Long-term hormonal follow-up after human Puumala hantavirus infection.

OBJECTIVE: Nephropathia epidemica (NE) is a haemorrhagic fever with renal syndrome (HFRS) caused by Puumala hantavirus (PUUV). Pituitary haemorrhage and hypopituitarism may complicate recovery from acute NE. DESIGN: Forty-seven of our recent cohort of 58 NE patients volunteered to be re-examined in order to estimate the burden of hormonal deficiency 4 to 8 years after the acute illness. Two patients had suffered from pituitary haemorrhage, but many others exhibited pituitary oedema during their acute infection. In this study, we searched for symptoms of hormonal deficiency, performed hormonal laboratory screening, and most patients underwent pituitary MRI examination. RESULTS: The pituitary size had diminished in all patients in whom MRI was performed (P < 0·001). One patient with acute phase haemorrhage had made a complete recovery while the other continued to require hormonal substitution. In addition, hormonal laboratory abnormalities were observed in nine other patients; these being attributable to several reasons, for example independent peripheral hormonal diseases, side effects of medication or other secondary causes such as obesity. None of them had signs of late-onset pituitary insufficiency caused by their previous NE. Health-related quality of life (mean and median 15D score) of patients was comparable to that of age-standardized general population. CONCLUSIONS: None of our patients had developed obvious late-onset hypopituitarism despite of the fact that pituitary gland can be affected during acute NE. We recommend requesting a history of hantavirus infection whenever the possibility of pituitary dysfunction is suspected at least in patients originating from regions with high NE infection rate.

Repolarization abnormalities in patients with subarachnoid and intracerebral hemorrhage: predisposing factors and association with outcome.

BACKGROUND: Electrocardiographic (ECG) abnormalities are frequent in patients with intracranial insult. In this study, we evaluated the factors predisposing to the repolarization abnormalities, i.e., prolonged corrected QT (QTc) interval, ischemic-like ECG changes and morphologic end-repolarization abnormalities, and examined the prognostic value of these abnormalities in patients with subarachnoid and intracerebral hemorrhages requiring intensive care. METHODS: This was a prospective, observational clinical study in a university-level intensive care unit. Clinical characteristics, the level of consciousness, and findings in primary head computed tomography were recorded on admission. The study period was divided into three 2-day sections. In each section, a 12-lead ECG, transthoracic echocardiography, the results of standard blood electrolytes and cardiac troponin I, as well as the rate of vasoactive and sedative drug infusions were recorded. Repolarization abnormalities such as prolongation of the QTc interval (millisecond), ischemic-like ECG changes, and morphologic end-repolarization abnormalities (present/absent) were evaluated and analyzed. The 1-year functional outcome was determined using the Glasgow Outcome Score. RESULTS: During the 2-year study period, 108 patients were included in the study. Different repolarization abnormalities were frequent in both types of hemorrhage. Prolongation of the QTc interval was predisposed by female gender (ß, 24.5; P = 0.010) and the use of propofol (ß, 30.5; P = 0.001). The predisposing factor for ischemic-like ECG changes were male gender (odds ratio [OR], 5.9; P = 0.003) and for morphological end-repolarization abnormalities aneurysmatic bleeding (OR, 13.0; P = 0.002). Ischemic-like ECG changes were common, in 87/108 patients during the study period, and were associated with a poorer 1-year functional outcome (OR, 4.7; lower 95% confidence interval, 1.5; P = 0.010). CONCLUSIONS: Each repolarization abnormality has characteristic predisposing factors. Ischemic-like ECG changes are common and are associated with a poorer 1-year functional outcome.

Neurogenic pulmonary edema in patients with nontraumatic intracerebral hemorrhage: predictors and association with outcome.

BACKGROUND: Neurogenic pulmonary edema (NPE) is a well-recognized phenomenon after intracranial insult. In this study, we evaluated the predictors for NPE and its association with outcome in patients with intensive care unit-treated nontraumatic intracranial hemorrhage. METHODS: This was a prospective, observational clinical study in a university-level intensive care unit. Clinical characteristics, level of consciousness, and Acute Physiology and Chronic Health Evaluation (APACHE) II score were recorded on admission and the findings of primary head computed tomography were reviewed. A chest radiograph and arterial blood gas analysis were taken serially and NPE was determined as acute bilateral infiltrates in chest radiograph and hypoxemia. Echocardiography and cardiac and inflammatory markers were recorded. The 1-year outcome was assessed using the Glasgow Outcome Scale. RESULTS: NPE developed in 38 (35%) of the 108 patients included. Predictors for NPE were higher APACHE II score (≥20, odds ratio 6.17, P = 0.003) and higher interleukin-6 plasma concentration (>40 pg/mL, odds ratio 5.62, P = 0.003). Of patients with 0, 1, or 2 predictors mentioned above, 4%, 37%, and 65% had NPE, respectively. NPE was associated with a higher 1-year mortality (37% vs 14%, P = 0.007, respectively), but with an unchanged functional outcome after 1 year (Glasgow Outcome Scale score 1-3, 53% vs 51%, P > 0.9). CONCLUSIONS: Predictors for NPE are the severity of disease defined by APACHE II scores and higher levels of systemic inflammatory mediators. NPE is associated with a higher 1-year mortality, but not with a poorer 1-year functional outcome.

Expression of VEGF and collagen XVIII in meningiomas: correlations with histopathological and MRI characteristics.

BACKGROUND: The objective of this study was to assess the possibility of predicting histological characteristics of meningiomas on the basis of preoperative MRI and the correlation of the expression of vascular endothelial growth factor (VEGF) and collagen XVIII with histological parameters already established as predictive of the course of these tumors. METHODS: Expression of VEGF and collagen XVIII as well as other histological characteristics was examined in meningioma tissues from 20 patients. Preoperative MRI, including dynamic imaging of contrast enhancement, was analyzed. Times to maximum enhancement and maximum intensity increase were noted from dynamic imaging. The relative intensity of the tumor in fluid-attenuated inversion recovery (FLAIR), T2-weighted and contrast enhanced T1-weighted images, as well as volumes of tumor and edema, was calculated. The edema-tumor volume ratio was defined as the edema index (EI). RESULTS: Both VEGF and collagen XVIII were expressed in all meningioma samples. Edema was present in 60 % of cases. The strongest correlation of VEGF expression was to EI. Among histological parameters, microvessel density (MVD) and cellularity correlated moderately with VEGF. Collagen XVIII expression correlated strongly with the maximal intensity increase after contrast agent administration (ρ = 0.71, P = 0.001) as well as with MVD and intensity of the meningioma on FLAIR images. CONCLUSION: Meningiomas with faster and more intense enhancement in dynamic studies, indicative of good tumor blood supply and permeability of vasculature, are associated with high levels of collagen XVIII and VEGF expression. Occurrence of peritumoral edema in meningiomas is strongly correlated with expression of VEGF.

Signs of general inflammation and kidney function are associated with the ocular features of acute Puumala hantavirus infection.

BACKGROUND: Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), a type of viral haemorrhagic fever with renal syndrome (HFRS). This febrile infection may affect the kidneys, central nervous system (CNS), and the eye. Acute illness is associated with increased tissue permeability and tissue oedema, and many patients experience reduced vision. The aim of this study was to explore the physiological events associated with the ocular features of acute NE. METHODS: This was a prospective study of 46 NE patients who were examined during the acute infection and 1 month after hospitalization. Visual acuity, refraction, intraocular pressure (IOP), and ocular dimensions were evaluated. Cerebrospinal fluid and blood samples were collected, brain magnetic resonance imaging and electroencephalography were recorded, and HLA haplotype was analyzed. The degrees of tissue oedema and fluid imbalance were evaluated. RESULTS: CNS examinations did not reveal the source of the ocular changes in acute NE. The plasma C-reactive protein concentration correlated with the lens thickness and the IOP. The plasma creatinine level was associated with the change in anterior chamber depth. However, oliguric and polyuric patients displayed similar ocular findings. Patients positive for the DR3-DQ2 haplotype experienced the least diminished visual acuity. CONCLUSIONS: The level of systemic inflammation rather than CNS involvement appears to account for the ocular changes during acute PUUV infection, and the severity of kidney dysfunction may also have a significant role. In addition, the genetic properties of the host may well explain the ocular features of acute hantavirus infection.

Young male patients are at elevated risk of developing serious central nervous system complications during acute Puumala hantavirus infection.

BACKGROUND: Our aim was to characterize clinical properties and laboratory parameters in patients with or without cerebrospinal fluid (CSF) findings suggestive of central nervous system (CNS) involvement, and especially those who developed serious CNS complications during acute nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) infection. METHODS: A prospective cohort of 40 patients with acute NE and no signs of major CNS complications was analyzed. In addition, 8 patients with major CNS complications associated with NE were characterized. We collected data of CNS symptoms, CSF analysis, brain magnetic resonance imaging (MRI) results, electroencephalography (EEG) recordings, kidney function, and a number of laboratory parameters. Selected patients were evaluated by an ophthalmologist. RESULTS: Patients with a positive CSF PUUV IgM finding or major CNS complications were more often males (p < 0.05) and they had higher plasma creatinine values (p < 0.001) compared to those with negative CSF PUUV IgM. The degree of tissue edema did not explain the CSF findings. Patients with major CNS complications were younger than those with negative CSF PUUV IgM finding (52.9 vs. 38.5 years, p < 0.05). Some patients developed permanent neurological and ophthalmological impairments. CONCLUSIONS: CNS and ocular involvement during and after acute NE can cause permanent damage and these symptoms seem to be attributable to true infection of the CNS rather than increased tissue permeability. The possibility of this condition should be borne in mind especially in young male patients.

Early rebleeding after coiling of ruptured intracranial aneurysms.

BACKGROUND: Early rebleeding after coiling of a ruptured intracranial aneurysm (IA) may cause disability or death. The incidence and predictors of early rebleeding have previously been sparsely investigated. PURPOSE: To assess the incidence and risk factors of early rebleeding after coiling of a ruptured IA and to analyze the outcome of the patients suffering early rehemorrhage. MATERIAL AND METHODS: The data of 194 consecutive acutely (within 3 days) coiled patients with saccular ruptured IAs were analyzed. Age, gender, hypertension, aneurysm multiplicity, Hunt et Hess (HH) grade, intracerebral hematoma (ICH), intraventricular hematoma (IVH), external ventricular drainage (EVD), aneurysm location and size, and the grade of the initial aneurysm occlusion were tested to find the risk factors for early rebleeding. The outcome of the patients suffering rehemorrhage was verified. RESULTS: Early rebleeding after coiling occurred in 7 patients out of 194 (3.6%). The presence of an ICH at admission and HH grade 3­5 before coiling were significant risk factors for rebleeding. An early rehemorrhage appeared as an enlargement of the initial ICH in all of these patients. Six of seven patients had good outcome (Glasgow Outcome Scale, GOS, 3­5). Logistic regression analysis did not find any other statistically significant risk factors. CONCLUSION: The incidence of early rebleeding after acutely coiled ruptured IA was 3.6%. Risk factors for post-procedural rehemorrhage were the presence of ICH on the initial CT and HH grade 3­5 before coiling. Early rebleeding appeared exclusively as an enlargement of the initial ICH and not an increased amount of blood in the subarachnoid space.

Unjustified CT examinations in young patients.

The doses of radiation from computed tomography (CT) are relatively high, yet CT is being increasingly utilized. Furthermore, the radiation-induced lifetime risk of cancer mortality is higher at younger age. The purpose of this study was to find out whether previous CT examinations done on patients aged under 35 years were justified, and if not, whether there would have been other, more justifiable imaging modalities available. Fifty CT examinations of the head and 30 CT examinations each of the lumbar spine, cervical spine, abdomen, nasal sinuses and trauma were evaluated consecutively since the beginning of the year 2005 by using electronic patient files, the referral guidelines for imaging recommended by the European Commission and certain principles of classification. Seventy-seven per cent of the CT examinations of the lumbar spine, 36% of the head, 37% of the abdomen, 20% of the nasal sinuses and 3% of the cervical spine were unjustified. Most of these unjustified examinations could have been replaced by magnetic resonance imaging. In order to reduce utilization of ionizing radiation, both the referring practitioner and the radiologist responsible for the examination should carefully consider the justification for CT examinations and the possibility of using other imaging modalities.

Pulse repetition time and contrast enhancement: simulation study of Gd-BOPTA and conventional contrast agent at different field strengths.

OBJECTIVES: To investigate theoretically enhancement and optimal pulse repetition times for Gd-BOPTA and Gd-DTPA enhanced brain imaging at 0.23, 1.5, and 3.0 T. METHODS: The theoretical relaxation times of unenhanced, conventional contrast agent (Gd-DTPA) and new generation contrast agent (Gd-BOPTA) enhanced glioma were calculated. Then, simulation of the signals and contrasts as a function of concentration and pulse repetition time (TR) in spin echo sequence was done at 0.23, 1.5, and 3.0 T. The effect of echo time (TE) on tumor-white matter contrast was also clarified. Three patient cases were imaged at 0.23 T as a test of principle. RESULTS: Gd-BOPTA may give substantially better glioma-to-white matter contrast than Gd-DTPA but is more sensitive to the length of TR. These characteristics are accentuated at 0.23 T. Optimal TR lengths are shorter for Gd-BOPTA than for Gd-DTPA enhanced imaging at all field strengths. TR optimized for Gd-DTPA may thus give suboptimal contrast in Gd-BOPTA enhanced imaging. Higher enhancement with Gd-BOPTA is further accentuated by short TE. CONCLUSION: Appropriate TRs at 0.23 T appear to be approximately 300 to 400 milliseconds and 250 to 300 milliseconds, at 1.5 T 500 to 600 milliseconds and 400 to 450 milliseconds and at 3.0 T 550 to 650 milliseconds and 475 to 525 milliseconds using Gd-DTPA and Gd-BOPTA, respectively. For Gd-BOPTA enhanced imaging, it seems justified to optimize TR according to contrast and seek options like parallel excitation (Hadamard encoding) for increasing the number of slices and SNR.

Enhancement of brain tumors in 0.23-T low-field MRI: comparison of edema attenuated inversion recovery (EDAIR) sequences with T1-weighted sequence.

RATIONALE AND OBJECTIVES: The aim of this study is to explore whether edema attenuated inversion recovery (EDAIR) sequences could be used to improve tumor contrast in contrast-enhanced low-field 0.23-Tesla magnetic resonance imaging (MRI) using 0.1 mmol/kg of gadolinium-based contrast agent. MATERIALS AND METHODS: Ten patients with brain tumors were examined by using the following contrast-enhanced sequences: T1-weighted spin echo, EDAIR with inversion time (TI) of 600 milliseconds, and EDAIR with TI of 800 milliseconds. Images were assessed both quantitatively and qualitatively. RESULTS: Results suggest that tumor contrast enhancement in low-field MRI can be improved without increasing contrast agent dose. EDAIR 600 appears to be optimal in most cases. CONCLUSIONS: This inversion recovery sequence could be applicable as an additional sequence in the imaging of metastases in low-field MRI, as well as imaging of any other enhancing brain tumors or lesions in low-field MRI.

Serum S100ß as a prognostic marker in patients with non-traumatic intracranial hemorrhage.

BACKGROUND: The serum concentration of S100ß protein reportedly predicts outcomes after brain injury. We examined the prognostic accuracy of S100ß in patients with non-traumatic intracranial hemorrhage. METHODS: This was a prospective, observational study of patients with non-traumatic intracranial hemorrhage treated in the intensive care unit at our university hospital. Computed tomography imaging findings and the level of consciousness on admission were recorded. Serum S100ß concentration was measured serially during the first six days of admission. Patients with subarachnoid hemorrhage (SAH group) or intracerebral hemorrhage (ICH group) were analyzed separately. The 3-month and 1-year functional outcomes were assessed using the Glasgow Outcome Scale (GOS). RESULTS: Of 108 patients enrolled, 66 were included in the SAH group and 42 in the ICH group. High initial S100ß concentration was associated with Glasgow Coma Score 3-6 on admission (SAH group 0.61 µg/L versus 0.15 µg/L, P=0.001 and ICH group 1.00 µg/L versus 0.42 µg/L, P=0.005). Initial S100ß concentration correlated with ICH volume (rho=0.50, P<0.001) and IVH Sum Score (rho=0.30, P=0.013). The thresholds for the initial S100ß concentration with 100% specificity for poor outcome (GOS 1-3) were 1.40 µg/L for SAH and 1.76 µg/L for ICH group. ORs varied between 3.1 and 6.1 for S100ß on poor outcome in the SAH group. Increasing S100ß level during study period was associated with poor outcome in the SAH group. CONCLUSIONS: Serum S100ß concentration corresponds with the severity of neurological insult and predicts poor outcome in patients with non-traumatic intracranial hemorrhage.

Muscle computed tomography patterns in patients with the mitochondrial DNA mutation 3243A>G.

Computed tomography provides a sensitive method for investigating skeletal muscle changes in neuromuscular diseases, but this method has not been applied to mitochondrial myopathies. We characterized the pattern of muscle involvement in patients with the 3243A>G mutation in mitochondrial DNA (mtDNA), the common MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) mutation. Twenty-four patients, age 19-73 years, with 3243A>G were examined. Clinical evaluation included assessment of muscle strength and functional capacity. All the patients underwent muscle computed tomography, and muscle samples from 17 of them were examined for the presence of ragged red fibres and for the 3243A>G heteroplasmy. Venous blood lactate at rest and serum creatine kinase were determined. Clinical myopathy was found in six patients, while nine showed mild muscle weakness and nine had normal muscle function. The upper and lower limbs were equally affected, but the proximal muscles were more severely affected than the distal ones. CT revealed abnormalities in the muscles of 13 patients (54%; 95% confidence interval, 33-76%), including the six with clinical myopathy and seven without clinical myopathy. Myopathic changes were found most frequently in the pelvic muscles, with predominant involvement of the gluteus maximus. These data show that CT reveals frequent abnormal findings in the muscle of patients with the 3243A>G mtDNA mutation. Muscle CT is a useful adjunct to clinical evaluation in these patients.

Dynamic MR imaging of brain tumors in low field using undersampled projection reconstruction.

A new application of the projection reconstruction method was developed, enabling dynamic T(1)-weighted contrast-enhanced magnetic resonance image (MRI) of brain tumors in a low-field imager. Two undersampled projection reconstruction spin echo sequences were implemented in an open low-field (0.23-T) MR imager, one with 64 and another with 42 projections in [0,pi], repetition time 150 ms, echotime 15 ms, and six slices were used in both sequences. The possibility of using these sequences to image dynamic contrast enhancement of brain tumors was studied in laboratory experiments and in two patient cases, one with fibrotic and the other with meningothelial meningioma. The laboratory experiments showed a nearly linear response in signal intensity to the concentration of gadopentetate dimeglumine in purified water up to 1.25 mM. Increasing concentrations up to 5.0 mM did not significantly affect the signal intensity, though starting from 3.0 mM concentration T(2) shortening decreased intensities slightly. The patient cases showed results consistent with an earlier study performed in a high-field imager. The results show that the studied sequences can be used to follow dynamic contrast enhancement in a low-field imager.

Computer-assisted diagnosis by temporal subtraction in postoperative brain tumor patients: a feasibility study.

RATIONALE AND OBJECTIVES: To introduce and evaluate a novel, image fusion-based technique that can be used to compare the findings of primary and control brain magnetic resonance imaging scans, with special attention to the differences found in this comparison. MATERIALS AND METHODS: A new technique named "colored difference mapping" was applied to the brain examinations of five patients. The possible changes in the magnetic resonance imaging findings were analyzed by the colored difference mapping technique and by using conventional film reading and the results were compared. RESULTS: Colored difference mapping accurately depicts the differences between successive magnetic resonance images and reveals small changes that are difficult to perceive in a visual evaluation. CONCLUSION: Colored difference mapping is suitable for comparison of images between two different radiologic examinations and helps to show even minimal changes in brain tissues.

A portable diagnostic workstation based on a Webpad: implementation and evaluation.

A wireless hand-held Webpad device was used to review a sample set of cranial computerized tomography (CT) studies to assess its diagnostic capabilities and its feasibility as a portable diagnostic workstation for radiology. The data-set consisted of 30 head CT studies of emergency cases. Two neuroradiologists and a senior radiologist participated in the evaluation of the portable workstation. They used a Web-based viewer that we developed, which provided all the major functionalities required for radiological image review. The reported radiological findings and diagnoses were compared with a gold standard, comprising a set of diagnoses previously formulated by a consensus panel of radiologists who had reviewed the original studies. The diagnoses made using the Webpad were correct (no major discrepancies) in 82 out of 90 interpretations (91%), which is comparable to the accuracy reported in image review with a conventional radiological workstation. The average total working time per diagnosis was 5 min 25 s (range 2-12 min). The simplicity of use of the system and its low cost make it suitable for distributing radiological studies within hospital facilities.

Survey of inappropriate use of magnetic resonance imaging.

OBJECTIVE: There are concerns that not all costly advanced imaging is appropriate. However, studies about the appropriateness of magnetic resonance imaging (MRI) are sparse. The aim of this study was to review various MRI examinations done at a university hospital to determine whether there is inappropriate use. METHODS: Altogether 150 common MRIs (upper abdomen or liver, lumbar spine, knee, head and head of children performed under anaesthesia, 30 each) were reviewed consecutively. The referrals and corresponding patient files were analysed by senior radiologists and the indications of the examinations were compared to the referral criteria. RESULTS: Seven per cent of the examinations were deemed inappropriate. All the MRIs of the head done on children were indicated. One to three examinations in all other subgroups were not indicated. The most common appropriate indications were ambiguous hepatic, pancreatic or adrenal lesions, prolonged lower back pain, suspicion of meniscus rupture, brain malignancy and developmental disorder of a child, respectively. CONCLUSIONS: Although the proportion of inappropriate examinations was not high; financial issues and the growing number of patients referred for MRI are of concern. Education and regular use of up-to-date referral guidelines could help to further improve appropriateness. MAIN MESSAGES: •Seven per cent of the MRI examinations analysed were inappropriate at a university hospital. •Everyday practices of a hospital may contribute to the level of appropriateness. •A survey of indications for previous MRI examinations might be helpful in various institutions.

Mild traumatic brain injury diagnosis frequently remains unrecorded in subjects with craniofacial fractures.

BACKGROUND: Traumatic brain injuries (TBI) in subjects with craniofacial fractures are usually diagnosed by emergency room physicians. We investigated how often TBI remains unrecorded in these subjects, and whether diagnostic accuracy has improved after the implementation of new TBI guidelines. METHODS: All subjects with craniofacial fractures admitted to Oulu University Hospital in 1999 and in 2007 were retrospectively identified. New guidelines for improving the diagnostic accuracy of TBI were implemented between 2000 and 2006. Clinical symptoms of TBI were gathered from notes on hospital charts and compared to the recorded diagnoses at discharge. Logistic regression was used to identify independent predictors for TBI to remain unrecorded. RESULTS: Of 194 subjects with craniofacial fracture, 111(57%) had TBI, 40 in 1999 and 71 in 2007. Fifty-one TBIs (46%) remained unrecorded at discharge, 48 being mild and 3 moderate-to-severe. Subjects with unrecorded TBI were significantly less frequently referred to follow-up visits. Failures to record the TBI diagnosis were less frequent (29/71, 41%) in 2007 than in 1999 (22/40, 55%), but the difference was not statistically significant. The most significant independent predictor for this failure was the clinical specialty (other than neurology/neurosurgery) of the examining physician (p<0.001). The subject's alcohol intoxication did not hamper the diagnosis of TBI. CONCLUSIONS: TBIs remain frequently unrecorded in subjects with craniofacial fractures. Recording of mild TBI slightly but insignificantly improved after the implementation of new guidelines.

Central nervous system-related symptoms and findings are common in acute Puumala hantavirus infection.

BACKGROUND: Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS) also called nephropathia epidemica (NE). Recent case reports and retrospective studies suggest that NE may damage the pituitary gland. Based on these observations, our goal was to explore the nature of this complication prospectively. METHODS: A total of 58 hospitalized patients with acute NE volunteered to participate. Central nervous system (CNS) symptoms were recorded, cerebrospinal fluid (CSF) samples were collected, human leukocyte antigen (HLA) haplotype was analyzed, brain magnetic resonance imaging (MRI) was acquired, and electroencephalography (EEG) was recorded. Patients with abnormal pituitary MRI finding were examined by an endocrinologist. RESULTS: Most patients experienced CNS symptoms, and half of the CSF samples were positive for PUUV IgM, elevated protein level, or leukocyte count. CSF of patients negative for DR15(2)-DQ6 haplotype was less frequently affected. MRI revealed pituitary hemorrhage in two patients; these two patients suffered sudden loss of vision associated with headache, and they both developed hypopituitarism. Only one patient required long-term hormonal replacement therapy. CONCLUSION: CNS-related symptoms and inflammation in the CSF are common in acute NE. Genetic properties of the host may predispose to CNS involvement. It does seem that pituitary injury and subsequent hormonal insufficiency may complicate the recovery.