Brett Theeler

Post-traumatic headaches in civilians and military personnel: a comparative, clinical review.

Post‐traumatic headache (PTH) is the most frequent symptom after traumatic brain injury (TBI). We review the epidemiology and characterization of PTH in military and civilian settings. PTH appears to be more likely to develop following mild TBI (concussion) compared with moderate or severe TBI. PTH often clinically resembles primary headache disorders, usually migraine. For migraine‐like PTH, individuals who had the most severe headache pain had the highest headache frequencies. Based on studies to date in both civilian and military settings, we recommend changes to the current definition of PTH. Anxiety disorders such as post‐traumatic stress disorder (PTSD) are frequently associated with TBI, especially in military populations and in combat settings. PTSD can complicate treatment of PTH as a comorbid condition of post‐concussion syndrome. PTH should not be treated as an isolated condition. Comorbid conditions such as PTSD and sleep disturbances also need to be treated. Double‐blind placebo‐controlled trials in PTH population are necessary to see whether similar phenotypes in the primary headache disorders and PTH will respond similarly to treatment. Until blinded treatment trials are completed, we suggest that, when possible, PTH be treated as one would treat the primary headache disorder(s) that the PTH most closely resembles.

Adult pilocytic astrocytomas: Clinical features and molecular analysis

BACKGROUND Adult pilocytic astrocytomas (PAs) are rare and have an aggressive clinical course compared with pediatric patients. Constitutive Ras/RAF/MAPK signaling appears to be an important oncogenic event in sporadic PA. We evaluated clinical data and molecular profiles of adult PAs at our institution. METHODS We identified 127 adult PAs in our institutional database. Cases with available tissue were tested for BRAF-KIAA1549 fusion/duplication (B-K fusion) by fluorescence in situ hybridization and submitted for mutation profiling using the Sequenom mutation profiling panel. Subgroup analyses were performed based on clinical and molecular data. RESULTS The majority of adult PAs are supratentorial. Twenty-two percent of cases had an initial pathologic diagnosis discordant with the diagnosis made at our institution. Recurrence was seen in 42% of cases, and 13% of patients died during follow-up. Adjuvant radiotherapy following surgical resection was associated with a statistically significant decrease in progression-free survival (P = .004). B-K fusion was identified in 20% (9 of 45) of patients but was not associated with outcome. No BRAF V600E mutations (0 of 40 tested) were found. CONCLUSION This was the largest single institution series of adult PA. A significant proportion of adult PAs follow an aggressive clinical course. Our results support a period of observation following biopsy or surgical resection. B-K fusion in adult PA does not influence outcome, and BRAF V600E mutation appears to be a very rare event. Further study of tumor biology and optimal treatment is needed, given a more aggressive clinical behavior.

Neurological involvement and characterization in acquired hemophagocytic lymphohistiocytosis in adulthood

OBJECTIVE To describe the neurological and neuroradiological features of acquired hemophagocytic lymphohistiocytosis (HLH) in adulthood by reporting a series of cases. METHODS Ten consecutive patients who were diagnosed with HLH at Medstar Georgetown University Hospital and Walter Reed National Military Medical Center were evaluated for neurological involvement. All underwent clinical neurological evaluation, and when indicated CSF analysis and MR imaging of the brain. Data were gathered and analyzed retrospectively. RESULTS Seven of the ten patients with HLH had neurological involvement. Mean age at onset was 50 (range: 21 to 73). Four patients were males. Prominent clinical features included mild to severe encephalopathy and seizures. Other findings included hemiparesis and spastic tetraparesis. Neuroimaging revealed a wide spectrum of abnormalities including cortical and subcortical edema, gadolinium enhancement, hemorrhage, and diffusion restriction. Basal ganglia involvement was present in four out of seven patients. Three patients died due to multisystem organ failure, and the other patients displayed varying degrees of recovery. CONCLUSIONS The neurological features of acquired HLH in adults have not been previously reported. These seven patients demonstrate the spectrum of neurological involvement that can occur. The diagnosis of HLH should be considered in patients who are systemically ill with unexplained fevers and hyperferritinemia who have evidence of inflammation in the CNS.

Adult brainstem gliomas: Correlation of clinical and molecular features

BACKGROUND Brainstem gliomas are rare in adults and overall have superior survival outcomes compared to pediatric brainstem gliomas. PATIENTS AND METHODS We conducted a retrospective data and tissue analysis of all adult patients (≥ 18 years old) with World Health Organization (WHO) Grade II, III, and IV brainstem gliomas in the University of Texas MD Anderson Cancer Center institutional database from 1990 to 2012. RESULTS We identified 143 cases in adults ages 18 and over. There were 28 glioblastomas, 43 anaplastic astrocytomas, 15 diffuse astrocytomas, and 11 gliomas not otherwise specified, and in 46 cases the diagnosis was made radiographically. 128 (89.5%) cases were classified radiographically as diffuse and of the focal tumors, 9 of the 15 were WHO Grade III or IV tumors. Increasing tumor grade and contrast enhancement were associated with significantly reduced overall survival. The median overall survival for the entire cohort was 32.1 months similar to previously published studies. Two of 25 grade II and III tumors, and 1 of 17 glioblastomas had IDH1 mutations on immunohistochemical testing. Nine cases had sufficient tissue for mutation profiling, 1 case had a BRAF V600E mutation and 2 had 2 PIK3CA mutations. CONCLUSIONS Survival outcomes for adult WHO Grade II to IV brainstem gliomas were similar to supratentorial IDH1 wild-type tumors of similar grade and histology. Potentially actionable mutations can be identified from small biopsy samples in a subset of adult brainstem gliomas.

Association of reversible splenial lesion syndrome (RESLES) with Anti-VGKC autoantibody syndrome: a case report

A 50-year-old male presented with complaints of fatigue, confusion, and memory problems. Neurological evaluation revealed altered cognition, unsteady gait, ataxia, dysmetria, and weakness. MRI of the brain was initially unremarkable. Over several days, the patient experienced improvement of symptoms and a follow-up MRI revealed a small lesion in the splenium of the corpus callosum seen on diffusion weighted and T2 sequences. The patient was discovered to have elevated anti-voltage gated potassium channel serum autoantibodies. Follow-up MRI revealed resolution of the splenial lesion. The patient was treated with intravenous immune globulin, and improved back to his pre-treatment baseline. We believe this to be the first case of a reversible splenial lesion syndrome as a manifestation of the anti-voltage gated potassium channel autoantibody syndrome, and propose a pathophysiologic mechanism.

Synchronous rosette-forming glioneuronal tumor and diffuse astrocytoma with molecular characterization: A case report

Rosette-forming glioneuronal tumor (WHO grade I) is a rare neoplasm primarily arising in young adults that is characterized by distinctive neurocytic rosette formation, a spindled glial component resembling pilocytic astrocytoma, and a high incidence of PIK3CA mutation. Low-grade diffuse astrocytoma (WHO grade II), on the other hand, is far more common and is characterized by a high incidence of IDH mutation. Here we report a patient with simultaneous presentation of a midbrain-cerebellar rosetteforming glioneuronal tumor and a cerebral diffuse astrocytoma. Molecular characterization of both tumors confirmed characteristic, mutually exclusive, distinct signatures, with the rosette-forming glioneuronal tumor exhibiting a previously unreported novel PIK3CA gene mutation.

Bevacizumab use in disseminated choroid plexus papilloma

Choroid plexus papilloma (CPP) is a rare primary neuroectodermal tumor of the choroid plexus, comprising\1 % of intracranial tumors in adults [1]. These tumors commonly present in the 4th ventricle, arising from the caudal roof, with signs and symptoms of CSF obstruction, such as headache, diplopia, and ataxia. CPP corresponds to WHO grade I, and is usually benign, requiring solely surgical resection [1]. Atypical CCP can behave more aggressively and is considered WHO grade II [1]. Occasionally, there can be malignant transformation to a choroid plexus carcinoma (WHO grade III) at recurrence or with metastasis. CPP and atypical CCP tend to remain as isolated nodules but rare leptomeningeal dissemination can occur, even while the tumor retains distinctly low-grade histological characteristics [2]. Since disseminated CPP is rare, there is no standardized treatment. Many patients receive focal radiotherapy to the spine and there are reports of various chemotherapy regimens [2, 3]. Some patients will remain stable without any additional treatment, making evaluation of evaluation of stable disease (SD) problematic. There have been no previous reports of the use of bevacizumab therapy for disseminated CPP. We present two patients with disseminated CPP who derived clinical benefit from bevacizumab therapy administered for progressive disease.

Ependymomas arising outside of the central nervous system: A case series and literature review

BACKGROUND Extracranial and extraspinal ependymomas are extremely rare tumors mostly published in the literature as case reports. METHODS MD Anderson Cancer Center institutional database was screened for patients with extra CNS ependymomas over a 25 year period. RESULTS Eight patients with extra CNS ependymoma were identified. Five cases originated in the sacrum or subcutaneous sacral area, and the other 3 cases originating in the breast, lung and adnexa of the uterus. By histology, most cases were myxopapillary ependymomas (5 cases), 2 cases were grade II ependymoma and 1 case was an anaplastic ependymoma. Metastases occurred in 6 cases and 3 patients died due to progressive disease. Most cases required surgery, radiation and chemotherapy. CONCLUSION Extra CNS ependymomas are very rare tumors that tend to metastasize, even though most cases are histologically classified as low grade ependymomas.

PIK3CA mutation in a mixed dysembryoplastic neuroepithelial tumor and rosette forming glioneuronal tumor, a case report and literature review

BACKGROUND Rosette forming glioneuronal tumors are rare, World Health Organization (WHO) grade I novel tumors frequently affecting the fourth ventricle or posterior fossa with typical neuronal pseudorosettes. RGNTs have been described as possessing additional histologic features of DNETs or pilocytic astrocytomas. Activating PIK3CA mutations have been identified as recurring genetic event in RGNTs. METHODS We report a 35year old man who presented with binocular diplopia, headache, and was found to have a third ventricle tumor. Tumor pathology and oncogene evaluation were conducted. RESULTS The tumor demonstrated histologic features consistent with mixed RGNT/DNET. Genetic studies revealed a PIK3CA mutation in exon 9 (E545K, C. 1633G>A) without IDH1, p53, 1p19q chromosomal co-deletion, or BRAF mutations. A literature search revealed six cases of PIK3CA mutations in RGNTs and seven cases of mixed RGNT/DNET. No cases of mixed RGNT/DNET with a PIK3CA mutation have been described. CONCLUSION This is the first documented case of an RGNT/DNET with an activating PIK3CA mutation. The presence of a PIK3CA mutation aids histologic classification in the setting of mixed histology, and may have implications for targeting the PI3K/AKT/mTOR pathway in this tumor type.

Management of Acute Concussion in a Deployed Military Setting

Opinion statementThe DoD has established clinical guidelines and policies creating a system of care for the management of battlefield concussion. Within these instructions, medical providers have standardized guidance for screening and diagnosing concussion, along with guidelines for treating common concussion symptoms. Underlying these policies is the principle that concussion is an important injury, and SMs need to be removed from combat during the acute period to ensure full recovery before return to duty. As our understanding of concussion advances, the DoD will incorporate these advances into the current system of care, ensuring that SMs have the highest level of care possible for concussions sustained on the battlefield.