Pontine stroke in a patient with Chronic Progressive External Ophthalmoplegia (CPEO): a case report.

BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease with slowly progressive bilateral ptosis and symmetric ophthalmoplegia due to a genetic mutation that results in defective oxidative phosphorylation. Common genes that are implicated in CPEO include POLG, RRM2B, ANT1 and PEO1/TWNK. Here, we report a case of a patient diagnosed with CPEO caused by a novel mutation in PEO/TWNK after suffering a right pontine stroke. CASE PRESENTATION: A 70-year-old man with history of chronic progressive bilateral ptosis and ophthalmoplegia, as well as similar ocular symptoms in his father and grandfather, presented with acute onset of right hemifacial weakness and dysarthria. Brain MRI revealed an acute ischemic stroke in the right dorsal pons. The patient did not experience diplopia due to severe baseline ophthalmoplegia. Creatine kinase was elevated to 6,080 U/L upon admission and normalized over the course of one week; electromyography revealed a myopathic process. Genetic testing revealed a novel mutation c.1510G > A (p. Ala504Thr) in a pathogenic "hot spot" of the C10ORF2 gene (TWNK/PEO1), which is associated with CPEO. The mutation appears to be deleterious using several pathogenicity prediction tools. CONCLUSIONS: This case report describes a patient with late-onset CPEO caused by a novel, likely pathogenic, mutation in the TWNK gene. Although the patient presented with a pontine stroke, it manifested with solely new onset facial palsy, as he had a severe underlying ophthalmoplegia secondary to his CPEO.

Olfactory Dysfunction Predicts the Development of Depression in Older US Adults.

Neuroanatomic connections link the olfactory and limbic systems potentially explaining an association between olfactory dysfunction and depression. Some previous studies have demonstrated that olfactory dysfunction is associated with increased depressive symptoms. However, these studies were cross-sectional and unable to establish which develops first. We used longitudinal data to determine if impaired odor identification increased subsequent depressive symptoms or vice versa. We assessed olfaction and depression in the National Social Life, Health, and Aging Project, a nationally representative, 15-year longitudinal study of older US adults. Olfaction was measured using a validated odor identification test (Sniffin' Sticks). Depressive symptoms were measured using a modified version of the validated Center for Epidemiological Studies Depression Scale. Multivariable logistic regression models examined the temporal relationships between developing olfactory dysfunction and depression while accounting for demographics, disease comorbidities, alcohol use, smoking, and cognition. Older adults with olfactory dysfunction had concurrent frequent depressive symptoms (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.00-1.43). Among healthy adults at baseline, those who had olfactory dysfunction were more likely to develop frequent depressive symptoms 5 or 10 years later (OR = 2.22, 95% CI = 1.13-4.37). Conversely, those with frequent depressive symptoms at baseline were not more likely to develop olfactory dysfunction 5 or 10 years later. We show for the first time that olfactory dysfunction predicts subsequent development of depression in older US adults. These data support screening for depression in older adults with chemosensory impairment and set the stage for disentangling the relationship between olfaction and depression.

Amantadine: A new treatment for refractory electrical status epilepticus in sleep.

PURPOSE: Electrical status epilepticus in sleep (ESES) is an electrographic abnormality linked to language abnormalities and cognitive dysfunction and specifically associated with Landau-Kleffner syndrome (LKS), the syndrome of continuous spike and wave in slow-wave sleep (CSWS), and autistic regression with epileptiform EEG (AREE). As first-line therapies for treatment of ESES display inadequate efficacy and confer substantial risk, we set out to describe our center's experience with amantadine in the treatment of ESES. METHODS: Patients with video-EEG-confirmed ESES who received amantadine were retrospectively identified in a clinical EEG database. Spike-wave index, before and after amantadine exposure, was compared in a pairwise fashion. In an exploratory analysis, we cataloged reported changes in language functioning, cognition, and autistic features, which accompanied treatment. RESULTS: We identified 20 patients with ESES-associated syndromes. Median cumulative weighted average amantadine dosage was 2.1 mg/kg/d (interquartile range (IQR): 1.1, 4.5), and median duration of therapy was 11.5 months (IQR: 7.8, 26.6). In comparison with median baseline spike-wave index (76%), post-amantadine spike-wave index (53%) was reduced, with P = 0.01. Six (30%) patients exhibited complete (or nearly complete) resolution of ESES. A majority of patients exhibited subjective cognitive, linguistic, or behavioral benefit. Amantadine was generally well-tolerated despite substantial dosage and duration of therapy. CONCLUSIONS: This study suggests that amantadine may be effective in the treatment of ESES-associated syndromes but warrants replication in a more rigorous study.

Very-High-Dose Prednisolone Before ACTH for Treatment of Infantile Spasms: Evaluation of a Standardized Protocol.

BACKGROUND: There is ongoing debate regarding the comparative effectiveness of adrenocorticotropic hormone and prednisolone in the treatment of infantile spasms. With a large cohort and extended follow-up, we set out to evaluate a protocol in which adrenocorticotropic hormone is reserved for prednisolone nonresponders. METHODS: The following standardized hormonal therapy protocol was adopted. Patients initially receive prednisolone (8 mg/kg/day [maximum 60 mg/day], divided in three daily doses for 14 days). Prednisolone responders taper it over 14 days, whereas prednisolone nonresponders immediately transition to natural adrenocorticotropic hormone (150 U/m2/day, divided in two daily doses for 14 days). We evaluated short-term response, defined as video-electroenecphaloagraphy-confirmed resolution of both epileptic spasms and hypsarrhythmia on day 14, without relapse for 28 additional days. We then evaluated long-term relapse and calculated the rates of sustained response at six, 12, and 18 months. RESULTS: We identified 102 children with infantile spasms who were treated with prednisolone. Prior exposure to hormonal therapy and vigabatrin was observed among 12% and 35% of patients, respectively. Sixty (59%) patients responded to prednisolone, and 13 (33%) prednisolone nonresponders then responded to adrenocorticotropic hormone. Cumulative response to prednisolone and adrenocorticotropic hormone (if needed) was higher among treatment-naive patients (84%) than among patients with prior exposure to first-line treatment (51%), with P < 0.001. Relapse was relatively common among all subgroups. CONCLUSION: Short-term response to prednisolone was favorable and higher among treatment-naive patients. These data suggest that prednisolone is a reasonable approach to initial therapy and that adrenocorticotropic hormone exhibits substantial efficacy after prednisolone failure.