Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

VPS13C-associated Parkinson's disease: Two novel cases and review of the literature.

VPS13C is a protein-coding gene involved in the regulation of mitochondrial function through the endolysosomal pathway in neurons. Homozygous and compound heterozygous VPS13C mutations are etiologically associated with early-onset Parkinson's disease (PD). Moreover, recent studies linked biallelic VPS13C mutations with the development of dementia with Lewy bodies (DLB). Neuropathological studies on two mutated subjects showed diffuse Lewy body disease. In this article, we report the clinical and genetic findings of two subjects affected by early-onset PD carrying three novel VPS13C mutations (i.e., one homozygous and one compound heterozygous), and review the previous literature on the genetic and clinical findings of VPS13C-mutated patients, contributing to the knowledge of this rare genetic alpha-synucleinopathy.

Continuous subcutaneous apomorphine infusion allowing awake deep brain stimulation in a Parkinson's disease patient.

BACKGROUND: Subthalamic Deep Brain Stimulation (DBS) have demonstrated in the last decades to determine an important clinical improvement in advanced and selected Parkinson's disease (PD) patients. However, only a minority of parkinsonian patients meet the criteria to undergo DBS, and the surgical procedure itself is often stressful, especially for patients experiencing severe OFF state. Subcutaneous Apomorphine continuous administration is suitable as an adjunctive therapy capable of improving a suboptimal DBS result. Here we hypothesize a possible role for subcutaneous apomorphine infusion to alleviate severe OFF state in parkinsonian patients undergoing DBS, thus allowing intraoperative microrecording and patient's collaboration during clinical testing. CASE PRESENTATION: A 68-year-old man, suffering from a very long PD-history, characterized by a severe akinetic status and dramatic non-motor features while in OFF, underwent Subthalamic-DBS keeping a slight but continuous apomorphine infusion (1.8 mg/hour), able to guarantee the right degree of patient's collaboration without interfering with microelectrode recordings. There were no intra or perioperative complications and after the procedure he experienced a marked clinical benefit, being able to stop apomorphine administration. CONCLUSIONS: Here we described the first Subthalamic DBS procedure performed with a low and stable dopaminergic stimulation guaranteed by subcutaneous Apomorphine continuous infusion. For its rapidity of action and prompt reversibility, apomorphine could be particularly suitable for use during difficult surgical procedures in PD, allowing more therapeutic opportunities for patients who would otherwise be excluded from the DBS option.

The Choice of Leg During Pull Test in Parkinson's Disease: Not Mere Chance.

Background: Parkinson's disease (PD) starts asymmetrically and it maintains a certain degree of asymmetry throughout its course. Once functional disability proceeds, people with PD can change their dominant hand due to the increased disease severity. This is particularly true for hand dominance, while no studies have been performed so far exploring the behavioral changes of lower limb utilization in PD according to the lateralized symptom dominance. In the current study, we aim to track the foot preference of participants with PD to respond to the Pull Test. Methods: Forty-one subjects suffering from PD, with a H&Y scale ≤ 2, were recruited. A motor evaluation was performed, including the motor part of the MDS-UPDRS, its axial and lateralized scores (for more and less affected side), two Timed Tests, namely Time to Walk a standard distance (TW, in seconds) and Time Up and Go Test (TUG, in seconds), and the Pull Test. The preferred foot (right or left) involved in the step backward was recorded. Thirty-seven healthy controls underwent a motor assessment which included the Pull Test and the Timed Tests. Both participants with PD and controls were right-handed. To evaluate the relationship between the response to Pull-Test and PD-symptoms, subjects with PD were further divided into two groups: (1) Right more affected side (Right-MAS), and (2) Left more affected side (Left-MAS). Results: Both groups of subjects with PD (Right-MAS and Left-MAS) during the Pull Test shifted significantly their leg use preference toward the opposite side than the more affected side: Right-MAS used preferentially their left leg (71%) and vice versa (p < 0.001). The limb preference shift was especially true for Left-MAS group that almost invariably used their right, dominant leg to respond to the Pull Test (95%). Similar results were obtained comparing people with PD and Controls. Conclusions: This study shows that the limb used to respond to the Pull Test generally predicts the contralateral side of worse PD involvement. As the disease takes place, it prevails over hemispheric dominance: right-handed subjects with left side PD-onset and worse lateralization tend to be hyper-right-dominant, while right-handed subjects with right side PD-onset and worse impairment tend to behave as left-handers. Lateralization of symptoms in PD is still a mysterious phenomenon; more studies are needed to better understand this association and to optimize tailored rehabilitation programs for people with PD.

Neurological Involvement in the Course of Scleromyxedema: A Case Report.

Scleromyxedema is a rare disease of unknown etiology primarily affecting the skin, characterized by generalized papular eruption, dermal fibroblast proliferation with mucin deposition, and a monoclonal gammopathy. Neurological impairment is a rare but sometimes fatal complication of scleromyxedema that should be rapidly identified to prevent significant morbidity and mortality. A 63-year-old Caucasian man had a 2-year history of scleromyxedema, and was under immunosuppressive treatment with ciclosporine and methotrexate. The patient came to our attention because of sudden neurological dysfunction with altered sensorium, confusion, and dysarthria. After a few hours since admission, the patient developed left hemiparesis, followed after 2 days by right hemiparesis. The brain computed tomography and cerebrospinal fluid examination results were normal. Brain magnetic resonance imaging (MRI) showed a bilateral cortical hyperintense signal on T2 sequences with leptomeningeal enhancement. Extensive serological and liquoral evaluations were performed without significant findings. After steroid initiation, a remarkable neurological improvement was noticed. The dramatic and immediate response of the patient's to steroid and MRI data strongly suggested a dysimmune etiology. Over the ensuing week, the patient's language, motor, and sensory functions continued to improve. Two weeks after admission, the patient was discharged to home without significant neurological sequelae.

The THRombolysis and STatins (THRaST) study.

OBJECTIVE: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. METHODS: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. RESULTS: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007). CONCLUSION: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.

Long-term treatment with oxcarbazepine in clinical practice.

Oxcarbazepine (up to 1800 mg daily orally) was given for 12 months to 61 adult epileptic patients in clinical practice, as monotherapy (n=52) or adjunctive therapy (n=9). Patients on monotherapy became seizure-free (76.9%) or experienced > or = 75% seizure rate reduction, with two exceptions. In the adjunctive therapy group, one patient became seizure-free and two experienced a 50-75% seizure rate reduction. These seizure-free rates are higher than those reported in the literature. The drug was well tolerated; only two patients withdrew because of intolerance (3.3%). Long-term data is essential when evaluating a drug for lifelong treatment. This study contributes to the growing body of 12-month evidence on oxcarbazepine.