Differences in globus pallidus neuronal firing rates and patterns relate to different disease biology in children with dystonia.

BACKGROUND: The pathophysiology underlying different types of dystonia is not yet understood. We report microelectrode data from the globus pallidus interna (GPi) and globus pallidus externa (GPe) in children undergoing deep brain stimulation (DBS) for dystonia and investigate whether GPi and GPe firing rates differ between dystonia types. METHODS: Single pass microelectrode data were obtained to guide electrode position in 44 children (3.3-18.1 years, median 10.7) with the following dystonia types: 14 primary, 22 secondary Static and 8 progressive secondary to neuronal brain iron accumulation (NBIA). Preoperative stereotactic MRI determined coordinates for the GPi target. Digitised spike trains were analysed offline, blind to clinical data. Electrode placement was confirmed by a postoperative stereotactic CT scan. FINDINGS: We identified 263 GPi and 87 GPe cells. Both GPi and GPe firing frequencies differed significantly with dystonia aetiology. The median GPi firing frequency was higher in the primary group than in the secondary static group (13.5 Hz vs 9.6 Hz; p=0.002) and higher in the NBIA group than in either the primary (25 Hz vs 13.5 Hz; p=0.006) or the secondary static group (25 Hz vs 9.6 Hz; p=0.00004). The median GPe firing frequency was higher in the NBIA group than in the secondary static group (15.9 Hz vs 7 Hz; p=0.013). The NBIA group also showed a higher proportion of regularly firing GPi cells compared with the other groups (p<0.001). A higher proportion of regular GPi cells was also seen in patients with fixed/tonic dystonia compared with a phasic/dynamic dystonia phenotype (p<0.001). The GPi firing frequency showed a positive correlation with 1-year outcome from DBS measured by improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-m) score (p=0.030). This association was stronger for the non-progressive patients (p=0.006). INTERPRETATION: Pallidal firing rates and patterns differ significantly with dystonia aetiology and phenotype. Identification of specific firing patterns may help determine targets and patient-specific protocols for neuromodulation therapy. FUNDING: National Institute of Health Research, Guy's and St. Thomas' Charity, Dystonia Society UK, Action Medical Research, German National Academic Foundation.

A healthy nation: strengthening child health research in the UK.

Despite a general acknowledgment that research in children is necessary and ethical, the evidence base for child-specific treatments is still sparse. We investigated children's biomedical and health services research in the UK in relation to training, infrastructure and activity, research evidence, and visibility. We show that excellent opportunities for career researchers exist through a competitive, national integrated academic training programme, but that the number of academic paediatricians has decreased by 18% between 2000 and 2011, falling from 11·3% to 5·9% of the consultant workforce. The potential for rapid delivery of studies in children through the National Health Service (NHS) is not being realised: clinical trainees are poorly equipped with core research skills; most newly appointed consultant paediatricians have little or no research experience; less than 5% of contracted consultant time supports research; less than 2·5% of the 2 million children seen in the NHS every year are recruited to studies; and ten of the 20 UK children's hospitals do not have a clinical research facility. Support through National Institute for Health Research networks is good for studies into drugs, but inconsistent for non-drug research; less than 5% of registered studies involve children and only one children's biomedical research centre has been allocated funding from 2012. Of the UK annual public and charitable biomedical research expenditure of roughly £2·2 billion, about 5% is directed at child health research. The scant evidence base is impeding the development of clinical guidance and policy-less than 20% of the outputs of the National Institute for Health and Clinical Excellence are applicable to children. Paediatric representation on major research boards is weak. Parent and young people's advocacy is fragmented, and their views are insufficiently heeded by regulatory bodies. The strong UK Government commitment to biomedical research has not been translated fully to research for children. The power of research in children to turn the tide of the growing burden of non-communicable, chronic, adult diseases that have their origins in early life, to benefit the health of an ageing population and future generations, and to reduce health-care costs is inadequately recognised. On the basis of our findings, we make several recommendations to improve early-years research, including the formation of multidisciplinary, cross-institutional groups of clinical and non-clinical child health researchers and their access to diagnostic and laboratory facilities suitable for children; a unified Children's Research Network for drug studies and non-drug studies; regulatory assessment of research that is proportionate and based on consistent national criteria; an expansion of research posts; support for parents' and young people's advocacy; collaboration between children's research charities; improved research training for paediatric trainees; and closer integration of child health research with core NHS activities.

Good outcome following emergency decompressive craniectomy in a case of malignant middle cerebral artery infarction in a 14-month-old infant.

We report the case of a 14-month-old infant presenting with unresponsiveness and seizure following thoracic surgery. Imaging showed full territory left middle cerebral artery infarct and signs of raised intracranial pressure (ICP) that required emergency decompressive craniectomy (DC). The child made a good functional recovery. We discuss the case.

Clonidine use in the outpatient management of severe secondary dystonia.

OBJECTIVE: To evaluate the safety, efficacy and effective dosage of clonidine in the outpatient (OP) management of secondary dystonia. METHODS: A retrospective analysis of children and young people (CAYP) prescribed clonidine in an OP clinic between January 2011 and November 2013 for dystonia management. Of 224 children receiving clonidine, 149/224 did not have a movement disorder and 12/224 had no data leaving 63 movement disorder cases, 15/63 managed as in-patients, 15/48 suffered from tics leaving 33/63 for OP evaluation. Clonidine effectiveness was assessed by 'yes/no' criteria in improving 5 areas: seating, sleep, pain, tone and involuntary movements. RESULTS: 2/33 motor cases had insufficient data; 7/33 had concurrent therapy leaving 24/33 for analysis. Improvement in at least one area was reported by 20/24 (83%) CAYP: Improved seating tolerance 14/24, and sleep 15/24; reduced pain 15/24; improved tone 16/24 and involuntary movements 17/24. Starting doses ranged from 1 mcg/kg OD to 2 mcg/kg TDS with optimum doses reached on average at 9.5 months follow-up. Maximum dose reached was 75 mcg/kg/day given in 8 divided doses. Average maximum daily dose was 20 mcg/kg/day. The commonest frequency of administration was 8 hourly. Side effects were reported in 11/24 CAYP and discontinued in 1/24 for lack of clinical effectiveness, 1/24 for side effects and 4/24 due to both lack of effectiveness and side effects. CONCLUSION: Clonidine was effective in secondary dystonia management in 83% of cases. A starting dose of 1 mcg/kg TDS was well tolerated and safely escalated. Prospective objective evaluation is now required to confirm the efficacy of clonidine.

Safety and efficacy of high-dose enteral, intravenous, and transdermal clonidine for the acute management of severe intractable childhood dystonia and status dystonicus: An illustrative case-series.

OBJECTIVE: Acute dystonia in children is distressing, painful and can progress to life-threatening status dystonicus. Typical management involves benzodiazepines which can result in respiratory depression requiring PICU admission. Clonidine is less respiratory-depressant, and by facilitating sleep, switches dystonia off. It can also be administered via enteral, continuous intravenous infusion, and transdermal slow release routes. We describe the dose range and safety profile of clonidine management in a case-series of children with severe acute exacerbation of dystonia in a tertiary hospital setting. METHODS: The management of 5 children (3 female, age range 8-14 years) suffering from an acute exacerbation of secondary dystonia requiring hospital admission at the Evelina London Children's Hospital was reviewed. The average and maximum dose of clonidine in mcg/kg/h and routes of administration were recorded for each day of hospital admission. Co-administration of any other medical treatments for dystonia and their route of administration were also recorded. Cardiovascular and respiratory clinical status were measured by recording the daily mean and maximum Paediatric Early Warning Scores (PEWS). RESULTS: Clonidine was administered via enteral, intravenous, and transdermal routes at a median dose of 2.5 mcg/kg/h (range 0.1-9 mcg/kg/h). Administration of high dose clonidine was associated with decreased use of benzodiazepines, morphine, and propofol: avoiding invasive respiratory support for ¾ cases during admission. Clonidine doses via all routes of administration did not correlate with poorer PEWS scores (p = 0.839). Both high dose intravenous and transdermal clonidine where found to be effective. CONCLUSIONS: High dose clonidine administered via different routes can be used in the acute management of severe exacerbations of dystonia. Its use in our cohort was not associated with significant cardio-respiratory depression even at doses as high as 9 mcg/kg/h.

Legal risks in a changing practice environment.

A general working definition of medical malpractice is provided. Relevant factual situations as well as applicable decisional and statutory laws are delineated. This information will allow the nurse to understand the legal standards that apply to nursing practice in a variety of health care environments.

The saphenous nerve: an external method for identifying its exit from the adductor canal.

The saphenous nerve is the largest and longest branch of the femoral nerve. At its proximal origin, it travels with the femoral artery. The nerve passes lateral to medial in the adductor canal to emerge subcutaneously and supply the medial side of the knee. This investigation analyzes the course of the nerve in 24 lower extremities (12 right, 12 left) and offers a standardized measuring system for externally pinpointing the nerve's exit from the canal. This study may benefit physicians who treat patients with knee pain of obscure etiology. It probably will have direct application to saphenous nerve injection by physicians as part of a pain-management program.

Surgical treatment of chronic lower extremity neuropathic pain.

The current authors retrospectively reviewed 147 lower extremity peripheral nerve procedures in 114 patients (average age, 42 years) with chronic lower extremity neuropathic pain to determine whether surgical treatment based on an empirically derived algorithm could reduce pain and improve function. This algorithm assigns crush, stretch, and chronic transection injuries to treatment with transection and containment. Peripheral nerve stimulation was used in conjunction with transection and containment for patients with more chronic presentations for whom previous transections had been unsuccessful. Patients with adhesive neuralgia underwent revision neurolysis with vein wrapping. Patients with repetitive nerve trauma (overuse) underwent primary or revision neurolysis. Duration of symptoms averaged 37 months, and mechanisms of nerve injury included chronic transection, crush, adhesive neuralgia, stretch, repetitive trauma, and idiopathic etiology. Time to followup averaged 38 months. Pain and dysfunction were ranked from 0 points (no pain or dysfunction) to 10 points (pain prompting request for amputation or functional deficit warranting wheelchair use); preoperative and followup work status were documented. Average pain and dysfunction scores improved: 8.8 to 5.6 points and 7.6 to 5.0 points, respectively. Of the 114 patients, 52 (46%) patients improved their work status, including 35 of 87 (40%) involved in workers' compensation. There were no statistically significant differences in outcome based on mechanism of nerve injury or type of procedure. The consistent average improvement suggests this algorithm assigns the appropriate procedure to a given mechanism of injury.

Complex salvage procedures for severe lower extremity nerve pain.

From 1995 to 1999, the senior author did revision nerve release and vein wrapping (58 limbs in 58 patients) or peripheral nerve stimulation (62 limbs in 62 patients) to relieve intractable lower extremity nerve pain. Vein wrapping was done if the patient had temporary relief after a previous nerve release, if there was evidence of scarring around the nerve, and if nerve pain was triggered by mechanical stimulation. Peripheral nerve stimulation was done when previous nerve operations provided no relief or if the nerve pain was more constant and spontaneous without mechanical provocation. The duration of symptoms preoperatively averaged 52 months, and the number of previous peripheral neurosurgical interventions averaged 2.5. Postoperatively, the average pain improvement was rated as 60% for the patients who had vein wrapping and 41% for the patients who had peripheral nerve stimulation. Of the patients who had vein wrapping, 53% were satisfied, 14% were somewhat satisfied, and 33% were dissatisfied. Of the patients who had peripheral nerve stimulation, 61% were satisfied, 21% were somewhat satisfied, and 18% were dissatisfied. Most patients (78%) stated they would undergo the procedures again.