Deep brain stimulation in acute management of status dystonicus

Abstract

Plasma Phenylalanine Level in Dopa-Responsive DystoniaDYT5 is a condition characterized by levodopa (L-dopa) responsive dystonia (DRD) that shows childhood onset and marked diurnal fluctuation. Patients with DYT5 have heterozygous mutations in the GCH1 gene, which codes for GTP cyclohydrolase I (GTPCH), a rate-limiting enzyme in tetrahydrobiopterin (BH 4 ) synthesis. 1 BH 4 is a cofactor for aromatic amino acid hydroxylases including tyrosine hydroxylase (TH), phenylalanine hydroxylase (PAH), and tryptophan hydroxylase. 2 In patients with DYT5, production of dopamine is suppressed due to the decrease of BH 4 because TH is a rate-limiting enzyme in dopamine synthesis. The lack of BH 4 may also affect the activity of PAH, and patients with complete GTPCH deficiency show hyperphenylalaninemia. However, hyperphenylalaninemia has not been reported in patients with DYT5. 3 Therefore, we examined blood phenylalanine levels in patients with DYT5 compared with controls to determine whether the decrease of BH 4 in DYT5 affects PAH activity.Blood samples for analysis of amino acids were obtained from seven patients with DRD 4 and heterozygous mutations of GCH1, 24 patients with dopa nonresponsive dystonia (non-DRD), and 12 controls. The samples were collected in a tube containing EDTA, and plasma was obtained for analysis of phenylalanine and tyrosine levels using an auto-amino acid analyzer (HS-3000; Hitachi, Tokyo, Japan). All data are expressed as means 6 SD. The data were analyzed by analysis of variance (ANOVA) with multiple comparison using the Bonferroni method. A significant difference was defined as a P value < 0.05.The phenylalanine and tyrosine levels in the plasma of patients with DYT5, patients with non-DRD, and controls are shown in Figure 1. The phenylalanine levels in the DYT5 (81.1 6 26.6 lmol/L), non-DRD (60.5 6 14.5 lmol/L), and control (58.7 6 9.1 lmol/L) groups were all within the normal range. However, the phenylalanine level in patients with DYT5 was significantly higher than those in the other groups (P 5 0.027 by ANOVA). Multiple comparison also indicated that the level of plasma phenylalanine in patients with DYT5 was significantly higher than those in patients with non-DRD (P 5 0.043) and in controls (P 5 0.040). There was no significant difference in the plasma phenylalanine levels between patients with non-DRD and controls. There were no significant differences in plasma tyrosine levels among all the groups. BH 4 deficiency causes hyperphenylalaninemia and a decrease of dopamine production, because it suppresses the activity of PAH and TH. Patients with a homozygous mutation in the GCH1 gene are reported to show hyperphenylalaninemia, in addition to DRD. Patients with DYT5 having only a heterozygous mutation in GCH1 also show symptoms of DRD, but do not have hyperphenylalaninemia. Our results indicated that blood phenylalanine levels in patients with DYT5 are within the normal range, but are higher than those in controls, which suggests that the activity of PAH is partially affected by the decre...

Deep Brain Stimulation for Status Dystonicus: A Case Series and Review of the Literature

“…In addition to the 5 cases presented here, we identified in the literature 18 additional cases of SD treated with DBS as an acute therapy modality (table 5) [6,19,20,21,22,23,24,25,26,27,28]. The dystonic crisis was effectively terminated in 17 of these 18 patients, with a time course ranging from a few days to 3 months postoperatively.…”

“…Frequently reported sequelae of SD include airway compromise, rhabdomyolysis, hyperpyrexia, renal failure, pain, and dehydration. To date, there have been fewer than 70 cases of SD reported in the literature [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. These cases are characterized by widely varying etiologies, clinical courses, treatments, and outcomes.…”

“…Medications reported to have some benefit include propofol, tetrabenazine, trihexyphenidyl, baclofen (both oral and intrathecal), dopamine agonists, benzodiazepines, and benzhexol [11,12,19,25]. Reported surgical interventions include unilateral and bilateral thalamotomy [1,12], pallidotomy [5,6,9,11,27], pallido-thalamotomy [3], and most recently deep brain stimulation (DBS) [6,19,20,21,22,23,24,25,26,27,28]. There is no consensus regarding the optimal strategy for treating SD, and in many cases it is unclear whether the intervention(s) were truly effective or the crisis simply dissipated of its own accord.…”

“…Coubes et al [23] first reported the successful use of pallidal DBS for the treatment of acute SD in 1999. Since then, only a few additional case reports have been published [6,19,20,21,22,23,24,25,26,27,28,29], and there is no consensus as to the optimal programming parameters or lead configurations. Here we describe a case series of 5 patients with DYT1-associated dystonia who presented in SD and were treated with early initiation of pallidal stimulation, and provide a review of the relevant literature.…”

Tolerance of early pallidal stimulation in pediatric generalized dystonia

“…When children present with status dystonicus, an emergency pallidal DBS may be a life-saving option. 18,44,46 In our Case 2, however, this catastrophic condition followed a period in which the patient's symptom had developed a tolerance to pallidal DBS. As our case illustrates, because of the uncertainty of the long-term benefits and risks of pallidal DBS in patients who may be too young, careful consideration should be given to all possible treatment options, such as the use of extensive intramuscular botulinum toxin, intrathecal baclofen, and/or temporary sedation with intravenous anesthetic.…”