Neurology Research Papers - Academia.edu (original) (raw)

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterised by bilateral vestibular schwannomas and other CNS tumours including meningiomas and spinal schwannomas. Occasionally, peripheral neuropathy occurs in these... more

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterised by bilateral vestibular schwannomas and other CNS tumours including meningiomas and spinal schwannomas. Occasionally, peripheral neuropathy occurs in these patients but this is the first report of focal amyotrophy. Clinical, electrophysiological, and imaging data from four NF2 patients seen at a specialist neurofibromatosis clinic over a 4 year period are described in whom symptomatic focal amyotrophy preceded the diagnosis of NF2. Two presented with wasting and weakness of a single muscle group, several years before NF2 was diagnosed. In one patient a mononeuritis multiplex was the presenting feature of NF2, and in one patient focal wasting and weakness developed after the diagnosis of NF2 was made. In none of the four cases could a focal peripheral nerve or root neurofibroma be identified despite extensive imaging with MRI, and the limitations of neuroimaging for identifying a structural cause in patients with NF2 with a focal peripheral nerve lesion is discussed. It is likely that NF2 may aVect peripheral nerve structures in a manner distinct from a compressive schwannoma.

Nerve biopsy is a valuable tool in the diagnostic work-up of peripheral neuropathies. Currently, major indications include interstitial pathologies such as suspected vasculitis and amyloidosis, atypical cases of inflammatory neuropathy... more

Nerve biopsy is a valuable tool in the diagnostic work-up of peripheral neuropathies. Currently, major indications include interstitial pathologies such as suspected vasculitis and amyloidosis, atypical cases of inflammatory neuropathy and the differential diagnosis of hereditary neuropathies that cannot be specified otherwise. However, surgical removal of a piece of nerve causes a sensory deficit and -in some cases -chronic pain. Therefore, a nerve biopsy is usually performed only when other clinical, laboratory and electrophysiological methods have failed to clarify the cause of disease. The neuropathological work-up should include at least paraffin and resin semithin histology using a panel of conventional and immunohistochemical stains. Cryostat section staining, teased fiber preparations, electron microscopy and molecular genetic analyses are potentially useful additional methods in a subset of cases. Being performed, processed and read by experienced physicians and technicians nerve biopsies can provide important information relevant for clinical management.

India: We read the article by Liu et al. 1 with interest. As the aging population grows, good geriatric medical services all over the world are needed. Developed countries are close to fulfilling these requirements, but problems exist in... more

India: We read the article by Liu et al. 1 with interest. As the aging population grows, good geriatric medical services all over the world are needed. Developed countries are close to fulfilling these requirements, but problems exist in developing and third world countries like India, where adequate infrastructure and data are lacking. There are regional differences in dementia prevalence (0.8%-4.1%), which could be due to ethnic diversity, education level, diet, social customs/rituals, and medical infrastructure. 2 The incidence of degenerative dementia in India is far less compared to the West, but stroke, infection, malnutrition, and alcohol contribute to most dementia. 3 The use of curcumin-widely used in India-is considered protective for dementia, 2 yet patients need more than is offered. There are provisions for free medicine and some imaging in many parts of India, but more complex investigation is costly, which adds to the existing problem. Medicines like donepezil, memantine, and rivastigmine also come at a price. The free drug distribution protocol needs to be upgraded.

Brain death (BD) should be understood as the ultimate clinical expression of a brain catastrophe characterized by a complete and irreversible neurological stoppage, recognized by irreversible coma, absent brainstem reflexes, and apnea.... more

Brain death (BD) should be understood as the ultimate clinical expression of a brain catastrophe characterized by a complete and irreversible neurological stoppage, recognized by irreversible coma, absent brainstem reflexes, and apnea. The most common pattern is manifested by an elevation of intracranial pressure to a point beyond the mean arterial pressure, and hence cerebral perfusion pressure falls and, as a result, no net cerebral blood flow is present, in due course leading to permanent cytotoxic injury of the intracranial neuronal tissue. A second mechanism is an intrinsic injury affecting the nervous tissue at a cellular level which, if extensive and unremitting, can also lead to BD. We review here the methodology of diagnosing death, based on finding any of the signs of death. The irreversible loss of cardio-circulatory and respiratory functions can cause death only when ischemia and anoxia are prolonged enough to produce an irreversible destruction of the brain. The sign of such loss of brain functions, that is to say BD diagnosis, is fully reviewed.

NB: Out of Stock. The 2nd edition, entitled "Neurology: Self-Assessment for MRCP(UK) Neurology SCE", was published in 2023 and is found here: https://www.academia.edu/96771620/Neurology_Self_Assessment_for_MRCP_UK_Neurology_SCE
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You will find 792 questions of different formats, distributed into 3 chapters. The 215 multiple choice questions of chapter one will surf you onto a rapid review of information to consolidate your background knowledge of neuro-anatomy, neuro-physiology, neuro-pharmacology, neuro-pathology,…etc. In addition, testing the clinical aspects of various diseases is also included. Chapter two will self-assess you in terms of how to make a provisional diagnosis, what features refute or confirm your preliminary diagnosis, how to investigate, what to do next, the best treatment option, and the prognosis of various diseases. The photographic materials are found in chapter three. You will encounter various neurological complications/manifestations/signs of system diseases as well. Brain CT scan, MRI, MRV, and EEG images,…etc of common diseases will test your ability to interpret/read/analyze their diagnosis and management. About 490 pages, full-color, on white.

Background: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed... more

Background: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed early in the disease course. Objective: To establish reliable biochemical markers of cerebral disease progression in patients with ALD to aid in treatment planning. Methods: The authors used proton magnetic resonance spectroscopy (MRS) in combination with LCModel analysis to quantify brain metabolites in small volumes (3 to 16 mL) in the occipital and frontal white matter and the splenium of the corpus callosum of 17 unsedated patients and 26 healthy volunteers (adult n ϭ 21, age-matched n ϭ 5) at 4 tesla. Results: Absolute concentrations of 12 metabolites were reliably determined, seven of which were established as markers of lesion development. Among these, creatine and choline containing compounds were the weakest markers while N-acetylaspartate, glutamine, and lipids ϩ lactate were the strongest. The large extent of changes in the markers enabled detection of early neurochemical changes in lesion formation prior to detection of abnormalities by conventional MRI. Concentrations of a number of metabolites were also significantly different between normal appearing white matter of patients and controls indicating biochemical alterations in the absence of cerebral disease. Neurochemical improvements following HCT were measured in six patients. Conclusions: The progression of adrenoleukodystrophy, as well as effectiveness of its treatment, can be assessed with high precision using high field 1 H magnetic resonance spectroscopy in individual patients without the need for sedation. balt4/znl-neurol/znl-neurol/znl00305/znl9349-05a simmsl S‫8؍‬ 12/8/

Neurofeedback is emerging as a promising technique that enables self-regulation of ongoing brain oscillations. However, despite a rise in empirical evidence attesting to its clinical benefits, a solid theoretical basis is still lacking on... more

Neurofeedback is emerging as a promising technique that enables self-regulation of ongoing brain oscillations. However, despite a rise in empirical evidence attesting to its clinical benefits, a solid theoretical basis is still lacking on the manner in which neurofeedback is able to achieve these outcomes. The present work attempts to bring together various concepts from neurobiology, engineering, and dynamical systems so as to propose a contemporary theoretical framework for the mechanistic effects of neurofeedback. The objective is to provide a firmly neurophysiological account of neurofeedback, which goes beyond traditional behaviorist interpretations that attempt to explain psychological processes solely from a descriptive standpoint whilst treating the brain as a ‘black box’. To this end, we interlink evidence from experimental findings that encompass a broad range of intrinsic brain phenomena: starting from ‘bottom-up’ mechanisms of neural synchronization, followed by ‘top-down’ regulation of internal brain states, moving to dynamical systems plus control-theoretic principles, and concluding with activity-dependent as well as homeostatic forms of brain plasticity. In support of our framework, we examine the effects of neurofeedback in several brain disorders, including attention-deficit hyperactivity (ADHD) and post-traumatic stress disorder (PTSD). The central thesis put forward is that neurofeedback tunes brain oscillations toward a homeostatic set-point which maintains optimal network flexibility and stability (i.e. self-organized criticality).

We read the article by Haut et al. with interest. 1 The authors report on the ability of some patients with epilepsy to predict the occurrence of their seizures. As suggested by the authors, this ability may rely on prodromes or warning... more

We read the article by Haut et al. with interest. 1 The authors report on the ability of some patients with epilepsy to predict the occurrence of their seizures. As suggested by the authors, this ability may rely on prodromes or warning and initial symptoms. Preictal dysphoria is a phenomenon well described by patients and their relatives, but the frequency, duration, and clinical features have been only occasionally investigated. The last systematic study specifically dedicated to this subject was published in 1986. 2 It is evident that mood changes preceding the occurrence of seizures represent a neglected area of research in epileptology and neuropsychiatry of epilepsy that, conversely, may have important clinical implications. Research concerning seizure-alerting dogs is also of interest. 3 It is possible that this phenomenon could be interlinked with preictal dysphoria-that dogs' behaviors are influenced by specific mood changes of the owner occurring in the preictal phase. It is now accepted that the end of the seizure is not the end of the problem, 4 but what precedes the seizure can be equally interesting.

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220... more

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).Methods:Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.Results:A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was ident...

Placental blood flow was measured with the aid of radioactive microspheres, in normal (N) and manifest diabetic (MD) rats, and related to fetal body growth and incidence of congenital malformations. The total blood flow in the placentae... more

Placental blood flow was measured with the aid of radioactive microspheres, in normal (N) and manifest diabetic (MD) rats, and related to fetal body growth and incidence of congenital malformations. The total blood flow in the placentae of the MD rats was decreased to about one-half of the normal flow on gestational days 20 and 22. The placentae of the MD offspring were enlarged, whereas the fetuses in this group were smaller than normal. Thus, the placental blood flow per placental weight was drastically decreased in the MD fetuses on both days 20 and 22. In contrast, the placental blood flow per fetal weight was not different in the N and MD groups on gestational day 20 whereas it was decreased in the MD offspring on gestational day 22. Placental blood flow in the malformed fetuses of the MD group did not differ significantly from that in the nonmalformed MD fetuses.

Fractional tubular reabsorption (FTR) of free and acyl carnitine was measured in 15 patients with various selective tubular transport defects and in 19 patients with more generalized tubular dysfunction (Fanconi syndrome). FTR of free... more

Fractional tubular reabsorption (FTR) of free and acyl carnitine was measured in 15 patients with various selective tubular transport defects and in 19 patients with more generalized tubular dysfunction (Fanconi syndrome). FTR of free carnitine was normal in all patients with a selective tubulopathy, FTR of acyl carnitine was normal in most, and plasma carnitine levels were normal without exception. In these patients, there was no evidence for the existence of a defective renal transport mechanism shared by carnitine. In the patients with Fanconi syndrome, mean FTR of free and acyl carnitine was low; their plasma carnitine levels were lowered and correlated with the FTR. In individual patients, FTR of free and acyl carnitine also correlated with the severity of the disease. In the group of Fanconi syndrome patients, FTR of free and acyl carnitine correlated linearly with that of valine. We concluded that the lowering of plasma carnitine in the patients with Fanconi syndrome was caused by excessive loss of carnitine in urine. Its pathophysiological significance remained to be established.

Objectives-It has been shown that atrophy of medial temporal lobe structures such as the hippocampus and entorhinal cortex shown on MRI may distinguish patients with Alzheimer's disease from healthy controls. However, the diagnostic value... more

Objectives-It has been shown that atrophy of medial temporal lobe structures such as the hippocampus and entorhinal cortex shown on MRI may distinguish patients with Alzheimer's disease from healthy controls. However, the diagnostic value of visual inspection and volumetry of medial temporal lobe atrophy (MTA) on MRI in a clinical setting is insuYciently known. Methods-Medial temporal lobe atrophy in 143 patients was visually rated from hard copies, using a 0-4 rating scale and a comparison was made with the volumes (cm 3 ) of the medial temporal lobe as estimated with volumetry, using a stereological method. All patients were recruited in an unselected way in a clinical setting in the centre for memory impairments at the Huddinge University Hospital. Patients with Alzheimer's disease (n=41), patients with other dementias (vascular dementia, frontotemporal dementia, and unspecified dementia; n=36) as well as non-demented subjects (n=66) were included. Medial temporal atrophy and volumetry were evaluated as a diagnostic tool by performing logistic regression analysis including age, sex, and mini mental state examination (MMSE) score and calculating the sensitivity and specificity and percentage correct classification.

Controversy continues regarding the safety and efficacy of tissue plasminogen activator (tPA) for stroke outside major centers. We reviewed charts from 1998 to 2004 of 493 patients admitted with TIA or stroke to our small rural hospital.... more

Controversy continues regarding the safety and efficacy of tissue plasminogen activator (tPA) for stroke outside major centers. We reviewed charts from 1998 to 2004 of 493 patients admitted with TIA or stroke to our small rural hospital. There was a 4% tPA treatment rate with no symptomatic intracranial hemorrhage and zero mortality. IV tPA can be safe and effective in the treatment of acute stroke despite the size of the institution.

An 11-year-old boy presented with a 3-month history of progressive left foot drop. Clinical findings were consistent with left peroneal mononeuropathy, but neurophysiologic studies failed to demonstrate signs of peroneal nerve entrapment.... more

An 11-year-old boy presented with a 3-month history of progressive left foot drop. Clinical findings were consistent with left peroneal mononeuropathy, but neurophysiologic studies failed to demonstrate signs of peroneal nerve entrapment. Magnetic resonance neurography revealed a peroneal intraneural ganglion cyst (PIG) (figure, A-D). The patient underwent surgical resection of the PIG, resulting in mild improvement of symptoms. PIG are thought to originate from the articular branch of the peroneal nerve (figure, B). 1 Only 12 cases have been described in patients younger than 18 years. 2 Radiologic investigation should be considered in children with atypical peroneal palsy in order to detect uncommon causes that may be surgically treatable.

To define a safe and effective dose of Dysport for treating hip adductor spasticity. Patients with definite or probable multiple sclerosis, and disabling spasticity affecting the hip adductor muscles of both legs, were randomised to one... more

To define a safe and effective dose of Dysport for treating hip adductor spasticity. Patients with definite or probable multiple sclerosis, and disabling spasticity affecting the hip adductor muscles of both legs, were randomised to one of four treatment groups. Dysport (500, 1000, or 1500 Units), or placebo was administered by intramuscular injection to these muscles. Patients were assessed at entry, and 2, 4 (primary analysis time-point), 8, and 12 weeks post-treatment. A total of 74 patients were recruited. Treatment groups were generally well matched at entry. The primary efficacy variables-passive hip abduction and distance between the knees-improved for all groups. The improvement in distance between the knees for the 1500 Unit group was significantly greater than placebo (p = 0.02). Spasm frequency was reduced in all groups, but muscle tone was reduced in the Dysport groups only. Pain was reduced in all groups, but improvements in hygiene scores were evident only in the 1000 ...

Objective: To perform a meta-analysis on the effect of lowering homocysteine levels via B vitamin supplementation on cerebrovascular disease risk. Methods: Using clinical trials published before August 2012 to assess stroke events, we... more

Objective: To perform a meta-analysis on the effect of lowering homocysteine levels via B vitamin supplementation on cerebrovascular disease risk. Methods: Using clinical trials published before August 2012 to assess stroke events, we used relative risks (RRs) with 95% confidence intervals (95% CIs) to measure the association between B vitamin supplementation and endpoint events using a fixed-effects model and x 2 tests. We included 14 randomized controlled trials with 54,913 participants in this analysis. Results: We observed a reduction in overall stroke events resulting from reduction in homocysteine levels following B vitamin supplementation (RR 0.93; 95% CI 0.86-1.00; p 5 0.04) but not in subgroups divided according to primary or secondary prevention measures, ischemic vs hemorrhagic stroke, or occurrence of fatal stroke. There were beneficial effects in reducing stroke events in subgroups with $3 years follow-up time, and without background of cereal folate fortification or chronic kidney disease (CKD). Some trials that included CKD patients reported decreased glomerular filtration rate with B vitamin supplementation. We conducted detailed subgroup analyses for cyanocobalamin (vitamin B 12) but did not find a significant benefit regarding intervention dose of vitamin B 12 or baseline blood B 12 concentration. Stratified analysis for blood pressure and baseline participant medication use showed benefits with .130 mm Hg systolic blood pressure and lower antiplatelet drug use in reducing stroke risk. Conclusions: B vitamin supplementation for homocysteine reduction significantly reduced stroke events, especially in subjects with certain characteristics who received appropriate intervention measures. Neurology â 2013;81:1298-1307 GLOSSARY CI 5 confidence interval; CKD 5 chronic kidney disease; GFR 5 glomerular filtration rate; HBP 5 high blood pressure; MI 5 myocardial infarction; RCT 5 randomized controlled trial; RR 5 relative risk; SBP 5 systolic blood pressure; VISP 5 Vitamin Intervention for Stroke Prevention trial.

V ertigo and dizziness account for 2.6 million US emergency department (ED) visits per year, ≈4% attributable to stroke. 1 Roughly 250 to 500 000 involve a high-risk-for-stroke clinical presentation known as acute vestibular syndrome... more

V ertigo and dizziness account for 2.6 million US emergency department (ED) visits per year, ≈4% attributable to stroke. 1 Roughly 250 to 500 000 involve a high-risk-for-stroke clinical presentation known as acute vestibular syndrome (AVS). 2 AVS is a well-defined clinical syndrome of severe, continuous vertigo, or dizziness, nausea or vomiting, gait instability, head motion intolerance, and nystagmus lasting days to weeks. 2-4 Most AVS patients have a benign peripheral vestibular cause (vestibular neuritis or nonbacterial labyrinthitis), but ≈25% have brain stem or cerebellar strokes. 2 Other central causes, such as multiple sclerosis, are uncommon. 2 Distinguishing dangerous central from benign peripheral vestibular causes can be challenging. Half of stroke patients presenting with AVS have no focal neurological signs. 2 In the first 24 hours after onset of symptoms, computed tomography accurately detects cerebellar hemorrhages but not ischemic strokes (16% sensitivity). 5 Even magnetic resonance imaging of the brain with diffusion-weighted imaging (MRI-DWI) identifies only ≈80% of posterior fossa infarctions in the first day. 2 Three bedside eye movement findings (Head Impulse test, Nystagmus, Test-of-Skew [HINTS]) differentiate central from peripheral causes of AVS, even outperforming early MRI (Table I in the online-only Data Supplement). 2 This is not Background and Purpose-Strokes can be distinguished from benign peripheral causes of acute vestibular syndrome using bedside oculomotor tests (head impulse test, nystagmus, test-of-skew). Using head impulse test, nystagmus, test-ofskew is more sensitive and less costly than early magnetic resonance imaging for stroke diagnosis in acute vestibular syndrome but requires expertise not routinely available in emergency departments. We sought to begin standardizing the head impulse test, nystagmus, test-of-skew diagnostic approach for eventual emergency department use through the novel application of a portable video-oculography device measuring vestibular physiology in real time. This approach is conceptually similar to ECG to diagnose acute cardiac ischemia. Methods-Proof-of-concept study (August 2011 to June 2012). We recruited adult emergency department patients with acute vestibular syndrome defined as new, persistent vertigo/dizziness, nystagmus, and (1) nausea/vomiting, (2) head motion intolerance, or (3) new gait unsteadiness. We recorded eye movements, including quantitative horizontal head impulse testing of vestibulo-ocular-reflex function. Two masked vestibular experts rated vestibular findings, which were compared with final radiographic gold-standard diagnoses. Masked neuroimaging raters determined stroke or no stroke using magnetic resonance imaging of the brain with diffusion-weighted imaging obtained 48 hours to 7 days after symptom onset. Results-We enrolled 12 consecutive patients who underwent confirmatory magnetic resonance imaging. Mean age was 61 years (range 30-73), and 10 were men. Expert-rated video-oculography-based head impulse test, nystagmus, test-ofskew examination was 100% accurate (6 strokes, 6 peripheral vestibular). Conclusions-Device-based physiological diagnosis of vertebrobasilar stroke in acute vestibular syndrome should soon be possible. If confirmed in a larger sample, this bedside eye ECG approach could eventually help fulfill a critical need for timely, accurate, efficient diagnosis in emergency department patients with vertigo or dizziness who are at high risk for stroke. (Stroke. 2013;44:1158-1161.) Key Words: diagnosis ■ diagnostic techniques, neurological ■ dizziness ■ sensitivity and specificity ■ vertigo

Aims. To identify service models that provided care coordination for people with long-term neurological conditions in the UK. Background. The successful management of long-term neurological conditions needs sophisticated management across... more

Aims. To identify service models that provided care coordination for people with long-term neurological conditions in the UK. Background. The successful management of long-term neurological conditions needs sophisticated management across several health, social care and other service boundaries, as well as involvement of people with long-term neurological conditions and their support network. Yet, fragmentation of, and limited access to, support has been evident for over 20 years. Design. This study employed a mixed-method approach, including a systematic review, qualitative case studies and a quantitative national survey. This paper reports findings from the qualitative case study element of the research. Methods. In-depth (qualitative) case studies were conducted in six neurology 'service systems' in the UK representing geographic and demographic diversity. The research took place between November 2007-May 2008. The concept of 'continuity of care' was used as a framework for our case studies. Qualitative methods, including telephone and face-to-face interviews, were used to explore people's experience of continuity of care. Data were managed and analyzed using the Framework technique. Findings. Neurology nurse specialists were able to contribute to all elements of continuity of care for people with long-term neurological conditions. Conclusion. Their specialist knowledge about the condition and local services, flexibility, coordinating role, and their holistic and collaborative approach to practice, are key factors in nurse specialists promoting continuity of care. Nurse specialists exist in many different clinical areas and in many countries. Findings about the importance of their role in promoting continuity of care have important implications for UK and international policy and practice.

ObjectiveTo develop and prospectively evaluate a method of epileptic seizure detection combining heart rate and movement.MethodsIn this multicenter, in-home, prospective, video-controlled cohort study, nocturnal seizures were detected by... more

ObjectiveTo develop and prospectively evaluate a method of epileptic seizure detection combining heart rate and movement.MethodsIn this multicenter, in-home, prospective, video-controlled cohort study, nocturnal seizures were detected by heart rate (photoplethysmography) or movement (3-D accelerometry) in persons with epilepsy and intellectual disability. Participants with >1 monthly major seizure wore a bracelet (Nightwatch) on the upper arm at night for 2 to 3 months. Major seizures were tonic-clonic, generalized tonic >30 seconds, hyperkinetic, or others, including clusters (>30 minutes) of short myoclonic/tonic seizures. The video of all events (alarms, nurse diaries) and 10% completely screened nights were reviewed to classify major (needing an alarm), minor (needing no alarm), or no seizure. Reliability was tested by interobserver agreement. We determined device performance, compared it to a bed sensor (Emfit), and evaluated the caregivers’ user experience.ResultsTwen...

The clinical and visual evoked potential (VEP) findings were analysed in 18 patients with anterior ischaemic optic neuropathy. The VEP studies showed a variety of abnormalities which could be interpreted as being the result of... more

The clinical and visual evoked potential (VEP) findings were analysed in 18 patients with anterior ischaemic optic neuropathy. The VEP studies showed a variety of abnormalities which could be interpreted as being the result of subcomponent interaction consequent upon loss or attenuation of the normal macular-derived P100 component. Delay of normal VEP subcomponents was not seen. The VEP findings were non-specific but pointed to a severe disturbance of transmission in optic nerve fibres subserving central vision. No significant changes were observed with time in most cases indicating a static monophasic process with no significant recovery.

Objectives-To determine (a) the proportion of patients referred to general neurology outpatient clinics whose symptoms are medically unexplained; (b) why they were referred; (c) health status and emotional disorder in this group compared... more

Objectives-To determine (a) the proportion of patients referred to general neurology outpatient clinics whose symptoms are medically unexplained; (b) why they were referred; (c) health status and emotional disorder in this group compared with patients whose symptoms are explained by "organic" neurological disease. Methods-The prospective cohort study with case note follow up at 6 months was carried out in the regional neurology service in Lothian, Scotland with 300 newly referred outpatients. Neurologists rated the degree to which patients' symptoms were explained by organic disease (organicity), GPs' reasons for referral, health status (SF-36), anxiety, and depressive disorders (PRIME-MD), Results-Of 300 new patients 11% (95% confidence interval (95% CI) 7%-14%) had symptoms that were rated as "not at all explained" by organic disease, 19% (15% to 23%) "somewhat explained", 27% (22% to 32%) "largely explained", and 43% (37% to 49%) "completely explained" by organic disease. Reason for referral was not associated with "organicity". Comparison of these groups showed that although physical function was similar, the median number of physical symptoms and pain were greater in patients with lower organicity ratings (p<0.0005, p<0.0005). Depressive and anxiety disorders were more common in patients with symptoms of lower organicity (70% of patients in the not at all group had an anxiety or depressive disorder compared with 32% in the completely explained group (p<0.0005). Conclusion-One third of new referrals to general neurology clinics have symptoms that are poorly explained by identifiable organic disease. These patients were disabled and distressed. They deserve more attention.

Objective: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. Methods: We studied... more

Objective: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. Methods: We studied Ashkenazi Jews with exceptional longevity (n ϭ 158; age 99.2 Ϯ 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. Results: Subjects with MMSE Ͼ 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p ϭ 0.02), and those with the VV genotype were more likely (61% vs 30%, p ϭ 0.02) to have MMSE Ͼ 25. Subjects with the VV genotype had lower levels of CETP (1.73 Ϯ 0.11 vs 2.12 Ϯ 0.10 g/mL, p ϭ 0.01), higher high-density lipoprotein (HDL) levels (p ϭ 0.02), and larger lipoprotein particles (p ϭ 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p ϭ 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. Conclusions: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD.

The diagnosis of rare inherited diseases is becoming more and more complex as an increasing number of clinical conditions appear to be genetically heterogeneous.

Brain metastases (BM) are one the most lethal and poorly managed clinical complications in cancer patients. These secondary tumors represent the most common intracranial neoplasm in adults, most frequently originating from lung cancer,... more

Brain metastases (BM) are one the most lethal and poorly managed clinical complications in cancer patients. These secondary tumors represent the most common intracranial neoplasm in adults, most frequently originating from lung cancer, breast cancer, and cutaneous melanoma. In primary brain tumors, such as gliomas, recent advances in DNA methylation profiling have allowed for a comprehensive molecular classification. Such data provide prognostic information, in addition to helping predict patient response to specific systemic therapies. However, epigenetic alterations of metastatic brain tumors with specific biological and translational relevance still require much further exploration. Using the widely employed Illumina Infinium HumanMethylation 450K platform, we have generated a cohort of genome-wide DNA methylomes from ninety-six needle-dissected BM specimens from patients with lung cancer, breast cancer, and cutaneous melanoma with clinical, pathological, and demographic annotations. This resource offers an unprecedented and unique opportunity to identify novel DNA methylation features influencing the behavior of brain metastasis, and thus accelerate the discovery of BM-specific theranostic epigenetic alterations. Design Type(s) disease state design • DNA methylation profiling by array design Measurement Type(s) DNA residue methylation Technology Type(s) DNA methylation profiling assay Factor Type(s) Primary Malignant Neoplasm • Tumor Subtype Sample Characteristic(s) Homo sapiens • brain

Background/aim: Hallucinations are the special ability to experience phenomena that are not visible to normal individuals. Hallucinations, delusions, and confabulations are common symptoms between neurology and psychiatry. Nervous disease... more

Background/aim: Hallucinations are the special ability to experience phenomena that are not visible to normal individuals. Hallucinations, delusions, and confabulations are common symptoms between neurology and psychiatry. Nervous disease that manifests with hallucinatory symptoms like this is one of them due to right hemispheric stroke. The authors report cases of new-onset organic hallucinosis. and stroke in brain regions similar to the salience network (insular cortex, parietal cortex, and striatum). Case: A 43-year-old man comes to the ER Sanglah Hospital Denpasar, Bali Indonesia with complaints of slurred speech using an incomprehensible language, and repeating the same words. Talking about seeing a shadow following him but actually not there. Patients often experience sleep disorders, from the results of neurological physical examination found right eye ptosis, pupil anisokor, nerve III dextra complete lesion, supranuclear left NVII paresis, supranuclear left NXII paresis, left flaccid hemiparesis. Psychiatric status obtained unnatural appearance, looks confused, verbal and visual contact is sufficient, mood dysphoric, confused affect and there is no harmony. The thought process obtained realistic, coherent, preoccupation with pain. Perceptual disturbances in the form of visual and auditory hallucinations. Insomnia mixed type and there is hypobulia. Psychomotor calm on examination, history increases. Narcissistic personality traits and defense mechanisms of ego repression. Grade 4 view. CT scan of the head with and without contrast shows subacute ischemic cerebral infarction in the right internal capsule to the right thalamus and midbrain Conclusion: Organic hallucinosis occur in nonhemorrhagic stroke caused by thrombosis process if an infarction is found in the right hemisphere.

Background Some patients with neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) have similar clinical features do not have Anti-Aquaporin-4 (AQP4) antibody and may have a different condition with different outcomes with regard... more

Background Some patients with neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) have similar clinical features do not have Anti-Aquaporin-4 (AQP4) antibody and may have a different condition with different outcomes with regard to motor disability Objectives To determine whether the AQP4 antibody has a relationship with the prognosis of transverse myelitis in terms of motor disability Methods Sera of 34 patients with NMO (n=27) and NMOSD with isolated or recurrent myelitis (n=7) were all investigated for the presence of AQP4 antibody by a cell-based indirect immunofluorescence assay (IIFA). The prognostic values of anti-AQP4 antibody were evaluated in terms of a good motor prognosis (able to walk unaided for at least 100 metres) and a poor motor prognosis (with aid to walk at least 100 metres or a worse condition). Results In our study, the anti-AQP4 antibody9s seropositivity in all cases was 61.8[percnt] (n=21), was 59.3[percnt] in NMO and 71.4[percnt] in NMOSD cases. An...

When serial neurocognitive assessments are performed, 2 main factors are of importance: test-retest reliability and practice effects. With children, however, there is a third, developmental factor, which occurs as a result of maturation.... more

When serial neurocognitive assessments are performed, 2 main factors are of importance: test-retest reliability and practice effects. With children, however, there is a third, developmental factor, which occurs as a result of maturation. Child tests recognize this factor through the provision of age-corrected scaled scores. Thus, a ready-made method for estimating the relative contribution of developmental versus practice effects is the comparison of raw (developmental and practice) and scaled (practice only) scores. Data from a pool of 507 Portuguese children enrolled in a study of dental amalgams (T. A. DeRouen, B. G. Leroux, et al., 2002; T. A. DeRouen, M. D. Martin, et al., 2006) showed that practice effects over a 5-year period varied on 8 neurocognitive tests. Simple regression equations are provided for calculating individual retest scores from initial test scores.

It has been hypothesized that freezing of gait (FOG) in parkinsonian patients (PD) might be triggered by a breakdown in the normal symmetry of gait. In this study, we evaluated the relationship between asymmetry of gait and FOG and the... more

It has been hypothesized that freezing of gait (FOG) in parkinsonian patients (PD) might be triggered by a breakdown in the normal symmetry of gait. In this study, we evaluated the relationship between asymmetry of gait and FOG and the effects of intensive treadmill treatment on asymmetry. We studied 30 patients with (FOG?) and 30 without (FOG-) freezing in ''on'' stage. Patients underwent a 4-week rehabilitation treatment using a treadmill with auditory and visual cues and were evaluated at enrolment and at the end of rehabilitation. Outcome measures were gait speed, stride length, asymmetry of gait, Sixminute walking test (6MWT), Unified Parkinson's Disease Rating Scale (UPDRS) II-III, Berg Balance Scale, Timed Up and Go Test, comfortable-fast gait speeds, freezing of gait questionnaire (FOGQ). At enrolment, no differences in gait parameters were observed between the two groups, which differed only in UPDRS_II and BBS. Both FOG? and FOG-patients spent more time on the left foot (time on left/time on right foot 1.37, p = 0.002, 1.18, p = 0.016, respectively). Rehabilitation determined a homogeneous improvement in both groups of patients for all variables except UPDRS_II and balance, for which a better improvement was observed in FOG? patients. The improvement in FOGQ in FOG? patients was significantly correlated to the improvement in asymmetry of gait (Spearman R = 0.46, p = 0.013). Our data support a direct involvement of the asymmetry of gait in the development of FOG in PD. Treadmill training is effective in improving gait and balance in PD FOG? patients and this might be related to a reduction of asymmetric gait.

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials.... more

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are (1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; (2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and (3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent.

Objective: The diagnosis of multiple sclerosis (MS) rests on confirmation of central nervous system inflammatory disease that is disseminated in space and time, as evidenced clinically or by magnetic resonance imaging (MRI). The 2010... more

Objective: The diagnosis of multiple sclerosis (MS) rests on confirmation of central nervous system inflammatory disease that is disseminated in space and time, as evidenced clinically or by magnetic resonance imaging (MRI). The 2010 McDonald criteria simplified MRI requirements, and newly proposed that the criteria are also suitable for the diagnosis of pediatric MS. Methods: In a national prospective incident cohort study of children with acute demyelination observed for a minimum of 24 months, baseline and serial clinical and MRI examinations were used to retrospectively evaluate the 2010 and 2005 McDonald criteria using clinically relapsing disease as the gold standard. Results: Of 212 eligible participants, 34 experienced 2 or more clinical attacks, 58 met the 2010 criteria, and 42 met 2005 McDonald criteria. The 2010 criteria demonstrated high sensitivity (100%), specificity (86%), positive predictive value (76%), and negative predictive value (100%) for children older than 11 years with non-acute disseminated encephalomyelitis (ADEM) presentations, as did the 2005 McDonald criteria. In younger children with a non-ADEM presentation, PPV of the 2010 criteria was only 55%. None of the 50 children with ADEM met clinical criteria for MS, but 10 met 2010 and 4 met 2005 criteria. Interpretation: Both 2005 and 2010 McDonald criteria identify children with relapsing-remitting MS, although caution is suggested when applying these criteria in younger children. The 2010 McDonald criteria are simple and enable an early diagnosis of MS, but are not suited for application in the context of ADEM-like presentations. ANN NEUROL 2012;72:211-223 View this article online at wileyonlinelibrary.com. Additional supporting information can be found in the online version of this article. V C 2012 American Neurological Association 211

Objective: To discuss the American Academy of Neurology (AAN)'s Top Five Recommendations in the Choosing Wisely campaign promoting high-value neurologic medicine and physician-patient communication. The AAN published its Top Five... more

Objective: To discuss the American Academy of Neurology (AAN)'s Top Five Recommendations in the Choosing Wisely campaign promoting high-value neurologic medicine and physician-patient communication. The AAN published its Top Five Recommendations in February 2013 in collaboration with the American Board of Internal Medicine Foundation and Consumer Reports.

O n t a r i o , Canada Technetium-99m l a b e l l e d Salbutamol was administered through a tracheostomy t o v e n t i l a t e d r a b b i t s by e i t h e r an MDI (5 puffs,lOOpg/puff) aided with a s p a c e r (MV15 Aemhantber, T r u d e... more

O n t a r i o , Canada Technetium-99m l a b e l l e d Salbutamol was administered through a tracheostomy t o v e n t i l a t e d r a b b i t s by e i t h e r an MDI (5 puffs,lOOpg/puff) aided with a s p a c e r (MV15 Aemhantber, T r u d e l l , Canada) (Groupl, n=7); o r by n e b u l i z a t i o n (10DpgIkg i n 3ml Technetium-9% l a b e l l e d 5% albumin). Nebulization was c a r r i e d o u t f o r 20 min. with a J e t (Hudson, USA) (Group 2, n = l l ) o r U l t r a s o n i c d e v i c e (Siemens, Sweden) using e i t h e r a s t a n d a r d (Group 3, n=6) o r a small (Group 4, n=7) r e s e r v o i r .

Disruptive behavior can have a significant impact on care delivery, which can adversely affect patient safety and quality outcomes of care. Disruptive behavior occurs across all disciplines but is of particular concern when it involves... more

Disruptive behavior can have a significant impact on care delivery, which can adversely affect patient safety and quality outcomes of care. Disruptive behavior occurs across all disciplines but is of particular concern when it involves physicians and nurses who have primary responsibility for patient care. There is a higher frequency of disruptive behavior in neurologists compared to most other nonsurgical specialties. Disruptive behavior causes stress, anxiety, frustration, and anger, which can impede communication and collaboration, which can result in avoidable medical errors, adverse events, and other compromises in quality care. Health care organizations need to be aware of the significance of disruptive behaviors and develop appropriate policies, standards, and procedures to effectively deal with this serious issue and reinforce appropriate standards of behavior. Having a better understanding of what contributes to, incites, or provokes disruptive behaviors will help organizations provide appropriate educational and training programs that can lessen the likelihood of occurrence and improve the overall effectiveness of communication among the health care team.

Objective: To investigate the influence of aging on conventional MRI and magnetic resonance spectroscopy (MRS) findings of mucopolysaccharidosis (MPS) patients and to test the correlation of enzyme levels, urinary glycosaminoglycans... more

Objective: To investigate the influence of aging on conventional MRI and magnetic resonance spectroscopy (MRS) findings of mucopolysaccharidosis (MPS) patients and to test the correlation of enzyme levels, urinary glycosaminoglycans (GAG), and neuroimaging findings.