Intrathecal methylprednisolone for intractable postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a neuropathic pain disorder that affects mostly
the elderly and which is often refractory to currently available treatments.
Many patients suffer severe physical and social disabilities as a consequence
of their chronic pain. One randomized controlled trial was publisched in which
intrathecal administration of methylprednisolone proved an effective and safe
treatment for intractable PHN. However, because of potential side effects and
lack of replication of the trial this treatment is not generally accepted.
Additional data are required to validate these promising results.
Pharmacokinetic data of intrathecal administered methylprednisolone are
lacking.

To measure the effectiveness of intrathecal methylprednisolone and lidocaine on
reducing PHN.
Measurement of mthylprednisolone concentrations in cerebrospinal fluid (Part I
only).

This is a monocenter, randomised, double-blind controlled trial with a 2 year
follow-up period.

For 2 weeks (the prestudy period) patients are treated with paracetamol and
NSAIDs. During this period (and afterward) concomitant PHN medication
maintained on a stable dose is allowed. After this period study drugs are
injected into the lumbar intrathecal space once a week for 4 subsequent weeks
by an experienced anesthesiologist.

The study consist of two parts. The first 10 patients will be included in part
I, the remaining patients in part II.

Part I:
The index group will receive injections with 60 milligram methylprednisolone
and 60 milligram lidocaine, the placebo group will receive 60 milligram of
lidocaine. The potential neurotoxic preservatives are removed from the
methylprednsiolone. Just before each injection samples of cerebrospinal fluid
are obtained in all patients. Also, 1, 4 and 8 weeks after the last injection
samples of cerebrospinal fluid will be taken from the index group. To remain
blinding of the subjects, patients in the placebo group will receive a
subcutaneous sham-puncture (not perforating the dura) at 1, 4 and 8 weeks after
the last injection. Pain is evaluated at randomisation, before the first spinal
injection, before the fourth spinal injection and then 4 weeks, 8 weeks, 6
months, 1 year and 2 years after the end of treatment. The EQ5D questionnaire
will be used to evaluate the subject's perception of the general quality of
life.

After Part I an interim analysis will be done on the pharmacokinetic data. When
appropriate, adjustments will be made for patients included in Part 2 of the
study.

Deel II:
The index group will receive injections with 60 milligram methylprednisolone
and 60 milligram lidocaine, the placebo group will receive 60 milligram of
lidocaine. The potential neurotoxic preservatives are removed from the
methylprednsiolone. Just before each injection samples of cerebrospinal fluid
are obtained in all patients. Pain is evaluated at randomisation, before the
first spinal injection, before the fourth spinal injection and then 4 weeks, 8
weeks, 6 months, 1 year and 2 years after the end of treatment. The EQ5D
questionnaire will be used to evaluate the subject's perception of the general
quality of life.

We are planning to offer this new treatment to this group of patients who have
no other treatment options left. We prefer to do so in a research setting for
above mentioned reasons (see section E9a).
Spinal anesthesia is a routine procedure that is used millions of times each
year. It is safe and rarely associated with neurologic complications [1].
The burden for the subjects in the index group in Part I will be 3 additional
punctions for obtaining cerebrospinal fluid. The other subjects in Part I of
the study will receive three placebo punctions in which the needle will be
introduced through the subcutaneous tissues to the intraspinal ligaments,
without perforation of the dura.
The risks associated with intrathecal punctions when using a 25 Gauge
pencil-point needle by an experienced anesthesiologist are very small. Many
patients report that a spinal injection is less painfull than a venapuncture.

[1] Horlocker et al. A retrospective review of 4767 consecutive spinal
anesthetics: central nervous system complications. Anesth Analg 1997; 84: p.
578-84.