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Neurological aspects of biological and chemical terrorism
1. Neurological Aspects of Biological and
Chemical Terrorism
Prepared by: Dr. Kshitij Bansal
Department of Neurology
GMC, Kota
2. Introduction: Bioterrorism
• Bioterrorism involves the deliberate release of viruses, bacterias and their by-products (eg
toxins) to cause morbidity and mortality in humans, animals or plants.
• All bioterrorism agents are naturally occurring organisms or toxins that can cause sporadic
disease under natural circumstances, but on occasion, medical manipulation has been
attempted to increase resistance to antibiotics or increase organism virulence.
• Bioterrorism is an attractive weapon because biological agents are relatively easy and
inexpensive to obtain, can be easily disseminated and can cause widespread fear and panic
beyond the actual physical damage.
Aven T, Guikema S. On the Concept and Definition of Terrorism Risk. Risk Anal. 2015 Dec;35(12):2162-71.
3. Key Features of Biological Agents used as Bioweapons
• High morbidity and mortality
• Potential for person to person spread
• Low infective dose and highly infectious by
aerosol
• Lack of rapid diagnostic capability
• Lack of universally available effect vaccine
• Potential to cause anxiety
• Available of pathogens and feasibility of
production.
• Environmental stability
• Database of prior research and development
• Potential to be “weaponised”
5. Das S, Kataria VK. Bioterrorism : A Public Health Perspective. Med J Armed Forces India. 2010 Jul;66(3):255-60. doi: 10.1016/S0377-1237(10)80051-6. Epub 2011 Jul 21. PMID: 27408313; PMCID: PMC4921253.
6. History
• 400 BC - Scythian archers used arrows dipped in blood and manure.
• 300 BC - Persian, Greek and Roman literature provide examples of using animal cadavers to
contaminate water supplies.
• 190 BC - Hnnibal hurled venomous snakes onto enemy ships of Kings Eumenes.
• 1155 - Battle of Tortona - Barbarossa put dead bodies in enemy water supplies.
• 1346 - Siege of Caffa - Mongols catapulted bodies of plague victims over the city walls.
• 1718 - Reval, Estonia - Russians tried the same tactics against Sweden.
7. History
• 1763 - French & Indian War - During the Pontiac Rebellion in New England, British forces
gave smallpox inoculated blankets to Native Americans.
• 1915 - 18 - World War I - German BW Program:
• Developed anthrax, glanders, cholera and wheat fungus as weapons.
• 1932 - 1945 - World War II - Japanese BW Pogram:
• Operated a secret facility (Unit 731) testing BW agents on Chinese prisoners.
8. History
• 1972 - Biological Weapons Convention
• 1979 - Accidental release of B. Anthracis spores at bioweapon research centre, Sverdlovsk,
U.S.S.R
• 1989 - 92 - Scientists from the former U.S.S.R. involved in biological weapons research defect
to the West.
• 1984 - Rajnesh cult members contaminate salad bar with Salmonella typhimurium in Oregon.
• 1992 - Ricin attack planned by Minnesota militia.
• 2001 - Anthrax releases in FL, DC, NY, NJ.
9. Botulism
• Botulism is a neuroparalytic syndrome that results from the systemic effects of an exo
neurotoxin produced by the gram-positive, rod-shaped, spore-forming, obligate anaerobic
bacterium Clostridium botulinum
• Botulinum neurotoxin is considered the deadliest toxin known due to its high potency and
lethality, with a lethal dose (LD50 - the amount required to kill 50% of a test sample) of 1 ng
to 3 ng (nanograms) of toxin per kilogram (kg) of body mass.
10. Pathophysiology
• The flaccid paralysis of botulism is the result of irreversible inhibition of acetylcholine (ACh)
release at the presynaptic nerve terminal of the body's neuromuscular junctions (NMJs).
• Botulinum neurotoxin is a 150kDa protein that comprises a 100kDa heavy chain and 50kDa
light chain linked by a single disulfide bridge.
• There are eight distinct serotypes of BoNT, A (BoNT/A) through H (BoNT/H), based on
recognition by polyclonal serum. Toxin subtypes A, B, E, and rarely F, G, and H cause human
disease.
11.
12.
13. When to Suspect
• Classic Triad
• Symmetric, descending flaccid paralysis with prominent bulbar palsies
• Afebrile
• Clear Sensorium
• Bulbar palsies summarised as “4 Ds”
• Diplopia, dysarthria, dysphonia, dysphagia
• Prominent autonomic involvement in form of paralytic ileum, constipation, urinary retention,
dilated or poorly reacting pupils.
14. A 14 year old with Botulism. Note the weakness of his eye muscle and the drooping eyelids in
the image to the left, and the large and non-moving pupils in the right image
16. Treatment
• Intensive care immediately
• Ventilator for respiratory failure.
• Botulinum antitoxin
• Derived from equine source
• CDC distributes.
• Used on a case by case basis
17. • Anthrax in caused by a sporulating gram - positive rod, Bacillus Anthracis.
• Human disease largely occurs through contact with animal products, such as animals skins,
where the bacillus form converts back to the spore form.
• In 2001, however, 22 cases of anthrax occurred in the United States as an act of bioterrorism
through the postal system, placing anthrax on the forefront of bioterrorism.
Anthrax
19. When to Suspect
• Symptoms starts with fever, nausea, vomiting and muscle aches.
• Cutaneous manifestations in form of papule, vesicles and later on eschar formation.
20. Neurological Manifestations
• Neurological manifestations in form of headache, recurrent vomiting, confusion followed by altered
sensorium with presence of meningeal signs.
• CSF findings
• Raised protein
• Low Sugar
• Raised WBC count
• Presence of the RBCs
• Positive Gram stain
• Imaging: Subarachanoid, intracerebral and intraventricular hemorrhage and leptomeningeal enhancement.
Pohanka M. Bacillus anthracis as a biological warfare agent: infection, diagnosis and countermeasures. Bratislava Medical Journal. 2020 Jan 1;121(3):175-81.
21. Meyer MA. Neurologic Complications of Anthrax: A Review of the Literature. Arch Neurol. 2003;60(4):483–488. doi:10.1001/archneur.60.4.483
22.
23.
24. Management
• Diagnosis is made by culture of the blood, sputum, pleural fluid, cerebrospinal fluid or skin
• Treatment
• Ciprofloxacin
• Doxycyclin
• Treatment of Anthrax Meningitis
• Ciprofloxacin plus
• Vancomycin / Penicillin / Chloramphenicol
25. • Ebola virus disease is one of the deadliest patho- gens known to man, with a mortality rate
between 25–90% depending on the species and outbreak of Ebola.
• Due to its high mortality, Ebola has been categorised in Category A agents by CDC.
Ebola Virus Disease
26. Acute Neurological Manifestations
• Most commonly, patients will complain of a nonspecific headache, which often presents as an
early symptom.
• Altered mental status, from mild confusion to delirium with hallucinations, may also occur,
but may be secondary to a host of variables, including electrolyte abnormalities and shock.
• Patient may also develop meningoencephalitis as manifested by classical meningeal signs,
delirium, eye movement abnormalities, and frontal re- lease signs
• When the meningeal signs gradually resolves and the patient may develop decreased short-
term memory, hypomania, hyperphagia and insomnia and mild cerebellar signs.
33. Neurological Manifestations
• Three different types of paralysis are recognised based largely on the time of occurrence and
their differing pathophysiology.
• Type I paralysis or acute paralysis
• Type II paralysis or Intermediate Syndrome.
• Type III paralysis or Organophosphate-induced delayed polyneuropathy.
Singh S, Sharma N. Neurological syndromes following organophosphate poisoning. Neurol India 2000;48:308
34. Type I Paralysis or Acute Paralysis
• It is seen during the initial cholinergic phase.
• This is when large number of both muscarinic and nicotinic receptors are occupied by
acetylcholine, leading to persistent depolarisation at neuromuscular junction.
• Clinical features include muscle fasciculation, cramps, twitching and weakness.
• At this stage, the patient may require ventilatory support due to the weakness of the respiratory
muscles leading to respiratory depression and arrest.
35. Type II Paralysis / Intermediate Syndrome
• Intermediate syndrome is a distinct clinical entity that occurs 24 to 96 hours after the ingestion of an OP
compound.
• Approximately 10-40% of the patients treated for acute poisoning develop this illness.
• The onset of the IMS is often rapid with progression of muscle weakness from the:
• Ocular muscles
• Neck muscle (the patient can not raise their head from the pillow)
• Proximal Limbs
• Respiratory muscles (intercostals and diaphragm) over the course of 24 hours.
36. Clinical Features
• Clinical manifestation of IMS typically occur within 24 to 96 hours, and affect conscious
patients without falsiculation or other cholinergic signs.
• Markes weakness of neck flexion and varying degree of proximal limb muscle weakness,
manifesting as weakness of shoulder abduction and hip flexion are the constant clinical
features.
• Respiratory insufficiency is common and frequently draws medical attention to the onset of the
syndrome.
• Other possible manifestations are involved of muscles innervated by motor cranial nerves and
decreased deep tendon reflexes.
• Sensory impairment is not clinical manifestation of IMS
37. Type III Paralysis or Organophosphate-induced delayed
polyneuropathy (OPIDP)
• It is a sensory-motor distal axon apathy that usually occurs after ingestion of large doses of an
organophosphorus compound.
• The neuropathy presents as a weakness and ataxia following a latent period of 2-4 weeks.
• Initial stimulation causes excitatory fasciculation, which then progresses to an inhibitory
paralysis. The cardinal symptoms are distal weakness of the hands and feet.
• This often is preceded by calf pain, and in some cases, parasthesia of the distal part of the
limbs. Delayed CNS signs include tremor, anxiety and coma.
38. Management of OP Poisoning
Initial Stabilisation of the patient
• Clear airway
• Adequate ventilation because the patient with acute organophosphate poisoning (ACC)
commonly presents with respiratory distress.
• Oxygen - Circulation - iv access
39. Decontamination
• Dermal spills: wash pesticide spills from the patient with soap and water and remove and
discard contaminated clothes, shoes and any other material made from leather.
• Gastric lavage: Consider for presentations within 1 or 2 hours, when the airway is protected. A
single aspiration of the gastric contents may be as useful as lavage.
• Activated charcoal: 50 g may be given orally or nasogastrically to patients who are cooperative
or intubated, particularly if they are admitted within one or two hours or have severe toxicity.
40. Antidotes in the treatment of OP poisoning
• Atropine: Reverses the muscarinic features.
• Oxime: Reactivate cholinesterase and reverses the nicotinic features.
41. Atropine
• Initial dose: 0.5-2 mg IV every 5-10 min until atropinization.
• Continuous infusion (8mg atropine in 100ml NS) at rate of 0.02-0.08 mg/kg/hr (0.25-1.0
ml/kg/hr) with additional 1-5 mg bolus.
• May require about 40-1500 mg/day
• For at least 5-7 days
• Watch out for OVER ATROPINIZATION.
42. Target end points for Atropine therapy
• Clear chest on auscultation with no wheeze
• Heart rate > 80 / min
• Pupils no longer pin point (does not imply that pupils must be dilated)
• Dry axilla
• Systolic BP > 80 mm Hg
Dilated pupils is not a reliable sign of initial atropinisation or end point for atropine therapy.
43. Pralidoxime
• An oxide that reactivated phosphorylate cholinesterase.
• Effects: Skeletal-neuromuscular junctions (counteracts weakness, fasciculation and respiratory
depression)
• Administration within 48 hours of poison ingestion.
• IV 1-2gm in 100cc of NS over 30 min (at a rate not exceeding 200mg/min), repeat in 1 hour if muscle
weakness persist, then at 8-12 hours interval if cholinergic sings recur.
• Severe case: IV infusion 500ml / hr (max 12gm in 24 hours)
• Started after maximal atropinization.
44. • Cyanide gases could potentially cause sudden mass casualties.
• Hydrogen Cyanide and cyanogen chloride are highly volatile liquids with boiling points near
room temperature.
• Hydrogen Cyanide has an odour reminiscent of bitter almonds.
• It has been used as a poison in mass homicides and suicides. During World War II, the Nazis
used cyanide as an agent of genocide in gas chambers.
Hydrogen Cyanide
46. Clinical Manifestations of Acute Cyanide Poisoning
• The clinical manifestations can be divided into early and late categories.
• Some early central nervous system findings are headache, dizziness, confusion, and mydriasis.
These are due to tissue hypoxia, and seizures and coma can develop as it progresses to an
altered level of consciousness.
• Early respiratory and cardiovascular findings include tachypnea and tachycardia, while late
findings include apnea, hypotension, and cardiac arrhythmia.
• Patients with cyanide poisoning will not be cyanotic but will have a cherry red color due to
excess oxygen in the bloodstream.
Chin, R. G., & Calderon, Y. (2000). Acute cyanide poisoning: a case report. The Journal of emergency medicine, 18(4), 441-445
47. Delayed Neurological Manifestations
• Mainly extra pyramidal symptoms in form of dystonia, Parkinsonism and akathisia.
• Primarily occurs due to hypoxic-ischemic damage leading to cell loss on the reticular zone of
substantia nigra.
• Patients usually responds to Levodopa and Apomorphine.
• Cerebellar and sensorimotor cortex can also be affected because of their high oxygen
dependency.
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51. References
• Harrison’s Principles of Internal Medicine: 20th Edition
• Martin CO, Adams HP Jr. Neurological aspects of biological and chemical terrorism: a review for neurologists. Arch Neurol. 2003
Jan;60(1):21-5.
• Arnon, S. S., Schechter, R., Inglesby, T. V., Henderson, D. A., Bartlett, J. G., Ascher, M. S., ... & Working Group on Civilian
Biodefense. (2001). Botulinum toxin as a biological weapon: medical and public health management. Jama, 285(8), 1059-1070.
• Inglesby, T. V., O'Toole, T., Henderson, D. A., Bartlett, J. G., Ascher, M. S., Eitzen, E., ... & Working Group on Civilian
Biodefense. (2002). Anthrax as a biological weapon, 2002: updated recommendations for management. Jama, 287(17), 2236-2252.
• Senanayake, N., & Karalliedde, L. (1987). Neurotoxic effects of organohosphorus insecticides. New England Journal of Medicine,
316(13), 761-763.
• Chin, R. G., & Calderon, Y. (2000). Acute cyanide poisoning: a case report. The Journal of emergency medicine, 18(4), 441-445.
