neurological manifestations of scorpion sting

NEUROLOGICAL MANIFESTATIONS OF SCORPION STING

Scorpion sting is an acute life threatening , time limiting medical emergency

CASE

A 36 years old male patient non hypertensive, non diabetic was admitted to our hospital with h/o scorpion sting 3 days ago on the right little toe on 1/7/2011.

He developed excruciating pain locally followed by profuse sweating, vomiting, headache, within one hour of sting

After 2 hours patient became unconscious for 1 hour. On regaining consciousness patient was irritable and was unable to move left upper limb and lower limb and with facial asymmetry.

He was referred to our hospital after 3 days. On examination patient was irritable with GCS of E3M5V3 -11/15, profuse sweating, peripheries were cold, pulse rate of 100/minute and blood pressure of 100/70mm of Hg

Pupils 3mm, bilateral reacting normally with left hemiperesis (Power in left upper limb and lower limb 3/5). There were no local signs of sting.

During hospital stay patient had wide fluctuations of B.P ranging from 100/60mm of Hg to 160/90mm of Hg

Respiratory system, cardiovascular system examination was normal

INVESTIGATIONS

Hemoglobin – 13.8 gm%ESR: 20mm/1hrTLC: 15600/cummDifferential Leukocyte Count – N-89%, L-7%, M-4%Platelet Count: 2.82 lakhs/cumm BT-3 Min 30sec, CT: 7 MinsPT(T)- 13.6 Secs (Control 12.3)APTT - 32.9 Secs (Control-31.1)RBS – 130mg/dlECG: Normal sinus rhythm2D ECHO: No RWMA

Normal LV functionLVEF: 60%

He was treated conservatively (antioedema measures,adequate hydration, prazosin)

Patient improved sensorium wise after 3 days and became conscious, coherent and motor deficit improved after 1 week

CT SCAN BRAIN (PLAIN)

Hematoma in right frontal and left caudate with intraventricular extension

CT ANGIO

CT Angio is normal

SCORPION STING

INTRODUCTION

Out of 1500 scorpion species, 50 are dangerous to humans.

Scorpion stings cause a wide range of conditions, from severe local skin reactions to neurologic, respiratory, and cardiovascular collapse.

VARIOUS TYPES AROUND WORLD Buthus - Mediterranean area, from Spain to the Middle

East Parabuthus - Western and Southern Africa Mesobuthus – Throughout Asia Buthotus (ie, Hottentotta) - Across southern Africa to

southeast Asia Tityus - Central America, South America, and the

Caribbean Leiurus - Northern Africa and the Middle East Androctonus - Northern Africa to Southeast Asia   Centruroides - Southern United States, Mexico

Among the 86 species of scorpions in India ,only 2 are of medical importance.

They are…Mesobuthus tamulus ( Indian red scorpion )Palamneus swammerdam (Black scorpion)

In general, scorpions are not aggressive. They do not hunt for prey; they wait for it.

Scorpions are nocturnal creatures They hunt during the night and hide in

crevices and burrows during the day to avoid the light.

Thus, accidental human stinging occurs when scorpions are touched while in their hiding places, with most of the stings occurring on the hands and feet.

Scorpions use their pincers to grasp their prey;

then, they arch their tail over their body to drive their stinger into the prey to inject their venom, sometimes more than once.

The scorpion can voluntarily regulate how much venom to inject with each sting.

The striated muscles in the stinger allow regulation of the amount of venom ejected, which is usually 0.1-0.6 mg

If the entire supply of venom is used, several days must elapse before the supply is replenished.

The potency of the venom varies with the species, with some producing only a mild flu and others producing death within an hour.

Generally, the venom is distributed rapidly into the tissue if it is deposited into a venous structure.

VENOM

Scorpion venom is a water-soluble, antigenic, heterogenous mixture, as demonstrated on electrophoresis studies.

This heterogeneity accounts for the variable patient reactions to the scorpion sting.

VENOM

Scorpion venom – toxins are polypeptides . Various enzymes are…..AcetylcholinesteraseAlkaline phosphataseAcid phosphatase5’nucleotidaseHyaluronidaseRibonuclease,deoxyribonuclease……

VENOM MECHANISM OF ACTION The primary targets of scorpion venom are

voltage-dependent ion channels, of which sodium channels are the best studied.

The long-chain polypeptide neurotoxin causes stabilization of voltage-dependent sodium channels in the open position, leading to continuous, prolonged, repetitive firing of the somatic, sympathetic, and parasympathetic neurons.

This repetitive firing results in autonomic and neuromuscular overexcitation symptoms, and it prevents normal nerve impulse transmissions

Many end-organ effects are secondary to this excessive excitation.

VENOM MECHANISM OF ACTION Autonomic excitation leads to

cardiopulmonary effects. Somatic and cranial nerve hyperactivity

results from neuromuscular overstimulation. Additionally, serotonin may be found in

scorpion venom and is thought to contribute to the pain associated with scorpion envenomation.

VENOM MECHANISM OF ACTION

Furthermore, it results in release of excessive neurotransmitters such as epinephrine, norepinephrine, acetylcholine, glutamate, and aspartate.

Meanwhile, the short polypeptide neurotoxin blocks the potassium channels.

The binding of these neurotoxins to the host is reversible, but different neurotoxins have different affinities.

The stability of the neurotoxin is due to the 4 disulfide bridges that fold the neurotoxin into a very compact 3-dimensional structure, thus making it resistant to pH and temperature changes

PATHOPHYSIOLOGY

CLINICAL FEATURES

NEUROTOXIC LOCAL EFFECTS

Local evidence of a sting may be minimal or absent in as many as 50% of cases of neurotoxic scorpion stings.

A sharp burning pain sensation at the sting site, followed by pruritus, erythema, local tissue swelling, and ascending hyperesthesia, may be reported.

This paresthesia feels like an electric current, persists for several weeks, and is the last symptom to resolve before the victim recovers.

Hyperthermia Tachypnea Tachycardia Hypertension Arrhythmia Pulmonary edema Hyperglycemia Diaphoresis Piloerection Restlessness and

apprehension Hyperexcitability and

convulsions

Bronchoconstriction Bradycardia Hypotension Salivation, lacrimation,

urination, diarrhea, and gastric emesis (SLUDGE)

Rhinorrhea and bronchorrhea

Goose pimple skin Loss of bowel and bladder

control Priapism Dysphagia Miosis Generalized weakness

SYMPATHETIC PARASYMPATHETIC

AUTONOMIC EFFECTS

CRANIAL NERVE EFFECTS

  Classic roving or rotary eye movements Blurred vision Tongue fasciculations Loss of pharyngeal muscle control Difficulty swallowing Excessive salivary secretions Respiratory difficulty.

CENTRAL NERVOUS SYSTEM

Infrequently encountered but invariably fatal. Encephalopathy, Convulsions within 1-2 hours of sting Stroke -both cerebral hemorrhage and thrombosis Central respiratory failure

These manifestations are similar to strychnine like effect and spurt of BP secondary to catecholomine release occasionally leads to rupture of intracerebral artery resulting in intracerebral bleed and also cerebral infarcts due to thrombosis due to coagulant nature of venom and autonomic storm induced vasospasm

SOMATIC EFFECTS

Rigidity and spasticity in muscles of the

limbs Involuntary muscle spasms Twitching Clonus and contractures Alternating opisthotonous from inactivation

of sodium channels, leading to increased sodium and calcium uptake

Increased tendon reflexes, especially prolongation of the relaxation phase

Piloerection accompanied by goose pimples

The signs of the envenomation are determined by the scorpion species, venom composition, and the victim's physiological reaction to the venom.

The signs occur within a few minutes after the sting and usually progress to a maximum severity within 5 hours.

The signs last for 24-72 hours and do not have an apparent sequence.

Thus, predicting the evolution of signs over time is difficult.

Furthermore, a false recovery followed by a total relapse is common.

CARDIOVASCULAR Myocarditis Gallop rhythm Hypertension or hypotension Arrythmias Conduction blocks Myocardial infarction Congestive heart failure Shock Pulmonary edema

Develop within 30 min to 3 hours after a sting due to myocardial dysfunction

RESPIRATORY

Dyspnea Cyanosis Hemoptysis ARDS

GASTRO INTESTINAL

Acute pancreatitis - intra-pancreatic conversion of trypsinogen to trypsin

Pseudo pancreatic cyst Rise in liver enzymes Necrosis of liver

RENAL

Hematuria Oliguria Acute renal failure

METABOLIC

Acidosis Hyperglycemia Hyperkalemia Raised free fatty acids Raised cholesterol & triglycerides

SYSTEMIC INFLAMMATORY RESPONSE

SIRS is triggered due to increased levels of Interleukin -6 IL-1a IL-1beta IFN-gamma Alpha 1-antitrypsin

GRADING OF SEVERITY

Santhana krishnan grading GRADE 1 –peripheral circulatory failure good GRADE 2 – GRADE 1 + myocarditis prognosis GRADE 3 – GRADE 2 + CNS failures

MANAGENENT

SUPPORTIVE

ABC O2 inhalations Inj TT Benzodiazepines NSAIDS Local ice packs Xylocaine infiltration IV fluids

MANAGEMENT

Prazosin–A competitive post-synaptic alpha1,

adreno-receptor antagonist–should be the first line of management

Suppresses sympathetic outflow Activates venom-inhibited potassium

channels. Decreases the preload, afterload and blood

pressure without increasing the heart rate. Reverses the metabolic and hormonal effects

of alpha receptors stimulation

By accumulating c GMP counters vasoconstriction induced by

endothelins prevents further myocardial injury

Peak concentration is reached in 1-3hours and plasma half life is about 2-3hours. Clinically, it starts acting in 1 hour and maximum action occurs at the end of three hours.

Prazosin is a cellular and pharmacologic antidote to the actions of scorpion venom and it is also cardioprotective.

DOSAGE

Available as 1 mg/2.5mg/5mg tablets. The dose recommended is 30

microgram/kg/dose Sustained release tablets are not

recommended in this condition. Prazosin repeated in the same dose at the

end of 3 hours according to clinical response And later every 6 hours till extremities are

warm, dry and peripheral veins are visible easily

SVIMS Experience: Oral L-carnitine is useful to treat patients with scorpion ting envenomation, myocarditis and shock (Rajasekhar D, Mohan A. Natl Med J India 2007)

It should not be given as prophylaxis in children when pain is the only symptom. First dose phenomenon

Can be given irrespective of blood pressure

provided there is no hypovolemia The time lapse between the sting and

administration of prazosin for symptoms of autonomic storm determines the outcome

L-CARNITINE

SVIMS Experience: Oral L-carnitine is useful to treat patients with scorpion ting envenomation, myocarditis and shock

(Rajasekhar D, Mohan A. Natl Med J India 2006)

SCORPION ANTIVENOM

Scorpion venoms reach their target too rapidly to be neutralized and anti-venom within 30 minutes of sting may reverse their effect

Antivenom against the toxins of Indian scorpions is not available for clinical use

UNHELPFUL RX

Lytic Cocktail (Pethidine + Promethazine + Chlorpromazine )

Morphine Steroids Atropine Nifidepine Ace Inhibitors (Captopril)

COMPLICATIONS

Dilated cardiomyopathy Ankylosis of small joints if the sting occurs at a

joint Rhabdomyolysis Persistent paresthesias Antivenin anaphylaxis and serum sickness Respiratory arrest Cardiac arrest Shock Seizures Death

PROGNOSIS

In the pre-prazosin era (1961-1983), 25-30% fatality due to pulmonary edema was reported in scorpion victims

Since the use of prazosin (1984 onwards) the mortality in these victims is reduced to less than 1%

KEY MESSAGES

Scorpion venom is a potent sympathetic stimulator Cardiac manifestations are common in Indian red

scorpion envenomation Both hemorrhagic and ischemic strokes are known to

occur CNS involvement indicates poor prognosis Alpha receptors stimulation plays a major role in

evolution of myocardial dysfunction and acute pulmonary edema in victims of scorpion sting

Prazosin–an alpha adrenoreceptor antagonist–is antidote to venom action

Time lapse between the sting and administration of Prazosin for autonomic storm determines the outcome

REFERENCES1) Rai M. Intracerebral hemorrhage following scorpion bite.:Neurology. 1990;40:1801

2) Udayakumar, N, Rajendiran, C, Srinivasan, AV. Cerebrovascular manifestations in scorpion sting: a case series. Indian J Med Sci 2006; 60: 241–244.

3) Raichur, DV, Magar, VS, Wari, PK, Chandragouda, DK. Hemiplegia and motor aphasia following scorpion sting. Indian J Med Sci 2001; 68: 669–670

4) Bonilha, L, et al. Epilepsy due to a destructive brain lesion caused by a scorpion sting. Arch Neurol 2004; 61: 1294–129

5) Bawaskar HS, Bawaskar PH. Scorpion sting. J Assoc Physicians India. 1998; 46: 388 – 392

6) Kavathale, Khan A et al. Scorpion – Stings the limb and stuns the heart? J Assoc Physicians India 1999; 47: 1045 – 1046

7) Sundararaman T, Olithselvann M et al. Scorpion envenomation as a risk factor for development of dilated cardiomyopathy. J Assoc Physicians India 1999; 47: 1047 – 1050

8) Elatrous S et al. Dobutamine in severe scorpion envenomation. Effects on standard haemodynamics, right ventricular performance and tissue oxygenation. Chest 1999; 116: 748 – 753

9) Bawaskar HS, Bawaskar PH. Prazosin therapy and Scorpion envenomation. J Assoc Physicians India. 2000; 48: 1175 – 1180

10) Natu VS et al. Efficacy of Species Specific Anti-scorpion Venom Serum (AScVS) against severe serious scorpion stings ( Mesobuthus tamulus concanesis Pocock) – an experience from Rural Hospital in Western Maharashtra. J Assoc. Phys of India 2006; 54: 283 - 287