bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Joint Reaching Movements and Eye-Hand Tracking in Cerebellar Incoordination: Investigation of a Patient with Complete Loss of Purkinje Cells
Authors: Becker W.J. , Morrice B.L. , Clark A.W. , Lee R.G.
Published: July 2016

Performance on an eye-hand tracking task and a multi-joint reaching movement to a visual target was studied in a patient with stable cerebellar ataxia and in control subjects. The patient subsequently died and a full neuropathological examination was performed. The neuropathological findings were similar to those seen in patients with paraneoplastic cerebellar degeneration, but no tumor was found at autopsy eight years after onset of the patient's cerebellar syndrome. A severe cerebellar cortical degeneration with complete Purkinje cell loss was demonstrated, whereas cerebellar nuclei and brainstem structures showed no neuronal loss. Tracking performance by the patient was characterized by abnormally large numbers of high velocity movements and hand direction reversals, and by excessive lagging of the hand behind the target in time. In the multi-joint reaching movement, the patient showed a delay in movement onset at the elbow joint compared to movement onset at the shoulder joint. The velocity profile of the movement at the shoulder joint was abnormal. The duration of the acceleration phase was poorly correlated with both peak angular velocity and the duration of the deceleration phase. One of the most striking findings was the inability of the patient to consistently produce the same movement direction from trial to trial while reaching to the same target. Our data suggests that the cerebellar cortex is involved in multiple aspects of motor control including visuomotor integration mechanisms.
Differential Vulnerability to Excitatory Amino Acid-Induced Toxicity and Selective Neuronal Loss in Neurodegenerative Diseases
Authors: Weiss John H. , Choi Dennis W.
Published: July 2016

Neurodegenerative diseases are characterized by selective degeneration of certain biochemically distinct subpopulations of central neurons. Studies of the intrinsic vulnerability of such neurons to injury by excitatory amino acids in vitro, as well as study of neurologic syndromes produced in animals or humans by ingestion of environmental excitatory amino acid neurotoxins may suggest a link between excitotoxicity, and the pathogenesis of certain neurodegenerative diseases.
Molecular Interactions Modulating Neuronal Survival and Growth
Authors: Riopelle R.J. , Dow K.E. , Verge V.M.K. , Richardson P.M.
Published: July 2016

The extracellular environment of the neuron provides a heterogeneous milieu of survival and growth modulating molecular species subserving regulatory signals that operate in development, meditate activity-dependent enduring changes in synaptic connectivity, and promote or inhibit survival and axonal regeneration following insult. Parallel distributed processing networks in neurons, activated by these molecular species, can likely be recruited selectively to serve specific needs of the organism.
Neuronal Loss in a Lower Motor Neuron Disease Induced by a Murine Retrovirus
Authors: Jolicoeur Paul
Published: July 2016

An animal model of neuronal loss induced by a murine retrovirus is described. The neurological disease is manifested by a lower limb paralysis and is characterized as a spongiform myeloencephalopathy. The primary determinant of neurovirulence has been mapped within the viral env sequences and a secondary determinant is present within the LTR region. A model of pathogenesis, suggesting that the disease is receptor-mediated, is proposed.
Electroencephalography, Magnetic Resonance Imaging and Pathology in Patients Treated Surgically for Temporal Lobe Epilepsy
Authors: Feindel William , Robitaille Yvon , Tampieri Donnatella , Goossens Lutgart , Li Maria , Melançon Denis
Published: July 2016

In a consecutive series of 40 patients selected by EEG studies for surgical treatment of temporal lobe seizures, magnetic resonance imaging showed structural lesions in 25% and signal abnormalities, usually in the mesial temporal region, in another 35%. Pathological changes included structural lesions in over 30% of patients and sclerosis of the amygdala in almost half of the series. These findings further substantiate the implication of the amygdala in the pathogenesis of temporal lobe seizures with automatism and amnesia.
Temporal Lobectomy: Review of 100 Cases with Major Hippocampectomy
Authors: Feindel William , Rasmussen Theodore
Published: July 2016

One hundred consecutive patients between 1961 and 1980, with temporal lobectomy including excision of half or more of the hippocampal formation, have been analyzed for degree of reduction of seizures. Thirty-nine percent have become and remained seizure free for follow-up period of 2 to 24 years (median 12 years). Another 24 patients achieved a marked reduction in seizure tendency as defined in the report and 25 showed a lesser degree of improvement. In fifteen patients no change in seizure frequency was recorded. Thus in this series of 100 patients, a complete or marked reduction of the seizure tendency was achieved in 63%.
Relevance of Removal of Limbic Structures in Surgery for Temporal Lobe Epilepsy
Authors: Olivier André
Published: July 2016

We have briefly reviewed the experimental and clinical evidence for the importance of the amygdala and hippocampal formation in temporal lobe epilepsy. More specifically, we have analyzed our own experience in patients with temporal lobe epilepsy investigated with intracerebral stereotaxic electrodes and operated by various modalities of resection. Our results, in agreement with previous experimental and clinical work, provide further evidence for an overwhelming predominance of limbic participation in temporal lobe epilepsy. As a result, more and more selective procedures are being carried out involving the mesial structures. However, this shift has been slow and progressive because of the proven value of cortico-amygdalo-hippocampectomy which provides excellent results on seizure tendency with low morbidity.
Familial periodic ataxia responsive to acetazolamide
Authors: Bouchard J.P. , Roberge C. , Gelder N.M. van , Barbeau A.
Published: July 2016

Twocases,afather and son, of recurrent cerebellarataxiain the same family are reported, suggestingafamilial trait for the dysfunction. In the older male the onset of each episode (30-90 min.) was signalled by dysarthria which then progressed towards gait ataxia; the son presented closely similar clinical symptoms. Physical examination and blood chemistry revealed no obvious neurological deficit or biochemical abnormalities, with the exception of I-III and III-IV evoked auditory wave interpeak latencies, which were found markedly abnormal on the left side in the father but not in the son; the EEG of both individuals showed some diffuse, slow wave abnormalities. A low dose of acetazolamide, 250 mg daily, has successfully repressed recurrence of the attacks over the past six months. Temporary withdrawal for 14 days of the carbonic anhydrase inhibitor in the father coincided with two observed ataxic episodes.
Distribution of apolipoprotein E phenotypes in Friedreich's ataxia
Authors: Bouthillier D. , Nestruck A.C. , Milne R. , Sing C.F. , Barbeau A. , Davignon J.
Published: July 2016

Allelic polymorphism at the apolipoprotein E (apo E) gene locus (alleles ɛ2, ɛ3 and ɛ4) is responsible for the existence of 6 discrete electrophoretic phenotypes of plasma apo E. Since the presence of the ɛ2 allele in the genotype tends to be associated with higher triglyceride levels, a study was undertaken to determine if a higher frequency of this allele could account for the presence of higher plasma triglycerides in subsets of patients with Friedreich's Ataxia. The frequency of the apo E phenotypes was determined in 37 subjects with Friedreich's Ataxia and compared with that of 102 normolipidemic and 102 hyperlipidemic individuals. There was no increased prevalence of the E3/2 phenotype and the ɛ2 allele in the Friedreich's sample as is found in a hyperlipidemic sample. Furthermore, the ɛ2 subset did not have significantly higher plasma triglycerides than the non-ɛ2 subset and the hypothesis was rejected. On the other hand, there was a trend for a decreased frequency of the E4/3 phenotype in the Friedreich's sample relative to the hyperlipidemic group but the difference did not reach statistical significance. The apo E phenotype distribution was also measured in a smaller sample of Charlevoix-Saguenay disease; this led to the discovery of two siblings with the relatively rare E2/2 phenotype and unexpectedly low levels of plasma lipid and lipoprotein concentrations. Plasma apolipoprotein E concentrations in both diseases were within the normal range except for subjects bearing the E2/2 phenotype.
The Encephalopathy of Sepsis
Authors: Jackson Alan C. , Gilbert Joseph J. , Young G. Bryan , Bolton Charles F.
Published: July 2016

Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.
Electrophysiological Disorders in Multiple Sclerosis and Optic Neuritis
Authors: Sanders E.A.C.M. , Reulen J.P.H. , Hogenhuis L.A.H. , van der Velde E.A.
Published: July 2016

Visual evoked response (VER), auditory brainstem evoked response (ABER), somatosensory evoked response (SSER), blink reflex and electronystagmographic (ENG) investigative methods were applied to a group of 89 patients with Multiple Sclerosis (MS) and Optic Neuritis (ON). The MS patients were classified as definite (n = 31), probable (n = 31) and possible (n = 27).

The aim of this study was to determine the diagnostic value of the five electrophysiological tests in MS. VER and ABER recordings were found to reveal the highest number of asymptomatic abnormalities (33 and 31 percent respectively). The combination of VER, ABER and ENG revealed all possible electrophysiological disorders. As these tests are completely non-invasive it is proposed, that a combination of two of these three tests is useful for the detection of a second silent lesion in patients with suspected MS showing purely spinal signs (VER, ENG, ABER) and/or a history of uncomplicated ON (ABER, ENG).
Monitoring of Sensory Evoked Potentials During Surgery of Skull Base Tumours
Authors: Gentili F. , Lougheed W.M. , Yamashiro K. , Corrado C.
Published: July 2016

Despite advances in instrumentation and the use of microsurgical techniques, neurosurgical procedures involving extensive areas of skull base or other critical areas of brain still carry significant risk for neurological injury. The use of intraoperative recording of sensory evoked potentials (SEP) has been advocated to monitor neurologic function during these major neurosurgical procedures to reduce the risk of injury to neural structures.

This report summarizes our experience with intraoperative monitoring of SEP in over 200 patients, and details our findings in a group of 12 patients with skull base and posterior fossa tumours. Somatosensory evoked potentials (SSEP) were monitored in all patients, and brain stem auditory evoked potentials (BAEP) in five. While minor changes in BAEP and SSEP parameters were noted in most patients, significant changes occurred in five. Irreversible loss of BAEP in one patient was associated with complete hearing loss postoperatively. Marked, persistent alteration of both BAEP and SSEP was associated with postoperative brainstem dysfunction. No patient with stable BAEP and SSEP at the end of the procedure suffered additional neurological deficit.

We conclude that intraoperative SEP monitoring may be valuable in minimizing neural injury during major neurosurgical procedures.
Craniopharyngiomas
Authors: Hoffman Harold J.
Published: July 2016

A review has been carried out of those patients with a craniopharyngioma who were treated initially in our institution and had a microsurgical excision of their tumour during the period of time when newer and sophisticated modalities of investigation and treatment were available. Twenty-nine patients with craniopharyngioma were treated initially by microsurgical excision of their tumour at the Hospital for Sick Children from January 1976 to June 1985. In 21 a total removal of the tumour was performed, and there has been no clinical evidence of recurrence. No deaths were recorded in any of the 29 patients. The principal morbidity has resulted from endocrine deficits that these patients exhibit.
Intrathecal Synthesis of Autoantibodies to Myelin Basic Protein in Multiple Sclerosis
Authors: Catz Ingrid , Warren Kenneth G.
Published: July 2016

A solid phase radioimmunoassay was used to detect anti-myelin basic protein (MBP) antibodies in the CSF and serum of multiple sclerosis (MS) patients and controls. CSF and serum samples were assayed prior to acid hydrolysis in order to detect free anti-MBP as well as after acid hydrolysis to measure the total (free and bound) amount of antibody. An anti-MBP index controlling for serum levels as well as the degree of breakdown of the blood brain barrier was used to estimate intrathecal synthesis of anti-MBP. MS patients with acute exacerbations or chronically progressive disease have significantly elevated levels of both free and total CSF anti-MBP. The anti-MBP index is also significantly increased in MS patients with both forms of active disease. Anti-MBP antibodies are intrathecally produced in MS patients with active disease.
High Dose Anticholinergic Therapy in Adult Dystonia
Authors: Lang Anthony E.
Published: July 2016

Forty-four adult patients with various forms of dystonia were treated with anticholinergics slowly increased to maximum tolerated doses. Thirty-seven per cent of the 35 idiopathic dystonia patients had a moderate to marked improvement with an average dosage of 21.5 mg of trihexyphenidyl. Younger patients with a shorter duration of dystonia and those who tolerated higher doses tended to benefit most. However there were exceptions to all of these factors. None of the nine patients with symptomatic dystonias improved more than mildly and most had no benefit despite the use of dosages similar to those resulting in improvement in idiopathic dystonia patients. Side effects were common. These often forced drug withdrawal at lower doses than those which might have resulted in improvement. These results suggest that high dose anticholinergics should be the first line of therapy for disabling dystonia.
The Concurrence of Multiple Sclerosis and Amyotrophic Lateral Sclerosis
Authors: Hader Walter J. , Rozdilsky Bohdan , Nair Cheranada P.
Published: July 2016

We report the clinical and pathological findings of the unusual combination of two idiopathic central nervous system diseases, multiple sclerosis and amyotrophic lateral sclerosis in a 56 year old physician with a twenty-seven year history of a disease initially characterized by relapses and remissions, followed by an eight year quiescent period. During the last year of life there was rapid deterioration with development of generalized weakness, atrophy, weight loss and fasciculations of body and tongue, and associated difficulty with swallowing and sudden respiratory failure. The autopsy confirmed characteristic “burned out” plaques of multiple sclerosis and anterior horn cell and axonal degeneration of amyotrophic lateral sclerosis.
Modification of Motor Output to Compensate for Unanticipated Load Conditions During Rapid Voluntary Movements
Authors: Lee R.G. , Lucier G.E. , Mustard B.E. , White D.G.
Published: July 2016

Mechanisms responsible for load compensation during fast voluntary movements were investigated in 20 normal subjects trained to carry out rapid wrist flexions against a standard load. When an unanticipated increase in load occurred, there was a compensatory increase in agonist EMG and decrease in antagonist EMG. Unanticipated decreases in load produced reciprocal changes with a decrease in agonist EMG and an increase in antagonist EMG. The latency of these EMG changes was quite short and compatible with a spinal reflex mechanism rather than a long loop response. The results suggest that mechanisms exist at the spinal level to allow rapid modification of motor programs when unanticipated load conditions are encountered on initiation of movement.
Optic Neuritis and Myelopathy in Systemic Lupus Erythematosus
Authors: Oppenheimer Stephen , Hoffbrand B.I.
Published: July 2016

The optic neuritis of systemic lupus erythematosus (S.L.E.) more frequently results in the persistence of a central scotoma or complete blindness after a single attack than demyelinating optic neuritis, although the initial clinical presentations may be identical. A significant number of patients, however, recover normal vision. Optic neuritis may be the presenting symptom of S.L.E. and as myelopathy may also occur in the course of the disease, confusion with multiple sclerosis may result, especially if there are no arthritic, cutaneous nor visceral manifestations. We report a case of lupus optic neuritis associated with anticardiolipin antibodies and a circulating lupus anticoagulant and suggest these may be a marker for vasculitic optic neuritis and play a role in its aetiology.
Free and Total Serum Valproate Concentrations: Their Relationship to Seizure Control, Liver Enzymes and Plasma Ammonia in Children
Authors: Farrell Kevin , Abbott Frank S. , Orr James M. , Applegarth Derek A. , Jan James E. , Wong Peter K.
Published: July 2016

The relationships between total and free serum valproate (VPA) concentrations and seizure control, serum liver enzyme activity and plasma ammonia concentration were studied in 61 epileptic children. Enzymeimmunoassay (EMIT)Rmethods gave higher values of total VPA concentration than gas-liquid chromatography (GLC) methods. In over 80% of children with complete seizure control the ranges of total VPA concentration were 140-420 umol/L with GLC methods and 210-560 umol/L with EMIT methods. The range of free VPA concentrations in 78% of children with complete seizure control was 8.8-26.4 umol/L. Increased liver enzyme activity was observed in 6 of the 61 children and raised plasma ammonia concentration in 11 of 50 children. Plasma ammonia concentration was related to total serum VPA but was not related to free serum VPA. Increased serum liver enzyme activity was related to VPA dose per kg but not to free or total serum VPA concentration. Thus free VPA concentrations do not appear to be more useful than total VPA concentrations in predicting seizure control and do not correlate with liver enzyme activity or plasma ammonia concentration.
Early Onset Parkinson's Disease in Saskatchewan - Environmental Considerations for Etiology
Authors: Rajput A.H. , Uitti Ryan J. , Stern W. , Laverty W.
Published: July 2016

The cause of idiopathic Parkinson's Disease (PD) is not known but it is believed to be related to some environmental agent(s). Given a long preclinical interval and onset of symptomatology around age 60 years, it becomes impossible to identify and analyze all prior environmental factors satisfactorily. To circumvent these difficulties we evaluated the childhood environment in those PD patients whose symptoms began at age 40 years or earlier. Twenty-one such cases were born and raised in the province of Saskatchewan. Nineteen of these 21 patients spent the first 15 years of life exclusively in rural Saskatchewan. Detailed population analysis indicates a strong predisposition to early onset idiopathic Parkinson's Disease (EPD) in those raised in rural areas (p = 0.0154). All but one case utilized exclusively well water for the first 15 years of life — a trait significantly different from that expected in the provincial population. It is concluded that rural Saskatchewan environments contribute to EPD and that well water used in childhood should be considered as a potential vehicle for the etiological agent.
The Age of Onset of Parkinson's Disease: Etiological Implications
Authors: Teräväinen H. , Forgach L. , Hietanen M. , Schulzer M. , Schoenberg Bruce , Calne D.B.
Published: July 2016

We have conducted a hospital-based survey of the age-specific prevalence of Parkinson's disease in 551 patients from Helsinki and Vancouver. We conclude that the disorder may be starting earlier than previously and we discuss the implications of this finding for the etiology of Parkinson's disease.
Inclusion Body Myositis Associated with Systemic Sarcoidosis
Authors: Danon Moris J. , Perurena Osvaldo H. , Ronan Salve , Manaligod Jose R.
Published: July 2016

We report an autopsy study of a 64-year-old female with systemic sarcoidosis. In addition many muscles showed typical light and electron microscopic features of inclusion body myositis. To our knowledge this association has not been previously reported.
Neurological Abnormalities Associated with Severity of Dementia in Alzheimer's Disease
Authors: Huff F. Jacob , Growdon John H.
Published: July 2016

Abnormal findings on neurological examination were evaluated in 165 patients with a clinical diagnosis of Alzheimer's disease who attended a memory disorders clinic. Severity of dementia was measured by the Blessed Dementia Scale, and associations of abnormalities with dementia severity were evaluated using logistic regression. Presence of aphasia, apraxia, and primitive reflexes on neurological examination were strongly associated with severity, and weak associations were observed for abnormalities of muscle tone and gait. Among these associated neurological features, only aphasia and apraxia were present in mildly demented cases with sufficient frequency to suggest utility as diagnostic signs early in the course of the disease.
Cortical Biopsy Results in Alzheimer Disease: Correlation with Cognitive Deficits
Authors: Martin E.M. , Wilson R.S. , Penn R.D. , Fox J.H. , Clasen R.A. , Savoy S.M.
Published: July 2016

This paper reports neuropsychologic and pathologic data for eleven patients with a clinical diagnosis of probable Alzheimer disease (AD) according to recently proposed NINCDS criteria. In all cases, the clinical diagnoses were verified by cortical biopsy using histopathologic criteria for definite AD. Similar tissue samples from nine non-demented autopsied patients were also evaluated and none received an histopathologic diagnosis of AD. Correlations between cortical plaque counts and neuropsychologic test scores are also presented. These data have important implications for 1) the accuracy of clinical diagnosis in AD; 2) the validity of NINCDS criteria for the clinical and pathologic diagnosis of AD; and 3) the utility of cognitive test scores as indicators of disease severity.
Early Identification of Dementia
Authors: McGlone J. , Gupta S.
Published: July 2016

Currently the diagnosis of progressive organic dementia is one of exclusion offered only after cognitive decline is well advanced. Early in the disease process, memory complaints most often bring elderly people to the attention of their family physician .This behaviour represents the first step in the process of giving a patient the medical diagnosis of organic dementia, yet no systematic method has been developed to gather such subjective information and evaluate its medical significance. We are developing a memory complaints questionnaire and a brief non-threatening memory screening instrument to help identify organic dementia in its earliest stages. The screening device will be related to more sophisticated neuropsychological measures of dementia and it should be sensitive to mental deterioration over short periods of time. The instruments will document perceived and objective changes in memory and will help the physician attribute their findings to normal aging, depression and/or degenerative CNS disease.
Cognitive Assessment in Alzheimer's Disease: Cross-Sectional and Longitudinal Perspectives
Authors: Kaszniak Alfred W. , Wilson Robert S. , Fox Jacob H. , Stebbins Glenn T.
Published: July 2016

This paper describes select results of a longitudinal study of 62 mild to moderate Alzheimer's disease (AD) patients, in comparison to 60 age-matched healthy controls. Initial neurologic, radiologic, psychiatric, laboratory and cognitive examinations, required two full days, followed by one-day examinations at annual intervals. Of the total original sample, 31 AD patients and 39 controls could actually be followed for three annual examinations. Cognitive examination data confirmed cross-sectional (group discriminative) validity of memory and language measures, and showed the expected longitudinal deterioration in the AD sample, with controls maintaining consistent performance over the three years. However, those measures showing largest group differences at initial examination were not the best for tracking patient deterioration over time. Implications of these results for the selection of cognitive assessment measures are discussed.
The Differential Diagnosis of Alzheimer's Disease: Conceptual and Methodological Issues
Authors: Tierney Mary C. , Reid David W. , Zorzitto Maria L. , Gary Snow W. , Fisher Rory H. , Campbell-Taylor Irene , Lewis Anthony
Published: July 2016

The study of Alzheimer's disease is hampered by insufficient knowledge of its cause. It can best be described as a syndrome whose clinical and pathological features, and their associations over time, need to be more carefully examined. Issues which impede our understanding of this syndrome include the lack of: (a) a singular “gold standard” for its identification; (b) longitudinal studies with appropriate comparison groups and neuropathological follow-up; and (c) standardized multifaceted clinical assessment procedures. Our awareness of the significance of these issues has led us to undertake a large-scale prospective, longitudinal investigation of 399 dementing and normal individuals at Sunnybrook Medical Centre. As a result of problems identified, it is proposed that research efforts across various Canadian centres be coordinated to best utilize available resources and expertise.
The Blood-Brain Barrier in Alzheimer's Disease
Authors: Vinters Harry V. , Pardridge William M.
Published: July 2016

The current evidence for and against abnormalities of the blood-brain barrier in “normal” aging and Alzheimer's disease is reviewed. Recent studies of cerebral amyloid angiopathy, a microangiopathy commonly observed in Alzheimer's disease and one suggested to result from blood-brain barrier derangement, are discussed with particular attention to the biochemical nature of the vascular amyloid material, and features it shares with the amyloid found in senile plaque cores and with neurofibrillary tangles. Modern techniques that will probably clarify blood-brain barrier pathophysiology are reviewed.
Anatomy and Pathology of the Basal Ganglia
Authors: McGeer P.L. , McGeer E.G. , Itagaki S. , Mizukawa K.
Published: July 2016

Neurotransmitters of the basal ganglia are of three types: I, amino acids; II, amines; and III, peptides. The amino acids generally act ionotropically while the amines and peptides generally act metabotropically. There are many examples of neurotransmitter coexistence in basal ganglia neurons. Diseases of the basal ganglia are characterized by selective neuronal degeneration. Lesions of the caudate, putamen, subthalamus and substantia nigra pars compacta occur, respectively, in chorea, dystonia, hemiballismus and parkinsonism. The differing signs and symptoms of these diseases constitute strong evidence of the functions of these various nuclei. Basal ganglia diseases can be of genetic origin, as in Huntington's chorea and Wilson's disease, of infectious origin as in Sydenham's chorea and postencephalitic parkinsonism, or of toxic origin as in MPTP poisoning. Regardless of the etiology, the pathogenesis is often regionally concentrated for reasons that are poorly understood. From studies on Parkinson and Huntington disease brains, evidence is presented that a common feature may be the expression of HLA-DR antigen on reactive microglia in the region where pathological neuronal dropout is occurring.
Pharmacotherapy of Spasticity: Some Theoretical and Practical Considerations
Authors: Rice G.P.A.
Published: July 2016

The availability of new antispasticity agents has greatly extended the therapeutic arm of the neurologist and has obviated the need for destructive neurosurgical procedures in many instances. Baclofen remains the single most useful agent, but in certain circumstances, benzodiazepines and dantrolene sodium are useful alternative or adjunctive treatments. Tizanidine has been recently introduced, and early experience with this agent appears to be favourable. A variety of new drugs are awaiting further evaluation. The effective use of these agents demands an understanding of their principal mechanisms of action, knowledge of their predictable side effects, and a familiarity with the underlying neurological disorders. The monitoring of clinical efficacy is difficult and is often dependent upon subjective evaluation. The application of electrophysiological studies might facilitate the monitoring of treatment and the prediction of optimum treatment strategies forindividual patients. The use of these pharmacological agents, from the perspective of a clinician, will be discussed.
The Physiology of Idiopathic Dystonia
Authors: Marsden C.D. , Rothwell John C.
Published: July 2016

Dystonia is mysterious and its pathophysiology is uncertain. The fundamental motor abnormality is an abnormality of muscle command signals, such that the wrong agonists may be activated for too long, there is abnormal co-contraction of agonist and antagonists, and there is excessive and misdirected action of synergists and postural fixators. The result is action dystonia. In addition, muscle spasms may occur spontaneously. The peripheral motor apparatus, the corticomotoneurone pathway, and (as far as is known) the proprioceptive feedback machinery, are all intact in primary dystonia. However, a defect of interneuronal machinery has been identified in both the brainstem and spinal cord. In blepharospasm there is hyperexcitability of the lower brainstem interneurones responsible for the R2 component of the blink reflex. In the dystonic arm there is loss of the later phases of la reciprocal inhibition from extensors to flexors. Both deficits may be due to loss of normal basal ganglia inputs onto interneurones. The known sites of focal lesions that may cause symptomatic dystonia all impair basal ganglia output. However, whether such abnormal interneuronal function is sufficient to explain dystonia is not known. Among many unanswered questions are 1) are the cortical instructions for movement specified correctly, and 2) what is responsible for the spontaneous dystonic spasms?
The Computerized Tomographic Appearance of Angiographically Occult Arteriovenous Malformations of the Brain
Authors: Leblanc Richard , Ethier Roméo
Published: July 2016

Eight patients with a histologically proven angiographically occult arteriovenous malformation of the brain had plain and infused computed tomographic (CT) examinations. In five cases angiography revealed a hypovascular mass and in three cases the angiogram was normal. On CT examination a high density lesion (six cases) and ventricular asymmetry (five cases) were demonstrated. In three patients presenting with intracerebral hemorrhage, the high density appearance and ventricular compression were accounted for by the presence of hematoma. In three of five seizure patients the high density lesion was associated with calcification while ipsilateral (one case) and contralateral (one case) enlargement of the lateral ventricle was seen. In five of the eight cases the vascular nature of the lesion was suggested by vascular enhancement of the infused CT scan. Glioma was a common misdiagnosis.
Friedreich’s Ataxia With Nephrotic Syndrome and Convulsive Disorder: Clinical and Neurophysiological Studies With Renal and Nerve Biopsies and An Autopsy
Authors: Watters G.V. , Zlotkin S.H. , Kaplan B.S. , Humphreys P. , Drummond K.N.
Published: July 2016

In a sibship of four, Friedreich’s ataxia and minimal lesion nephrotic syndrome occurred in two siblings, a third sibling had Friedreich’s ataxia, but no evidence of nephrotic syndrome; the fourth sibling had neither condition. The chance of Friedreich’s ataxia and minimal lesion nephrotic syndrome occurring in two siblings is small, and suggested a common immunological abnormality. High dose prednisone and antimetabolites given for the nephrotic syndrome did not appear to affect the course of Friedreich’s ataxia.

The two siblings with Friedreich’s ataxia and nephrotic syndrome developed epilepsy at age 15 years. All three children with Friedreich’s ataxia had abnormal electroencephalograms (EEGs). These epileptiform EEG abnormalities were probably inherited from the mother, who had spike wave epilepsy. The neurologic deficits of Friedreich’s ataxia, in turn, may have allowed the EEG trait to be expressed as a seizure disorder. The progressive ataxia and epileptic, sometimes myoclonic, seizures in these patients and the dentate nucleus changes in the autopsied patient were consistent with the diagnosis of dyssynergia cerebellaris myoclonica. This suggested that the latter disorder may represent a coincidence of two genetic entities: Friedreich’s ataxia and spike wave epilepsy.
The Crossed Adductor Reflex in Humans: An EMG Study
Authors: Teasdall Robert D. , Den Ende H. Van
Published: July 2016

Crossed adductor reflexes were recorded electromyographically in ten patients with bilateral lesions of the upper motor neuron. Three of these had a femoral neuropathy. Following blows directed to either the tendon of the adductor muscle or to the medial epicondyle of the femur, large amplitude responses of short latency were recorded from the ipsilateral adductor muscle while small amplitude responses of short latency and large amplitude responses of long latency were recorded from the contralateral adductor. The responses of short latency which were recorded from the ipsilateral and contralateral adductor muscles ranged from 18 to 27 ms. The contralateral responses of long latency ranged from 60 to 67 ms. On tapping the patella or patellar tendon, large amplitude responses of short latency were recorded from the contralateral adductor muscles while the ipsilateral adductor responses were absent. These responses resulted from stretch of the ipsilateral and contralateral adductor muscles. The contralateral responses were mediated across the midline by an extraspinal mechanical pathway.
Spinal Subdural Hematoma in Association with Anticoagulant Therapy
Authors: Russell Neville , Maroun F.B. , Jacob J.C.
Published: July 2016

A case of spinal subdural hematoma occurring in association with anticoagulant therapy is reported. Seven similar cases from the literature are reviewed with emphasis on the clinical features, investigation, and the results of treatment. The prognosis for recovery is good, only if the condition is diagnosed and the clot evacuated before severe spinal cord compression and subsequent ischemic necrosis has occurred.
Positional Vertigo and Nystagmus of Central Origin
Authors: Watson P. , Barber H.O. , Deck J. , Terbrugge K.
Published: July 2016

Four cases are described illustrating the clinical features of positional vertigo and nystagmus due to posterior fossa tumors and a case of obstructive hydrocephalus. In these cases positional vertigo was the first and only presenting symptom of central nervous system disease. One case of subependymoma of the fourth ventricle and one with hydrocephalus had characteristic symptoms of benign positional vertigo; each showed positional nystagmus of the benign paroxysmal type.
Cerebrovascular Permeability in Mechanically Induced Hypertension
Authors: Nag Sukriti , Robertson David M. , Dinsdale Henry B.
Published: July 2016

Our previous studies of cerebrovascular permeability in angiotensin-induced acute hypertension demonstrated that the principal mechanism resulting in increased permeability is enhanced pinositose. In order to exclude the possibility that the enhanced pinositose was a direct effect of exogenous angiotensin, cerebrovascular permeability alterations were studied in nonpharmacologically induced acute hypertension.

Rats receiving horseradish peroxidase (HRP) intravenously, were sacrificed 2½ minutes after the onset of hypertension induced by placing a clip on the abdominal aorta. These animals showed the same pattern of permeability alterations as had been observed previously in animals with angiotensin-induced acute hypertension. Focal segments of penetrating arterioles in the temporal and parietal cortex showed increased permeability to HRP. Permeable vessels showed increased numbers of pinocytotic vesicles and the interendothelial junctions revealed no alterations. Enhanced pinocytosis appears to be the principal mechanism resulting in increased cerebrovascular permeability in this model as well suggesting that the alterations of cerebrovascular permeability observed previously in angio-tensin-induced acute hypertension occur due to the hypertensive state and are not a direct drug effect of exogenous angiotensin.
Effect of L-Tryptophan on Spasmodic Torticollis
Authors: Lal S. , Young S.N. , Kiely M.E. , Hoyte K. , Baxter D.W. , Sourkes T.L.
Published: July 2016

The effect of L-tryptophan, a precursor of serotonin, and placebo were studied in eight patients with spasmodic torticollis. L-Tryptophan (5gpo as a single dose) which increased free plasma tryptophan 20-53 fold improved only one out of six patients. Two out of three patients, including the subject who improved following an oral load of tryptophan, improved with L-tryptophan combined with nicotinamide, a tryptophan pyrrolase inhibitor, when administered for 1-3 weeks. However, the magnitude of clinical improvement was not impressive. Our findings suggest that impairment of serotonergic function is not a general finding in spasmodic torticollis though it may play a minor role in the manifestation of this movement disorder in some patients. The present study emphasizes some of the difficulties in evaluating therapeutic response, namely, the intrinsic variability of the disorder, the response to placébo in some subjects and the limitations of methods for measuring change.
Clinical Progression of Giant-Axonal Neuropathy over a Twelve Year Period
Authors: Dooley Joseph M. , Oshima Yasufumi , Becker Laurence E. , Murphy E. Gordon
Published: July 2016

Giant-axonal neuropathy (GAN), a chronic peripheral neuropathy with associated Central Nervous System dysfunction and tight curly hair, is described in a 17-year-old girl. Biopsies of this girl’s muscle and nerve are characteristic of this condition. Her clinical course over a 12 year period characterizes a disease of a slowly progressive nature.
A Simple and Reproducible Experimental in Vivo Glioma Model
Authors: Auer R.N. , Maestro R.F. Del , Anderson R.
Published: July 2016

A simple and reproducible injection technique has been developed for inducing an in vivo experimental astrocytoma model in rats. Newborn rats were injected with a suspension of astrocytoma C-6 cells in doses ranging from 5 to 1 X 105cells. The optimum dose of tumor cells was found to be between 104and 105cells, with a consistent 100% take rate seen above 1 X 104injected cells. The injection of less than 104cells resulted in a decreased ability to induce tumors, and a prolonged survival. The pathology was consistent with that of a glioblastoma multiforme. The tumor showed a diffuse infiltrating border, necrosis, and pseudopalisading. Light microscopy revealed undifferentiated tumor cells while electron microscopy demonstrated rough endoplasmic reticulum, Golgi complexes, mitochondria, and the occasional cilium and centriole. The nature of the astrocytoma C-6 cell line, and the advantages, disadvantages and possible uses of the model are discussed.
The Somatosensory Evoked Potential
Authors: Eisen Andrew
Published: July 2016

Three decades have elapsed since Dawson (1947) recorded the first somatosensory evoked potential (SEP). Simple superimposition of individual responses was possible because the patient had progressive myoclonic epilepsy. In this disease the SEP amplitude is much enhanced (Shibasaki et al, 1978; Kelly et al, 1981). Subsequently Dawson (1951, 1954) presented his averager to the Physiological Society, thereby initiating the present-day explosive growth of evoked potentials.

SEPs are made up of components with varying latencies. The components are best identified by latency and polarity as recorded at the scalp (P = positive and N = negative). Nevertheless, the nomenclature of somatosensory evoked potentials can be extremely confusing, mainly because the same component can have a different polarity depending on the electrode montage used. Generally speaking (but this is not a firm rule), far-field (subcortical) potentials are positive in polarity when a non-cephalic reference is used, whereas these same components have a negative polarity when the reference is on the scalp. It is therefore useful to always indicate the recording montage being employed. In addition, use of absolute latencies in the terminology can cause confusion because they are dependent upon length and body height. For example, the brachial plexus component usually occurs at about 9 msec, but may extend to as long as 11 or more msec in a very tall individual. Subsequent components then become difficult to identify in relation to normal means.
The Effects of Intermittent Insulin Therapy on the Autonomic Neuropathy in the Streptozotocin Diabetic Rat
Authors: Monckton George , Pehowich Enid
Published: July 2016

An ultrastructural study of the dorsal sympathetic ganglia, chain, and myenteric plexus is described in the streptozotocin diabetic rat after intermittent insulin treatment. The observations described cover the first two weeks following induction of diabetes in which insulin was administered subcutaneously twice daily. Significant regenerative changes were seen with marked axonal sprouting noted at three days. Degenerative changes were seen to be less severe than those in untreated animals. It is concluded that the improvement in the neuropathic changes with insulin treatment supports a transient primary role of the streptozotocin in causing the neuropathy — but that the subsequent improvement seems to be related to the partial control of the diabetes.
A Six-Month Phosphatidylcholine Trial in Friedreich’s Ataxia
Authors: Filla A. , Campanella G.
Published: July 2016

In a six-month open pilot study, pure phosphatidylcholine was administered intravenously (2.5g daily for a month) and orally (5g daily for five months) to sixteen patients with Friedreich’s ataxia (FA) and seven patients with other inherited ataxias. Only the oral treatment achieved a mild but significant, 25% improvement, mainly of “central” symptoms in the FA patients at stage 2 of the illness, that is, still able to walk without support and to lead an independent life. However, the drug was ineffective in the more advanced cases. These results are discussed and compared with those obtained with lecithin by other authors.
Sodium Valproate in the Treatment of the Intractable Childhood Epileptic
Authors: Keene D.L. , Metrakos K. , Watters G.V. , Sherwin A.
Published: July 2016

Sixty-five children with seizure disorders, who had been treated with multiple anticonvulsants but were poorly controlled, were selected from the Montreal Children’s Hospital Convulsive Disorder Clinic and Neurology Service and were treated with sodium valproate (valproate). All types of seizure disorders were included in the group.

Rapid oral absorption of the drug lead to peak plasma levels in one to three hours (later peaks occurring if administered after meals). A mean plasma half-life of 12.8 hours was calculated. Correlation between oral dose and plasma levels was poor. The side effects which occurred in this study were trivial. Drug interactions occurred with phenobarbital, diphenylhydantoin and clonazepam.

Sixty percent of patients had a greater than 50% reduction in seizure frequency with sodium valproate, but the best response was in generalized absence seizures. Since all types of seizures responded to some degree, a trial of sodium valproate is warranted in intractable seizure disorders of childhood regardless of classification.
Orientation-Specific Visual Evoked Potential Deficits in Multiple Sclerosis
Authors: Coupland Stuart G. , Kirkham Trevor H.
Published: July 2016

Checkerboard pattern reversal visual evoked potentials (VEPs) have proved useful in the confirmation of optic nerve disease in patients with multiple sclerosis (MS). Recently, evidence of orientation-specific loss in contrast sensitivity and the presence of orientation-specific visual evoked potential (VEP) deficits in MS patients has been obtained using sinusoidal gratings as stimuli. This study reports the presence of orientation-specific VEP delay in MS using the conventional checkerboard pattern presented in two orientations: normally oriented (check condition) or diagonally oriented (diamond condition).

Peak latency values of the N70 and P100 components of the VEP were statistically analyzed using appropriate ANOVA and nonparametric statistics. As a group MS patients showed significant VEP delays under check and diamond pattern conditions. However, individual subject analysis revealed that about 20% of the MS population show VEP delay to only one pattern orientation. It was shown that by including a diamond pattern condition the diagnostic yield of VEP delay in these clinically definite MS patients was increased 11% over that obtained with check stimulation alone.
Mechanisms of Brain Damage in Twins
Authors: Norman Margaret G.
Published: July 2016

The brains of 18 twins dying in the perinatal period showed a variety of lesions. Eleven had subependymal cell plate hemorrhage which had ruptured into the lateral ventricles in five. Five had periventricular damage. Three had anoxic neuronal damage. One acardiac monster had bilateral cerebral infarction. One pair had unequal sized brains, probably due to unequal intrauterine nutrition. Twins have a high perinatal mortality and morbidity; as well, intrauterine events may alter brain growth and development in each twin unequally, so they are an imperfect model to study the effect of genes and environment on intelligence.
Auditory Brainstem Response Abnormalities in Autistic Children
Authors: Taylor M.J. , Rosenblatt B. , Linschoten L.
Published: July 2016

In an attempt to clarify issues of brainstem dysfunction and hearing thresholds in autistic children, we studied the Auditory Brainstem Responses (ABRs) in 32 children who clearly fit within the criteria of autism established by the National Society for Autistic Children (1977). ABRs were recorded between Cz and ipsilateral ear in response to click stimuli. Interwave latencies and auditory threshold in each ear were determined. Of the 32 children, 11 had moderate hearing loss (8 bilaterally) and 3 had severe to profound hearing loss, all bilaterally. 8 of the 14 with hearing loss also had associated features (e.g., perinatal encephalopathy). The I-III andI-Vinterwave latencies were significantly longer in the autistic children compared to normal control children; the increased conduction times were found mainly in the early portion of the auditory brainstem pathway. These data confirm some earlier reports of ABR abnormalities in autistic children and are concordant with some theories of the etiological basis of autism. The high incidence of hearing loss in these children is significant and routine ABR testing is recommended.