Hu-antibody-positive patients with or without cancer have similar clinical profiles.
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Publications and source records attributed to A Twijnstra.
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The clinical course of astrocytoma grade II (AII) is highly variable and not reflected by histological characteristics. As one of the best prognostic factors, higher age identifies rapid progressive A II. For patients over 35 years of age, an aggressive treatment is normally propagated. For patients under 35 years, there is no clear guidance for treatment choices, and therefore also the necessity of histopathological diagnosis is often questioned. We studied the additional prognostic value of the proliferation index and the detection of genetic aberrations for patients with A II. The tumour samples were obtained by stereotactic biopsy or tumour resection and divided into two age groups, that is 18-34 years (n=19) and > or =35 years (n=28). Factors tested included the proliferation (Ki-67) index, and numerical aberrations for chromosomes 1, 7, and 10, as detected by in situ hybridisation (ISH). The results show that age is a prognostic indicator when studied in the total patient group, with patients above 35 years showing a relatively poor prognosis. Increased proliferation index in the presence of aneusomy appears to identify a subgroup of patients with poor prognosis more accurately than predicted by proliferation index alone. We conclude that histologically classified cases of A II comprise a heterogeneous group of tumours with different biological and genetic constitution, which exhibit a highly variable clinical course. Immunostaining for Ki-67 in combination with the detection of aneusomy by ISH allows the identification of a subgroup of patients with rapidly progressive A II. This is an extra argument not to defer stereotactic biopsy in young patients with radiological suspicion of A II.
Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurologist is of little value to provide information of the neurologic status.
OBJECTIVE: The aim of this study was to determine the incidence of olfactory dysfunction after mild traumatic brain injury (MTBI). Damage to the olfactory bulbs or frontal cortex has been reported in MTBI, but olfactory dysfunction after MTBI has not been studied in a prospective way before. DESIGN: Patients with first-time MTBI were included. Patients' olfactory threshold values (Hyposmia Utility Kit by Olfacto-Labs) were measured 2 weeks after the trauma. Associations between olfactory threshold values and individual symptoms and S-100B and NSE concentrations were examined, using multiple linear regression analysis, adjusting for the influence of age. RESULTS: Twenty-two per cent of 111 included patients had hyposmia and 4% had anosmia. Thresholds at 2 weeks showed no significant associations with the presence of symptoms at the ER, nor with early concentrations of S-100B or NSE. CONCLUSIONS: Although a high prevalence of olfactory dysfunction was found, no correlation was found between olfactory dysfunction and acute parameters of MTBI.
In 1999, a Task Force on Mild Traumatic Brain Injury (MTBI) was set up under the auspices of the European Federation of Neurological Societies. Its aim was to propose an acceptable uniform nomenclature for MTBI and definition of MTBI, and to develop a set of rules to guide initial management with respect to ancillary investigations, hospital admission, observation and follow-up.
BACKGROUND: Outcome after mild traumatic brain injury (MTBI) is determined largely by the appearance of post-traumatic complaints (PTC). The prevalence of PTC after six months is estimated to be between 20 and 80%. Bed rest has been advocated to prevent PTC but its effectiveness has never been established. OBJECTIVE: To evaluate the effect of bed rest on the severity of PTC after MTBI. METHODS: Patients presenting with MTBI to the emergency room were randomly assigned to two intervention strategies. One group was advised not to take bed rest (NO) and the other to take full bed rest (FULL) for six days after the trauma. The primary outcome measures were severity of PTC on a visual analogue scale and physical and mental health on the medical outcomes study 36 item short form health survey (SF-36) at two weeks and three and six months after the trauma. RESULTS: Between October 1996 and July 1999, 107 (54 NO, 53 FULL) patients were enrolled. Outcome variables in both groups clearly improved between two weeks and six months. After adjustment for differences in baseline variables, most PTC tended to be somewhat more severe in the FULL group six months after the trauma, but no significant differences were found. Neither were there any significant differences in the outcome parameters between the two groups after three months. Two weeks after the trauma, most PTC in the FULL group were slightly less severe than those in the NO group, and physical subscores of the SF-36 in the FULL group were slightly better. These differences were not significant. Patients in the FULL group reported significantly less dizziness during the intervention period. CONCLUSIONS: As a means of speeding up recovery of patients with PTC after MTBI, bed rest is no more effective than no bed rest at all. Bed rest probably has some palliative effect within the first two weeks after the trauma.
OBJECTIVES: To identify parameters at first presentation after mild traumatic brain injury (MTBI) that are predictive of the severity of post-traumatic complaints (PTC) after six months. Early recognition of patients with MTBI who are at risk of developing PTC would be useful because early follow up at the outpatient clinic may help to reduce the severity of these complaints in the long run. METHODS: The presence of symptoms in the emergency room (ER) (headache, dizziness, nausea, vomiting, and neck pain) and biochemical markers (neurone specific enolase and S-100B) in serum were assessed as possible predictive variables for the severity of PTC. Outcome variables were the severity of 16 PTC six months after the trauma. RESULT: After six months, the severity of most complaints had declined to pretrauma levels but medians for headache, dizziness, and drowsiness were still increased. In a series of 79 patients, 22 (28%) reported one or more PTC after six months. After adjustment for baseline variables, an at least twofold increased severity of all PTC subgroups was reported by those patients reporting headache, dizziness, or nausea in the ER. A twofold increased severity of "cognitive" and "vegetative" PTC was also found in those with increased concentrations of biochemical serum markers at first presentation. The prevalence of full recovery after six months increased from 50% in patients with three symptoms to 78% in those with no symptoms in the ER. Inclusion of biochemical markers showed that all 10 patients with no symptoms in the ER and normal markers recovered fully. CONCLUSIONS: The presence of headache, dizziness, or nausea in the ER after MTBI is strongly associated with the severity of most PTC after six months. Identifying MTBI patients in the ER without headache, dizziness, nausea, or increased serum marker concentrations may be a promising strategy for predicting a good outcome.
BACKGROUND: Myasthenia gravis and the Lambert-Eaton myasthenic syndrome (LEMS) may have a similar distribution of muscle weakness. Deciding on a diagnosis of myasthenia gravis or LEMS on clinical grounds may therefore be difficult. OBJECTIVE: To compare the localisation of initial muscle weakness and the distribution of weakness at the time of maximum severity in patients with myasthenia gravis and LEMS. SUBJECTS: 101 patients with myasthenia gravis and 38 patients with LEMS. RESULTS: In myasthenia gravis, initial weakness involved extraocular muscles in 59%, bulbar muscles in 29%, and limb muscles in 12% of the patients. In LEMS no patient had ocular weakness, 5% had bulbar weakness, and 95% had weakness of the limbs as the first symptom (p < 0.001). At the point of maximum severity, weakness in myasthenia gravis was purely ocular in 25%, oculobulbar in 5%, restricted to the limbs in 2%, and present in both oculobulbar muscles and limbs in 68%. At this point, none of the LEMS patients had weakness restricted to extraocular or bulbar muscles (p = 0.002). The legs were affected in all LEMS patients, whereas in 12 patients with generalised myasthenia gravis limb weakness was restricted to the arms (p = 0.024). CONCLUSIONS: In a patient suspected to have a myasthenic syndrome whose first symptom is ocular weakness, LEMS is virtually excluded. Limb weakness confined to the arms is only found in generalised myasthenia gravis and not in LEMS. Muscle weakness in myasthenia gravis tends to develop in a craniocaudal direction, and in the opposite direction in LEMS.
The authors examined the use of chromosomal analysis by in situ hybridization to differentiate between nonneoplastic reactive gliosis and astrocytomas in cases in which routine histology was inconclusive. Numerical chromosomal aberrations were found in 80% of low-grade astrocytoma specimens and in none of the reactive gliosis specimens. Aneusomic tumor cells were detected in four of 13 stereotactic samples with an initially inconclusive tissue diagnosis, three of which were later diagnosed as astrocytoma. The in situ hybridization procedure may have additional value in the differential diagnosis of reactive gliosis versus low-grade astrocytoma.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder, in which antibodies against voltage-gated calcium channels located at nerve terminals cause muscle weakness and autonomic dysfunction. In approximately half of the patients the autoimmune process is initiated by a tumor. In the other half of patients no tumor is found and the etiology is unknown. The aims of this study were to investigate the strength of HLA-associations with nontumor LEMS (NT-LEMS) and to study the relation of HLA-haplotypes with age at onset of LEMS and other clinical features. Therefore, typing of HLA class I and II was performed in 19 patients with NT-LEMS, who were clinically evaluated. NT-LEMS was significantly associated with alleles of both HLA-class I (i.e. HLA-B8) as well as -class II (i.e. HLA-DR3 and -DQ2). HLA-B8+ patients had significantly younger age at onset of LEMS and tended to be female. This study shows that HLA-class I haplotype is associated with a distinct phenotype in NT-LEMS.
OBJECTIVES: The aim of the study was to determine whether serum concentrations of neuron-specific enolase (NSE) and S100-B in mild traumatic brain injury (MTBI) patients are higher than in serum of healthy controls. MATERIAL AND METHODS: Blood samples from 104 MTBI patients were taken shortly after the trauma for measurement of S-100B and NSE in serum. In 92 healthy persons these markers were also measured. Marker concentrations in serum of patients and controls were compared. In the patient group the relation between serum-marker concentrations and clinical symptoms and signs, that occurred shortly after the traumatic event, were evaluated. RESULTS: Median NSE concentration was only slightly higher in patients (9.8 microg/l; 10 to 90 percentile range 6.9 to 14.3 microg/ l) than in controls (9.4 microg/l; 6.3 to 13.3 microg/l). Median S-100B concentration was significantly higher in patients (0.25 microg/l; 0.00 to 0.68 microg/l) than in controls (0.02 microg/l; 0.00 to 0.13 microg/l). An association was found between S-100B concentrations and vomiting in patients. CONCLUSIONS: S-100B is a useful marker for brain damage in MTBI patients and seems to be associated with the presence of vomiting after the trauma.
Brain injury is classified clinically as severe, moderate or mild brain injury characteristics, including admission Glasgow coma score, duration of unconsciousness and post-traumatic amnesia and any focal neurological findings. Most traumatic brain injuries are classified as mild traumatic brain injury (MTBI). Headache, nausea and dizziness are frequent symptoms after MTBI and may continue for weeks to months after the trauma. MTBI may also be complicated by intracranial injuries. Experimental animal models and post-mortem studies have shown axonal damage and dysfunction in MTBI. This damage is mostly localized in the frontal lobes. Serum S-100 and NSE have been reported to be markers for the seventy of brain damage. In the literature, indications for radiodiagnostic evaluation following MTBI have been the subject of debate. Radiographs of the skull are used to exclude skull fractures, but are not useful for an evaluation of brain injury. Computed tomography of the brain seems to be the best way to exclude the development of relevant intracranial lesions. MTBI has a good clinical outcome, although a substantial group of patients develop post-concussional complaints (PCC). There is little information on the effectiveness of various methods suggested for reducing the frequency of PCC.
Mild traumatic brain injury (MTBI) accounts for most traumatic brain injuries and is an important cause of morbidity. Recent studies in various European countries have shown that no consensus exists about management of patients with MTBI. This study describes the management of MTBI patients in various European hospitals. A short questionnaire covering the areas of interest was sent to several EFNS members in European countries. The results of the inquiry show that there is, at present, no consensus about criteria for, or management of MTBI in European hospitals.
OBJECTIVE: To measure the incidence of traumatic head or brain injury in the catchment area of the Academic Hospital Maastricht (AZM), the Netherlands. DESIGN: Retrospective. METHOD: Data were collected about head injury patients who visited the emergency room of the AZM in 1997 by separate forms that were filled out for each patient who came to the emergency room. Data were added from admission records and radiology records. The AZM had a catchment area of approximately 231,000 people. RESULTS: The emergency room was attended by 1933 patients with traumatic head or brain injury. Head trauma without signs of brain injury was diagnosed in 1440 patients (74%) mild brain injury in 467 (24%) and moderate or severe brain injury in 26 (1%). The mean age was 30 years (range: 0-97) and 29% of all patients were below the age of 15. Two-thirds (67%) of patients were male. An X-ray of the skull was performed in 15% of the cases. In 7% of these X-rays a relevant abnormality was found. Eleven per cent of patients were admitted for observation. The incidence rate of traumatic head or brain injury in 1997 was 836/100,000 and the incidence of admission 88/100,000. The causes were a fall (43%), traffic accident (22%), violence (15%), sports injuries (7%), accidents during work (4%), or other/unknown (9%). CONCLUSION: Most patients with head or brain injury had mild injuries (99%, sole head injury or mild brain injury). Compared with other studies, the annual frequency of hospital admissions was low.
PURPOSE: In this study we evaluated the usefulness of MR-imaging in the detection of asymptomatic brain metastases (BM) at the initial diagnosis in patients with small cell lung cancer (SCLC) and studied the follow-up of these patients. PATIENTS AND METHODS: One-hundred and twenty-five patients with SCLC were investigated with MR-imaging. RESULTS: In 112 patients with normal neurological findings, MR-imaging of the brain demonstrated BM in 17 patients (15%). Six of these 17 patients were therefore upgraded to extensive disease (ED). Two of these 17 patients died during chemotherapy because of progressive disease and 3 patients became neurologic symptomatic with progressive disease on MR-imaging of the brain. After completion of chemotherapy a repeated MR-imaging of the brain in the remaining 12 patients showed 1 complete remission, 4 partial remission and 7 progressive disease of the BM. CONCLUSION: This study showed that at presentation an unexpectedly high percentage of SCLC patients had asymptomatic BM on MR-imaging. We propose that MR-imaging of the brain should be included in the staging of SCLC patients as well for staging, prognosis and therapy.
PURPOSE: Although cytologic examination of CSF is the primary method for the evaluation of response to therapy for leptomeningeal metastases (LMMs), the procedure's sensitivity decreases throughout the course of protracted therapy. We studied whether this response could be monitored more accurately through the detection of numerical chromosomal aberrations by interphase cytogenetics, using fluorescence in situ hybridization (FISH). PATIENTS AND METHODS: Seven patients treated for LMMs and with a known numerical aberration for chromosome 1 in their pretreatment CSF were included in this study. Up to 16 consecutive CSF samples were analyzed by means of the fluorescence in situ hybridization (FISH) technique for cells with aberrant chromosome 1 content. The results of routine cytology and FISH analyses were compared and were correlated with each patient's neurologic status. RESULTS: Routine cytology detected malignancies in only 24 of the 76 samples, all of which were classified as chromosomally abnormal by FISH (except for two samples that could not be evaluated). Moreover, FISH demonstrated aneusomic cells in 32 additional samples, which could therefore be classified as malignant. The FISH results correlated better with patient neurologic status in that more malignant cells were detected in the CSF of neurologically deteriorating patients. CONCLUSION: Using FISH in addition to performing routine cytologic examination of CSF led to a more accurate evaluation of response to treatment in patients treated for LMMs.
OBJECTIVE: To study the presenting features and value of routine diagnostic procedures in patients with leptomeningeal metastases (LMM) related to the primary malignancy to improve diagnostic assessment. METHODS: The authors studied the presenting features and value of routine diagnostic procedures in relation to the histology of primary malignant disease in 45 patients with LMM of solid (n = 30) or hematologic (n = 15) malignancies. RESULTS: Patients with solid LMM present mostly with spinal or radicular symptoms (53%), whereas patients with hematologic LMM more often show cranial nerve dysfunction at presentation (53%). Multifocal neurologic symptoms were seen in 67% of patients. The first CSF cytology demonstrated malignant cells more frequently in solid LMM compared with hematologic LMM (73% versus 53%). Extralumbar punctures increased the sensitivity of cytology to a greater extent in hematologic LMM than in solid LMM (34% versus 10%). Abnormal neuroimaging findings were found more often in solid LMM than in hematologic LMM (67% versus 40%). Increased total CSF protein in combination with either multifocal neurologic symptoms or abnormal neuroimaging findings was found in 73% of patients with a negative first CSF cytology. CONCLUSIONS: Patients with LMM presented differently depending on the histology of the primary tumor. In patients with a negative first CSF cytologic examination, multiple lumbar punctures increased the diagnostic accuracy, especially in hematologic LMM. LMM could also be diagnosed in patients with known cancer if total CSF protein was increased in combination with either multifocal neurologic symptoms or abnormal neuroimaging findings, preferably MRI.