Prolonged Spasms Research Articles

Longitudinal assessment of blepharospasm severity in patients with long disease duration

IntroductionBlepharospasm (BSP) represents one of the most common idiopathic adult-onset dystonia. A few longitudinal observations indicated progression and worsening of BSP severity within 16 years of onset. Information is lacking about the trend of BSP severity in the later stages of the disease. MethodsThe study comprised 15 women and 3 men that underwent a standardized video protocol at two time points: 14 ± 9 years after BSP onset and 11 ± 2 years later. BSP severity was rated by the Blepharospasm Severity Rating Scale (BSRS). Two independent observers reviewed 36 videos in a pseudo-randomized order, yielding satisfactory agreement. ResultsMean total severity score was 7.6 ± 3.9 years at baseline, 6.4 ± 2.5 at the last examination (p = 0.14). The last video examination showed a stable BSRS score in 14/18 patients, while the score of 4 patients decreased by two points or more, due to disappearance (n.3) or reduction (n.1) of prolonged spasms with complete rim closure. Over the long term, the BoNT dosage increased in those who improved, but remained stable in the other patients. On follow-up examination, dystonia spread to the lower face or neck in two new patients. No significant correlations emerged between disease duration and BSP severity. The presence of sensory trick significantly correlated with disease duration but not with BSP severity. DiscussionThis study provides novel information on the long-term prognosis in patients with idiopathic BSP, showing that severity of BSP may not worsen in the later stages of the disease.

Status Epilepticus Manifested as Continuous Epileptic Spasms.

Objective: The etiology and outcome of status epilepticus with continuous epileptic spasms have not been fully understood; and only rare cases have been reported in the literature. Here, we described 11 children, who manifested continuous epileptic spasms with various etiologies and different outcomes.Methods: This is a case series study designed to systematically review the charts, video-electroencephalography (video-EEG), magnetic resonance images, and longitudinal follow-up of patients who presented continuous epileptic spasms lasting more than 30 min.Results: Median age at onset was 2 years old, ranging from 2 months to 5.6 years. The etiology of continuous epileptic spasms for these 11 cases consisted of not only some known electro-clinical epilepsy syndromes like West Syndrome and Ohtahara Syndrome, but also secondary symptomatic continuous epileptic spasms, caused by acute encephalitis or encephalopathy, which extends the etiological spectrum of continuous epileptic spasms. The most characteristic feature of these 11 cases was prolonged epileptic spasms, lasting for a median of 13.00 days (95% CI: 7.26–128.22 days). The interictal EEG findings typically manifested as hypsarrhythmia or its variants, including burst suppression. Hospital stays were much longer in acute symptomatic cases than in primary epileptic syndromic cases (59.67 ± 50.82 vs. 15.00 ± 1.41 days). However, the long-term outcomes were extremely poor in the patients with defined electro-clinical epilepsy syndromes, including severe motor and intellectual developmental deficits (follow-up of 4.94 ± 1.56 years), despite early diagnosis and treatment. Continuous epileptic spasms were refractory to corticosteroids, immuno-modulation or immunosuppressive therapies, and ketogenic diet.Conclusion: Continuous epileptic spasms were associated with severe brain impairments in patients with electro-clinical syndromes; and required long hospital stays in patients with acute symptomatic causes. We suggest to include continuous epileptic spasms in the international classification of status epilepticus, as a special form. Further investigations are required to better recognize this condition, better understand the etiology, as well as to explore more effective treatments to improve outcomes.

A neural network-based software to recognise blepharospasm symptoms and to measure eye closure time

Blepharospasm (BSP) is an adult-onset focal dystonia with phenomenologically heterogeneous effects, including, but not limited to, blinks, brief or prolonged spasms, and a narrowing or closure of the eyelids. In spite of the clear and well-known symptomatology, objectively rating the severity of this dystonia is a rather complex task since BSP symptoms are so subtle and hardly perceptible that even expert neurologists can rate the gravity of the pathology differently in the same patients. Software tools have been developed to help clinicians in the rating procedure. Currently, a computerised video-based system is available that is capable of objectively determining the eye closure time, however, it cannot distinguish the typical symptoms of the pathology. In this study, we attempt to take a step forward by proposing a neural network-based software able not only to measure the eye closure, time but also to recognise and count the typical blepharospasm symptoms. The software, after detecting the state of the eyes (open or closed), the movement of specific facial landmarks, and properly implementing artificial neural networks with an optimised topology, can recognise blinking, and brief and prolonged spasms. Comparing the software predictions with the observations of an expert neurologist allowed assessment of the sensitivity and specificity of the proposed software. The levels of sensitivity were high for recognising brief and prolonged spasms but were lower in the case of blinks. The proposed software is an automatic tool capable of making objective ‘measurements’ of blepharospasm symptoms.

Disease progression in blepharospasm: a 5-year longitudinal study.

The clinical manifestation of dystonic spasms in blepharospasm (BSP) patients may be heterogeneous. Whether the varying phenomenology of eyelid spasms becomes manifest sequentially during the course of the disease or aggregates in separate clusters according to different disease courses is still unclear. For this purpose, the clinical features in BSP patients were evaluated longitudinally over a 5-year period and also the blink reflex recovery cycle was tested in a subgroup of BSP patients. Sixty BSP patients were videotaped at time 0 and after approximately 5years of follow-up. Two experts in movement disorders, who were blinded to the video order, reviewed the videotapes and scored the severity of BSP using the Blepharospasm Severity Rating Scale. Changes in the R2 recovery index were also evaluated in 18 patients twice, i.e. upon enrolment and at the follow-up. The severity of BSP worsened significantly over the 5-year follow-up period owing to the appearance or the increased duration and frequency of prolonged spasms. It was also found that the blink reflex recovery cycle worsened at follow-up in comparison with the baseline. This study shows that the disease progression of BSP is characterized by the appearance or worsening of prolonged spasms. Prolonged spasms are accompanied by changes in the excitability of brainstem interneurons. Aging-related effects may exacerbate the pathophysiological mechanisms underlying spasms.

A Neonate with Exaggerated Startle and Tonic Spasms

AbstractHyperekplexia is a rare, potentially treatable inherited disorder of glycinergic neurotransmission, which is characterized by neonatal onset exaggerated startle response to somatosensory, auditory stimuli, and episodic tonic spasm. Prolonged tonic spasms can be life-threatening and associated with apnea and bradycardia. Awareness about this condition avoids misdiagnosis such as tonic seizures and epilepsy. We describe a term newborn with episodic tonic stiffness mistaken for seizures. Classical exaggerated startle reaction, positive head retraction response to glabellar tap, and characteristic video electroencephalogram confirmed the diagnosis.

Clinical heterogeneity in patients with idiopathic blepharospasm: A cluster analysis

BackgroundIdiopathic blepharospasm is a clinically heterogeneous condition. It is not known whether the various manifestations become manifest sequentially during the course of the disease or aggregate in separate clusters identifying subpopulations of patients. MethodsEighty-nine patients with idiopathic blepharospasm were assessed using k-means cluster analysis to identify relatively homogeneous groups on the basis of low-intragroup/high-intergroup differences across a set of selected variables. ResultsThe results suggest that there may be three groups of patients. Group 1 included patients who had prolonged muscle spasms leading to complete rim closure associated with brief and/or prolonged spasms with incomplete rim closure, the most severe blepharospasm, and a greater tendency to spread to adjacent segments. Group 2 included patients characterized by prolonged spasms with partial rim closure, either alone or associated with brief spasms whereas Group 3 included patients with brief spasms with complete rim closure, the least severe blepharospasm, and the lowest tendency to spread. The severity of Group 2 blepharospasm was between that observed in Group 1 and Group 3, while the tendency to spread was similar to Group 3. The three groups did not differ for disease duration, age of onset, sex and other clinical features. The observation that inhibition of the R2 component of the blink reflex recovery cycle was more abnormal in Groups 1/2 2 than in Group 3 at least in part validates our classification. ConclusionsThe present study suggests that blepharospasm patients may be classified in different subtypes according to the type of spasms, severity of the condition and tendency to spread.

Blepharospasm 40 years later.

Forty years ago, C.D. Marsden proposed that blepharospasm should be considered a form of adult-onset focal dystonia. In the present paper, we provide a comprehensive overview of the findings regarding blepharospasm reported in the past 40 years. Although prolonged spasms of the orbicularis oculi muscles remain the clinical hallmark of blepharospasm, patients with blepharospasm may be characterized by various types of involuntary activation of periocular muscles. In addition to motor features, blepharospasm patients may also have nonmotor manifestations, including psychiatric, mild cognitive, and sensory disturbances. The various motor and nonmotor symptoms are not present in all patients, suggesting that blepharospasm is phenomenologically a heterogeneous condition. This emphasizes the need for tools for severity assessment that take into account both motor and nonmotor manifestations. The cause of blepharospasm remains elusive, but several lines of evidence indicate that blepharospasm is a multifactorial condition in which one, or several, as yet unknown genes together with epigenetic and environmental factors combine to reach the threshold of the disease. Although blepharospasm was originally believed to be solely a basal ganglia disorder, neurophysiological and neuroimaging evidence point to anatomical and functional involvement of several brain regions. The contribution of multiple areas has led to the hypothesis that blepharospasm should be considered as a network disorder, and this might reflect the varying occurrence of motor and nonmotor manifestations in blepharospasm patients. Despite advances in the aetiology and pathophysiology, treatment remains symptomatic. © 2017 International Parkinson and Movement Disorder Society.

The Effects of Drinking Coffee While Recovering from Colon and Rectal Resection Surgery.

Aim:Resection surgery on the colon and rectum are changing both anatomical and physiological relations within the abdominal cavity. Delayed functions of the gastrointestinal tract, flatulence, failure of peristalsis, prolonged spasms and pain, limited postoperative recovery of these patients increase the overall cost of treatment. Early consumption of coffee instead of tea should lead to faster restoration of normal function of the colon without unwanted negative repercussions.Method:This study is designed as a prospective-retrospective clinical study and was carried out at the Surgery Center Tuzla, during the year 2013/ 2014. Sixty patients were randomized in relation to the type of resection surgery, etiology of disease-malignant benign, and in relation to whether they were coffee users or not. Patients were divided into two groups. The first group of thirty patients was given 100 ml of instant coffee divided into three portions right after removing the nasogastric tube, first postoperative day, while the second group of thirty patients got 100 ml of tea. Monitored parameter was: time of first stool and the second group of monitored parameters was: whether there was returning of nasogastric tube or not, increased use of laxatives, whether there was anastomotic leak, radiologic and clinical dehiscence, audit procedures, or lethal outcomes in the treatment of patients.Results:A total of 61 patients were randomized into two groups of 30 int he group of tea and coffee 29 in the group, two patients were excluded from the study because they did not consume coffee before surgery. Time of getting stool in the postoperative period after elective resection surgery on the colon and rectum is significantly shorter after drinking coffee for about 15h (p <0.01). Also, the length of hospital stay was significantly shorter after drinking coffee (p <0.01). Time of hospitalization in subjects/respondents coffee consumers on average lasted 8.6 days with consumers of tea for 16 days. The incidence of postoperative complications was significantly lower after consumption of coffee (p <0.05).Conclusion:Postoperative consumption of coffee is a safe and effective way to accelerate the establishment of the bowel function after colorectal resection surgery.

A Quest for Better Understanding of Biochemical Changes in Fibromyalgia Syndrome

Fibromyalgia Syndrome (FMS) is one of the least understood pain syndrome in medicine today, which is a chronic disorder characterized by persistent and widespread pain, with an estimated prevalence of 2–4 % in the adult general population (3.4 % for women and 0.5 % for men). The defining symptoms of FMS are chronic widespread pain and fatigue. Other symptoms include tingling of the skin, prolonged muscle spasms, weakness in the limbs, nerve pain, muscle twitching and chronic sleep disturbances. Many patients of FMS also experience cognitive dysfunction. The initial FMS criteria included tenderness on pressure (tender points) in at least 11 of 18 defined anatomic sites with the presence of widespread pain. However, in the recent criteria it is clear that apart from the pain other seminal features of the disorder such as cognitive dysfunction, unrefreshing sleep, fatigue and mood disorders also play an important role in the diagnosis. FMS is also considered to be a disorder of central pain processing that produces heightened responses to painful stimuli (hyperalgesia) and painful responses to non-painful stimuli (allodynia). Therefore, the heightened state of pain transmission may be due to increase in pronociceptive neurotransmitters, such as substance P and glutamate. Thus, the pain of FMS is often accompanied by one or more manifestations, such as affective moods, cognitive insecurity, autonomic dysfunction, or irritable bowel syndrome. The etiology and pathogenesis of FMS are still not fully understood. Several novel factors such as dysfunction of neurotransmitters, cytokines, sleep disturbances, perturbed circadian rhythm of cortisol and melatonin, free radical mediated oxidative damage and toxic metals seem to be involved.

Hypoventilation in glycine-receptor antibody related progressive encephalomyelitis, rigidity and myoclonus

Glycine receptor (GlyR) antibodies have been identified in patients with rigidity and hyperekplexia, but the clinical phenotype associated with these antibodies has not been fully elucidated. The clinical features in two additional patients with GlyR antibodies are described. A 55-year-old man presented with stimulus-induced hyperekplexia and rigidity in the lower limbs and trunk. He initially responded to benzodiazepines, but presented after 18months with severe, painful, prolonged spasms associated with supraventricular and ventricular arrhythmias, hypoventilation and oxygen desaturation requiring intubation. He improved following treatment with clonazepam, baclofen and immunomodulatory therapies. A 58-year-old woman presented with stiffness in the legs and hyperekplexia associated with hypoventilation, at times leading to loss of consciousness. She responded to benzodiazepines and has remained in remission. The clinical picture associated with GlyR antibodies includes autonomic dysfunction, cardiac arrhythmias and hypoventilation. It is important to recognise these serious complications early to limit mortality from this treatable condition.

Oromandibular dystonia: A clinical report

Oromandibular dystonia (OMD) consists of prolonged spasms caused by contraction of the muscles of the mouth and mandible and involves the muscles of mastication, facial expression, tongue, and eye lids. A multidisciplinary treatment approach is presented including the fabrication of a dental prosthesis to reduce/eliminate the symptoms of OMD. Etiology and treatment issues are discussed, emphasizing the importance of an interdisciplinary treatment approach.

EEG findings in an adult with severe case of alobar holoprosencephaly

Holoprosencephaly is a category of congenital brain malformation that is frequently associated with epilepsy. Epileptic spasms and partial seizures are reported with a variety of electrographic ictal and interictal EEG findings. We report a case of severe alobar holoprosencephaly with cortical tissue limited to inferior–anterior–frontal areas and a thin mantle over the posterior areas, and no appreciable connective fibers to the subcortical structures. Interictal EEG consisted mainly of 2–3 Hz irregular delta activity during wakefulness and sleep. Clinical seizures had two different semiologies: (1) epileptic spasms lasting 0.5 s during state change and (2) prolonged tonic spasms lasting 5–8 s followed by appendicular clonic activity, abnormal nystagmoid eye movements and eye flutter lasting 5–8 s. Preceding the epileptic spasms, there was 1–2 s of electrodecrement in the EEG. During prolonged tonic spasms there was also electrodecrement in the EEG. No other electrographic activity was seen. Due to lack of any appreciable connecting fibers between cortical and subcortical structures, these findings suggest an increase in brain stem excitability with inefficient (or lack of) cortical modulation as a possible underlying mechanism for epileptic spasms in this patient.

Salvage of compromised free flaps in trauma cases with combined modalities

Using the microsurgical technique for reconstruction in trauma cases represents a challenge for the reconstructive surgeon. Several methods of salvaging of a compromised free flap have been reported, among them: intravenous heparin washing, thrombolitic therapy, thrombectomy, use of grafts and others. Here, we present our experience from nine cases and a review of the literature regarding the use of various modalities for free flap salvage in trauma cases, and their results. Data was collected from trauma cases in our institutions over a period of 2 years, where reconstruction was performed using microsurgical techniques, and where subsequent complications required some type of salvage procedure. The techniques that were used for the salvage included: intravascular irrigation with heparin, papaverine and lidocaine; administration of continuous intravenous heparin, use of the Fogarty catheter, flap washing with streptokinase, and adventitia stripping. The free flaps used were latissimus dorsi, serratus anterior, and the anteromedial thigh flap. Either vein or artery thromboses were identified during the procedure or immediately after surgery in seven patients. Two patients had prolonged spasms of the recipient artery with low flow. In all cases, the No. 2 Fogarty catheter was used for thrombectomy and also for release of the vessel spasm. There was only one complete failure among these patients, and partial necrosis was encountered in three. From our experience and review of the literature, we offer an algorithm for determining treatment strategies in a range of flap salvage situations.

Stiff-person syndrome

The stiff-person syndrome (SPS) is a rare neurologic disorder of uncertain cause, characterized by severe and incapacitating axial and proximal limb rigidity due to continuous motor unit activity. Rigidity is often enhanced by anxiety, sudden movements or external stimuli causing intermittent painful muscle spasms, often leading to skeletal deformity. Variants of this disorder include focal involvement of one limb (“stiff-limb syndrome”), or additional neurological symptoms suggestive of involvement of subcortical gray matter (“progressive encephalomyelitis with rigidity and myoclonus”) (PEWR) and occasionally secondary to malignant disease (paraneoplastic SPS). Antineuronal antibodies often associated with other auto-immune diseases are characteristic features of this disorder. The disease follows a progressive, unremitting course, resulting in pronounced disability, if left untreated. This unusual syndrome was first described by Moersch and Woltman in 1956 [1]. The authors coined the term “stiff-man syndrome” in reporting 14 patients with clinical features of progressive fluctuating muscular rigidity and spasms. Their first case, a 49year-old man, initially complained of a feeling of tightness of the neck musculature of variable occurrence. Over a period of 4 years this disorder progressively affected the muscles of the shoulder, back, abdomen, and thighs, causing the muscles to appear stiff and “board-like”. Continuous muscle contraction causing pronounced stiffness of the axial and limb muscles forced the patient to walk in a peculiar way that was both slow and awkward. Voluntary movement or passive displacement of the limbs triggered prolonged and painful muscle spasms. If severe enough, the spasms caused postural instability and falls. In the words of the authors, the patient would fall like a “wooden man”. The additional 13 patients in the original report were similar in all respects. The clinical features of this previously unreported condition were described in detail in Moersch and Woltman’s paper. No other signs of central or peripheral nervous system involvement were

Oromandibular dystonia: A dental approach

Oromandibular dystonia consists of prolonged spasms of contraction of the muscles of the mouth and jaw. Primary idiopathic forms and secondary forms exist. Secondary dystonia develops due to environmental factors; some cases of cranial dystonia after dental procedure have been reported, but the causal relationship between these procedures and dystonia remains unclear. Traumatic situations in the mouth, such as poor aligned dentures or multiple teeth extractions may cause an impairment of proprioception of the oral cavity, leading to subsequent development of dystonia. The clinical characteristics of oromandibular dystonia are classified according to the affected muscles. The muscles involved may be the muscles of mastication, muscles of facial expression, or the muscles of the tongue. At present, there is no known cure for OMD. The mainstay of treatment for most focal dystonia is botulinum toxin injections. It is important for the dentist to be familiar with oromandibular dystonia, as it can develop after dental treatment and is often misdiagnosed as a dental problem.

Changes in sensory-evoked synaptic activation of motoneurons after spinal cord injury in man

Following spinal cord injury (SCI), prolonged muscle spasms are readily triggered by brief sensory stimuli. Animal and indirect human studies have shown that a substantial portion of the depolarization of motoneurons during a muscle spasm comes from the activation of persistent inward currents (PICs). The brief (single pulse) sensory stimuli that trigger the PICs and muscle spasms in chronically spinalized animals evoke excitatory post-synaptic potentials (EPSPs) that are broadened to more than 500 ms, the duration of depolarization required to activate a PIC in the motoneuron. Thus, in humans, we investigated if post-synaptic potentials (PSPs) evoked from brief (<20 ms) sensory stimulation are changed after SCI and if they are broadened to > or =500 ms to more readily activate motoneuron PICs and muscle spasms. To estimate both the shape and duration of PSPs in human subjects we used peristimulus frequencygrams (PSFs), which are plots of the instantaneous firing frequency of tonically active single motor units that are time-locked to the occurrence of the sensory stimulus. PSFs in response to cutaneomuscular stimulation of the medial arch or toe of the foot, a sensory stimulus that readily triggers muscle spasms, were compared between non-injured control subjects and in spastic subjects with chronic (>1 year), incomplete SCI. In non-injured controls, a single shock or brief (<20 ms) train of cutaneomuscular stimulation produced PSFs consisting of a 300 ms increase in firing rate above baseline with an interposed period of reduced firing. Parallel intracellular experiments in motoneurons of adult rats revealed that a 300 ms EPSP with a fast intervening inhibitory PSP (IPSP) reproduced the PSF recorded in non-injured subjects. In contrast, the same brief sensory stimulation in subjects with chronic SCI produced PSFs of comparatively long duration (1200 ms) with no evidence for IPSP activation, as reflected by a lack of reduced firing rates after the onset of the PSF. Thus, unlike non-injured controls, the motoneurons of subjects with chronic SCI are activated by very long periods of pure depolarization from brief sensory activation. It is likely that these second-long EPSPs securely recruit slowly activating PICs in motoneurons that are known to mediate, in large part, the many seconds-long activation of motoneurons during involuntary muscle spasms.

The value of the per oral pneumocolon in the study of the distal ileal loops

To verify the diagnostic accuracy of per oral pneumocolon in the identification of both normal and pathological patterns in patients with suspected or proven small bowel disease. Per oral pneumocolon was performed after small bowel follow-through examinations in a series of 42 selected patients. The terminal ileum visibility, the loop location and possible pathological patterns were evaluated separately before and after insufflation. In post-insufflation images the presence/absence of reflux and grade of reflux were evaluated. The diagnostic quality of per oral pneumocolon as compared with per oral small bowel examination was superior in 23 of the 42 patients (54.8%; group 1), similar in nine of the 42 (21.4%; group 2), and inferior in 10 of the 42 (23.8%; group 3). Transvalvular reflux was present in 22 of 23 (95.6%) patients from group 1 and only in one of 10 patients (10%) from group 3 (p<0.001: statistically significant difference). Among the 24 of 42 (57.1%) patients with suspected or proven Crohn's disease, per oral pneumocolon increased the confidence with which the ileum was considered normal in 12 patients and it allowed a better evaluation of the disease extent and the differentiation between prolonged spasms and stenosis in five patients. In conclusion per oral pneumocolon should be performed after a small bowel follow-through examination in selected patients.

Exacerbation of Chronic Pain following Spinal Cord Injury

Because of the high prevalence and the refractory nature of pain following spinal cord injury (SCI), it is important to increase the understanding of what factors aggravate different types of pain. This information is related to pain generating mechanisms and may thus be useful in the diagnosis and management of these difficult pain conditions. The aims of the present study were to (1) identify variables (factors) that exacerbate chronic pain associated with SCI and (2) define the relationships among these patterns of pain exacerbation, specific pain characteristics, and psychological features. A sample out of 159 (75.5%) people with SCI and chronic pain, volunteered to participate in a mail survey. Over 50% of the sample indicated that prolonged sitting, infections, fatigue, muscle spasms, cold weather, and sudden movements exacerbated their pain. A principal components analysis detected five sets of factors that were reported to magnify pain: negative mood, prolonged afferent activity (bowel, bladder, somatic), weather, voluntary physical activity, and transient somatic afferent activity. Negative mood and prolonged afferent activity were frequently and significantly associated with both pain characteristics and psychosocial issues. A multiple regression analysis revealed that a combination of decreased activity levels due to pain (t = 3.54; p < 0.001), pain located in the frontal aspects of torso (including genitals) (t = 2.29; p < 0.05), "burning" (t = 2.26; p < 0.05), or "electric" (t = 2.09; p < 0.05) pain, and a limited perception of life control (t = -2.16; p < 0.05) was significantly associated with a high extent of pain aggravation (R2 = 0.39; p < 0.000).

Role of motoneurons in the generation of muscle spasms after spinal cord injury.

Motoneurons in the spinal cord have intrinsic voltage-dependent persistent inward currents (PICs; e.g. persistent calcium currents) that amplify synaptic inputs by three- to five-fold in addition to providing a sustained excitatory drive that allows motoneurons to fire repetitively following a brief synaptic excitation. In this study, we examined whether prolonged involuntary muscle spasms in subjects with long-term injury to the spinal cord are mediated by the activation of PICs in the motoneuron. To examine this in the human, we used a paired motor unit analysis technique where the firing frequency of one motor unit of the pair (control unit) was used to estimate the synaptic drive to the motoneuron pool, including the drive to a second higher-threshold motor unit of the pair (test unit). The degree to which a motoneuron PIC helped to sustain the discharge of a test motor unit (self-sustained firing) was determined from the reduction in control unit firing at de-recruitment (DeltaF) compared with recruitment of the test unit. This DeltaF value corresponds to the reduction in synaptic drive needed to counteract the intrinsic PIC and, thus, was used an indirect measure of this current. In the nine motor unit pairs studied, the average estimated synaptic drive, or control unit firing rate, required to recruit a test motor unit at the onset of a muscle spasm was significantly higher (by 43%) than the estimated synaptic drive during de-recruitment at the end of a muscle spasm. This indicated that a motoneuron PIC, and associated self-sustained firing, facilitated the firing of the test units during the prolonged muscle spasms. In addition, in all subjects tested (seven out of seven), we observed that following a muscle spasm or voluntary contraction, spontaneous and self-sustained firing of motor units could continue for many seconds, even minutes, at very low discharge rates (average 5.2 +/- 1.6 Hz) with extremely low spike-to-spike variability (coefficient of variation = 5.4 +/- 1.6%). Moreover, increases in synaptic drive (noise) to the spontaneously firing units with voluntary muscle contractions or muscle spasms increased both the mean firing rate of the motor units in addition to their firing variability. This suggests that the slow spontaneous firing commonly observed in chronic spinal injury likely occurs without appreciable synaptic noise and is likely driven to a substantial degree by PICs intrinsic to the motoneuron because it is self-sustained and very regular.

Measuring patient benefit from botulinum toxin in the treatment of dystonia. Feasibility of cost-utility analysis.

The dystonias are a group of movement disorders arising from CNS dysfunction and characterised by involuntary and prolonged spasms of muscle contraction. Recently there has been increasing demand for treatment with botulinum toxin (BT), a relatively expensive neurological paralytic agent. As there has been no systematic assessment of patient benefit from BT, this study was undertaken to develop and test a methodology for assessing the cost utility of BT therapy for patients with dystonias. A generic health status instrument, the EuroQOL, was completed at regular intervals over at least 6 months by 130 patients with a current diagnosis of dystonia. A general population tariff was used to calculate quality-adjusted life-year (QALY) gains from BT treatment, and relevant cost data were obtained from patients and medical records. The cost-per-QALY estimates ranged considerably, depending on the type of dystonia, the duration of BT treatment, type of health-related quality-of-life (HR-QOL) tariff used and baseline characteristics of participants. The study findings reflect the general clinical impression of BT: that it can benefit patients with dystonia, but the benefit may be small compared with many treatments for other diseases. The nature of the disease and its cyclical treatment caused practical difficulties in recruiting participants, administering questionnaires and in estimating QALY gains.