Executive and behavioral deficits share common neural substrates in frontotemporal lobar degeneration - a pilot FDG-PET study.

Behavioral and executive dysfunctions are typical symptoms of frontotemporal lobar degeneration, associated with its subtypes frontotemporal and semantic dementia. Although both functions depend on the frontal lobes, no study has yet compared their neural correlates in frontotemporal lobar degeneration. Accordingly, we correlated clinical scores of behavioral and executive deficits with glucose utilization as measured by [(18)F]fluorodeoxyglucose positron emission tomography in 17 patients with frontotemporal lobar degeneration and 9 age- and sex-matched control subjects. Impairment in executive functions was measured by the Behavioral Assessment of the Dysexecutive Syndrome, a modified Stroop paradigm and/or the Tower of Toronto Test. Behavioral deficits were examined with the Neuropsychiatric Inventory. Executive dysfunction was correlated with diminished glucose utilization in frontomedial and frontolateral cortices. Brain regions included the anterior cingulate and midcingulate gyri, anterior medial frontal cortex, and left frontolateral cortex. Behavioral deficits were associated with mainly frontomedial networks, particularly the anterior medial frontal cortex, gyrus rectus, and area subcallosa. Our pilot study reveals partially overlapping neural correlates of executive and behavioral dysfunction in frontotemporal lobar degeneration. The results suggest that some behavioral deficits, namely disinhibition and appetite and eating abnormalities, are particularly related to executive dysfunction. This hypothesis might be further explored in studies involving larger patient groups.

Clinical findings in the chronic phase of traumatic brain injury: data from 12 years' experience in the Cognitive Neurology Outpatient Clinic at the University of Leipzig.

BACKGROUND: There are many unresolved issues in the diagnosis and treatment of persons with traumatic brain injury (TBI) in its post-acute and chronic phases. This article deals with two problems of clinical importance: (i) the interrelationships between structural brain damage, brain function, and clinical outcome, and (ii) post-traumatic epilepsy. METHODS: Exploratory, retrospective analysis of clinical, neuroradiological (MRI), and neuropsychological data of all patients with TBI who were treated in a cognitive neurology outpatient clinic of a German university hospital over a period of 12 years (n=320). RESULTS: 156 patients (48.8%) had brain contusions, 83 of them (25.9%) as the sole neuroradiological abnormality. Traumatic micro-hemorrhages were seen in 148 patients (46.2%) and were the sole neuroradiological abnormality in 79 of them (24.7%). 49 patients (15.3%) had no structural brain lesion. There was no obvious correlation between the neuroradiological findings and the clinical outcome, as measured either by a general outcome parameter such as the extended Glasgow Outcome Scale (GOSE) or by neuropsychological testing. 47 patients (14.7%) had post-traumatic epilepsy; its occurrence was positively correlated with the presence of brain contusions, but not with an isolated diagnosis of diffuse axonal injury (DAI). CONCLUSION: A comparison of the findings of neuroradiological studies and neuropsychological tests among patients in the chronic phase of traumatic brain injury does not reveal any simple relationship between structural and functional brain abnormalities. Diffuse axonal injury is often present in combination with other findings, and it may well be the only structural abnormality in many cases; therefore, all symptomatic patients should undergo MRI of the brain. Patients with isolated DAI seem to be less prone to post-traumatic epilepsy than those with brain contusions.

Cognitive dysfunction, urinary retention, and a lesion in the thalamus--beware of possible toxocariasis of the central nervous system.

Toxocariasis of the central nervous system is usually characterized by an eosinophilic meningitis, encephalitis or myelitis. We here report a patient with an at least 7 years history of unexplained neurologic signs and symptoms. MRI showed a cystic lesion in the left thalamus, compatible with a parasitic infection. Blood and CSF analyses were positive for Toxocara canis IgG Western-blot, but were otherwise unremarkable. The case report raises the question whether there are chronic or late variants of this disease.

Aerophagia and belching after herpes simplex encephalitis.

The etiology of abnormal belching is not known. Currently, it is being subsumed under "functional gastroduodenal disorders." Here, we report the unusual case history of a patient who developed aerophagia and consecutive excessive belching in association with herpes simplex encephalitis. The case report adds to the limited information about potential organic geneses of belching. Implications for possible medical therapies are discussed.

Comparative magnetic resonance imaging at 1.5 and 3 Tesla for the evaluation of traumatic microbleeds.

Traumatic microbleeds (TMBs) can be regarded as a radiological marker of diffuse axonal injury (DAI). We sought to investigate the impact of the field strengths on the depiction of TMBs by T2*-weighted gradient echo magnetic resonance imaging (MRI). By the use of comparative MRI of 14 patients (age range, 22-62 years) on 1.5- and a 3 T (Tesla) systems at a median time interval of 61 months after traumatic brain injury (TBI), we found 239 (range 0.5-48.5, median 7.5) TMBs at 1.5 T, and 470 (range 2-118, median 18.5) TMBs at 3 T, respectively (p=0.001). However, in all but one patients MRI at 1.5 T also clearly showed TMBs. A significant negative correlation between the number of TMBs and the time interval TBI-MRI was observed, which was weaker for the imaging at 3 T (r(s)=-0.798; p=0.001; and r(s)=-0.649; p=0.012, respectively). In conclusion, T2*-weighted gradient-echo MRI at 3 T is superior as compared to MRI at 1.5 T for the detection of TMBs. Nevertheless, in clinical practice, MRI at 1.5 T seems to be sufficient for this purpose. MRI at 3 T may be appropriate if there is a strong clinical suspicion of DAI, despite unremarkable routine MRI, and possibly also if evidence of DAI is sought after a long interval from trauma.

Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies.

It is well known that traumatic brain injury particularly affects the frontal lobes. Consequently, patients often suffer from executive dysfunction and behavioral disturbances. Accordingly, our study aimed at investigating patients after traumatic brain injury with two tasks involving different functional processes and structural networks supported by the frontal lobes. Two paradigms were applied: the Stroop color-word task and a task in which subjects had to inhibit imitative response tendencies. We selected a patient group solely with diffuse axonal injury, as this type of injury is homogenous and is correlated with cognitive dysfunction more than focal contusions. To evaluate long-term effects most relevant for rehabilitation, we selected a patient group whose brain injuries dated back several years. Our results show that patients with diffuse axonal injury inhibited imitative responses more successfully than control subjects, whereas executive processes examined with the Stroop task were unaltered. Interestingly, impairments were tightly correlated both with the length of the post-traumatic amnesia predicting outcome in traumatic brain injury and with behavioral disturbances. Impairments in the imitation-inhibition task may indicate alterations in an anterior frontomedian neural network even years after traumatic brain injury.

Neurovascular coupling is impaired in cerebral microangiopathy--An event-related Stroop study.

Small-vessel disease or cerebral microangiopathy is a common finding in elderly people leading finally to subcortical ischemic vascular dementia. Because cerebral microangiopathy impairs vascular reactivity and affects mainly the frontal lobes, we hypothesized that brain activation decreases during an event-related color-word matching Stroop task. 12 patients suffering from cerebral microangiopathy were compared with 12 age-matched controls. As an imaging method we applied functional near-infrared spectroscopy, because it is particularly sensitive to the microvasculature. The Stroop task led to activations in the lateral prefrontal cortex. Generally, the amplitude of the hemodynamic response was reduced in patients in tight correlation with behavioral slowing during the Stroop task and with neuropsychological deficits, namely attentional and executive dysfunction. Interestingly, patients showed an early deoxygenation of blood right after stimulation onset, and a delay of the hemodynamic response. Whereas the amplitude of the hemodynamic response is reduced in the frontal lobes also with normal aging, data suggest that impairments of neurovascular coupling are specific for cerebral microangiopathy. In summary, our findings indicate frontal dysfunction and impairments of neurovascular coupling in cerebral microangiopathy.

The clinical spectrum of blunt cerebrovascular injury.

BACKGROUND: Incidence, prevalence, and clinical impact of blunt cerebrovascular injury (BCVI) are unknown. There are no standardized recommendations for screening. REVIEW SUMMARY: A databank of 306 patients with a history of trauma was searched for all subjects with a proven or suspected concomitant BCVI. All patients had undergone MRI for the evaluation of traumatic and vascular cerebral lesions. The diagnosis of BCVI relies on angiographic and/or ultrasound findings. By way of illustration, the case histories of the patients are reported. Eleven subjects (3.6%) were identified. In 8 patients (2.6%), the diagnosis of BCVI can be regarded as proven; in 3 patients (0.98%), a diagnosis of BCVI is probable. The patients could be sorted into the following categories: (i) patients with BCVI and early strokes, (ii) patients with BCVI and late strokes, (iii) patients with early strokes and no detectable BCVI/vessel abnormality, (iv) patients with occult BCVI. Evidence of cerebral ischemia/stroke was present in 9 patients (82%, or 2.9% of all patients). In all patients with stroke, it was the major or sole cause of disability. CONCLUSIONS: BCVI and BCVI-related strokes are not rare. The time window for the development of ischemic complications is highly variable and may be longer than is currently assumed. Even if clinically silent, a diagnosis of BCVI has medicolegal implications and may influence therapy and prognosis in later life. Because of the association of BCVI and motor vehicle accidents, screening is suggested in these patients, and ultrasound could be a practical tool. Although there is substantial suspicion for BCVI in individual trauma patients suffering from stroke, the diagnosis cannot always been proven.

Cognitive sequelae of diffuse axonal injury.

BACKGROUND: The results of recent studies on cognitive disability after traumatic brain injury-associated diffuse axonal injury (DAI) are inconsistent. In these studies, the diagnosis of DAI relied on cranial computed tomography. OBJECTIVE: To further clarify the extent and severity of a possibly DAI-associated cognitive impairment by the use of magnetic resonance imaging (MRI) and detailed neuropsychological testing. DESIGN AND PARTICIPANTS: From a databank of 299 patients with traumatic brain injury, 18 patients (age range, 17-50 years; median initial Glasgow Coma Scale score, 5) who showed an MRI lesion pattern compatible with pure DAI were identified. All of the patients had undergone MRI on a 3-T system. Pure DAI was defined by the findings of traumatic microbleeds on T2*-weighted gradient-echo images in the absence of otherwise traumatic or nontraumatic MRI abnormalities. MAIN OUTCOME MEASURES: Neuropsychological performance in the categories of attention and psychomotor speed, executive functions, spans, learning and memory, and intelligence 4 to 55 months (median, 9 months) after traumatic brain injury. RESULTS: All of the patients showed impairments of 1 or more cognitive subfunctions, and no cognitive domain was fundamentally spared. Memory and executive dysfunctions were most frequent, the former reaching a moderate to severe degree in half of the patients. In comparison, deficits of attention, executive functions, and short-term memory were mostly mild. Correlations between the amount of traumatic microbleeds and specific or global cognitive performance were absent. CONCLUSIONS: An MRI lesion pattern compatible with isolated DAI is associated with persistent cognitive impairment. The traumatic microbleed load is no sufficient parameter for the assessment of DAI severity or functional outcome.

Circadian variability is negligible in primary visual cortices as measured by fNIRS.

Neural activation leads to an increase of regional cerebral blood flow. Most of the functional imaging studies implicitly assume that variability of the hemodynamic response throughout a single day is negligible. To test this assumption we measured brain activation by functional near-infrared spectroscopy (fNIRS) in the visual cortex of ten subjects six times throughout the day, from 0800-1800 h, during an event-related checkerboard paradigm. Concentration of oxygenated hemoglobin increased, whereas concentration of deoxygenated hemoglobin decreased at each time point examined, without significant influences of daytime. Variability of the hemodynamic response was higher across subjects than for single subjects across day. In conclusion, our study is the first one supporting the common practice of ignoring circadian variability in functional imaging studies.

Spontaneous slow hemodynamic oscillations are impaired in cerebral microangiopathy.

Small-vessel disease or cerebral microangiopathy (CMA) is a common finding in elderly people. It is related to a variety of vascular risk factors and may finally lead to subcortical ischemic vascular dementia. Because vessel stiffness is increased, we hypothesized that slow spontaneous oscillations are reduced in cerebral hemodynamics. Accordingly, we examined spontaneous oscillations in the visual cortex of 13 patients suffering from CMA, and compared them with 14 age-matched controls. As an imaging method we applied functional near-infrared spectroscopy, because it is particularly sensitive to the microvasculature. Spontaneous low-frequency oscillations (LFOs) (0.07 to 0.12 Hz) were specifically impaired in CMA in contrast to spontaneous very-low-frequency oscillations (0.01 to 0.05 Hz), which remained unaltered. Vascular reagibility was reduced during visual stimulation. Interestingly, changes were tightly related to neuropsychological deficits, namely executive dysfunction. Vascular alterations had to be attributed mainly to the vascular risk factor arterial hypertension. Further, results suggest that the impairments might be, at least partly, reversed by medical treatment such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Results indicate that functional near-infrared spectroscopy may detect changes in the microvasculature due to CMA, namely an impairment of spontaneous LFOs, and of vascular reagibility. Hence, CMA accelerates microvascular changes due to aging, leading to impairments of autoregulation.

Serial 18F-fluoro-2-deoxy-D-glucose positron emission tomography and magnetic resonance imaging of paraneoplastic limbic encephalitis.

OBJECTIVES: To review and expand the existing literature of magnetic resonance imaging (MRI) and positron emission tomography (PET) of paraneoplastic limbic encephalitis (PLE). METHODS: We performed serial MRI and 18F-fluoro-2-deoxy-D-glucose (FDG)-PET in a patient with anti-Ma2-positive PLE. In addition, we reviewed the relevant literature by conducting a search in the Medline database. RESULTS: We found a total of 7 published patient studies of possible or probable PLE containing both MRI and PET data. In 1 of these reports, the diagnosis of PLE can be regarded as proven. The results of the previous studies are controversial. Epileptic activity and inflammation are assumed to be underlying mechanisms of increased FDG uptake. In our study, we found a focal tracer accumulation in the left medial temporal lobe, which increased during the first 9 months of follow-up and corresponded with an increase of serum anti-Ma2 antibody titers. The MRI findings showed a hyperintense signal change in the left medial temporal lobe without contrast enhancement, which remained unchanged over time. CONCLUSIONS: The results of functional and structural imaging in PLE may differ substantially. Results of FDG-PET can demonstrate focal hypermetabolism over a long time, which may indicate therapeutic potential. A prospective study with more patients will be needed to clarify the relevance of PET as a possible outcome measure in PLE. Future studies should include scalp or semi-invasive electroencephalographic recordings during PET acquisition.

Diffuse axonal injury associated with chronic traumatic brain injury: evidence from T2*-weighted gradient-echo imaging at 3 T.

BACKGROUND AND PURPOSE: Diffuse axonal injury is frequently accompanied by tissue tear hemorrhages. We examined whether high field strength T2*-weighted gradient-echo imaging performed during the chronic stage of traumatic brain injury may have advantages in the evaluation of diffuse axonal injury as compared with T1- and T2-weighted MR imaging. METHODS: Prospective MR imaging of 66 patients (age range, 17-57 years) was performed using a 3-T system 3 to 292 months (median, 23.5 months) after traumatic brain injury. T1-, T2-, T2*-hypointense and T2-hyperintense foci of 1- to 15-mm diameter were registered in 10 brain regions by two readers separately. Foci that appeared hypointense both on the T1- and T2- and/or on the T2*-weighted images were defined as traumatic microbleeds. RESULTS: For 46 (69.7%) of the patients, T2*-weighted gradient-echo imaging revealed traumatic microbleeds. Hyperintense foci were observed on the T2-weighted images of only 15 (22.7%) patients. T2*-weighted imaging showed significantly more traumatic microbleeds (P =.000) than did T1- and T2-weighted imaging. Interobserver agreement was strong (kappa = 0.79, tau = 0.749, P =.000). For 14 (21.2%) of the patients, T2*-weighted gradient-echo imaging revealed traumatic microbleeds in the corpus callosum, whereas for only two (3%), hyperintense callosal lesions were seen on the T2-weighted images. Although a significant correlation existed between the total amount and callosal appearance of traumatic microbleeds and Glasgow Coma Scale scores (P =.000), no correlation existed with extended Glasgow Outcome Scale scores. CONCLUSION: T2*-weighted gradient-echo imaging at high field strength is a useful tool for the evaluation of diffuse axonal injury during the chronic stage of traumatic brain injury. Diffuse axonal injury-related brain lesions are mainly hemorrhagic. The relevance of diffuse axonal injury for long-term clinical outcome is uncertain.

Characterization of cerebral microangiopathy using 3 Tesla MRI: correlation with neurological impairment and vascular risk factors.

PURPOSE: To investigate whether clinical and neuropsychological impairment in cerebral small-vessel disease (CSVD) can be evaluated by means of morphological magnetic resonance imaging (MRI). MATERIALS AND METHODS: MRI at 3 Tesla in T2- and T1-weighted sequences was evaluated in 44 patients with cerebral microangiopathy, and 30 patients with combined cerebral micro- and macroangiopathy. The MR characteristics were correlated to clinical data, attentional impairment, and the patients' individual vascular risk factor profiles. Fifteen healthy age-matched control subjects participated in the study to assess MR signal changes in nonhypertensive elderly subjects. RESULTS: Patients and normal controls differed significantly in the extent of MR signal changes. A close relation between age, obesity, hypertension, and MR signal abnormalities was evident in all patients. Patients with pure CSVD additionally showed an association between their MR-defined severity of disease and their degree of neurological impairment, and their vascular risk score. In contrast, attentional impairment did not relate to the MR-defined severity of CSVD. CONCLUSION: MR signal changes in CSVD show a close relationship to some risk factors of individual patients.