Стимуляция спинного мозга в лечении запущенной формы болезни Паркинсона

Резюме

Цель работы - описание нового подхода к лечению не отвечающих на медикаментозную терапию пациентов с болезнью Паркинсона с применением минимально инвазивной стимуляции спинного мозга (ССМ).

Материал и методы. 75-летний пациент с 10-летней историей болезни Паркинсона и неконтролируемой дискинезией верхних конечностей без осложнений перенес тестовую ССМ посредством чрескожного введения 2 временных 8-контактных электродов (Medtronic Inc., Minneapolis, MN), установленных на уровень С3-С4-С5-С6 для ССМ.

Результаты. После начала пробной спинальной стимуляции у пациента полностью исчезли дис- кинезия и дистония в руках и ногах, и 2 нед спустя пациенту были имплантированы постоянные электроды и подзаряжаемый генератор. В течение последующего 12-месячного наблюдения пациент показывал устойчивый контроль дискинезии и дистонии.

Заключение. ССМ предлагает альтернативное лечение для пациентов с изнурительными симптомами поздней стадии болезни Паркинсона, решивших не использовать более инвазивные виды хирургического вмешательства.

Ключевые слова:глубокая стимуляция мозга, дискинезия, дистония, электростимуляция, болезнь Паркинсона, стимуляции спинного мозга

Клин. и эксперимент. хир. Журн. им. акад. Б.В. Петровского. - 2014. - 4. - С. 53-56.

Treatment of Parkinson disease (PD) is aimed at controlling the symptoms and not on curing or preventing progression of this neurological disorder. When PD progresses lifelong symptomatic treatment evolves and unfortunately all symptomatic drugs have the potential to induce side effects.

Levodopa is the most potent anti-PD drug but many patients utilizing this medication experience various problems which can be more disabling then the disease itself when fluctuations in motor performances and abnormal involuntary movements like dyskinesias and dystonia seen.

In 1817 James Parkinson described the major clinical features of this chronic, progressive disease and he was first to open the surgical or lesional concept of treatment of PD when reported contralateral cessation of tremor following cerebrovascular accident in a patient. In the past one hundred years attempts to lesioning of motor cortex and then subcortical stractures were made [1-3]. Development of stereotactic techniques [4] for placing of subcortical lesions relieved tremor in high percentage of treated patients, decrease operative mortality and morbidity. The introduction of deep brain stimulation (DBS) 20 years ago [5] has brought the treatment of PD on the new level by allowing control of major symptoms associated with advanced PD like tremor, rigidity, dyskinesias. DBS is ef- fective, reversible technique with low morbidity in comparison to traditional neuroablative techniques. However, adverse effects of this treatment option include falls, depression, motor dysfunction, head- aches, pain, speech disorder and deaths reported after DBS [6]. To this date there are no reports in literature about the effects of SCS on the symptoms related to advance PD.

Methods

A 75-year-old male patient with a ten-year history of PD presented with intractable dyskinesias in upper extremities and also moderate dystonia and bradykinesia in lower extremities. He was treated in the past by experienced neurologist specialized in movement disorders. All necessary adjustments were made in the dosing, timing and frequency of medications to reduce levodopa related dyskinesias. Upon presentation to our clinic the patient was taken madopar (levodopa 100 mg-beserazide 25 mg) one capsule three times per day and piribedil 50 mg one tablet three times daily. The patient was also involved in the physical and occupational therapy for rehabilitation purpose. His past medical history was unremarkable with the exception of well controlled hypertension and the patient was very active prior to the time when late stage of PD brought intractable dyskinesias. He encountered extreme difficulty to execute activities of daily living and was not able to drive an automobile. He was offered DBS by neurosurgeon but declined neurosurgical intervention because of concerns about potential complications and sought alternative treatment options for his intractable arm dyskinesias. In our clinic he was offered SCS trial with placement of percutaneous cervical epidural leads and the patient chose to proceed with this less invasive option. No psychological evaluation was performed prior to SCS procedure. This study was approved by IRB to characterize the safety and efficacy of SCS for control of symptoms related to Parkinson disease.

Two 8-electrode standard Octad Leads (Medtronic Inc., Minneapolis, MN) was placed in the epidural space percutaneously through the T3-T4 intervertebral space with final electrodes positioned between C3, C4, C5 and C6 (Fig. 1). The procedure was done with C-arm guidance in an ambulatory surgical center with use local anesthesia only. Both leads were connected to a temporary extension cord and to an external stimulator. During intraoperative testing different stimulation parameters were used with the purpose to achieve control of the dyskinesias in the upper extremities. When parameter settings of amplitude 1,5 volts, pulse width 350 microseconds, and frequency 50 Hz the patient felt parenthesis in both arms but at the same time dyskinesias got worse. All ranges of pulse width and frequency on the level of sensory threshold led to exaggerated dyskinesia. The extent of dyskinesias was becoming worse by increasing amplitude above the sensory threshold level. The amplification of dyskinesias at sensory threshold was minimal with pulse width 210 microseconds and frequency 50 Hz and they were completely aborted at these parameters when we brought the amplitude down to sub-threshold level 0,5 volts. During the two day SCS trial the patients experienced complete disappearance of dyskinesia in upper extremities and dystonia in both arms and legs. Post-stimulation effect lasted for 90 seconds after turning stimulation off. Stimulator parameters programmed for amplitude 0,5 volts, pulse width 210 microseconds, and frequency 20 Hz. The temporary leads were removed after two days of continuous stimulation.

Two weeks later the patient underwent implantation with permanent leads and Restore Ultra rechargeable generator (Medtronic Inc., Minneapolis, MN). Preoperatively we discussed with the patient the options for location of the implanted generator and he chose the left supragluteal area. Each of the two permanent leads were anchored to fibroaponeurotic tissue in the wound created in the upper lumbar area (Fig. 2) with 2-0 nonabsorbable suture of braided polyester (Ethibond) and Titan Anchors (Medtronic Inc., Minneapolis, MN). The leads were tunneled to the left supragluteal area where the subcutaneous pocket was created for the generator. Leads were then connected to a Restore Ultra rechargeable generator (Fig. 3). The procedures were performed in an ambulatory surgery center with intravenous sedation and local anesthesia administered by the surgeon. The post-operative course was uneventful. The initiation of spinal cord stimulation after implantation started right after the surgery in recovery unit.

Results

No complications were reported during the SCS trial, permanent implantation and post-operative period. The patient was discharged home that day, after education regarding use of external programmer for SCS. The stimulation was conducted continuously, for 24 hours per day. At twelve month follow-up visit the patient had sustained control of dyskinesias and dystonia with permanent SCS.

Electrode polarities were set as follow:

First lead:

0(off) 1(+) 2(-) 3(+) 4(-) 5(+) 6(off) 7(off)

Second lead:

8(off) 9(off) 10(+) 11(-) 12(+) 13(-) 14(+) 15(off)

Stimulator parameters remained the same like during the trial and were programmed for amplitude 0.5 volts, pulse width 210 microseconds, and frequency 20 Hz

Before the SCS trial, Unified Parkinson’s Disease Rat- ing Scale (UPDRS) III motor score was 33 “OFF” medication and was reduced to 12 after implantation of SCS.

Discussion

At present time DBS is regarded as one of the effective surgical options for treatment of PD with documented effect on bradykinesia, dystonia, rigidity, and tremor. The route through which DBS alleviates symptoms associated with PD is still debated and further studies needed to elucidate the mechanism behind this therapy. It is still unclear what stimulation target produces best control of Parkinson’s symptoms and attenuate levodopa-induced motor complication of PD. The traditional targets for patients with advanced PD experiencing dyskinesia and dystonia are the subthalamic nucleus (STN) and the globus pallidus internus (GPi) [7-9]. DBS may lead to modulation of pathologic activity of STN in parkinsonian brain [10, 11]and normalizes deactivation of the premotor area in association with control of resting tremor and rigidity [12].

SCS has been used for various chronic pain conditions over last three decades and multiple studies proved its efficacy in the treatment of intractable, chronic pain with a variety of causes [13] with new implications for this technology dynamically evolving. To date there is no published reports about use of SCS for treatment of symptoms of PD. Our data can bring many questions for further investigations and discussion and one of them why SCS aggravated dyskinesias at sensory threshold level and aborted dyskinesias at sub-threshold level.

Conclusion

SCS appears to be an effective option in the treatment of patients with advanced Parkinson disease and may allow patients to achieve better control of the symptoms compared to pharmacological treatment and avoid potential serious complications related to surgical procedures. This technique may be an option for patients who do not respond to best medical therapy or defer surgical treatment including DBS. We need further studies to help elucidate the mechanism behind effect of SCS on control of symptoms related to Parkinson disease and confirm long-term advantages of this promising and minimally invasive treatment. Additional data analysis is needed to evaluate therapeutic benefit of SCS for this patient at long-term follow-up.

Reference

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