Journal meeting

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Journal meeting

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Pharmacological therapy of spinal cord injury
during the acute phase

• Ref Spinal Cord (2000) 38,71-76
• Setting France

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Introduction1

• The initial results concerning neurological
  improvement after early administration of heavy
  dose of methylprednisolone to spinal cord injury
  victims appeared very promising. However
  ,clinical studies that followed dampened the
  initial enthusiasm
• In France, no pharmacological treatment is
  currently recommended in this indication

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Introduction2

• The present trial assessed neurological recovery
  1 year after administration, within 8 h of spinal
  injury, of methylprednisolone, nimodipine, or the
  two combined, in comparison with no
  pharmacological treatment. The side effects of
  these treatments and the impact of early spinal
  surgery on functional recovery were also
  evaluated.

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Patients and Methods 1

• Study design prospective, randomized clinical
  trial
• 106 patients who had spinal trauma (including 48
  with paraplegia and 58 with tetraplegia) were
  randomly separated into four groups

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Patients and Methods 2

• First groupM methylprednisolone (30 mg/kg over
  1 h, followed by 5.4 mg/kg/h for 23 h)
• Second group N nimodipine( 0.015 mg/kg/h for 2
  h followed by 0.03 mg/kg/h for 7 days,
• Third group MN (both agents)

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Patients and Methods 3

• Fourth group P (neither medication)
• Neurological assessment (ASIA score) was
  performed by blinded senior neurologist before
  treatment and at 1-year follow-up
• Early spinal decompression and stabilization was
  performed as soon as possible after injury

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Patients and Methods 4

• Patient select conducted between 1990/11 to
  1995/3 at hospital Pellegrin, France.
• Inclusion criteria were age ,older than 15 years
  and younger than 65 years, and hospitalization
  within 8 h of vertebral trauma with spinal cord
  involvement.

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Patients and Methods 5

• Exclusion criteria were a pattern of nerve-root
  involvement, cauda equina syndrome, open spinal
  lesions, pregnancy, multiple trauma, head injury
  with GCS lt13, pulmonary contusion, hemodynamic
  instability that persisted despite
  volumeexpansion, Map lt 60 mmHg, previous
  treatment by corticoids or calsium channel
  blockers, or a history of DM, stomach ulcer ,
  liver failure , or cardiovascular disorder

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Patients and Methods 6

• The following data were noted age, sex,
  circumstances of trauma, results of neurological
  examination at admission and 1 year later
  according to the classification of the American
  Spinal Injury Association (ASIA), and the amount
  of time between the accident and the
  administration of the treatment.

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Patients and Methods 7

• Conscious level Glasgow coma scale
• The injury severity score (ISS) was also record
• For the patients who necessitated surgery during
  the first 24 h , the amount of time between the
  accident and the operation was recorded as was
  the amount of intra- operative bleeding

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Patients and Methods 8

• Complications were noted, including
  metabolic(hyperglycemia), infectious(pneumonia,sep
  ticemia, UTI) cardiovascular and digestive
  disorders
• The duration of assisted ventilation and that of
  the overall hospital stay were recorded.

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Results1

• 100 patients were reassessed at 1 year.5 patient
  died. 1 refuse follow up.
• Neurological improvement was seen in each group
  ( Plt0.0001), however no additional neurological
  benefit from treatment was observed.
• infection complications occurred more often in
  patients treated with M.(66 v.s 45), this
  difference was not significant(Table 3)

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Table 1
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Table 2
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Table 3
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Table 4
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Results2

• Although motor recovery was less complete in the
  patients who were treated with M.and who
  initially developed hyperglycemia ( ASIAml 56
  versus 62), the different was not significant.
• .Early surgery (49 patients underwent surgery
  within 8 h of their accident) did not influence
  the neurological outcome.(lt 8 h v.s 8-24 hASIAml
  
• 64 v.s 65)

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Results3

• The only predictor of the latter was the extent
  of the spinal injury(complete or incomplete
  lesion)

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Discussion 1

• Consequently, the validity of the observed
  improvement after 1 year is a reliable finding.
  In the patients with complete spinal-cord injury,
  this improvement, when present, involved the
  level of the lesion and the two adjacent caudal
  level to various degrees.the greatest
  amelioration was noted in the patients who had
  incomplete cord lesions.

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Discussion 2

• The results must be interpreted with caution
  since the number of patients in each group may
  have been insufficient.
• Although US administration of methlprednisolone
  has become standard procedure,FDA has not
  authorized it

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Discussion 3

• The second obstacle to comparing studies is the
  absence of consensual terminology in the initial
  neurological evaluation. The currently
  recommended scores proposed by the ASIA allow a
  very precise analysis of spinal cord
  involvement,but the use of ASIA score is not yet
  widespread

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Discussion 4

• In several experimental models of spinal cord
  injury, the early administration of nimodipine
  reduced the drop in spinal cord blood flow in the
  proximity of the lesion compared to placebo, but
  the benefit in terms of neurological recovery
  remains to be demonstrated.

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Discussion 5

• Patients with a neurological dysfunction have
  been shown to have a deficient lymphocyte
  response and impaired natural killer cytotoxic
  activity, which would at least partially explain
  their increased susceptibility to infection

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Discussion 6

• The usefulness of early surgery remains in the
  forefront of the treatment of spinal-cord injury.
  Because the persistence of spinal cord
  compression is correlated with neurological
  worsening and a risk of secondary displacement.

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Conclusion

• The present study confirms the absence of
  pharmacological therapy in this indication.
  Because of the paucity of clinical studies that
  demonstrate the efficacy of pharmacological
  treatment in the spinal injury during the acute
  phase, systematic use of pharmaceutical agents
  should be reconsidered.