Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial.

AIMS: Migraine with aura and patent foramen ovale (PFO) are associated. The Percutaneous Closure of PFO in Migraine with Aura (PRIMA) trial is a multicentre, randomized trial to investigate the effect of percutaneous PFO closure in patients refractory to medical treatment. METHODS: Migraine with aura patients and PFO who were unresponsive to preventive medications were randomized to PFO closure or medical treatment. Both groups were given acetylsalicylic acid 75-100 mg/day for 6 months and clopidogrel 75 mg/day for 3 months. The primary endpoint was reduction in monthly migraine days during months 9-12 after randomization compared with a 3-month baseline phase before randomization. The committee reviewing the headache diaries were blinded to treatment assignment. RESULTS: One hundred and seven patients were randomly allocated to treatment with an Amplatzer PFO Occluder (N = 53) or control with medical management (N = 54). The trial was terminated prematurely because of slow enrolment. Eighty-three patients (40 occluder, 43 control) completed 12-month follow-up. Mean migraine days at baseline were 8 (±4.7 SD) in the closure group and 8.3 (±2.4) in controls. The primary endpoint was negative with -2.9 days after PFO closure vs. -1.7 days in control group (P = 0.17). Patent foramen ovale closure caused five adverse events without permanent sequelae. CONCLUSION: In patients with refractory migraine with aura and PFO, PFO closure did not reduce overall monthly migraine days.

Actinomycosis masquerading as malignancy.

We describe a patient who presented with neurological symptoms and radiological findings consistent with metastatic malignancy in several sites. However, no obvious primary site of tumour was identified and the patient later went on to develop clinical features of sepsis whilst using palliative dexamethasone therapy. A diagnosis of actinomycosis was eventually made on open lung biopsy and the patient recovered completely on penicillin V. This case serves to illustrate the need to obtain a formal tissue diagnosis whenever possible in all cases of suspected malignancy, in addition to exposing the weaknesses inherent in empiric diagnoses.

Characterizing behavioral and cognitive dysexecutive changes in progressive supranuclear palsy.

Frontal lobe dysfunction is a prominent feature of many neurological disorders. Early diagnosis may be enhanced by establishing a profile of cognitive, behavioral, and emotional change. Traditional psychometric assessment focuses on cognitive dysfunction and fails to identify behavioral changes, particularly those associated with orbitofrontal dysfunction. We examined progressive supranuclear palsy (PSP), a prototypical subcortical dementia with frontal features, using commonly available neuropsychological measures and a modification of the Katz Adjustment Scale-Relatives (KAS-R), an instrument first developed to assess dysexecutive changes in head-injured patients. Executive tests identified deficits in reasoning, planning, set shifting, verbal fluency, information processing speed, and response initiation. On the KAS-R, changes in apathy, social withdrawal, and independence were observed, with little change in belligerence, social irresponsibility, uncooperativeness, obstreperousness, anxiety, and depression. The results show the potential utility of this instrument in characterizing behavioral and emotional changes associated with frontal lobe dysfunction in neurodegenerative disease.