Re: 글루텐을 제거한 식단을 하고 als가 치료된 사례

[문형철]

https://www.ajnr.org/content/31/5/880

Abstract

SUMMARY: CD is an autoimmune-mediated disorder of the gastrointestinal tract. Initial symptom presentation is variable and can include neurologic manifestations that may comprise ataxia, neuropathy, dizziness, epilepsy, and cortical calcifications rather than gastrointestinal-hindering diagnosis and management. We present a case of a young man with progressive neurologic symptoms and brain MR imaging findings worrisome for ALS. During the diagnostic work-up, endomysium antibodies were discovered, and CD was confirmed by upper gastrointestinal endoscopy with duodenal biopsies. MR imaging findings suggestive of ALS improved after gluten-free diet institution.

CD는 자가면역 매개성 위장관 질환입니다. 초기 증상은 다양하며 위장관 장애 진단 및 관리보다는 운동실조, 신경병증, 현기증, 간질, 피질 석회화 등의 신경학적 증상을 보일 수 있습니다. 루게릭병이 우려되는 진행성 신경 증상과 뇌 MR 영상 소견을 보인 한 젊은 남성의 사례를 소개합니다. 진단 검사 중 엔도미시움 항체가 발견되었고, 십이지장 생검을 포함한 상부 위장관 내시경 검사에서 루게릭병이 확진되었습니다. 루게릭병을 암시하는 MR 영상 소견은 글루텐 프리 식단을 시행한 후 개선되었습니다.

Abbreviations ALSamyotrophic lateral sclerosisCDceliac diseaseFLAIRfluid-attenuated inversion recoveryIgAimmunoglobulin

A

CD is an inflammatory condition of the small intestine also called celiac sprue, nontropical sprue, and gluten-sensitive enteropathy. The most common presenting symptoms include diarrhea, steatorrhea, weight loss, iron deficiency anemia, and abdominal distension. Imaging findings specific to the brain have been reported primarily involving the periventricular white matter.

CD는 셀리악 스프루, 비열대성 스프루, 글루텐 민감성 장병증이라고도 하는 소장의 염증성 질환입니다. 가장 흔하게 나타나는 증상으로는 설사, 지방 설사, 체중 감소, 철분 결핍성 빈혈, 복부 팽만감 등이 있습니다. 뇌와 관련된 영상 소견은 주로 뇌실 주변 백질과 관련된 것으로 보고되었습니다.

Case Report

A 32-year-old man with a 1-year history of balance difficulties presented with 1 week of worsening symptoms, including hand tremors and gait disturbance. Admission review of systems revealed a 60-pound (27.22 kg) weight loss during the past year, which he attributed to diarrhea consisting of 3–4 loose stools per day. Physical examination showed a broad-based gait leaning to the right, dysmetria with right finger-to-nose, hyperreflexia, an upgoing right toe, right lower extremity weakness, and right foot drop. Sensation was normal. Laboratory studies revealed a slightly elevated phosphorus concentration (4.8 mg/dL), but findings were otherwise normal. Brain MR imaging showed abnormal increased signal intensity on T2 and FLAIR in the bilateral corona radiata, extending inferiorly into the corticospinal tracts without contrast enhancement (Fig 1).

1년간 균형 장애 병력이 있는 32세 남성이 손 떨림과 보행 장애를 포함한 증상 악화를 호소하며 1주일간 입원했습니다. 시스템 입원 검토 결과 지난 1년 동안 체중이 60파운드(27.22kg) 감소했으며, 이는 하루에 3~4회 묽은 변을 보는 설사 때문인 것으로 밝혀졌습니다. 신체 검사 결과 오른쪽으로 기울어진 걸음걸이, 오른쪽 손가락과 코가 맞닿는 부조화, 과반사, 오른쪽 발가락이 위로 올라가고 오른쪽 하지 약화, 오른쪽 발이 떨어지는 증상을 보였습니다. 감각은 정상이었습니다. 실험실 검사 결과 인 농도가 약간 상승(4.8 mg/dL)했지만 다른 소견은 정상이었습니다. 뇌 MR 영상에서 양측 코로나 방사상의 T2 및 FLAIR 신호 강도가 비정상적으로 증가하여 조영증강 없이 피질척수까지 열등하게 확장된 것으로 나타났습니다(그림 1).

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Fig 1.

FLAIR images from initial brain MR imaging demonstrate abnormal increased signal intensity in the white matter of the centra semiovale and bilateral corticospinal tracts.

Initial diagnostic considerations included ALS and Friedrich ataxia. Electromyelography findings of the right upper and lower extremities were normal. Total spine MR imaging and CT findings of the chest, abdomen, and pelvis were normal. CSF findings for herpes simplex virus, human herpesvirus 6 cytomegalovirus, varicella-zoster virus, Epstein-Barr virus, and Venereal Disease Research Laboratory test were negative, but +4 oligoclonal bands were noted. Findings were negative for paraneoplastic antibodies. Ataxia work-up included a positive antiendomysial antibody titer of 1:160. Duodenal biopsies yielded crypt hyperplastic villous atrophy with numerous intraepithelial lymphocytes, most consistent with gluten-sensitive enteropathy.

초기 진단 고려 사항에는 루게릭병과 프리드리히 운동 실조증이 포함되었습니다. 우측 상지 및 하지의 근전도 검사 소견은 정상이었습니다. 흉부, 복부, 골반의 전체 척추 MR 영상 및 CT 소견은 정상이었습니다. 단순 포진 바이러스, 인간 헤르페스 바이러스 6 거대 세포 바이러스, 수두 대상 포진 바이러스, 엡스타인-바 바이러스 및 성병 연구 실험실 검사에 대한 CSF 소견은 음성이었지만 +4 올리고 클로날 밴드가 관찰되었습니다. 부신 생물 항체 검사 결과는 음성이었습니다. 운동 실조증 검사에서는 항내막 항체 역가가 1:160으로 양성이었습니다. 십이지장 생검 결과 글루텐 민감성 장병증과 가장 일치하는 수많은 상피 내 림프구가 있는 토굴 과형성 융모 위축이 발견되었습니다.

The patient started a strict gluten-free diet with improvement of symptoms during the next several months. Repeat brain MR imaging (23 months after initial presentation) revealed resolution of initial abnormalities (Fig 2 ). Continued physical therapy and a gluten-free diet have been prescribed.

환자는 엄격한 글루텐 프리 식단을 시작했고 이후 몇 달 동안 증상이 개선되었습니다. 반복적인 뇌 MR 영상 촬영(최초 증상 발현 후 23개월 후)에서 초기 이상 소실이 확인되었습니다(그림 2 ). 지속적인 물리 치료와 글루텐 프리 식단이 처방되었습니다.

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Fig 2.

Follow-up FLAIR images after a gluten-free diet show complete resolution of signal-intensity abnormalities.

Discussion

CD is an inflammatory condition of the small intestine also called celiac sprue, nontropical sprue, and gluten-sensitive enteropathy.1 The disease appears in early childhood and has a second peak in the third-to-fourth decades. Males and females are equally affected, and its incidence has increased in Northern Europe and the United States.2,3 Multiple other disorders have been associated with CD, including Down syndrome, insulin-dependent diabetes mellitus, IgA deficiency, and rheumatoid arthritis.1

CD는 셀리악 스프루, 비열대성 스프루, 글루텐 민감성 장병증이라고도 하는 소장의 염증성 질환입니다.1 이 질환은 유아기에 나타나며 3~40대에 두 번째 정점을 이룹니다. 남성과 여성이 똑같이 영향을 받으며, 북유럽과 미국에서 발병률이 증가했습니다.2,3 다운 증후군, 인슐린 의존성 당뇨병, IgA 결핍, 류마티스 관절염 등 여러 다른 질환이 CD와 연관되어 있습니다.1

Symptoms are precipitated in genetically predisposed individuals by ingestion of foods containing gluten, such as wheat, rye, and barley. Consumption of triggering foods leads to an autoimmune-mediated inflammatory response in the small intestine, resulting in villous atrophy and malabsorption.3 The most common presenting symptoms include diarrhea, steatorrhea, weight loss, iron deficiency anemia, and abdominal distension.

유전적 소인이 있는 사람은 밀, 호밀, 보리 등 글루텐이 함유된 식품을 섭취할 경우 증상이 악화됩니다. 유발 식품을 섭취하면 소장에서 자가 면역 매개 염증 반응이 일어나 융모 위축과 흡수 장애가 발생합니다.3 가장 흔하게 나타나는 증상으로는 설사, 지방 설사, 체중 감소, 철분 결핍 빈혈, 복부 팽만감 등이 있습니다.

The diagnosis is sometimes difficult to make given that not all patients present in the same manner and that symptoms overlap other gastrointestinal disorders. Half of patients have iron deficiency anemia or osteoporosis, without diarrhea. Diagnostic eval‎uation for CD consists of antibody testing and duodenal biopsy.4 The most sensitive and specific antibodies for its confirmation are tissue transglutaminase IgA and endomysial IgA antibodies. Due to the low specificity compared with tissue transglutaminase and endomysium antibodies, gliadin antibodies should no longer be used in the diagnostic work-up for CD. Duodenal biopsies are still the criterion standard for tissue diagnosis and reveal villous atrophy5 and increased intraepithelial lymphocytes.6

모든 환자가 같은 방식으로 증상을 보이는 것은 아니며 다른 위장 질환과 증상이 겹치기 때문에 진단이 어려운 경우도 있습니다. 환자의 절반은 설사 없이 철분 결핍성 빈혈이나 골다공증을 동반합니다. CD 진단 평가는 항체 검사와 십이지장 생검으로 이루어집니다.4 진단에 가장 민감하고 특이적인 항체는 조직 트랜스글루타미나제 IgA 및 내막 IgA 항체입니다. 조직 트랜스글루타미나제 및 엔도미시움 항체에 비해 특이도가 낮기 때문에 글리아딘 항체는 더 이상 CD 진단 검사에 사용해서는 안 됩니다. 십이지장 생검은 여전히 조직 진단의 기준 표준이며 융모 위축5 및 상피내 림프구 증가를 확인합니다.6

Neurologic findings associated with CD disease were initially reported in 1966 by Cooke and Smith.7 Most common symptoms are ataxia and neuropathy, followed by epilepsy, ALS and multiple sclerosis-like symptoms, isolated motor neuron disorders, sensory ataxia, and dizziness. These complications may arise as consequences of vitamin and mineral deficiencies. Other authors discuss a potential pathophysiologic role of antigliadin antibodies in a neurotoxic autoimmune process.8

CD 질환과 관련된 신경학적 소견은 1966년 쿡과 스미스에 의해 처음 보고되었습니다.7 가장 흔한 증상은 운동 실조와 신경 병증이며, 간질, 루게릭병 및 다발성 경화증 유사 증상, 고립 운동 신경 세포 장애, 감각 실조, 현기증 등이 그 뒤를 잇습니다. 이러한 합병증은 비타민과 미네랄 결핍의 결과로 발생할 수 있습니다. 다른 저자들은 신경독성 자가면역 과정에서 항글리아딘 항체의 잠재적인 병태생리학적 역할에 대해 논의합니다.8

MR imaging is used primarily in the diagnostic work-up of CD-associated conditions. Nonspecific periventricular white matter lesions of various sizes with increased T2/FLAIR signal intensity and without enhancement have been described.9,10 The lesions may be unilateral and bilateral.11 Occipital calcifications have also been reported. In 2007, Turner et al12 reported a case of CD mimicking ALS with T2/FLAIR signal-intensity abnormalities in the left corticospinal tract, which improved on a gluten-free diet. Our patient also showed abnormal signal intensity involving both corticospinal tracts on MR imaging. His symptoms and MR imaging lesions improved and resolved, respectively, on appropriate treatment of CD. Ours is the second patient reported with this group of findings. Because ALS is a progressive and untreatable disease while CD is easily treatable, considering the latter as a cause of neurologic disorders in patients with ALS-like symptoms may be indicated.

MR 영상은 주로 CD 관련 질환의 진단 검사에 사용됩니다. T2/FLAIR 신호 강도가 증가하고 증강이 없는 다양한 크기의 비특이적 뇌실 주변 백질 병변이 기술되었습니다.9,10 병변은 일측성 또는 양측성일 수 있습니다.11 후두 석회화도 보고되었습니다. 2007년에 Turner 등12은 좌측 피질척수에서 T2/FLAIR 신호 강도 이상이 있는 루게릭병을 모방한 CD 사례가 글루텐 프리 식단으로 개선되었다고 보고했습니다. 우리 환자도 MR 영상에서 양쪽 피질척수관과 관련된 비정상적인 신호 강도를 보였습니다. 이 환자의 증상과 MR 영상 병변은 적절한 CD 치료로 각각 개선되고 해결되었습니다. 이 환자는 이러한 소견이 보고된 두 번째 환자입니다. 루게릭병은 진행성이며 치료가 불가능한 질환인 반면, CD는 쉽게 치료할 수 있기 때문에 루게릭병과 유사한 증상을 보이는 환자에서 신경 장애의 원인으로 후자를 고려하는 것이 필요할 수 있습니다.

References

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• Received June 23, 2009.
• Accepted after revision July 3, 2009.

• Copyright © American Society of Neuroradiology

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