We report a case of subacute combined spinal cord degeneration (SCD) caused by vegetarianism and autoimmune gastritis, which is rarely reported in Japan, and which showed improvement in symptoms and imaging findings after vitamin B12 administration. As delayed treatment can lead to irreversible damage, we suggest that patients with characteristic abnormal signals in the posterior cervical cord should be examined while considering the possibility that SCD may occur even in the absence of a history of gastrectomy or heavy drinking. We also describe the patient’s reversible abnormal signals in the cerebral white matter on magnetic resonance imaging, indicative of an early sign of leukoencephalopathy associated with vitamin B12 deficiency

Harada, Masafumi

Kida, Yukari

Kudo, Chiaki

Matsushita, Tomoki

Sakamoto, Yuko

Shimazu, Hideki

Tanakami, Akihito

English

Tokushima University Institutional Repository

299CASE REPORTA case of subacute combined spinal cord degeneration and suspected leukoencephalopathy associated with vitamin B12 deficiency showing improved imaging findings after vitamin B12 administrationTomoki Matsushita1, Yuko Sakamoto2, Akihito Tanakami2, Hideki Shimazu2, Chiaki Kudo3, Yukari Kida1, and Masafumi Harada11Department of Radiology, Tokushima University Hospital, Tokushima, Japan, 2Department of Radiology, Yoshinogawa Medical Center, Tokushima, Japan, 3Department of Internal medicine, Yoshinogawa Medical Center, Tokushima, JapanAbstract : We report a case of subacute combined spinal cord degeneration (SCD) caused by vegetarianism and autoimmune gastritis, which is rarely reported in Japan, and which showed improvement in symptoms and imaging findings after vitamin B12 administration. As delayed treatment can lead to irreversible damage, we suggest that patients with characteristic abnormal signals in the posterior cervical cord should be examined while considering the possibility that SCD may occur even in the absence of a history of gastrectomy or heavy drinking. We also describe the patient’s reversible abnormal signals in the cerebral white matter on magnetic resonance imaging, indicative of an early sign of leukoencephalopathy associated with vitamin B12 deficiency. J. Med. Invest. 69 : 299-301, August, 2022Keywords : subacute combined spinal cord degeneration, vitamin B12, autoimmune gastritis, vegetarianism, leukoencephalopathyINTRODUCTION Subacute combined spinal cord degeneration (SCD) is a neu-rodegenerative disease caused by vitamin B12 deficiency. It typically occurs after total gastrectomy, but may also be caused by autoimmune gastritis (AIG), small intestinal diseases, veg-etarianism, and chronic alcoholism. We report a case of SCD, which was suspected of being caused by vitamin B12 deficiency associated with autoimmune gastritis and vegetarianism, and wherein the imaging findings were improved following vitamin B12 administration. We also report the patient’s imaging findings suggesting reversible leukoencephalopathy due to vitamin B12 deficiency, which is less frequently reported than SCD. CASE REPORTA 55-year-old woman with a history of bladder cancer, appen-dicitis, and cesarean section was admitted because of fever and difficulty in moving. She experienced numbness in her fingers and toes for the preceding 2 weeks, and developed fever and weakness in her lower limbs 3 days before admission. She was alert and well-oriented, evident cognitive dysfunction was not ob-served. The physical and neurological examinations revealed a body temperature of 38.2°C, gait disturbance, muscle weakness, numbness in the limbs, and disorder of skilled movements. On the manual muscle test (MMT), muscle strength was 4 / 4 both in the upper and lower limbs. Babinski reflex, increased deep tendon reflex, cranial nerves disorder was absent. She did not smoke or drink, and had been on a vegetarian diet. Specifically, she had avoided animal products such as meat, fish, and eggs for approximately 6 years. A blood test showed macrocytic anemia (hemoglobin, 8.6 g / dL ; normal range 12.0-15.0 g / dL, mean corpuscular volume, 105.1 fL ; normal range 79.0-100 fL) and low serum vitamin B12 levels (<50 pg / mL ; normal range 180-914 pg / mL). A urine test revealed urinary tract infection (> 100 white blood cells per high-power field) and abdominal computed to-mography (CT) revealed renal enlargement and peri-renal fat stranding ; thus, her fever was suspected of being caused by acute pyelonephritis. After antibiotic treatment, the patient was completely cured.Fluid-attenuated inversion recovery (FLAIR) and diffu-sion-weighted imaging (DWI) of brain magnetic resonance imaging (MRI) demonstrated slight hyperintensity in the sple-nium of the corpus callosum and subcortical white matter in the frontal lobe (Fig1). These areas did not show low apparent diffu-sion coefficient (ADC) values and gadolinium enhancement on contrast-enhanced MRI. T2-weighted image (T2WI) and short tau inversion recovery (STIR) of cervical MRI demonstrated the cervical cord swelling and hyperintensity of posterior columns, so called “inverted V sign,” extending from the level of the C2 to the C6 vertebrae (Fig 2). This abnormal intensity area did not exhibit gadolinium enhancement on contrast-enhanced MRI, similar to white matter lesions in the brain. The patient was di-agnosed with SCD and the initial stage of leukoencephalopathy associated with vitamin B12 deficiency was suspected.Concurrently with vitamin B12 administration, the cause of vi-tamin B12 deficiency was investigated. Additional tests revealed that she was positive for the anti-intrinsic factor antibody and negative for the anti-Helicobacter pylori antibody with endoscop-ic gastric atrophy. These findings suggested AIG ; herefore, the vegetarian diet along with AIG was suspected of having resulted in vitamin B12 deficiency. The patient was treated with 500 - 1000μg / day of mecobal-amin intramuscularly for two weeks with a combination of 1000μg / day of cyanocobalamin intravenously for the first 10 The Journal of Medical Investigation    Vol. 69  2022　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　Received for publication February 7, 2022 ; accepted March 11, 2022.Address correspondence and reprint requests to Tomoki Matsushita, Department of Radiology, Tokushima University Hospital, Kuramoto-cho, Tokushima, 770- 8503, Japan and Fax : +81-886-33-7468.300 T. Matsushita, et al.  subacute combined spinal cord degenerationdays, and got to walk by herself. After discharge, intramuscular injection three times a week is continuing by her family doctor, which dosage is adjusted according to symptoms. Approximately 7 months later, on follow-up MRI, cervical cord swelling and high signal intensity in the white matter of the brain and cervical spine disappeared (Fig1, 2). However, slight numbness in the limbs was still remained. It was probably going to be a lasting symptom. The patient continued vitamin B12 supplementation at her family doctor.DISCUSSIONSCD typically occurs after gastrectomy (1) ; however, the current case was unique as there was no history of gastrectomy. The SCD in this case was considered to have been caused by a combination of AIG-associated malabsorption and inadequate food intake due to vegetarianism. An additional unique aspect was that the brain MRI scan demonstrated reversible abnormal signal intensity, indicative of “leukoencephalopathy associated with vitamin B12 deficiency.”Orally ingested vitamin B12 needs the intrinsic factor, pro-duced by the parietal cells of the gastric mucosa, to be absorbed into the body (2). AIG is an autoimmune disease that causes mu-cosal atrophy in the gastric fundic gland region due to anti-pari-etal cell and anti-intrinsic antibodies, resulting in malabsorption of vitamin B12 (1). The prevalence of autoimmune gastritis in as-ymptomatic individuals undergoing medical checkups is 0.49% in Japan ; this disease is not very rare (3). However, there are relatively few reported cases of SCD caused by AIG. We suggest some reasons for this discrepancy as follows : 1) AIG is often masked by atrophic gastritis associated with H. pylori infection, especially in Japan, and is easily missed by inexperienced en-doscopists (3) ; 2) vitamin B12 has an intrinsic factor-independent absorption pathway (4), and 3) it takes quite a few years before vitamin B12 deficiency develops after the onset of malabsorption, as shown after gastrectomy (5, 6). In the present case, SCD was considered to have been caused not only by AIG, but a combina-tion of AIG and an unbalanced diet. The imaging findings of SCD are characterized by a mildly enlarged spinal cord and continuous hyperintensity on T2WI in the craniocaudal direction, especially the posterior and lateral columns in the lower cervical to upper thoracic spinal cord (7, 8, 9). If appropriate treatment is given in the early stages of the disease, the spinal cord swelling and abnormal signals on MRI will disappear, but if treatment is delayed, the condition may Fig 1.　brain MRI – FLAIR (A – before, A’ – after ), DWI (B – before, B’ – after), ADC map (C – before, C’ – after)Slight hyperintensity changes in the splenium of the corpus callosum and subcortical white matter in the frontal lobe were detected before treatment (A, B). These areas did not show low intensity in ADC maps (C). Seven months after treatment initiation, these abnormal signals almost disappeared (A’, B’, C’).Fig 2.　cervical MRI – T2WI (A, B – before, A’, B’ – after)The first MRI revealed cervical cord swelling and hyperintensity of the posterior column, the so-called “inverted V sign,” extending from the level of the C2 to the C6 vertebrae (A, B). Seven months after treatment initiation, these abnormal findings disappeared (A’, B’).301The Journal of Medical Investigation   Vol. 69  August  2022not improve (2). Moreover, gadolinium-enhancement or non-en-hancement is not constant (2, 7). In the present case, cervical MRI scan demonstrated typical signal changes, so called the “inverted V” shape on T2WI and STIR which disappeared on repeated MRI. This treatment was initiated within 2-3 weeks of awareness of symptoms and the patient showed almost full re-covery. However, permanent damage has been reported ; there-fore, diagnosis and  treatment should begin as soon as possible. Reports of vitamin B12 deficiency-associated leukoencephalop-athy are quite rare, and we could not find any reports regarding its association with AIG and vegetarianism. Based on a review of the PubMed database from 1983 to 2021 using the keywords “vitamin B12,” “cobalamin,” and “leukoencephalopathy,” 20 refer-ences were found, of which less than 10 were reports of leukoen-cephalopathy associated with vitamin B12 deficiency, similar to this case. MRI findings of leukoencephalopathy associated with vitamin B12 deficiency reportedly includes multiple focal or con-fluent T2WI / FLAIR-high signal intensities in the periventricu-lar white matter, with some reports showing abnormal signals in the cerebellum (2, 10, 11). There are few reports describing DWI, with some reports indicating that it was completely or partially reversible (12, 13), whereas others showed a high signal but no description of responsiveness to treatment (14). Moreover, we could not find any reports describing ADC map. In the present case, it was difficult to make a definitive diagnosis of leukoen-cephalopathy associated with vitamin B12 deficiency because the distribution of the signals was limited and their intensity was faint compared to those of previously reported images. However, the signal abnormality was improved on repeated MRI, there-fore, it was considered that it might have been the initial stage of leukoencephalopathy. It is believed that hyperintensity on DWI with restricted water diffusion on ADC maps in SCD is consistent with the co-existence of intramyelin edema (2), and leukoencephalopathy associated with vitamin B12 deficiency may be caused by a sim-ilar mechanism. In this case, however, the brain MRI scan only revealed a faint hyperintensity on DWI and did not show lower ADC values, suggesting that intramyelin edema had not yet been complete. This might be related to the reversibility of the imaging findings and good response to treatment.CONCLUSIONWe encountered a case of SCD caused by vitamin B12 defi-ciency due to AIG and vegetarianism, which is rarely reported in Japan. Furthermore, brain MRI revealed abnormal signal intensity, which was suspected to be the initial stage of leuko-encephalopathy associated with vitamin B12 deficiency. If treat-ment is delayed, irreversible damage may occur. Therefore, when characteristic signal changes in the posterior cervical spinal cord are observed, SCD should be considered even in the absence of a history of gastrectomy or heavy drinking and the causes of vitamin B12 deficiency should be investigated. Further, attention should be paid to the presence or absence of a high signal on DWI or lower ADC values which may reflect the condition of intramy-elin edema and therapeutic response. CONFLICT OF INTERESTNoneREFERENCES1. 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subacute combined spinal cord degeneration

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