Intoxications (and Infections of the Nervous System)

Question 1

What are the different types of intoxications?

Answer 1

• Bacterial toxins
  
  • Tetanus via tetanospasmin
  • Botulism via botulinum
• Environmental
  
  • exposure may occur in the workplace, need to ask about pts occupation, whether fellow workers are sick.
  • may also be due to hobby/recreational or abuse
    
    • Lead
    • Organic solvents
    • CO
• Illicit or recreational drugs
  
  • Cocaine
  • Amphetamines
  • PCP
  • LSD
• Alcohol

Question 2

Bacterial Toxin (A): Tetanospasmin

Answer 2

• exotoxin of Clostridium tetani, tetanospasmin
• produced anaerobically in dirty (soil-contaminated) wounds, unsterile IV needles of drug abusers
• PathoPhys: after hours to weeks, exotoxin (tetanospasmin) binds to interneurons of brain, brain stem, spinal cord (interneurons), preventing release of inhibitory NT: glycine and GABA
• CP: motor neuron disinhibition:
  
  • begins days to TWO weeks after exotoxin exposure
  • spread of exotoxin through the bloodstream causes:
    
    • diffuse muscle spasms
    • generalized convulsive seizures- from cortical disinhibition (generalized tetanus)
  • severe, prolonged, painful spasms in muscles near wound (localized if there is only limtied retrograde axonal transport of tetanospasmin near wound), or generalized, including jaws, face, respiratory muscles
    
    1. trismus/lockjaw=clenching jaw
    2. risus sardonicus=grimacing smile
    3. opisthotonus=arching back
• Diagnosis: made on clinical grounds + hx of exotoxin exposure
• Tx: ICU care (with mechanical ventilation)
  
  • neuromuscular blockade
  • sedation
  • anticonvulsants
  • human tetanus immune globulin
  • antibiotics (for the wound infection)

Question 3

Bacterial Toxin (B): Botulinum toxin

Answer 3

• exotoxin of Clostridium botulinum, produced anaerobically in improperly canned or prepared food or in wound infections
  
  • adequate cooking destroys existing heat-sensitive exotoxin;
• exotoxin (most potent poison known) binds to presynaptic nerve terminals preventing ACh release from LMN and PS nerves
• severity of paralysis depends on amount of exotoxin eaten
  
  • skeletal muscle, bowel, bladder, salivary glands
• Cp: symptoms begin after 12-48 hrs
  
  • early: ptosis, diplopia, and pupillary paralysis
  • later: dysphagia, facial, limb, and respiratory weakness may occur
  • potentially: respiratory paralysis
• Diagnosis: clinical picture, EMG test (brain MRI), bioassay for exotoxin (takes days)
• Prognosis: good (gradual, spontaneous after days to weeks) with excellent ICU care (mechanical ventilation is needed)
• Tx: guanidine (oral drug) helps facilitate ACh release from motor nerve endings

Question 4

Environmental Toxin (A): Lead

Answer 4

• adults (workplace paint, glazing, lead batteries)
  
  • CP: peripheral neuropathy (with prominent focal neuropathies like wrist drop)–flick o da wrist
• children in substandard housing ingest flakes of lead-based paint
  
  • CP: encephalopathy, abdominal pain–dummy with tummy ache
• Diagnosis: confirmed by high serum, urine lead levels
• Tx: chelation agents-guided by elevated serum lead levels

Question 5

Environmental Toxin (B): CO

Answer 5

• odorless gas (detected with specialized monitors), greater affinity for hemoglobin than oxygen does
• sources: malfunctioning heaters, unventilated automobile exhaust in garages
• CP:
  
  • early: HA, vomiting, blurred vision
  • late: coma, seizures, cardiopulmonary arrest
• Diagnosis: confirmed by elevated CO blood level
• Tx: hyperbaric oxygen chamber or inhalation of 100% oxygen
• Prognosis: survivors may have residual deficits of memory or cognitions (amnesia)
  
  • After a few weeks: signs of Parkinsonism from sensitivity of the BG to CO

Question 6

Environmental Toxin (C): Organic Solvents

Answer 6

• chemical plant exposure, glue/adhesive sniffers
• CP: encephalopathy or peripheral neuropathy
  
  • ​sniffers: peripheral neuropathy over time
• Diagnosis: clinical

Question 7

Illicit or Recreational Drugs

Answer 7

• During intoxication (“on a high”)
  
  • head trauma, intracranial hemorrhage (during euphoria, impaired judgment, altered consciousness, hallucinations)
  • drug-induced seizures
• During drug withdrawal
• Drug-related stroke syndrome in a younger, otherwise healthy pt or atypical pt
  
  • Differential Diagnosis: drug-induced vasoconstriction or abrupt HTN causes cerebral ischemic infarction or brain hemorrhage
  • COCAINE most common; amphetamines, phencyclidine (PCP), LSD also reported
    
    • uncommonyl iv drug-abusers having vasculitis

Question 8

Alcohol Toxicity

Answer 8

• Acute intoxication
  
  • social disinhibition, impaired consciousness, cerebellar dysfunction
    
    • ​cerebellar dysfunction Cp: dysarthria, dysmetria, nystagmus, and ataxia
  • secondary head trauma
    
    • CP: unsteady, groggy, inebriated pt stumble and fall
  • All across, symptoms resolve as the blood alcohol level falls
  • very high levels may lead to coma, deathAlcohol Withdrawal syndrome
• Alcohol withdrawal syndrome:
  
  • when drink binge ends
  • early, hypersympathetic stage (tremulous, sweaty, tachycardic, jittery);
  • 12 hrs-3 days after drinking stopped: limited number/cluster of generalized tonic-clonic seizures
    
    • any partial or focal seizure (or onset) suggests a focal lesion requiring further investigation (brain scan)
  • 3-4 days after drinking stopped: later stage of delirium tremens, with fluctuating motor and autonomic activity, confusion, hallucinations
  • deliriums, coexisting infections or head trauma may prove fatal
  • Tx: benzodiazepines for sedation and seizure control, provide hospitalization, hydration and metabolic support, thiamine supplementation

Question 9

Chronic Alcoholism Syndromes

Answer 9

• caused by alcohol itself, malnutrition or vitamin deficiencies, beverage contaminants or (repeated head) injuries when drunk->neurological problems
  
  • Ex head trauma: subdural hematomas, cerebral hemorrhage, polyneuropathy
• Wernicke-Korsakoff syndrome
  
  • Cause: deficiency of Vit B1 (Thiamine)–mostly from alcoholics
  • acute Wernicke encephalopathy
    
    • CP: nystagmus, ophthalmoplegia, gait ataxia, confusion)
    • Tx: correctible with (hours to days of) thiamine supplementation
  • Korsakoff psychosis the chronic phase due to severe or recurrent deficinency
    
    • amnestic syndrome is prominent with frequent confabulation (“story telling”)
    • Path: tiny petechial hemorrhages and gliosis occur in vicinity of 3rd and 4th ventricles and connecting aqueduct
• alcoholic cerebellar degeneration (anterior-superior vermis)
  
  • CP: gait ataxia, dysmetria of lower limbs
• central pontine myelinosis
  
  • occurs with alcoholics and other pts who undergo overly rapid correction of severe hyponatremia
• peripheral neuropathy (rarely myopathy)
• dementia (controversial)