Re: 파킨슨 호전 케이스 논문(centering prayer 매일 30분, 2년) 2016년...

[문형철]

https://mindandculture.org/wordpress6/wp-content/uploads/2018/05/SmartDursoMorganMcNamara-A-Potential-Case-of-Remission-of-Parkinsons-Disease.pdf

Abstract:

We present the case of a 78-year-old male who, 16 years ago, was diagnosed with Parkinson’s disease (PD) by a neurologist. He initially presented with lefthand tremor, stooped posture, shuffling gait, and frequent falls, which eventually progressed to bilateral motor symptoms after 3 years. Since 2012, his symptoms and signs have almost completely remitted, and he has been off all pharmacotherapy for that time. The accuracy of the initial PD diagnosis is supported by an appropriate clinical presentation, history of positive response to Sinemet, and an abnormal SPECT DaT scan; thus this case suggests the possibility of remission of symptoms in some patients. We propose that the patient’s long history of meditation practice may have been one contributing factor of this improvement as meditation has been shown to release dopamine in the striatum.

초록: 

78세 남성 환자가 

16년 전 신경과 전문의에 의해 파킨슨병(PD)으로 진단받은 사례를 

보고합니다. 

환자는 초기에는 

왼쪽 손 떨림, 구부정한 자세, 걸음걸이 장애, 빈번한 낙상 증상을 보였으며, 

3년 후 양측 운동 증상으로 진행되었습니다. 

lefthand tremor, stooped posture, shuffling gait, and frequent falls,

which eventually progressed to bilateral motor symptoms after 3 years.

2012년부터 증상과 징후가 거의 완전히 완화되었으며, 

이 기간 동안 모든 약물 치료를 중단했습니다. 

초기 PD 진단은 

적절한 임상 소견, 시네메트에 대한 긍정적 반응의 병력, 이상적인 SPECT DaT 검사 결과로 

뒷받침됩니다. 

따라서 

이 사례는 

일부 환자에서 증상 완화의 가능성을 시사합니다. 

우리는 환자의 장기간 명상 실천이 

이 개선의 한 요인이 되었을 수 있다고 제안합니다. 

명상은 

선조체에서 도파민을 방출한다는 것이 알려져 있기 때문입니다.

We propose that the patient’s long history of meditation practice may have been one contributing factor of this improvement as meditation has been shown to release dopamine in the striatum.

선조체 는 기저핵에서 가장 큰 본체이다. 조가비핵(putamen) , 미상핵(caudate) ,  편도체 (amygdala)로 이루어져있으며 한편 조가비핵(외측핵)과 창백핵(내측핵)은 함께  렌즈핵 (lenticular nuleus)으로 다루어진다. 보통 기저핵으로 선조체를 가리키는 경우도 있다. "선조체(Corpus Striatum)"라는 용어는 이 곳을 가로지르는 신경섬유들의 크고 작은 수많은 다발들(백질)로 인해 특정 방향으로 잘렸을 때 줄무늬가 보이는 것에서 기인한다. 선조체 내의 구조는 엄청나게 복잡하다. 이곳의 신경세포 중 96% 정도는 중간크기 가시뉴런(Medium spiny neurons)이고 이들은  GABA 성 세포들(즉, 그들의 타겟을 저해함)이며 세포체는 작고 수지상 조직(Dendrite)은 수상돌기(Dendritic spine)로 빽빽하게 덮혀있으며 주로 시상과 피질로부터 신호를 받는다. 그 다음으로 많은, 2% 정도를 차지하는 세포타입은 매끈한 수지상 조직을 가진 콜린성 중간뉴런(interneuron)들이다. 그리고 여러 다른 종류의 중간뉴런들이 나머지를 차지하고 있다.

Introduction

Parkinson’s disease (PD) is an incurable, progressive neurodegenerative disease characterized by loss of dopaminergic neurons in the substantia nigra. The disease pathology tends to initiate unilaterally, resulting in unilateral motor symptoms, which can define a PD diagnosis. Although PD is diagnosed clinically, SPECT DaT scans are often used to validate a PD diagnosis. These scans are SPECT scans using the DaT radionuclide that binds to the pre-synaptic striatal dopamine reuptake transporter; in a patient with PD, the scan will typically demonstrate asymmetric loss of signal in the striatal regions. In current practice, diagnostic SPECT DaT scans are qualitatively assessed by radiologists, which complicates interpretation of the scan. To reduce interpretative difficulties, SPECT DaT scan images can be coregistered to the patient’s MPRAGE scan, an anatomical MRI, for enhanced anatomical localization. The voxel intensities can then be used to quantify the asymmetry of DAT binding, indicating asymmetric striatal dopaminergic integrity and thus PD. We performed this and other clinical analyses on the case reported in this paper. We present here a 78-year-old male patient who was diagnosed with PD over fifteen years ago but whose symptoms have since remitted. The patient was diagnosed clinically with PD by a neurologist, and we provide the quantification of his diagnostic SPECT DaT scan as validation of this diagnosis. Intriguingly, this patient has a long history of involvement in meditative practice. Meditation has been shown to elicit dopaminergic effects, which may counteract the early dopaminergic dysfunction that forms the basis of PD. As such, we posit that decades of potentially dopaminergically protective meditative practice may have contributed, at least in part, to the remission of this patient’s parkinsonian symptoms. This also suggests the potential utility of meditation as a non-pharmacological adjunctive intervention for patients with PD. Thus, we offer with this case study the possibility of remission of symptoms in patients with PD and the potential contribution of meditation to such a remission.

파킨슨병(PD)은 

흑질의 도파민 신경세포 손실로 특징지어지는 

치료가 불가능한 진행성 신경퇴행성 질환입니다. 

이 질환의 병리학적 과정은 

일반적으로 한쪽에서 시작되어 한쪽의 운동 증상을 유발하며, 

이는 파킨슨병 진단의 기준이 될 수 있습니다. 

파킨슨병은 임상적으로 진단되지만, 

SPECT DaT 검사는 파킨슨병 진단을 확인하기 위해 자주 사용됩니다. 

이 검사는 도파민 재흡수 운반체에 결합하는

 DaT 방사성 동위 원소를 사용한 SPECT 검사입니다. 

파킨슨병 환자의 경우, 

검사는 일반적으로 뇌의 스트라이아탈 부위에서 신호 감소가 비대칭적으로 나타납니다. 

현재 임상 실무에서 진단용 SPECT DaT 검사는 

방사선과 의사에 의해 정성적으로 평가되며, 

이는 검사 해석을 복잡하게 합니다. 

해석 어려움을 줄이기 위해 SPECT DaT 검사 이미지를 환자의 MPRAGE 검사(해부학적 MRI)와 정합시켜 해부학적 위치를 명확히 할 수 있습니다. 이후 픽셀 강도를 사용하여 DaT 결합의 비대칭성을 정량화할 수 있으며, 이는 스트라이아탈 도파민 신경계 기능의 비대칭성을 나타내어 PD를 시사합니다. 우리는 이 논문에서 보고된 사례에 대해 이 분석을 포함한 기타 임상 분석을 수행했습니다. 

우리는 

15년 전에 PD로 진단받았지만 증상이 

이후 완화된 78세 남성 환자를 소개합니다. 

이 환자는 신경과 의사에 의해 임상적으로 PD로 진단되었으며, 

우리는 이 진단 확인을 위해 그의 진단용 SPECT DaT 스캔의 정량화를 제공합니다. 

흥미롭게도 

이 환자는 장기간 명상 실천에 참여해 왔습니다. 

명상은 도파민 효과를 유발할 수 있으며, 

이는 PD의 기반이 되는 초기 도파민 기능 장애를 억제할 수 있습니다. 

따라서, 

수십 년간의 잠재적으로 도파민 보호 효과를 가진 명상 실천이 

이 환자의 파킨슨 증상 완화에 부분적으로 기여했을 가능성을 제기합니다. 

이는 파킨슨병 환자를 위한 비약물적 보조 치료법으로서

 명상의 잠재적 유용성을 시사합니다. 

따라서 

이 사례 연구를 통해 파킨슨병 환자의 증상 완화 가능성과 

명상이 이에 기여할 수 있는 잠재적 역할을 제시합니다.

Case presentation

This 78-year-old male initially presented in 2000 with a moderate left-hand tremor noted on finger-to-nose testing, stooped posture, shuffling gait with decreased arm swing bilaterally, and a history of frequent falls, which he described as “tripping over his feet”. He was referred to a neurologist in the Brockton VA Hospital Neurology Clinic in Brockton, MA and subsequently diagnosed with PD. He was started on Sinemet 10/100 3x daily, which the patient and his neurologist found to ameliorate his symptoms and signs. The patient stated his gait had improved with less shuffling and no falls. His medications upon presentation to the neurologist were lansoprazole, ranitidine, ibuprofen, and aspirin, none of which have documented side effects mimicking or confounding parkinsonian diagnoses. He had no prior drug abuse history or any known history of exposure to pesticides or heavy metals. He led a religious lifestyle, having joined a monastery in 1978 for about a decade. He had taught himself to pray using a technique of “centering prayer” that involved a daily deep meditation of at least 30 min.

In 2003, the patient progressed to bilateral motor symptoms, including cogwheeling and bradykinesia in the right upper extremity. This same year, the patient came under the care of one of the authors (RD). From 2003 to 2012, he was seen approximately on a yearly basis. He primarily received Sinemet 25/100 2 tabs 3-4x per day. On different visits, he would have subtle motor findings that varied but occasionally involved mild cogwheeling in either or both upper extremities, rest tremor in either upper limb, and bilateral upper limb bradykinesia. On one visit, he stated that he had worsening symptoms if he forgot a dose of Sinemet, but overall there was no clear development of “on-off”. In 2011, he participated in pharmacologic research that involved on five separate occasions (about 1 week apart) fasting from all medication and food overnight and then receiving a dose of oral carbidopa and 2 hours later 200 mg of stable-isotope labeled levodopa.

His fasting UPDRS (Unified Parkinson’s disease rating scale) Part III motor score in one study was 22/108, which improved to 14/108 after the study labeled levodopa. In the other four studies, his UPDRS Part III fasting score ranged from 7-9/108 with no improvement after the study carbidopa and stable-isotope labeled levodopa. All studies were scored by the same neurologist. Due to the absence of typical “on-off” phenomena, it was decided to taper and discontinue his Sinemet. He accomplished this in 2012 without any worsening of motor signs, and he has since been off of all forms of pharmacotherapy. The patient never underwent any surgical or other nonpharmacological interventions. His last 2 exams in 2014 were characterized by a gait with stooped posture without any shuffling, festination or difficulty with turns. He had mild bradykinesia in both hands but no cogwheeling or tremor in his limbs.

사례 소개

이 78세 남성 환자는 

2000년에 처음 내원하여 

손가락-코 검사 시 좌측 손의 중등도 떨림, 구부정한 자세, 양측 팔의 흔들림 감소와 함께 

어색한 걸음걸이를 보였으며, 

자주 넘어지는 증상을 호소했습니다. 

환자는 “발에 걸려 넘어진다”고 설명했습니다. 

그는 

매사추세츠주 브록턴의 브록턴 VA 병원 신경과 클리닉의 신경과 전문의에게 소개되어 

파킨슨병(PD)으로 진단받았습니다. 

환자는 

Sinemet 10/100을 하루 3회 복용하기 시작했으며, 

환자 및 신경과 전문의는 이 약물이 증상과 징후를 완화시킨다고 평가했습니다.

 환자는 보행이 개선되어 삐걱거림이 줄고 낙상이 없게 되었다고 보고했습니다. 신경과 전문의에게 내원 시 복용 중인 약물은 lansoprazole, ranitidine, ibuprofen, aspirin이었으며, 이 중 어느 약물도 파킨슨병 진단과 혼동되거나 유사한 부작용이 기록되지 않았습니다. 그는 과거 약물 남용 이력이나 농약 또는 중금속 노출 이력이 없었습니다. 

그는 종교적인 생활을 영위했으며, 

1978년에 약 10년간 수도원에 입회했습니다. 

그는 매일 최소 30분간의 깊은 명상을 통해 

'센터링 기도'라는 기법으로 기도하는 것을 스스로 배웠습니다.

중심 기도는 고대 전통에 뿌리를 둔 현대 기독교의 명상적 실천 방법으로, 내면의 침묵과 개방성을 통해 하나님과의 더 깊은 관계를 키우는 것을 목표로 합니다.

중심 기도란 무엇인가?

중심 기도는 말없이 침묵으로 드리는 기도 방법으로, 수행자가 관상 기도의 선물—생각, 말, 감정 너머에 있는 하나님의 현존을 경험하는 것—을 받을 수 있도록 준비. 이는 영적 훈련이자 하나님과의 관계를 깊이 하는 방법이며, 대화에서 신과의 교감으로 넘어가는 과정.

기원과 발전

이 실천은 1970년대 매사추세츠주 성 요셉 수도원에서 트라피스트 수도사 토마스 키팅, 윌리엄 메닝거, 바질 펜닝턴에 의해 개발되었습니다. 그들은 The Cloud of Unknowing과 같은 기독교 신비주의 텍스트에서 영감을 받아 현대 기독교인들에게 고대 관상적 실천을 접근 가능하게 만들려고 했습니다

신학적 기반

중심 기도(Centering Prayer)는 기독교 관상 전통, 특히 사막의 아버지들, 아빌라의 테레사, 십자가의 요한, 토마스 머튼의 가르침에서 비롯되었습니다. 이 기도는 하나님이 각 사람 안에 거하신다는 믿음에 뿌리를 두고 있으며, 기도는 말하는 것만큼이나 듣기와 현재에 머무는 것에도 동일하게 초점을 맞춥니다

실천 지침

1. 편안하게 앉아 눈을 감고, 이완하고, 마음을 가라앉히세요.
2. 성스러운 단어(예: “평화”, “사랑”, “예수”)를 선택하여 하나님의 현존에 동의하는 의도의 상징으로 삼습니다.
3. 생각, 감정, 또는 산만함이 느껴질 때마다 성스러운 단어를 부드럽게 떠올리며 이를 앵커로 사용합니다.
4. 산만해지면 판단 없이 부드럽게 성스러운 단어로 돌아갑니다.
5. 10~20분 동안 침묵을 유지한 후, 마지막 몇 분은 조용히 휴식합니다

목적과 의도

목적은 마음을 비우거나 특정 상태를 달성하는 것이 아니라, “하나님의 현존과 행동에 동의하는 것”입니다. 이는 개인적인 노력을 포기하고 단순히 하나님과 함께 있는 것, 신성한 변혁에 대한 개방성을 키우는 것입니다

다른 기도와의 차이점

설교나 성경 묵상과 달리, 중심 기도(Centering Prayer)는 생각, 이미지, 또는 말에 초점을 맞추지 않습니다. 대신 내적 침묵과 수용성에 초점을 맞추며, 모든 생각—심지어 영적 생각까지도—놓아주고 하나님의 현존 속에서 쉼을 취하는 것입니다

2003년, 

환자는 양측 운동 증상(우측 상지에서의 톱니바퀴 운동과 운동 느림)으로

 진행되었습니다. 

같은 해, 환자는 저자 중 한 명(RD)의 진료를 받기 시작했습니다.

 2003년부터 2012년까지 약 1년 간격으로 진료를 받았으며, 

주로 시네메트 25/100 2정 3~4회/일을 투여받았습니다. 

다양한 진료 시에는 미묘한 운동 증상이 나타났으며, 이는 변동되었지만 가끔 양측 상지 중 하나 또는 양쪽에 경도의 cogwheeling, 상지 중 하나에 휴식 시 떨림, 양측 상지 운동 느림이 포함되었습니다. 한 방문 시, 

그는 Sinemet 복용을 잊었을 때 증상이 악화된다고 언급했지만, 

전반적으로 “on-off” 현상의 명확한 진행은 관찰되지 않았습니다. 

2011년, 

그는 약물 연구에 참여했으며, 

이 연구는 5회(약 1주 간격)에 걸쳐 모든 약물과 식사를 밤새 금식한 후 

경구용 카르비도파를 투여받고 

2시간 후 안정 동위 원소 표지 레보도파 200mg을 투여받는 방식으로 진행되었습니다.

한 연구에서

 그의 금식 상태에서의 UPDRS(통합 파킨슨병 평가 척도) 제3부 운동 점수는 22/108이었으며, 

연구에서 투여된 레보도파 후 14/108로 개선되었습니다. 

다른 네 연구에서는 

금식 상태에서의 UPDRS 제3부 점수가 7-9/108 사이였으며, 

연구에서 투여된 카르비도파와 안정 동위 원소 표지 레보도파 후 개선이 없었습니다. 

모든 연구는 동일한 신경과 의사에 의해 평가되었습니다. 

전형적인 '온-오프' 현상이 관찰되지 않아 

시네메트를 점차 감량 후 중단하기로 결정되었습니다. 

그는 2012년에 운동 증상의 악화 없이 이를 완료했으며, 

이후 모든 형태의 약물 치료를 중단했습니다. 

환자는 수술이나 기타 비약물적 치료를 받은 적이 없습니다. 

2014년 마지막 2회 검진 시 구부정한 자세로 걸으며, 

걸음걸이의 어색함, 급히 걸음, 회전 어려움은 관찰되지 않았습니다. 

양손에 경도의 운동 느림이 있었으나 

사지에는 톱니바퀴 현상이나 떨림은 없었습니다.

His last 2 exams in 2014 were characterized by a gait with stooped posture without any shuffling, festination or difficulty with turns. He had mild bradykinesia in both hands but no cogwheeling or tremor in his limbs.

Differential diagnosis and imaging

Vascular parkinsonism

The patient underwent a head CT in 2013, which was negative for vascular parkinsonism and normal pressure hydrocephalus.

Frontotemporal dementia

Clinical exam by a neurologist revealed no signs of dementia. The patient’s score on the Mini Mental State Examination (MMSE) was 27/30, which falls above the 26/30 age- and education level-adjusted cutoff score for cognitive dysfunction [1], indicating normal cognitive status and thereby ruling out any dementing process such as Frontotemporal Dementia or Lewy Body Dementia.

Parkinson’s disease

The patient underwent a SPECT DaT scan in 2014 to clarify the accuracy of the initial PD diagnosis, which was assessed clinically by a radiologist as abnormal. His only medications at this time were alendronate, terazosin, ASA, and calcium; these medications do not interfere with SPECT DaT results.

차별적 진단 및 영상 검사
혈관성 파킨슨증
환자는 2013년에 두부 CT 검사를 받았으며, 혈관성 파킨슨증 및 정상압 수두증에 대한 소견은 음성으로 나타났습니다.

전두측두엽 치매
신경과 전문의의 임상 검진 결과 치매 증상이 관찰되지 않았습니다. 환자의 미니 정신 상태 검사(MMSE) 점수는 27/30으로, 연령 및 교육 수준 조정 기준치인 26/30을 초과하여 인지 기능 장애를 나타내는 기준치를 충족하지 않았습니다[1]. 이는 정상적인 인지 상태를 의미하며, 전두측두엽 치매나 레비체 치매와 같은 치매 과정을 배제합니다.

파킨슨병

환자는 

2014년에 초기 파킨슨병 진단 정확도를 확인하기 위해 

SPECT DaT 검사를 받았으며,

 방사선과 의사에 의해 임상적으로 이상 소견으로 평가되었습니다. 

당시 환자의 유일한 약물은 알렌드로네이트, 테라조신, 아스피린, 칼슘이었으며, 

이 약물은 SPECT DaT 검사 결과에 영향을 미치지 않습니다.

Image quantification

To further investigate the accuracy of the diagnosis, the SPECT scan was coregistered to the patient’s Magnetization Prepared Rapid Gradient Echo (MPRAGE), a high resolution anatomical MRI, and quantified using a voxel-based analysis. He underwent the MPRAGE as part of the Cognition & Parkinson’s Project. The MPRAGE and SPECT scans were coregistered using the FreeSurfer image processing and analysis software, mitigating the lack of anatomical localization in the SPECT scan due to its poor resolution [2, 3]. The voxel-based quantification involved the voxel intensities of the caudate and putamen. The mean intensity of the pericalcarine gyrus served as an intensity baseline as it has been shown to have little to no dopaminergic activity in SPECT DaT scans [4]. The percentage of voxels exceeding four intensity thresholds in each striatal region was quantified, based off the SPECT quantification method developed by Seibyl et al. [3].

이미지 정량화
진단의 정확성을 더욱 조사하기 위해 SPECT 검사는 환자의 고해상도 해부학적 MRI인 Magnetization Prepared Rapid Gradient Echo (MPRAGE)와 정합되었으며, 픽셀 기반 분석을 통해 정량화되었습니다. 환자는 인지 및 파킨슨병 프로젝트의 일환으로 MPRAGE 검사를 받았습니다. MPRAGE 및 SPECT 검사는 FreeSurfer 이미지 처리 및 분석 소프트웨어를 사용하여 정합되었으며, SPECT 검사의 낮은 해상도로 인한 해부학적 위치 지정 부족을 완화했습니다 [2, 3]. 픽셀 기반 정량화는 뇌의 caudate 및 putamen 부위의 픽셀 강도를 포함했습니다. SPECT DaT 검사에서 도파민 활성이 거의 또는 전혀 없는 것으로 알려진 pericalcarine gyrus의 평균 강도는 강도 기준선으로 사용되었습니다 [4]. 각 스트라이아탈 부위에서 4개의 강도 임계값을 초과하는 픽셀의 비율은 Seibyl 등 [3]이 개발한 SPECT 정량화 방법을 기반으로 계산되었습니다.

The patient’s SPECT scan coregistered to his MPRAGE is shown in Figure 1. The gold arrows show that the tail of the right hemispheric putamen (outlined by the white box) is absent, accounting for the patient’s initial lefthand rest tremor. This is supported by the quantification data on the putamen. The same SPECT scan quantification was performed on another patient diagnosed with PD after presenting with right-hand tremor 2 years before the acquisition of his SPECT DaT scan. Therefore, this patient’s caudate and putamen served as “control” regions because they were minimally affected by the disease as of yet. The case patient’s right putamen is the more affected hemisphere (MAH), corresponding to the patient’s initial left-hand rest tremor. The “control” patient’s left putamen is the MAH, corresponding to his initial right-side symptom presentation. In the case patient, the left caudate had more voxels than the right caudate with intensities that exceeded each pericalcarine threshold. There were no voxels in either the left or the right caudate with intensities that exceeded six times the pericalcarine baseline. Presumably due to the long duration of the case patient’s disease, both his left and right caudate had lower intensities than either the left or right “control” caudate. The case patient’s left putamen had more voxels than the right putamen with intensities that exceeded each pericalcarine threshold. Of particular interest, the case patient’s right putamen had much lower voxel intensities than the “control” patient’s left putamen, corresponding to his longer disease duration. As the putamen is the striatal region associated with the motor symptoms of PD, the lower voxel intensities in the case patient’s right putamen (Table 1) correspond to his initial left-hand rest tremor.

환자의 SPECT 영상과 MPRAGE 영상이 정합된 결과는 그림 1에 표시되어 있습니다. 금색 화살표는 오른쪽 반구 내의 putamen(흰색 상자로 표시된 부분)의 꼬리 부분이 결여되어 있음을 보여줍니다. 이는 환자의 초기 왼쪽 손 휴식 시 떨림의 원인을 설명합니다. 이 결과는 putamen에 대한 정량화 데이터로 뒷받침됩니다. 같은 SPECT 스캔 정량화 분석은 PD로 진단받은 다른 환자에게도 수행되었습니다. 이 환자는 SPECT DaT 스캔 촬영 2년 전에 오른손 떨림 증상을 보였습니다. 따라서 이 환자의 뇌의 꼬리핵과 푸타멘은 질병의 영향이 최소화된 “대조군” 지역으로 사용되었습니다. 사례 환자의 오른쪽 푸타멘은 더 영향을 받은 반구(MAH)로, 환자의 초기 왼쪽 손 휴식 떨림과 일치합니다. “대조군” 환자의 왼쪽 푸타멘은 MAH로, 그의 초기 오른쪽 증상 발현과 일치합니다. 사례 환자에서 왼쪽 뇌두체는 오른쪽 뇌두체보다 각 페리카르카인 임계값을 초과하는 강도를 가진 픽셀이 더 많았습니다. 좌측 또는 우측 뇌두핵에서 피리카르린 기준치의 6배를 초과하는 강도의 픽셀은 없었습니다. 환자의 장기간 질병 지속 기간으로 인해, 그의 좌측 및 우측 뇌두핵은 “대조군”의 좌측 또는 우측 뇌두핵보다 강도가 낮았습니다. 환자의 좌측 푸타멘은 우측 푸타멘보다 피리카르린 임계값을 초과하는 강도의 픽셀 수가 더 많았습니다. 특히 주목할 점은 환자의 오른쪽 푸타멘의 픽셀 강도가 “대조군” 환자의 왼쪽 푸타멘보다 훨씬 낮았으며, 이는 환자의 더 긴 질병 기간과 일치합니다. 푸타멘은 파킨슨병의 운동 증상과 관련된 스트라이아탈 부위이므로, 환자의 오른쪽 푸타멘의 낮은 픽셀 강도(표 1)는 그의 초기 왼쪽 손 떨림과 일치합니다.

Discussion

We present an apparent case of remission of symptoms in PD. Parkinson’s disease is a progressive, neurodegenerative disease without a cure in which patients tend to progress from unilateral motor symptoms to bilateral motor and neuropsychological symptoms. We define remission in this case report as an amelioration of signs and symptoms of Parkinson disease in the absence of pharmacologic intervention. The patient was clinically diagnosed with PD by a neurologist in the Brockton VA Neurology Clinic 16 years ago. Then, his diagnosis was substantiated by a diagnostic SPECT DaT scan, as per current clinical practice. Finally, the SPECT scan was quantified, and the data attest to the validity of the initial diagnosis. The patient has been off all anti-parkinsonian pharmacotherapy since 2012 with no clear symptoms or signs of PD. Previously published cases of putative PD remission reveal complicated disease histories and offer compelling evidence for alternative explanations such as drug-induced parkinsonism through a history of drug use [5] and vascular parkinsonism through evidence of ischemic stroke [6]. One group reported that a patient’s PD symptoms remitted during a course of immunotherapy for treatment of melanoma, though the symptoms returned after course completion [7]. It is well recognized that PD symptoms and signs can be improved in settings where external or mental stimuli seem to bypass existing motor disability. Some examples of this kinesia paradoxa have been described with visual cueing [8, 9], emotional stress [10], change in motivation [11] and the addition of rhythm through music and dance [12–15]. For some of these actions, the ventral striatum, which processes motivation and emotion, has been proposed as a possible anatomical substrate.

우리는 파킨슨병(PD)에서 증상의 완화 사례를 보고합니다. 

파킨슨병은 치료법이 없는 진행성 신경퇴행성 질환으로, 

환자들은 일반적으로 일측성 운동 증상에서 양측성 운동 및 신경심리학적 증상으로 진행됩니다. 

본 사례 보고에서 증상 완화는 

약물 치료 없이 파킨슨병의 증상 및 징후가 개선된 상태로 정의합니다.

 환자는 

16년 전 브록턴 VA 신경과 클리닉에서 신경과 의사에 의해 임상적으로 

파킨슨병으로 진단받았습니다. 

이후 현재 임상 관행에 따라 진단용 SPECT DaT 검사로 

진단이 확인되었습니다. 

최종적으로 

SPECT 검사가 정량화되었으며, 

데이터는 초기 진단이 유효함을 입증합니다. 

환자는 

2012년부터 모든 파킨슨병 치료제를 복용하지 않았으며, 

파킨슨병의 명확한 증상이나 징후가 없습니다. 

이전 발표된 PD 완화 사례는 

복잡한 질병 경과를 보여주며, 

약물 사용 이력을 통해 약물 유발성 파킨슨증[5]이나 허혈성 뇌졸중 증거를 통해 

혈관성 파킨슨증[6]과 같은 대체 설명을 제시하는 강력한 증거를 제공합니다.

 한 연구 그룹은 

멜라노마 치료를 위한 면역요법 과정에서 환자의 파킨슨병 증상이 완화되었으나, 

치료 종료 후 증상이 재발했다고 보고했습니다[7]. 

외부 또는 정신적 자극이 

기존 운동 장애를 우회하는 환경에서 파킨슨병 증상 및 징후가 개선될 수 있다는 점은 

잘 알려져 있습니다. 

이 키네시아 파라독스의 일부 사례는 

시각적 단서[8, 9], 감정적 스트레스[10], 동기부여 변화[11], 음악과 춤을 통한 리듬 추가[12–15]와 

연관되어 설명되었습니다. 

이러한 행동 중 일부에서는 

동기부여와 감정을 처리하는 복측 선조체(ventral striatum)가 

가능한 해부학적 기저 구조로 제안되었습니다.

The patient meditates for at least 30 minutes daily using a practice called “centering prayer”, which he learned during his brief time as a postulate in a Franciscan monastery, 37 years ago. In this technique, he focuses his mind on a single religious word to reach a meditative state. He states that he feels less “PD-like” when he meditates so he began to reinvest energy in his meditation practice after his PD onset. There are numerous possibilities that may account for this symptom remission, such as a previously uncharacterized disease progression, an unusually positive response to Levodopa, or the therapeutic contributions of healthy lifestyle habits. One possibility that we would like to bring to the attention of the reader is that the increased intensity of the patient’s meditation practice may have contributed to his improvement in parkinsonian signs and symptoms in the absence of medication. One study found that, during Kundalini meditation, putamen activation significantly increase using fMRI [16]. This is a salient attestation of our suggestion as the Hindu yogic practice of Kundalini meditation is based on a similar principle to “centering prayer”, where practitioners maintain attention on a single word to reach a meditative state [16]. Furthermore, the Kundalini study participants had been regular meditators for only four years, whereas this patient has practiced a similar technique for nearly 40 years [16]. This patient’s consistent, meditation-induced activation of the putamen for so many decades could have increased its dopaminergic tone, counteracting the DA loss of PD, and thus possibly contributing in part to the remission of his symptoms.

환자는 

37년 전 프란치스코회 수도원에서 수련생으로 지낸 짧은 기간 동안 배운 

'센터링 기도'라는 명상 기술을 매일 최소 30분 동안 실천하고 있습니다. 

이 기술에서 

그는 단 하나의 종교적 단어에 마음을 집중시켜 

명상 상태에 이릅니다.

 그는 명상을 할 때 

'PD와 유사한 증상'이 덜 느껴진다고 밝히며, 

PD 발병 후 명상 실천에 다시 에너지를 투자하기 시작했습니다. 

이 증상 완화의 원인은 다양할 수 있습니다. 

예를 들어, 

이전에 알려지지 않은 질병 진행, 

레보도파에 대한 이례적으로 긍정적인 반응, 

건강한 생활 습관의 치료적 기여 등이 포함됩니다. 

독자의 주목을 끌고 싶은 한 가지 가능성은 

환자의 명상 실천 강도가 

약물 없이 파킨슨 증상 개선에 기여했을 수 있다는 점입니다. 

한 연구에서 쿠ン달리니 명상 중 fMRI를 통해 

푸타멘 활성화가 유의미하게 증가했다는 결과가 나왔습니다[16]. 

이는 우리 제안의 중요한 증거로, 

힌두 요가 명상인 쿠ン달리니 명상은 

'중심 기도'와 유사한 원리에 기반을 두고 있으며,

 수행자가 단일 단어에 집중해 명상 상태에 도달하는 방식입니다[16]. 

또한, 쿠ン달리니 연구 참가자들은 4

년간 정기적으로 명상을 실천해 왔지만, 

이 환자는 유사한 기술을 약 40년간 실천해 왔습니다[16]. 

 This patient’s consistent, meditation-induced activation of the putamen for so many decades could have increased its dopaminergic tone, counteracting the DA loss of PD, and thus possibly contributing in part to the remission of his symptoms.

이 환자의 수십 년간 지속된 명상 유발 푸타멘 활성화는 

도파민 분비 기능을 증가시켜 파킨슨병의 도파민 손실을 상쇄하고, 

따라서 증상 완화에 부분적으로 기여했을 수 있습니다.

There is growing evidence of the tangible effects that meditation practices exert on the striatum, particularly in the light of recent advances in functional mapping that have revealed corticostriatal modulatory networks, which may mediate cognitive influences, including those produced by meditation, on striatal dopaminergic functioning. Dense modulatory projections from the ventromedial and orbito-prefrontal areas primarily influence the ventral striatum, the rostral caudate nucleus, and the putamen; additional sensorimotor areas project more caudally, primarily to the putamen [17]. Reciprocal connections from limbic sites, including the hippocampus, project back to the basal ganglia and the prefrontal cortex [17]. Thus, these newly discovered corticostriatal networks provide the functional neuroanatomy via which mind-body interventions, such as this patient’s meditative practice, can influence the neurologic symptoms of PD. The influence of these modulatory networks on dopaminergic functioning is further supported by studies specifically investigating the influence of meditation on both striatal dopaminergic functioning, which could then in turn mitigate Parkinson’s disease symptoms. For instance, Kjaer et al. demonstrated via [11C]raclopride PET scans that striatal DA increased bilaterally during meditation as compared to a non-meditative rest state [18]. This decrease in binding potential of [11C]raclopride, indicating an increase of endogenous DA, was significant in the ventral striatum [18], suggesting the possibility of “increased dopaminergic tone” during meditative states in these regions [18].

명상 실천이 

striatum에 미치는 구체적인 영향에 대한 증거가 점점 더 쌓이고 있습니다. 

특히 최근 기능적 매핑 기술의 발전으로 발견된 

corticostriatal modulatory networks는 명상을 포함한 인지적 영향이

striatal dopaminergic functioning 에 미치는 메커니즘을 매개할 수 있음을 시사합니다. 

There is growing evidence of the tangible effects that meditation practices exert on the striatum, particularly in the light of recent advances in functional mapping that have revealed corticostriatal modulatory networks, which may mediate cognitive influences, including those produced by meditation, on striatal dopaminergic functioning

복측 내측 및 전두엽-안와 부위에서 나오는 밀집된 조절 투사 신경섬유는 

주로 복측 스트라이아툼, 전방 꼬리핵, 및 푸타멘에 영향을 미칩니다. 

추가적인 감각운동 부위는 

주로 푸타멘으로 더 후방으로 투사됩니다 [17]. 

한계부 영역(예: 해마)에서 

기저핵과 전전두피질로 돌아가는 상호 연결이 존재합니다[17]. 

따라서 이 새롭게 발견된 대뇌피질-스트라이아탈 네트워크는 이 환자의 명상 실천과 같은 마음-신체 개입이 파킨슨병의 신경학적 증상에 영향을 미칠 수 있는 기능적 신경해부학적 기반을 제공합니다. 이러한 조절 네트워크가 도파민 기능에 미치는 영향은 명상이 스트라이얼 도파민 기능에 미치는 영향을 구체적으로 조사한 연구들에 의해 추가로 지원됩니다. 이는 다시 PD 증상을 완화할 수 있습니다. 

예를 들어, Kjaer 등[18]은 [11C]raclopride PET 스캔을 통해 명상 중 스트라이얼 DA가 비명상 휴식 상태에 비해 양측에서 증가함을 보여주었습니다. [11C]raclopride의 결합 잠재력 감소는 내인성 도파민 증가를 나타내며, 이는 복부 스트라이아툼에서 유의미했습니다[18]. 이는 이러한 지역에서 명상 상태에서 “도파민 활성 증가”의 가능성을 시사합니다[18].

Pagnoni et al. proposed that regular meditation may, over time, help to counteract normal age-related striatal shrinkage and dopaminergic reduction [19]. Their MPRAGE study found that meditators did not experience the same extent of age-related decrease in grey matter volume as controls, and this was most apparent in the bilateral putamen [19]. Therefore, consistent meditative practice may offer a benefit to PD patients suffering from striatal DA loss. Recently, Pickut et al. found that, using MPRAGE scans, PD patients who participated in an eight-week mindfulness meditation program exhibited significantly increased striatal grey matter density [20]. The authors pointed out that, as the striatum is a target for dopaminergic therapy in PD, this increase in striatal grey matter density could manifest physically as symptomatic relief [20]. One fMRI study found that cerebral blood flow was higher in the putamen of long-term meditators than in non-meditators [21]. In this study, the long-term meditators had been regularly practicing meditation for at least fifteen years [21]. As this patient’s history of meditative practice is more than twice as long, he may have similar functional brain changes that contributed to his recovery.

파그노니 등(Pagnoni et al.)은 

규칙적인 명상이 시간이 지나면서 정상적인 연령 관련 

스트라이아탈 위축과 도파민계 감소에 대항하는 데 도움이 될 수 있다고 제안했습니다[19]. 

그들의 MPRAGE 연구에서 명상 그룹은 

대조군과 비교해 연령 관련 회백질 부피 감소가 동일한 정도를 보이지 않았으며, 

이는 양측 푸타멘에서 가장 명확히 관찰되었습니다[19]. 

따라서 

일관된 명상 실천은 스트라이아탈 도파민 손실을 겪는 파킨슨병 환자에게

 이점을 제공할 수 있습니다. 

최근 Pickut 등[20]은 

MPRAGE 스캔을 사용해 8주간의 마음챙김 명상 프로그램에 참여한 파킨슨병 환자들이 

스트라이얼 회백질 밀도가 유의미하게 증가했음을 발견했습니다. 

저자들은 

스트라이얼이 파킨슨병의 도파민 치료 표적 부위임을 지적하며, 

이 회백질 밀도 증가가 증상 완화로 물리적으로 나타날 수 있다고 강조했습니다[20]. 

한 fMRI 연구에서는 장기 명상 실천자의 뇌 혈류가 비명상 실천자보다 뇌의 푸타멘 부위에서 더 높게 나타났습니다 [21]. 

이 연구에서 장기 명상 실천자들은 최소 15년간 정기적으로 명상을 실천해 왔습니다 [21]. 

이 환자의 명상 실천 기간이 그보다 두 배 이상 길기 때문에, 

그의 회복에 기여한 유사한 기능적 뇌 변화가 있을 수 있습니다.

Conclusions

This case has implications for both the effects of meditation practice and the clinical understanding of PD. If the patient’s motor symptom remission was indeed due, in part, to his meditation practice, then this case could lend further evidence for the potential benefits of meditation as a non-pharmacological adjunct therapy for PD. We are unable to offer insight as to why the patient presented with PD in the face of such possible benefits of long-term meditation practice; however, intensity of engagement with the practice likely increased after the diagnosis, and he may have benefited from this more intensive practice. Regardless of the role of the patient’s meditation, this case demonstrates the possibility of PD symptom remission.

결론

이 사례는 명상 실천의 효과와 파킨슨병(PD)의 임상적 이해 모두에 시사점을 제공합니다. 

만약 환자의 운동 증상 완화가 부분적으로 명상 실천 때문이었다면, 

이 사례는 PD에 대한 비약물적 보조 치료법으로 명상의 잠재적 이점을 입증하는 추가적인 증거가 될 수 있습니다. 

우리는 

장기적인 명상 실천의 잠재적 이점에도 불구하고 

환자가 PD를 발병한 이유에 대해 명확히 설명할 수 없습니다. 

그러나 

진단 후 명상 실천에 대한 참여 강도가 증가했을 가능성이 있으며, 

이로 인해 더 집중적인 실천으로부터 혜택을 받았을 수 있습니다.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. This work was conducted at Boston VA Healthcare System, Jamaica Plain Campus at 150 S. Huntington Ave., Jamaica Plain, MA, 10461. Research funding: This work was supported by The John Templeton Foundation under Grant #7733510. Employment or leadership: None declared. Honorarium: None declared. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.