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Chronic cerebellar stimulation for cerebral palsy--five-year study.

Two hundred sixty-two patients were implanted with cerebellar stimulator systems since February 1974. Cerebral Palsy (CP) patients constituted 88% (230) of this series. The age range was 3 to 53 years with 70% under 20 years of age. Half the CP series were severely affected with the rest being moderately to mildly involved. Athetosis was present in 50%. The primary effect of CCS has been a lowering of spastic muscle tone in 90% of the patients. Improvements in control of immature reflexes such as startle response, head control, scissoring, balance and sitting occur in the first month. Athetosis progressively decreases to a 50% level. In the moderate mild CP group abilities improve over the first six months leading to better feeding, dressing, and ambulation with clearer speech and less drooling. After six months, 25 of 48 patients were out of wheelchairs, walking. A further 47 patients were ambulating better. No deaths from surgery. Five have died during the 5 years from other causes. Eleven patients (4%) have had infected systems. Equipment problems especially with malfunctioning radio receivers (40%) have served as blind controls--spasticity returning and abilities decreasing. Replacements with another receiver or with a totally implantable lithium powered pacemaker (May 1979) have lead to a return of benefits. Post-mortem findings indicate the low current levels (0.8 uC/sqcm) applied intermittently produced no appreciable damage to the cerebellar cortex.

Adolescent↗

Impaired viscoelastic behaviour of spastic plantarflexors during passive stretch at different velocities.

OBJECTIVE: The aim of this study was to evaluate the effect of velocity on non-reflexly induced resistive torque (RT) responses of the spastic plantarflexors (PFs) of subjects with spinal cord injuries. DESIGN: Descriptive study, transversal. BACKGROUND: In spastic muscles, non-reflex changes such as increased muscle stiffness, contractures and atrophy have been reported. These changes probably alter muscle tensile properties and viscoelastic behaviour. METHODS: Six subjects with chronic (1-3 yr) spinal cord injuries (SCI) and 12 normal controls (CTLs) participated in this study. Passive ankle dorsiflexions (DFs), ranging from -35 degrees to 5 degrees of DF, were randomly imposed at 5 degrees /s, 10 degrees /s, 20 degrees /s, 40 degrees /s, 60 degrees /s, 120 degrees /s and 180 degrees /s using an isokinetic dynamometer (Kin-Com(TM)). Unwanted muscle activity was detected using surface electrodes on the soleus and tibialis anterior muscles. RESULTS: The results show first that RT rose with increasing velocity; the RT increment reached statistical (analysis of variance (ANOVA); Scheffé post-hoc procedure) significance (P < 0.01) at a lower velocity for the CTLs (40 degrees /s) group than for the SCI group (60 degrees /s). Second, significantly (t-test; P < 0.001) larger net increments of RT (RT at each velocity minus RT at 5 degrees /s) were found for the CTLs at 180 degrees /s than for the SCI group whose RT plateaued at 60 degrees /s. Finally, whereas the RT-velocity relationship was linear (r = 0.94) in the CTLs, that of the SCI group followed a power regression model (r = 0.85). CONCLUSIONS: These results show that the spastic PFs of the subjects with SCIs have an impaired velocity-sensitive behaviour, especially at high velocities of stretch where greater resistance is expected.

Journal Article↗

Electrophysiological analysis of the mode of action of muscle relaxants in spasticity.

Variations in four electrophysiological tests (H/M, T/M, vibratory inhibition, and recovery curve of Hoffmann's reflex following stimulation at the ankle) were studied following a single administration of four myorelaxant drugs: diazepam (10 mg intramuscularly), baclofen (20 mg intramuscularly), tizanidine (4 mg orally), and idrocilamide (60 mg intramuscularly). Fifty-one spastic patients, divided into four groups, were tested. All four drugs reduced the H/M and T/M ratios very slightly. Only diazepam and tizanidine reinforced vibratory inhibition. Diazepam and tizanidine did not modify the abnormal recovery curves, however, whereas baclofen and idrocilamide did. Reinforcement of vibratory inhibition suggests an increase in presynaptic inhibition mediated by gamma-aminobutyric acid; changes in recovery curves are likely due to modifications of interneuronal reactivity. Matching myorelaxants to the predominant pathophysiological abnormality detected by electrophysiological exploration may lead to better treatment of spasticity.

Baclofen↗

Voiding dysfunction in patients with spastic paraplegia: urodynamic evaluation and response to continuous intrathecal baclofen.

Patients with hereditary spastic paraplegia (HSP), a degenerative central nervous system disorder characterized by progressive lower extremity spasticity, frequently experience symptoms of voiding dysfunction. Urodynamic evaluation of patients with HSP has not been reported, and the etiology of voiding dysfunction remains unexplained. We present our evaluation of three men (ages 42-62 years) with this rare syndrome. Urgency of urination was a uniform and dominant complaint, and two patients regularly experienced urge incontinence. Other symptoms included frequency (n = 3), nocturia (n = 3), and diminished force of stream (n = 1). Postvoid residual volumes were less than 25 ml in all patients. On urodynamic evaluation the two patients with urge incontinence displayed cystometric evidence of involuntary detrusor contractions. Pelvic floor EMG recordings suggested detrusor-sphincter dyssynergia (DSD). In addition, one patient exhibited markedly diminished bladder compliance (1.0 ml/cm H2O) and capacity (50 ml). All patients reported marked symptomatic improvement when treated with continuous intrathecal baclofen. Evaluation during baclofen treatment revealed increases in bladder compliance and capacity, with apparent resolution of DSD in one patient. Voiding symptoms in these patients most likely arise from a neurogenic etiology; however, a contributory role for chronic outlet obstruction from striated muscle spasticity may also exist.

Adult↗

High-frequency electrical conduction block of mammalian peripheral motor nerve.

A quick-acting, quick-reversing method for blocking action potentials in peripheral nerves could be used in the treatment of muscle spasticity and pain. A high-frequency alternating-current (HFAC) sinusoidal waveform is one possible means for providing this type of block. HFAC was used to block peripheral motor nerve activity in an in vivo mammalian model. Frequencies from 10 to 30 kHZ at amplitudes of between 2 and 10 V were investigated. A complete and reversible motor block was obtained at all frequencies. The block threshold amplitudes showed a linear relationship with frequency, the lowest threshold being at 10 kHZ. HFAC block has three phases: an onset response; a period of asynchronous firing; and a steady state of complete or partial block. The onset response and the asynchronous firing can be minimized by using an optimal frequency-amplitude combination. In general, the onset response was lowest for the combination of 30 kHZ and 10 V.

Action Potentials↗

Serotonin facilitates a persistent calcium current in motoneurons of rats with and without chronic spinal cord injury.

In the months after spinal cord transection, motoneurons in the rat spinal cord develop large persistent inward currents (PICs) that are responsible for muscle spasticity. These PICs are mediated by low-threshold TTX-sensitive sodium currents (Na PIC) and L-type calcium currents (Ca PIC). Recently, the Na PIC was shown to become supersensitive to serotonin (5-HT) after chronic injury. In the present paper, a similar change in the sensitivity of the Ca PIC to 5-HT was investigated after injury. The whole sacrocaudal spinal cord from acute spinal rats and spastic chronic spinal rats (S2 level transection 2 mo previously) was studied in vitro. Intracellular recordings were made from motoneurons and slow voltages ramps were applied to measure PICs. TTX was used to block the Na PIC. For motoneurons of chronic spinal rats, a low dose of 5-HT (1 microM) significantly lowered the threshold of the Ca PIC from -56.7 +/- 6.0 to -63.1 +/- 7.1 mV and increased the amplitude of the Ca PIC from 2.4 +/- 1.0 to 3.0 +/- 0.73 nA. Higher doses of 5-HT acted similarly. For motoneurons of acute spinal rats, low doses of 5-HT had no significant effects, whereas a high dose (about 30 microM) significantly lowered the threshold of the L-Ca PIC from -58.5 +/- 14.8 to -62.5 +/- 3.6 mV and increased the amplitude of the Ca PIC from 0.69 +/- 1.05 to 1.27 +/- 1.1 nA. Thus Ca PICs in motoneurons are about 30-fold supersensitive to 5-HT in chronic spinal rats. The 5-HT-induced facilitation of the Ca PIC was blocked by nimodipine, not by the I(h) current blocker Cs(+) (3 mM) or the SK current blocker apamin (0.15 microM), and it lasted for hours after the removal of 5-HT from the nCSF, even increasing initially after removing 5-HT. The effects of 5-HT make motoneurons more excitable and ultimately lead to larger, more easily activated plateaus and self-sustained firing. The supersensitivity to 5-HT suggests the small amounts of endogenous 5-HT below the injury in a chronic spinal rat may act on supersensitive receptors to produce large Ca PICs and ultimately enable muscle spasms.

Anesthetics, Local↗

Palliative care in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disease in adults. The clinical picture consists of generalized fasciculations, progressive atrophy and weakness of the skeletal muscles, spasticity and pyramidal tract signs, dysarthria, dysphagia, and dyspnea. Pseudobulbar affect is common. Disease-specific treatment options are still unsatisfactory. Therapeutic nihilism is not justified as a large array of palliative measures available to enhance the quality of life of patients and their families. Because of its clinical characteristics, ALS represents a paradigm for palliative care in neurological diseases. Numerous projects are being undertaken worldwide in an effort to enlarge the evidence base for palliative interventions in ALS. Palliative care in ALS is a multidisciplinary effort requiring careful coordination. An open and empathic disclosure of the diagnosis is essential. Nutritional deficiency caused by dysphagia can be relieved by a percutaneous endoscopic gastrostomy. Respiratory insufficiency can be effectively treated by non-invasive home mechanical ventilation. The terminal phase of the disease should be discussed at the latest when symptoms of dyspnea appear, in order to prevent unwarranted fears of "choking to death." Psychological and spiritual care of patients and families are important. Collaboration with hospice institutions and completion of advance directives can be of invaluable help in the terminal phase.

Amyotrophic Lateral Sclerosis↗

Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose.

INTRODUCTION: Baclofen is frequently used to treat muscle spasticity due to spinal cord injury and multiple sclerosis. Baclofen overdose can lead to coma, respiratory depression, hyporeflexia, and flaccidity. An abrupt decrease in the dose of baclofen due to surgery or a rapid tapering program may result in severe baclofen withdrawal syndrome manifesting hallucinations, delirium, seizures, and high fever. Severe baclofen withdrawal syndrome secondary to intentional overdose, however, has not received mention. CASE REPORT: A 42-year-old male receiving chronic baclofen therapy, 20 mg/d, attempted suicide by ingesting at least 800 mg of baclofen. He was found in coma 2 hours postingestion with depressed respirations, areflexia, hypotonia, bradycardia, and hypotension. Treatment with intravenous fluids, atropine, dopamine, and hemodialysis was associated with restoration of consciousness within 2 days but disorientation, hallucinations, fever, delirium, hypotension, bradycardia, and coma developed during the following week. Baclofen withdrawal syndrome was not diagnosed until hospital day 9, when reinstitution of baclofen rapidly stabilized his condition. Oral overdosage of baclofen causes severe neurological and cardiovascular manifestations due to its GABA and dominant cholinergic effects. Severe baclofen withdrawal syndrome is manifest by neuropsychiatric manifestations and hemodynamic instability. Caution should be exercised after a baclofen overdose in patients receiving chronic baclofen therapy.

Adult↗

Botulinum toxin A for myofascial trigger point injection: a qualitative systematic review.

Botulinum toxin injection is used to treat various pain conditions including muscle spasticity, dystonia, headache and myofascial pain. Results are conflicting regarding the use of Botulinum toxin for trigger point injection in terms of improvement in pain. The aim of this study was to carry out a systematic review to assess the evidence for efficacy of Botulinum toxin A (BTA) compared with placebo for myofascial trigger point injection. Electronic databases on Medline, Cochrane Library, Scopus, CINAHL were queried using key words such as "botulinum toxin", "myofascial pain", "trigger point", "chronic pain" and "musculoskeletal pain". Relevant published randomized controlled trials that described the use of BTA as injection therapy for trigger points were considered for inclusion. The five-item 0-16 point Oxford Pain Validity Scale (OPVS) was used as a selection criteria for suitable clinical trials. Trials were also assessed based on quality using the Oxford Rating Scale. Data extracted from qualified trials included outcome measures such as pain intensity and pain pressure threshold. All studies were ranked according to the OPVS and the authors' conclusions were compared. Five clinical trials met the inclusion criteria. One trial concluded that BTA was effective, and four concluded that it was not effective for reducing pain arising from trigger points. OPVS scores ranged from 8 to 14 with the negative studies corresponding with higher validity scores. The current evidence does not support the use of BTA injection in trigger points for myofascial pain. The data is limited and clinically heterogeneous.

Botulinum Toxins, Type A↗

The effect of pharmacologic acetylcholine receptor on fibrillation and myotonia in rat skeletal muscle.

Myotonic discharges in rats given 20, 25-diazacholesterol hydrochloride and fibrillation discharges in denervated rat muscle both were silenced by procaine hydrochloride, tetrodotoxin or ischemia, or potassium chloride (after initial activation). They both were activated by succinylcholine, but only the fibrillations were silenced by alpha-bungarotoxin or atropine sulfate. It is hypothesized that fibrillations and diazacholesterol-induced myotonia are mediated through mechanisms involving ionic channels, that both can be produced by activation of the junctional/nonjunctional acetylcholine receptors (or some mechanism coupled to the receptors), but that an unfettered alpha-bungarotoxin-binding portion of the acetylcholine-receptor molecule and an unblocked atropine-binding site are obligatory only for production of fibrillations.

Acetylcholine↗

Spastic paraparesis, mental retardation, and cutaneous pigmentation disorder. A new syndrome.

Four siblings in a family with a highly consanguineous background presented with an unusual combination of spastic paraparesis, muscle wasting, microcephaly, mental retardation, skeletal deformities, and cutaneous manifestations, ie, hypopigmented and hyperpigmented lesions and graying of the hair. An extensive workup including electromyography, muscle biopsy, and chromosomal analysis was unrewarding. An autosomal recessive inheritance is probable. A similar entity was recently reported from israel. The possibility that this previously unrecognized condition represents a new syndrome is suggested.

Adolescent↗

Juvenile and adult rat neuromuscular junctions: density, distribution, and morphology.

Anatomical and physiological differences in neuromuscular junctions (NMJs) between juvenile and adult muscle may partially explain the variability in clinical results following chemodenervation with botulinum toxin or nerve repair in children and adults. We evaluated NMJ density, distribution, and morphometry in biceps brachii and gastrocnemius muscles from juvenile and adult rats. Motor endplates were stained with Karnovsky-Roots methods, and NMJ density (number/gram muscle tissue) was determined. The NMJ morphometry was quantitated with alpha-bungarotoxin labeling using confocal microscopy. Juvenile rats had a greater NMJ density in both muscles compared with adult rats. Juveniles and adult rats had a similar NMJ distribution in both muscles. In juvenile muscles NMJs occupied approximately 50% of the surface area and 70% of the length, width, circumference, and gutter depth compared with adult muscles. Our study demonstrates that although NMJs are smaller, juvenile muscles have a higher NMJ density than do adult muscles with similar distributions. If these age-dependent differences in NMJ density are obtained in humans, they may account, at least in part, for the better recovery that occurs in children than adults after nerve repair and also suggest that the dosage of botulinum toxin (units per kg) for chemodenervation may need to be increased in juveniles.

Aging↗

Gentle dorsal root retraction and dissection can cause areflexia: implications for intraoperative monitoring during "selective" partial dorsal rhizotomy.

During partial dorsal rhizotomy (PDR), intraoperative dorsal rootlet stimulation often evokes nonreflex, rather than reflex, motor responses that are due to costimulation of adjacent ventral roots. Intraoperative areflexia typically predicts that motor responses evoked by dorsal rootlet stimulation are nonreflexive. The cause of areflexia during PDR is in part due to anesthesia, but other mechanisms are likely to play a role as well. In this study of three consecutive patients undergoing lumbosacral neurosurgery, soleus H-reflexes evoked by tibial nerve stimulation at the popliteal fossa were found to suddenly decline in amplitude following retraction and gentle dissection of the S-1 dorsal root. In one areflexic patient, dorsal rootlet stimulation proximal to the main site of dissection evoked soleus H-reflexes, although they could not be evoked by tibial nerve stimulation. We conclude that the gentle retraction and dissection of dorsal rootlets that occurs during PDR can induce conduction block of reflex afferents. High-intensity dorsal rootlet stimulation distal to the site of conduction block may then evoke not reflex responses, but rather nonreflex motor responses, due to the costimulation of adjacent ventral roots.

Cerebral Palsy↗