Intracranial hematolymphoid malignancies: A case series with molecular characterization.

OBJECTIVE: Central nervous system (CNS) manifestations of hematologic malignancies are uncommon and often have a poor prognosis. As hematologic neoplasms are typically chemotherapy- and radiotherapy-sensitive, surgical resection is usually not indicated; thus, opportunities for in-depth characterization of CNS hematologic tumors are limited. Here, we report four cases of rare intracranial hematologic tumors requiring surgical intervention, allowing for histopathologic and genomic characterization. METHODS: The clinical course, genetic perturbations, and histopathological features are described for a case of 1) primary marginal zone B-cell lymphoma of the dura as well as cases of brain metastases of 2) cutaneous T-cell lymphoma, 3) acute myeloid leukemia/myeloid sarcoma, and 4) multiple myeloma. Targeted DNA sequencing, fluorescence in situ hybridization, cytogenetic analysis, flow cytometry and immunohistochemical staining were used to assess the lesions. RESULT: Molecular and histopathological characterizations of four unusual presentations of hematolymphoid diseases involving the CNS are presented. Genetic abnormalities were identified in each lesion, including chromosomal aberrations and single nucleotide variants resulting in missense or nonsense mutations in oncogenes. CONCLUSIONS: Our case series provides insight into unique pathological phenotypes of hematologic neoplasms with atypical CNS involvement. We offer targets for future studies by identifying potentially pathogenic genetic variants in these lesions, as the full implications of the novel molecular abnormalities described remain unclear.

A rare case of chordoma presenting as a Pancoast tumor.

The notochord is the defining structure of all chordate embryos. It is a midline structure ventral to the ectoderm, neural plates, and neural arch. Remnants of the notochord ultimately give rise to the nucleus pulposus. The function of the notochord is to organize the surrounding structures. Chordoma is a rare malignant bone tumor arising from remnants of the notochord. These tumors are indolent and can present as incidental or locally advanced involving adjacent structures. These tumors typically present at the skull base and sacral spine but more rarely can be seen on the cervical and thoracic spine. Rare cases of chordoma invading the brachial plexus have been recorded. Surgical resection is the mainstay of treatment for chordomas. We would like to discuss a novel presentation of a chordoma as a Pancoast tumor, and aim to highlight the clinical importance of accurate diagnosis and planning therapy along with poor prognosis of incomplete surgical resection.

The Decline of Deep Brain Stimulation for Obsessive-Compulsive Disorder Following FDA Humanitarian Device Exemption Approval.

Background: In February 2009, the US Food and Drug Administration (FDA) granted Humanitarian Device Exemption (HDE) for deep brain stimulation (DBS) in the anterior limb of the internal capsule (ALIC) for the treatment of severely debilitating, treatment refractory obsessive-compulsive disorder (OCD). Despite its promise as a life altering treatment for patients with otherwise refractory, severely debilitating OCD, the use of DBS for the treatment of OCD has diminished since the FDA HDE endorsement and is now rarely performed even at busy referral centers. We sought to identify factors hindering OCD patients from receiving DBS therapy. Materials and Methods: University of Florida (UF) clinical research databases were queried to identify patients evaluated as potential candidates for OCD DBS from January 1, 2002 to July 30, 2020. A retrospective review of these patients' medical records was performed to obtain demographic information, data related to their OCD, and details relevant to payment such as third-party payer, study participation, evaluation prior to or after HDE approval, and any stated factors prohibiting surgical intervention. Results: Out of 25 patients with severe OCD identified as candidates for DBS surgery during the past 18 years, 15 underwent surgery. Prior to FDA HDE approval, 6 out of 7 identified candidates were treated. After the HDE, only 9 out of 18 identified candidates were treated. Seven of the 9 were funded by Medicare, 1 paid out of pocket, and 1 had "pre-authorization" from her private insurer who ultimately refused to pay after the procedure. Among the 10 identified OCD DBS candidates who were ultimately not treated, 7 patients-all with private health insurance-were approved for surgery by the interdisciplinary team but were unable to proceed with surgery due to lack of insurance coverage, 1 decided against surgical intervention, 1 was excluded due to medical comorbidities and excessive perceived surgical risk, and no clear reason was identified for 1 patient evaluated in 2004 during our initial NIH OCD DBS trial. Conclusion: Based on compelling evidence that DBS provides substantial improvement of OCD symptoms and markedly improved functional capacity in 2 out of 3 patients with severely debilitating, treatment refractory OCD, the FDA approved this procedure under a Humanitarian Device Exemption in 2009, offering new hope to this unfortunate patient population. A careful review of our experience with OCD DBS at the University of Florida shows that since the HDE approval, only 50% of the severe OCD patients (9 of 18) identified as candidates for this potentially life altering treatment have been able to access the therapy. We found the most common limiting factor to be failure of private insurance policies to cover DBS for OCD, despite readily covering DBS for Parkinson's disease, essential tremor, and even dystonia-another HDE approved indication for DBS. We have identified an inherent discrimination in the US healthcare system against patients with medication-refractory OCD who are economically challenged and do not qualify for Medicare. We urge policy makers, insurance companies, and hospital administrations to recognize this health care disparity and seek to rectify it.

Influence of stereotactic imaging on operative time in deep brain stimulation.

BACKGROUND: Various techniques are used across institutions for implantation of deep brain stimulation (DBS) leads. The most used techniques for each step include preoperative MRI fused to in-frame CT, intraoperative fluoroscopy, and postoperative CT, but postimplantation MRI also is used, as it was at our center. We present the quality assurance study performed at our institution after a change from postimplantation MRI performed across the hospital to postimplantation in room CT. METHODS: Retrospective chart review of 123 patients who underwent bilateral DBS leads placement without same-day generator placement that was performed. The patients were divided by the type of postoperative imaging that was obtained. Patients were excluded if a unilateral lead placement was performed, if the case was a revision of an existing lead or deviated from the normal protocol. Operative room times and procedure times for each group were analyzed with Wilcoxon rank sums test (WRST) to determine any significant differences between groups. RESULTS: Postoperative MRI was performed for 82 patients, while postoperative CT was performed for 41 patients. A WRST showed a significant reduction in both operative room time (209 min to 170 min, P < 0.0001) and procedure time (140 min to 126 min, P = 0.0019). CONCLUSION: In-room CT allowed for a significant reduction in operative room time. Lower operative room time has been associated with increased patient comfort, and decreased cost. CT did not alter the revision rate for procedures. The significant reduction in procedure time may be attributed to increased team familiarity with procedure over time.

A Review of Neuromodulation for Treatment of Complex Regional Pain Syndrome in Pediatric Patients and Novel Use of Dorsal Root Ganglion Stimulation in an Adolescent Patient With 30-Month Follow-Up.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a disorder in which pain and discomfort are out of proportion to the amount of tissue damage. While prevalence is 20.57 per 100,000 adults, it has not been studied in the U.S. pediatric population. Conservative treatment options include pharmacologic, behavioral, and psychological treatment. If these fail, invasive therapies such as sympathetic blocks and neuromodulation may be performed. The ACCURATE study demonstrated efficacy of dorsal root ganglion (DRG) stimulation for the treatment of refractory CRPS, but did not include pediatric patients and there are no reported cases of its use in the pediatric population. We review the use of neuromodulation for CRPS in pediatric patients and present a novel case using DRG stimulation in an adolescent patient. MATERIALS AND METHODS: A literature search was performed for any studies of neuromodulation as treatment of pediatric CRPS. The literature is reviewed and the case of a 17-year-old female with CRPS treated with DRG stimulation is presented. RESULTS: A 15-year-old female developed CRPS type I of the left ankle after a sports injury. She was unable to wear a shoe or venture outside the home due to pain, swelling, and allodynia. Conservative therapies, including medications, physical therapy, and lumbosacral sympathetic plexus blocks, failed. At age 17, she underwent DRG stimulator lead placement targeting the left L4 and L5 nerve roots. Her therapy provided 100% relief of pain within four days of placement and was sustained at 30-month follow-up. CONCLUSIONS: DRG stimulation has been shown to significantly alter the symptomatology in patients with CRPS. This case suggests that DRG stimulation may be as effective for the treatment of refractory CRPS in pediatric patients as in adults.