bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilirubin Metabolism — Preliminary Investigation
Authors: Barbeau A. , Breton G. , Lemieux B. , Butterworth R.F.
Published: July 2016

In our studies, high total bilirubin values in the plasma were noted in cases of Friedreich's ataxia. A bimodal distribution of the values indicated the possible presence of two subgroups of patients. In these kindred, we demonstrated an elevation in unconjugated bilirubin with features similar to those reported in Gilbert's syndrome: normal liver function tests, elevation after fasting and day to day variability. We also report preliminary experiments indicating that bilirubin levels may be taurine dependent. We postulate that the defect could be a secondary component of the ataxic disease, possibly indicating a defect in membrane transport.
Amino Acid Metabolism in Friedreich's Ataxia
Authors: Lemieux B. , Barbeau A. , Beroniade V. , Shapcott D. , Breton G. , Geoffroy G. , Melançon S.
Published: July 2016

A study of amino acids determined by sequential Multi-sample Amino Acid Automatic Analyzer in plasma, urine and cerebrospinal fluid (CSF) in patients with Friedreich's ataxia and control subjects has revealed a number of mathematically significant variations from normal. Of practical physiological importance are the following: a high urinary excretion of alanine with slightly elevated plasma levels; a low plasma and CSF concentration of aspartic acid in the resence of normal urinary values and finally a low CSF concentration of taurine accompanied by normal plasma levels, but elevated urinary output and renal clearance rates. We postulate that the modifications in alanine and aspartic acid are less specific and probably secondary, but there could be a genetic defect in the membrane transport of taurine and the other β-amino acids in Friedreich's ataxia.
Pyruvate Metabolism in Friedreich's Ataxia
Authors: Barbea A. , Butterworth R.F. , Ngo T. , Breton G. , Melançon S. , Shapcott D. , Geoffroy G. , Lemieux B.
Published: July 2016

Friedreich's ataxia patients show evidence of an abnormally elevated and prolonged response of pyruvate and lactate to a glucose load, with normal fasting levels. However, there is a bimodal distribution of this response with high and low pyruvate responders. This trait appears to be determined genetically, However, although in vivo tests suggest low oxidation of pyruvate, we were unable to confirm any in vitro impairment of each of the components of the pyruvate dehydrogenase (PDH) complex. We conclude that the defect is in the metabolic regulation of PDH, probably at the E3(lipoamide dehydrogenase) step.
Neurological Disease and Its Management in Malaysia Belah Otak
Authors: Richardson P.M.
Published: July 2016

The pattern of neurological illness in Malaysia and some of the factors which influence its surgical treatment are described.
Polyglycolic Acid Suture in Peripheral Nerve II: Sutured Sciatic Nerve
Authors: Hudson Alan R. , Hunter Daniel
Published: July 2016

This experiment investigates the holding property of polyglycolic acid suture in repair of divided dog sciatic nerves and the influence of absorption of this synthetic material on regeneration. The conclusion is that PGA maintains its tensile strength sufficiently long to allow both physical union and good regeneration of the divided nerve. The suture absorption does not influence regeneration.
Gliosis and Glioma Distinguished by Acridine Orange
Authors: Sarnat Harvey B. , Curry Bernadette , Rewcastle N.B. , Trevenen Cynthia L.
Published: July 2016

Acridine orange fluorochrome of nucleic acids was applied to sections of cerebral tissue from 20 patients showing acute or chronic reactive gliosis. The results were compared with the findings in 39 well differentiated and malignant astrocytomas. The orange cytoplasmic fluorescence of ribonucleic acid is lacking in reactive astrocytes of all ages including gemistocytes, but is uniformly present in astrocytoma cells. Acridine orange is a useful supplementary stain for distinguishing between astrocytosis and astrocytoma, paticularly for small cerebral biopsies showing scattered or diffusely infiltrating pleomorphic glial cells.
Botulinum Toxin for Benign Essential Blepharospasm, Hemifacial Spasm and Age-Related Lower Eyelid Entropion
Authors: Carruthers Jean , Stubbs Harrison A.
Published: July 2016

Purified botulinum A exotoxin was used in the treatment of forty seven patients with benign essential blepharospasm, 11 patients with hemifacial spasm and 2 patients with age-related entropion. The treatment was effective in all three groups for an average of 3-4 months when symptoms recurred and repeated chemodenervation with toxin was needed. The commonest complication was transient ptosis with an overall frequency of 7.8%. This incidence increased to 11.1% with toxin doses higher than 25 units per orbicularis. The treatment was well accepted by the patients, who were subsequently able to return to pre-blepharospasm lifestyles.
The Natural History of Multiple Sclerosis
Authors: Weinshenker B.G. , Ebers G.C.
Published: July 2016

Studies which have attempted to define the outcome of multiple sclerosis (MS) have methodologic difficulties arising from patient referral biases and the length of follow-up required, which make prospective studies of an inception cohort unrealistic. Means to improve the validity of retrospective natural history studies are suggested. Results of existing series are summarized and compared. Survival is only rarely shortened by MS, but disability to the point of requiring aids for ambulation occurs in 30-70% of patients by 15 years from onset of symptoms. Disagreement as to the percentage of patients who are ultimately bedridden by MS likely arises in large part due to differences in patient ascertainment and follow-up. The need to develop early clinical markers for the patient at high risk for rapid development of major disability is stressed.
The Relationship Between Timing of Surgery and Operative Complications in Aneurysmal Subarachnoid Hemorrhage
Authors: Tucker William S.
Published: July 2016

The optimal timing of definitive aneurysm repair following subarachnoid hemorrhage remains a controversial issue. In order to examine whether the timing of surgery alters the incidence of certain technical difficulties and complications associated with intracranial aneurysm repair, data from two recent co-operative studies were examined. The cases submitted to the International Co-operative Study on Timing of Aneurysm Surgery by the University of Toronto hospitals, and the cases submitted from multiple centres to the Three-Dose Multicentre Randomized Double-Blind Nimodipine Study were evaluated with regard to operative difficulties and complications, comparing early (≤ 3 days) and late (≥ 4 days) surgery following subarachnoid hemorrhage. No significant differences were found in the incidence of such technical problems between the early and late surgical groups. If differences in outcome occur between comparable groups of patients operated early and late after aneurysm rupture, factors other than surgical technical complications may be responsible.
Cochlear Nerve Monitoring During Cerebellopontine Angle Operations
Authors: Rowed D.W. , Nedzelski J.M. , Cashman M.Z. , Stanton S. , Harrison R.V.
Published: July 2016

The authors present their experience with intraoperative monitoring of cochlear nerve action potentials (AP) in 30 adult patients. Operative procedures were acoustic neuroma excision with attempted hearing preservation and selective vestibular neurectomy in patients with incapacitating Meniere's disease and serviceable hearing (SRT<50 db, discrimination >60%). Loss of AP is detected rapidly and has been demonstrated after manipulation of the cochlear nerve and after coagulation of small arteries on the tumour capsule. Presence of an AP at the end of the procedure usually correlates with postoperative preservation of hearing. AP monitoring appears to be a reliable means of detecting potentially reversible changes in cochlear nerve function intraoperatively.
Calcification in a Recent Cerebral Infarct - Radiologic and Pathologic Correlation
Authors: Parisi J. , Place C. , Nag S.
Published: July 2016

This 60 year old male developed a right hemiplegia and aphasia. A C.T. head scan showed a cerebral infarct which appeared hyperdense on a subsequent scan done 18 days after presentation. This was interpreted as indicating a hemorrhagic transformation resulting in discontinuation of anticoagulation therapy. At autopsy, the area of infarction in the left frontoparietal hemisphere appeared intensely green due to breakdown of the blood-brain barrier in the presence ofjaundice. A striking finding on microscopy was the presence of calcium salts throughout the area of infarction but most prominent in the grey matter at the periphery of the infarct corresponding to the areas which appeared hyperdense on the CT head scan and stained intensely with bilirubin. There was no evidence of recent hemorrhage. This case illustrates that calcification can occur within weeks after the onset of a recent cerebral infarct and should be considered when interpreting the development of C.T. scan hyperdensity in recent cerebral infarcts.
Diagnosis of Central Nervous System Lupus
Authors: O'Connor Paul
Published: July 2016

Central nervous system (CNS) involvement in systemic lupus erythematosus is a major source of patient morbidity and mortality. The recognition of nervous system lupus is hampered by the diagnostic insensitivity and non-specificity of the various testing modalities that are currently available. A review of the effectiveness of diagnostic tests for CNS lupus is presented. Areas of current research in this area are examined. Because of the diversity of neurologic manifestations in this disorder and their complex pathogenesis, no single test is sufficient to establish the diagnosis rapidly and accurately in all cases, now or for the foreseeable future.
Evoked Potential Studies in Friedreich's Ataxia and Progressive Early Onset Cerebellar Ataxia
Authors: Vanasse M. , Garcia-Larrea L. , Neuschwander Ph. , Trouillas P. , Mauguière F.
Published: July 2016

We recorded somatosensory evoked potentials (SEP) in 15 patients affected by Friedreich's ataxia (FA) and in 9 patients with progressive early onset cerebellar ataxia (PEOCA). Brainstem auditory evoked potentials (BAEP) were also recorded in 14 FA patients and in five PEOCA patients. SEP results showed clear differences between groups of FA, evidence of peripheral involvement was seen in all patients, with absence of the N9 potential or a major reduction of its amplitude. In patients in whom central responses could be recorded, conduction velocity was normal or near normal up to the brainstem but was reduced from brainstem to cerebral cortex. Four patients with PEOCA had SEP abnormalities similar to those seen in FA. In the five other patients, the amplitude and latency of N9 were normal but conduction velocity was reduced from brainstem to cerebral cortex. In FA, BAEP were abnormal in all patients with a disease duration of four years or more but were normal in four of the five PEOCA patients. Systematic evoked potential recording is useful in the investigation of hereditary ataxias.
Do the Corticospinal and Corticobulbar Tracts Mediate Functions in the Human Newborn?
Authors: Sarnat Harvey B.
Published: July 2016

Unlike the numerous dispersed bulbospinal pathways that are already well myelinated at term, the more compact corticospinal and corticobulbar tracts are only beginning their myelination cycle in late gestation and do not complete it until two years of age. During this same period, these pathways also develop extensive ramification of terminal axonal segments, growth of collateral axons, and proliferation of synapses. Despite their immaturity in the fullterm human newborn, several proposed functions may be attributed to the descending pathways from the neonatal cerebral cortex: a) a contribution to the differential development of passive muscle tone and resting postures; in general they function as an antagonist to the “subcorticospinal pathways” in mediating proximal flexion and distal extension, except for the rubrospinal tract which is probably synergistic with the corticospinal tract; b) enhancement of tactile reflexes originating in the brainstem and spinal cord, including suck and swallow; c) relay of epileptic activity of cortical origin; d) inhibition of complex stereotyped motor reflexes including many phenomena formerly termed “subtle seizures”; e) a possible influence on muscle maturation, particularly in relaying cerebellar impulses that modify the histochemical differentiation of myofibres. However, the bulbospinal tracts are probably more influential on muscle development. The corticospinal and corticobulbar tracts subserve different needs in the newborn than at older ages, but are functionally important pathways even at birth.
Abnormalities in Iron Metabolism in Multiple Sclerosis
Authors: Valberg Leslie S. , Flanagan Peter R. , Kertesz Ann , Ebers George C.
Published: July 2016

High iron concentrations have been reported in the brains of multiple sclerosis victims. To determine if there are abnormalities in general iron metabolism indicative of iron overload in MS, measurements of transferrin saturation, serum ferritin and red cell ferritin in 31 female and 18 male patients were compared to the results in 49 age- and sex-matched healthy controls. Compared to controls, mean serum ferritin in MS was high, whereas transferrin saturation and red cell ferritin were similar. High values in one or more individual test results were observed in eleven MS patients. They were prevalent in patients who required bilateral assistance to walk or were confined to a chair, and appeared to be related to the severity of the disease. An investigation was made into the relationship of the high serum ferritin values in MS to the HLA-A3 histocompatibility antigen, a marker of the hemochromatosis gene which is prevalent in MS. A statistically significant interaction was not found between serum ferritin and the presence of HLA-A3.
Bilateral Hypoglossal Palsies: A Late Complication of Curative Radiotherapy
Authors: Johnston Eamon F. , Hammond Alex J. , Cairncross J. Gregory
Published: July 2016

A 57 year old man developed bilateral hypoglossal nerve palsies 6 years after radiotherapy for carcinoma of the uvula. Follow-up over 2 years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement. Reactive fibrosis and vascular insufficiency secondary to radiation and may have lead to hypoglossal nerve compression and infarction.
Neuropathology of Heart Transplantation
Authors: Ang L.C. , Gillett J.M. , Kaufmann J.C.E.
Published: July 2016

The neuropathology of 18 cardiac transplant recipients was reviewed with the clinical findings. Pathological changes were noted in the central nervous system (CNS) in 94% of the patients, the most frequent being cerebral vascular in origin (72%). Eight patients (44%) had multiple cerebral infarcts and morphologically, a large number of these antedated the transplantation. In addition 4 patients had acute focal ischemic changes which occurred after transplantation. Intracranial hemorrhage was noted in 5 patients (28%), including one case of fatal intracerebral hemorrhage following an acute hypertensive episode after the transplantation. While systemic infection was common (10 patients), there were only 5 cases of intracranial infection; including 3 cases of cytomegalovirus infection, one of candidiasis and one of aspergillosis. Post-transplant seizures, occurring in a third of the patients, were related to a variety of causative factors such as sepsis, intracranial hemorrhage, cerebral ischemia, metabolic encephalopathy and cyclosporin neurotoxicity. Of note in this series was the absence of CNS lymphoma or other systemic lymphoproliferative disorder.
PET Studies of Parkinsonian Patients Treated with Autologous Adrenal Implants
Authors: Guttman M. , Burns R.S. , Martin W.R.W. , Peppard R.F. , Adam M.J. , Ruth T.J. , Allen G. , Parker R.A. , Tulipan N.B. , Calne D.B.
Published: July 2016

Transplantation of autologous adrenal medulla tissue into the striatum has recently been proposed as a treatment for Parkinson's disease. We report the use of positron emission tomography (PET) to evaluate patients who had adrenal implants placed into the right caudate. 6-[18F] fluoro-L-dopa (6-FD) scans were performed to study the integrity and activity of the implant, and the nigrostriatal dopamine system before and six weeks after transplantation surgery. [68Ga] Gallium-ethylenediaminetetraacetate (Ga) scans were also performed to assess the blood brain barrier. The Ga scans performed on two patients showed increased permeability of the blood brain barrier at the surgical site. 6-FD PET scans in five patients did not show a consistent change in striatal uptake following adrenal medullary implantation after six weeks. Further assessment of implant viability with 6-FD PET scans after longer follow up may provide useful information if the blood-brain barrier becomes re-established with the passage of time.
The Effects of Body Weight Support on the Locomotor Pattern of Spastic Paretic Patients
Authors: Visintin M. , Barbeau H.
Published: July 2016

The effects of mechanically supporting a percentage of body weight on the gait pattern of spastic paretic subjects during treadmill locomotion was investigated. Electromyographic (EMG), joint angular displacement and temporal distance data were simultaneously recorded while 7 spastic paretic subjects walked at 0% and 40% body weight support (BWS) at their maximal comfortable treadmill speed. Forty percent BWS produced a general decrease in EMG mean burst amplitude for the lower limb muscles investigated with instances of more appropriate EMG timing in relation to the gait cycle. The joint angular displacement data at 40% BWS revealed straighter trunk and knee alignment during the weight bearing phase especially at initial foot-floor contact and midstance. An increase in single limb support time and a decrease in percentage total double support time were evident at 40% BWS. An increase in stride length and maximum comfortable walking speed was also seen with BWS. The use of BWS during treadmill locomotion as a therapeutic approach to retrain gait in neurologically impaired patients is discussed.
Temporal Intermittent Rhythmic Delta Activity (TIRDA) in the Diagnosis of Complex Partial Epilepsy: Sensitivity, Specificity and Predictive Value
Authors: Reiher Jean , Beaudry Michel , Leduc Charles P.
Published: July 2016

Temporal interictal rhythmic delta activity or TIRDA was found in 45 of the 127 recordings of patients with complex partial epilepsy (CPE) referred for both awake and sleep EEC TIRDA was more abundant during drowsiness and light sleep; it occurred more characteristically as trains of 50-100 µv sinusoidal or saw-toothed l-4Hz activity, recorded predominantly from anterior temporal regions. When occurring bilaterally and independently, TIRDA varied from side to side. TIRDA is often found in association with anterior temporal spikes or sharp waves (TS) particularly during sleep, as observed in 43 out of 45 EEGs. TIRDA can nevertheless occur as an isolated abnormality, as noted in two sleep and 12 awake study recordings. Because of its high specificity and positive predictive value over a large range of prevalence, TIRDA should be singled out as an accurate interictal indicator of CPE. In patients with isolated TIRDA, the cost of prolonged EEG recording during sleep for the purpose of activating TS has to be weighed against the yield of eventually confirming the obvious.
Inclusion Body Myositis Associated with Progressive Dysphagia: Treatment with Cricopharyngeal Myotomy
Authors: Danon Moris J. , Friedman Michael
Published: July 2016

A 68-year-old man known to have inclusion body myositis underwent a cricopharyngeal myotomy in an attempt to improve his progressive dysphagia. Morphological studies from tissues obtained during this procedure showed the diagnostic features typical of this chronic inflammatory myopathy. To our knowledge this is the first pathological demonstration of inclusion body myositis involving the pharyngeal skeletal musculature.
The Relationship Between Alzheimer's Disease, Parkinson's Disease and Motor Neuron Disease
Authors: Calne Donald B. , Eisen Andrew
Published: July 2016

We argue against the dominant status assigned to conventional microscopy in the categorization of disorders such as Alzheimer's disease, Parkinson's disease and ALS. As an example we criticize the emphasis that has been placed on correlating the presence of Lewy bodies with the diagnosis of Parkinson's disease. In essence, we submit that Parkinson's disease can exist without Lewy bodies, and Lewy bodies can exist without Parkinson's disease. Nevertheless, we consider that the newer techniques available to histology have led to an important concept that constitutes a shared feature for Alzheimer's disease. Parkinson's disease and ALS; they are all characterized by the deposition of cytoskeletal debris in tissue, so they may perhaps be collectively termed the “Cytoskeletal Disorders”.
Association Between Alzheimer Disease and Amyotrophic Lateral Sclerosis?
Authors: Frecker M.F. , Fraser F.C , Andermann E. , Pryse-Phillips W.E.M.
Published: July 2016

We report two cases of Alzheimer disease (AD) — one of them familial — in which the patient also had amyotrophic lateral sclerosis (ALS), and one patient with familial AD who had a son with ALS. Three further cases of probable ALS were found in pedigrees of AD reported from the literature. It is proposed that this association is not coincidental, but may suggest an etiological factor in common.
PET, CT, and MRI Imaging of Neuronal Migration Anomalies in Epileptic Patients
Authors: Falconer John , Wada Juhn A. , Martin Wayne , Li David
Published: July 2016

During the investigation of intractable epilepsy, neuronal migration anomalies [NMA] were discovered in three patients. The first patient had abnormally positioned gray matter within the walls of both lateral ventricles. The second patient had a post operative cystic area in the right parietal-occipital lobes and an area of NMA within the right temporal lobe. The third patient had abnormally thickened gray matter in the right operculum. Long term CCTV-EEG monitoring of these three patients revealed ictal discharges originating from the area of abnormal gray matter in patients 2 and 3. PET scanning showed the areas of NMA in all three patients to have similar metabolic activity to normal gray matter. These cases illustrate the value of various imaging modalities and suggest some interesting physiology of a spectrum of neuronal migration anomalies.
Cerebrospinal Fluid Pressure and Prolactin in Empty Sella Syndrome
Authors: Maira Giulio , Anile Carmelo , Marinis Laura De , Mancini Antonio , Barbarino Antonino
Published: July 2016

In 58 female patients with the primary empty sella (PES) syndrome, a study of the CSF dynamics was done by evaluating both the absorptive reserve by a lumbar infusion test at constant rate, and/or the ICP increase occurring during REM phase of nocturnal physiological sleep. In 33, prolactin (PRL) dynamics were also investigated evaluating both the response to sequential stimulating test with thyrotropin-releasing hormone (TRH) and metoclopramide (MCP) and/or the circadian variation of PRL levels. Impairment of CSF dynamics was found in the 84% who had a hormonal pattern characterized by an increase of the PRL response to TRH and MCP and a decrease of the PRL circadian variation. Twenty-one patients with impaired CSF dynamics underwent CSF shunting procedures with disappearance of the signs of intracranial hypertension. They also had restoration of normal PRL dynamics but the endocrine alterations improved only moderately. Altered CSF dynamics play a role in the pathogenesis of the PES syndrome. A correlation between elevated ICP and the hypothalamo-hypophyseal control of PRL secretion may exist.
Regional Cerebral Glucose Metabolism in Turner Syndrome
Authors: Clark C. , Klonoff H. , Hayden M.
Published: July 2016

Regional cerebral glucose metabolism was examined in females with Turner syndrome, a sex chromosome abnormality. Previous studies have found a visual/spatial cognitive anomaly in these women but, to date, no abnormalities in brain structure or function have been associated with the condition. In the present study, decreases in regional metabolism were found in the occipital and parietal cortex. The involvement of the occipital cortex, although consistent with the observed cognitive anomalies, has not been suggested previously as an area dysfunction. Because the occipital cortex is a primary sensory cortex, the reduction of glucose metabolism in the parietal cortex may reflect a lack of innervation from the occipital cortex. Besides insight into the functional specialization of the brain, these findings are also consistent with previous reports on animals regarding the effects of estrogen in brain maturation.
The High Incidence of Valproate Hepatotoxicity in Infants May Relate to Familial Metabolic Defects
Authors: Appleton R.E. , Farrell K. , Applegarth D.A. , Dimmick J.E. , Wong L.T.K. , Davidson A.G.F.
Published: July 2016

The incidence of fatal hepatic failure associated with valproic acid (VPA) therapy is highest in children under the age of three years, particularly in those with developmental delay. The pathogenesis of VPA hepatotoxicity is unclear but may relate to the accumulation of a toxic metabolite of VPA which impairs fatty-acid oxidation. We describe two unrelated infants with developmental delay who developed hepatic failure while receiving VPA. Siblings of both children subsequently developed hepatic steatosis and intractable seizures without being exposed to VPA. This suggests that that the two children who developed liver failure when receiving VPA may have had a familial metabolic disorder. Familial metabolic disorders may account partly for the higher incidence of fatal hepatotoxicity described in infants receiving VPA.
The Value of CT Scans for Children with Headaches
Authors: Dooley J.M. , Camfield P.R. , O'Neill M. , Vohra A.
Published: July 2016

We studied the value of CT scans for all children referred because of headache to one secondary and one tertiary pediatric centre during a 1 year period. Of 117 children who were seen by the Pediatric Neurology Service, at the I.W.K. Children's Hospital, 4 had CT scans and only 1 of these was abnormal. The consultant Pediatrician saw 40 children because of headache. CT scans were done on 3 of these patients and all were normal. None of the children who had a clinical assessment alone had unrecognized neurological disease during 20 months of follow-up. Therefore only 1 of 157 children had significant intracranial pathology. We conclude that CT scans have a limited role in the management of children with headache.
Clobazam as an Add-on Drug in the Treatment of Refractory Epilepsy of Childhood
Authors: Keene D.L. , Whiting S. , Humphreys P.
Published: July 2016

We report the results of a double-blind cross-over study comparing clobazam and placebo in the treatment of refractory childhood epilepsy. Fifty-two percent of patients had greater than 50% reduction in their seizure frequency when taking the clobazam. During the placebo phase no patient recorded a greater than 50% reduction in seizure frequency. Sex, age, seizure type, intellect did not appear to differentiate clobazam responsive from nonresponsive patients. Only 2/21 patients had behavioral changes on the drug sufficiently severe to require the patient to drop out of the study prematurely. Drug interactions between clobazam and the other anticonvulsant medicines did not occur.
Hypervolemic-Hemodilution and Hypertension During Temporary Middle Cerebral Artery Occlusion in Rats: The Effect on Blood-Brain Barrier Permeability
Authors: Cole Daniel J. , Drummond John C. , Matsumura Jerry S. , Marcantonio Suzzanne , Chi-Lum Bonnie I.
Published: July 2016

The effect of hypervolemic-hemodilution, with and without hypertension, on blood-brain barrier permeability was investigated in rats, after 180 minutes of middle cerebral artery occlusion (MCAo), and 60 minutes of reperfusion. One of the following conditions was maintained during MCAo: 1) Control — hematocrit and blood pressure were not manipulated; 2) Hypervolemic-Hemodilution/Normotension — the hematocrit was decreased to 30%; 3) Hypervolemic-Hemodilution/Hypertension — the hematocrit was decreased to 30% and mean arterial pressure increased by 30 mmHg with phenylphrine. In all groups, Evans Blue was administered, and its concentration determined by spectrophotometric assay. Evans Blue (μg{g-1 of brain tissue [mean ± SD]) was greater in the Hypervolemic- Hemodilution/Hypertension group (71 ± 20) versus the Control (13 ± 9) and Hypervolemic-Hemodilution/ Normotension (17 ± 10) groups (p < 0.05). No other differences were present. These results support the hypothesis that during MCAo, hypervolemic-hemodilution/hypertensive therapy effects an increase in blood-brain barrier permeability in the early period of reperfusion.
The Cycling Pool of Cells within Human Brain Tumors:In SituCytokinetics Using the Monoclonal Antibody Ki-67
Authors: Tsanaclis Ana Maria , Robert Françoise , Michaud Jean , Brem Steven
Published: July 2016

Brain tumor growth results from the relative proportion of cells contained in three populations: a) cycling/proliferative; b) quiescent (Go)/static, and c) terminally differentiated/dying. The cycling compartment can be detected by the mouse monoclonal Ki-67 antibody, an available, rapid, safe, sensitive, and specific method for immunostaining of proliferative cells. We report the Ki-67 labeling index (LI) in 48 brain tumors. Malignant brain tumors have elevated Lis, ranging from 6.0% to 56.9%: anaplastic astrocytoma, 8.0 ± 7.3; glioblastoma multiforme, 10.1 ±4.2; germinoma, 11.7; medulloblastoma, 13.1 ± 6.6; metastases, 40.3 ± 13.1. By contrast, slow-growing tumors showed lower values (P < .001), approaching 1%: acoustic schwannoma, 0.4 ± 0.6; pituitary adenoma, 1.3 ± 1.9; meningioma, 1.2 ± 1.2; low-grade astrocytoma, < 1; pilocytic astrocytoma, 5.6. Human brain tumors can therefore be ranked according to the percentage of cycling cells with the acoustic schwannoma among the least proliferative and the metastatic carcinoma among the most proliferative. Within a given histotype, the Ki-67 LI may have prognostic and therapeutic implications for the individual patient. Already important for neuro-oncology research, the Ki-67 labeling index should be added to the armamentarium of the clinical neuropathologist to complement the standard histopathologic diagnosis with a cytokinetic analysis of cellular proliferation.
Familial Amyotrophic Lateral Sclerosis, 1850-1989: A Statistical Analysis of the World Literature
Authors: Strong M.J. , Hudson A.J. , Alvord W.G.
Published: July 2016

We present clinical and pathologic data on four previously unreported familial ALS pedigrees and review and analyze by descriptive and exploratory statistical techniques all published cases of familial ALS (1850-1989). In contrast to the age-dependent incidence of sporadic ALS, the age of onset of familial ALS is normally distributed about a mean of 45.7 years (std. dev. 11.3 years). Survival curves for the familial ALS data also demonstrate a skewed distribution with a median survival time of 24 months with 74% surviving at 12 months, 48% at 24 months and 23% surviving at 60 months. The patient characteristics of age at onset of disease, sex and focus of disease onset are unrelated variables and age at onset of disease is the only predictor of survival (Cox's proportional hazard model, chi-square 14.74, p = 0.0001). By applying accelerated failure time models with a log-normal baseline distribution, estimated probabilities for survival adjusted by age at onset were calculated. It was found that the older the age at disease onset, the shorter the survival.
Single Photon Emission Computed Tomography Using 99mTc-HM-PAO in the Routine Evaluation of Alzheimer's Disease
Authors: Hurwitz T.A. , Ammann W. , Chu D. , Clark C. , Holden J. , Brownstone R.
Published: July 2016

Regional cerebral blood flow was studied in 7 patients with clinically suspected Alzheimer's disease and 10 normal controls by single photon computed emission tomography (SPECT) using HM-PAO. All patients with Alzheimer's disease and no controls had parietal lobe hypoperfusion which was usually bilateral. In patients with more severe dementia hypoperfusion extended into the frontal lobes. Parietal lobe hypoperfusion corresponds to parietal lobe degeneration which is the one of the first neocortical regions to show the typical degenerative changes of Alzheimer's disease. SPECT with HM-PAO is a non-invasive investigation available in most nuclear medicine departments and complements existing tests in the routine evaluation of patients presenting with dementia.
Assessment of Cognitive Impairment: The Role of CT
Authors: Varga Marica , Wortzman George , Freedman Morris
Published: July 2016

The value of CT as a routine screening procedure in the investigation of cognitive impairment is being increasingly challenged. To address this issue, we reviewed the records of 175 patients with intellectual deficits admitted to a Behavioural Neurology Unit over a two-year period. In the vast majority of cases, ie. 82%, the CT served essentially to confirm the clinical impression and added no new diagnostic information that impacted the management of the presenting problem. In 15% of cases the CT scan was helpful for diagnosis, especially in the differentiation between Alzheimer's disease and multi-infarct dementia.
The Effect of Tricyclic Antidepressants on Cortex- and Amygdala-Kindled Seizures in the Rat
Authors: Yacobi R. , Burnham W.M.
Published: July 2016

The anticonvulsant effects of amitriptyline, imipramine, nortriptyline and desipramine were tested against focal and generalized seizures, triggered from either the amygdala or the cortex in fully kindled rats. Tests were administered on a 72- or a 24-hour schedule. Significant seizure suppression was achieved with only one drug, amitriptyline, and it occurred only at toxic or near-toxic doses. The differential, low-dose suppression of amygdala-kindled seizures, reported in earlier studies, was not seen in the present experiments. It may occur only in the short-interval test paradigms used by previous experimenters.
Synaptic Dysgenesis
Authors: Becker L.E.
Published: July 2016

Synapse formation is a complex, incompletely understood process that has received only limited investigation in man despite the importance of synaptic dysfunction in common disorders such as epilepsy and mental retardation. This review explores synaptic differentiation, focussing on the morphologic maturation of synapses. Since differentiation depends on many antecedent developmental events, synaptogenesis can be affected by several factors: errors in neuronal proliferation, migration, and differentiation. The challenge to the neurobiologist is to detect and evaluate the minor alterations in neuronal differentiation that could account for the structural basis of the clinical manifestations. Trisomy 21 is an example of a condition in which the cytoarchitecture of the cerebral cortex is not obviously altered, yet mental retardation is consistently present; research neurobiologic techniques are making possible documentation of its structural basis. Epilepsy is another example in which examination of surgically removed cerebral cortex reveals subtle cortical dysplasias helpful in understanding the basis for the abnormal electrical discharge. Further exploration of synaptogenesis, particularly the influence of gene products and epigenetic factors on synapse maturation, will increase our understanding of the pathogenesis of conditions in which “morphology” seems normal but function is abnormal.
The Case for Conservative Management of Venous Angiomas
Authors: Kondziolka Douglas , Dempsey Peter K. , Lunsford L. Dade
Published: July 2016

Venous angiomas (developmental venous anomalies) are vascular malformations increasingly recognized in general neurosurgical or neurological practice. They are associated with intracranial hemorrhage, seizures, or progressive neurological deficits or found as incidental findings in patients who present with headaches or have neuroimaging studies for investigation of unrelated neurological disorders. Since venous angiomas drain normal cerebral tissue within a functionally normal arterial territory, resection can lead to venous infarction. This report studies 27 patients with venous angiomas, all of whom had conservative treatment. The venous angioma was considered to be responsible for the onset of neurological symptoms in 14 patients (7 with hemorrhage, 3 with hemorrhage and seizures, 2 with seizures, one with an extrapyramidal movement disorder, and one with motor deficit). Thirteen patients had incidental lesions (8 with headache, and 5 with unrelated neurological symptoms). Ten venous angiomas were in the posterior fossa; seven in the cerebellum. Location did not correlate with symptomatic presentation. No patient with hemorrhage required surgical evacuation of the hematoma. No patient died or had significant morbidity during the follow-up interval (mean of 3.7 years). Venous angiomas are low flow, low resistance vascular malformations, many of which are not associated with neurological sequelae. Our series supports the concept that surgical removal or radiosurgical obliteration should not be performed unless a patient has a second life threatening hemorrhage.
Treatment of Heredo-Degenerative Ataxias with Amantadine Hydrochloride
Authors: Botez M.I. , Young Simon N. , Botez Thérèse , Pedraza Olga L.
Published: July 2016

Amantadine hydrochloride (AH) was administered (200 mg/day) for more than three months to 17 patients with Friedreich's ataxia (FA) and to 12 patients with olivopontocerebellar atrophies (OPCA) in an open clinical trial. Reaction time (RT) and movement time (MT) with the right and left hand were measured before and after treatment. A striking improvement on both RT and MT was observed in the OPCA group (on seven out of eight measures), whereas in the FA patients improvement was seen only in two out of four MT measures with no improvement in RT. Both groups had low levels of homovanillic acid (HVA) in their cerebrospinal fluid before treatment, relative to their controls. However, improvement with AH was not related to HVA levels.
Modulation of Locomotor Patterns and Spasticity with Clonidine in Spinal Cord Injured Patients
Authors: Stewart J.E. , Barbeau H. , Gauthier S.
Published: July 2016

This double blind cross-over study, involving 9 chronic spinal cord injured (SCI) patients (6 paraplegic and 3 paretic), was a first attempt to investigate the effects of the noradrenergic agonist, clonidine, on the modulation of the locomotor pattern and spasticity in patients with spinal cord lesions. Electromyographic (EMG), footswitch and video recordings were made as the patients walked on a treadmill with the support of an overhead harness if needed. Overground locomotion was also assessed in the paretic patients. All 3 spastic paretic patients had kinematic deviations and abnormal EMG recruitment profiles during the premedication or placebo sessions. With clonidine therapy one patient demonstrated a marked improvement in locomotor function. This patient progressed from non-ambulation to limited independent ambulation as the extent of coactivation in antogonist muscles decreased. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine. In the paraplegic patients, clonidine did not elicit locomotor activity, although there were marked reductions in stretch reactions and clonus during assisted locomotion. They remained incapable of locomotion, either during the control period or during the clonidine therapy. These results indicate that clonidine may be a potentially useful medication for both locomotion and certain manifestations of spasticity in SCI patients but further investigation is warranted.
H-Reflex Modulation During Walking in Spastic Paretic Subjects
Authors: Yang J.F. , Fung J. , Edamura M. , Blunt R. , Stein R.B. , Barbeau H.
Published: July 2016

Hoffmann (H) reflexes were elicited from the soleus muscle during treadmill walking in 21 spastic paretic patients. The soleus and tibialis anterior muscles were reciprocally activated during walking in most patients, much like that observed in healthy individuals. The pattern of H-reflex modulation varied considerably between patients, from being relatively normal in some patients to a complete absence of modulation in others. The most common pattern observed was a lack of H-reflex modulation through the stance phase and slight depression of the reflex in the swing phase, considerably less modulation than that of normal subjects under comparable walking conditions. The high reflex amplitudes during periods of the step cycle such as early stance seems to be related to the stretch-induced large electromyogram bursts in the soleus in some subjects. The abnormally active reflexes appear to contribute to the clonus encountered during walking in these patients. In three patients who were able to walk for extended periods, the effect of stimulus intensity was examined. Two of these patients showed a greater degree of reflex modulation at lower stimulus intensities, suggesting that the lack of modulation observed at higher stimulus intensities is a result of saturation of the reflex loop. In six other patients, however, no reflex modulation could be demonstrated even at very low stimulus intensities.
Auricular Myoclonus
Authors: Kirk Andrew , Heilman Kenneth M.
Published: July 2016

We describe a young man with a two and a half year history of idiopathic irregular contractions of an antitragicus muscle in the absence of a more generalized movement disorder. These contractions persisted in sleep and could not be replicated voluntarily. Because proximal nerve block temporarily eliminated the movements and complex hand movements reduced their amplitude and frequency, we suspect a central generator. However, these movements were not associated with any known pathologic condition.
New Biochemical Insights to Unravel the Pathogenesis of Alzheimer's Lesions
Authors: Roher Alex E. , Palmer Kenneth C. , Capodilupo John , Wakade Arun R. , Ball Melvyn J.
Published: July 2016

Purification of amyloid plaque core proteins (APCP) from Alzheimer's disease brains to complete homogeneity and in high yield permitted its chemical fractionation and characterization of its components. APCP is mainly made of β-amyloid (βA) and an assortment of glycoproteins (accounting for 20%) rich in carbohydrates compatible with N-and O-linked saccharides. When added to tissue culture of sympathetic and sensory neurons APCP and βA inhibited neuritic sprouting, a reversible phenomenon at low doses. Higher concentrations of both substances kill the neurons in culture. APCP is significantly more toxic than βA, suggesting the minor components may play an important role in increasing the toxicity of βA. If the observed toxic effects of APCP in situ are occurring in vivo during the course of AD, then the accumulation of these extracellular proteins could be largely responsible for some of the neuronal death observed in this neuropathology.
Relationships Between Interictal Spiking and Seizures: Human and Experimental Evidence
Authors: Gotman Jean
Published: July 2016

Epileptic seizures of focal origin often occur unpredictably as do interictal spikes. It is often assumed that spikes increase prior to seizures of focal origin and that antiepileptic medication affects spikes and seizures in a parallel fashion. We review evidence that this assumption is invalid and that there is a clear dissociation between spikes and seizures: increases in spiking before seizures have not been clearly documented; decreases in antiepileptic medication do not result directly in increased spiking; seizures are often followed by long-lasting increases in spiking; finally, seizures are no more likely when spikes are frequent than when spikes are rare. It therefore appears that spikes and seizures are two quite distinct phenomena, both originating in the epileptic focus but varying over time differently from what is most often believed.
The natural history of Machado-Joseph disease: An analysis of 138 personally examined cases
Authors: Barbeau A. , Roy M. , Cunha L. , Vincente A.N. de , Rosenberg R.N. , Nyhan W.L. , MacLeod P.L. , Chazot G. , Langston L.B. , Dawson D.M. , Coutinho P.
Published: July 2016

We have examined 138 cases of a disorder previously described in people of Portuguese origin and which has received many names. By computer analysis of 46 different items of a standardized neurological examination carried out in each patient, we have been able to delineate the main components of the clinical presentation, to conclude that the marked variability in clinical expressions does not negate the homogeneity of the disorder, and to describe the natural history of this entity which should be called, for historical reasons, “Machado-Joseph Disease”.

This hereditary disease has an autosomal dominant pattern of inheritance, presenting as a progressive ataxia with external ophthalmoplegia, and should be classified within the group of “Ataxic multisystem degenerations”. When the disease starts before the age of 20, it may present with marked spasticity, of a non progressive nature but often so severe that it can be accompanied by “Gegenhalten” countermovements and dystonic postures but little frank dystonia. There are few true extrapyramidal symptoms except akinesia. When the disease starts after the age of 50, the clinical spectrum is mostly that of an amyotrophic polyneuropathy with fasciculations accompanying the ataxia. For all the other cases the clinical picture is a c.ontinuum between these two extremes, the main determinant of the clinical phenotype being the age of onset and a secondary factor, the place of origin of the given kindred. The ataxic and amyotrophic components are clearly progressive with time in contrast to the spasticity component. Although the majority of known cases are of Portuguese origin, this is not obligatory. The next research endeavour should be a search for the chromosomal site of the gene, using molecular biology technology such as those for recombinant DNA.
Recessive ataxia in Acadians and “Cajuns”
Authors: Barbeau A. , Roy M. , Sadibelouiz M. , Wilensky M.A.
Published: July 2016

The physician exposed to a large number of patients with a recessive form of ataxia, will occasionally observe slower progression forms which lack many of the severe features or cardinal symptoms of Friedreich's disease. We have studied 31 such cases in Acadians of the Maritime Provinces of Canada, and in their separated “cousins” from Louisiana, now called “Cajuns”. These patients are compared to a consecutive series of 22 Friedreich's disease cases in French Canada.

It is shown that the age of onset is slightly later, but the progression much slower and the age at death older in the Acadian patients. These cases develop signs of pyramidal and posterior column involvement gradually and later than the classical Friedreich. As a result, pes cavus and scoliosis are less marked, as well as muscle weakness and cardiomyopathy. On the other hand, the rate of progression of areflexic ataxia, the “core disease”, is identical in both groups. The main difference in progression rates of the disorders occurs after 10-12 years of evolution, thus after the period of hormono-ponderal growth.

These differences, coupled to the diverging genetic and genealogical backgrounds, are sufficiently large for the presumption of distinct disorders. Whether they are due to allelic mutations, linked but different genes, genes affecting the same metabolic pathway, but elsewhere or to completely distinct entities, will have to be left to further studies, but their existence in completely different populations and milieux is worthy of report.