Effect Of Intrathecal Baclofen Research Articles

Intrathecal baclofen therapy in severe head injury, first time in Nepal, a technique suitable for underdeveloped countries

Intrathecal baclofen (ITB) has been found to be helpful not only for spasticity but also for unconsciousness in a vegetative patient. This is the first case of ITB in Nepal, and here we discuss the effectiveness of ITB for spasticity in a patient in vegetative state. We also discuss about a simple technique for ITB used in Nepal where baclofen pump is not available. Here, we present a case of a 40-year-old male patient who had severe head injury with diffuse axonal injury treated conservatively. He went on to a vegetative state and subsequently developed severe spasticity of all the limbs. ITB was started under the guidance of one of the authors , Prof. Taira. Baclofen was injected to the spinal intrathecal space through a catheter which is used for spinal anesthesia. Spasticity improved significantly and his higher mental function also showed signs of improvement. He finally became fully conscious and well oriented. ITB is very useful in cases of severe spasticity and vegetative condition, a state of unconsciousness lasting longer than a few weeks. Even with a simple technique in the absence of baclofen pump, ITB can be used with its optimum effect.

Effects of intrathecal baclofen on daily care in children with secondary generalized dystonia: A pilot study

Aim Treatment options for dystonic cerebral palsy (CP) are limited. Our aims were to determine whether intrathecal baclofen (ITB) improves daily care, decreases dystonia and decreases pain in patients with dystonic CP. Methods Patients received randomized blinded treatment with ITB or placebo. Scores on problems of daily care were recorded and dystonia, pain and comfort were assessed. Results Four patients (three males, average age 12 years 6 months) were included (all Gross Motor Function Classification System level V). During the trial period problem scores and dystonia scores decreased in all four patients. Conclusion In this pilot study we report positive functional effects of ITB trial treatment in four patients with dystonic CP. A randomized trial with a larger cohort is needed to verify these results.

Neurophysiological evidence for muscle tone reduction by intrathecal baclofen at the brainstem level

Objective Intrathecal baclofen (ITB) is an efficient treatment modality for severe spasticity that is considered to act at the spinal level. Its influence on phasic spasticity is usually determined clinically by testing muscle reflexes, and on tonic spasticity by using scores such as the Modified Ashworth Scale (MAS). Neurophysiological techniques, e.g., soleus H reflex, may provide additional information regarding ITB efficacy. There is, however, only scarce information available on time–response relationships of clinical and neurophysiological measures of spasticity obtained at different levels along the neuroaxis. Methods Fourteen patients with severe spastic paraparesis underwent serial evaluation of MAS in upper and lower limbs and serial testing of H reflex in soleus and flexor carpi radialis muscles, T wave in quadriceps and biceps brachii muscles, and blink reflex (BR) with and without prepulse, at baseline, and 15, 30, 60, 90, 120, and 180 min following ITB bolus application. Results ITB bolus application caused significant suppression of soleus H reflex after 15 min and of quadriceps T wave after 30 min, while MAS dropped significantly after 60 min together with significant suppression of BR R2 area without and with prepulse stimulation. H reflex in flexor carpi radialis and T wave in biceps brachii were not significantly suppressed by ITB. The time course of early changes in soleus H max/ M max ratio and quadriceps T wave indicates a suppression of hyperreflexia at the spinal level, while a later reduction of MAS synchronously with suppression of BR with and without prepulse concurs with a brainstem effect of ITB. Conclusion Temporal concurrence between suppression of brainstem reflexes and desired suppression of lower limb muscle hypertonia after ITB bolus application suggests that both may be at least partially mediated from a common CNS region of activity. Significance Our data concur with a significant brainstem action of ITB.

Poster 307: The Effect of Intrathecal Baclofen on Bone Density in Patients With Cerebral Palsy

Poster 307: The Effect of Intrathecal Baclofen on Bone Density in Patients With Cerebral Palsy

Incidence and Identification of Intrathecal Baclofen Catheter Malfunction

A retrospective chart review was undertaken of cases of intrathecal baclofen (ITB) pump/catheter malfunction and the diagnostic tests performed to identify the problem. An internal review was performed to develop a diagnostic flow chart to have a systematic method for identifying ITB pump and catheter complications. Retrospective chart review. Tertiary care hospital. A total of 167 adult patients currently followed in outpatient clinic with intractable spasticity and ITB pump implanted between January 1994 and May 2009. None. Catheter malfunction was identified either by anterior/posterior and lateral thoracic/lumbar radiographs, fluoroscopic guided side port access, contrast agent injection followed by CT (fluoro/CT) scan, or indium radionuclide studies. During the study period, 33 patients had 37 catheter revisions. Radiographs were obtained in all cases; fluoro/CT studies in 22, and indium studies in 6. Four cases had both fluoro/CT and indium studies. A total of 13 cases (35.1%) were diagnosed with radiographs; 9 cases (24.3%) were diagnosed by inability to withdraw cerebral spinal fluid from the side port; 13 cases (35.1%) were diagnosed with fluoro/CT studies; and 2 cases (5.4%) were diagnosed with indium studies. Fluoro/CT studies demonstrated subdural catheter location in 7 cases. A total of 2 of 4 cases with both fluoro/CT and indium studies had normal-appearing indium scans and an abnormal fluoro/CT study confirming subdural catheter placement. On the basis of an internal review of the diagnostic studies used to identify patients with suspected ITB pump/catheter malfunction, a troubleshooting flow chart was developed. Timely identification and correction of potential ITB complications could improve the clinical effectiveness of ITB and may reduce unnecessary health-care costs.

Effect of intrathecal baclofen, botulinum toxin type A and a rehabilitation programme on locomotor function after spinal cord injury: A case report

A few studies have reported the use of botulinum toxin injections after spinal cord injury, as this is the gold standard to treat focal spasticity. We report such a case here. A 38-year-old woman who had become paraplegic and care-dependent secondary to cervico-thoracic intramedullary ependymoma, presented 8 months later with painful lower limb spasticity, which was being treated with oral anti-spastic and benzodiazepine drugs with no therapeutic effect. We treated the patient with intrathecal baclofen to reduce her spasticity and in order to avoid the major side-effects of high dosages of oral baclofen. After motor rehabilitation programmes, which included functional electrical stimulation, the patient was able to wear an advanced reciprocating gait orthosis. However, she experienced painful muscle spasms in her toes of the feet that limited her gait. Therefore, she was also treated with bilateral injections of botulinum toxin type A into the flexor digitorum brevis muscles. The patient reported relief of spasms and pain, enabling her to wear an advanced reciprocating gait orthosis and facilitating rehabilitation programmes. The use of botulinum toxin type A may be an important adjunctive therapy to increase the therapeutic effect of baclofen on spasticity in small muscles, resulting in a more focal effect, and improving the use of orthoses and the effectiveness of rehabilitation programmes in patients after spinal cord injury.

‘Satisfaction with intrathecal baclofen treatment in paediatric patients with progressive neurological disease’

SIR–Intrathecal baclofen (ITB) treatment could be a beneficial treatment option in paediatric patients with progressive neurological disorders causing spasticity. Since its introduction in the 1980s,1 ITB has been mainly recommended for individuals with severe spasticity refractory to oral treatment2–4 and is proven to be effective for reduction of spasticity, especially in patients with stable underlying conditions such as cerebral palsy,2,3,5–7 traumatic brain injury,2,5,6 and spinal cord injury.1,3,6 We noticed that the experiences with ITB in paediatric patients with progressive neurological disorders are limited. In addition, although minor complications occur frequently,2,7 most individuals and their caregivers are satisfied with ITB treatment.7,8 We retrospectively studied the overall satisfaction of caregivers with ITB treatment in a group of children and adolescents from our centre with progressive neurological disorders causing spasticity. For this purpose, we selected six patients from a total cohort of nine paediatric patients with ITB treatment (Medtronic Inc, Minneapolis, MN, USA; three males, three females; mean age 11y 8mo, [SD 4y 5mo]), with progressive neurological disorders (Table I) starting in childhood. The remaining three patients from the total cohort were not using ITB at the time of the survey. We analyzed whether the treatment effects met the expectations of the caregivers and how they would score the level of overall satisfaction on a scale from 0 to 10 (0 being the poorest score and 10 being the most optimal score). For this purpose we used standard questionnaires.9 Medical records were checked for complications related to surgery and ITB treatment and for treatment goals. The mean time since pump implantation was 3 years 4 months (SD 2y 11mo, range 6mo–6y 8mo) and the mean age at time of pump insertion was 8 years 4 months (SD 3y, range 4–13y). Reduction of spasticity or spasms, facilitation of care, and reduction of pain were the main goals for initiating ITB treatment. Medical records of the six patients still using ITB reported several complications related to ITB hardware, and surgery, including catheter migration in two patients (Table I). One of the patients experienced an overdose of ITB due to a mistake in programming the pump while having his dosage adjusted. The same patient experienced increase of spasticity due to a nearly empty ITB 10ml pump. The following side effects of ITB treatment were reported in the questionnaires: increased drooling, increased swallowing difficulties, decreased head balance, abdominal discomfort, and constipation (Table I). Each of these complaints was reported once. Back pain due to worsening scoliosis was reported twice. In two patients, the caregivers reported increased tolerance of ITB with frequent pump adjustments consequently. Overall satisfaction scored 7.5 (SD 1.6, range 6–10). For detailed results, see Table I. The caregivers of four patients were satisfied with ITB (nr 1–4), mean satisfaction score 8.0 (SD 1.8, range 6–10). The caregiver of patient 5, stated that they were not satisfied although a score of 7.0 was reported. This dissatisfaction was due to not being able to see full results of ITB yet, because of a short follow-up since pump implantation. The caregiver of patient 6 was partially satisfied due to improvement in dressing, personal hygiene spasms, and pain; but on the other hand noted worsening of swallowing, constipation, head balance, trunk stability, back pain, and worsening scoliosis (satisfaction score 6.0). We are aware of the fact that this is a retrospective study and we only present a small number of patients. Still, we think this study shows clearly and similar to other studies3,8,10,11 that most caregivers are overall satisfied with the effects of ITB treatment. Dissatisfaction was related to unfulfilled goals or related to negative effects of ITB on functioning. Considering the present results with moderate to good satisfaction, ITB is, in our opinion, a valuable treatment option in patients with progressive neurological diseases.

Effect of Intrathecal Baclofen on Dystonia in Children With Cerebral Palsy and the Use of Functional Scales

The literature available shows that spasticity in patients with cerebral palsy (CP) is reduced by intrathecal baclofen (ITB) treatment, and various studies suggest that this treatment can also be used in dystonic patients. The aim of the present study was to evaluate dystonia treated with ITB in children with CP. Data of 19 patients affected by dystonia as an outcome of infant CP in patients belonging to level V of Gross Motor Function Classification System treated with ITB were collected. The mean age at implant is 8.49 years.The patients are assessed using Barry-Albright Scale and Burke-Fahn-Marsden Scale before treatment and at 3, 6, and 12 months postimplant. The results showed a statistically significant improvement (P < 0.001) in the total scores of the 2 scales after just 3 months of treatment, an improvement that was maintained for the 1-year period of follow-up. The results also revealed a reduction in dystonias, an improvement in posture, and an easing of the task of the caregivers in managing the patient as a result of treatment with ITB. In patients belonging to level V of Gross Motor Function Classification System and treated with ITB, a decrease in frequency and severity of dystonia is observed. This improvement eases caregiver in patient management. Therapeutic Level IV.

Effects of Intrathecal Baclofen on Perceived Sexual Functioning in Men With Spinal Cord Injury

Background/Objective: Reports in the literature suggest that administration of intrathecal baclofen to control spasticity may have deleterious effects on erectile function in men with spinal cord injury (SCI). A prospective study was conducted to document any changes in perceived sexual function after implant of a baclofen pump.Methods: Seven adult men with SCI (ASIA A or B) who received intrathecal baclofen through an implantable pump for treatment of severe spasticity were followed for an average of 670 days (22.4 months) after implant. Perceived sexual function was assessed using the Brief Sexual Function Inventory. Severity of spasticity and overall health-related quality of life were also assessed.Results: Participants reported improvements in spasticity severity and overall health-related quality of life. Two of 7 participants reported some negative changes in perceived sexual function after baclofen pump implant, noted in the areas of reduced sex drive and problems with erections (frequency, rigidity, difficulty in achieving). However, most participants reported minimal effects on sexual function, and 2 participants reported marked improvement in perceived sexual function from pre- to post-implant. Analysis of changes in perceived sexual function over time suggest that problems may be associated with an increase in baclofen dose and may be reversible with a reduction in dose.Conclusions: Intrathecal baclofen may impact perceived sexual function particularly at higher doses. However, the effects seem to be reversible with withdrawal or reduction of baclofen administration.

Progression of Scoliosis in Patients With Spastic Quadriplegia After the Insertion of an Intrathecal Baclofen Pump

Medical and radiographic review of 19 consecutive patients with spastic quadriplegia before and after intrathecal baclofen pump insertion with special attention paid to progression of scoliosis. Many orthopedic surgeons who treat spastic quadriplegic patients have noticed a trend of marked scoliosis progression after the administration of intrathecal baclofen (ITB) via subcutaneous pump and catheter. The purpose of this study is to quantify scoliosis progression in this patient population before and after baclofen administration and compare this to published natural history data. The authors had noted rapid progression of scoliosis in spastic quadriplegic patients after intrathecal baclofen pump insertion. This had been noted at other centers, but no significant statistical analysis had been done comparing prepump to postpump scoliosis progression in these patients. To document the magnitude and rate of scoliosis progressions after the placement of an ITB pump, the charts and radiographs of 19 consecutive nonambulatory patients with spastic quadriplegia and an ITB pump were reviewed. To document the rate of scoliosis progression, each patient had at least 2 pre and 2 postpump insertion spinal radiographs made. All radiographs were made with the patients in the supine position without orthoses. A board-certified orthopedic surgeon reviewed these radiographs. Skeletal maturity was assessed using Risser grading. Catheter tip location and rate of baclofen administration were recorded. For 19 patients with complete radiographic data, average Cobb angles were 10.2 degrees before pump insertion and 25 degrees at an average of 20.9 months after pump insertion (P < 0.0001). These 19 patients had a mean rate of change in their Cobb angles of 1.825%/year before pump insertion and 10.95 degrees /year at an average of 23.9 months after pump insertion (P = 0.024). These results represent a 6-fold increase in the curve progression rate after pump insertion. There was no association between catheter tip location or rate of Baclofen infusion on curve progression. In published data, the rate of progression of scoliosis in skeletally immature nonambulatory patients with cerebral palsy was 4.5 degrees /year. In this study, the average rate of progression of the scoliosis for the immature was 9.02 degrees /year. For the skeletally mature bed-ridden patients, the worst-case natural history progression was 4.4 degrees /year. The comparable rate of change in skeletally mature (Risser 5) nonambulatory patients (n = 6) in this study was 28.4 degrees /year. This study demonstrates a significant increase in the rate of scoliotic curve progression after ITB pump placement when compared with published natural history data. The evidence of the beneficial effects of ITB on spasticity has been confirmed, and as larger, prospective randomized studies are conducted, the authors think that support for continued use of this treatment will increase. However, early bracing and spinal fusion may be warranted to prevent significant increases in spinal deformity if scoliosis is anticipated to progress more than 10 degrees /yr for patients with spastic quadriplegia and ITB pump. The authors are now performing spinal fusions for curves that exceed 40 degrees to 50 degrees in the presence of an ITB pump as recommended by previous reviews of scoliosis and accompanying quadriplegia.

Poster 162: Changes in Bladder Function After Initiation of Intrathecal Baclofen in Patients With Supraspinal Spasticity: A Report of 2 Cases

Setting: Tertiary care hospital. Patients: 2 female patients, ages 30 and 15 years, with spastic quadriparesis, one due to cerebral palsy and one due to traumatic brain injury. Case Descriptions: Both patients have had pumps placed for intrathecal baclofen (ITB) administration to manage spasticity, had not had urinary problems associated with oral baclofen, and had a change in urinary status following ITB administration. Urodynamic studies were performed to assist with urinary management after pump implantation due to new onset urinary retention. Both had stable urinary management with infrequent urinary tract infections (UTIs). Assessment/Results: Urinary management prior to pump implantation was timed voiding with episodes of urinary incontinence, with low post void residuals. Both patients had frequent UTIs and urinary retention after pump implantation. Urodynamic studies showed detrusor sphincter dyssynergia with normal bladder compliance and poorly contracting detrusor. Intermittent catheterization was initiated, although it was not continued long term. Discussion: There are reports of the positive and negative effects of ITB on spinal-mediated neurogenic bladders. However, there are fewer reports about patients with supraspinal spasticity receiving ITB, and none reporting urodynamics. There are several mechanisms for urinary dysfunction, and ITB may have variable effects on some of them. In the patients reported here, new onset urinary retention may be a factor in a decreased micturition reflex, resulting in normal detrusor compliance but ineffective detrusor contraction. There appeared to be little ITB effect on pelvic floor muscle activity. Conclusions: Urinary function can change following initiation of ITB in patients with supraspinal spasticity. Documentation of urinary function preimplant is important for long-term management, and urinary function should be monitored after ITB initiation. Urodynamics are useful for diagnosis and treatment if bladder function changes occur.

Intrathecal baclofen in children with spastic cerebral palsy: a double‐blind, randomized, placebo‐controlled, dose‐finding study

Intrathecal baclofen (ITB) therapy can be very effective in the treatment of intractable spasticity, but its effectiveness and safety have not yet been thoroughly studied in children with cerebral palsy (CP). The aims of this double-blind, randomized, placebo-controlled, dose-finding study were to select children eligible for continuous ITB infusion, to assess the effective ITB bolus dose, and to evaluate the effects, side effects, and complications. Outcome measures included the original Ashworth scale and the Visual Analogue Scale for individually formulated problems. We studied nine females and eight males, aged between 7 and 16 years (mean age 13y 2mo [SD 2y 9mo]). Twelve children had spastic CP and five had spastic-dyskinetic CP. One child was classified on the Gross Motor Function Classification System at Level III, two at Level I V, and 14 at Level V. The test treatment worked successfully for all 17 children with an effective ITB bolus dose of 12.5 microg in one, 20 microg in another, 25 microg in 10, and 50 microg in five children. ITB significantly reduced muscle tone, diminished pain, and facilitated ease of care. The placebo did not have these effects. Nine side effects of ITB were registered, including slight lethargy in seven children. Fourteen children had symptoms of lowered cerebrospinal fluid pressure. We conclude that ITB bolus administration is effective and safe for carefully selected children with intractable spastic CP.

Interaction of ventriculoperitoneal shunt and baclofen pump

The authors present three cases of children with shunted hydrocephalus and intrathecal delivery of baclofen via an implanted pump. Each case illustrates a potential interaction of these devices. A review of the pertinent charts, operative notes, and discharge summaries was performed, along with examination of the pertinent literature. The first case illustrates that a change in the pharmacology or effect of intrathecal baclofen may be caused by a failure of a shunt affecting cerebrospinal fluid clearance. The second case illustrates that patients can have ventricular changes with any procedure that accesses the thecal space, even with a functioning shunt. The third case illustrates that ensuring that a patient's shunt is functional before implantation of a baclofen pump is imperative. As the potential pool of patients with both shunted hydrocephalus and need for intrathecal baclofen grows, clinicians should be aware of potential serious interactions.

Effect of intrathecal baclofen on sleep and respiratory function in patients with spasticity

To prospectively evaluate the effect of pump-infused intrathecal baclofen infusion (ITB) in therapeutic doses on sleep quality and on daytime and nighttime respiratory function in patients with severe spasticity. We prospectively evaluated 20 consecutive patients (mean +/- SD age 45 +/- 13 years). We assessed spasticity and obtained polysomnography, pulmonary function tests, and resting energy expenditure measurements 1 week before and at least 8 days after pump implantation. Patients stopped oral baclofen upon pump implantation but continued other medications unchanged. We report descriptive statistics as means +/- SD. Most of the patients had multiple sclerosis (n = 9) or spinal cord injury (n = 8); there was one case each of cerebral palsy, hereditary spastic paraplegia, and Friedreich ataxia. Before and after ITB initiation, mean Ashworth scores were 2.75 +/- 0.85 and 1.15 +/- 0.36, and mean spasm scores were 3.75 +/- 0.55 and 1.00 +/- 0.56. ITB improved total sleep time (p = 0.05) and sleep efficiency (p = 0.01) and reduced periodic leg movements (p = 0.02). ITB did not modify sleep-related respiratory events, lung function tests, CO2 rebreathing response, or resting energy expenditure. Compared with oral baclofen, intrathecal baclofen infusion did not affect respiratory function and improved sleep continuity. Intrathecal baclofen infusion in therapeutic doses may act at the spinal level rather than at the supraspinal level.

Intrathecal baclofen therapy in children

Since its introduction in the late 1980s, intrathecal baclofen (ITB) therapy has become the standard treatment for severe generalized spasticity and dystonia in children. Treatment with ITB decreases spasticity in the upper and lower extremities and has been associated with improved function and decreased musculoskeletal contractures. In addition, ITB decreases generalized secondary dystonia and has been associated with improved comfort and ease of care in approximately 85% and with improved function in approximately 33% of patients. Continued effectiveness of ITB in treating spasticity has been observed for up to 17 years, and its effectiveness in treating dystonia has been observed for up to 10 years. Although ITB therapy is frequently associated with complications such as infections, catheter malfunctions, and cerebrospinal fluid leaks, the benefits of therapy appear to outweigh the risks. Additional investigation is needed to determine the effects of ITB on other movement disorders such as athetosis and chorea.

Placebo controlled utility and feasibility study of the H-reflex and flexor reflex in spastic children treated with intrathecal baclofen

ObjectiveTo evaluate feasibility and utility of the soleus H-reflex and tibialis anterior flexor reflex (FR) in identifying spinal cord neuronal response to intrathecal baclofen (ITB) in children with severe spastic cerebral palsy. MethodsDuring a randomized, double-blind, placebo-controlled dose-escalation test treatment, maximum H amplitude/maximum M amplitude (H/M ratio) and FR parameters were bilaterally recorded at baseline and 2–3h after intrathecal bolus administration of placebo and increasing doses of baclofen until both an improvement in the individual treatment goal(s) and a one-point reduction on the Ashworth scale were observed. ResultsElectrophysiological data of 14 children were studied. The H-reflex was feasible in 13 children, the FR threshold area in 9 and the FR, elicited with supramaximal stimulation, in only one child. After ITB, the H/M ratio significantly decreased (left: 0.67±0.47 to 0.15±0.18, P=0.005; right: 0.55±0.32 to 0.14±0.19, P=0.002) without placebo effect. FR threshold area after ITB, only decreased significantly in children not taking oral baclofen (left: 146±53 to 41±54mVms, P=0.000; right: 156±80 to 66±48mVms, P=0.002). ConclusionsThis is the first randomized, double-blind, placebo-controlled dose-escalation study in spastic children demonstrating the soleus H-reflex to be a feasible and objective measure to quantify the decreasing motoneuron excitability in response to ITB bolus administration. Only in children not taking oral baclofen, FR threshold area can also be used as an objective outcome measure, yet feasibility is limited. SignificanceWe suggest introducing the H-reflex as the electrophysiological gold standard for the evaluation of the effect of ITB in spastic children.

Measurement of Peripheral Muscle Resistance in Rats with Chronic Ischemia-Induced Paraplegia or Morphine-Induced Rigidity Using a Semi-Automated Computer-Controlled Muscle Resistance Meter

In experimental and clinical studies, an objective assessment of peripheral muscle resistance represents one of the key elements in determining the efficacy of therapeutic manipulations (e.g. pharmacological, surgical) aimed to ameliorate clinical signs of spasticity and/or rigidity. In the present study, we characterize a newly developed limb flexion resistance meter which permits a semi-automated, computer-controlled measurement of peripheral muscle resistance (PMR) in the lower extremities during a forced flexion of the ankle in the awake rat. Ischemic paraplegia was induced in Sprague-Dawley rats by transient aortic occlusion (10 min) in combination with systemic hypotension (40 mm Hg). After ischemia the presence of spasticity component was determined by the presence of an exaggerated EMG activity recorded from gastrocnemius muscle after nociceptive or proprioceptive afferent activation and by velocity-dependent increase in muscle resistance. Rigidity was induced by high dose (30 mg/kg, i.p.) of morphine. Animals with defined ischemic spasticity or morphine-induced rigidity were then placed into a plastic restrainer and a hind paw attached by a tape to a metal plate driven by a computer-controlled stepping motor equipped with a resistance transducer. The resistance of the ankle to rotation was measured under several testing paradigms: (i) variable degree of ankle flexion (40 degrees, 50 degrees, and 60 degrees), (ii) variable speed/rate of ankle flexion (2, 3, and 4 sec), (iii) the effect of inhalation anesthesia, (iv) the effect of intrathecal baclofen, (v) the effect of dorsal L2-L5 rhizotomy, or (vi) systemic naloxone treatment. In animals with ischemic paraplegia an increased EMG response after peripheral nociceptive or proprioceptive activation was measured. In control animals average muscle resistance was 78 mN and was significantly increased in animals with ischemic spasticity (981-7900 mN). In ischemic-spastic animals a significant increase in measured muscle resistance was seen after increased velocity (4 > 3 > 2 sec) and the angle (40 degrees > 50 degrees > 60 degrees) of the ankle rotation. In spastic animals, deep halothane anesthesia, intrathecal baclofen or dorsal rhizotomy decreased muscle resistance to 39-80% of pretreatment values. Systemic treatment with morphine induced muscle rigidity and corresponding increase in muscle resistance. Morphine-induced increase in muscle resistance was independent on the velocity of the ankle rotation and was reversed by naloxone. These data show that by using this system it is possible to objectively measure the degree of peripheral muscle resistance. The use of this system may represent a simple and effective experimental tool in screening new pharmacological compounds and/or surgical manipulations targeted to modulate spasticity and/or rigidity after a variety of neurological disorders such as spinal cord traumatic or ischemic injury, multiple sclerosis, cerebral palsy, or Parkinson's disease.

Objective assessment of gait after intrathecal baclofen in hereditary spastic paraplegia

Sirs: Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) are heterogeneous neurodegenerative disorders. On physical examination spasticity of the lower limbs is often predominant, whereas paraparesis may be mild [1, 2]. The gait disorder of SSP/HSP patients which is the cardinal source of disability in these patients has been recently characterized [3]. The treatment of spastic paraplegia is symptomatic and limited to oral antispastic drugs and physiotherapy. In 1984 Penn [4] showed that intrathecal baclofen (ITB) could alleviate spinal cord spasticity. The efficacy of ITB on spasticity has been proven in several studies [5, 6]. In these studies ITB was used as a symptomatic treatment to reduce painful spasm and muscle contractions in mostly wheelchair bound patients. However, SSP/HSP patients are often able to walk even in advanced stages of their disease. Therefore, ITB therapy in SSP/HSP has the special requirement of reducing spasticity but preserving gait function. So far most clinical trials on spasticity rely on rating scales such as the modified “Ashworth Scale of Spasticity” (ASH), which may not adequately reflect the functional benefit in gait in SSP/HSP patients. In the particular case of ITB therapy for SSP/HSP the indication for an ITB pump implantation should moreover be based on the global clinical impression of gait improvement after an ITB test injection. Unfortunately, there are no scientific operational data to test the functional benefit of ITB in SSP/HSP. Here we describe the clinical effect of ITB in 10 patients, who were all treated with oral antispastic drugs and ongoing physiotherapy. Additionally we tested the usefulness of a three-dimensional movement analysis system for the selection of candidates for an ITB pump implantation. The gait of 10 SSP/HSP patients before and after a testing dose of 25 or 50 μg ITB was examined with this method, which is described elsewhere in detail [7]. In cooperation with the responsible physiotherapists we clinically distinguished responders (group 1; n = 5) from non responders (group 2; n = 5) based on the global clinical impression of gait improvement after ITB. Group 1 was recommended for an ITB pump implantation, whereas group 2 was not. With respect to spastic tone SSP/HSP patients showed a significant reduction of the ASH after ITB (p = 0.014). These result are comparable to the study of Penn et al. who analysed the effect of ITB via an implanted pump system [6]. We found an increased gait velocity accompanied by larger step length and a reduced step width after ITB in all patients, but no significant change in other kinematic gait parameters at a self chosen comfortable speed. Additionally, gait analysis was also performed with a fixed velocity of 1 km/h to eliminate the variable influence of speed. Under this condition group 1 presented an increased range of motion (ROM) of the ankle angle. Furthermore group 1 showed a reduction of the minimum knee angle as shown in a patient in Fig. 1. Gait parameters alone, however, did not allow us to separate clinical responders and non responders. An ITB pump implantation was performed in three of the five screened patients of group 1. Two patients did not opt for ITB owing to subjective unsteadiness and weakness in the lower extremities. We were able to collect follow up gait analysis data of two patients under chronic ITB. Both patients showed an effect of chronic ITB (mean dosage 60 μg/day), which was equivalent to the effect of the test bolus (Fig. 2). In conclusion, our findings show that ITB is a potential treatment option in SSP/HSP. However, only 50 % of our patients were recommended for a pump implantation. Therefore it can be assumed that all patients showed a variable effect of ITB that was probably too strong and a formerly existing weakness was unmasked by the ITB in some patients. In the quantitative gait analysis an improvement of gait was documented in the gait velocity and the step length. However, gait analysis alone was not able to discriminate between clinical responders and non-responders. This may be due to the relatively small number of investigated patients. If so, in the individual patient the clinical examination of gait before and after bolus injection of ITB in a multidisciplinary assessment by a neurologist and physiotherapists experienced with gait disorders is decisive and cannot be replaced by a technical assessment alone.

DIETARY GLYCINE INHIBITS BLADDER ACTIVITY IN NORMAL RATS AND RATS WITH SPINAL CORD INJURY

The influence of dietary glycine on bladder activity, and on glutamate and glycine levels in the serum and lumbosacral cord was examined in rats with or without spinal cord injury (SCI). A total of 84 female rats were divided into an intact and an SCI group. Each group of rats was divided into 7 subgroups. Two intact and 2 SCI subgroups were fed a standard diet and the remaining subgroups were fed diets containing 0.1% to 3% glycine. After 4 weeks isovolumetric cystometry was performed with rats under urethane anesthesia. Following cystometry glutamate and glycine levels in the serum and lumbosacral cord were measured as well as the glycine receptor alpha1 mRNA level in the lumbosacral cord. Dietary glycine (1% to 3%) prolonged the interval between bladder contractions in intact rats but did not change the amplitude of contractions. On the other hand, dietary glycine (1% to 3%) prolonged the interval and decreased the amplitude of bladder contractions in SCI rats. The glycine levels in the serum and lumbosacral cord of SCI rats on the standard diet were respectively 43% and 45% lower than those in intact rats on the standard diet. Dietary glycine (1% to 3%) increased the serum glycine level in intact and SCI rats but the glycine receptor alpha1 mRNA level in the lumbosacral cord was unchanged. Dietary glycine crosses the blood-brain barrier and inhibits the micturition reflex pathway in the lumbosacral cord but SCI and/or dietary glycine do not influence glycine receptor expression.

Spasticity patients: special considerations

Spasticity is a frequent symptom of central nervous system disorders, and in many patients has a significant subjective and objective impact. Intrathecal baclofen (ITB) therapy is increasingly utilized to treat severe spasticity refractory to oral antispasticity medications, based on a growing body of evidence demonstrating its efficacy in various conditions. Because ITB involves significant risks, careful patient selection, thorough multidisciplinary patient evaluation and education, treatment planning, standardized surgical techniques, and aggressive management are required to maximize treatment benefits. Further research is needed to explore the long-term effects of ITB on function and subjective health status.