bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent Cerebral Infarction during Anticoagulation Therapy in Patients with Mitral Valve Prolapse
Authors: Shuaib Ashfaq , Murphy William F.
Published: July 2016

Mitral valve prolapse has been associated with an increased risk of transient or lasting ischemic events. Recurrence is uncommon after initiation of antiplatelet or anticoagulant therapy. In this communication we report two patients, both female, who had mitral valve prolapse as the major risk factor for cerebrovascular disease and who developed cerebral infarction despite anticoagulation. The cerebral infarctions were bilateral and extensive in one patient and led to the patient's death. In the second case, three infarctions resulted in moderate disability.
Two Types of Spheroid Bodies in the Nigral Neurons in Parkinson's Disease
Authors: Yamada Tatsuo , Akiyama Haruhiko , McGeer Patrick L.
Published: July 2016

Dendritic spheroid bodies (SBs) and Lewy bodies (LBs) were identified in comparable numbers in the substantia nigra pars compacta (SBC) of nine parkinsonian cases and one case of striatonigral degeneration but were not found irt cases of Huntington's disease or neurologically normal controls. The immunohistochemical profile of the SBs in dystrophic dendrites of nigrostriatal dopaminergic neurons was remarkably similar to that of the LBs found within dendrites or free of the SNC neuropil. Both types of inclusions stained positively with antibodies to tyrosine hydroxylase, ubiquitin and microtubule-associated protein-2 (MAP2), and negatively for Tau-2, although they had different ultrastructural appearances. A few intracellular LBs were stained by antibodies to neurofilament proteins (NFs) 68, 160, and 200 kD, but dendritic SBs and extracellular LBs were not so stained. These data indicate that dendritic SBs and extracellular LBs may have a common molecular pathogenetic origin in Parkinson's disease. On the other hand, the SBs seen in the pars reticulata (SNR) and in the distal nigrostriatal axons even in control cases were generally stained by antibodies to NFs and ubiquitin but not to MAP2. This latter staining pattern in similar to that shown by SBs in the anterior horn in ALS and in the cerebellum of neurologically normal brains and is believed typical of axonal as opposed to dendritic SBs.
Myotonic Dystrophy: An Electrophysiological Study of Cognitive Deficits
Authors: Ragazzoni Aldo , Pinto Francesco , Taiuti Rosanna , Silveri Maria Caterina
Published: July 2016

Patients with Myotonic Dystrophy (MyD) frequently suffer from a dysfunction of the primary sensory pathways, as documented by abnormalities of short-latency evoked potentials. Impairment of intellectual functions has been less extensively investigated. Short-latency brainstem auditory evoked potentials (BAEPs) as well as long-latency auditory event-related potentials (ERPs) were recorded from 5 female and 6 male patients affected by MyD. A simple discrimination (“oddball”) paradigm was used to record ERPs to tones from Fz, Cz, Pz. Both BAEPs and ERPs were significantly altered as compared to normals. BAEP abnormalities were detected in 9 patients and ERP components N2 and P3 were delayed or absent for all patients, who nonetheless correctly discriminated between tones. These data indicate that CNS dysfunction in MyD involves not only primary sensory systems but also neural mechanisms underlying cognitive events and ERP generation.
Accessory Nerve Palsy: A Review of 23 Cases
Authors: Berry H. , MacDonald E.A. , Mrazek A.C.
Published: July 2016

In a series of 23 patients, the commonest cause of accessory nerve palsy was surgical trauma at the time of lymph node biopsy. The less common causes were penetrating or blunt trauma and a few were of spontaneous onset. There was involvement of adjacent motor sensory nerves in about half of the patients. The prognosis was better following blunt trauma, stretch injuries and after a spontaneous onset. The anatomical relationships of the accessory nerve and aspects of the clinical picture and management are discussed.
Complications of the Transsphenoidal Approach to Sellar Lesions
Authors: Reddy Kesava , Fewer Derek , West Michael
Published: July 2016

Transsphenoidal surgery is currently performed extensively for lesions of the sella turcica. The mortality and morbidity of this surgical approach are minimal, and the results satisfactory overall. Only a few studies have addressed the complications of this approach. The authors present a retrospective study of 200 transsphenoidal procedures in 196 patients over an eleven year period. There was one death due to meningitis. Major morbidity consisted of intraventricular hemorrhage in three patients, false aneurysm of the internal carotid artery in one patient and thalamic infarction in another patient. Minor morbidity details are presented. The pathogenesis of the most serious of these complications along with possible preventive measures are discussed.
Current Status of Radiosurgery for Arteriovenous Malformations
Authors: Schwartz Michael , O'Brien Peter , Davey Phillip , Young Charlene , Willinsky Robert , Catton Charles
Published: July 2016

Cerebral arteriovenous malformations (AVM), regardless of the mode of discovery, have an annual risk of hemorrhage of approximately 4 percent. A progressive obliterative vasculitis culminating in the occlusion of an AVM may be induced by the administration of radiation doses of approximately 20 Gy given in a single fraction. The process takes about two years and occlusion occurs in approximately 80% of patients so treated. Such a dose may be accurately administered to AVMs up to 3 cm in diameter with very little radiation imparted to the adjacent brain by means of multiple highly collimated radially arranged cobalt sources (the Gamma Knife) or by means of a modified linear accelerator turned through an arc or arcs with the target AVM as the centre of rotation. The Gamma Knife and the modified linear accelerator have nearly equal accuracy. Recent experience with modified linear accelerators indicates efficacy equal to the Gamma Knife. Both devices are effective treatment for small AVMs but the cost of modifying a pre-existing linear accelerator is only a few percent of the acquisition and installation costs of the Gamma Knife.
The Association between Polycystic Kidney Disease and Cerebral Aneurysms
Authors: Fehlings Michael G. , Gentili Fred
Published: July 2016

Rupture of cerebral aneurysms is an important cause of morbidity and mortality in patients with adult polycystic kidney disease (PKD). In the present paper, we review the literature regarding the association of cerebral aneurysms and PKD and emphasize, by means of a case report, the importance of familial clustering of aneurysms in patients with PKD. We conclude that the prevalence of intracranial aneurysms in patients with PKD approaches 40% and is likely significantly higher in patients with PKD and a positive family history for cerebral aneurysm. We recommend that screening cerebral angiography be strongly considered in all patients with PKD and a family history of cerebral aneurysm or subarachnoid hemorrhage.
New Approaches to the Treatment of Age-Related Brain Disorders
Authors: Da Prada M.
Published: July 2016

Two novel reversible enzyme inhibitors involved in monoamine metabolism are described. The novel and reversible inhibitors are the catechol-O-methyl-transferase (COMT) inhibitor, Ro 40-7592 (3,4-dihydroxy-4'-methyl-5-nitrobenzophenone), and the monoamine oxidase type-B (MAO-B) inhibitor, Ro 19-6327 (N-(2-aminoethyl)-5-chloro-2-pyridine carboxamide HC1). These may be of special therapeutic benefit in Parkinson's and Alzheimer's diseases.
Anomalous Gene Expression in Alzheimer Disease: Cause or Effect
Authors: McLachlan D.R.C. , Lukiw W.J. , Mizzen C. , Percy M.E. , Somerville M.J. , Sutherland M.K. , Wong L.
Published: July 2016

Altered chromatin conformation and increased amounts of aluminum have been observed in the brains of patients with Alzheimer disease. These factors have been shown to affect gene regulation. In this report, we describe how these changes may selectively alter the pool size of the human light chain neurofilament gene and play a fundamental role in the expression of this disease.
Treatment of Alzheimer's Disease: Hopes and Reality
Authors: Gauthier S. , Gauthier L. , Bouchard R. , Quirion R. , Sultan S.
Published: July 2016

The relative failure of symptomatic therapeutic trials for Alzheimer's disease using non-selective cholinergic agonists brings about the need for longitudinal studies with parallel designs aimed at disease stabilization, using trophic substances or amyloid suppressors.
Preoperative Electroencephalographic Investigation in Frontal Lobe Epilepsy: Electroencephalographic and Electrocorticographic Recordings
Authors: Quesney L.F.
Published: July 2016

The first section of this article deals with specific anatomic and pathophysiologic factors which contribute to a poor EEG localization of the interictal epileptic abnormality and to the unreliable seizure onset localization commonly reported in patients with frontal lobe epilepsy. The localizing effectiveness of long term EEG monitoring was reviewed in four different groups of frontal lobe epileptic patients who underwent preoperative EEG investigation with extracranial and intracranial electrodes. The results of this study reveal a continuum distribution of interictal epileptic disturbances, ranging from focal abnormalities to lobar or multi-lobar epileptogenesis. A frontal lobe localization of the seizure generator based on ictal recordings obtained with extracranial electrodes is rather poor and much more reliable results can be obtained by depth-electroencephalography.
Introduction à l'Etude Clinique des Crises Epileptiques Rétrorolandiques
Authors: Baucaud J. , Talairach J. , Munari C. , Giallonardo T. , Brunet P.
Published: July 2016

An introduction to the clinical study of postrolandic epileptic seizures. We reviewed, in 145 epilectics studied with SEEG, 800 clinical and electrographic seizures originating from the post-rolandic areas (590 spontaneous Sz and 260 induced by stimulation). The intra-cranial electrodes were implanted using a technique described by Talairach et al. (1974). Seizure onsets were recorded in the centro-parietal region (64 patients) in the partietal49 and in the occipital region.15 Additionally in 15 patients, mixed Sz onset were recorded. One hundred and eight (108) patients underwent surgical removal of their epileptic focus. (69 on the right, 39 on left.) 65% were cured (Sz free or occas Sz, f/up 3 years). The main ictal cal features are discussed. Emphasis is placed on the role of the operculo-insular cortex in the functional organization in man, based on Sz arising from the supra-temporal (fronto-pariental) cortex. The study of the pattern of onset and spread of seizures originating in the post-rolandic areas and of their clinical correlates allow a topographic differential diagnosis.
Localization of Epileptic Foci in Children
Authors: Blume Warren T. , Kaibara Masako
Published: July 2016

Electroencephalographic and neuro-imaging data were correlated with the lobe of cortical resective surgery among 48 patients age 16 years or less with medically intractable partial seizures. Decisions about surgery were determined by clinical judgement and therefore our results reflect the weight of these factors in clinical practise. Neuroimaging disclosed a lesion over the operated lobe in 32 patients (67%). Multiple EEGs demonstrated a most active spike focus over the operated lobe in 32 patients (67%). Although only 34 patients had a recorded seizure, this clearly arose over the operated lobe in 23 (68% of the 34 patients; 48% of series). Persistent focal delta activity appeared in 20 of the 48 patients (42%). No instance was encountered in which false lateralization of regional or focal interictal EEG spikes or delta when normal apiculate phenomena were excluded. Thus, the scalp EEG remains a valuable guide to epileptogenesis, even among young patients, and should continue to play a major role in determining the region of cortical resection. Effectiveness of cortical resection for seizure control was clearly better among patients with a single major lesion and among those with normal intelligence.
Relative Localizing Value of Common Tests used in the Preoperative Investigation of Epileptic Patients
Authors: Saint-Hilaire Jean-Marc , Richer Francois , Turmel André , Rouleau Isabelle , Bouvier Guy
Published: July 2016

We have compared the relative localizing value of common tests in the presurgical evaluation of epilepsy in 73 patients with depth electrode (SEEG) confirmed epileptogenic foci and excellent surgical outcome. We found the tests of abnormality (CT, amytal, neuropsychology) to be frequently non-informative and often discordant with SEEG. The EEG was concordant with the SEEG in 38% of cases and provided lateralization in 78%. EEG was less localizing than ictal behavior in frontals but not in temporals. The need for SEEG is rather evident in these results but could become attenuated by the development of the localizing power of scalp EEG.
Electrophysiological Analysis of Human Neocortex In Vitro: Experimental Techniques and Methodological Approaches
Authors: Avoli M. , Hwa G.G.C. , Kostopoulos G. , Olivier A. , Villemure J.-G.
Published: July 2016

In this review we summarize a number of technical and methodological approaches that have been used in our laboratory to study human brain slices maintained in vitro. The findings obtained in the course of these studies appear to be relevant in establishing he mechanisms that underlie physiological phenomena of the human brain such as synaptic plasticity or responses to neuroactive drugs. Moreover, these data are important for understanding certain fundamental mechanisms of epilepsy. In this respect, however, we aution that the mechanisms that apply to different forms of clinical epilepsy might be ifficult to find given the variability present in the pathogenesis of human epilepsy.
Bilateral Pathological Damage in Temporal Lobe Epilepsy
Authors: Babb Thomas L.
Published: July 2016

Patients with drug-refractory temporal lobe epilepsy can be treated successfully with surgical resection of one temporal lobe, especially when the resection includes the hippocampus. Although intrahippocampal recordings usually localize seizure onsets to one hippocampus, there are bilaterally-independent interictal spikes, occasional contralateral seizure onsets and post-resection seizures that implicate contralateral damage and epileptogenicity. Post-mortem onquantified studies of both hippocampi in epileptics have revealed incidences of bilateral hippocampal sclerosis, mostly being asymmetric. The present paper reports on two post-mortem cases of bilateral, asymmetric cell loss in patients with physiologically-verified hippocampal epilepsy. In one patient the damage was severe bilaterally, but only slightly greater damage in one hippocampus. In the second patient, damage in one hippocampus was as severe as in the first patient; however the contralateral hippocampus appeared undamaged. However, cell counts revealed losses of over 30% in three different hippocampal subregions, indicating a mild form of asymmetric bilateral damage in patient two.
Evidence that Charcot-Marie-Tooth disease with tremor coincides with the Roussy-Levy syndrome
Authors: Barbieri F. , Filla A. , Ragno M. , Crisci C. , Santoro L. , Corona M. , Campanella G.
Published: July 2016

We report data on 3 members of a family affected by a dominantly inherited disorder closely resembling Roussy-Levy syndrome (RLS). Electrophysiological findings showed a marked decrease of motor and sensory conduction velocities and EMG signs of mild neurogenic damage. Light and electron microscopy of sural nerve biopsy showed a hypertrophic neuropathy with diffuse onion-bulb formations and marked decrease of large size fibers. Teased fiber preparations evidenced reduced internodal lengths and segmental demyelination. Other data from the literature on RLS are reviewed and discussed. The hypothesis that RLS is not a disease entity but a hypertrophic-type of Charcot-Marie-Tooth disease with essential tremor (HMSN type 1) is strongly supported.
Evidence that Charcot-Marie-Tooth disease with tremor coincides with the Roussy-Levy syndrome
Authors: Chouza C. , Caamaño J.L. , De Medina O. , Bogacz J. , Oehninger C. , Vignale R. , De Anda G. , Novoa E. , De Bellis R. , Cardozo H. , Crispino B. , Romero S. , Correa H. , Feres S.
Published: July 2016

Four members of a family with consanguineous relationships, the proband and his three children (2 sons and 1 daughter) are affected with Familial Spastic Ataxia and with Ehlers-Danlos' Syndrome with platelet aggregation dysfunction. In the four cases, this exceptional association appears remarkably homogeneous both in clinical and laboratory studies. The two syndromes are of dominant-autosomic transmission and probably originated in a new mutation which presumably maintained a genetic linkage. Spastic ataxia is characterized by a precocious onset and a slow evolution. The first-born son shows a dominant pyramidal syndrome with mild ataxia suggesting that it is a transitional form of familial spastic paraplegia. The Ehlers-Danlos syndrome pertains to form II or “mitis” with moderate skin hyperelasticity and joint hypermobility. The abnormal platelet aggregation curves have the same profile in all the patients. The first-born son also presents a mitral valve prolapsus as we may find either in Ehlers-Danlos syndrome or in spastic ataxia.
The neuropathology of “typical” Friedreich's ataxia in Quebec
Authors: Lamarche J.B. , Lemieux B. , Lieu H.B.
Published: July 2016

We present the pathological data from the autopsies performed on 6 Friedreich's disease patients since the start of the Quebec Cooperative Study. All patients met the strict diagnostic criteria of the QCSFA. The anatomical lesions found in the peripheral and central nervous system were similar in all 6 cases and do not differ from those described in the literature. The clinical findings correlate closely with the histological lesions found in the peripheral nervous system and spinal cord. The evidence of segmental demyelination and remyelination in the spinal ganglia and posterior roots further supports the dying-back axonopathy hypothesis.
Cardiac malic enzyme in Friedreich's disease
Authors: Barbeau A. , Charbonneau M. , Cloutier T. , Lemieux B.
Published: July 2016

We measured the activity of cytosolic and of mitochondrial malic enzyme in the hearts from 4 patients with Friedreich's disease and from two non-ataxic control subjects. There was a wide variability in the results and the slight overall decreases in both enzyme activities were not considered to be statistically significant. From these and other results, we conclude that deficient mitochondrial malic enzyme activity is not a constant or primary feature of Friedreich's disease.
Spinal Cord Infarction in Disease and Surgery of the Aorta
Authors: R.T Ross
Published: July 2016

Diseases of the aorta and surgery of the aorta can produce spinal cord damage. There are major variations in blood supply to the spinal cord between individuals. The spinal cord may be tamponaded by increased spinal fluid pressure subsequent to clamping the aorta. Both of these factors may contribute to spinal cord infarction. The available methods and procedures to protect the spinal cord during surgery are discussed.
A Pilot Study on the Use of Botulinum Toxin in Spasmodic Torticollis
Authors: Tsui J.K. , Eisen A. , Mak E. , Carruthers J. , Scott A. , Calne D.B.
Published: July 2016

Dystonic torticollis has been treated with local injections of botulinum toxin in a single blind study of 12 patients. A significant decrease of abnormal movements was recorded, and pain improved. Further studies are desirable to define the optimum dosage and site for injections, and the long term effects of repeated injections.
Interstitial Irradiation of Skull Base Tumours
Authors: Bernstein Mark , Gutin Philip H.
Published: July 2016

The rationale for interstitial irradiation of tumours in and around the skull base is reviewed, and the experience accumulated with pituitary adenomas, meningiomas, and chordomas is summarized. Intracystic irradiation for craniopharyngiomas is also reviewed.
Photo-Dynamic Therapy: Cavitary Photo-Illumination of Malignant Cerebral Tumours Using a Laser Coupled Inflatable Balloon
Authors: Muller Paul J. , Wilson Brian C.
Published: July 2016

Interest in photodynamic therapy of malignant brain tumours has been growing in recent years as intra-operative laser applications become more available.

We have developed an inflatable balloon which can be coupled to an argon dye pump laser in order to deliver light to a brain tumour cavity created by the subtotal resection of tumour. Eight patients with primary malignant brain tumours have been treated with photodynamic therapy (PDT) using this device. The 8 patients tolerated the treatment well; morbidity attributable to the PDT was acceptably low.
1985 Silversides Lecture: Unusual Vascular Events in the Territory of the Posterior Cerebral Artery
Authors: Fisher C.M.
Published: July 2016

There is an unusual type of vascular episode in the territory of the posterior cerebral artery which remains relatively unknown. Ten cases are presented in which a posterior cerebral artery deficit developed suddenly in dramatic fashion with headache, visual symptoms, sensory and motor deficits and signs of third nerve involvement. Nine of the patients were female and one was male. Seven were under the age of 33. In all instances there was a permanent neurologic sequela, usually a hemianopia. A similar case was described in 1901. The nature of the underlying process remains obscure, but the evidence favors accompanied migraine in which a particularly severe attack results in permanent damage. The term “catastrophic migraine” is suggested.
The Use of Shunting Devices for Cerebrospinal Fluid in Canada
Authors: Hoffman Harold J. , Smith May S.M.
Published: July 2016

The use of diversionary CSF shunting devices for the treatment of hydrocephalus has been surveyed in Canada. Various factors influencing the operation of shunting devices, the characteristics of commercial shunts and the causes of shunt malfunction are described. Suggestions are made as to how to reduce the incidence of shunt malfunction.
Creutzfeldt-Jakob Disease: Correlation of Focal Electroencephalographic Abnormalities and Clinical Signs
Authors: Eggertson Douglas E. , Pillay Neelan
Published: July 2016

Three patients are described with pathologically verified Creutzfeldt-Jakob disease (CJD) who presented with localizing clinical signs accompanied by focal electroencephalographic abnormalities including periodic lateralized epileptiform discharges (PLEDS). With further progression of the disease, diffuse background slowing and continuous bisynchronous periodic discharges appeared in all three cases. There was good correlation between the initial focal clinical manifestations and the EEG findings.
Malignant Intracranial Fibrous Histiocytomas. Histologic, Ultrastructural and Immunohistochemical Studies of Two Cases
Authors: Sima A.A.F. , Ross R.T. , Hoag G. , Rozdilsky B. , Diocee M.
Published: July 2016

Two cases of malignant intracranial fibrous histiocytoma are presented. In Case 1 the tumour arose from the meninges and showed a disseminated spread throughout the neuroaxis. In the second case the tumour appeared to arise from within the brain substance. In this case surgical intervention and radiotherapy appeared to have achieved a cure, since no residual tumour was found at autopsy.

The tumours were examined using ultrastructural and immunohistochemical techniques, which appeared advantageous in delineating this rare tumour from other intracranial neoplasms.
Primary Malignant Tumours of the Trigeminal Nerve
Authors: Maroun F.B. , Sadler M. , Murray G.P. , Mangan M. , Mathieson G. , Jacob J.C. , Kwan A.
Published: July 2016

We report a case of primary malignant schwannoma of the trigeminal nerve, and review the 5 previously reported cases. Clinical presentation, along with radiological and pathological features are discussed.
Pharmacological Modification of Bradykinin Induced Breakdown of the Blood-brain Barrier
Authors: Raymond Jennifer J. , Robertson David M. , Dinsdale Henry B.
Published: July 2016

Internal carotid artery infusion of bradykinin caused extensive breakdown of the blood-brain barrier to protein as demonstrated by the extravasation of the marker, horseradish peroxidase, into vessel walls and the adjacent parenchyma. Pretreatment of the animals with indomethacin, trifluoperazine, or imidazole significantly reduced the quantity of abnormally permeable vessels as determined by light microscopy. By electron microscopy, it was determined that bradykinin caused an intense increase in the number of pinocytotic vesicles in the permeable segments, but no change in the interendothelial junctions. After imidazole pretreatment, although the extent of the permeability change was markedly reduced, the intensity of pinocytotic activity in the involved areas was not altered.
Cerebral Evoked Potentials in Multiple Sclerosis
Authors: Javidan Manouchehr , McLean Donald R. , Warren Kenneth G.
Published: July 2016

Multimodal evoked potentials were analyzed from 58 possible, 62 probable and 100 definite (total 220) multiple sclerosis (MS) patients. Visual evoked potentials (VEP) were most frequently abnormal yielding 39%, 69%, 84% in the three diagnostic groups respectively. Median nerve sensory evoked potentials (SEP) yielded abnormalities in 26%, 65%, 79% respectively. Brainstem auditory evoked responses (BAER) were abnormal in 17%, 39%, 66% respectively. We measured the combined amplitude (CA) of waves III, IV, V in the BAER of these patients as an objective measure of amplitude asymmetry. The CA was considered abnormal if it was 1SD below the lowest CA value in the control group. The CA was abnormal in 9.2% of BAER with normal central conduction time. The BAER diagnostic yield in MS patients increased 11% by using CA analysis.
Cardiac Tachyarrhythmias in Hereditary Long QT Syndromes Presenting as a Seizure Disorder
Authors: Sundaram M.B.M. , McMeekin J.D. , Gulamhusein S.
Published: July 2016

Patients with hereditary long QT disorders — Romano-Ward Syndrome and Jervell Lange-Nielsen Syndrome — sometimes present with seizures due to cardiac tachyarrhythmias. Two such patients are presented, emphasizing diagnostic clues — syncope, seizures with onset in early life, precipitation of attacks by emotional or physical stress, positive family history of sudden death and/or seizures, normal EEG and prolonged QT interval on ECG. Treatment is usually with adequate doses of sympathetic betablockers.
Effects of Extracellular Matrix Proteins on the Growth and Differentiation of an Anaplastic Glioma Cell Line
Authors: Rutka James T.
Published: July 2016

Efforts to determine the factors responsible for reversing malignancy in the central nervous system may not only increase our understanding of the growth of primary human brain tumors, but may eventually prove to be of therapeutic benefit as well. We therefore devised a model system to study the effects of extracellular matrix (ECM) proteins on the malignant phenotype of an anaplastic glioma line, U-343 MG-A. Well-characterized cultures derived from normal human leptomeninges were grown to confluence and maintained for 2 weeks. The pia-arachnoid cells were then removed with detergent and base, leaving behind an ECM enriched in laminin, fibronectin, types I and IV collagen, and procollagen III. U-343 MG-A tumor cells planted on top of this normal ECM were profoundly growth inhibited, developed multiple slender cytoplastic processes similar to those of normal astrocytes, and expressed more GFAP per cell than did tumor cells growing on plastic alone. The growth of U-343 MG-A tumor cells in flasks coated with purified fibronectin or laminin was not significantly inhibited. However, U-343 MG-A cultures grown in flasks coated with type I or IV collagen showed decreased cellular proliferation and altered cell morphology. Conditioned medium from U-343 MG-A tumor cells growing on plastic alone contained a 64 kD activated metalloprotease. U-343 MG-A tumor cells growing on the pia-arachnoid ECM do not demonstrate such proteolytic activity. We conclude that the tumor cell microenvironment is extremely important in modulating the growth and differentiation of an anaplastic glioma cell line. It is hoped that an increased knowledge of the production of ECM components and their effects on malignant glioma cell growth, migration and differentiation will lead to the development of new approaches to improve the prospects of patients with primary malignant brain tumors.
Serial Recordings of Multimodality Evoked Potentials in Multiple Sclerosis:
A Four Year Follow-Up Study
Authors: Iragui Vicente J. , Wiederholt Wigbert C. , Romine John S.
Published: July 2016

Pattern reversal visual, brain-stem auditory, and short latency median nerve somatosensory evoked potentials (EPs) were evaluated in a prospective study over 4 years in 20 patients with clinically definite sclerosis (MS). Standardized neurological examinations were done at regular intervals and correlated with EP findings. The highest incidence of EP abnormalities occurred in the visual system followed by the somatosensory and auditory systems. Clinical relapse was usually accompanied by EP deterioration, but clinical improvement often occurred without parallel EP recovery. EP changes were not always related to clinical symptoms and often took place during remission periods in the absence of clinical changes. There was no significant correlation between clinical and electrophysiological progression within any given sensory modality. The progression of clinical disability, however, showed a fairly good correlation with the overall progression of EP abnormalities. We conclude that EPs complement the neurological exam in the evaluation of MS and may have a place in the investigation of the effects of therapeutic agents on the neurological status in MS.
The Value of Prolonged Electroencephalographic and Video Monitoring in Diagnosis of Seizure Disorders
Authors: Willmer J.P. , Brunet D.G.
Published: July 2016

Prolonged electroencephalographic and video monitoring of ictal events is useful in aiding the diagnosis of complicated seizure disorders. Forty eight patients admitted to a neurology service were assessed with this technique. Twenty five (54%) had their diagnoses changed, six (14%) had their diagnoses confirmed and the remaining patients had inconclusive studies. Therapy is modified by the results and in addition both patient and staff education is enhanced through the use of this equipment.
Intravenous Abuse of Propylhexedrine (Benzedrex®) and the Risk of Brainstem Dysfunction in Young Adults
Authors: Fornazzari Luis , Carlen Peter L. , Kapur Bhushan M.
Published: July 2016

In 1949, amphetamine sulfate was replaced by propylhexedrine in the nasal decongestant agent
Benzedrex® because of psychosis, sudden death, and widespread abuse. Propylhexedrine is not without risks, and reported cases of psychosis, myocardial infarction, pulmonary vascular disease and pulmonary hypertension, and sudden death are well documented in the medical literature. We are reporting 2 cases of definite brainstem dysfunction and 5 cases of transient diplopia secondary to IV abuse of Benzedrex®. This widely abused drug is prepared by heating Benzedrex® and hydrochloric acid, and the resulting crystals are dissolved in water for injection. This agent is called “stove-top speed”. All 7 patients had transient diplopia, within seconds after injection. One patient had evidence of a right-internuclear opthalmoplegia, and another had a depressed right gag reflex and paralysis of the right half of the tongue. The deficits in these two patients, persisted for many months. In young adults with history of drug abuse, the IV use of Benzedrex® should be considered in the differential diagnosis of transient or permanent focal brainstem deficits.
The Significance of White Matter Lucencies on CT Scan in Relation to Cognitive Impairment
Authors: Steingart A. , Lau K. , Fox A. , Diaz F. , Fisman M. , Hachinski V. , Merskey H. ,   University of Western Ontario Dementia Study Group
Published: July 2016

As part of a prospective clinicopathological study a cohort of “normal” elderly volunteers (n = 110) has been investigated with CT scans, psychometric testing (Extended Scale for Dementia) and neurological examination. CT scans were evaluated by a neuroradiologist for the presence or absence of white matter lucencies (WML). WML were defined as patchy or diffuse areas of decreased attenuation involving only white matter and with no change in adjacent ventricles or sulci.

The 12 subjects with WML had lower scores on the ESD than the 98 subjects without WML (mean ESD with WML 229.5± 14; without WML 236.7±8.6, t-test p<.01) and the difference remains significant even after adjusting for the possible confounding effects of age (ANCOVA, P<.043).
Transmitter-replacement Therapy in Alzheimer's Disease Using Intracerebroventricular Infusions of Receptor Agonists
Authors: Gauthier S. , Leblanc R. , Quirion R. , Carlsson G. , Beaulieu M. , Bouchard R. , Dastoor D. , Ervin F. , Gauthier L. , Gauvin M. , Henry J. , Palmour R. , Robitaille Y.
Published: July 2016

Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action.
Chromatin Structure in Scrapie and Alzheimer's Disease
Authors: McLachlan D.R. Crapper , Lukiw W.J. , Cho H.J. , Carp R.I. , Wisniewski H.
Published: July 2016

Scrapie affected brains exhibit a number of pathological features in common with the human neurodegenerative condition, Alzheimer's disease. The present report describes studies on chromatin structure seen in these two disease processes.

Chromatin associated proteins influence transcriptional activity of DNA through an effect upon chromatin structure. We examined chromatin structure by: (1) measuring the capacity of the enzyme micrococcal nuclease to release mono- and dinucleosomes from isolated nuclei and (2) measuring DN A-histone interactions by examining the effect of ambient tonicity upon the release of chromatin proteins.

In two strains of mice infected with two strains of scrapie agent there was reduced accessibility to micrococcal nuclease and an increased content on dinucleosomes of the histone HI and Hl° types. These changes precede clinical signs of scrapie and resemble those found in the human conditions of Alzheimer's and Pick's disease. Scrapie mouse brain differs from Alzheimer brain in that scrapie does not alter histone-DNA interactions as monitored by ionically induced histone release from chromatin. Despite similarities, the scrapie agent appears to operate upon different molecular mechanisms than those found in Alzheimer's disease.
Family Studies of Alzheimer's Dementia: Results and Prospects
Authors: Heston Leonard L. , Morris Marcia L.
Published: July 2016

Studies of families located through a proband with dementia of the Alzheimer type have demonstrated transmission of the disorder within families, probably through shared genes. Increasing closeness of genetic relationship and increasing severity of illness are both associated with increasing risk to relatives. Families a.t high risk are especially valuable for studies of the biology of dementing illness including, in particular, their molecular genetics. Associations at several levels between Down's syndrome and Alzheimer's dementia provide important clues for molecular hypotheses.
Challenges and Opportunities of Clinicopathological Investigation in Longitudinal Studies of Alzheimer's Disease
Authors: Ball M.J.
Published: July 2016

After organizational involvement in a clinicopathological investigation of Alzheimer's Disease for a decade, the present appears an appropriate time to reflect upon both the major challenges encountered as well as the exciting opportunities presented by such a longitudinal study.

Problematic areas have included: (a) brevity of research grant intervals (generally one- or two-year); (b) turnover of support personnel, as a consequence; (c) limited biostatistical and data management expertise dedicated to the Study objectives; (d) limited neuropsychological manpower in this specialized sphere; (e) “distillate” effect of postmortem retrieval, by which only some of the many clinical cases expire during any grant period, only some of those receive autopsy permission, only some of those demonstrate (pure) Alzheimer's Disease neuropathologically, and only some are harvested quickly enough for specialized (e.g. biochemical) analyses; (f) ensuring the scientific optimization of available tissue samples; and (g) paucity of cases dying in the early stages of the illness.

Significant achievements include: (a) demonstration of the opportunities for young researchers committed to careers in behavioral neurology, psychogeriatrics or neurodegenerative pathology; (b) development of improved testing protocols for psychometric, electroencephalographic and neuroradiological evaluation of the demented elderly; (c) ethical enrolment both of a large cohort of Alzheimer patients and a sizeable normative (control) population; (d) public cooperation permitting a postmortem compliance rate exceeding 75%; (e) rapid autopsy retrieval times (50% < 6 hours); (f) utilization of human postmortem synaptosomal preparations for neurochemical investigations; (g) availability of fresh autopsy tissues for other specialized techniques (e.g. magnetic resonance spectroscopy, in situ hybridization); and (h) a collegial forum for the regular exchange of scientific data.

While the challenges to be met are certainly not unique to our Study, the interdisciplinary and longitudinal nature of this approach could magnify their potentially retardatory effect upon research quality. By contrast, however, surmounting these hurdles enables the participant scientists to share in an incomparable opportunity for observational insights into the cellular and pathogenetic mechanisms underlying the cognitive decline of Alzheimer patients. The vigour with which my numerous collaborators at the University of Western Ontario meet such challenges may serve as a model for other Alzheimer centres where a similar research system is likewise expected to justify the anticipation of its supportive funding agencies, and of the patients whom we are pledged to comfort.
Post-Mortem Neurochemical Changes in Alzheimer's Disease Compared With Normal Ageing
Authors: Rossor M. , Mountjoy C.Q.
Published: July 2016

Selective neuronal degeneration with concomitant changes in neurotransmitter systems are features of both normal ageing and Alzheimer's disease. There are, however, important neurochemical differences in cerebral cortex. Choline acetyltransferase declines with age in frontal cortex in contrast to the prominent change in the temporal cortex in Alzheimer's disease. The loss of somatostatin, and the recently reported reciprocal change in corticotropin-releasing factor and receptors are not seen with ageing. However, age itself may have an important influence on the neurochemical deficits in Alzheimer's disease which are restricted in the older patients. The problems of post-mortem studies in the analysis of ageing and possible approaches to this are discussed.
In Vitro31P NMR Spectroscopy Detects Altered Phospholipid Metabolism in Alzheimer's Disease
Authors: Miatto Orietta , Gonzalez R. Gilberto , Buonanno Ferdinando , Growdon John H.
Published: July 2016

In order to study possible metabolic derangements in Alzheimer's disease (AD), we performed phosphorus 31 nuclear magnetic resonance (31P NMR) spectroscopy on brain samples obtained at autopsy from 7 patients with AD and 9 control subjects. Aqueous solutions of brain tissue contained well-defined peaks of intermediate compounds in phospholipid metabolism, including the phosphomonoesters phosphocholine and phosphoethanolamine, and the phosphodiesters glycerophosphorylcholine and glycerophosphorylethanolamine. 3IP NMR spectra also displayed the inorganic phosphorus signal, which provides an index to the in vivo concentration of high-energy compounds.

We found evidence for altered phospholipid metabolism in that relative levels of phosphomonoesters were decreased, and phosphodiesters increased, in frontal and parietal regions of patients with AD compared to control subjects. The inorganic phosphorus resonance peaks were similar in AD and control subjects, suggesting that energy stores are not diminished in AD. These preliminary data are consistent with the hypothesis that abnormalities in phospholipid metabolism contribute to possible neuronal membrane dysfunction and impaired cholinergic neurotransmission in AD.
Quantitative X-Ray Computed Tomography (CT) in Dementia of the Alzheimer Type (DAT)
Authors: Luxenberg J.S. , Friedland R.P. , Rapoport S.I.
Published: July 2016

Dementia of the Alzheimer type (DAT) has proven to be difficult to diagnose using computerized X-ray tomography (CT). To improve the identification of DAT with CT, several different quantitative approaches have been tried. Brain parenchymal density measurements and a variety of linear indices of ventricular size have failed to reliably separate DAT patients from age matched controls. Measures of ventricular volume improve discrimination, but overlap with controls persists. The inadequacy of a single CT study to diagnose DAT is clearly related to the overlap of brain atrophy in DAT and healthy aging, a finding which has also been noted in post-mortem studies. Estimating the rate of ventricular enlargement from quantitative measurements of ventricular size on successive CT scans may allow the physician to take advantage of the progressive nature of DAT, improving separation of DAT patients from healthy controls.
Physiology of the Basal Ganglia and Pathophysiology of Parkinson's Disease
Authors: Lee Robert G.
Published: July 2016

This paper reviews current concepts concerning the anatomical organization and functions of the basal ganglia focusing mainly on the role of the basal ganglia in control of movement. Results of several studies which have been carried out on patients with Parkinson's disease are also reviewed and discussed as examples of altered normal physiological mechanisms.
Aging of the Nigrostriatal Pathway in Humans
Authors: Calne Donald B. , Peppard R.F.
Published: July 2016

Progressive degeneration of functionally related groups of neurons occurs in certain infective, toxic, nutritional and genetically determined neurological diseases. It also takes place in normal aging, and several of the regions that undergo selective decay with the passage of time seem to be the same target regions that are afflicted in degenerative disorders such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS). Infective etiology is relatively easy to exclude by a combination of immunological tests and transfer experiments. Genetic causation can be rendered unlikely when large kindreds are available for study. Nutritional deprivation and acute or subacute toxicity are accessible to explanation by examining the environment. The most difficult mechanism of pathogenesis to refute is chronic toxic damage, where the lesion may derive from long-term exposure to a relatively widespread noxious agent or agents. Variations in involvement of individuals within a population may stem from differing capacities to activate or inactivate a toxin. Inherent in this concept of etiology is recognition that compensatory potential within the central nervous system may contribute to prolonged existence of subclinical lesions so that a latent period may exist for several decades, between causal event and the onset of symptoms. Furthermore, progressive clinical deterioration may take place even though the cause may have been transient, many years before. The histological features associated with Parkinson's disease, Alzheimer's disease and ALS may be nonspecific indicators of neuronal “illness”, there being a predilection for certain morphological markers to appear more frequently in particular circumstances and particular regions associated with the pathology of particular diseases.
The Use of the MPTP-Treated Mouse as an Animal Model of Parkinsonism
Authors: Heikkila Richard E. , Sonsalla Patricia K.
Published: July 2016

The MPTP-treated mouse has proven to be a valuable model of parkinsonism. For example, C57 black mice treated with MPTP exhibit a large decrement in the neostriatal content of dopamine and its metabolites, a marked reduction in the capacity of neostriatal synaptosomal preparations to accumulate [3H]dopamine, a large decrease in neostriatal tyrosine hydroxylase activity, a marked loss of nerve cells in the zona compacta of the substantia nigra, and pronounced behavioral deficits. These biochemical, pathological and behavioral deficits are similarly observed in MPTP-treated primates and in humans with idiopathic parkinsonism. A great deal of our current knowledge concerning MPTP has come from experimentation carried out in the mouse.
Hypothesis: A Role for Quinolinic Acid in the Neuropathology of Glutaric Aciduria Type I
Authors: Heyes Melvyn P.
Published: July 2016

Glutaric aciduria type I is an autosomal recessive metabolic disorder of children associated with severe dystonic motor disturbances and degeneration in the cerebral cortex, striatum and cerebellum. Biochemical studies demonstrate a deficiency in the enzyme glutaryl-CoA dehydrogenase. This enzyme metabolizes substrate derived from dietary tryptophan that could otherwise be converted to quinolinic acid within the brain. The law of mass action predicts that the production of quinolinic acid should be increased in glutaric aciduria type I. Quinolinic acid is a potent neurotoxin and convulsant when it is injected into the central nervous system of experimental animals. This paper argues that quinolinic acid may accumulate within the brain and cause the neuropathology of glutaric aciduria type I.
Current Status of Levodopa Therapy in Idiopathic Parkinson's Disease
Authors: Gauthier S. , Gauthier L.
Published: July 2016

Levodopa is currently used at all stages of Parkinson's disease, particularly from Stage 3 onward. Most patients start levodopa within four years of the onset of disease, earlier in the akineto-rigid patients (average delay of 2.1 years) than in those where resting tremor predominates (average delay of 3.4 years). Advanced age (>80) is no deterrent to the use of levodopa if required. Wearing off is most noticeable in Stage 3 or after 10 years of therapy with levodopa. An inverse correlation was found between age and wearing off, suggesting a marked sensitivity of younger patients to levodopa. Future studies on the use of dopamine agonists should thus be stratified according to age.