bluuebunny/crossref_metadata_2025 huggingface dataset:
Encephalitis and aseptic meningitis, Olmsted County, Minnesota, 1950–1981: I. Epidemiology
Authors: Beghi Ettore , Nicolosi Alfredo , Kurland Leonard T. , Mulder Donald W. , Hauser W. Allen , Shuster Lynne
Published: January 2005

All cases fulfilling stated criteria for encephalitis and aspectic meningitis in Olmsted County, Minnesota, for the period 1950 through 1981 were identified. This is, to our knowledge, the first such incidence and trend study in a delineated population, providing rates per 100,000 person‐years of 7.4 for encephalitis (189 cases) and 10.9 for aseptic menigitis (283 cases). These are about twelve and six times higher, respectively, than the rates reported by the Centers for Disease Control. The rates have been stable over successive 5‐ or 10‐year periods except for a recent increase in aseptic meningitis. Both conditions were more common in the summer months, in childhood, and among males. Viral identification using conventional laboratory tests has improved with time; in the period 1970 through 1981, virus type was specified in about one‐fourth of the cases. The most common agents identified were California and mumps viruses in encephalitis, and entero and mumps viruses in aseptic meningitis. Antecedent and/or concurrent infections were noted in 42 and 35% of encephalitis and aseptic meningitis cases, respectively. No case due to mumps, measles, or rubella viruses has occurred since 1972, reflecting the impact of immunizations. Recovery was reported at the end of the acute phase in 95% of patients with aseptic meningitis, and there were no deaths. Seventy‐eight percent of encephalitis patients recovered completely; the case fatality rate was 3.8%. Of the encephalitis cases, 2% were diagnosed initially postmortem.
Neurofilament breakdown products in degenerating rat and human peripheral nerves
Authors: Trojanowski J. Q. , Lee Virginia M.‐Y. , Schalaepfer W. W.
Published: January 2005

The fate of neurofilament (NF) proteins was examined in sections of nerves from rats that survived for 3 to 90 days following nerve transection, using anti‐NF monoclonal antibodies and immunohistochemical techniques. The same methods were also applied to twenty‐three human nerve biopsy specimens. Granular debris with NF immunoreactivity was observed in the rat nerves for up to 21 days after transection. Similar granular debris with NF protein immunoreactivity was observed in nerve biopsy speciments from patients with axonal degeneration. This change was most evident in specimens that demonstrated abundant ovoids in teased fiber preparations and in a patient with a recent traumatic nerve transection. Similar granular debris was not observed in normal rat or human nerves. We conclude that degenerating NF proteins have a distinctive granular appearance and that NF immunoreactivity can be demonstrated in NF breakdown products with immunohistochemical techniques for prolonged periods of time in rat and human nerves undergoing axonal degeneration. Immunohistochemical studies with anti‐NF monoclonal antibodies offer a novel approach to the evaluation of human nerve biopsy specimens.
Classic and generalized variants of Pick's disease: A clinicopathological, ultrastructural, and immunocytochemical comparative study
Authors: Munoz‐Garcia D. , Ludwin S. K.
Published: January 2005

Six sporadic cases of dementia with lobar atrophy and neuronal cytoplasmic inclusions (Pick's disease) could be separated into two groups on the basis of the involvement of subcortical structures, the distribution and the histochemical, immunochemical, and ultrastructural characteristics of the inclusions, and possibly the age at onset. The first group (classic) was characterized by predominantly cortical atrophy and the presence in the hippocampus and neocortex of argyrophilic cytoplasmic inclusion bodies that reacted with a monoclonal antibody against neurofilament proteins and antitubulin antisera. Ultrastructurally the bodies were composed of straight fibrils of variable diameter, averaging 15 nm, and long‐period constricted fibrils. The second group (generalized) showed subcortical as well as cortical atrophy. Cortical and subcortical cytoplasmic inclusions contained RNA and stained poorly with silver and antibodies against neurofilaments and microtubules. Ultrastructurally the straight fibrils composing the bodies were coated with granular material, presumed to be derived from ribosomes. The generalized cases occurred in younger patients than did the classic cases in this series.
The risk of intracerebral hemorrhage during oral anticoagulant treatment: A population study
Authors: Wintzen A. R. , de Jonge H. , Loeliger E. A. , Bots G. T. A. M.
Published: January 2005

In a retrospective study of 166 patients, all admitted to the University Hospital, Leiden, The Netherlands, between January 1, 1970 and December 31, 1979, we estimated the relative risk of intracerebral hemorrhage from oral anticoagulant therapy. The risk was more than ten times higher for patients over 50 years of age than for similarly aged untreated individuals in the general population. Within this age group the risk was influenced by neither age nor sex. Hypertension, present in 80% of the patients, was the most important predisposing condition; the risk of bleeding rose with increasing intensity of anticoagulation. There was no substantial difference in clinical condition at onset, rate of Progression, mortality, or degree of recovery between patients with anticoagulant‐associated hemorrhage and those with spontaneous intracranial hemorrhage.
Familial occurrence of amyotrophic lateral sclerosis, parkinsonism, and dementia
Authors: Schmitt Horst P. , Emser Wendelin , Heimes Christian
Published: January 2005

We report here on a 59‐year‐old man from southwest Germany who died after a 14‐year course of an illness characterized by progressive dementia, parkinsonism, and amyotrophic lateral sclerosis. Postmortem examination revealed Alzheimer's neurofibrillary tangles in the substantia nigra, innominata, locus ceruleus, parahippocampal gyrus, and less frequently in the hippocampus and the cerebral cortex. Investigation of the patient's pedigree back to the 17th century revealed nine additional family members who had exhibited signs of amyotrophic lateral sclerosis or parkinsonism‐dementia or both. The pedigree suggests that a recessive trait with genetic epistasis is responsible for the disorder.
Multiple sclerosis immune complexes: An analysis of component antigens and antibodies
Authors: Coyle P. K. , Procyk‐Dougherty Zora
Published: January 2005

Serum immune complexes were isolated from 21 patients with multiple sclerosis and 23 control subjects, who were normal or had other neurological diseases, and the probed for neurotropic viral and brain‐reactive components. Multiple sclerosis complexes contained antibody to herpes simplex (13 cases), measles (8 cases), cytomegalovirus (5 cases), and rubella virus (5 cases). In some complexes, herpes simplex or cytomegalovirus antigen was detected along with antibody. Myelin basic protein or antibody to myelin basic protein was found in the complexes of 7 patients with multiple sclerosis and 2 patients with other neurological diseases. Serum complexes containing antibody reactive with galactocerebroside and ganglioside were present in 12 patients with multiple sclerosis and 3 with other neurological diseases. Over 60% of the multiple sclerosis group had IgM and IgA serum complexes, including 5 patients with very high IgA complex levels. This study suggests that patients with multiple sclerosis have ongoing systemic virus production with resultant immune complex formation. In addition, they often have serum complexes that contain brain‐reactive components.
Muscle fiber degeneration and necrosis in muscular dystrophy and other muscle diseases: Cytochemical and immunocytochemical data
Authors: Cornelio F. , Dones I.
Published: January 2005

Serial consecutive frozen sections from 164 muscle biopsy specimens were studied cytochemically. We localized calcium and albumin as endogenous markers of extracellular fluid penetration and C3 and C9 complement components as markers of muscle fiber necrosis. In both Duchenne dystrophy and congenital muscular dystrophy, a significant percentage of fibers were overloaded with calcium and penetrated by albumin. Most of these fibers appeared opaque with trichrome stain. C3 and C9 complement appeared only in necrotic fibers, which invariably were also penetrated by albumin. These observations support previous findings that muscle fiber necrosis is linked to massive inflow of extracellular fluid and complement activation. In addition, in both Duchenne and congenital dystrophies, numerous nonnecrotic fibers are penetrated by calcium‐rich extracellular fluid.
Human brain glucose utilization and cognitive function in relation to age
Authors: Duara R. , Grady PhD C. , Haxby PhD J. , Ingvar D. , Sokoloff L. , Margolin R. A. , Manning PhD R. G. , Cutler N. R. , Rapoport S. I.
Published: January 2005

Brain oxidative metabolism was examined with positron emission tomography and {18F}2‐deoxy‐D‐glucose in 40 healthy men aged 21 to 83 years, under conditions of reduced visual and auditory stimulation. The mean cerebral metabolic rate for glucose (CMRglc) equaled 4.6 to 4.7 mg. 100 gm−1· min−1 and did not correlate significantly with age (p > 0.05). Regional cerebral metabolic rates for glucose (rCMRglc) and Q ratios (rCMRglc/CMRglc), which had lower coefficients of variation than did rCMRglc, also did not correlate with age. Hyperfrontality of cerebral metabolism was absent at all ages. Age decrements were demonstrated in the error score on the Benton Revised Visual Retention Test and in the Performance Subtest scaled score of the Wechsler Adult Intelligence Scale (WAIS) but not in the Verbal Subtest scaled score of the WAIS. The cognitive test scores did not correlate with brain metabolic rates. The results indicate that brain oxidative metabolism, when measured under resting conditions with reduced sensory input, is not reduced in relation to age in healthy men. Furthermore, no significant relations between intelligence and resting cerebral metabolism are evident.
Antispasticity drugs: Mechanisms of action
Authors: Davidoff Robert A.
Published: January 2005

Several different drugs are now used, or are potentially useful, to treat patients with spasticity. Although these compounds vary in their actions on spinal neurons and reflex arcs, it is possible to formulate reasonable hypotheses regarding their modes of action. The benzodiazepines bind to specific benzodiazepine receptors linked to classic γ‐aminobutyric acid (GABA) receptors located on the terminals of primary afferent fibers. This binding results in an increased affinity of the GABA receptor for the amino acid, an augmented flux of chloride ions across the terminal membrane, and an increase in the amount of presynaptic inhibition. Baclofen activates GABAB receptors putatively located on the same terminals. Activation of these receptors retards the influx of calcium ions into the terminals, thereby reducing the evoked release of excitatory amino acids and possibly other transmitters. Progabide and its metabolites act on both classic and GABAB receptors. Glycine works on specific inhibitory receptors located on spinal interneurons and motoneurons. The phenothiazines act on the brainstem to alter the function of fusimotor fibers. Phenytoin and carbamazepine reduce the afferent output of muscle spindles. Dantrolene diminishes the activation of the contractile process in muscle fibers by reducing the release of calcium ions from the sarcoplasmic reticulum. This review summarizes the data supporting these concepts.
Abnormal breathing patterns during sleep in diabetes
Authors: Mondini Susanna , Guilleminault Christian
Published: January 2005

Nineteen diabetic patients, 12 type I (insulin‐dependent) and 7 type II (late‐onset, non‐insulin‐dependent), underwent nocturnal polygraphic monitoring after a daytime medical evaluation that included tests of vagal responses and, in 6 patients, pulmonary function and hypercapnic and hypercapnic and hypoxic responses. Five lean type I patients had abnormal sleep‐related breathing patterns with central or obstructive sleep apnea and brief breathing irregularities during states 3 to 4 non‐rapid‐eye‐movement sleep, compared with only 1 overweight type II diabetic with moderate obstructive sleep apnea. There was no correlation between daytime ventilatory study findings and abnormal breathing patterns during sleep, but there was a clear relationship between neuropathy and sleep‐related breathing abnormalities in type I insulin‐dependent diabetics.
Amnesia in monkeys after lesions of the mediodorsal nucleus of the thalamus
Authors: Zola‐Morgan Stuart , Squire Larry R.
Published: January 2005

Recent successes in developing an animal model of human amnesia in the monkey have made it feasible to try to identify with certainty the specific structures in the diencephalon and medial temporal region that cause amnesia when damaged. Monkeys with small lesion restricted largely to the posterior portion of the mediodorsal nucleus of the thalamus were given a test of memory sensitive to human amnesia and a second test that is analogous to the skill‐based tasks performed normally by manesic patients. The monkeys exhibited a marked impairment on the first test and performed normally on the second. The results show that circumscribed lesions of the mediodorsal nucleus can cause substantial amnesia.
Information processing speed in Friedreich's ataxia
Authors: Hart Robert P. , Kwentus Joseph A. , Leshner Robert T. , Frazier Robert
Published: January 2005

Three patients with Friedreich's ataxia and six controls matched by age and vocabulary and information scores on the Wechsler Adult Intelligence Scale‐Revised were administered a measure of short‐term memory scanning. Patients with Friedreich's ataxia demonstrated a deficit in information processing speed in the relative absence of impairment in attention, memory, language, judgement, reasoning, and other cognitive functions. The short term memory scanning procedure may be useful in documenting cognitive slowing and in distinguishing this impairment from the motor abnormality often associated with a subcortical brain disorder.
Cardiovascular regulation and lesions of the central nervous system
Authors: Talman William T.
Published: January 2005

The central nervous system has an important role in the second‐to‐second regulation of cardiac activity and vasomotor tone. Central lesions that lead to a disturbance in autonomic activity tend to cause electrocardiographic and pathological evidence of myocardial damage, cardiac arrhythmias, and disturbances of arterial blood pressure regulation. To a great extent such cardiovascular disturbances result from alterations in sympathetic activity. Similar alterations in sympathetic activity can occur under conditions of emotional stress and precipitate cardiac arrhythmias that can themselves lead to the syndrome of sudden death. Experimental and clinical evidence suggests that central neural mechanisms may be involved in this important human syndrome, but no central lesion has yet been identified to account for it. Recent experimental evidence, derived from hypertension research, suggests that chemical disturbances in the central nervous system, without accompanying structural lesions, may be found to explain cardiovascular disturbances such as sudden death and hypertension.
Reversible diabetic nerve dysfunction: Structural correlates to electrophysiological abnormalities
Authors: Sima Anders A. F. , Brismar Tom
Published: January 2005

Structural alterations of the nodal and paranodal areas were examined in the posterior tibial nerve in insulin‐depleted and insulin‐treated diabetic BB rats. The early metabolic phase of the distal symmetrical polyneuropathy was characterized by paranodal axonal swellings and nodal bulgings of the axon. These alterations correlate with intraaxonal sodium accumulation and decreased sodium equilibrium potentials which account for the early nerve conduction defect. Both the structural and electrophysiological abnormalities were completely normalized after vigorous insulin therapy. In the chronic diabetic polyneuropathy the paranodal area showed loss of paranodal axoglial junctions and paranodal myelin retraction. These changes may be partially responsible for the impaired electrical activity at the node as exemplified by irreversibly impaired sodium permeability and nerve conduction.
Pharmacokinetics of trihexyphenidyl after short‐term and long‐term administration to dystonic patients
Authors: Burke Robert E. , Fahn Stanley
Published: January 2005

Although trihexyphenidyl has been used effectively for many years in the treatment of Parkinson's disease, little is known about its pharmacokinetics. Using a sensitive radioreceptor assay for anticholinergic drugs, we assayed trihexyphenidyl in human serum and studied its pharmacokinetics following short‐term and long‐term administration to patients with dystonia. Previously untreated patients had a biphasic semilogarithmic plot of serum concentration–time consisting of an initial rapid distribution phase and a later slower elimination phase. Patients on long‐term treatment showed only the slower elimination phase. Elimination followed first‐order kinetics and was rapid, with a half‐life of 3.7 ± 0.4 (SEM) hours. There was no relationship between half‐life and peak serum level, age, duration of therapy, or etiology or severity of dystonia. Although acute anticholinergic side effects paralleled the rise and fall of serum anticholinergic levels, the response of dystonia did not.
Volume depletion and natriuresis in patients with a ruptured intracranial aneurysm
Authors: Wijdicks E. F. M. , Vermeulen M. , ten Haaf J. A. , Hijidra A. , Bakker W. H. , van Gijn J.
Published: January 2005

We studied the sodium balance and changes in plasma volume by an isotope dilution technique in the first week after an aneurysmal subarachnoid hemorrhage in 21 patients. In 11 of the patients, the plasma volume decreased by more than 10%. This was accompanied by a negative sodium balance and hyponatremia in 6 patients, a negative sodium balance without hyponatremia in 4 patients, and a positive sodium balance in 1 patient. Together with a decrease in plasma volume, blood urea nitrogen content increased and body weight decreased. Three patients developed hyponatremia without a decrease in plasma volume. Serum vasopressin was measured in 14 of the 21 patients. The values were elevated on admission and declined in the first week, regardless of the presence of hyponatremia. These findings indicate that natriuresis and hyponatremia in aneurysmal subarachnoid hemorrhage reflect salt wasting and not inappropriate secretion of antidiuretic hormone and that these changes should be corrected by fluid replacement rather than by fluid restriction.
Treatment of central nervous system sarcoidosis with radiotherapy
Authors: Bejar Jose M. , Kerby Gerald R. , Ziegler Dewey K. , Festoff Barry W.
Published: January 2005

This report documents the twelve‐year follow‐up of a patient with neurosarcoidosis with multiple progressive central nervous system manifestations. Increased somnolence and seizure activity were associated with proliferation of nodular enhancing brain lesions, as seen on serial computed tomographic (CT) scans. Initially he responded to corticosteroid treatment, but gradually this response became unsatisfactory. After whole‐brain irradiation with a total dose of 3,000 rads, his clinical symptoms improved with disappearance of the enhancing brain lesions seen on CT scan.
Galactosialidosis: Low β‐galactosidase activity in serum after long‐term clotting
Authors: Sakuraba Hitoshi , Iimori Yuichi , Suzuki Yoshiyuki , Kint Jos A. , Akagi Masao
Published: January 2005

Serum β‐galactosidase activity was found to be markedly increased in clotting blood from normal subjects, but patients with galactosialidosis showed only a slight increase of this enzyme activity. Consequently, the β‐galactosidase activity was low in serum after long‐term clotting in patients with this disease. The mechanism of the enzyme activation is unknown. The use of anticoagulants completely inhibited the activation.
Brachial plexus neuropathy in the population of Rochester, Minnesota, 1970–1981
Authors: Beghi Ettore , Kurland Leonard T. , Mulder Donald W. , Nicolosi Alfredo
Published: January 2005

Brachial plexus neuropathy (BPN) is a clinical entity of unknown cause characterized by the acute or subacute onset of pain and weakness, with occasional atrophy of the arm muscles. Information on the incidence of the disease in a delineated population is lacking, as the data available on BPN have come essentially from case reports or selected series. Using the Mayo Clinic records–linkage system as the source of data, 579 clinical records were reviewed of Rochester, Minnesota, residents in which a diagnosis suggestive of BPN was reported for the period 1970 through 1981. Eleven cases fulfilled all criteria, providing an overall annual incidence rate of 1.64 cases per 100,000 population. An infectious disease and/or tetanus toxoid immunization preceded the onset of BPN in 4 cases. The upper brachial plexus was involved in 6 cases, the lower brachial plexus in 2, and the whole plexus in 3; in 1 case there was bilateral BPN. The neuropathy ran a mild to moderate course in 10 cases, and complete recovery was recorded in 6, with slight residua in the others. The occurrence of antecedent events and the features of the disease are supportive of the concept of an immune‐mediated process.
Complex partial seizures of frontal lobe origin
Authors: Williamson Peter D. , Spencer Dennis D. , Spencer Susan S. , Novelly Robert A. , Mattson Richard H.
Published: January 2005

Complex partial seizures of medial or orbital frontal origin were documented in 10 of 90 patients with intractable epilepsy who were studied with depth electrodes. The clinical features that, in part, served to distinguish these seizures from complex partial seizures originating elsewhere included brief, frequent attacks, complex motor automatisms with kicking and thrashing, sexual automatisms, vocalization, and frequent development of complex partial status epilepticus. The constellation of clinical characteristics was often bizarre, leading to the erroneous diagnosis of hysteria. Stereotyped attack patterns helped establish the diagnosis of epilepsy. Interictal and ictal scalp electroencephalograms were often not helpful and were sometimes misleading.
Autoimmune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic protein antigen
Authors: Jaeckle Kurt A. , Graus Francesc , Houghton Alan , Cardon‐Cardo Carlos , Nielsen Surl L , Posner Jerome B.
Published: January 2005

Sera from 6 of 12 patients with paraneoplastic cerebellar degeneration (PCD) contained anti–Purkinje cell antibodies, as determined by indirect immunofluorescence on frozen sections of normal human cerebellum. Samples of cerebrospinal fluid from 2 of the patients with serum antibodies were tested, and both specimens contained anti–Purkinje cell antibody. The anti‐Purkinje cell antibodies were polyclonal, fixed complement, and were present in all patients at serum dilutions of 1:1,000 or greater. Antibody activity could not be suppressed by preabsorption of sera with human or animal brain and tissue powders or with fresh crude human cerebellar extracts. No anti–Purkinje cell antibodies were detected in control sera from 167 neurologically normal cancer patients, 32 normal volunteers, 10 patients with other causes of cerebellar degeneration, or 8 patients with other paraneoplastic neurological diseases. Preliminary evidence suggests that the Purkinje antigen is a protein that is often concentrated in the periphery of the cytoplasm in disc‐shaped structures. Patients with antibodies often developed signs of PCD near the time of detection of the tumor and had relentless progression of neurological disease. Patients without antibodies frequently had cancer for months to years before PCD developed, and often had spontaneous stabilization of neurological disease with time. Four patients without and 3 patients with antibodies underwent plasmapheresis without response.
Recovery of herpesviruses from cerebrospinal fluid of immunodeficient homosexual men
Authors: Dix Richard D. , Bredesen Dale E. , Erlich Kim S. , Mills John
Published: January 2005

Over a one‐year period the cerebrospinal fluid (CSF) obtained from a series of homosexual men immunocompromised with either Hodgkin's disease or acquired immune deficiency syndrome (AIDS) was cultured to assess the frequency with which infectious viruses could be recovered. Of 58 patients examined, 4 (6.9%) had CSF cultures that showed a cytopathology consistent with a virus infection. All isolates proved to be herpesviruses. Cytomegalovirus (CMV) and varicella‐zoster virus were isolated from CSF obtained from 2 patients with neurological features consistent with a subacute encephalitis common among AIDS patients. CMV was also recovered from the CSF of an AIDS patient who developed an ascending myelitis of herpesvirus origin. Finally, a CSF sample obtained from an immunodeficient homosexual man who showed no detectable neurological abnormalities consistently yielded herpes simplex virus type 1 in culture. These results suggest that seeding of the CSF with infectious virus is an uncommon event in this patient population. However, our experience should not dissuade attempts to culture viruses from CSF in similar cases. Successful isolations may prove beneficial in the diagnosis of an accompanying neurological illness and facilitate treatment with antiviral therapy when indicated.
Reversible go–no go deficits in a case of frontal lobe tumor
Authors: Leimkuhler M. E. , Mesulam M.‐M.
Published: January 2005

A 50‐year‐old woman had been treated for a psychiatric disorder for three years. Findings during the elementary neurological examination were essentially normal. However, a computed tomographic scan revealed a large meningioma in the falx involving the medial aspects of the frontal lobes bilaterally. Neuropsychological examination demonstrated deficits in complex attentional tasks and also many errors of commission in the go–no go test. Following surgical excision of the tumor, her go–no go performance became normal. This patient shows that damage to the medial frontal lobe can cause deficits in go–no go performance, and that these deficits can be reversible following resolution of the lesion.
Polymorphonuclear neutral protease activity in multiple sclerosis and other diseases
Authors: Guarnieri Biancamaria , Lolli Francesco , Amaducci Luigi
Published: January 2005

Polymorphonuclear neutral protease activity (PMN‐NPA) was examined in 87 patients with definite multiple sclerosis (MS) (48 active, 39 inactive), 49 patients with other neurological diseases (OND), 24 patients with immune‐mediated non‐neurological diseases (INND), and 32 normal subjects. PMN‐NPA was found to be significantly increased in active MS compared with inactive MS and compared with each of the control groups. No differences were found between the group of normal subjects and the groups of patients with OND, INND, or inactive MS. Levels of PMN‐NPA were significantly higher in the OND group than in inactive MS group. The differences for INND versus normal controls, neurological controls, and patients with inactive MS were not significant. No significant differences have been detected between active and inactive INND. These results suggest that PMN‐NPA may be useful in the diagnosis and evaluation of MS.
Fragile X syndrome: Associated neurological abnormalities and developmental disabilities
Authors: Wisniewski K. E. , French J. H. , Fernando S. , Brown W. T. , Jenkins E. C. , Friedman E. , Hill A. L. , Miezejeski C. M.
Published: January 2005

The fragile X syndrome is a frequent cause of developmental disabilities. It is associated primarily with nonprogressive X‐linked mental retardation. The neurodevelopmental abnormalities of 25 males and 3 females are described. Mental retardation was mild in 4, moderate in 11, severe in 6, and profound in 2 patients, while 4 patients had only learning disabilities. The presence or absence of a developmental disability could not be determined in the youngest (8 months). Seven patients had had infantile autism and 7 had epilepsy. Generally no major focal neurological abnormalities were observed but most of the patients exhibited minor signs. The severity of developmental disabilities in our patients varied between and within families and between genders. All adult males had macroorchidism. Unusual facial features were present in 13 males but none were seen in the females. Familial occurrences were found in 18 cases (64%); 10 cases (36%) were sporadic. Overall, males were more severely affected than females. Diagnostic tests including computed tomographic scans, electroencephalograms, and evoked potentials did not disclose any specific abnormalities.
A clinicopathological study of 323 patients with oligodendrogliomas
Authors: Ludwig Carol L. , Smith Michael T. , Godfrey Alfred D. , Armbrustmacher V. W.
Published: January 2005

All patients with oligodendrogliomas (554) from the repository of the Armed Forces Institute of Pathology were retrospectively analyzed. The pathological diagnosis was confirmed in 323 patients and each case was graded according to a previously established grading system. The clinical features of these 323 verified cases of oligodendroglioma are presented, analyzed, and compared with findings in previous studies. There is a significant age skew according to tumor grade, with 68% of patients with grade A tumors under 40 years and 83% of patients with grade D tumors over 40 years of age. Headache was the most common symptom, followed by seizure, visual loss, papilledema, paralysis, and dementia. No symptoms showed a statistically significant correlation with tumor grade. However, tumor grading allowed significant prognostic statements to be made. Attention is drawn to several often neglected symptoms of oligodendrogliomas: ataxia, hemorrhage, stroke, and cerebrospinal fluid spread. This is, to our knowledge, the largest clinicopathological study of oligodendrogliomas to date.
Age differences in intercorrelations between regional cerebral metabolic rates for glucose
Authors: Horwitz Barry , Duara Ranjan , Rapoport Stanley I.
Published: January 2005

Patterns of cerebral metabolic intercorrelations were compared in the resting state in 15 healthy young men (ages 20 to 32 years) and 15 healthy elderly men (ages 64 to 83 years). Controlling for whole‐brain glucose metabolism, partial correlation coefficients were determined between pairs of regional cerebral metabolic rates for glucose determined by positron emission tomography using [18F]fluorodeoxyglucose and obtained in 59 brain regions. Compared with the young men, the elderly men had fewer statistically significant correlations, with the most notable reductions observed between the parietal lobe regions, and between the parietal and frontal lobe regions. These results suggest that cerebral functional interactions are reduced in healthy elderly men.
Spontaneous dissection of the cervical internal carotid artery
Authors: Mokri Bahram , Sundt Thoralf M. , Wayne O. Houser , Piepgras David G.
Published: January 2005

We studied 36 patients (21 women and 15 men) with spontaneous dissection of the internal carotid arteries. The ages of these patients ranged from 21 to 63 years. Focal unilateral headache was the most common symptom. Other common clinical manifestations (in decreasing order of frequency) included focal cerebral ischemic symptoms, oculosympathetic paresis, bruits, light‐headedness, and neck pain. Less common symptoms were syncope, amaurosis fugax, scalp tenderness, swelling in the neck, and dysgeusia. Common angiographic manifestations (in decreasing order of frequency) were elongated, irregular, and frequently tapered narrowing of the lumen; abrupt luminal reconstitution (often at the carotid canal); aneurysms; intimal flaps; slow internal carotid artery–middle cerebral artery flow; tapered occlusion; and distal branch occlusions. The incidence of hypertension in these patients was considerably higher than that in the general population. Angiographic evidence of fibromuscular dysplasia was found in 14% of the patients, but atherosclerotic changes were uncommon. Follow‐up ranged from 14 to 140 months (mean, 58.5 months). Twenty‐three patients with 29 dissected internal carotid arteries were also restudied angiographically. The stenosis of the internal carotid artery either completely resolved or substantially improved in more than 85% of the dissected vessels. About two‐thirds of the dissecting aneurysms either resolved or decreased in size. Clinically more than 85% of the patients had an excellent or complete recovery. Recurrence of the dissection or rupture of a dissecting aneurysm was not noted. Despite their disconcerting appearance on angiography, spontaneous dissections of the internal carotid arteries are often associated with a good prognosis.
Striatal dopamine depletion, dopamine receptor stimulation, and GABA metabolism: Implications for the therapy of Parkinson's disease
Authors: Bennett James P.
Published: January 2005

Dopamine‐denervated rat striata exhibit increased synaptosomal gamma‐aminobutyric acid (GABA) synthetic capacity (glutamate decarboxylase activity) without an alteration in GABA transport capacity. Stimulating denervated striatal dopamine receptors with apomorphine selectively increases in vivo steadystate striatal GABA turnover. The striatal response in animals to isolated loss of dopamine innervation is an increase in glutamate decarboxylase activity, not the decrease frequently found in the brains of patients with Parkinson's disease. Neurochemical expression of denervated striatal dopamine receptor stimulation may involve increased synaptic activity of striatal GABA neurons. For these reasons, enhancement of basal ganglia GABA function may improve responsiveness to dopamimetic therapies in patients with Parkinson's disease.
Distribution of the molecular forms of acetylcholinesterase in human brain: Alterations in dementia of the Alzheimer type
Authors: Fishman Eric B. , Siek Gordon C. , MacCallum Robert D. , Bird Edward D. , Volicer Ladislav , Marquis Judith K.
Published: January 2005

Acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, is a heterogeneous enzyme that can be separated into multiple molecular forms. A tetrameric membrane‐bound form (G4) and a monomeric soluble form (G1) are the two predominant enzyme species in mammalian brain. The distribution of AChE molecular forms was defined by sucrose density gradients of 11 anatomical regions of postmortem brains from 10 patients with dementia of the Alzheimer type (DAT) and 14 nondemented controls of similar ages. The results demonstrate an overall loss of protein and enzyme activity in all areas of the DAT brains studied and a selective loss of the G4 form of AChE in Brodmann areas 9, 10, 11, 21, 22, and 40, and the amygdala. There was no change in the G4/G1 ratio in areas 17 and 20, in the hippocampus, or in the cerebellum. There was a high regional correlation of the G4/G1 ratios with published values for choline acetyltransferase activity but lower correlation with total AChE activity. We propose that there is a predominant loss of the G4 form of AChE in DAT and that this loss is correlated with the degeneration of presynaptic elements.
Progressive multifocal leukoencephalopathy and magnetic resonance imaging
Authors: Levy Jody D. , Cottingham Karen L. , Campbell Robert J. , Moore Gregory K. , Gyorkey Ference , Ashizawa Tetsuo , Goldman Arnold M.
Published: January 2005

Progressive multifocal leukoencephalopathy developed in a homosexual man with underlying Hodgkin's disease. Computed tomography and magnetic resonance imaging of the brain demonstrated multiple lesions, more in gray than white matter. Brain biopsy established the diagnosis of progressive multifocal leukoencephalopathy. Magnetic resonance imaging was found useful for detecting brain lesions and for localizing an accessible lesion for biopsy.
Uptake of radiolabeled ions in normal and ischemia‐damaged brain
Authors: Dienel Gerald A. , Pulsinelli William A.
Published: January 2005

The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (63Ni, 99TcO4, 22Na, and [3H]tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of 65Zn, 59Fe, 32PO4, and 147Pm in postischemic brain were similar to or less than those in normal brain. The concentration of [14C]EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that 99TcO4, 22Na, 65Zn, and 59Fe were distributed more uniformly throughout the brain than were 32PO4, 63Ni, and 147Pm. At 24 or 48 hours after ischemia, 63Ni, 99TcO4, and 22Na were preferentially concentrated in the damaged striatum and hippocampus, whereas 65Zn, 59Fe, 32PO4, and 147Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO4, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography.
Successful treatment with tocainide of recessive generalized congenital myotonia
Authors: Streib Erich W.
Published: January 2005

A patient with recessive generalized congenital myotonia and severe, disabling weakness underwent various forms of treatment while being monitored electrophysiologically. Phenytoin, verapamil, and acetazolamide were ineffective, but tocainide yielded good results. Improvement was dose‐dependent, and was limited by irritability and action tremor when the patient was taking 1,600 mg per day.
Narcolepsy following cerebral hypoxic ischemia
Authors: Rivera Victor M. , Meyer John S. , Hata Takashi , Ishikawa Yoshiki , Imai Akira
Published: January 2005

A 51‐year‐old man with non‐HLA‐DR2 histocompatibility developed classic signs and symptoms of the narcoleptic tetrad soon after recovering from an episode of cardiopulmonary insufficiency, which occurred during induction of surgical anesthesia. Symptoms included excessive daytime sleepiness, hypnagogic hallucinations, sleep paralysis, and cataplexy. The diagnosis was confirmed by repeated polysomnographic examinations in the sleep laboratory. Cerebral hemodynamic changes during the onset of sleep showed remarkable increases of cerebral blood flow during the onset of rapid‐eye‐movement sleep similar to those reported previously in patients with narcolepsy. Magnetic resonance imaging showed focal regions of abnormal spin‐echo signals in the ventral pons.
Clinical correlation with anti‐peripheral‐nerve myelin antibodies in Guillain‐Barré syndrome
Authors: Koski Carol L. , Gratz Edward , Sutherland John , Mayer Richard F.
Published: January 2005

Anti‐peripheral‐nerve myelin antibodies (anti‐PNM Ab) can be detected in the serum of all patients with acute‐phase Guillain‐Barré syndrome (GBS) thus far tested. Correlation of the titer of this antibody with the clinical course would help to establish a role for the humoral immune system in the pathophysiology of GBS. In this study, anti‐PNM Ab levels were measured in serial serum samples of 7 patients with GBS with an assay that detects antibodies bound to peripheral nerve myelin antigens by fixation of the first component of complement. Although the titers of anti‐PNM Ab detected in these patients varied between 0 and 256 U/ml, the antibody titer was always highest on admission (35 to 256 U/ml) and rapidly declined during a one‐to‐three‐week period. Disappearance of antibodies or very low levels of them correlated with cessation of progression and considerable clinical improvement as documented by increased pulmonary vital capacity and muscular strength. Low but measurable antibody titers (5 to 12 U/ml) were frequently found up to four months following the acute neurological deficit. The close temporal relationship between anti‐PNM Ab titer and the clinical course in GBS suggests that antibody most likely participates through complement activation in peripheral nerve demyelination.
Adult‐onset autosomal dominant limb‐girdle muscular dystrophy
Authors: Chutkow Jerry G. , Heffner Reid R. , Kramer Andrew A. , Edwards John A.
Published: January 2005

We describe a kindred with a rare autosomal dominant myopathy limited to the limb‐girdle muscles, beginning insidiously any time from the late second through the sixth decades and followed by slow progression. Pelvifemoral precedes scapulohumeral weakness, and proximal appendicular involvement antedates limited distal paresis. Expressivity varies and includes an asymptomatic myopathy (preclinical or subclinical) and a nonmanifesting carrier state that extends well into the eighth decade. A variety of nonspecific changes are present in muscle on light, enzyme histochemical, and electron microscopic examination; of these changes, “rimmed” or autophagic vacuoles are the most characteristic. We identified one very similar previously reported genealogy. The similarities between the two unrelated families clearly establish this dystrophic process as a distinct genetic entity; their differences suggest genetic heterogeneity.
Immunoreactive myelin basic protein in cerebrospinal fluid of patients with peripheral neuropathies
Authors: Cornblath David R. , Griffin John W. , Tennekoon Gihan I.
Published: January 2005

The presence of myelin basic protein (MBP)–like material in cerebrospinal fluid (CSF) usually reflects breakdown of central nervous system myelin. Immunoreactive MBP levels were measured in 70 CSF specimens from 66 patients with a variety of peripheral neuropathies. Immunoreactive MBP was present in CSF in 70% (16 of 23) of patients with biopsy‐proved chronic demyelinating polyneuropathies, whereas in neuropathies producing primarily axonal damage it was present in only 22% (5 of 23). In Guillain‐Barré syndrome, 45% (9 of 20) of patients had immunoreactive MBP in the CSF. We conclude that MBP‐like material is present in the CSF of most patients with longstanding demyelinating polyradiculoneuropathies and probably reflects detection of peripheral nervous system P1 protein.
Perforant pathway changes and the memory impairment of Alzheimer's disease
Authors: Hyman B. T. , Van Hoesen G. W. , Kromer L. J. , Damasio A. R.
Published: January 2005

The perforant pathway is a large neuronal projection that arises from layers II and III of the entorhinal cortex of the parahippocampal gyrus. It is the principal source of cortical input to the hippocampal formation. In 11 cases of Alzheimer's disease, we have found that neurofibrillary tangles develop in the cells of origin of the perforant pathway. In addition, the termination zone of the perforant pathway, in the outer two thirds of the molecular layer of the dentate gyrus, contains a distinct layer of neuritic plaques. None of the 8 control subjects had such changes. These profound alterations effectively disconnect the hippocampal formation from the association and limbic cortices. Because of the central role of the hippocampus and parahippocampal gyrus in learning, it is likely that pathological changes in the perforant pathway, by precluding normal hippocampal operation, account for some aspects of the memory impairment in Alzheimer's disease.
Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjögren's syndrome
Authors: Malinow K. , Yannakakis G. D. , Glusman S. M. , Edlow D. W. , Griffin J. , Pestronk A. , Powell D. L. , Ramsey‐Goldman R. , Eidelman B. H. , Medsger T. A. , Alexander E. L.
Published: January 2005

Sensory neuropathies, particularly trigeminal neuropathy, have been recognized as neurological complications of Sjögren's syndrome, but the pathogenesis has not been established. We describe a woman with primary Sjögren's syndrome who developed a progressive debilitating subacute sensory neuronopathy. Results of electrophysiological studies were consistent with involvement of the trigeminal and dorsal root ganglia. A thoracic dorsal root ganglion biopsy showed lymphocytic infiltration and degeneration of ganglion cells. We believe that this is the first description of biopsy‐documented dorsal root ganglionitis in a subacute sensory neuronopathy associated with Sjögren's syndrome and that the finding suggests an immunopathogenic basis.
Primary central nervous system lymphoma in acquired immune deficiency syndrome: A clinical and pathological study
Authors: So Yuen T. , Beckstead Jay H. , Davis Richard L.
Published: January 2005

Twenty cases of primary lymphoma of the centratl nervous system associated with acquired immune deficiency syndrome were seen over a period of four years and were studied clinically and pathologically. Biopsy established the diagnosis in 11 cases, and autopsy confirmed it in 9. Multicentricity was demonstrated in all cases for which there was adequate autopsy material. Both large‐cell immunoblastic and small noncleaved lymphomas were seen, and marker studies in 5 patients established that the lymphomas were of B‐cell origin. Neurological symptoms and signs, cerebrospinal fluid characteristics, and radiographic appearance were reviewed. The clinical and radiographic picture is nonspecific and histological confirmation is essential for diagnosis. Although the tumor appears to be radiosensitive, prognosis is extremely poor, with an average survival of less than two months.
Effect of testosterone on muscle protein synthesis in myotonic dystrophy
Authors: Griggs Robert C. , Halliday David , Kingston William , Moxley Richard T.
Published: January 2005

Muscle wasting in myotonic dystrophy may result from decreased muscle anabolic processes rather than from increased catabolism. Male patients with myotonic dystrophy often have low levels of circulating androgens, and androgen administration has been shown to increase their muscle mass. We have studied the effect of testosterone enanthate administration (3 mg/kg weekly for 3 months) on muscle and whole body protein synthesis in 6 male patients with myotonic dystrophy. Muscle protein synthesis was estimated from the rate of isotope incorporation into muscle protein obtained by quadriceps muscle biopsy during a primed continuous infusion of L‐{1‐13C}leucine. Testosterone administration resulted in a significant increase in muscle protein synthesis in all patients. Whole body protein synthesis did not increase, indicating that protein synthesis in other tissues may have declined. Muscle ribonucleic acid content rose significantly in response to testosterone administration, suggesting that testosterone initiated its effect by hormone receptor interaction with muscle nuclei.