Impact of Deep Brain Stimulation therapy on the vertebral sagittal balance in Parkinson’s disease patients

doi:10.21203/rs.3.rs-3244750/v1

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Research Article

Impact of Deep Brain Stimulation therapy on the vertebral sagittal balance in Parkinson’s disease patients

https://doi.org/10.21203/rs.3.rs-3244750/v1

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published 08 Dec, 2023

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Background

Parkinson’s Disease (PD) is characterized by cardinal motor signs: 4-6 Hz resting tremor, rigidity and bradykinesia. In addition, 3-18% of PD patients have camptocormia, an abnormal forward flexion of the thoracolumbar spine, which may have a negative impact on patients' quality of life. Different possible treatments have been suggested for such a condition, but no one is resolutive.

This study aims to define the possible impact of DBS, with selective targeting on the dorso-lateral region of STN, on the sagittal balance of patients affected by PD.

Patients and Methods

Among all patients undergone DBS procedures in our Institution, we selected 8 subjects, 4 female and 4 males, with selective targeting on the dorso-lateral region of the Subthalamic Nucleus (STN) because of camptocormia and other severe postural changes. Radiological assessments of spinal balance parameters before surgery and at 6 and 12 months post-surgery were carried out.

Results

Comparison of preoperative and postoperative spine X-ray data showed that patients showed a statistically significant improvement in dorsal kyphosis angle (D-Cobb) 12 months after the operation.

Conclusions

Deep Brain Stimulation with selective targeting of the dorsal lateral part of the STN may induce changes of the posture in patients with Parkinson’s Disease 12 months after the operation, which appears to improve in this small sample size, but larger observational and controlled trials would be required to confirm this observation.

Parkinson’s Disease

DBS therapy

Postural instability

Camptocormia

Sagittal Balance

Postural instability is not infrequent in subjects with Parkinson Disease (PD), and it is due to a combination of trunk incoordination, orthostatic hypotension and sensorimotor integration deficits. These alterations can lead to clinical syndromes including degenerative scoliosis, myopathy-induced postural deformity, Pisa syndrome, anterocollis and camptocormia [1, 11, 29, 58], which ultimately impact the patients’ quality life, contributing to increase difficulty with transfers, gait, ability to live independently at home (ADLs – Activities of Daily Life) and increasing the risk of falls [2]. Camptocormia (curved spine syndrome) is the major postural change in PD, with a prevalence of 18% [1, 27, 28, 43, 54, 57]. The term derives from the Greek kamptos (to bend) and kormos (trunk) [57, 62] and was coined by Rosanoff-Saloff and Souques in 1915 to describe the forward flexion posture of some soldiers in World War I, who had to move through the trenches in a bent posture [28, 36, 64]. It is an axial postural deformity characterized by an extreme forward flexion of the thoracolumbar spine that persists for more than 3 months, which often worsens during standing or walking, but improves or even disappears in the recumbent position [41, 62].

Strategies for treatment of camptocormia in PD subjects include levoDOPA therapy (with a minimal or no effects), type-A botulinum toxin injection into the rectus abdominis muscle, ultrasound-guided type-A botulinum toxin injection into the iliopsoas muscle [18, 24, 25, 60, 65], intrathecal baclofen infusion, deep brain stimulation (DBS) targeting the subthalamic nucleus or Globus Pallidus Internus [23, 57, 62], spinal surgery and magnetic trans-spinal stimulation [5]. DBS, especially, when effective in helping to improve PD motor symptoms, can be the cause of postoperative improvement also of camptocormia and other postural changes.

The aim of our study is to evaluate whether Deep Brain Stimulation (DBS), with selective targeting of the dorsolateral region of Subthalamic Nucleus (STN), may impact on camptocormia, and, therefore, the sagittal balance in Parkinson’s Disease patients. The aim of this study was not to propose any novel location of the DBS-STN stimulation as the primary treatment for camptocormia in PD patients.

Patient demographics

Among all patients operated upon for PD by means of Deep Brain Stimulation therapy at the Division of Neurosurgery of the Federico II University of Naples, 8 non-consecutive subjects with abnormal values of all the parameters used for defining the sagittal balance of the spine (4 females [average 59.7 years] and 4 males [average 50.5 years]) were selected. They were assessed using spine radiographs, including 10 cm of the femoral head, in both antero-posterior and latero-lateral projections, in order to define the sagittal and pelvic indexes.

All patients enrolled in this study were on pre-operative medical therapy, which also included LevoDOPA. The average of the pre-surgical dose of the LevoDOPA, calculated as LEDD (LevoDOPA Equivalent Daily Dose), was 1087.25 mg/day (range 500–2415; S.D. 609.21); the average 1-year postoperative LEDD was 758.625 (range 300–1524; S.D.: 382.85) (p < 0.001; C.I. = 95%) (see Table 1).

Table 1

*Patients’ characteristic*
Sex	4 M
	4 F
Age (years)	average	55.125
	s.d.	11.28
	range	40–69
Disease duration before DBS (years)	average	9.625
	s.d.	3.7
	range	5–14
UPDRS pre on-MED	average	72.25 (part II: 49.25)
	s.d.	25.132 (part II: 17.03)
	range	34–108 (part II: 28–71)
UPDRS pre off-MED	average	89.625 (part II: 67.75)
	s.d.	30.57 (part II: 14.74)
	range	40–129 (part II: 50–88)
UPDRS post on-MED, on-STIM	average	45.125 (part II: 25.125)
	s.d.	20.12 (part II: 13.74)
	range	14–70 (part II: 9–51)
LEDD pre (mg/day)	average	1087.25
	s.d.	609.21
	range	500–2415
LEDD post (mg/day)	average	758.625
	s.d.	382.85
	range	300–1524
LEDD pre-op Vs LEDD post-op: p < 0.001, C.I.=95%
UPDRS: Unified Parkinson's Disease Rating Scale; UPDRS-part II: Motor Experiences of Daily Living, for assessment of disability in Parkinson's Disease.

Inclusion and exclusion criteria

Surgical eligibility has been assessed by a multidisciplinary team of neurosurgeons, neurologists, psychiatrists and neuropsychologists through the Core Assessment Program for Surgical Interventional Therapies in Parkinson’s disease (CAPSIT-PD).

Inclusion and exclusion criteria are listed in Table 2.

Table 2

Inclusion/exclusion criteria
Inclusion criteria	Exclusion criteria
Patients with complete pre- and postoperative postural evaluation	Traumatic spine diseases (vertebral fractures, osteoporotic fractures, etc.)
Patients with reliable map of the leads’ positioning in the STN	Advanced degenerative spine disease
Availability of complete radiological data of the spine (preoperative baseline assessment, 6- and 12-month postoperative evaluations)	Previous spondylodiscitis
Presence of camptocormia	Previous major spine surgery

Treatment

Based on the symptoms of PD, the multidisciplinary team suggested the most appropriate target for DBS treatment; all patients underwent the bilateral implantation of a DBS system with selective targeting on the dorsolateral region of the STN [17].

The operation was commonly performed in two steps: (i) the lead positioning in the selected target using the stereotactic frame, in awake surgery using the dexmedetomidine for sedation during some parts of the procedure, and with the aid of the intraoperative neuromonitoring (either the microregistration and stimulation) for the target confirmation and for stimulation-related complication avoidance; (ii) the lead extensions and the pulse generator positioning, under general anesthesia.

Preoperative planning was performed for each patient using MRI-specific sequences for the needs of the DBS planning (FLAIR, MP-RAGE, MP2-RAGE) to compute suitable patient-specific DBS lead trajectories that optimize the avoidance of specific critical brain structures. The MRI images are fused with the CT (Computed Tomography) obtained after the stereotactic frame application; the tridimensional coordinates of the chosen target and the coordinates of the chosen entry point (usually in the pre-coronal, bilateral, paramedian frontal region) are obtained, which, ultimately, define the lead trajectories.

Such standard algorithm [33] has been employed in all the included patients.

Pre- and post-operative evaluation

Biplanar antero-posterior and latero-lateral full-standing radiograms, including the proximal 10 cm of the femurs (including the femoral heads) were obtained preoperatively and at follow-up visits, and analyzed for standard spinal and spinopelvic parameters (Tables 1 and 3). Follow-up assessments were obtained 3 to 5 days after the DBS operation, and at 6 and 12 months thereafter. The evaluated parameters were: Pelvic Tilt (PT), D-Cobb (AKA Thoracic Kyphosis [TK]), L-Cobb (or Lumbar Lordosis [LL]), Sacral Slope, C₇ Sagittal Vertical Axis (SVA).

Table 3

Pre- and post-operative sagittal balance indexes
		mean	S.D.	minimum	maximum
PT	pre-op	17.375	9.164	3	30
	6 m	16.375	7.726	2	17
	12 m	16.625	10.350	2	32
						p-value pre-op Vs 6 m post-op	0.797
						p-value pre-op Vs 12 m post-op	0.813
						p-value 6 m post-op Vs 12 m post-op	0.931
SS	pre-op	39.5	7.58	30	54
	6 m	38.75	6.58	32	52
	12 m	41.625	7.35	35	54
						p-value pre-op Vs 6 m post-op	0.818
						p-value pre-op Vs 12 m post-op	0.361
						p-value 6 m post-op Vs 12 m post-op	0.087
SVA	pre-op	3.36	3.13	0	7.6
	6 m	3.27	4.05	0	11.5
	12 m	3.85	7.81	-3	18
						p-value pre-op Vs 6 m post-op	0.364
						p-value pre-op Vs 12 m post-op	0.690
						p-value 6 m post-op Vs 12 m post-op	0.370
L-Cobb	pre-op	57.75	15.38	26	73
	6 m	62.50	9.62	50	74
	12 m	61.67	14.22	47	85
						p-value pre-op Vs 6 m post-op	0.497
						p-value pre-op Vs 12 m post-op	0.981
						p-value 6 m post-op Vs 12 m post-op	0.613
D-Cobb	pre-op	33.87	14.16	10	50
	6 m	43.37	14.38	15	60
	12 m	53.16	12.92	36	70
						p-value pre-op Vs 6 m post-op	0.266
						p-value pre-op Vs 12 m post-op	0.021
						p-value 6 m post-op Vs 12 m post-op	0.440

The sagittal balance parameters were defined as follows (see Fig. 1):

Pelvic Tilt (PT): the angle between the vertical line and the line connecting the center of the sacral endplate to the axis of the femoral heads;

Sacral Slope (SS): is measured between the tangent line to the superior endplate of S₁ and the horizontal plane;

Sagittal Vertical Axis (SVA): the distance from the C₇ vertical line to the posterior aspect of the superior endplate of the sacrum;

Lumbar Lordosis (LL) or L-Cobb: the angle between the point of inflection from lumbar lordosis to thoracic kyphosis and the upper plate of S₁;

Thoracic Kyphosis (TK) or D-Cobb: the angle between the upper T1 endplate and the lower T₁₂ end-plate. Many measurements are made at the level of the upper end-plate of T₄, since T₁ might be poorly visualized due to the interposition of the shoulders. According to Le Huec and Hasegawa [34], the average kyphotic angle between T₁ and T₄ is 8°-10° [61].

On the first postoperative day, a CT scan of the brain, integrated with X-rays radiograms extended to the right subclavian region, was performed to check the correct positioning and the integrity of the leads and of the other components of the DBS system. The images of the postoperative CT scan were fused with the images of the preoperative MRI using the SureTune™ software (Medtronic, Minneapolis, MN, USA) to obtain a detailed and tridimensional localization of the electrodes inside the STN [44, 45, 56].

IRB/Ethics Committee Approval and Informed Consent

This study is based on research involving human participants. However, since it does not report any experimental treatment nor a randomized controlled trial, and the involved subjects received the standard treatment in our institutions, with no modifications of the treatment protocols, the IRB/Ethics committee approval was not needed and was not sought.

Pre- and post-operative X-ray radiographs of the column, including 10 cm of the femoral heads, in both antero-posterior and latero-lateral projections are obtained in all the PD patients undergoing DBS therapy in our Institution, and is part of our pre- and post-operative diagnostic protocol. Consequently, the 8 patients enrolled in this study did not receive any different diagnostic nor therapeutic protocol that was different from all other operated patients.

All subjects signed a procedure-specific written informed consent, and the form was included in the patient files. Written informed consent also took into account the medical record data of patients for use in medical research. The study was not inclusive of minors.

Following collection, the data were anonymized prior to statistical analysis.

Statistical analysis

All data analyses were performed using the IBM^® SPSS^® package (version 27.0.1.0). Results are expressed as means ± SD for both discrete and continuous variables. For the assessment of within-subject changes between T₀, T₁ and T₂ the 2-tailed paired t-tests was used to compute the differences of the means. A value of p ≤ 0.05 was considered significant with a confidence interval of 95%. The LEDD (Levo-DOPA Equivalent Daily Dose) was evaluated using a free online calculator (https://www.parkinsonsmeasurement.org/toolBox/levodopaEquivalentDose.htm).

The results of the psychiatric rating scales of the 8 patients enrolled in the study are summarized in Tables 1 and 3. The average length of disease duration before the DBS operation was 9.625 years (s.d. 3.7 years, 5–14 years). Preoperatively, the average on-MED UPDRS score was 72.25, s.d. 25.32, range 34–108 (part II: average 49.25, s.d. 17.03, range 28–71); the average off-MED UPDRS score was 89.625, s.d. 30.57, range 40–129 (part II: average 67.75, s.d. 17.03, range 50–88).

At the 12-month follow-up evaluation we found a significant improvement in PD global symptoms at the UPDRS (-40.22%; p = 0.002) (see Fig. 3).

At the time of the surgical operation, all the enrolled patients presented motor fluctuations related with the with the levo-DOPA dose, which made difficult the interpretation of the FOGs. At 6-month and 12-month follow-up visit, none of the patients had FOG nor presented falls.

All patients presented a clinical subjective evidence of an improved posture at 6 and 12 months after the DBS operation (Fig. 2) and all patients confirmed self-reported postural improvement at the follow-up visits. Such data were confirmed by a phone interview with the family members and/or caregivers of all the enrolled patients. The comparison of pre-operative and full post-operative spine X-rays in antero-posterior and lateral projections did not reveal significant statistical changes in all postural indices in the 8 patients. Indeed, there has been limited, although not statistically significant, improvement in the sagittal index of the vertical axis twelve months after surgery (at 6 months p = 0.364; at 12 months p = 0.690). The preoperative median SVA was 3.36, while it was 3.27 after six months and 3.85 after twelve months (Table 3). There was a limited improvement of the Sacral Slope index after 6 months (Table 3), even though it was not statistically significant, while such angle increased again at the 12-month analysis. The evaluation of dorsal kyphosis angles (D-Cobb) (pre-operative mean 33.87), increased at six months (mean 43.37) and at twelve months after DBS (mean 53.16); this index instead, showed a statistically significative improvement after 12 months (p = 0.021).

Using the SureTune software and a comparative analysis, it was noted a direct correlation between the correct placement of the electrodes in the dorso-lateral region of STNs and the improvement of the sagittal balance. The electrodes were located within the STN for all patients (see Fig. 3); however, the patients with one or both electrodes located in a more medial and/or anterior position were those displaying a minor improvement of the postural indexes.

This manuscript presents some limitations: i) the absence of a control population of PD patient not treated with DBS therapy; ii) the relatively small sample size that may limit the generalization of the results and, finally, iii) the retrospective design of the study. The subjects were not consecutive because we enrolled only those patients who, at the preoperative spine radiographs, had all the postural parameters that were abnormal, including camptocormia, and who were operated upon by means of STN-DBS.

The aim of our study was not to propose any novel location of the STN stimulation as the primary treatment for camptocormia in PD patients nor to propose the only DBS therapy to address such symptom. Following up all PD patients operated in our Institution, we observed that at 6 and 12 months after surgery those subjects who preoperatively presented abnormal values of all the indexes used for defining the sagittal balance of the spine had some clinical improvement of the postural changes, despite the lower dose of medical therapy taken. We aimed to quantify such improvements by measuring some sagittal postural indexes at the 6- and 12-month follow-up visits and correlated any possible change of one or more of such indexes with the positioning of the DBS leads inside the different portions of the subthalamic nuclei, bilaterally. We observed that, when both the DBS leads are in the dorsal-lateral portion of the STN, there is a higher chance of post-operative improving of the PD-induced postural changes. Data from previous studies indicate that motor symptoms of PD are influenced by the positioning of the leads in the different portions of the STN (dorsolateral, medial and anterior) and a great effort should be used selectively positioning the leads in the dorsolateral portion of the STN [19, 26, 55, 56].

Postural instability (PI) is a dysfunction of postural reflexes, which is generally a manifestation of the late stages of the Parkinson’s disease and generally occurs after the onset of non-motor symptoms. It represents a disabling feature of PD. Several other factors may contribute to postural instability in PD patients, as well as other Parkinsonian syndromes: orthostatic hypotension, age-related sensory changes, and the ability to integrate visual, vestibular and proprioceptive inputs. This postural instability induces difficulties with transfers, gait disorders, inability to live independently at home, and is the major cause of falls [11].

Among the possible postural changes in subjects with PD, camptocormia patients consists in a severe flexion of the trunk and shoulders, with arms adherent to the thorax, intra-rotate and partially flexed forearms, adducted and slightly flexed legs, and feet pointed inward. There is no consensus on the degree of thoraco-lumbar flexion for defining camptocormia. Most authors use an arbitrary parameter of at least 45° flexion of the thoraco-lumbar spine during standing or walking [4, 36, 41, 42, 49, 64]. The deformity generally develops within 10 years of PD onset and responds poorly to levodopa treatment [22].

Margraf et al. proposed to include, in the definition of camptocormia, typical objective and subjective complaints, impairment of related daily activities, inability to drive a car and to carry objects in front of the body or difficulties in looking people in the eyes [41, 42].

From a biomechanical perspective, camptocormia affects the sagittal balance of patients with PD, as an attempt to adapt the spinal column to the pathological condition. In particular, the reduction of lumbar lordosis leads to a compensatory retroversion of the pelvis, with a consequential increment of the Pelvic Tilt (PT), a decrement of the Sacral Slope (SS), a reduction of D-cobb angle (angle of dorsal kyphosis) and an anterior push of the body center of gravity, causing Sagittal Vertical Axis (SVA) increase [12, 14, 35, 51].

Although there are many possible etiologies causing camptocormia, two hypotheses are the most well-recognized: i) a dystonia of trunk flexors, which is thought to arise from a non-dopaminergic neuronal dysfunction in the basal ganglia that disrupts the reticulospinal pathway. This may lead to imbalanced muscle contractions between the trunk flexors and extensors; ii) a focal myopathy of trunk extensors, including paravertebral muscles, characterized by the fatty degeneration of muscles at MRI and myopathic changes on electromyography [57]. Recent studies indicates that these two assumptions are not necessarily mutually exclusive [23].

Many treatments have been proposed in order to improve camptocormia and its effects on sagittal balance, such as: pharmacological therapy, magnetic trans-spinal stimulation, spinal surgery, intramuscular injection of botulinum toxin or lidocaine and deep brain stimulation. Each of these strategies has been proved some advantages [23, 37, 38, 48, 52, 57, 62].

Medical therapy with Levodopa has obtained discordant results[1, 3, 7, 31] even though several series have shown the responsiveness of camptocormia to dopaminergic drugs or the synergic effect of DBS and levodopa [6]. Nevertheless, Mano reported a case of camptocormia induced by dopaminergic therapy [40].

Botulinum toxin and lidocaine injections could promote the reduction of the thoracic-lumbar curvature angle, with a rather rapid improvement, but only at high doses and with an increased likelihood of side effects manifestations. Moreover, the therapeutic effects of this treatment are temporary [18, 24, 25, 60, 65].

Different studies demonstrated the efficacy of magnetic trans-spinal stimulation on camptocormia. The effects are, unfortunately, only transitory as well [21].

Spinal surgery offers the main advantage of providing a positive outcome in shorter times. However, this is an invasive procedure associated with side effects, long-time post-operative hospitalization, and a high rate of surgical revisions. Thus, it should be avoided in patients with comorbidities or not enough motivated to walk, especially for long-segment spinal fusion [8, 9, 32, 39, 47].

Deep Brain Stimulation has shown to cause an important improvement of the postural changes in PD patients with camptocormia, which is second only to the one obtained with spinal surgery, but with the advantage of obtaining positive effects on the other symptoms as well, with a minor complication rate [55]. The most common form of surgical therapy used for treating camptocormia in PD patients is bilateral STN-DBS and is effective in treating motor symptoms in PD patients. However, it presents a greater variability of effects on spinal deformities, with even the possibility of worsening the posture [48].

Treatment of camptocormia was defined by the algorithm proposed by Upadhyaya et al. [62]. They suggested that medical therapy should be considered the first-line treatment, followed by DBS for selected patients. Spinal surgery should be reserved for patients not deemed suitable for DBS and with associated radiculopathy/myelopathy, whereas no surgical intervention is indicated in subjects who have no indication for DBS treatment and who have no signs or symptoms of myelopathy/radiculopathy. In this scenario, it is important to consider that the efficiency of DBS is influenced by various factors and the choice of surgical target plays an important role [15, 16, 55]. It is known that the STN is functionally divided into 3 domains: motor, limbic and associative. The motor pathways are in the dorsolateral region, where neurons are further organized in a somatotopic pattern. Indeed, the posterior zone contains motor neurons aimed at the muscles of the trunk. As a result, stimulation of this part of the STN can have positive effects on posture and camptocormia after DBS [15, 16, 53].

The relevant literature does not provide sufficient information on how the DBS can cause objective changes to the sagittal balance indexes and, to our knowledge, this is the first study on how the DBS procedure, when successful in selectively targeting the dorso-lateral region of STN, can positively impact on camptocormia, as a symptom, and on sagittal balance, this last being the result of more complex group of symptoms and signs.

Our data permit to exclude the role of levo-DOPA in determining the improvement of the sagittal balance in the patients in this study. This for two main reasons: i) despite the presurgical therapy with levo-DOPA, the subjects had developed the postural changes anyway; ii) because DBS therapy has been shown to be effective for better control of motor and non-motor symptoms of PD, the 1-year post-operative LEDD (levo-DOPA Equivalent Daily Dose) was significantly lower that the pre-operative LEDD (p < 0.001).

In previous studies describing exclusively this symptom/sign, camptocormia was evaluated using the motor subscore of the Burke-Fahn-Mardsen scale (BFM) [20]. In our manuscript we decided to evaluate the impact of the DBS on the global alignment of the spine, using the parameters of the sagittal balance commonly used among vertebral surgeons.

In our series, the radiographic analysis of sagittal balance showed a statistically significant increase in D-Cobb angle, 12 months after surgery, related to a decrease in thoracic kyphosis and to an improvement of camptocormic posture. Furthermore, although not statistically relevant, it was possible to see a limited reduction of Pelvic Tilt (PT) associated with an initial increase of the Sacral Slope, with a consequent increase of lumbar lordosis, which is strictly related to the D-Cobb parameter. Finally, the SVA was not significantly affected. The condition of “not worsening of spino pelvic” parameters is correlated to the low risk of falling, according to the Tinetti’s score [12].

We may argue that the improvement of the D-Cobb index may be due to the selective implantation of the electrodes in the motor area of the STN, which leads to improvement of dystonia of the trunk flexors and, therefore, of the camptocormia [23, 57]. The typical pathological adaptation of the spine in PD subjects causes the progressive reduction of Sacral Slope and Lumbar Lordosis with pelvic retroversion (increase of Pelvic Tilt) and camptocormia (reduction of D-Cobb). In our series, we observed an increase of the Sacral Slope and the Lumbar Lordosis, which prevented the pathological alterations and reducing the risk of falling.

A fortiori, we performed a comparative analysis between the location of the electrodes and the variation of sagittal balance parameter. The results showed statistically significant improvements in posture in patients where the electrode was placed in the dorsolateral region of the STN. These results reinforce our hypothesis, underlining the greater relevance of proper placement of electrodes in this region to restore balance between flexor and extensor muscles.

Considering the possible different results in treating the postural changes with targeting the Subthalamic Nucleus (STN) or the Globus Pallidus internus (GPi), which represent the two main targets of the DBS tharapy when managing subjects with PD, we must consider that the superiority of one target above the other is yet to be determined. Stimulation of the STN provides a faster control on tremor symptoms and allows for a greater reduction in dopaminergic medication, with the main limitation of a greater risk of cognitive decline and mood changes. Being more commonly used for the treatment of dystonia, stimulation of the GPi seems to provide a better outcome on control of dyskinesias in patients affected by PD [50]. Concerning specifically the effects of different target selection on camptocormia improvement, a recent metanalysis by Wang et al. reported similar results for both STN and GPi stimulation [63]. Nevertheless, their results could be limited by the larger number of patients treated by STN stimulation (136 patients) than patients treated by GPi stimulation (13 patients).

The longer these postural changes occurred, the less effective DBS therapy was in reversing chronic skeletal vertebral changes [55], and fatty degeneration of the extensor muscles of the trunk can negatively hinder the restoration of balance between the benders and the extensors of the trunk. In addition, it is important to consider that thoracic kyphosis is the first spinal parameter that changes during Parkinson's disease and lumbar lordosis is correlated with it [13].

From our preliminary results, Deep Brain Stimulation therapy with selective targeting of the dorsal lateral portion of the STN appears to induce an improvement of the posture changes in Parkinson’s Disease patients 12 months after the operation. We present evidence towards DBS helping dorsal kyphosis Cobb angle and data that suggests that the more dorsal-lateral STN leads were more effective. Therefore, larger observational and controlled clinical trials with long term follow up are necessary to better evaluate DBS efficacy on sagittal balance of Parkinson patients. We will continue to enroll patients into this protocol while continuing to follow up our patients, in order to assess any possible further changes of the sagittal balance parameters and of the postural indexes, also using EMG studies to assess whether the postural changes were caused by dystonia, myopathy or both.

Ethical Approval: This study is based on research involving human participants. However, the involved subjects received the standard treatment in our institution, with no modifications of the treatment protocols. The IRB/Ethics committee approval was not needed and was not sought.

Competing Interests: None of the authors have received any funding from any institution, including personal relationships, interests, grants, employment, affiliations, patents, inventions, honoraria, consultancies, royalties, stock options/ownership, or expert testimony for the last 12 months.

Authors' Contributions:

Teresa Somma

Research project: Conception, Organization, and Execution.

Fabrizio Fellico

Research project: data collection and analysis.

Andrea De Rosa

Research project: Execution.

Manuscript: Writing of the first draft.

Andrea Bocchino

Research project: Execution.

Manuscript: Writing of the first draft.

Sergio Corvino

Manuscript: Review and Critique.

Antonio Milone
Research project: data collection and analysis.

Paolo Cappabianca

Manuscript: Review and Critique.

Felice Esposito

Research project: Conception, Organization, and Execution.

Statistical Analysis: Design, Execution, Review and Critique.

Manuscript: Review and Critique.

Funding: No funds of any source were received nor used in conjunction with this study

Availability of data and materials: all data and materials are included in the manuscript, figures and tables.

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Impact of Deep Brain Stimulation therapy on the vertebral sagittal balance in Parkinson’s disease patients

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