Motor Evoked Potentials in Newly Diagnosed and Treated Patients With Wilson Disease.

PURPOSE: To investigate whether patients with Wilson disease have abnormal motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation. METHODS: In a prospective, observational, single-center study, transcranial magnetic stimulation was used to examine MEPs recorded from the abductor digiti minimi in 24 newly diagnosed treatment-naive patients and 21 treated patients with Wilson disease. RESULTS: Motor evoked potentials were recorded in 22 (91.7%) newly diagnosed treatment-naive patients and in 20 (95.2%) treated patients. Abnormal MEP parameters were found in a similar proportion of newly diagnosed and treated patients: MEP latency (38% vs. 29%), MEP amplitude (21% vs. 24%), central motor conduction time (29% vs. 29%), and resting motor threshold (68% vs. 52%). Abnormal MEP amplitude (P = 0.044) and resting motor threshold (P = 0.011) were more frequent in treated patients with brain MRI abnormalities but not in newly diagnosed patients. We did not observe significant improvement in MEPs parameters after 1 year of treatment introduction in eight examined patients. However, in one patient where MEPs were initially nondetectable, they were present 1 year after treatment introduction with zinc sulfate, although MEPs were not in the normal range. CONCLUSIONS: Motor evoked potential parameters did not differ between newly diagnosed and treated patients. There was no significant improvement in MEP parameters one year after treatment introduction. Further studies conducted on large cohorts are necessary to determine the usefulness of MEPs in detecting pyramidal tract damage and improvement after anticopper treatment introduction in Wilson disease.

Autonomic nervous system dysfunction in Wilson's disease - A systematic literature review.

INTRODUCTION: In Wilson's disease (WD), copper accumulation can result in neurological manifestations, particularly extrapyramidal symptoms. There are some data that the autonomic nervous system (ANS) may also be affected, and we aimed to systematically review available studies evaluating ANS dysfunction in WD. MATERIAL AND METHODS: We conducted a systematic review of the literature using the PubMed database (up to 31st August 2020), with search terms including "autonomic" and "function" and "Wilson's disease". RESULTS: Fourteen studies, including 297 patients with neurological, hepatic or psychiatric forms of WD were retrieved. The most frequent methods used for ANS evaluation were orthostatic tests, which were performed in seven studies, with a number of other tests less frequently used. The incidence of ANS abnormalities ranged from ~8% to 79.2%, depending on the evaluation method. ANS abnormalities in patients with WD were often clinically asymptomatic. The features of dysautonomia were more common among patients with neurological symptoms and ANS abnormalities were more common in patients with severe brain injury. Studies confirmed both sympathetic and parasympathetic ANS impairment. The pathophysiology of ANS damage was not clear but may result from central, peripheral nervous system and direct cardiac involvement. Clear improvements were observed in four studies after anti-copper therapy initiation. CONCLUSION: Both sympathetic and parasympathetic divisions of the ANS may be affected in WD. The observed ambiguities regarding ANS abnormalities in WD patients may arise from small study groups, differences in methodology, and a lack of comprehensive ANS evaluation; however, the results indicate that further studies are warranted.

Fluoxetine for stroke recovery improvement - the doubleblind, randomised placebo-controlled FOCUS-Poland trial.

AIM OF STUDY: The Fluoxetine Or Control Under Supervision (FOCUS)-Poland trial tested in a Polish cohort the hypothesis that fluoxetine improves recovery after stroke. CLINICAL RATIONALE FOR STUDY: Some studies have suggested that fluoxetine may improve functional outcomes after stroke, but these results needed confirmation. Between 2012 and 2014, large clinical trials were initiated by the FOCUS Trial Collaboration. Recently, results from the UK, Sweden, Australia, New Zealand and Vietnam have been published. We here present the results of the FOCUS trial conducted in Poland. MATERIAL AND METHODS: This was a randomised, double-blind, placebo-controlled study based on the FOCUS trial protocol. Patients who had a persisting neurological deficit were randomly assigned 2-15 days after stroke onset to receive for six months either fluoxetine 20 mg/day or a placebo. The primary outcome was functional status measured using the modified Rankin Scale (mRS) at six months after randomisation. Functional status at 12 months was also assessed, as was neurological deficit at six and 12 months. Data was also collected on adverse events. RESULTS: Between 19 December 2014 and 13 March 2018, 30 patients were given fluoxetine and 31 were given a placebo. For the primary outcome, the distribution across mRS categories was similar for the fluoxetine and placebo groups at six months (common odds ratio 0.88; 95% confidence interval 0.31-2.50; p = 0.81), and there was no difference at 12 months (p = 0.864). There were no differences between groups in stroke recovery or in motor function recovery of the affected hand. There were no significant differences in any other secondary outcomes at six or 12 months. Patients given fluoxetine were less likely than those given the placebo to receive new antidepressant medication within six months (2 [6.67%] vs. 4 [12.90%]). CONCLUSIONS AND CLINICAL IMPLICATIONS: Consistent with other trials based on the FOCUS protocol, fluoxetine did not improve motor recovery or general stroke outcome at six and 12 months in the Polish cohort studied. However, patients receiving fluoxetine required therapy with additional antidepressant medication less frequently.

Prediction of Recovery and Outcome Using Motor Evoked Potentials and Brain Derived Neurotrophic Factor in Subacute Stroke.

INTRODUCTION AND OBJECTIVES: Motor evoked potentials (MEPs) have been postulated to be useful in predicting recovery in patients with motor impairment. We aimed to investigate whether MEPs elicited by transcranial magnetic stimulation (TMS), serum brain derived neurotrophic factor (BDNF) and its genotype have prognostic value on stroke recovery in patients with hand paresis due to stroke. METHODS: This was an observational cohort study. Patients underwent TMS with MEPs from abductor digiti minimi evaluation between 2-14 (D0) and 30 days (D30) after stroke and their impact on motor function of the upper limb and general outcome was assessed after 3 months (D90). The presence of a BDNF gene polymorphism was determined and serum BDNF concentrations were measured at D0, D30 and D90. RESULTS: The presence of MEPs and their amplitude at rest and in effort significantly correlated with improvement of upper-limb paresis and general outcome after 3 months. Resting motor threshold did not have prognostic value. Central motor conduction time and MEP latency less consistently predicted stroke outcome or motor deficit improvement. Neither BDNF polymorphisms nor BDNF concentration at D0, D30 and D90 corresponded with the degree of paresis or the independence of patients 3 months after stroke. CONCLUSIONS: The presence of MEPs and their amplitude are useful predictors of upper-limb motor function recovery and general outcome after stroke. BDNF concentration and its genotype had no prognostic value. Further studies conducted on large cohorts are necessary to determine the usefulness of these methods in motor recovery and stroke outcome prediction.

Transcranial Magnetic Stimulation-Induced Motor Evoked Potentials in Hirayama Disease: Systematic Review of the Literature.

PURPOSE: Hirayama disease (HD) is a rare motor disorder mainly affecting young men, characterized by atrophy and unilateral weakness of forearm and hand muscles corresponding to a C7-T1 myotome distribution. The progression is self-limited. The etiology of HD is unclear. The usefulness of motor evoked potentials (MEPs) in pyramidal tracts damage evaluation still appears to be somehow equivocal. METHODS: We searched PubMed for original articles, evaluating the use of transcranial magnetic stimulation elicited MEPs in HD using keywords "motor evoked potentials Hirayama" and "transcranial magnetic stimulation Hirayama." RESULTS: We found seven articles using the above keywords that met inclusion criteria. The number of participants was small, and diagnostic procedures varied. There were also differences in methodology. Abnormal central motor conduction time was found in 17.1% of patients in one study, whereas it was normal in two other studies. Peripheral motor latency was evaluated in one study, which found abnormally increased peripheral motor latencies in at least one tested muscle in 16 of 41 HD patients (39.0%). Abnormal MEP parameters were found in three studies in 14.3% to 100% patients. In one study they were not evaluated, in three other studies they were normal, and in one they were normal also in standard and flexed neck position In one study, inconsistent results were found in MEP size after neck flexion in patients after treatment with neck collar. CONCLUSIONS: Although MEP parameters may be abnormal in some HD patients, these have not been thoroughly assessed. Further studies are indispensable to evaluate their usefulness in assessing pyramidal tract damage in HD.

Difficulties in diagnosis and treatment of Wilson disease-a case series of five patients.

Wilson disease (WD) may present symptomatically at any age. There is great variability in the neurological symptoms present, in the clinical state of WD patients, and in the response to decoppering therapy. Early diagnosis and compliance with anti-copper therapy are essential. Here we present five different WD cases to illustrate different problems encountered during diagnosis and treatment. The first case demonstrates that decoppering therapy may be very effective even with severe neurological symptoms. In addition, we see the importance of family screening, especially among the proband's siblings. Case 2 shows that we must be very careful during diagnosis. In the reported family, WD was diagnosed in the father of the proband although her brother had liver pathology but not caused by WD. Other cases teach us that decoppering therapy with d-penicillamine must be introduced slowly because of the high risk of neurological deterioration, especially in patients with typical WD brain changes even without neurological signs. We also have to consider concomitant therapies in WD patients. Neuroleptics may cause exacerbation and should be used at a low dose and for the shortest period possible. A full consideration for the issues surrounding the diagnosis and treatment of WD can lead to optimised care with reduced risk of progression and disability.

Mitochondrial protein associated neurodegeneration - case report.

Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic disorders with a progressive extrapyramidal syndrome and excessive iron deposition in the brain, particularly in the globus pallidus and substantia nigra. We present the case of a 31-year-old woman with mitochondrial protein associated neurodegeneration (MPAN). MPAN is a new identified subtype of NBIA, caused by mutations in C19orf12 gene. The typical features are speech and gait disturbances, dystonia, parkinsonism and pyramidal signs. Common are psychiatric symptoms such as impulsive or compulsive behavior, depression and emotional lability. In almost all cases, the optic atrophy has been noted and about 50% of cases have had a motor axonal neuropathy. In the MRI on T2- and T2*-weighted images, there are hypointense lesions in the globus palidus and substantia nigra corresponding to iron accumulation.