Intrathecal baclofen for generalized dystonia: A case report

853

CLINICAL NOTE

Intrathecal Baclofen for Generalized Dystonia: A Case Report Michael S. Jaffe, DO, Linda J. Nienstedt, MD ABSTRACT. Jaffe MS, Nienstedt LJ. Intrathecal baclofen for generalized dystonia: a case report. Arch Phys Med Rehabil 2001;82:853-5. Dystonia is an abnormal movement characterized by sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Primary generalized dystonia usually evolves to a debilitating condition, often unresponsive to oral pharmacologic regimens or physical rehabilitation. We present the case of a patient with idiopathic adult-onset generalized dystonia who was recalcitrant to oral therapies. This patient was treated with intrathecal baclofen therapy and responded dramatically with improved functional abilities, resolution of chronic pain, and an improved rating on the dystonia scale. Key Words: Baclofen; Case report; Dystonia; Rehabilitation. © 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation NTRATHECAL BACLOFEN (ITB) has been used to treat spasticity in persons with spinal cord injury (SCI), cerebral Ipalsy, brain injury, and multiple sclerosis (MS). Several 1-4

groups5-7 have studied the use of ITB for generalized dystonia with discouraging results. Dystonia is characterized by sustained simultaneous contractions of agonist and antagonist muscles, resulting in a disorder of movement.1 Its movement pattern differs from hypertonic spasticity, which is characterized by a velocity-dependent increase in tonic reflexes, exaggerated muscle stretch reflexes, and spreading of reflexes.2 Dystonias, in the context of movement disorders, are defined with relation to their onset in childhood or adulthood and by their relation to underlying diseases or hereditary predisposition (secondary, symptomatic). Environmental factors, hereditary neurologic disorders, parkinsonian syndromes, and psychiatric syndromes may cause generalized dystonia.3 Primary dystonias are those without identifiable associations. The basal ganglia has been implicated in a variety of movement disorders. Symptomatic dystonias are often associated with pathologic lesions in the putamen of the basal ganglia that can occasionally be shown on neuroimaging studies. Conversely, primary generalized dystonia— by definition ideopathic—is not associated with any known pathologic lesion. However, a recent report4 has shown that stimulation of the globus pallidus interna may have an affect on primary generalized dystonias, therefore, implicating this region further.

From the Departments of Physical Medicine and Rehabilitation (Jaffe), and Neurology (Nienstedt), Southern California Permanente Medical Group, San Diego, CA. Accepted in revised form August 7, 2000. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Reprint requests to Michael Jaffe, DO, Dept of PM&R, Kaiser Permanente, 4405 Vandever Ave, San Diego, CA 92120. 0003-9993/01/8206-6009$35.00/0 doi:10.1053/apmr.2001.23268

Gamma-aminobutyric acid (GABA) is a neurotransmitter found in several prominent basal ganglia projection pathways.1 In a model of basal ganglia function developed by DeLong et al,5 motor output is modulated by the corticobasal gangliothalamocortical circuit. Continuous infusion of ITB might improve dystonia by modulating this circuit, thus, inhibiting the excessively stimulated supplemental premotor and motor cortex.6 We present the case of 1 patient with generalized dystonia who responded favorably to ITB. CASE DESCRIPTION The patient is a right-handed, 70-year-old retired aerospace engineer who has been in good health throughout most of his life. He presented to our neurology clinic with a 6-year history of dystonia. This initially began with twitching movements of the head to the left, as well as orobuccolingual dystonic movements. He eventually developed a segmental, then generalized, dystonia. Head magnetic resonance imaging at another institution showed no abnormalities. The patient denied any exposure to antipsychotic medications or toxins before the onset of his symptoms. He had no family history of dystonia and was not of Jewish origin. Serologic studies were all normal. The patient failed to respond to dopaminergic medications, polypharmacologic regimens including benzodiazepines, high doses of anticholinergics, risperidone, trazodone, and gabapentin. On July 28, 1999, the patient was hospitalized for progressing malnutrition and cachexia. Infected excoriations of the tongue and mouth were identified, as well as a left lower-lobe pneumonia. After a swallow study verified a dysphagia, a percutaneous endoscopic gastrostomy tube was placed. At the time of the hospitalization, the patient’s family felt that they could no longer take care of him. The patient required dependent care for all of his hygienic needs and activities of daily living. He was bed bound because of the complexity of his movement disorder. He experienced pain from his movement disorder and was taking hydrocodone around the clock for pain management. He was being treated intravenously with 1 to 2mg of lorazepam every 4 hours. His family wanted a final hospital evaluation before sending him to a nursing home. A consultation by the psychiatrist showed that the patient did not meet criteria for depressive disorder. A repeat computed tomography scan of the brain showed no significant abnormalities. Serum chemistries, copper levels, and ceruloplasmin levels were also within normal limits. On physical examination, the patient was cognitively alert and oriented times 4 and his speech was severely dysarthric. The patient had severe dystonic movements of the face involving the oromandibular musculature and also had blepharospasm. Excoriations around the head and face were present. The patient required diapers and wore a padded glove on his left hand to prevent self-injury. Dystonic movements spread caudally to affect the torso, arms, and legs. These movements were somewhat relieved with voluntary movement. There were no contractures of the extremities. The patient’s motor strength was rated at 5/5 for all major muscle groups. There were no sensory deficits on examination. The patient’s Ashworth scale for tone of the extremities was rated at 2. In light of the patient’s discomfort and recalcitrant medical condition, we concluded that a trial of ITB would be prudent. Arch Phys Med Rehabil Vol 82, June 2001

854

INTRATHECAL BACLOFEN FOR GENERALIZED DYSTONIA, Jaffe

Table 1: FIM Rating Criteria and Patients’ Pre- and Postimplant FIM Scores FIM Rating Criteria

7 Complete independence 6 Modified independent Modified dependence 5 Supervision 4 Minimal assist (subject ⫽ 75%⫹) 3 Moderate assist (subject ⫽ 50%⫹) Complete Dependence 2 Maximal assist (subject ⫽ 25%⫹) 1 Total assist (subject ⫽ 0%⫹)

Preimplant

Self-Care Eating Grooming Bathing Dressing upper body lower body Toileting Sphincter Control Bladder management Bowel management Mobility (transfers) Bed, chair, wheelchair Toilet Tub, shower Locomotion Walking Stairs Communication Comprehension Expression Social Cognition Social interaction Problem solving Memory Total FIM

No helper

Helper

Postimplant (6wk)

2 1 1

3 3 2

1 1 2

3 3 5

3 3

5 5

2 2 2

3 5 3

2 1

3 1

3 1

4 2

1 1 4 35

2 2 4 61

The screening test took place during the patient’s hospitalization. The test dose was performed by using 100␮g of baclofen through a lumbar puncture at L4 –5. The patient was evaluated on an hourly basis by a physical therapist for 8 hours. Functional changes were recorded. At 3 hours postinfusion, the patient showed the maximum effects of the test dose. The patient was resting comfortably throughout the trial and reported a marked decrease in pain. Although some tongue thrusting movements remained, his facial muscles were relaxed and there was no tongue biting. The patient did not experience any adverse effects during the test dose. The care team, the patient, and the patient’s son agreed that the implantation of an ITB pump system for ITB therapy was appropriate. On September 15, the intrathecal pump was implanted. The starting dose of baclofen was 100␮g/d. The patient was followed up in the department of physical medicine and rehabilitation 5 days postoperatively and was seen every 2 weeks for pump management. The baclofen pump was titrated up to 550␮g/d after 6 weeks. The patient’s dystonic movements decreased markedly. At 6 weeks, the patient was able to walk with stand-by assistance for household distances. At 3 months Arch Phys Med Rehabil Vol 82, June 2001

postimplantation, his ambulation progressed to short community distances. He was supervised for toileting and bladder and bowel management, but no longer required maximal assistance. No further medications for pain management were required. Overall, the patient’s FIM™ instrument score changed from 35 to 61 over 6 weeks (table 1). The patient’s dystonia scale score improved from 3 to 1 (scale range, 0 –3) (table 2). DISCUSSION The difficulty in treating severe generalized dystonias is well known to neurologists, physiatrists, and other specialists who treat these patients. Anticholinergics, dopaminergics, benzodiazepines, anticonvulsants, and tetrabenzine have had their place in treatment.1 The difficulty in treating severe generalized dystonia is exemplified by these patients classically showing progressive overall decline, as our patient did. Continuous ITB administration has become a powerful tool in the treatment of spasticity caused by SCI, brain injury, cerebral palsy, and MS.6-9 However, ITB in the treatment of dystonia has largely been disappointing. Ford et al10 studied 25 patients with severe generalized dystonia treated with ITB and found no significant response. Penn et al11 initiated ITB therapy for 1 generalized dystonia patient with only minimal response. Albright et al12 treated 5 generalized dystonia patients with ITB. Only 1 of these patients showed functional gains, though 4 of 5 showed some improvement. Baclofen is an agonist at the GABA-B receptor in the spinal cord and brain. GABA is the main inhibitory neurotransmitter in the central nervous system.13 Spasticity of cerebral origin represents a net loss of descending vestibulospinal, reticulospinal, and corticospinal tract inhibition to motoneurons. Baclofen acts both pre- and postsynaptically by facilitating GABAmediated interneuron inhibition. The clinical effects are decreased resistance to passive range of motion, decreased hyperreflexia, and reduction in spasms and clonus. The indwelling ITB catheter is placed between T5 and L1. The concentration of ITB is greatest in the lumbar cistern with a lumbar to cisterna magna ratio of 4:1. Why this patient with generalized dystonia responded to ITB is an enigmatic question. We offer 3 hypotheses for our patient’s exceptional response. First, generalized dystonia is a cerebral-mediated disorder. ITB concentrates in the lumbar region. However, higher placement of the indwelling catheter may have an effect. A recent study14 showed the improved efficacy of ITB for upper extremity spasticity with higher placement of the indwelling catheter. Our patient had the catheter placed at the T8 level, which may have resulted in possibly higher cerebral levels of ITB. A second mechanism could be related to patients’ individual sensitivities to baclofen. There is no standard dosing for ITB. We have patients with ITB doses ranging from 35 to 1000␮g/d without a linear correlation to the amount of spasticity being treated. Our patient may have been more sensitive to the medication, improv-

Table 2: The Global Dystonia Scale Global Dystonia Score

0 1 2 3

Definition of Dystonia

No dystonia Mild dystonia with little impairment Moderate dystonia with obvious or pronounced movements and spasms Severe dystonia preventing ambulation or the performance of daily living activities

INTRATHECAL BACLOFEN FOR GENERALIZED DYSTONIA, Jaffe

ing its efficacy. A third possibility exists. The cause of generalized dystonia is unknown and many pathophysiologic mechanisms are possible as causative factors. This patient’s favorable outcome may be based on the particular cause of his dystonia. CONCLUSION ITB therapy has been used as a final option of treatment in dystonic patients and has been met with discouraging response. In the present case study, our patient had a well-established primary generalized dystonia with progression of his illness to the stage of full dependent care. With use of ITB in this patient, the dystonia clearly improved. The patient realized major functional gains, attained the level of supervised care at home, and discontinued pain medication. The reason for our patient’s response to ITB therapy is speculative. Perhaps his response was related to higher cerebral levels of baclofen with higher catheter placement. The multifactorial cause of dystonia also must be considered as a major role. Based on our experience, we conclude that an ITB trial should be considered more routinely as part of the management in patients with primary generalized dystonia. References 1. Watts RL, Koller WC, editors. Movement disorders: neurologic principles and practice. New York: McGraw-Hill; 1997. 2. DeLisa J, Gans B, editors. Rehabilitation medicine. 2nd ed. Philadelphia: Lippincott; 1993. 3. Fahn S, Marsden D, Jankovic J, editors. A comprehensive review of movement disorders for the clinical practitioner. Proceedings of the 3rd Annual Course for Movement Disorders; 1993 Aug 2-5; Aspen (CO). New York: Columbia University College of Physicians and Surgeons; 1993.

855

4. Kumar R, Dagher A, Hutchinson W, Land A, Lozano A. Globus pallidus deep brain stimulation for generalized dystonia: clinical and PET investigation. Neurology 1999;53:871-4. 5. DeLong M, Crutcher M, Geogopoulos A. Primate globus pallidus and subthalamic nucleus: functional organization. J Neurophysiol 1987;53:530-43. 6. Albright AL, Barry MJ, Painter MJ, Shultz B. Infusion of intrathecal baclofen for generalized dystonia in cerebral palsy. J Neurol 1998;88:73-6. 7. Azouvi P, Mane M, Thiebaut JB, Denys P, Remy-Neris O, Bussel B. Intrathecal baclofen administration for control of severe spinal spasticity: functional improvement and long-term follow-up. Arch Phys Med Rehabil 1996;77:35-9. 8. Meythaler J, Guin-Renfroe S, Grabb P, Hadley M. Long-term continuously infused intrathecal baclofen for spastic-dystonia hypertonia in traumatic brain injury: 1-year experience. Arch Phys Med Rehabil 1999;80:13-9. 9. Ordia J, Fisher E, Adamski E, Spatz E. Chronic intrathecal delivery of baclofen by a programmable pump for the treatment of severe spasticity. J Neurosurg 1996;85:452-7. 10. Ford B, Green P, Louis E, Petzinger G, Bressman S, Goodman, et al. Use of intrathecal baclofen in the treatment of patients with dystonia. Arch Neurol 1996;53:1241-6. 11. Penn R, Gianino J, York M. Intrathecal baclofen for motor disorders. Mov Disord 1995;10:675-7. 12. Albright AL, Barry MJ, Fasick P, Barron W, Shultz B. Continuous intrathecal baclofen infusion for symptomatic generalized dystonia. Neurosurgery 1996;5:934-8; discussion 938-9. 13. Kroin J. Intrathecal drug administration: present use and future trends. Clin Pharmacokinet 1992;22:319-26. 14. Grabb P, Guin-Renfroe S, Meythaler J. Midthoracic catheter tip placement for intrathecal baclofen administration in children with quadriplegic spasticity. Neurosurgery 1999;45:833-6.

Arch Phys Med Rehabil Vol 82, June 2001