Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease

Abstract

BackgroundThe EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN‐DBS) and best medical treatment (BMT) was superior to BMT alone.ObjectiveThis prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN‐DBS and BMT over 2 years, and secondary outcomes included non‐speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician‐ and patient‐reported assessments.MethodsSTN‐DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation—for STN‐DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN‐DBS and BMT groups from baseline to 24 months.ResultsOver the 2‐year period, changes in speech intelligibility and MPT, as well as patient‐reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN‐DBS and BMT groups, on medication and OFF STN‐DBS, with patients in the STN‐DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN‐DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III.ConclusionAt this early stage of the patients' disease, STN‐DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient‐reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Emerging therapies for neuromodulation in Parkinson's disease

“…The authors studied patients with an average disease duration of seven years who had recently reported levodopa-induced motor complications. This study confirmed the superiority of early STN-DBS for quality of life and motor improvement and it weighed the potential higher risk of serious adverse events, such as impaired wound healing (3.2 ​%), intracerebral abscess/edema (1.6 ​%), or the need for reoperation (1.6 ​%) [ [115] , [116] , [117] ].…”

“…Another prospective study enrolled 30 PD patients without any motor complications and reported that an earlier surgical approach revealed a reasonable safety profile and offered a potential longer period for overall symptom relief [ 117 , 118 ]. Many DBS experts worry that considering DBS after PD diagnosis and before the appearance of motor fluctuations may increase the risk of including patients with atypical parkinsonism or risk overtreating patients who may never develop the degree of disability requiring DBS [ 119 ].…”

Long-term effects of subthalamic nucleus deep brain stimulation on speech in Parkinson’s disease

“…Moreover, it has been previously reported that speech intelligibility may worsen 1 year after surgery when compared with those under a control group under optimal medical treatment 7 . The majority of the studies regarding the effects of STN-DBS on speech focused on short-term follow-up 7 – 11 while few studies have assessed the long-term effects 2 , 12 – 14 . In particular, a previous study reported a worsening of speech intelligibility at five and eight years after surgery in the off-medication condition 12 , while another acoustic study reported variation of the long-term averaged spectrum (LTAS) descriptors for reading and monologue in different stimulation conditions in the long-term after surgery 14 .…”

Effects of deep brain stimulation of the subthalamic nucleus on patients with Parkinson's disease: a machine-learning voice analysis

“…Alternatively, a mechanism for explaining the STN-DBS-related worsening of dysarthria in PD would imply a specific pathophysiological effect of electric stimulation on target neuronal populations. The DBS implanted in the STN may activate antidromically axons of the hyperdirect pathway (i.e., cortico-subthalamic fibers), which in turn may lead to abnormal activation of cortical areas involved in voice production, thus leading to stuttering and spastic speech (16,19,53,(62)(63)(64). Another reasonable mechanism would imply the spread of current from STN to contiguous brain structures owing to horizontal propagation of the electric field and the related volume of tissue activation (VTA) (65).…”