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Adrenomyeloneuropathy (AMN) is a rare inherited condition where affected individuals develop slowly progressive spastic paraparesis with a gradual decline in walking ability. There is no cure for AMN and treatment focuses on supportive measures and aids. One treatment option is functional electrical stimulation (FES), a treatment, approved by The National Institute for Health and Care Excellence (NICE), for managing foot drop in upper motor neuron disorders. Limited evidence exists for its use in AMN patients. We describe the effects of FES in an individual case and more broadly within a cohort of 21 patients successfully treated with FES. Patients with AMN referred for FES typically report frequent falls (71%) and foot drop (57%) as the most common barriers to walking. When using FES, walking speed at baseline (0.70 m/s [SD = 0.2]) was maintained at the 2‐year review (0.68 m/s [SD = 0.2]) with a persistent orthotic effect (improvement in walking speed when device on vs. off) seen from wearing FES over the same 2‐year period (11%–19%). Patient walking satisfaction (visual analogue scale: 0 – very dissatisfied; 10 – very satisfied) was also greater when comparing no‐FES versus FES over the same period (Year 1: 2.5 vs. 7.7; Year 2: 2.1 vs. 6.1). FES is not effective in all patients. Twelve patients referred found no benefit from the device; although there was no clear evidence, this was related to the degree of AMN associated peripheral neuropathy. However, FES is a safe, cost‐effective treatment option and should be considered, along with assessment in a multidisciplinary clinic, for all AMN patients with walking difficulties.

Neurorehabilitation is often thought of as a stand-alone process occurring in a defined unit. However, patients with neurological conditions make up a large proportion of general medical admissions and GP consultations. They often present with an upper motor neurone syndrome that requires careful management of their weakness, disordered motor control, spasticity and bladder/bowel dysfunction. Spasticity management can be particularly challenging, but rewarding if physical and pharmacological measures are used appropriately and in a timely manner. This review attempts to explain the process of rehabilitation and how this can improve the care of neurological patients in all settings. Through the basic principles of rehabilitation – assessment, goal-setting, intervention and evaluation – function can be optimized while preventing complications and minimizing distress to patients, families and carers.

Increasing numbers of patients have an intrathecal baclofen pump implanted as part of spasticity management. Neurologists may be asked about the management of these devices when patients attend emergency departments for unrelated illnesses. Occasionally, the intrathecal baclofen system itself will directly lead to an acute presentation. Furthermore, the presence of an intrathecal baclofen pump needs consideration when requesting investigations, particularly MR imaging. This review aims to increase understanding of intrathecal baclofen treatment, highlighting serious complications and outlining considerations for routine investigations. Neurologists may still need advice from the intrathecal baclofen specialist team.

Objective: To develop an algorithm for the selection of adults with disabling spasticity for treatment with intrathecal baclofen (ITB) and/or botulinum toxin type A (BoNT A). Methods: A European Advisory Board of 4 neurologists and 4 rehabilitation specialists performed a literature review on ITB and BoNT A treatment for disabling spasticity. An online survey was sent to 125 physicians and 13 non-physician spasticity experts. Information on their current clinical practice and level of agreement on proposed selection criteria was used to inform algorithm design. Consensus was considered reached when ≥75% of respondents agreed or were neutral. Results: A total of 79 experts from 17 countries completed the on-line survey (57%). Agreement was reached that patients with multi-segmental or generalized disabling spasticity refractory to oral drugs are the best candidates for ITB (96.1% consensus), while those with focal/segmental disabling spasticity are ideal candidates for BoNT A (98.7% consensus). In addition the following are good candidates for ITB (% consensus): bilateral disabling spasticity affecting lower limbs only (97.4%), bilateral (100%) or unilateral (90.9%) disabling spasticity affecting lower limbs and trunk, and unilateral or bilateral disabling spasticity affecting upper and lower extremities (96.1%). Conclusion: This algorithm will support the management of adult patients with disabling spasticity by aiding patient selection for ITB and/or BoNT A treatments.

The objective of this study was to determine the impact on health-related quality of life of functional electrical stimulation used to improve walking in people with multiple sclerosis and to explore cost-effectiveness.A retrospective analysis of patient records was conducted.This study used outpatient therapy service as the study setting.Data from 82 consecutive patients with multiple sclerosis attending for set up with functional electrical stimulation were analysed.Patients were seen at baseline, three and six months for support in use of functional electrical stimulation, and data were collected at baseline and six months.The EQ-5D-5L and walking speed were collected at baseline and six months after using functional electrical stimulation. The Psychosocial Impact of Assistive Device Scale was collected at six months. EQ-5D-3L utilities were derived and cost-effectiveness analysis was completed utilizing a five-year time horizon and methodology published by National Institute for Health and Care Excellence.Significant differences (Functional electrical stimulation is a cost-effective treatment to improve walking speed and health-related quality of life in people with multiple sclerosis.

Evaluate long-term efficacy and safety of ITB in treating MS-related spasticity over ∼ 20 years of service provision in a single centre.A single centre prospective observational cohort study was performed. Eligible subjects underwent ITB trial by bolus dose via lumbar puncture and responders proceeded to pump implantation. Demographics, spasticity scores (Ashworth), spasm score (Penn), stiffness, pain and discomfort (Visual Analogue Scale), mobility (10 M walk), spasticity treatment, and ITB doses were analysed longitudinally.106 people were included with 568 patient years of data. Ashworth, Penn and VAS/NRS mean scores improved post-trial compared with baseline (p 0.001). Sustained efficacy was reported on Ashworth, Penn and VAS scores over time. After 1 year, 73 (69%) discontinued all oral antispasticity medications. Complication rates were low at 0.05 complications per pump year and mostly mechanical (usually catheter) related. In 8 ambulatory subjects, 7 (87%) continued to walk one year after pump insertion, 5 (62%) were still walking at time of analysis (mean follow up 3.4 years).ITB is an effective and safe long term treatment for refractory MS related spasticity. Efficacy was sustained over time and the majority of subjects subsequently discontinued systemic medications. In a small cohort, ability to walk was preserved, indicating ITB should be considered earlier in this cohort.

Objectives: To assess the feasibility of a multi-site randomised controlled trial to evaluate the effect of functional electrical stimulation on bradykinesia in people with Parkinson’s disease. Design: A two-arm assessor blinded randomised controlled trial with an 18 weeks intervention period and 4 weeks post-intervention follow-up. Setting: Two UK hospitals; a therapy outpatient department in a district general hospital and a specialist neuroscience centre. Participants: A total of 64 participants with idiopathic Parkinson’s disease and slow gait −1. Interventions: Functional electrical stimulation delivered to the common peroneal nerve while walking in addition to standard care compared with standard care alone. Main measures: Feasibility aims included the determination of sample size, recruitment and retention rates, acceptability of the protocol and confirmation of the primary outcome measure. The outcome measures were 10 m walking speed, Unified Parkinson’s Disease Rating Scale (UPDRS), Mini Balance Evaluation Systems Test, Parkinson’s Disease Questionnaire-39, EuroQol 5-dimension 5-level, New Freezing of Gait questionnaire, Falls Efficacy Score International and falls diary. Participants opinion on the study design and relevance of outcome measures were evaluated using an embedded qualitative study. Results: There was a mean difference between groups of 0.14 ms−1 (CI 0.03, 0.26) at week 18 in favour of the treatment group, which was maintained at week 22, 0.10 ms−1 (CI –0.05, 0.25). There was a mean difference in UPDRS motor examination score of –3.65 (CI –4.35, 0.54) at week 18 which was lost at week 22 –0.91 (CI –2.19, 2.26). Conclusion: The study design and intervention were feasible and supportive for a definitive trial. While both the study protocol and intervention were acceptable, recommendations for modifications are made.

BackgroundSpasticity is a common problematic symptom in Multiple Sclerosis with over one third of patients failing first line therapies. Intrathecal baclofen is a safe and efficacious option for treatment resistant spasticity. Anecdotally patients report improved concentration/cognitive performance when switching to intrathecal baclofen (ITB) from systemic medications.AimTo explore whether subjects who proceed with ITB pump implantation for spasticity management and reduce oral anti-spasticity agents will have improved cognitive function.MethodsSubjects were admitted for trial of ITB via lumbar puncture and subsequent pump implantation. Spasticity and cognitive measures before ITB trial and 3 months post implant were recorded. Paired t-test or Wilcoxon Signed Ranks test was used for within subject change and effect sizes (Cohen's dz) were calculated. Subgroup analysis of those on ≥2, or ≤ 1 spasticity medications at baseline was performed.Results27 subjects with MS completed per protocol. Mean age 46 years [26 – 56], disease duration 15 years [6 – 26], RRMS = 3, SPMS = 17 and PPMS=7. The majority were on multiple spasticity medications. Spasticity scores significantly improved post pump implant. Mean ITB dose at 3 months was 143 mcg / day and 19 discontinued all other treatments for spasticity. There was no deterioration on any cognitive or mood measure. An improvement of moderate effect size was found in Backwards Digit Span (d=0.41, p=0.059) and HADS – anxiety (d=0.37, p=0.097). Fatigue Severity Scale score decreased substantially (d=0.81, p=0.005). Small improvements in Symbol Digit Modalities Test score (d=0.24) and Sustained Attention to Response Task response time (d=0.23) were non-significant. Performance on other measures did not change. Effect sizes were larger in subgroup on ≥2 oral spasticity medications at baseline, compared to the group on ≤1 medication (SDMT, d=0.42 vs d=0.07; Backwards digit span 0.45 vs 0.28; HADS-anxiety 0.39 vs 0.32; HADS-depression d=0.32 vs 0.05 and FSS, d= 1.14 vs 0.42).ConclusionsIn a pilot study exploring the impact of ITB on cognition, spasticity scores improved universally and beneficial effects on some measures of fatigue, anxiety, auditory attention and verbal working memory were found. Improvement of speed of processing in those withdrawing higher doses of oral medication was also demonstrated suggesting that switching to ITB has added cognitive and psychological benefits for people with MS.

Objective: Functional electrical stimulation is used to improve walking speed and reduces falls in people with upper motor neurone foot-drop. Following anecdotal observations of changes in bladder symptoms, an observational study was performed to explore this association further. Design: A total of 47 consecutive patients attending for setup with functional electrical stimulation during a six-month period were asked to complete a questionnaire assessing bladder symptoms (ICIQ-OAB (International Consultation on Incontinence Questionnaire Overactive Bladder)) at baseline and three months during routine appointments. Subjects: In all, 35 (75%) had multiple sclerosis and the other 12 subjects had a total of 9 diagnoses including 3 with stroke. Other conditions included cerebral palsy, motor neurone disease, hereditary spastic paraparesis, meningioma and spinocerebellar ataxias. Results: Improvement in overactive bladder symptoms was not significant in the whole cohort, however, was significant in patients with multiple sclerosis ( n = 35; mean change in ICIQ-OAB score 1.0, P = 0.043). Specifically, significant improvements were seen in urgency and urge incontinence in multiple sclerosis patients. There was a significant negative correlation of moderate strength within the multiple sclerosis cohort between baseline walking speed and subsequent change in ICIQ-OAB score (correlation coefficient of r = −0.40, P = 0.046). Thus, greater changes in bladder symptoms were seen with lower baseline walking speeds. Conclusion: The results of this exploratory study suggest that functional electrical stimulation use does improve overactive bladder symptoms in people with multiple sclerosis. Further exploration is needed to study this association and explore whether the mechanism is similar to that of percutaneous tibial nerve stimulation, a recognized treatment for the overactive bladder.

Objectives Intrathecal baclofen (ITB) pumps are an effective treatment for spasticity; however infection rates have been reported in 3-26% of patients in the literature. The multidisciplinary ITB service has been established at The National Hospital for Neurology and Neurosurgery, UCLH, Queen Square, London for over 20 years. Our study was designed to clarify the rate of infection in our ITB patient cohort and secondly, to formulate and implement best practice guidelines and to determine prospectively, whether they effectively reduced infection rates. Methods Clinical record review of all patients receiving ITB pre-intervention; January 2013-May 2015, and following practice changes; June 2016-June 2018. Results Four of 118 patients receiving ITB during the first time period (3.4%, annual incidence rate of infection 1.4%) developed an ITB-related infection (three following ITB pump replacement surgery, one after initial implant). Infections were associated with 4.2% of ITB-related surgical procedures. Three of four pumps required explantation. Following change in practice (pre-operative chlorhexidine skin wash and intraoperative vancomycin wash of the fibrous pocket of the replacement site), only one of 160 ITB patients developed infection (pump not explanted) in the second time period (0.6%, annual incidence rate 0.3%). The infection rate related to ITB surgical procedures was 1.1%. In cases of ITB pump replacement, the infection rate was reduced to 3.3% from 17.6%. Conclusions This study suggests that a straightforward change in clinical practice may lower infection rates in patients undergoing ITB therapy.

Spasticity is a frequent and disabling symptom in people with Multiple Sclerosis (MS). Intrathecal baclofen (ITB) is an effective but infrequently used treatment in ambulant people.To evaluate the impact of ITB on ambulation in people with moderate to severe MS related spasticity.Data was collected prospectively regarding spasticity and ambulation at baseline, after ITB trial via lumbar puncture, 3 months and annually thereafter.30 subjects; Mean age 47.9 (26-64), 67% female, mean EDSS 6.5 [6.5-7.5]. Reduction in mean Ashworth score (pre 1.44: post 0.98, p0.001) and Penn spasm score (pre 3: post 1; p0.001) was shown. 20 people (67%) proceeded with implantation; lower limb MRC power was predictive of proceeding to pump (OR 2.98; 95% CI 1.01 - 8.7; p0.05). In those proceeding to implantation there was no difference in 10mTW at 1 year (ANOVA (F(3,24) = 2.6, p=0.13). Currently, 15 (75%) remain ambulatory (mean 3.75 years, range 1-9). After implant, 17 (85%) discontinued all oral anti-spasticity treatments conferring other benefits.Ambulation in people with MS can be preserved for several years whilst effectively treating spasticity with ITB with careful patient selection; ITB should not be considered a last resort.

© 2016 John Wiley & Sons, Ltd. This chapter addresses the nature of disability, how it can best be ameliorated, which training techniques and medical treatments are most effective, particularly after single incident brain injury, and the organisational structures required for their optimal delivery. A holistic biopsychosocial individualised multi-dimensional rehabilitation programme includes: reiterative multi-disciplinary assessment, problem definition and measurement, goal-setting and treatment planning, treatment delivery, evaluation of effectiveness, and reassessment with a view to further treatment. Non-invasive therapy interventions and task-related training in the context of neural damage are an integral part of the rehabilitation process after a neurological event, and aim to optimise a person's functional ability. Cardio-respiratory training and exercise classes may reverse the detraining effects of immobility and reduced activity seen in many chronic conditions. Symptoms related to neurological impairments caused by either single incident or chronic progressive conditions can cause distress and impact on function.

The main responsibilities of the physiotherapist as part of the multidisciplinary team (MDT) include assessing the individual’s spasticity before the planned trial, and recording a selection of baseline outcome measures and agreeing the main goal of treatment with the individual and MDT. This chapter presents the physiotherapy guidelines for intrathecal baclofen (ITB) therapy. For the pump implant, chest physiotherapy should be carried out prior to surgery. For pump replacement, the initial steps include assessing the individual’s spasticity pre-operatively and recording baseline outcome measures and agree the main goal of continuing treatment. It is standard practice at a pump refill appointment for the individual’s spasticity management to be reviewed, the ITB pump refilled and the ITB/oral medications reviewed. The physiotherapist should assess individuals with a new ITB pump 4–6 weeks post-operatively to review their tone, spasms, joint range, level of function and goal achievement.

Background People with Hereditary and Sporadic Spastic Parapresis (SP) walk with a stiff legged gait characterised by a lack of knee flexion. Objective We investigated the relationship between lower limb strength and stiffness and knee flexion during swing phase while walking in 20 people with SP and 18 matched controls. Methods Maximal isometric strength was measured using a dynamometer. Passive stiffness and spasticity was assessed during motor-driven slow (5°/s) and fast (60°/s) stretches at the ankle and knee while the subject was relaxed or preactivating the muscle. Walking was assessed using 3D motion analysis. Results Isometric muscle strength was decreased in people with SP with over a 50% reduction in strength being found in the ankle dorsiflexors. Passive stiffness, assessed during slow stretches, was 35% higher in the plantarflexors in people with SP (P 0.05). Lower knee flexion during swing phase was associated with reduced knee flexion velocity at the end of stance phase which in turn was associated with reduced plantarflexor strength and increased passive stiffness in the knee extensors. Conclusions The relative importance of muscle paresis and passive stiffness in limiting walking in SP suggests that these impairments should be the target of future therapies.

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is ‘The trainee consistently demonstrates a knowledge of the pathophysiology of various specific impairments including spasticity’. Spasticity is an extremely common feature of chronic neurological conditions and, if badly managed, it can result in pain, contractures and pressure sores, all of which can impact on function. It is therefore essential that a multidisciplinary management strategy is in place to help the individual manage their particular situation through education with timely access to interventions including instigation of a physical management programme and medication such as baclofen, tizanidine, dantrolene, benzodiazepines and gabapentin. Further treatment options for focal spasticity are botulinum toxin and phenol nerve blocks or intrathecal baclofen or phenol for predominant lower limb spasticity. Ongoing assessment with the use of appropriate outcome measures can both guide choice of treatment and monitor efficacy.

Objective Evaluate the efficacy of THC:CBD (Nabiximols) for resistant MS-related spasticity (MS-rs). Background Spasticity is a problematic symptom in MS. THC:CBD is a second line agent for MS-rs in people presenting side effects (SEs) or inadequate response to other treatments. Design/Methods Patients failing ≥2 treatments for spasticity were offered THC:CBD. Outcomes were measured at baseline. At 2 weeks telephone review was conducted and at 4 weeks face to face review.Responders continued medication for 3 months and were reviewed at 6 monthly intervals therafter. Spasticity Numerical Rating-Scale (NRS), Multiple Sclerosis Spasticity Scale-88 (MSSS-88), walking ability, concomitant medications and side effects (SE) were recorded. Clinical Responders (CR) were defined as having a≥20% reduction in NRS score, Non Responders (NR) were offered alternative options including Intrathecal Baclofen (ITB). Results 102 subjects were treated, 24 discontinued THC:CBD within 2 weeks, 78 attended 4 week review. 32%were CRs with improvement in NRS (p Conclusions THC:CBD provided symptomatic relief in a significant number of patients and can serve as alternative to ITB.

Objective: To assess the effect of intrathecal baclofen on spastic dysarthia in cerebral palsy. Design: Single case study. Methods: Functional outcome measures, including the Assessment of Intelligibility of Dysarthric Speech, were performed before and after a trial of intrathecal baclofen in an adult patient with spastic dysarthria due to cerebral palsy. The patient proceeded to intrathecal baclofen pump implantation and was reassessed after six months of continuous intrathecal baclofen therapy. Results: Improvement in function including speech intelligibility was seen following the intrathecal baclofen trial. The improvement was sustained at six months post pump implantation. Conclusions: Intrathecal baclofen improved functional intelligibility of speech in a carefully selected subject. The Assessment of Intelligibility of Dysarthric Speech was found to be a useful quantitative tool to assess the effect of intrathecal baclofen on spastic dysarthria.

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Objective To determine how postural sway is affected in people with spastic paraparesis (pwSP) and the impact of different impairments. Methods In 20 pwSP and 18 matched healthy controls standing postural sway was measured with eyes open and closed. Vibration threshold, isometric ankle and hip muscle strength and ankle stiffness with the participant at rest or preactivating the muscle was measured. Results Antero-posterior (AP) and medio-lateral (ML) sway was higher in pwSP. Muscle strength was reduced and ankle stiffness increased in pwSP. Increased vibratory threshold was seen in 35% of participants. Higher total ankle stiffness ( R 2 =0.44) was associated with lower AP sway with eyes open whilst hip abductor weakness was associated with increased ML sway with eyes open ( R 2 =0.36) or closed ( R 2 =0.47) or AP sway with the eyes closed ( R 2 =0.48). Conclusions The degree of postural sway was related to muscle paresis of the hip abductors particularly in the ML direction and under conditions of reduced sensory input. People with higher total ankle stiffness have less AP sway suggesting that this may help to stabilise the body.

Magnetic resonance imaging (MRI) has become an accepted tool for monitoring therapeutic trials in relapsing-remitting and secondary progressive multiple sclerosis (MS); it is however unclear whether such MRI markers are equally applicable to primary progressive MS (PPMS). Forty-two patients with PPMS were reviewed five years after commencing a two-year MRI and clinical study. Clinical measures recorded at baseline and five years included both the Expanded Disability Status Scale and the MS functional composite. MRI data collected at baseline and two years included T1 and T2 lesion loads, the number of new brain and cord lesions, and measures of both brain and cord atrophy. The study demonstrated that both the number of new T2 lesions and rate of increase in ventricular volume over two years were modestly predictive of subsequent disease progression and therefore may be useful tools in the testing of new therapeutic agents in PPMS.

Purpose: To evaluate the ability of a B-spline active surface technique to detect cervical spinal cord atrophy due to multiple sclerosis (MS) compared with intensity based contouring.Materials and Methods: In a previously reported study, the cervical spinal cords of 28 MS patients and 13 age-matched controls were imaged with a volume acquired inversion prepared fast spoiled gradient echo sequence at baseline and after one year. The images were reanalyzed using the B spline technique and the results compared with the results obtained in the original report using intensity based contouring.Results: The mean cervical spinal cord volume determined by the active surface programme was 6487 mm(3) in 28 patients compared with 7117 mm(3) in controls (P = 0.002, corrected for age and gender). The patients' cervical spinal cord volumes were associated with expanded disability status scale scores (parameter estimate = -1.21 x 10(-3), r(2) = 0.39, P = 0.001). The patients cervical spinal cord volumes did not decrease significantly over one year, unlike the mean cervical spinal cord areas at C2/3 calculated using intensity-based contouring.Conclusion: The active surface technique can detect cervical spinal cord atrophy due to MS, which has functional significance. However, this methodology is less sensitive at detecting small serial changes compared with the previously reported method.

Background: Spasticity is an extremely common, distressing and disabling symptom of multiple sclerosis. Limited data suggest the associated health care costs correlate with increasing severity and place a high economic burden on individuals, health care systems and society. Objective: The aim of this study was to quantify the impact of multiple sclerosis spasticity on health care resources and the associated costs at different levels of severity in people with multiple sclerosis in the United Kingdom. Methods: An online survey was carried out to understand the resources used in the management of spasticity in multiple sclerosis. The questionnaire asked health care specialists to estimate their involvement and the resource use associated with different levels of spasticity, and the survey outputs were used to derive the resource costs. Results: The level and cost of care substantially increased with the degree of spasticity. Key factors contributing to high annual costs per patient were home care, hospital admissions and high-cost items, such as hospital beds. Conclusions: Based on the survey results, it can be assumed that managing spasticity early and effectively could result in substantial cost savings, in addition to the improvements in health-related quality of life.

Objective: Patients with nontraumatic spinal cord lesions account for between one fourth and one half of all spinal cord injuries. In the management of this group of patients, an understanding of factors influencing functional improvement is essen tial to help define the most appropriate rehabilitation programme. Although it is pos sible to predict accurately the functional outcome for an individual patient with a com plete traumatic spinal cord injury, few studies have looked at prognostic factors in patients with nontraumatic spinal cord disease. The aim of this study was to determine which, and how well, factors assessed on admission to a rehabilitation unit relate to functional improvement in this group. Methods: The study sample consists of 100 patients with an incomplete nontraumatic spinal cord lesion who underwent inpatient neurorehabilitation. Possible prognostic factors were sought by identifying those vari ables with a significant difference in the Functional Independence Measure (FIM) motor change score above and below the median. A step-wise multiple regression analysis was then performed to determine which variables influenced functional out come. Results: Patients with larger functional gains had significantly lower disability scores on admission, a shorter time between symptom onset and rehabilitation, and a longer length of stay. They were more likely to have a cervical lesion and evidence of neurologic recovery. Multiple regression analysis demonstrated that the FIM motor score on admission and the time between symptom onset and rehabilitation predicted 54% of the variance of the FIM motor score gain. Conclusions: This finding suggests that early rehabilitation is an important factor in securing a good outcome. Key Words: Rehabilitation-Spinal cord lesion-Functional outcome.

Acanthocytosis occurs because of ultrastructural abnormalities of the erythrocyte membranous skeleton resulting in reduced membrane fluidity. At least three hereditary neurological conditions are associated with it, although as yet the pathogenesis of the neurological features is unknown. In abetalipoproteinaemia, an autosomal recessive condition, vitamin E deficiency results in a progressive spinocerebellar syndrome associated with peripheral neuropathy and retinitis pigmentosa. Neuroacanthocytosis is also probably an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysarthria, areflexia, seizures and dementia. McLeod syndrome is an X-linked recessive disorder usually presenting in males as a benign myopathy with areflexia, in association with a particular abnormality of expression of Kell blood group antigens. However, occasionally the neurological features are more severe and indistinguishable from those of neuroacanthocytosis. Recent advances in molecular genetics may assist better understanding of the disease mechanisms and the search for more effective treatments.

Introduction: Visual loss or papilloedema has been linked to hypocalcaemia for many years. The pathogenesis is unclear, although raised intracranial pressure has often been implicated. Case report: We report a 36-year-old gentleman with hypocalcaemia secondary to pseudohypoparathyroidism presenting as bilateral sequential (five years apart) severe visual loss with normal cerebrospinal fluid pressure. Conclusions: The most likely cause is sequential anterior ischaemic optic neuropathies (AION), perhaps precipitated by hypocalcaemia. Despite the fact that this may be a chance association, we feel it is justified for all patients with AION to undergo a metabolic screen, including serum calcium level, in order to exclude a treatable cause and prevent subsequent AION in the unaffected eye.

Objective: To investigate the variation in T1 and T2 relaxation times of normal appearing white matter (NAWM) and lesions in multiple sclerosis (MS) throughout the brain. Background: The magnetic resonance imaging (MRI) sequence fast FLAIR (fluid attenuated inversion recovery) has demonstrated overall increased lesion detection when compared to conventional or fast spin echo (FSE) but fewer lesions in the posterior fossa and spinal cord. The reasons for this are unknown, but may be due to variations in the T1 and T2 relaxation times within NAWM and MS lesions. Method: Ten patients and 10 controls underwent MRI of the brain which involved FSE, fast FLAIR and the measurement of T1 and T2 relaxation times. Results: Of 151 lesions analysed (22 infra-tentorial, 129 supra-tentorial), eight were missed by the fast FLAIR sequence. T1 and T2 relaxation times in normal controls were longer in the infra-tentorial, than supra-tentorial, region. Patient NAWM relaxation times were prolonged compared with control values in both regions. Lesions demonstrated longer relaxation times than either control white matter or patient NAWM in both regions, however this difference was less marked infra-tentorially. The eight posterior fossa lesions not visible on the fast FLAIR sequence were characterised by short T1 and T2 relaxation times which overlapped with the patient NAWM for both T1 and T2 and with control values for T2 relaxation times. Conclusion: Both lesion and NAWM relaxation time characteristics vary throughout the brain. The T1 and T2 relaxation times of infra-tentorial lesions are closer to the relaxation times of local NAWM than supra-tentorial lesions, resulting in reduced contrast between posterior fossa lesions and the background NAWM. Consequently the characteristics of some lesions overlap with those of NAWM resulting in reduced conspicuity. By utilising this information, it may be possible to optimise fast FLAIR sequences to improve infra-tentorial lesion detection.

The unique clinical characteristics of primary progressive multiple sclerosis (PPMS) pose particular diagnostic difficulties, both in excluding other causes of progressive syndromes and in confirming the diagnosis of MS, which is not adequately addressed by current diagnostic criteria. This article presents new diagnostic criteria developed by a group of investigators on the basis of a review of their considerable experience with PPMS. (We conclude that at least 1 year of clinical progression must be documented before a diagnosis of PPMS is made.) Three levels of diagnostic certainty have been defined-definite, probable, and possible--based on clinical findings, abnormal cerebrospinal fluid, abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord, and evoked potentials. In definite PPMS, evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is required: (1) nine brain lesions, (2) two spinal cord lesions, or (3) four to eight brain lesions and one spinal cord lesion. Preliminary testing of these criteria was carried out on a cohort of 156 patients participating in a European natural history study of PPMS: 64% fulfilled the criteria for definite PPMS, 35% for probable PPMS, and only 1% for possible PPMS. These criteria now require prospective validation in a cohort of newly diagnosed patients and by postmortem examination.

Objective: To assess the potential of registered volumetric MRI in measuring rates of atrophy in MS. Background: Pathologic and imaging studies suggest that the development of permanent neurologic impairment in MS is associated with progressive brain and spinal cord atrophy. Atrophy has been suggested as a potential marker of disease progression. Conventional atrophy measurements requiring manual outlining are time-consuming and subject to reproducibility problems. Registration of serial MRI may offer a useful alternative in that cerebral losses may be measured directly from automated subtraction of brain volumes. Methods: Twenty-six patients with MS and 26 age- and gender-matched controls had two volumetric brain MR studies 1 year apart. Baseline brain and ventricular volumes were measured using semiautomated techniques, and follow-up scans were registered to baseline. Rates of cerebral atrophy were calculated directly from the registered scans. Results: Baseline brain volumes in the MS group were smaller (mean difference 78 mL [95% CI 13 to 143; p = 0.02]) and ventricular volumes greater (mean difference 12 mL [95% CI 6 to 18; p < 0.001]) than controls. The rate of cerebral atrophy in the MS group (0.8% per year) was over twice that of controls (0.3%), and the rate of ventricular enlargement was five times greater than the controls (1.6 versus 0.3 mL/year). Conclusion: Progressive cerebral atrophy is an important feature of MS. Registration-based measurements are sensitive and reproducible, allowing progressive atrophy to be detected within 1 year and may have potential as a marker of progression in monitoring therapeutic trials.

Patients with primary progressive multiple sclerosis have atypical clinical and magnetic resonance imaging (MRI) characteristics which present unique problems in designing and recruiting to therapeutic trials. The first randomised controlled therapeutic trial specifically for primary progressive multiple sclerosis is now underway. Although only an exploratory phase II study, it has provided further insight into difficulties in diagnosis, classification and choice of clinical and MRI outcome measures. Patients with primary progressive multiple sclerosis have a wide differential diagnosis and do not readily conform to the Poser criteria. They may therefore present diagnostic uncertainty, particularly as their classification often relies on a retrospective history. This was highlighted during the recruitment to this study of interferon-beta1a. Of the 138 patients referred with a definite diagnosis of primary progressive multiple sclerosis only 50 were enrolled in the study. Of the 88 patients not included, 50% either did not have primary progressive multiple sclerosis, or the diagnosis was not secure. Outcome measures pose particular problems. Clinically the focus must be on progression, and the measure should be both responsive and reliable. In relation to MRI, the currently recommended measures for therapeutic trials in relapsing/remitting and secondary progressive multiple sclerosis show little change in primary progressive multiple sclerosis, and therefore more pathologically specific MRI measures are required. Strict clinical guidelines and further developments in clinical and MRI measures are required to facilitate future therapeutic trials in primary progressive multiple sclerosis.

A sensitive magnetic resonance imaging (MRI) method to measure spinal cord cross-sectional area with the potential to monitor disease progression has recently been developed. As changes in cord area due to disease are usually small, assessment of the reliability of the methodology is essential in serial studies of spinal cord atrophy. The aim of this study was to institute and evaluate a protocol of quality assurance to determine long-term reproducibility of serial studies. Serial MRI of the spinal cord was carried out in five healthy volunteer controls over 1 year. Cross-sectional spinal cord areas were measured in a total of 46 scans. The mean coefficient of variation of all subjects over one year was 1.35%. The intra-observer coefficient of variation for same scan analysis was 0.63%. This study has confirmed high reliability of our serial data over one year and the on-going quality assurance protocol enables continuing evaluation of the reproducibility of results in serial studies. Quality assurance is an essential and practical component of all serial MRI studies, without which the clinical implications of change cannot be reliably evaluated.

Recent reports have suggested that fluid attenuated inversion recovery (FLAIR) is a technique superior to conventional (CSE) or fast spin echo (FSE) T2-weighted sequences in detecting intrinsic lesions both in the brain and spinal cord. We report our experience of an inversion recovery prepared FSE, which we refer to as fast FLAIR, in a comparative study of ten patients with clinically definite multiple sclerosis (MS) who underwent cervical cord and brain imaging with both FSE and fast FLAIR. The results showed that in the cerebral hemispheres fast FLAIR detected more lesions than FSE (P < 0.001). However, FSE detected more lesions than fast FLAIR in the posterior fossa (P = 0.02) and in the cord fast FLAIR was much inferior detecting only 2 of 33 lesions seen on FSE. Estimating the T2 relaxation times of lesions in each of three areas (periventricular, posterior fossa, cervical cord) showed that the T2 value of posterior fossa and cervical cord lesions was significantly lower than that of periventricular lesions, suggesting that the lesion composition is different and consequently their imaging appearances are different. In conclusion, although fast FLAIR improves the detection of MS lesions in the cerebral hemispheres, its substantially lower sensitivity in the posterior fossa and spinal cord is a potentially important limitation to its use as a tool for the diagnosis of MS and for monitoring therapies. Further studies are needed to elucidate the mechanisms underlying the loss of sensitivity.

Objectives: To investigate in people with spastic paraparesis (SP): 1) the factors contributing to foot drop and reduced toe clearance while walking; 2) short-term effects of bilateral functional electrical stimulation (FES) of the common peroneal nerve. Materials and Methods: Long term (>0.5 years) users of FES with SP were compared to matched controls (N = 11 per group). Ankle strength and plantarflexor stiffness and walking kinematics were objectively recorded. The effects of FES on: 1) perceived efficacy; 2) muscle torque and ankle motion; 3) clinical outcome measures and walking kinematics were assessed. Results were compared using an analysis of covariance. Results: Ankle weakness and stiffness is higher among people with SP. Higher plantarflexor stiffness is associated with reduced swing phase dorsiflexion; higher toe clearance while walking is associated with increased hip flexion. FES increases dorsiflexor torque, improves toe clearance and dorsiflexion in swing phase, and significantly improves walking speed (p < 0.05). Conclusions: There are multiple causes of tripping in people with SP; FES reduces foot drop and improves walking speed.

The majority of patients with multiple sclerosis (MS) have symptoms of spasticity that increasingly impair function as the disease progresses. With appropriate treatment, however, quality of life can be improved. Oral antispasticity medications are useful in managing mild spasticity but are frequently ineffective in controlling moderate to severe spasticity, because patients often cannot tolerate the adverse effects of increasing doses. Intrathecal baclofen (ITB) therapy can be an effective alternative to oral medications in patients who have a suboptimal response to oral medications or who cannot tolerate dose escalation or multidrug oral regimens. ITB therapy may be underutilized in the MS population because clinicians (a) are more focused on disease-modifying therapies rather than symptom control, (b) underestimate the impact of spasticity on quality of life, and (c) have concerns about the cost and safety of ITB therapy. Delivery of ITB therapy requires expertly trained staff and proper facilities for pump management. This article summarizes the findings and recommendations of an expert panel on the use of ITB therapy in the MS population and the role of the physician and comprehensive care team in patient selection, screening, and management.

While there are many opportunities for the prevention or reversal of disease, health care systems worldwide are dominated by people with chronic diseases and conditions. In the USA for example, patients with chronic conditions account for nearly 80% of health care costs. In the UK, neurological damage accounts for 40% of people severely disabled and who require daily help, and for most of those with complex disabilities resulting from a combination of physical, cognitive and behavioural problems. Any health care system is thus confronted on a daily basis with a demand to meet this need from fi nite resources.

Sibling concurrence of pathologically confirmed prion disease has only been reported in association with pathogenic mutation of the prion protein gene (PRNP). Here, we report 2 siblings with classic neuropathologic features of sporadic Creutzfeldt-Jakob disease unexplained by PRNP mutation or known risk factors for iatrogenic transmission of prion infection. Possible explanations include coincidental occurrence, common exposure to an unidentified environmental source of prions, horizontal transmission of disease, or the presence of unknown shared genetic predisposition.

Intrathecal baclofen is a GABA-receptor agonist and one of the mainstay treatments of severe spasticity due to multiple sclerosis (MS). The authors report a case on the use of intrathecal baclofen administered using a Medtronic Synchromed II infusion pump. A healthy male infant (2.68 kg, Apgars 9 and 10) was born at 36 weeks gestation by cesarean section, under general anesthetic. This is the fifth reported case of intrathecal baclofen administered during pregnancy and adds to the knowledge that thus far it is relatively safe in pregnancy and may in fact be safer for the infant than oral baclofen. This is the first case report of the use of intrathecal baclofen in pregnancy and MS.