Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS® System: Efficacy and description of chronic electrophysiological recordings

ObjectivesDescribe changes in clinical seizure frequency and electrophysiological data recorded in patients with medically-intractable seizures and periventricular nodular heterotopias (PVNH) treated with the RNS® System (NeuroPace, Inc., Mountain View, CA).MethodsClinical seizures from eight patients (mean follow-up of 10.1 years) were analyzed pre- and post-treatment. Chronic ambulatory electrocorticograms (ECoGs) recorded from PVNHs, hippocampus and neocortex were evaluated to identify the earliest electrographic seizure onset type, pattern of spread, and interictal characteristics.ResultsMean reduction in disabling seizures was 85.7 % (n = 8); seven patients had >50% seizure reduction and two were seizure-free in the final year of analysis. Seizure rate showed a progressive reduction over the course of the study with the highest rate of improvement in the first two to three years after implantation. Four of seven patients with one PVNH lead and a second lead in the hippocampus or neocortex had some electrographic seizures first recorded at either lead location, suggesting two foci or seizure propagation patterns. Low voltage fast type activity was the prominent seizure onset pattern. Interictal ECoG power was lower in PVNH than hippocampus.ConclusionsRNS® System treatment substantially reduced clinical seizure frequency in patients with PVNH. Analysis of ictal ECoG records suggests PVNH may be involved in seizure generation.SignificanceChronic ECoG recordings suggest PVNH tissue can actively participate in epileptogenic networks. Direct brain-responsive neurostimulation is a safe and effective treatment option in such patients, progressively reducing seizure rate over a period of years.     

Tumour-like lesions of the spleen

Tumour-like lesions of the spleen are very rare lesions but can cause diagnostic confusion due to their varying morphologic patterns. These lesions behave in a benign fashion. Included in this group are hamartomas, sclerosing angiomatoid nodular transformation (SANT), inflammatory pseudotumors, and possibly IgG4-related disease. Clinically, these lesions are often discovered incidentally on imaging or at autopsy. However radiological and morphological findings can be misleadingly worrisome. It is therefore important to be familiar with these lesions to distinguish them from malignant lesions.     

Automated morphometric magnetic resonance imaging analysis for the detection of periventricular nodular heterotopia

Purpose: To describe a novel magnetic resonance imaging (MRI) postprocessing technique for the detection of periventricular nodular heterotopia (PNH) and to evaluate its diagnostic value. The method is a further development of voxel‐based morphometric analysis with focus on a region of interest around the lateral ventricles to increase the sensitivity and specificity for automated detection of abnormally located gray matter in this area. Methods: T₁‐weighted MRI volume data sets were normalized and segmented in statistical parametric mapping (SPM 5 software), and the distribution of gray matter was compared to a normal database. As a new approach, individual masks derived from segmentation of the lateral ventricles were used to restrict the search for ectopic gray matter to the periventricular area. PNH were automatically detected by localizing the maximum deviation from the normal database in this area, provided that the z‐score exceeded a certain threshold. The optimal z‐score threshold for maximum sensitivity and specificity was determined by a receiver operating characteristic (ROC) curve analysis. The method was applied in 40 patients with PNH and 400 controls. Key Findings: PNH were detected in 37 of 40 patients, and false positives were found in 34 of 400 controls, amounting to 92.5% sensitivity and 91.5% specificity. In 17 of the patients in whom PNH could be identified, these lesions had been overlooked in the past, and in 8 patients even in the high‐resolution MRI subsequently used for postprocessing. Significance: The results suggest that automated morphometric MRI analysis with focus on ectopic gray matter in the periventricular areas facilitates the evaluation of MRI data and increases the sensitivity for the detection of PNH.     

贵州儿童甲状腺肿消长情况追踪调查与分析

目的 探讨实施全民食盐加碘(USI)措施后，贵州省儿童甲状腺肿(甲肿)及其消长规律。方法 2001年4月采用点面结合的“典型调查”方法调查贵州省儿童的甲状腺肿情况，2003年10月采用群体追踪调查的方法，对2001年调查的同一人群开展甲肿消长情况的流行病学现况追踪调查。结果 2003年共有效追踪调查了1702名学生。其中在240例原检出Ⅰ度甲肿的学生中，139例转变为正常，转变率57．92％。15例转变Ⅱ度，转变率为6．25％。86例未改变，占35．83％。在28例原检出Ⅱ度甲肿的学生中，7例转为正常，2例转为I度，总体转变率42．86％。在追踪调查的1434名正常学生中，新发甲肿率为6．69％。结论 贵州省8～10岁儿童甲肿率逐年下降，但降幅非常缓慢，儿童甲肿多数会随时间推移自行减轻或恢复正常，只有少数会加重。     

Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report

Rationale:Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene.Patient concerns:We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband''s older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms.Diagnoses:The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband''s genome that absented in any other analyzed family member, suggesting its de novo origin.Interventions and outcomes:The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus.Lessons:We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available.     

Compressive optic neuropathy (CON) in Graves’ disease caused by hypertrophy of levator and superior rectus muscles: A case report

Rationale:Enlargemento of the medial rectus is the most predominant factor of compressive optic neuropathy (CON) in Graves‘ disease. This case report indicates that CON could develop only from the hypertrophic superior levator and superior rectus (SL/SR) muscle in a patient with poorly controlled Graves‘ disease, and described the possible risk of FT₃-thyrotoxicosis with a prominent goiter to develop the current rare case with a review of the literature.Patient concerns:A 66-year-old woman undergoing endocrine management of hyperthyroidism with prominent goiter visited the Department of Ophthalmology due to right-eye upper-eyelid retraction.Diagnoses:At initial presentation, the right and left margin reflex distance-1 (MRD-1) was 3.2 mm and 2.1 mm, respectively, and no proptosis or visual dysfunction was observed. Despite insufficient hormonal regulation, she refused to undergo goiter removal. The upper eyelid retraction gradually worsened to 7.7 mm of MRD-1, followed by the onset of 20 prism diopters (PD) of the right hypertropia, resulting in right-eye CON after 6 months. Her free thyroxin level was 3.88 ng/dl and free triiodothyronine was 24.90 pg/ml. Computed tomography and magnetic resonance imaging showed only SL/SR enlargement in the right orbit.Interventions:Intravenous steroid and radiation therapy resulted in visual improvement; however, a prominent upper eyelid retraction and 35PD of hypertropia remained in her right eye. Orbital decompression, upper retraction repair, and superior rectus recession were performed to prevent the recurrence of CON and correct any disfigurement.Outcomes:The combination of conventional intravenous steroid pulse therapy, radiotherapy, and orbital decompression was effective, and no recurrence was observed for more than 1.5-years postoperatively.Lessons:Enlargement of the SL/SR muscle complex may independently induce the CON. We believe that strict attention should be paid to patients with triiodothyronine thyrotoxicosis with progressive eyelid retraction and hypertropia.     

An outline concerning the potential use of recombinant human thyrotropin for improving radioiodine therapy of multinodular goiter

Radioiodine ((131)I) treatment for nontoxic and toxic multinodular goiter (MNG) is an alternative therapeutic procedure used especially for patients with contraindication for surgery. Several studies have been conducted in recent years assessing the use of recombinant human TSH (rhTSH) in increasing (131)I uptake in MNGs. This procedure also decreases the activity level of the administered (131)I, changes the distribution of (131)I in the thyroid, lowers the absorption dose, and dramatically reduces the volume of the goiter (50-75% of the baseline volume). A major disadvantage, however, is the induction of hypothyroidism in a relatively large number of patients. A transient increase in thyroid volume and tenderness was noted in the first week of treatment. Also a short period (2-4 weeks) of hyperthyroidism was observed in most patients with potential consequences particularly for the elderly. Still, there has been no evidence to date that the adverse effects outweigh the positive results of using rhTSH. The use of rhTSH in benign goiter disease has not yet been approved worldwide, but its positive activity in MNG is remarkable and promising.     

Enlargement of Intrathoracic Goiter with Unilateral Phrenic Nerve Paralysis Leading to Cardiopulmonary Arrest

As an intrathoracic goiter expands, it causes airway stenosis and phrenic nerve paralysis, and slight respiratory stimuli can trigger sudden life-threatening hypoventilation. A 78-year-old obese woman with a large intrathoracic goiter was found unconscious with agonal breathing in her room early in the morning. Cardiopulmonary resuscitation restored spontaneous circulation. She underwent surgical removal of the goiter; however, she required long-term mechanical ventilation because of atelectasis due to phrenic nerve paralysis. In patients with large intrathoracic goiters, difficulty breathing on exertion and diaphragm elevation on chest X-ray may be significant findings predicting future respiratory failure.