De Novo Mutations Affecting the Catalytic Cα Subunit of PP2A, PPP2CA, Cause Syndromic Intellectual Disability Resembling Other PP2A-Related Neurodevelopmental Disorders.

Type 2A protein phosphatases (PP2As) are highly expressed in the brain and regulate neuronal signaling by catalyzing phospho-Ser/Thr dephosphorylations in diverse substrates. PP2A holoenzymes comprise catalytic C-, scaffolding A-, and regulatory B-type subunits, which determine substrate specificity and physiological function. Interestingly, de novo mutations in genes encoding A- and B-type subunits have recently been implicated in intellectual disability (ID) and developmental delay (DD). We now report 16 individuals with mild to profound ID and DD and a de novo mutation in PPP2CA, encoding the catalytic Cα subunit. Other frequently observed features were severe language delay (71%), hypotonia (69%), epilepsy (63%), and brain abnormalities such as ventriculomegaly and a small corpus callosum (67%). Behavioral problems, including autism spectrum disorders, were reported in 47% of individuals, and three individuals had a congenital heart defect. PPP2CA de novo mutations included a partial gene deletion, a frameshift, three nonsense mutations, a single amino acid duplication, a recurrent mutation, and eight non-recurrent missense mutations. Functional studies showed complete PP2A dysfunction in four individuals with seemingly milder ID, hinting at haploinsufficiency. Ten other individuals showed mutation-specific biochemical distortions, including poor expression, altered binding to the A subunit and specific B-type subunits, and impaired phosphatase activity and C-terminal methylation. Four were suspected to have a dominant-negative mechanism, which correlated with severe ID. Two missense variants affecting the same residue largely behaved as wild-type in our functional assays. Overall, we found that pathogenic PPP2CA variants impair PP2A-B56(δ) functionality, suggesting that PP2A-related neurodevelopmental disorders constitute functionally converging ID syndromes.

Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features.

Human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2) has been previously associated with intellectual disability and developmental delay in three patients. Here, we describe six patients with developmental delay, intellectual disability, and dysmorphic features with de novo likely gene-damaging variants in HIVEP2 identified by whole-exome sequencing (WES). HIVEP2 encodes a large transcription factor that regulates various neurodevelopmental pathways. Our findings provide further evidence that pathogenic variants in HIVEP2 lead to intellectual disabilities and developmental delay.

Needle-stick injury: a rising bio-hazard.

BACKGROUND: Needle stick injury has been identified as the foremost health allied concern and the specialty of dentistry is not an exception. Its incidence can be reduced when a dental practitioner is completely proverbial to the standard cross-infection control measures. This study was intended to assess the knowledge, attitude and practices among the dental practitioners regarding Needle Stick Injuries and associated risk factors. METHODS: This survey was carried out in the Oral Surgery Department, Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Karachi. Dental practitioners of different job categories were conveniently approached by the BDS students. They all were provided with a structured and validated, self-administered questionnaire. Descriptive statistics and Chi-square test was applied with 5% level of significance. RESULTS: All 100 (55 females and 45 males) practitioners agreed to participate in the study. Prevalence of Needle Stick Injury observed was 30% with no significant relationship with the demographic characteristics. Seventy-four percent of the participants were aware of the universal guidelines. Majority (88%) of the dental personnel believed that recapping of needles should be performed soon after use and 53% knew about needle-less safety devices. These injuries were experienced by 30% of the respondents, of which just 28% were reported. CONCLUSION: Dental practitioners were at high risk of getting Needle Stick Injuries in dental offices. Most of them had knowledge about it but there was lack of practice of universal precautions.

Case Report: Laser Ablation Guided by State of the Art Source Imaging Ends an Adolescent's 16-Year Quest for Seizure Freedom.

Epilepsy surgery is the most effective therapeutic approach for children with drug resistant epilepsy (DRE). Recent advances in neurosurgery, such as the Laser Interstitial Thermal Therapy (LITT), improved the safety and non-invasiveness of this method. Electric and magnetic source imaging (ESI/MSI) plays critical role in the delineation of the epileptogenic focus during the presurgical evaluation of children with DRE. Yet, they are currently underutilized even in tertiary epilepsy centers. Here, we present a case of an adolescent who suffered from DRE for 16 years and underwent surgery at Cook Children's Medical Center (CCMC). The patient was previously evaluated in a level 4 epilepsy center and treated with multiple antiseizure medications for several years. Presurgical evaluation at CCMC included long-term video electroencephalography (EEG), magnetoencephalography (MEG) with simultaneous conventional EEG (19 channels) and high-density EEG (256 channels) in two consecutive sessions, MRI, and fluorodeoxyglucose - positron emission tomography (FDG-PET). Video long-term EEG captured nine focal-onset clinical seizures with a maximal evolution over the right frontal/frontal midline areas. MRI was initially interpreted as non-lesional. FDG-PET revealed a small region of hypometabolism at the anterior right superior temporal gyrus. ESI and MSI performed with dipole clustering showed a tight cluster of dipoles in the right anterior insula. The patient underwent intracranial EEG which indicated the right anterior insular as seizure onset zone. Eventually LITT rendered the patient seizure free (Engel 1; 12 months after surgery). Retrospective analysis of ESI and MSI clustered dipoles found a mean distance of dipoles from the ablated volume ranging from 10 to 25 mm. Our findings highlight the importance of recent technological advances in the presurgical evaluation and surgical treatment of children with DRE, and the underutilization of epilepsy surgery in children with DRE.

Surface Microhardness Of Microhybrid And Nanocomposite After Storage In Mouth Washes.

BACKGROUND: Dental composites are aesthetic direct restorative material. However, the effect of mouthwashes on the durability of the material is controversial. This study evaluated and compared the influence of mouthwash composition on the surface hardness of nanofilled (Z350XT) and microhybrid (P60) resin composites. METHODS: Comparative in-vitro study was conducted over 6 months at Multan Medical & Dental College. Sixty-four disc-shape specimens of each {nanofilled (Z350XT) and microhybrid (P60)} resin composite were prepared and stored in distilled water at 37°C for 24 hours. The baseline microhardness reading (To) was recorded by Vickers micro-hardness tester. Samples were then randomly divided into four groups (n=16) and stored in Listerine Cool Mint, Colgate Plax, Clinica and distilled water (control). The hardness test was repeated after 12 hours and 24 hours of storage. RESULTS: Nanocomposite (Z350XT) had statistically (p<0.01) higher surface hardness. A significant reduction (p≤0.05) in microhardness was observed after immersion of samples in mouthwashes. The reduction in surface hardness was dependent on the immersion time and composition of mouthwashes. Listerine Cool Mint (alcohol-based mouthwash) had greatest degradation effect. CONCLUSIONS: Mouth rinses negatively impacted the surface microhardness of the tested resin-based materials. Alcohol-based mouthwashes had greater potential for reducing microhardness. Microhybrid composite appears to be a more suitable material for restoring teeth in patients accustomed to using regular mouthwashes.

Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome.

DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.

Palliative functional hemispherectomy for treatment of refractory status epilepticus associated with Alpers' disease.

PURPOSE: Palliative epilepsy surgery is considered for patients that would benefit from surgical therapy for intractable epilepsy but are not candidates for curative procedures. In many cases, the goals of therapy focus on improved quality of life more than seizure freedom. We discuss the use of epilepsy surgery for refractory status epilepticus, as well as the rationale and ethical considerations for employing a palliative procedure in otherwise fatal diseases. METHODS: We present a child with Alpers' disease presenting with refractory status epilepticus which was treated with functional hemispherectomy after failure of multiple typical therapies. Hemispherectomy allowed for the child to be extubated and ultimately discharged to home with her family. Unfortunately, the child died several months later after developing new-onset liver failure in the setting of a viral illness. CONCLUSION: Functional hemispherectomy was effective for the treatment of refractory status epilepticus in Alpers' disease. We believe that the procedure resulted in improved quality of life which was the primary outcome goal. Palliative procedures should be considered in diseases with ultimate fatal outcome when the short-term benefits outweigh the risks. The ethical aspects of treatment must be carefully considered to insure treatment is provided in the best interest of the patient.

Liposuction in Gynecomastia: An Assessment of the Suction-assisted Arthroscopic Shaver Versus Open Disc Excision Techniques.

Introduction Gynecomastia is a common problem of the male breasts, which imposes a great psychological burden on patients. It is mostly bilateral and frequently asymmetrical. Surgical management of gynecomastia has undergone significant changes over the past few decades. Currently, the predominant mode of treatment includes liposuction of the fibro-fatty tissue either alone or in combination with the removal of the glandular tissue by the open excision technique or arthroscopic shaver. This study aims to compare both techniques in terms of hematoma formation, nipple necrosis, reoperation, contour irregularities, acceptability of scarring, asymmetry, and patient satisfaction. Methods The study has been conducted at Shifa International Hospital, Islamabad, from May 2018 to September 2019. Sixty patients were included in the study. All the patients had bilateral gynecomastia and Simon's Grade II-A or II-B. The study sample was divided into two equal groups. Group A underwent liposuction combined with open disc excision while Group B underwent liposuction coupled with disc excision via suction-assisted arthroscopic shaver. Postoperatively, all the patients received follow-up for a minimum period of six months. Results In a cohort of 60 patients, the mean age was 25.76±5.38 years. There were minor differences noted in terms of hematoma formation, nipple necrosis, rates of re-operation, and contour irregularities between open disc excision and arthroscopic disc excision, respectively (p-value > 0.05). About eight patients reported asymmetry in open disc excision as compared to 10 in arthroscopic disc excision. The acceptability of scarring was reported as equal in both groups. Mean patient satisfaction was based on the visual analog scale (VAS) scale was 8.25 in both groups. No statistical difference regarding patient satisfaction was noted in both groups (p-value 0.126). Conclusion Our study concludes that arthroscopic shaver-assisted disc excision despite being a novel and minimally invasive technique does not hold superiority over conventional open disc excision for the management of gynecomastia. Furthermore, in a developing country like Pakistan, there is a lack of expertise with the procedure and a need for more training among plastic surgeons.

Determining the Optimal Number of MEG Trials: A Machine Learning and Speech Decoding Perspective.

Advancing the knowledge about neural speech mechanisms is critical for developing next-generation, faster brain computer interface to assist in speech communication for the patients with severe neurological conditions (e.g., locked-in syndrome). Among current neuroimaging techniques, Magnetoencephalography (MEG) provides direct representation for the large-scale neural dynamics of underlying cognitive processes based on its optimal spatiotemporal resolution. However, the MEG measured neural signals are smaller in magnitude compared to the background noise and hence, MEG usually suffers from a low signal-to-noise ratio (SNR) at the single-trial level. To overcome this limitation, it is common to record many trials of the same event-task and use the time-locked average signal for analysis, which can be very time consuming. In this study, we investigated the effect of the number of MEG recording trials required for speech decoding using a machine learning algorithm. We used a wavelet filter for generating the denoised neural features to train an Artificial Neural Network (ANN) for speech decoding. We found that wavelet based denoising increased the SNR of the neural signal prior to analysis and facilitated accurate speech decoding performance using as few as 40 single-trials. This study may open up the possibility of limiting MEG trials for other task evoked studies as well.

Does the Duration and Severity of Symptoms Have an Impact on Relief of Symptoms after Carpal Tunnel Release?

Rationale Carpal tunnel syndrome (CTS) is the most frequently encountered compressive neuropathy of the upper limb. The treatment of CTS ranges from conservative management to carpal tunnel release. Many patients with misconception about the potential morbidity and with the hope of successful conservative treatment delay the surgical release of carpal tunnel. This delay results in reduced recovery of sensory and motor median nerve function. Objective The aim of this study was to evaluate the influence of preoperative duration and severity of symptom on the outcome of carpal tunnel surgery. Method It included 45 cases of CTS, all treated with limited access open carpal tunnel release. The duration of symptoms (i.e., pain, numbness, tingling, waking up at night because of pain/numbness, difficulty in grasping small objects, and their preoperative severity) was noted using Boston CTS questionnaire. To investigate the outcome, patients were divided into three groups based on their duration of symptoms. Result Group1: The severity of symptoms was reduced to normal in a short period of time in patients who presented with duration of symptoms less than 6 months. Group 2: Patients in whom symptoms lasted for 6 to 12 months had reduced or delayed recovery of hand function as compared with first group. Group 3: Patients who had symptoms for more than 12 months had incomplete recovery of grip strength. Return to normal function took the longest time (median: 16 weeks) in this group. Conclusion This study suggests that patients who present late have delayed/incomplete relief of symptoms after carpal tunnel release.

Preservation of a subcutaneous pocket for vagus nerve stimulation pulse generator during magnetoencephalography. Technical note.

Patients with epilepsy and an implanted vagus nerve stimulation (VNS) device who are referred for consideration of definitive epilepsy surgery (removal of the epileptogenic cortex) may require magnetoencephalography (MEG), a study requiring explantation of the pulse generator, as part of their evaluation. Nonetheless, these patients may not wish to abandon palliative VNS therapy should definitive surgery prove unsuccessful or impossible. To avoid obliteration of the pocket by scar tissue after the pulse generator is explanted, the authors have preserved the dead space in several patients with insertion of a similarly sized silicone block. This block is easily replaced with the pulse generator if continued VNS therapy is appropriate, and is left in place in patients who appear to no longer require VNS therapy. Upon completion of MEG, if pulse generator replacement proves desirable, atraumatic retrieval of the electrode connector pin and body is easy. Silicone block implantation during what may prove to be temporary device explantation facilitates reuse of the original pulse generator implantation site and atraumatic distal electrode wire retrieval.

Management protocol of mandibular fractures at Pakistan Institute of Medical Sciences, Islamabad, Pakistan.

BACKGROUND: Maxillofacial trauma is very frequent and associated with a high incidence of mandibular fractures. Although there is universal agreement as to the treatment goals and basic therapeutic principles of reduction and stabilization, a variety of currently accepted treatment modalities indicate a lack of consensus. The authors evaluate the incidence, etiology, management and complications of 344 mandibular fractures in 228 patients treated in the Department of Plastic and Reconstructive Surgery at Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan, during a three year period. Indications and techniques for closed and open treatment of mandibular fractures are reviewed along with any complications of these fractures or their management. METHODS: A total of 344 mandibular fractures in 228 patients were included in this study. The sex, age, etiology, presentation, fracture characteristics, associated injuries, various methods of management and any pre or postoperative complications were evaluated. RESULTS: Although various devices and techniques have been used to treat these fractures, modern plate and screw fixation systems have proved to provide the best rigid stabilization, early mobility and associated with least complications. There was a satisfactory bone healing in all the patients and a minimal complication rate associated with open reduction and internal fixation (ORIF). CONCLUSION: Mandibular fractures occur with high frequency in road traffic accidents and interpersonal violence. They are among the most common types of facial fractures treated by the plastic surgeons. They must be managed carefully to maintain the function of the mandible, reestablish proper occlusion, and minimize secondary complications. Open reduction and internal fixation has proven to be the most effective method for treatment of mandibular fractures.

Flexor tendon injuries of hand: experience at Pakistan Institute of Medical Sciences, Islamabad, Pakistan.

BACKGROUND: Flexor tendon injury is one of the most common hand injuries. This initial treatment is of the utmost importance because it often determines the final outcome; inadequate primary treatment is likely to give poor long tem results. Various suture techniques have been devised for tendon repair but the modified Kessler's technique is the most commonly used. This study was conducted in order to know the cause, mechanism and the effects of early controlled mobilization after flexor tendon repair and to assess the range of active motion after flexor tendon repair in hand. METHODS: This study was conducted at the department of Plastic Surgery, Pakistan Institute of Medical Sciences, Islamabad from 1st March 2002 to 31st August 2003. Only adult patients of either sex with an acute injury were included in whom primary or delayed primary tendon repair was undertaken. In all the patients, modified Kessler's technique was used for the repair using non-absorbable monofilament (Prolene 4-0). The wound was closed with interrupted non-absorbable, polyfilament (Silk 4-0) suture. A dorsal splint extending beyond the finger tip to proximal forearm was used with wrist in 20-30 degrees palmer flexion, metacarpophalangeal (MP) joint flexed at 60 degrees. Passive movements of fingers were started from the first post operative day, and for controlled, active movements, a dynamic splint was applied. RESULTS: During this study, 33 patients with 39 digits were studies. 94% of the patients had right dominated hand involvement. 51% had the complete flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) injuries. Middle and ring fingers were most commonly involved. Thumb was involved in 9% of the patients. Zone III(46%) was the commonest to be involved followed by zone II (28%). Laceration with sharp object was the most frequent cause of injury. Finger tip to distal palmer crease distance (TPD) was < 2.0 cm in 71% cases (average 2.4cm) at the end of 2nd postoperative week. Total number of patients was 34 at the end of 6th week. TPD was < 2.0 cm in 55% patients and < 1.0 cm in 38% cases (average 1.5cm) at the end of 6th week. Total 9 patients were lost to the follow up at the end of 8th week. TPD was < 1.0 cm in 67% (average 0.9 cm) at the end of 8th postoperative week. No case of disruption of repair was noted during the study. CONCLUSION: Early active mobilization programme is essential after tendon repair. Majority of the patients (92%) had fair to good results at the end of 2nd week which increased to 97% at the end of 8th week to good to excellent.

Coregistration of multimodal imaging is associated with favourable two-year seizure outcome after paediatric epilepsy surgery.

Multimodal coregistration uses multiple image datasets coregistered to an anatomical reference (i.e. MRI), allowing multiple studies to be viewed together. Commonly used in intractable epilepsy evaluation and generally accepted to improve localization of the epileptogenic zone, data showing that coregistration improves outcome is lacking. We compared seizure freedom following epilepsy surgery in paediatric patients, evaluated before and after the use of coregistration protocols at our centre, to determine whether this correlated with a change in outcome. We included paediatric epilepsy surgery patients with at least one anatomical and one functional neuroimaging study as part of their presurgical evaluation. Preoperatively designated palliative procedures and repeat surgeries were excluded. Multiple pre-, peri-, and postoperative variables were compared between groups with the primary outcome of seizure freedom. In total, 115 were included with an average age of 10.63 years (0.12-20.7). All evaluations included video-EEG (VEEG) and MRI. Seven (6%) had subtraction single-photon emission CT (SPECT), 46 (40%) had positron emission tomography (PET), and 62 (54%) had both as part of their evaluation. Sixty (52%) had extratemporal epilepsy and 25 (22%) were MRI-negative. Sixty-eight (59%) had coregistration. Coregistered patients were less likely to undergo invasive EEG monitoring (p=0.045) and were more likely to have seizure freedom at one (p=0.034) and two years (p<0.001) post-operatively. A logistic regression accounting for multiple covariates supported an association between the use of coregistration and favourable post-surgical outcome. Coregistered imaging contributes to favourable postoperative seizure reduction compared to visual analysis of individual modalities. Imaging coregistration is associated with improved outcome, independent of other variables after surgery. Coregistered imaging may reduce the need for invasive EEG monitoring, likely due to improved confidence in presurgical localization. These findings support the use of multimodal coregistered imaging as part of the presurgical assessment in patients evaluated for surgical treatment of intractable epilepsy.

Magnetic resonance imaging-guided laser interstitial thermal therapy as treatment for intractable insular epilepsy in children.

OBJECTIVE Seizure onset within the insula is increasingly recognized as a cause of intractable epilepsy. Surgery within the insula is difficult, with considerable risks, given the rich vascular supply and location near critical cortex. MRI-guided laser interstitial thermal therapy (LiTT) provides an attractive treatment option for insular epilepsy, allowing direct ablation of abnormal tissue while sparing nearby normal cortex. Herein, the authors describe their experience using this technique in a large cohort of children undergoing treatment of intractable localization-related epilepsy of insular onset. METHODS The combined epilepsy surgery database of Cook Children's Medical Center and Dell Children's Hospital was queried for all cases of insular onset epilepsy treated with LiTT. Patients without at least 6 months of follow-up data and cases preoperatively designated as palliative were excluded. Patient demographics, presurgical evaluation, surgical plan, and outcome were collected from patient charts and described. RESULTS Twenty patients (mean age 12.8 years, range 6.1-18.6 years) underwent a total of 24 LiTT procedures; 70% of these patients had normal findings on MRI. Patients underwent a mean follow-up of 20.4 months after their last surgery (range 7-39 months), with 10 (50%) in Engel Class I, 1 (5%) in Engel Class II, 5 (25%) in Engel Class III, and 4 (20%) in Engel Class IV at last follow-up. Patients were discharged within 24 hours of the procedure in 15 (63%) cases, in 48 hours in 6 (24%) cases, and in more than 48 hours in the remaining cases. Adverse functional effects were experienced following 7 (29%) of the procedures: mild hemiparesis after 6 procedures (all patients experienced complete resolution or had minimal residual dysfunction by 6 months), and expressive language dysfunction after 1 procedure (resolved by 3 months). CONCLUSIONS To their knowledge, the authors present the largest cohort of pediatric patients undergoing insular surgery for treatment of intractable epilepsy. The patient outcomes suggest that LiTT can successfully treat intractable seizures originating within the insula and offers an attractive alternative to open resection. This is the first description of LiTT applied to insular epilepsy and represents one of only a few series describing the use of LiTT in children. The results indicate that seizure reduction after LiTT compares favorably to that after conventional open surgical techniques.

Management of phalangeal fractures of hand.

BACKGROUND: Phalangeal fractures are approximately 10% of all the fractures of skeletal system. Most fractures are functionally stable. Surgical treatment is necessary when fracture is displaced and reduction is not possible. This study was conducted in order to study the aetiology, features and management of the phalangeal fractures of hand. METHODS: This descriptive study was conducted in the department of Plastic Surgery, Pakistan Institute of medical Sciences, Islamabad from June 1st 2002 to July 31st 2003. Adult patients of either sex with acute injury presenting in the out-patient department and emergency department were included whereas patients below the age of 13 years and patients with amputated digits were excluded. The site and side of fracture were noted. All patients were X-rayed pre-operatively. These patients were divided into two groups. Group A comprised of those patients in whom only closed reduction was done. Group B comprised of patients in whom operative procedure was carried out. Various modalities used were percutaneous Kirschner wire fixation, open reduction and internal fixation with K-wires, screws, microplates and dental wires/ after operation, immobilization of fracture site was done for 3 4 weeks. Chi square test was used for statistical analysis of complications in both the groups. RESULTS: 51 fractures were seen in 43 men and 8 fractures in 8 females. Mean age of the patients of group A was 35.6 years as compared to 29.5 years of group B. 31% fractures were associated with soft tissue injury. Ring finger was the commonest to be involved in 36% patients. Left hand (64%) was commonly involved. Left proximal phalanx (31%) was the most frequently injured part. Intraarticular fractures were seen in 10% cases. 15 fractures were treated conservatively and some kind of operative modality was used in 44 fractures. Crush injury remained the commonest cause. In 36% patients fractures were fixed with K-wire using open reduction and internal fixation technique. In 22% patients, only percutaneous K-wire was used. In two patients, dynamic traction device was used. One case of post operative infection was noticed in group B. Whereas only one case of malunion and one case of limited joint movement and stiffness was noted in group A. CONCLUSIONS: Results of both the closed reduction and open reduction and internal fixation were equally good (p < 0.05). If there is any soft tissue injury, it is advisable to use open reduction and internal fixation technique.

Relapsing-remitting, corticosteroid-sensitive, varicella zoster virus optic neuritis.

We report a 13-year-old male who presented with bilateral disc edema after a febrile illness. Rapid loss of vision prompted corticosteroids treatment, which reversed the visual loss and optic disc findings. Both his visual function and disc edema proved exceedingly sensitive to steroids, and he required increasingly slow and prolonged corticosteroids taper to avoid relapse over a period of 1 year. Ultimately, profound visual loss was reversed three times and only after exceptionally slow steroid weaning. Comprehensive systemic investigations and neuroimaging were initially unrevealing. Late in the course of disease, evidence of seroconversion was identified in his serum and cerebrospinal fluid with positive varicella zoster virus antibodies titers. Varicella zoster virus-related optic nerve pathology may present clinically with profound visual loss and disc edema and may reverse only with high-dose corticosteroids treatment. Physicians should carefully consider retesting with late varicella zoster virus titer in patients with relapsing-remitting, steroid-sensitive optic neuritides.

Phenytoin and phenobarbital stable isotope studies in neonates.

A pharmacokinetic study of phenytoin and phenobarbital with nonradioactive isotopes was performed in nine neonates in an intensive care unit setting. A single-pulse dose of either labeled phenobarbital (1,3-(15)N, 2-(13)C) or labeled phenytoin (2-(13)C, 1, 3-(15)N) was administered to neonates who manifested gestation between 25 and 40 weeks and were receiving maintenance medication. Blood samples were collected at fixed intervals, and with a computerized gas chromatography mass spectrometry system, plasma concentrations of the labeled and unlabeled drug in relation to time administered were obtained. According to the calculations obtained from labeled analogue, several kinetic characteristics related to drug absorption, clearance, and elimination were determined. The use of a nonradioactive labeled isotope overcomes the limitations of conventional pharmacokinetic methodology and can be specifically useful in neonates and infants in whom volumes of distribution are rapidly changing and steady state is not achieved.