Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.     

Conjunctival Melanoma in Asian Indians: A Study of 42 Patients

Purpose: To describe the clinical features, treatment, and outcomes of conjunctival melanoma in Asian Indians.

Methods: Retrospective study of 42 patients.

Results: The mean age at presentation of conjunctival melanoma was 43 years (median, 45 years; range, 9–78 years). There were 20 (48%) males and 22 (52%) females. Nineteen patients (45%) had a known history of a preexisting pigmented conjunctival lesion. Bulbar conjunctiva (n = 28; 67%) was the most common tumor epicenter, and medial ocular surface quadrant (n = 15; 36%) was more commonly involved. The mean tumor basal diameter was 12 mm (median, 10 mm; range, 4–30 mm), and the mean tumor thickness was 4 mm (median, 2 mm; range, 1–30 mm). Majority of the patients had a pigmented tumor (n = 33; 79%). The tumors arose de novo (n = 17, 41%) or were associated with conjunctival nevus (n = 9; 21%) or primary acquired melanosis (n = 16, 38%). Wide excisional biopsy, adjunctive cryotherapy, and amniotic membrane grafting were performed in 27 (71%) patients, 11 (29%) underwent orbital exenteration, and 4 were lost to follow-up prior to definitive treatment. Over a mean follow-up period of 24 months (median, 9 months; range, <1 to 136 months), four (11%) patients had tumor recurrence, seven (18%) had locoregional lymph node metastasis, and four (11%) developed systemic metastasis and died due to metastatic disease.

Conclusion: Conjunctival melanoma predominantly occurs in middle-aged Asian Indians and is associated with a high rate of systemic metastasis and death.     

Can neuroimaging help aphasia researchers? Addressing generalizability,variability, and interpretability

Neuroimaging studies of individuals with brain damage seek to link brain structure and activity to cognitive impairments, spontaneous recovery, or treatment outcomes. To date, such studies have relied on the critical assumption that a given anatomical landmark corresponds to the same functional unit(s) across individuals. However, this assumption is fallacious even across neurologically healthy individuals. Here, we discuss the severe implications of this issue, and argue for an approach that circumvents it, whereby: (i) functional brain regions are defined separately for each subject using fMRI, allowing for inter-individual variability in their precise location; (ii) the response profile of these subject-specific regions are characterized using various other tasks; and (iii) the results are averaged across individuals, guaranteeing generalizabliity. This method harnesses the complementary strengths of single-case studies and group studies, and it eliminates the need for post hoc “reverse inference” from anatomical landmarks back to cognitive operations, thus improving data interpretability.     

Retinoblastoma: Achieving new standards with methods of chemotherapy

The management of retinoblastoma (RB) has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC) is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC) is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms “RB,” and “treatment,” “chemotherapy,” “systemic chemotherapy,” “IVC,” “IAC,” “periocular chemotherapy,” or “intravitreal chemotherapy.” Relevant English language articles were extracted, reviewed, and referenced appropriately.     

Epibulbar schwannoma in a 12-year-old boy: A case report and review of literature

Schwannomas are benign, encapsulated, primary neurilemmal tumors composed of proliferating Schwann cells. Schwannomas are commonly seen in the orbit, but are rare on the epibulbar surface. Herein, we report a case of a 12-year-old boy who presented to us with a slow-growing painless subconjunctival mass in the left eye. There was no intraocular extension of the mass and intra-operatively, the mass could be clearly delineated and was excised off the underlying sclera. Histopathological examination of the mass showed typical features of schwannoma and immunohistochemistry helped to confirm the diagnosis. There was no recurrence of the lesion observed at follow-up 26 months after surgery. Here, we describe this uncommon tumor and review the available literature. Although rare, an epibulbar schwannoma should be considered in the differential diagnosis of an amelanotic, painless subconjunctival nodular mass. Excision of the lesion is the recommended treatment.     

Late-Onset Suicide: A Dementia Prodrome?

ObjectivesThis study examined whether late-onset (versus early-onset) suicidal behavior is associated with worse cognition.MethodsParticipants included 278 adults aged 50+ years (56 nonpsychiatric comparison group; 67 nonsuicidal depressed older adults; 63 depressed suicide ideators; and 44 late-onset (55+ years) and 48 early-onset suicide attempters (<55 years). Using a case-control design, this study examined group differences in global cognition, episodic memory, information processing speed, and executive functioning, assessed using the Repeatable Battery of Neuropsychological Status and the Trail Making Test from the Delis-Kaplan Executive Function System. Linear regression was used for data analyses.ResultsBoth attempter groups displayed worse executive functioning than nonsuicidal depressed older adults. Late-onset attempters additionally displayed poorer global cognition and processing speed than nonsuicidal depressed older adults and poorer memory than early-onset attempters.ConclusionsLate-onset suicidal behavior is associated with worse performance in a broad range of cognitive domains, possibly reflective of a dementia prodrome.