bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood Manganese Correlates with Brain Magnetic Resonance Imaging Changes in Patients with Liver Disease
Authors: Hauser Robert A. , Zesiewicz Theresa A. , Martinez Carlos , Rosemurgy Alexander S. , Olanow C.W. 
Published: February 2016

ABSTRACT:Background: Chronic liver failure is associated with high signal abnormalities in the basal ganglia on Tl-weighted magnetic resonance imaging of the brain. These abnormalities are strikingly similar to those seen following manganese intoxication. As dietary manganese is normally cleared by the liver, we hypothesize that hepatic dysfunction could lead to manganese overload and account for the MR1 abnormalities seen in patients with chronic liver disease.Methods: We measured blood manganese concentrations in eleven patients with biopsy-proven hepatic cirrhosis and eleven healthy age and sex-matched controls. We also performed semi-quantitative measures of Tl signal abnormalities on MRI in the patients with chronic liver disease.Results: Patients with cirrhosis had significantly higher blood manganese concentrations (20.6 ± 10.2 mcg/L) than controls (7.2 ± 2.7, p = .0013). In addition, semi-quantitative scores of TI-weighted signal hyperintensity on MRI correlated with blood manganese concentration in patients with cirrhosis (r = .65, p = .029).Conclusions: These findings demonstrate that chronic liver disease is associated with manganese overload and suggest that manganese is responsible for the Tl-weighted signal hyperintensity seen on MRI of patients with liver disease. As manganese intoxication is known to cause parkinsonism and an encephalopathy similar to those which occur with chronic liver disease, it is possible that manganese toxicity contributes to the development of these symptoms in liver damaged patients and that therapies which prevent or reduce manganese overload may have clinical benefit.
Paraneoplastic Limbic Encephalitis in Hodgkin’s Disease
Authors: Deodhare Sanjeev , O’Connor Paul , Ghazarian Danny , Bilbao Juan M. 
Published: February 2016

ABSTRACT:Background: Oat cell carcinoma of the lung is the most common cause of paraneoplastic limbic encephalitis. Association with other malignancies, in particular Hodgkin’s disease, is very rare. Case Report: This 23-year-old male presented with a six month history of progressive alteration in mental status, which consisted of insomnia, short-term memory loss, depression and cognitive impairment. Gadolinium MRI of the head showed intense bilateral contrast enhancement affecting the medial aspects of the temporal lobes in the region of the amygdala and hippocampus. The brain biopsy showed minimal neuronal loss with intense perivascular lymphocytic cuffing and microglia] nodules. Polymerase chain reaction for herpes simplex and cytomegalovirus were negative. With prednisone treatment, the patient’s neurologic status stabilized but did not improve. Four months later, he presented with left axillary lymphadenopathy. Lymph node biopsy was diagnostic of Hodgkin’s disease. During the chemotherapy, his lymphadenopathy subsided and his neurologic and mental status improved. When seen last after completion of his chemotherapy, one year after presentation, he had resumed normal social activities and was enrolled in a university language course. Conclusion: This is the first reported case in the English literature of a biopsy proven paraneoplastic limbic encephalitis associated with Hodgkin’s disease. Hodgkin’s disease should be thought of as a possible cause of paraneoplastic limbic encephalitis in the appropriate clinical setting.
Tirilazad Prevention of Reperfusion Edema After Focal Ischemia in Cynomolgus Monkeys
Authors: Boisvert Donald P. , Hall Edward D. 
Published: February 2016

ABSTRACT:Background:The purpose of the present investigation was to determine if post-ischemic treatment with the 21-aminosteroid lipid peroxidation inhibitor tirilazad mesylate (U-74006F) could affect reperfusion brain edema during the first 3h following a 3h period of middle cerebral artery occlusion-induced focal ischemia in cynomolgus monkeys.Methods:Adult female cynomolgus monkeys (N = 14) were subjected under halothane anesthesia to a 3h period of middle cerebral artery occlusion, followed by 3h of reperfusion. U-74006F, 3.0 mg/kg i.v. or citrate vehicle, was administered 10 min before beginning reperfusion. Multiple spin-echo (8 echoes: TE = 26.3 msec; TR = 3.0 sees; 2.35 Tesla) magnetic resonance imaging was performed every 30 min, beginning at lh after reperfusion. Transverse relaxation rates (T2) for the caudate, putamen, cortex, insular cortex, parietal cortex and central white matter were calculated as an index of focal brain edema. After the final images, corresponding regions were removed for determination of water content by the wet weight/dry weight method.Results:The T2 measurements strongly suggested the presence of post-reperfusion edema in all gray matter, but not white matter, regions at 1 h after reperfusion in vehicle-treated animals. Significant attenuation of edema development was seen in the putamen and insular cortex in U-74006F-treated animals. An effect was also observed in the parietal cortex, but none in the caudate. The measurement of water content at 3h after reperfusion yielded similar results.Conclusions:These results showing the ability of U-74006F to attenuate post-reperfusion brain edema support the concept that lipid peroxidation is a significant mediator of reperfusion brain edema after focal ischemia. The therapeutic window for U-74006F’s anti-edema effect appears to be at least 3h after the onset of focal ischemia since delaying treatment until just before reperfusion largely prevented subsequent edema in cortical regions and the putamen. The effects of U-74006F on edema may play a mechanistic role in the compound’s reported neuroprotective efficacy in a variety of focal ischemia models.
Experimental Study of NADPH-Diaphorase Positive Neurons in Nucleus Accumbens of Rats
Authors: Zhao Yan , Huang Ke-Wei 
Published: February 2016

AbstractBackgroundIn order to explain the mechanism for the sparing of the nucleus accumbens in several pathologic conditions, the accumbens, caudate and putamen were examined in an experimental model.MethodsThe neurons in these regions from twenty adult rats were stained for the enzyme nicotinamide adenine dinucleotide phosphate (NADPH-diaphorase) and quantified.ResultsPositive neurons in the nucleus accumbens were more abundant than in the caudate and putamen.ConclusionsSince these neurons have been shown to be resistant to ischemia and degeneration, it is suggested that the mechanism for the sparing of the nucleus accumbens is related to the presence of a large number of NADPH-diaphorase positive neurons.
Sudden Death in Multiple Sclerosis Associated with Sun Exposure: a Report of Two Cases
Authors: Avis Simon P. , Pryse-Phillips William EM. 
Published: February 2016

AbstractBackgroundTwo cases of sudden unexpected deaths in patients with multiple sclerosis were investigated by the Office of The Chief Forensic Pathologist.MethodCase studies.ResultsMarked similarities of the deaths, including circumstances, scene examination, and autopsy findings including a complete drug screen were recorded.ConclusionsExposure to high ambient temperature may pose a danger to patients with multiple sclerosis. Mechanisms of death and the potential dangers to patients with clinically widespread disease are discussed.
Loss of Heterozygosity Analysis of Chromosomes 9, 10 and 17 in Gliomas in Families
Authors: Watling Christopher J. , van Meyel Donald J. , Ramsay David A. , Macdonald David R. , Cairncross J. Gregory 
Published: February 2016

ABSTRACT:Background:Studies of sporadic malignant gliomas have identified structural abnormalities in a number of chromosomal regions, especially losses of DNA on 9p, 10 and 17p.Purpose:We undertook the following molecular analysis in families with glioma to determine the frequency of chromosomal losses in these regions and to test the utility of microsatellite markers in demonstrating losses of heterozygosity.Methods:Genomic DNA was extracted from tumor tissue and venous blood from 20 patients with a family history of glioma. Dinucleotide repeat polymorphisms (microsatellites) were analyzed by polymerase chain reaction to assess loss of constitutional heterozygosity (LOH) on 9p, 10 and 17p. Three polymorphic markers on chromosome 9 (D9S104, D9S161, D9S165), one on chromosome 10 (D10S209), and two on 17p (D17S786, D17S796) were used. Autoradiographic films were analyzed for LOH after radioactively labelled polymerase chain reaction products were resolved on denaturing formamide-acrylamide gels.Results:Of 20 patients informative for at least one of three chromosome 9 markers, 12 (60%) showed LOH at one or more loci; of 9 informative for the chromosome 10 marker, 4 (44%) showed LOH; and of 16 informative for at least one of two chromosome 17 markers, 7 (44%) showed LOH at one or both loci. These LOH rates do not include instances of tumor nullizygosity (0 – 35%) and therefore represent minimum frequencies of chromosomal losses at these loci.Conclusions:Microsatellite markers can be used to detect LOH in archival glioma tissue. As in sporadic gliomas, frequent LOH was observed on 9p (9p21-22), 10 and 17p, supporting the notion that these regions may harbour tumor suppressor genes important in glioma development. Further work will be required to determine whether the proportion of LOH in these chromosomal regions is higher in familial gliomas than sporadic ones, as might occur with an inherited suppressor gene conferring susceptibility to gliomas in families.
Clinical Testing in Diabetic Peripheral Neuropathy
Authors: Feldman Eva L. , Stevens Martin J. 
Published: February 2016

Abstract:Diabetic polyneuropathy is a complex disease of progressive nerve fiber loss. Initial screening and diagnosis in clinical practice usually depend on assessment of subjective complaints. A need exists for objective, simple, and reproducible assessment tools that can be readily used in clinical practice. The importance of early diagnosis is highlighted by the recent North American Diabetes Control and Complications Trial where intensive insulin therapy reduced the risk of developing diabetic neuropathy by 61%. At the University of Michigan, we have developed an outpatient neuropathy program. Patients are given a questionnaire and a brief screening examination, designated the Neuropathy Screening Instrument. Diabetic neuropathy is confirmed and staged in patients with a positive Neuropathy Screening Instrument, by a quantitative neurologic examination and nerve conduction studies, designated the Diabetic Neuropathy Score. The Michigan program has been compared with well-established instruments and has been found to be sensitive and reproducible for screening and diagnosis. We believe the program provides a valuable tool for the clinician in the practice setting and should allow diagnosis and intervention earlier in the course of diabetic neuropathy.
End-Stage Complications of Diabetic Neuropathy: Foot Ulceration
Authors: Boulton Andrew J.M. 
Published: February 2016

Abstract:Diabetic polyneuropathy is a major complication of diabetes mellitus that frequently leads to foot ulceration. Because of economic impact of foot ulceration and subsequent amputation, major initiatives are under way in the United States and the United Kingdom to reduce their incidence by up to 50%. Although diabetic ulcers may have an ischemic and neuropathic component, the majority are neuropathic. Results from studies have shown a strong association between the neuropathy and the subsequent development of foot ulcers. However, other predisposing factors such as high foot pressures, inappropriate footwear, and other extrinsic pressure usually must be present, together with neuropathy, to cause foot ulcers. Therefore, the challenge to the physician is to identify the patient at risk and intervene so as to educate and prevent the occurrence of foot ulcers.
Cognitive Side Effects of Antiepileptic Drugs
Authors: Meador Kimford J. 
Published: February 2016

Abstract:All of the established antiepileptic drugs (AEDs) can produce cognitive side effects, which are increased with polypharmacy and with increasing dosage and anticonvulsant blood levels. However, cognitive side effects are usually modest for AED monotherapy with anticonvulsant blood levels within the standard therapeutic ranges. Further, these effects are offset in part by reduced seizure activity. Controversy exists regarding possible differential cognitive effects of AEDs. A large portion of the literature examining the comparative cognitive effects of AEDs is limited by inadequate study designs. When these design flaws are considered, there is no convincing evidence of clinically significant differences in cognitive side effects of AEDs except possibly for bromide, phenobarbital and benzodiazepines. The role of cognitive side effects should be kept in proper perspective when choosing AED therapy. The cognitive side effects of anticonvulsant drugs may be overt but many times are rather subtle. It is important though to be able to recognize these effects and to put them into perspective as to how they affect our patients.
Autosomal Recessive, Fatal Infantile Hypertonic Muscular Dystrophy Among Canadian Natives
Authors: Lacson A.G. , Seshia S.S. , Sarnat H.B. , Anderson J. , DeGroot W.R. , Chudley A. , Adams C. , Darwish H.Z. , Lowry R.B. , Kuhn S. , Lowry N.J. , Ang L.C. , Gibbings E. , Trevenen C.L. , Johnson E.S. , Hoogstraten J. 
Published: February 2016

Abstract:We describe eleven mid-western Canadian aboriginal infants with a unique, progressive muscle disorder. All except one had muscle biopsy and/or autopsy. The infants were normal newborns who rapidly developed rigidity of all skeletal muscles, with early, respiratory insufficiency. Death occurred before 18 months of age. Electromyography showed increased insertion activity and profuse fibrillation potentials; motor unit potentials and interference pattern are normal until late in the course. Pathologic features include progressive, granular to powdery Z-band transformation, myofibrillar loss, and muscle regeneration. SDS-gel electrophoresis of one muscle sample revealed increased 54kDa and reduced 80kDa protein fractions. This disease differs from other conditions with Z-band alterations because of continuous muscle activity and relentless clinical progression. The clinical features, elevated serum creatine kinase, electromyographic and muscle biopsy findings suggest a dystrophic process. The recognition of this condition as an autosomal recessive disorder allows appropriate genetic counselling.
Cortical Excitability in Amyotrophic Lateral Sclerosis: A Clue to Pathogenesis
Authors: Eisen Andrew , Pant Bhanu , Stewart Heather 
Published: February 2016

ABSTRACT:Motor evoked potentials (MEPs) were recorded from selected non-wasted, non-denervated hand muscles in 40 patients with Amyotrophic Lateral Sclerosis (ALS) with both upper and lower motor neuron signs. In most the compound muscle action potential (CMAP) of the target muscle was normal. Compared to the control group, cortical threshold in ALS varied considerably and there was a significant (r2= 0.702) inverse, exponential, correlation between cortical threshold and MEP/CMAP ratio. There was a linear correlation between threshold and disease duration (r2= 0.66) so that early in the disease threshold was normal and later the motor cortex could not be stimulated. It is suggested that early in ALS normal threshold reflects glutamate-induced hyper-excitability of the corticomotoneuron. The findings lend support to the hypothesis that ALS is primarily a disease of the corticomotoneuron.
Focal Cerebral Ischemia in Rats: Effect of Hemodilution with α-α Cross-Linked Hemoglobin on Brain Injury and Edema
Authors: Cole Daniel J. , Schell Randall M. , Drummond John C. , Pryzbelski Robert J. , Marcantonio Suzzane 
Published: February 2016

ABSTRACT:The effect of hemodilution, with α-α cross-linked hemoglobin (DCLHb), on brain injury and edema was assessed after temporary middle cerebral artery occlusion in rats. Injury was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC) stain and edema by microgravimety. Part A: DCLHb was given to maintain one of the following hematocrits (Hct) and normotension: 1) 45/Hct, 2) 30/Hct, 3) 16/Hct, or 4) 9/Hct. Brain injury (% of ischemic hemisphere, mean ± SD) was less in the 30/Hct group (31 ±4) versus the 45/Hct group (42 ± 5); and in the 16/Hct (20 ± 3) and 9/Hct (19 ± 4) groups versus the 45/Hct and 30/Hct groups. Edema was less in the hemodiluted groups versus the 45/Hct group. Part B: DCLHb was given to maintain one of the following hematocrits and hyper (HTN) − or normotension (Norm): 1) 45/Norm, 2) 30/Norm, 3) 30/HTN, 4) 16/Norm, or 5) 16/HTN. In hematocrit matched groups hypertension decreased brain injury (30/HTN − 24 ± 2 < 30/Norm − 34 ± 4; and 16/HTN − 17 ± 3 < 16/Norm − 24 ± 4). Edema was not effected by hypertension. These results suggest that hemodilution with DCLHb decreases focal ischemic injury, and is most effective when given in a manner that induces hypertension.
Significance of Parkinsonian Manifestations in Essential Tremor
Authors: Rajput A.H. , Rozdilsky B. , Ang L. , Rajput Alex 
Published: February 2016

ABSTRACT:Parkinsonian features, notably resting tremor may be seen in some essential tremor patients but the significance of those is unknown. The reported risk of parkinsonism in essential tremor patients varies from being unchanged to 35 times higher than expected. We studied 9 patients with essential tremor who had autopsies. In 6 of the 9 (66%) resting tremor was noted and in 3 (33%) cases fully developed parkinsonism was noted. The parkinsonism was consequent to neuroleptic usage in 2 and to basal ganglia status lacunaris and cribrosus in one case but no consistent abnormalities were noted in 3 essential tremor only and 3 essential tremor plus resting tremor cases. We conclude that resting tremor is an age-related natural evolution in some essential tremor patients. We recommend that the additional diagnosis of parkinsonism in the essential tremor be made only when resting tremor, bradykinesia and rigidity are all evident. The risk of ideopathic Parkinson's disease in essential tremor cases is similar to the general population.
Substance P-like Immunoreactivity and Analgesic Effects of Vibratory Stimulation on Patients Suffering From Chronic Pain
Authors: Guieu Régis , Tardy-Gervet Marie-Françoise , Giraud Pierre 
Published: February 2016

ABSTRACT:By applying vibratory stimulation to patients suffering from pain, it is possible to set up an inhibitory control on the pain pathways which is based on the activation of large-sized afferent fibres. The exact mechanisms responsible for these analgesic effects still remain to be determined, however. For this purpose, we investigated in the present study whether or not the analgesic effects were accompanied by a decrease in the CSF substance P-like immunoreactivity levels (SPLI) of seven patients suffering from chronic pain, who were fitted with a ventriculo-peri-toneal drain. The SPLI levels were determined before and after 30-min vibratory stimulation sessions. The results show that the SPLI levels decreased as the result of the vibration, but this decrease seems to be too slight to account for the pain relief obtained.
Excessive Fragmentary Myoclonus: Time of Night and Sleep Stage Distributions
Authors: Lins Otavio , Castonguay Michelle , Dunham Wayne , Nevsimalova Sonya , Broughton Roger 
Published: February 2016

ABSTRACT:Excessive fragmentary myoclonus during sleep consists of high amounts of brief twitch-like movements occurring asynchronously and asymmetrically in different body areas and has been reported to occur in association with a number of sleep disorders. It was analyzed using a new technique of quantification, the fragmentary myoclonus index (FMI). The FMI exhibited high rates in all stages of sleep but with a somewhat lower frequency in slow wave sleep explaining, as well, a significantly lower rate in the first hour after sleep onset compared to later hours. There was no evidence for greater sleep fragmentation or lighter sleep compared to a matched patient group in whom it had not been noted.
Paroxysmal Dyskinesia Associated with Hypoglycemia
Authors: Schmidt Brian J. , Pillay Neelan 
Published: February 2016

ABSTRACT:The association of movement disorders with hypoglycemia has been rarely noted in the past. We recently observed 2 patients with documented hypoglycemia and paroxysmal dyskinesias. One patient had evidence of an insulin-secreting tumor. The other patient had insulin-dependent diabetes, and also experienced recurrent episodes of hypoglycemic hemiparesis. Classical adrenergic symptoms of hypoglycemia were absent in both patients. Our observations support the concept that the development of neuroglycopenic symptoms cannot be predicted from blood glucose measurements alone, but must depend on other factors controlling the availability or metabolism of glucose in the brain.
Intrathecal Baclofen – The Importance of Catheter Position
Authors: Hugenholtz Herman , Nelson Robert F. , Dehoux Eric 
Published: February 2016

ABSTRACT:In a patient receiving intrathecal baclofen injections for intractable trunk and leg spasms, positioning the subarachnoid catheter tip just caudal to the spinal segments innervating the spastic muscles enhanced the spasmolytic effect of bolus injections of intrathecal baclofen on the affected muscles. Such selective positioning of subarachnoid catheters may facilitate segmental spasmolysis with lower intrathecal doses of baclofen and provide an important alternative to relying only on ascending CSF concentration gradients of baclofen from chronic lumbar intrathecal infusion.
Pathogenesis of Mesial Temporal Sclerosis
Authors: Elizabeth Pringle C. , Warren T. Blume , David G. Munoz , Stan Leung L. 
Published: February 2016

ABSTRACT:A relationship between epilepsy and damage to mesial temporal structures has long been recognized. Recent advances have clarified somewhat the issue of whether the pathological changes seen in mesial temporal sclerosis represent the cause or the effect of seizures. This paper reviews mesial temporal sclerosis from an historical perspective and summarizes recent developments in the fields of excitotoxicity, selective vulnerability, and synaptic reorganization as they pertain to the pathogenesis of mesial temporal sclerosis.
Tremorgenic Encephalopathy: A Role of Mycotoxins in the Production of CNS Disease in Humans?
Authors: Gordon K.E. , Masotti R.E. , Waddell W.R. 
Published: February 2016

ABSTRACT:We describe a young man who, shortly after exposure to moldy silage, developed a neurological syndrome consisting of dementia and a remarkable tremor which was precipitated by movement. All symptoms resolved within one week. Despite investigation, no definitive diagnosis was reached. We propose that this patient's illness may have resulted from inhalation exposure to a tremorgenic mycotoxin.
Consequences of Peripheral Nerve Demyelination: Basic and Clinical Aspects
Authors: Jun Kimura 
Published: February 2016

ABSTRACT:The essential function of a nerve fiber centers on the transmission of impulses. Slowing of conduction velocities merely delays conveyance of information but failure of conduction abolishes the function. Rate-dependent block may falsify input by disturbing the neural coding. The diagnosis of conduction block is complicated by phase cancellation and many other physiologic and technical factors, which may mimic the condition. The conduction block may be reversed by increasing action current with such agents as 4-aminopirizine as well as by reducing the threshold for excitation with a sodium - potassium pump inhibitor such as digitalis. Although their mechanisms of action are poorly understood, imunogloblin and imunosuppressive agents are also effective in some clinical entities like multifocal motor neuropathy with persistent conduction block.