bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurofibrillary Tangles in the Dementia of “Normal Pressure” Hydrocephalus
Authors: Ball Melvyn J.
Published: July 2016

Routine neuropathological examination could not explain the dramatic improvement exhibited by one patient with “normal pressure” hydrocephalus after shunting. The improved patient contrasted remarkably with the unchanged condition of four others also shunted successfully. The five brains were analysed by quantitative morphometry to determine the degree of neurofibrillary tangle formation in mesial temporal neurons. The density of tangle-bearing nerve cells in the four unimproved cases was markedly greater than in age-matched control brains from nineteen normal subjects, and fell in the same range as that of eight dements with neuropathologically confirmed Alzheimer's disease. The density of the one who recovered was within normal limits.

The duration of dementia before shunting, and the total duration of dementia in these five patients rank in the same order as their degree of neurofibrillary formation. Furthermore, a positive linear correlation exists between the Tangle Indices and the total duration of dementia. The data suggest that early diagnosis may improve the chances of reversing the dementia of normal pressure hydrocephalus before histological alterations prove too severe.
Some Neurophysiological Effects of Cerebellar Stimulation in Man
Authors: Upton Adrian R.M. , Cooper Irving S.
Published: July 2016

This paper presents the results of neurophysiological studies of the effects of cerebellar stimulation on H reflexes, late reflexes, blink reflexes, evoked potentials and EEG patterns in 18 human subjects (Male 13, Female 5, Age 25.8 ±10.0, Epileptic 9, Cerebral Palsy 9).

In addition to the effects of cerebellar stimulation on the H reflex studies on salens we assessed V1 and V2, “late” responses (Upton et al., 1971), cortical somatosensory evoked potentials (SSEP) after median nerve stimulation, and visual evoked responses (VER) after flash stimulation. Experiments were extended to assess recovery curves of all the potentials and we examined the effects of changes on the rate or voltage of cerebellar stimulation.

Cerebellar stimulation was inhibitory to all the responses except the visual evoked potentials. Serial studies in five patients produced consistent results. Preoperative and postoperative results were compared in two patients with no significant difference in the results in the absence of cerebellar stimulation.

Ipsilateral cerebellar stimulation (CS) had the greatest inhibitory effects on H, V1 and V2 responses in the arm and leg whereas contralateral CS produced the greatest effects on cortical SSEPs. There was a greater bilateral effect on SSEPs and reflex responses after right CS than left CS and this may be the first indication of “dominance” in the cerebellar hemispheres. Cerebellar stimulation in patients on diphenylhydantoin produced minimal effects on SSEP“s and this observation has led to further studies in patients taking diphenylhydantoin.

Recovery of amplitude of the reflex and cortical responses took eight to 30 minutes after one minute of cerebellar stimulation. Serial CS of one minute on and one minute off produced increasing inhibition of SSEP's and reflexes for up to five stimulations. Recovery after cessation of cerebellar stimullion was associated with rebound excitation in six patients, the rebound being noted in the amplitude of H reflexes and SSEP's as well as in the frequency of paroxysmal spike and wave discharges in the EEG.

The correlation of the results of such quantitative neurophysiological tests with clinical improvement may allow prediction of clinical results after cerebellar stimulation. These techniques have already been used to measure the threshold of stimulation and may allow optimal stimulation characteristics to be assessed. The prolonged neurophysiological effects of stimulation may allow the use of maximum effective intervals between optimal epochs of stimulation so that any cerebellar damage can be minimized.
Friedreich's Ataxia: Preliminary Results of some Genealogical Research
Authors: Barbeau A. , Le Siege M. , Breton G. , Coallier R. , Bouchard J.P.
Published: July 2016

A preliminary genealogical investigation of all the known ancestors from the year 1608 of 4 apparently unrelated French Canadian kindreds with Friedreich’s ataxia reveals that the original ataxia gene in the province of Quebec was present within a core of no more than 10 families living in Quebec City in the mid-1600's.
Nerve Conduction Studies and Electromyography in Friedreich's Ataxia
Authors: Peyronnard J.M. , Lapointe L. , Bouchard J.P. , Lamontagne A. , Lemieux B. , Barbeau A.
Published: July 2016

Twenty-six of 50 patients were investigated with nerve conduction studies and electromyography using a standard protocol and were compared to the findings in 50 normal control subjects. Almost all cases of typical Friedreich's ataxia had absent sensory action potentials (SAP) in the digital (92%) or sural (96%) nerves. The others had markedly decreased S.A.P's. In these same patients motor conduction auvelocities were either normal or only slightly decreased. In the second, atypical group of 9 patients, the motor conduction velocities were considerably decreased.

Because of the absence of sensory action potentials in Friedreich's ataxia, and that the absence was noted in our very mild cases, it is proposed that this measure be used to facilitate early diagnosis.
Glucose and Insulin Metabolism in Friedreich's Ataxia
Authors: Shapcott D. , Melancon S. , Butterworth R.F. , Khoury K. , Collu R. , Breton G. , Geoffroy G. , Lemieux B. , Barbeau A.
Published: July 2016

Our prospective survey of 50 ataxic patients confirms the previous finding of frequent clinical or chemical diabetes in Friedreich's ataxia. Eighteen percent of our typical cases have clinical diabetes and 40% at least an abnormal glucose tolerance curve. However, this finding does not appear to be specific to that form of ataxia. Furthermore, we have shown that most patients with ataxia have normal or low fasting insulin levels, but a hyperinsulinic response to a glucose load.
Friedreich's Ataxia 1976 — An Overview
Authors: Barbeau A.
Published: July 2016

The prospective investigation of 50 cases of possible Friedreich's ataxia has permitted the clinical and biochemical delineation of the typical disease and an hypothesis on its pathogenesis. A tentative definition of the disorder could read: “Friedreich's ataxia is a progressive degenerative disease always inherited in an autosomal recessive fashion and characterized by a cardiomyopathy and a ganglioneuropathy with dying back phenomenon. It is probably secondary to a defect in the membrane transport of taurine and β -alanine and/or a defect in the regulation of pyruvate oxidation.” The existence of two pathogenetically distinct distinct entities with the same phenotype is a strong possibility.
Lissencephaly
Authors: Norman Margaret G. , Roberts Maureen , Sirois J. , Tremblay L.J.M.
Published: July 2016

The first reported case of lissencephaly resulting from a consanguinous union strengthens the supposition that in some cases, it is transmitted as an autosomal recessive trait. Comparison of this case with a sporadically occuring case of lissencephaly, with different cortical morphology, suggests that lissencephaly may be an example of either varying gene expressivity or gene-tic heterogeneity. Lissencephaly and pachygyria may eventually be shown to be due to different causes, some inherited, some acquired. The classical examples of lissencephaly are different morphologically from a case in which antenatal cytomegalovirus infection had produced a small smooth brain. This suggests that antenatal viral infections are destructive rather than teratogenic.
Disorders of Neuronal Migration
Authors: Barth Peter G.
Published: July 2016

Neuronal migration constitutes one of the major processes by which the central nervous system takes shape. Detailed knowledge about this important process now exists for different brain regions in rodent and monkey models as well as in the human. In the human, distinct genetic, chromosomal and environmental causes are known that affect neuronal migration, often in a morphologically distinct pattern, but the underlying pathological mechanisms are largely unknown. This review is intended to integrate our basic knowledge of the field with the accumulated intelligence on a large number of disorders and syndromes that represent the human part of the story.
Distribution of Extracellular Matrix Proteins in Primary Human Brain Tumours: An Immunohistochemical Analysis
Authors: Rutka James T. , Myatt Craig A. , Giblin Jane R. , Davis Richard L. , Rosenblum Mark L.
Published: July 2016

Using immunohistochemical techniques, we localized several glycoproteins of the extracellular matrix in paraffin-embedded sections of 4 normal brain and 38 primary intracranial tumour specimens. All specimens were positively immunostained to various degrees by monoclonal antibodies to type IV collagen and procollagen III and by antisera to laminin and fibronectin. Staining was consistently most intense at sites of contact between neuroepithelial and mesenchymal or leptomeningeal elements; there was no demonstrable staining within or between neuroepithelial elements in the neuropil. Tumour cells from meningiomas and from the sarcomatous portion of a gliosarcoma were positively immunostained for fibronectin and laminin. The integrity of the glial limitans externa was demonstrated by the positive linear reaction product produced by immunostains for type IV collagen and laminin, even in the most malignant gliomas. The deposition of extracellular matrix glycoproteins at the glial-mesenchymal interface observed in this study of primary human brain tumours is a manifestation of one of the interactions between tumour and stromal cells in the central nervous system. A loss of coordination and an alteration in the interactions between epithelial cells and stromal cells across extracellular matrices such as basement membranes are thought to be fundamental steps in the development and progression of cancer. Further characterization studies focusing on other markers of the extracellular matrix are needed to elucidate completely the function of this structure in the central nervous system.
Massive Cerebral Edema Associated with Meningioma
Authors: Jagadha Venkita , Deck John H.N.
Published: July 2016

Cerebral edema is a well-known complication of malignant astrocytoma and metastatic brain tumour. Though far less frequent, the association of cerebral edema with meningioma is also recognized; this is unpredictable and sometimes out of proportion to tumour size. We describe three cases where the mass effect was due to severe edema, rather than the tumour itself and was responsible for a catastrophic clinical presentation. The mechanisms responsible for the development of severe edema with meningioma which have been previously proposed are reviewed. They include tumour size, location, histologic subtype, cellularity, mitotic activity, vascularity and the presence of excretory-secretory activity. None of these consistently correlate with cerebral edema. Our cases suggest that spontaneous hemorrhage into the tumour may be the common factor responsible for severe cerebral edema. It is stressed that though a decidedly rare complication, cerebral edema secondary to meningioma should be entertained in the differential diagnosis of acute neurologic deterioration of these patients.
Astrocytomas: Old and Newly Recognized Variants, Their Spectrum of Morphology and Antigen Expression
Authors: Kepes John J.
Published: July 2016

The relationship between the morphology of astrocytomas and their prognosis is complex, with the localization of the tumour, the predominant cell type and the degree of anaplasia all playing an important part in determining the patient's future. Since many astrocytomas have a diversity of patterns, small needle biopsies taken from just one or a few areas may fail to elucidate the principal features of a given tumour. In addition to the astrocytoma subtypes listed in the WHO's International Histological Classification of brain tumours, new entities have been observed in the last few years. These include lipidized forms, such as the relatively benign pleomorphic xanthoastrocytoma and the highly malignant lipidized glioblastoma. Neoplastic astrocytes are capable of forming basal laminae and of phagocytosis, and often contain alpha-1-antitrypsin, features that may lead to confusing them with histiocytes. They may be arranged in a whorled pattern imitating meningiomas, their myxoid intercellular stroma may assume the morphology of cartilage and closely packed tumour cells in “epitheloid” astrocytomas come close to imitate metastatic carcinoma. Some astrocytomas contain cells indistinguishable from those of granular cell tumours of other tissues. The presence of reactive lymphocytes in astrocytomas and reactive astrocytes in malignant lymphomas can be the source of confusion between those two kinds of neoplasms.
Triphasic Waves: Clinical Correlates and Morphology
Authors: Sundaram Mecheri B.M. , Blume Warren T.
Published: July 2016

Twenty-six (41%) of 63 consecutive patients with triphasic waves had various types of metabolic encephalopathies while 37 patients (59%) had non-metabolic encephalopathies, usually senile dementia. Triphasic waves were not found to be specific for any single type of metabolic encephalopathy.

Etiology was more closely linked to conscious level at recording than any morphological or distributional feature of the triphasic waves themselves. Thus, all 31 alert patients had non-metabolic encephalopathies while all 13 comatose patients had metabolic encephalopathies.

The second, positive, component (Wave II) most often had the highest voltage while equally maximal Waves I and II occurred next most commonly. Triphasic waves were most often maximally expressed anteriorly.

Among patients with metabolic encephalopathies, a posterior-anterior delay or lag of the wave II peak occurred more commonly than did the better known anterior-posterior lag. Lags occurred with both metabolic and nonmetabolic conditions, but were more common with the former. No difference in quantity or mode of appearance existed between the metabolic and non-metabolic groups when matched for conscious level.

Prognosis for patients with either metabolic or non-metabolic encephalopathies was unfavourable. Only 4 of 24 metabolic and one of 35 non-metabolic patients were well at follow-up over 2 years later.

Forty percent of EEGs with sharp and slow wave complexes (slow spike waves) had sporadically-appearing triphasic waves. The relative amplitudes of the 3 components differed from triphasic waves in other conditions: equally maximal Waves II and III were the most usual form.
Fenestration of the Supraclinoid Internal Carotid Artery
Authors: Findlay J. Max , Chui Mario , Muller Paul J.
Published: July 2016

A twenty-eight year old woman presenting with subarachnoid hemorrhage was found at angiography to have a left anterior cerebral-anterior communicating artery aneurysm. Also identified was a fenestration of the right supraclinoid internal carotid artery with an associated accessory middle cerebral artery. This appears to be the second reported case of fenestration of the intracranial internal carotid artery. Fenestrations of cerebral vessels and their possible embryologic origins are briefly reviewed.
Colour Vision Abnormalities in Multiple Sclerosis
Authors: Harrison Alexandra C. , Becker Werner J. , Stell William K.
Published: July 2016

A battery of colour vision tests was employed to evaluate visual function in patients with multiple sclerosis (M.S.). Colour deficits were found in 45% of patients tested with the Ishihara plates and 42.5% of patients tested with the FM 100-Hue test. 65% of M.S. patients failed at least one of the tests.

The colour vision deficits were not restricted to patients with optic neuritis or with visual evoked potential (VEP) abnormalities and there was no significant correlation between an abnormal VEP latency and a colour vision deficit. Colour vision testing may be a useful option to consider in the investigation of M.S. patients, even if there is no other evidence of visual system involvement.
CT Findings in Late-Onset Epilepsy
Authors: Sayette V. de la , Cosgrove R. , Melanson D. , Ethier R.
Published: July 2016

We reviewed the CT findings of 387 patients with new-onset seizures after the age of 50. Seizures were generalized in 212 patients, focal in 160, and indeterminant in 15. CT scanning revealed cerebral atrophy in 113 cases, ischemic lesions in 75, cerebral neoplasms in 20, and no abnormality in 177 cases. Tumours were found in only three patients with generalized seizures, and all three had focal neurological deficits at the time of CT diagnosis, while 17 neoplasms were discovered in patients with a focal seizure disorder. The majority of patients with late-onset epilepsy have a normal CT scan with cerebral atrophy being the most common abnormality detected. Cerebral vascular disease appears to be the most frequently identified cause of late-onset epilepsy, while cerebral neoplasms are uncommon.
A Technique for Rapid Non-Suture Vascular Anastomosis
Authors: Gentili Fred , Lougheed W.M. , Yoshijima Sunao , Hondo Hideki , MacKay Margot B.
Published: July 2016

In an attempt to overcome some of the difficulties inherent in vascular anastomosis using standard suture methods, we have developed a technique that allows for rapid non-suture anastomosis of blood vessels. The technique has been used in over 400 anastomoses, including interposition vein grafts in rat, rabbit and dog vessels ranging in size from 0.7 mm to 3 mm in diameter. Animals have been followed for over 1 year ostoperatively with serial angiography and histological evaluation including scanning electron microscopy. Stress studies have compared the biomechanical properties of both non-suture and suture anastomosis. The overall patency rate in non-suture end-to-end anastomoses using an interposition vein graft was 85% at 1 year follow up. Histological evaluation revealed a healing pattern that was temporally similar to that of the suture technique. Stress tests revealed no significant difference between suture and non-suture technique. These studies reveal that the non-suture technique compares favourably with the suture technique, and demonstrate the feasibility of applying this technique to man.
Deafferentation Pain in Man and Animals as it Relates to the DREZ Operation
Authors: Nashold Blaine S.
Published: July 2016

As a resident of Dr. Penfield, I was impressed by his clinical analysis of each patient's complex medical problem. This always included a detailed history and physical examination by the “Neuro” staff with added information gathered by Dr. Penfield during his personal interviews with each patient. This clinical information was later reinforced by extensive operative notes and hand drawn pictures by Dr. Penfield along with photographic studies of the operative site. I soon realized how important it was to collect complete documentation on each patient.
Multicore Myopathy: Not Always a Benign Entity
Authors: Shuaib Ashfaq , Martin Justin M.E. , Mitchell L. Brent , Brownell A. Keith W.
Published: July 2016

Four patients with Multicore Myopathy, a rare morphologically distinct myopathy, are described. Although previously considered to be a non-progressive or only slowly progressive myopathy, progression to significant disability was seen in three of our cases. The association of cardiac disease with Multicore Myopathy has not been previously emphasised. All four patients in this study had a cardiomyopathy, and heart disease was the cause of death in two of the patients. Multicore Myopathy is not always a benign entity. Cardiac involvement, when present, adversely affects prognosis.
Cerebral Metastases from Malignant Melanoma
Authors: Mendez Ivar M. , Del Maestro Rolando F.
Published: July 2016

Six hundred and fifty-two patients with histologically proven primary malignant melanoma have been followed by the London Regional Cancer Centre from 1960 to 1985. Neurological signs and symptoms secondary to metastases to the brain developed in fifty-five patients (8.4%). The median age was 49 years; 71% were male and 29% female. Multiple lesions were found in 61% and a single metastasis in 39%. The most common site for the primary lesion was the trunk in males (44%) and the lower limb in females (37%). Six month survival for patients with a single metastasis was 58% if surgical excision was possible and 25% of these patients survived greater than two years. In patients with multiple metastases that received radiotherapy, survival times of greater than six months were found in 12% of the patients. Patients with a single metastasis appear to benefit by being managed by surgical removal of the lesion.
Hypomelanosis of Ito. Neurological Complications in 34 Cases
Authors: Pascual-Castroviejo Ignacio , López-Rodriguez Luisa , Medina María de la Cruz , Salamanca-Maesso Cipriano , Herrero Carmen Roche
Published: July 2016

We studied 34 Spanish children with hypomelanosis of Ito. This disease has an incidence of 1 per 1000 new patients consulting a paediatric neurological service, or 1 per 8000-10,000 unselected patients in a children's hospital. About 94% of our patients show noncutaneous abnormalities. Mental retardation (IQ below 70) was present in 64.7%; another 14.7% had an IQ between 70 and 90, usually associated with poor school performance. Four children exhibited autistic behaviour. Seizures of various types were present in 53% of cases. Other skin alterations in addition to the typical hypomelanosis were observed in 38% of our cases: caf6-au-lait spots, angiomatous nevi, nevus marmorata, nevus of Ota, Mongolian blue spot, heterochromia of the iris or hair, and other nonspecific pigmentations. Other associated disorders occur inconsistently and include macrocephaly, microcephaly, h6mihypertrophy, kyphoscoliosis, coarse facial features, genital anomalies, inguinal hernia, congenital heart disease, hypertelorism, and abnormalities of the teeth, feet and eyes. Autosomal dominant inheritance is demonstrated in some but not all cases.
Cerebral Arteriovenous Malformations with Associated Arterial Aneurysms: Hemodynamic and Therapeutic Considerations
Authors: Kondziolka Douglas , Nixon Bruce J. , Lasjaunias Pierre , Lasjaunias Pierre , Tucker William S. , TerBrugge Karel , Spiegel Sanford M.
Published: July 2016

The common vascular anomalies of cerebral aneurysm and arteriovenous malformation may exist independently, or together as part of a closely related hemodynamic pairing. Resection or embolization of an AVM may be followed by a decrease in local blood flow, and lead to regression of a suitably situated proximal aneurysm. However, aneurysms located outside the angioarchitecture of the AVM, which remain flow-unrelated to the malformation, will likely not regress, and may in fact enlarge. Two cases are presented which demonstrate these vascular relationships, in order to better understand the regional hemodynamics of these anomalies prior to surgical or endovascular treatment planning.
Myopathy in Primary Systemic Amyloidosis
Authors: Roke M.E. , Brown W.F.E. , Boughner D. , Ang L.C. , Rice G.P.A.
Published: July 2016

Involvement of the peripheral nervous system by amyloidosis is common. It is less well recognized that amyloid can directly infiltrate and weaken skeletal muscle. We report a case of a 73-year-old woman, known to have cardiac amyloidosis, who developed profound weakness secondary to amyloid myopathy. Review of the 8 other well documented cases in the literature has revealed a rather homogeneous syndrome. Proximal weakness, muscle stiffness, pseudohypertrophy and myalgia constitute the principal features. This syndrome usually develops in cases with well recognized generalized amyloidosis. Amyloid is deposited within the basal lamina of blood vessels and muscle fibers.
Intrathecal Fibrinolytic Therapy after Subarachnoid Hemorrhage: Dosage Study in a Primate Model and Review of the Literature
Authors: Findlay J.M. , Weir B.K.A. , Kanamaru K. , Grace M. , Gordon P. , Baughman R. , Howarth A.
Published: July 2016

Because of the naturally low fibrinolytic activity of CSF many erythrocytes entrapped in subarachnoid blood clot undergo hemolysis in situ, releasing vasogenic oxyhemoglobin (OxyHb) in high concentrations around the basal cerebral arteries. In order to promote more rapid clearance of erythrocytes from the basal subarachnoid cisterns we are currently investigating intrathecal thrombolytic therapy with human, recombinant, tissue plasminogen activator (rt-PA) in a primate model of subarachnoid hemorrhage (SAH) and cerebral vasospasm (VSP). In the present study 16 monkeys were divided into 4 groups of 4, and each group received a different dose of sustained-release gel rt-PA at the time of experimental SAH. Cerebral angiography seven days later showed that whereas no VSP occurred in the groups receiving 0.5 or 0.75 mg of rt-PA, mild to moderate VSP occurred in the groups receiving 0.125 or 0.25 mg of rt-PA. Analysis of the combined 2 smaller dosage groups revealed significant (P<0.05) reduction of lumen caliber in the clotside internal carotid (C3 and C4), proximal anterior cerebral (A1) and middle cerebral (MCA) arteries. Gross subarachnoid clot remained in all of the animals in the 0.125 and 0.25 mg dose groups, in 2 of the animals in the 0.5 mg dose group, and none of the animals in the 0.75 mg dose group. It was concluded that 0.75 mg of gel rt-PA is sufficient to completely lyse a 4.25 ml SAH and prevent VSP in our primate model. The literature on fibrinolysis and erythrocyte clearance in cerebrospinal fluid (CSF) is reviewed.
Dendritic Pathology: An Overview of Golgi Studies in Man
Authors: Jagadha Venkita , Becker Laurence E.
Published: July 2016

Study of dendritic morphology through Golgi impregnation techniques has significantly furthered our understanding of neuronal development, maturation, and senescence. It has also provided insight into the pathogenesis of a wide spectrum of disease processes ranging from brain malformations to degenerative disorders. Golgi impregnation remains virtually the only method for demonstrating dendritic morphology. It delineates the profile of the individual neuron and its dendritic ramifications with unsurpassed clarity. Although it has been widely applied to experimental neuroscience involving animal tissue, its application to human material has been limited. This review summarizes the information on dendritic development and pathology in the human brain revealed by the use of the Golgi method.
Effect of Knee Joint Angle on a Heteronymous lb Reflex in the Human Lower Limb
Authors: Brooke J.D. , Mcllroy W.E.
Published: July 2016

Altered efficacy, from change in receptor discharge with different positions of the knee, was investigated in a heteronymous lb reflex of the human leg. The electrical stimulus was low threshold, to the common peroneal nerve. The divergence of the group I afferents was studied in the electromyograms (EMGs) of ipsilateral and contralateral thigh muscles. The stimulus evoked ipsilateral, short latency, excitation in the three quadriceps muscles studied and inhibition in the knee flexor semitendinosus (ST), with prior contraction of target muscles. This excitation and inhibition did not alter when studied over the range of the knee joint. The stimulus did not evoke responses in contralateral thigh muscles, contracted or relaxed. It is concluded that (1) any change in convergence from discharge of receptors, during extension of the limb, is small and sub-threshold, and (2) this spinal proprioceptive level of neural control appears to be directed primarily to the single limb.
La variabilité du phénotype dans la dystrophie myotonique de Steinert
Authors: Bouchard Jean-Pierre
Published: July 2016

Phenotype Variability in Myotonic Dystrophy Myotonic dystrophy, best known in the French literature as Steinert disease, is a dominantly inherited disorder. When the gene is fully expressed, it shows a characteristic clinical picture. Myopathy and myotonia are the main features, but this is a systemic disease which may involve many other organs such as the central nervous system, eyes, bones, endocrine system, etc. With the complete picture, physical and behavioral features make the diagnosis easy, only to be confirmed by neurological and ophthalmologic examination and/or electromyography. This work reviews the main clinical signs seen in the classical form of the disease. We also want to stress the variability of that picture. Finally, we describe a new dysmorphic sign in myotonic dystrophy: large prominent cupped auricles. Although not recognized, prominauris has been illustrated in a number of publications on myotonic dystrophy. Three of our adult male patients presenting the congenital form of the disease at birth have been investigated to rule out concomitant fragile-X syndrome. Both syndromes include mental retardation and dysmorphic ears. Our patients show the usual testicular atrophy, whereas the fragile-X syndrome includes testicular hypertrophy. Cytogenetic studies were normal. Old clinical description and new physical signs may lack prestige in the perspective of recent molecular biological breakthroughs, but to recognize the disease and help patients live with it will always be the role of practitioners.
Ascertainment of Informative Alzheimer Disease Families from the IMAGE Project Registry for Genetic Linkage Analysis Studies
Authors: Gautrin D. , Nalbantoglu J. , Lacoste-Royal G. , Grenon M. , Gauthier S. , Bouchard R. , Mathieu J. , Robitaille Y. , Doyon L.-P. , Bergman H. , Cholette A. , de Braekeleer M. , Bouchard G. , Gauvreau D.
Published: July 2016

Genetic linkage analysis requires the identification and documentation of large families with many affected members present, preferably in more than one generation. The IMAGE Project has been establishing a population- based Alzheimer disease (AD) registry in the Saguenay - Lac-Saint-Jean region of the Province of Quebec. The population of this region has a well-documented ancestry, with reliable genealogical records (since 1842) computerized by SORER We have recently begun to investigate the pedigrees of selected probands (definite, probable and possible) from the IMAGE registry in order to identify informative pedigrees for genetic linkage analysis. Interviews were carried out with close relatives of the probands (at least one informant per sibship) to identify secondary AD cases. The questionnaires used pertain to the accuracy of genealogical records, to family medical history and to a retrospective diagnosis of AD for people with cognitive deficits. By these means, we have documented a large extended pedigree in which a total of 15 individuals with cognitive deficits were ascertained over three generations. Of these cases, 7 are still living and there is autopsy confirmation in another one. Computer simulations using the program SIMLINK revealed that this is a potentially informative family for linkage analysis. Horizontal extension of the pedigree to second cousins of the proband is now being carried out. This will render the family IMAGE/1 even more informative in genetic linkage analysis studies.
Strategies for the Identification of Novel Brain Specific Genes Affected in Alzheimer Disease
Authors: Walker D.G. , Boyes B.E. , McGeer P.L. , McGeer E.G.
Published: July 2016

The pathological changes that occur in Alzheimer disease (AD) brain lead to a large loss of various classes of neurons and the production of novel proteinaceous elements such as neuritic plaques and neurofibrillary tangles. For the neuronal loss to occur and these elements to arise, there must be a disturbance in the expression or regulation of genes that code for proteins required for normal cell maintenance, or perhaps even for the expression of genes unique to AD. We describe the construction of a cDNA library from the human substantia innominata and strategies for isolating genes that are expressed differentially between brain regions and which may be affected by AD. Some of the results obtained using these strategies and a preliminary description of a novel brain specific mRNA of 15.5kb, whose expression is increased in AD affected temporal cortex, are presented.
Absence of Responses to Microstimulation at the Hand-Face Border in Baboon Primary Motor Cortex
Authors: Samulack Donald D. , Waters Robert S. , Dykes Robert W. , McKinley Patricia A.
Published: July 2016

Intracortical microstimulation (ICMS) was used to map the primary motor cortex of four adult female baboons, anesthetized with a mixture of halothane and nitrous oxide and supplemented with sodium pentobarbital. The sequence of observed muscle contractions in response to ICMS provided evidence of an orderly mototopic representation of the tongue, face, hand, forearm and upper body. A zone of cortex unresponsive to microstimulation was consistently observed at the border between the face and hand representation of the mototopic map. This zone was observed in all four animals and was consistent over time. Repeated confirmations of the unresponsive nature of these regions were obtained both early and late in the same experiment. No motor-unit responses or muscle contractions were detected by electromyographic (EMG) recording during stimulation of the unresponsive zones. The absence of both visually observed and EMG-recorded contractions and the fact that muscle contractions could be elicited from adjacent regions of cortex with ICMS as low as 1-5 μA provide compelling evidence that the finding reflects a true physiological condition rather than an experimental artifact.
Receptive-field Size of S1 Cortical Neurones is Altered by Methaqualone via a GABA Mechanism
Authors: Hicks T.P. , Kaneko T. , Oka J.-I.
Published: July 2016

Methaqualone (Mtq; quaaludes or 'ludes) is a controlled substance, having a molecular structure related to the imidiazobenzodiazepine series of drugs, that has gained some notoriety recently due to its history of widespread abuse on the street. Users report experiencing peripheral paresthesia and transient numbness on body parts receiving dense cutaneous innervation (lips, fingertips, etc.). Since the receptive-field (RF)-sizes of many primary somatosensory (SI) cortical neurones are controlled by local, gamma-aminobutyric acid (GABA)-mediated inhibitory processes, we tested Mtq to see whether its clinical symptoms might have a basis in an action through central GABA-mediated synaptic processes. This report supports this contention and describes a likely pharmacological mechanism involved as one being related to the Ro 15-1788-sensitive benzodiazepine (Bzd) recognition site(s) of the GABA receptor complex.
The Second Canadian Conference on Multiple Sclerosis
Authors: Weinshenker Brian G. , Nelson Robert
Published: July 2016

The epidemiology of multiple sclerosis (MS) and the planning and interpretation of clinical therapeutic trials were the subjects of a symposium on MS held on June 13, 1989. Several speakers addressed whether MS is a genetic or an environmental disease. An environmental trigger would resolve the relatively low penetrance of the disease in susceptible individuals, although the alternative hypothesis that MS is a multigenic disease would also account for this observation. Clinical trials have to date failed to confirm the efficacy of any immunosuppressive or other agent in the management of progressive MS. Magnetic resonance imaging (MRI) appears to be highly sensitive for monitoring the activity of MS. Preliminary evidence suggests that MRI activity correlates with longitudinal clinical assessments of disability. Immunologic tests, while valuable in determining pathophysiology of MS, have not been strongly correlated with clinical outcome.
Neuropathie Sensitivo-Motrice Héréditaire avec ou sans Agénésie du Corps Calleux: Étude Radiologique et Clinique de 64 Cas
Authors: Mathieu Jean , Bédard Fernand , Prévost Claude , Langevin Pierre
Published: July 2016

In 1971, Andermann and Andermann described an autosomal recessive syndrome found within the Charlevoix and the Saguenay populations (Quebec, Canada) characterized by agenesis of the corpus callosum (ACC) associated with motor and sensory neuropathy, mental retardation and dysmorphic features. A study of CT in 64 patients demonstrated a total ACC in 37 cases (57.8%), partial ACC in 6 cases (9.4%) and the presence of the corpus callosum in 21 cases (32.8%). The latter was confirmed by MRI in 3 cases. CT of patients without ACC revealed a high frequency of developmental or degenerative midline anomalies, particularly interhemispheric fissure enlargement and posterior fossa atrophy. The clinical presentation and the natural course of the neuropathy, the intellectual impairment and the behavioural manifestations are identical amongst individuals with or without ACC. Individuals with or without ACC are found within the same family and often within the same sibship. These observations support the hypothesis of a single genetic syndrome in which the constant manifestation is the motor and sensory neuropathy.
Coordination of a Multi-Joint Movement in Normal Humans and in Patients with Cerebellar Dysfunction
Authors: Becker W.J. , Kunesch E. , Freund H.-J.
Published: July 2016

The contribution of the cerebellar cortex to coordination of a multi-joint throwing movement was studied by measuring various movement and EMG parameters while normal control subjects and patients with cerebellar cortical atrophy threw a ball at a target. Although patients did not throw as accurately as controls, several coordination measurements were normal in the patients. These included parameters used by us to assess elbow-wrist coordination and the coordination of hand opening with activation of more proximal arm muscles. Postural support for the movement at the shoulder was also normal in that the shoulder was not pushed backwards by the reaction forces resulting from the rapid forward acceleration of the forearm and hand. In contrast, however, patients were unable to coordinate the muscles so as to produce the same hand direction from trial to trial when throwing at the same target. In addition, EMG onset times were abnormal in the antagonist muscles relative to agonist EMG bursts and kinematic parameters of the movement. In conclusion, our patients with cerebellar cortical atrophy showed abnormalities in visual-motor coordination, in that they were unable to consistently produce the appropriate hand direction in response to a visual target. Agonist-antagonist relationships were also impaired. Other aspects of coordination, such as the relative timing of EMG onsets of agonist muscles, even when these were active at different joints, were normal.
Parkinsonism with Neuroacanthocytosis
Authors: Peppard R.F. , Lu C.S. , Chu Nai-Shin , Teal P. , Martin W.R.W. , Calne D.B.
Published: July 2016

Two patients with neuroacanthocytosis are described. One presented with parkinsonism and the other resembled diurnal dystonia of the Segawa type. Both patients responded well to dopaminomimetic therapy. A PET scan with fluorodopa revealed a nigrostriatal deficit in the first patient.
Paraneoplastic Encephalomyelitis and Subacute Dysautonomia due to an Occult Atypical Carcinoid Tumour of the Lung
Authors: Veilleux M. , Bernier J.P. , Lamarche J.B.
Published: July 2016

A case of paraneoplastic encephalomyelitis and subacute pandysautonomia associated with an occult atypical carcinoid tumour of the lung is described. The main clinical features were lethargy, impaired memory, constipation, and orthostatic hypotension. Neurological investigation was unremarkable except for mononuclear pleocytosis and increased protein level in the cerebrospinal fluid (CSF). Tests of autonomic function revealed a low plasma norepinephrine level, a marked drop of blood pressure (BP) to vertical tilt and Valsalva maneuver, and a marked rise of BP to dilute norepinephrine infusion. A few days prior to death, the patient became hypothermic and had repeated episodes of respiratory arrest associated with transient atrioventricular block on the electrocardiogram (ECG). A polysomnography study confirmed a sleep apnea syndrome. Autopsy revealed an atypical carcinoid tumour in one tracheobronchial lymph node, widespread lymphocytic infiltrates and loss of neurones in the cerebral, cerebellar and brainstem gray matter, the spinal cord and roots, and the paravertebral sympathetic ganglia as well as microglial and astrocytic proliferation in the central nervous system.
Fatal Streptokinase-Induced Intracerebral Haemorrhage in Cerebral Amyloid Angiopathy
Authors: Ramsay D.A. , Penswick J.L. , Robertson D.M.
Published: July 2016

A fatal intracerebral haemorrhage (ICH) associated with streptokinase (SK) treatment of an acute myocardial infarction is described. Autopsy examination showed a lobar ICH and severe cerebral amyloid angiopathy (CAA). The close temporal relationship between SK administration and intracranial haemorrhage, the absence of pretreatment risk factors for ICH, and the presence of CAA suggests that these are related phenomena. Accordingly: 1. There may be a synergistic relationship between CAA and intracranial haemorrhage induced by fibrinolytic agents; 2. Thrombolytic agents may induce more frequent than expected intracranial haemorrhage in conditions associated with a high incidence of CAA, notably old age and Alzheimer's disease; 3. A regional defect in haemostasis other than vessel fragility may contribute to the intracranial haemorrhagic predisposition of CAA; 4. Autopsy examination of cases of ICH is an essential part of the audit of clinical trials of fibrinolytic agents.
Multiple Sclerosis in French Canadians: Evidence for HLA Class II Susceptibility and Resistance Genes
Authors: Haegert D.G. , Michaud M. , Francis G.S.
Published: July 2016

HLA class II DRBI, DQB1 and DQA1 gene probes were used to study DNA from unrelated French Canadian multiple sclerosis (MS) patients and controls by restriction fragment length polymorphism (RFLP) analysis. An MS-associated and linked series of allele-specific RFLPs or allogenotypes was identified among this relatively homogeneous ethnic group; the allogenotypes include DRwl5, DQw6 and a DQA1 allogenotype termed DQαlb. An additional allogenotype which cross-hybridizes with DQA1 and is termed DQA2 upper (DQA2U), was shown not only to be part of the MS-associated extended haplotype, but also to be independently associated with MS in DRwl5-negative patients. Conversely a second DQA2 allogenotype, termed DQA2 lower (DQA2L) and a DQB1 allogenotype (DQw7) linked to DQA2L showed negative correlations with MS. It seems likely that the relationship of the HLA class II gene region to MS is complex and that MS susceptibility may reflect interaction between disease susceptibility and resistance genes.
The Mechanism of Embolic Watershed Infarction: Experimental Studies
Authors: Pollanen M.S. , Deck J.H.N.
Published: July 2016

The mechanism for the preferential distribution of emboli to cerebral arterial bordcrzone regions, known to cause some watershed infarcts was studied. We hypothesized that emboli of a specific size range are selectively directed to the arterial borderzones due to the tendency of emboli to bypass the small arterial branches which emerge proximal to major borderzones. To test this hypothesis we perfused the brains of cadavers with suspensions of 90-210 µm glass microspheres and chemically extracted the particles from various arterial territories and a watershed zone. Particles in the 150-210 µm size range were found to be preferentially distributed to the watershed zone whereas particles less than 150 µm in size were randomly dispersed in leptomeningeal arteries of all vascular regions. To assess the role of branch size on the concentration of emboli at bifurcations, we perfused artificial analogs of evenly and unevenly branching bifurcations with suspensions of 90-150 µm and 150-210 µm particles. Branching cylinders with symmetrical branches contained the same concentration of particles, independent of particle size. In contrast, when one branch was one-quarter the size of the other, the concentration of 150-210 µm particles in the asymmetric branch was approximately 65% of the main trunk. Particles 90-150 µm in size were evenly distributed despite variation in branch size. These results indicate that emboli, of a limited range of size, may be selectively propagated to the distal ramifications of subarachnoid arteries located in the watershed zone rather than diverging into small calibre branches which arise along the way.
Similarities of Guamanian ALS/PD to Post-Encephalitic Parkinsonism/ALS: Possible Viral Cause
Authors: Hudson Arthur J. , Rice George P.A.
Published: July 2016

Guamanian amyotrophic lateral sclerosis with parkinsonism-dementia (ALS/PD) has been the subject of intensive study since its discovery in 1947 because of its extraordinarily high incidence in a small ethnic group (Chamorros) whose dietary lack and customs have suggested possible causes. As yet, these and other suspected causes have eluded proof. Because of marked similarities between Guamanian ALS/PD and late onset post-encephalitic (encephalitis lethargica) parkinsonism and ALS it is suggested that they have a common cause. The parkinsonism and ALS in the two disorders are clinically very similar and neuropathological studies have shown a very similar distribution of neurofibrillary tangles in neurons. Some clinical differences, such as ocular features in the post-encephalitic cases and dementia in Guamanian ALS/PD, can be explained by differences in the severity of infection and the interval between the encephalitis and onset of sequelae. Although unproven, influenza A (HswilNl strain) has long been suspected as the cause of encephalitis lethargica because of simultaneous pandemics of the two diseases in the 1920s. Because influenza A can persistently infect cells and has a marked propensity to mutate it is an optimal candidate among other RNA viruses for delayed nervous system infection as a possible cause of ALS/PD.
1990 Richardson Lecture — Challenges for Neurology in the Nineties: Will We Survive?
Authors: Martin Joseph B.
Published: July 2016

It is a great honor for me to present the Richardson Lecture this year. Although I was not personally acquainted with Dr. Richardson, his contributions to Canadian neurology are legendary, not the least of which is immortalized in the disease he and his colleagues first described in 1964: Steele-Richardson-Olszewski syndrome.

I have entitled my talk “Challenges for Neurology in the 90s: Will We Survive?”, to highlight some of the issues that I believe are important for us to consider as we embark upon our academic enterprise during the last decade of the 20th century. There are a number of opportunities as well as, potentially, major difficulties that we face, and I wish to focus attention on some of them.
MPTP-Induced Neurotoxicity and the Quest for a Preventative Therapy for Parkinson's Disease
Authors: Furtado J.C.S. , Mazurek Michael F.
Published: July 2016

Less than 10 years have passed since the discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is capable of producing parkinsonism in both humans and non-human primates. In that time, there has been considerable interest in the possibility that the pathogenesis of idiopathic Parkinson's disease (PD) might involve a process analogous to that of MPTP toxicity. One hypothesis holds that PD might arise, at least in part, from exposure to an MPTP-like environmental toxin. Rapid progress has been made towards elucidating the precise mechanism by which MPTP exerts toxicity, and clarifying the relationship of MPTP toxicity to idiopathic PD. The goal of these efforts is to develop a therapy that inhibits the underlying disease process in PD.