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Continuous intrathecal baclofen infusion alleviates autonomic dysfunction in patients with severe supraspinal spasticity
  1. R BECKER,
  2. U SURE,
  3. M PETERMEYER,
  4. H BERTALANFFY
  1. Department of Neurosurgery, Philipps-University Hospital Marburg, Germany
  1. Dr Ralf Becker, Department of Neurosurgery, Philipps-University Hospital, Baldingerstraβe, 35033 Marburg, Germany. Telephone 0049 6421 286448; fax 0049 6421 286415.

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Continuous intrathecal baclofen infusion (CIBI) is a widely accepted therapy for the treatment of severe spinal spasticity. There is increasing evidence that CIBI has similar effects on patients with supraspinal spasticity resulting from either hypoxic or traumatic brain injury.1 A proportion of patients with supraspinal spasticity present with additional autonomic dysfunction. These dysfunctions are often unresponsive to conventional antiadrenergic medication. Patients may present with severe arterial hypertension, tachycardia, hyperhidrosis, hypersalivation, and bronchial hypersecretion. Mortality is mainly influenced by these symptoms. In addition to antiadrenergic medication sedatives and analgesics are often required. During intensive care treatment such medication often leads to a prolongation of artificial ventilation and delayed rehabilitation. During rehabilitation autonomic instability additionally interferes with physiotherapeutic activity.

In the follow up of patients with severe supraspinal spasticity we noted the positive influence of intrathecal baclofen infusion on autonomic instability.1 Study of the literature did not disclose similar findings. So far, it had not yet been pointed out that CIBI has a positive influence on symptoms originating from severe hypoxic or traumatic brain damage.

Eighteen patients with severe tetraspasticity from either hypoxic or traumatic brain injury were treated with CIBI. Before admission all patients were treated with maximum doses of various oral antispastic agents.

The interval between event and bolus test varied between 1 and 62 months (median 8 months).

After a positive response to an intrathecal baclofen bolus application a pump (Medtronic Synchromed 8611H) was implanted for CIBI.

During the further treatment of these patients it was noted that six of 18 patients had severe autonomic dysfunction, unresponsive to conservative medical treatment (30% of the original communication1).

Tachycardia, arterial hypertension or hypotension, often associated with agitation, hyperhidrosis, hypersalivation, and tracheobronchial hypersecretion were regarded as autonomic dysfunction associated with severe spasticity. These symptoms were graded qualitatively as not present, present and improved, or present and unchanged. This assessment was made from physicians’ and nurses’ documentation of symptoms in the patient files and from the observations of relatives. Due to the retrospective character of the study, a further quantitative assessment could not be performed.

Six out of the 18 patients had severe autonomic dysfunction and spasticity. Three patients had hypoxic and three severe traumatic brain injury. Two patients were severely disabled and four were in a vegetative state. The interval from primary event to pump implantation ranged from 4 to 24 months. The mean follow up was 16.8 (8–23) months and the mean daily dose of intrathecal baclofen was 408 μg (range 100–600 μg).

Four patients presented with severe spasticity (Ashworth score 5), one with an initial Ashworth score of 4 and one with an Ashworth score of 3. The following autonomic dysregulation symptoms were seen: tachycardia (3/6), arterial hyper-/hypotension (2/6), hyperhidrosis (4/6), hypersalivation (5/6), tracheobronchial hypersecretion (5/6). Agitation was seen in five of six patients. In five patients the symptoms disappeared with intrathecal baclofen therapy. In one patient (No 3), a 33 year old woman, in a persistent vegetative state after hypoxic brain injury originating from non-suicidal strangulation, the autonomic dysfunctions did not improve with intrathecal baclofen but disappeared after the additional application of intrathecal morphine. The outcome concerning the autonomic dysfunctions is shown in the table.

Patients surviving severe traumatic or hypoxic brain injury regularly have a variable period of deep coma with flexion and extension spasms and severe autonomic dysfunction that might persist over months. Later, many patients die from autonomic dysfunction or severe infections. Most of the survivors develop severe spasticity and still have autonomic dysfunction. The effects of CIBI on autonomic dysfunction have not yet been examined in the literature, although these symptoms appear in about 30% of patients with supraspinal spasticity in our series.

The patients presented had severe autonomic dysfunction and were unresponsive to conservative medical therapy. Intrathecal baclofen infusion improved most of the symptoms so that no additional medication was necessary. One patient did not improve until additional intrathecal morphine was applied. The improvement of symptoms after intrathecal morphine administration might suggest a central analgesic effect of baclofen enabling a reduction of autonomic dysfunction. Spinal inhibition of excitatory transmission might enhance the positive effect of CIBI on severe autonomic dysfunctions.

GABA-B receptors are widely distributed throughout the CNS.2 The action of GABA-B receptors on autonomic regulations, especially in pathological conditions, is unknown.

Sympathetic and cardiovascular depressant effects of balofen have been shown with local application of GABA-A and GABA -B receptor agonists and antagonists at the rostral ventrolateral medulla (RVLM) of the rat, in the cat ventromedial and posterior hypothalamus, and in isolated spinal cord preparations.3-5 However, it was possible to increase blood pressure with injection into the anterior hypothalamus and nucleus tractus solitarius.5

Autonomic nervous system regulation, involving different regions of the CNS, is complex. Concerning the positive effect of intrathecal baclofen on autonomic dysfunction the findings presented should be confirmed in different clinical situations—for instance, in patients with acute midbrain syndrome. So far, we have restricted the indication for intrathecal baclofen therapy to the treatment of patients in a stable clinical condition.1 However, after these preliminary findings we now support an early treatment to achieve an autonomic stabilisation and early prevention of contractures in patients with supraspinal spasticity.

The following conclusions can be drawn:

(1) Improvement of autonomic dysfunctions with continuous intrathecal GABA-B agonist application was achieved in all patients treated and should be considered by others.

(2) The use of CIBI offers a treatment of otherwise unresponsive autonomic instability in the acute medical setting.

(3) The pharmacological background of these findings needs further investigation. Our preliminary findings should be confirmed in pharmacological test settings.

References

Table 1

Autonomic dysfunctions during the course of treatment

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