Management of spasticity associated pain with botulinum toxin A.

Lesions of the central nervous system often result in an upper motor neuron syndrome including spasticity, paresis with pyramidal signs, and painful spasms. Pharmacological treatment with oral antispasticity drugs is frequently associated with systemic side effects which limit their clinical use. Botulinum Toxin A (BtxA) injected in spastic muscles has been shown to be effective in reducing muscle tone, but only few studies have reported pain relief as additional benefit. Therefore, we investigated the effects of local BtxA injections in 60 patients with acute (< 12 months) and chronic spasticity and pain in a prospective multicenter study. Target muscles for BtxA were selected on the basis of clinical examination. Intramuscular BtxA injections were placed in muscles exhibiting increased muscle tone in combination with pain during passive joint movement. Patients received a mean total dose of 165.7 +/- 108.2 [30-400] units BOTOX((R)) per treatment session in a mean 3.4 +/- 1.5 muscles. Baseline and follow-up (mean 5.9 weeks) measures included a patient self-assessment of pain and function on a five-level scale, a physician's evaluation of function, and a global rating of response to BtxA. Fifty-four of sixty patients experienced improvement in pain without subjective functional improvement. The effects were comparable in acute (n = 17) and chronic (n = 43) spasticity. Physician's assessment of gain in function increased significantly (p < 0.05) only in patients with chronic spasticity. No serious adverse event was observed. Mild reversible side effects (local pain, hematoma, edema, mild weakness) were observed in four patients. In conclusion, we found that intramuscular BtxA injections are a potent, well-tolerated treatment modality to significantly reduce spasticity-related local pain. This problem may be a main indication, especially in patients with poor response or intolerable side effects to oral medication.

Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia.

We observed a marked prolongation of the transcranially evoked silent period during continuous intrathecal administration of high doses of the gamma-aminobutyric acid (GABA)B receptor agonist baclofen in a patient with generalized dystonia. Size of motor evoked potentials and central conduction time remained unchanged during intrathecal baclofen administration. The selective prolongation of the silent period during high-dose continuous intrathecal baclofen therapy supports the notion that GABA(B)-ergic intracortical interneurons play a part in the generation of the transcranially evoked silent period.

Intrathecal baclofen therapy for stiff-man syndrome and progressive encephalomyelopathy with rigidity and myoclonus.

We report on eight patients with stiff-man syndrome (SMS) or its "plus" variant, progressive encephalomyelopathy with rigidity and myoclonus (PERM) receiving intrathecal baclofen via pump. In six of the patients, follow-ups continued for approximately 2.5 to 6.5 years after pump implantation. Intrathecal baclofen was an effective last-resort alternative for patients who responded poorly to or did not tolerate oral antispasticity medications. General mobility increased, and spasms and rigidity were reduced; however, no complete remissions were observed either before or after pump implantation. PERM patients showed more severe and rapid progression of symptoms and more attacks of autonomic dysregulation than SMS patients. They also required higher doses and more rapid dosage increases. Complications of intrathecal baclofen therapy included spasm-induced rupture of the catheter, catheter dislocation causing radicular symptoms, and pump malfunction resulting in inaccurate dosage administration. Patients suffered fewer side effects with intrathecal baclofen than with oral medication, but overdose resulted in a transient, comalike state in one patient and sudden dosage reduction due to pump failure was fatal in another.

Intrathecal baclofen in tetanus: four cases and a review of reported cases.

OBJECTIVE: Spasms in patients with generalized tetanus can be suppressed by a spinal intrathecal infusion of baclofen. We report on four patients and review reported cases treated by this method elsewhere. DESIGN: Intrathecal baclofen infusion was started with a bolus dose (300-500 micrograms) and continued at a steady rate of 500-1000 micrograms/day. The dose was increased in daily steps as needed. RESULTS: Doses of baclofen of 500, 1000, or 2000 micrograms/day were effective in three patients, while 1500 micrograms/day was insufficient in the fourth. Bradycardia and hypotonia occurred in one patient at a dose of 2000 micrograms/day but resolved after the dose was reduced to 1500 micrograms/day. Another patient developed hypotonia when a bolus of 500 micrograms was given after a steady infusion of 1500 micrograms/day. Voluntary movements were preserved in one and returned in two patients when sedation, induced by initial diazepam infusions, receded. The fourth patient needed diazepam during most of the treatment with intrathecal baclofen and required mechanical ventilation while being treated with baclofen. CONCLUSIONS: A catheter position higher than T11 would possibly have yielded better results. It may be necessary to adapt the dose during the course of the illness. The preservation of respiratory drive and voluntary movements is the main advantage of treating tetanus with intrathecal baclofen. Additionally it helps to reduce sympathetic hyperactivity. Mortality may thereby be reduced.

Relationships between delayed ischemic dysfunctions and intracranial hemodynamics following subarachnoid hemorrhage.

Delayed ischemic dysfunctions (DID) are one of the main complications following subarachnoid hemorrhage. It was the aim of our study to analyse the possible prognostic value of different transcranial Doppler ultrasonography parameters and to elucidate the risk of developing DID with particular reference to the intracranial pressure. The relative change of mean blood flow velocity and of corresponding cerebral circulatory resistance index as well as the intracranial pressure were determined in 44 patients with spontaneous subarachnoid hemorrhage. No relationship was found between the occurrence and extent of DID and the relative change of mean flow velocity during the clinical course. In contrast, there was a significant correlation between the relative change of the cerebral circulatory resistance index and the occurrence of DID. While patients without or with reversible DID showed a decreased resistance index compared to the initial value (without DID: -17% +/- 15%; reversible DID: -3% +/- 14%), patients with irreversible DID had a significant increase of the resistance index (+14% +/- 9%). Accordingly, patients with irreversible DID showed a significant increase of intracranial pressure compared to the patients with reversible DID. We conclude that the evaluation of relative changes of the cerebral circulatory resistance index by bedside monitoring is a useful tool to predict the occurrence of subarachnoid hemorrhage-associated DID and has therapeutic impact.

Lasting reduction of severe spasticity after ending chronic treatment with intrathecal baclofen.

OBJECTIVE: To investigate whether the dose of intrathecal baclofen necessary for a sufficient reduction of muscle tone and spasms changes during treatment of severe spasticity. METHODS: A group of 27 patients received intrathecal baclofen for 61 (SD 18) months. RESULTS: Spasticity remained absent or strongly reduced after stopping the intrathecal baclofen infusion in seven patients. The dose of baclofen could be reduced to 40% of that dose which was originally necessary in 10 patients. The dose remained the same or increased slightly in 10 patients. Possible reasons for the continuing reduction of spasticity after terminating long term intrathecal baclofen infusion in some patients could be: lasting morphological changes in spinal cord neurons by second messenger controlled modulation of gene expression, a toxic effect of baclofen on spinal neurons, muscular atrophy, inflammation due to the catheter, or progression of multiple sclerosis. CONCLUSIONS: A higher initial daily dose of intrathecal baclofen might lead to a faster, lasting suppression of spasticity and the development of spastic symptoms might even be prevented by pre-emptive treatment with baclofen in patients with newly acquired lesions of the spinal cord.

Influence of baclofen upon the alpha-motoneuron in spasticity by means of F-wave analysis.

Intrathecal baclofen dramatically improves severe spastic syndromes. This improvement is likely related to reduced excitability of alpha-motoneurons. To investigate the influence of baclofen upon the alpha-motoneuron, we analyzed F-waves before and after intrathecal baclofen bolus injection (usually 50 micrograms) as well as after administration of different, constantly delivered doses (60-200 micrograms/day). Intrathecal baclofen bolus decreased the maximum F-wave amplitude (Fp) from an initial value of 9% of the maximum M amplitude (Mmax) (= F/M-ratio) to 2.4% of the Mmax after 130-180 min, reduced the mean F-wave amplitude 60% within 150 min, and shortened the mean duration by 40-60% after 130-180 min. Constantly delivered baclofen of 100 micrograms/day reduced the F/M-ratio from 5% to 2%, the mean F-wave amplitude by 40-80%, and the F-wave mean duration by 40-80%. The minimum F-wave latency did not change after bolus or during steady state administration. The findings indicate that the F-wave mean and maximum amplitude as well as the mean duration are altered in a quantifiable manner following intrathecal baclofen application.

[Local injection treatment with botulinum toxin A in severe arm and leg spasticity]. / Lokale Injektionsbehandlung mit Botulinum-Toxin A bei schwerer Arm- und Beinspastik.

In patients with predominantly focal spasticity, oral antispastic drugs are relatively ineffective or cause unwanted side effects of central origin. Therefore we treated patients disabled by focal spasticity with local injections of Botulinum-Toxin A (Porton Products BOTOX). Efficacy, dosage, side-effects and injection technique were examined. 11 patients (mean age 48 years) with severe focal spasticity of the flexor muscles of the hand and arm (5 patients), the adductor muscles of the legs (5) or the plantar flexors of the foot (1) due to multiple sclerosis, cervical myelopathy or stroke-related hemi-paresis were treated with BOTOX. Rating scales, including Ashford spasticity scale, pain scale and a hygienic rating scale, were used to evaluate the efficacy. 25 to 30 ng (1000-1200 MU Porton) were injected in the flexor group of the hand or arm and 42 to 50 ng (1680-2000 MU Porton) BOTOX in the adductor group of one leg. 10 of the patients showed an improvement of at least one point on the scales for spasticity, pain and hygiene. Effects could be observed after 4-7 days and lasted for 6-13 weeks. There were no unwanted side-effects. We conclude that BOTOX is an alternative to the systemic application of antispastic drugs. Focal spasticity and pain can be successfully reduced and hygienic care is facilitated.

[POEMS syndrome: a contribution to differential diagnosis of polyneuropathy]. / Das POEMS-Syndrom: Ein Beitrag zur Differentialdiagnose der Polyneuropathie.

The POEMS syndrome is a synopsis of different symptoms such as polyneuropathy, organomegaly, endocrine disturbances, M-protein and skin changes. The leading symptoms are neuropathy and the skin symptoms. Additionally, a monoclonal light chain gammopathy is often found. The administration of immunosuppressive drugs yields a substantial improvement in some cases. We report here about a 72 year old lady who fell ill with a rapidly progressive neuropathy accompanied by hyperpigmentation and a morphea-like induration of the skin. A biopsy of the sural nerve showed a demyelinating axonal neuropathy and a focal vasculitis. Isoelectric focussing revealed oligoclonal bands in cerebrospinal fluid and serum. The cortisol serum level was very low and there were signs of a latent diabetes mellitus. These clinical features correspond to the POEMS syndrome. The prescription of initially 1 mg and later 0.5 mg prednisone improved the patient's condition dramatically.

Brain stimulation-induced changes of phonation in the squirrel monkey.

In 11 squirrel monkeys (Saimiri sciureus), the brain stem was systematically explored with electrical brain stimulation for sites affecting the acoustic structure of ongoing vocalization. Vocalization was elicited by electrical stimulation of different brain structures. A severe deterioration of the acoustical structure of vocalization was obtained during stimulation of the caudoventral part of the periaqueductal grey, lateral parabrachial area, cortico-bulbar tract, nucl. ambiguus and surrounding reticular formation, facial nucleus, hypoglossal nucleus, solitary tract nucleus and along the fibres crossing the midline at the level of the hypoglossal nucleus. It is suggested that these structures are part of, or at least have direct access to, the motor coordination mechanism of phonation. Complete inhibition of phonation was obtained from the raphe and raphe-near reticular formation.