Browsing by Author "Marks, Warren"
Now showing 1 - 4 of 4
- Results Per Page
- Sort Options
Item A Case Study of Deafness-Dystonia-Optic Neuropathy & Treatments(2017-03-14) Hamby, Tyler; Marks, Warren; Reed, Mary-Ann; Aalbers, Brian; Honeycutt, John; Durand, ChristopherPurpose: DDON, also known as Mohr-Tranebjaerg syndrome is an inherited disorder of an Xp22 mutation of the mitochondrial transport protein TIMM8A. This mutation leads to progressive dystonia, otic neuropathy, and visual disturbances. Most patients will progress to dementia by early adulthood. Methods: We report on a teenage male with DDON and the treatments he received at Cook Children’s Medical Center (CCMC). Results: A 15-year-old patient with a prior diagnosis of DDON presented to CCMC for treatment of worsening dystonia. He communicated by gesture and sign language, and relied on a iPad. His increasing dystonia made him incapable of communicating effectively, particularly dystonia of the upper extremities. He was was previously treated with botulinum toxin chemodenervation, however, that treatment had lost efficacy as a relief of dystonia. He received Deep Brain Stimulation (DBS) of the globus pallidus internus (GPi). Since receiving DBS implants, several programming adjustments have been made and have led to a decrease in severity of symptoms. The patient was also started on a trial of baclofen to decrease muscle dystonia. Following a good response to trial, the patient was implanted with an intra-thecal baclofen pump (ITB) to decrease the dystonia of the trunk and lower extremities that had progressed. Over five years of treatment, scores on disability scales such as the Burke-Fahn-Marsden dystonia scale have slowly worsened as the disease has progressed. Concern was expressed about efficacy of the treatment, so a trial of observed time without DBS was performed. Marked worsening of disability was noted, showing that therapy has slowed the progression of this patient’s disease. Future care includes monitoring of DBS implants and transitioning care to another provider closer to the patient’s home. Conclusions: This is the fourth known case of DBS used in DDON treatment. This is also the first reported combination of ITB and DBS. Compared to other cases, this patient’s outcomes with DBS have not been as marked, due to some unique brain anatomy. ITB is a unique treatment for DDON and has shown some of the most efficacious results for this patient.Item Deep Brain Stimulation in Pediatric Status Dystonicus: A Case Series Investigation on Rapid Activation & ICU Stays(2024-03-21) Schneider, Glen; Marks, WarrenPurpose: Status dystonicus (SD) is a life-threatening movement disorder characterized by a sudden and severe worsening of generalized dystonia, often complicated by rhabdomyolysis with associated metabolic and respiratory consequences, including death. Deep brain stimulation (DBS) is a potential treatment modality for pharmaco-resistant SD (PRSD) which, despite growing interest in its use, requires further research into ideal patient selection and optimum timing for device activation. Timely deployment of this therapy can lead to shorter ICU stays and better outcomes for patients by reducing the need for additional invasive procedures and escalating pharmaceutical therapy. Methods: This is a retrospective case series of 6 consecutive pediatric SD patients who were admitted to the PICU at Cook Children’s Medical Center between October 2010 and March 2022. Following their admission, these patients were treated with DBS and were all subsequently discharged from the ICU. We examined ICU time between patients who underwent rapid activation of DBS systems and those who delayed the start of this intervention. Results: Patients with acquired forms of dystonia demonstrated a mean ICU stay of 58 following DBS activation, and patients with genetic dystonias had a mean stay of 18 days after the procedure. Rapid deployment of DBS systems and two stage procedures were associated with more positive patient outcomes, Conclusions: SD is a condition with a wide range of clinical presentations and responsiveness to treatment. This unpredictability and variation in disease outcomes emphasizes the need for further controlled studies to clarify optimal timing and patient selection for DBS. Ethical and parental concerns regarding the recruitment of children into clinical trials remains a major limiting factor to this goal, making meaningful clinical reports and data sharing between care centers essential in advancing the collective understanding of this condition and in optimizing patient care.Item Myalgic Beckers Muscular Dystrophy Due to an Exon 15 Point Mutation: Case Series and Literature Review(2022) Tavallaee, Zachary; Hamby, Tyler; Marks, WarrenBackground: Dystrophinopathies result from mutations to the DMD gene. Presentation varies from asymptomatic elevations in creatine kinase levels to early loss of ambulation and significant impairment as seen in Duchenne's muscular dystrophy. We report 5 boys in 3 families with heterogenous phenotypes due to a point mutation in the DMD gene: a hemizygous tyrosine-to-cysteine change in exon 15 (c.1724T>C) resulting in an amino acid substitution of leucine to proline at codon 575. The specific mutation on DMD c.1724T>C (p.Leu575Pro) is listed in the Clinvar database as a variant of unknown significance. Our report provides contributing evidence that this genetic alteration should be classified as pathogenic. Case Information: Our 3 patients above the age of 2 years presented with elevated creatine kinase levels, myalgia after exercise, and occasional muscle cramping. Our 2 patients below the age of 2 years presented with elevated creatine kinase levels and no other findings. This mutation has been reported before, with 3 prior patients presenting with similar clinical findings of myalgia, myoglobinuria, and occasional muscle cramping. Some similarities among all 8 patients include elevated creatine kinase levels, no muscle weakness, no calf hypertrophy, and no Gower sign. Discussion: Of note, these patients can present initially with elevated liver function enzymes, as seen with 1 of our patients, and our report raises awareness that dystrophinopathies should be considered before undergoing costly gastrointestinal testing. Two of the 8 patients presented with neuropsychiatric disorders: 1 with attention-deficit/hyperactivity disorder (ADHD) and 1 with autism. This suggests that ADHD and autism may be a presenting feature of dystophinopathies, and creatine kinase levels should be considered in their evaluation. This report elucidates the clinical presentation of the mutation on DMD c. 1724T>C.Item Probable genetic vulnerabilities that can account for the pathophysiology of cerebral palsy(2023) Ntekim, Nedeke; Butson, Carter; Hamby, Tyler; Acord, Stephanie; Marks, WarrenPURPOSE:Cerebral palsy (CP) is a nonprogressive brain and movement disorder that manifests as abnormal muscle tone. Despite the increase in cesarean sections, the rates of CP have remained constant. Research has shown that 14% of CP cases of cases have a likely causative single gene mutation and up to 31% have several genetic variations. However, no single gene has been found to explain all the symptoms of CP. The aim of the present study was to use patient’s genetic reports to determine what percentage of patients had a causative/putative gene to explain symptoms and to identify the role of those genes. The pathogenic alleles identified may warrant screenings to assess for secondary risks. METHODS: Using Invitae CP spectrum disorders panel, we analyzed the positive CP genetic reports of the 31 patients tested from November 2020 and July 2022 from a single pediatric neurology practice. We collected information about patient demographics, pathogenic alleles, and variants of uncertain significance (VUS). RESULTS: Of the 31 positive genetic reports, 30 patients (97%) had at least one pathogenic allele found; Twenty-nine pathogenic alleles were identified: four (13.8%) with autosomal dominant (AD) diseases, and seven (24.1%) with both AD and recessive (AR) diseases. Some of the pathogenic alleles found were CACNA1A (n=2), CREBBP (n=1), CTNNB1 (n=1), ATM (n=1). CONCLUSION: Many of the genes identified were associated with a movement disorder that shares features of CP, including spasticity or dystonia. The incidence of genetic findings and the high yield of dominant disorders and potential secondary risks suggest the need for both patient management and family counseling.