postmortem brain needle biopsy by nasal route and 1 postmortem liver biopsy) were Negative for known virus causing acute encephalitis like JE, Nipah, West Nile and Chandipura. Some specimens were processed for the discovery of novel agents; however, no agent has been found. 
Treatment of children in the hospital
All children after emergency management of securing airway, breathing, maintaining circulation, received treatment as per standard protocol of Heat Stroke in the form of control of temperature (by sponging, air circulation, cooling), standard anti-convulsants, fluids and electrolytes, nutrition, and other symptomatic and supportive measures. Corticosteroids were not employed and mannitol was used as anti-brain edema.
The outcome of illness
The disease progressed rapidly and 30 out of 50 children died (mostly within 12-48 h of illness) with a case fatality of 60%. Moderate to severe residual neurologic deficit was found in 20% of survivors. Those who survived recovered quite dramatically within 72 h of admission without any deficit. The number of children died were 21 of 35 in 2005 (60%), 10 of 15 in 2011 (66.66%). Only 19 children out of 50 (38%) survived and about 15 uneventfully.
Recent years have witnessed a large number of morbidity and deaths due to heat-related illnesses across the globe. It has become a matter of great social and medical concern. The World Health Organization (WHO) estimates that the warming and precipitation trends due to anthropogenic climate change of the past 30 years claim over 150000 lives annually  Evidences of heat wave incidences available from different parts of India, e.g., Orissa, Bihar, Andhra Pradesh, Maharashtra, clearly indicate that most mortality took place outdoor, among those who live at poverty threshold. A heat wave in 1998-99 claimed 1470 lives and 1662 morbidity in Orissa.  Over 1000 lives were lost in Andhra Pradesh (AP) in 2002 when the temperature touches 50°C and over 1600 lives in2003in the whole of the India.  An epidemiologic study in the United States estimated the incidence of heat stroke 17.6-26.5 per lac population  In Saudi Arabia, the incidence varies seasonally from 22 to 250 cases per lac population and the crude mortality rate is estimated at 50%. 
Our studies of 50 patients with classical heat hyperpyrexia, clinical findings were consistent with that of earlier studies. ,,,,, Neurological manifestations were present in all cases. Direct thermal effect compounded by breakdown of the blood brain barrier (BBB) and profound brain swelling were responsible. Neuro-pathological study of heat-injured victims at autopsy showed, degenerative neuronal changes which have been attributed to hyperthermia whereas edema, congestion, micro-hemorrhage are mainly secondary phenomena coincident with shock. , Change in the cerebellum were said to be more consistent and more rapidly than other parts of the brain. , Neurological deficit (20%) in our study was comparable to other study.  Neurological involvement characterized by deep coma, flaccid paralysis, hyper-reflexia and seizure has a high incidence of permanent neurological deficit.  In the present study mortality rate (60%) was similar to other studies. , Prolonged coma despite adequate cooling is a poor prognostic sign suggesting more severe damage to the cerebrum and this observation was similar to those of Shibolet  and Tham et al.  Contrast enhanced CT of head uniformly showed feature of diffuse cerebral edema without any focal lesion.  In other similar studies of heat stroke, the described radiological finding include loss of gray-white matter differentiation, patchy high signal intensity of the white matter of cerebral hemisphere and corpus striatum, central pontinemyelinolysis vascular boundary zone infract and in latter stage diffuse cerebral atrophy. ,
Vomiting and diarrhea were relatively uncommon gastrointestinal manifestation seen in our series which occurring in 4% of cases, which also observed by Tham et al.  The cause of diarrhea had been postulated to be the result of thermal alternation of gut flora or massive exudation of fluid into the hollow viscous because of thermal damage of the mucosal lining of the gut. The episode of diarrhea was mild and resolved spontaneously with only simple supportive measure.
Severe metabolic disturbances were common. Twenty-five patients (50%) have hyponatremia and five patients (10%) have hypokalaemia, partially attributable to the increase Na+H+ pump activity in patient with hyperthermia and is partially attributable to sweating and dehydration.  Hyperkalaemia may be due to activation of Renin-Angiotensin mechanism due to dehydration leadings to hypovolumia. Hyperglycemia (blood glucose>120 mg/dl) seen in 14 cases (20%) probably reflected the state of dehydration and increased catecholamine activity in response to stress.  The biochemical abnormalities as a whole were easily correctable and none of our cases had complication resulting from rapid correction and overloading.
Japanese encephalitis/known viral encephalitis as the cause for the present epidemic has been ruled out after negative results from various apex centers of: (i) Outbreak occurred in June coinciding with the height of environmental temperature and high humidity, (ii) Predilection of children below 12 years, (iii) Siblings were also affected (iv) No prodromal symptoms, (iv) Duration of illness (onset of first symptom to death) was quite short, (vi) Case fatality rate over 50%, (vii) High fever convulsion and coma in all cases, (viii) CT brain showing either diffuse edema or a normal study, (ix) Post mortem brain biopsy did not reveal any evidence of inflammation in brain or liver, (x) Normal CSF study, (xi) Till date, no infective etiology have been found, (xii) Seizure got controlled with cold sponging and simple anticonvulsant drugs.
Heat related illnesses are increasing with global warming. Yet the public perception of the hazards of high environmental temperature is often poor and underplayed by public media, political and even the medical community. Because behavioral responses are important in the management of temperature elevations, heatstroke may be entirely preventable. Greater awareness will help recognizing and treating this disorder at an early stage. Delay in treatment leads to high mortality, warranting a high index of clinical suspicion in appropriate setting. Heat Stroke is a multi system disorder affecting many systems and organs (MODS) simultaneously brain, kidneys, lungs, liver and gastrointestinal tract being serious and life threatening. Prompt diagnosis and treatment can result in good recovery of most patients. The most important objective in the treatment of heat hyperpyrexia is to decrease body temperature as quickly as possible while supporting the cardiovascular and respiratory systems. Heat hyperpyrexia is inherently preventable and the recurrence of such an epidemic is likely to be avoided only with aggressive implementation of a community-wide disaster plan. This emphasizes the need for education at all level of medical care in conjunction with an aggressive pre-hospital prevention and rescue plan when faced with this type of environmental catastrophe.
Source of Support: None, Conflict of Interest: NoneDOI: 10.4103/1755-6783.115203
[Table 1], [Table 2], [Table 3]