Haploinsufficiency of PRRT2 Leading to Familial Hemiplegic Migraine in Chromosome 16p11.2 Deletion Syndrome.

Microdeletion in the 16p11.2 loci lead to a distinct neurodevelopmental disorder with intellectual disability and autism spectrum disorder in addition to dysmorphia, macrocephaly, and increased body mass index. One of the deleted genes in this region is PRRT2 which codes for proline-rich transmembrane protein 2. Heterozygous variants in PRRT2 cause four distinct neurological disorders including benign familial infantile epilepsy (BFIE), paroxysmal kinesigenic dyskinesia (PKD), PKD with infantile convulsions, and familial hemiplegic migraine (FHM). A 13-year-old male with a known history of 16p11.2 deletion and resultant cognitive delay presented with sudden onset of headache, left-sided weakness, facial droop, and aphasia concerning for acute ischemic stroke. Magnetic resonance imaging of the brain was performed urgently which did not reveal any acute processes and his presentation met criteria for hemiplegic migraine. There have been reports of PKD and BFIE in this microdeletion syndrome; however, our proband is the first case that presented with FHM related to haploinsufficiency of PRRT2. This report highlights the importance of counseling patient families regarding acute paroxysmal presentations in this syndrome.

Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder.

Neurodevelopmental disorders (NDD) are common, with 1-3% of general population being affected, but the etiology is unknown in most individuals. Clinical whole-exome sequencing (WES) has proven to be a powerful tool for the identification of pathogenic variants leading to Mendelian disorders, among which NDD represent a significant percentage. Performing WES with a trio-approach has proven to be extremely effective in identifying de novo pathogenic variants as a common cause of NDD. Here we report six unrelated individuals with a common phenotype consisting of NDD with severe speech delay, hypotonia, and facial dysmorphism. These patients underwent WES with a trio approach and de novo heterozygous predicted pathogenic novel variants in the KAT6A gene were identified. The KAT6A gene encodes a histone acetyltransfrease protein and it has long been known for its structural involvement in acute myeloid leukemia; however, it has not previously been associated with any congenital disorder. In animal models the KAT6A ortholog is involved in transcriptional regulation during development. Given the similar findings in animal models and our patient's phenotypes, we hypothesize that KAT6A could play a role in development of the brain, face, and heart in humans. © 2016 Wiley Periodicals, Inc.

Home direct-to-consumer telehealth solutions for children with mental health disorders and the impact of Covid-19.

Delivery of mental health treatment in the home can close gaps in care. Telehealth also provides access to healthcare that has been disrupted due to the COVID-19 pandemic. In 2016, a home direct-to-consumer telehealth program was initiated. Mental health encounters made up a significant portion of all telehealth encounters and COVID-19 had a significant impact on accelerating the utilization of telehealth. Telemental health has been more successful at meeting targeted volumes than the overall health system. Of all the mental health diagnoses before and during COVID-19, attention deficit hyperactivity disorder, Autism Spectrum Disorder, and Anxiety Disorder were most common. The direct-to-consumer telehealth program saved patients a significant amount of travel miles and associated time, based on data from the period before COVID-19. Payment reimbursement for direct-to-consumer telehealth professional services was similar to reimbursement for in-person visits. This program demonstrates direct-to-consumer telehealth is a feasible and acceptable care modality for a variety of youth mental health disorders.

Subtotal splenic embolization is a safe and effective treatment for isolated splenic vascular tumors associated with consumptive coagulopathy.

Consumptive coagulopathy is a known complication of large vascular tumors. We describe 2 episodes of consumptive coagulopathy in young children, which were secondary to isolated splenic vascular tumors. One child was successfully treated by subtotal embolization of the spleen, whereas the second child required splenectomy after an initial embolization improved--but did not fully control--his consumptive coagulopathy.

Children's Hospital Ambulatory Response to the 2019 Novel Coronavirus Disease (COVID-19) Pandemic.

The 2019 novel coronavirus disease (COVID-19) pandemic produced an abrupt and near shutdown of nonemergent patient care. Children's National Hospital (CNH) mounted a multidisciplinary, coordinated ambulatory response that included supply chain management, human resources, risk management, infection control, and information technology. To ensure patient access, CNH expanded telemedicine and instituted operational innovations for outpatient procedures. While monthly in-person ambulatory subspecialty visits decreased from 25 889 pre-COVID-19 to 4484 at nadir of the COVID-19 pandemic, telemedicine visits increased from 70 to 13 539. Further studies are needed to assess the impact of innovations in health care delivery and operations that the crisis prompted.

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study.

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

Active Case Finding for Rheumatic Fever in an Endemic Country.

Background Despite the high burden of rheumatic heart disease in sub-Saharan Africa, diagnosis with acute rheumatic fever (ARF) is exceedingly rare. Here, we report the results of the first prospective epidemiologic survey to diagnose and characterize ARF at the community level in Africa. Methods and Results A cross-sectional study was conducted in Lira, Uganda, to inform the design of a broader epidemiologic survey. Key messages were distributed in the community, and children aged 3 to 17 years were included if they had either (1) fever and joint pain, (2) suspicion of carditis, or (3) suspicion of chorea, with ARF diagnoses made by the 2015 Jones Criteria. Over 6 months, 201 children met criteria for participation, with a median age of 11 years (interquartile range, 6.5) and 103 (51%) female. At final diagnosis, 51 children (25%) had definite ARF, 11 (6%) had possible ARF, 2 (1%) had rheumatic heart disease without evidence of ARF, 78 (39%) had a known alternative diagnosis (10 influenza, 62 malaria, 2 sickle cell crises, 2 typhoid fever, 2 congenital heart disease), and 59 (30%) had an unknown alternative diagnosis. Conclusions ARF persists within rheumatic heart disease-endemic communities in Africa, despite the low rates reported in the literature. Early data collection has enabled refinement of our study design to best capture the incidence of ARF and to answer important questions on community sensitization, healthcare worker and teacher education, and simplified diagnostics for low-resource areas. This study also generated data to support further exploration of the relationship between malaria and ARF diagnosis in rheumatic heart disease/malaria-endemic countries.

Intradermal botulinum toxin type A injection effectively reduces residual limb hyperhidrosis in amputees: a case series.

OBJECTIVE: To study the effectiveness of botulinum toxin type A (BTX-A) therapy for residual limb hyperhidrosis, prosthesis fit and function, and residual and phantom limb pain in patients with limb amputation. DESIGN: Consecutive case series. SETTING: Outpatient physical medicine and rehabilitation clinic. PARTICIPANTS: Walter Reed Army Medical Center patients (N=8) with unilateral traumatic upper- or lower-limb amputation. INTERVENTION: BTX-A was injected transdermally in a circumferential pattern around the residual limb by using a 1-cm matrix grid. MAIN OUTCOME MEASURE: A 10-cm continuous Likert visual analog scale was used to assess residual limb sweating and pain and prosthesis fit and function before and 3 weeks after BTX-A injections. RESULTS: Patients reported a significant reduction in sweating and improvement in prosthesis fit and function after treatment. However, residual limb and phantom pain were unaffected by treatment. CONCLUSIONS: BTX-A may be an effective treatment for residual limb hyperhidrosis, resulting in subjective improvement in prosthesis fit and functioning. BTX-A should be considered as a method to manage excessive sweating in the residual limb of traumatic amputees.

Rotavirus-induced seizures in childhood.

Rotavirus infection is a frequent cause of gastroenteritis in children and accounts for significant morbidity and mortality, especially in the developing world. Less well recognized is the association of rotavirus-induced central nervous system dysfunction, which has been associated with seizure, encephalopathy, and death. Symptoms may vary widely, however, and children can experience short afebrile convulsions as the only manifestation of rotavirus encephalopathy. We report 4 further cases of rotavirus-induced seizures with mild neurologic manifestations. The condition is reviewed and practical management strategies are suggested.

Hemiataxia: A Novel Presentation of Anti-NMDA Receptor Antibody Mediated Encephalitis in an Adolescent.

Anti-NMDA receptor antibody associated encephalitis as a cause of new-onset neuropsychiatric manifestations in children and adults can represent a significant diagnostic challenge for clinicians. Clinical signs often include encephalopathy, new-onset psychosis, and movement phenomenon. Although orofacial dyskinesias were initially identified as a characteristic movement phenomenon in this type of encephalitis, an expanded range of abnormalities has recently been reported, including isolated ataxia. We report a case of isolated hemiataxia in a young adult with mild initial psychiatric manifestations. A personal and family history of preceding neuropsychiatric symptoms produced diagnostic confusion and resulted in a significant diagnostic and therapeutic delay. Our case confirms the unilateral movement manifestations that have been emphasized in recent reports. Additionally, it confirms the need for involvement of neurologic as well as psychiatric services in the evaluation of such cases and emphasizes the importance of the neurologic examination in presentations with an initial psychiatric predominance.

Treatment of chronic low back pain with successive injections of botulinum toxin a over 6 months: a prospective trial of 60 patients.

OBJECTIVES: The aim of this study was to evaluate the effects of two successive neurotoxin treatments for chronic low back pain using multiple pain rating scales in an open-label, prospective study. METHODS: Adult patients with chronic low back pain received multiple paraspinal muscle injections with a maximum dosing of 500 units of botulinum A toxin per session. Those with a beneficial clinical response received a second treatment at 4 months. Pain was assessed by visual analog scale (VAS), modified low back pain questionnaire (OLBPQ), and a clinical low back pain questionnaire (CLBPQ) at baseline, 3 weeks, 2 months, 4 months, and 6 months after the first treatment. RESULTS: Eighteen women and 42 men, ages 21 to 79 years (mean 46.6 years), with low back pain of a mean duration of 9.1 years were included. Significant improvement in back and radicular pain occurred at 3 weeks in 60% and at 2 months in 58% of the cohort. Beneficial clinical response to the first injection predicted response to reinjection in 94%. A significant minority of patients had a sustained beneficial effect from the first injection at 4 (16.6%) and 6 months (8.3%). Two patients had a transient flu-like reaction after the initial treatment. CONCLUSIONS: Botulinum toxin A improves refractory chronic low back pain with a low incidence of side effects. The beneficial clinical response is sustained with a second treatment.

Obesity Prevention and Screening.

Obesity is widespread, associated with several physical and psychosocial comorbidities, and is difficult to treat. Prevention of obesity across the lifespan is critical to improving the health of individuals and society. Screening and prevention efforts in primary care are an important step in addressing the obesity epidemic. Each period of human development is associated with unique risks, challenges, and opportunities for prevention and intervention. Screening tools for overweight/obesity, although imperfect, are quick and easy to administer. Screening should be conducted at every primary care visit and tracked longitudinally. Screening tools and cutoffs for overweight and obesity vary by age group.

Prolonged Activity Restriction After Concussion: Are We Worsening Outcomes?

The current treatment of concussion or mild traumatic brain injury (mTBI) is primarily based on expert consensus. Most clinical practice guidelines advise cognitive and physical rest after injury including withdrawal from normal life activities such as school attendance, sports participation, and technology use until symptoms resolve. Some individuals who sustain an mTBI experience persistent physical, cognitive, and mental health problems. Activity restriction itself may contribute to protracted recovery and other complications. Williamson's Activity Restriction Model of Depression, formulated more than 20 years ago, is central to this hypothesis. We review research evidence for potential harms of prolonged activity restriction and report an mTBI case as an example of how an "activity restriction cascade" can unfold. According to this model, psychological consequences of removal from validating life activities, combined with physical deconditioning, contribute to the development and persistence of postconcussive symptoms after mTBI in some youth. A modification to mTBI guidelines that emphasizes prompt reengagement in life activities as tolerated is encouraged.

Paroxysmal tonic upgaze and partial tetrasomy of chromosome 15: a novel genetic association.

Paroxysmal tonic upgaze of childhood is an eye movement abnormality characterized by periodic episodes of conjugate upward eye deviation. Although the spectrum of paroxysmal tonic upgaze has broadened considerably, a specific pathophysiology has not been elucidated. We report an infant with paroxysmal tonic upgaze who presented to his pediatrician with associated hypotonia and gross motor delay. High-resolution chromosome analysis demonstrated a supernumerary dicentric bisatellited marker chromosome. Analysis revealed partial tetrasomy of 15q. Given the significant amount of euchromatin demonstrated, it is likely that the chromosomal abnormalities are causative for the constellation of manifestations in this patient. To date, a specific genetic abnormality has not been associated with paroxysmal tonic upgaze. The finding of a genetic association with paroxysmal tonic upgaze might help characterize the substrate for ophthalmologic manifestations. Further study in this chromosomal region in patients with paroxysmal tonic upgaze is warranted.

Visual disturbance associated with postoperative cerebellar mutism.

Cerebellar mutism is an uncommon complication of posterior fossa surgery. Manifestations include disturbances of articulation, prosody, and pitch, and, if severe, complete mutism. Symptoms are independent of recognizable cortical or brainstem injury, and recovery is variable, with permanent deficits frequently observed. Cerebellar dysfunction is commonly invoked as an etiology, although controversy remains concerning the mechanism. Visual impairment has been reported only once before in the setting of this disorder. We report a confirmatory case of sudden, severe visual loss in association with cerebellar mutism after resection of a midline medulloblastoma in a 7-year-old.

Ectodermal dysplasia and brain cystic changes: confirmation of a novel neurocutaneous syndrome.

Ectodermal dysplasia is a rare congenital disorder characterized by dry, brittle hair, dental malformations, and skin abnormalities. It is thought to be the result of embryonic ectodermal dysgenesis, affecting tissues and structures that are widely separated but with common developmental origins. Recently, this disorder has been associated with a unique neuroimaging appearance, consisting of widely dilated perivascular spaces. This association has been proposed as a novel neurocutaneous syndrome, identified in one report as "cerebrum polycystica vera." We report a similar patient with dilated perivascular spaces associated with dermatologic manifestations consistent with ectodermal dysplasia. This patient was otherwise normal, without neurocognitive deficit. Additional neuroimaging findings included widespread white-matter high signal intensity on T2-weighted magnetic resonance imaging, as well as normal findings on magnetic resonance spectroscopy. This case confirms the association of ectodermal dysplasia and brain cystic changes and appears to expand the phenotypic manifestations that may be seen in such patients.

Orofacial automatisms induced by acute withdrawal from high-dose midazolam mimicking nonconvulsive status epilepticus in a child.

Nonconvulsive Status Epilepticus (NCSE) is not uncommon in children, and can be challenging to diagnose and treat. Etiologies vary widely and include infection, trauma and acute withdrawal from medications such as anticonvulsants. We report a child who experienced orofacial dyskinesias concerning for NCSE after withdrawal from high dose benzodiazepines andopiates. Automonic signs typically associated with sedative withdrawal were absent and treatment with benzodiazepines did not improve his symptoms. Diagnostic testing was negative, including electroencephalogram, and resolution was complete within five days. Our case demonstrates the orofacial dyskinesias that may occur during sedative medication withdrawal, and highlights potential confusion with non-convulsive status epilepticus.

Successful treatment of recalcitrant restless legs syndrome with botulinum toxin type-A.

STUDY OBJECTIVE: We report the effective use of injected BTX-A to treat refractory restless legs syndrome (RLS). METHODS: This is an observational case series of 3 patients meeting the essential diagnostic criteria for RLS whose symptoms were refractory to or who refused oral medication. Areas of maximal discomfort were injected as described below. RESULTS: Patient #1, a 58-year-old man with refractory RLS, received injections in both legs. The effect persisted for 12 weeks after injections. He temporarily stopped taking gabapentin. He experienced a mild increase in a timed run. Patient #2, a 38-year-old man with refractory RLS, received BTX-A injections in both legs and his lumbar paraspinal muscles. Three days after injection, he reported great improvement. Within 1 month, his Epworth Sleepiness Scale score had decreased from 19 to 5. He stopped oral therapy during the peak therapeutic period. There were no untoward effects. Patient #3, a 38-year-old woman had a prolonged sleep latency due to RLS. BTX-A was administered in the legs. In 2 days, her discomfort and her subjective sleep latency improved. Both the urge to move and nocturnal restlessness resolved for 10 weeks. There were no untoward effects in all patients, and the response was repeated in successive injection cycles. CONCLUSIONS: Intramuscular BTX-A alleviated symptoms, reduced medication use, and/or reduced daytime sleepiness with minimal, if any, untoward effects. BTX-A should be further investigated in controlled studies as a treatment of RLS.

Treatment of refractory, chronic low back pain with botulinum neurotoxin A: an open-label, pilot study.

OBJECTIVE: To study the short- and long-term effects of botulinum neurotoxin A (BoNT-A, Botox, Allergan Inc.) on refractory chronic low back pain. DESIGN: The effect of botulinum neurotoxin A on chronic low back pain was prospectively studied in 75 patients with repeated treatments over a period of 14 months. Pain intensity (visual analog scale [VAS]), pain frequency (pain days), and perceived functional status (Oswestry scale) were assessed at baseline, 3 weeks, and at 2, 4, 6, 8, 10, 12, and 14 months. BoNT-A was injected into para-spinal muscles at 4-5 levels (between L1 and S1) unilaterally or bilaterally. The dose per site varied from 40 to 50 units. The total dose per session ranged from 200 to 500 units. Reinjections were performed at 4 months only when pain returned. RESULTS: At 3 weeks, 40 patients (53%) and at 2 months, 39 patients (52%) reported significant pain relief. The change in VAS, Oswestry score, and pain days was significant compared with baseline at 2 months after each injection period (P < 0.005) and remained so over subsequent treatments. Among initial responders, 91% continued responsiveness over the length of the study. Three patients (4%), after the first treatment, had a mild flulike reaction that lasted 2-5 days. CONCLUSION: Botulinum neurotoxin A may be beneficial in patients with chronic low back pain. A favorable initial response predicts subsequent responsiveness. The treatment is well tolerated, and side effects are mild and transient.