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Biomarkers of Alzheimer disease.

A definitive diagnosis of Alzheimer disease (AD) depends on finding widespread neurofibrillary tangles and plentiful neuritic plaques in the brain of an individual with a clinical diagnosis of progressive dementia. Using contemporary diagnostic criteria, the antemortem diagnosis of probable AD in centers specialized for AD is confirmed 80% to 90% of the time. There is the suspicion, but no firm data, that diagnostic accuracy is much lower outside of practices dedicated to patients with dementia. Furthermore, the diagnostic workup is expensive. In most settings, the evaluation generally includes a careful medical history and physical examination; neurologic examination (and psychiatric consultation as indicated); laboratory blood studies to exclude underlying metabolic and medical illnesses that masquerade as AD; a mental status assessment and formal cognitive tests; and a computed tomographic scan or magnetic resonance imaging of the brain. Because these procedures are time-consuming and costly, there is a need to identify biological tests that can circumvent aspects of this workup and point the physician to the correct diagnosis. It would be highly desirable to measure a substance or substances in blood or urine samples or cerebrospinal fluid (CSF) that would lead to a positive diagnosis of AD without the need for specialized dementia clinics and the expense and time of standard diagnostic evaluations. In response to this need, the Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging convened a working group in 1997 to examine the status of various antemortem markers for AD. The consensus statement of this group, entitled "Molecular and Biochemical Markers of AD," was published in 1998. The consensus statement first defined the characteristics of an ideal biomarker, and then outlined the steps required for a proposed biomarker to achieve acceptance by the medical community. Finally, the statement reviewed the current state of all proposed biological markers. The workshop participants observed that none of the current biomarkers had yet achieved universal acceptance and concluded none fully met the consensus criteria for an ideal marker. Nonetheless, several tests were identified as good markers for familial AD, and several other tests showed promise as a diagnostic aid for sporadic AD. The purpose of this review is to put these recommendations into a practical context. What does the consensus statement tell the practicing clinician? How do the opinions in the consensus statement affect clinical practice in diagnosing and treating patients with dementia?

Alzheimer Disease↗

Investigating the causes of vertigo in breast cancer survivors.

The vertigo symptom in breast cancer survivors has rarely been mentioned. The aim of this study was to investigate the causes of vertigo in breast cancer survivors with vertigo. From May 1997 to April 2003, 36 consecutive female breast cancer survivors with vertigo underwent a battery of tests including physical examination, neurological examination, serum lipid profile, plain chest radiograph, whole body bone scan, liver sonography, audiometry, electronystagmography (ENG) and MRI scan. Based on these tests, the causes of vertigo were attributed to peripheral labyrinthine origin in 14 patients (39%) and central origin in 22 patients (61%) consisting of 11 cases of vascular insufficiency, eight of hyperlipidemia and three of posterior fossa metastases (8%). The latter included one case of cerebellopontine angle and two of cerebellum, accompanied by extracranial systemic metastases, e.g., of the lung, bone or liver. In conclusion, vertigo in breast cancer survivors warrants concern, especially in those with extra-cranial systemic metastasis accompanied by headache. In addition to 8% occurrence of posterior fossa metastasis, other possible causes for vertigo in breast cancer survivors consist of vascular insufficiency, hyperlipidemia and labyrinthine lesion.

Adult↗

Dural cavernous angioma of the posterior sagittal sinus: case report.

BACKGROUND: Extraaxial cavernous hemangiomas (cavernomas) are very rare lesions, and less than 20 descriptions of these lesions outside the middle fossa have been reported. In this report, we describe a dural cavernous angioma involving the posterior sagittal sinus and discuss the clinical, radiological, operative, and histological features of this very uncommon lesion. CASE DESCRIPTION: A 31-year-old right-handed male presented with headache and decreasing visual acuity. Severe bilateral papilledema was found on fundoscopic examination. Neurological examination demonstrated a minor right temporal field cut. Brain magnetic resonance imaging with contrast demonstrated a 2.5 x 2.5 cm hyperintense enhancing mass in the midline, which was contiguous with the posterior margin of the falx cerebri. The patient underwent a bilateral occipital craniotomy centered on the lesion. The histological features were consistent with cavernous angioma. CONCLUSION: This report demonstrates that although extra axial cavernomas are quite rare, they must be included in the differential diagnosis of enhancing lesions along the posterior sagittal sinus. The operative removal of these lesions can be quite treacherous and usually requires a careful reapproximation of the patent sinus after lesion excision.

Adult↗

Non-opioid analgesics and the risk of restless leg syndrome-a spurious association?

OBJECTIVES: The aim of this study was to evaluate the prevalence and risk factors of restless leg syndrome in a secondary care patient population maintained on tricyclic and serotonin re-uptake inhibiting antidepressants. STUDY DESIGN: Prospective observational study. STUDY POPULATION: Two hundred and forty-three patients of a single practice specializing in the treatment of affective and anxiety disorders. Patients younger than 30 years and those with neurologic diseases such as Parkinson's disease, multiples sclerosis and dementia were excluded, as well as those with schizophrenia or other illusional disturbances, eating disorders, histories of opioid or codeine-containing analgesic abuse or of alcohol or illicit drug abuse. Patients remained in the study population only if they had gained complete or partial recovery of their anxiety and/or depressive symptoms and been treated for at least 6 months in the practice's ambulatory care (85.0% of the patients were finally included). METHODS: Histories of leg discomfort, akathisia, medication use and socio-demographic factors were assessed at the time of enrolment. RLS was assumed if all minimal criteria of the international RLS study group were fulfilled. RLS patients also had a neurologic examination focusing on signs and symptoms of neuropathy. It is unclear whether those without RLS were also examined neurologically. RLS case status was assessed at 6-month intervals for patients in the study. It is unclear if the reported RLS prevalence reflects case status at enrolment and/or during the treatment course. The prevalence of various pain syndromes, as well as the intake of analgesics and average coffee intake per day was compared between those with and without RLS. Lifetime and current treatment exposure to antidepressants and dopamine antagonists was evaluated according to RLS status. It is unclear what the mean treatment time was. Various univariant, descriptive statistics were used. The statistical analysis and logistic regression was applied using RLS case status as the dependent and co-morbidities, and medications/treatments as independent variables. RESULTS: The prevalence of RLS among the patients included in the analysis was 27.0%, with female patients more often affected than men (31.0% vs. 19.0%). RLS symptom severity during the course of treatment was low for 43 of 65 cases. Somatic co-morbidities were more prevalent in RLS affected women and less prevalent in RLS affected men than in gender specific non-RLS patients. No significant differences were observed for lifetime exposure to dopamine antagonist between those with and without RLS (38.0% vs. 35.0%). Chronic pain syndromes were observed more often in RLS cases (women: 86.0% vs. 32.0%, men: 62.5% vs. 29.0%). Twelve percent of those without RLS and 75.0% of RLS cases had a history of regular intake of analgesics prior to study enrolment. In a multivariate logistic regression model the authors found RLS case status to be associated with the intake of analgesics (OR: 25.5, P<0.001), psychiatric co-morbidity (OR: 2.97, P=0.01) and an interaction between age and the intake of analgesics (OR: 2.6, P=0.03). CONCLUSIONS: A 27.0% prevalence of RLS was found in this highly selected population treated with tricyclic and serotonin re-uptake inhibiting antidepressants. The authors infer from their results that regular intake of analgesics is a risk factor for RLS and that the observed association of gender with RLS might be explained by a higher intake of analgesics in women compared to men. They further conclude that the intake of analgesics, rather than the pain co-morbidity itself, enhances the risk of RLS.

Journal Article↗

European comparison of costs and quality in the prevention of secondary complications in Type 2 diabetes mellitus (2000-2001).

AIMS: To compare the out-patient costs and process quality of preventing secondary complications in patients with Type 2 diabetes mellitus in France, Germany, Italy, The Netherlands, Sweden, Switzerland, and the UK. METHODS: A total of 188 European physician practices assessed annual services for one hypothetical average patient (cost evaluation) and 178 practices reported retrospective data on one or two real patients (quality evaluation) in 2000/2001. In countries with a detailed fee-for-service schedule (Germany, Italy, and Switzerland) reimbursement fees were used to approximate costs. These fee-for-service schedules were also used to develop index (average) fees for all countries, in order to measure resource utilization. The following process quality indicators were evaluated: control of HbA1c; control of lipids; urine test for (micro)albuminuria; control of blood pressure; foot examination; neurological examination; eye examination; and patient education. For each country an average quality rating was calculated by weighting the response to each quality indicator with the level of scientific evidence. RESULTS: Average quality ratings ranged from 0.40 in The Netherlands to 0.62 in the UK (0 = lowest rating; 1 = highest rating). Total annual costs for secondary prevention were higher in Switzerland than in Germany and Italy (EUR475, EUR381, and EUR283, respectively). Resource utilization was highest in Germany and lowest in the UK. CONCLUSIONS: The overall quality of preventive services documented was found to be poor in the seven European countries studied. The UK rated as both the most effective and the most efficient country in providing secondary prevention in Type 2 diabetes.

Adolescent↗

A case of associative visual agnosia: neuropsychological findings and theoretical considerations.

A 61-year-old right-handed man fell downstairs and was found unconscious. There was no abnormality in the general physical examinations. Neurological examinations revealed a quadrantanopia. Neuropsychological examination revealed an impairment in recent verbal memory, alexia, agraphia, object agnosia, color naming difficulty, prosopagnosia, and visuospatial constructional disability. CT scan demonstrated subcortical hematomas in the temporo-occipital regions of both hemispheres. MRI demonstrated extensive low-intensity lesions in the lingual, fusiform and posterior inferior temporal gyri on both hemispheres. Both inferior longitudinal fasciculi were also affected. His neuropsychological deficits seem best described as a typical form of associative visual agnosia. From the results of neuroradiological findings, the authors emphasize that associative visual agnosia might be produced by an intrahemispheric disconnection between the visual cortices and the temporal lobes which are supposed to be the storage site of the engrams of visual memories. Moreover, the neuropsychological findings suggest that the visuo-constructional ability to convert the two-dimensional input to the three-dimensional construction and the capacity of three-dimensional imagination were severely impaired in our patient. It was considered that these neuropsychological features play an important role in the recognition difficulties of associative visual agnosia.

Agnosia↗

Current evidence for the organic etiology of spastic dysphonia.

For over 100 years it has been universally assumed in the literature that spastic dysphonia is a functional or psychoneurotic voice disorder. In the last few years, new data have accumulated that support the concept that spastic dysphonia is caused by an organic, rather than a functional, abnormality. Histologic examination of segments of the recurrent laryngeal nerve removed from patients with spastic dysphonia has revealed myelin abnormalities in 30% of the nerves examined. Neurologic examination indicated brain stem or basal ganglia disturbances in some patients who had no apparent nerve disease.

Axons↗

Clinical genetic evaluation of the child with mental retardation or developmental delays.

This clinical report describes the clinical genetic evaluation of the child with developmental delays or mental retardation. The purpose of this report is to describe the optimal clinical genetics diagnostic evaluation to assist pediatricians in providing a medical home for children with developmental delays or mental retardation and their families. The literature supports the benefit of expert clinical judgment by a consulting clinical geneticist in the diagnostic evaluation. However, it is recognized that local factors may preclude this particular option. No single approach to the diagnostic process is supported by the literature. This report addresses the diagnostic importance of clinical history, 3-generation family history, dysmorphologic examination, neurologic examination, chromosome analysis (> or =650 bands), fragile X molecular genetic testing, fluorescence in situ hybridization studies for subtelomere chromosome rearrangements, molecular genetic testing for typical and atypical presentations of known syndromes, computed tomography and/or magnetic resonance brain imaging, and targeted studies for metabolic disorders.

Child↗

Medical implications of marijuana use.

The effect of marijuana smoking was studied in 28 healthy young adult men who had previously smoked marijuana for approximately 5 years each. The subjects were hospitalized on a closed research ward for 31 days during which comprehensive psychological, physiological, and medical observations and tests were done. Physical examinations, neurological examinations, chest X-rays, electrocardiograms, and clinical laboratory tests were all within normal limits. Marijuana produced inconstant changes in pulse rate and blood pressure in these studies. Six subjects were found to have significant reduction in resting vital capacity during the baseline period of the study which were felt to be related to their prior marijuana smoking. In contradistinction to these findings, 12 of 15 subjects had statistically significant increases in peak expiratory flow rate immediately following marijuana smoking. Body temperature tended to be slightly reduced during marijuana use.

Adult↗

[Replantation surgery of the penis. A case report].

By the case of a subtotal traumatical amputation of the penis seen in our services, we discuss the advantages of a replantation by microsurgical technique. After presentation of the operational procedure and the management of the postoperative course the results of a thorough examination by questioning, physical examination, neurological examination including EMG testing of the bulbo-cavernous-reflex, Rigiscan NTM and angiography of the penal arteries are discussed. A review of the literature shows the advantages of the microsurgical technique but also the astonishing results by the former, conventional technique which still presents a possibility if microsurgery is not available.

Adult↗

[An autopsy case of syringomyelia associated with Chiari malformation and basilar impression].

The authors report one autopsy case of syringomyelia associated with Chiari malformation and basilar impression. The pathogenesis of syringomyelia in our case is discussed. This 37-year-old man complained of progressive difficulty in swallowing and walking for two years. He had noticed dysarthria for six months before admission. (Examination) Neurological examination showed dysarthria, down beat nystagmus, disturbance of IXth nerve, Xth nerve and XIth nerve, and cerebellar ataxia. Deep tendon reflexes were hyperactive in the upper and lower extremities. Babinski's sign was positive bilaterally. Neuroradiological examination demonstrated basilar impression and Chiari malformation. (Operation) Suboccipital craniectomy and laminectomy of upper cervical vertebra were performed with dural plasty. Postoperatively he acquired some improvement, but soon after he was worse. He died of respiratory disturbance. (Postmortem examination) Though the central canal was obliterated at the C4 level, the syrinx extended from the C5 to Th7 level. From the C5 to C8, the syrinx was present in the areas of central gray matter, extending into the left dorsal horn, where it communicated with subarachnoid space. Furthermore, the abnormal vessels were noticeable around the syrinx. At the Th2 level, they were also shown in central grey matter where no syrinx existed. (Conclusion) The etiology of syringomyelia in our case was not explained by Gardner's hydrodynamic theory. We suggested that intramedullary abnormal vessels played an important part for the formation of the syringomyelia.

Adult↗

Iohexol lumbar myelography: clinical study.

Forty-three patients underwent lumbar myelography with the new, nonionic contrast medium iohexol. Multiple laboratory examinations, neurologic examinations, and electrocardiograms showed no significant alterations after intrathecal injection of the contrast agent. Mild electroencephalographic changes were seen in one patient. Nineteen adverse reactions occurred in 13 patients; only one of them was considered severe. No patient experienced a seizure, auditory or visual hallucination, or similar neuropsychologic reaction. This is a distinct improvement over the side effects described for previous water-soluble contrast agents. The adverse reactions occurring with iohexol myelography are fewer in number and less severe than with metrizamide myelography, and radiographic visualization obtained with iohexol is equal to that obtained with metrizamide. With iohexol, it appears that the most disturbing and disabling neuropsychologic reactions have been reduced to an acceptable minimum.

Adult↗

[A case with an isolated cortical vein thrombosis].

A 45-year-old man was admitted to our hospital because of generalized seizure. He had epilepsy and mental retardation since age of two. On admission temperature was 37.9 degrees C but, nuchal rigidity and Kernig's sign were not present. There were no other abnormal findings on physical examination. Neurological examination revealed consciousness disturbance, generalized seizure and mental retardation. Right hemiparesis gradually developed after generalized seizure. Laboratory data did not show any abnormalites to induce cerebral venous thrombosis. A brain MRI revealed hyperintensity on T2-weighted images and slightly enhanced on T1-weighted images in the left frontal lobe, using Gd-DTPA. An increased signal was also noted in the superior sagittal sinus on T1-weighted images. The superior sagittal sinus was patent but the cortical vein in the left frontal lobe was not demonstrated on cerebral angiography. A diagnosis of an isolated cortical vein thrombosis was made by exploratory craniotomy. Anticoagulation with heparin was started. Although the cortical vein thrombosis usually co-exsists with dural sinus thrombosis, an isolated cortical vein thrombosis like this case was rather rare. A case with cerebral venous thrombosis localized only in the left frontal cortical vein is reported, but definitive etiology is not known.

Cerebral Cortex↗

Nerve injuries in anterior shoulder dislocations.

A retrospective study was conducted to determine the incidence of nerve injuries in anterior dislocations of the shoulder and to determine if a neurological examination is routinely performed in such cases. One hundred and fifteen shoulder dislocations in 100 patients (74 males, 26 females; mean age 35+/-18 years) were reviewed. Eighty-seven patients were examined for neurological injuries prior to reduction and 8 of these patients (9.2%) were found to have sustained neurological injuries. Following reduction, neurological examination was performed in 85 patients. Three patients who were not examined initially prior to reduction were subsequently found to have nerve injuries after reduction. Seven patients (7%) were not examined for neurological injury both before and after reduction of the dislocation. Eleven patients were found to have sustained nerve injuries in the final analysis. Axillary nerve injuries were the most common, occurring in 8 patients. In conclusion, nerve injuries are common in shoulder dislocations. The importance of performing and documenting the findings of neurological examination anterior shoulder dislocations needs to be reiterated.

Adolescent↗

[Quantification of the gnostic sensitivity via measurement of the vibration threshold and of finger tip sensation].

OBJECTIVE: Quantification of vibration perception and fingertip sensation in routine neurological examination. SETTING: Neurological Clinic, University Hospital, Groningen, the Netherlands. DESIGN: Prospective, controlled investigation. METHODS: Vibration perception and fingertip sensation were quantified in a large group of normal control persons of various ages and in neurological patients and compared with the usual sensory tests at routine neurological examination. The vibration perception limit was measured with a biothesiometer without accelerometer, the fingertip sensation with a device for two-point discrimination slightly modified according to Renfrew ('Renfrew meter'). Concordance of the tests was studied by calculating kappa values. RESULTS: The normal values of both sensory qualities had a log-normal distribution and increased with age. The values obtained with the Renfrew meter correlated well with those of the two-point discrimination and stereognosis but were systematically higher than those indicated by Renfrew. CONCLUSION: Both methods appear useful at routine neurological examination if certain measuring precautions are taken.

Adolescent↗

Validity and reproducibility of a screening examination for neurological abnormality in persons exposed to methylmercury.

The validity and reliability of methods of screening for neurologic abnormality were assessed as part of an investigation of an outbreak of methylmercury exposure in two northern Canadian communities. Four hundred and forty-five Cree Indians were examined by one of five neurologists in a complete neurologic examination and by a trained paramedical observer in a short screening examination which included a selection of tests from the complete examination. The screening examinations were recorded on videotape and those for 176 men were reviewed by the five neurologists and the paramedical observer 1 year after the field studies. The prevalence of abnormality assessed in the field screening examination was greater than that assessed during the complete neurologic examination, for neurologic features included in both examinations. However, agreement between examinations in identifying individuals with abnormality was poor with the sensitivity of the screening examination falling under 50% for half of the neurologic features examined. In contrast, specificity was over 80% for 14 of 18 features. Review of the videotapes revealed marked interobserver variation in the assessment of the prevalence of neurologic abnormality and poor agreement with the neurologic examinations in the identification of abnormality in individuals, with kappa less than 0.2 for most neurologic features. The levels of agreement between the neurologic examinations and the screening examinations conducted in the field and by videotape review suggest that neither screening examination provides equivalent information in the identification of the presence of abnormality to that obtained in the neurologic examination.

Female↗

[Emergency neurology consultations in the university hospital setting: contribution of the neurologist to inpatient management].

While outpatient management for chronic neurological diseases is well-established, the impact of inpatient neurological examination in emergency room and university hospital remain largely underestimated. We prospectively studied the role of the neurologist in patient management, in a primary care university hospital. Over a period of 12 months, we prospectively recorded the demographics of patients requiring examination in the emergency room, the initial suspected neurological diagnosis of the emergency room, the final diagnosis of the neurology team, and the patients' outcomes. For each patient, the time between admission, the call and the neurological examination were recorded. Neurological examinations were performed in 2220 patients in whom 75.6 p.100 were performed in the emergency room. These latter patients corresponded to 14 p.100 of all patients admitted in the emergency room. Of examined patients, 52 p.100 were male and mean age was 56.9 +/- 21 years. The time between admission and examination was 32 min. (+/- 36 min), irrespective of the day of the week, and depended on the suspected diagnosis: shorter in stroke and status epilepticus (p<0.05), and longer in loss of consciousness and vertigo (p<0.01). Forty-four percent of the examinations took place in the evening and night. The reasons for examinations were: stroke (28.3 p.100), epilepsy (17.7 p.100), headaches (8.4 p.100), loss of consciousness (7.9 p.100), cognitive dysfunctions (4.1 p.100), neuropathies (4 p.100) and miscellaneous (8.1 p.100). Neurological examinations modified neurological diagnosis and treatment in more than 86 p.100 of the patients. Following neurological examination, 17.2 p.100 of the patients were able to go home, while the rest were admitted to the stroke unit (27.2 p.100), the general neurological unit (27.3 p.100) or in other departments (28.3 p.100), of which intensive care unit (5.3 p.100) or neurosurgery (5.9 p.100). Emergency neurologic examination improves neurological diagnosis and has a positive impact both on treatment and, more globally, in patient management.

Consultants↗