Nonspecific White Matter Changes Research Articles

Differentiating multiple sclerosis from non-specific white matter changes using a convolutional neural network image classification model

BackgroundThe diagnosis of multiple sclerosis (MS) relies heavily on neuroimaging with magnetic resonance imaging (MRI) and exclusion of mimics. This can be a challenging task due to radiological overlap in several disorders and may require ancillary testing or longitudinal follow up. One of the most common radiological MS mimickers is non-specific white matter disease (NSWMD). We aimed to develop and evaluate models leveraging machine learning algorithms to help distinguish MS and NSWMD. MethodsAll adult patients who underwent MRI brain using a demyelinating protocol with available electronic medical records between 2015 and 2019 at Cleveland Clinic affiliated facilities were included. Diagnosis of MS and NSWMD were assessed from clinical documentation. Those with a diagnosis of MS and NSWMD were matched using total T2 lesion volume (T2LV) and used to train models with logistic regression and convolutional neural networks (CNN). Performance metrices were reported for each model. ResultsA total of 250 NSWMD MRI scans were identified, and 250 unique MS MRI scans were matched on T2LV. Cross validated logistic regression model was able to use 20 variables (including spinal cord area, regional volumes, and fractions) to predict MS compared to NSWMD with 68.0% accuracy while the CNN model was able to classify MS compared to NSWMD in two independent validation and testing cohorts with 77% and 78% accuracy on average. ConclusionAutomated methods can be used to differentiate MS compared to NSWMD. These methods can be used to supplement currently available diagnostic tools for patients being evaluated for MS.

Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions.

Adult-onset leukodystrophies though individually rare are not uncommon. This group includes several disorders with isolated adult presentations, as well as several childhood leukodystrophies with attenuated phenotypes that present at a later age. Misdiagnoses often occur due to the clinical and radiological overlap with common acquired disorders such as infectious, immune, inflammatory, vascular, metabolic, and toxic etiologies. Increased prevalence of non-specific white matter changes in adult population poses challenges during diagnostic considerations. Clinico-radiological spectrum and molecular landscape of adult-onset leukodystrophies have not been completely elucidated at this time. Diagnostic approach is less well-standardized when compared to the childhood counterpart. Absence of family history and reduced penetrance in certain disorders frequently create a dilemma. Comprehensive evaluation and molecular confirmation when available helps in prognostication, early initiation of treatment in certain disorders, enrollment in clinical trials, and provides valuable information for the family for reproductive counseling. In this review article, we aimed to formulate an approach to adult-onset leukodystrophies that will be useful in routine practice, discuss common adult-onset leukodystrophies with usual and unusual presentations, neuroimaging findings, recent advances in treatment, acquired mimics, and provide an algorithm for comprehensive clinical, radiological, and genetic evaluation that will facilitate early diagnosis and consider active treatment options when available. A high index of suspicion, awareness of the clinico-radiological presentations, and comprehensive genetic evaluation are paramount because treatment options are available for several disorders when diagnosed early in the disease course.

Structural Changes in Brain Magnetic Resonance Imaging Associated With Psychogenic Non-epileptic Seizures: An Analytical Cross-Sectional Study.

Background Psychogenic non-epileptic seizures (PNES) are often seen as indicators of poor motor and sensory function caused by psychological responses to stressful experiences. A seizure might trigger these reactions. The aim of our study was to assess the structural changes in brain MRI associated with psychogenic non-epileptic seizures. Methodology A retrospective analytical cross-sectional study at the Department of Medicine and Neurology, Ayub Teaching Hospital, Abbottabad, was conducted from October 2020 to September 2021. The medical records of patients with confirmed PNES were collected and retrospectively evaluated. Results Medical records and MRI scans were accessible for 52 patients with PNES; 10 patients were excluded from the study. The average age of the patients (standard deviation) was 34 (±9) years, and the average age at onset was 31.6 (±5.8) years. Based on the video-EEG recordings, 57.1% of patients (n=24) were classified as having broadly generalized motor seizures, 40% of patients (n=17) were classified as having predominantly akinetic seizures defined primarily by blank spells, and only one patient was classified as having focal motor seizures. Only three patients (7%) had a positive epilepsy family history. Twenty-four (47.6%) patients with brain MRI scans reported abnormal findings, while 22 (52.4%) had normal MRI findings. The majority of patients with abnormal MRIs had nonspecific white matter changes (50%), mesial temporal sclerosis (15%), and cysts (15%). In a statistical analysis, age at the beginning of PNES (p = 0.04), duration of PNES (p=0.01), concomitant epilepsy (p = 0.05), generalized motor seizures (p= 0.03), and focal motor seizures (p= 0.02) were strongly associated with abnormal brain MRI findings. Conclusion Research reveals that persons with PNES have a higher-than-average prevalence of anatomical brain abnormalities. The main takeaway is that these findings lend credence to the growing body of data suggesting that PNES may not be a medical mystery but rather a disorder with physical foundations in the brain. Important implications for diagnosing and treating PNES patients are discussed, as are the outcomes of earlier neuroimaging investigations of PNES. Studying the involvement of structural brain anomalies in the etiology of psychogenic non-epileptic seizures requires further well-designed multicenter studies with larger sample sizes and a consistent imaging approach (PNES). It is crucial to consider any confounding variables, such as co-occurring mental diseases, while designing this study.

Targeting the Diagnosis in an Adolescent with Epilepsy and Intellectual Disability through Next-Generation Metabolic Screening.

A 16-year-old boy, born to consanguineous parents in Syria and living as a refugee in the Netherlands since the age of 14 years, was admitted to our tertiary pediatric intensive care unit with status epilepticus after discontinuation of valproic acid. He was treated with valproic acid since early infancy for seizures of unknown cause, but as he had been seizure-free for many years, discontinuation was attempted. Brain magnetic resonance imaging showed nonspecific white matter abnormalities and changes attributable to prolonged seizures or meningitis, such as brain fullness with mildly effaced ventricles and mild meningeal enhancement in the precentral gyri. Chromosomal microarray analysis showed a normal XY profile. Biochemical screening for inherited metabolic disorders (IMD) was performed through next-generation metabolic screening (NGMS) (1), an ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (Agilent 6545 QTOF) metabolomics approach, validated under ISO15189 accreditation as first-tier diagnostic screening for IMD in our laboratory. In short, a panel of known IMD-related metabolites is filtered from the untargeted metabolomics data for initial diagnostic interpretation. For each patient, significantly altered metabolites are identified, and a semiquantitative fold change compared to controls is evaluated. The NGMS IMD-metabolite panel is frequently updated to include novel diagnostic metabolites encountered in the untargeted metabolomics data in a research setting. For example, the metabolites 2S, 6S- and 2S; 6R-oxopropylpiperidine-2-carboxylic acid; 6-oxopiperidine-2-carboxylic acid; and 6-(carboxymethyl)piperidine-2-carboxylic acid were recently added to the panel as novel biomarkers for pyridoxine dependent epilepsy due to deficiency of α-aminoadipic semialdehyde dehydrogenase, encoded by ALDH7A1 (PDE-ALDH7A1) (2, 3). PDE-ALDH7A1 is a defect in lysine catabolism (Fig. 1), leading to secondary deficiency of pyridoxine (vitamin B6) through complexation with accumulating piperideine-6-carboxylic acid.

Incidence of Stroke and Other Brain Imaging Findings in Adult Patients with Sickle Cell Disease: A Retrospective Study

Background: Vaso-occlusion and hemolytic anemia are the main features of sickle cell disease. Central Nervous system complications of sickle cell disease (SCD) can include silent cerebral infarcts (SCI), hemorrhagic or ischemic strokes, seizures and Moyamoya syndrome. SCI is the most common neurological complications in SCD. SCI patients have abnormal Magnetic Resonance Imaging (MRI) of the brain with normal neurological examination and no history of stroke. More precisely, Casella et al in the Silent Cerebral Infarct Multi-Center Clinical trial (SIT) defined infarct as MRI signal abnormality that was at least 3 mm in one dimension and that was visible in two planes on fluid-attenuated inversion recovery T2 -weighted images, as determined by agreement of two of the three study neuroradiologists. SCI in children is associated with lower Intelligence Quotient and increased risk of stroke.Methods: In this retrospective study we reviewed 100 adult patients at our Comprehensive Sickle Cell Center. We looked at the incidence of documented stroke and other neurological complications in SCD patients. We reviewed the hospital records of SCD patients for any incidental brain imaging (MRI brain or Computed Tomography(CT) brain) findings, done as inpatient or in the emergency room as part of hospital visits.Results: Out of the 100 patients, 14 patients had documented stroke. On the review of other 86 patients, 10 patients had MRI brain, 23 patients had CT brain, and 53 patients had no brain imaging record. Out of the 10 patients with MRI brain, 7 patient had significant findings- 3 patients had small vessel ischemic changes, 1 patient with chronic petechial hemorrhage of cerebellar vermis, 1 patient with ischemic changes and Chiari malformation type 1 (CTM 1), 1 patient with CTM 1 and non-specific white matter changes and 1 patient with CTM 1 alone. Out of the 22 CT of the brain and 1 CT angiogram of brain, 2 imaging showed ischemic changes and the angiogram showed large cerebral vessel narrowing. Therefore, on our review, 19 patients out of 100 were found to have stroke and 24 out of 100 had significant neurological findings. However, only 14 out of 19 patients had documented stroke. 7 out the 10 patients with MRI brain had significant incidental neurological findings. The number of adult SCD patients with neurological findings in our cohort could have been higher, if we had brain imaging record for the 53 other patients.Conclusion: This study shows that there is a heavy burden of neurological complications in SCD patients and SCI is under-diagnosed. MRI brain is superior to CT brain in detecting neurological complications in SCD patients. SIT showed that regular blood-transfusion significantly reduced the recurrence of cerebral infarct in children with SCI. Finding of SCI in adults also warrants consideration for follow up brain imaging, neurology referral and discussion of treatment modalities including chronic blood transfusion and hydroxyurea therapy. CTM 1 can also be associated with SCD. In CTM 1, tonsil herniates 5 millimeter or below foramen magnum. SCD may cause increased thickness of calvarium from extramedullary hematopoiesis in skull, which can result in cranio-cephalic disproportion with cerebellar ectopia and subsequent CTM 1. Because of high incidence of neurological complications in SCD patients, routine screening with MRI brain should be considered in adult SCD patients. DisclosuresIdowu: Forma Therapeutics, Inc.: Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ironwood: Research Funding.

Retinal haemorrhage in infants investigated for suspected maltreatment is strongly correlated with intracranial pathology

To test the two prevailing hypotheses regarding the aetiology of infant retinal haemorrhage: (a) traction forces exerted by the lens and/or corpus vitreum on the retina during infant shaking or (b) retinal vessel leakage secondary to intracranial pathology and raised intracranial pressure. Comparison of medical findings and reported type of trauma in infants investigated for suspected physical abuse with presence (n=29) or non-presence of retinal haemorrhage (RH) (n=119). Intracranial pathology was recorded in 15 (13%) of the non-RH cases and in 27 (97%) of the RH cases (p<0.0001). All 18 infants with bilateral RH had intracranial pathology. Of 27 infants subjected to witnessed or admitted shaking, two were in the group with RH. One had a single unilateral RH and no intracranial pathology. The other had bilateral RH and intracranial pathology with non-specific white matter changes, acute subdural and subarachnoid haemorrhages, and suspected cortical venous thrombosis. In 15 RH cases, there was no trauma reported and no findings other than RH and intracranial pathology. Accidental blunt head trauma was reported in 7 RH cases. The present study indicates that RH in infants is secondary to intracranial pathology of non-specific aetiology.

Reader Response: Early Postmortem Brain MRI Findings in COVID-19 Non-survivors.

I read the article by Coolen et al.1 with interest. The wide range of manifestations of the coronavirus disease 2019 (COVID-19) pandemic is not yet known. In their article, Coolen et al. reported 2 patients presenting with subcortical micro- and macrobleeds, 1 patient with cortico-subcortical edematous changes evocative of PRES, and the last patient presenting with nonspecific deep white matter changes. Multiple neuroradiologic patterns attributable to the coronavirus have been reported.2,3 Recently, various cerebral hemorrhagic disorders have been reported, including both intraparenchymal hemorrhages and diffuse microhemorrhages of the white matter. Extensive and isolated white matter microhemorrhages are found in patients hospitalized in intensive care units for various causes.4 Regarding PRES, it has been suggested that SARS-CoV-2 could act as a triggering factor for the development of rapid autoimmune and/or autoinflammatory dysregulation and lead to the endothelial dysfunction. The neuropathologic findings from the autopsies of 18 patients with COVID-19 infection from a recent article showed only hypoxic changes and did not show encephalitis or other specific brain changes referable to the virus.5 Considering this, the radiologic abnormalities reported by the authors do not appear to be related to encephalitis or vasculitis due to coronavirus but appear to be related to hypoxemia or autoinflammatory dysregulation.

A novel compound heterozygous mutation in MYSM1 gene in a 1-month-old girl: a bone marrow failure syndrome 4 family survey and literature review

目的报道1例MYSM1基因复合杂合变异致骨髓衰竭综合征4型患儿临床表现及全外显子检测结果，同时报道其家系全外显子检测结果，为早期诊断此类骨髓衰竭综合征提供典型案例。方法报道1例1月龄骨髓衰竭综合征4型患儿临床诊断过程，并对患儿及其家系成员外周血DNA进行全外显子测序，使用BWA、GATK等软件对测序结果进行注释分析。结果本例1月龄骨髓衰竭综合征4型患儿，表现为全血细胞减少、多指畸形，影像学示非特异性脑白质改变及囊肿，淋巴细胞亚群分类示CD3−CD19+ B细胞降低。通过家系全外显子测序检测，鉴定患儿携带分别遗传自父母的MYSM1基因复合杂合性变异NM_001085487.2:c.1607_c.1611delAAGAG和c.1432C>T。家系验证证实先证者父亲携带的c.1432C>T突变来源于先证者祖父，先证者母亲携带的c.1607_c.1611delAAGAG突变来自于先证者外祖父，其他家系成员均不携带突变。结论本研究新发现MYSM1致病性变异c.1607_c.1611delAAGAG，国内外尚未见报道。本例为BMFS4的早期诊断提供了典型案例，并扩展了MYSM1基因致病性变异谱和表型谱。

Brain MRI characteristics in neuromyelitis optica spectrum disorders: A large multi-center retrospective study in China

PurposeTo investigate the brain MRI features in neuromyelitis optica spectrum disorders (NMOSD) and its clinical relevance in a large multi-center cohort in China. Methods270 NMOSD patients were recruited from seven centers. The brain MRI were classified as normal, NMOSD-specific lesions, multiple sclerosis-like, nonspecific white matter changes. Brain volumes including whole brain, white, gray matter, cortex and subcortex gray matter volume were measured. The relationship between MRI measures, clinical disability and cognitive impairment were investigated. Results98 patients (36.3%) had normal brain MRI; 48 patients (17.7%) had NMOSD-specific lesions located in dorsal brainstem, corticospinal tract corpus, callosum and periependymal lesions surrounding the ventricular system; 16 patients (6%) had multiple sclerosis-like lesions; and 108 patients (40%) had nonspecific white matter changes. NMOSD patients with brain lesions had a trend of lower subcortex gray matter volume compared to patients without lesions. 52.5% patients with normal brain MRI and 50.8% patients with abnormal brain MRI showed cognitive impairment. No significant differences were identified in brain volume between cognitive impairment and cognitive preserved groups. ConclusionIn this large multicenter NMOSD cohort, nonspecific white matter changes were the most common findings (40%). NMOSD patients with brain lesions demonstrated a trend of having lower brain volume than patients without lesions. Approximately 50% NMOSD patients presented cognitive impairment independent of brain lesions.

Early postmortem brain MRI findings in COVID-19 non-survivors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuroinvasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. In this prospective, monocentric, case series study, consecutive patients who fulfilled the following inclusion criteria benefited from an early postmortem structural brain MRI: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest CT scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. Among the 62 patients who died of COVID-19 from March 31, 2020, to April 24, 2020, at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical microbleeds and macrobleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES; 1 decedent), and nonspecific deep white matter changes (1 decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed. Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. Brainstem MRI findings do not support a brain-related contribution to respiratory distress in COVID-19.

Combined Use of Clinical, Lesion Topography, and Thalamic Volume Helps Differentiating Multiple Sclerosis from its Mimickers

Early diagnosis of multiple sclerosis (MS) is important. Non-specific white matter changes usually confound earlier diagnosis. Cross-sectional, global and regional studies have shown that brain volume estimates are of diagnostic and prognostic relevance to the management of the disease; however, it did not reach an individual patient level of precision. We aimed to use both conventional (subjective lesion count) and advanced (brain volume and thalamic volume) magnetic resonance imaging (MRI) measures to investigate the ability of these measures to differentiate MS from other mimickers. Seventy MS patients and seventy-two age- and sex-matched healthy controls were recruited for this study. A third group of patients diagnosed with MS mimickers who presented with symptoms that might be attributed to MS, and had multiple white matter lesions was also included. Whole brain volume and thalamic volume were evaluated for all groups using FSL software pipelines (SIENAX and FIRST respectively). Z scores were calculated for brain and thalamic volume from healthy controls group and two standard deviations below the mean were considered the cut-off value for comparison. Brain and thalamic volumes differed significantly between the study groups. Brain volume correlated significantly with thalamic volume in healthy controls (p<0.00, r=0.59) and MS group (p<0.00, r=0.76), but not in the MS mimickers group (p=0.26, r=0.27). A significantly low brain volume was observed in 7 MS patients (10%) and a significantly low thalamic volume was observed in 15 MS patients (21%). Only one subject from MS mimickers group showed a significant low brain volume (5%); otherwise no significant thalamic atrophy was observed in this group. Thalamic and brain atrophy occur early in MS. Non-specific white matter changes do not contribute significantly to brain volume changes. Hemispheric volume changes may occur in MS mimickers but not particularly thalamic atrophy. Cross-sectional volumetric evaluation may add some valuable information in distinguishing MS patients from common radiological mimickers of the disease.

Peripheral facial nerve palsy

(A) Neurosarcoidosis. Addition information on work up includes blood work showing unremarkable basic metabolic panel, liver function, complete blood count with differential, and serum calcium levels. A serum angiotensin converting enzyme (ACE) level was 109 U/L (9–67 U/L). CSF ACE was 9 U/L (<15 U/L). The diagnosis of Neurosarcoidosis was made. Sarcoidosis is a multi-systemic granulomatous inflammatory disease of unknown etiology. Neurological involvement can occur in up to 5% of patients with sarcoidosis. The neurological manifestation can vary widely from cranial neuropathies such as optic neuritis and peripheral seventh nerve palsy to spinal cord involvement to meningeal disease [1Spiegel D. Morris K. Rayamajhi U. Neurosarcoidosis and the complexity in its differential diagnosis: a review.Innovat Clin Neurosci. 2012; 9: 10-16PubMed Google Scholar, 2Hoyle J.C. Jablonski C. Newton H. Neurosarcoidosis: clinical review of a disorder with challenging inpatient presentations and diagnostic considerations.Neurohospitalist. 2014; 4: 94-101Crossref PubMed Scopus (32) Google Scholar]. The diagnosis of neurosarcoidosis should be suspected in a patient with neurological symptoms who already has an established diagnosis of systemic or pulmonary sarcoid. MRI of the brain may show nonspecific white matter changes or hydrocephalus; however, with the administration of gadolinium contrast, enhancement of the cranial nerves, meninges or the hypothalamic-pituitary axis may be observed [[2]Hoyle J.C. Jablonski C. Newton H. Neurosarcoidosis: clinical review of a disorder with challenging inpatient presentations and diagnostic considerations.Neurohospitalist. 2014; 4: 94-101Crossref PubMed Scopus (32) Google Scholar]. Lastly, biopsy should be considered to confirm the diagnosis. In patients with neurological disease only, biopsy of the meninges or other enhancing lesions would be considered. In patients with systemic disease, biopsy can be obtained from involved skin, lymph node or lung using direct guidance, transbronchial biopsy, or CT-guided biopsy. CSF analysis consistent with neurosarcoidosis includes lymphocytic pleocytosis, elevated protein, oligoclonal bands, and elevated angiotensin converting enzyme (ACE) levels. CSF lymphocytic pleocytosis may occur in 31–83% of patients, elevated protein may be seen in 41–83%, and oligoclonal bands may be found in 27–37% of patients with neurosarcoidosis. An elevated CSF angiotensin converting enzyme (ACE) levels is not highly sensitive but is relatively specific: it also can be elevated in carcinomatosis and infections of the central nervous system [[3]Ibitoye R.T. Wilkins A. Scolding N.J. Neurosarcoidosis: a clinical approach to diagnosis and management.J Neurol. 2017; 264: 1023-1028Crossref PubMed Scopus (48) Google Scholar]. Fluorodeoxyglucose positron emission tomography scan may also be considered to rule out systemic areas of involvement in patients who have not manifested with systemic symptoms. Patient’s history and symptoms were most consistent with the diagnosis of neurosarcoidosis especially considering the results discussed above. In this case, Bell’s palsy, multiple sclerosis, neuroborreliosis, and Ramsay-Hunt were less likely given patient’s presenting symptoms and diagnostic workup. Bell’s palsy is a diagnosis of idiopathic peripheral facial nerve palsy. Serum and CSF Lyme testing was negative and patient had denied exposure to tick bite thus ruling out peripheral facial nerve palsy secondary to lyme. Similarly, Ramsay-Hunt was unlikely as there was no ear pain and CSF was negative for VZV and HSV PCR. MRI findings of the brain did not reveal FLAIR-T2 hyperintensities to support diagnosis of multiple sclerosis. The following are the Supplementary data to this article: Download .xml (.0 MB) Help with xml files Supplementary data 1 Peripheral facial nerve palsyJournal of Clinical NeuroscienceVol. 69PreviewA 44 year-old right-handed female with a past medical history of hypothyroidism presented with a left facial droop and dysgeusia. In the weeks prior, she had experienced intermittent diplopia, transient decreased left eye visual acuity, frontal headache, and nausea without vomiting. The patient’s history was also notable for dyspnea, fever, night-sweats, myalgia, nonproductive cough, and wheezing for two months, with unintentional 10 lb weight loss. The patient was undergoing workup for these symptoms that to date had revealed 3 sub-centimeter right upper lobe lung nodules and mediastinal and hilar lymphadenopathy. Full-Text PDF

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

EEG in Sarcoidosis Patients Without Neurological Findings

Sarcoidosis is a multisystem granulomatous disease affecting nervous system in 5% to 10% of patients. Magnetic resonance imaging (MRI) is accepted as the most sensitive method for detecting neurosarcoidosis. However, the most common findings in MRI are the nonspecific white matter lesions, which may be unrelated to sarcoidosis and can occur because of hypertension, diabetes mellitus, smoking, and other inflammatory or infectious disorders, as well. Autopsy studies report more frequent neurological involvement than the ante mortem studies. The aim of this study is to assess electroencephalography (EEG) in sarcoidosis patients without neurological findings in order to display asymptomatic neurological dysfunction. We performed EEG on 30 sarcoidosis patients without diagnosis of neurosarcoidosis or prior neurological comorbidities. Fourteen patients (46.7%) showed intermittant focal and/or generalized slowings while awake and not mentally activated. Seven (50%) of these 14 patients with EEG slowings had nonspecific white matter changes while the other half showed EEG slowings in the absence of MRI changes. We conclude that EEG slowings, when normal variants (psychomotor variant, temporal theta of elderly, frontal theta waves) are eliminated, may be an indicator of dysfunction in brain activity even in the absence of MRI findings. Hence, EEG may contribute toward detecting asymptomatic neurological dysfunction or probable future neurological involvement in sarcoidosis patients.

Evaluation of Pre-Hematopoietic Cell Transplantation (HCT) Brain MRI and Neurologic Complications of Pediatric Patients Undergoing HCT for Hematologic Malignancies.

Adverse neurologic complications (NC) occur commonly in pediatric patients with hematologic malignancies both pre- and post-allogeneic hematopoietic cell transplant (HCT). Given this known risk, we previously obtained pre-HCT brain magnetic resonance imaging (MRI) to document baseline abnormalities but utility of this and findings are not well described. This study aimed to ( a) determine the prevalence and risk factors for abnormal brain MRI and ( b) determine prevalence and risk factors for development of new NC during and 2 years post-HCT. Retrospective chart review included 102 patients with hematologic malignancies who underwent allogeneic HCT between 2000 and 2009 at University of California San Francisco (UCSF) Children's Hospital and included standard HCT data, brain MRI reports, and NC and symptoms pre- and post-HCT. Forty-three percent of patients had abnormal findings on pre-MRI, most commonly nonspecific white matter changes. Neurologic symptoms pre-HCT was the only significant risk factor for abnormal MRI. Eleven patients (11%) developed post-HCT NC. Non-Caucasian race was the only significant risk factor for new NC. Although abnormal pre-HCT brain MRI is common, these findings are not predictive of subsequent NC post-HCT. Therefore routine surveillance may not be informative for that purpose, particularly when general anesthesia is required, which can have detrimental neurocognitive effects. Etiology of NC in pediatric HCT is likely multifactorial and may include genetic and ethnic predispositions.

MULTIMODAL NEUROREHABILITATION AND CLINICAL NUTRITION PROGRAM IMPROVE PURSUITS AND DRIVING ABILITY IN 69 YEAR OLD FEMALE

Event Abstract Back to Event MULTIMODAL NEUROREHABILITATION AND CLINICAL NUTRITION PROGRAM IMPROVE PURSUITS AND DRIVING ABILITY IN 69 YEAR OLD FEMALE David J. Clark1* 1 Carrick Institute of Clinical Neuroscience and Rehabilitation, United States Background: A 69 year old woman presented with chief complaints of difficulty moving the left leg during walking, subjective problems with maintaining balance, back and hip pain, and difficulty driving. Symptoms began twelve years prior subsequent to a fall and head injury. MRI one year prior to presentation discovered extensive and non-specific white matter changes likely secondary to small vessel ischemic disease. Methods: Neurological examination revealed freezing during dual tasking of gait, Grade 2 on the Unified Parkinson’s Disease Rating Scale (UPDRS) on the left side during finger tapping and fist making tests, small amplitude titubation, normal strength and sensation in all 4 limbs. VNG testing revealed large amplitude square wave jerks with a right bias, saccadic horizontal pursuits with gains as follows: 0.1 Hz 0.66, at 0.2 Hz 0.77, and at 0.4 Hz 0.58. VNG showed saccadic vertical pursuits with gains as follows: at 0.1 Hz 0.63, at 0.2 Hz 0.40 and 0.4 Hz 0.22. Patient was treated with a three day multimodal rehabilitation program utilizing a gap stimulus and small amplitude saccades. Then, for two weeks the patient was placed on an anti-inflammatory diet, and supplement protocol featuring turmeric, resveratrol and omega fatty acids. Results: After the initial three days of treatment the horizontal pursuit gains had changed to the following: at 0.1 Hz 62, at 0.2 Hz 75 and at 0.4 Hz 0.73. The amplitude of the square wave jerks had decreased. After two weeks of the anti-inflammatory diet and supplementation the horizontal pursuit gains had improved as follows: at 0.1 Hz 0.82, at 0.2 Hz 0.74, at 0.4 Hz 0.72. The frequency of the square wave jerks was unchanged but the amplitude was smaller than before treatment. The patient reported that driving was no longer difficult. Patient did not exhibit freezing during dual tasking of gait. Fist making and finger tapping tests were Grade 1 UPDRS. Conclusion: The author suggests further investigation into the combination of multimodal forms of neurorehabilitation with anti-inflammatory diet and supplementation in the treatment of patients with saccadic pursuits and square wave jerks subsequent to head injury. Keywords: smooth pursuit eye movements, Head injury, Gait Disorders, Neurologic, Square wave jerks, driving Conference: International Symposium on Clinical Neuroscience: Clinical Neuroscience for Optimization of Human Function, Orlando, United States, 7 Oct - 9 Oct, 2016. Presentation Type: Poster Presentation Topic: Abstracts ISCN 2016 Citation: Clark DJ (2016). MULTIMODAL NEUROREHABILITATION AND CLINICAL NUTRITION PROGRAM IMPROVE PURSUITS AND DRIVING ABILITY IN 69 YEAR OLD FEMALE . Front. Neurol. Conference Abstract: International Symposium on Clinical Neuroscience: Clinical Neuroscience for Optimization of Human Function. doi: 10.3389/conf.fneur.2016.59.00062 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 01 Sep 2016; Published Online: 07 Sep 2016. * Correspondence: Dr. David J Clark, Carrick Institute of Clinical Neuroscience and Rehabilitation, Cape Canaveral, FL, United States, mail@doctordavidclark.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers David J Clark Google David J Clark Google Scholar David J Clark PubMed David J Clark Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

More clinical observations on migraine associated with monocular visual symptoms in an Indian population.

Context:Retinal migraine (RM) is considered as one of the rare causes of transient monocular visual loss (TMVL) and has not been studied in Indian population.Objectives:The study aims to analyze the clinical and investigational profile of patients with RM.Materials and Methods:This is an observational prospective analysis of 12 cases of TMVL fulfilling the International Classification of Headache Disorders-2nd edition (ICHD-II) criteria of RM examined in Neurology and Ophthalmology Outpatient Department (OPD) of Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh from July 2011 to October 2012.Results:Most patients presented in 3rd and 4th decade with equal sex distribution. Seventy-five percent had antecedent migraine without aura (MoA) and 25% had migraine with Aura (MA). Headache was ipsilateral to visual symptoms in 67% and bilateral in 33%. TMVL preceded headache onset in 58% and occurred during headache episode in 42%. Visual symptoms were predominantly negative except in one patient who had positive followed by negative symptoms. Duration of visual symptoms was variable ranging from 30 s to 45 min. None of the patient had permanent monocular vision loss. Three patients had episodes of TMVL without headache in addition to the symptom constellation defining RM. Most of the tests done to rule out alternative causes were normal. Magnetic resonance imaging (MRI) brain showed nonspecific white matter changes in one patient. Visual-evoked potential (VEP) showed prolonged P100 latencies in two cases. Patent foramen ovale was detected in one patient.Conclusions:RM is a definite subtype of migraine and should remain in the ICHD classification. It should be kept as one of the differential diagnosis of transient monocular vision loss. We propose existence of “acephalgic RM” which may respond to migraine prophylaxis.

MRI features in 17 patients with l2 hydroxyglutaric aciduria

l-2-Hydroxyglutaric (l-2-HG) aciduria is a rare inherited metabolic disease usually observed in children. Patients present a very slowly progressive deterioration with cerebellar ataxia, mild or severe mental retardation, and various other clinical signs including extrapyramidal and pyramidal symptoms, and seizures Goffette et al. [1]. This leukencephalopathy was first described in 1980 Duran et al. [2]. Brain magnetic resonance imaging (MRI) demonstrates nonspecific subcortical white matter (WM) loss, cerebellar atrophy and changes in dentate nuclei and putamen Steenweg et al. [3]. The diagnosis is highlighted by increased levels of l-2-HG in body fluids such as urine and cerebrospinal fluid.The purpose of this study is to retrospectively describe the brain MRI features in l-2-HG aciduria.

P86. Epilepsy associated with autoimmune encephalitis with DPPX and aquaporin-4 antibodies

Various new antibodies (abs) that target surface neuronal antigens have been recently discovered. This has led to a new interpretation of Autoimmune Encephalitis (AE). These Encephalitis syndromes are less often associated with cancer and respond well to treatment with immunotherapy in comparison to encephalitis associated with antibodies against intracellular structures. Literature describes 4 cases of AE with auto-abs against neuronal surface protein dipeptidyl-peptidase-like protein-6 (DPPX), a subunit of the Kv4.2 potassium channels. All patients exhibited similar symptoms including subacute onset of progressive cognitive dysfunction, agitation, myoclonic jerks, resting tremor, hyperreflexia and seizures. Pleocytosis (11–117/μl) in cerebrospinal fluid (CSF) withintrathecal production of IgG or oligoclonal bands (OCBs) was confirmed. 3 patients developed severe diarrhoea andweight loss. MRIs of brain revealed nonspecific white matter changes (Boronat et al., 2013; Suchecki et al., 2014). 3 new cases of DPPX auto-abs associated with progressive encephalomyelitis withrigidity and myoclonus were published in 2014(Balint, 2014). Guiding symptoms were cerebellar ataxia with hyperreflexia andtrunk stiffness. We present a 65years old female patient with initial progressive affective dysfunction, loss of drive and interests andshort-term memorydysfunction. Later on, dyscognitive seizures and resting tremor with fluctuating myoclonic jerks evolved. At admission to the hospital patient had almost no recollection of the last three months. MRI showednonspecific changes in white matter. EEG demonstrated pronounced IRDAs. In CSF 4 white blood cells with intrathecal production of IgG und OCBs were detected.Additionally Hashimoto-thyroiditis was observed.With a cell-based assay and immunofluorescence DPPX-abs in serum (titer 1:3,000,000) and CSF (1:200) were detected. Further serum analysis revealed positive aquaporin-4-abs (titer 1:375). Due to seizures and myoclonic jerks levetiracetam was started. On prolonged oral prednisolon therapy (100mg daily over 3months, currently reduced to 50mg daily) patient achieved progressive improvement of neurologic impairments. In rehabilitation immunosuppression with azathioprine had been started. As a result of this treatment, patient remains stable. A tumor search was inconclusive. In summary, recently described abs against DPPX were evaluated as a cause of patient's symptoms. Moreover, aquaporin-4-abs, which are held specific for neuromyelitis optica, were detected before any evidence of NMO and may be interpreted along with Hashimoto-thyroiditis as a propensity to autoimmune diseases. It is possible that aquporin-4-abs are presentyears before the NMO onset. Cooccurrence of these two rare abs with focus on central nervous system has not yet been described. Reports of coexistence of NMO and autoimmune diseases, which affect the peripheral nervous system (e.g. Myasthenia gravis ) or diseases of rheumatic origin (e.g. Sjogren-Syndrome) were already published.

The impact of different aetiologies on the cognitive performance of frontal patients

Neuropsychological group study methodology is considered one of the primary methods to further understanding of the organisation of frontal ‘executive’ functions. Typically, patients with frontal lesions caused by stroke or tumours have been grouped together to obtain sufficient power. However, it has been debated whether it is methodologically appropriate to group together patients with neurological lesions of different aetiologies. Despite this debate, very few studies have directly compared the performance of patients with different neurological aetiologies on neuropsychological measures. The few that did included patients with both anterior and posterior lesions.We present the first comprehensive retrospective comparison of the impact of lesions of different aetiologies on neuropsychological performance in a large number of patients whose lesion solely affects the frontal cortex. We investigated patients who had a cerebrovascular accident (CVA), high (HGT) or low grade (LGT) tumour, or meningioma, all at the post-operative stage. The same frontal ‘executive’ (Raven's Advanced Progressive Matrices, Stroop Colour-Word Test, Letter Fluency-S; Trail Making Test Part B) and nominal (Graded Naming Test) tasks were compared. Patients' performance was compared across aetiologies controlling for age and NART IQ scores. Assessments of focal frontal lesion location, lesion volume, global brain atrophy and non-specific white matter (WM) changes were undertaken and compared across the four aetiology.We found no significant difference in performance between the four aetiology subgroups on the ‘frontal’ executive and nominal tasks. However, we found strong effects of premorbid IQ on all cognitive tasks and robust effects of age only on the frontal tasks. We also compared specific aetiology subgroups directly, as previously reported in the literature. Overall we found no significant differences in the performance of CVA and tumour patients, or LGT and HGT patients or LGT, HGT and meningioma's on our four frontal tests. No difference was found with respect to the location of frontal lesions, lesion volume, global brain atrophy and non-specific WM changes between the subgroups.Our results suggest that the grouping of frontal patients caused by different aetiologies is a pragmatic, justified methodological approach that can help to further understanding of the organisation of frontal executive functions.