bluuebunny/crossref_metadata_2025 huggingface dataset:
New anatomical and functional imaging methods
Authors: Prichard James W. , Brass Lawrence M.
Published: January 2005

Powerful new methods for imaging both brain anatomy and brain function are appearing at an increasing rate. The modern era of minimally invasive, highly informative, neurological diagnostic imaging methods began with the introduction of x‐ray computed tomography in the 1970s. More recently, positron emission tomography and single‐photon emission computed tomography have been used extensively in research on normal and pathological brain function, and they are finding specific medical applications. Nuclear magnetic resonance methods are in widespread use for neurological diagnosis only a decade after they became available. Rapid development of new techniques based on the same principles, and implementable on clinical instruments with relatively minor modifications, will expand the range of nuclear magnetic resonance measurement capabilities considerably in the near future. These technological innovations and others yet to come have major implications for the practice of neurology. The most important one is an increase in relative value among clinical diagnostic skills of history taking and mental status examination, which will remain largely beyond the reach of technology.
Skeletal muscle toxoplasmosis in patients with acquired immunodeficiency syndrome: A clinical and pathological study
Authors: Gherardi R. , Baudrimont M. , Lionnet F. , Salord J.‐M. , Duvivier C. , Michon C. , Wolff M. , Marche C.
Published: January 2005

The present article describes the clinical pathological findings in 5 human immunodeficiency virus (HIV)‐infected patients with muscle toxolasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse ecephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement; included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti‐Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4%of muscle fibers close to or remote from necrotic fibers and inflammatory infitrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin.
Familial adult‐onset muscular dystrophy with leukoencephalopathy
Authors: van Engelen Baziel G. M. , Leyten Quint H. , Bernsen Pieter L. J. A. , Gabreëls Fons J. M. , Joosten Ed M. G. , ter Laak Henk J. , Ruijs Mechelien B. M. , Hamel Ben C. J. , Cruysberg Johan R. M. , Barkhof Frederik , Valk Jaap
Published: January 2005

We report on 3 siblings with an adult‐onset, predominantly distal muscle weakness. In the female index patient this was associated with epilepsy and a progressive spastic ataxic gait, while the 2 other siblings had no appreciable clinical nervous system involvement. Additional investigations revealed muscular dystrophy and leukoencephalopathy in all 3 siblings. We conclude that this familial adult‐onset muscular dystrophy associated with leukoencephalopathy represents a newly recognized autosomal recessive syndrome.
Long‐term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa‐responsive dystonia
Authors: Nygaard Torbjoern G. , Takahashi Hirohide , Heiman Gary A. , Snow Barry J. , Fahn Stanley , Calne Donald B.
Published: January 2005

Dopa‐responsive dystonia (DRD) is one form of childhood‐onset idiopathic torsion dystonia. Adult‐onset parkinsonism has appeared in several previously unaffected members in families with DRD suggesting that this may be an additional phenotypical expression of the disease. We report a family with DRD in which 2 women and 1 man, unaffected by dystonia, developed tremor‐onset parkinsonism after age 50 years. The women continue on a low dosage of levodopa after 9 and 13 years of treatment, with a stable, nearly complete, symptomatic response. This contrasts to the typical long‐term treatment complications observed in patients with Parkinson's disease. We assessed nigrostriatal dopaminer‐gic function in the proband, with typical DRD, and the 2 women with parkinsonism using 6‐{18F}fluoro‐L‐dopa positron emission tomography. All 3 had normal striatal 6‐{18F}fluoro‐L‐dopa uptake. These observations provide compelling evidence that “benign” adult‐onset parkinsonism may be an expression of the disease in some members of families with DRD and does not support consideration of the DRD gene as a risk factor for development of Parkinson's disease. There may be considerable clinical heterogeneity in DRD depending on the age at onset.
Suppression of postischemic epileptiform activity with MK‐801 improves neural outcome in fetal sheep
Authors: Tan William K. M. , Williams Chris E. , Gunn Alistair J. , Mallard Carina E. , Gluckman Peter D.
Published: January 2005

To determine the effect of suppression of epileptiform activity that develops after hypoxic‐ischemic injury in the immature brain, chronically instrumented near‐term fetal sheep (119–133 days) were subjected to 30 minutes of complete cerebral ischemia: 6 were given a 0.3‐mg/kg bolus of MK‐801 at 6 hours after the insult followed by continuous infusion of 1 mg/kg over the next 36 hours, and were compared to 6 control sheep. Electrocorticographic activity and edema within the parasagittal region of the cortex were quantified with real‐time spectral analysis and impedance measurements, respectively. Histological outcome was assessed 72 hours later. The intense epileptiform activity seen from 9 ± 2 to 30 ± 3 hours in the control group was completely suppressed in the MK‐801‐treated group. The onset of secondary cortical edema was delayed from 9.4 ± 1.1 hours to 14.8 ± 0.7 hours (p < 0.01). Neuronal damage was reduced, particularly in the lateral cortex and hippocampus (p < 0.05). Infarction of the parasagittal cortex was not prevented. These results suggest that N‐methyl‐D‐aspartate‐mediated epileptiform activity that develops after a global hypoxic‐ischemic insult worsens neuronal outcome in the immature brain.
Childhood peripheral neuropathy with autoantibodies to myelin glycoprotein Po
Authors: Jelloun‐Dellagi S. Ben , Dellagi K. , Burger D. , Younes‐Chennoufi A. Ben , Hentati F. F. , Steck A. , Hamida M. Ben
Published: January 2005

The serum of a 4‐year‐old child with severe hypertrophic peripheral neuropathy contained high‐titer polyclonal antibodies, mainly of IgG class, reacting with the 30‐kd Po glycoprotein of peripheral nerve. This was demonstrated by indirect immunofluorescence, immunoblot analysis of myelin proteins, and enzyme‐linked immunosorbent assay with purified Po glycoprotein. The antibodies did not react with myelin‐associated glycoprotein, sulfated glycuronic acid‐containing paraglo‐boside (SGPG and SGLPG), or other peripheral nerve glycolipids or gangliosides. To our knowledge this is the first report of strong antibody activity specifically directed against Po. This antibody may play a causative role in the pathogenesis of the peripheral neuropathy in this patient.
The audiospinal reaction in parkinsonian patients reflects functional changes in reticular nuclei
Authors: Delwaide P. J. , Pepin J. L. , de Noordhout A. Maertens
Published: January 2005

Audiospinal facilitation using the soleus H‐reflex as a test was compared in 16 control subjects and 23 parkinsonian patients. In the patients, facilitation was significantly reduced during the 75 to 150 msec after the conditioning stimulation. This reduction was seen bilaterally even in patients with a hemisyndrome. It was corrected by L‐dopa but not by anticholinergic agents. Facilitation at the 75‐msec delay showed an inverse linear correlation with the bradykinesia intensity (r = ‐0.7, p < 0.01). The results argue in favor of a reduced excitability of the nucleus reticularis pontis caudalis from which a reticulospinal tract emanates as effector of the audiospinal facilitation. This would represent another example of dysfunction of reticular nuclei in Parkinson's disease.
Crossed aphasia with visceral situs inversus
Authors: Cohen Laurent , Gény Christian , Hermine Oliver , Gray Francoise , Degos Jean‐Denis
Published: January 2005

A patient presenting the association of anomalous cerebral dominance for language, as revealed by crossed aphasia, and partial visceral situs inversus is described. Although it cannot be excluded that the two abnormalities coincided by chance, it is suggested that they both resulted from a single aberration of development.
Delayed peripartum vasculopathy: Cerebral eclampsia revisited
Authors: Raps Eric C. , Galetta Steven L. , Broderick Magie , Atlas Scott
Published: January 2005

Over a 2‐Year Period, we treated 4 postpartum patients with acute neurologic problems appearing 4 to 9 days after delivery. Three patients either had no proteinuria or edema and therfore did not meet all accepted clinical criteria for the diagnosis of eclampisa. Magnetic resonance imaging (MRI) of the brain in all patients demonstrated high‐signal foci most prominent in the parietooccipital regions and the subcortical white matter. Cerebral angiogram in 2 patients revealed diffuse vasospasm. In 3 patients, MRI abnormalities resolved. MRI and angiographic abnormalities in our patients are identical to those of patients meeting accepted criteria for eclampisa. Our experience suggest that the current criteria for the diagnosis of eclampsia are too stingent, both in terms of clinical picture and days postpartum to cerebral mainfestations.
Isolation of HTLV‐II from a patient with chronic, progressive neurological disease clinically indistinguishable from HTLV‐I‐associated myelopathy/tropical spastic paraparesis
Authors: Jacobson Steven , Lehky Tanya , Nishimura Masataka , Robinson Susan , McFarlin Dale E. , Dhib‐Jalbut Suhayl
Published: January 2005

An increasing spectrum of diseases has been shown to be associated with the human T‐cell lymphotropic virus type I (HTLV‐I), most notably a chronic, progressive myelopathy termed HTLV‐I‐associated myelopathy/tropical spastic paraparesis and adult T‐cell leukemia. HTLV‐II is a close relative of HTLV‐I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV‐I‐associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV‐II in the absence of any other detectable human retrovirus. Antibodies to HTLV were deteced in both serum and cerebrospinal fluid, with typical HTLV‐II banding patterns on Western blots. HTLV‐II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of the virus revealed a 99.5% homology with prototype HTLV‐II. These results serve to alert the medical community to the possibility that in addition to HTLV‐I, HTLV‐II may be associated with a neurological disorder.
Mechanical hyperalgesias in neuropathic pain patients: Dynamic and static subtypes
Authors: Ochoa José L. , Yarnitsky David
Published: January 2005

Two behavioral kinds of mechanical hyperalgesia can be clearly discerned by clinical criteria in patients with neuropathic syndromes, i.e., a dynamic type, elicitable by lightly stroking the symptomatic skin, and a static type, elicitable by steadily applying gentle pressure on it. Of 28 patients studied, 19 had dynamic and 18 had static type mechanical hyperalgesia (9 expressed both types). Experimental compression–ischemia nerve block totally abolished the dynamic hyperalgesia in all patients except in 2, in whom it was markedly diminished. Disappearance of dynamic hyperalgesia occurred contemporaneously with block of myelinated A fibers, as expressed by abolition of the sensations of touch and cold, monitored quantitatively. Static hyperalgesia, however, outlasted A‐fiber block in 15 of 18 patients; the phenomenon persisted during the stage when only unmyelinated fibers were available for impulse conduction. It is thus concluded that, at the primary afferent level, dynamic hyperalgesia is mediated by myelinated fibers, whereas static hyperalgesia depends on unmyelinated afferents. These two kinds of hyperalgesia represent discrete pathophysiological entities with distinct clinical connotations.
Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine–enhancing magnetic resonance imaging lesions
Authors: Smith M. E. , Stone L. A. , Albert P. S. , Frank J. A. , Martin R. , Armstrong M. , Maloni H. , McFarlin D. E. , McFarland H. F.
Published: January 2005

It is now well established that clinically stable patients with relapsing–remitting multiple sclerosis have ongoing disease activity when evaluated by serial gadolinium–enhanced (Gd‐DTPA) magnetic resonance imaging (MRI) scans. Despite this, the relationship between clinical disease and MRI lesions, though suspected, has not been extensively documented. The relationship between Gd‐DTPA MRI lesions, and clinical disease was examined in this study of 9 patients with mild relapsing–remitting multiple sclerosis (Expanded Disability Status Scale [EDSS] <3.5) who had 24 to 37 monthly Gd‐DTPA MRI scans, neurological examinations, and EDSS score assignments. The area and frequency of Gd‐DTPA lesions were examined during months with and without clinical worsening as measured by EDSS. Forty‐one episodes of clinical worsening were noted during the study. A significant association was observed between these periods of clinical worsening and MRI parameters, including increases in total number, number of new lesions, and the total area of enhancement. Logistic regression analysis showed a signficant effect of the number and area of Gd‐DTPA MRI lesions on both the onset and continuation of clinical worsening, confirming an imporant relationship between clinical disease and an increase in cerebral Gd‐DTPA MRI activity. A relationship with long‐term disability was suggested, but cannot be confirmed without longer follow‐up of these patients.
Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community‐dwelling elderly persons and their first‐degree relatives
Authors: Mayeux Richard , Ottman Ruth , Tang Ming‐Xin , Noboa‐Bauza Lourdes , Marder Karen , Gurland Barry , Stern Yaakov
Published: January 2005

We performed a community‐based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease(AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first‐degree relatives of the patients and 1,238 first‐degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4–9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first‐degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1–5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head‐injured relatives of patients (RR = 5.9; 95% CI, 2.3–14.8) and head‐injured relatives of control subjects (RR = 6.9; 95% CI, 2.5–18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation.
Pretectal eyelid retraction and lag
Authors: Galetta Steven L. , Gray Lawrence G. , Raps Eric C. , Schatz Norman J.
Published: January 2005

We report 2 patients who had eyelid retraction and eyelid lag with minimal impairment of vertical gaze. In both patients, magnetic resonance imaging demonstrated a circumscribed unilateral lesion immediately rostral and dorsal to the red nucleus involving the lateral periaqueductal gray area. Our clinical and radiological findings support the existence of a premotor eyelid control center in the region of the nucleus of the posterior commissure.
Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dememtia
Authors: Wesselingh Steven L. , Power Christopher , Glass Jonathan D. , Tyor William R. , McArthur Justin C. , Farber Joshua M. , Griffin John W. , Griffin Diane E.
Published: January 2005

The pathogenesis of the dementia associated with human immunodeficieny virus (HIV) infection is unclear, but has been postulated to be due to indirect effects of HIV infection including the local production of cytokines. To determine which cytokines are produced in the nervous system and to identify and correlations with dementia, cytokine and HIV messenger RNA expression was analyzed by reverse transcriptase‐polymerase chain reaction in the brains from 24 HIV‐ infected patients with and without dementia and 9 HIV uninfected control subjects. Levels of tumor necrosis factor‐α messenger RNA were significantlyhigher and levels of interleukin (IL)‐4 messenenger RNA were significantly lower in demented compared to nondemented HIV‐infected parients. Demented patients als had lower IL‐1β levels than did nondemented patients. No significant differences were detected in the amounts of leukemia inhibitory factor, IL‐6, transforming growth factor β1 and β2 monokine induced bygamma interferon‐2 (MIC‐2), or interferon‐Y Messenger RNSs IL‐10 and IL‐2 messenger RNAs wre undetectable in all brains examined. Cytokine messenger RNA levels in nondemented HIV‐positivew patients were similar to those in HIV‐negative control subjects. HIV transcripts were more abundant in subcortical white matter than in the basal ganglia, cortex, or deep white matter. Our findings suggest a possible role for tumor necrosis factor‐α in the development of neurological dysfunction. Increased levels of tumor necrosis factor‐α in the development of neurological dysfunction. Increased levels of tumor necrosis factor‐α messenger RNA were not associated with increased levels of IL1β messenger RNA, suggesting differential regulation of these monokines in acquired immunodeficiency syndrome dementia. Levels of IL‐4 messenger RNA were decreased in dementia and the loss of this and other macrophage downregulatory factors in demented patients may contribute to the increased expression of tumor necrosis factor‐α.
Phenotypic heterogeneity in families with the myoclonic epilepsy and ragged‐red fiber disease point mutation in mitochondrial DNA
Authors: Graf W. D. , Sumi S. M. , Copass M. K. , Ojemann L. M. , Longstreth W. T. , Shanske S. , Lombes A. , DiMauro S.
Published: January 2005

Two families with a point mutation in mtDNA associated with myoclonic epilepsy and ragged‐red fiber disease showed pronounced clinical heterogeneity. The mothers of the two families had adult‐onset myopathy with ragged‐red fibers, partial deficiency of cytochrome c oxidase, and sensory neuropathy. Members of the first family had variable clinical features of progressive ataxic‐myoclonic encephalomyopathy and of the other family, primarily adult‐onset myiopathy. There was a point mutation from A to G at uncleotide pair 8344 located in the tRNALys gene of the tmDNA of all patients tested, three in family 1, and the mother of Family 2.This clinical heterogeneity may reflect the effects of varying proportions of mutant and wild‐type mt DNA in the different organ systems in each individual.
Magnetic resonance imaging of brain and the neuromotor disorder in endemic cretinism
Authors: Ma Tai , Lian Z. C. , Qi S. P. , Heinz E. Ralph , DeLong G. Robert
Published: January 2005

Neurological endemic cretinism, resulting from severe iodine deficiency, is characterized by mental deficiency, deafmutism, and a spastic–rigid motor disorder. Its neuropathology and pathophysiology have been investigated very little. We report the clinical and magnetic resonance imaging brain scan findings of 3 adult Chinese cretins. All show an apparent magnetic resonance imaging abnormality in the globus pallidus and substantia nigra, with hyperintensity on T1‐weighted images and hypointensity on T2‐weighted images. The motor abnormality, characterized by truncal and proximal limb–girdle rigidity and spasticity, with relative sparing of the hands and feet, is analogous to other extrapyramidal disorders. Endemic cretinism is a unique form of cerebral palsy of potential interest for students of human neuromotor development.
Adhesion molecule expression on cerebrospinal fluid T lymphocytes: Evidence for common recruitment mechanisms in multiple sclerosis, aseptic meningitis, and normal controls
Authors: Svenningsson Anders , Hansson Göran K. , Andersen Oluf , Andersson Rune , Patarroyo Manuel , Stemme Sten
Published: January 2005

The expression of T‐cell surface antigens was investigated in the cerebrospinal fluid (CSF) and peripheral blood of 11 patients with multiple sclerosis, 6 patients with aseptic meningitis, and 16 healthy subjects. A panel of monoclonal antibodies to adhesion and activation proteins was used in combination with an anti‐CD3 antibody in dual‐color flow cytometry. The problem of low cell numbers in the CSF from normal individuals was overcome by use of a modified staining procedure in microtiter plates, enabling analysis of as few as 5,000 cells. The majority of T cells in the CSF of the three patient groups exhibited the phenotype of memory cells (CD45RO+). CSF T cells also expressed significantly higher levels of several adhesion and activation molecules, including very late activation (VLA) antigens 3 through 6, lymphocyte function‐associated (LFA) antigen 1, LFA‐3, CD2, CD26, and CD44. Comparison between the different categories revealed that peripheral blood T cells from patients with multiple sclerosis expressed significantly lower amounts of the VLA integrins 4 and 5 as well as their common β subunit CD29, compared with normal control subjects. No differences between patients with multiple sclerosis and control subjects could, however, be seen regarding the distribution of memory/naive cells or CD4+/CD8+ cells in peripheral blood. Our data support a hypothesis that memory T cells with a high expression of several adhesion molecules are selectively recruited to the central nervous system compartment, under both pathological and normal conditions. We also provide evidence for an altered expression of adhesion molecules on peripheral blood T cells in patients with multiple sclerosis that is independent of the memory cell phenotype as defined by the expression of the CD45RO epitope.
The prevalence of computed tomographic abnormalities of the cerebrum in 100 consecutive children symptomatic with the human immune deficiency virus
Authors: DeCarli C. , Civitello L. A. , Brouwers P. , Pizzo P. A.
Published: January 2005

Qualitative analysis of 100 consecutive computed tomographic (CT) studies of the brain in children with symptomatic but untreated acquired immunodeficiency syndrome was performed. After excluding children with associated medical illnesses that might confound the diagnosis of encephalopathy or alter brain structure, an abnormality of at least one of the measures of ventricular size, cortical atrophy, white matter attenuation (leukoaraiosis), or cerebral calcification was found in 86% of the patients studied. Ventricular enlargement was the most common abnormality, followed by cortical atrophy, leukoaraiosis, and cerebral calcification. Cerebellar atrophy was an unexpected but relatively common finding in 12% of the children. Sixty‐five percent of the children were encephalopathic at the time of evaluation. All 16 children with cerebral calcification were encephalopathic and had acquired human immunodeficiency virus (HIV) through vertical transmission. Encephalopathic children were significantly younger and had significantly greater abnormality ratings on each CT measure when compared with the nonencephalopathic children. Discriminant analysis using age and the qualitative CT measures was applied as a method to identify the presence of encephalopathy. CT measures proved to have a specificity and a sensitivity of only 76%. We conclude that abnormalities of cerebral structure are seen in a high percentage of children symptomatic with HIV. Although most of the children are encephalopathic, CT abnormalities are seen in children without encephalopathy, suggesting presymptomatic brain disease. The presence of cerebral calcification on CT suggests in utero infection with HIV and the presence of encephalopathy. Although not diagnostic of encephalopathy, routine use of CT in pediatric patients with acquired immunodeficiency syndrome may add significant additional information about the mode of HIV transmission and potential presymptomatic brain disease.
Cortical vascular abnormalities in the syndrome of celiac disease, epilepsy, bilateral occipital calcifications, and folate deficiency
Authors: Bye Annie M. E. , Andermann Frederick , Robitaille Yves , Oliver M. , Bohane T. , Andermann Eva
Published: January 2005

The pathological changes in the syndrome of celiac disease, folate deficiency, bilateral occipital calcifications, and intractable epilepsy have not been previously described. A child with this disorder had a field defect correlating with active lateralized epileptic discharges and asymmetrical lesions. After resection of the right occipital lobe she was seizure free for 4 years. A cortical vascular abnormality with patchy pial angiomatosis, fibrosed veins, and large jagged microcalcifications was found. These pathological abnormalities were similar though not identical to those found in the Sturge‐Weber syndrome.
Role of the left and right supplementary motor areas in memory‐guided saccade sequences
Authors: Gaymard B. , Rivaud S. , Pierrot‐Deseilligny C.
Published: January 2005

Six right‐handed patients with a lesion affecting the left (3 patients) or right (3 patients) supplementary motor area were studied using single and sequential memory‐guided saccade paradigms. Accuracy of single saccades was preserved in both groups, compared to control subjects, and the chronology of saccade sequences was disturbed in the group with the left lesion but not in the group with the right lesion. The results suggest that neither side of the supplementary motor area is involved in spatial memory, and that the left supplementary motor area plays a greater role in motor sequencing than does the right supplementary motor area.
A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's syndrome
Authors: de Vries D. Daniëlle , van Engelen Baziel G. M. , Gabreëls Fons J. M. , Ruitenbeek Wim , van Oost Bernard A.
Published: January 2005

By direct sequencing, we have discovered a novel heteroplasmic mutation (T←C) at nucleotide position 8993 in the mitochondrial ATPase 6 gene in a family with Leigh's syndrome. Another mutation in the same codon (T8993G) has been reported before in Leigh's syndrome. As these two mutations led to different amino acid substitutions, it provides strong evidence for the relevance of ATP synthase dysfunction in maternally inherited Leigh's syndrome.
Impairment of retinal increment thresholds in Huntington's disease
Authors: Paulus Walter , Schwarz Guntram , Werner Annette , Lange Herwig , Bayer Andreas , Hofschuster M. , Müller Norbert , Zrenner Eberhart
Published: January 2005

We have investigated detection thresholds for a foveal blue test light using a Maxwellian view system in 61 normal subjects, 19 patients with Huntington's chorea, 14 patients with Tourette's syndrome, and 20 patients with schizophrenia. Ten measurements were made: The blue test light (1 degree diameter, 500 msec duration) was presented either superimposed on a yellow adaptation field (5 degree diameter) or 500 msec after switching off this field (transient tritanopia effect). In both cases five different background intensities were presented. The only abnormality found was in patients with Huntington's chorea. During adaptation these patient's thresholds are significantly higher than normal (p<0.005). No change was found in the transient tritanopia effect. Huntington's disease causes degeneration of several different transmitter systems in the brain. Increment threshold testing allows for noninvasive investigation of patients and confirms the involvement of the retina in the degenerative process in Huntington's chorea.
Interictal indices of temporal seizure origin
Authors: Blume Warren T. , Borghesi Joanna L. , Lemieux John F.
Published: January 2005

Two studies assessed the value of temporal lobe interictal electroencephalographic (EEG) spikes and delta in indicating side of temporal epileptogenesis. The first study determined laterality of spikes/delta in awake recordings of 56 patients whose seizures all began unilaterally as proven by (1) EEG‐recorded seizures and (2) >90% improvement after lobectomy. Spikes of 52 (93%) and delta of 46 (82%) patients predominated or appeared exclusively ipsilateral to seizure origin. Neither predominated contralaterally in any patient. The second study investigated laterality of temporal seizures in a separate group of 156 patients with various side vs side spike or delta ratios on 1 to ≥4 awake recordings. Ninety‐nine of 104 patients (95%) with temporal spikes on four or more awake recordings had most or all seizures ipsilateral to most spikes, including 79 of 80 (99%) of those with ≥3 side vs side spike ratios. Among the 120 patients with high (≥3) side vs side spike ratios, most or all seizures of 118 (98%) originated ipsilateral to most spikes. Predominant seizure origin also correlated with lateralized arrhythmic delta—from 90% ipsilateral seizures of those with one EEG with delta to 100% with ≥4 such EEGs. Data from these two studies using opposite directions of analysis (seizures ← spikes/delta and spikes/delta → seizures) demonstrate high correlations between laterality of interictal and ictal entities, particularly if temporal spikes clearly predominate on one side and if unilateral temporal delta activity persists over several recordings. Such correlations suggest that the awake interictal scalp EEG cannot be ignored when assessing laterality of temporal epileptogenesis.
Autosomal dominant Lewy body parkinsonism in a four‐generation family
Authors: Waters C. H. , Miller C. A.
Published: January 2005

We report a family with autosomal dominant parkinsonism. The propositus developed parkinsonism at a relatively young age (45 years) and came to autopsy after a 6‐year illness. She had typical features of Parkinson's disease except for an absence of rest tremor, although this was present in other family members. A diagnosis of Lewy body parkinsonism was confirmed by neuropathological examination. Additional pathological features included the presence of cortical Lewy bodies and anti‐ubiquitin‐positive neurites in the cornu Ammonis 2 and 3 (CA2‐3) region of the hippocampus. This kindred is similar both clinically and pathologically to a few previously reported pedigrees, further strengthening recent evidence of a genetic etiology of some forms of Parkinson's disease.
Long‐latency event‐related potentials in asymptomatic human immunodeficiency virus type 1 infection
Authors: Connolly Sean , Manji Hadi , McAllister Ruth H. , Fell Mary , Loveday Clive , Kirkis Chris , Herns Mary , Sweeney Brian , Sartawi Omar , Durrance Pauline , Griffin Geraldine B. , Boland Mary , Fowler Clare J. , Newman Stanton P. , Weller Ian V. D. , Harrison Michael J. G.
Published: January 2005

As part of the Medical Research Council prospective study of the neurological and neuropsychological complications of human immunodeficiency virus (HIV) infection, long‐latency event‐related potentials were recorded in a cohort of homosexual and bisexual men. The latencies and amplitudes of the potentials, recorded from three scalp sites, were compared with the scores from neuropsychological tests of memory, attention, and concentration and with markers of immune function. The findings from 94 men were analyzed in the cross‐sectional study of whom 47 were HIV seropositive without symptoms or signs of HIV type 1 (HIV‐1) infection, 24 had progressed to the symptomatic stages of the disease, and 23 were persistently HIV seronegative. There were no consistently significant differences between the three subject groups in mean latencies and amplitudes of the P300 and N200 or in the numbers of abnormal P300 latencies. There were no significant correlations between either the neuropsychological tests scores or the immune measures (CD4 lymphocyte count and β2 microglobulin level) and the neurophysiological parameters. On repeated testing an average of 2 years later, there was no evidence of a significant trend towards deterioration in 30 HIV‐seropositive subjects who remained asymptomatic compared with 22 HIV seronegatives. These findings indicate that there is no neurophysiological evidence of cognitive dysfunction in the asymptomatic stages of HIV‐1 infection.
Spontaneous palpebromandibular synkinesia: A localizing clinical sign
Authors: Pullicino Patrick M. , Jacobs Lawrence , McCall Willard D. , Garvey Michael , Ostrow Peter T. , Miller Lucia L.
Published: January 2005

In the classical corneomandibular reflex (CMR), corneal stimulation elicits a bilateral eyelid blink and a brisk anterolateral jaw movement. We here describe 14 patients with a spontaneous palpebromandibular (eyelid–jaw) synkinesia (SPMS) in whom jaw movements, similar to those in CMR, regularly accompanied spontaneous eye blinks without an external corneal stimulus. Eleven of the patients with SPMS also had CMRs on corneal stimulation. Four patients had clinical and imaging evidence of brainstem lesions above the mid‐pons, 5 patients had autopsy or imaging evidence of both bilateral cerebral and upper brainstem lesions, and 5 patients had clinical or imaging evidence of bilateral cerebral dysfunction. Topical corneal anesthesia administered to patients who had both CMR and SPMS blocked the CMR but had no effect on the SPMS. In patients with both SPMS and CMR, measurements of latency from onset of orbicularis oculi electromyographic activity to onset of lateral pterygoid EMG activity, and mandibular kinesiography of jaw velocity and direction showed that the eyelid–jaw synkinesias of CMR and SPMS had similar characteristics. We conclude that SPMS is pathophysiologically the same as the eyelid–jaw synkinesia of CMR and both synkinesias originate centrally, probably in the pons. In CMR, the jaw movement is primarily related to the blink rather than the corneal stimulus, but corneal stimulation may be necessary to overcome a higher threshold for expression of the synkinesia than in patients with SPMS. Like CMR, SPMS emerges in patients with upper brainstem or bilateral cerebral lesions and SPMS may therefore be a useful localizing clinical sign.
Abnormality of the α‐ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer's disease
Authors: Sheu Kwan‐Fu Rex , Cooper Arthur J. L. , Koike Kichiko , Koike Masahiko , Lindsay J. Gordon , Blass John P.
Published: January 2005

To test whether previously demonstrated reductions in the activity of the α‐ketoglutarate dehydrogenase complex (KGDHC) in Alzheimer's disease (AD) brain also occur in morphologically normal AD tissues, we examined KGDHC in cultured skin fibroblasts from patients with familial AD (FAD). KGDHC activity was reduced by 44% in the FAD cells (p < 0.002) from the 4 families studied, including a within‐kindred comparison of affected and escape subjects in the chromosome 14q24.3‐linked Nova Scotia kindred. The activities of several other glutamate‐ and glutamine‐metabolizing enzymes were normal in the FAD cells, as was the activity of another mitochondrial multienzyme dehydrogenase complex, that for pyruvate. Mixing experiments indicated that the abnormality of KGDHC activity in FAD fibroblasts was not due to an inhibitor or to excess protease activity. KGDHC is a complex of three proteins. Immunoblots for the E2k component under conditions of optimal protease inhibition revealed the expected 46‐kd species in both AD and non‐AD fibroblasts, but the patient cells also regularly contained an additional 29‐kd species that was absent or present in minimal amounts in the controls. Immunoblotting demonstrated no abnormalities in the E1k and E3 components. Other studies indicate that the human gene for E2k resides on chromosome 14q24.3, in a region associated with FAD in a number of families including the KGDHC‐deficient Nova Scotia kindred. The persistence of abnormalities in KGDHC and particularly in its E2k component in FAD fibroblasts indicates that abnormalities of this autosomally coded nuclear component are an intrinsic part of the AD process, and the possible role of this abnormality in the pathogenesis of AD is discussed.
Andersen's syndrome: Potassium‐sensitive periodic paralysis, ventricular ectopy, and dysmorphic features
Authors: Tawil Rabi , Ptacek Louis J. , Pavlakis Steven G. , DeVivo Darryl C. , Penn Audrey S. , Özdemir Coskun , Griggs Robert C.
Published: January 2005

Andersen's syndrome is a clinically distinct form of potassium‐sensitive periodic paralysis associated with cardiac dysrhythmias. The subtle nature of the cardiac and dysmorphic features may delay the recognition of this syndrome and its potentially lethal cardiac dysrhythmias. The genetic defect in Andersen's syndrome is not genetically linked to other forms of potassium‐sensitive periodic paralysis and is probably distinct from the long QT syndrome locus.
Predictive value of induction of psychogenic seizures by suggestion
Authors: Lancman Marcelo E. , Asconapé Jorge J. , Craven William J. , Howard George , Penry J. Kiffin
Published: January 2005

Induction by suggestion has previously been reported to be effective in the diagnosis of psychogenic seizures (PS). However, the sensitivity and specificity of this procedure has not previously been studied. Results of induction of PS by suggestion were analyzed in 93 patients with purely PS. The diagnosis of PS was based on the recording of a clinical event on video‐electroencephalography, the absence of clinical or electroencephalographic evidence of epilepsy, and the subsequent followup and withdrawal of anticonvulsants supporting the diagnosis of PS. A control group was composed of 20 patients with epilepsy in which induction was tried. Both groups were comparable for age, sex, and educational level. Induction was performed following a standardized protocol. The test was carried out placing a colored patch on the neck. The test was considered positive when the induced clinical events were typical, according to a witness familiar with the patient's seizures. Induction was positive in 72 of 93 cases with PS and in none with epilepsy. Sensitivity of this test for the diagnosis of PS was 77.4%, specificity 100%, positive predictive value 100%, and negative predictive value 48.7%.
Elevated basic fibroblast growth factor in the serum of patients with Duchenne muscular dystrophy
Authors: D'Amore P. A. , Brown R. H. , Ku P‐T. , Hoffman E. P. , Watanabe H. , Arahata K. , Ishihara T. , Folkman J.
Published: January 2005

The mechanism whereby dystrophin deficiency leads to excessive fibrosis and muscle degeneration is not known. The absence of dystrophin in skeletal muscle is associated with reduced plasma membrane stability as evidenced by elevated serum levels of the cytoplasmic enzyme creatine kinase. Basic fibroblast growth factor, a cytoplasmic polypeptide growth regulator that stimulates connective tissue synthesis, induces satellite cell proliferation, and suppresses myogenic differentiation, is made by skeletal muscle. We hypothesize that dystrophin deficiency leads to the constant release of basic fibroblast growth factor, which in turn contributes to fibrosis and muscle weakness by stimulating connective tissue and suppressing skeletal muscle differentiation. As an initial step in testing this hypothesis, we measured basic fibroblast growth factor in the serum of Duchenne muscular dystrophy patients. We found that whereas basic fibroblast growth factor was undetectable in the serum of normal individuals (n = 200), levels were elevated in 11 of 18 patients with Duchenne muscular dystrophy.
Myo‐leukoencephalopathy in twins: Study of 3243‐myopathy, encephalopathy, lactic acidosis, and strokelike episodes mitochondrial DNA mutation
Authors: Degoul F. , Diry M. , Pou‐Serradell A. , Lloreta J. , Marsac C.
Published: January 2005

Two dizygotic twins with myopathy and leukoencephalopathy are described. The female twin had an incomplete from of MELAS syndrome (myopathy, encephalopathy, lactic acidosis, and strokelike episodes) with severe myopathy, epileptic seizures without strokelike episodes. The male twin presented clinical features exclusively of myopathy and subclinical leukoencephalopathy. The MELAS mitochondrial DNA point mutation (MELAS‐3243) was found by southern blot and polymerase chain reaction in muscle, skin fibroblasts, and blood of the female twin and was not detected in the skin fibroblasts nor in the blood of the mother, nor in any of the tissues tested in the male twin. The absence of mutation in male twin tissues raises questions about the pathogenetic significance of the mutation in this family.
Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with late‐onset Alzheimer's disease
Authors: Peacock M. L. , Murman D. L. , Sima A. A. F. , Warren J. T. , Roses A. D. , Fink J. K.
Published: January 2005

Amyloid plaques in Alzheimer's disease contain β‐amyloid, encoded by portions of exons 16 and 17 of the amyloid precursor protein. The specific association of rare amyloid precursor protein mutations with some kindreds with early‐onset familial Alzheimer's disease suggests that specific abnormalities in amyloid precursor protein may contribute to the pathogenesis of Alzheimer's disease. Until now, there has been no evidence suggesting that amyloid precursor protein mutations could be involved in late‐onset or sporadic Alzheimer's disease. We used reverse transcription–polymerase chain reaction, denaturing gradient gel electrophoresis, and direct DNA sequencing to analyze amyloid precursor protein exons 16 and 17 from postmortem cerebellar samples from patients with histologically confirmed Alzheimer's disease and control subjects. We found a novel point mutation, substitution of cytosine for guanine, at nucleotide 2119 (amyloid precursor protein 770 messenger RNA transcript) in a patient with late‐onset Alzheimer's disease. This substitution deletes a BglII site and substitutes aspartate for glutamine at codon 665. Denaturing gradient gel electrophoresis analysis showed that this mutation was absent in 40 control subjects and 127 dementia patients. Whether this mutation is a rare but normal variant or contributes to the development of Alzheimer's disease is not known. The BglII restriction fragment length polymorphism enables investigators to determine the frequency of this polymorphism in normal subjects and Alzheimer's disease patients.
Cerebellar α‐Ketoglutarate dehydrogenase activity is reduced in spinocerebellar ataxia type 1
Authors: Mastrogiacomo Frank , Kish Stephen J.
Published: January 2005

We measured the activity of the thiamine pyrophosphate–dependent enzyme α‐ketoglutarate dehydrogenase complex in postmortem brain of 12 patients with the spinocerebellar ataxia type 1 form of olivopontocerebellar atrophy. α‐Ketoglutarate dehydrogenase complex activity measured in the absence of thiamine pyrophosphate was markedly reduced (−72%) in olivopontocerebellar atrophy cerebellar cortex. Decreased activity of this key rate‐limiting Krebs cycle enzyme could compromise cerebellar energy metabolism and excitatory amino acid synthesis and thereby contribute to the brain dysfunction of olivopontocerebellar atrophy.
Correlation of magnetization transfer ration with clinical disability in multiple sclerosis
Authors: Gass A. , Barker G. J. , Kidd D. , Thorpe J. W. , MacManus D. , Brennan A. , Tofts P. S. , Thompson A. J. , McDonald W. I. , Miller D. H.
Published: January 2005

We performed spin echo magnetic resonance imaging with and without application of an off‐resonance saturation pulse in 43 patients with multiple selerosis (MS), 10 age‐matched controls, and 4 elderly asymptomatic patients with the radiological diagnosis of small‐vessel disease. Magnetization transfer (MT) ration images were obtained from these. All MS subgroups (primary progressive, secondary progressive, benign, early relapsing–remitting) showed significantly lower average lesion MT ratios than small‐vessel disease patients. Secondary progressive MS patients showed significantly lower lesion MT ratios than those with benign disease, and there was an inverse correlaion of disability with average lesion MT ratio. The degree of reduction of MT ratios is an indicator of the extent of tissue destruction. Thus, reduced MT ratios in MS may provide an indication of the degree of demyelination and axonal loss, both of which are likely to cause functional deficits in MS. We conclude that MT measurement is (1) a robust quantitative method that may increase the pathological specificity of magnetic resonance imaging, (2) has the potential to differentiate demyelination in MS from less destructive pathological changes, and (3) may be useful in monitoring modifications in tissue structure brought about by treatment.
Are the associations between Alzheimer's disease and polymorphisms in the apolipoprotein E and the apolipoprotein CII genes due to linkage disequilibrium?
Authors: Tsuda T. , Lopez R. , Rogaeva E. A. , Freedman M. , Rogaev E. , Drachman D. , Pollen D. , Haines J. , Liang Y. , McLachlan D. R. Crapper , Duara R. , St George‐Hyslop P.
Published: January 2005

Allele frequencies for polymorphisms in the aplipoprotein E and the apolipoprotein CII genes were determined in subjects of Ashkenazi Jewish origin with lateonset Alzheimer's disease and in unaffected control subjects from the same ethnic group. A significant association was observed between late‐onset Alzheimer's disease and the ε4 (112Cys→Arg) allele of apolipoprotein E; however, no association was detected with apolipoprotein CII. These results suggest that the association with ε4 is probably not due to linkage disequilibrium.