Eun Yeon Joo

Cerebral perfusion changes in mesial temporal lobe epilepsy: SPM analysis of ictal and interictal SPECT

We examined cerebral perfusion changes in mesial temporal lobe epilepsy (mTLE) by the statistical parametric mapping of brain single photon emission computed tomography (SPECT) images of 38 mTLE patients and 19 normal controls. Ictal and interictal SPECTs were compared with control SPECTs by independent t test, and ictal and interictal SPECTs by paired t test. We evaluated the number of heterotopic neurons in temporal lobe white matter, white matter changes of the anterior temporal lobe (WCAT) and ictal hyperperfusion of the temporal stem (IHTS). Left mTLE showed interictal hypoperfusion in the ipsilateral hippocampus, bilateral thalami, and paracentral lobules. Right mTLE showed hypoperfusion in bilateral hippocampi, contralateral insula, bilateral thalami, and paracentral lobules. Both mTLEs showed ictal hyperperfusion in bilateral temporal lobes with ipsilateral predominance, and in the anterior frontal white matter bilaterally. By paired t test, ictal hyperperfusion was found in the ipsilateral temporal lobe, temporal stem, hippocampus, thalamus, putamen, insula, and bilateral precentral gyri, whereas ictal hypoperfusion was found in bilateral frontal poles and middle frontal gyri. Fifteen patients showed WCAT and 19 showed IHTS, a weak correlation was observed between WCAT and IHTS (r = 0.377, P = 0.02). WCAT was found to correlate with an early seizure onset age. In 35 patients, heterotopic neurons were found in the white matter of the resected temporal lobe, but the number of heterotopic neurons did not correlate with WCAT or IHTS. In summary, the cerebral perfusion patterns of mTLE suggest interictal hypofunction and ictal activation of the cortico-thalamo-hippocampal-insular network and ictal hypoperfusion of the anterior frontal cortex.

Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry.

STUDY OBJECTIVES Despite compelling evidence from animal studies indicating hippocampal subfield-specific vulnerability to poor sleep quality and related cognitive impairment, there have been no human magnetic resonance imaging (MRI) studies investigating the relationship between hippocampal subfield volume and sleep disturbance. Our aim was to investigate the pattern of volume changes across hippocampal subfields in patients with primary insomnia relative to controls. DESIGN Pointwise morphometry allowed for volume measurements of hippocampal regions on T1-weighted MRI. SETTING University hospital. PATIENTS Twenty-seven unmedicated patients (age: 51.2 ± 9.6 y) and 30 good sleepers as controls (50.4 ± 7.1 y). INTERVENTIONS N/A. MEASUREMENTS We compared hippocampal subfield volumes between patients and controls and correlated volume with clinical and neuropsychological features in patients. RESULTS Patients exhibited bilateral atrophy across all hippocampal subfields (P < 0.05 corrected). Cornu ammonis (CA) 1 subfield atrophy was associated with worse sleep quality (higher Pittsburgh Sleep Quality Index and higher arousal index of polysomnography) (r < -0.45, P < 0.005). The volume of the combined region, including the dentate gyrus (DG) and CA3-4, negatively correlated with verbal memory, verbal information processing, and verbal fluency in patients (|r| > 0.45, P < 0.05). Hemispheric volume asymmetry of this region (left smaller than right) was associated with impaired verbal domain functions (r = 0.50, P < 0.005). CONCLUSION Hippocampal subfield atrophy in chronic insomnia suggests reduced neurogenesis in the dentate gyrus (DG) and neuronal loss in the cornu ammonis (CA) subfields in conditions of sleep fragmentation and related chronic stress condition. Atrophy in the CA3-4-DG region was associated with impaired cognitive functions in patients. These observations may provide insight into pathophysiological mechanisms that make patients with chronic sleep disturbance vulnerable to cognitive impairment. CITATION Joo EY, Kim H, Suh S, Hong SB. Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry.

The Relationship between Hippocampal Volume and Cognition in Patients with Chronic Primary Insomnia

Background and Purpose Differences in hippocampal volume (HV) were compared between chronic primary insomniacs (PIs) and good sleepers (GSs), and the relationship between HV and memory function in PIs was investigated to clarify the effect of chronic sleep deprivation on brain structure and cognition. Methods Twenty PIs (mean age, 50 years; 18 females) and 20 age-, gender-, and education-matched GSs were enrolled. Brain magnetic resonance imaging (MRI) was performed on a 1.5-T MRI scanner. Left and right HV and intracranial volume (ICV) were measured manually. Nighttime polysomnography and neuropsychological testing were also applied to all subjects. Group differences in HV were analyzed and the relationships between HV and sleep questionnaire data, nighttime polysomnography, and neuropsychological findings were evaluated. Results Compared to GSs, PIs exhibited significantly increased sleep latency and arousal index and a decreased percentage of REM sleep in nighttime polysomnography, as well as impaired verbal and visual memory, and frontal lobe function. Absolute HV and ICV did not differ significantly between PIs and GSs. In the PIs, right and left HVs were negatively correlated with the duration of insomnia and the arousal index, and positively correlated with the recognition of visual memory. In addition, free recall in verbal memory was positively correlated with left HV in PIs. Conclusions These findings suggest that chronic sleep deprivation impairs memory and frontal lobe function, and that a long duration of insomnia and poor sleep quality contribute to a bilateral reduction in HV.

Cerebral perfusion abnormality in narcolepsy with cataplexy

To investigate abnormal cerebral perfusion in narcoleptics with cataplexy, 25 narcoleptics with cataplexy and 25 normal controls were enrolled in this study. Cerebral perfusion was measured by brain single photon emission computed tomography (SPECT) using 99mTc-ethylcysteinate dimer. Patients and normal controls had not received any medication prior to the SPECT scan. Differences in cerebral perfusion between narcoleptics and normal controls were subjected to statistical parametric mapping (SPM) analysis. Overnight polysomnography and multiple sleep latency test (MSLT) were performed in all patients. Brain SPECT was carried out on all patients and normal controls during the waking state. Clinical symptoms and MSLT results of all patients are in accord with the International Classification of Sleep Disorders criteria for narcolepsy. MSLT showed a short mean sleep latency (1.69 +/- 1.0 min) and 2-5 sleep onset REM periods in individual patient. SPM analysis of brain SPECT showed hypoperfusion of the bilateral anterior hypothalami, caudate nuclei, and pulvinar nuclei of thalami, parts of the dorsolateral/ventromedial prefrontal cortices, parahippocampal gyri, and cingulate gyri in narcoleptics [P < 0.05 by Students t test with false discovery rate (FDR) correction]. Significant hypoperfusion in the white matter of frontal and parietal lobes was also noted in narcoleptics. This study shows reduced cerebral perfusion in subcortical structures and cortical areas in narcoleptics. The distribution of abnormal cerebral perfusion is concordant with the pathway of the cerebral hypocretin system and may explain the characteristic features of narcolepsy, i.e., cataplexy, emotional lability, and attention deficit.

Glucose hypometabolism of hypothalamus and thalamus in narcolepsy

It has been hypothesized that hypothalamus is involved in narcolepsy. The relative difference between cerebral glucose metabolism of 24 narcoleptic patients and 24 normal controls was studied using 18F‐fluorodeoxy glucose positron emission tomography. Patients with narcolepsy showed significantly reduced cerebral glucose metabolism in bilateral rectal and subcallosal gyri, the medial convexity of right superior frontal gyrus, bilateral precuneus, right inferior parietal lobule, and in left supramarginal gyrus (uncorrected p < 0.001). Bilateral posterior hypothalami and mediodorsal thalamic nuclei showed hypometabolism with significance at the level of corrected p < 0.05, with small volume correction. This study showed cerebral glucose hypometabolism of the hypothalamus‐thalamus‐orbitofrontal pathways in the narcoleptic brain. Ann Neurol 2004

Cerebral perfusion changes during cataplexy in narcolepsy patients.

To localize cerebral perfusion differences during cataplexy, brain SPECT subtraction was performed between cataplexy and baseline awake period or REM sleep in patients with narcolepsy. During cataplexy, subtracted SPECT showed hyperperfusion in right amygdala, bilateral cingulate gyri, basal ganglia, thalami, premotor cortices, sensorimotor cortices, right insula, and brainstem, and hypoperfusion in prefrontal cortex and occipital lobe. This result suggests that cataplexy is produced by the activation of amygdalo-cortico-basal ganglia–brainstem circuit.

The role of ketogenic diet in the treatment of refractory status epilepticus

Ketogenic diet (KD) is known to be effective in intractable epilepsy. However, the role of KD in refractory status epilepticus (RSE) has not been well described. The aim of this study is to explore the role of KD in patients with RSE. We retrospectively reviewed the medical records of four children and one adult with RSE between October 2006 and August 2010. All presented with status epilepticus (SE) that was presumed to be associated with viral encephalitis. After we failed to control the seizures with standard measures for SE, we tried KD. The overall seizure frequency decreased to <50% of baseline in median eight (1–19) days. At one month of KD, two patients were seizure‐free, one patient showed >90% seizure reduction, and the others had >75% decrease without generalized seizures. With improvement in the RSE, we were able to taper the antiepileptic drugs (AEDs) and wean patients from prolonged mechanical ventilation. The adverse events of KD in RSE included aspiration pneumonia, gastroesophageal reflux, constipation, and hypertriglyceridemia. Those results demonstrate that KD can be a valuable therapeutic option for patients with RSE.

Resection of individually identified high‐rate high‐frequency oscillations region is associated with favorable outcome in neocortical epilepsy

High‐frequency oscillations (HFOs) represent a novel electrophysiologic marker of endogenous epileptogenicity. Clinically, this propensity can be utilized to more accurately delineate the resection margin before epilepsy surgery. Currently, prospective application of HFOs is limited because of a lack of an exact quantitative measure to reliably identify HFO‐generating areas necessary to include in the resection. Here, we evaluated the potential of a patient‐individualized approach of identifying high‐rate HFO regions to plan the neocortical resection.

Effects of levetiracetam as a monotherapy on bone mineral density and biochemical markers of bone metabolism in patients with epilepsy.

PURPOSE Antiepileptic drugs (AEDs) may have adverse effects on bone metabolism and bone mineral density (BMD). The aim of this study is to determine the changes of bone metabolism and BMD in epilepsy patients who are undergoing levetiracetam (LEV) monotherapy. METHODS Drug-naïve, sixty-one patients with recent onset epilepsy were recruited (24 female, 37 males; mean age: 31.0±13.1 years) in this study. We measured calcium, phosphate, bone alkaline phosphatase, parathyroid hormone, osteocalcin, insulin-like growth factor (IGF)-1, C-telopeptide, vitamin D3 levels and bone density measurements with DEXA method before and after LEV administration of mean duration 14.16±3.36 months. RESULTS T score in lumbar spine (L1-L4) was significantly increased with the correction of multiple T tests using Bonferronis test across LEV monotherapy (p=0.0401). However, no significant change was observed in other parameters for BMD and T score. Repeated measures ANOVA with Bonferronis correction of confounders such as sex, age, and treatment duration revealed significant increase in T score in lumbar spine (p=0.0164). The level of average LEV dosage itself did not reveal any significant association with BMD and bone metabolism. CONCLUSIONS We suggest that LEV monotherapy may have no harmful effect on bone strength and metabolism for 1 year.

Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

Objective To investigate gray matter concentration changes in the brains of narcoleptic patients. Materials and Methods Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images. Results Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05). Conclusion Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy.