bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute demyelinating disease in a chimpanzee three years after inoculation of brain cells from a patient with MS
Authors: Rorke Lucy Balian , Iwasaki Yuzo , Koprowski Hilary , Wroblewska Zofia , Gilden Donald H. , Warren Kenneth G. , Lief Florence S. , Hoffman Steven , Cummins Larry B. , Rodriguez Arthur R. , Kalter Seymour S.
Published: January 2005

Brain cells from a patient with classic multiple sclerosis were inoculated intracerebrally into the frontal lobe of a newborn chimpanzee. The animal developed acute quadriplegia three years, two months later and was killed four days after the onset of symptoms. Central nervous system lesions were primarily localized in the spinal cord at root entry zones; these were characterized by demyelination and regeneration of myelin by Schwann cells.
Mechanisms underlying hemispatial neglect
Authors: Heilman Kenneth M. , Valenstein Edward
Published: January 2005

If patients with left‐sided hemispatial neglect bisect lines incorrectly because hemianopia or sensory hemiinattention prevents them from seeing how far the line extends to the left, a strategy that ensures their seeing the left side of the line in their normal field should improve performance. If patients have hemispatial hypokinesia, moving the line toward the normal half of body space should improve performance.

Six patients with left‐sided neglect from right hemisphere infarctions were required to identify a letter at either the right or the left end of a line before bisecting that line. The task was given with the lines placed at either the right, the center, or the left of the body midline.

Performance in trials when subjects were required to look to the left before bisecting a line did not differ from when they were required to look right. Performance was significantly better when the line was placed to the right side of the body than to the left. These observations support the hypothesis that patients with hemispatial neglect have hemispatial hypokinesia. An alternative hypothesis is that these subjects had a hemispatial memory defect. Although they saw the left side of the line in their normal field, they were incapable of forming a stable trace and performed as if they did not see the left side of the line.
Phosphorylation of the membrane‐bound acetylcholine receptor: Inhibition by diphenylhydantoin
Authors: Gordon Adrienne S. , Milfay Dale , Diamond Ivan
Published: January 2005

Purified postsynaptic membranes can be used as a model system to study the regulation of synaptic membrane proteins. These membranes contain protein kinase activity that phosphorylates the acetylcholine receptor (AChR). We find that diphenylhydantoin (DPH) interacts with these membranes to inhibit phosphorylation of the membrane‐bound AChR. DPH appears to alter the availability of postsynaptic membrane proteins for phosphorylation by a synaptic membrane protein kinase. The concentration of DPH that produces half‐maximal inhibition of AChR phosphorylation is about 5 × 10−5 M. This suggests that one of the specific effects of DPH in the nervous system may be related to inhibition of phosphorylation of postsynaptic membrane proteins.
Osmotic opening of the blood‐brain barrier and local cerebral glucose utilization
Authors: Pappius H. M. , Savaki H. E. , Fieschi C. , Rapoport S. I. , Sokoloff L.
Published: January 2005

The effects of osmotic opening of the blood‐brain barrier (BBB) on local cerebral glucose utilization (LCGU) were studied in rats with the carbon 14–deoxyglucose method. The BBB was opened to Evans blue dye by unilateral carotid artery perfusion with hypertonic mannitol solution. (14C)‐Deoxyglucose was injected 15 minutes or two to three hours later. Osmotic opening of the BBB resulted in focal areas of intense LCGU in affected areas of the perfused hemisphere. In the contralateral hemisphere, glucose utilization was diminished, especially in cerebral cortical areas. The effects were reversible. LCGU was normal in both hemispheres when permeability to Evans blue returned to normal two to three hours after carotid perfusion. In 3 to 5 experiments the administration of high doses of intravenous diazepam immediately following carotid artery perfusion with mannitol prevented an increase in LCGU in the perfused hemisphere but did not prevent lowering of LCGU in the contralateral hemisphere. Increased LCGU following osmotic opening of the BBB was not accompanied by a rise in local cerebral blood flow as measured by the iodoantipyrine method. Blood flow was, in fact, significantly decreased.
Bolus versus steady‐state infusion for determination of CSF outflow resistance
Authors: Sullivan Humbert G. , Miller J. Douglas , Griffith Richard L. , Carter Walter , Rucker Sarah
Published: January 2005

For rapid changes in cerebrospinal fluid volume an exponential relationship was demonstrated between CSF pressure and CSF volume in 15 cats. This relationship was valid over a CSF pressure range from 7 to 50 mm Hg and for acute increases of up to 9% of total CSF volume (∼ 13 ml for humans). Our data agree well with previous reports for the cat. A similar relationship has been shown in the dog and in humans. It has been claimed that, given the equations for CSF bulk flow and the exponential relationship between CSF pressure and CSF volume, one can calculate CSF outflow resistance by observing the decay of CSF pressure after a bolus injection into the CSF space. This claim was evaluated in an additional 18 cats. In these animals CSF outflow resistance calculated by the bolus method was compared with resistance calculated by a steady‐state infusion method over the CSF outflow resistance range of 74 to 293 mm Hg/ml min−1. Resistance calculated by the bolus method underestimated resistance calculated by the steady‐state method, and this underestimate grew larger with increasing resistance. The bolus technique is therefore not a valid method for determining CSF outflow resistance. The explanation offered for these results is that the decay of CSF pressure after a bolus injection into the CSF space occurs not only because of runoff of the injected volume of CSF but also because of “pressure relaxation” of the brain parenchyma around the CSF space. The phenomenon of pressure relaxation was not considered in developing the equation for calculation of CSF outflow resistance by the bolus technique. The time dependency of pressure relaxation allows for a fundamental element of hysteresis within the CSF space. A method of quantifying this element of hysteresis is suggested.
Cerebral color blindness: An acquired defect in hue discrimination
Authors: Pearlman Alan L. , Birch Jennifer , Meadows John C.
Published: January 2005

In contrast to the traditional view that striate visual cortex (area 17) is surrounded by two homogeneous cortical areas (areas 18 and 19), recent studies have shown that mammalian extrastriate visual cortex contains several anatomically and functionally distinct subregions. One such region, the V‐4 complex of the rhesus monkey, is highly specialized for the analysis of color information, suggesting that a lesion in a homologous region might produce a defect in color vision while sparing other visual functions.

We have studied a patient whose clinical syndrome supports this suggestion: a 44‐year‐old man with normal color vision suffered two cerebral infarctions that produced first a right and then a left superior homonymous quadrantanopia and also caused prosopagnosia, topographical disorientation, and severely impaired color vision. Computed tomography demonstrated extensive lesions in both inferior occipital lobes in the territories of the lateral branches of the posterior cerebral arteries, involving the lingual and medial occipitotemporal gyri bilaterally; these gyri contain the inferior portion of striate cortex and segments of extrastriate visual cortex. The patient had no difficulty in giving the correct color names associated with common objects presented either verbally or in outline drawings. Standardized testing with the Farnsworth‐Munsell 100‐hue test, the Nagel anomaloscope, and a method that tests for just‐noticeable differences between monochromatic stimuli all showed that the patient's ability to distinguish one color from another was markedly impaired but not totally absent. In contrast, visual acuity, reading, visually guided eye movements, and stereopsis were normal. Cells in the V‐4 complex of monkey extrastriate cortex are highly specialized for distinguishing one color from another; the hue discrimination deficit that was demonstrated in this patient with cerebral color blindness indicates that a region or regions with similar function has been damaged.
Mucocutaneous eruptions due to antiepileptic drug therapy in children
Authors: Pollack Michael A. , Burk Peter G. , Nathanson Gerald
Published: January 2005

Three children with bullous erythema multiforme and 1 with toxic epidermal necrolysis associated with antiepileptic drug therapy are described. One patient is unique because of seven mucocutaneous eruptions caused by three classes of antiepileptic drugs. Lymphocyte stimulation by antiepileptic drugs could not be demonstrated in the 2 patients in whom appropriate studies were performed, and no precipitating antibodies to antiepileptic drugs were found. Observation of four diagnostic and therapeutic principles, which are illustrated by the course of our patients, may reduce the incidence of life‐threatening mucocutaneous eruptions and simplify the long‐term management of individuals in whom such reactions occur.
Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia
Authors: Wisniewski Krystyna , Jervis George A. , Moretz Roger C. , Wisniewski Henryk M.
Published: January 2005

A brief description is given of neurofibrillary changes of the paired helical filament type in a variety of chronic neurological diseases. These include subacute sclerosing panencephalitis, lead encephalopathy, tuberous sclerosis, Down syndrome, Hallervorden‐Spatz disease, and lipofuscinosis. In these conditions, with the exception of Hallervorden‐Spatz disease, neurofibrillary changes were previously recognized but paired helical filaments were identified only in some cases. Moreover, in the present series, the age of patients at death was often younger than in previously recorded cases.
The decreasing incidence of primary intracerebral hemorrhage: A population study
Authors: Furlan Anthony J. , Whisnant Jack P. , Elveback Lila R.
Published: January 2005

This population study describes the experience with primary intracerebral hemorrhage (PIH) in residents of Rochester, MN, for the 32‐year period from 1945 through 1976. The average annual age‐adjusted incidence rate for PIH was 12.1 per 100,000 population, and the incidence for all cases of spontaneous intracerebral hemorrhage was 15.2 per 100,000. The PIH rates were higher for males than for females, and they increased steadily with age. When patients on long‐term anticoagulant therapy were excluded, there was a steady decrease in the average annual age‐adjusted incidence rate for PIH in each succeeding 8‐year interval since 1945. Prehemorrhage hypertension, present overall in 89% of patients, was much more frequent and severe in the earlier years of the study. The frequency and severity of prehemorrhage hypertension also varied inversely with age in the population with PIH. The median age at the onset of PIH increased from 65 years for the period 1945 through 1952 to 71 years for 1969 through 1976.
Effect of phenytoin on bone and vitamin D metabolism
Authors: Bell Rodney D. , Pak Charles Y. C. , Zerwekh Joseph , Barilla Donald E. , Vasko Michael
Published: January 2005

Calcium and vitamin D metabolism were evaluated in 5 adult epileptic patients before and during treatment with phenytoin. Significant decreases occurred in serum concentrations of calcium, albumin, and 25‐hydroxycholecalciferol. The decreases in serum calcium paralleled those in serum albumin. Significant increases occurred in serum alkaline phosphatase and 1α,25‐dihydroxycholecalciferol, in urinary hydroxyproline, and in the fractional gastrointestinal absorption of calcium. Urinary cyclic adenosine monophosphate and serum parathyroid hormone did not change.

The results suggest that the bone disease resulting from phenytoin therapy may be associated with a deficiency of 25‐hydroxycholecalciferol and not of 1α,25‐dihydroxycholecalciferol, and that reduced gastrointestinal absorption of calcium or changes in parathyroid function may not be necessary for the development of bone disease.
Debrancher deficiency: Neuromuscular disorder in 5 adults
Authors: DiMauro Salvatore , Hartwig Geoffrey B. , Hays Arthur , Eastwood Abraham B. , Franco Richard , Olarte Marcelo , Chang Myung , Roses Allen D. , Fetell Michael , Schoenfeldt Richard S. , Stern Lawrence Z.
Published: January 2005

Five patients, 4 men and 1 woman, had adult‐onset and slowly progressive weakness. There was distal wasting in 2, hepatomegaly in 3, and congestive heart failure in 2. Electromyography showed a mixed pattern with abundant fibrillations. Serum creatine phosphokinase was increased 5‐to 45‐fold. Blood glucose failed to respond to epinephrine or glucagon, and venous lactate did not rise after ischemic exercise. Muscle biopsy showed vacuolar myopathy affecting both fiber types. By electron microscopy the vacuoles corresponded to large pools of glycogen not limited by a membrane. Glycogen concentration was 3 to 5 times normal in muscle and 7 to 21 times normal in erythrocytes. In the presence of iodine, muscle glycogen showed a spectrum characteristic of phosphorylase‐limit‐dextrin. Debrancher activity was measured by a spectrophotometric assay and by a radioactive reverse reaction. The activity was lacking in muscle and erythrocytes of 4 patients according to both assays; in 1 patient the reverse reaction was not impaired.

Though previously reported in only 5 patients, debrancher deficiency myopathy may not be rare and should be considered in the differential diagnosis of adult‐onset hereditary myopathies.
Paraneoplastic vasculitis of nerve: A remote effect of cancer
Authors: Johnson Peter C. , Rolak Loren A. , Hamilton Robert H. , Laguna Jose F.
Published: January 2005

The development of mononeuritis multiplex brought three men to medical attention weeks to months prior to the diagnosis of a malignancy. In each case, sural nerve biopsy exhibited active wallerian degeneration with vasculitis. Two of the men died and at autopsy were found to have clinically unrecognized oat cell carcinoma and carcinomatous sensory neuropathy with brainstem encephalitis. The third patient is still alive but was found to have a lymphoma and has subsequently developed a liposarcoma. The vasculitis in all 3 cases seems limited mainly to the peripheral nervous system. Mononeuritis multiplex due to vasculitis may represent a new remote effect of cancer on the nervous system.
Abnormal auditory evoked potentials in hereditary motor‐sensory neuropathy
Authors: Satya‐Murti Saty , Cacace Anthony T. , Hanson Peggy A.
Published: January 2005

From a kinship with a dominantly inherited motor‐sensory neuropathy, we studied 2 brothers with brainstem auditory evoked potentials and behavioral audiometric tests. They had abnormal prolongation of I‐III interpeak intervals. Wave V was poorly developed. Conventional audiometric tests did not reveal a peripheral hearing loss. It is probable that their auditory nerves and spiral ganglia are undergoing a pathophysiological process analogous to that of their peripheral nerves.
Cytomegalovirus infection of the adult nervous system
Authors: Duchowny Michael , Caplan Louis , Siber George
Published: January 2005

In 2 patients, 1 with brachial plexus neuropathy and another with relapsing chronic encephalitis, the acute neurological syndrome was accompanied by fever, tachycardia, abnormal liver function, and atypical lymphocytosis. Cytomegalovirus (CMV) infection was documented in both patients by viral isolation and a fourfold rise in complement‐fixation titer. CMV may produce peripheral neuropathy, brachial plexus neuropathy, or an acute or chronic meningoencephalitis in previously healthy adults without immune deficiency.
Self‐limited granulomatous angiitis of the cerebellum
Authors: Beresford H. Richard , Hyman Roger A. , Sharer Leroy
Published: January 2005

A middle‐aged woman presented with clinical evidence of rapidly progressive cerebellar dysfunction and had radiographic evidence of a cerebellar mass. Biopsy of the lesion disclosed granulomatous angiitis. She recovered completely, the only treatment being dexamethasone given for five days after surgery.
Does a defect of energy metabolism in the nerve fiber underlie axonal degeneration in polyneuropathies?
Authors: Spencer Peter S. , Sabri Mohammad I. , Schaumburg Herbert H. , Moore Cyril L.
Published: January 2005

A number of chemically unrelated neurotoxic compounds and several types f metabolic abnormalities cause strikingly similar patterns of distal symmetrical polyneuropathy in humans and animals. Experimental studies with laboratory species have demonstrated that many toxic polyneuropathies are associated with distal and retrograde axonal degeneration occurring in vulnerable nerve fiber tracts in the central as well as the peripheral nervous system. This has been termed central‐peripheral distal axonopathy.

Recent observations from the authors' laboratories regarding (1) the spatial‐temporal evolution of nerve fiber degeneration in experimental toxic neuropathies and (2) the inhibition of glycolytic enzymes by chemically unrelated neurotoxic compounds point to a common metabolic basis for many distal axonopathies. It is postulated that neurotoxic compounds deplete energy supplies in the axon by inhiniting nerve fiber enzymes required for the maintenance of energy synthesis. Resupply of enzymes from the neuronal soma fails to meet the increased demand for enzyme replacement in the axon, causing the concentration of enzymes to drop in distal regions. This leads to a local blockade of energy‐dependent axonal transport, which produces a series of pathological changes culminating in distal nerve fiber degeneration. The idea provides a working hypothesis with which to study the cause of inherited and acquired human and animal polyneuropathies.
Intracellular redox states under halothane and barbiturate anesthesia in normal, ischemic, and anoxic monkey brain
Authors: Sundt Thoralf M. , Anderson Robert E. , Michenfelder John D.
Published: January 2005

Cortical reflectance, mean arterial blood pressures, electroencephalograms, and cortical blood flow were continuously recorded together with fluorescence of reduced pyridine nucleotides (PN) at various carbon dioxide tensions before, during, and following middle cerebral artery occlusion in 10 squirrel monkeys receiving halothane or barbiturate anesthesia. Measurements were continued through a nitrogen breathing cycle and to death produced by anoxia. The anesthetic agent produced no detectable differences in PN fluorescence in cerebral tissue during ischemia and anoxia. The known cerebral protective action of barbiturates is apparently unrelated to the intracelular redox state.
The TO strains of Theiler's viruses cause “slow virus—like” infections in mice
Authors: Lipton Howard L. , Dal Canto Mauro C.
Published: January 2005

Intracerebral inoculation of mice with tissue culture–adapted TO strains of Theiler's mouse encephalomyelitis viruses results in a clinical disease consisting of spastic paralysis due to demyelination after a lengthy incubation period. Thus, in effect, these ordinary picornaviruses are capable of causing a slow infection in their natural host, the mouse. In addition, through the use of tissue culture–adapted virus stocks, virus content in mouse tissues now can be accurately quantified by standard plaque assay.
Botulism, type A, and treatment with guanidine
Authors: Kaplan Jonathan E. , Davis Larry E. , Narayan Venkat , Koster John , Katzenstein David
Published: January 2005

In a double‐blind crossover study in which patients received placebo or active drug for varying periods, we evaluated the ability of guanidine hydrochloride (20 to 35 mg/kg per day perorally) to improve the rate of recovery in patients with moderate or severe botulism, type A, intoxication. Among 14 patients who received conventional botulism therapy, there was no improvement in recovery rate in those who received guanidine compared with the nontrated group. Individual patients in the treated group showed neither an acceleration in their rate of improvement when they received guanidine nor a regression in their progress when the drug was stopped. Individual patients, likewise, noted no subjective improvement when they received the drug compared with the placebo. Treatment with guanidine does not enhance recovery from botulism.
Ocular tilt reaction with peripheral vestibular lesion
Authors: Halmagyi G. Michael , Gresty Michael A. , Gibson William P. R.
Published: January 2005

Following inadvertent destruction of the left vestibular labyrinth during stapedectomy, a patient developed a transient abnormality of posture consisting of leftward ocular counterrolling, leftward head tilting, and a right‐over‐left skew deviation. This postural pattern, known as the “ocular tilt reaction,” is the normal compensatory response of the dependent utricle to tilting. In this patient, the unopposed action of the intact right utricle was presumably responsible for the appearance of a normal leftward ocular tilt reaction.
Cytoarchitectonic abnormalities in developmental dyslexia: A case study
Authors: Galaburda Albert M. , Kemper Thomas L.
Published: January 2005

A patient is reported who had a well‐documented history of developmental dyslexia. Reading difficulties were present in other male members of the immediate family. Gross anatomical and cytoarchitectonic analysis of the brain in serial sections showed a consistently wider left cerebral hemisphere, an area of polymicrogyria in the left temporal speech region, and mild cortical dysplasias in limbic, primary, and association cortices of the left hemisphere.
γ‐Hydroxybutyric acid is not a GABA‐mimetic agent in the spinal cord
Authors: Osorio Ivan , Davidoff Robert A.
Published: January 2005

γ‐Hydroxybutyric acid (GHB), a pharmacologically active central nervous system constituent, has been postulated to function as a γ‐aminobtyric acid (GABA) agonist. This hypothesis was tested directly on GABAergic synapses in isolated, superfused frog spinal cord.

Addition of GHB to the superfustate produced effects on primary afferent terminals that were distinctly different from the effects of GABA. Thus, although both compounds depressed dorsal root potentials, GHB hyperpolarized terminals while GABA depolarized the same structures. The GABA responses were antagonized by bicuculline and picrotoxin, but these alkaloids did not change GHB's actions. In addtion, GHB altered neither high‐affinity uptake by cord slices, nor potassium‐evoked release of tritiated GABA from them. GHB did not directly release GABA from spinal slices preloaded with [3H]GABA.

These observations suggest that the central nervous system actions of GHB are not dependent upon its ability to activate GABAergic synapses or to modify GABAergic mechanisms.
Activation of cortical circuits during interictal spikes
Authors: Collins Robert C. , Caston Torris V.
Published: January 2005

Penicillin, bicuculline, and strychnine were used as topical convulsants in unanesthetized rats to study aspects of interictal spiking. Bicuculline (0.1 mM) was more potent than penicillin (3.0 mM) or strychnine (1.5 mM) in initiating simple discharges, and at only slightly higher doses caused complex spikes and afterdischarges with motor convulsions. Penicillin caused similar types of discharges at much higher concentrations (> 50 mM), but strychnine failed to produce either complex spikes or afterdischarges. Penicillin and bicuculline were similar in causing an increase in utilization of carbon 14‐deoxyglucose in cortical layers I to III and V. Strychnine increased metabolism in layer V, with individual columns running from this base to the surface. Areas of decreased metabolism highlighted the strychnine focus and are probably related to a “pericolumnar inhibition” mediated by γ‐aminobutyric acid. Such inhibition would be blocked in the penicillin and bicuculline focus‐an effect which might be responsible for the genesis of complex spikes and afterdischarges and a more uniform activation of cortical metabolism.
Hereditary myoclonus and progressive distal muscular atrophy
Authors: Jankovic Joseph , Rivera Victor M.
Published: January 2005

Myoclonus occurs in a variety of pathological conditions, some inherited. We recently evaluated 3 members of a Louisiana‐Texas family with an autosomal dominant disorder manifested by adult‐onset, generalized, stimulus‐sensitive myoclonus and slowly progressive distal muscle weakness and wasting. The analyses of cerebrospinal fluid homovanillic acid and 5‐hydroxyindoleacetic acid before and after probenecid provided some evidence of impaired turnover of central dopamine and serotonin. Treatment with clonazepam resulted in complete and lasting improvement of the myoclonus. A postmortem examination in 1 member of the family revealed chiefly neuronal degeneration of the anterior horn cells, Clarke's nucleus, and the lower cranial nerve nuclei. A similar syndrome has not previously been reported.
Treatment of chronic relapsing inflammatory polyradiculoneuropathy by plasma exchange
Authors: Server Alfred C. , Lefkowith James , Braine Hayden , McKhann Guy M.
Published: January 2005

A 58‐year‐old man developed recurrent episodes of symmetrical motor weakness associated with acroparesthesias and areflexia. The cerebrospinal fluid protein was elevated and nerve conduction velocities were slowed. There was no evidence of systemic disease or toxic exposure, and a diagnosis of chronic relapsing inflammatory polyradiculoneuropathy was made. The patient improved during treatment with corticosteroids, but steroid‐induced complications necessitated discontinuance. A recrudescence of symptoms prompted a search for alternative therapy, and plasma exchange was tried. A marked improvement in strength was noted following each course of plasma exchange, suggesting that further similar trials are justified.
Multiple endocrine neoplasia, type 2b: Phenotype recognition; neurological features and their pathological basis
Authors: James Dyck Peter , Carney J. A. , Sizemore G. W. , Okazaki H. , Brimijoin W. S. , Lambert E. H.
Published: January 2005

Sixteen patients affected with multiple endocrine neoplasia, type 2b (MEN 2b), were evaluated by clinical, neurological, nerve conduction and electromyographic, and postmortem examinations. Eight of the 11 patients examined clinically had symptoms: 5, neurogenic constipation; 1, failing vision due to hypertrophied corneal nerves; 1, neuromuscular symptoms and pes cavus; and 1, facial disfigurement. Expression of the dominantly inherited MEN 2b gene is more variable than previously known. When neuromuscular findings are present alone, the features may be those of peroneal muscular atrophy. Because 10 of the 11 patients had sufficiently full expression of the dominantly inherited gene—“Marfanlike” body build, full and fleshy lips, whitish yellow nodules (neuromas) on the tip and edges of the tongue, pes cavus, or peroneal muscular atrophy the presence of MEN 2b was recognized and a search for the usually associated medullary thyroid carcinoma was instigated. In addition to the recognized involvement of autonomic nerves, we have confirmed that somatic motor and sensory neurons may be involved. Findings at postmortem evaluation indicate that symptoms can be attributed to neuroma formation: a characteristic adventitious plaque of tissue composed of hyperplastic, interlacing bands of Schwann cells and myelinated fibers overlay the posterior column of the spinal cord.
Deficiency of arylsulfatase B in 2 brothers aged 40 and 38 years. (Maroteaux‐Lamy syndrome, type B)
Authors: Pilz H. , von Figura K. , Goebel H. H.
Published: January 2005

Two brothers, aged 40 and 38 years, suffered from dysplastic features, coarse facies, bone and skeletal abnormalities, deformities of spine, and joint impairments. Body heights were 168 and 164 cm, respectively. Enlargement of liver and spleen, cardiac insufficiency, marked corneal clouding, and hernias were absent. Both patients had signs of cervical and lumbar radiculopathy and cervical myelopathy (tetraspastic syndrome).

Vacuoles, acid phosphatase‐positive granules, and metachromatic inclusions were found in peripheral lymphocytes; granulocytes and monocytes contained azurophilic hypergranulation. By electron microscopy, clear membrane‐bound vacuoles were noted in lymphocytes (but not in neutrophils), fibroblasts, Schwann cells, mural cells of the vasculature, and epidermal cells.

Leukocytes, urine, and cultured skin fibroblasts revealed a deficiency of arylsulfatase B (N‐acetylgalactosamine 4‐sulfate sulfatase). The 6‐year‐old daughter of one of the patients has an intermediate level of this enzyme. Fibroblasts exhibited a constant intracellular accumulation of 35S‐labeled mucopolysaccharides. The urine of one of the brothers showed an abnormal mucopolysacchariduria; in both, the presence of urinary dermatan sulfate could be demonstrated. These findings conform to the mild B variant of Maroteaux‐Lamy syndrome with high longevity.
Extraocular muscle biopsy in chronic progressive external ophthalmoplegia
Authors: Ringel Steven P. , Bruce W. Wilson , Barden Michael T.
Published: January 2005

A quantitative assessment of the pathological changes in extraocular muscle is presented in 8 patients with chronic progressive external ophthalmoplegia (CPEO). Serial cross‐sections of extraocular muscle were stained with a battery of histochemical and immunohistochemical techniques and compared with 36 normal extraocular muscles and 1 muscle from a patient who had longstanding third nerve palsy with anomalous reinnervation.

Several of the patient had a striking increase in the number of ragged‐red fibers in extraocular muscle, particularly if frequent ragged‐red fibers also were found on limb muscle biopsy. One patient demonstrated extrajunctional acetylcholine receptor (AChR) in a small percentage of fibers, although this finding was not present in the reinnervated muscle. Numerous darkly staining central regions were noted in the ocular muscle fibers of a patient with Stephens syndrome (CPEO, peripheral neuropathy, and cerebellar disease) and in the reinnervated muscle. A patient with myotubular myopathy had single central nuclei in both limb and ocular muscle. All patients demonstrated in their extraocular muscles variation in both the size and distribution of each of the three histochemical fiber types.

Extraocular muscule biopsy proved to be a safe, reliable technique. As a similar quantitative analysis is applied to the study of further patients, a better understanding of the pathogenesis of CPEO should be possible.
Creutzfeldt‐Jakob disease in France: II. Clinical characteristics of 124 consecutive verified cases during the decade 1968–1977
Authors: Brown Paul , Cathala Françoise , Sadowsky Doris , Gajdusek D. C.
Published: January 2005

One hundred twenty‐four consecutive cases of Creutzfeldt‐Jakob disease (CJD) in France, verified by biopsy or autopsy between 1968 and 1977, were analyzed with respect to their clinical characteristics. The series comprised equal numbers of men and women, with the most frequent age at onset being 60 to 64 years and the most frequent duration, two to three months. A prodromal illness was observed in more than one‐third of the patients. Clinical presentations and symptom frequencies are tabulated, and a multifactor analysis has been performed to obtain those combinations of symptoms and signs which occurred at least as often as the triad of dementia, myoclonus, and a positive electroencephalogram. Two groups of atypical cases are also emphasized: one with sudden, strokelike presentation and rapidly evolving illness of less than 2 moths' duration, and the other with a long clinical course of between 2 and 10 years.
Creutzfeldt‐Jakob disease in France: III. Epidemiological study of 170 Patients dying during the decade 1968–1977
Authors: Brown Paul , Cathala Francoise , Gajdusek D. C.
Published: January 2005

Systematic search for Creutzfeldt‐Jakob disease (CJD) in France yielded a total of 170 patients dying between 1968 and 1977. The overall annual mortality rate from CJD for France was 0.32 case per million persons, with by far the highest rate (1.33 cases per million) in the most densely populated parts of Paris. A highly significant correlation between population density and the mortality rate of CJD in the Paris urban agglomeration was consistent with the hypothesis of human‐to‐human disease transmissison, although in the rest of France CJD occurred at equally low rates among rural and urban populations. Temporospatial case clustering was not observed, nor could occupation, surgery, or potential exposure to scrapie be associated with an increased risk of contracting CJD. Six to 9% of cases were familial, analysis of which discouraged the notion of a familial “common exposure” in favor of genetic transmission of susceptibility to the virus or of the virus itself. A prospective epidemiological study of newly occurring cases of CJD, especially familial and geographically isolated cases, is being undertaken in the hope of identifying the means by which CJD is naturally acquired.
Clinical correlations of CT scan‐detected calcifications of the basal ganglia
Authors: Murphy Martin J.
Published: January 2005

A review of CT scans of 7,081 patients demonstrated calcifications of the basal ganglia in 53. The calcifications were evident in the skull roentgenograms of only 4 patients out of 40 in whom both CT scans and plain roentgenograms were available, demonstrating the superior resolution of this new method. Seventy‐five percent of the patients were older than 50 years of age. Of the younger patients, 5 had had prior cranial irradiation; 1 had received cranial irradiation and intrathecal methotrexate therapy for meningeal leukemia; and 2 others had deep‐seated arteriovenous malformations. Serum concentrations of calcium and phosphorus were normal in all 46 patients in whom they were measured.

We conclude that the detection of small calcifications of the basal ganglia in persons above 50 years of age is infrequently associated with either clinical signs of basal ganglia dysfunction or calcium and phosphorus abnormalities. Calcium deposition in these patients may be related to vascular changes associated with aging. In younger patients a specific pathogenetic factor or underlying process is frequently found.
Failure of electroencephalography to diagnose brain death in comatose children
Authors: Ashwal Stephen , Schneider Sanford
Published: January 2005

Two isoelectric electroencephalograms obtained 24 hours apart support a clinical diagnosis of brain death in prolonged coma. Without documentation of electrocerebral silence, physicians are reluctant to discontinue vital support systems. A radionuclide bolus technique has been developed that documents the absence of cerebral blood flow in suspected brain death and supplements the flat EEG.

In a recent review of this technique, all 27 adults who had EEG activity maintained the integrity of their cerebral blood flow. This contrasts to our studies of 5 children, all of whom demonstrated persistent EEG activity but had no evidence of cerebral blood flow by either the isotope bolus technique (5 patients) or cerebral angiography (4 patients). These children (mean age, 7 months) lacked cephalic reflexes and were maintained on assisted ventilation for an average of 15 days. Multiple electroencephalographic tracings persistently demonstrated low‐voltage cortical activity over this time. Despite the lack of cerebral blood flow, all patients were continued on respiratory support. At autopsy, extensive brain liquefaction necrosis was noted. In comatose children, EEG monitoring may be of limited value while cerebral blood flow measurements can provide more practical and prognostic information.
Central nervous system maturation in the stressed premature
Authors: Holmes Gregory L. , Logan William J. , Kirkpatrick Barry V. , Meyer Edwin C.
Published: January 2005

The developmental sequence of sleep cycles has been found to be a useful index of central nervous system maturation in premature infants. To determine the effects of severe reversible stress on the maturation of sleep cycles, 6‐ to 8‐hour sleep studies were done on 10 premature infants with severe hyaline membrane disease (HMD) and 10 healthy premature babies. The studies were done in the neonatal intensive care unit and included patients from 30 weeks' gestation to term and in all stages of the disease.

Prior studies were confirmed showing that percentage of quiet sleep increases, transitional sleep changes little, and active sleep decrease from 30 weeks' gestation to term. In infants with severe HMD, the percentage of quiet sleep was less and active sleep higher than in unstressed infants of similar age who acted as controls. Once the infants revovered from HMD, sleep patterns became similar to those found in the control group. These data suggest that when respiratory distress occurs in the premature infant, there is a transient delay in central nervous system maturation as measured by sleep cycle analysis.
Cerebellar control of ocular gaze stability
Authors: Zee David S. , Leigh R. John , Mathieu‐Millaire Francine
Published: January 2005

The ability to hold an eccentric position of gaze has been attributed to a brainstem network termed the ocular motor neural integrator. For this integrator to function properly, an intact cerebellum is necessary. This report describes a patient with cerebellar dysfunction who showed an unusual form of nystagmus: each slow phase had a waveform of increasing velocity. This contrasts with gaze paretic nystagmus, the more typical manifestation of cerebellar disorder, in which each slow phase has a waveform of decreasing velocity. Based on these observations and results from basic research, we propose that (1) the cerebellum controls neural integration in the brainstem by a positive feedback loop, and (2) pathological alterations in the strength of transmission (or gain) through the feedback loop cause the eyes to drift off target, with either an exponentially increasing (gain too high) or decreasing (gain too low) velocity.
Immunocytochemical method to identify myelin basic protein in oligodendroglia and myelin sheaths of the human nervous system
Authors: Itoyama Yasuto , Sternberger Nancy H. , Kies Marian W. , Cohen Steven R. , Richardson Edward P. , Webster Henry DeF.
Published: January 2005

To study the distribution of basic protein (BP) and other myelin constituents immunocytochemically in human nervous tissue, we modified the unlabeled antibody enzyme (peroxidase‐antiperosidase) method. The technique is described here. Because the availability of unfixed tissue from human central nervous system is limited, we tested the method on blocks that had been fixed in formalin and embedded in paraffin, fixed and stored in 4% formalin, or frozen at autopsy and stored. We obtained the best results with paraffin blocks. BP antiserum scained oligodendroglia and myelin sheaths in the developing human nervous system. In the adult, myelin sheaths were well stained. Also, abnormalities associated with myelin breakdown could be identified in multiple sclerosis lesions. The results suggest that this method will be useful in studying the cellular distribution of myelin components in human demyelinating diseases.
Immunocytochemical observations on the distribution of myelin‐associated glycoprotein and myelin basic protein in multiple sclerosis lesions
Authors: Itoyama Yasuto , Sterhberger Nancy H. , Webster Henry DeF. , Quarles Richard H. , Cohen Steven R. , Richardson Edward P.
Published: January 2005

To study the distribution of myelin‐associated glycoprotein (MAG) in human nervous tissue and in multiple sclerosis (MS) lesions, we used paraffin sections and our modification of the peroxidase‐antiperoxidase technique. Sections of MS lesions also were treated with antiserum to basic protein (BP) and with histological stains for axons and myelin sheaths. In tissue from normal developing central nervous system, oligodendroglia, their processes, and newly formed myelin sheaths were intensely stained by MAG antiserum. In adults, MAG was found in periaxonal regions of myelinated fibers of the central and peripheral nervous system. The most striking finding in MS lesions was the extension of decreased MAG immunostaining into white matter that appeared normal when treated with BP antiserum or luxol fast blue. In acute early MS lesions the decrease in MAG immunostaining extended far beyond the margin of acute demyelination, where the BP staining of degenerating sheaths often was increased. In chronic inactive plaques, this decrease in periaxonal MAG immunostaining was limited to relatively few fibers in a thin rim around each lesion. These observations suggest that in MS, immunoreactivity of periaxonal MAG is altered before myelin breakdown begins. Early in degeneration, myelin sheaths and their fragments often were more intensely stained by BP antiserum than normal sheaths; later the staining intensity decreased. In shadow plaques, BP antiserum stained some oligodendroglia. Their appearance and location among thinly myelinated axons suggested that these oligondendroglia were forming new sheaths around previously demyelinated axons.
Effects of manipulation of the sensorimotor system on focal motor seizures in the monkey
Authors: Hosokawa Shinichi , Iguchi Takahiko , Caveness William F. , Kato Motohiro , O'Neill Raymond R. , Wakisaka Shinichiro , Malamut Barbara L.
Published: January 2005

During focal motor seizures induced by injecting penicillin into the face‐hand area of the right motor cortex of 24‐month‐old monkeys, the sensorimotor system was manipulated by three methods. Elimination, by a paralytic agent, of proprioceptive input from contracting muscles and joints did not alter the electrographic expression of the seizure or the pattern of local glucose utilization in cortical or subcortical components of the sensorimotor system. An overall increase in the rate of energy metabolism occurred in the paralyzed monkeys with electrographic seizures. Cryogenic destruction of up to 90% of the ipsilateral ventral caudal globus pallidus had no effect on electrographic or clinical expression of the seizure. Electrical stimulation of the ipsilateral ventral caudal globus pallidus caused reproducible maximum expression of electrographic and clinical seizure phenomena for the 90‐second duration of the stimulus.
Neurotonia: Impulse‐induced repetitive discharges in motor nerves in peripheral neuropathy
Authors: Warmolts John R. , Mendell Jerry R.
Published: January 2005

Delayed relaxation of muscle following voluntary contraction was an unusual feature of a mild chronic sensorimotor peripheral neuropathy in an adult. This abnormality resulted from rapid repetitive discharges in motor nerves occurring only in response to passing impulses; there was no spontaneous nerve discharge. Voluntary contraction of affected muscles generated involuntary high‐frequency discharges of motor unit potentials, which persisted briefly after attempted relaxation. Nerve blocks localized independent zones of hyperexcitability in distal and proximal sections of nerve from which such repetitive discharges could be triggered. Intravenous administration of phenytoin diminished the discharge. Examination of intramuscular nerve bundles revealed loss of myelinated nerve fibers with numerous sprouting and remyelinating axons. These findings, along with muscle biopsy changes of neurogenic atrophy and type grouping, strongly favor an axonal neuropathy. An explanation for the repetitive nerve discharge is slow waning of heightened excitability of a motor nerve after passage of an impulse.
Transient global amnesia
Authors: Shuping J. Ross , Rollinson Russell D. , Toole James F.
Published: January 2005

Transient global amnesia (TGA) was found in 41 of 76 patients admitted to the North Carolina Baptist Hospital with temporary disturbances of memory. Risk factors for stroke were present in 26(63%) of these 41 patients, and additional risk factors developed in 9 (27%) of the 33 patients available for follow‐up. Follow‐up evaluation in 33 patients (80%) for periods ranging from 1 to 17 years (mean, 60.3 months) revealed a low rate of recurrence (18%) and a still lower rate of progression to stroke (6%). No transient ischemic attacks were reported during this period. In 2 patients, multiple recurrences of TGA ceased after treatment of the underlying condition (polycythemia in 1 case and myxomatous degeneration of the mitral valve in the other).
Glutamate dehydrogenase deficiency in three patients with spinocerebellar syndrome
Authors: Plaitakis Andreas , Nicklas William J. , Desnick Robert J.
Published: January 2005

Four nicotinamide‐adenine dinucleotide phosphate‐requiring enzymes were measured in disrupted cultured skin fibroblasts from a 19‐year‐old patient with juvenile onset of a spinocerebellar and extrapyramidal syndrome. There was marked reduction in the activity of glutamate dehydrogenase (GDH) (22% of mean control activity); GDH activity was also decreased in homogenates of leukocytes from this patient (38% of mean control activity). GDH activity was measured in the leukocytes of two siblings afflicted with adult‐onset spinocerebellar syndrome and found to be decreased in both (29% and 31% of mean control activity); an unaffected sibling had normal GDH activity. Mixing experiments with control fibroblast and leukocyte homogenates did not show the presence of a GDH inhibitor in cells from these patients. This allosterically regulated enzyme was stimulated by adenosine 5′‐diphosphate (10−3 M) and inhibited by guanosine 5′‐triphosphate (10−3 M) in both fibroblast and leukocyte homogenates; these changes occurred in equal proportions in the patients and controls. The decreased fibroblast and leukocyte GDH activity persisted at different concentrations of the enzyme's substrates and with successive passages of cultured fibroblasts. GDH may have an important role in the metabolism of glutamate, a putative neurotransmitter in cerebellum, brainstem, and spinal cord. A genetic deficiency of GDH may underlie some forms of spinocerebellar ataxias.
Chronic leigh disease: A genetic and biochemical study
Authors: Plaitakis Andreas , Whetsell William O. , Cooper Jack R. , Yahr Melvin D.
Published: January 2005

The large family of a 21‐year‐old man who died of Leigh disease was investigated for evidence of neurological abnormalities and presence of the adenosine triphosphate‐thiamine diphosphate phosphoryltransferase inhibitor factor. Of 217 persons (seven generations) included in the pedigree, 68 were examined neurologically and biochemically. Fourteen (20%), 5 of whom had abnormal neurological findings, were found to excrete the inhibitor factor. Clinical manifestations varied from severe neurological affliction to subtle deficits. A chronic relapsing course was frequently encountered, with exacerbations occurring in association with apparent metabolic stress. Parental consanguinity was identified in the propositus as well as in other family members with neurological abnormalities. Males and females were affected, and no vertical transmission of the trait was found. These multigenerational data suggest that Leigh disease in adults is inherited in an autosomal recessive manner and has variable degrees of expression with a wide spectrum of neurological manifestations.