Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica's experience.

BACKGROUND: Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population. OBJECTIVE: To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations. METHODS: DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants' sociodemographic and clinical characteristics were also obtained from their medical records. RESULTS: Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens. CONCLUSIONS: This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.

Chronic stress inhibits hypothalamus-pituitary-thyroid axis and brown adipose tissue responses to acute cold exposure in male rats.

PURPOSE: Cold exposure activates the hypothalamus-pituitary-thyroid (HPT) axis, response blunted by previous acute stress or corticosterone administration. Chronic stressors can decrease serum T3 concentration, and thyrotropin-releasing hormone (Trh) expression in the paraventricular nucleus (PVN), but impact on the response to cold is unknown; this was studied in rats submitted to daily repeated restraint (rRes) that causes habituation of hypothalamus-pituitary-adrenal (HPA) axis response, or to chronic variable stress (CVS) that causes sensitization and hyperreactivity. METHODS: Wistar male adult rats were submitted to rRes 30 min/day, or to CVS twice a day, for 15 days. On day 16, rats were exposed 1 h to either 5 or 21 °C. Parameters of HPT and HPA axes activity and of brown adipose tissue (BAT) cold response were measured; gene expression in PVN and BAT, by RT-PCR; serum hormone concentration by radioimmunoassay or ELISA. RESULTS: Compared to naïve animals, Crh and corticosterone concentrations were attenuated at the end of rRes, but increased at the end of CVS treatments. Cold exposure increased mRNA levels of Crh, Trh, and serum concentration of thyrotropin in naïve, but not in rRes or CVS rats; corticosterone increased in all groups. Cold induced expression of thermogenic genes in BAT (Dio2 and Ucp1) in naïve but not in stressed rats; Adrb3 expression was differentially regulated. CONCLUSION: Both types of chronic stress blunted HPT and BAT responses to cold. Long-term stress effects on noradrenergic and/or hormonal signaling are likely responsible for HPT dysfunction and not the type of chronic stressor.

Orbital metastases from breast cancer: A retrospective analysis of 28 cases.

Breast cancer account about half of the cases of orbital malignancies due to metastasis. The prognosis is adverse, with average survival from 2 to 34 months. OBJECTIVE: To analyze the clinical and pathological characteristics and outcomes of patients with orbital metastasis from breast cancer. MATERIAL AND METHODS: A retrospective, cross-sectional study of 28 patients seen in the Oncology Hospital of the National Medical Center XXI Century, from February 2003 to February 2019. RESULTS: Of the 28 patients, the median age was 50.8 years. The average time from the diagnosis of breast cancer to the development of orbital metastases was 64 months. 42.8% of the patients were stage IV of onset. The lobular vs ductal ratio was 5.2:1. 92.8% of the cases had luminal profile (one case with overexpression of HER-2), while only one case was triple negative. The most frequent symptoms were: decrease in visual acuity (64.2%), pain (57.1%), amaurosis (28.5%), alterations in mobility (28.5%) and edema (21.4%). Bilateral activity was presented in 25%. A third of the patients received local treatment (radiotherapy, surgery, anti-VEGFR). Overall survival was 67.5 months (1-184 months); however, the overall survival from the diagnosis of orbital metastasis was 26.4 months (1-98 months), with an average progression-free survival of 13.7 months (1-48 months). CONCLUSION: Ophthalmologic evaluation should be performed on all patients with breast cancer and ocular symptoms. Early local treatment should be offered in order to prevent severe complications and reduce the negative impact on quality of life.

[Clinical characteristics and progress of patients with migrainous headaches monitored in the Headache Unit in a paediatric referral hospital]. / Características clínicas y evolución de los pacientescon cefalea migrañosa seguidos en la Unidad deCefaleas de un hospital pediátrico de referencia.

AIM: To analyse the clinical characteristics and course of migraine patients who were attended in the Headache Unit of a paediatric referral hospital. PATIENTS AND METHODS: We conducted a retrospective observational study of children monitored in the Headache Unit of the Neurology Service who satisfied the International Headache Society diagnostic criteria for migraine, with a follow-up lasting more then six months. The following were excluded from the study: patients who failed to comply with the treatment or clinical monitoring, or whose medical data were incomplete. RESULTS: There was a predominance of patients aged between 7 and 12 years, with no differences as regards sex. Bilateral and frontal migraine without aura predominated (74%), with episodes lasting between 3 and 12 hours, and the throbbing type accounted for 45% of cases. The most common accompanying symptoms were photophobia (86%) and phonophobia (88%). Except for the second visit, the tendency of the group without prophylactic treatment was favourable. When prophylactic treatment was indicated, a favourable response was observed (p < 0.05), and no significant differences were found as regards the type of medication employed. A total of 73% of the patients were discharged, and most of them required three visits; 30% of the patients treated reported some kind of side effects. CONCLUSIONS: Migraine at the paediatric age is characterised by short but intense episodes of headache that are mostly located in the frontal area. Progress is satisfactory without pharmacological measures in a high percentage of patients. When prophylactic medication was required (due to the patient's presenting frequent episodes of migraine with high scores on the PedMIDAS rating scale), a favourable response was obtained (p < 0.05), with some side effects.