Degenerative cervical myelopathy

Degenerative cervical myelopathy

The assessment, diagnosis, operative and nonoperative management of degenerative cervical myelopathy (DCM) have evolved rapidly over the last 20 years. A clearer understanding of the pathobiology of DCM has led to attempts to develop objective measurements of the severity of myelopathy, including technology such as multiparametric magnetic resonance imaging, biomarkers, and ancillary clinical testing. New pharmacological treatments have the potential to alter the course of surgical outcomes, and greater innovation in surgical techniques have made surgery safer, more effective and less invasive. Future developments for the treatment of DCM will seek to improve the diagnostic accuracy of imaging, improve the objectivity of clinical assessment, and increase the use of surgical techniques to ensure the best outcome is achieved for each individual patient 1).

Goel was troubled by the fact that his several PubMed and MEDLINE indexed articles on the subject published in leading journals dedicated to the study of the spine have not found any place in the huge reference list of 137 articles 2)

Definition

Epidemiology

Etiology

Pathophysiology

A review of Tetreault et al. summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies 3).

Clinical features

Patients may initially experience minimal symptoms 4) 5) but subsequently often develop pain, sensory deficits especially affecting their hands and feet, spasticity, imbalance, bladder symptoms, and experience frequent falls 6).

Diagnosing DCSM has traditionally relied on presence of clinical symptoms, including clumsy hands, paralysis of the lower extremities, gait disturbances, urinary/bowel incontinence and severe neurological dysfunction disturbances, urinary/bowel incontinence, and severe neurological dysfunction 7) 8).

Many people with cervical spondylosis or CSM are asymptomatic. However, patients with CSM are at higher risk of spinal cord injury (SCI) following minor injury.

Only a small percentage of people with spondylosis go on to develop symptoms consistent with cervical spondylotic myelopathy (CSM), which can cause significant and disabling neurological deficits, leading to loss of function, morbidity, and mortality.

In addition, diabetes mellitus (DM) is a frequent comorbidity for people of this age and may impact the severity of CCM.

Scales

European myelopathy score.

As a widespread used scale, the Modified Japanese Orthopaedic Association scale (mJOA) should be translated and culturally adapted 9).

see Cervical spine stenosis scales

Diagnosis

Treatment

Outcome

Randomized, controlled trials

A National Institutes of Health-funded (1R13AR065834-01) investigator meeting was held before the initiation of the trial to bring multiple stakeholders together to finalize the study protocol. Study investigators, coordinators, and major stakeholders were able to attend and discuss strengths of, limitations of, and concerns about the study. The final protocol was approved for funding by the Patient-Centered Outcomes Research Institute (CE-1304-6173). The trial began enrollment on April 1, 2014 10).

Case series

References

1)

Wilson JRF, Badhiwala JH, Moghaddamjou A, Martin AR, Fehlings MG. Degenerative Cervical Myelopathy; A Review of the Latest Advances and Future Directions in Management. Neurospine. 2019 Sep;16(3):494-505. doi: 10.14245/ns.1938314.157. Epub 2019 Aug 26. PubMed PMID: 31476852; PubMed Central PMCID: PMC6790745.
2)

Goel A. Degenerative Cervical Myelopathy. Neurospine. 2019 Dec;16(4):793-795. doi: 10.14245/ns.1938384.192. Epub 2019 Dec 31. PubMed PMID: 31905465.
3)

Tetreault L, Goldstein CL, Arnold P, Harrop J, Hilibrand A, Nouri A, Fehlings MG. Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine. Neurosurgery. 2015 Oct;77 Suppl 4:S51-67. doi: 10.1227/NEU.0000000000000951. PubMed PMID: 26378358.
4)

Kovalova I, Kerkovsky M, Kadanka Z, Kadanka Z Jr, Nemec M, Jurova B, Dusek L, Jarkovsky J, Bednarik J. Prevalence and Imaging Characteristics of Nonmyelopathic and Myelopathic Spondylotic Cervical Cord Compression. Spine (Phila Pa 1976). 2016 Dec 15;41(24):1908-1916. PubMed PMID: 27509189.
5)

Martin AR, De Leener B, Cohen-Adad J, Cadotte DW, Nouri A, Wilson JR, Tetreault L, Crawley AP, Mikulis DJ, Ginsberg H, Fehlings MG. Can microstructural MRI detect subclinical tissue injury in subjects with asymptomatic cervical spinal cord compression? A prospective cohort study. BMJ Open. 2018 Apr 13;8(4):e019809. doi: 10.1136/bmjopen-2017-019809. PubMed PMID: 29654015; PubMed Central PMCID: PMC5905727.
6)

Davies BM, Mowforth OD, Smith EK, Kotter MR. Degenerative cervical myelopathy. BMJ. 2018 Feb 22;360:k186. doi: 10.1136/bmj.k186. Review. PubMed PMID: 29472200; PubMed Central PMCID: PMC6074604.
7)

Guan L, Chen X, Hai Y, et al. High-resolution diffusion tensor imaging in cervical spondylotic myelopathy: A preliminary follow-up study. NMR Biomed. 2017
8)

Sampath P, Bendebba M, Davis JD, et al. Outcome of patients treated for cervical myelopathy. A prospective, multicenter study with independent clinical review. Spine (Phila Pa 1976) 2000;25(6):670–76.
9)

Augusto MT, Diniz JM, Rolemberg Dantas FL, Fernandes de Oliveira M, Rotta JM, Botelho RV. Development of the Portuguese version of the modified Japanese Orthopaedic Association Score: cross-cultural adaptation, reliability, validity and responsiveness. World Neurosurg. 2018 Jun 1. pii: S1878-8750(18)31127-6. doi: 10.1016/j.wneu.2018.05.173. [Epub ahead of print] PubMed PMID: 29864576.
10)

Ghogawala Z, Benzel EC, Heary RF, Riew KD, Albert TJ, Butler WE, Barker FG 2nd, Heller JG, McCormick PC, Whitmore RG, Freund KM, Schwartz JS. Cervical Spondylotic Myelopathy Surgical Trial: Randomized, Controlled Trial Design and Rationale. Neurosurgery. 2014 Oct;75(4):334-346. PubMed PMID: 24991714.

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.
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