Deviation of DBS Recording Microelectrodes during Insertion Assessed by Intraoperative CT.

INTRODUCTION: Intraoperative microelectrodes recording with the Ben Gun microdrive system are often used during DBS surgery. An accurate location of these microelectrodes will directly influence the interest of this recording. We have studied the imprecision of implantation of these microelectrodes. METHODS: We have analyzed the stereotactic position of 135 microelectrodes implanted with the Ben Gun microdrive during DBS surgery of 16 patients with advanced Parkinson's disease. An intracranial CT was obtained and integrated to a stereotactic planification system. We recorded the stereotactic coordinates of the 5 microelectrodes inserted simultaneously in a cross-shape. The coordinates of each microelectrode were compared with coordinates of the other 4 electrodes inserted simultaneously with the Ben Gun and visible on the same iCT image. Thus, this procedure avoids errors from image fusion and from brain shift. We calculate (1) the three-dimensional Euclidian deviation of microelectrodes, (2) the deviation in X- and Y-axes on reconstructed probe's eye view MR images, and (3) the deviation from the 2-mm theoretical distance between the central electrode and 4 satellite microelectrodes. RESULTS: The median deviation was 0.64 mm in 3-D and 0.58 mm in 2-D probe's eye view. Satellite electrodes were located from the central electrode theoretically at 2.0 mm and practically within the range 1.9-2.1 mm, 1.5-2.5 mm, 1.0-3.0 mm, and 0.5-3.5 mm for, respectively, 9.3%, 53.7%, 88.0%, and 98.1%, thus highlighting the significant deviation from the theoretical distance. Position imprecisions were similar for the 4 satellite microelectrodes. The imprecision was similar in X-axis and Y-axes and statistically less in Z-axis. For bilateral implantation, the second implantation of the same patient was not associated with a greater risk of deviation of the microelectrodes than for the first side implanted. CONCLUSION: A significant percentage of microelectrodes for MER can deviate substantially from their theoretical target during DBS procedures. An iCT can be used to estimate the potential deviation of microelectrodes and improve the interpretation of MER during the procedure.

Effectiveness and safety of safinamide in routine clinical practice in a Belgian Parkinson's disease population: an open-label, levodopa add-on study.

BACKGROUND: Safinamide is a recent multimodal antiparkinsonian drug that inhibits monoamine oxidase B and modulates the glutamatergic system with positive effects on motor and nonmotor symptoms of Parkinson's disease (PD). This post-hoc analysis of the European SYNAPSES study provides first-time data on the use of safinamide in routine clinical practice in Belgium. OBJECTIVE: To describe the efficacy and safety of safinamide in Belgian PD patients in real-life conditions. METHODS: Post-hoc analysis of the Belgian cohort from the European SYNAPSES trial, which was an observational, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months. Analyses were performed in the overall population and according to different criteria such as the age limit (> 75 years), presence or absence of relevant comorbidities, presence or absence of psychiatric conditions such as depression and anxiety, patients on levodopa monotherapy or levodopa in combination with other treatments, patients on rasagiline before inclusion or not. RESULTS: Of the 172 patients included, 29.2% were > 75 years, 58.9% had relevant comorbidities and 32.7% had psychiatric conditions. Almost all the patients reported motor (98.8%) or non-motor (86.3%) symptoms. During the study, 36.3% of patients reported drug-related reactions. The adverse drug reactions were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroups of patients. Almost 35% of the patients demonstrated a clinically significant improvement in the UPDRS and 50% of the patients with wearing-off at baseline, did not report wearing-off anymore after one year of treatment. Patients under levodopa monotherapy compared to patients receiving levodopa combined with other antiparkinsonian treatments benefit more from safinamide treatment. Patients switched from rasagiline to safinamide seemed also to benefit more from safinamide treatment. CONCLUSION: The study confirms the excellent safety and efficacy profile of safinamide, particularly in more vulnerable groups of patients such as the elderly and patients with significant comorbidities or psychiatric conditions such as depression or anxiety.

Stroke in thrombotic thrombocytopenic purpura induced by thyrotoxicosis: a case report.

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease involving the platelet aggregation and resulting in hemolytic anemia, thrombocytopenia, and microvascular occlusion. Although frequent neurologic features are headache and confusion, focal deficit is described in 30% of the cases. There are a lot of causes inducing thrombotic thrombocytopenic, but reports are lacking when associated with Grave disease. We describe the case of a 51-year-old Caucasian woman presenting a 24-hour story of sudden onset of dysarthria and left superior limb palsy. Four months before, she developed severe hyperthyroidism associated with petechiae, hemolytic anemia, thrombocytopenia, and schistocytes at blood film examination. Relapse of TTP in association with Grave disease was diagnosed. There are few reports describing association between Grave disease and TTP with only mild neurologic involvement. We described, to our knowledge, the first case of acute ischemic stroke secondary to thrombotic thrombocytopenic induced by thyrotoxicosis.

Intestinal levodopa infusion: the Belgian experience.

Data concerning efficacy, safety, and patient satisfaction of levodopa/carbidopa intestinal gel (LCIG, Duodopa, AbbVie, Wavre, Belgium) infusion in routine clinical practice were needed to maintain reimbursement of the drug in Belgium. Patients with advanced Parkinson's disease in 27 neurology centers across Belgium were included. Of 100 patients who underwent naso-intestinal (NI) evaluation with LCIG, 67 received permanent treatment with LCIG via percutaneous endoscopic gastrostomy and jejunal tube (PEG/J). Efficacy was evaluated at baseline (on levodopa) and during a follow-up (FU) visit (on LCIG) using the Unified Parkinson's Disease Rating Scale (UPDRS) IV. Patient appraisal of the Duodopa system was evaluated using a visual analog scale for therapy compliance, user-friendliness, and global appreciation. Safety was assessed by reporting suspected adverse drug reactions (ADRs) and medical device-related complaints. FU evaluations were conducted in 37 patients. Significant improvement at FU was observed for motor complications (UPDRS IV) as the mean change from baseline to FU was -6.3 (95 % CI -8.1 to -4.5). Patient appraisal showed high scores for hospital delivery, user-friendliness, and patient global appreciation, as well as family appreciation of the system on daily life. Few ADRs and system malfunctions were reported, with no unexpected ADRs. In conclusion, the symptoms and impact of Parkinsonism improved markedly when LCIG PEG/J was initiated.

Phenotypical characterization of α-galactosidase A gene mutations identified in a large Fabry disease screening program in stroke in the young.

OBJECTIVE: In the Belgian Fabry Study (BeFaS), the prevalence of Fabry disease was assessed in 1000 young patients presenting with stroke, unexplained white matter lesions or vertebrobasilar dolichoectasia. The results of the BeFaS suggested that Fabry disease may play a role in up to 1% of young patients presenting with cerebrovascular disease. However, the clinical relevance was unclear in all cases. We report on detailed phenotyping in subjects identified with α-galactosidase A (α-Gal A) enzyme deficiency or GLA mutations identified in the BeFaS (n=10), and on the results of family screening in this population. METHODS: Family screening was performed to identify additional mutation carriers. Biochemical and/or clinical evaluation of all subjects (BeFaS index patients and relatives carrying a GLA mutation) was performed. RESULTS: Genetic family screening revealed 18 additional GLA mutation carriers. Bloodspot α-Gal A enzyme activity was normal in all GLA mutation carriers, even in 2 males with the p.A143T mutation. Plasma Gb3 and lyso-Gb3 levels were normal in all subjects. Elevated Gb3 in urine was detected in 2 subjects. Some classic clinical signs of Fabry disease, like angiokeratoma or cornea verticillata, could not be detected in our population. Cardiac symptoms of Fabry disease were found in 6 out of 10 p.A143T carriers. No signs of cerebrovascular disease were found in the relatives with a GLA mutation. CONCLUSIONS: We could not identify mutations causing the classical clinical phenotype of Fabry disease in our cerebrovascular disease population. Enzyme activity analysis in bloodspots and plasma may fail to identify late-onset variants of Fabry disease. We recommend genetic testing when an atypical, late-onset variant of Fabry disease is suspected in a male cerebrovascular disease patient. However, this may lead to the identification of non-disease causing or controversial genetic variants.

Interobserver reproducibility of the interpretation of I-123 FP-CIT single-photon emission computed tomography.

OBJECTIVES: I-123 ioflupane (FP-CIT) single-photon emission computed tomography is a recognized tool in the diagnosis of Parkinsonian syndromes. In practice, data interpretation relies on visual and semiquantitative analyses. Good interobserver reproducibility is a prerequisite before claiming the robustness of a technique. This study aimed at evaluating interobserver reproducibility of this approach. METHODS: Thirty nuclear medicine physicians participated in the study. Data included FP-CIT images and semiquantitative measurements of 12 cases, covering a wide spectrum of scintigraphic patterns and for which a 'true' clinical diagnosis based on long-term follow-up was available. Interobserver agreement was defined, for each case, as the highest percentage reached among the three proposed answers with complete agreement arbitrarily set at 80% or more. Variability in an individual observer's sensitivity to assess data as normal, equivocal or abnormal was scored using a three-point scale. RESULTS: Response rate was 99.7%. Among the three possible answers,'normal' accounted for 41.2% of the total, 'abnormal' for 49.8% and 'equivocal' for 8.1%. The mean interobserver agreement was 76% (range: 37-100%), with complete agreement being reached only in five cases. The interpretation proposed by most observers accorded to clinical diagnosis in 75% of the cases. Abnormalities of the central nervous system were encountered in all the cases with disagreement between the observer's interpretation and clinical diagnoses. An important variability in the observers' sensitivity was seen. CONCLUSION: In the particular setting of this preliminary study evaluating the reproducibility of FP-CIT single-photon emission computed tomography interpretation in a group of nuclear medicine physicians with various experiences, interobserver agreement was suboptimal. Collegial discussion and standardized interpretation criteria could contribute to an improved reproducibility.

FP-CIT SPECT in clinically inconclusive Parkinsonian syndrome during amiodarone treatment: a study with follow-up.

OBJECTIVES: To evaluate whether dopamine transport system imaging by FP-CIT single-photon emission computed tomography (SPECT) can be helpful to differentiate idiopathic Parkinson's disease (IPD) from secondary Parkinsonism induced by amiodarone. METHODS: Twenty-two patients with Parkinsonism during amiodarone therapy were evaluated by clinical neurological examination and FP-CIT SPECT. Thereafter, amiodarone was discontinued whenever possible and antiparkinsonian treatment was modified, if required. Clinical neurological status was reevaluated within a year of the SPECT examination. RESULTS: At baseline, clinical neurological examination was quite similar in all patients. No clinical symptom was able to clearly orientate the diagnosis toward IPD or drug-induced Parkinsonism. Using SPECT, the number of normal and abnormal patients was evenly distributed. In the abnormal SPECT group, amiodarone was modified in seven patients of whom six improved at follow-up. Antiparkinsonian treatment had been modified in all the patients. In the four cases with no amiodarone changes, clinical improvement was noted if antiparkinsonian treatment was optimized (three patients). In the 11 normal SPECT patients, amiodarone was modified in five patients. All patients ameliorated (two) or even normalized (three). In the six patients with normal SPECT in whom amiodarone had not been modified, symptoms remained stable despite the absence of antiparkinsonian treatment. CONCLUSION: In patients treated with amiodarone, IPD is sometimes clinically difficult to differentiate from drug-induced Parkinsonism. Using FP-CIT, a normal scan suggests drug-induced Parkinsonism, hence, there is no need for antiparkinsonian treatment and all possible attempts to reduce or preferably stop amiodarone. An abnormal scan, on the other hand, indicates IPD. In this case, treating IPD seems to have more impact on motor changes than modifying the antiarrhythmic drug.