Subthalamic deep brain stimulation for Parkinson’s disease outcome

Subthalamic deep brain stimulation for Parkinson’s disease outcome

The surgical and clinical outcomes of asleep DBS for Parkinson’s disease are comparable to those of awake DBS 1).


Suboptimal targeting within the STN can give rise to intolerable sensorimotor side effects, such as dysarthria, contractions and paresthesias 2) 3) 4). eye movement perturbations, and psychiatric symptoms 5) 6) 7), limiting the management of motor symptoms. The small size of the STN motor territory and the consequences of spreading current to immediately adjacent structures obligate precise targeting. Neurosurgeons therefore rely on a combination of imaging, electrophysiology, kinesthetic responses, and stimulation testing to accurately place the DBS lead into the sensorimotor domain of STN 8) 9) 10).

Deep Brain Stimulation has been associated with post-operative neuropsychology changes, especially in verbal memory.

Deep brain stimulation (DBS) of subthalamic nucleus (STN) is widely accepted to treat advanced Parkinson disease (PD). However, published studies were mainly conducted in Western centers 11).

High frequency subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal motor signs of Parkinson’s disease (PD) and attenuates STN alpha/beta band neural synchrony in a voltage-dependent manner. While there is a growing interest in the behavioral effects of lower frequency (60 Hz) DBS, little is known about its effect on STN neural synchrony.

Low-frequency stimulation of the subthalamic nucleus via the optimal contacts is effective in improving overall motor function of patients with Parkinson Disease 12). In Parkinson’s disease significantly improved important aspects of QoL as measured by PDQ-39. The improvements were maintained at 2 years follow-up except for social support and communication. Sobstyl et al., demonstrated a positive correlation between changes in the off condition of motor UPDRS scores and Unified Dyskinesia Rating Scale in several PDQ-39 dimensions, whereas fluctuation UPDRS scores were negatively correlated with PDQ-39 mobility scores 13).

The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement.

A study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes 14).

References

1)

Wang J, Ponce FA, Tao J, Yu HM, Liu JY, Wang YJ, Luan GM, Ou SW. Comparison of Awake and Asleep Deep Brain Stimulation for Parkinson’s Disease: A Detailed Analysis Through Literature Review. Neuromodulation. 2019 Dec 12. doi: 10.1111/ner.13061. [Epub ahead of print] Review. PubMed PMID: 31830772.
2) , 9)

Benabid AL, Chabardes S, Mitrofanis J, Pollak P: Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol 8:67–81, 2009
3) , 10)

Groiss SJ, Wojtecki L, Südmeyer M, Schnitzler A: Deep brain stimulation in Parkinson’s disease. Ther Adv Neurol Disorder 2:20–28, 2009
4)

Zhang S, Zhou P, Jiang S, Wang W, Li P: Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease: a report of 12 cases. Medicine (Baltimore) 95:e5575, 2016
5)

Kulisevsky J, Berthier ML, Gironell A, Pascual-Sedano B, Molet J, Parés P: Mania following deep brain stimulation for Parkinson’s disease. Neurology 59:1421–1424, 2002
6)

Mallet L, Schüpbach M, N’Diaye K, Remy P, Bardinet E, Czernecki V, et al: Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior. Proc Natl Acad Sci U S A 104:10661–10666, 2007
7)

Raucher-Chéné D, Charrel CL, de Maindreville AD, Limosin F: Manic episode with psychotic symptoms in a patient with Parkinson’s disease treated by subthalamic nucleus stimulation: improvement on switching the target. J Neurol Sci 273:116–117, 2008
8)

Abosch A, Timmermann L, Bartley S, Rietkerk HG, Whiting D, Connolly PJ, et al: An international survey of deep brain stimulation procedural steps. Stereotact Funct Neurosurg 91:1–11, 2013
11)

Chiou SM, Lin YC, Huang HM. One-year Outcome of Bilateral Subthalamic Stimulation in Parkinson Disease: An Eastern Experience. World Neurosurg. 2015 Jun 10. pii: S1878-8750(15)00709-3. doi: 0.1016/j.wneu.2015.06.002. [Epub ahead of print] PubMed PMID: 26072454.
12)

Khoo HM, Kishima H, Hosomi K, Maruo T, Tani N, Oshino S, Shimokawa T, Yokoe M, Mochizuki H, Saitoh Y, Yoshimine T. Low-frequency subthalamic nucleus stimulation in Parkinson’s disease: A randomized clinical trial. Mov Disord. 2014 Jan 21. doi: 10.1002/mds.25810. [Epub ahead of print] PubMed PMID: 24449169.
13)

Sobstyl M, Ząbek M, Górecki W, Mossakowski Z. Quality of life in advanced Parkinson’s disease after bilateral subthalamic stimulation: 2 years follow-up study. Clin Neurol Neurosurg. 2014 Sep;124:161-5. doi: 10.1016/j.clineuro.2014.06.019. Epub 2014 Jun 23. PubMed PMID: 25051167.
14)

Cui Z, Pan L, Song H, Xu X, Xu B, Yu X, Ling Z. Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease. J Neurosurg. 2016 Jan;124(1):62-9. doi: 10.3171/2015.1.JNS141534. Epub 2015 Aug 14. PubMed PMID: 26274983.

Recurrent glioblastoma outcome

Recurrent glioblastoma outcome

In the first large prospective comparative cohort study of recurrent glioblastoma Mukherjee et al. from St George’s Hospital Atkinson Morley Wing, demonstrate that repeat resection confers a small but significant benefit in survival and quality of life over non-operative treatment. Best prognosis is associated with: younger age, KPS ≥ 80, late recurrenceMGMT promoter methylation, and EOR > 80 % 1).


Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response.

In a study, Cardona et al., explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM.

They assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status.

Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%).

BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy 2).


In the series of Tejada y col., recurrence pattern was local only in 65.5 % of patients and non-local in 34.5 %. The univariate and multivariate analysis showed that greater preoperative tumor volume in T1 gadolinium enhanced sequences, was the only variable with statistical signification (p < 0.001) for increased rate of non-local recurrences, although patients with MGMT methylation and complete resection of enhancing tumor presented non-local recurrences more frequently. PFS was longer in patients with non-local recurrences (13.8 vs. 6.4 months; p = 0.019, log-rank). However, OS was not significantly different in both groups (24.0 non-local vs. 19.3 local; p = 0.9). Rate of non-local recurrences of patients treated with fluorescence guided surgery and standard radiochemotherapy was higher than previously published, especially in patients with longer PFS. Greater preoperative enhancing tumor volume was associated with increased rate of non-local recurrences 3).

Survival after repeat surgery was decreased in patients with recurrent GBM involving the subventricular zone SVZ at recurrence (p = 0.022). No other prognostic factors for survival after repeat surgery were identified. This finding may have prognostic and therapeutic significance 4).

References

1)

Mukherjee S, Wood J, Liaquat I, Stapleton SR, Martin AJ. Craniotomy for recurrent glioblastoma: Is it justified? A comparative cohort study with outcomes over 10 years. Clin Neurol Neurosurg. 2019 Oct 24;188:105568. doi: 10.1016/j.clineuro.2019.105568. [Epub ahead of print] PubMed PMID: 31739155.
2)

Cardona AF, Rojas L, Wills B, Ruiz-Patiño A, Abril L, Hakim F, Jiménez E, Useche N, Bermúdez S, Mejía JA, Ramón JF, Carranza H, Vargas C, Otero J, Archila P, Rodríguez J, Rodríguez J, Behaine J, González D, Jacobo J, Cifuentes H, Feo O, Penagos P, Pineda D, Ricaurte L, Pino LE, Vargas C, Marquez JC, Mantilla MI, Ortiz LD, Balaña C, Rosell R, Zatarain-Barrón ZL, Arrieta O. A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma. Clin Transl Oncol. 2019 Feb 23. doi: 10.1007/s12094-019-02066-2. [Epub ahead of print] PubMed PMID: 30798512.
3)

Tejada S, Díez-Valle R, Aldave G, Marigil M, de Gallego J, Domínguez PD. Factors associated with a higher rate of distant failure after primary treatment for glioblastoma. J Neurooncol. 2014 Jan;116(1):169-75. doi:10.1007/s11060-013-1279-z. Epub 2013 Oct 18. PubMed PMID: 24135848; PubMed Central PMCID: PMC3889292.
4)

Sonoda Y, Saito R, Kanamori M, Kumabe T, Uenohara H, Tominaga T. The Association of Subventricular Zone Involvement at Recurrence with Survival after Repeat Surgery in Patients with Recurrent Glioblastoma. Neurol Med Chir (Tokyo). 2013 Dec 27. [Epub ahead of print] PubMed PMID: 24390189.

Degenerative cervical myelopathy outcome

Degenerative cervical myelopathy outcome

Preoperative duration of symptoms may significantly impact outcomes in patients treated surgically for degenerative cervical myelopathy (DCM).

Tetreault et al. analyzed whether duration of symptoms is associated with preoperative functional impairment, disability, and quality of life and (ii) determine the optimal timing for decompressive surgery.

Patients with DCM were prospectively enrolled in either the AOSpine North American or International study at 26 global sites (n = 757). Postoperative functional impairment was evaluated at 1-yr using the modified Japanese Orthopaedic Association (mJOA) score. Change scores between baseline and 1-yr were computed for the mJOA. Duration of symptoms was dichotomized into a “short” and “long” group at several cut-offs. Analysis of covariance was used to evaluate differences in change scores on the mJOA between the duration of symptoms groups in 4-mo increments.

The cohort consisted of 424 men and 255 women, with a mean duration of symptoms of 26.1 ± 36.4 mo (0.25-252 mo). Duration of symptoms was not correlated with preoperative mJOA, Nurick, Neck Disability Index, or Short-Form (SF)-36 Physical and Mental Component Scores. Patients with a duration of symptoms shorter than 4 mo had significantly better functional outcomes on the mJOA than patients with a longer duration of symptoms (>4 mo). Thirty-two months was also a significant cut-off.

Patients who are operated on within 4 mo of symptom presentation have better mJOA outcomes than those treated after 4 mo. It is recommended that patients with DCM are diagnosed in a timely fashion and managed appropriately 1).


Zileli et al. conducted a study to review the literature systematically to determine the most reliable outcome measures, important clinical and radiological variables affecting the prognosis in cervical spondylotic myelopathy patients. A literature search was performed for articles published during the last 10 years. As functional outcome measures they recommended to use modified Japanese Orthopaedic Association scaleNurick scale, and Myelopathy Disability Index. Three clinical variables that affect the outcomes are age, duration of symptoms, and severity of the myelopathy. Examination findings require more detailed study to validate their effect on the outcomes. The predictive variables affecting the outcomes are hand atrophy, leg spasticityclonus, and Babinski sign. Among the radiological variables, the curvature of the cervical spine is the most important predictor of prognosis. Patients with instability are expected to have a poor surgical outcome. Spinal cord compression ratio is a critical factor for prognosis. High signal intensity on T2-weighted magnetic resonance images is a negative predictor for prognosis. The most important predictors of outcome are preoperative severity and duration of symptoms. T2 hyperintensity and cord compression ratio can also predict outcomes. New radiological tests may give promising results in the future 2).


Left untreated degenerative cervical myelopathy can lead to spastic tetraparesis 3).

A study investigating quality of life in DCM patients indicated they suffer among the worst SF36 health scores of all chronic diseases 4).

Cervical spondylotic myelopathy surgery outcome

References

1)

Tetreault L, Wilson JR, Kotter MRN, Côté P, Nouri A, Kopjar B, Arnold PM, Fehlings MG. Is Preoperative Duration of Symptoms a Significant Predictor of Functional Outcomes in Patients Undergoing Surgery for the Treatment of Degenerative Cervical Myelopathy? Neurosurgery. 2019 Nov 1;85(5):642-647. doi: 10.1093/neuros/nyy474. PubMed PMID: 30445506.
2)

Zileli M, Maheshwari S, Kale SS, Garg K, Menon SK, Parthiban J. Outcome Measures and Variables Affecting Prognosis of Cervical Spondylotic Myelopathy: WFNS Spine Committee Recommendations. Neurospine. 2019 Sep;16(3):435-447. doi: 10.14245/ns.1938196.098. Epub 2019 Sep 30. PubMed PMID: 31607075.
3)

Chen LF, Tu TH, Chen YC, Wu JC, Chang PY, Liu L, Huang WC, Lo SS, Cheng H. Risk of spinal cord injury in patients with cervical spondylotic myelopathy and ossification of posterior longitudinal ligament: a national cohort study. Neurosurg Focus. 2016 Jun;40(6):E4. doi: 10.3171/2016.3.FOCUS1663. PubMed PMID: 27246487.
4)

Oh T, Lafage R, Lafage V, Protopsaltis T, Challier V, Shaffrey C, Kim HJ, Arnold P, Chapman J, Schwab F, Massicotte E, Yoon T, Bess S, Fehlings M, Smith J, Ames C. Comparing Quality of Life in Cervical Spondylotic Myelopathy with Other Chronic Debilitating Diseases Using the Short Form Survey 36-Health Survey. World Neurosurg. 2017 Oct;106:699-706. doi: 10.1016/j.wneu.2016.12.124. Epub 2017 Jan 5. PubMed PMID: 28065875.
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