Transcranial doppler sonography is not a valid diagnostic tool for detection of basilar artery stenosis or in-stent restenosis: a retrospective diagnostic study.

BACKGROUND: There are contradictory reports concerning the validity of transcranial sonography (TCD and TCCS) for examinations of the basilar artery. Here we investigated sensitivity and specificity of transcranial sonography for the detection of basilar artery stenosis and in-stent-restenosis compared to cerebral angiography. METHODS: We analyzed data of 104 examinations of the basilar artery. The association between sonographic peak systolic velocity (PSV) and degree of stenosis obtained by cerebral angiography was evaluated applying Spearman's correlation coefficient. Receiver Operating Characteristics (ROC) curves and areas under the curve (AUC) were calculated for the detection of a ≥50% stenosis defined by angiography. Optimal cut-off was derived using the Youden-index. RESULTS: A weak but statistically significant correlation between PSV and the degree of stenosis was found (n=104, rho=0.35, p<0.001). ROC analysis for a detection of ≥50% stenosis showed an AUC of 0.70, a sensitivity of 74.0% and a specificity of 65.0% at the optimal cut off of 124 cm/s. Results were consistent when analyzing examinations done in stented and unstented arteries separately (TCD VS DSA/CTA in unstented artery: AUC=0.66, sensitivity 61.0%, specificity 65.0%, TCD/TCCS VS DSA in stented artery: AUC=0.63, sensitivity 71.0%, specificity 82.0%). Comparing TCCS measurements exclusively to angiography, ROC analysis showed an AUC of 1.00 for the detection of an in-stent-restenosis ≥50% with a sensitivity and specificity of 100% when a PSV of 132 cm/s was used as a cut off value. CONCLUSION: Validity of TCD in the assessment of basilar artery stenosis or in-stent restenosis is poor. First results for TCCS are promising, but due to the small samplesize further studies with larger samples sizes are warranted.

Contrast-enhanced shunt series ("shuntography") compare favorably to other shunt imaging modalities in detecting shunt occlusion.

BACKGROUND: Obstruction is a common cause of ventriculo-peritoneal shunt failure. Head computed tomography and plain x-ray examinations of shunt tubing ("shunt series") are routinely used in patients readmitted for reemerging symptoms but are of limited value. The validity of shunt series can be improved by applying contrast agent into the system (contrast-enhanced shunt series, a.k.a. a "shuntogram" or "shuntography"). We hypothesized that contrast-enhanced shunt series have a high predictive value for shunt revision surgeries. METHODS: We retrospectively re-evaluated 107 contrast-enhanced shunt series and reviewed the patient histories. We defined outcome parameters for calculating the utility of a pathological contrast-enhanced shunt series in predicting revision surgery. RESULTS: Of 107 contrast-enhanced shunt series, 41 examinations were positive for obstruction, mainly of the ventricular (36.5 %) and the peritoneal catheter (48.8 %). Within 30 days, 35 successful revision surgeries and 3 revision surgeries without resolution of symptoms were performed. In two cases the shunt tubing was found to be patent. Sixty-six negative examinations resulted in two revision surgeries, in addition to ten surgeries not attempting to restore patency. After 30 days, the specificity of contrast-enhanced shunt series for shunt failure identification was calculated at 92.8 %, the sensitivity at 94.7 %, the positive predictive value at 87.8 %, and the negative predictive value at 97.0 %. CONCLUSIONS: The contrast-enhanced shunt series method is a highly specific examination with a negative predictive value exceeding that of head computed tomography and plain shunt series. Compared to radionuclide marker studies, contrast-enhanced shunt series demonstrate better spatiotemporal resolution, enabling focused local surgical repair.

Clinical findings and diagnosis in genetic prion diseases in Germany.

To describe the clinical syndrome and diagnostic tests in patients with genetic prion diseases (gPD) in Germany. Clinical features, MRI, EEG, and CSF markers were studied in 91 patients (28 D178N, 20 E200K, 17 inserts, 13 V210I, 8 P102L, 5 E196K). Dementia (35 %) and ataxia (29 %) were the most common initial symptoms and signs. A wide variety and high frequency of neurological/psychiatric symptoms and signs was found during disease course in all patients independently of the type of the mutation. Psychiatric manifestations were frequent (87 %). Neuropsychological abnormalities were observed in 67 %, and aphasia was the most common disturbance (45 %). In E200K, V210I and D178N patients, visual/oculomotor deficits were followed by ataxia early in the disease. Dementia followed by ataxia at onset was common in patients with insert and E196K mutation. P102L patients had isolated ataxia over a longer time period followed by pyramidal signs. Dementia was present only late in the disease course. All clinical routine tests such as MRI, EEG and CSF tests were less sensitive than in sporadic CJD. We provide the first detailed analysis of clinical signs and symptoms in a large group of patients with gPD. Frequency of clinical symptoms and signs was similar in different mutations in a later disease course, but the sequence of occurrence may be of great diagnostic importance. CSF markers were shown to be more sensitive than MRI and EEG.

Female gender predisposes for cerebrospinal fluid overdrainage in ventriculoperitoneal shunting.

BACKGROUND: Gravitational valves (GVs) prevent overdrainage in ventriculoperitoneal shunting (VPS). However, there are no data available on the appropriate opening pressure in the shunt system when implementing a GV. We performed a retrospective analysis of hydrocephalic patients who were successfully treated with VPS which included one or more GV. METHOD: In this retrospective study in adult VPS patients with GVs, we analysed all available data, including the most recent computed tomography (CT) scans, to determine the best adjustments for alleviating any symptoms of overdrainage and underdrainage. Vertical effective opening pressure (VEOP) of the entire shunt system, including the differential pressure valve, was determined. RESULTS: One hundred and twenty-two patients were eligible for the study. Of these, female patients revealed a higher VEOP compared with males (mean, 35.6 cmH2O [SD ± 2.46] vs 28.9 cmH2O [SD ± 0.87], respectively, p = 0.0072, t-test). In patients older than 60 years, lower VEOPs, by a mean of 6.76 cmH2O ± 2.37 (p = 0.0051), were necessary. Mean VEOP was found to be high in idiopathic intracranial hypertension (IIH; 41.6 cmH2O) and malresorptive and congenital HC (35.9 and 36.3), but low in normal pressure HC (27.5, p = 0.0229; one-way ANOVA). In the total cohort, body mass index (BMI) and height did not correlate with VEOP. Twelve patients required a VEOP of more than 40 cmH2O, and in eight of these patients this was accomplished by using multiple GVs. All but one of these eight patients were of female gender, and none of the latter were treated for normal pressure hydrocephalus (NPH) (p = 0.0044 and p = 0.0032, Fisher's exact test). CONCLUSIONS: In adult VPS patients, female gender increases the risk of overdrainage requiring higher VEOPs. Initial implantation of adjustable GV should be considered in female patients treated with VP shunts for pathology other than NPH.

The Pattern of Brain Microhemorrhages After Severe Lung Failure Resembles the One Seen in High-Altitude Cerebral Edema.

OBJECTIVES: After suffering from severe acute respiratory distress syndrome, several patients show generalized brain alterations and atrophy. A distinctive morphologic pattern of cerebral injury, however, has not been found so far. DATA SOURCES: We present the history of three patients who survived severe acute respiratory distress syndrome. In these patients, MRI of the brain showed multiple microhemorrhages predominantly in the splenium of the corpus callosum. An identical pattern of microhemorrhages has previously been described in mountaineers who suffered from high-altitude cerebral edema. CONCLUSIONS: This report demonstrates that patients after treatment for acute respiratory distress syndrome and high-altitude cerebral edema show congruent cerebral injuries. Further investigation into the similarities of the causative conditions and neurologic consequences might reveal underlying pathophysiologic mechanisms and clinical implications of this observation.

Impact of Vaccination Status on Outcome of Patients With COVID-19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

Alberta Stroke Program Early CT Scale evaluation of multimodal computed tomography in predicting clinical outcomes of stroke patients treated with aspiration thrombectomy.

BACKGROUND AND PURPOSE: Patient selection is crucial in the endovascular treatment of acute ischemic stroke patients. Baseline computed tomographic (CT) images, evaluated with the Alberta Stroke Program Early CT Scale (ASPECTS), are considered significant predictors of outcome. In this study, we evaluated CT images and perfusion parameters, analyzed with ASPECTS, as final outcome predictors after endovascular stroke treatment. METHODS: We analyzed a cohort of patients with acute ischemic stroke and endovascular treatment. Patients with an occlusion of the M1 segment and multimodal CT imaging were included. CT perfusion data were reconstructed using commercial software. Two experienced neuroradiologists separately reviewed and scored CT and CT perfusion images with the ASPECTS score. Parameters were compared between patients with poor and with favorable follow-up outcome. Significantly different variables were further analyzed by forward stepwise logistic regression. RESULTS: Fifty-one patients were included in our study. Baseline characteristics did not differ between patients with favorable and poor outcomes. No significant difference in recanalization status, the various times, or CT ASPECTS was demonstrated between these 2 groups. Significant differences were demonstrated for age (P=0.0049), cerebral blood volume ASPECTS (P=0.0007), and between cerebral blood volume and cerebral blood flow ASPECTS (P=0.0045). Cerebral blood volume ASPECTS>7 demonstrated the highest sensitivity and specificity for favorable outcome with 84% and 79%, respectively. CONCLUSIONS: CT perfusion parameters, evaluated with ASPECTS, are optimal predictors of outcome and are more sensitive and specific than CT ASPECTS in the prediction of favorable outcome. Use of these parameters in treatment decisions could reduce futile recanalizations.

Magnetic resonance imaging in E200K and V210I mutations of the prion protein gene.

Magnetic resonance imaging (MRI), with diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR), is a useful diagnostic investigation for Creutzfeldt-Jakob disease (CJD). Amendment of the diagnostic criteria for sporadic CJD (sCJD) to include defined MRI alterations has just recently been proposed. We analyzed MRI scans with FLAIR and/or DWI available of 29 patients with the E200K or the V210I mutation, and a control group of 29 sCJD patients to compare the MRI lesion profile and evaluate the applicability of new MRI criteria to genetic CJD patients. FLAIR images of all 29 patients and controls and DWI images of 15 genetic CJD and 13 sCJD were rated by 2 neuroradiologists blinded to diagnosis and genetic testing. In genetic CJD (gCJD) patients, hyperintensities on FLAIR could be found in the putamen in 55% and the caudate nucleus in 66% and on DWI in 33% and 60%, respectively. Lesion profile and frequency of hyperintensities did not differ significantly from the findings in sCJD. New diagnostic MRI criteria yield similar sensitivity for gCJD and sCJD, being 79% and 72%, respectively. MRI provides useful information in E200K and V210I gCJD patients. The alterations strongly resembled those seen in sCJD, once again demonstrating the similarity of the clinical syndrome in patients with these particular mutations.

Diagnosing cerebral aneurysms by computed tomographic angiography: meta-analysis.

OBJECTIVE: Cerebral aneurysms can cause substantial morbidity and mortality, specifically if they rupture, leading to nontraumatic subarachnoid hemorrhage (SAH). This meta-analysis summarizes evidence about the accuracy of noninvasive computed tomographic (CT) angiography for diagnosing intracranial aneurysms in symptomatic patients. METHODS: Four databases including PubMed were searched without language restrictions from January 1995 to February 2010. Two independent reviewers selected and extracted 45 studies that compared CT angiography with digital subtraction angiography (DSA) and/or intraoperative findings in patients suspected of having cerebral aneurysms. Data from eligible studies were used to reconstruct 2 x 2 contingency tables on a per-patient basis in at least 5 diseased and 5 nondiseased patients, with additional data on a per-aneurysm basis when available. RESULTS: The 45 included studies generally were of high methodological quality. Among the 3,643 patients included, about 86% had nontraumatic SAH, and 77% had cerebral aneurysms. Overall, CT angiography had a pooled sensitivity of 97.2% (95% confidence interval, 95.8-98.2%) for detecting and specificity of 97.9% (95.7-99.0%) for ruling out cerebral aneurysms on a per-patient basis. On a per-aneurysm basis, the pooled sensitivity was 95.0% (93.2-96.4%), and the specificity 96.2% (92.9-98.0%). The diagnostic accuracy of CT angiography with 16- or 64-row multidetector CT was significantly higher than that of single-detector CT, especially in detecting small aneurysms of ≤ 4 mm in diameter. INTERPRETATION: CT angiography has a high accuracy in diagnosing cerebral aneurysms, specifically when using modern multidetector CT. In the future, CT angiography may increasingly supplement or selectively replace DSA in patients suspected of having a cerebral aneurysm.

Mechanical thrombectomy for acute ischemic stroke in COVID-19 patients: multicenter experience in 111 cases.

BACKGROUND: Data on the frequency and outcome of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in patients with COVID-19 is limited. Addressing this subject, we report our multicenter experience. METHODS: A retrospective cohort study was performed of consecutive acute stroke patients with COVID-19 infection treated with MT at 26 tertiary care centers between January 2020 and November 2021. Baseline demographics, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at discharge and 90 days were noted. RESULTS: We identified 111 out of 11 365 (1%) patients with acute or subsided COVID-19 infection who underwent MT due to LVO. Cardioembolic events were the most common etiology for LVO (38.7%). Median baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score were 16 (IQR 11.5-20) and 9 (IQR 7-10), respectively. Successful reperfusion (mTICI ≥2b) was achieved in 97/111 (87.4%) patients and 46/111 (41.4%) patients were reperfused completely. The procedure-related complication rate was 12.6% (14/111). Functional independence was achieved in 20/108 (18.5%) patients at discharge and 14/66 (21.2%) at 90 days follow-up. The in-hospital mortality rate was 30.6% (33/108). In the subgroup analysis, patients with severe acute COVID-19 infection requiring intubation had a mortality rate twice as high as patients with mild or moderate acute COVID-19 infection. Acute respiratory failure requiring ventilation and time interval from symptom onset to groin puncture were independent predictors for an unfavorable outcome in a logistic regression analysis. CONCLUSION: Our study showed a poor clinical outcome and high mortality, especially in patients with severe acute COVID-19 infection undergoing MT due to LVO.

Dura mater graft-associated Creutzfeldt-Jakob disease: the first case in Korea.

Since 1987, dura mater graft-associated iatrogenic Creutzfeldt-Jakob disease (dCJD) has been reported in many countries. We report the first case of dCJD in Korea. A 54-yr-old woman, who underwent resection of the meningioma in the left frontal region and received a dura mater graft 23 yr ago presented with dysesthesia followed by psychiatric symptoms and ataxia. Her neurological symptoms rapidly progressed to such an extent that she exhibited myoclonus, dementia, and pyramidal and extrapyramidal signs within 8 weeks. The 14-3-3 protein was detected in her cerebrospinal fluid; however, an electroencephalogram did not reveal characteristic positive sharp wave complexes. Diffusion-weighted magnetic resonance images, obtained serially over 64 days, revealed the rapid progression of areas of high signal intensity in the caudate nucleus and cingulate gyrus to widespread areas of high signal intensity in the cortex and basal ganglia. Pathological examination of brain biopsy specimens confirmed the presence of spongiform changes and deposition of prion protein in the neurons and neuropils.

Robot-assisted image-guided transcranial magnetic stimulation for somatotopic mapping of the motor cortex: a clinical pilot study.

PURPOSE: Shape and exact location of motor cortical areas varies among individuals. The exact knowledge of these locations is crucial for planning of neurosurgical procedures. In this study, we have used robot-assisted image-guided transcranial magnetic stimulation (Ri-TMS) to elicit MEP response recorded for individual muscles and reconstruct functional motor maps of the primary motor cortex. METHODS: One healthy volunteer and five patients with intracranial tumors neighboring the precentral gyrus were selected for this pilot study. Conventional MRI and fMRI were obtained. Transcranial magnetic stimulation was performed using a MagPro X100 stimulator and a standard figure-of-eight coil positioned by an Adept Viper s850 robot. The fMRI activation/Ri-TMS response pattern were compared. In two cases, Ri-TMS was additionally compared to intraoperative direct electrical cortical stimulation. RESULTS: Maximal MEP response of the m. abductor digiti minimi was located in an area corresponding to the "hand knob" of the precentral gyrus for both hemispheres. Repeated Ri-TMS measurements showed a high reproducibility. Simultaneous registration of the MEP response for m. brachioradialis, m. abductor pollicis brevis, and m. abductor digiti minimi demonstrated individual peak areas of maximal MEP response for the individual muscle groups. Ri-TMS mapping was compared to the corresponding fMRI studies. The areas of maximal MEP response localized within the "finger tapping" activated areas by fMRI in all six individuals. CONCLUSIONS: Ri-TMS is suitable for high resolution non-invasive preoperative somatotopic mapping of the motor cortex. Ri-TMS may help in the planning of neurosurgical procedures and may be directly used in navigation systems.

Untreated glioblastoma multiforme: increased myo-inositol and glutamine levels in the contralateral cerebral hemisphere at proton MR spectroscopy.

PURPOSE: To use localized in vivo proton magnetic resonance (MR) spectroscopy of the contralateral hemisphere in patients with glioblastoma multiforme (GBM) to detect alterations in cerebral metabolites as potential markers of infiltrating GBM cells. MATERIALS AND METHODS: The study was approved by the ethics committee, and written informed consent was obtained. Twenty-two patients with newly diagnosed and untreated GBM underwent in vivo single-voxel short echo time proton MR spectroscopy with a 3-T MR imaging system. Absolute metabolite concentrations in the hemisphere contralateral to the tumor were compared with data from five patients with low-grade gliomas (LGGs) and from a group of 14 age-matched control subjects by using analysis of variance and subsequent t tests or corresponding nonparametric tests. RESULTS: In the contralateral hemisphere, MR spectroscopy revealed increased concentrations of myo-inositol and glutamine. Mean myo-inositol levels were significantly increased in patients with GBM (3.6 mmol/L +/- 0.8 [standard deviation]) relative to levels in control subjects (3.1 mmol/L +/- 0.6; P = .03) and tended to be higher relative to levels in patients with LGG (2.7 mmol/L +/- 0.8; P = .09). Mean glutamine concentrations in patients with GBM (3.4 mmol/L +/- 0.9) differed significantly from those in control subjects (2.7 mmol/L +/- 0.7; P = .01); mean concentrations in patients with GBM differed from those in patients with LGG (2.4 mmol/L +/- 0.5; P = .01). There were no significant differences between data in patients with LGG and in control subjects. CONCLUSION: Increased concentrations of myo-inositol and glutamine in the contralateral normal-appearing white matter of GBM patients are consistent with mild astrocytosis and suggest the detectability of early neoplastic infiltration by using proton MR spectroscopy in vivo.

Evaluation of angiographic computed tomography in the follow-up after endovascular treatment of cerebral aneurysms--a comparative study with DSA and TOF-MRA.

Following coil embolization of intracranial aneurysms, many centers perform at least one digital subtraction angiography (DSA) continuing with time-of-flight magnetic resonance angiography (TOF-MRA). Angiographic computed tomography (ACT) provides high-resolution data from a rotational acquisition of a c-arm-mounted flat panel detector. This study evaluates possible advantages of applying ACT in aneurysm follow-up. In 22 patients DSA examinations with a rotational acquisition were performed. Rotational data were processed into an isotropic high-resolution volume. TOF-MRA was performed the day before DSA. Three experienced neuroradiologists performed a rating of the occlusion rate and a subjective method comparison. Weighted kappa statistics were calculated to assess the level of interobserver agreement. Compared to DSA, the diagnostic value of ACT as well as of TOF-MRA was rated to be inferior, although the sensitivity of detecting residual necks was higher with both techniques. Compared to TOF-MRA, ACT achieves favorable ratings only in aneurysms after stent-remodeling. Interobserver agreement was high for all techniques. Ratings of the occlusion rate correlated highly between all observers (r>0.85, p<0.001, respectively). In selected patients ACT can add valuable diagnostic information to DSA. TOF-MRA remains a highly sensitive method for aneurysm follow-up.

High-resolution maps of magnetization transfer with inherent correction for RF inhomogeneity and T1 relaxation obtained from 3D FLASH MRI.

An empirical equation for the magnetization transfer (MT) FLASH signal is derived by analogy to dual-excitation FLASH, introducing a novel semiquantitative parameter for MT, the percentage saturation imposed by one MT pulse during TR. This parameter is obtained by a linear transformation of the inverse signal, using two reference experiments of proton density and T(1) weighting. The influence of sequence parameters on the MT saturation was studied. An 8.5-min protocol for brain imaging at 3 T was based on nonselective sagittal 3D-FLASH at 1.25 mm isotropic resolution using partial acquisition techniques (TR/TE/alpha = 25ms/4.9ms/5 degrees or 11ms/4.9ms/15 degrees for the T(1) reference). A 12.8 ms Gaussian MT pulse was applied 2.2 kHz off-resonance with 540 degrees flip angle. The MT saturation maps showed an excellent contrast in the brain due to clearly separated distributions for white and gray matter and cerebrospinal fluid. Within the limits of the approximation (excitation <15 degrees , TR/T(1) less sign 1) the MT term depends mainly on TR, the energy and offset of the MT pulse, but hardly on excitation and T(1) relaxation. It is inherently compensated for inhomogeneities of receive and transmit RF fields. The MT saturation appeared to be a sensitive parameter to depict MS lesions and alterations of normal-appearing white matter.

Brain biopsy in patients with suspected Creutzfeldt-Jakob disease.

OBJECT: Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder with diagnostic criteria defined as a combination of clinical symptoms, electroencephalography findings, cerebrospinal fluid (CSF) analysis, and MR imaging results. Special subtypes are known to present with an atypical course and test findings that can complicate the clinical diagnosis. In such patients a brain biopsy can support the clinical approach. METHODS: The authors studied the records on 26 brain biopsies conducted in patients with suspected CJD who had been referred to the CJD Surveillance Unit in Germany between 1993 and 2005. RESULTS: Of the 26 included patients, 11 suffered from neuropathologically confirmed CJD, which in 5 cases had been deemed clinically "probable" and in 2 had been deemed "possible." The disease in the remaining 4 patients had been categorized as "other" prior to neuropathological confirmation of CJD. The results of 15 brain biopsies showed no features of prion disease. None of these 15 patients had received a probable diagnosis of CJD, 4 had a possible diagnosis, and 11 had received a diagnosis of "other." Three of the cases classified as other and none of those with CJD presented with pleocytosis in the CSF. In 73% of the other cases, biopsy sampling did not reveal any results characteristic of CJD but did not provide specific findings on which to base a differential diagnosis. Autopsy confirmed the biopsy diagnosis of CJD in all cases, and additionally confirmed that CJD was not present in 3 patients who had nondiagnostic biopsy results. CONCLUSIONS: Biopsy sampling may be helpful in the diagnostic approach to rare cases of dementia for which a reliable diagnosis cannot be established on the basis of clinical symptoms, CSF parameters, electroencephalography, and MR imaging results.