bluuebunny/crossref_metadata_2025 huggingface dataset:
Malaysian Siblings with Friedreich Ataxia and Chorea: A Novel Deletion in the Frataxin Gene
Authors: Spacey Siân D. , Szczygielski Blazej I. , Young Sean P. , Hukin Juliette , Selby Kathy , Snutch Terrance P.
Published: December 2014

Background:

Friedrich ataxia (FRDA1) is most often the result of a homozygous GAA repeat expansion in the first intron of the frataxin gene (FRDA gene). This condition is seen in individuals of European, North African, Middle Eastern and Indian descent and has not been reported in Southeast Asian populations. Approximately 4% of FRDA1 patients are compound heterozygotes. These patients have a GAA expansion on one allele and a point mutation on the other and have been reported to have an atypical phenotype.

Objective:

To describe a novel dinucleotide deletion in the FRDA gene in two Malaysian siblings with FRDA1.

Setting:

Tertiary referral university hospital setting. Patients and

Methods:

A previously healthy 10-year-old Malaysian boy, presented with fever, lethargy, headaches, dysarthria, dysphagia, vertigo and ataxia which developed over a one week period. His neurological exam revealed evidence of dysarthria and ataxia, mild generalized weakness and choreoform movements of the tongue and hands. His reflexes were absent and Babinski sign was present bilaterally. A nine-year-old sister was found to have mild ataxia but was otherwise neurologically intact.

Results:

Molecular genetic studies demonstrated that both siblings were compound heterozygotes with a GAA expansion on one allele and a novel dinucleotide deletion on the other allele.

Conclusion:

We describe a novel dinucleotide deletion in the first exon of the FRDA gene in two siblings with FRDA1. Additionally this is the first report of FRDA1 occurring in a family of southeast Asian descent, it demonstrates intrafamilial phenotypic variability, and confirms that atypical phenotypes are associated with compound heterozygosity.
Modafinil in Endozepine Stupor. A Case Report
Authors: Scott Sharon , Ahmed Iftekhar
Published: December 2014

Background:

Endozepine-4 stupor is a rare disorder. It presents with recurrent episodes of stupor and coma. Endozepine-4 levels are elevated during an attack with electroencephalogram showing fast activity during the ictal phase. There is no specific treatment and various drugs have been tried without long-term benefit.

Method:

We used the vigilance promoting drug modafinil to prevent such attacks in a case presented with endozepine stupor.

Results:

The vigilance promoting drug modafinil prevented recurrent episodes of stupor and coma in this patient at a dose of 200 mg/day for a period of six months. Upon withdrawal of the drug, the patient experienced recurrent episodes and on reinstitution of modafinil she has remained asymptomatic in the following one year.
Prognostic Value of Evoked Responses and Event-Related Brain Potentials in
Authors: Wang Jing Tian , Young G. Bryan , Connolly John F.
Published: December 2014

The behaviourally unresponsive patient, unable to exhibit the presence of cognition, constitutes a conundrum for health care specialists. Prognostic uncertainty impedes accurate management decisions and the application of ethical principles. An early, reliable prognosis is highly desirable. In this review investigations studying comatose patients with coma of different etiologies were selected. It is concluded that objective prognostication is enhanced by the use of electrophysiological tests. Persistent abnormalities of brainstem auditory evoked potentials and short-latency somatosensory evoked potentials reliably indicate the likelihood of irreversible neurological deficit or death. Meanwhile, the presence of “cognitive” event-related brain potentials (e.g., P300 and mismatch negativity) reflects the functional integrity of higher level information processing and, therefore, the likelihood of capacity for cognition. An approach that combines clinical and electrophysiological values provides optimal prediction of outcome and level of disability.
Standardized Finger-Nose Test Validity for Coordination Assessment in an Ataxic Disorder
Authors: Gagnon Cynthia , Mathieu Jean , Desrosiers Johanne
Published: December 2014

Objectives:

Evaluation of coordination with the Finger-Nose Test is an essential part of the neurological examination. This study explored the convergent and discriminant construct validity of the Standardized Finger-Nose Test (SFNT) in a neuromuscular disorder with ataxic features.

Method:

A cross-sectional study was carried out with 24 participants with recessive spastic ataxia of Charlevoix-Saguenay. Convergent construct validity was tested by correlating the SFNTwith other upper extremity function tests, a functional independence measure and social participation. Upper extremity function tests included gross and fine dexterity (Box and Block Test and Purdue Pegboard), upper extremity strength (dynamometry) and global upper extremity performance (TEMPA). The Functional Independence Measure (FIM) and the Assessment of Life Habits scale (LIFE-H) measured functional independence and social participation respectively. Discriminant construct validity was explored by comparing performance on the SFNT between two age groups (< 40 years and ³ 40 years).

Results:

Convergent validity of the SFNT was demonstrated by moderate to strong correlations with gross and fine finger dexterity (r = 0.82-0.84), global upper extremity performance (0.74-0.79), functional independence (r = 0.74) and social participation (r = 0.78). Upper extremity coordination of the older group was significantly lower than in the younger group, suggesting the ability of the SFNT to discriminate between different levels of function.

Conclusion:

This study demonstrated the convergent and discriminant construct validity of the SFNT in a neuromuscular disorder with ataxic features.
Localization of Nestin in Amygdaloid Kindled Rat: An Immunoelectron Microscopic Study
Authors: Nakagawa Toshitaka , Miyamoto Osamu , Janjua Najma A. , Auer Roland N. , Nagao Seigo , Itano Toshifumi
Published: December 2014

Background:

Nestin is a class VI intermediate filament protein, expressed during early embryonic development in mammals. Postnatally, nestin and its mRNA are down-regulated and gradually disappear. Recently, nestin expression has been detected in the adult nervous system, and it has been suggested that this protein may be related to neurogenesis, although, its role in the mechanism of neurogenesis is not known.

Methods:

The present study examined the localization of nestin in CNS tissue of the amygdaloid kindled rat by light and electron microscopy.

Results:

Kindled animals showed nestin expression mainly in the piriform cortex and the perirhinal cortex. By light microscopy, nestin was shown to be expressed in astrocytes, neurons, and endothelial cells. Electron microscopy demonstrated nestin expression in endothelial cells, astrocytic perivascular end feet, the rare pericyte, neurons and oligodendrocytes.

Conclusion:

We conclude that epilepsy causes widespread nestin expression in many cell types in the CNS, including non-neural cells.
Cowden Disease with Lhermitte-Duclos Disease: Case Report
Authors: Prabhu Sujit S. , Aldape Kenneth D. , Bruner Janet M. , Weinberg Jeffrey S. , Weinberg Jeffrey S.
Published: December 2014

Background:

We report a case and review the recent literature describing 36 patients with both Lhermitte-Duclos disease (LDD) and Cowden disease (CD). Lhermitte-Duclos disease, or dysplastic gangliocytoma, is a benign hamartomatous condition involving the cerebellum. The presenting symptoms are usually headaches, gait ataxia, and symptoms of lower cranial nerve involvement. Cowden disease is a rare autosomal dominant disease that usually presents with multiple mucocutaneous lesions. Patients with CD are prone to multiple systemic malignancies, the most common of which is breast cancer. Recent studies have demonstrated an association between LDD and CD.

Methods:

A 44-year-old woman with a previous history of breast cancer, multiple benign skin lesions, Hashimoto's thyroiditis, and chronic headaches presented with exacerbation of her headaches during the previous year. Magnetic resonance imaging of the brain revealed a right cerebellar nonenhancing mass and an acquired tonsillar herniation.

Results:

The patient underwent resection of the right cerebellar mass, posterior fossa decompression, C1 and C2 laminectomies, and a duraplasty. Pathologic examination confirmed LDD. The patient recovered well after surgery, with immediate improvement of her headaches.

Conclusion:

The association between LDD and CD has been under-recognized and under-reported. Recognition of this association has direct clinical relevance, because diligent monitoring of individuals with LDD and CD may lead to the early detection of systemic malignancies.
Fourth Ventricular Neurocytoma: Case Report and Review of the Literature
Authors: Cook Douglas J. , Christie Sean D. , Macaulay Robert J.B. , Rheaume Dorianne E. , Holness Renn O.
Published: December 2014

Objectives:

Central neurocytoma is a tumour that typically occurs in young adults in close association with the lateral and third ventricles of the cerebrum.

Methods:

We report the unusual case of a central neurocytoma that developed in the fourth ventricle of a 59-year-old woman and metastasized to the upper cervical canal. Subtotal excision and adjuvant radiotherapy were used to treat the lesion. Microscopic evaluation, discussion of the pathologic differential diagnosis and theories of the histogenesis of the tumour are presented. Results and

Conclusion:

Fourth ventricular neurocytoma is rare and has only been reported twice previously. It appears most likely that this tumour arises from subependymal progenitor cell lines.
Progress in Clinical Neurosciences: Cognitive Markers of Progression in Alzheimer's Disease
Authors: Behl Pearl , Stefurak Taresa L. , Black Sandra E.
Published: December 2014

The objective of this review is to summarize the literature on Alzheimer's disease progression utilizing cognitive batteries to track change over time. Studies published in English and obtained through PubMed searches (1983-2004) were included i) if they had a longitudinal design and followed probable Alzheimer's patients diagnosed by National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association or Diagnostic and Statistical Manual III/IV criteria, and ii) if the techniques used for serial assessment were well-established in terms of validity and reliability. Longitudinal studies examining Alzheimer's disease progression report highly variable annual rates of change in decline rate. It remains unclear if this reflects disease subgroups or stage-related rate of decline. In conclusion a combination of stage-appropriate cognitive tests such as the Mattis Dementia Rating Scale and the Severe Impairment Battery, along with appropriate statistical methods to account for individual variability in decline rates, can capture the progression of Alzheimer disease and may be useful in further investigation.
HIV-Related Neurological Syndromes Reduce Health-Related Quality of Life
Authors: Pandya Rupang , Krentz Hartmut B. , Gill M. John , Power Christopher , Gill M. John
Published: December 2014

Background:

Human immunodeficiency virus (HIV) infection frequently results in neurological complications but the impact of different neurological syndromes on patients' quality of life remains unknown.

Methods:

We investigated health-related quality of life (HRQoL) parameters among HIV/Acquired Immune Deficiency Syndrome (AIDS) patients with and without neurological disease, including 11 dimensions of HRQoL within the Medical Outcomes Short-form Health Survey-HIV.

Results:

Comparisons of sociodemographic and systemic clinical variables did not differ between HIV/AIDS patients with (n=94) and without (n=75) neurological disease. However, patients with neurological diseases exhibited significantly lower HRQoL scores compared to matched controls, which was most evident among HIV/AIDS patients with cognitive impairment and sensory neuropathy. Prospective analysis revealed diminishing HRQoL scores prior to neurological diagnosis followed by a progressive and sustained improvement in HRQoL scores after intervention over a 96-week period.

Conclusions:

These studies indicate that while HIV-related neurological diseases are associated with reduced HRQoL scores, enhanced neurological care has a positive impact on HIV/AIDS patients' overall well-being.
Resolution-Dependent Estimates of Multiple Sclerosis Lesion Loads
Authors: Erskine M.K. , Cook L.L. , Riddle K.E. , Mitchell J.R. , Karlik S.J.
Published: December 2014

Background:

Changes in brain lesion loads assessed with magnetic resonance imaging obtained at 1.5 Telsa (T) are used as a measure of disease evolution in natural history studies and treatment trials of multiple sclerosis.

Methods:

A comparison was made between the total lesion volume and individual lesions observed on 1.5 T images and on high-resolution 4 T images. Lesions were quantified using a computer-assisted segmentation tool.

Results:

There was a 46% increase in the total number of lesions detected with 4 T versus 1.5 T imaging (p<0.005). The 4 T also showed a 60% increase in total lesion volume when compared with the 1.5 T (p<0.005). In several instances, the 1.5 T scans showed individual lesions that coalesced into larger areas of abnormality in the 4 T scans. The relationship between individual lesion volumes was linear (slope 1.231) showing that the lesion volume observed at 4 T increased with the size of the lesion detected at 1.5 T. The 4 T voxels were less than one quarter the size of those used at 1.5 T and there were no consistent differences between their signal-to-noise ratios.

Conclusions:

The increase in signal strength that accompanied the increase in field strength compensated for the loss in signal amplitude produced by the use of smaller voxels. This enabled the acquisition of images with improved resolution, resulting in increased lesion detection at 4 T and larger lesion volumes.
Inspiratory Muscle Training and the Perception of Dyspnea in Parkinson's Disease
Authors: Inzelberg Rivka , Peleg Nana , Nisipeanu Puiu , Magadle Rasmi , Carasso Ralph L. , Weiner Paltiel
Published: December 2014

Background:

Pulmonary and respiratory muscle function impairment are common in patients with Parkinson's disease (PD). Inspiratory muscle training may improve strength, dyspnea and functional capacity in healthy subjects and in those with chronic obstructive pulmonary disease. This study investigated the effect of specific inspiratory muscle training (SIMT) on pulmonary functions, inspiratory muscle performance, dyspnea and quality of life, in patients with PD.

Patients and Methods:

Twenty patients with PD (stage II and III Hoehn and Yahr scale) were recruited for the study and were divided into two groups: a) ten patients who received SIMT and b) ten patients who received sham training, for three months. Pulmonary functions, the respiratory muscle strength and endurance, the perception of dyspnea (POD) and the quality of life were studied before and within one week after the training period. All subjects trained daily, six times a week, each session consisting of 1/2 hour, for 12 weeks.

Results:

Following the training period, there was a significant improvement, in the training group but not in the control group, in the following parameters: inspiratory muscle strength, (PImax, increased from 62.0±8.2 to 78.0±7.5 cm of H2O (p<0.05), inspiratory muscle endurance (increased from 20.0±2.8 to 29.0±3.0 cm of H2O (p<0.05), and the POD (decreased from 17.9±3.2 to 14.0±2.4 units (p<0.05). There was a close correlation between the increase in the inspiratory muscle performance and the decrease in the POD.

Conclusions:

The inspiratory muscle performance may be improved by SIMT in patients with PD. This improvement is associated with a significant decrease in their POD.
Neurofibromatosis Type 1 in a Pediatric Population: Ste-Justine's Experience
Authors: Boulanger J.M. , Larbrisseau A.
Published: December 2014

Background:

To date, few pediatric series of neurofibromatosis type 1 (NF-1) have been described in the literature even though it is the most frequently encountered phakomatosis.

Methods:

We reviewed 987 charts of pediatric patients with a presumptive diagnosis of NF-1 who were evaluated at Ste-Justine hospital from January 1, 1991 to July 31, 2002. Patients who presented with two or more cardinal criteria were diagnosed with NF-1. Clinical and laboratory data were retrospectively collected, including: demographics, neuroimaging and presence or absence of associated symptoms or signs of NF-1.

Results:

A total of 279 patients were diagnosed with NF-1. The mean age at diagnosis was 3.4 years. Ninety-nine percent of the patients had café au lait spots and 47% had a first degree relative with NF-1. Almost 60 percent (59.6%) of those seen by an ophthalmologist had Lisch nodules. Optic glioma was found in in 14.7%, cutaneous neurofibromas in 38.4%, plexiform neurofibromas in 24.7%, neurofibrosarcoma in 1.8%, learning disabilities in 39%, attention deficit disorder in 40.5%, osseous dysplasias in 7.2%, pseudoarthrosis in 3.6%, precocious puberty in 3.2% and short stature in 17.9%. Magnetic resonance, when performed, showed hyperintense T2 lesions in 87.1% of cases. The mean period of follow-up was 7.4 years.

Conclusion:

Neurofibromatosis type 1 is a multisystemic disorder associated with increased risk of malignancy. It can be diagnosed at a very young age and clinical follow-up is advised. To our knowledge, this is the largest single center study of NF-1 in a pediatric population.
Progress in Clinical Neurosciences: A Forum on the Early Management of Parkinson's Disease
Authors: Lang Anthony E. , Miyasaki Janis , Olanow C. Warren , Stoessl A. Jon , Suchowersky Oksana
Published: December 2014

There are numerous concerns related to treatment choices involving early dopaminergic therapy in Parkinson's disease. These include the effect on the underlying progression of the neurodegenerative process as well as the development of motor complications such as fluctuations and dyskinesias. A number of recent basic and clinical studies have provided new insights but have also added confusion and controversy. This report summarizes presentations and discussion dealing with these issues from a one-day symposium involving Canadian Movement Disorders neurologists.
Neurological Complications of Kernicterus
Authors: AlOtaibi Suad F. , Blaser Susan , MacGregor Daune L.
Published: December 2014

Objective and Background:

Prevention of bilirubin encephalopathy relies on the detection of newborns who are at risk of developing serious hyperbilirubinemia. The objective of this study was to reassess the clinical syndrome of kernicterus as neurodiagnostic studies have become more readily available and can be used to evaluate these infants.

Methods:

The study population was neonates born at term or near term admitted to The Hospital for Sick Children in Toronto, Ontario, Canada, between January 1990 and May 2000. During the study period, there were 9776 admissions (average number of admissions per year – 888 infants). The inclusion criteria were that patients had total serum bilirubin levels of > 400μmol/L at the time of diagnosis and no evidence of hypoxic ischemic encephalopathy. Records were reviewed to establish neurodevelopment outcomes.

Results:

Twelve neonates (nine males) were identified. Bilirubin levels at the time of diagnosis ranged from 405 to 825μmol/L. Causes of these elevated levels included glucose-6-phosphate dehydrogenase deficiency (seven patients), dehydration (three patients), sepsis (one patient), and was undetermined in one patient. Abnormal visual evoked potentials were found in three of nine patients and abnormal brainstem auditory evoked potentials in seven of ten patients. Abnormal electroencephalograms were documented in five patients studied. Brain magnetic resonance imaging results were abnormal in three of four patients.

Conclusions:

Magnetic resonance imaging typically showed an increased signal in the posteromedial aspect of the globus pallidus and was, therefore, useful in the assessment of the structural changes of chronic bilirubin encephalopathy after kernicterus.
Anomalous Internal Carotid Anastomosis to Contralateral Anterior Cerebral Artery
Authors: Murai Yasuo , Ikeda Yukio , Sato Hidetaka , Yamamoto Yasuhiro , Teramoto Akira
Published: December 2014

Background:

Many anomalies and variants in vascular anatomy have been reported in relation to the anterior cerebral artery (ACA). Patients and

Patients and Methods:

We encountered an apparently novel anomaly in a 30-year-old man admitted for disturbance of consciousness following a traffic accident. Computed tomography revealed an acute subdural hematoma and subarachnoid hemorrhage.

Results and conclusions:

No vascular abnormalities related to the hemorrhage were detected by conventional angiography, so we concluded that the bleeding was of traumatic origin. Anomalous origin of the ACA was disclosed incidentally, with both A1 segments arising from the right internal carotid artery; no normal A1 segment of the left ACA was visualized. We discuss possible bases for this anomalous origin.
Nephrotic Syndrome in a Multiple Sclerosis Patient Treated with Interferon β1a
Authors: Auty Anthony , Saleh Abdulkarim
Published: December 2014

Background:

Interferon β has become standard therapy for reducing relapse frequency in relapsing/remitting Multiple Sclerosis (RRMS). Several different preparations are available including interferon β1a (Avonex, Rebif) and interferon β1b (Betaferon/Betaseron). For the most part these preparations have been considered safe. Recently there have been concerns relating to liver1 and now kidney toxicity.

Case Report:

We present a case of a 28-yr old male who developed a severe case of nephrotic syndrome while being treated for relapsing/remitting Multiple Sclerosis (RRMS) with weekly injections of interferon β1a.

Subsequent course:

The nephrosis resolved almost completely once the interferon was stopped and after immunosuppressive treatment. At its peak the daily protein loss was 35.82 g. Kidney biopsy demonstrated membranous glomerulonephritis.

Discussion:

Two other case reports of nephrotic syndrome have been reported in the literature. This latest (third) report suggests that the safety profile should be reexamined and at least raises the question of potential renal toxicity of interferons in MS.
The Epileptic Encephalopathies of Infancy and Childhood
Authors: Wirrell Elaine , Farrell Kevin , Whiting Sharon
Published: December 2014

The epileptic encephalopathies comprise a group of devastating seizure syndromes which begin in infancy and early childhood and usually result in intractable epilepsy. While some syndromes are relatively easily diagnosed early in their course, others take time to evolve, hampering an early, confident diagnosis. Epileptic encephalopathies are associated with slowing of cognitive function and evolution of severe behavioral disorders, which are often more distressing to families than the epilepsy. While an underlying etiology may explain some of this co-morbidity, many children have no identifiable etiology found for their seizures. In these “idiopathic” cases, recurrent subtle seizures, frequent epileptiform discharge and non-convulsive status epilepticus probably all play a role in deterioration of cognitive function and evolution of behavior disorders. This paper will review the most common epileptic encephalopathy syndromes, discuss the cognitive and behavioral co-morbidities and review current therapeutic options.
tPA use for Stroke in the Registry of the Canadian Stroke Network
Authors: Nadeau Janel O. , Shi Steven , Fang Jiming , Kapral Moira K. , Richards Janice A. , Silver Frank L. , Hill Michael D. ,   on behalf of the investigators for the Registry of the Canadian Stroke Network
Published: December 2014

Background:

Thrombolytic therapy with recombinant tissue plasminogen activator (tPA) has been shown to be cost-effective and safe. Thrombolysis for stroke with tPA is now a standard of care in North America. However, it is only used on a small percentage of patients.

Methods:

The Registry of the Canadian Stroke Network was a consent-based stroke registry from 21 hospital sites across Canada. Using the thrombolysis data in phase 1 and 2 of the Registry, we sought to describe the use of stroke thrombolysis and its outcomes.

Results:

A total of 4107 patients were diagnosed with ischemic stroke in phase 1 and 2 of the Registry, of which 8.9% were treated with tPA. In consented tPA patients, the method of tPA administration was 85.8% IV only, 9.0% IA only, and 5.2% IV/IA combined. Patients had a median onset-to-treatment time of 167 minutes [IQR 140-188]. One quarter (25.5%) of eligible candidates (time from onset <150 minutes) were treated with tPA. Protocol violations occurred in 27.7% (67/242) of patients with 14.9% (10/67) mortality. Overall, in-hospital mortality was 11.6%. Lower Canadian Neurological Scale score and higher glucose level were predictive of mortality The symptomatic intracerebral hemorrhage (ICH) rate (phase 2 only) was 4.3%. The mean Stroke Impact Scale-16 score at six months was 73.2, approximately equivalent to a modified Rankin scale score of 2.

Conclusions:

At selected hospitals in Canada, thrombolysis use is higher than previously reported rates. Thrombolysis continues to be safe and effective in Canada.
Adult Onset Spinocerebellar Ataxia in a Canadian Movement Disorders Clinic
Authors: Kraft Scott , Furtado Sarah , Ranawaya Ranjit , Parboosingh Jillian , Bleoo Stacey , McElligott Karen , Bridge Peter , Spacey Sian , Das Shyamal , Suchowersky Oksana
Published: December 2014

Background:

The spinocerebellar ataxias (SCAs) are a genetically and clinically heterogeneous group of neurodegenerative disorders. Relative frequencies vary within different ethnic groups and geographical locations.

Objectives:

1) To determine the frequencies of hereditary and sporadic adult onset SCAs in the Movement Disorders population; 2) to assess if the fragile X mental retardation gene 1 (FMR1) premutation is found in this population.

Methods:

A retrospective chart review of individuals with a diagnosis of adult onset SCA was carried out. Testing for SCA types 1, 2, 3, 6, 7, and 8, Dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich ataxia and the FMR1 expansion was performed.

Results:

A total of 69 patients in 60 families were identified. Twenty-one (35%) of the families displayed autosomal dominant and two (3.3%) showed autosomal recessive (AR) pattern of inheritance. A positive but undefined family history was noted in nine (15%). The disorder appeared sporadic in 26 patients (43.3%). In the AD families, the most common mutation was SCA3 (23.8%) followed by SCA2 (14.3%) and SCA6 (14.3%). The SCA1 and SCA8 were each identified in 4.8%. FA was found in a pseudodominant pedigree, and one autosomal recessive pedigree. One sporadic patient had a positive test (SCA3).Dentatorubral-pallidoluysian atrophy and FMR1 testing was negative.

Conclusion:

A positive family history was present in 53.3% of our adult onset SCA patients. A specific genetic diagnosis could be given in 61.9% of dominant pedigrees with SCA3 being the most common mutation, followed by SCA2 and SCA6. The yield in sporadic cases was low. The fragile X premutation was not found to be responsible for SCA.
Visual Defects Associated with Vigabatrin: A Study of Epileptic Argentine Patients
Authors: Moreno María Cecilia , Giagante Brenda , Saidon Patricia , Kochen Silvia , Benozzi Jorge , Rosenstein Ruth E.
Published: December 2014

Objective:

The aim of the present study was to assess visual alterations in a population of Argentine patients treated with the antiepileptic drug vigabatrin.

Methods:

Twenty patients receiving vigabatrin and 15 patients receiving carbamazepine were examined with automated perimetry using a Humphrey 120-point full screening strategy. In addition, scotopic flash electroretinograms were performed.

Results:

Of 20 patients treated with vigabatrin, two were unable to cooperate with testing. Of the remaining 18 patients, all but two showed at least one non-detected point inside the central 40° of the visual field of each eye. Of the 15 carbamazepine-treated patients, three were unable to perform the study. None of the remaining 12 patients showed visual field defects. Both a- and b-wave amplitudes of the scotopic electroretinogram were significantly reduced in 12 patients receiving vigabatrin.

Conclusions:

Visual field defects among patients on vigabatrin therapy may occur with a higher frequency than previously recognized. The Humphrey 120-points full field screening test and electroretinography are useful tools to assess the visual dysfunction associated with vigabatrin.
Cannabinoids and Dopamine Receptors' Action on Calcium Current in Rat Neurons
Authors: Vásquez C. , Navarro-Polanco R. , Hernández G. , Ruiz J. , Guerra D.G. , Baltazar L.M. , Huerta M. , Trujillo X.
Published: December 2014

Objective:

To study the effects of cannabinoid, glutamate, and dopamine agonists and antagonists on the calcium current in rat sympathetic neurons.

Methods:

Calcium current was recorded using the whole-cell variant of the patch-clamp technique. After expression in neuronal membranes of the cannabinoid CB1, glutamate mGluR2, or dopamine D1 receptor (by microinjection of the relevant receptor's cDNA into the neuron's nucleus) agonists' and antagonists' effects were observed.

Results:

Applications of agonists of the expressed receptor (0.1-10 µM) decreased the calcium current. The calcium current was increased after application of cannabinoid antagonists (AM251 and AM630); these compounds thus act as inverse agonists in this preparation. Glutamate and dopamine antagonists had no effects on the calcium current by themselves. Combined application of cannabinoids and dopamine, but not glutamate, agonists produced a decrement in the calcium current that was bigger than either of the effects seen when one agonist was applied alone.

Conclusions:

These results suggest that cannabinoid with dopamine receptors have an interactive inhibitory effect on the calcium current in this preparation, indicating that within the nervous system, receptor interactions may be important in the regulation of ion-channel functions.
The Role of Chemotherapy in the Treatment of Malignant Astrocytomas
Authors: Mathieu David , Fortin David
Published: December 2014

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.
Cervico-Oculo-Acoustic Syndrome in a Male with Consanguineous Parents
Authors: Di Maio L. , Marcelli V. , Vitale C. , Menzione M. , De Giorgio A. , Briganti F. , Perretti A. , Marciano E. , Filla A. , De Michele G.
Published: December 2014

Background:

The cervico-oculo-acoustic syndrome comprises Klippel-Feil anomaly, sensorineural deafness and Duane's retraction syndrome. Polygenic, autosomal dominant, and X-linked inheritance have been hypothesized. The disorder has rarely been reported in males.

Case Report:

A 42-year-old male, born of consanguineous parents, presented with Duane's syndrome, mixed hearing loss, C2-C3 fusion, neck stiffness, and right facial palsy. A variety of cardiac, neurological and urogenital anomalies occurred in his relatives. The electro-oculographic studies showed impaired abduction and adduction of the right eye and impaired abduction of the left eye. Vergence, vertical eye movements and peripheral vestibular responses were normal. Somatosensory evoked potentials showed absence of the N13 peak and brainstem auditory evoked potentials bilateral delay of the I-III interpeak latencies.

Conclusions:

Consanguinity of the patient's parents, not previously reported, suggests autosomal recessive inheritance, but autosomal dominant inheritance is indicated by the family history. The pattern of the oculomotor deficit is consistent with bilateral dysplasia of the abducens nuclei with preserved internuclear neurons in the right abducens nucleus. Neurophysiological investigations revealed lower brainstem and cervical cord involvement.
Propionibacterium Acnes Infections After Cranial Neurosurgery
Authors: Kelly Michael E. , Fourney Daryl R. , Guzman Raphael , Sadanand Venkatraman , Griebel Robert W. , Sanche Stephen E.
Published: December 2014

Background:

Propionibacterium acnes (P. acnes) is a relatively avirulent organism that is part of the normal skin flora. Most patient isolates are considered contaminants but, in a small subset of patients, particularly in the post-neurosurgery setting, the organism can cause significant infections. We reviewed our experience with the occurrence and management of P. acnes infections after cranial neurosurgical procedures over a five-year period.

Methods:

Patients with positive cultures for P. acnes between 1996 and 2001 were identified by review of the Saskatoon Health Region microbiology laboratory database. Of the 141 positive cultures, a review of hospital records identified six patients with P. acnes infections after neurosurgical procedures. A review of the literature related to P. acnes associated CNS infections was conducted.

Results:

All patients had undergone a craniotomy or burrhole placement, and one patient had received prior radiotherapy. There were no P. acnes-related ventriculoperitoneal shunt infections. All patients presented with scalp swelling and three had purulent discharge. Symptoms occurred more than two months after the initial surgery in five of six patients, while one patient developed symptoms three years post-operatively. Management for all patients included removal of the craniotomy flap and treatment with parenteral antibiotics, followed in most cases by oral antibiotics. A good response without relapse of infection was seen in five patients; one patient had recurrent infection after cranioplasty.

Conclusion:

P. acnes is a rare but important cause of infection after craniotomy. Wound debridement, removal of the bone flap and adequate antibiotic coverage result in cure in the majority of patients.
Bilateral Agenesis of the Hippocampal Dentate Gyrus in a Neurologically Normal Adult
Authors: Clark Arthur W. , Sarnat Harvey B.
Published: December 2014

Background:

Ontogenic development of granule cells in the hippocampal dentate gyrus is influenced by genes including WNT3, EMX2, NEUROD, and LEF1. Dentate granule cells continue to be generated from stem cell precursors postnatally and during adult life, and are implicated in normal and abnormal neurological function. Developmental privation of dentate granule cells is rare and essentially always occurs in the context of other neurodevelopmental abnormalities. We have found no previous reports of severe, selective agenesis of dentate granule cells in humans.

Methods:

A gross and microscopic examination of the brain included appropriate histochemical and immunohistochemical preparations and examination of the hippocampal formation at multiple levels bilaterally.

Results:

This neurologically normal 82-year-old man was found to have bilateral agenesis of the hippocampal dentate gyrus, no identifiable dentate granule cells, and moderate disorganization of the pyramidal cell layer of Ammon's horn. We found no neurodevelopmental abnormalities outside the hippocampus.

Conclusion:

The hippocampal architectural alterations in this patient are similar to those associated with a murine Lef1 mutation, but our human case does not have the other congenital deficits reported in the Lef1-null mouse. Bilateral agenesis of the hippocampal dentate gyrus, and apparent failure of regeneration of dentate granule cells from stem cells in adult life, may occur without overt clinical neurological deficits.
Altered Mental Status and a Retro-auricular Mass
Authors: Segal Lauren M. , Walker Angela , Marmor Eric , Stern Errol , Levental Mark , Glikstein Rafael S. , Schipper Hyman M.
Published: December 2014

A 29-year-old woman was found lying unconscious in the shower. There was a two-day history of headache and dizziness. In the emergency room, she was initially stuporous (Glasgow Coma Scale 10/15), afebrile, bradycardic and hypertensive. She exhibited roving, conjugate eye movements, left facial paresis (including frontalis), left ptosis, diffuse hypotonia, extensor plantar responses bilaterally and a 1.5 cm warm, fluctuant mass with surrounding erythema behind the left ear (Figure 1). Otoscopy revealed a bulge in the posterior wall of the left external auditory canal.
Whiplash and Concussion: Similar Acute Changes in Middle-Latency SEPs
Authors: Zumsteg Dominik , Wennberg Richard , Gütling Eva , Hess Klaus
Published: December 2014

Objective:

Middle-latency somatosensory evoked potentials (SEPs) following median nerve stimulation can provide a sensitive measure of cortical function. We sought to determine whether the mechanical forces of whiplash injury or concussion alter normal processing of middle-latency SEPs.

Methods:

In a cross-sectional pilot study 20 subjects with whiplash were investigated (50% between 0.5-2 months and 50% between 6-41 months post injury) and compared to 83 healthy subjects using a standard middle-latency SEP procedure. In a subsequent prospective study subjects with either acute whiplash (n=13) or Grade 3 concussion (n=16) were investigated within 48 hours and again three months post injury.

Results:

In the pilot study the middle-latency SEP component N60 was significantly increased in the ten subjects investigated within two months after whiplash. In contrast, the ten subjects examined more than six months after injury showed normal latencies. In the prospective study N60 latencies were increased after whiplash and concussion when tested within 48 hours of injury. At three months, latencies were improved though still significantly different from controls post whiplash and concussion.

Conclusion:

Both whiplash injury and concussion alter processing of the middle-latency SEP component N60 in the acute post traumatic period. The acute changes appear to normalize between three-six months post injury. The SEP similarities suggest that the overlapping clinical symptomatology post whiplash and concussion may reflect a similar underlying mechanism of rotational mild traumatic brain injury.
Effects of High Stimulus Frequencies on SEPs of Patients with Neuro-Behcet's Disease
Authors: Turker Hande , Cengiz Nilgun , Akar Handan , Onar Musa K. , Us Onder
Published: December 2014

Background:

Behcet's disease is a multisystemic vascular inflammatory disorder of unknown origin. It is relatively rare and central nervous system involvement is seen in 5% of affected individuals. Somatosensory evoked potentials (SEPs) can provide information that shows the presence of clinically unsuspected lesions in the central nervous system of these patients. However, the effects of changing the stimulus frequencies on latencies of SEP potentials and central conduction time (CCT) in patients with neuro-Behcet's disease (NB) have not been studied yet. In this study, our aim was to reveal these effects to investigate whether the change of stimulus frequencies could be of convenient use in obtaining more accurate CCT estimations in SEP studies of these patients.

Methods:

We performed median nerve SEPs of 14 patients with NB and 15 healthy volunteers. We changed the stimulus frequency: 2 Hz, 4Hz, 6Hz and 9Hz in successive recordings and statistically compared the changes on SEP potentials and peak and onset CCT in the neuro-Behcet (NB) group and the normal group.

Results:

Our results indicated that the onset CCT values of the NB group were higher than the normal group at 4Hz and 9Hz stimulations. However, the comparison of peak CCT in the NB group and the normal group did not show any statistically meaningful differences at all stimulation frequencies.

Conclusion:

Onset CCT has not been measured before in former SEP studies of patients with NB. We highly recommend measuring onset CCT at higher stimulation frequencies in order to reveal central conduction time pathologies in these patients.
Purification of the NF2 Tumor Suppressor Protein from Human Erythrocytes
Authors: Jindal Hitesh K. , Yoshinaga Kazumi , Seo Pil-Soo , Lutchman Mohini , Dion Patrick A. , Rouleau Guy A. , Hanada Toshihiko , Chishti Athar H.
Published: December 2014

Background:

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease predisposing individuals to the risk of developing tumors of cranial and spinal nerves. The NF2 tumor suppressor protein, known as Merlin/Schwanomin, is a member of the protein 4.1 superfamily that function as links between the cytoskeleton and the plasma membrane.

Methods:

Upon selective extraction of membrane-associated proteins from erythrocyte plasma membrane (ghosts) using low ionic strength solution, the bulk of NF2 protein remains associated with the spectrin-actin depleted inside-out-vesicles. Western blot analysis showed a ~70 kDa polypeptide in the erythrocyte plasma membrane. Furthermore, quantitative removal of NF2 protein from the inside-out-vesicles was achieved using 1.0 M potassium iodide, a treatment known to remove tightly-bound peripheral membrane proteins.

Results:

These results suggest a novel mode of NF2 protein association with the erythrocyte membrane that is distinct from the known membrane interactions of protein 4.1. Based on these biochemical properties, several purification strategies were devised to isolate native NF2 protein from human erythrocyte ghosts. Using purified and recombinant NF2 protein as internal standards, we quantified approximately ~41-65,000 molecules of NF2 protein per erythrocyte.

Conclusion:

We provide evidence for the presence of NF2 protein in the human erythrocyte membrane. The identification of NF2 protein in the human erythrocyte membrane will make it feasible to discover novel interactions of NF2 protein utilizing powerful techniques of erythrocyte biochemistry and genetics in mammalian cells.
Study Design in Dementia Drug Trials
Authors: MacKnight Chris
Published: December 2014

A great deal of progress has been made in the management of Alzheimer's disease and other dementias over the past 25 years. Much remains to be achieved, however. This article discusses some of the issues surrounding study design. In the absence of an accepted biological marker of progression, it is unlikely that a novel study design, such as randomized start or withdrawal, in itself could provide convincing evidence of disease modification. Biological markers will also be crucial in the development of therapies aimed at specific processes, and of immunotherapies.
The Role of Functional Assessment as an Outcome Measure in Antidementia Treatment
Authors: Massoud Fadi
Published: December 2014

Functional assessment refers to the evaluation of performance in basic activities of daily living, instrumental activities of daily living, professional duties, and hobbies. This assessment is particularly relevant in the evaluation of cognitive impairment. In fact, functional decline represents a core feature of dementia according to the DSM-IV criteria. Clinically, functional deterioration represents a diagnostic marker, can be used to chart the course of the disease, and as a prognostic marker as it contributes significantly to caregiver burden and institutionalization. For all these reasons, functional assessment has been widely used as an outcome measure in intervention trials of Alzheimer disease (AD). Appropriate function assessment scales have been developed for use in clinical trials of AD. Studies have shown that functional decline benefits from pharmacological interventions in AD and some other cognitive syndromes. This benefit translates into a stabilization ranging between 6 to 12 months compared to a gradual deterioration in the placebo group. There is rarely reversibility for IADL's lost. There are no functional scales specifically designed for assessment of subjects with non-AD cognitive impairment. Scales specifically developed for Mild Cognitive Impairment and other dementias are needed.
Quality of Life in Dementia
Authors: Naglie Gary
Published: December 2014

There is a growing consensus that quality of life (QOL) is an important outcome for assessing the effectiveness of interventions for dementia, but there is no agreement about how to best measure it. Various approaches to QOL assessment have been employed to measure the QOL of persons with dementia, including patient self-report, caregiver proxy report and observational assessment by trained observers. Furthermore, several dementia-specific measures of QOL have been developed, and several generic measures of QOL have been used to assess QOL in dementia. However, to date, QOL has rarely been included as an outcome measure in clinical trials of pharmacotherapy for dementia. This manuscript reviews the current state of knowledge about QOL assessment in dementia.
Imaging Biomarkers and their Role in Dementia Clinical Trials
Authors: Chertkow Howard , Black Sandra
Published: December 2014

There are five potential major roles for neuroimaging with respect to dementia; 1) as a cognitive neuroscience research tool, 2) for prediction of which normal or slightly impaired individuals will develop dementia and over what time frame, 3) for early diagnosis of Alzheimer's disease (AD) in demented individuals, (sensitivity) and separation of AD from other forms of dementia (specificity), 4) for monitoring of disease progression, and 5) for monitoring response to therapies. Focusing on the last role, no single imaging approach is yet ideal, as all trade-off speed, cost, and accuracy. Functional imaging (SPECT and PET) is best suited to tracking symptomatic therapy response, and anatomic (MRI volumetric) imaging or amyloid PET are more suited to reflect dementia modulation studies. The potential for imaging with respect to pharmacological studies of dementia - to provide surrogate markers for drug studies, to improve diagnosis, to speed evaluation of outcomes, and to decrease sample sizes - is huge. At the present time, however, no single measure has sufficient proven reliability, replicability, or robustness, to replace clinical primary outcome measures.