Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical Warfareimpacts of survival of otherwise lethal cyanide intoxicationsis necessarily framed by the few published casereports that follow survivors over time. 127,162–170 Thesereports indicate that the major system resulting inclinically relevant pathology is the central nervoussystem, particularly the brain, but also to some extentthe spinal cord. 171Cyanide does not uniformly affect all brain cells. Forexample, CA1 neurons in the hippocampus are moresusceptible than CA3 cells to metabolic inhibition bycyanide. 172 Nearly all long-term neurological sequelaeof acute high-dose exposure result from damage tothe basal ganglia and sensorimotor cortex, with additionaldefects referencing cerebellar Purkinje neurons.Cell death occurs slowly after brief ischemia. Currenttheory favors cellular apoptosis as the mechanism ofdemise as opposed to necrotic death. 163,167 Casualtieswith long-term effects manifest parkinsonian-likeconditions and akinetic rigid syndromes, typicallyafter intervals of weeks to months. Usually lackingare tremor, pathological reflexes, disorders of sensitivity,or intellectual deficits. Occasionally, the clinicalpicture partially improves over time. Some patientsdemonstrate partial improvement with medication.The following eight case synopses address the neuroanatomicalpathology of survivors of large cyanidedoses, with brief summaries of overall presentationand radiological/histopathologic features. (Note thatadvancing technologies allow gradually improvedunderstanding of functional as well as anatomicalconsequences of survival from potentially lethal cyanideintoxications.)Case Study 11-1. An 18-year-old male surviveda 975- to 1,300-mg KCN ingestion. 176 He developedparkinsonian syndrome, characterized primarily byakinesia and rigidity, and died 19 months later. Theautopsy revealed major destructive changes in theglobus pallidus and putamin. The substantia nigrawas intact.Case Study 11-2. A 29-year-old male survived a500-mg KCN ingestion. 162 Within 3 weeks he developedslowed and cumbersome speech and impairedswallowing. Within 4 weeks he overshot his trunkmovements with postural change and had stiff gait,flat facies, hypokinesia, unmodulated speech, dyscoordinationof speech, cogwheel phenomenon, severebradydiadochokinesia, brisk monosynaptic reflexes,and absence of pathologic reflexes. T2-weighted magneticresonance imaging (MRI) showed symmetricalsignal elevation in both putamina. By 5 months, hisclinical status was improved, although slow speechand pronounced bradydiadochokinesia of upper limbspersisted. The putamina were hypodense on MRI.Case Study 11-3. A 46-year-old male surviveda 1,500-mg KCN ingestion. 167 Within 3 days he hadmild difficulty with tandem gait and halting speech.Examination 3 weeks after recovery revealed markedbradykinesia; masked facies; slow, shuffling gait;mild rigidity; and weak dysphonic voice. Little tremorwas present. MRI 12 months after ingestion revealedmultiple, bilaterally symmetrical areas of high-signalintensity in the globus pallidus and posterior putamenon T2-weighted images. A 6-fluorodopa positron emissiontomography revealed diffuse decreased activity influoridopa in the basal ganglia and markedly decreasedactivity in the posterior regions of the basal ganglia,similar to patients with parkinsonism.Case Study 11-4. A 28-year-old male survived a800-mg KCN ingestion. 164 Within several weeks hedeveloped extrapyramidal signs including markeddrooling, profound micrographia, masked facies, mildintention tremor, and cogwheel rigidity. MRI 3 monthsafter poisoning demonstrated wedge-shaped areas ofincreased signal intensity in the T2-weighted images,particularly in the globus pallidi. Repeat scanning 12months later disclosed no change in the extent of basalganglial abnormality but showed the development ofmild cerebellar atrophy.Case Study 11-5. A 31-year-old male with epilepsyrecovered fully after ingesting 20 to 40 gm KCN dissolvedin milk. 166 As long as 1.5 years after the poisoning,he showed no signs or symptoms. His temporallobe epilepsy was unchanged. Memory and intelligencewere unaffected. T1-weighted images on MRI at day51 demonstrated bilaterally symmetrical high-signalintensity in both putamina. Both regions becameisointense to white matter by day 146 and remainedso by day 286.Case Study 11-6. A 27-year-old female surviveda 300-mg KCN ingestion. 165 Over the next 2 monthsshe developed gradually progressive stiffness andweakness of all four limbs, along with unclear speech,severe hyperkinetic dysarthria due to dystonia, mildleft facial weakness, generalized lead pipe rigidity,and bradykinesia. She also demonstrated hemiplegicdystonia with bilateral involvement characterized byflexed upper limbs, extended lower limbs, and normaldeep tendon reflexes with flexor plantar responses.Her upper limbs were flexed and supinated, with fingerstightly flexed and thumb strongly opposed. Herneck and spine were rigidly extended. She showed notendency to spontaneous improvement. Cranial com-388