Search

A 74-year-old farmer presented to the emergency department with a subacute history of progressive dyspnoea, wheeze and dysphonia. He was treated for an exacerbation of asthma with poor response to pharmacological therapy. Investigation of dysphonia via laryngoscopy identified a bilateral vocal cord palsy. Subsequently, the patient developed an episode of life-threatening stridor and hypercapnic respiratory failure requiring an emergency tracheostomy. Neurology input identified evidence of widespread muscle fasciculations on clinical examination. MRI of the brain and cervical spine were unremarkable. Electromyogram testing identified changes of acute denervation in several limbs consistent with a diagnosis of motor neuron disease (MND). Bilateral vocal cord palsy has been rarely reported in the literature as the heralding symptom resulting in the diagnosis of MND. In patients with a subacute onset of dysphonia, dyspnoea and stridor, MND should be a differential diagnosis.

Due to possible sensory impairments in people with Parkinson's disease, several methodological aspects of electrical stimulation as a potential cueing method remain to be explored. This study aimed to investigate the applicability and tolerability of sensory and motor electrical stimulation in 10 people with Parkinson's disease. The study focused on assessing the electrical stimulation voltages and visual analogue scale discomfort scores at the electrical sensory, motor, discomfort, and pain thresholds. Results show that sensory electrical stimulation at the tibialis anterior, soleus, hamstrings, and quadriceps stimulation sites was applicable and tolerable for 6/10, 10/10, 9/10, and 10/10 participants, respectively. Furthermore, motor electrical stimulation at the tibialis anterior, soleus, hamstrings, and quadriceps stimulation sites were applicable and tolerable for 7/10, 7/10, 7/10, and 8/10 participants, respectively. Interestingly, the thresholds for the lower leg were higher than those of the upper leg. The data presented in this paper indicate that sensory and motor electrical stimulation is applicable and tolerable for cueing applications in people with Parkinson's disease. Sensory electrical stimulation was applicable and tolerable at the soleus and quadriceps sites. Motor electrical stimulation was not tolerable for two participants at any of the proposed stimulation sites. Therefore, future studies investigating motor electrical stimulation cueing, should apply it with caution in people with Parkinson's disease.

Immune checkpoint inhibitors have transformed the treatment of advanced malignancy, while increasing the risk of immune-related adverse events. A 56-year-old woman who had received nivolumab for stage 4 renal cell carcinoma subsequently developed altered behaviour, memory deficits and worsening of previously stable epilepsy. MR scan of the brain showed bilateral FLAIR (fluid-attenuated inversion recovery) hyperintensity of the mesial temporal lobes, and there were anti-Ma2 antibodies in both serum and cerebrospinal fluid. She was treated with corticosteroids but developed further clinical relapses requiring immunoglobulin and rituximab. The immune-related adverse events relating to immune checkpoint inhibitors are an emerging challenge for the neurologist. Some cases are refractory and require serial immunosuppression.

Our research team previously developed an accelerometry-based device, which can be worn on the waist during daily life activities and detects the occurrence of dyskinesia in patients with Parkinson’s disease. The goal of this study was to analyze the magnitude of correlation between the numeric output of the device algorithm and the results of the Unified Dyskinesia Rating Scale (UDysRS), administered by a physician. In this study, 13 Parkinson’s patients, who were symptomatic with dyskinesias, were monitored with the device at home, for an average period of 30 minutes, while performing normal daily life activities. Each patient’s activity was simultaneously video-recorded. A physician was in charge of reviewing the recorded videos and determining the severity of dyskinesia through the UDysRS for every patient. The sensor device yielded only one value for dyskinesia severity, which was calculated by averaging the recorded device readings. Correlation between the results of physician’s assessment and the sensor output was analyzed with the Spearman’s correlation coefficient. The correlation coefficient between the sensor output and UDysRS result was 0.70 (CI 95%: 0.33–0.88; p = 0.01). Since the sensor was located on the waist, the correlation between the sensor output and the results of the trunk and legs scale sub-items was calculated: 0.91 (CI 95% 0.76–0.97: p

The cause of progressive disability in Primary Progressive Multiple Sclerosis (PPMS) is unknown. Pathogenic genes have been described in some MS cases that may contribute to progressive disability, independent of immune – mediated mechanisms ( Jia et al., 2018 ). The autosomal dominant SPG4 (Spastin) mutation is the most common genotype in Hereditary Spastic Paraplegia ( Solowska and Baas, 2015 ) and has been found in some patients with Relapsing Remitting Multiple Sclerosis ( Mead et al., 2001 , Yazici et al., 2013 ). Here, we describe the novel association of PPMS and the SPG4 (Spastin) mutation, in a patient with a family history of Hereditary Spastic Paraplegia, and discuss the therapeutic implications. While this single case report cannot discrimiate between simple co-occurence and the possibility of a pathogenic association, our report invites larger scale investigation.

Background Cognitive difficulties experienced by people with multiple sclerosis (MS) impact their quality of life and daily functioning, from childcare and work, to social and self-care activities. Despite the high prevalence of cognitive difficulties seen in MS, there is a lack of developed programmes that target cognition, while also supporting patients by helping them to function well in everyday life. The Cognitive Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention. It addresses the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the current research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS. The focus is on feasibility outcomes as well as functioning associated with cognitive difficulty and secondary outcomes related to cognition, fatigue and quality of life. Methods One hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment as usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The primary outcome measure is the goal attainment scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention and at 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants’ perspectives will also be examined as part of the feasibility study. Discussion Results will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. In the event that results indicate efficacy, study findings will suggest that COB-MS requires consideration as a means of enhancing cognitive and daily functioning in people living with MS. Trial registration ISRCTN: ISRCTN11462710. Registered on 9 September 2019.

The aim of this service evaluation study was to establish the extent of concordance in decision-making between the senior attending neurologist and the advanced nurse practitioner (ANP) in neurology, regarding identification and management of 15 participants with multiple sclerosis and reporting potential new/escalating neurological symptoms via the ANP telephone support service. Results showed 100% agreement between neurologist and ANP regarding whether to manage patient concerns via telephone or in the outpatient clinic. In the patients seen in clinic, no inconsistencies were noted in neurological findings recorded by both clinicians. Diagnostic concordance was 93.4%, with 80% management concordance between the ANP and neurologist. There was 100% agreement between the ANP and neurologist regarding the need for treatment escalation. The analysis of this study suggests that diagnostic and management decision-making provided by the ANP for patients with potential relapses and/or treatment escalation is on a par with that of the neurologist, which is the traditional model of care. Our findings support the increasing role of the ANP in the active and independent care of patients with MS.

More et al.1 are to be applauded for their article in this issue of Neurology: Clinical Practice on disaster neurology and its relevance to the on-going coronavirus disease 2019 (COVID-19) pandemic. At first glance, the relationship between this pandemic and a natural disaster is not obvious. However, as countries struggle with limitations in medical resources and having to make difficult decisions about who should have priority in receiving medical care or vaccines as they become available, the skills needed to provide care in an austere environment become clear. In addition, as medical professionals who are experts in hospitalist and intensive care unit medicine become overstretched, it is natural that neurologists and neurology providers, who at least understand medical care and have been exposed to internal medicine at some point during training, will naturally become called on to help take care of patients with COVID-19. For example, during the spring surge of cases which overwhelmed hospitals in New York City, the US military responded, recalling to duty many reserve physicians, nurses, and other healthcare providers and assigning them to support civilian healthcare operations. Neurologists, pathologists, pediatricians, and other specialists suddenly found themselves receiving on-the-job training to manage critically ill COVID patients.

Neuropsychiatric signs and symptoms occur frequently in individuals with multiple sclerosis (MS), either as the initial presenting complaint prior to a definitive neurological diagnosis or more commonly with disease progression. However, the pathogenesis of these comorbid conditions remains unclear and it remains difficult to accurately elucidate if neuropsychiatric symptoms or conditions are indicators of MS illness severity. Furthermore, both the disease process and the treatments of MS can adversely impact an individual's mental health. In this review, we discuss the common neuropsychiatric syndromes that occur in MS and describe the clinical symptoms, aetiology, neuroimaging findings and management strategies for these conditions.

Although the hypothesis that an underlying defect in somatosensory processing could facilitate a quintessentially motor phenomenon such as dystonia initially sounded counterintuitive or too speculative to many, there is now a substantial body of evidence pointing to altered proprioceptive or tactile sensory processing and sensory-motor integration as central to the pathophysiology of dystonia.1,2 The involvement of sensory-motor integration in the basic mechanisms of dystonia is clearly evoked by clinical features such as the geste antagoniste (also known as sensory trick) that our patients with cervical or cranial dystonia deploy regularly. The fact that the geste antagoniste, which in most cases is the combination of an active movement and tactile or proprioceptive stimulation provoked or facilitated by the same movement, is probably the most efficient, even if strikingly transient, remedy to counteract dystonia speaks in favor of the centrality of sensory-motor integration in the pathophysiology of dystonia. An essential component of motor control is the ability to sense the position (proprioception) and movement (kinesthesia) of our body.

We report a case of severe amnestic syndrome following theophylline overdose. A woman in her early 30s was admitted to hospital where she developed status epilepticus following an intentional overdose of theophylline and lansoprazole. She developed a profound acidosis and required intubation in the intensive care unit. Following extubation the patient was noted to have a severe amnestic syndrome with poor short-term memory. A work-up to exclude infectious, autoimmune and paraneoplastic causes for encephalitis was undertaken. Cerebrospinal fluid analysis was normal and autoimmune encephalitis titres were negative. Initial MRI brain imaging demonstrated hyperintensities of the mesial temporal lobes bilaterally. Follow-up imaging at 4 months identified further interval reduction but persistent hippocampal hyperintensities. Theophylline toxicity with corresponding amnestic syndrome and hippocampal hyperintensities has been rarely reported. We believe this case with persistent abnormal Montreal Cognitive Assessment Score at 12 months correlates with persistent hippocampal abnormalities seen on imaging.

Registrar: ‘Hello, am I speaking with the consultant neurologist on-call?’ Consultant: ‘Regrettably! Yes that’s me. What is it?’ R : ‘Hi this is Dr Richter, medical reg. on call. Sorry to disturb you so late, but we’ve got a FAST1 positive in A&E.’ C : ‘A what?’ R : ‘A FAST-positive patient.’ C : ‘I assume that’s worse than a FAST-negative patient then. Go on.’ R : ‘Well the NIHSS2 is 24 but her GCS3 4 is 12 currently. Before we got the CT, I was worried about a subarachnoid, because her Hunt & Hess5 was 4.’ C : ‘Gosh.’ R : ‘But thankfully the CT showed no bleed, but the ASPECTS6 was 6.’ C : ‘Six, did you say? That doesn’t sound too bad. At least it’s not 10 or something.’ R : ‘Actually 10 is a normal score. You really don’t want an ASPECTS lower than 6.’ C : ‘I see. So what are you recommending to do?’ R : ‘Well, time is brain, Professor, and I think it would be good to keep our door-to-needle stats …

Among Parkinson’s disease (PD) motor symptoms, freezing of gait (FOG) may be the most incapacitating. FOG episodes may result in falls and reduce patients’ quality of life. Accurate assessment of FOG would provide objective information to neurologists about the patient’s condition and the symptom’s characteristics, while it could enable non-pharmacologic support based on rhythmic cues. This paper is, to the best of our knowledge, the first study to propose a deep learning method for detecting FOG episodes in PD patients. This model is trained using a novel spectral data representation strategy which considers information from both the previous and current signal windows. Our approach was evaluated using data collected by a waist-placed inertial measurement unit from 21 PD patients who manifested FOG episodes. These data were also employed to reproduce the state-of-the-art methodologies, which served to perform a comparative study to our FOG monitoring system. The results of this study demonstrate that our approach successfully outperforms the state-of-the-art methods for automatic FOG detection. Precisely, the deep learning model achieved 90% for the geometric mean between sensitivity and specificity, whereas the state-of-the-art methods were unable to surpass the 83% for the same metric.

Several factors are thought to contribute to inadequate seizure control in patients with juvenile myoclonic epilepsy (JME), including drug resistance, neuropsychiatric comorbidity, and poor lifestyle choices. Recent evidence supports the existence of frontal lobe microstructural deficits and behavioral changes that may contribute to poor seizure control in a minority of patients. Counseling patients on the importance of adequate sleep hygiene and alcohol restriction is an important part of the management strategy for patients with JME. However, information is lacking on how these lifestyle restrictions impact on patients with JME. We conducted a qualitative descriptive analysis of the social impact of JME on 12 patients, from their own perspective. We identified four prominent themes: the importance of alcohol use as a social “norm”, how JME affected relationships, decision making (risk versus consequences), and knowledge imparting control. Given that these restrictions were interpreted by patients as social “curfews”, we suggest that the term “Cinderella Syndrome” encapsulates the perceived imperative to be home before midnight. Our findings underscore the importance for clinicians to recognize that in counseling patients with JME about lifestyle adjustments, there may be a significant social consequence unique to this patient group.

A 13-year-old girl presented with a 4-year history of abnormal gait. At age 9, her parents noticed that she would run awkwardly “on the balls of her feet” and subsequently, that the rhythm of her running would break down with sustained exercise. There was no diurnal variation in her symptoms. There was no history of perinatal insults and early development was normal. There was no significant medical or psychiatric comorbidity and her family history was unremarkable. Examination of the patient's gait is demonstrated in video 1 at [Neurology.org][1]. The authors thank the patient and her parents for agreeing to this case presentation. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000004231

Background The term “Clinically Isolated Syndrome” (CIS) was introduced to describe a first clinical neurologic episode suggestive of an inflammatory demyelinating CNS disorder. Thereafter, the risk of developing clinically definite multiple sclerosis ranges from 20% to 80%, depending on a number of prognostic factors. Although the concept of CIS has been an important component in improving our understanding of risk levels in Multiple Sclerosis and prognosis, communicating uncertainty in this context remains a challenge for both patients and their clinicians. We therefore wished to explore both the patients understanding of the concept of CIS and the subsequent impact of a diagnosis. We also explored the concept of CIS from the clinician's perspective. Methods The study uses a qualitative descriptive design involving both a semi-structured interview of patients with CIS as well as a short questionnaire sent to practising clinicians in the Republic of Ireland. Narrative data was coded onto themes. Results Thirty CIS patients were interviewed. The majority of patients understood the term “CIS” but not the link between CIS and MS. Two themes were identified: emotional reactions following CIS diagnosis; and terminology and communication. Confusion and anxiety among patients due to inconsistent communication of CIS was identified. Of the thirty-three clinicians surveyed, only thirty-nine per cent found the term “CIS” clinically useful. Eighteen per cent of clinicians diagnosed MS from the CIS case vignette provided. Conclusion In the diagnosis of a first demyelinating event, use of the term “CIS” is confusing to patients and inconsistent among clinicians. We suggest that the term “CIS” be abandoned in favour of terminology that reflects both its pathogenesis and inherent risk of subsequent MS.

Among Parkinson's disease (PD) symptoms, freezing of gait (FoG) is one of the most debilitating. To assess FoG, current clinical practice mostly employs repeated evaluations over weeks and months based on questionnaires, which may not accurately map the severity of this symptom. The use of a non-invasive system to monitor the activities of daily living (ADL) and the PD symptoms experienced by patients throughout the day could provide a more accurate and objective evaluation of FoG in order to better understand the evolution of the disease and allow for a more informed decision-making process in making adjustments to the patient's treatment plan. This paper presents a new algorithm to detect FoG with a machine learning approach based on Support Vector Machines (SVM) and a single tri-axial accelerometer worn at the waist. The method is evaluated through the acceleration signals in an outpatient setting gathered from 21 PD patients at their home and evaluated under two different conditions: first, a generic model is tested by using a leave-one-out approach and, second, a personalised model that also uses part of the dataset from each patient. Results show a significant improvement in the accuracy of the personalised model compared to the generic model, showing enhancement in the specificity and sensitivity geometric mean (GM) of 7.2%. Furthermore, the SVM approach adopted has been compared to the most comprehensive FoG detection method currently in use (referred to as MBFA in this paper). Results of our novel generic method provide an enhancement of 11.2% in the GM compared to the MBFA generic model and, in the case of the personalised model, a 10% of improvement with respect to the MBFA personalised model. Thus, our results show that a machine learning approach can be used to monitor FoG during the daily life of PD patients and, furthermore, personalised models for FoG detection can be used to improve monitoring accuracy. Part of this project has been performed within the framework of the MASPARK project which is funded by La Fundació La Marató de TV3 20140431. This work also forms part of the framework of the FP7 project REMPARK ICT-287677, which is funded by the European Community. peer-reviewed

To extend our studies on glycolipid-reactive invariant Natural Killer T-cell (iNKT-cell) function in multiple sclerosis (MS), we investigated the stimulatory activities of two myelin-derived glycolipids that are poly-acetylated derivatives of β-galactosylceramide designated as fast-migrating cerebrosides (FMC) by thin-layer chromatography. In healthy subjects, FMC stimulation of peripheral blood cells significantly expanded iNKT-cells similar to α-GalCer and induced significant increases in Th1, Th2 and Th17 cytokines. In marked contrast, MS patients failed to respond to FMCs or to α-GalCer stimulation indicating an anergic response. We propose that myelin-derived FMC glycolipids stimulate iNKT-cell responses in vivo and this is blocked in MS.

A 38-year-old right-handed man was referred for investigation of a 20-year history of progressive behavior change and involuntary movements. Symptom onset was in his late teens. Up until that time he had achieved age-appropriate motor and cognitive milestones and had completed normal schooling. There was no family history of dementia or movement disorders.

HighlightsThe necessary algorithms to evaluate the occurrence of dopaminergic-induced dyskinesias in the activities of daily life are developed.Sensor placement at the waist provides a good resolution for almost any choreic dyskinesias and provides a good usability and comfort to the patient.A new frequency based approach is proposed to evaluate the occurrence of dyskinesias.The algorithm presented has been evaluated on a database of signals of 92 PD patients and provides specificities and sensitivities above 90%. BackgroundAfter several years of treatment, patients with Parkinson's disease (PD) tend to have, as a side effect of the medication, dyskinesias. Close monitoring may benefit patients by enabling doctors to tailor a personalised medication regimen. Moreover, dyskinesia monitoring can help neurologists make more informed decisions in patient's care. ObjectiveTo design and validate an algorithm able to be embedded into a system that PD patients could wear during their activities of daily living with the purpose of registering the occurrence of dyskinesia in real conditions. Materials and methodsData from an accelerometer positioned in the waist are collected at the patient's home and are annotated by experienced clinicians. Data collection is divided into two parts: a main database gathered from 92 patients used to partially train and to evaluate the algorithms based on a leave-one-out approach and, on the other hand, a second database from 10 patients which have been used to also train a part of the detection algorithm. ResultsResults show that, depending on the severity and location of dyskinesia, specificities and sensitivities higher than 90% are achieved using a leave-one-out methodology. Although mild dyskinesias presented on the limbs are detected with 95% specificity and 39% sensitivity, the most important types of dyskinesia (any strong dyskinesia and trunk mild dyskinesia) are assessed with 95% specificity and 93% sensitivity. ConclusionThe presented algorithmic method and wearable device have been successfully validated in monitoring the occurrence of strong dyskinesias and mild trunk dyskinesias during activities of daily living.

Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56-year-old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that perineuritis forms part of the pathogenesis in acute Lyme neuroborreliosis.

We describe a case of a 45-year-old man who presented with a transient syndrome consisting of headache with neurological deficits. Neuroimaging including brain angiography was normal. Cerebrospinal fluid (CSF) analysis revealed an elevated protein and lymphocytic pleocytosis. The diagnosis of a syndrome of Headache and Neurological Deficits with CSF Lymphocytosis (HaNDL) was made after excluding all the other possible causes for the patient's presentation. He made an excellent recovery following a short course of naproxen sodium.

Gómez-Herreros, Fernando et al., Topoisomerase II (TOP2) removes torsional stress from DNA and facilitates gene transcription by introducing transient DNA double-strand breaks (DSBs). Such DSBs are normally rejoined by TOP2 but on occasion can become abortive and remain unsealed. Here we identify homozygous mutations in the TDP2 gene encoding tyrosyl DNA phosphodiesterase-2, an enzyme that repairs 'abortive' TOP2-induced DSBs, in individuals with intellectual disability, seizures and ataxia. We show that cells from affected individuals are hypersensitive to TOP2-induced DSBs and that loss of TDP2 inhibits TOP2-dependent gene transcription in cultured human cells and in mouse post-mitotic neurons following abortive TOP2 activity. Notably, TDP2 is also required for normal levels of many gene transcripts in developing mouse brain, including numerous gene transcripts associated with neurological function and/or disease, and for normal interneuron density in mouse cerebellum. Collectively, these data implicate chromosome breakage by TOP2 as an endogenous threat to gene transcription and to normal neuronal development and maintenance, This work was funded in the Caldecott laboratory by the Medical Research Council (MRC; MR/J006750/1 and G0901606/1) and Cancer Research UK (C6563/A16771), in the Cortes-Ledesma laboratory by the Spanish government (SAF2010-21017, RYC-2009-03928 and JAE-Doc 2010-011) and European Union (PERG07-2010-268466), in the El-Khamisy laboratory by the Wellcome Trust (fellowship 085284 and grant 091043) and the Lister Institute of Preventative Medicine (fellowship), and in part by the Netherlands Organization for Health Research and Development (ZonMW; VIDI grant 917-86-319 to B.B.A.d.V.), the GENCODYS project (EU-7th-2010-241995 to B.B.A.d.V. and A.P.M.d.B.), a Brainwave–Irish Epilepsy Association/Medical Research Charities Group of Ireland/Health Research Board award (2009/001) and a Health Research Board of Ireland Translational Research Scholars award. Control samples were funded by National Institute for Mental Health (NIMH) awards (RC2MH089915, K01MH098126, R01MH099216 and R01MH097971), the Epi4K Gene Discovery in Epilepsy study (National Institute for Neurological Disorders and Stroke (NINDS) U01NS077303), the Epilepsy Genome/Phenome Project (EPGP; NINDS U01NS053998), the Center for HIV/AIDS Vaccine Immunology (CHAVI) study (National Institute of Allergy and Infectious Diseases (NIAID) UO1AIO67854), the Ellison Medical Foundation New Scholar award (AG-NS-0441-08), SAIC-Frederick, Inc. (M11-074) and Biogen Idec, Inc.

Object. Pallidotomy for the treatment of medically refractory Parkinson's disease (PD) has enjoyed renewed popularity. However, the optimal surgical technique, lesion location, and long-term effectiveness of pallidotomy remain subjects of debate. In this article the authors describe their surgical technique for performing pallidotomy without using microelectrode guidance, and the clinical and radiological results of this procedure.Methods. Patients were evaluated preoperatively by using a battery of validated clinical rating scales and magnetic resonance (MR) imaging of the brain. Individuals with severe treatment-refractory idiopathic PD who were believed to be good candidates for surgery underwent computerized tomography scanning— and MR imaging—guided stereotactic pallidotomy. Intraoperative macrostimulation was used to optimize lesion placement and to avoid injury to nearby structures. Lesion location and size were calculated from MR imaging sequences of the brain obtained within the first 24 hours after surgery and again 3 months later. Clinical examinations were conducted at 1.5, 3, 6, 12, and 24 months after surgery.Seventy-five patients (mean age 61 years, range 38–79 years) underwent unilateral pallidotomy. Significant improvements were observed in the “off” period scores for the activities of daily living portion of the Unified Parkinson's Disease Rating Scale (UPDRS), the UPDRS motor scores, total “on” time, levodopa-induced dyskinesias, and contralateral tremor. These improvements were maintained 24 months postoperatively. The mean lesion volume measured on the immediate postoperative MR image was 73 ± 5.4 mm3. Radiological analysis suggests that initial lesion volume does not predict outcome. The only permanent major complication was a single visual field defect.Conclusions. Pallidotomy performed without using microelectrode guidance is a safe and effective treatment for selected patients with medically refractory PD.

Background Calreticulin (CRT) is a chaperone protein, which aids correct folding of glycosylated proteins in the endoplasmic reticulum (ER). Under conditions of ER stress, CRT is upregulated and may be displayed on the surface of cells or be secreted. This ‘ecto-CRT’ may activate the innate immune response or it may aid clearance of apoptotic cells. Our and other studies have demonstrated upregulation of ER stress markers CHOP, BiP, ATF4, XBP1 and phosphorylated e-IF2 alpha (p-eIF2 alpha) in biopsy and post-mortem human multiple sclerosis (MS) samples. We extend this work by analysing changes in expression of CRT, BiP, CHOP, XBP1 and p-eIF2 alpha in a rat model of inflammatory demyelination. Demyelination was induced in the spinal cord by intradermal injection of recombinant mouse MOG mixed with incomplete Freund’s adjuvant (IFA) at the base of the tail. Tissue samples were analysed by semi-quantitative scoring of immunohistochemically stained frozen tissue sections. Data generated following sampling of tissue from animals with spinal cord lesions, was compared to that obtained using tissue derived from IFA- or saline-injected controls. CRT present in rat serum and in a cohort of human serum derived from 14 multiple sclerosis patients and 11 healthy controls was measured by ELISA. Results Stained tissue scores revealed significantly (p Conclusion This data highlights the potential importance of CRT and other ER stress proteins in inflammatory demyelination.

We present the case of a pregnant woman who experienced a cerebral venous sinus thrombosis resulting in brain death at 13 weeks gestation. We discuss the management of the mother and foetus following this tragic event. We also discuss the complex medical, legal and ethical issues that arose following maternal brain death. The central question is whether continuing maternal organ supportive measures in an attempt to prolong gestation to attain foetal viability is appropriate, or whether it constitutes futile care. Successful maintenance of maternal brain somatic function to facilitate foetal maturation in utero has been reported. While the gestational age of the foetus is central to resolving this issue, there is no clear upper physiological limit to the prolongation of somatic function following brain death. Furthermore, medical experience regarding prolonged somatic support is limited. Finally, the legal rights conferred on the foetus may vary significantly depending on the jurisdiction in which the maternal brain death occurs and may have important implications. A consensus building approach, involving the family, is essential to resolving these potentially conflicting issues.

I beg to differ with Professor Turner’s suggestion that modern ‘discerning’ clinicians can omit Romberg’s test from their repertoire. Medical students (and patients) frequently fail to appreciate the contribution of the proprioceptive …

A 48-year-old woman presented with intermittent horizontal diplopia without preceding trauma or significant past medical history. She had right sided retro-orbital pain. Clinical examination showed right abducens nerve palsy. Investigations showed elevated total protein and erythrocyte sedimentation rate, but all other biochemical investigations were normal. Serum protein electrophoresis showed elevated IgG and free kappa light …

A 45-year-old man presented to the emergency department (ED) after falling down two flights of stairs. He had bilateral raccoon eyes, subconjunctival haemorrhages and CSF otorrhoea suggestive of skull base fracture (SBF). Although he had difficulty speaking and responded inappropriately, giving the impression of mixed dysphasia, written communication was normal, and he complained of deafness and dizziness. Facial motion was barely perceptible and complete eye closure was not possible, consistent with grade 5 facial palsies on the House-Brackmann facial nerve grading system. Bell’s phenomena (Fig. 1) and dysarthrophonia secondary to facial weakness were marked. He was also mildly ataxic. Computed tomography (CT) imaging confirmed extensive SBF and audiometric testing confirmed bilateral deafness. High-resolution axial petrous temporal bone CT (Fig. 2) demonstrated fractures involving the facial canals. The right-sided fracture traversed the fundus of the internal auditory canal, likely transecting the cochlear nerve, and the left-sided fracture involved the otic capsule, likely disrupting auditory and vestibular function. Fig. 1 a A 45-year-old man with facial diplegia. b Patient attempting to close both eyes producing bilateral Bell’s phenomenon. c Magnification of b demonstrating marked bilateral Bell’s phenomenon (more pronounced on the right side) Fig. 2 Right and left axial petrous temporal bone CT. Right axial CT shows a medial subtype of horizontal temporal bone fracture. There is a fracture of the posterior petrous surface (white arrow) extending anteriorly through the fundus of the internal auditory ... Post-traumatic facial nerve palsy complicates 1.5% of SBFs involving the temporal bones [1]. Petrous temporal bone fractures may disrupt the facial nerve, membranous labyrinth and inner ear. While cranial nerves seven and eight may be injured by petrous temporal bone fractures, concomitant bilateral facial weakness and deafness in this setting is extremely rare [2]. Most post-traumatic facial nerve injuries recover with conservative management and time [3, 4]. This case illustrates how bilateral facial weakness and deafness may be mistaken for mixed dysphasia and highlights the need to consider it in patients with apparent speech disturbances in the ED.

Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56-year-old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that perineuritis forms part of the pathogenesis in acute Lyme neuroborreliosis.

We report an explosive presentation of neurological Behcet disease, in an Irish male patient. We present the clinical and radiological findings in our patient and discuss a novel and effective therapeutic approach. We review other treatment modalities of patients with neurological involvement.

Multiple sclerosis (MS) is an autoimmune disorder characterised by clinical relapse and remission and pathological demyelination with varying inflammation. Because it is suggested that T-cells expressing natural killer cell receptors (NKR) play important roles in regulating human autoimmune diseases, we have quantified populations of T-cells expressing the NKR CD56, CD161 and CD94 in the peripheral blood of MS patients, in healthy control subjects (HS) and in patients with other neurological diseases (OND). CD161(+) T-cells and CD94(+) T-cells were significantly decreased in MS patients with primary progressive disease and secondary progressive disease respectively whereas CD56(+) T-cell numbers were unchanged. In contrast NKT-cells that express the invariant Valpha24-Jalpha18(+) T-cell receptor identified here by specific receptor antibody and CD1d-tetrameric PBS57-loaded complexes, were increased in MS patients compared with HS. Reductions in CD161(+) T-cells and CD94(+) T-cells relative to HS were also observed in the OND group and this was particularly prominent in Parkinsonian patients. A striking functional finding was that while NKT-cells in unfractionated peripheral blood from healthy subjects expanded in number and produced IFN-gamma upon stimulation with alpha-galactosylceramide, NKT-cells from MS patients did not. Thus we have identified alterations in a number of potentially important lymphocyte sub-populations warranting further investigation in the immune response in MS.

With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntington's disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy-five clinicians experienced in the evaluation of patients with early HD and six non-clinicians were shown a videotape compiled from the film archives of the United States–Venezuela Collaborative HD Research Project. Observers were asked to rate a 2–3-minute segment of the motor examination for each of 17 at-risk subjects. The rating scale ranged from 0 (normal) to 4 (unequivocal extrapyramidal movement disorder characteristic of HD). As measured by a weighted κ statistic, there was substantial agreement among the 75 clinicians in the judgment of unequivocal motor abnormalities comparing scale ratings of 4 with ratings that were not 4 (weighted κ = 0.67; standard error (SE) = 0.09). Agreement among the non-clinicians was only fair (weighted κ = 0.28; SE = 0.10). Even under the artificial conditions of a videotape study, experienced clinicians show substantial agreement about the signs that constitute the motor manifestations of illness in subjects at risk for HD. We expect these findings to translate to a similar level of interobserver agreement in the clinical trial setting involving experienced investigators examining live patients. © 2005 Movement Disorder Society

Teaching the fundamentals of clinical neurology to medical students is fraught with difficulty.1,2 While most teachers agree on the primacy of a student eliciting a comprehensive and coherent history as part of formulating a diagnosis, opinion is divided on the role of the neurologic examination in the diagnostic process. Some clinicians prefer to engage in a comprehensive screening neurologic examination of the patient before arriving at a diagnostic impression, while others favor a more focused, restricted examination, testing a hypothesis based on data from the patient's history. Medical students bear witness to these differing examination styles when observing senior clinicians at work. Indeed, many seasoned neurologists reflect on their own days in training and recall (not always with fondness) the eminent Professor painstakingly advancing down the neuroaxis through cranial nerves, myotomes, dermatomes, and obscure reflexes until arriving at the denouement that is inevitably the Babinski response. Others among us may recall ourselves, with a touch of dismay, going to endless trouble to master the myriad of eponymous signs that make up the complete neurologic examination, only to observe our Professor take a precise history and follow it up with a cursory flick …

OBJECTIVE—To test the hypothesis that differential regional dopamine transporter (DAT) gene expression may underlie the selective vulnerability of certain nigral dopaminergic neurons in Parkinson's disease, DAT mRNA expression was examined in neuronal subpopulations of human postmortem ventral mesencephalon from patients with Parkinson's disease and controls. METHODS—Radioactive in situ hybridisation histochemistry using a polymerase chain reaction derived ribonucleotide probe for DAT was performed on sections of ventral mesencephalon from the brains of five donors with no history of neurological illness and from five patients with pathologically established Parkinson's disease. The number of silver grains overlying melanised neurons from the paranigral nucleus, dorsal and ventral tier, and pars lateralis of the substantia nigra pars compacta were compared with each other and to background labelling by using a one way factorial analysis of variance (ANOVA) with a significance level of 5%. RESULTS—In control brains, there was intense DAT mRNA expression in the ventral midbrain with no significant difference in mRNA concentrations among the four regions studied. In the Parkinson's disease brains, there was an overall decrease in the intensity of DAT mRNA expression in the surviving dopaminergic neurons. There were no significant differences in signal between regions in either the control or parkinsonian brains. CONCLUSION—Taken together, these findings do not support the hypothesis that differential regional DAT gene expression underlies the selective vulnerability of certain nigral dopaminergic neurons in Parkinson's disease, as the vulnerable neurons of the substantia nigra pars compacta do not express more DAT mRNA than the resistant paranigral neurons.