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Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials
(Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Tags: CORRECTIONS Source Type: research

Author response: Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology
We appreciate the comments of Machado et al. and Melegari et al. on our guideline, which provided recommendations to reduce brain injury following cardiopulmonary resuscitation (CPR).1 (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Geocadin, R. G., Wijdicks, E., Dubinsky, R. M., Ornato, J. P., Torbey, M. T., Suarez, J. I. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Letter Re: Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology
We read with interest the article by Geocadin et al.1 and found the conclusion of importance. Over the last 2 years, we observed a group of 32 patients treated with mild therapeutic hypothermia after an out-of-hospital nontraumatic cardiac arrest. When considering the effect of the cardiac arrest on the patients' subsequent outcomes in the short and middle term, a sharp difference between 2 conditions was observed. A cardiac arrest complicated by a not-shockable rhythm and a circulatory instability is usually accompanied by a worsening cerebral edema. These 2 signs, clearly connected to each other, are strong predictors of...
Source: Neurology - November 27, 2017 Category: Neurology Authors: Melegari, G., Barbieri, A., Manenti, A., Bertellini, E., Giuliani, E. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Letter Re: Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology
The American Academy of Neurology guidelines remarked on required recommendations to reduce brain injury after successful cardiopulmonary resuscitation (CPR).1 Nonetheless, it seems contradictory that prehospital cooling as an adjunct to therapeutic hypothermia (TH) is decidedly ineffectual in further improving neurologic outcome and survival.1 (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Machado, C., Estevez, M., Leisman, G. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Editors' Note
: In "Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology," the authors concluded that prehospital cooling did not improve neurologic outcome or survival in patients who subsequently underwent in-hospital therapeutic hypothermia. Drs. Machado et al. comment that studies in animals and of accidental hypothermia have shown a benefit to early hypothermia, and that, intuitively, any neuroprotective intervention should be initiated as soon as possible. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Alcauskas, M., Galetta, S. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Radiation-induced spinal nerve root cavernous malformations as a rare cause of radiculopathy
A 48-year-old man with Hodgkin lymphoma presented with insidious painless asymmetric ankle then thigh weakness 16 years after mantle-field radiation. EMG was consistent with a motor lumbosacral polyradiculopathy. CSF had 15 white blood cells/μL, protein 387 mg/dL, and normal glucose. Nodular enhancing lesions were seen on lumbar MRI (figure 1). Caudal root biopsy demonstrated mulberry-shaped vascular abnormalities (figure 2) and thickened endoneurial vessel walls without inflammation. Workup for leptomeningeal carcinomatosis and inflammatory and infectious disease was negative. High-dose steroids produced no clinical im...
Source: Neurology - November 27, 2017 Category: Neurology Authors: Rastogi, K., Klein, C. J., O'Toole, J. E., Jhaveri, M. D., Malik, R. Tags: MRI, All Clinical Neurology, All Neuromuscular Disease, All Oncology, All Spinal Cord NEUROIMAGES Source Type: research

Pyruvate dehydrogenase complex-E2 deficiency causes paroxysmal exercise-induced dyskinesia
We report a patient with intellectual disability and this unique phenotype associated with homozygous missense mutation in the DLAT gene (c.470T>G; p.Val157Gly) that encodes the E2 component of the pyruvate dehydrogenase complex (PDC). This case of PED associated with DLAT mutations broadens the phenotypic spectrum for this ultra-rare condition and widens the range of potentially treatable PEDs. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Friedman, J., Feigenbaum, A., Chuang, N., Silhavy, J., Gleeson, J. G. Tags: All Movement Disorders, Dystonia CLINICAL/SCIENTIFIC NOTES Source Type: research

Practice guideline: Cervical and ocular vestibular evoked myogenic potential testing: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology
Objective: To systematically review the evidence and make recommendations with regard to diagnostic utility of cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP, respectively). Four questions were asked: Does cVEMP accurately identify superior canal dehiscence syndrome (SCDS)? Does oVEMP accurately identify SCDS? For suspected vestibular symptoms, does cVEMP/oVEMP accurately identify vestibular dysfunction related to the saccule/utricle? For vestibular symptoms, does cVEMP/oVEMP accurately and substantively aid diagnosis of any specific vestibular disorder besides SCDS? Methods: The guideline pane...
Source: Neurology - November 27, 2017 Category: Neurology Authors: Fife, T. D., Colebatch, J. G., Kerber, K. A., Brantberg, K., Strupp, M., Lee, H., Walker, M. F., Ashman, E., Fletcher, J., Callaghan, B., Gloss, D. S. Tags: All Neurotology, Evoked Potentials/Visual, Evoked Potentials/Auditory SPECIAL ARTICLE Source Type: research

Low-dose aspirin and risk of intracranial bleeds: An observational study in UK general practice
Conclusion: Low-dose aspirin is not associated with an increased risk of any type of ICB and is associated with a significantly decreased risk of SAH when used for ≥1 year. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Cea Soriano, L., Gaist, D., Soriano-Gabarro, M., Bromley, S., Garcia Rodriguez, L. A. Tags: All Cerebrovascular disease/Stroke, Case control studies, Risk factors in epidemiology ARTICLE Source Type: research

Predicting clinical decline in progressive agrammatic aphasia and apraxia of speech
Conclusions: Rate of decline of each of the 4 clinical features assessed was associated with different baseline clinical and regional MRI predictors. Our findings could help improve prognostic estimates for these patients. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Whitwell, J. L., Weigand, S. D., Duffy, J. R., Clark, H. M., Strand, E. A., Machulda, M. M., Spychalla, A. J., Senjem, M. L., Jack, C. R., Josephs, K. A. Tags: Volumetric MRI, Prognosis, Dementia aphasia ARTICLE Source Type: research

Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study
Conclusions: Our prospective findings provide evidence for what may be an early contributory role of systemic inflammation in neurodegeneration and cognitive aging. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Walker, K. A., Hoogeveen, R. C., Folsom, A. R., Ballantyne, C. M., Knopman, D. S., Windham, B. G., Jack, C. R., Gottesman, R. F. Tags: MRI, All Immunology, All Medical/Systemic disease, Alzheimer's disease, Risk factors in epidemiology ARTICLE Source Type: research

Early weight loss in parkinsonism predicts poor outcomes: Evidence from an incident cohort study
Conclusion: Weight loss occurs in early parkinsonism and is greater in atypical parkinsonism than in PD. Early weight loss in parkinsonism has prognostic significance, and targeted dietary interventions to prevent it may improve long-term outcomes. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Cumming, K., Macleod, A. D., Myint, P. K., Counsell, C. E. Tags: Parkinson's disease/Parkinsonism, Prognosis, All epidemiology, Natural history studies (prognosis) ARTICLE Source Type: research

Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension
Conclusions: In chronic hemiparesis, single abobotulinumtoxinA (Dysport Ipsen) administration reduced muscle tone. Repeated administration over a year was well-tolerated and improved walking speed and likelihood of achieving community ambulation. Clinicaltrial.gov identifiers: NCT01249404, NCT01251367. Classification of evidence: The double-blind phase of this study provides Class I evidence that for adults with chronic spastic hemiparesis, a single abobotulinumtoxinA injection reduces lower extremity muscle tone. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Gracies, J.-M., Esquenazi, A., Brashear, A., Banach, M., Kocer, S., Jech, R., Khatkova, S., Benetin, J., Vecchio, M., McAllister, P., Ilkowski, J., Ochudlo, S., Catus, F., Grandoulier, A. S., Vilain, C., Picaut, P., On behalf of the International Abobotul Tags: Gait disorders/ataxia, Botulinum toxin, All Clinical trials ARTICLE Source Type: research

High risk of postpartum relapses in neuromyelitis optica spectrum disorder
Conclusions: The postpartum period is a particularly high-risk time for initial presentation of NMOSD. In contrast to published observations in multiple sclerosis, in neuromyelitis optica, relapse rate during pregnancy was also increased, although to a lesser extent than after delivery. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Klawiter, E. C., Bove, R., Elsone, L., Alvarez, E., Borisow, N., Cortez, M., Mateen, F., Mealy, M. A., Sorum, J., Mutch, K., Tobyne, S. M., Ruprecht, K., Buckle, G., Levy, M., Wingerchuk, D., Paul, F., Cross, A. H., Jacobs, A., Chitnis, T., Weinshenker, B Tags: Devic's syndrome ARTICLE Source Type: research

Monitoring disease activity in multiple sclerosis using serum neurofilament light protein
Objective: To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS). Methods: NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the UmanDiagnostics NF-light...
Source: Neurology - November 27, 2017 Category: Neurology Authors: Novakova, L., Zetterberg, H., Sundström, P., Axelsson, M., Khademi, M., Gunnarsson, M., Malmeström, C., Svenningsson, A., Olsson, T., Piehl, F., Blennow, K., Lycke, J. Tags: Cerebrospinal Fluid, Multiple sclerosis ARTICLE Source Type: research

Assessing association of comorbidities with treatment choice and persistence in MS: A real-life multicenter study
Objective: To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort. Methods: We included newly diagnosed patients (2010–2016) followed in 20 MS centers and collected demographic and clinical data. We evaluated baseline factors related to the presence of comorbidities and the association between comorbidities and the clinical course of MS and the time to the first treatment switch. Results: The study cohort included 2,076 patients. Data on comorbidities were available for 1,877/2,076 patients (90.4...
Source: Neurology - November 27, 2017 Category: Neurology Authors: Laroni, A., Signori, A., Maniscalco, G. T., Lanzillo, R., Russo, C. V., Binello, E., Lo Fermo, S., Repice, A., Annovazzi, P., Bonavita, S., Clerico, M., Baroncini, D., Prosperini, L., La Gioia, S., Rossi, S., Cocco, E., Frau, J., Torri Clerici, V., Signor Tags: Multiple sclerosis, All epidemiology ARTICLE Source Type: research

Increased relapse rate during pregnancy and postpartum in neuromyelitis optica
Neuromyelitis optica spectrum disorder (NMOSD) is a serious relapsing disease with a predilection for relapses in spinal cord and optic nerve. The presence of antibodies directed against the aquaporin-4 (AQP4) water channel has helped to distinguish NMOSD from multiple sclerosis (MS).1 A female preponderance exists in NMOSD and MS, although the overrepresentation of women in NMOSD is considerably greater, approaching a ratio of 8:1.2 The effect of pregnancy and the postpartum period on NMOSD disease expression and the effect of NMOSD on pregnancy outcomes are relatively unknown. In MS, reduced relapse rates during pregnanc...
Source: Neurology - November 27, 2017 Category: Neurology Authors: Banwell, B., Marrie, R. A. Tags: EDITORIALS Source Type: research

Comorbidities in MS are associated with treatment intolerance and disability
Since the 1990s, an increasing number of disease-modifying therapies (DMTs) have been approved to treat multiple sclerosis (MS), bringing increasing choice and efficacy. With this has come greater complexity for patients in what should be a shared decision-making process, involving oral treatment or injections, with varying frequency of administration and need for laboratory monitoring. Risks are variable, and efficacy may be also. The complexity increases for women in childbearing years. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: McDonnell, G. V., Cohen, J. A. Tags: EDITORIALS Source Type: research

Spotlight on the November 28 issue
(Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Gross, R. A. Tags: IN FOCUS Source Type: research

How comorbid conditions affect the choice of treatment in multiple sclerosis
A person can have more than one medical illness at the same time. For instance, a person could have headaches and also have low thyroid. In some cases, the medical illnesses are unrelated. In other instances, the comorbid illnesses occur together more often than by chance alone. In medicine, comorbid illnesses are very common. Many prior Patient Pages have discussed some of these associations. For people with multiple sclerosis (MS), having a comorbid medical condition is common. In some studies, 40%–66% of people with MS will also have another, associated, medical condition. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Karceski, S. Tags: All Demyelinating disease (CNS), Multiple sclerosis PATIENT PAGES Source Type: research

Teaching NeuroImages: Brain imaging findings in acute methanol toxicity
A 35-year-old man presented to the hospital in status epilepticus. CT of the head revealed bilateral basal ganglia hemorrhage (figure, A). Serum osmolality was elevated at 372 mmol/kg and methanol level was 34 mmol/L. He was admitted to the intensive care unit. MRI of the brain (figure, B–D) demonstrated extensive white matter diffusion restriction and basal ganglia hemorrhage. Care was withdrawn on postadmission day 6, with the patient dying shortly thereafter. Methanol toxicity classically presents with putaminal necrosis, presumed secondary to cellular hypoxia from formate-induced cytochrome oxidase inhibition.1 R...
Source: Neurology - November 27, 2017 Category: Neurology Authors: Anderson, D., Beecher, G., Emery, D., Khadaroo, R. G. Tags: CT, MRI, All Toxicology, Alcohol, Other toxicology RESIDENT & amp;amp; FELLOW SECTION Source Type: research

Mystery Case: A 61-year-old woman with lower extremity paralysis and sensory loss
A 61-year-old woman presented to the hospital with acute onset of numbness and weakness in the lower extremities. Her symptoms rapidly progressed, reaching maximal intensity within hours. She developed acute urinary retention but without bulbar or upper extremity involvement. There was no constitutional symptom or preceding trauma. Prior medical conditions included hypertension, hyperlipidemia, left-sided sciatica, and low back pain. Family history was unremarkable. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Manners, J., Jadhav, A. P., Xia, Z. Tags: All Clinical Neurology, All Spinal Cord, Arteriovenous malformation, Transverse myelitis RESIDENT AND FELLOW SECTION Source Type: research

The rest of the iceberg
The easily recognizable motor symptoms of Parkinson disease (PD) are just the tip of the iceberg. Beneath the surface lurk over 20 nonmotor symptoms ranging from nuisance to life-threatening. As anyone familiar with the fate of the Titanic can tell you, these are game changers. (Source: Neurology)
Source: Neurology - November 27, 2017 Category: Neurology Authors: Cook, D. G., Hall, K. W., Hall, L. L., Schmidt, T. A., Sumrall, M. A., Tuck, K. K. Tags: Parkinson's disease/Parkinsonism REFLECTIONS: NEUROLOGY AND THE HUMANITIES Source Type: research

Author response: Dementia risk in renal dysfunction: A systematic review and meta-analysis of prospective studies
We thank Prof. Kawada for the interest in our article,1 and agree that the exact mechanisms underlying the relationship between renal dysfunction and cognitive impairment or dementia are not fully understood. In our article, we discussed several suggested potential mechanisms.1 These might work additively, or synergistically, and include shared vascular risk factors or a direct effect of uremic toxins.1,2 (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Deckers, K., Camerino, I., van Boxtel, M. P. J., Verhey, F. R. J., Irving, K., Brayne, C., Kivipelto, M., Starr, J. M., Yaffe, K., de Leeuw, P. W., Köhler, S. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Letter re: Dementia risk in renal dysfunction: A systematic review and meta-analysis of prospective studies
Deckers et al.1 conducted random effects meta-analyses on the prospective association between potential markers of renal dysfunction and development of cognitive impairment or dementia. Pooled odds ratios (95% confidence intervals) of albuminuria and estimated glomerular filtration rate
Source: Neurology - November 20, 2017 Category: Neurology Authors: Kawada, T. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Author response: Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society
We wholeheartedly agree with the comments of Stanton et al. on our sudden unexpected death in epilepsy guideline article.1 (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Gloss, D., French, J. A., Hesdorffer, D. C., Smithson, W. H., Harden, C. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Letter re: Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society
The new guideline by the American Academy of Neurology (AAN) and the American Epilepsy Society (AES) on sudden unexpected death in epilepsy (SUDEP) is a landmark.1 The communication between medical professionals and patients about SUDEP risk remains unacceptably low. Tragically, family members often first learn about SUDEP after their loved one's death. Every patient and parent deserves to know the risks of epilepsy. For the first time, the AAN and AES recommend that neurologists inform them about SUDEP, the most common cause of epilepsy-related death.1 (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Stanton, T., Harding, R., Gattone, P., Friedman, D., Geiger, A., Devinsky, O., Rosbeck, K. L., Vogel-Farley, V., Meskis, M. A., Singer, A., Miller, A. B., Miller, I. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Editors' Note
: In the American Academy of Neurology and the American Epilepsy Society practice guideline on sudden unexpected death in epilepsy (SUDEP) incidence rates and risk factors, Harden et al. made recommendations to clinicians caring for people with epilepsy including the need to inform their patients about SUDEP, the most common cause of epilepsy-related death. Commenting on the guideline, Stanton et al. note that certain pediatric populations (children with Dravet syndrome, Dup15q syndrome) face a significantly higher risk of SUDEP. (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Karam, C., Griggs, R. C. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Quinidine-associated skin discoloration in KCNT1-associated pediatric epilepsy
A 9-month-old boy with migrating partial seizures of infancy due to a de novo KCNT1 mutation c.2278A>T (p.Ile760Phe) developed bluish discoloration of the hands, feet, and lips (figure) during a 9-month trial of quinidine (40 mg/kg/d; level 3.4 μg/mL).1 There was no exposure to other medications that cause pigmentary changes. Given minimal improvement in seizures and development, quinidine was stopped. Discoloration persisted at 3 months but markedly improved by the 6-month follow-up. Though common with other potassium channel blockers (ezogabine and quinine), such discoloration has only rarely been reported with qui...
Source: Neurology - November 20, 2017 Category: Neurology Authors: Baumer, F. M., Sheehan, M. Tags: Antiepileptic drugs NEUROIMAGES Source Type: research

TRMT5 mutations are associated with features of complex hereditary spastic paraparesis
Mitochondrial DNA (mtDNA) encodes for 22 tRNAs (mt-tRNA) that undergo posttranscriptional modification.1,2 A specific nucleotide adjacent to the anticodon of mt-tRNA (position 37) is methylated (m1G37) to enhance translational efficiency/fidelity.3 The gene tRNA methyltransferase 5 (TRMT5) encodes a protein involved in m1G37 formation for some mitochondrial tRNAs3,4 and has been associated with combined oxidative phosphorylation deficiency 26 (COXPD26) (OMIM 616539). (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Tarnopolsky, M. A., Brady, L., Tetreault, M., For the Care4Rare Canada Consortium Tags: Spastic paraplegia, Muscle disease, Mitochondrial disorders CLINICAL/SCIENTIFIC NOTES Source Type: research

Epidemiology of recurrent traumatic brain injury in the general population: A systematic review
Conclusions: rTBI is an important contributor to the general population TBI burden. Certain risk factors can help identify individuals at higher risk of these repeated injuries. However, higher quality research that improves on rTBI surveillance methodology is needed. (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Lasry, O., Liu, E. Y., Powell, G. A., Ruel-Laliberte, J., Marcoux, J., Buckeridge, D. L. Tags: All Trauma, Brain trauma, All epidemiology, Incidence studies, Risk factors in epidemiology VIEWS & amp;amp; REVIEWS Source Type: research

Caudate nucleus as a component of networks controlling behavior
The striatum participates in parallel corticobasal ganglia–thalamocortical loops interconnecting its different territories with areas of the frontal lobe, forming partially segregated motor, oculomotor, associative, and limbic circuits.1 Human studies using resting-state fMRI2–4 and diffusion tensor imaging5–10 confirm the presence of a functional parcellation of the human striatum, particularly the caudate nucleus,11 based on segregated corticostriatal connections. However, the corticostriatal connections are complex, and there are extensive interactions among functional territories.12 Furthermore, the d...
Source: Neurology - November 20, 2017 Category: Neurology Authors: Graff-Radford, J., Williams, L., Jones, D. T., Benarroch, E. E. Tags: CLINICAL IMPLICATIONS OF NEUROSCIENCE RESEARCH Source Type: research

Spaceflight-induced changes in white matter hyperintensity burden in astronauts
Conclusions: Long-duration exposure to microgravity is associated with an increase in periventricular WMH in astronauts. This increase was linked to an increase in ventricular CSF volume documented in ISS astronauts. There was no associated change in or abnormal levels of WMH volumes in deep white matter as reported in U-2 high-altitude pilots. (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Alperin, N., Bagci, A. M., Lee, S. H. Tags: MRI, Volumetric MRI, Case control studies ARTICLE Source Type: research

Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline
Objective: To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline. Methods: Amyloid-positive participants with AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSpMRI], limbic predominant [LPMRI], typical AD [tADMRI]) were defined according to an algorithm analogous to one recently propo...
Source: Neurology - November 20, 2017 Category: Neurology Authors: Risacher, S. L., Anderson, W. H., Charil, A., Castelluccio, P. F., Shcherbinin, S., Saykin, A. J., Schwarz, A. J., For the Alzheimer's Disease Neuroimaging Initiative Tags: MRI, Alzheimer's disease ARTICLE Source Type: research

Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration
Objectives: To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity. Methods: We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI...
Source: Neurology - November 20, 2017 Category: Neurology Authors: Weston, P. S. J., Poole, T., Ryan, N. S., Nair, A., Liang, Y., Macpherson, K., Druyeh, R., Malone, I. B., Ahsan, R. L., Pemberton, H., Klimova, J., Mead, S., Blennow, K., Rossor, M. N., Schott, J. M., Zetterberg, H., Fox, N. C. Tags: Alzheimer's disease ARTICLE Source Type: research

Multiparametric MRI changes persist beyond recovery in concussed adolescent hockey players
Conclusions: Changes persisted well after players' clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated. (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Manning, K. Y., Schranz, A., Bartha, R., Dekaban, G. A., Barreira, C., Brown, A., Fischer, L., Asem, K., Doherty, T. J., Fraser, D. D., Holmes, J., Menon, R. S. Tags: MRI, fMRI, MRS, DWI, Brain trauma ARTICLE Source Type: research

GABA alterations in pediatric sport concussion
Conclusions: GABA/Cre appears increased in a region colocalized with working memory task activation after sport concussion. Further work extending these results in larger samples and at time points across the injury episode will aid in refining the clinical significance of these observations. (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Friedman, S. D., Poliakov, A. V., Budech, C., Shaw, D. W. W., Breiger, D., Jinguji, T., Krabak, B., Coppel, D., Lewis, T. M., Browd, S., Ojemann, J. G. Tags: fMRI, MRS, Adolescence, Brain trauma ARTICLE Source Type: research

Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke
Conclusions: Global SVD burden is associated with increased BBB leakage in both acutely ischemic and nonischemic area. Our results support that SVD score has construct validity, and confirm a relation between SVD and BBB disruption also in patients with acute stroke. (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Arba, F., Leigh, R., Inzitari, D., Warach, S. J., Luby, M., Lees, K. R., On behalf of the STIR/VISTA Imaging Collaboration Tags: MRI, All Cerebrovascular disease/Stroke ARTICLE Source Type: research

Evolution of DWI lesions in cerebral amyloid angiopathy: Evidence for ischemia
Conclusions: Based on their neuroimaging signature as well as their association with chronic cortical CMIs, DWI lesions appear to have an ischemic origin and represent one part of the CMI spectrum. (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: van Veluw, S. J., Lauer, A., Charidimou, A., Bounemia, N., Xiong, L., Boulouis, G., Fotiadis, P., Ayres, A., Gurol, M. E., Viswanathan, A., Greenberg, S. M., Vernooij, M. W. Tags: DWI, Intracerebral hemorrhage ARTICLE Source Type: research

Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: A prospective study
Objective: In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci. Methods: Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0–4) showed excellent interrater reliability (k = 0.87). The association of cSS with m...
Source: Neurology - November 20, 2017 Category: Neurology Authors: Charidimou, A., Boulouis, G., Roongpiboonsopit, D., Auriel, E., Pasi, M., Haley, K., van Etten, E. S., Martinez-Ramirez, S., Ayres, A., Vashkevich, A., Schwab, K. M., Goldstein, J. N., Rosand, J., Viswanathan, A., Greenberg, S. M., Gurol, M. E. Tags: MRI, Cohort studies, Intracerebral hemorrhage ARTICLE Source Type: research

Neurofilaments in blood: (Almost) facing clinical application
Neurodegeneration is a critical pathophysiologic process of Alzheimer disease (AD) and related dementias, and correlates better with cognitive symptoms than the sole presence of pathologic proteins such as β-amyloid or α-synuclein. Thus, the identification of a biomarker that tracks with neurodegeneration is critical for following disease progression from the preclinical through the clinical phases and assessing rate of progression or therapeutic utility. The identification of a blood-based biomarker of neurodegeneration would be the Holy Grail. Compared to neuroimaging CSF collection, a blood draw is much less ...
Source: Neurology - November 20, 2017 Category: Neurology Authors: Mielke, M. M., Otto, M. Tags: EDITORIALS Source Type: research

Ischemic lesions and superficial siderosis in CAA: Partners in crime or innocent bystanders?
Cerebral amyloid angiopathy (CAA), first described in 1927 as a congophilic angiopathy associated with amyloid plaque in brains of patients with Alzheimer dementia,1 has an association with large and small intracranial hemorrhages (ICH). The differential diagnosis of ICH therefore includes CAA, especially in older patients or those without hypertension. The widely used Boston Criteria for diagnosis of CAA in vivo rely on the hemorrhagic characteristics of the disease.2 The pathophysiology of ICH in CAA remains uncertain. Thus, its prognosis, risk stratification, and clinical management present a challenge. Additional imagi...
Source: Neurology - November 20, 2017 Category: Neurology Authors: Marshall, R. S., Lioutas, V.-A. Tags: EDITORIALS Source Type: research

Spotlight on the November 21 issue
(Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Gross, R. A. Tags: IN FOCUS Source Type: research

Teaching NeuroImages: Myeloperoxidase-anti-neutrophil cytoplasmic antibody-positive hypertrophic pachymeningitis
A 49-year-old woman with chronic epistaxis presented with painless left monocular vision loss. Notable findings on examination of the left eye included visual acuity of 20/200 and relative afferent pupillary defect. MRI of the brain revealed enhancement of the left optic nerve sheath and diffuse dural thickening (figure). Laboratory workup yielded only lymphocytic pleocytosis (12 white blood cells) and positive serologies for perinuclear anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase (MPO) antibodies. Dural biopsy showed multifocal dense lymphoplasmacytic infiltration with vasculitis and reactive fi...
Source: Neurology - November 20, 2017 Category: Neurology Authors: Culbertson, C. J., Lummus, S. C., Gold, C. A. Tags: MRI, All Immunology, Vasculitis, All Neuro-ophthalmology, Optic nerve RESIDENT AND FELLOW SECTION Source Type: research

Clinical Reasoning: An 82-year-old man with worsening gait
An 82-year-old man with hypothyroidism presented with difficulty walking. (Source: Neurology)
Source: Neurology - November 20, 2017 Category: Neurology Authors: Chew, S., Vodopivec, I., Berkowitz, A. L. Tags: Autoimmune diseases, Gait disorders/ataxia, Stiff person syndrome RESIDENT AND FELLOW SECTION Source Type: research

Author response: Effects of orthostatic hypotension on cognition in Parkinson disease
We thank Guaraldi et al. for their comment on our article,1 and for drawing our attention to their work assessing cognitive function in patients with peripheral autonomic disorders, pure autonomic failure (PAF), and autoimmune autonomic neuropathy.2 The results in their study are similar to our results in Parkinson disease (PD),2 and to data we reported earlier on reversible cognitive impairment in individuals with orthostatic hypotension (OH) due to the peripheral disorder autoimmune autonomicganglionopathy.3 Cognitive changes in all of these studies are most significant in the domains of attention and executive functioni...
Source: Neurology - November 13, 2017 Category: Neurology Authors: Centi, J., Freeman, R., Gibbons, C. H., Neargarder, S., Canova, A. O., Cronin-Golomb, A. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Letter re: Effects of orthostatic hypotension on cognition in Parkinson disease
We read with interest the article by Centi et al.,1 which investigated the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in 18 patients with idiopathic Parkinson disease (PD) with OH (PDOH) and 19 patients with PD without OH and 18 controls.1 The authors demonstrated that, during upright posture, PDOH exhibited a transient wider range of deficits in executive function, memory, and visuospatial function in excess of those found in PD without OH. (Source: Neurology)
Source: Neurology - November 13, 2017 Category: Neurology Authors: Guaraldi, P., Poda, R., Calandra-Buonaura, G., Solieri, L., Sambati, L., Gallassi, R., Cortelli, P. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Author response: Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course analysis of CHANCE
We appreciate Drs. Gutierrez and Lekic's emphasis on the time-course analysis of dual antiplatelet therapy (DAPT) by intracranial arterial stenosis (ICAS) in their comments on our article.1 Only 1,089 patients were included in the imaging substudy.2 In patients with ICAS, 19 (8.2%), 3 (1.3%), and 0 ischemic strokes in the DAPT group (n = 231) vs 25 (10.0%), 6 (2.4%), and 0 in the aspirin alone group (n = 250), and 4 (1.7%), 0, and 2 (0.9%) bleeding in the DAPT group vs 1 (0.4%), 0, and 0 in the aspirin alone group, occurred at the first, second, and third week, respectively. In patients without ICAS, 11 (3.7%), 1 (0.3%), a...
Source: Neurology - November 13, 2017 Category: Neurology Authors: Pan, Y., Wang, Y., Wang, Y. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Letter re: Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course analysis of CHANCE
We read with interest the article by Pan et al.,1 which reported that the use of dual antiplatelet therapy (DAPT) showed an early benefit, compared to aspirin alone, for secondary ischemic stroke prevention after a minor stroke or TIA. The absolute risk reduction in the first week after the indexed event was 4.5%.1 The authors previously reported a nonsignificant absolute risk reduction in recurrent ischemic stroke of 2.3% with DAPT compared to aspirin alone in Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) participants with intracranial arterial stenosis (ICAS) over the 90-day fo...
Source: Neurology - November 13, 2017 Category: Neurology Authors: Gutierrez, J., Lekic, T. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research

Editors' Note
: In "Risks and benefits of clopidogrel–aspirin in minor stroke or TIA: Time course analysis of CHANCE," authors Pan et al. compared the use of dual antiplatelet therapy (DAPT) with aspirin alone for secondary stroke prevention in patients after a minor stroke or TIA. Drs. Gutierrez and Lekic point out that DAPT appeared to have a greater benefit than aspirin alone in patients with intracranial arterial stenosis (ICAS) in the first 2 weeks and ask the authors to provide a time-course analysis for the risk of ischemic stroke and hemorrhage by ICAS status. (Source: Neurology)
Source: Neurology - November 13, 2017 Category: Neurology Authors: Alcauskas, M., Galetta, S. Tags: WRITECLICK & amp;reg; EDITOR ' S CHOICE Source Type: research