Beare-Stevenson syndrome: two Dutch patients with cerebral abnormalities

Beare-Stevenson syndrome (BSS) is a rare autosomal-dominant condition characterized by cutis gyrata, craniosynostosis, acanthosis nigricans, anogenital anomalies, and a prominent umbilical stump. In 1996, two mutations in the fibroblast growth factor receptor 2 gene were found to cause this syndrome, thereby including BSS in the fibroblast growth factor receptor gene-related craniosynostosis spectrum. Until now, 12 patients with fibroblast growth factor receptor 2 gene-related BSS have been described. We report what is to our knowledge the first 2 Dutch patients with this syndrome, both caused by the mutation Tyr375Cys in the fibroblast growth factor receptor 2 gene. The patients exhibited a simplified gyral pattern, an abnormal posterior fossa, and an abnormal hippocampus on cranial magnetic resonance imaging. We discuss the clinical and radiologic findings in fibroblast growth factor receptor 2 gene-related BSS.     

Electrocardiographic abnormalities in patients treated with clozapine

BACKGROUND: Cardiovascular side effects of clozapine are not uncommon, but few systematic studies of these effects have been performed. In this study, we reviewed data on the electrocardiographic (ECG) abnormalities in patients treated with clozapine. METHOD: Sixty-one patients treated with clozapine were selected from the Seoul National University Hospital Treatment-Resistant Schizophrenia Clinic. A retrospective chart review was conducted to identify ECG abnormalities and cardiovascular side effects. RESULTS: The prevalence of ECG abnormalities in patients who had been using antipsychotics other than clozapine was 13.6% at baseline, which increased significantly to 31.1% after commencement of clozapine treatment. Among the 53 patients without baseline ECG abnormalities, 13 showed new-onset ECG abnormalities after using clozapine. Normal ECG under previous antipsychotic medication reduced the risk of new-onset ECG abnormalities, whereas increased age was found to increase the risk. The occurrence of orthostatic hypotension or tachycardia was not related to the development of ECG abnormalities. Most of the newly developed abnormalities had little clinical significance, and they tended to occur during the initial phase of treatment. In 10 patients, ECGs normalized despite the continued use of clozapine. Clozapine increased corrected QT interval (QTc) in a dose-dependent fashion; however, the clinical significance of this observation is uncertain. Pathologic prolongation of QTc was found to be rare. CONCLUSION: Although a substantial portion of patients treated with clozapine developed ECG abnormalities, most of the abnormalities were benign and did not hinder further treatment.     

Radiotherapy-induced cerebral abnormalities in patients with low-grade glioma

Abnormalities on CT or MRI and neuropsychological performance in patients with low-grade glioma, with (n = 23) or without (n = 16) prior cerebral radiotherapy, were evaluated. Cerebral atrophy was observed in 14 of 23 patients (61%) treated with prior radiotherapy, and in 1 of 16 patients (6%) without prior radiotherapy. White matter abnormalities were observed in six patients, all of whom were treated with prior radiotherapy. These radiologic cerebral abnormalities correlated with cognitive performance.     

Self-reported memory problems in everyday activities in patients with epilepsy treated with antiepileptic drugs

ObjectiveThe goal of this study was to assess everyday memory complaints in a large cohort of patients with epilepsy treated with antiepileptic drugs and to determine demographic, clinical, and emotional state factors associated with patients’ self-perception of memory disturbances.MethodsThis cross-sectional epidemiological study was carried out in routine clinical practice using the Questionnaire of Memory Efficiency (QME) and the Hospital Anxiety and Depression Scale (HADS).ResultsSix hundred sixty-one patients were recruited. The time since epilepsy diagnosis was 17.3 years (SD = 12.5); the number of seizures in the past year 13.8 (SD = 4.8); the proportion of patients free of seizures in the last year 42.5%; the proportion of patients with partial seizures 73.2%; and the proportion of patients on monotherapy 56.3%. Total QME score was 110.0 (SD = 18.6). Depression and anxiety scores and polytherapy explained 38.7% of the QME variance.ConclusionsSubjective memory functioning in this cohort of patients with epilepsy was relatively good. Complaints expressed by these patients are explained mainly by the presence of depressive and anxiety symptoms.     

MRI findings in patients with spastic cerebral palsy. II: correlation with type of cerebral palsy

The authors studied MR images of the brain in 152 patients, aged 1 to 19 years (mean 3.3), who had spastic cerebral palsy (CP) and were attending two hospitals in Japan in 1993 and 1994. Eighty-one patients had diplegia, 45 had quadriplegia, and 26 had hemiplegia. Of patients with diplegia, 72 had periventricular leukomalacia (PVL) and very few had other types of lesions. In patients with quadriplegia, three main types of brain lesions were observed: PVL in 12 patients, term-type brain injury in 22, and brain anomaly in 10. In the 26 patients with hemiplegia, 17 had a unilateral lesion (rare in patients with diplegia and quadriplegia), and bilateral lesions were seen in seven others.     

Long-term sickness absence among patients with chronic fatigue syndrome

Chronic fatigue syndrome is associated with high levels of occupational disability. Consecutive out-patients at a chronic fatigue syndrome treatment service were studied for associations between occupational status, symptom severity and cognitive and behavioural responses to symptoms. All patients had high symptom levels; however, those on long-term sickness absence had significantly more physical fatigue (β = 0.098, P<0.05) and worse sleep (β = 0.075, P<0.05). Patients with long-term sickness absence also demonstrated more embarrassment avoidance cognitions (β = 0.086, P<0.05) and avoidance resting behavioural responses (β = 0.078, P<0.05). Identifying and addressing avoidance behaviours and cognitions regarding embarrassment in interventions may enhance the chances of individuals returning to work.     

偏头痛脑白质异常的MRI表现

目的探讨偏头痛脑白质异常(WMAs)的MRI表现。方法选取70例偏头痛患者并行MRI检查,女性51例,男性19例,年龄为18~50岁,平均年龄36.21±8.9岁。选取同期健康体检者并行MRI检查70例对照组,女性53例和男性17例,年龄为18~50岁,平均年龄35.32±8.6岁。运用SPSS13.0软件对数据进行分析。结果显示偏头痛组中有23例WMAs,表现为皮质下脑白质内等T1长T2信号影,Flair高信号;对照组中有6例WMAs。偏头痛组WMAs的比例(32.86%,23/70)明显高于对照组(8.57%,6/70)(χ2=12.57,P0.01)。偏头痛组中有先兆偏头痛患者WMAs的比例(48.39%,15/31)明显高于无先兆偏头痛患者(20.51%,8/39)(χ2=6.08,P0.05)。结论偏头痛患者WMAs的发生率较高,且有先兆偏头痛患者较无先兆偏头痛患者更高。     

Remote cerebral hematomas in patients treated with intravenous rt-PA

The frequency, clinical presentation, radiological features, and prognosis of remote cerebral hematomas (rPH) are not well known. We report our experience in patients treated with intravenous rt-PA. We reviewed our database of consecutive patients treated at our hospital from 1999 to 2008. We used the inclusion/exclusion criteria of the ECASS-2 study from 1999 to 2003, and the criteria of the SITS-MOST study since 2004. A follow-up CT scan was obtained in all of the patients within the first 36 h of treatment. Cerebral hemorrhagic complications were classified as hemorrhagic infarction (HI-1/HI-2) and parenchymal hematoma (PH-1/PH-2). The rPH was defined as any extra-ischemic hemorrhagic lesion observed in the follow-up CT. A favorable outcome was defined as a score 0–1 on the Rankin scale at 3 months. We treated 210 patients (mean age 67.6 ± 12.4 years, 56% were men). The median initial NIHSS score was 14. Patients with rPH (n = 7) had a mean age of 72.4 ± 7.5 years and 43% were men. The median initial NIHSS score was 15. Three patients had multifocal rPH; three patients had a single rPH and in one patient the rPH was associated with a PH-2. rPH were lobar in six patients and in brainstem in one patient, symptomatic in five patients and asymptomatic in two patients. The outcome was unfavorable in all of them; four deaths (57%) were recorded. Remote cerebral hemorrhage is an infrequent complication after rt-PA treatment (3.3%), it is usually lobar and symptomatic and has an uniformly unfavorable outcome.     

Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome

Presence of MRI brain abnormalities in patients with Chronic Fatigue Syndrome (CFS) was determined and the profile of MRI abnormalities was compared between 39 CFS patients, 18 with (CFS-Psych) and 21 without (CFS-No Psych) a DSM-III-R Axis I psychiatric diagnosis since illness onset, and 19 healthy, sedentary controls (HC). Two neuroradiologists, blind to group membership, separately read the MR films using a detailed protocol for rating and categorizing abnormal signal changes. When findings were incongruent, the two neuroradiologists met to try to reach consensus, otherwise a third neuroradiologist evaluated the MR images and served as a tie-breaker. The CFS-No Psych group showed a significantly larger number of brain abnormalities on T2 weighted images than the CFS-Psych and HC groups. Cerebral changes in the CFS-No Psych group consisted mostly of small, punctate, subcortical white matter hyperintensities, found predominantly in the frontal lobes. No significant difference was found when both CFS groups were combined and compared to the HC group. The use of stratification techniques is an important strategy in understanding the pathophysiology of CFS. This frontal lobe pathology could explain the more severe cognitive impairment previously reported in this subset of CFS patients.     

Brain response abnormalities during verbal learning among patients with schizophrenia

Patients with schizophrenia often show verbal learning deficits that have been linked to the pathophysiology of the disorder and result in functional impairment. This study examined the biological basis of these deficits by comparing the brain response of patients with schizophrenia (n=17) to that of healthy comparison participants (n=14) during a verbal paired-associates learning task using functional magnetic resonance imaging (fMRI). Brain response during new word learning was examined within and between groups in two a priori regions of interest, the inferior frontal gyrus and hippocampus, and across the whole brain. In regions of group difference, we also examined the relationship of brain response during learning to later recall of the word pairs. Despite successful matching of levels of word-pair recall, patients' brain response during new learning was abnormal in bilateral regions within the inferior frontal gyrus, a small region in left posterior hippocampus, and other areas within the frontal, parietal and temporal cortex compared with healthy individuals. In some regions, but not in the hippocampus, patients with the most normal brain response also remembered the most word pairs following scanning. Thus, verbal learning deficits found among patients with schizophrenia appear to be related to hypofunction of distributed brain networks.     

Fatigue in multiple sclerosis: Interrelations between fatigue complaints, cerebral MRI abnormalities and neurological disability

Although fatigue is a frequent complaint of patients with multiple sclerosis (MS), little is known about the origins of multiple-sclerosis-associated fatigue. Our primary focus was to study if the extent of cerebral abnormalities, as shown on magnetic resonance imaging (MRI), had any relation with the frequency and intensity of fatigue complaints of patients with a definite diagnosis of MS. Fatigue severity was rated by the patients with the use of a 2-week diary and a fatigue questionnaire, while conventional T1- and T2-weighted MRI provided several measures for cerebral abnormalities. In total, 72% of 45 patients reported to be seriously fatigued at least several times a week over the last 3-month period. Fatigue severity was not related to the total extent of cerebral abnormalities, or to MRI-based atrophy measures. Regional lesion load did not differ between fatigued and non-fatigued subjects. Although neurological disability, as measured by the Expanded Disability Status Scale (EDSS) and Neurological Rating Scale (NRS), did correlate significantly with most MRI measures, it showed no relation with fatigue severity. Neurological progression rates and number of exacerbations in the 2-year period prior to assessment were not significantly associated with the fatigue measures. Therefore, our findings suggest that differences in levels of self-reported fatigue in patients with multiple sclerosis cannot merely be explained by the degree of clinical disease activity, neurological disability or the extent of MRI abnormalities. These results are compared to other research findings and the possible role of alternative factors influencing fatigue in multiple sclerosis are discussed.     

脑动静脉畸形γ刀放射治疗后脑水肿发生情况分析

目的 探讨脑动静脉畸形γ刀放射治疗后不同随访阶段放射性脑水肿的发生率.方法 回顾性分析广州医学院第二附属医院放射科自1995年1月至2010年12月十余年间内经γ刀治疗的脑动静脉畸形患者的临床资料,共经磁共振检查随访351例次.统计γ刀术后不同随访阶段放射性脑水肿发生率并采用采用x2检验分析. 结果 γ刀放射治疗后本组患者放射性脑水肿阳性率为36.2％;不同随访阶段放射性脑水肿阳性率分别为:≤12月43.0％,13～36月45.3％,37～60月23.1％,61～120月13.6％,＞120月5.9％;各随访阶段间放射性脑水肿的发生率比较差异有统计学意义(x2=26.514,P=0.000). 结论 放射性脑水肿是脑动静脉畸形γ刀治疗后最常见的并发症之一,部分患者可出现顽固性放射性脑水肿.γ刀治疗后第一阶段(≤12月)、第二阶段(13～36月)放射性脑水肿发生率较高,应临床密切关注.     

Callosal anomalies in patients with spinal dysraphism: correlation of clinical and neuroimaging features with hemispheric abnormalities

Dysgenesis of the corpus callosum can occur in association with spinal dysraphic lesions. Clinical and neuroimaging features were reviewed in 23 patients (12 male, 11 female; mean age 11.3 years) with caudal spinal dysraphism (myeloschisis in eight, meningomyelocele in 10, and lumbosacral lipoma in five) to characterize types and degrees of callosal and other cerebral anomalies. T1- and T2-weighted magnetic resonance images were obtained, and the total midsagittal cross-sectional area of the corpus callosum was determined. The corpus callosum appeared normal in nine patients and was abnormal in 14. In five patients the corpus callosum was narrow, with all regions present; the cerebral hemispheres were hypoplastic. Two patients with dysgenesis of frontal, parietal, and occipital lobes had a small, partly agenetic corpus callosum. In the remaining seven patients the posterior third of the corpus callosum was absent or hypoplastic; six of them had ventriculomegaly that selectively affected the occipital horns (colpocephaly). All callosal anomalies were accompanied by hemispheric ones. This supports a disordered developmental relationship between the corpus callosum and the hemispheres as a cause. Spinal dysraphism can no longer be considered a single developmental abnormality, given the frequent association of other defects.     

Determination of cerebrovascular reactivity by means of FMRI signal changes in cerebral microangiopathy: a correlation with morphological abnormalities

BACKGROUND AND PURPOSE: A reduced cerebrovascular reactivity (CR) is a risk factor of cerebrovascular disease. In this study, we implemented a protocol to assess CR by means of functional MRI (fMRI) using hyperventilation. SUBJECTS AND METHODS: In 5 patients with cerebral microangiopathy (CM/lacunar infarction and white matter degeneration), 6 healthy elderly subjects (age-matched control), and 6 young healthy subjects, the CR in response to hyperventilation was evaluated by fMRI using gradient echo-planar Imaging. The percentage signal change normalized by end-tidal CO(2) value was measured in various brain regions. RESULTS: All subjects performed hyperventilation well without adverse reaction and significant gross motion. Patients with CM showed significant qualitative and quantitative differences (p < 0.05) as compared to controls. The volume of gray matter showing significant CR was significantly reduced in patients: by 40% in comparison to the age-matched elderly control group and by 60% when compared with the young controls. The CR impairment was most pronounced in the frontal cortices with a drastically reduced magnitude of the magnetic resonance (MR) signal change in the patients (-0.62 +/- 0.2% in patients versus -2.0 +/- 0.36% in age-matched controls, p < 0.0001). A strong relation was evident between the fMRI-based CR reduction in patients with CM and the individual severity of structural MR abnormalities (p = 0.002). CONCLUSION: This study demonstrates that fMRI-based signal changes in response to hyperventilation reliably reflect cerebral vasoreactivity. The protocol is feasible in healthy young and elderly controls and patients with CM. Quantitative and qualitative assessment of the signal decrease in the T(2)-weighted MR sequence and coregistration with individual anatomical data allow the generation of an individual cerebral vasoreactivity map. Future research will address the effect of CR reduction on neuropsychological parameters in patients with CM.