Deep Brain Stimulation in Classical Galactosemia: A Case‐Report

Galactosemia is an umbrella term referring to a rare metabolic disorder including classical galactosemia, clinical variant galactosemia and biochemical variant galactosemia.1 Various movement disorders including parkinsonism have been described in classical galactosemia.2 We reported a few years ago the case of a patient, who presented parkinsonism with dopaminergic denervation, mild cognitive impairment, and mild cerebellar ataxia in a context of classical galactosemia with Gln188Arg homozygote mutation on the galactose-1-phosphate uridylyltransferase (GALT) gene.3 His tremor worsened progressively during his sixth decade, consequently to a disrupted diet. Physical examination showed left-predominant asymmetrical parkinsonism with severe and disabling resting, postural and action tremor (see Video 1, segment 1 and Fig. 1A). Despite medical treatment with propranolol (80 mg per day) and L-DOPA (800 mg/day) associated with an optimal diet excluding galactose and lactose, no significant improvement oftremor was observed. Therefore, the patient, who is left-handed, underwent unilateral right-sided ventral intermedius nucleus (VIM) thalamic deep brain stimulation (DBS) (VERCISE Genus R16*, CARTESIA directional electrodes*, Boston Scientific, USA) (Fig. 2). The coordinates of the active contact were 13.5 mm lateral right, 6.7 mm posterior to the mid commissural point, and 1.5 mm cranial to the anterior commissure-posterior commissure plane. Rapid and major improvement was observed immediately after surgery using monopolar stimulation (contact L1.9; 3 mA/60 μs/130 Hz), allowing propranolol suppression (Video 1, segment 2 and Fig. 1B). No side effect was observed except transient left hand paresthesia. Three months after surgery, the patient estimated the improvement at 60% for his left-hand tremor. Ataxia did not worsen, opening the opportunity to a bilateralization of the procedure in the future. This is, to our knowledge, the first case of thalamic DBS in classical galactosemia. DBS (mainly VIM DBS) is a classical treatment for disabling essential tremor or Parkinson's disease tremor, but other types of tremors may also benefit from DBS, and other targets of stimulation such as zona incerta or posterior subthalamic area may be considered.4, 5 In the present case, we chose VIM-DBS instead of subthalamic nucleus DBS to improve this disabling tremor which was non-levodopa responsive despite the presence of parkinsonian syndrome and dopaminergic denervation. We observed major antitremoric efficacy of VIM-DBS without deterioration of the mild cognitive impairment and gait ataxia that were secondary to the disease. This is an important point as ataxia is one of the most common side-effects of VIM-DBS.6 The present case illustrates that VIM DBS should be considered in patients with disabling tremor due to classical galactosemia allowing an important quality of life improvement. (1) Research project: A. conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. N.B.: 1A, 1C, 3A E.S.: 1C, 3B A.J.: 1C, 3B P.J.: 1C, 3B T.D.: 1C, 3B C.L.: 1C, 3B S.P.: 1C, 3B S.T.: 1A, 1C, 3B Ethical Compliance Statement: Patient's informed written consent was obtained for this case report and the Video 1. The authors confirm that the approval of an institutional review board was not required for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the Previous 12 Months: ST received honoraria from Abbvie, Boston, Medtronic, Merz for board or conferences; ES received honoraria from Boston and BrainLab for board or conferences; PJ received honoraria from Abbvie, and Medtronic for board and conferences; TD has no financial disclosures or conflicts of interest to declare; AJ: has no financial disclosures or conflicts of interest to declare. S.P. received honoraria from Abbvie for scientific advice; CL: received honoraria from Medtronic. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.