Thomas Guthke

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 agematched 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.

Text comprehension after brain injury: left prefrontal lesions affect inference processes.

Comprehending language in context requires inferencing, particularly for the establishment of local coherence. In the neurolinguistic literature, an inference deficit after right hemisphere brain damage has been postulated, but clinical observation and imaging data suggest that left-frontal lesions might also result in inference deficits. In the present experiment, 25 nonaphasic patients performed a coherence judgment task requiring them to indicate a pragmatic connection between 2 successively presented sentences. Patients with left-temporal or right-frontal lesions performed the task well. In contrast, patients with left- and bifrontal lesions exhibited the most severe deficit. Both error rates and response times were elevated for coherent trials as compared with incoherent trials. These results confirm that the left-frontal lobe contributes to inference processes.

Assessment of story comprehension deficits after brain damage

A story comprehension task was specifically developed for the clinical diagnosis of text comprehension deficits. The performance of 49 healthy control participants on qualitatively different Yes/No questions confirmed that both salience and explicitness of information had an impact on question difficulty. An unselected group of brain damaged patients (n=96) made more errors, particularly on questions about implicit information. The subgroup of patients with left-hemispheric vascular aetiology (n=18) had particular difficulties with stated details, patients with right-hemispheric vascular aetiology (n=12) with implicit main ideas, and patients with traumatic brain injury (n=34) were most impaired on implicit information. Correlations with neuropsychological test scores also confirmed that the questions successfully tapped different subprocesses of comprehension. Performance on implicit main ideas was correlated with tests of executive functions, whereas the performance on the other three question types was correlated with long-term memory and verbal learning. These results suggest that the story comprehension test is a useful diagnostic tool for neuropsychological assessment.

Morphometry demonstrates loss of cortical thickness in cerebral microangiopathy

ObjectiveTo evaluate the role of MR morphometry in the characterization of cerebral microangiopathy (CMA) in relation to clinical and neuropsychological impairment.Subjects and Methods3D MR images of 27 patients and 27 age–matched controls were morphometrically analysed for regional thickness. The normalized values were related to the patients’ clinical and neuropsychological scores. The patients were categorised according to the amount of structural MR signal changes. A ventricle index reflecting internal atrophy was related to MR morphology and cortical thickness as an indicator for external atrophy.ResultsCortical thickness was significantly reduced in the patients group (3.03mm ± 0.26 vs. 3.22mm ± 0.13 in controls, p = 0.001). The severest loss of cortical thickness occurred in severe CMA. Internal and external atrophy evolved in parallel and both showed a significant relationship with structural MR–abnormalities (p < 0.05; r = –0.7; r = 0.67; r = –0.74, respectively). Neuropsychological performance correlated strongly with the loss of cortical thickness.ConclusionsCortical thickness was identified as the most sensitive parameter to characterize CMA. A strong correlation was found of morphometric parameters to the severity of CMA based on a score derived from T2–weighted MRI. The degree of cortical atrophy was directly related to the degree of neuropsychological impairment. Our findings suggest that the cortical thickness is a valid marker in the structural and clinical characterization of CMA.

Change of perspective in discourse comprehension: Encoding and retrieval processes after brain injury

Damage to frontal areas has been associated with nonaphasic language disturbances in which word and sentence level processes remain largely intact but text level processes are impaired. Most studies providing evidence for these language deficits have concentrated on text production. To study text comprehension of nonaphasic patients, we adopted the paradigm of Anderson and Pichert (1978) that was developed to separate encoding from retrieval processes. Subjects read a story under one of two alternative perspectives and subsequently recalled it. After this first recall, they were instructed to now adopt the second perspective and to recall the story once more. Twenty-four brain-injured patients participated. Each patients lesion was evaluated with respect to the involvement of right- and/or left-frontal regions. Seven patients showed unilateral left-frontal lesions, five patients unilateral right-frontal lesions, four patients had bilateral frontal damage, and the lesions of the remaining eight patients did not involve frontal areas. The only factor predicting behavioral results was the presence of a left-frontal lesion. For patients without frontal lesions and patients with unilateral right-frontal lesions, we replicated previously reported results. Encoding relevant information was recalled better than other information. Furthermore, the switch of perspective aided recall of perspective relevant information during the second recall. In contrast, patients with left-frontal or bilateral frontal lesions could not make use of the perspective instructions. While they showed comparable recall performance, as well as sensitivity to the relative ease of information, neither the encoding instructions nor the switch instructions had an impact on the recall patterns. These results suggest that left-frontal damage leads to an impairment of goal directed text processing skills.

Characterization of Cerebral Small Vessel Disease by Proton Spectroscopy and Morphological Magnetic Resonance

This study sought to investigate whether clinical and neuropsychological impairment in cerebral small vessel disease (CSVD) can be evaluated by proton spectroscopy (1H-MRS) and structural magnetic resonance (MR) imaging. Sixteen patients with CSVD and 15 healthy age-matched controls participated in the study. In addition to spectroscopic and structural MR examination all patients underwent a comprehensive clinical and neuropsychological investigation. Significant differences in between patients and controls were revealed by 1H-MRS in the parietal white matter: decreased metabolic ratios of N-acetyl aspartate to choline (NAA/Cho; patients: 1.37 ± 0.17, control: 1.72 ± 0.25, p < 0.001) and of N-acetyl aspartate to creatin (NAA/Cr; patients: 1.41 ± 0.15, control: 1.66 ± 0.2, p < 0.01) indicated a pathological state. Evaluation of spectroscopic and neuropsychological data revealed a close relation between attentional impairment, i.e. delayed cerebral transmission time and decreased NAA/Cho and NAA/Cr (r = 0.62, p = 0.014). In sum, 1H-MRS allowed a clear discrimination between patients with CSVD and age-matched normal controls. Moreover, comparisons of 1H-MRS and neuropsychological data suggested that NAA metabolic levels, and particularly the delay in cerebral transmission time, could be potential predictors of the severeness of attentional impairment.

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.

Neuropsychiatric findings in anti-Ma2-positive paraneoplastic limbic encephalitis

In 1999, a novel paraneoplastic entity in patients with testicular cancer, paraneoplastic limbic encephalitis (PLE), and antibodies against Ma2 was reported.1 We describe a man with anti-Ma2-positive PLE in metastasized testicular cancer. In the summer of 1999, a 39-year-old previously healthy man developed obsessive doubts that his central heating was leaking water. He started to check the equipment >10 times/day. Additional rituals of checking lights, doors, and windows developed. In December 1999, obsessive–compulsive disorder (OCD) was diagnosed. In January 2000, the patient noticed a lump in his right testicle. Orchiectomy and retroperitoneal lymph dissection followed. The histologic examination showed a differentiated nonmetastasized teratoma and a seminoma-in-situ. In August 2000, a first generalized seizure occurred. Since June 2001, memory deficits, gustatory sensory auras, and moderate chronic daily headache were reported. We saw the patient in November 2001, when tests on verbal memory confirmed serious deficits in learning and recognizing new information, especially during delayed recall. Episodic and semantic knowledge decreased in accordance with a temporal gradient. Repeated MRI showed a nonenhancing T2-hyperintense signal change in the left hippocampus. Scalp EEG inconstantly showed left temporal sharp slow-wave activity. …