Chorea-acanthocytosis associated with Tourettism.

We report on a case of Chorea-acanthocytosis (ChAc) in association with Tourettism that consisted of motor and vocal tics, attention deficit-hyperactivity disorder, and obsessive-compulsive disorder in addition to the typical symptoms of ChAc. The subject was compared with his elder sister who had the same disease but milder clinical profile and neuroradiological findings. The [(18)F]-2-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) findings did not explain the differences in symptomatology between the patient and his sister, although they may have correlated with severity.     

Positron emission tomography with [(18)F]FDG in the diagnosis of Creutzfeldt-Jakob disease (CJD)

The aim of this study was to explore the sites of metabolic changes with [¹⁸F]2-fluoro-2-desoxy-D-glucose (FDG) and positron emission tomography (PET) in patients with Creutzfeldt-Jakob disease and to correlate the findings with clinical symptoms. Static [¹⁸F]FDG-PET studies of eight patients with the diagnosis of confirmed or probable CJD were retrospectively analysed by two physicians from departments of nuclear medicine independently with a strong interrater agreement (κ=0,98). The clinical data of the patients, based on a standardized evaluation by physicians from the German Creutzfeldt-Jakob disease surveillance study, was correlated with the PET findings. [¹⁸F]FDG-PET shows widespread hypometabolism in CJD. All patients had a reduction of cerebral glucose metabolism in at least one temporal or parietal region. Additionally in 7 of our own 8 cases and 3 of 4 cases from the literature the occipital lobe, the cerebellum or the basal ganglia were involved. These findings differ from typical patterns of hypometabolism in Alzheimer's disease and other neurodegenerative disorders. In two thirds of the cases the distribution was markedly asymmetric. Myoclonus was present in five out of our eight own cases. Our data suggest that myoclonus might correlate with metabolic impairment of contralateral parietal and temporal lobes. In three of four patients with visual symptoms FDG uptake was reduced in the visual cortex bilaterally. Typical hyperintensities on MRI were only found in two of the eight cases at the time of PET-studies. Our results demonstrate that [¹⁸F]FDG-PET appears to be a sensitive investigation in CJD and could be useful to differentiate CJD from other neurodegenerative disorders. Received: 27 November 2000, Received in revised form: 11 September 2001, Accepted: 2 November 2001     

Novel mutations c.[5121_5122insAG]+[6859C>T] of the SPG11 gene associated with cerebellum hypometabolism in a Chinese case of hereditary spastic paraplegia with thin corpus callosum

Hereditary spastic paraplegia (HSP) is a very heterogeneous disease, both genetically and clinically. To date, approximately 52 loci and 31 genes have been reported to be involved in the causality of HSP. The pattern of inheritance of the disease can be autosomal dominant, autosomal recessive, or X-linked recessive. Autosomal recessive HSP with thin corpus callosum (ARHSP-TCC) is one form of this disease, and a recessive gene, SPG11, is responsible for 41–77% of all ARHSP-TCC cases. SPG11 encodes the protein SPATACSIN, which is most prominently expressed in the cerebellum. However, little is known about its function. Despite diverse clinical presentations, diffuse hypometabolism in the cerebellum has not been reported previously. We have identified an HSP-TCC patient that presented with prominent intellectual disability rather than spasticity. ¹⁸Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸FDG-PET/CT) examination showed diffuse hypometabolism in both cerebella. Mutation screening of the SPG11 gene using Sanger sequencing identified the novel compound heterozygous mutation c.[5121_5122insAG]+[6859C>T] (p.[I1708RfsX2]+[Q2287X]) in the patient. The mother bears the c.5121_5122insAG mutation, which results in a frameshift and is predicted to truncate the 735 amino acids from the C-terminus, and the father carries the c.6859C>T mutation, which terminates the 157 amino acids from the C-terminus. Therefore, these mutations may result in the loss of function of wild-type SPATACSIN. Our results suggest that SPATACSIN may be involved in cerebella metabolism, and the novel mutations provide more data for the mutational spectrum of this gene, which will aid in the development of quick and accurate genetic diagnostic tools for this disease.     

Bilateral thalamic damage,cortical hypometabolism and behavioural disturbances

Thalamic damage could be responsible for reduced metabolism in anterior cortical areas. In order to investigate an anatomical lesion and impairment of regional blood flow (rCBF) in distant cortical areas, we studied by magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) a patient with bilateral thalamic infarction, who presented with sudden consciousness impairment, drowsiness, gaze paralysis, dysphagia and bilateral Babinski sign. Three weeks later the neurological symptoms disappeared, but a severe mental deterioration was evident MRI showed thalamic bilateral damage of posterior and medial areas, involving part of the pulvinar, more evident for the right thalamus. A ^99mTc-HMPAO SPECT showed a decrease of rCBF over frontal and parietal regions, more evident for the right hemisphere. Six months later a severe memory impairment was still evident and MRI and SPECT picture were unchanged. The persistent memory defect could be related to a loss of cortical activation following the thalamic damage. The absence of primary lesions of cortical regions on CT scan and MRI and the neuroanatomical considerations on the diffuse projections running from medial nuclei and pulvinar to large parts of anterior neocortex supported this hypothesis.     

低氧耐受极限与低氧预适应

人和动物对低氧的耐受极限随种系进化、个体发育和条件变化而不同。低氧预适应 ,通过以重复低氧暴露和HIF 1表达为基础、在组织细胞水平上调动起来的一系列耐低氧的级联反应 ,可显著提高机体对低氧的耐受极限 ,预期将为防 /治和抗 /耐低氧提供一种崭新而古老的策略。     

Association of dysphagia with altered brain glucose metabolism in Parkinson's disease

Aims

Dysphagia is a major clinical concern in Parkinson's disease (PD). However, the relationship between the development of phase-specific dysphagia and the regional brain glucose metabolism remains unclear. Our objective was to investigate the distributions of brain glucose metabolism specific to oral and pharyngeal phases of dysphagia in PD.

Methods

In this retrospective cross-sectional study, patients with PD who underwent videofluoroscopic swallowing study (VFSS) and ¹⁸F-fluorodeoxy-glucose positron emission tomography at intervals of <1 month were included. Each swallow was assessed by the binarized Videofluoroscopic Dysphagia Scale with 14 subitems, seven each for the oral and pharyngeal phases. Metabolism mapping was performed by superimposing significant clusters of subitems belonging to each of the two phases using voxel-wise Firth's penalized binary logistic regression model, adjusting for age and PD duration at VFSS.

Results

Eighty-two patients with PD who met the inclusion criteria were included in the analysis. The oral phase dysphagia-specific overlap map showed hypermetabolism in the right inferior temporal gyrus, bilateral cerebellum, superior frontal gyrus, and anterior cingulate cortices. Hypometabolism in the bilateral orbital and triangular parts of the inferior to middle frontal gyrus was also correlated with the occurrence of oral phase dysphagia. The development of pharyngeal phase dysphagia was related to hypermetabolism of posterior aspects of the bilateral parietal lobes, cerebellum, and hypometabolism of the mediodorsal aspects of anterior cingulate and middle to superior frontal gyri.

Conclusion

These findings suggest that phase-specific distribution of brain glucose metabolism may explain the dysphagia of PD.     

Correlation of severity of FDG-PET hypometabolism and interictal regional delta slowing in temporal lobe epilepsy

PURPOSE: We investigated the association of severity of hypometabolism detected by positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) and persistence of interictal EEG focal slowing in patients with refractory temporal lobe epilepsy. METHODS: Eighty temporal lobes of 40 consecutive patients with intractable temporal lobe epilepsy (mean age, 43.5 years) were studied. All patients underwent video-EEG monitoring, magnetic resonance imaging (MRI), and FDG-PET. Patients with either normal MRI or with unilateral mesial temporal sclerosis, but no other structural abnormality, were included. Interictal EEG delta slowing was graded as none, infrequent (one episode or less/hour), intermediate (more than one episode/hour), or continuous. PET hypometabolism was graded as none, mild, moderate, or severe. RESULTS: The severity of temporal lobe hypometabolism with PET was significantly correlated with the amount of delta activity in the interictal EEG, independent of MRI findings (Spearman r = 0.46; p < 0.0005). CONCLUSIONS: This observation suggests related underlying pathophysiologic mechanisms for metabolic and electrical dysfunction in temporal lobe epilepsy.     

Relationship between preoperative hypometabolism and surgical outcome in neocortical epilepsy surgery

Purpose: Fluorine‐18‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) hypometabolism has been used to localize the epileptogenic zone. However, glucose hypometabolism remote to the ictal focus is common and its relationship to surgical outcome has not been considered in many studies. We investigated the relationship between surgical outcome and FDG‐PET hypometabolism topography in a large cohort of patients with neocortical epilepsy. Methods: We identified all patients (n = 68) who had interictal FDG‐PET between 1994 and 2004 and who underwent resective epilepsy surgery with follow up for more than 2 years. The volumes of significant FDG‐PET hypometabolism involving the resected epileptic focus and its surrounding regions (perifocal hypometabolism) and those distant to and not contiguous with the perifocal hypometabolism (remote hypometabolism) were determined statistically using Statistical Parametric Mapping (voxel threshold p = 0.01, extent threshold ≥250 voxels, uncorrected cluster‐level significance p < 0.05) and were compared with magnetic resonance imaging (MRI) and clinical and demographic variables using a multiple logistic regression model to identify independent predictors of seizure outcome. Key Findings: Remote hypometabolism was present in 39 patients. Seizure freedom was 49% (19 of 39 patients) in patients with glucose hypometabolism remote from the epileptogenic zone compared to 90% (26 of 29 patients) in patients without remote hypometabolism. In 43 patients with an MRI‐identified lesion, seizure freedom was 79% (34 of 43 patients). In patients with normal MRI, cortical dysplasia was the predominant pathologic substrate. Multiple logistic regression analysis identified a larger volume of significant remote hypometabolism (p < 0.005) and absence of a MRI‐localized lesion (p = 0.006) as independent predictors of continued seizures after surgery. Significance: In patients with widespread glucose hypometabolism that is statistically significant when compared to controls, epilepsy surgery may not result in complete seizure freedom despite complete removal of the MRI‐identified lesion. The volume of significant glucose hypometabolism remote to the ictal‐onset zone may be an independent predictor of the success of epilepsy surgery.     

Analysis of positron emission tomography hypometabolic patterns and neuropsychiatric symptoms in patients with dementia syndromes

Aims

To estimate the proportions of specific hypometabolic patterns and their association with neuropsychiatric symptoms (NPS) in patients with cognitive impairment (CI).

Methods

This multicenter study with 1037 consecutive patients was conducted from December 2012 to December 2019. ¹⁸F-FDG PET and clinical/demographic information, NPS assessments were recorded and analyzed to explore the associations between hypometabolic patterns and clinical features by correlation analysis and multivariable logistic regression models.

Results

Patients with clinical Alzheimer's disease (AD, 81.6%, 605/741) and dementia with Lewy bodies (67.9%, 19/28) mostly had AD-pattern hypometabolism, and 76/137 (55.5%) of patients with frontotemporal lobar degeneration showed frontal and anterior temporal pattern (FT-P) hypometabolism. Besides corticobasal degeneration, patients with behavioral variant frontotemporal dementia (36/58), semantic dementia (7/10), progressive non-fluent aphasia (6/9), frontotemporal lobar degeneration and amyotrophic lateral sclerosis (3/5), and progressive supranuclear palsy (21/37) also mostly showed FT-P hypometabolism. The proportion of FT-P hypometabolism was associated with the presence of hallucinations (R = 0.171, p = 0.04), anxiety (R = 0.182, p = 0.03), and appetite and eating abnormalities (R = 0.200, p = 0.01) in AD.

Conclusion

Specific hypometabolic patterns in FDG-PET are associated with NPS and beneficial for the early identification and management of NPS in patients with CI.     

Functional deprivation promotes amyloid plaque pathogenesis in Tg2576 mouse olfactory bulb and piriform cortex

Cerebral hypometabolism and amyloid accumulation are principal neuropathological manifestations of Alzheimer’s disease (AD). Whether and how brain/neuronal activity might modulate certain pathological processes of AD are interesting topics of recent clinical and basic research in the field, and may be of potential medical relevance in regard to both the disease etiology and intervention. Using the Tg2576 transgenic mouse model of AD, this study characterized a promotive effect of neuronal hypoactivity associated with functional deprivation on amyloid plaque pathogenesis in the olfactory pathway. Unilateral naris‐occlusion caused β‐secretase‐1 (BACE1) elevation in neuronal terminals in the deprived relative to the non‐deprived bulb and piriform cortex in young adult mice. In parallel with the overall age‐related plaque development in the forebrain, locally increased BACE1 immunoreactivity co‐occurred with amyloid deposition first in the piriform cortex then within the bulb, more prominent on the deprived relative to the non‐deprived side. Biochemical analyses confirmed elevated BACE1 protein levels, enzymatic activity and products in the deprived relative to non‐deprived bulbs. Plaque‐associated BACE1 immunoreactivity in the bulb and piriform cortex was localized preferentially to swollen/sprouting glutamatergic axonal terminals, with Aβ immunoreactivity occurring inside as well as around these terminals. Together, these findings suggest that functional deprivation or neuronal hypoactivity facilitates amyloid plaque formation in the forebrain in a transgenic model of AD, which operates synergistically with age effect. The data also implicate an intrinsic association of amyloid accumulation and plaque formation with progressive axonal pathology.     

Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis

OBJECTIVES: To assess the prognostic factors determining seizure remission after temporal lobectomy for intractable epilepsy associated with mesial temporal sclerosis (MTS) at pathology. METHODS: The clinical and investigative features of 116 consecutive patients who had temporal lobe surgery for drug-resistant epilepsy and MTS at pathology were assessed using actuarial statistics and logistic regression analysis. RESULTS: At a median follow-up of 63 months the probability of achieving at least a 1-year period of continuous seizure freedom was 67%. Factors contributing to a favourable outcome were interictal EEG localization to the operated lobe and the absence of secondarily generalized seizures. These were also selected in the multivariate analysis, although at lower statistical significance (P=0.08 and 0.09, respectively). Perinatal complications were associated with a significantly worse outcome but overall, complicated febrile convulsions and congruent neuropsychological deficits were not significantly predictive variables. CONCLUSIONS: The present findings may aid in the non-invasive presurgical assessment of patients with intractable TLE and clinical and neuroimaging evidence of MTS.     

颞叶孤立性胶质母细胞瘤的手术治疗分析

目的 探讨颞叶孤立性胶质母细胞瘤的手术方法及疗效。方法 回顾性分析2016年7月至2020年5月手术治疗的38例颞叶孤立性胶质母细胞瘤的临床资料。接受肿瘤全切除+前颞叶切除术（ALT）治疗14例（ALT组）,行常规颞叶肿瘤全切除术治疗24例（常规组）。术后随访6~28个月,中位数15个月;术后3、12个月采用KPS评分评估神经功能状态,其中KPS评分≥70分为预后良好;根据RANO标准评估肿瘤进展,国际抗癫痫联盟分级1级定义为癫痫完全控制;记录总生存期（OS）和无进展生存期（PFS）。结果 ALT组术后脑室开放率（100%,14/14）明显高于常规组（33.3%,8/24;P<0.001）。ALT组与常规组术后1年癫痫完全控制率（64.3% vs. 66.7%）、术后肿瘤进展率（78.5% vs. 70.8%）、术后3个月预后良好率（92.9% vs. 66.7%）均无统计学差异（P>0.05）。ALT组术后1年预后良好率（78.6%,11/14）明显高于常规组（41.7%,10/24;P<0.05）。ALT组中位PFS和中位OS较常规组均明显延长（P<0.05）。多因素Cox比例回归风险模型分析显示,ALT是延长PFS（OR=7.3;95% CI 1.105~47.422;P=0.037）和OS（OR=7.8;95% CI 1.117~55.183;P=0.041）的独立预测因子。结论 对于颞叶孤立性胶质母细胞瘤,在全切除肿瘤基础上,进行ALT,可明显改善病人预后。     

Cerebellar Hypometabolism in Focal Epilepsy Is Related to Age of Onset and Drug Intoxication

Summary: Purpose: We wished to investigate the cerebellar depression of regional cerebral glucose metabolism (rCMRGlu) in patients with focal epilepsy.
Method: In 170 consecutive patients with medically refractory, focal epilepsy the rCMRGlu was measured in cerebellum and brain.
Results: rCMRGlu was markedly decreased in both cerebellar hemispheres and slightly in brain. The cerebellum to brain rCMRGlu ratio was significantly decreased in patients with seizure manifestation in infancy, but was normal due to a progressive decrease in brain rCMRGlu in later age. A subgroup of patients with focal epilepsy involving the frontal lobe had a reduced cerebellum/brain rCMRGlu ratio, whereas in patients with mesiotemporal lobe epilepsy (MTLE), the rCMRGlu was decreased to the same degree in cerebellum and brain. The difference in the cerebellum/brain rCMRGlu ratio between the two groups was accounted for by the younger age of the patients with focal epilepsy involving the frontal lobe, however. In another subgroup of patients with a documented history of critical drug intoxications, the cerebellar rCMRGlu was severely decreased, resulting in a significantly reduced cerebellum/brain rCMRGlu ratio.
Conclusion: Our retrospective study suggests that the cerebellum is particularly vulnerable in infancy to ongoing epileptic activity and high dosage of antiepileptic drugs (AEDs).     

The temporal unraveling of autobiographical memory narratives in patients with temporal lobe epilepsy or excisions

Medial temporal lobe epilepsy (TLE), a condition known to affect the integrity and function of medial temporal lobe structures such as the hippocampus, has been shown to disrupt memory for real‐life episodes. Here, patients with unilateral TLE, patients who received a unilateral temporal lobe resection to cure TLE, and healthy controls produced free narratives of autobiographical memories (AMs). To assess temporal resolution, narratives were segmented into bits of information, or details, which were classified according to how precisely they could be located within the time course of the AM. Categories included details corresponding to the entire AM, to parts or subevents within the AM, and to actions taking place within seconds to minutes. The number of details per category was tallied and compared between patients and controls. Temporal order was assessed by determining the correct (internally consistent) chronological order of the sequence of events within the narrative. Results indicate that while patients' memory for the parts or subevents of personal episodes was intact, as was their temporal order, their memory for the minute‐by‐minute unraveling of the episode was impaired. We believe this loss of temporally specific details may contribute to the reduced vividness of AM recollection in TLE patients. Our findings provide further evidence that patients with hippocampal damage retrieve skeletal AMs for which the gist of the memory is maintained, but the specific details are lost. © 2010 Wiley‐Liss, Inc.     

Auditory temporal envelope processing in a patient with left-hemisphere damage

Abstract

Auditory temporal envelope processing was investigated in a patient showing a mild speech identification impairment following left-hemisphere damage. Three tasks evaluated the patient's ability to: (1) detect a sinusoidal amplitude modulation (SAM) applied to a white noise, as a function of modulation rate (i.e. her ‘temporal modulation transfer function’ or TMTF); (2) discriminate between two white noises amplitude modulated by time-reversed temporally asymmetric envelopes; and (3) identify white noises amplitude modulated by the temporal envelope of speech stimuli. Measurements of intensity discrimination thresholds were performed as a control task. Compared to normal data, the results obtained with the brain-damaged patient showed: (1) increased thresholds for the detection of SAM; (2) increased thresholds for the discrimination of temporal asymmetry; and (3) a deficit in the identification of speechenvelope noise stimuli. In contrast, intensity discrimination thresholds were within the normal range. Taken together, the results indicate a general impairment in auditory temporal acuity, which is now specified as a deficit in the coding of envelope rate and shape, and a deficit in the ability to use temporal envelope cues in speech processing. These results support the hypothesis that left-hemisphere damage is associated with an impairment in time analysis, which may cause, in turn, speech intelligibility disorders.     

Anatomical Variations,Mimics, and Pitfalls in Imaging of Patients with Epilepsy

Epilepsy is among one of the most common neurologic disorders. The role of magnetic resonance imaging (MRI) in the diagnosis and management of patients with epilepsy is well established, and most patients with epilepsy are likely to undergo at least one or more MRI examinations in the course of their disease. Recent advances in high‐field MRI have enabled high resolution in vivo visualization of small and intricate anatomic structures that are of great importance in the assessment of seizure disorders. Familiarity with normal anatomic variations is essential in the accurate diagnosis and image interpretation, as these variations may be mistaken for epileptogenic foci, leading to unnecessary follow‐up imaging, or worse, unnecessary treatment. After a brief overview of normal imaging anatomy of the mesial temporal lobe, this article will review a few important common and uncommon anatomic variations, mimics, and pitfalls that may be encountered in the imaging evaluation of patients with epilepsy.